Image-Guided High-Dose Rate Brachytherapy in Cervix Carcinoma Using Balloon Catheter and Belt Immobilization System.

PubMed

Fan, Qiyong; Yeung, Anamaria R; Amdur, Robert; Helmig, Richard; Park, Justin; Li, Jonathan; Kahler, Darren; Liu, Chihray; Lu, Bo

2017-06-01

The efficacy of image-guided high-dose rate brachytherapy for cervical cancer is limited by the ineffective rectal sparing devices available commercially and the potential applicator movement. We developed a novel device using a balloon catheter and a belt immobilization system, serving for rectal dose reduction and applicator immobilization purposes, respectively. The balloon catheter is constructed by gluing a short inflatable tube to a long regular open-end catheter. Contrast agent (10) cm 3 is injected into the inflatable end, which is affixed to the tandem and ring applicator, to displace the posterior vaginal wall. The belt immobilization system consists of a specially designed bracket that can hold and fix itself to the applicator, a diaper-like Velcro fastener package used for connecting the patient's pelvis to the bracket, and a buckle that holds the fasteners to stabilize the whole system. The treatment data for 21 patients with cervical cancer using both balloon catheter and belt immobilization system were retrospectively analyzed. Computed tomography and magnetic resonance images, acquired about 30 minutes apart, were registered to evaluate the effectiveness of the immobilization system. In comparison with a virtual rectal blade, the balloon decreased the rectal point dose by 34% ± 4.2% (from 276 ± 57 to 182 ± 38 cGy), corresponding to an extra sparing distance of 7.9 ± 1.1 mm. The maximum sparing distance variation per patient is 1.4 ± 0.6 mm, indicating the high interfractional reproducibility for rectum sparing. With the immobilization system, the mean translational and rotational displacements of the applicator set are <3 mm and <1.5°, respectively, in all directions. The rectal balloon provides significant dose reduction to the rectum and it may potentially minimize patient discomfort. The immobilization system permits almost no movement of the applicator during treatment. This work has the potential to be promoted as a standardized solution for high-dose rate treatment of cervical cancer.

In vivo real-time rectal wall dosimetry for prostate radiotherapy

PubMed Central

Hardcastle, Nicholas; Cutajar, Dean L.; Metcalfe, Peter E.; Lerch, Michael L. F.; Perevertaylo, Vladimir L.; Tomé, Wolfgang A.; Rosenfeld, Anatoly B.

2010-01-01

Rectal balloons are used in external beam prostate radiotherapy to provide reproducible anatomy and rectal dose reductions. This is an investigation into the combination of a MOSFET radiation detector with a rectal balloon for real time in vivo rectal wall dosimetry. The MOSFET used in the study is a radiation detector that provides a water equivalent depth of measurement of 70μm. Two MOSFETs were combined in a face-to-face orientation. The reproducibility, sensitivity and angular dependence were measured for the dual MOSFET in a 6MV photon beam. The dual MOSFET was combined with a rectal balloon and irradiated with hypothetical prostate treatments in a phantom. The anterior rectal wall dose was measured in real time and compared with the planning system calculated dose. The dual MOSFET showed angular dependence within ± 2.5% in the azimuth and +2.5%/-4% in the polar axes. When compared with an ion chamber measurement in a phantom, the dual MOSFET agreed within 2.5% for a range of radiation path lengths and incident angles. The dual MOSFET had reproducible sensitivity for fraction sizes of 2-10Gy. For the hypothetical prostate treatments the measured anterior rectal wall dose was 2.6% and 3.2% lower than the calculated dose for 3DCRT and IMRT plans. This was expected due to limitations of the dose calculation method used at the balloon cavity interface. A dual MOSFET combined with a commercial rectal balloon was shown to provide reproducible measurements of the anterior rectal wall dose in real time. The measured anterior rectal wall dose agreed with the expected dose from the treatment plan for 3DCRT and IMRT plans. The dual MOSFET could be read out in real time during the irradiation, providing capability for real time dose monitoring of the rectal wall dose during treatment. PMID:20571209

The association of rectal equivalent dose in 2 Gy fractions (EQD2) to late rectal toxicity in locally advanced cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University.

PubMed

Tharavichtikul, Ekkasit; Meungwong, Pooriwat; Chitapanarux, Taned; Chakrabandhu, Somvilai; Klunklin, Pitchayaponne; Onchan, Wimrak; Wanwilairat, Somsak; Traisathit, Patrinee; Galalae, Razvan; Chitapanarux, Imjai

2014-06-01

To evaluate association between equivalent dose in 2 Gy (EQD2) to rectal point dose and gastrointestinal toxicity from whole pelvic radiotherapy (WPRT) and intracavitary brachytherapy (ICBT) in cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University. Retrospective study was designed for the patients with locally advanced cervical cancer, treated by radical radiotherapy from 2004 to 2009 and were evaluated by rectosigmoidoscopy. The cumulative doses of WPRT and ICBT to the maximally rectal point were calculated to the EQD2 and evaluated the association of toxicities. Thirty-nine patients were evaluated for late rectal toxicity. The mean cumulative dose in term of EQD2 to rectum was 64.2 Gy. Grade 1 toxicities were the most common findings. According to endoscopic exam, the most common toxicities were congested mucosa (36 patients) and telangiectasia (32 patients). In evaluation between rectal dose in EQD2 and toxicities, no association of cumulative rectal dose to rectal toxicity, except the association of cumulative rectal dose in EQD2 >65 Gy to late effects of normal tissue (LENT-SOMA) scale ≥ grade 2 (p = 0.022; odds ratio, 5.312; 95% confidence interval, 1.269-22.244). The cumulative rectal dose in EQD2 >65 Gy have association with ≥ grade 2 LENT-SOMA scale.

The association of rectal equivalent dose in 2 Gy fractions (EQD2) to late rectal toxicity in locally advanced cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University

PubMed Central

Meungwong, Pooriwat; Chitapanarux, Taned; Chakrabandhu, Somvilai; Klunklin, Pitchayaponne; Onchan, Wimrak; Wanwilairat, Somsak; Traisathit, Patrinee; Galalae, Razvan; Chitapanarux, Imjai

2014-01-01

Purpose To evaluate association between equivalent dose in 2 Gy (EQD2) to rectal point dose and gastrointestinal toxicity from whole pelvic radiotherapy (WPRT) and intracavitary brachytherapy (ICBT) in cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University. Materials and Methods Retrospective study was designed for the patients with locally advanced cervical cancer, treated by radical radiotherapy from 2004 to 2009 and were evaluated by rectosigmoidoscopy. The cumulative doses of WPRT and ICBT to the maximally rectal point were calculated to the EQD2 and evaluated the association of toxicities. Results Thirty-nine patients were evaluated for late rectal toxicity. The mean cumulative dose in term of EQD2 to rectum was 64.2 Gy. Grade 1 toxicities were the most common findings. According to endoscopic exam, the most common toxicities were congested mucosa (36 patients) and telangiectasia (32 patients). In evaluation between rectal dose in EQD2 and toxicities, no association of cumulative rectal dose to rectal toxicity, except the association of cumulative rectal dose in EQD2 >65 Gy to late effects of normal tissue (LENT-SOMA) scale ≥ grade 2 (p = 0.022; odds ratio, 5.312; 95% confidence interval, 1.269-22.244). Conclusion The cumulative rectal dose in EQD2 >65 Gy have association with ≥ grade 2 LENT-SOMA scale. PMID:25061573

Rectal bleeding after high-dose-rate brachytherapy combined with hypofractionated external-beam radiotherapy for localized prostate cancer: Impact of rectal dose in high-dose-rate brachytherapy on occurrence of grade 2 or worse rectal bleeding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akimoto, Tetsuo; Katoh, Hiroyuki; Kitamoto, Yoshizumi

2006-06-01

Purpose: To evaluate the incidence of Grade 2 or worse rectal bleeding after high-dose-rate (HDR) brachytherapy combined with hypofractionated external-beam radiotherapy (EBRT), with special emphasis on the relationship between the incidence of rectal bleeding and the rectal dose from HDR brachytherapy. Methods and Materials: The records of 100 patients who were treated by HDR brachytherapy combined with EBRT for {>=}12 months were analyzed. The fractionation schema for HDR brachytherapy was prospectively changed, and the total radiation dose for EBRT was fixed at 51 Gy. The distribution of the fractionation schema used in the patients was as follows: 5 Gy xmore » 5 in 13 patients; 7 Gy x 3 in 19 patients; and 9 Gy x 2 in 68 patients. Results: Ten patients (10%) developed Grade 2 or worse rectal bleeding. Regarding the correlation with dosimetric factors, no significant differences were found in the average percentage of the entire rectal volume receiving 30%, 50%, 80%, and 90% of the prescribed radiation dose from EBRT between those with bleeding and those without. The average percentage of the entire rectal volume receiving 10%, 30%, 50%, 80%, and 90% of the prescribed radiation dose from HDR brachytherapy in those who developed rectal bleeding was 77.9%, 28.6%, 9.0%, 1.5%, and 0.3%, respectively, and was 69.2%, 22.2%, 6.6%, 0.9%, and 0.4%, respectively, in those without bleeding. The differences in the percentages of the entire rectal volume receiving 10%, 30%, and 50% between those with and without bleeding were statistically significant. Conclusions: The rectal dose from HDR brachytherapy for patients with prostate cancer may have a significant impact on the incidence of Grade 2 or worse rectal bleeding.« less

Vaginal motion and bladder and rectal volumes during pelvic intensity-modulated radiation therapy after hysterectomy.

PubMed

Jhingran, Anuja; Salehpour, Mohammad; Sam, Marianne; Levy, Larry; Eifel, Patricia J

2012-01-01

To evaluate variations in bladder and rectal volume and the position of the vaginal vault during a 5-week course of pelvic intensity-modulated radiation therapy (IMRT) after hysterectomy. Twenty-four patients were instructed how to fill their bladders before simulation and treatment. These patients underwent computed tomography simulations with full and empty bladders and then underwent rescanning twice weekly during IMRT; patients were asked to have full bladder for treatment. Bladder and rectal volumes and the positions of vaginal fiducial markers were determined, and changes in volume and position were calculated. The mean full and empty bladder volumes at simulation were 480 cc (range, 122-1,052) and 155 cc (range, 49-371), respectively. Bladder volumes varied widely during IMRT: the median difference between the maximum and minimum volumes was 247 cc (range, 96-585). Variations in rectal volume during IMRT were less pronounced. For the 16 patients with vaginal fiducial markers in place throughout IMRT, the median maximum movement of the markers during IMRT was 0.59 cm in the right-left direction (range, 0-0.9), 1.46 cm in the anterior-posterior direction (range, 0.8-2.79), and 1.2 cm in the superior-inferior direction (range, 0.6-2.1). Large variations in rectal or bladder volume frequently correlated with significant displacement of the vaginal apex. Although treatment with a full bladder is usually preferred because of greater sparing of small bowel, our data demonstrate that even with detailed instruction, patients are unable to maintain consistent bladder filling. Variations in organ position during IMRT can result in marked changes in the position of the target volume and the volume of small bowel exposed to high doses of radiation. Copyright © 2012 Elsevier Inc. All rights reserved.

Vaginal Motion and Bladder and Rectal Volumes During Pelvic Intensity-Modulated Radiation Therapy After Hysterectomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jhingran, Anuja, E-mail: ajhingra@mdanderson.org; Salehpour, Mohammad; Sam, Marianne

2012-01-01

Purpose: To evaluate variations in bladder and rectal volume and the position of the vaginal vault during a 5-week course of pelvic intensity-modulated radiation therapy (IMRT) after hysterectomy. Methods and Materials: Twenty-four patients were instructed how to fill their bladders before simulation and treatment. These patients underwent computed tomography simulations with full and empty bladders and then underwent rescanning twice weekly during IMRT; patients were asked to have full bladder for treatment. Bladder and rectal volumes and the positions of vaginal fiducial markers were determined, and changes in volume and position were calculated. Results: The mean full and empty bladdermore » volumes at simulation were 480 cc (range, 122-1,052) and 155 cc (range, 49-371), respectively. Bladder volumes varied widely during IMRT: the median difference between the maximum and minimum volumes was 247 cc (range, 96-585). Variations in rectal volume during IMRT were less pronounced. For the 16 patients with vaginal fiducial markers in place throughout IMRT, the median maximum movement of the markers during IMRT was 0.59 cm in the right-left direction (range, 0-0.9), 1.46 cm in the anterior-posterior direction (range, 0.8-2.79), and 1.2 cm in the superior-inferior direction (range, 0.6-2.1). Large variations in rectal or bladder volume frequently correlated with significant displacement of the vaginal apex. Conclusion: Although treatment with a full bladder is usually preferred because of greater sparing of small bowel, our data demonstrate that even with detailed instruction, patients are unable to maintain consistent bladder filling. Variations in organ position during IMRT can result in marked changes in the position of the target volume and the volume of small bowel exposed to high doses of radiation.« less

Polyethylene glycol hydrogel rectal spacer implantation in patients with prostate cancer undergoing combination high-dose-rate brachytherapy and external beam radiotherapy.

PubMed

Yeh, Jekwon; Lehrich, Brandon; Tran, Carolyn; Mesa, Albert; Baghdassarian, Ruben; Yoshida, Jeffrey; Torrey, Robert; Gazzaniga, Michael; Weinberg, Alan; Chalfin, Stuart; Ravera, John; Tokita, Kenneth

2016-01-01

To present rectal toxicity rates in patients administered a polyethylene glycol (PEG) hydrogel rectal spacer in conjunction with combination high-dose-rate brachytherapy and external beam radiotherapy. Between February 2010 and April 2015, 326 prostate carcinoma patients underwent combination high-dose-rate brachytherapy of 16 Gy (average dose 15.5 Gy; standard deviation [SD] = 1.6 Gy) and external beam radiotherapy of 59.4 Gy (average dose 60.2 Gy; SD = 2.9 Gy). In conjunction with the radiation therapy regimen, each patient was injected with 10 mL of a PEG hydrogel in the anterior perirectal fat space. The injectable spacer (rectal spacer) creates a gap between the prostate and the rectum. The rectum is displaced from the radiation field, and rectal dose is substantially reduced. The goal is a reduction in rectal radiation toxicity. Clinical efficacy was determined by measuring acute and chronic rectal toxicity using the National Cancer Center Institute Common Terminology Criteria for Adverse Events v4.0 grading scheme. Median followup was 16 months. The mean anterior-posterior separation achieved was 1.6 cm (SD = 0.4 cm). Rates of acute Grade 1 and 2 rectal toxicity were 37.4% and 2.8%, respectively. There were no acute Grade 3/4 toxicities. Rates of late Grade 1, 2, and 3 rectal toxicity were 12.7%, 1.4%, and 0.7%, respectively. There were no late Grade 4 toxicities. PEG rectal spacer implantation is safe and well tolerated. Acute and chronic rectal toxicities are low despite aggressive dose escalation. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Predictors of Rectal Tolerance Observed in a Dose-Escalated Phase 1-2 Trial of Stereotactic Body Radiation Therapy for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, D.W. Nathan; Cho, L. Chinsoo; Straka, Christopher

2014-07-01

Purpose: To convey the occurrence of isolated cases of severe rectal toxicity at the highest dose level tested in 5-fraction stereotactic body radiation therapy (SBRT) for localized prostate cancer; and to rationally test potential causal mechanisms to guide future studies and experiments to aid in mitigating or altogether avoiding such severe bowel injury. Methods and Materials: Clinical and treatment planning data were analyzed from 91 patients enrolled from 2006 to 2011 on a dose-escalation (45, 47.5, and 50 Gy in 5 fractions) phase 1/2 clinical study of SBRT for localized prostate cancer. Results: At the highest dose level, 6.6% ofmore » patients treated (6 of 91) developed high-grade rectal toxicity, 5 of whom required colostomy. Grade 3+ delayed rectal toxicity was strongly correlated with volume of rectal wall receiving 50 Gy >3 cm{sup 3} (P<.0001), and treatment of >35% circumference of rectal wall to 39 Gy (P=.003). Grade 2+ acute rectal toxicity was significantly correlated with treatment of >50% circumference of rectal wall to 24 Gy (P=.010). Conclusion: Caution is advised when considering high-dose SBRT for treatment of tumors near bowel structures, including prostate cancer. Threshold dose constraints developed from physiologic principles are defined, and if respected can minimize risk of severe rectal toxicity.« less

Prostate volumetric‐modulated arc therapy: dosimetry and radiobiological model variation between the single‐arc and double‐arc technique

PubMed Central

Jiang, Runqing

2013-01-01

This study investigates the dosimetry and radiobiological model variation when a second photon arc was added to prostate volumetric‐modulated arc therapy (VMAT) using the single‐arc technique. Dosimetry and radiobiological model comparison between the single‐arc and double‐arc prostate VMAT plans were performed on five patients with prostate volumes ranging from 29−68.1 cm3. The prescription dose was 78 Gy/39 fractions and the photon beam energy was 6 MV. Dose‐volume histogram, mean and maximum dose of targets (planning and clinical target volume) and normal tissues (rectum, bladder and femoral heads), dose‐volume criteria in the treatment plan (D99% of PTV; D30%,D50%,V17Gy and V35Gy of rectum and bladder; D5% of femoral heads), and dose profiles along the vertical and horizontal axis crossing the isocenter were determined using the single‐arc and double‐arc VMAT technique. For comparison, the monitor unit based on the RapidArc delivery method, prostate tumor control probability (TCP), and rectal normal tissue complication probability (NTCP) based on the Lyman‐Burman‐Kutcher algorithm were calculated. It was found that though the double‐arc technique required almost double the treatment time than the single‐arc, the double‐arc plan provided a better rectal and bladder dose‐volume criteria by shifting the delivered dose in the patient from the anterior–posterior direction to the lateral. As the femoral head was less radiosensitive than the rectum and bladder, the double‐arc technique resulted in a prostate VMAT plan with better prostate coverage and rectal dose‐volume criteria compared to the single‐arc. The prostate TCP of the double‐arc plan was found slightly increased (0.16%) compared to the single‐arc. Therefore, when the rectal dose‐volume criteria are very difficult to achieve in a single‐arc prostate VMAT plan, it is worthwhile to consider the double‐arc technique. PACS number: 87.55.D‐, 87.55.dk, 87.55.K‐, 87.55.Qr

SU-E-T-284: Dose Plan Optimization When Using Hydrogel Prostate-Rectum Spacer: A Single Institution Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rajecki, M; Thurber, A; Catalfamo, F

2015-06-15

Purpose: To describe rectal dose reduction achieved and techniques used to take advantage of the increased peri-rectal spacing provided by injected polyethylene-glycol. Methods: Thirty prostate cancer patents were 2:1 randomized during a clinical trial to evaluate the effectiveness of injected poly-ethylene glycol hydrogel (SpaceOAR System) in creating space between the prostate and the anterior rectal wall. All patients received a baseline CT/MR scan and baseline IMRT treatment plan. Patients were randomized to receive hydrogel injection (n=20) or Control (n=10), followed by another CT/MR scan and treatment plan (single arc VMAT, 6 MV photons, 79.2 Gy, 44 fractions). Additional optimization structuresmore » were employed to constrain the dose to the rectum; specifically an avoidance structure to limit V75 <15%, and a control structure to limit the maximum relative dose <105% in the interface region of the anterior rectal wall and the prostate planning target volume. Dose volumetric data was analyzed for rectal volumes receiving 60 through 80 Gy. Results: Rectal dose reduction was observed in all patients who received the hydrogel. Volumetric analysis indicates a median rectal volume and (reduction from baseline plan) following spacer application of 4.9% (8.9%) at V60Gy, 3.8% (8.1%) at V65Gy, 2.5% (7.2%) at V70Gy, 1.6% (5.8%) at V75Gy, and 0.5% (2.5%) at V80Gy. Conclusion: Relative to planning without spacers, rectal dose constraints of 5%, 4%, 3%, 2%, 1% for V60, V65, V70, V75, and V80, should be obtainable when peri-rectal spacers are used. The combined effect of increased peri-rectal space provided by the hydrogel, with strict optimization objectives, resulted in reduced dose to the rectum. To maximize benefit, strict optimization objectives and reduced rectal dose constraints should be employed when creating plans for patients with perirectal spacers. Clinical Trial for SpaceOAR product conducted by Augmenix,Inc. The research site was paid to be a participating site.« less

Quantifying Unnecessary Normal Tissue Complication Risks due to Suboptimal Planning: A Secondary Study of RTOG 0126.

PubMed

Moore, Kevin L; Schmidt, Rachel; Moiseenko, Vitali; Olsen, Lindsey A; Tan, Jun; Xiao, Ying; Galvin, James; Pugh, Stephanie; Seider, Michael J; Dicker, Adam P; Bosch, Walter; Michalski, Jeff; Mutic, Sasa

2015-06-01

The purpose of this study was to quantify the frequency and clinical severity of quality deficiencies in intensity modulated radiation therapy (IMRT) planning in the Radiation Therapy Oncology Group 0126 protocol. A total of 219 IMRT patients from the high-dose arm (79.2 Gy) of RTOG 0126 were analyzed. To quantify plan quality, we used established knowledge-based methods for patient-specific dose-volume histogram (DVH) prediction of organs at risk and a Lyman-Kutcher-Burman (LKB) model for grade ≥2 rectal complications to convert DVHs into normal tissue complication probabilities (NTCPs). The LKB model was validated by fitting dose-response parameters relative to observed toxicities. The 90th percentile (22 of 219) of plans with the lowest excess risk (difference between clinical and model-predicted NTCP) were used to create a model for the presumed best practices in the protocol (pDVH0126,top10%). Applying the resultant model to the entire sample enabled comparisons between DVHs that patients could have received to DVHs they actually received. Excess risk quantified the clinical impact of suboptimal planning. Accuracy of pDVH predictions was validated by replanning 30 of 219 patients (13.7%), including equal numbers of presumed "high-quality," "low-quality," and randomly sampled plans. NTCP-predicted toxicities were compared to adverse events on protocol. Existing models showed that bladder-sparing variations were less prevalent than rectum quality variations and that increased rectal sparing was not correlated with target metrics (dose received by 98% and 2% of the PTV, respectively). Observed toxicities were consistent with current LKB parameters. Converting DVH and pDVH0126,top10% to rectal NTCPs, we observed 94 of 219 patients (42.9%) with ≥5% excess risk, 20 of 219 patients (9.1%) with ≥10% excess risk, and 2 of 219 patients (0.9%) with ≥15% excess risk. Replanning demonstrated the predicted NTCP reductions while maintaining the volume of the PTV receiving prescription dose. An equivalent sample of high-quality plans showed fewer toxicities than low-quality plans, 6 of 73 versus 10 of 73 respectively, although these differences were not significant (P=.21) due to insufficient statistical power in this retrospective study. Plan quality deficiencies in RTOG 0126 exposed patients to substantial excess risk for rectal complications. Copyright © 2015 Elsevier Inc. All rights reserved.

Image-guided intensity-modulated radiotherapy for prostate cancer: Dose constraints for the anterior rectal wall to minimize rectal toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peterson, Jennifer L., E-mail: peterson.jennifer2@mayo.edu; Buskirk, Steven J.; Heckman, Michael G.

2014-04-01

Rectal adverse events (AEs) are a major concern with definitive radiotherapy (RT) treatment for prostate cancer. The anterior rectal wall is at the greatest risk of injury as it lies closest to the target volume and receives the highest dose of RT. This study evaluated the absolute volume of anterior rectal wall receiving a high dose to identify potential ideal dose constraints that can minimize rectal AEs. A total of 111 consecutive patients with Stage T1c to T3a N0 M0 prostate cancer who underwent image-guided intensity-modulated RT at our institution were included. AEs were graded according to the Common Terminologymore » Criteria for Adverse Events, version 4.0. The volume of anterior rectal wall receiving 5 to 80 Gy in 2.5-Gy increments was determined. Multivariable Cox regression models were used to identify cut points in these volumes that led to an increased risk of early and late rectal AEs. Early AEs occurred in most patients (88%); however, relatively few of them (13%) were grade ≥2. At 5 years, the cumulative incidence of late rectal AEs was 37%, with only 5% being grade ≥2. For almost all RT doses, we identified a threshold of irradiated absolute volume of anterior rectal wall above which there was at least a trend toward a significantly higher rate of AEs. Most strikingly, patients with more than 1.29, 0.73, or 0.45 cm{sup 3} of anterior rectal wall exposed to radiation doses of 67.5, 70, or 72.5 Gy, respectively, had a significantly increased risk of late AEs (relative risks [RR]: 2.18 to 2.72; p ≤ 0.041) and of grade ≥ 2 early AEs (RR: 6.36 to 6.48; p = 0.004). Our study provides evidence that definitive image-guided intensity-modulated radiotherapy (IG-IMRT) for prostate cancer is well tolerated and also identifies dose thresholds for the absolute volume of anterior rectal wall above which patients are at greater risk of early and late complications.« less

Estimation of Rectal Dose Using Daily Megavoltage Cone-Beam Computed Tomography and Deformable Image Registration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akino, Yuichi, E-mail: akino@radonc.med.osaka-u.ac.jp; Department of Radiology, Osaka University Hospital, Suita, Osaka; Yoshioka, Yasuo

2013-11-01

Purpose: The actual dose delivered to critical organs will differ from the simulated dose because of interfractional organ motion and deformation. Here, we developed a method to estimate the rectal dose in prostate intensity modulated radiation therapy with consideration to interfractional organ motion using daily megavoltage cone-beam computed tomography (MVCBCT). Methods and Materials: Under exemption status from our institutional review board, we retrospectively reviewed 231 series of MVCBCT of 8 patients with prostate cancer. On both planning CT (pCT) and MVCBCT images, the rectal contours were delineated and the CT value within the contours was replaced by the mean CTmore » value within the pelvis, with the addition of 100 Hounsfield units. MVCBCT images were rigidly registered to pCT and then nonrigidly registered using B-Spline deformable image registration (DIR) with Velocity AI software. The concordance between the rectal contours on MVCBCT and pCT was evaluated using the Dice similarity coefficient (DSC). The dose distributions normalized for 1 fraction were also deformed and summed to estimate the actual total dose. Results: The DSC of all treatment fractions of 8 patients was improved from 0.75±0.04 (mean ±SD) to 0.90 ±0.02 by DIR. Six patients showed a decrease of the generalized equivalent uniform dose (gEUD) from total dose compared with treatment plans. Although the rectal volume of each treatment fraction did not show any correlation with the change in gEUD (R{sup 2}=0.18±0.13), the displacement of the center of gravity of rectal contours in the anterior-posterior (AP) direction showed an intermediate relationship (R{sup 2}=0.61±0.16). Conclusion: We developed a method for evaluation of rectal dose using DIR and MVCBCT images and showed the necessity of DIR for the evaluation of total dose. Displacement of the rectum in the AP direction showed a greater effect on the change in rectal dose compared with the rectal volume.« less

Evaluation of linear array MOSFET detectors for in vivo dosimetry to measure rectal dose in HDR brachytherapy.

PubMed

Haughey, Aisling; Coalter, George; Mugabe, Koki

2011-09-01

The study aimed to assess the suitability of linear array metal oxide semiconductor field effect transistor detectors (MOSFETs) as in vivo dosimeters to measure rectal dose in high dose rate brachytherapy treatments. The MOSFET arrays were calibrated with an Ir192 source and phantom measurements were performed to check agreement with the treatment planning system. The angular dependence, linearity and constancy of the detectors were evaluated. For in vivo measurements two sites were investigated, transperineal needle implants for prostate cancer and Fletcher suites for cervical cancer. The MOSFETs were inserted into the patients' rectum in theatre inside a modified flatus tube. The patients were then CT scanned for treatment planning. Measured rectal doses during treatment were compared with point dose measurements predicted by the TPS. The MOSFETs were found to require individual calibration factors. The calibration was found to drift by approximately 1% ±0.8 per 500 mV accumulated and varies with distance from source due to energy dependence. In vivo results for prostate patients found only 33% of measured doses agreed with the TPS within ±10%. For cervix cases 42% of measured doses agreed with the TPS within ±10%, however of those not agreeing variations of up to 70% were observed. One of the most limiting factors in this study was found to be the inability to prevent the MOSFET moving internally between the time of CT and treatment. Due to the many uncertainties associated with MOSFETs including calibration drift, angular dependence and the inability to know their exact position at the time of treatment, we consider them to be unsuitable for in vivo dosimetry in rectum for HDR brachytherapy.

Rectal Bleeding After High-Dose-Rate Brachytherapy Combined With Hypofractionated External-Beam Radiotherapy for Localized Prostate Cancer: The Relationship Between Dose-Volume Histogram Parameters and the Occurrence Rate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Okamoto, Masahiko, E-mail: masaoka@showa.gunma-u.ac.jp; Ishikawa, Hitoshi; Ebara, Takeshi

2012-02-01

Purpose: To determine the predictive risk factors for Grade 2 or worse rectal bleeding after high-dose-rate brachytherapy (HDR-BT) combined with hypofractionated external-beam radiotherapy (EBRT) for prostate cancer using dose-volume histogram analysis. Methods and Materials: The records of 216 patients treated with HDR-BT combined with EBRT were analyzed. The treatment protocols for HDR-BT were 5 Gy Multiplication-Sign five times in 3 days or 7 Gy Multiplication-Sign three, 10.5 Gy Multiplication-Sign two, or 9 Gy Multiplication-Sign two in 2 days. The EBRT doses ranged from 45 to 51 Gy with a fractional dose of 3 Gy. Results: In 20 patients Grade 2more » or worse rectal bleeding developed, and the cumulative incidence rate was 9% at 5 years. By converting the HDR-BT and EBRT radiation doses into biologic effective doses (BED), the BED{sub 3} at rectal volumes of 5% and 10% in the patients who experienced bleeding were significantly higher than those in the remaining 196 patients. Univariate analysis showed that a higher rectal BED{sub 3-5%} and the use of fewer needles in brachytherapy were correlated with the incidence of bleeding, but BED{sub 3-5%} was found to be the only significant factor on multivariate analysis. Conclusions: The radiation dose delivered to small rectal lesions as 5% is important for predicting Grade 2 or worse rectal bleeding after HDR-BT combined with EBRT for prostate cancer.« less

Assessing correlations between the spatial distribution of the dose to the rectal wall and late rectal toxicity after prostate radiotherapy: an analysis of data from the MRC RT01 trial (ISRCTN 47772397)

NASA Astrophysics Data System (ADS)

Buettner, Florian; Gulliford, Sarah L.; Webb, Steve; Sydes, Matthew R.; Dearnaley, David P.; Partridge, Mike

2009-11-01

Many studies have been performed to assess correlations between measures derived from dose-volume histograms and late rectal toxicities for radiotherapy of prostate cancer. The purpose of this study was to quantify correlations between measures describing the shape and location of the dose distribution and different outcomes. The dose to the rectal wall was projected on a two-dimensional map. In order to characterize the dose distribution, its centre of mass, longitudinal and lateral extent, and eccentricity were calculated at different dose levels. Furthermore, the dose-surface histogram (DSH) was determined. Correlations between these measures and seven clinically relevant rectal-toxicity endpoints were quantified by maximally selected standardized Wilcoxon rank statistics. The analysis was performed using data from the RT01 prostate radiotherapy trial. For some endpoints, the shape of the dose distribution is more strongly correlated with the outcome than simple DSHs. Rectal bleeding was most strongly correlated with the lateral extent of the dose distribution. For loose stools, the strongest correlations were found for longitudinal extent; proctitis was most strongly correlated with DSH. For the other endpoints no statistically significant correlations could be found. The strengths of the correlations between the shape of the dose distribution and outcome differed considerably between the different endpoints. Due to these significant correlations, it is desirable to use shape-based tools in order to assess the quality of a dose distribution.

Comparing photon and proton-based hypofractioned SBRT for prostate cancer accounting for robustness and realistic treatment deliverability.

PubMed

Goddard, Lee C; Brodin, N Patrik; Bodner, William R; Garg, Madhur K; Tomé, Wolfgang A

2018-05-01

To investigate whether photon or proton-based stereotactic body radiation therapy (SBRT is the preferred modality for high dose hypofractionation prostate cancer treatment. Achievable dose distributions were compared when uncertainties in target positioning and range uncertainties were appropriately accounted for. 10 patients with prostate cancer previously treated at our institution (Montefiore Medical Center) with photon SBRT using volumetric modulated arc therapy (VMAT) were identified. MRI images fused to the treatment planning CT allowed for accurate target and organ at risk (OAR) delineation. The clinical target volume was defined as the prostate gland plus the proximal seminal vesicles. Critical OARs include the bladder wall, bowel, femoral heads, neurovascular bundle, penile bulb, rectal wall, urethra and urogenital diaphragm. Photon plan robustness was evaluated by simulating 2 mm isotropic setup variations. Comparative proton SBRT plans employing intensity modulated proton therapy (IMPT) were generated using robust optimization. Plan robustness was evaluated by simulating 2 mm setup variations and 3% or 1% Hounsfield unit (HU) calibration uncertainties. Comparable maximum OAR doses are achievable between photon and proton SBRT, however, robust optimization results in higher maximum doses for proton SBRT. Rectal maximum doses are significantly higher for Robust proton SBRT with 1% HU uncertainty compared to photon SBRT (p = 0.03), whereas maximum doses were comparable for bladder wall (p = 0.43), urethra (p = 0.82) and urogenital diaphragm (p = 0.50). Mean doses to bladder and rectal wall are lower for proton SBRT, but higher for neurovascular bundle, urethra and urogenital diaphragm due to increased lateral scatter. Similar target conformality is achieved, albeit with slightly larger treated volume ratios for proton SBRT, >1.4 compared to 1.2 for photon SBRT. Similar treatment plans can be generated with IMPT compared to VMAT in terms of target coverage, target conformality, and OAR sparing when range and HU uncertainties are neglected. However, when accounting for these uncertainties during robust optimization, VMAT outperforms IMPT in terms of achievable target conformity and OAR sparing. Advances in knowledge: Comparison between achievable dose distributions using modern, robust optimization of IMPT for high dose per fraction SBRT regimens for the prostate has not been previously investigated.

Dose Constraint for Minimizing Grade 2 Rectal Bleeding Following Brachytherapy Combined With External Beam Radiotherapy for Localized Prostate Cancer: Rectal Dose-Volume Histogram Analysis of 457 Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shiraishi, Yutaka; Yorozu, Atsunori; Ohashi, Toshio, E-mail: ohashi@rad.med.keio.ac.jp

2011-11-01

Purpose: To determine the rectal tolerance to Grade 2 rectal bleeding after I-125 seed brachytherapy combined with external beam radiotherapy (EBRT), based on the rectal dose-volume histogram. Methods and Materials: A total of 458 consecutive patients with stages T1 to T3 prostate cancer received combined modality treatment consisting of I-125 seed implantation followed by EBRT to the prostate and seminal vesicles. The prescribed doses of brachytherapy and EBRT were 100 Gy and 45 Gy in 25 fractions, respectively. The rectal dosimetric factors were analyzed for rectal volumes receiving >100 Gy and >150 Gy (R100 and R150) during brachytherapy and formore » rectal volumes receiving >30 Gy to 40 Gy (V30-V40) during EBRT therapy in 373 patients for whom datasets were available. The patients were followed from 21 to 72 months (median, 45 months) after the I-125 seed implantation. Results: Forty-four patients (9.7%) developed Grade 2 rectal bleeding. On multivariate analysis, age (p = 0.014), R100 (p = 0.002), and V30 (p = 0.001) were identified as risk factors for Grade 2 rectal bleeding. The rectal bleeding rate increased as the R100 increased: 5.0% (2/40 patients) for 0 ml; 7.5% (20/267 patients) for >0 to 0.5 ml; 11.0% (11/100 patients) for >0.5 to 1 ml; 17.9% (5/28 patients) for >1 to 1.5 ml; and 27.3% (6/22 patients) for >1.5 ml (p = 0.014). Grade 2 rectal bleeding developed in 6.4% (12/188) of patients with a V30 {<=}35% and in 14.1% (26/185) of patients with a V30 >35% (p = 0.02). When these dose-volume parameters were considered in combination, the Grade 2 rectal bleeding rate was 4.2% (5/120 patients) for a R100 {<=}0.5 ml and a V30 {<=}35%, whereas it was 22.4% (13/58 patients) for R100 of >0.5 ml and V30 of >35%. Conclusion: The risk of rectal bleeding was found to be significantly volume-dependent in patients with prostate cancer who received combined modality treatment. Rectal dose-volume analysis is a practical method for predicting the risk of development of Grade 2 rectal bleeding.« less

Low dose of rectal thiopental sodium for pediatric sedation in spiral computed tomography study.

PubMed

Akhlaghpoor, Shahram; Shabestari, Abbas Arjmand; Moghdam, Mohsen Shojaei

2007-06-01

The aim of this study was to determine the effectiveness of reduced new dose in rectal sedation by thiopental sodium for computed tomography (CT) diagnostic imaging. A total of 90 children (mean age, 24.21 month +/- 13.63 [standard deviation]) underwent spiral CT study after rectal administration of thiopental sodium injection solution. The new dose ranged from 15 to 25 mg/kg with a total dose of 350 mg. The percentage of success and adverse reaction were evaluated. Sedation was successful in 98% of infants and children with an average time of 8.04 min +/- 6.87 (standard deviation). One of the cases found desaturation, two experienced vomiting, 14 found rectal defecation, and two experienced hyperactivity. No prolonged sedation was observed. Rectal administration of thiopental sodium for pediatric CT imaging is safe and effective even for hyperextend position by new reduced dose of the drug. This procedure could be easily done in the CT department under supervision of the radiologist.

The Effectiveness of the Rectal Administration of Low-dose Diclofenac for the Prevention of Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis.

PubMed

Okuno, Mitsuru; Shiroko, Junko; Taguchi, Daisuke; Yamaguchi, Kimihiro; Takada, Jun; Imai, Susumu; Sato, Hiroyuki; Thanabashi, Shinobu

2018-03-30

Objective A 50-100-mg rectal dose of nonsteroidal anti-inflammatory drugs (NSAIDs; diclofenac or indomethacin) has been shown to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). However, this is higher than the recommended 25-mg dose that is commonly administered to Japanese patients. The objective of this study was to evaluate the safety and efficacy of 25-mg rectal dose of diclofenac in preventing PEP. Methods Between January 2016 and March 2017, a total of 147 patients underwent ERCP with or without the rectal administration of diclofenac (25 mg) 20 min before the procedure. A retrospective analysis was conducted to evaluate the efficacy and safety of this dose in preventing PEP. Results Thirteen patients (8.8%) developed PEP: 3 patients (4.1%) in the diclofenac group and 10 (13.7%) in the control group (p=0.0460). After ERCP, there were no cases of gastrointestinal hemorrhage, ulceration, acute renal failure, or death. A multivariate logistic regression analysis revealed that the non-administration of rectal diclofenac was a risk factor for PEP (odds ratio=3.530; 95% confidence interval=1.017-16.35; p=0.0468). Conclusions A 25-mg rectal dose of diclofenac might prevent PEP.

Do Intermediate Radiation Doses Contribute to Late Rectal Toxicity? An Analysis of Data From Radiation Therapy Oncology Group Protocol 94-06

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tucker, Susan L., E-mail: sltucker@mdanderson.org; Dong, Lei; Michalski, Jeff M.

2012-10-01

Purpose: To investigate whether the volumes of rectum exposed to intermediate doses, from 30 to 50 Gy, contribute to the risk of Grade {>=}2 late rectal toxicity among patients with prostate cancer receiving radiotherapy. Methods and Materials: Data from 1009 patients treated on Radiation Therapy Oncology Group protocol 94-06 were analyzed using three approaches. First, the contribution of intermediate doses to a previously published fit of the Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model was determined. Next, the extent to which intermediate doses provide additional risk information, after taking the LKB model into account, was investigated. Third, the proportionmore » of rectum receiving doses higher than a threshold, VDose, was computed for doses ranging from 5 to 85 Gy, and a multivariate Cox proportional hazards model was used to determine which of these parameters were significantly associated with time to Grade {>=}2 late rectal toxicity. Results: Doses <60 Gy had no detectable impact on the fit of the LKB model, as expected on the basis of the small estimate of the volume parameter (n = 0.077). Furthermore, there was no detectable difference in late rectal toxicity among cohorts with similar risk estimates from the LKB model but with different volumes of rectum exposed to intermediate doses. The multivariate Cox proportional hazards model selected V75 as the only value of VDose significantly associated with late rectal toxicity. Conclusions: There is no evidence from these data that intermediate doses influence the risk of Grade {>=}2 late rectal toxicity. Instead, the critical doses for this endpoint seem to be {>=}75 Gy. It is hypothesized that cases of Grade {>=}2 late rectal toxicity occurring among patients with V75 less than approximately 12% may be due to a 'background' level of risk, likely due mainly to biological factors.« less

Local Hypothermia as a Radioprotector of the Rectal Wall During Prostate Stereotactic Body Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hrycushko, Brian A., E-mail: Brian.Hrycushko@utsouthwestern.edu; Chopra, Rajiv; Sayre, James W.

Purpose: To compare the single-fraction dose-related incidence of rectal obstruction and/or bleeding in normothermic and hypothermic rectums of a rat model. Methods and Materials: A 1.9-cm length of rectum was irradiated with a single fraction in 57 Sprague-Dawley rats using a dedicated image-guided small animal irradiator and Monte Carlo–based treatment planning system. All rats had a rectal temperature control apparatus placed during irradiation and were stratified to achieve either a normothermic (37°C) or hypothermic (15°C) rectal wall temperature. Radiation was delivered to a 1-cm-diameter cylindrical volume about the cooling device and rectal wall. The radiation dose was escalated from 16 Gy upmore » to 37 Gy to assess the dose response in each arm. The primary endpoint of this study was rectal obstruction and/or bleeding during a follow-up of 180 to 186 days. Histologic scoring was performed on all study rats. Results: Probit analysis showed a dose associated with a 50% incidence of rectal obstruction of 24.6 Gy and 40.8 Gy for normothermic and hypothermic arms, respectively. The occurrence of obstruction and/or bleeding correlated with the posttreatment histologic score for normothermic rats; however, there was no difference in histologic score between normothermic and hypothermic rats at the highest dose levels evaluated. Conclusions: A significant radioprotective effect was observed using local hypothermia during a single large dose of radiation for the functional endpoint of rectal obstruction and/or bleeding. A confirmatory study in a large animal model with anatomic and physiologic similarities to humans is suggested.« less

Quantifying Unnecessary Normal Tissue Complication Risks due to Suboptimal Planning: A Secondary Study of RTOG 0126

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moore, Kevin L., E-mail: kevinmoore@ucsd.edu; Schmidt, Rachel; Moiseenko, Vitali

Purpose: The purpose of this study was to quantify the frequency and clinical severity of quality deficiencies in intensity modulated radiation therapy (IMRT) planning in the Radiation Therapy Oncology Group 0126 protocol. Methods and Materials: A total of 219 IMRT patients from the high-dose arm (79.2 Gy) of RTOG 0126 were analyzed. To quantify plan quality, we used established knowledge-based methods for patient-specific dose-volume histogram (DVH) prediction of organs at risk and a Lyman-Kutcher-Burman (LKB) model for grade ≥2 rectal complications to convert DVHs into normal tissue complication probabilities (NTCPs). The LKB model was validated by fitting dose-response parameters relative tomore » observed toxicities. The 90th percentile (22 of 219) of plans with the lowest excess risk (difference between clinical and model-predicted NTCP) were used to create a model for the presumed best practices in the protocol (pDVH{sub 0126,top10%}). Applying the resultant model to the entire sample enabled comparisons between DVHs that patients could have received to DVHs they actually received. Excess risk quantified the clinical impact of suboptimal planning. Accuracy of pDVH predictions was validated by replanning 30 of 219 patients (13.7%), including equal numbers of presumed “high-quality,” “low-quality,” and randomly sampled plans. NTCP-predicted toxicities were compared to adverse events on protocol. Results: Existing models showed that bladder-sparing variations were less prevalent than rectum quality variations and that increased rectal sparing was not correlated with target metrics (dose received by 98% and 2% of the PTV, respectively). Observed toxicities were consistent with current LKB parameters. Converting DVH and pDVH{sub 0126,top10%} to rectal NTCPs, we observed 94 of 219 patients (42.9%) with ≥5% excess risk, 20 of 219 patients (9.1%) with ≥10% excess risk, and 2 of 219 patients (0.9%) with ≥15% excess risk. Replanning demonstrated the predicted NTCP reductions while maintaining the volume of the PTV receiving prescription dose. An equivalent sample of high-quality plans showed fewer toxicities than low-quality plans, 6 of 73 versus 10 of 73 respectively, although these differences were not significant (P=.21) due to insufficient statistical power in this retrospective study. Conclusions: Plan quality deficiencies in RTOG 0126 exposed patients to substantial excess risk for rectal complications.« less

The pharmacokinetics of a single rectal dose of paracetamol (40 mg x kg(-1)) in children with liver disease.

PubMed

Cormack, C R H; Sudan, S; Addison, R; Keating, J; Sherwood, R A; Ashley, E M C; Howell, Tanya

2006-04-01

The aim of our study was to measure the serum paracetamol concentrations achieved following a single rectal loading dose of 40 mg x kg(-1) in children with chronic liver disease. We recruited 17 children (3-15 years, 10.6-75 kg) undergoing minor surgical procedures under general anesthesia. Paracetamol was administered at the end of surgery and blood samples were taken for analysis at 2, 3, 4, 6 and 8 h postdose. The mean Cmax of 11.4 mg x l(-1) [coefficient of variation (CV) 66%] was achieved at a Tmax of 2.7 h (CV 42%). The relative bioavailability (F) of the suppository formulation was not estimated, but clearance (Cl/F) estimates 0.73 l x kg(-1) x h(-1) (CV 87%) and time-concentration profiles for these children were similar to the normal pediatric population. There are currently no biologic markers available for monitoring possible hepatotoxicity in this cohort of patients with liver disease, but our data suggest that a single-dose suppository is a satisfactory analgesic alternative.

Volumetric-modulated arc therapy in postprostatectomy radiotherapy patients: A planning comparison study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Forde, Elizabeth, E-mail: eforde@tcd.ie; Kneebone, Andrew; Northern Clinical School, University of Sydney, New South Wales

2013-10-01

The purpose of this study was to compare postprostatectomy planning for volumetric-modulated arc therapy (VMAT) with both single arc (SA) and double arcs (DA) against dynamic sliding window intensity-modulated radiotherapy (IMRT). Ten cases were planned with IMRT, SA VMAT, and DA VMAT. All cases were planned to achieve a minimum dose of 68 Gy to 95% of the planning target volume (PTV) and goals to limit rectal volume >40 Gy to 35% and >65 Gy to 17%, and bladder volumes >40 Gy to 50% and >65 Gy to 25%. Plans were averaged across the 10 patients and compared for meanmore » dose, conformity, homogeneity, rectal and bladder doses, and monitor units. The mean dose to the clinical target volume and PTV was significantly higher (p<0.05) for SA compared with DA or IMRT. The homogeneity index was not significantly different: SA = 0.09; DA = 0.08; and IMRT = 0.07. The rectal V40 was lowest for the DA plan. The rectal V20 was significantly lower (p<0.05) for both the VMAT plans compared with IMRT. There were no significant differences for bladder V40 or rectal and bladder V65. The IMRT plans required 1400 MU compared with 745 for DA and 708 for SA. This study shows that for equivalent dose coverage, SA and DA VMAT plans result in higher mean doses to the clinical target volume and PTV. This greater dose heterogeneity is balanced by improved low-range rectal doses and halving of the monitor units.« less

PEG spacer gel and adaptive planning vs single plan in external prostate radiotherapy—clinical dosimetry evaluation

PubMed Central

2015-01-01

Objective: Spacer gel is used to reduce the rectal dose in prostate radiotherapy. It is injected to increase the distance between the prostate and rectum. During the course of external radiotherapy treatment, physiological changes in rectal volume exist. When using polyethylene glycol material, such as DuraSeal® (Covidien, Mansfield, MA), gel resorption also occurs. Together, these factors alter the original dose plan distribution. Methods: External dose planning and calculations were simulated using images acquired from 10 patients who were treated with brachytherapy and gel. The CT series was taken relative to gel injection: pre 1 day, post 1 day, post 1 month and post 2 months. Adaptive planning was compared with a single plan. Results: Adaptive planning shows better results compared with the single plan used in the total treatment course; however, the effect is minor. Conclusion: Gel usage is clearly favourable to rectal DVH. Using adaptive planning with gel improves rectal DVH but is not necessary according to this study. Advances in knowledge: Spacer gel is used in prostate radiotherapy to increase distance between the prostate and the rectum, thus reducing the rectal doses. During the treatment course, gel resorption exists which affects the rectal doses. The usefulness of adaptive planning to compensate this resorption effect has not been studied before. PMID:26370300

A study on rectal dose measurement in phantom and in vivo using Gafchromic EBT3 film in IMRT and CyberKnife treatments of carcinoma of prostate

PubMed Central

Ganapathy, K.; Kurup, P. G. G.; Murali, V.; Muthukumaran, M.; Subramanian, S. Balaji; Velmurugan, J.

2013-01-01

The objective of this study is to check the feasibility of in vivo rectal dose measurement in intensity-modulated radiotherapy (IMRT) and CyberKnife treatments for carcinoma prostate. An in-house pelvis phantom made with bee's wax was used in this study. Two cylindrical bone equivalent materials were used to simulate the femur. Target and other critical structures associated with carcinoma prostate were delineated on the treatment planning images by the radiation oncologist. IMRT treatment plan was generated in Oncentra Master Plan treatment planning system and CyberKnife treatment plan was generated in Multiplan treatment planning system. Dose measurements were carried out in phantom and in patient using Gafchromic EBT3 films. RIT software was used to analyze the dose measured by EBT3 films. The measured doses using EBT3 films were compared with the TPS-calculated dose along the anterior rectal wall at multiple points. From the in-phantom measurements, it is observed that the difference between calculated and measured dose was mostly within 5%, except for a few measurement points. The difference between calculated and measured dose in the in-patient measurements was higher than 5% in regions which were away from the target. Gafchromic EBT3 film is a suitable detector for in vivo rectal dose measurements as it offers the possibility of analyzing the dose at multiple points. In addition, the method of extending this in vivo rectal dose measurement technique as a tool for patient-specific quality assurance check is also analyzed. PMID:24049320

Dosimetry of intracavitary placements for uterine and cervical carcinoma: results of orthogonal film, TLD, and CT-assisted techniques.

PubMed

Kapp, K S; Stuecklschweiger, G F; Kapp, D S; Hackl, A G

1992-07-01

A total of 720 192Ir high-dose-rate (HDR) applications in 331 patients with gynecological tumors were analyzed to evaluate the dose to normal tissues from brachytherapy. Based on the calculations of bladder base, bladder neck, and rectal doses derived from orthogonal films the planned tumor dose or fractionation was altered in 20.4% of intracavitary placements (ICP) for cervix carcinoma and 9.2% of ICP for treatment of the vaginal vault. In 13.8% of intracervical and 8.1% of intravaginal treatments calculated doses to both the bladder and rectum were greater than or equal to 140% of the initially planned dose fraction. Doses at the bladder base were significantly higher than at the bladder neck (p less than 0.001). In 17.5% of ICP the dose to the bladder base was at least twice as high as to the bladder neck. The ratio of bladder base dose to the bladder neck was 1.5 (+/- 1.19 SD) for intracervical and 1.46 (+/- 1.14 SD) for intravaginal applications. The comparison of calculated doses from orthogonal films with in-vivo readings showed a good correlation of rectal doses with a correlation coefficient factor of 0.9556. CT-assisted dosimetry, however, revealed that the maximum doses to bladder and rectum were generally higher than those obtained from films with ratios of 1-1.7 (average: 1.44) for the bladder neck, 1-5.4 (average: 2.42) for the bladder base, and 1.1-2.7 (average: 1.37) for the rectum. When doses to the specified reference points of bladder neck and rectum from orthogonal film dosimetry were compared with the corresponding points on CT scans, similar values were obtained for both methods with a maximum deviation of +/- 10%. Despite the determination of multiple reference points our study revealed that this information was inadequate to predict doses to the entire rectum and bladder. If conventional methods are used for dosimetry it is recommended that doses to the bladder base should be routinely calculated, since single point measurements at the bladder neck seriously underestimate the dose to the bladder. Also the rectal dose should be determined at several points over the length of the implant due to the wide range of anatomic variations possible.

SU-E-T-257: Development of a New Endorectal Balloon with An Unfoldable Radiochromic Film for In-Vivo Rectal Dosimetry During Prostate Cancer Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jeang, E; Lim, Y; Cho, K

Purpose: We developed an endorectal balloon for in-vivo rectal dosimetry in two-dimensions, and evaluated its dosimetric properties for the radiation treatment of prostate cancer. Methods: The endorectal balloon for in-vivo rectal dosimetry is equipped with a radiochromic film so that two-dimensional dose distribution can be measured in the rectal wall. The film is unrolled as the balloon is inflated, and it is rolled as the balloon is deflated. The outer diameter of the balloon is about 14 mm before inflating it, but its outer diameter can be increased up to about 50 mm after inflating it with 80 ml distilledmore » water. The size of the film is 80(L) x 64(W) mm2, so large as to measure a dose distribution of an anterior half of the rectal wall. After it was inserted into a fabricated rectal phantom, the phantom was scanned by a CT scanner and 5 Gy was delivered to a target inside the phantom with a 15 MV photon beam in AP direction. Finally, the dose distribution measured in the endorectal balloon was compared with that of the treatment plan. Results: The two dose distributions were compared each other in the parallel and the perpendicular directions along an axis of the balloon. The two dose profiles analyzed from the radiochromic film agreed well with the plan within 3% for 15 MV photon beam. Conclusion: An endorectal balloon for two-dimensional in-vivo rectal dosimetry was developed and its dosimetric effectiveness was evaluated for the radiation treatment of prostate cancer. The measured dose distributions showed good agreement with the plans.« less

Principal component analysis-based pattern analysis of dose-volume histograms and influence on rectal toxicity.

PubMed

Söhn, Matthias; Alber, Markus; Yan, Di

2007-09-01

The variability of dose-volume histogram (DVH) shapes in a patient population can be quantified using principal component analysis (PCA). We applied this to rectal DVHs of prostate cancer patients and investigated the correlation of the PCA parameters with late bleeding. PCA was applied to the rectal wall DVHs of 262 patients, who had been treated with a four-field box, conformal adaptive radiotherapy technique. The correlated changes in the DVH pattern were revealed as "eigenmodes," which were ordered by their importance to represent data set variability. Each DVH is uniquely characterized by its principal components (PCs). The correlation of the first three PCs and chronic rectal bleeding of Grade 2 or greater was investigated with uni- and multivariate logistic regression analyses. Rectal wall DVHs in four-field conformal RT can primarily be represented by the first two or three PCs, which describe approximately 94% or 96% of the DVH shape variability, respectively. The first eigenmode models the total irradiated rectal volume; thus, PC1 correlates to the mean dose. Mode 2 describes the interpatient differences of the relative rectal volume in the two- or four-field overlap region. Mode 3 reveals correlations of volumes with intermediate doses ( approximately 40-45 Gy) and volumes with doses >70 Gy; thus, PC3 is associated with the maximal dose. According to univariate logistic regression analysis, only PC2 correlated significantly with toxicity. However, multivariate logistic regression analysis with the first two or three PCs revealed an increased probability of bleeding for DVHs with more than one large PC. PCA can reveal the correlation structure of DVHs for a patient population as imposed by the treatment technique and provide information about its relationship to toxicity. It proves useful for augmenting normal tissue complication probability modeling approaches.

Human Collagen Injections to Reduce Rectal Dose During Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Noyes, William R., E-mail: noyes@cancercenternd.com; Hosford, Charles C.; Schultz, Steven E.

Objectives: The continuing search for interventions, which address the incidence and grade of rectal toxicities associated with radiation treatment of prostate cancer, is a major concern. We are reporting an investigational trial using human collagen to increase the distance between the prostate and anterior rectal wall, thereby decreasing the radiation dose to the rectum. Methods: This is a pilot study evaluating the use of human collagen as a displacing agent for the rectal wall injected before starting a course of intensity-modulated radiotherapy (IMRT) for prostate cancer. Using a transperineal approach, 20 mL of human collagen was injected into the perirectalmore » space in an outpatient setting. Computerized IMRT plans were performed pre- and postcollagen injection, and after a patient completed their radiotherapy, to determine radiation dose reduction to the rectum associated with the collagen injection. Computed tomography scans were performed 6 months and 12 months after completing their radiotherapy to evaluate absorption rate of the collagen. All patients were treated with IMRT to a dose of 75.6 Gy to the prostate. Results: Eleven patients were enrolled into the study. The injection of human collagen in the outpatient setting was well tolerated. The mean separation between the prostate and anterior rectum was 12.7 mm. The mean reduction in dose to the anterior rectal wall was 50%. All men denied any rectal symptoms during the study. Conclusions: The transperineal injection of human collagen for the purpose of tissue displacement is well tolerated in the outpatient setting. The increased separation between the prostate and rectum resulted in a significant decrease in radiation dose to the rectum while receiving IMRT and was associated with no rectal toxicities.« less

Automatically-generated rectal dose constraints in intensity-modulated radiation therapy for prostate cancer

NASA Astrophysics Data System (ADS)

Hwang, Taejin; Kim, Yong Nam; Kim, Soo Kon; Kang, Sei-Kwon; Cheong, Kwang-Ho; Park, Soah; Yoon, Jai-Woong; Han, Taejin; Kim, Haeyoung; Lee, Meyeon; Kim, Kyoung-Joo; Bae, Hoonsik; Suh, Tae-Suk

2015-06-01

The dose constraint during prostate intensity-modulated radiation therapy (IMRT) optimization should be patient-specific for better rectum sparing. The aims of this study are to suggest a novel method for automatically generating a patient-specific dose constraint by using an experience-based dose volume histogram (DVH) of the rectum and to evaluate the potential of such a dose constraint qualitatively. The normal tissue complication probabilities (NTCPs) of the rectum with respect to V %ratio in our study were divided into three groups, where V %ratio was defined as the percent ratio of the rectal volume overlapping the planning target volume (PTV) to the rectal volume: (1) the rectal NTCPs in the previous study (clinical data), (2) those statistically generated by using the standard normal distribution (calculated data), and (3) those generated by combining the calculated data and the clinical data (mixed data). In the calculated data, a random number whose mean value was on the fitted curve described in the clinical data and whose standard deviation was 1% was generated by using the `randn' function in the MATLAB program and was used. For each group, we validated whether the probability density function (PDF) of the rectal NTCP could be automatically generated with the density estimation method by using a Gaussian kernel. The results revealed that the rectal NTCP probability increased in proportion to V %ratio , that the predictive rectal NTCP was patient-specific, and that the starting point of IMRT optimization for the given patient might be different. The PDF of the rectal NTCP was obtained automatically for each group except that the smoothness of the probability distribution increased with increasing number of data and with increasing window width. We showed that during the prostate IMRT optimization, the patient-specific dose constraints could be automatically generated and that our method could reduce the IMRT optimization time as well as maintain the IMRT plan quality.

Comparison of antipyretic effectiveness of equal doses of rectal and oral acetaminophen in children.

PubMed

Karbasi, Sedigha Akhavan; Modares-Mosadegh, Moneyreh; Golestan, Motahhareh

2010-01-01

To compare a dose of oral and rectal acetaminophen and to evaluate acceptability of rectal acetaminophen, since oral and rectal acetaminophen is widely used as an antipyretic agent in febrile children and the comparative effectiveness of these two preparations is not well established. In this prospective parallel group designed study, 60 children who presented to the emergency department or outpatient pediatric clinic at a tertiary hospital and aged from 6 months to 6 years with rectal temperature over 39 degrees C were enrolled. Patients were randomly assigned to two equal-sized groups. Group 1 received 15 mg/kg acetaminophen rectally and group 2 received the same dose orally. Temperature was recorded at baseline and 1 and 3 hours after drug administration. In the first group, mean decrease in temperature, 1 and 3 hours after administration of acetaminophen was 1.07+/-0.16 (p < 0.001) and 1.74+/-0.25 degrees C (p < 0.001), respectively, and in the second group it was 1.98+/-0.19 (p < 0.001) and 1.70+/-0.14 degrees C (p < 0.001), respectively (p > 0.05). Rectal and oral acetaminophen preparations have equal antipyretic effectiveness in children. The rectal route proved to be as acceptable as the oral one among parents.

Modeling late rectal toxicities based on a parameterized representation of the 3D dose distribution

NASA Astrophysics Data System (ADS)

Buettner, Florian; Gulliford, Sarah L.; Webb, Steve; Partridge, Mike

2011-04-01

Many models exist for predicting toxicities based on dose-volume histograms (DVHs) or dose-surface histograms (DSHs). This approach has several drawbacks as firstly the reduction of the dose distribution to a histogram results in the loss of spatial information and secondly the bins of the histograms are highly correlated with each other. Furthermore, some of the complex nonlinear models proposed in the past lack a direct physical interpretation and the ability to predict probabilities rather than binary outcomes. We propose a parameterized representation of the 3D distribution of the dose to the rectal wall which explicitly includes geometrical information in the form of the eccentricity of the dose distribution as well as its lateral and longitudinal extent. We use a nonlinear kernel-based probabilistic model to predict late rectal toxicity based on the parameterized dose distribution and assessed its predictive power using data from the MRC RT01 trial (ISCTRN 47772397). The endpoints under consideration were rectal bleeding, loose stools, and a global toxicity score. We extract simple rules identifying 3D dose patterns related to a specifically low risk of complication. Normal tissue complication probability (NTCP) models based on parameterized representations of geometrical and volumetric measures resulted in areas under the curve (AUCs) of 0.66, 0.63 and 0.67 for predicting rectal bleeding, loose stools and global toxicity, respectively. In comparison, NTCP models based on standard DVHs performed worse and resulted in AUCs of 0.59 for all three endpoints. In conclusion, we have presented low-dimensional, interpretable and nonlinear NTCP models based on the parameterized representation of the dose to the rectal wall. These models had a higher predictive power than models based on standard DVHs and their low dimensionality allowed for the identification of 3D dose patterns related to a low risk of complication.

Postoperative analgesic efficacy of single high dose and low dose rectal acetaminophen in pediatric ophthalmic surgery

PubMed Central

Gandhi, Ranju; Sunder, Rani

2012-01-01

Background: Analgesic efficacy of rectal acetaminophen is variable in different surgical procedures. Little data is available on its efficacy in ophthalmic surgeries. We conducted this prospective, randomized, double blind study to evaluate and compare the efficacy of single high dose and low dose rectal acetaminophen in pediatric ophthalmic surgery over a 24 hour period. Materials and Methods: 135 children scheduled for elective ophthalmic surgery were randomly allocated to one of the three groups, high, low, or control (H, L, or N) and received rectal acetaminophen 40 mg/kg, 20 mg/kg or no rectal drug respectively after induction of general anesthesia. Postoperative observations included recovery score, hourly observational pain score (OPS) up to 8 hours, time to first analgesic demand, and requirement of rescue analgesics and antiemetics over a 24 hour period. Results: Nineteen of 30 (63%) of children in group N required postoperative rescue analgesic versus 5/48 (10%) of group H (P <0.0001) and 10/47 (23%) of group L (P =0.0005) during 24 hour period. Mean time to requirement of first analgesic was 206±185 min in group H, 189±203min in group L, and 196 ±170 min in group N (P=0.985). OPS was significantly lower in group H and L compared to group N during first 8 hours. Requirement of rescue antiemetic was 18.7% in group H as compared to 23% each in group L and group N (P >0.5). Conclusions: Single dose rectal acetaminophen can provide effective postoperative analgesia for pediatric ophthalmic surgery at both high dose (40 mg/kg) and low dose (20 mg/kg) both in early postoperative and over a 24 hour period. PMID:23225924

Role of step size and max dwell time in anatomy based inverse optimization for prostate implants

PubMed Central

Manikandan, Arjunan; Sarkar, Biplab; Rajendran, Vivek Thirupathur; King, Paul R.; Sresty, N.V. Madhusudhana; Holla, Ragavendra; Kotur, Sachin; Nadendla, Sujatha

2013-01-01

In high dose rate (HDR) brachytherapy, the source dwell times and dwell positions are vital parameters in achieving a desirable implant dose distribution. Inverse treatment planning requires an optimal choice of these parameters to achieve the desired target coverage with the lowest achievable dose to the organs at risk (OAR). This study was designed to evaluate the optimum source step size and maximum source dwell time for prostate brachytherapy implants using an Ir-192 source. In total, one hundred inverse treatment plans were generated for the four patients included in this study. Twenty-five treatment plans were created for each patient by varying the step size and maximum source dwell time during anatomy-based, inverse-planned optimization. Other relevant treatment planning parameters were kept constant, including the dose constraints and source dwell positions. Each plan was evaluated for target coverage, urethral and rectal dose sparing, treatment time, relative target dose homogeneity, and nonuniformity ratio. The plans with 0.5 cm step size were seen to have clinically acceptable tumor coverage, minimal normal structure doses, and minimum treatment time as compared with the other step sizes. The target coverage for this step size is 87% of the prescription dose, while the urethral and maximum rectal doses were 107.3 and 68.7%, respectively. No appreciable difference in plan quality was observed with variation in maximum source dwell time. The step size plays a significant role in plan optimization for prostate implants. Our study supports use of a 0.5 cm step size for prostate implants. PMID:24049323

Predictive factors and management of rectal bleeding side effects following prostate cancer brachytherapy.

PubMed

Price, Jeremy G; Stone, Nelson N; Stock, Richard G

2013-08-01

To report on the incidence, nature, and management of rectal toxicities following individual or combination brachytherapy following treatment for prostate cancer over a 17-year period. We also report the patient and treatment factors predisposing to acute ≥ grade 2 proctitis. A total of 2752 patients were treated for prostate cancer between October 1990 and April 2007 with either low-dose-rate brachytherapy alone or in combination with androgen depletion therapy (ADT) or external beam radiation therapy (EBRT) and were followed for a median of 5.86 years (minimum 1.0 years; maximum 19.19 years). We investigated the 10-year incidence, nature, and treatment of acute and chronic rectal toxicities following BT. Using univariate, and multivariate analyses, we determined the treatment and comorbidity factors predisposing to rectal toxicities. We also outline the most common and effective management for these toxicities. Actuarial risk of ≥ grade 2 rectal bleeding was 6.4%, though notably only 0.9% of all patients required medical intervention to manage this toxicity. The majority of rectal bleeding episodes (72%) occurred within the first 3 years following placement of BT seeds. Of the 27 patients requiring management for their rectal bleeding, 18 underwent formalin treatment and nine underwent cauterization. Post-hoc univariate statistical analysis revealed that coronary artery disease (CAD), biologically effective dose, rectal volume receiving 100% of the prescription dose (RV100), and treatment modality predict the likelihood of grade ≥2 rectal bleeding. Only CAD, treatment type, and RV100 fit a Cox regression multivariate model. Low-dose-rate prostate brachytherapy is very well tolerated and rectal bleeding toxicities are either self-resolving or effectively managed by medical intervention. Treatment planning incorporating adjuvant ADT while minimizing RV100 has yielded the best toxicity-free survival following BT. Copyright © 2013 Elsevier Inc. All rights reserved.

Predictive Factors and Management of Rectal Bleeding Side Effects Following Prostate Cancer Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Price, Jeremy G.; Stone, Nelson N.; Stock, Richard G., E-mail: Richard.Stock@mountsinai.org

2013-08-01

Purpose: To report on the incidence, nature, and management of rectal toxicities following individual or combination brachytherapy following treatment for prostate cancer over a 17-year period. We also report the patient and treatment factors predisposing to acute ≥grade 2 proctitis. Methods and Materials: A total of 2752 patients were treated for prostate cancer between October 1990 and April 2007 with either low-dose-rate brachytherapy alone or in combination with androgen depletion therapy (ADT) or external beam radiation therapy (EBRT) and were followed for a median of 5.86 years (minimum 1.0 years; maximum 19.19 years). We investigated the 10-year incidence, nature, andmore » treatment of acute and chronic rectal toxicities following BT. Using univariate, and multivariate analyses, we determined the treatment and comorbidity factors predisposing to rectal toxicities. We also outline the most common and effective management for these toxicities. Results: Actuarial risk of ≥grade 2 rectal bleeding was 6.4%, though notably only 0.9% of all patients required medical intervention to manage this toxicity. The majority of rectal bleeding episodes (72%) occurred within the first 3 years following placement of BT seeds. Of the 27 patients requiring management for their rectal bleeding, 18 underwent formalin treatment and nine underwent cauterization. Post-hoc univariate statistical analysis revealed that coronary artery disease (CAD), biologically effective dose, rectal volume receiving 100% of the prescription dose (RV100), and treatment modality predict the likelihood of grade ≥2 rectal bleeding. Only CAD, treatment type, and RV100 fit a Cox regression multivariate model. Conclusions: Low-dose-rate prostate brachytherapy is very well tolerated and rectal bleeding toxicities are either self-resolving or effectively managed by medical intervention. Treatment planning incorporating adjuvant ADT while minimizing RV100 has yielded the best toxicity-free survival following BT.« less

Oral versus rectal ibuprofen in healthy volunteers.

PubMed

Vilenchik, Rolanda; Berkovitch, Matitiahu; Jossifoff, Azaria; Ben-Zvi, Zvi; Kozer, Eran

2012-01-01

Ibuprofen is a safe and effective non steroidal anti-inflammatory drug (NSAID). Ibuprofen suppositories are marketed in Europe; but data regarding pharmacokinetics of rectal vs. oral ibuprofen in humans is scarce. The objective of this study is to compare the pharmacokinetics of single-dose rectal vs. oral ibuprofen in healthy adult volunteers. Ten healthy adult male volunteers, aged 20-37 years, received in a non-blind, cross-over setting, two formulations of ibuprofen. First, a 400 mg (about 5 mg/kg) of racemic ibuprofen suppository; second (after a three week washout period) the same dosage of ibuprofen syrup. Blood samples were collected before dosing and for 12 hours after administration. Pharmacokinetics analysis was preformed. Mean peak plasma concentration (Cmax) of rectal ibuprofen was considerably lower, and the mean time to peak (Tmax) considerably longer, compared to oral ibuprofen. Absorption of rectal ibuprofen was considerably lower than oral ibuprofen, with a relative bioequivalence of 63%. Rectal ibuprofen reached therapeutic plasma concentration (>10 µg/ml) 45 minutes after dosing and remained in that range for four hours. The values of Vd/F and CL/F also differ significantly after rectal and oral administration, while no difference was found in the elimination rate constant (Kel) or half-life elimination (t1/2). Racemic ibuprofen suppository has lower bioavailability compared with ibuprofen syrup. Therapeutic plasma concentrations of ibuprofen were reached 45 minutes after dosing and remained in that range for 4 hours. Ibuprofen suppositories can contribute to the management of fever and pain when the oral route is not available.

Low-dose rectal diclofenac for prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a randomized controlled trial.

PubMed

Otsuka, Taiga; Kawazoe, Seiji; Nakashita, Shunya; Kamachi, Saori; Oeda, Satoshi; Sumida, Chinatsu; Akiyama, Takumi; Ario, Keisuke; Fujimoto, Masaru; Tabuchi, Masanobu; Noda, Takahiro

2012-08-01

Acute pancreatitis is a common complication of endoscopic retrograde cholangiopancreatography (ERCP). Rectal nonsteroidal anti-inflammatory drugs (specifically, 100 mg of diclofenac or indomethacin) have shown promising prophylactic activity in post-ERCP pancreatitis (PEP). However, the 100-mg dose is higher than that ordinarily used in Japan. We performed a prospective randomized controlled study to evaluate the efficacy of low-dose rectal diclofenac for the prevention of PEP. Patients who were scheduled to undergo ERCP were randomized to receive a saline infusion either with 50 mg of rectal diclofenac (diclofenac group) or without (control group) 30 min before ERCP. The dose of diclofenac was reduced to 25 mg in patients weighing <50 kg. The primary outcome measure was the occurrence of PEP. Enrollment was terminated early because the planned interim analysis found a statistically significant intergroup difference in the occurrence of PEP. A total of 104 patients were eligible for this study; 51 patients received rectal diclofenac. Twelve patients (11.5%) developed PEP: 3.9% (2/51) in the diclofenac group and 18.9% (10/53) in the control group (p = 0.017). After ERCP, the incidence of hyperamylasemia was not significantly different between the two groups. Post-ERCP pain was significantly more frequent in the control group than in the diclofenac group (37.7 vs. 7.8%, respectively; p < 0.001). There were no adverse events related to diclofenac. Low-dose rectal diclofenac can prevent PEP.

Poor rectal absorption of trimethoprim/sulphamethoxazole in treating Pneumocystis carinii pneumonia.

PubMed Central

Dorr, R. T.; Powell, J. R.; Heick, M.; Barry, D. W.

1981-01-01

A 24-year-old female with Hodgkin's disease and Pneumocystis carinii pneumonia was tested with trimethoprim/sulphamethoxazole (TMP/SMX) tablets. Because treatment failure was feared owing to chronic emesis potentially resulting in incomplete drug absorption, the same TMP/SMX dose was administered by rectal suppositories after the 5th day of oral dosing. The relative fractions (rectal/oral) or the suppository dose absorbed for TMP and SMX were 3.0% and 19.5% respectively. When TMP/SMX treatment is required and the oral route is not practical, the investigational i.v. preparation should be obtained. PMID:6973756

Modelling second malignancy risks from low dose rate and high dose rate brachytherapy as monotherapy for localised prostate cancer.

PubMed

Murray, Louise; Mason, Joshua; Henry, Ann M; Hoskin, Peter; Siebert, Frank-Andre; Venselaar, Jack; Bownes, Peter

2016-08-01

To estimate the risks of radiation-induced rectal and bladder cancers following low dose rate (LDR) and high dose rate (HDR) brachytherapy as monotherapy for localised prostate cancer and compare to external beam radiotherapy techniques. LDR and HDR brachytherapy monotherapy plans were generated for three prostate CT datasets. Second cancer risks were assessed using Schneider's concept of organ equivalent dose. LDR risks were assessed according to a mechanistic model and a bell-shaped model. HDR risks were assessed according to a bell-shaped model. Relative risks and excess absolute risks were estimated and compared to external beam techniques. Excess absolute risks of second rectal or bladder cancer were low for both LDR (irrespective of the model used for calculation) and HDR techniques. Average excess absolute risks of rectal cancer for LDR brachytherapy according to the mechanistic model were 0.71 per 10,000 person-years (PY) and 0.84 per 10,000 PY respectively, and according to the bell-shaped model, were 0.47 and 0.78 per 10,000 PY respectively. For HDR, the average excess absolute risks for second rectal and bladder cancers were 0.74 and 1.62 per 10,000 PY respectively. The absolute differences between techniques were very low and clinically irrelevant. Compared to external beam prostate radiotherapy techniques, LDR and HDR brachytherapy resulted in the lowest risks of second rectal and bladder cancer. This study shows both LDR and HDR brachytherapy monotherapy result in low estimated risks of radiation-induced rectal and bladder cancer. LDR resulted in lower bladder cancer risks than HDR, and lower or similar risks of rectal cancer. In absolute terms these differences between techniques were very small. Compared to external beam techniques, second rectal and bladder cancer risks were lowest for brachytherapy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Relative bioavailability, metabolism and tolerability of rectally administered oxcarbazepine suspension.

PubMed

Clemens, Pamela L; Cloyd, James C; Kriel, Robert L; Remmel, Rory P

2007-01-01

Maintenance of effective drug concentrations is essential for adequate treatment of epilepsy. Some antiepileptic drugs can be successfully administered rectally when the oral route of administration is temporarily unavailable. Oxcarbazepine is a newer antiepileptic drug that is rapidly converted to a monohydroxy derivative, the active compound. This study aimed to characterise the bioavailability, metabolism and tolerability of rectally administered oxcarbazepine suspension using a randomised, crossover design in ten healthy volunteers. Two subjects received 300 mg doses of oxcarbazepine suspension via rectal and oral routes and eight received 450 mg doses. A washout period of at least 2 weeks elapsed between doses. The rectal dose was diluted 1:1 with water. Blood samples and urine were collected for 72 hours post-dose. Adverse effects were assessed at each blood collection time-point using a self-administered questionnaire. Plasma was assayed for oxcarbazepine and monohydroxy derivative; urine was assayed for monohydroxy derivative and monohydroxy derivative-glucuronide. Maximum plasma concentration (C(max)) and time to reach C(max) (t(max)) were obtained directly from the plasma concentration-time curves. The areas under the concentration-time curve (AUCs) were determined via non-compartmental analysis. Relative bioavailability was calculated and the C(max) and AUCs were compared using Wilcoxon signed-rank tests. Mean relative bioavailability calculated from plasma AUCs was 8.3% (SD 5.5%) for the monohydroxy derivative and 10.8% (SD 7.3%) for oxcarbazepine. Oxcarbazepine and monohydroxy derivative C(max) and AUC values were significantly lower following rectal administration (p < 0.01). The total amount of monohydroxy derivative excreted in the urine following rectal administration was 10 +/- 5% of the amount excreted following oral administration. Oral absorption was consistent with previous studies. The most common adverse effects were headache and fatigue with no discernible differences between routes. Monohydroxy derivative bioavailability following rectal administration of oxcarbazepine suspension is significantly lower than following oral administration, most likely because of poor oxcarbazepine water solubility. It is unlikely that adequate monohydroxy derivative concentrations can be achieved with rectal administration of diluted oxcarbazepine suspension.

Bioavailabilities of rectal and oral methadone in healthy subjects

PubMed Central

Dale, Ola; Sheffels, Pamela; Kharasch, Evan D

2004-01-01

Aims Rectal administration of methadone may be an alternative to intravenous and oral dosing in cancer pain, but the bioavailability of the rectal route is not known. The aim of this study was to compare the absolute rectal bioavailability of methadone with its oral bioavailability in healthy humans. Methods Seven healthy subjects (six males, one female, aged 20–39 years) received 10 mg d5-methadone-HCl rectally (5 ml in 20% glycofurol) together with either d0-methadone intravenously (5 mg) or orally (10 mg) on two separate occasions. Blood samples for the LC-MS analyses of methadone and it's metabolite EDDP were drawn for up to 96 h. Noninvasive infrared pupillometry was peformed at the same time as blood sampling. Results The mean absolute rectal bioavalability of methadone was 0.76 (0.7, 0.81), compared to 0.86 (0.75, 0.97) for oral administration (mean (95% CI)). Rectal absorption of methadone was more rapid than after oral dosing with Tmax values of 1.4 (0.9, 1.8) vs. 2.8 (1.6, 4.0) h. The extent of formation of the metabolite EDDP did not differ between routes of administration. Single doses of methadone had a duration of action of at least 10 h and were well tolerated. Conclusions Rectal administration of methadone results in rapid absorption, a high bioavailability and long duration of action. No evidence of presystemic elimination was seen. Rectal methadone has characteristics that make it a potential alternative to intravenous and oral administration, particularly in cancer pain and palliative care. PMID:15255797

Rectal artemisinins for malaria: a review of efficacy and safety from individual patient data in clinical studies

PubMed Central

Gomes, Melba; Ribeiro, Isabela; Warsame, Marian; Karunajeewa, Harin; Petzold, Max

2008-01-01

Background Rectal administration of artemisinin derivatives has potential for early treatment for severe malaria in remote settings where injectable antimalarial therapy may not be feasible. Preparations available include artesunate, artemisinin, artemether and dihydroartemisinin. However each may have different pharmacokinetic properties and more information is needed to determine optimal dose and comparative efficacy with each another and with conventional parenteral treatments for severe malaria. Methods Individual patient data from 1167 patients in 15 clinical trials of rectal artemisinin derivative therapy (artesunate, artemisinin and artemether) were pooled in order to compare the rapidity of clearance of Plasmodium falciparum parasitaemia and the incidence of reported adverse events with each treatment. Data from patients who received comparator treatment (parenteral artemisinin derivative or quinine) were also included. Primary endpoints included percentage reductions in parasitaemia at 12 and 24 hours. A parasite reduction of >90% at 24 hours was defined as parasitological success. Results Artemisinin and artesunate treatment cleared parasites more rapidly than parenteral quinine during the first 24 hours of treatment. A single higher dose of rectal artesunate treatment was five times more likely to achieve >90% parasite reductions at 24 hours than were multiple lower doses of rectal artesunate, or a single lower dose administration of rectal artemether. Conclusion Artemisinin and artesunate suppositories rapidly eliminate parasites and appear to be safe. There are less data on artemether and dihydroartemisinin suppositories. The more rapid parasite clearance of single high-dose regimens suggests that achieving immediate high drug concentrations may be the optimal strategy. PMID:18373841

Relative bioavailability and plasma paracetamol profiles of Panadol suppositories in children.

PubMed

Coulthard, K P; Nielson, H W; Schroder, M; Covino, A; Matthews, N T; Murray, R S; Van Der Walt, J H

1998-10-01

To determine the relative bioavailability and plasma paracetamol concentration profiles following administration of a proprietary formulation of paracetamol suppositories to postoperative children. Study A-eight children undergoing minor surgery had blood samples collected following the rectal administration of either a 250 mg or 500 mg paracetamol suppository on one day and an equivalent oral dose on the following day. A mean dose of 13 mg/kg gave a mean Cmax (Tmax) of 7.7 mg/L (1.6 h) and 4.9 mg/L (2.0 h) following oral and rectal administration, respectively. The mean relative rectal bioavailability was 78% (95% confidence interval of 55-101%). Study B-20 children undergoing tonsillectomy and/or adenoidectomy were randomly assigned to receive a postoperative dose of 500 mg of paracetamol either as 2 x 250 mg liquid filled or 1 x 500 mg hard wax Panadol suppository. A mean dose of 25 mg/kg produced mean maximum plasma paracetamol concentrations of 13.2 mg/L and 14.5 mg/L at 2.1 and 1.9 h for the hard and liquid filled suppository, respectively. The absorption rate constants and areas under the curves suggested no difference in the rate or extent of absorption between the two formulations. Absorption of paracetamol following rectal administration of Panadol suppositories to postoperative children is slower and reduced as compared to oral therapy. The hard wax and liquid filled products have similar absorption characteristics. The usually quoted antipyretic therapeutic range for paracetamol is 10-20 mg/L, although 5 mg/L may be effective. A single rectal dose of 25 mg/kg will obtain this lower concentration within 1 h of administration and maintain it for up to 6 h. When given in an appropriate dose for analgesia, maximum plasma paracetamol concentrations would be available in the immediate postoperative period if the rectal dose was given 2 h before the planned end of the procedure.

The pharmacokinetics of a single oral or rectal dose of concurrently administered isoniazid, rifampin, pyrazinamide, and ethambutol in Asian elephants (Elephas maximus).

PubMed

P Brock, A; Isaza, R; Egelund, E F; Hunter, R P; Peloquin, C A

2014-10-01

Tuberculosis, caused by Mycobacterium tuberculosis, is a disease of concern in captive Asian elephants (Elephas maximus). Treatment for tuberculosis in elephants utilizes multidrug protocols combining isoniazid, rifampin, pyrazinamide, and/or ethambutol. In this study, a single, coformulated dose of isoniazid 5 mg/kg, rifampin 10 mg/kg, pyrazinamide 30 mg/kg, and ethambutol 30 mg/kg was administered orally to six Asian elephants, and rectally to five elephants using a cross-over design. Blood samples were collected serially over 24 h. Pyrazinamide and ethambutol concentrations were determined using validated gas chromatography assays. Isoniazid and rifampin concentrations were determined using validated high-performance liquid chromatography assays. Rectal isoniazid produced an earlier Tmax compared with oral administration. Oral isoniazid resulted in a comparatively lower Cmax , but higher AUC values compared with rectal isoniazid. Oral rifampin and oral ethambutol were well absorbed while rectal rifampin was not. Oral pyrazinamide produced comparatively higher Cmax and AUC values compared with rectal pyrazinamide. Results of this study indicate that currently recommended therapeutic monitoring sample collection times for rectal isoniazid and oral rifampin do not provide an accurate assessment of exposure for these drugs. This study demonstrates notable individual variability, indicating that dosing of these medications requires individual monitoring and provides additional information to guide the clinician when treating elephants. © 2014 John Wiley & Sons Ltd.

Carbon-Ion Radiation Therapy for Pelvic Recurrence of Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamada, Shigeru, E-mail: s_yamada@nirs.go.jp; Kamada, Tadashi; Ebner, Daniel K.

Purpose: Investigation of the treatment potential of carbon-ion radiation therapy in pelvic recurrence of rectal cancer. Methods and Materials: A phase 1/2 dose escalation study was performed. One hundred eighty patients (186 lesions) with locally recurrent rectal cancer were treated with carbon-ion radiation therapy (CIRT) (phase 1/2: 37 and 143 patients, respectively). The relapse locations were 71 in the presacral region, 82 in the pelvic sidewalls, 28 in the perineum, and 5 near the colorectal anastomosis. A 16-fraction in 4 weeks dose regimen was used, with total dose ranging from 67.2 to 73.6 Gy(RBE); RBE-weighted absorbed dose: 4.2 to 4.6 Gy(RBE)/fraction. Results: Duringmore » phase 1, the highest total dose, 73.6 Gy(RBE), resulted in no grade >3 acute reactions in the 13 patients treated at that dose. Dose escalation was halted at this level, and this dose was used for phase 2, with no other grade >3 acute reactions observed. At 5 years, the local control and survival rates at 73.6 Gy(RBE) were 88% (95% confidence interval [CI], 80%-93%) and 59% (95% CI, 50%-68%), respectively. Conclusion: Carbon-ion radiation therapy may be a safe and effective treatment option for locally recurrent rectal cancer and may serve as an alternative to surgery.« less

A comparison of salicylic acid levels in normal subjects after rectal versus oral dosing.

PubMed

Maalouf, Roger; Mosley, Mark; James Kallail, K; Kramer, Karen M; Kumar, Gaurav

2009-02-01

The common practice is to use 162 mg of aspirin orally in the emergency department (ED) for patients presenting with myocardial infarction. If the patient cannot take aspirin orally in the authors' facility, then 600 mg of aspirin is given rectally. However, no strong evidence exists as to whether the oral and rectal doses provide equivalent risk protection. The authors hypothesized that the salicylic acid levels for orally and rectally administered aspirin will not be similar, because of the different dosages used and the different routes of administration. The study sample consisted of healthy, nonpregnant, adult volunteers without active illness, who did not take any medication regularly. Each subject served as his or her own control to account for any confounding factors. The study was conducted on 2 days, separated by a 1-week washout period. On the first day, 162 mg of oral aspirin was chewed and swallowed. Salicylic acid levels were obtained at baseline (i.e., before taking the aspirin) and then 30, 60, and 90 minutes after dosing. The 600-mg aspirin suppository was self-administered 1 week later with a sample for laboratory measures again drawn at baseline and then 30, 60, and 90 minutes after dosing. Twenty-four subjects completed the study. The rectal suppository provided significantly more salicylic acid into the blood than the oral tablets over 90 minutes (p < 0.001). No statistical difference was noted between oral and rectal administration from baseline to 30 minutes (p > 0.05). However, mean salicylic acid levels from the rectal suppository were statistically higher than from the oral tablets from 30 to 60 minutes (p < 0.001) and from 60 to 90 minutes (p = 0.002). More than 60% of the subjects had an increasing salicylic acid level response over time to the rectal suppository. The salicylic acid level response to the oral administration was more evenly divided between those subjects whose salicylic acid levels peaked quickly and then fell or held steady (33%), those whose salicylic acid levels increased over time (29%), and those whose salicylic acid levels were measureable only after 60 minutes (25%). Although not statistically significant, these differences in group distributions for the type of salicylic acid level response between oral and rectal doses suggested the possibility of a rectal advantage. Whether the higher salicylic acid levels and faster absorption of the rectal aspirin translate into better clinical outcomes is unknown and cannot be concluded from our study. Previous evidence, however, has shown that 162 mg of aspirin chewed and swallowed provided lower mortality in patients presenting with myocardial infarction. Our results suggested the rectal administration of a 600-mg suppository provides sufficient levels of salicylic acid within 90 minutes to meet or exceed that of oral aspirin.

Differences in Radiation Dosimetry and Anorectal Function Testing Imply That Anorectal Symptoms May Arise From Different Anatomic Substrates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smeenk, Robert Jan, E-mail: r.smeenk@rther.umcn.nl; Hopman, Wim P.M.; Hoffmann, Aswin L.

2012-01-01

Purpose: To explore the influence of functional changes and dosimetric parameters on specific incontinence-related anorectal complaints after prostate external beam radiotherapy and to estimate dose-effect relations for the anal wall and rectal wall. Methods and Materials: Sixty patients, irradiated for localized prostate cancer, underwent anorectal manometry and barostat measurements to evaluate anal pressures, rectal capacity, and rectal sensory functions. In addition, 30 untreated men were analyzed as a control group. In 36 irradiated patients, the anal wall and rectal wall were retrospectively delineated on planning computed tomography scans, and dosimetric parameters were retrieved from the treatment plans. Functional and dosimetricmore » parameters were compared between patients with and without complaints, focusing on urgency, incontinence, and frequency. Results: After external beam radiotherapy, reduced anal pressures and tolerated rectal volumes were observed, irrespective of complaints. Patients with urgency and/or incontinence showed significantly lower anal resting pressures (mean 38 and 39 vs. 49 and 50 mm Hg) and lower tolerated rectal pressures (mean 28 and 28 vs. 33 and 34 mm Hg), compared to patients without these complaints. In patients with frequency, almost all rectal parameters were reduced. Several dosimetric parameters to the anal wall and rectal wall were predictive for urgency (e.g., anal D{sub mean}>38Gy), whereas some anal wall parameters correlated to incontinence and no dose-effect relation for frequency was found. Conclusions: Anorectal function deteriorates after external beam radiotherapy. Different incontinence-related complaints show specific anorectal dysfunctions, suggesting different anatomic and pathophysiologic substrates: urgency and incontinence seem to originate from both anal wall and rectal wall, whereas frequency seems associated with rectal wall dysfunction. Also, dose-effect relations differed between these complaints. This implies that anal wall and rectal wall should be considered separate organs in radiotherapy planning.« less

Predictors for Rectal and Intestinal Acute Toxicities During Prostate Cancer High-Dose 3D-CRT: Results of a Prospective Multicenter Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vavassori, Vittorio; Fiorino, Claudio; Rancati, Tiziana

2007-04-01

Purpose: To find predictors for rectal and intestinal acute toxicity in patients with prostate cancer treated with {>=}70 Gy conformal radiotherapy. Methods and Materials: Between July 2002 and March 2004, 1,132 patients were entered into a cooperative study (AIROPROS01-02). Toxicity was scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale and by considering the changes (before and after treatment) of the scores of a self-administered questionnaire on rectal/intestinal toxicity. The correlation with a number of parameters was assessed by univariate and multivariate analyses. Concerning the questionnaire, only moderate/severe complications were considered. Results: Of 1,132more » patients, 1,123 were evaluable. Of these patients, 375, 265, and 28 had Grade 1, 2, and 3 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity, respectively. The mean rectal dose was the most predictive parameter (p = 0.0004; odds ratio, 1.035) for Grade 2 or worse toxicity, and the use of anticoagulants/antiaggregants (p 0.02; odds ratio, 0.63) and hormonal therapy (p = 0.04, odds ratio, 0.65) were protective. The questionnaire-based scoring revealed that a greater mean rectal dose was associated with a greater risk of bleeding; larger irradiated volumes were associated with frequency, tenesmus, incontinence, and bleeding; hormonal therapy was protective against frequency and tenesmus; hemorrhoids were associated with a greater risk of tenesmus and bleeding; and diabetes associated highly with diarrhea. Conclusion: The mean rectal dose correlated with acute rectal/intestinal toxicity in three-dimensional conformal radiotherapy for prostate cancer, and hormonal therapy and the use of anticoagulants/antiaggregants were protective. According to the moderate/severe injury scores on the self-assessed questionnaire, several clinical and dose-volume parameters were independently predictive for particular symptoms.« less

Quantification of the spatial distribution of rectally applied surrogates for microbicide and semen in colon with SPECT and magnetic resonance imaging

PubMed Central

Cao, Ying J; Caffo, Brian S; Fuchs, Edward J; Lee, Linda A; Du, Yong; Li, Liye; Bakshi, Rahul P; Macura, Katarzyna; Khan, Wasif A; Wahl, Richard L; Grohskopf, Lisa A; Hendrix, Craig W

2012-01-01

AIMS We sought to describe quantitatively the distribution of rectally administered gels and seminal fluid surrogates using novel concentration–distance parameters that could be repeated over time. These methods are needed to develop rationally rectal microbicides to target and prevent HIV infection. METHODS Eight subjects were dosed rectally with radiolabelled and gadolinium-labelled gels to simulate microbicide gel and seminal fluid. Rectal doses were given with and without simulated receptive anal intercourse. Twenty-four hour distribution was assessed with indirect single photon emission computed tomography (SPECT)/computed tomography (CT) and magnetic resonance imaging (MRI), and direct assessment via sigmoidoscopic brushes. Concentration–distance curves were generated using an algorithm for fitting SPECT data in three dimensions. Three novel concentration–distance parameters were defined to describe quantitatively the distribution of radiolabels: maximal distance (Dmax), distance at maximal concentration (DCmax) and mean residence distance (Dave). RESULTS The SPECT/CT distribution of microbicide and semen surrogates was similar. Between 1 h and 24 h post dose, the surrogates migrated retrograde in all three parameters (relative to coccygeal level; geometric mean [95% confidence interval]): maximal distance (Dmax), 10 cm (8.6–12) to 18 cm (13–26), distance at maximal concentration (DCmax), 3.8 cm (2.7–5.3) to 4.2 cm (2.8–6.3) and mean residence distance (Dave), 4.3 cm (3.5–5.1) to 7.6 cm (5.3–11). Sigmoidoscopy and MRI correlated only roughly with SPECT/CT. CONCLUSIONS Rectal microbicide surrogates migrated retrograde during the 24 h following dosing. Spatial kinetic parameters estimated using three dimensional curve fitting of distribution data should prove useful for evaluating rectal formulations of drugs for HIV prevention and other indications. PMID:22404308

Short-term intravenous antimicrobial prophylaxis for elective rectal cancer surgery: results of a prospective randomized non-inferiority trial.

PubMed

Ishibashi, Keiichiro; Ishida, Hideyuki; Kuwabara, Kouki; Ohsawa, Tomonori; Okada, Norimichi; Yokoyama, Masaru; Kumamoto, Kensuke

2014-04-01

To investigate the non-inferiority of postoperative single-dose intravenous antimicrobial prophylaxis to multiple-dose intravenous antimicrobial prophylaxis in terms of the incidence of surgical site infections (SSIs) in patients undergoing elective rectal cancer surgery by a prospective randomized study. Patients undergoing elective surgery for rectal cancer were randomized to receive a single intravenous injection of flomoxef (group 1) or five additional doses (group 2) of flomoxef after the surgery. All the patients had received preoperative oral antibiotic prophylaxis (kanamycin and erythromycin) after mechanical cleansing within 24 h prior to surgery, and had received intravenous flomoxef during surgery. A total of 279 patients (including 139 patients in group 1 and 140 in group 2) were enrolled in the study. The incidence of SSIs was 13.7% in group 1 and 13.6% in group 2 (difference [95% confidence interval]: -0.2% [-0.9 to 0.7%]). The incidence of SSIs was not significantly different in patients undergoing elective rectal surgery who were treated using a single dose of postoperative antibiotics compared to those treated using multiple-dose antibiotics when preoperative mechanical and chemical bowel preparations were employed.

A Single-Dose Crossover Pharmacokinetic Comparison Study of Oral, Rectal and Topical Quetiapine in Healthy Adults.

PubMed

Leung, Jonathan G; Nelson, Sarah; Cunningham, Julie L; Thompson, Virginia H; Bobo, William V; Kung, Simon; Dierkhising, Ross A; Plevak, Matthew F; Lapid, Maria I

2016-08-01

Quetiapine is an oral atypical antipsychotic drug commonly used to treat a large number of neuropsychiatric disorders and conditions. However, a substantial number of patients who may benefit from treatment with quetiapine are unable to ingest quetiapine or other medications by mouth and thus require alternative routes of administration. There are currently no studies evaluating non-oral compounded dosage forms of quetiapine. We conducted a single-dose open-label crossover pharmacokinetic study in 10 healthy adults to determine whether quetiapine compounded as a rectal suppository or a topical cream achieved absorption similar to that achieved by a commercially available oral formulation. Rectal quetiapine produced an area under the plasma concentration-time curve from time zero to infinity (AUC∞) approximately 90 % greater than that produced by an equal (milligram per milligram) dose of oral quetiapine (15,333 ng/mL versus 8118.8 ng/mL, p = 0.005). However, only two of ten subjects who received topical quetiapine had detectable serum levels. When detected, serum levels achieved with topical quetiapine were delayed and low in comparison with those produced by the oral and rectal dosage forms. Our results suggest that rectal, but not topical, quetiapine may be useful in clinical settings. Clinical outcome studies of rectal quetiapine are needed.

Reducing rectal injury in men receiving prostate cancer radiation therapy: current perspectives

PubMed Central

Serrano, Nicholas A; Kalman, Noah S; Anscher, Mitchell S

2017-01-01

Dose escalation is now the standard of care for the treatment of prostate cancer with radiation therapy. However, the rectum tends to be the dose-limiting structure when treating prostate cancer, given its close proximity. Early and late toxicities can occur when the rectum receives large doses of radiation therapy. New technologies allow for prevention of these toxicities. In this review, we examine the evidence that supports various dose constraints employed to prevent these rectal injuries from occurring. We also examine the use of intensity-modulated radiation therapy and how this compares to older radiation therapy techniques that allow for further sparing of the rectum during a radiation therapy course. We then review the literature on endorectal balloons and the effects of their daily use throughout a radiation therapy course. Tissue spacers are now being investigated in greater detail; these devices are injected into the rectoprostatic fascia to physically increase the distance between the prostate and the anterior rectal wall. Last, we review the use of systemic drugs, specifically statin medications and antihypertensives, as well as their impact on rectal toxicity. PMID:28814898

Defining the rectal dose constraint for permanent radioactive seed implantation of the prostate.

PubMed

Albert, Michele; Song, Jun S; Schultz, Delray; Cormack, Robert A; Tempany, Clare M; Haker, Steve; Devlin, Phillip M; Beard, Clair; Hurwitz, Mark D; Suh, Wonsuk W; Jolesz, Ferenc; D'Amico, Anthony V

2008-01-01

This study was performed to define the rectal dose constraint that would predict late rectal bleeding requiring argon plasma coagulation (APC) following prostate brachy mono-therapy. Between February 1999 and April 2002, 91 patients with low risk prostate cancer underwent permanent I(125) radioactive seed implantation without the use of supplemental external beam radiation or androgen suppression therapy. Patients received both CT and MRI scans 6 weeks postimplant for evaluation of dosimetry. The CT and MRI scans were fused. Rectal volumes were contoured on the T2 weighted MR images. For those patients requiring APC, the date on which a patient reported rectal bleeding was recorded. A Cox regression analysis was performed to assess whether there was a significant association between the rectal volume (continuous) exceeding 100 Gy time rectal bleeding. Comparisons of estimates of rectal bleeding requiring APC were made using a 2-sided log rank test. There was a significant association (hazard ratio = 5.6 [95% confidence interval: 1.3, 23.8]; P = 0.002) between the rectal volume exceeding 100 Gy and rectal bleeding requiring APC. After a median follow-up of 4.25 (1-6) years, no patient with less than a median value of 8 cc of rectum exceeding 100 Gy required APC, whereas 20% (P = 0.004) were estimated to require APC within 3 years following treatment. Keeping the rectal volume receiving more than 100 Gy below 8 cc will minimize the risk of rectal bleeding requiring APC following I(125) permanent prostate brachy mono-therapy.

Genetic variation in C-reactive protein (CRP) in relation to colon and rectal cancer risk and survival

PubMed Central

Slattery, Martha L.; Curtin, Karen; Poole, Elizabeth M.; Duggan, David J.; Samowitz, Wade S.; Peters, Ulrike; Caan, Bette J.; Potter, John D.; Ulrich, Cornelia M.

2011-01-01

Background C-reactive protein (CRP), a biomarker of inflammation has been shown to be influenced by genetic variation in the CRP gene. Methods In this study, we test the hypothesis that genetic variation in CRP influences both the risk of developing colon and rectal cancer and survival. Two population-based studies of colon cancer (n=1574 cases, 1970 controls) and rectal (n=791 cases, 999 controls) were conducted. We evaluated four CRP tagSNPs: rs1205 (G>A, 3’ UTR); rs1417938 (T>A, intron); rs1800947 (G>C, L184L); and rs3093075 (C>A, 3’ flanking). Results The CRP rs1205 AA genotype was associated with an increased risk of colon cancer (OR 1.3, 95%CI 1.1-1.7), whereas the rs3093075 A allele was associated with a reduced risk of rectal cancer (OR 0.7, 95%CI 0.5-0.9). The strongest association for the rs1205 polymorphism and colon cancer was observed among those with KRAS2 mutations (OR 1.5, 95%CI 1.1-2.0). The CRP rs1205 AA genotype also was associated with an increased risk of CIMP+ rectal tumors (OR 2.5, 95% CI 1.2-5.3); conversely, the rs1417938 A allele was associated with a reduced risk of CIMP+ rectal tumors (OR 0.5, 95%CI 0.3-0.9). We observed interactions between CRP rs1800947 and BMI and family history of CRC in modifying risk of both colon and rectal cancer. Conclusions These data suggest that genetic variation in the CRP gene influences risk of both colon and rectal cancer development. PMID:20949557

Bioavailability of diazepam after intravenous, oral and rectal administration in adult epileptic patients.

PubMed Central

Dhillon, S; Oxley, J; Richens, A

1982-01-01

1 The absorption of single doses of diazepam in six adult epileptic subjects following intravenous, oral and rectal administration were studied in order to evaluate the usefulness of the latter in emergency situations in the adult. 2 Diazepam tablets (Valium, Roche) and rectal solution (Valium solution for intravenous administration) produced similar peak serum concentrations after delays of 15-90 min. 3 Two suppository formulations showed statistically significant differences in absorption characteristics. 4 Serum diazepam levels above 400 ng ml-1 (suggested to be necessary for a satisfactory anticonvulsant effect) were reached in only a few subjects after rectal doses of 10-20 mg of solution, and then usually after a delay of over 2 h. PMID:7059446

A retrospective analysis of rectal and bladder dose for gynecological brachytherapy treatments with GZP6 HDR afterloading system.

PubMed

Bahreyni Toossi, Mohammad Taghi; Ghorbani, Mahdi; Makhdoumi, Yasha; Taheri, Mojtaba; Homaee Shandiz, Fatemeh; Zahed Anaraki, Siavash; Soleimani Meigooni, Ali

2012-01-01

The aim of this work is to evaluate rectal and bladder dose for the patients treated for gynecological cancers. The GZP6 high dose rate brachytherapy system has been recently introduced to a number of radiation therapy departments in Iran, for treatment of various tumor sites such as cervix and vagina. Our analysis was based on dose measurements for 40 insertions in 28 patients, treated by a GZP6 unit between June 2009 and November 2010. Treatments consisted of combined teletherapy and intracavitary brachytherapy. In vivo dosimetry was performed with TLD-400 chips and TLD-100 microcubes in the rectum and bladder. The average of maximum rectal and bladder dose values were found to be 7.62 Gy (range 1.72-18.55 Gy) and 5.17 Gy (range 0.72-15.85 Gy), respectively. It has been recommended by the ICRU that the maximum dose to the rectum and bladder in intracavitary treatment of vaginal or cervical cancer should be lower than 80% of the prescribed dose to point A in the Manchester system. In this study, of the total number of 40 insertions, maximum rectal dose in 29 insertions (72.5% of treatment sessions) and maximum bladder dose in 18 insertions (45% of treatments sessions) were higher than 80% of the prescribed dose to the point of dose prescription. In vivo dosimetry for patients undergoing treatment by GZP6 brachytherapy system can be used for evaluation of the quality of brachytherapy treatments by this system. This information could be used as a base for developing the strategy for treatment of patients treated with GZP6 system.

A retrospective analysis of rectal and bladder dose for gynecological brachytherapy treatments with GZP6 HDR afterloading system

PubMed Central

Bahreyni Toossi, Mohammad Taghi; Ghorbani, Mahdi; Makhdoumi, Yasha; Taheri, Mojtaba; Homaee Shandiz, Fatemeh; Zahed Anaraki, Siavash; Soleimani Meigooni, Ali

2012-01-01

Aim The aim of this work is to evaluate rectal and bladder dose for the patients treated for gynecological cancers. Background The GZP6 high dose rate brachytherapy system has been recently introduced to a number of radiation therapy departments in Iran, for treatment of various tumor sites such as cervix and vagina. Materials and methods Our analysis was based on dose measurements for 40 insertions in 28 patients, treated by a GZP6 unit between June 2009 and November 2010. Treatments consisted of combined teletherapy and intracavitary brachytherapy. In vivo dosimetry was performed with TLD-400 chips and TLD-100 microcubes in the rectum and bladder. Results The average of maximum rectal and bladder dose values were found to be 7.62 Gy (range 1.72–18.55 Gy) and 5.17 Gy (range 0.72–15.85 Gy), respectively. It has been recommended by the ICRU that the maximum dose to the rectum and bladder in intracavitary treatment of vaginal or cervical cancer should be lower than 80% of the prescribed dose to point A in the Manchester system. In this study, of the total number of 40 insertions, maximum rectal dose in 29 insertions (72.5% of treatment sessions) and maximum bladder dose in 18 insertions (45% of treatments sessions) were higher than 80% of the prescribed dose to the point of dose prescription. Conclusion In vivo dosimetry for patients undergoing treatment by GZP6 brachytherapy system can be used for evaluation of the quality of brachytherapy treatments by this system. This information could be used as a base for developing the strategy for treatment of patients treated with GZP6 system. PMID:24377037

Influence of the intravenous contrast media on treatment planning dose calculations of lower esophageal and rectal cancers.

PubMed

Nasrollah, Jabbari; Mikaeil, Molazadeh; Omid, Esnaashari; Mojtaba, Seyed Siahi; Ahad, Zeinali

2014-01-01

The impact of intravenous (IV) contrast media (CM) on radiation dose calculations must be taken into account in treatment planning. The aim of this study is to evaluate the effect of an intravenous contrast media on dose calculations in three-dimensional conformal radiation therapy (3D-CRT) for lower esophageal and rectal cancers. Seventeen patients with lower esophageal tumors and 12 patients with rectal cancers were analyzed. At the outset, all patients were planned for 3D-CRT based on the computed tomography (CT) scans with IV contrast media. Subsequently, all the plans were copied and replaced on the scans without intravenous CM. The radiation doses calculated from the two sets of CTs were compared. The dose differences between the planning image set using intravenous contrast and the image set without contrast showed an average increase in Monitor Units (MUs) in the lower esophageal region that was 1.28 and 0.75% for 6 and 15 MV photon beams, respectively. There was no statistical significant difference in the rectal region between the two sets of scans in the 3D-CRT plans. The results showed that the dose differences between the plans for the CT scans with and without CM were small and clinically tolerable. However, the differences in the lower esophageal region were significant in the statistical analysis.

Life-saving rectal artesunate for complicated malaria in children.

PubMed

Pengsaa, Krisana; Sirivichayakul, Chukiat; Na-Bangchang, Kesara; Thaiarporn, Itthipon; Chaivisuth, Anong; Wongsuwan, Amnaj; Attanath, Phanorsri; Pojjaroen-Anant, Chanathep; Wisetsing, Pataraporn; Chanthavanich, Pornthep; Sabchareon, Arunee

2005-05-01

We report the effectiveness of two regimens of rectal artesunate formulation in treating 13 Thai children with cerebral/complicated falciparum malaria. The drug was given at an initial dose of 40 mg/kg bodyweight, in 3 or 4 divided doses in the first 24 hours, followed by 10 mg/kg bodyweight once daily for three consecutive days. Mefloquine, at a dose of 15 mg/kg bodyweight was given orally at 72 hours after the initial dose of artesunate, followed by 10 mg/kg bodyweight 6 hours later. Three cases with cerebral malaria gained consciousness within 20 hours of artesunate administration. The median time required for reduction of parasitemia by 90% of the initial value (P90) in 13 children was 11.2 hours. No recrudescence was observed in any of the patients during the 28-day follow-up period. Plasma concentrations of artesunate and dihydroartemisinin (active plasma metabolite of artesunate) measured in two patients who received the high initial dose regimen (20 mg/ kg bodyweight) suggested rapid absorption and adequate plasma concentrations of both compounds following the administration of artesunate via the rectal route. Further studies for the optimized regimen of rectal artesunate in the treatment of cerebral/complicated childhood falciparum malaria in areas of multidrug resistance are warranted.

Spatial features of dose-surface maps from deformably-registered plans correlate with late gastrointestinal complications

NASA Astrophysics Data System (ADS)

Moulton, Calyn R.; House, Michael J.; Lye, Victoria; Tang, Colin I.; Krawiec, Michele; Joseph, David J.; Denham, James W.; Ebert, Martin A.

2017-05-01

This study investigates the associations between spatial distribution of dose to the rectal surface and observed gastrointestinal toxicities after deformably registering each phase of a combined external beam radiotherapy (EBRT)/high-dose-rate brachytherapy (HDRBT) prostate cancer treatment. The study contains data for 118 patients where the HDRBT CT was deformably-registered to the EBRT CT. The EBRT and registered HDRBT TG43 dose distributions in a reference 2 Gy/fraction were 3D-summed. Rectum dose-surface maps (DSMs) were obtained by virtually unfolding the rectum surface slice-by-slice. Associations with late peak gastrointestinal toxicities were investigated using voxel-wise DSM analysis as well as parameterised spatial patterns. The latter were obtained by thresholding DSMs from 1-80 Gy (increment  =  1) and extracting inferior-superior extent, left-right extent, area, perimeter, compactness, circularity and ellipse fit parameters. Logistic regressions and Mann-Whitney U-tests were used to correlate features with toxicities. Rectal bleeding, stool frequency, diarrhoea and urgency/tenesmus were associated with greater lateral and/or longitudinal spread of the high doses near the anterior rectal surface. Rectal bleeding and stool frequency were also influenced by greater low-intermediate doses to the most inferior 20% of the rectum and greater low-intermediate-high doses to 40-80% of the rectum length respectively. Greater low-intermediate doses to the superior 20% and inferior 20% of the rectum length were associated with anorectal pain and urgency/tenesmus respectively. Diarrhoea, completeness of evacuation and proctitis were also related to greater low doses to the posterior side of the rectum. Spatial features for the intermediate-high dose regions such as area, perimeter, compactness, circularity, ellipse eccentricity and confinement to ellipse fits were strongly associated with toxicities other than anorectal pain. Consequently, toxicity is related to the shape of isodoses as well as dose coverage. The findings indicate spatial constraints on doses to certain sections of the rectum may be important for reducing toxicities and optimising dose.

Intensity Modulated Proton and Photon Therapy for Early Prostate Cancer With or Without Transperineal Injection of a Polyethylen Glycol Spacer: A Treatment Planning Comparison Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weber, Damien C., E-mail: damien.weber@unige.ch; Zilli, Thomas; Vallee, Jean Paul

2012-11-01

Purpose: Rectal toxicity is a serious adverse effect in early-stage prostate cancer patients treated with curative radiation therapy (RT). Injecting a spacer between Denonvilliers' fascia increases the distance between the prostate and the anterior rectal wall and may thus decrease the rectal radiation-induced toxicity. We assessed the dosimetric impact of this spacer with advanced delivery RT techniques, including intensity modulated RT (IMRT), volumetric modulated arc therapy (VMAT), and intensity modulated proton beam RT (IMPT). Methods and Materials: Eight prostate cancer patients were simulated for RT with or without spacer. Plans were computed for IMRT, VMAT, and IMPT using the Eclipsemore » treatment planning system using both computed tomography spacer+ and spacer- data sets. Prostate {+-} seminal vesicle planning target volume [PTV] and organs at risk (OARs) dose-volume histograms were calculated. The results were analyzed using dose and volume metrics for comparative planning. Results: Regardless of the radiation technique, spacer injection decreased significantly the rectal dose in the 60- to 70-Gy range. Mean V{sub 70Gy} and V{sub 60Gy} with IMRT, VMAT, and IMPT planning were 5.3 {+-} 3.3%/13.9 {+-} 10.0%, 3.9 {+-} 3.2%/9.7 {+-} 5.7%, and 5.0 {+-} 3.5%/9.5 {+-} 4.7% after spacer injection. Before spacer administration, the corresponding values were 9.8 {+-} 5.4% (P=.012)/24.8 {+-} 7.8% (P=.012), 10.1 {+-} 3.0% (P=.002)/17.9 {+-} 3.9% (P=.003), and 9.7 {+-} 2.6% (P=.003)/14.7% {+-} 2.7% (P=.003). Importantly, spacer injection usually improved the PTV coverage for IMRT. With this technique, mean V{sub 70.2Gy} (P=.07) and V{sub 74.1Gy} (P=0.03) were 100 {+-} 0% to 99.8 {+-} 0.2% and 99.1 {+-} 1.2% to 95.8 {+-} 4.6% with and without Spacer, respectively. As a result of spacer injection, bladder doses were usually higher but not significantly so. Only IMPT managed to decrease the rectal dose after spacer injection for all dose levels, generally with no observed increase to the bladder dose. Conclusions: Regardless of the radiation technique, a substantial decrease of rectal dose was observed after spacer injection for curative RT to the prostate.« less

Quantification of the spatial distribution of rectally applied surrogates for microbicide and semen in colon with SPECT and magnetic resonance imaging.

PubMed

Cao, Ying J; Caffo, Brian S; Fuchs, Edward J; Lee, Linda A; Du, Yong; Li, Liye; Bakshi, Rahul P; Macura, Katarzyna; Khan, Wasif A; Wahl, Richard L; Grohskopf, Lisa A; Hendrix, Craig W

2012-12-01

We sought to describe quantitatively the distribution of rectally administered gels and seminal fluid surrogates using novel concentration-distance parameters that could be repeated over time. These methods are needed to develop rationally rectal microbicides to target and prevent HIV infection. Eight subjects were dosed rectally with radiolabelled and gadolinium-labelled gels to simulate microbicide gel and seminal fluid. Rectal doses were given with and without simulated receptive anal intercourse. Twenty-four hour distribution was assessed with indirect single photon emission computed tomography (SPECT)/computed tomography (CT) and magnetic resonance imaging (MRI), and direct assessment via sigmoidoscopic brushes. Concentration-distance curves were generated using an algorithm for fitting SPECT data in three dimensions. Three novel concentration-distance parameters were defined to describe quantitatively the distribution of radiolabels: maximal distance (D(max) ), distance at maximal concentration (D(Cmax) ) and mean residence distance (D(ave) ). The SPECT/CT distribution of microbicide and semen surrogates was similar. Between 1 h and 24 h post dose, the surrogates migrated retrograde in all three parameters (relative to coccygeal level; geometric mean [95% confidence interval]): maximal distance (D(max) ), 10 cm (8.6-12) to 18 cm (13-26), distance at maximal concentration (D(Cmax) ), 3.8 cm (2.7-5.3) to 4.2 cm (2.8-6.3) and mean residence distance (D(ave) ), 4.3 cm (3.5-5.1) to 7.6 cm (5.3-11). Sigmoidoscopy and MRI correlated only roughly with SPECT/CT. Rectal microbicide surrogates migrated retrograde during the 24 h following dosing. Spatial kinetic parameters estimated using three dimensional curve fitting of distribution data should prove useful for evaluating rectal formulations of drugs for HIV prevention and other indications. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Probiotics for Rectal Volume Variation During Radiation Therapy for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ki, Yongkan; Kim, Wontaek, E-mail: rokwt@hanmail.net; Nam, Jiho

Purpose: To investigate the effect of the probiotic Lactobacillus acidophilus on the percentage volume change of the rectum (PVC{sub R}), a crucial factor of prostate movement. Methods and Materials: Prostate cancer patients managed with tomotherapy as a radical treatment were enrolled in the study to take a probiotic capsule containing 1.0 × 10{sup 8} colony-forming units of L acidophilus or a placebo capsule twice daily. Radiation therapy was performed at a dose of 78 Gy in 39 fractions. The PVC{sub R}, defined as the difference in rectal volume between the planning computed tomographic (CT) and daily megavoltage CT images, wasmore » analyzed. Results: Forty patients were randomized into 2 groups. The L acidophilus group showed significantly lower median rectal volume and median PVC{sub R} values than the placebo group. L acidophilus showed a significant reduction effect on the PVC{sub R} (P<.001). However, the radiation therapy fraction number did not significantly influence the PVC{sub R}. Conclusions: L acidophilus was useful in reducing the PVC{sub R}, which is the most important determining factor of prostate position, during radiation therapy for prostate cancer.« less

Efficacy and safety of rectal ibuprofen for patent ductus arteriosus closure in very low birth weight preterm infants.

PubMed

Demir, Nihat; Peker, Erdal; Ece, İbrahim; Balahoroğlu, Ragıp; Tuncer, Oğuz

2017-09-01

To compare rectal ibuprofen with oral ibuprofen for the closure of hemodynamically significant patent ductus arteriosus (hsPDA) in very low birth weight (VLBW) preterm infants. In a prospective, randomized study, 72 VLBW infants who had hsPDA received either rectal or oral ibuprofen. The plasma concentration of ibuprofen and renal functions were determined in both groups by the high-performance liquid chromatography (HPLC) method and cystatin-C (cys-C), respectively. The hsPDA closure rate of the group that received rectal ibuprofen was similar to oral ibuprofen (86.1% versus 83.3%) after the first course of the treatment (p = 0.745). A statistically significant difference was identified between the mean plasma cys-C levels before and after treatment in both the rectal and oral ibuprofen groups (p = 0.004 and p< 0.001, respectively). The mean plasma ibuprofen concentration was similar in both groups after the first dose (rectal 44.06 ± 12.4; oral, 48.28 ± 22.8) and the third dose (rectal, 45.34 ± 24.3; oral, 48.94 ± 24.8) (p > 0.05 for all values). Rectal ibuprofen is as effective as oral ibuprofen for hsPDA closure in VLBW infants. The rise in the cys-C level with rectal and oral treatment shows that patients with borderline renal function should be evaluated and followed closely.

How to identify rectal sub-regions likely involved in rectal bleeding in prostate cancer radiotherapy

NASA Astrophysics Data System (ADS)

Dréan, G.; Acosta, O.; Ospina, J. D.; Voisin, C.; Rigaud, B.; Simon, A.; Haigron, P.; de Crevoisier, R.

2013-11-01

Nowadays, the de nition of patient-speci c constraints in prostate cancer radiotherapy planning are solely based on dose-volume histogram (DVH) parameters. Nevertheless those DVH models lack of spatial accuracy since they do not use the complete 3D information of the dose distribution. The goal of the study was to propose an automatic work ow to de ne patient-speci c rectal sub-regions (RSR) involved in rectal bleeding (RB) in case of prostate cancer radiotherapy. A multi-atlas database spanning the large rectal shape variability was built from a population of 116 individuals. Non-rigid registration followed by voxel-wise statistical analysis on those templates allowed nding RSR likely correlated with RB (from a learning cohort of 63 patients). To de ne patient-speci c RSR, weighted atlas-based segmentation with a vote was then applied to 30 test patients. Results show the potentiality of the method to be used for patient-speci c planning of intensity modulated radiotherapy (IMRT).

Comparison of different contouring definitions of the rectum as organ at risk (OAR) and dose-volume parameters predicting rectal inflammation in radiotherapy of prostate cancer: which definition to use?

PubMed

Nitsche, Mirko; Brannath, Werner; Brückner, Matthias; Wagner, Dirk; Kaltenborn, Alexander; Temme, Nils; Hermann, Robert M

2017-02-01

The objective of this retrospective planning study was to find a contouring definition for the rectum as an organ at risk (OAR) in curative three-dimensional external beam radiotherapy (EBRT) for prostate cancer (PCa) with a predictive correlation between the dose-volume histogram (DVH) and rectal toxicity. In a pre-study, the planning CT scans of 23 patients with PCa receiving definitive EBRT were analyzed. The rectum was contoured according to 13 different definitions, and the dose distribution was correlated with the respective rectal volumes by generating DVH curves. Three definitions were identified to represent the most distinct differences in the shapes of the DVH curves: one anatomical definition recommended by the Radiation Therapy Oncology Group (RTOG) and two functional definitions based on the target volume. In the main study, the correlation between different relative DVH parameters derived from these three contouring definitions and the occurrence of rectal toxicity during and after EBRT was studied in two consecutive collectives. The first cohort consisted of 97 patients receiving primary curative EBRT and the second cohort consisted of 66 patients treated for biochemical recurrence after prostatectomy. Rectal toxicity was investigated by clinical investigation and scored according to the Common Terminology Criteria for Adverse Events. Candidate parameters were the volume of the rectum, mean dose, maximal dose, volume receiving at least 60 Gy (V 60 ), area under the DVH curve up to 25 Gy and area under the DVH curve up to 75 Gy in dependence of each chosen rectum definition. Multivariable logistic regression considered other clinical factors such as pelvine lymphatics vs local target volume, diabetes, prior rectal surgery, anticoagulation or haemorrhoids too. In Cohort 1 (primary EBRT), the mean rectal volumes for definitions "RTOG", planning target volume "(PTV)-based" and "PTV-linked" were 100 cm 3 [standard deviation (SD) 43 cm 3 ], 60 cm 3 (SD 26 cm 3 ) and 74 cm 3 (SD 31 cm 3 ), respectively (p < 0.01; analysis of variance). The mean rectal doses according to these definitions were 35 Gy (SD 8 Gy), 48 Gy (SD 4 Gy) and 44 Gy (SD 5 Gy) (p < 0.01). In Cohort 2 (salvage EBRT), the mean rectal volumes were 114 cm 3 (SD 47 cm 3 ), 64 cm 3 (SD 26 cm 3 ) and 81 cm 3 (SD 30 cm 3 ) (p < 0.01) and the mean doses received by the rectum were 36 Gy (SD 8 Gy), 49 Gy (SD 5 Gy) and 44 Gy (SD 5 Gy) (p < 0.01). Acute or subacute rectal inflammation occurred in 69 (71.9%) patients in Cohort 1 and in 43 (70.5%) in Cohort 2. We did not find a correlation between all investigated DVH parameters and rectal toxicity, irrespective of the investigated definition. By adding additional variables in multivariate analysis, the predictive ability was substantially improved. Still, there was essentially no difference in the probability of predicting rectal inflammation occurrence between the tested contouring definitions. The RTOG anatomy-based recommendations are questionable in comparison with functional definitions, as they result in higher variances in several relative DVH parameters. Moreover, the anatomy-based definition is no better and no worse in the predictive value concerning clinical end points. Advances in knowledge: Functional definitions for the rectum as OAR are easier to apply, faster to contour, have smaller variances and do not offer less information than the anatomy-based RTOG definition.

Poster - 47: A parametrized prediction model of rectal toxicity in focal SBRT of low risk prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stevens, Todd; Bauman, Glenn

There has been a recent trend towards watchful waiting in place of intervention for early stage prostate cancer (CaP). However, this approach can allow for disease progression, and subsequent whole-gland therapies such as prostatectomy and whole gland irradiation can result in functional deficits or rectal toxicities or both. A controversial alternative approach for this patient cohort is the use of focal therapy, where the treatment is focussed on an identified dominant index lesion (DIL). This work aims to investigate the treatment parameters for focal SBRT of the prostate under which clinically acceptable rectal NTCP levels can be achieved. For eachmore » of 25 low risk CaP patients, a hypothetical 2 cc DIL was modeled in the right-posterior quadrant of the prostate, and was used to build a PTV as the target for SBRT simulation. An SBRT prescriptions of 41 Gy and 37 Gy in 5 fractions were chosen, corresponding to the boost levels used in previous CaP dose escalation studies. DVH data were exported and used to calculate rectal NTCP values based on the Lyman-Kutcher-Burman (LKB) model using the QUANTEC reccommended model parameters. Rectal NTCP dependence on DIL-to-rectum separation, dose level, and DIL volume were investigated. The final goal of this ongoing work is to create a map of the maximum allowable prescription dose for a given patient geometry that achieves a clinically acceptable rectal NTCP level.« less

Reduced dose to urethra and rectum with the use of variable needle spacing in prostate brachytherapy: a potential role for robotic technology

PubMed Central

Vyas, Shilpa; Le, Yi; Zhang, Zhe; Armour, Woody

2015-01-01

Purpose Several robotic delivery systems for prostate brachytherapy are under development or in pre-clinical testing. One of the features of robotic brachytherapy is the ability to vary spacing of needles at non-fixed intervals. This feature may play an important role in prostate brachytherapy, which is traditionally template-based with fixed needle spacing of 0.5 cm. We sought to quantify potential reductions in the dose to urethra and rectum by utilizing variable needle spacing, as compared to fixed needle spacing. Material and methods Transrectal ultrasound images from 10 patients were used by 3 experienced planners to create 120 treatment plans. Each planner created 4 plan variations per patient with respect to needle positions: 125I fixed spacing, 125I variable spacing, 103Pd fixed spacing, and 103Pd variable spacing. The primary planning objective was to achieve a prostate V100 of 100% while minimizing dose to urethra and rectum. Results All plans met the objective of achieving prostate V100 of 100%. Combined results for all plans show statistically significant improvements in all assessed dosimetric variables for urethra (Umax, Umean, D30, D5) and rectum (Rmax, Rmean, RV100) when using variable spacing. The dose reductions for mean and maximum urethra dose using variable spacing had p values of 0.011 and 0.024 with 103Pd, and 0.007 and 0.029 with 125I plans. Similarly dose reductions for mean and maximum rectal dose using variable spacing had p values of 0.007 and 0.052 with 103Pd, and 0.012 and 0.037 with 125I plans. Conclusions The variable needle spacing achievable by the use of robotics in prostate brachytherapy allows for reductions in both urethral and rectal planned doses while maintaining prostate dose coverage. Such dosimetric advantages have the potential in translating to significant clinical benefits with the use of robotic brachytherapy. PMID:26622227

Reduced dose to urethra and rectum with the use of variable needle spacing in prostate brachytherapy: a potential role for robotic technology.

PubMed

Vyas, Shilpa; Le, Yi; Zhang, Zhe; Armour, Woody; Song, Daniel Y

2015-08-01

Several robotic delivery systems for prostate brachytherapy are under development or in pre-clinical testing. One of the features of robotic brachytherapy is the ability to vary spacing of needles at non-fixed intervals. This feature may play an important role in prostate brachytherapy, which is traditionally template-based with fixed needle spacing of 0.5 cm. We sought to quantify potential reductions in the dose to urethra and rectum by utilizing variable needle spacing, as compared to fixed needle spacing. Transrectal ultrasound images from 10 patients were used by 3 experienced planners to create 120 treatment plans. Each planner created 4 plan variations per patient with respect to needle positions: (125)I fixed spacing, (125)I variable spacing, (103)Pd fixed spacing, and (103)Pd variable spacing. The primary planning objective was to achieve a prostate V100 of 100% while minimizing dose to urethra and rectum. All plans met the objective of achieving prostate V100 of 100%. Combined results for all plans show statistically significant improvements in all assessed dosimetric variables for urethra (Umax, Umean, D30, D5) and rectum (Rmax, Rmean, RV100) when using variable spacing. The dose reductions for mean and maximum urethra dose using variable spacing had p values of 0.011 and 0.024 with (103)Pd, and 0.007 and 0.029 with (125)I plans. Similarly dose reductions for mean and maximum rectal dose using variable spacing had p values of 0.007 and 0.052 with (103)Pd, and 0.012 and 0.037 with (125)I plans. The variable needle spacing achievable by the use of robotics in prostate brachytherapy allows for reductions in both urethral and rectal planned doses while maintaining prostate dose coverage. Such dosimetric advantages have the potential in translating to significant clinical benefits with the use of robotic brachytherapy.

SU-F-T-328: Real-Time in Vivo Dosimetry of Prostate SBRT Boost Treatments Using MOSkin Detectors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Legge, K; O’Connor, D J; Cutajar, D

Purpose: To provide in vivo measurements of dose to the anterior rectal wall during prostate SBRT boost treatments using MOSFET detectors. Methods: Dual MOSkin detectors were attached to a Rectafix rectal sparing device and inserted into patients during SBRT boost treatments. Patients received two boost fractions, each of 9.5–10 Gy and delivered using 2 VMAT arcs. Measurements were acquired for 12 patients. MOSFET voltages were read out at 1 Hz during delivery and converted to dose. MV images were acquired at known frequency during treatment so that the position of the gantry at each point in time was known. Themore » cumulative dose at the MOSFET location was extracted from the treatment planning system at in 5.2° increments (FF beams) or at 5 points during each delivered arc (FFF beams). The MOSFET dose and planning system dose throughout the entirety of each arc were then compared using root mean square error normalised to the final planned dose for each arc. Results: The average difference between MOSFET measured and planning system doses determined over the entire course of treatment was 9.7% with a standard deviation of 3.6%. MOSFETs measured below the planned dose in 66% of arcs measured. Uncertainty in the position of the MOSFET detector and verification point are major sources of discrepancy, as the detector is placed in a high dose gradient region during treatment. Conclusion: MOSkin detectors were able to provide real time in vivo measurements of anterior rectal wall dose during prostate SBRT boost treatments. This method could be used to verify Rectafix positioning and treatment delivery. Further developments could enable this method to be used during high dose treatments to monitor dose to the rectal wall to ensure it remains at safe levels. Funding has been provided by the University of Newcastle. Kimberley Legge is the recipient of an Australian Postgraduate Award.« less

Long-Term Bone Marrow Suppression During Postoperative Chemotherapy in Rectal Cancer Patients After Preoperative Chemoradiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Newman, Neil B.; Sidhu, Manpreet K.; Baby, Rekha

Purpose/Objective(s): To quantify ensuing bone marrow (BM) suppression during postoperative chemotherapy resulting from preoperative chemoradiation (CRT) therapy for rectal cancer. Methods and Materials: We retrospectively evaluated 35 patients treated with preoperative CRT followed by postoperative 5-Fluorouracil and oxaliplatin (OxF) chemotherapy for locally advanced rectal cancer. The pelvic bone marrow (PBM) was divided into ilium (IBM), lower pelvis (LPBM), and lumbosacrum (LSBM). Dose volume histograms (DVH) measured the mean doses and percentage of BM volume receiving between 5-40 Gy (i.e.: PBM-V5, LPBM-V5). The Wilcoxon signed rank tests evaluated the differences in absolute hematologic nadirs during neoadjuvant vs. adjuvant treatment. Logistic regressionsmore » evaluated the association between dosimetric parameters and ≥ grade 3 hematologic toxicity (HT3) and hematologic event (HE) defined as ≥ grade 2 HT and a dose reduction in OxF. Receiver Operator Characteristic (ROC) curves were constructed to determine optimal threshold values leading to HT3. Results: During OxF chemotherapy, 40.0% (n=14) and 48% (n=17) of rectal cancer patients experienced HT3 and HE, respectively. On multivariable logistic regression, increasing pelvic mean dose (PMD) and lower pelvis mean dose (LPMD) along with increasing PBM-V (25-40), LPBM-V25, and LPBM-V40 were significantly associated with HT3 and/or HE during postoperative chemotherapy. Exceeding ≥36.6 Gy to the PMD and ≥32.6 Gy to the LPMD strongly correlated with causing HT3 during postoperative chemotherapy. Conclusions: Neoadjuvant RT for rectal cancer has lasting effects on the pelvic BM, which are demonstrable during adjuvant OxF. Sparing of the BM during preoperative CRT can aid in reducing significant hematologic adverse events and aid in tolerance of postoperative chemotherapy.« less

Long-Term Bone Marrow Suppression During Postoperative Chemotherapy in Rectal Cancer Patients After Preoperative Chemoradiation Therapy.

PubMed

Newman, Neil B; Sidhu, Manpreet K; Baby, Rekha; Moss, Rebecca A; Nissenblatt, Michael J; Chen, Ting; Lu, Shou-En; Jabbour, Salma K

2016-04-01

To quantify ensuing bone marrow (BM) suppression during postoperative chemotherapy resulting from preoperative chemoradiation (CRT) therapy for rectal cancer. We retrospectively evaluated 35 patients treated with preoperative CRT followed by postoperative 5-Fluorouracil and oxaliplatin (OxF) chemotherapy for locally advanced rectal cancer. The pelvic bone marrow (PBM) was divided into ilium (IBM), lower pelvis (LPBM), and lumbosacrum (LSBM). Dose volume histograms (DVH) measured the mean doses and percentage of BM volume receiving between 5-40 Gy (i.e.: PBM-V5, LPBM-V5). The Wilcoxon signed rank tests evaluated the differences in absolute hematologic nadirs during neoadjuvant vs. adjuvant treatment. Logistic regressions evaluated the association between dosimetric parameters and ≥ grade 3 hematologic toxicity (HT3) and hematologic event (HE) defined as ≥ grade 2 HT and a dose reduction in OxF. Receiver Operator Characteristic (ROC) curves were constructed to determine optimal threshold values leading to HT3. During OxF chemotherapy, 40.0% (n=14) and 48% (n=17) of rectal cancer patients experienced HT3 and HE, respectively. On multivariable logistic regression, increasing pelvic mean dose (PMD) and lower pelvis mean dose (LPMD) along with increasing PBM-V (25-40), LPBM-V25, and LPBM-V40 were significantly associated with HT3 and/or HE during postoperative chemotherapy. Exceeding ≥36.6 Gy to the PMD and ≥32.6 Gy to the LPMD strongly correlated with causing HT3 during postoperative chemotherapy. Neoadjuvant RT for rectal cancer has lasting effects on the pelvic BM, which are demonstrable during adjuvant OxF. Sparing of the BM during preoperative CRT can aid in reducing significant hematologic adverse events and aid in tolerance of postoperative chemotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Quality assessment for VMAT prostate radiotherapy planning based on data envelopment analysis

NASA Astrophysics Data System (ADS)

Lin, Kuan-Min; Simpson, John; Sasso, Giuseppe; Raith, Andrea; Ehrgott, Matthias

2013-08-01

The majority of commercial radiotherapy treatment planning systems requires planners to iteratively adjust the plan parameters in order to find a satisfactory plan. This iterative trial-and-error nature of radiotherapy treatment planning results in an inefficient planning process and in order to reduce such inefficiency, plans can be accepted without achieving the best attainable quality. We propose a quality assessment method based on data envelopment analysis (DEA) to address this inefficiency. This method compares a plan of interest to a set of past delivered plans and searches for evidence of potential further improvement. With the assistance of DEA, planners will be able to make informed decisions on whether further planning is required and ensure that a plan is only accepted when the plan quality is close to the best attainable one. We apply the DEA method to 37 prostate plans using two assessment parameters: rectal generalized equivalent uniform dose (gEUD) as the input and D95 (the minimum dose that is received by 95% volume of a structure) of the planning target volume (PTV) as the output. The percentage volume of rectum overlapping PTV is used to account for anatomical variations between patients and is included in the model as a non-discretionary output variable. Five plans that are considered of lesser quality by DEA are re-optimized with the goal to further improve rectal sparing. After re-optimization, all five plans improve in rectal gEUD without clinically considerable deterioration of the PTV D95 value. For the five re-optimized plans, the rectal gEUD is reduced by an average of 1.84 Gray (Gy) with only an average reduction of 0.07 Gy in PTV D95. The results demonstrate that DEA can correctly identify plans with potential improvements in terms of the chosen input and outputs.

The effect of anterior proton beams in the setting of a prostate-rectum spacer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Christodouleas, John P., E-mail: christojo@uphs.upenn.edu; Tang, Shikui; Susil, Robert C.

2013-10-01

Studies suggest that anterior beams with in vivo range verification would improve rectal dosimetry in proton therapy for prostate cancer. We investigated whether prostate-rectum spacers would enhance or diminish the benefits of anterior proton beams in these treatments. Twenty milliliters of hydrogel was injected between the prostate and rectum of a cadaver using a transperineal approach. Computed tomography (CT) and magnetic resonance (MR) images were used to generate 7 uniform scanning (US) and 7 single-field uniform dose pencil-beam scanning (PBS) plans with different beam arrangements. Pearson correlations were calculated between rectal, bladder, and femoral head dosimetric outcomes and beam arrangementmore » anterior scores, which characterize the degree to which dose is delivered anteriorly. The overall quality of each plan was compared using a virtual dose-escalation study. For US plans, rectal mean dose was inversely correlated with anterior score, but for PBS plans there was no association between rectal mean dose and anterior score. For both US and PBS plans, full bladder and empty bladder mean doses were correlated with anterior scores. For both US and PBS plans, femoral head mean doses were inversely correlated with anterior score. For US plans and a full bladder, 4 beam arrangements that included an anterior beam tied for the highest maximum prescription dose (MPD). For US plans and an empty bladder, the arrangement with 1 anterior and 2 anterior oblique beams achieved the highest MPD in the virtual dose-escalation study. The dose-escalation study did not differentiate beam arrangements for PBS. All arrangements in the dose-escalation study were limited by bladder constraints except for the arrangement with 2 posterior oblique beams. The benefits of anterior proton beams in the setting of prostate-rectum spacers appear to be proton modality dependent and may not extend to PBS.« less

The effect of anterior proton beams in the setting of a prostate-rectum spacer

PubMed Central

Christodouleas, John P.; Tang, Shikui; Susil, Robert C.; McNutt, Todd R.; Song, Danny Y.; Bekelman, Justin; Deville, Curtiland; Vapiwala, Neha; DeWeese, Theodore L.; Lu, Hsiao-Ming; Both, Stefan

2014-01-01

Studies suggest that anterior beams with in vivo range verification would improve rectal dosimetry in proton therapy for prostate cancer. We investigated whether prostate-rectum spacers would enhance or diminish the benefits of anterior proton beams in these treatments. Twenty milliliters of hydrogel was injected between the prostate and rectum of a cadaver using a transperineal approach. Computed tomography (CT) and magnetic resonance (MR) images were used to generate 7 uniform scanning (US) and 7 single-field uniform dose pencil-beam scanning (PBS) plans with different beam arrangements. Pearson correlations were calculated between rectal, bladder, and femoral head dosimetric outcomes and beam arrangement anterior scores, which characterize the degree to which dose is delivered anteriorly. The overall quality of each plan was compared using a virtual dose-escalation study. For US plans, rectal mean dose was inversely correlated with anterior score, but for PBS plans there was no association between rectal mean dose and anterior score. For both US and PBS plans, full bladder and empty bladder mean doses were correlated with anterior scores. For both US and PBS plans, femoral head mean doses were inversely correlated with anterior score. For US plans and a full bladder, 4 beam arrangements that included an anterior beam tied for the highest maximum prescription dose (MPD). For US plans and an empty bladder, the arrangement with 1 anterior and 2 anterior oblique beams achieved the highest MPD in the virtual dose-escalation study. The dose-escalation study did not differentiate beam arrangements for PBS. All arrangements in the dose-escalation study were limited by bladder constraints except for the arrangement with 2 posterior oblique beams. The benefits of anterior proton beams in the setting of prostate-rectum spacers appear to be proton modality dependent and may not extend to PBS. PMID:23578497

Treatment efficacy of azithromycin 1 g single dose versus doxycycline 100 mg twice daily for 7 days for the treatment of rectal chlamydia among men who have sex with men - a double-blind randomised controlled trial protocol.

PubMed

Lau, Andrew; Kong, Fabian; Fairley, Christopher K; Donovan, Basil; Chen, Marcus; Bradshaw, Catriona; Boyd, Mark; Amin, Janaki; Timms, Peter; Tabrizi, Sepehr; Regan, David G; Lewis, David A; McNulty, Anna; Hocking, Jane S

2017-01-06

Rectal infection with Chlamydia trachomatis is one of the most common bacterial sexually transmissible infections among men who have sex with men (MSM) with diagnosis rates continuing to rise. Current treatment guidelines recommend either azithromycin 1 g single dose or doxycycline 100 mg twice daily for 7 days. However, there are increasing concerns about treatment failure with azithromycin. We are conducting the first randomised controlled trial (RCT) to compare treatment efficacy of azithromycin versus doxycycline for the treatment of rectal chlamydia in MSM. The Rectal Treatment Study will recruit 700 MSM attending Australian sexual health clinics for the treatment of rectal chlamydia. Participants will be asked to provide rectal swabs and will be randomised to either azithromycin 1 g single dose or doxycycline 100 mg twice daily for 7 days. Participants will be asked to complete questionnaires about adverse drug reactions, sexual behaviour and drug adherence via short message service and online survey. The primary outcome is the treatment efficacy as determined by a negative chlamydia nucleic acid amplification test at 4 weeks post treatment. Secondary outcomes will utilise whole genome sequencing and mRNA assay to differentiate between treatment failure, reinfection or false positive results. Rectal chlamydia is an increasing public health concern as use of pre-exposure prophylaxis against HIV becomes commonplace. Optimal, evidence-based treatment is critical to halting ongoing transmission. This study will provide the first RCT evidence comparing azithromycin and doxycycline for the treatment of rectal chlamydia. The results of this trial will establish which treatment is more efficacious and inform international management guidelines. Australian New Zealand Clinical Trials Registry ACTRN12614001125617.

In-vivo rectal dose measurements with diodes to avoid misadministrations during intracavitary high dose rate brachytherapy for carcinoma of the cervix.

PubMed

Alecu, R; Alecu, M

1999-05-01

Our purpose in this paper is to present an in vivo dosimetry program designed both for measuring the rectal dose and for avoiding misadministrations in gynecological intracavitary implants. A device containing an energy compensated diode was specially designed for these measurements. Our calibration procedure as well as the clinical protocol is described. Measurements have been performed for 50 treatments delivered with a Fletcher Suit Delclos applicator. The calculated and in vivo measured values for the "20% reading," i.e., the dose delivered to the diode by the initial 20% of the total dwell time, agreed to within 15%.

Late rectal bleeding after 3D-CRT for prostate cancer: development of a neural-network-based predictive model

NASA Astrophysics Data System (ADS)

Tomatis, S.; Rancati, T.; Fiorino, C.; Vavassori, V.; Fellin, G.; Cagna, E.; Mauro, F. A.; Girelli, G.; Monti, A.; Baccolini, M.; Naldi, G.; Bianchi, C.; Menegotti, L.; Pasquino, M.; Stasi, M.; Valdagni, R.

2012-03-01

The aim of this study was to develop a model exploiting artificial neural networks (ANNs) to correlate dosimetric and clinical variables with late rectal bleeding in prostate cancer patients undergoing radical radiotherapy and to compare the ANN results with those of a standard logistic regression (LR) analysis. 718 men included in the AIROPROS 0102 trial were analyzed. This multicenter protocol was characterized by the prospective evaluation of rectal toxicity, with a minimum follow-up of 36 months. Radiotherapy doses were between 70 and 80 Gy. Information was recorded for comorbidity, previous abdominal surgery, use of drugs and hormonal therapy. For each patient, a rectal dose-volume histogram (DVH) of the whole treatment was recorded and the equivalent uniform dose (EUD) evaluated as an effective descriptor of the whole DVH. Late rectal bleeding of grade ≥ 2 was considered to define positive events in this study (52 of 718 patients). The overall population was split into training and verification sets, both of which were involved in model instruction, and a test set, used to evaluate the predictive power of the model with independent data. Fourfold cross-validation was also used to provide realistic results for the full dataset. The LR was performed on the same data. Five variables were selected to predict late rectal bleeding: EUD, abdominal surgery, presence of hemorrhoids, use of anticoagulants and androgen deprivation. Following a receiver operating characteristic analysis of the independent test set, the areas under the curves (AUCs) were 0.704 and 0.655 for ANN and LR, respectively. When evaluated with cross-validation, the AUC was 0.714 for ANN and 0.636 for LR, which differed at a significance level of p = 0.03. When a practical discrimination threshold was selected, ANN could classify data with sensitivity and specificity both equal to 68.0%, whereas these values were 61.5% for LR. These data provide reasonable evidence that results obtained with ANNs are superior to those achieved with LR when predicting late radiotherapy-related rectal bleeding. The future introduction of patient-related personal characteristics, such as gene expression profiles, might improve the predictive power of statistical classifiers. More refined morphological aspects of the dose distribution, such as dose surface mapping, might also enhance the overall performance of ANN-based predictive models.

Treatment Outcomes for Rectal Lymphogranuloma Venereum in Men Who Have Sex with Men Using Doxycycline, Azithromycin, or Both: A Review of Clinical Cases.

PubMed

Leeyaphan, Charussri; Ong, Jason J; Chow, Eric P F; Dimovski, Karolina; Kong, Fabian Y S; Hocking, Jane S; Howden, Ben; Bissessor, Melanie; Fairley, Christopher K; Bradshaw, Catriona; Read, Timothy; Chen, Marcus

2017-04-01

Treatment for rectal lymphogranuloma venereum where doxycycline 100 mg twice daily for 21 days was used-either alone or together with azithromycin 1 g single dose-resulted in microbiological cure of 97%. These data support doxycycline 100 mg twice daily for 21 days as the preferred treatment for rectal lymphogranuloma venereum.

Variation in the CYP19A1 gene and risk of colon and rectal cancer

PubMed Central

Slattery, Martha L.; Lundgreen, Abbie; Herrick, Jennifer S.; Kadlubar, Susan; Caan, Bette J.; Potter, John D.; Wolff, Roger K.

2011-01-01

CYP19A1, or aromatase, influences estrogen-metabolizing enzymes and may influence cancer risk. We examine variation in the CYP19A1 gene and risk of colorectal cancer using data from population-based case–control studies (colon n = 1,574 cases, 1,970 controls; rectal n = 791 cases, 999 controls). Four SNPs were statistically significantly associated with colon cancer and four were associated with rectal cancer. After adjustment for multiple comparisons, the AA genotype of rs12591359 was associated with an increased risk of colon cancer (OR 1.44 95% CI 1.16–1.80) and the AA genotype of rs2470144 was associated with a reduced risk of rectal cancer (OR 0.65 95% CI 0.50–0.84). Variants of CYP19A1 were associated with CIMP+ and CIMP+/KRAS2-mutated tumors. CT/TT genotypes of rs1961177 were significantly associated with an increased likelihood of a MSI+ colon tumor (OR 1.77 95% CI 1.26–2.37). We observed statistically significant interactions between genetic variation in NFκB1 and CYP19A1 for both colon and rectal cancer. Our data suggest the importance of CYP19A1 in the development of colon and rectal cancer and that estrogen may influence risk through an inflammation-related mechanism. PMID:21479914

Increased bioavailability of tacrolimus after rectal administration in rats.

PubMed

Sakai, Masayuki; Hobara, Norio; Hokama, Nobuo; Kameya, Hiromasa; Ohshiro, Susumu; Sakanashi, Matao; Saitoh, Hiroshi

2004-09-01

The oral bioavailability of tacrolimus is low and varies considerably in humans due to first-pass metabolism by cytochrome P450 (CYP) 3A4 and the active efflux mediated by P-glycoprotein. This study was undertaken to elucidate the usefulness of rectal administration of tacrolimus as an alternative route to improve its bioavailability. Tacrolimus powder was suspended in a suppository base (witepsol H-15) and the tacrolimus suppository was inserted into the anus of the rats. For comparison, tacrolimus was suspended in 0.5% sodium methylcellulose solution and administered orally to rats. The dose of tacrolimus was fixed to 2 mg/kg. Blood samples were collected periodically up to 24 h after dosing, and tacrolimus concentrations were assayed by microparticle enzyme immunoassay. The whole blood concentrations of tacrolimus after rectal administration were much greater than those after oral administration. The C(max) and AUC(0-24 h) values after rectal administration were 3.9- and 6.9-fold greater than those after oral administration, respectively. These results clearly suggest a possibility that rectal administration of tacrolimus is capable of improving its bioavailability and cutting the costs of tacrolimus treatment.

Pharmacokinetic profile of raltegravir, elvitegravir and dolutegravir in plasma and mucosal secretions in rhesus macaques.

PubMed

Massud, Ivana; Martin, Amy; Dinh, Chuong; Mitchell, James; Jenkins, Leecresia; Heneine, Walid; Pau, Chou-Pong; García-Lerma, J Gerardo

2015-05-01

Pharmacokinetic studies in animal models are important for assessing the prophylactic potential of antiretroviral drugs for HIV prevention. This study sought to identify clinically relevant doses of the marketed integrase inhibitors raltegravir, elvitegravir and dolutegravir in macaques and investigate drug penetration and antiviral activity in mucosal secretions. Macaques received one oral dose of raltegravir, elvitegravir or dolutegravir alone or in combination with emtricitabine and tenofovir disoproxil fumarate followed by drug level measurements in blood and rectal and vaginal secretions. Antiviral activity was investigated in TZM-bl cells exposed to SHIV162p3 in the presence of rectal secretions collected from treated animals. Plasma drug concentrations with 50 mg/kg raltegravir or elvitegravir were within the range seen in humans receiving 400-800 mg of raltegravir or 800 mg of unboosted elvitegravir but lower than with 150 mg of elvitegravir boosted with cobicistat. AUC0-24 values for dolutegravir increased proportionally with the dose, with a calculated human-equivalent dose of 20 mg/kg. Elvitegravir showed the highest penetration in rectal and vaginal fluids despite the absence of pharmacological boosting, followed by raltegravir and dolutegravir. Rectal secretions collected at 24 h from treated macaques blocked infection of TZM-bl cells by 50% at dilutions of 1/1000 (raltegravir), 1/800 (dolutegravir) and >1/30 000 (elvitegravir). We defined macaque doses of HIV integrase inhibitors that recapitulate human clinical doses, which will facilitate efficacy and dose escalation studies in macaques. High and sustained drug concentrations and activity in mucosal secretions suggest that integrase inhibitors are promising candidates for HIV prevention. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Adjuvant radiation therapy for bladder cancer: A dosimetric comparison of techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baumann, Brian C.; Noa, Kate; Wileyto, E. Paul

Trials of adjuvant radiation after cystectomy are under development. There are no studies comparing radiation techniques to inform trial design. This study assesses the effect on bowel and rectal dose of 3 different modalities treating 2 proposed alternative clinical target volumes (CTVs). Contours of the bowel, rectum, CTV-pelvic sidewall (common/internal/external iliac and obturator nodes), and CTV-comprehensive (CTV-pelvic sidewall plus cystectomy bed and presacral regions) were drawn on simulation images of 7 post-cystectomy patients. We optimized 3-dimensional conformal radiation (3-D), intensity-modulated radiation (IMRT), and single-field uniform dose (SFUD) scanning proton plans for each CTV. Mixed models regression was used to comparemore » plans for bowel and rectal volumes exposed to 35% (V{sub 35%}), 65% (V{sub 65%}), and 95% (V{sub 95%}) of the prescribed dose. For any given treatment modality, treating the larger CTV-comprehensive volume compared with treating only the CTV-pelvic sidewall nodes significantly increased rectal dose (V{sub 35%} {sub rectum}, V{sub 65%} {sub rectum}, and V{sub 95%} {sub rectum}; p < 0.001 for all comparisons), but it did not produce significant differences in bowel dose (V{sub 95%} {sub bowel}, V{sub 65%} {sub bowel}, or V{sub 35%} {sub bowel}). The 3-D plans, compared with both the IMRT and the SFUD plans, had a significantly greater V{sub 65%} {sub bowel} and V{sub 95%} {sub bowel} for each proposed CTV (p < 0.001 for all comparisons). The effect of treatment modality on rectal dosimetry differed by CTV, but it generally favored the IMRT and the SFUD plans over the 3-D plans. Comparison of the IMRT plan vs the SFUD plan yielded mixed results with no consistent advantage for the SFUD plan over the IMRT plan. Targeting a CTV that spares the cystectomy bed and presacral region may marginally improve rectal toxicity but would not be expected to improve the bowel toxicity associated with any given modality of adjuvant radiation. Using the IMRT or the SFUD plans instead of the 3-D conformal plan may improve both bowel and rectal toxicity.« less

SU-E-T-281: Reduction of Treatment Times in CyberKnife Prostate SBRT Using a Water Filled Rectal Balloon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Desai, P; Caroprese, B; McKellar, H

2014-06-01

Purpose: To illustrate 25% reduction in CyberKnife prostate SBRT treatment times using a water filled rectal balloon. Methods: We perform prostate SBRT using a 3800cGy in 4 fraction regimen prescribed between 51% 59% iso-dose lines to 95% of PTV using a CyberKnife System. The resultant heterogeneous dosimetry is analogous to HDR dosimetry. Our patients are treated in a feet first supine position to decrease treatment couch sag and also to position the prostate anatomy closer to the robot. CT imaging is performed with a Radiadyne Immobiloc rectal balloon filled with 45-50cc water placed firmly inside the patient's rectum. A treatmentmore » plan is developed from this CT study using Multiplan. The patient is treated every other day for 4 days using the rectal balloon for each fraction. Gold fiducials previously implanted inside the prostate are used for tracking by the CyberKnife system. Results: Critical structures comprise the usual GU anatomy of bladder, rectum, urethra, femoral-heads along with emphasis on doses to anterior rectal wall and rectal mucosa. The water filled rectal balloon localizes the rectum, which enables the physician to accurately contour both anterior rectal wall, and rectal mucosa. The balloon also has a gas release valve enabling better patient comfort. Rectum localization enables the CyberKnife system to make fewer corrections resulting in fewer treatment interruptions and time lost to re-adjustment for rectal motion, bowel filling and gas creation. Effective treatment times are reduced by 25% to approximately 45 minutes. Adoption of the balloon has required minimal change to our planning strategy and plan evaluation process. Conclusion: Patient follow-up comparisons show no difference in effectiveness of treatment with and without balloons We conclude that rectal balloons enhance patient comfort and decrease effective treatment times.« less

WE-AB-202-10: Modelling Individual Tumor-Specific Control Probability for Hypoxia in Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warren, S; Warren, DR; Wilson, JM

Purpose: To investigate hypoxia-guided dose-boosting for increased tumour control and improved normal tissue sparing using FMISO-PET images Methods: Individual tumor-specific control probability (iTSCP) was calculated using a modified linear-quadratic model with rectal-specific radiosensitivity parameters for three limiting-case assumptions of the hypoxia / FMISO uptake relationship. {sup 18}FMISO-PET images from 2 patients (T3N0M0) from the RHYTHM trial (Investigating Hypoxia in Rectal Tumours NCT02157246) were chosen to delineate a hypoxic region (GTV-MISO defined as tumor-to-muscle ratio > 1.3) within the anatomical GTV. Three VMAT treatment plans were created in Eclipse (Varian): STANDARD (45Gy / 25 fractions to PTV4500); BOOST-GTV (simultaneous integrated boostmore » of 60Gy / 25fr to GTV +0.5cm) and BOOST-MISO (60Gy / 25fr to GTV-MISO+0.5cm). GTV mean dose (in EQD2), iTSCP and normal tissue dose-volume metrics (small bowel, bladder, anus, and femoral heads) were recorded. Results: Patient A showed small hypoxic volume (15.8% of GTV) and Patient B moderate hypoxic volume (40.2% of GTV). Dose escalation to 60Gy was achievable, and doses to femoral heads and small bowel in BOOST plans were comparable to STANDARD plans. For patient A, a reduced maximum bladder dose was observed in BOOST-MISO compared to BOOST-GTV (D0.1cc 49.2Gy vs 54.0Gy). For patient B, a smaller high dose volume was observed for the anus region in BOOST-MISO compared to BOOST-GTV (V55Gy 19.9% vs 100%), which could potentially reduce symptoms of fecal incontinence. For BOOST-MISO, the largest iTSCPs (A: 95.5% / B: 90.0%) assumed local correlation between FMISO uptake and hypoxia, and approached iTSCP values seen for BOOST-GTV (A: 96.1% / B: 90.5%). Conclusion: Hypoxia-guided dose-boosting is predicted to improve local control in rectal tumors when FMISO is spatially correlated to hypoxia, and to reduce dose to organs-at-risk compared to boosting the whole GTV. This could lead to organ-preserving treatment strategies for locally-advanced rectal cancer, thereby improving quality of life. Oxford Cancer Imaging Centre (OCIC); Cancer Research UK (CRUK); Medical Research Council (MRC)« less

Azathioprine pharmacokinetics after intravenous, oral, delayed release oral and rectal foam administration.

PubMed Central

Van Os, E C; Zins, B J; Sandborn, W J; Mays, D C; Tremaine, W J; Mahoney, D W; Zinsmeister, A R; Lipsky, J J

1996-01-01

BACKGROUND: 6-Mercaptopurine and its prodrug azathioprine are effective medications for refractory inflammatory bowel disease. However, use of these drugs has been limited by concerns about their toxicity. Colonic delivery of azathioprine may reduce its systemic bioavailability and limit toxicity. AIM: To determine the bioavailability of 6-mercaptopurine after administration of azathioprine via three colonic delivery formulations. METHODS: Twenty four healthy human subjects each received 50 mg of azathioprine by one of four delivery formulations (each n = 6): oral; delayed release oral; hydrophobic rectal foam; and hydrophilic rectal foam. All subjects also received a 50 mg dose of intravenous azathioprine during a separate study period. Plasma concentrations of 6-mercaptopurine were determined by high pressure liquid chromatography. RESULTS: The bioavailabilities of 6-mercaptopurine after colonic azathioprine administration via delayed release oral, hydrophobic rectal foam, and hydrophilic rectal foam (7%, 5%, 1%; respectively) were significantly lower than the bioavailability of 6-mercaptopurine after oral azathioprine administration (47%) by Wilcoxon rank sum pairwise comparison. CONCLUSIONS: Azathioprine delivered to the colon by delayed release oral and rectal foam formulations considerably reduced systemic 6-mercaptopurine bioavailability. The therapeutic potential of these colonic delivery methods, which can potentially limit toxicity by local delivery of high doses of azathioprine, should be investigated in patients with inflammatory bowel disease. PMID:8881811

Phase II trial evaluating the feasibility of interdigitating folfox with chemoradiotherapy in locally advanced and metastatic rectal cancer.

PubMed

Michael, M; Chander, S; McKendrick, J; MacKay, J R; Steel, M; Hicks, R; Heriot, A; Leong, T; Cooray, P; Jefford, M; Zalcberg, J; Bressel, M; McClure, B; Ngan, S Y

2014-11-11

Patients (pts) with metastatic rectal cancer and symptomatic primary, require local and systemic control. Chemotherapy used during chemoradiotherapy (CRT) is adequate for radiosensitisation, but suboptimal for systemic control. The aim of this phase II study was to assess tolerability, local/systemic benefits, of a novel regimen delivering interdigitating intensive chemotherapy with radical CRT. Eligible pts had untreated synchronous symptomatic primary/metastatic rectal cancer. A total of 12 weeks of treatment with split-course pelvic CRT (total 50.4 Gy with concurrent oxaliplatin and 5-FU infusion) alternating with FOLFOX chemotherapy. All pts staged with CT, MRI and FDG-PET pre and post treatment. Twenty-six pts were treated. Rectal primary MRI stage: T3 81% and T4 15%. Liver metastases in 81%. Twenty-four pts (92%) completed the 12-week regimen. All patients received planned RT dose, and for both agents over 88% of patients achieved a relative dose intensity of >75%. Grade 3 toxicities: neutropenia 23%, diarrhoea 15%, and radiation skin reaction 12%. Grade 4 toxicity: neutropenia 15%. FDG-PET metabolic response rate for rectal primary 96%, and for metastatic disease 60%. Delivery of interdigitating chemotherapy with radical CRT was feasible to treat both primary and metastatic rectal cancer. High completion and response rates were encouraging.

HOSPITAL VARIATION IN SPHINCTER PRESERVATION FOR ELDERLY RECTAL CANCER PATIENTS

PubMed Central

Dodgion, Christopher M.; Neville, Bridget A; Lipsitz, Stuart R.; Schrag, Deborah; Breen, Elizabeth; Zinner, Michael J.; Greenberg, Caprice C.

2014-01-01

Purpose To evaluate hospital variation in the use of low anterior resection (LAR), local excision (LE) and abdominoperineal resection (APR) in the treatment of rectal cancer in elderly patients. Methods Using SEER-Medicare linked data, we identified 4,959 stage I–III rectal cancer patients over age 65 diagnosed from 2000–2005 who underwent operative intervention at one of 370 hospitals. We evaluated the distribution of hospital-specific procedure rates and used generalized mixed models with random hospital effects to examine the influence of patient characteristics and hospital on operation type, using APR as a reference. Results The median hospital performed APR on 33% of elderly rectal cancer patients. Hospital was a stronger predictor of LAR receipt than any patient characteristic, explaining 32% of procedure choice, but not a strong predictor of LE, explaining only 3.8%. Receipt of LE was primarily related to tumor size and tumor stage, which, combined, explained 31% of procedure variation. Conclusions Receipt of local excision is primarily determined by patient characteristics. In contrast, the hospital where surgery is performed significantly influences whether a patient undergoes an LAR or APR. Understanding the factors that cause this institutional variation is crucial to ensuring equitable availability of sphincter preservation. PMID:24750983

Dosimetric and radiobiological characterizations of prostate intensity-modulated radiotherapy and volumetric-modulated arc therapy: A single-institution review of ninety cases

PubMed Central

Khan, Muhammad Isa; Jiang, Runqing; Kiciak, Alexander; ur Rehman, Jalil; Afzal, Muhammad; Chow, James C. L.

2016-01-01

This study reviewed prostate volumetric-modulated arc therapy (VMAT) plans with intensity-modulated radiotherapy (IMRT) plans after prostate IMRT technique was replaced by VMAT in an institution. Characterizations of dosimetry and radiobiological variation in prostate were determined based on treatment plans of 40 prostate IMRT patients (planning target volume = 77.8–335 cm3) and 50 VMAT patients (planning target volume = 120–351 cm3) treated before and after 2013, respectively. Both IMRT and VMAT plans used the same dose-volume criteria in the inverse planning optimization. Dose-volume histogram, mean doses of target and normal tissues (rectum, bladder and femoral heads), dose-volume points (D99% of planning target volume; D30%, D50%, V30 Gy and V35 Gy of rectum and bladder; D5%, V14 Gy, V22 Gy of femoral heads), conformity index (CI), homogeneity index (HI), gradient index (GI), prostate tumor control probability (TCP), and rectal normal tissue complication probability (NTCP) based on the Lyman-Burman-Kutcher algorithm were calculated for each IMRT and VMAT plan. From our results, VMAT plan was found better due to its higher (1.05%) CI, lower (0.83%) HI and (0.75%) GI than IMRT. Comparing doses in normal tissues between IMRT and VMAT, it was found that IMRT mostly delivered higher doses of about 1.05% to the normal tissues than VMAT. Prostate TCP and rectal NTCP were found increased (1%) for VMAT than IMRT. It is seen that VMAT technique can decrease the dose-volume evaluation criteria for the normal tissues. Based on our dosimetric and radiobiological results in treatment plans, it is concluded that our VMAT implementation could produce comparable or slightly better target coverage and normal tissue sparing with a faster treatment time in prostate radiotherapy. PMID:27651562

In vivo quality assurance of volumetric modulated arc therapy for ano-rectal cancer with thermoluminescent dosimetry and image-guidance.

PubMed

Dipasquale, Giovanna; Nouet, Philippe; Rouzaud, Michel; Dubouloz, Angèle; Miralbell, Raymond; Zilli, Thomas

2014-06-01

To assess in vivo dose distribution using cone-beam computed tomography scans (CBCTs) and thermoluminescent dosimeters (TLDs) in patients with anal or rectal cancer treated with volumetric modulated arc therapy (VMAT). Intracavitary (IC) in vivo dosimetry (IVD) was performed in 11 patients using adapted endorectal probes containing TLDs, with extra measurements at the perianal skin (PS) for anal margin tumors. Measured doses were compared to calculated ones obtained from image fusion of CBCT with CT treatments plans. A total of 55 IC and 6 PS measurements were analyzed. IC TLD median planned and measured doses were 1.81 Gy (range, 0.25-2.02 Gy) and 1.82 Gy (range, 0.19-2.12 Gy), respectively. In comparison to the planned doses all IC TLD dose measurements differed by a median dose of 0.02 Gy (range, -0.11/+0.19 Gy, p=0.102) (median difference of 1.1%, range -6.1%/+10.6%). Overall, 95% of IC measurements were within ±7.7% of the expected percentage doses and only 1 value was above +10%. For PS measurements, only one was not within ±7.7% of expected values (i.e., -8.9%). Image guidance using CBCT for IVD with TLDs is helpful to validate the delivered doses in patients treated with VMAT for ano-rectal tumors. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Real-time in vivo rectal wall dosimetry using plastic scintillation detectors for patients with prostate cancer

PubMed Central

Wootton, Landon; Kudchadker, Rajat; Lee, Andrew; Beddar, Sam

2014-01-01

We designed and constructed an in vivo dosimetry system using plastic scintillation detectors (PSDs) to monitor dose to the rectal wall in patients undergoing intensity-modulated radiation therapy for prostate cancer. Five patients were enrolled in an Institutional Review Board–approved protocol for twice weekly in vivo dose monitoring with our system, resulting in a total of 142 in vivo dose measurements. PSDs were attached to the surface of endorectal balloons used for prostate immobilization to place the PSDs in contact with the rectal wall. Absorbed dose was measured in real time and the total measured dose was compared with the dose calculated by the treatment planning system on the daily CT image dataset. The mean difference between measured and calculated doses for the entire patient population was −0.4% (standard deviation 2.8%). The mean difference between daily measured and calculated doses for each patient ranged from −3.3% to 3.3% (standard deviation ranged from 5.6% to 7.1% for 4 patients and was 14.0% for the last, for whom optimal positioning of the detector was difficult owing to the patient’s large size). Patients tolerated the detectors well and the treatment workflow was not compromised. Overall, PSDs performed well as in vivo dosimeters, providing excellent accuracy, real-time measurement, and reusability. PMID:24434775

Real-time in vivo rectal wall dosimetry using plastic scintillation detectors for patients with prostate cancer

NASA Astrophysics Data System (ADS)

Wootton, Landon; Kudchadker, Rajat; Lee, Andrew; Beddar, Sam

2014-02-01

We designed and constructed an in vivo dosimetry system using plastic scintillation detectors (PSDs) to monitor dose to the rectal wall in patients undergoing intensity-modulated radiation therapy for prostate cancer. Five patients were enrolled in an Institutional Review Board-approved protocol for twice weekly in vivo dose monitoring with our system, resulting in a total of 142 in vivo dose measurements. PSDs were attached to the surface of endorectal balloons used for prostate immobilization to place the PSDs in contact with the rectal wall. Absorbed dose was measured in real time and the total measured dose was compared with the dose calculated by the treatment planning system on the daily computed tomographic image dataset. The mean difference between measured and calculated doses for the entire patient population was -0.4% (standard deviation 2.8%). The mean difference between daily measured and calculated doses for each patient ranged from -3.3% to 3.3% (standard deviation ranged from 5.6% to 7.1% for four patients and was 14.0% for the last, for whom optimal positioning of the detector was difficult owing to the patient's large size). Patients tolerated the detectors well and the treatment workflow was not compromised. Overall, PSDs performed well as in vivo dosimeters, providing excellent accuracy, real-time measurement and reusability.

SU-E-J-67: Evaluation of Adaptive MLC Morphing for Online Correction of Prostate Cancer Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sandhu, R; Qin, A; Yan, D

Purpose: Online adaptive MLC morphing is desirable over translational couch shifts to accommodate target position as well as anatomic changes. A reliable method of adaptive MLC segment to target during prostate cancer IMRT treatment is proposed and evaluated by comparison with daily online-image guidance (IGRT) correction and online-IMRT planning. Methods: The MLC adaptive algorithm involves following steps; move the MLC segments according to target translational shifts, and then morph the segment shape to maintain the spatial relationship between the planning-target contour and MLC segment. Efficacy of this method was evaluated retrospectively using daily-CBCT images on seven prostate patients treated withmore » seven-beam IMRT treatment to deliver 64Gy in 20 fractions. Daily modification was simulated with three approaches; daily-IGRT correction based on implanted radio-markers, adaptive MLC morphing, and online-IMRT planning, with no-residual variation. The selected dosimetric endpoints and nEUD (normalized equivalent uniform dose to online-IMRT planning) of each organ of interest were determined for evaluation and comparison. Results: For target(prostate), bladder and rectal-wall, the mean±sd of nEUD were 97.6%+3.2%, 103.9%±4.9% and 97.4%±1.1% for daily-IGRT correction; and 100.2%+0.2%, 108.9%±5.1% and 99.8%±1.2% for adaptive MLC morphing, respectively. For daily-IGRT correction, adaptive MLC morphing and online-IMRT planning, target D99 was <95% of the prescription dose in 30%, 0% and 0% of 140 fractions, respectively. For the rectal-wall, D5 exceeded 105% of the planned-D5 in 2.8%, 11.4% and 0% of 140 fractions, respectively. For the bladder, Dmax exceeded 105% of the planned-D5 in 2.8%, 5.6% and 0% of 140 fractions, respectively. D30 of bladder and rectal-wall were well within the planned-D30 for all three approaches. Conclusion: The proposed method of adaptive MLC morphing can be beneficial for the prostate patient population with large deformation and rotation. It is superior to the daily-IGRT correction, and comparable to the online-IMRT planning for dose to the target and rectal-wall.« less

Rectal balloon use limits vaginal displacement, rectal dose, and rectal toxicity in patients receiving IMRT for postoperative gynecological malignancies.

PubMed

Wu, Cheng-Chia; Wuu, Yen-Ruh; Yanagihara, Theodore; Jani, Ashish; Xanthopoulos, Eric P; Tiwari, Akhil; Wright, Jason D; Burke, William M; Hou, June Y; Tergas, Ana I; Deutsch, Israel

2018-01-01

Pelvic radiotherapy for gynecologic malignancies traditionally used a 4-field box technique. Later trials have shown the feasibility of using intensity-modulated radiotherapy (IMRT) instead. But vaginal movement between fractions is concerning when using IMRT due to greater conformality of the isodose curves to the target and the resulting possibility of missing the target while the vagina is displaced. In this study, we showed that the use of a rectal balloon during treatment can decrease vaginal displacement, limit rectal dose, and limit acute and late toxicities. Little is known regarding the use of a rectal balloon (RB) in treating patients with IMRT in the posthysterectomy setting. We hypothesize that the use of an RB during treatment can limit rectal dose and acute and long-term toxicities, as well as decrease vaginal cuff displacement between fractions. We performed a retrospective review of patients with gynecological malignancies who received postoperative IMRT with the use of an RB from January 1, 2012 to January 1, 2015. Rectal dose constraint was examined as per Radiation Therapy Oncology Group (RTOG) 1203 and 0418. Daily cone beam computed tomography (CT) was performed, and the average (avg) displacement, avg magnitude, and avg magnitude of vector were calculated. Toxicity was reported according to RTOG acute radiation morbidity scoring criteria. Acute toxicity was defined as less than 90 days from the end of radiation treatment. Late toxicity was defined as at least 90 days after completing radiation. Twenty-eight patients with postoperative IMRT with the use of an RB were examined and 23 treatment plans were reviewed. The avg rectal V40 was 39.3% ± 9.0%. V30 was65.1% ± 10.0%. V50 was 0%. Separate cone beam computed tomography (CBCT) images (n = 663) were reviewed. The avg displacement was as follows: superior 0.4 + 2.99 mm, left 0.23 ± 4.97 mm, and anterior 0.16 ± 5.18 mm. The avg magnitude of displacement was superior/inferior 2.22 ± 2.04 mm, laterally 3.41 ± 3.62 mm, and anterior/posterior 3.86 ± 3.45 mm. The avg vector magnitude was 6.60 ± 4.14 mm. For acute gastrointestinal (GI) toxicities, 50% experienced grade 1 toxicities and 18% grade 2 GI toxicities. For acute genitourinary (GU) toxicities, 21% had grade 1 and 18% had grade 2 toxicities. For late GU toxicities, 7% had grade 1 and 4% had grade 2 toxicities. RB for gynecological patients receiving IMRT in the postoperative setting can limit V40 rectal dose and vaginal displacement. Although V30 constraints were not met, patients had limited acute and late toxicities. Further studies are needed to validate these findings. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

An in vivo investigative protocol for HDR prostate brachytherapy using urethral and rectal thermoluminescence dosimetry.

PubMed

Toye, Warren; Das, Ram; Kron, Tomas; Franich, Rick; Johnston, Peter; Duchesne, Gillian

2009-05-01

To develop an in vivo dosimetry based investigative action level relevant for a corrective protocol for HDR brachytherapy boost treatment. The dose delivered to points within the urethra and rectum was measured using TLD in vivo dosimetry in 56 patients. Comparisons between the urethral and rectal measurements and TPS calculations showed differences, which are related to the relative position of the implant and TLD trains, and allowed shifts of implant position relative to the prostate to be estimated. Analysis of rectal dose measurements is consistent with implant movement, which was previously only identified with the urethral data. Shift corrected doses were compared with results from the TPS. Comparison of peak doses to the urethra and rectum has been assessed against the proposed corrective protocol to limit overdosing these critical structures. An initial investigative level of 20% difference between measured and TPS peak dose was established, which corresponds to 1/3 of patients which was practical for the caseload. These patients were assessed resulting in corrective action being applied for one patient. Multiple triggering for selective investigative action is outlined. The use of a single in vivo measurement in the first fraction optimizes patient benefit at acceptable cost.

Comparison of auricular and rectal temperature measurement in normothermic, hypothermic, and hyperthermic dogs.

PubMed

Konietschke, U; Kruse, B D; Müller, R; Stockhaus, C; Hartmann, K; Wehner, A

2014-01-01

Measurement of rectal temperature is the most common method and considered gold standard for obtaining body temperature in dogs. So far, no study has been performed comparing agreement between rectal and auricular measurements in a large case series. The purpose of the study was to assess agreement between rectal and auricular temperature measurement in normothermic, hypothermic, and hyperthermic dogs with consideration of different environmental conditions and ear conformations. Reference values for both methods were established using 62 healthy dogs. Three hundred dogs with various diseases (220 normothermic, 32 hypothermic, 48 hyperthermic) were enrolled in this prospective study. Rectal temperature was compared to auricular temperature and differences in agreement with regard to environmental temperature, relative humidity, and different ear conformations (pendulous versus prick ears) were evaluated using Pearson's correlation coefficient and Bland-Altman analysis. Correlation between rec- tal and auricular temperature was significant (r: 0.892; p  <  0.01). However, Bland-Altman plots showed an inacceptable variation of values (bias: 0.300 °C; limits of agreement: -0.606 to 1.206 °C). This variation was above a maximal clinical tolerance of 0.3 °C, which was established by experts' opinion (n = 16). Relative humidity had a significant influence (p   =   0.001), whereas environmental temperature did not. Variation between the two methods of measuring body temperature was clinically unacceptable. Although measurement of auricular temperature is fast, simple, and well tolerated, this method provides a clinically unacceptable difference to the rectal measurement.

Hospital variation in sphincter preservation for elderly rectal cancer patients.

PubMed

Dodgion, Christopher M; Neville, Bridget A; Lipsitz, Stuart R; Schrag, Deborah; Breen, Elizabeth; Zinner, Michael J; Greenberg, Caprice C

2014-09-01

The primary goal of an operation for rectal cancer is to cure cancer and, where possible, preserve continence. A wide range of sphincter preservation rates have been reported. This study evaluated hospital variation in the use of low anterior resection (LAR), local excision (LE), and abdominoperineal resection (APR) in the treatment of elderly rectal cancer patients. Using Surveillance, Epidemiology, and End Results-Medicare linked data, we identified 4959 patients older than 65 y with stage I-III rectal cancer diagnosed from 2000-2005 who underwent operative intervention at one of 370 hospitals. We evaluated the distribution of hospital-specific procedure rates and used generalized mixed models with random hospital effects to examine the influence of patient characteristics and hospital on operation type, using APR as a reference. The median hospital performed APR on 33% of elderly patients with rectal cancer. Hospital was a stronger predictor of LAR receipt than any patient characteristic, explaining 32% of procedure choice, but not a strong predictor of LE, explaining only 3.8%. Receipt of LE was primarily related to tumor size and tumor stage, which combined explained 31% of procedure variation. Receipt of LE is primarily determined by patient characteristics. In contrast, the hospital where surgery is performed significantly influences whether a patient undergoes an LAR or APR. Understanding the factors that cause this institutional variation is crucial to ensuring equitable availability of sphincter preservation. Copyright © 2014 Elsevier Inc. All rights reserved.

Genetic variation in RPS6KA1, RPS6KA2, RPS6KB1, RPS6KB2, and PDK1 and risk of colon or rectal cancer

PubMed Central

Slattery, Martha L.; Lundgreen, Abbie; Herrick, Jennifer S.; Wolff, Roger K.

2010-01-01

RPS6KA1, RPS6KA2, RPS6KB1, RPS6KB2, and PDK1 are involved in several pathways central to the carcinogenic process, including regulation of cell growth, insulin, and inflammation. We evaluated genetic variation in their candidate genes to obtain a better understanding of their association with colon and rectal cancer. We used data from two population-based case-control studies of colon (n=1574 cases, 1940 controls) and rectal (n=791 cases, 999 controls) cancer. We observed genetic variation in RPS6KA1, RPS6KA2, and PRS6KB2 were associated with risk of developing colon cancer while only genetic variation in RPS6KA2 was associated with altering risk of rectal cancer. These genes also interacted significantly with other genes operating in similar mechanisms, including Akt1, FRAP1, NFκB1, and PIK3CA. Assessment of tumor markers indicated that these genes and this pathway may importantly contributed to CIMP+ tumors and tumors with KRAS2 mutations. Our findings implicate these candidate genes in the etiology of colon and rectal cancer and provide information on how these genes operate with other genes in the pathway. Our data further suggest that this pathway may lead to CIMP+ and KRAS2-mutated tumors. PMID:21035469

Novel Parameter Predicting Grade 2 Rectal Bleeding After Iodine-125 Prostate Brachytherapy Combined With External Beam Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shiraishi, Yutaka, E-mail: shiraishi@rad.med.keio.ac.jp; Hanada, Takashi; Ohashi, Toshio

2013-09-01

Purpose: To propose a novel parameter predicting rectal bleeding on the basis of generalized equivalent uniform doses (gEUD) after {sup 125}I prostate brachytherapy combined with external beam radiation therapy and to assess the predictive value of this parameter. Methods and Materials: To account for differences among radiation treatment modalities and fractionation schedules, rectal dose–volume histograms (DVHs) of 369 patients with localized prostate cancer undergoing combined therapy retrieved from corresponding treatment planning systems were converted to equivalent dose-based DVHs. The gEUDs for the rectum were calculated from these converted DVHs. The total gEUD (gEUD{sub sum}) was determined by a summation ofmore » the brachytherapy and external-beam radiation therapy components. Results: Thirty-eight patients (10.3%) developed grade 2+ rectal bleeding. The grade 2+ rectal bleeding rate increased as the gEUD{sub sum} increased: 2.0% (2 of 102 patients) for <70 Gy, 10.3% (15 of 145 patients) for 70-80 Gy, 15.8% (12 of 76 patients) for 80-90 Gy, and 19.6% (9 of 46 patients) for >90 Gy (P=.002). Multivariate analysis identified age (P=.024) and gEUD{sub sum} (P=.000) as risk factors for grade 2+ rectal bleeding. Conclusions: Our results demonstrate gEUD to be a potential predictive factor for grade 2+ late rectal bleeding after combined therapy for prostate cancer.« less

Dosimetric evaluation of magnetic resonance-generated synthetic CT for radiation treatment of rectal cancer.

PubMed

Wang, Hesheng; Du, Kevin; Qu, Juliet; Chandarana, Hersh; Das, Indra J

2018-01-01

The purpose of this study was to assess the dosimetric equivalence of magnetic resonance (MR)-generated synthetic CT (synCT) and simulation CT for treatment planning in radiotherapy of rectal cancer. This study was conducted on eleven patients who underwent whole-body PET/MR and PET/CT examination in a prospective IRB-approved study. For each patient synCT was generated from Dixon MR using a model-based method. Standard treatment planning directives were used to create a four-field box (4F), an oblique four-field (O4F) and a volumetric modulated arc therapy (VMAT) plan on synCT for treatment of rectal cancer. The plans were recalculated on CT with the same monitor units (MUs) as that of synCT. Dose-volume metrics of planning target volume (PTV) and organs at risk (OARs) as well as gamma analysis of dose distributions were evaluated to quantify the difference between synCT and CT plans. All plans were calculated using the analytical anisotropic algorithm (AAA). The VMAT plans on synCT and CT were also calculated using the Acuros XB algorithm for comparison with the AAA calculation. Medians of absolute differences in PTV metrics between synCT and CT plans were 0.2%, 0.2% and 0.3% for 4F, O4F and VMAT respectively. No significant differences were observed in OAR dose metrics including bladder V40Gy, mean dose in bladder, bowel V45Gy and femoral head V30Gy in any techniques. Gamma analysis with 2%/2mm dose difference/distance to agreement criteria showed median passing rates of 99.8% (range: 98.5 to 100%), 99.9% (97.2 to 100%), and 99.9% (99.4 to 100%) for 4F, O4F and VMAT, respectively. Using Acuros XB dose calculation, 2%/2mm gamma analysis generated a passing rate of 99.2% (97.7 to 99.9%) for VMAT plans. SynCT enabled dose calculation equivalent to conventional CT for treatment planning of 3D conformal treatment as well as VMAT of rectal cancer. The dosimetric agreement between synCT and CT calculated doses demonstrated the potential of MR-only treatment planning for rectal cancer using MR generated synCT.

SU-F-J-122: Rectal Sparing Reproducibility in Prostate Cancer Patients Treated with Hydrogel Spacer and Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hedrick, S; Robison, B; Blakey, M

2016-06-15

Purpose: Rectal hydrogel spacer has been shown to improve rectal sparing in prostate radiotherapy. The purpose of this study was to determine the reproducibility of rectal sparing throughout treatment in patients undergoing proton therapy. Methods: At our facility, prostate cancer patients are treated with pencil beam scanning proton therapy, utilizing an endorectal balloon (ERB) or rectal spacer hydrogel (Gel) “SpaceOAR” implant. All patients were treated with a full bladder and empty rectum (low residue diet and stool softeners). A quality assurance CT (QACT) was performed periodically throughout treatment to ensure rectal filling consistency and sparing in 41 patients treated withmore » Gel. The treatment planning (TP) dose was calculated on each QACT and the rectum V90%, V75%, V65%, V50%, and V40% were recorded. QACT scans were acquired on day 0, week 1, week 3, and week 5. Results: 144 QACT scans were analyzed, each patient receiving 3–4 QACTs. Rectum V90% was within +/−1% of the TP dose in 70% of the QACTs and within +/−5% in 95% of scans. From previous data analyses, our ERB rectum V90% average is 6%. This value was used as an upper threshold for the Gel QACT analysis. 5 of the 41 patients (12%), corresponding to 7 QACTs, had a rectum V90% that exceeded 6% on one or more QACTs. However, the average rectal V90% measured over multiple QACTs never exceeded 6%. 55% of the QACTs had a rectum volume within 5cc of the TPCT volume, 68% were within 10cc. Conclusion: In this study, we have shown that a majority of our prostate patients can maintain consistent rectal sparing when treated with a hydrogel spacer. QACT rectal V90% exceeding our threshold was most often related to increased rectal filling and gas, which was addressed with improved dietary compliance and the intensification of stool softeners or laxatives.« less

RMP-02/MTN-006: A Phase 1 Rectal Safety, Acceptability, Pharmacokinetic, and Pharmacodynamic Study of Tenofovir 1% Gel Compared with Oral Tenofovir Disoproxil Fumarate

PubMed Central

Cranston, Ross D.; Kashuba, Angela; Hendrix, Craig W.; Bumpus, Namandjé N.; Richardson-Harman, Nicola; Elliott, Julie; Janocko, Laura; Khanukhova, Elena; Dennis, Robert; Cumberland, William G.; Ju, Chuan; Carballo-Diéguez, Alex; Mauck, Christine; McGowan, Ian

2012-01-01

Abstract This study was designed to assess the safety, acceptability, pharmacokinetic (PK), and pharmacodynamic (PD) responses to rectal administration of tenofovir (TFV) 1% vaginally formulated gel and oral tenofovir disoproxil fumarate (TDF). This study was designed as a phase 1, randomized, two-site (United States), double-blind, placebo-controlled study of sexually abstinent men and women. Eighteen participants received a single 300-mg exposure of oral TDF and were then randomized 2:1 to receive a single and then seven daily exposures of rectal TFV or hydroxyethyl cellulose (HEC) placebo gel. Safety endpoints included clinical adverse events (AEs) and mucosal safety parameters. Blood and colonic biopsies were collected for PK analyses and ex vivo HIV-1 challenge. No serious AEs were reported. However, AEs were significantly increased with 7-day TFV gel use, most prominently with gastrointestinal AEs (p=0.002). Only 25% of participants liked the TFV gel. Likelihood of use “if somewhat protective” was ∼75% in both groups. Indices of mucosal damage showed minimal changes. Tissue TFV diphosphate (TFV-DP) Cmax 30 min after single rectal exposure was 6–10 times greater than single oral exposure; tissue TFV-DP was 5.7 times greater following 7-day versus single rectal exposure. In vivo exposure correlated with significant ex vivo tissue infectibility suppression [single-rectal: p=0.12, analysis of covariance (ANCOVA) p=0.006; 7-day rectal: p=0.02, ANCOVA p=0.005]. Tissue PK–PD was significantly correlated (p=0.002). We conclude that rectal dosing with TFV 1% gel resulted in greater TFV-DP tissue detection than oral dosing with reduced ex vivo biopsy infectibility, enabling PK–PD correlations. On the basis of increased gastrointestinal AEs, rectally applied, vaginally formulated TFV was not entirely safe or acceptable, suggesting the need for alternative rectal-specific formulations. PMID:22943559

Rectal diazepam solution is as good as rectal administration of intravenous diazepam in the first-aid cessation of seizures in children with intractable epilepsy.

PubMed

Chiang, Lin-Mei; Wang, Huei-Shyong; Shen, Hsin-Hsien; Deng, Shin-Tang; Tseng, Chi-Hao; Chen, Yu-In; Chou, Ming-Liang; Hung, Po-Cheng; Lin, Kuang-Lin

2011-02-01

Acute seizures are readily recognizable episodes requiring urgent treatment. This study was conducted to compare the efficacy and safety of suppository use of rectal diazepam solution [Stesolid rectal tube (SRT), Alpharma, Inc., Lierskogen, Norway] with those of intravenous diazepam (IVD), Li Ta Pharma Co, Ltd., Taichung, Taiwan for control of acute seizures in children with intractable epilepsy. Subjects were patients, aged 1-18 years, with intractable epilepsy under at least three kinds of antiepileptic treatments. Caregivers were trained to rectally administer SRT or IVD (dosage varying from 0.2 to 0.5mg per kilogram of body weight) and to monitor respiration condition, seizure severity, and adverse drug effects. Among the 24 subjects, 9 males and 15 females, treated for a period of 3 months, the ages ranged from 2 to 18 years, with a mean of 9.1 years. Seizure types were generalized tonic and/or clonic. Seizure frequency varied from once per week to 20 times per day. Twenty-one (87.5%) of them had mental retardation and/or developmental delay, and 103 of the 127 (81.1%) IVD administrations and 90 of the 103 (87.3%) SRT administrations resulted in rapid cessation of seizures within 10 minutes. Each first dose failed to control seizures in 24 and 13 episodes, respectively. A second dose of IVD achieved cessation of seizure in 21 of the 24 episodes and a second dose of SRT in 12 of the 13 episodes within another 10 minutes. Four episodes (3 with rectal IVD and 1 with SRT) of prolonged seizure beyond 20 minutes needed IVD injection at our emergency room. Sedation occurred in 17% of patients, which was attributed to IVD in 8% and SRT in 9% of patients. No respiratory depression was attributable to IVD or SRT. There was no significant statistical difference in efficacy and safety between these two forms of diazepam. Rectal diazepam solution, administered by capable caregivers, is as effective and safe as rectal administration of IVD for children with intractable epilepsy. Copyright © 2011. Published by Elsevier B.V.

Diclofenac rectal suppository: an effective modality for perineal pain.

PubMed

Naz, Shabnam; Memon, Naila Yousuf; Sattar, Asma; Baloch, Rafia

2016-08-01

To determine the frequency of perineal pain after childbirth after a single dose of diclofenac rectal suppository. This cross-sectional study was conducted at Shaikh Zayed Women Hospital, Larkana, Pakistan, from April to September 2014, and comprised patients who were admitted to the labour room for normal vaginal delivery. A single dose of rectal diclofenac suppository of 100mg was given to the patients delivered vaginally or by second-stage emergency Caesarean section. Post-partum pain was noted after 12 and 24 hours of the administration of analgesia. SPSS 16 was used for data analysis. Of the 169 subjects, 63(37.28%) were aged 20 years or less, 85(50.3%) between 21 and 30 years, and 21(12.43%) between 31 and 40 years. Frequency of perineal pain was predominantly mild in 95(56%) patients, moderate in 60(35.5%) and severe in 14(8.28%). The use of non-steroidal anti-inflammatory rectal suppositories was found to be a simple and highly effective modality of reducing the perineal pain.

Renaissance of contact x-ray therapy for treating rectal cancer.

PubMed

Gérard, Jean-Pierre; Myint, Arthur Sun; Croce, Olivier; Lindegaard, Jacob; Jensen, Anie; Myerson, Robert; Hannoun-Lévi, Jean-Michel; Marcie, Serge

2011-07-01

Contact x-ray therapy (CXRT) with 50 kV has proven to be an efficient radiation therapy technique to achieve local control and rectal preservation for early rectal adenocarcinoma. Despite these results, CXRT has not been used due to the shortage of the no longer manufactured Philips RT 50™ unit. Recently, a new CXRT machine (Papillon 50™) became available on the market. This machine delivers a beam of 50 kV with a dose rate close to 15 Gy/min and has a percentage depth dose of 50% at 6-7 mm. The applicator size varies from 2-3 cm in diameter. Due to the original design of the main tube, treatment delivery is quick and more comfortable for the patients. An online viewing system incorporated in the tube allows a good visualization of the tumor with improved accuracy of radiation delivery. An international collaborative trial (Contact Endoscopic Microsurgery [CONTEM]) was set up to accrue approximately 300 cases of rectal adenocarcinoma staged T1, T2 or early T3 tumors in the UK, France, Denmark and Sweden. This trial should confirm the role of CXRT in curative treatment with organ preservation for early rectal cancers.

Advantages and limitations of navigation-based multicriteria optimization (MCO) for localized prostate cancer IMRT planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGarry, Conor K., E-mail: conor.mcgarry@belfasttrust.hscni.net; Bokrantz, Rasmus; RaySearch Laboratories, Stockholm

2014-10-01

Efficacy of inverse planning is becoming increasingly important for advanced radiotherapy techniques. This study’s aims were to validate multicriteria optimization (MCO) in RayStation (v2.4, RaySearch Laboratories, Sweden) against standard intensity-modulated radiation therapy (IMRT) optimization in Oncentra (v4.1, Nucletron BV, the Netherlands) and characterize dose differences due to conversion of navigated MCO plans into deliverable multileaf collimator apertures. Step-and-shoot IMRT plans were created for 10 patients with localized prostate cancer using both standard optimization and MCO. Acceptable standard IMRT plans with minimal average rectal dose were chosen for comparison with deliverable MCO plans. The trade-off was, for the MCO plans, managedmore » through a user interface that permits continuous navigation between fluence-based plans. Navigated MCO plans were made deliverable at incremental steps along a trajectory between maximal target homogeneity and maximal rectal sparing. Dosimetric differences between navigated and deliverable MCO plans were also quantified. MCO plans, chosen as acceptable under navigated and deliverable conditions resulted in similar rectal sparing compared with standard optimization (33.7 ± 1.8 Gy vs 35.5 ± 4.2 Gy, p = 0.117). The dose differences between navigated and deliverable MCO plans increased as higher priority was placed on rectal avoidance. If the best possible deliverable MCO was chosen, a significant reduction in rectal dose was observed in comparison with standard optimization (30.6 ± 1.4 Gy vs 35.5 ± 4.2 Gy, p = 0.047). Improvements were, however, to some extent, at the expense of less conformal dose distributions, which resulted in significantly higher doses to the bladder for 2 of the 3 tolerance levels. In conclusion, similar IMRT plans can be created for patients with prostate cancer using MCO compared with standard optimization. Limitations exist within MCO regarding conversion of navigated plans to deliverable apertures, particularly for plans that emphasize avoidance of critical structures. Minimizing these differences would result in better quality treatments for patients with prostate cancer who were treated with radiotherapy using MCO plans.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, R; Zhu, X; Li, S

Purpose: High Dose Rate (HDR) brachytherapy forward planning is principally an iterative process; hence, plan quality is affected by planners’ experiences and limited planning time. Thus, this may lead to sporadic errors and inconsistencies in planning. A statistical tool based on previous approved clinical treatment plans would help to maintain the consistency of planning quality and improve the efficiency of second checking. Methods: An independent dose calculation tool was developed from commercial software. Thirty-three previously approved cervical HDR plans with the same prescription dose (550cGy), applicator type, and treatment protocol were examined, and ICRU defined reference point doses (bladder, vaginalmore » mucosa, rectum, and points A/B) along with dwell times were collected. Dose calculation tool then calculated appropriate range with a 95% confidence interval for each parameter obtained, which would be used as the benchmark for evaluation of those parameters in future HDR treatment plans. Model quality was verified using five randomly selected approved plans from the same dataset. Results: Dose variations appears to be larger at the reference point of bladder and mucosa as compared with rectum. Most reference point doses from verification plans fell between the predicted range, except the doses of two points of rectum and two points of reference position A (owing to rectal anatomical variations & clinical adjustment in prescription points, respectively). Similar results were obtained for tandem and ring dwell times despite relatively larger uncertainties. Conclusion: This statistical tool provides an insight into clinically acceptable range of cervical HDR plans, which could be useful in plan checking and identifying potential planning errors, thus improving the consistency of plan quality.« less

Poster - Thur Eve - 76: A quality control to achieve planning consistency in arc radiotherapy of the prostate.

PubMed

Zeng, G; Murphy, J; Annis, S-L; Wu, X; Wang, Y; McGowan, T; Macpherson, M

2012-07-01

To report a quality control program in prostate radiation therapy at our center that includes semi-automated planning process to generate high quality plans and in-house software to track plan quality in the subsequent clinical application. Arc planning in Eclipse v10.0 was preformed for both intact prostate and post-prostatectomy treatments. The planning focuses on DVH requirements and dose distributions being able to tolerate daily setup variations. A modified structure set is used to standardize the optimization, including short rectum and bladder in the fields to effectively tighten dose to target and a rectum expansion with 1cm cropped from PTV to block dose and shape posterior isodose lines. Structure, plan and optimization templates are used to streamline plan generation. DVH files are exported from Eclipse to a quality tracking software with GUI written in Matlab that can report the dose-volume data either for an individual patient or over a patient population. For 100 intact prostate patients treated with 78Gy, rectal D50, D25, D15 and D5 are 30.1±6.2Gy, 50.6±7.9Gy, 65.9±6.0Gy and 76.6±1.4Gy respectively, well below the limits 50Gy, 65Gy, 75Gy and 78Gy respectively. For prostate bed with prescription of 66Gy, rectal D50 is 35.9±6.9Gy. In both sites, PTV is covered by 95% prescription and the hotspots are less than 5%. The semi-automated planning method can efficiently create high quality plans while the tracking software can monitor the feedback from clinical application. It is a comprehensive and robust quality control program in radiation therapy. © 2012 American Association of Physicists in Medicine.

Randomized pharmacokinetic cross-over study comparing two curcumin preparations in plasma and rectal tissue of healthy human volunteers

PubMed Central

Asher, Gary N.; Xie, Ying; Moaddel, Ruin; Sanghvi, Mitesh; Dossou, Katina S.S.; Kashuba, Angela D. M.; Sandler, Robert S.; Hawke, Roy L.

2016-01-01

Curcumin is poorly absorbed driving interest in new preparations. However, little is known about pharmacokinetics and tissue bioavailability between formulations. In this randomized, crossover study we evaluated the relationship between steady-state plasma and rectal tissue curcuminoid concentrations using standard and phosphatidylcholine curcumin extracts. There was no difference in the geometric mean plasma AUCs when adjusted for the 10-fold difference in curcumin dose between the two formulations. Phosphatidylcholine curcumin extract yielded only 20–30% plasma demethoxycurcumin and bisdemethoxycurcumin conjugates compared to standard extract, yet yielded 20-fold greater hexahydrocurcumin. When adjusting for curcumin dose, tissue curcumin concentrations were 5-fold greater for the phosphatidylcholine extract. Improvements in curcuminoid absorption due to phosphatidylcholine are not uniform across the curcuminoids. Furthermore, curcuminoid exposures in the intestinal mucosa are most likely due to luminal exposure rather than plasma disposition. Finally, once-daily dosing is sufficient to maintain detectable curcuminoids at steady-state in both plasma and rectal tissues. PMID:27503249

SU-E-J-97: Pretreatment Test and Post-Treatment Evaluation for Iso-NTCP Dose Guided Adapive Radiotherapy (DGART), Experience with Prostate Cancer Patients Treated with Rectal Balloons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, J; Thomas Jefferson UniversityHospital, Philadelphia, PA; Hardcastle, N

Purpose: To explore the feasibility of pretreatment test for iso-NTCP DGART and to compare the pretreatment test results with post-treatment evaluations. Methods: NTCP here refers to late rectal wall toxicity only and is calculated with the ring rectal wall DVH. Simulation for one time iso- NTCP DGART starts after half of the total dose was done for 10 patients to investigate if TCP gains could be achieved. Six patients were treated using a 12-fraction 4.3Gy technique and four using 16-fraction 3.63Gy technique. For each of the 12-fraction cases a VMAT plan was generated in Pinnacle3™ using the daily CT obtainedmore » prior to the 6th fraction. A pretreatment simulation was performed using only the first 6 daily CTs. The idea is to add the 6 original plan delivered doses with 6 DGART plan delivered doses by deformable dose accumulation (DDA) on each of the first 6 CTs, resulting in 6 rectal wall doses (RWDs) and NTCPs. The 95% confidence interval (95%CI) for the 6 NTCPs were computed.The posttreatment evaluation was done by: a) copy the DGART plan to 6 CTs for fraction 7–12 and calculate the 6 actual DGART delivered fractional doses; b) sum the 6 actual DGART doses with the 6 original plan delivered doses by DDA on each of the 12 CTs resulting in 12 post-treatment RWDs and NTCPs; c) boxplot the 12 post-treatment NTCPs. Results: Target dose gain is 0.76–1.93 Gy. The 95%CI widths of the pretreatment tests NTCPs were 1.1–2.7%. For 5 patients, the planned NTCP fell within the 95%CI. For 4 patients, the planned NTCP was lower than the 95%CI lines. Post-treatment results show that for 7 patients, the upper quartile was within the 95%CI; for 2 patients, the upper quartile were higher than the 95%CI. Conclusion: The pretreatment test yields conservative prediction of the actual delivered NTCP.« less

An improved distance-to-dose correlation for predicting bladder and rectum dose-volumes in knowledge-based VMAT planning for prostate cancer

NASA Astrophysics Data System (ADS)

Wall, Phillip D. H.; Carver, Robert L.; Fontenot, Jonas D.

2018-01-01

The overlap volume histogram (OVH) is an anatomical metric commonly used to quantify the geometric relationship between an organ at risk (OAR) and target volume when predicting expected dose-volumes in knowledge-based planning (KBP). This work investigated the influence of additional variables contributing to variations in the assumed linear DVH-OVH correlation for the bladder and rectum in VMAT plans of prostate patients, with the goal of increasing prediction accuracy and achievability of knowledge-based planning methods. VMAT plans were retrospectively generated for 124 prostate patients using multi-criteria optimization. DVHs quantified patient dosimetric data while OVHs quantified patient anatomical information. The DVH-OVH correlations were calculated for fractional bladder and rectum volumes of 30, 50, 65, and 80%. Correlations between potential influencing factors and dose were quantified using the Pearson product-moment correlation coefficient (R). Factors analyzed included the derivative of the OVH, prescribed dose, PTV volume, bladder volume, rectum volume, and in-field OAR volume. Out of the selected factors, only the in-field bladder volume (mean R  =  0.86) showed a strong correlation with bladder doses. Similarly, only the in-field rectal volume (mean R  =  0.76) showed a strong correlation with rectal doses. Therefore, an OVH formalism accounting for in-field OAR volumes was developed to determine the extent to which it improved the DVH-OVH correlation. Including the in-field factor improved the DVH-OVH correlation, with the mean R values over the fractional volumes studied improving from  -0.79 to  -0.85 and  -0.82 to  -0.86 for the bladder and rectum, respectively. A re-planning study was performed on 31 randomly selected database patients to verify the increased accuracy of KBP dose predictions by accounting for bladder and rectum volume within treatment fields. The in-field OVH led to significantly more precise and fewer unachievable KBP predictions, especially for lower bladder and rectum dose-volumes.

Dosimetric impact in the dose-volume histograms of rectal and vesical wall contouring in prostate cancer IMRT treatments.

PubMed

Gómez, Laura; Andrés, Carlos; Ruiz, Antonio

2017-01-01

The main purpose of this study was to evaluate the differences in dose-volume histograms of IMRT treatments for prostate cancer based on the delineation of the main organs at risk (rectum and bladder) as solid organs or by contouring their wall. Rectum and bladder have typically been delineated as solid organs, including the waste material, which, in practice, can lead to an erroneous assessment of the risk of adverse effects. A retrospective study was made on 25 patients treated with IMRT radiotherapy for prostate adenocarcinoma. 76.32 Gy in 36 fractions was prescribed to the prostate and seminal vesicles. In addition to the delineation of the rectum and bladder as solid organs (including their content), the rectal and bladder wall were also delineated and the resulting dose-volume histograms were analyzed for the two groups of structures. Data analysis shows statistically significant differences in the main parameters used to assess the risk of toxicity of a prostate radiotherapy treatment. Higher doses were received on the rectal and bladder walls compared to doses received on the corresponding solid organs. The observed differences in terms of received doses to the rectum and bladder based on the method of contouring could gain greater importance in inverse planning treatments, where the treatment planning system optimizes the dose in these volumes. So, one should take into account the method of delineating of these structures to make a clinical decision regarding dose limitation and risk assessment of chronic toxicity.

SU-E-T-29: A Dosimetric Study of Volumetric Modulated Arc Therapy with Simultaneous Integrated Boost for Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, T; Lin, X; Yin, Y

Purpose: To compare the dosimetric differences among fixed field intensity-modulated radiotherapy (IMRT) and double-arc volumetricmodulated arc therapy (VMAT) plans with simultaneous integrated boost in rectal cancer. Methods: Ten patients with rectal cancer previously treated with IMRT were included in this analysis. For each patient, two treatment techniques were designed for each patient: the fixed 7 fields IMRT and double-arc VMAT with RapidArc technique. The treatment plan was designed to deliver in one process with simultaneous integrated boost (SIB). The prescribed doses to the planning target volume of the subclinical disease (PTV1) and the gross disease (PTV2) were 45 Gy andmore » 55 Gy in 25 fractions, respectively. The dose distribution in the target, the dose to the organs at risk, total MU and the delivery time in two techniques were compared to explore the dosimetric differences. Results: For the target dose and homogeneity in PTV1 and PTV2, no statistically differences were observed in the two plans. VMAT plans showed a better conformity in PTV1. VMAT plans reduced the mean dose to bladder, small bowel, femur heads and iliac wings. For iliac wings, VMAT plans resulted in a statistically significant reduction in irradiated volume of 15 Gy, 20 Gy, 30 Gy but increased the 10 Gy irradiated volume. VMAT plans reduced the small bowel irradiated volume of 20 Gy and 30 Gy. Compared with IMRT plans, VMAT plans showed a significant reduction of monitor units by nearly 30% and reduced treatment time by an average of 70% Conclusion: Compared to IMRT plans, VMAT plans showed the similar target dose and reduced the dose of the organs at risk, especially for small bowel and iliac wings. For rectal cancer, VMAT with simultaneous integrated boost can be carried out with high quality and efficiency.« less

SU-E-J-39: Dosimetric Benefit of Implanted Marker-Based CBCT Setup for Definitive Prostatic Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhen, H; Wu, Z; Bluemenfeld, P

Purpose Daily setup for definitive prostatic radiotherapy is challenged by suboptimal visibility of the prostate boundary and daily variation of rectum shape and position. For patients with improved bowel preparation, we conducted a dosimetric comparison between prostate implanted marker (IM)-based daily setup and anterior rectal wall (ARW)-based setup, with the hypothesis that the former leads to adequate target coverage with better rectal sparing. Methods Five IMRT/VMAT prostate cases with implanted markers were selected for analysis. Daily CBCT showed improvement of the rectal volume compared to planning CT. For each patient, the prostate and rectum were contoured on three CBCT imagesmore » (fraction 5/15/25) with subsequent physician review. The CBCTs were then registered to a planning CT using IM-based registration. The deviation of ARW positions from planning CT to CBCT were analyzed at various sup-inf levels (−1.8 cm to 1.8 cm from level of prostate center). To estimate the potential dosimetric impact from ARW-based setup, the treatment plans were recalculated using A-P shifts ranging from −1mm to +6mm. Clinically important rectum DVH values including Dmax, D3cc and Dmean were computed. Results For the studied patients, we observed on average 32% rectum volume reduction from planning CT to CBCT. As a Results, the ARW on average shifts posteriorly by −1mm to +5mm, depending on the sup-inf level of observation, with larger shifts observed at more superior levels. Recalculation shows that when ARW shifts 1mm posteriorly, ARW-based CBCT setup leads to a 1.0%, 4.2%, and 3.2% increase in rectum Dmax, D3cc, and Dmean, respectively, compared to IM-based setup. The dosimetric deviations increase to 4.7%, 25.8% and 24.7% when ARW shifts 6mm posteriorly. No significant prostate-only dose difference was observed. Conclusion For patients with improved bowel preparation, IM-based CBCT setup leads to accurate prostate coverage along with significantly lower rectal dose, compared to ARW-based setup.« less

SU-E-J-221: A Novel Expansion Method for MRI Based Target Delineation in Prostate Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ruiz, B; East Carolina University, Greenville, NC; Feng, Y

Purpose: To compare a novel bladder/rectum carveout expansion method on MRI delineated prostate to standard CT and expansion based methods for maintaining prostate coverage while providing superior bladder and rectal sparing. Methods: Ten prostate cases were planned to include four trials: MRI vs CT delineated prostate/proximal seminal vesicles, and each image modality compared to both standard expansions (8mm 3D expansion and 5mm posterior, i.e. ∼8mm) and carveout method expansions (5mm 3D expansion, 4mm posterior for GTV-CTV excluding expansion into bladder/rectum followed by additional 5mm 3D expansion to PTV, i.e. ∼1cm). All trials were planned to total dose 7920 cGy viamore » IMRT. Evaluation and comparison was made using the following criteria: QUANTEC constraints for bladder/rectum including analysis of low dose regions, changes in PTV volume, total control points, and maximum hot spot. Results: ∼8mm MRI expansion consistently produced the most optimal plan with lowest total control points and best bladder/rectum sparing. However, this scheme had the smallest prostate (average 22.9% reduction) and subsequent PTV volume, consistent with prior literature. ∼1cm MRI had an average PTV volume comparable to ∼8mm CT at 3.79% difference. Bladder QUANTEC constraints were on average less for the ∼1cm MRI as compared to the ∼8mm CT and observed as statistically significant with 2.64% reduction in V65. Rectal constraints appeared to follow the same trend. Case-by-case analysis showed variation in rectal V30 with MRI delineated prostate being most favorable regardless of expansion type. ∼1cm MRI and ∼8mm CT had comparable plan quality. Conclusion: MRI delineated prostate with standard expansions had the smallest PTV leading to margins that may be too tight. Bladder/rectum carveout expansion method on MRI delineated prostate was found to be superior to standard CT based methods in terms of bladder and rectal sparing while maintaining prostate coverage. Continued investigation is warranted for further validation.« less

Helical tomotherapy significantly reduces dose to normal tissues when compared to 3D-CRT for locally advanced rectal cancer.

PubMed

Jhaveri, Pavan M; Teh, Bin S; Paulino, Arnold C; Smiedala, Mindy J; Fahy, Bridget; Grant, Walter; McGary, John; Butler, E Brian

2009-10-01

Combined modality treatment (neoadjuvant chemoradiotherapy followed by surgery) for locally advanced rectal cancer requires special attention to various organs at risk (OAR). As a result, the use of conformal dose delivery methods has become more common in this disease setting. Helical tomotherapy is an image-guided intensity modulated delivery system that delivers dose in a fan-beam manner at 7 degree intervals around the patient and can potentially limit normal tissue from high dose radiation while adequately treating targets. In this study we dosimetrically compare helical tomotherapy to 3D-CRT for stage T3 rectal cancer. The helical tomotherapy plans were optimized in the TomoPlan system to achieve an equivalent uniform dose of 45 Gy for 10 patients with T3N0M0 disease that was at least 5cm from the anal verge. The GTV included the rectal thickening and mass evident on colonoscopy and CT scan as well as with the help of a colorectal surgeon. The CTV included the internal iliac, obturator, and pre-sacral lymphatic chains. The OAR that were outlined included the small bowel, pelvic bone marrow, femoral heads, and bladder. Anatom-e system was used to assist in delineating GTV, CTV and OAR. These 10 plans were then duplicated and optimized into 3-field 3D-CRT plans within the Pinnacle planning system.The V[45], V[40], V[30], V[20], V[10], and mean dose to the OAR were compared between the helical tomotherapy and 3D-CRT plans. Statistically significant differences were achieved in the doses to all OAR, including all volumes and means except for V[10] for the small bowel and the femoral heads. Adequate dosimetric coverage of targets were achieved with both helical tomotherapy and 3D-CRT. Helical tomotherapy reduces the volume of normal tissue receiving high-dose RT when compared to 3D-CRT treatment. Both modalities adequately dose the tumor. Clinical studies addressing the dosimetric benefits are on-going.

Randomised clinical trial: study of escalating doses of NRL001 given in rectal suppositories of different weights.

PubMed

Bell, D; Pediconi, C; Jacobs, A

2014-03-01

The application of α-adrenoceptor agonists can improve faecal incontinence symptoms. The aim of this study was to investigate the pharmacokinetic and systemic effects of NRL001 administered as different strengths in 1 or 2 g suppositories. This randomised, double-blind, placebo controlled study included 48 healthy subjects. Group 1 consisted of two cohorts of 12 subjects administered either four single doses of 1 or 2 g rectal suppository with either 5, 7.5 or 10 mg NRL001, or matching placebo. Group 2 consisted of two cohorts of 12 subjects administered either four single doses of 1 or 2 g rectal suppository with either 10, 12.5 or 15 mg NRL001, or matching placebo. Doses were given in an escalating manner with placebo at a random position within the sequence. Tmax was at ~4.5 h post-dose for all NRL001 doses. Median AUC0-tz , AUC0-∞ and Cmax increased with increasing dose for both suppository sizes. The estimate of ratios of geometric means comparing 2 g with 1 g suppository, and regression analysis for dose proportionality, was close to 1 for the variables AUC0-tz , AUC0-∞ and Cmax (P > 0.05). For both suppository sizes, 20-min mean pulse rate was significantly decreased compared with placebo with all doses (P < 0.05). Blood pressure decreased overall. There were 144 adverse events (AEs) and no serious AEs reported during the study. All AEs were mild in severity. The regression analysis concluded that the doses were dose proportional. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

Rectal and sublingual administration of tacrolimus: a single-dose pharmacokinetic study in healthy volunteers.

PubMed

Stifft, Frank; Vanmolkot, Floris; Scheffers, Ingrid; van Bortel, Luc; Neef, Cees; Christiaans, Maarten

2014-11-01

The immunosuppressant tacrolimus is usually administered orally. When this is not feasible, other routes of administration may be useful. Previous research suggested that tacrolimus may be applied sublingually or rectally. Pharmacokinetic data are sparse. The aim of this study was to investigate and compare the pharmacokinetics of these alternative formulations with orally administered tacrolimus. Three single, fixed-dose formulations of tacrolimus were administered in a random sequence in 18 healthy subjects, using a cross-over study design. For sublingual administration, 3 mg of powder obtained from oral capsules was applied under the tongue for a period of 15 min without swallowing, with mouth rinsing afterwards. For rectal administration, a suppository containing 15 mg of the oral powder was used. Oral administration consisted of 7 mg of instant-release tacrolimus capsules (Prograf). Main pharmacokinetic outcome parameters were compared by anova. Sublingual administration showed no clinically significant exposure, contrary to rectal administration, where all subjects had clinically relevant exposure, with a lower relative bioavailability (78%), a lower maximal blood concentration and a later time of maximal blood concentration compared with oral administration. Sublingual administration of a single dose of tacrolimus does not result in systemic exposure if care is taken not to swallow saliva and to rinse the oral cavity afterwards. Rectal administration of tacrolimus results in clinically relevant systemic exposure and might represent an alternative formulation in case oral administration is not feasible. When used as a topical agent, systemic side-effects should be considered. © 2014 The British Pharmacological Society.

Rectal and sublingual administration of tacrolimus: a single-dose pharmacokinetic study in healthy volunteers

PubMed Central

Stifft, Frank; Vanmolkot, Floris; Scheffers, Ingrid; van Bortel, Luc; Neef, Cees; Christiaans, Maarten

2014-01-01

Aims The immunosuppressant tacrolimus is usually administered orally. When this is not feasible, other routes of administration may be useful. Previous research suggested that tacrolimus may be applied sublingually or rectally. Pharmacokinetic data are sparse. The aim of this study was to investigate and compare the pharmacokinetics of these alternative formulations with orally administered tacrolimus. Methods Three single, fixed-dose formulations of tacrolimus were administered in a random sequence in 18 healthy subjects, using a cross-over study design. For sublingual administration, 3 mg of powder obtained from oral capsules was applied under the tongue for a period of 15 min without swallowing, with mouth rinsing afterwards. For rectal administration, a suppository containing 15 mg of the oral powder was used. Oral administration consisted of 7 mg of instant-release tacrolimus capsules (Prograf). Main pharmacokinetic outcome parameters were compared by anova. Results Sublingual administration showed no clinically significant exposure, contrary to rectal administration, where all subjects had clinically relevant exposure, with a lower relative bioavailability (78%), a lower maximal blood concentration and a later time of maximal blood concentration compared with oral administration. Conclusions Sublingual administration of a single dose of tacrolimus does not result in systemic exposure if care is taken not to swallow saliva and to rinse the oral cavity afterwards. Rectal administration of tacrolimus results in clinically relevant systemic exposure and might represent an alternative formulation in case oral administration is not feasible. When used as a topical agent, systemic side-effects should be considered. PMID:24809233

Utilization of cone-beam CT for offline evaluation of target volume coverage during prostate image-guided radiotherapy based on bony anatomy alignment.

PubMed

Paluska, Petr; Hanus, Josef; Sefrova, Jana; Rouskova, Lucie; Grepl, Jakub; Jansa, Jan; Kasaova, Linda; Hodek, Miroslav; Zouhar, Milan; Vosmik, Milan; Petera, Jiri

2012-01-01

To assess target volume coverage during prostate image-guided radiotherapy based on bony anatomy alignment and to assess possibility of safety margin reduction. Implementation of IGRT should influence safety margins. Utilization of cone-beam CT provides current 3D anatomic information directly in irradiation position. Such information enables reconstruction of the actual dose distribution. Seventeen prostate patients were treated with daily bony anatomy image-guidance. Cone-beam CT (CBCT) scans were acquired once a week immediately after bony anatomy alignment. After the prostate, seminal vesicles, rectum and bladder were contoured, the delivered dose distribution was reconstructed. Target dose coverage was evaluated by the proportion of the CTV encompassed by the 95% isodose. Original plans employed a 1 cm safety margin. Alternative plans assuming a smaller 7 mm margin between CTV and PTV were evaluated in the same way. Rectal and bladder volumes were compared with the initial ones. Rectal and bladder volumes irradiated with doses higher than 75 Gy, 70 Gy, 60 Gy, 50 Gy and 40 Gy were analyzed. In 12% of reconstructed plans the prostate coverage was not sufficient. The prostate underdosage was observed in 5 patients. Coverage of seminal vesicles was not satisfactory in 3% of plans. Most of the target underdosage corresponded to excessive rectal or bladder filling. Evaluation of alternative plans assuming a smaller 7 mm margin revealed 22% and 11% of plans where prostate and seminal vesicles coverage, respectively, was compromised. These were distributed over 8 and 7 patients, respectively. Sufficient dose coverage of target volumes was not achieved for all patients. Reducing of safety margin is not acceptable. Initial rectal and bladder volumes cannot be considered representative for subsequent treatment.

The Value of Botox-A in Acute Radiation Proctitis: Results From a Phase I/II Study Using a Three-Dimensional Scoring System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vuong, Te, E-mail: tvuong@jgh.mcgill.ca; Waschke, Kevin; Niazi, Tamim

Purpose: Acute radiation proctitis (ARP) is a common side effect of pelvic radiotherapy, and its management is challenging in daily practice. The present phase I/II study evaluates the safety and efficacy of the botulinum toxin A (BTX-A) in ARP treatment for rectal cancer patients undergoing neoadjuvant high-dose-rate endorectal brachytherapy (HDREBT). Methods and Materials: Fifteen patients, treated with neoadjuvant HDREBT, 26-Gy in 4 fractions, received the study treatment that consisted of a single injection of BTX-A into the rectal wall. The injection was performed post-HDREBT and prior to the development of ARP. The control group, 20 such patients, did not receivemore » the BTX-A injection. Both groups had access to standard treatment with hydrocortisone rectal aerosol foam (Cortifoam) and anti-inflammatory and narcotic medication. The ARP was clinically evaluated by self-administered daily questionnaires using visual analog scores to document frequency and urgency of bowel movements, rectal burning/tenesmus, and pain symptoms before and after HDREBT. Results: At the time of this analysis, there was no observed systemic toxicity. Patient compliance with the self-administered questionnaire was 100% from week 1 to 4, 70% during week 5, and 40% during week 6. The maximum tolerated dose was established at the 100-U dose level, and noticeable mean differences were observed in bowel frequency (p = 0.016), urgency (p = 0.007), and pain (p = 0.078). Conclusions: This study confirms the feasibility and efficacy of BTX-A intervention at 100-U dose level for study patients compared to control patients. A phase III study with this dose level is planned to validate these results.« less

Voxel-based population analysis for correlating local dose and rectal toxicity in prostate cancer radiotherapy

NASA Astrophysics Data System (ADS)

Acosta, Oscar; Drean, Gael; Ospina, Juan D.; Simon, Antoine; Haigron, Pascal; Lafond, Caroline; de Crevoisier, Renaud

2013-04-01

The majority of current models utilized for predicting toxicity in prostate cancer radiotherapy are based on dose-volume histograms. One of their main drawbacks is the lack of spatial accuracy, since they consider the organs as a whole volume and thus ignore the heterogeneous intra-organ radio-sensitivity. In this paper, we propose a dose-image-based framework to reveal the relationships between local dose and toxicity. In this approach, the three-dimensional (3D) planned dose distributions across a population are non-rigidly registered into a common coordinate system and compared at a voxel level, therefore enabling the identification of 3D anatomical patterns, which may be responsible for toxicity, at least to some extent. Additionally, different metrics were employed in order to assess the quality of the dose mapping. The value of this approach was demonstrated by prospectively analyzing rectal bleeding (⩾Grade 1 at 2 years) according to the CTCAE v3.0 classification in a series of 105 patients receiving 80 Gy to the prostate by intensity modulated radiation therapy (IMRT). Within the patients presenting bleeding, a significant dose excess (6 Gy on average, p < 0.01) was found in a region of the anterior rectal wall. This region, close to the prostate (1 cm), represented less than 10% of the rectum. This promising voxel-wise approach allowed subregions to be defined within the organ that may be involved in toxicity and, as such, must be considered during the inverse IMRT planning step.

SU-C-213-07: Fabrication and Testing of a 3D-Printed Small Animal Rectal Cooling Device to Evaluate Local Hypothermia as a Radioprotector During Prostate SBRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hrycushko, B; Chopra, R; Futch, C

Purpose: The protective effects of induced or even accidental hypothermia on the human body are widespread with several medical uses currently under active research. In vitro experiments using human cell lines have shown hypothermia provides a radioprotective effect that becomes more pronounced at large, single-fraction doses common to SBRT treatments. Relevant to prostate SBRT, this work details the fabrication and testing of a 3D-printed cooling device to facilitate the investigation of the radioprotective effect of local hypothermia on the rat rectum. Methods: A 3cm long, two-channel rectal cooling device was designed in SOLIDWORKS CAD for 3D printing. The water intakemore » nozzle is connected to a 1mm diameter brass pipe from which water flows and circulates back around to the exit nozzle. Both nozzles are connected by plastic tubing to a water chiller pump. Following leak-proof testing, fiber optic temperature probes were used to evaluate the temperature over time when placed adjacent to the cooling device within a rat rectum. MRI thermometry characterized the relative temperature distribution in concentric ROIs surrounding the probe. CBCT images from a small-animal irradiator were evaluated for imaging artifacts which could affect Monte Carlo dose calculations during treatment planning. Results: The rectal temperature adjacent to the cooling device decreased from body temperature (37°C) to 15°C in 10–20 minutes from device insertion. Rectal temperature was maintained at 15±3°C during active cooling. MRI thermometry tests revealed a steep temperature gradient with increasing distance from the cooling device, with the desired temperature range maintained within the surrounding few millimeters. Conclusion: A 3D printed rectal cooling device was fabricated for the purpose of inducing local hypothermia in rat rectums. Rectal cooling capabilities were characterized in-vivo to facilitate an investigation of the radioprotective effect of hypothermia for late rectal toxicity following a single large dose of radiation. Funding support provided by RSNA research seed grant.« less

In vivo dosimetry using Gafchromic films during pelvic intraoperative electron radiation therapy (IOERT)

PubMed Central

Costa, Filipa; Gomes, Dora; Magalhães, Helena; Arrais, Rosário; Moreira, Graciete; Cruz, Maria Fátima; Silva, José Pedro; Santos, Lúcio; Sousa, Olga

2016-01-01

Objective: To characterize in vivo dose distributions during pelvic intraoperative electron radiation therapy (IOERT) for rectal cancer and to assess the alterations introduced by irregular irradiation surfaces in the presence of bevelled applicators. Methods: In vivo measurements were performed with Gafchromic films during 32 IOERT procedures. 1 film per procedure was used for the first 20 procedures. The methodology was then optimized for the remaining 12 procedures by using a set of 3 films. Both the average dose and two-dimensional dose distributions for each film were determined. Phantom measurements were performed for comparison. Results: For flat and concave surfaces, the doses measured in vivo agree with expected values. For concave surfaces with step-like irregularities, measured doses tend to be higher than expected doses. Results obtained with three films per procedure show a large variability along the irradiated surface, with important differences from expected profiles. These results are consistent with the presence of surface hotspots, such as those observed in phantoms in the presence of step-like irregularities, as well as fluid build-up. Conclusion: Clinical dose distributions in the IOERT of rectal cancer are often different from the references used for prescription. Further studies are necessary to assess the impact of these differences on treatment outcomes. In vivo measurements are important, but need to be accompanied by accurate imaging of positioning and irradiated surfaces. Advances in knowledge: These results confirm that surface irregularities occur frequently in rectal cancer IOERT and have a measurable effect on the dose distribution. PMID:27188847

SU-F-T-359: Incorporating Dose Volume Histogram Prediction Into Auto-Planning for Volumetric-Modulated Arc Therapy in Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, K; Chen, X; Wang, J

Purpose: To incorporate dose volume histogram (DVH) prediction into Auto-Planning for volumetric-modulated arc therapy (VMAT) treatment planning and investigate the benefit of this new technique for rectal cancer. Methods: Ninety clinically accepted VMAT plans for patients with rectal cancer were selected and trained in the RapidPlan for DVH prediction. Both internal and external validations were performed before implementing the prediction model. A new VMAT planning method (hybrid-VMAT) was created with combining the DVH prediction and Auto-Planning. For each new patient, the DVH will be predicted and individual DVH constrains will be obtained and were exported as the original optimization parametersmore » to the Auto-Planning (Pinnacle3 treatment planning system, v9.10) for planning. A total of 20 rectal cancer patients previously treated with manual VMAT (manual-VMAT) plans were replanned using this new method. Dosimetric comparisons were performed between manual VMAT and new method plans. Results: Hybrid-VMAT shows similar PTV coverage to manual-VMAT in D2%, D98% and HI (p>0.05) and superior coverage in CI (p=0.000). For the bladder, the means of V40 and mean dose are 36.0% and 35.6Gy for hybrid-VMAT and 42% and 38.0Gy for the manual-VMAT. For the left (right) femur, the means of V30 and mean dose are 10.6% (11.6%) and 17.9Gy (19.2Gy) for the hybrid-VMAT and 25.6% (24.1%) and 27.3Gy (26.2Gy) for the manual-VMAT. The hybrid-VMAT has significantly improved the organs at risk sparing. Conclusion: The integration of DVH prediction and Auto-Planning significantly improve the VMAT plan quality in the rectal cancer radiotherapy. Our results show the benefit of the new method and will be further investigated in other tumor sites.« less

Normal Tissue Complication Probability (NTCP) modeling of late rectal bleeding following external beam radiotherapy for prostate cancer: A Test of the QUANTEC-recommended NTCP model.

PubMed

Liu, Mitchell; Moiseenko, Vitali; Agranovich, Alexander; Karvat, Anand; Kwan, Winkle; Saleh, Ziad H; Apte, Aditya A; Deasy, Joseph O

2010-10-01

Validating a predictive model for late rectal bleeding following external beam treatment for prostate cancer would enable safer treatments or dose escalation. We tested the normal tissue complication probability (NTCP) model recommended in the recent QUANTEC review (quantitative analysis of normal tissue effects in the clinic). One hundred and sixty one prostate cancer patients were treated with 3D conformal radiotherapy for prostate cancer at the British Columbia Cancer Agency in a prospective protocol. The total prescription dose for all patients was 74 Gy, delivered in 2 Gy/fraction. 159 3D treatment planning datasets were available for analysis. Rectal dose volume histograms were extracted and fitted to a Lyman-Kutcher-Burman NTCP model. Late rectal bleeding (>grade 2) was observed in 12/159 patients (7.5%). Multivariate logistic regression with dose-volume parameters (V50, V60, V70, etc.) was non-significant. Among clinical variables, only age was significant on a Kaplan-Meier log-rank test (p=0.007, with an optimal cut point of 77 years). Best-fit Lyman-Kutcher-Burman model parameters (with 95% confidence intervals) were: n = 0.068 (0.01, +infinity); m =0.14 (0.0, 0.86); and TD50 = 81 (27, 136) Gy. The peak values fall within the 95% QUANTEC confidence intervals. On this dataset, both models had only modest ability to predict complications: the best-fit model had a Spearman's rank correlation coefficient of rs = 0.099 (p = 0.11) and area under the receiver operating characteristic curve (AUC) of 0.62; the QUANTEC model had rs=0.096 (p= 0.11) and a corresponding AUC of 0.61. Although the QUANTEC model consistently predicted higher NTCP values, it could not be rejected according to the χ(2) test (p = 0.44). Observed complications, and best-fit parameter estimates, were consistent with the QUANTEC-preferred NTCP model. However, predictive power was low, at least partly because the rectal dose distribution characteristics do not vary greatly within this patient cohort.

Enhanced rectal absorption and reduced local irritation of the anti-inflammatory drug ethyl 4-biphenylylacetate in rats by complexation with water-soluble beta-cyclodextrin derivatives and formulation as oleaginous suppository.

PubMed

Arima, H; Kondo, T; Irie, T; Uekama, K

1992-11-01

To improve the rectal delivery of ethyl 4-biphenylylacetate (EBA), a prodrug of the anti-inflammatory drug 4-biphenylylacetic acid (BPAA), the use of highly water-soluble 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) and heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DM-beta-CyD) was investigated and compared with the use of the parent beta-cyclodextrin (beta-CyD). Among the three beta-CyDs, HP-beta-CyD was best at improving the rectal bioavailability of EBA in rats after single and multiple administrations of oleaginous suppositories (Witepsol H-5) containing the complexes. To gain insight into the enhancing effect of beta-CyDs, the absorption behaviors of EBA (observed by monitoring BPAA as an active metabolite of EBA) and beta-CyDs themselves were examined in vitro, in situ, and in vivo. The in situ recirculation study revealed that the complexed form of EBA was less absorbable from the rectal lumen in the solution state, but this disadvantageous effect of beta-CyDs was compensated in part by the inhibition of the bioconversion of EBA to BPAA. When beta-CyDs were coadministered with EBA in vivo, however, rather high amounts of HP-beta-CyD (approximately 26% of dose) and DM-beta-CyD (approximately 21% of dose), compared with beta-CyD (approximately 5% of dose), were absorbed from the rat rectum. Thus, the enhancement of rectal absorption of EBA in vivo can be explained by the facts that the hydrophilic beta-CyDs increased the release rate of EBA from the vehicle and stabilized EBA in the rectal lumen and that the drug was partly absorbed in the form of the complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy and Safety of Low-Dose-Rate Endorectal Brachytherapy as a Boost to Neoadjuvant Chemoradiation in the Treatment of Locally Advanced Distal Rectal Cancer: A Phase-II Clinical Trial

PubMed Central

Omidvari, Shapour; Zohourinia, Shadi; Ansari, Mansour; Ghahramani, Leila; Zare-Bandamiri, Mohammad; Mosalaei, Ahmad; Ahmadloo, Niloofar; Pourahmad, Saeedeh; Nasrolahi, Hamid; Hamedi, Sayed Hasan

2015-01-01

Purpose Despite advances in rectal cancer treatment over the last decade, local control and risk of late side effects due to external beam radiation therapy (EBRT) remain as concerns. The present study aimed to investigate the efficacy and the safety of low-dose-rate endorectal brachytherapy (LDRBT) as a boost to neoadjuvant chemoradiation for use in treating locally advanced distal rectal adenocarcinomas. Methods This phase-II clinical trial included 34 patients (as the study arm) with newly diagnosed, locally advanced (clinical T3-T4 and/or N1/N2, M0) lower rectal cancer. For comparative analysis, 102 matched patients (as the historical control arm) with rectal cancer were also selected. All the patients were treated with LDRBT (15 Gy in 3 fractions) and concurrent chemoradiation (45-50.4 Gy). Concurrent chemotherapy consisted of oxaliplatin 130 mg/m2 intravenously on day 1 plus oral capecitabine 825 mg/m2 twice daily during LDRBT and EBRT. Results The study results revealed a significant differences between the study arm and the control arm in terms in the pathologic tumor size (2.1 cm vs. 3.6 cm, P = 0.001), the pathologic tumor stage (35% T3-4 vs. 65% T3-4, P = 0.003), and the pathologic complete response (29.4% vs. 11.7%, P < 0.028). Moreover, a significantly higher dose of EBRT (P = 0.041) was found in the control arm, and a longer time to surgery was observed in the study arm (P < 0.001). The higher rate of treatment-related toxicities, such as mild proctitis and anemia, in the study arm was tolerable and easily manageable. Conclusion A boost of LDRBT can optimize the pathologic complete response, with acceptable toxicities, in patients with distal rectal cancer. PMID:26361613

Efficacy and Safety of Low-Dose-Rate Endorectal Brachytherapy as a Boost to Neoadjuvant Chemoradiation in the Treatment of Locally Advanced Distal Rectal Cancer: A Phase-II Clinical Trial.

PubMed

Omidvari, Shapour; Zohourinia, Shadi; Ansari, Mansour; Ghahramani, Leila; Zare-Bandamiri, Mohammad; Mosalaei, Ahmad; Ahmadloo, Niloofar; Pourahmad, Saeedeh; Nasrolahi, Hamid; Hamedi, Sayed Hasan; Mohammadianpanah, Mohammad

2015-08-01

Despite advances in rectal cancer treatment over the last decade, local control and risk of late side effects due to external beam radiation therapy (EBRT) remain as concerns. The present study aimed to investigate the efficacy and the safety of low-dose-rate endorectal brachytherapy (LDRBT) as a boost to neoadjuvant chemoradiation for use in treating locally advanced distal rectal adenocarcinomas. This phase-II clinical trial included 34 patients (as the study arm) with newly diagnosed, locally advanced (clinical T3-T4 and/or N1/N2, M0) lower rectal cancer. For comparative analysis, 102 matched patients (as the historical control arm) with rectal cancer were also selected. All the patients were treated with LDRBT (15 Gy in 3 fractions) and concurrent chemoradiation (45-50.4 Gy). Concurrent chemotherapy consisted of oxaliplatin 130 mg/m(2) intravenously on day 1 plus oral capecitabine 825 mg/m(2) twice daily during LDRBT and EBRT. The study results revealed a significant differences between the study arm and the control arm in terms in the pathologic tumor size (2.1 cm vs. 3.6 cm, P = 0.001), the pathologic tumor stage (35% T3-4 vs. 65% T3-4, P = 0.003), and the pathologic complete response (29.4% vs. 11.7%, P < 0.028). Moreover, a significantly higher dose of EBRT (P = 0.041) was found in the control arm, and a longer time to surgery was observed in the study arm (P < 0.001). The higher rate of treatment-related toxicities, such as mild proctitis and anemia, in the study arm was tolerable and easily manageable. A boost of LDRBT can optimize the pathologic complete response, with acceptable toxicities, in patients with distal rectal cancer.

WE-G-17A-07: Investigation of the Influence of the Electron Return Effect (ERE) On the Dose Distribution in Rectal Cancer Patients On a 1.5T MR-Linac

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uilkema, S; Heide, U; Nijkamp, J

Purpose: The purpose of this planning study is to investigate the influence of the ERE on the day-to-day dose distribution in rectal cancer patients, where changes in gas-pockets frequently occur. Methods: Daily CT scans of 5 patients treated neo-adjuvant with 5x5Gy for rectal cancer were used. We optimized two plans on the planning CT (Monaco, 1 mm3 dosegrid), a conventional 7-field 6MV IMRT plan (Dconv) and a plan in the presence of a 1.5T field (Dmrl). We recalculated the plans on all repeat-CT scans and evaluated under/over-dosage of the daily CTVs. Changes of more than 1% were considered significant. Inmore » the bowel area, we investigated the relative dose changes due to the ERE, where the contribution of the ERE was separated from other effects such as attenuation. Results: Both plans were comparable and compliant with ICRU 62 for all patients. For 2 fractions in one patient under-dosage in the CTV was significant, due to a disappearing gas-pocket. Here the V95 was 96.82 and 97.36% in in Dmrl compared to 98.85 and 98.66% in Dconv, respectively. For 3 fractions in another patient appearing gas-pockets resulted in significant over-dosage of the CTV. In these fractions the V107 was 1.88–2.68% in Dmrl compared to 0.33–1.27% in Dconv. In the bowel area the dose changes attributable to the ERE were approximately ± 5% in 1cc, at low dose levels. Conclusion: We were able to calculate acceptable treatment plans with and without a magnetic field. The ERE was present in the Dmrl, but the volumetric effect within the CTV was limited. Outside the CTV relative dose differences were similar, but on small volumes at lower, less relevant dose levels. This suggests that there is no clinical relevant ERE on dose distributions in rectal cancer patients on a 1.5T MR-Linac.« less

A single dose of a MIV-150/Zinc acetate gel provides 24 h of protection against vaginal simian human immunodeficiency virus reverse transcriptase infection, with more limited protection rectally 8-24 h after gel use.

PubMed

Kenney, Jessica; Singer, Rachel; Derby, Nina; Aravantinou, Meropi; Abraham, Ciby J; Menon, Radhika; Seidor, Samantha; Zhang, Shimin; Gettie, Agegnehu; Blanchard, James; Piatak, Michael; Lifson, Jeffrey D; Fernández-Romero, José A; Zydowsky, Thomas M; Robbiani, Melissa

2012-11-01

Previously we showed that repeated vaginal application of a MIV-150/zinc acetate carrageenan (MIV-150/ZA/CG) gel and a zinc acetate carrageenan (ZA/CG) gel significantly protected macaques from vaginal simian human immunodeficiency virus reverse transcriptase (SHIV-RT) infection. Gels were applied either daily for 2 weeks or every other day for 4 weeks, and the animals were challenged 4-24 h later. Herein, we examined the effects of a single vaginal dose administered either before or after virus challenge. Encouraged by the vaginal protection seen with MIV-150/ZA/CG, we also tested it rectally. Vaginal applications of MIV-150/ZA/CG, ZA/CG, and CG gel were performed once 8-24 h before, 1 h after, or 24 h before and 1 h after vaginal challenge. Rectal applications of MIV-150/ZA/CG and CG gel were performed once 8 or 24 h before rectal challenge. While vaginal pre-challenge and pre/post-challenge application of MIV-150/ZA/CG gel offered significant protection (88%, p<0.002), post-challenge application alone did not significantly protect. ZA/CG gel reduced infection prechallenge, but not significantly, and the effect was completely lost post-challenge. Rectal application of MIV-150/ZA/CG gel afforded limited protection against rectal challenge when applied 8-24 h before challenge. Thus, MIV-150/ZA/CG gel is a highly effective vaginal microbicide that demonstrates 24 h of protection from vaginal infection and may demonstrate efficacy against rectal infection when given close to the time of HIV exposure.

A Single Dose of a MIV-150/Zinc Acetate Gel Provides 24 h of Protection Against Vaginal Simian Human Immunodeficiency Virus Reverse Transcriptase Infection, with More Limited Protection Rectally 8–24 h After Gel Use

PubMed Central

Kenney, Jessica; Singer, Rachel; Derby, Nina; Aravantinou, Meropi; Abraham, Ciby J.; Menon, Radhika; Seidor, Samantha; Zhang, Shimin; Gettie, Agegnehu; Blanchard, James; Piatak, Michael; Lifson, Jeffrey D.; Fernández-Romero, José A.; Zydowsky, Thomas M.

2012-01-01

Abstract Previously we showed that repeated vaginal application of a MIV-150/zinc acetate carrageenan (MIV-150/ZA/CG) gel and a zinc acetate carrageenan (ZA/CG) gel significantly protected macaques from vaginal simian human immunodeficiency virus reverse transcriptase (SHIV-RT) infection. Gels were applied either daily for 2 weeks or every other day for 4 weeks, and the animals were challenged 4–24 h later. Herein, we examined the effects of a single vaginal dose administered either before or after virus challenge. Encouraged by the vaginal protection seen with MIV-150/ZA/CG, we also tested it rectally. Vaginal applications of MIV-150/ZA/CG, ZA/CG, and CG gel were performed once 8–24 h before, 1 h after, or 24 h before and 1 h after vaginal challenge. Rectal applications of MIV-150/ZA/CG and CG gel were performed once 8 or 24 h before rectal challenge. While vaginal pre-challenge and pre/post-challenge application of MIV-150/ZA/CG gel offered significant protection (88%, p<0.002), post-challenge application alone did not significantly protect. ZA/CG gel reduced infection prechallenge, but not significantly, and the effect was completely lost post-challenge. Rectal application of MIV-150/ZA/CG gel afforded limited protection against rectal challenge when applied 8–24 h before challenge. Thus, MIV-150/ZA/CG gel is a highly effective vaginal microbicide that demonstrates 24 h of protection from vaginal infection and may demonstrate efficacy against rectal infection when given close to the time of HIV exposure. PMID:22737981

Morphological and immunohistochemical criteria of tissue response to radiotherapy in rectal cancer.

PubMed

Ionescu, S; Brătucu, E; Zurac, S; Staniceanu, F; Pătraşcu, Tr; Burcoş, Tr; Herlea, V; Degeratu, D; Popa, I; Cristian, D

2013-01-01

Given the context that rectal tumours respond to a certain degree to radiotherapy, a necessity arises for estimating a tumour's capacity to react to radiation from the very moment of diagnostic biopsy. We have histologically and immunohistochemically analysed tissues coming from 52 patients with rectal adenocarcinomas. Of the studied parameters, the ones presenting significant variation under radiotherapy in terms of statistics(p 0.05) were: colloid type (p=0.001), EGFR in the tumour(p=0.00045), EGFR in the normal epithelium (p=0.0017),VEGF in the tumour (p=0.0132) and VEGF in the tumour stroma (p=0.030). Our study follows the same trends as the medical literature we have consulted regarding the variation of EGFR and VEGF with radiotherapy, and the distinct note of our study relies in the observation that normal stroma in case of rectal tumors also reacts to radiotherapy, sometimes more aggressively than the tumor itself, especially in which concerns the nerve and muscle fibers. Celsius.

TU-EF-304-05: Anterior Proton Beams for Prostate Treatments Lead to Substantial Elevations in Modeled RBE-Weighted Rectal Dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Underwood, T; Dept. Medical Physics and Bioengineering, University College London; Giantsoudi, D

2015-06-15

Purpose: If a constant RBE of 1.1 is assumed, range-verified anterior oblique (AO) proton beams appear to offer the potential to reduce the mean dose delivered to the rectum, anterior rectal wall and penile bulb by a factor of ∼2 relative to standard bilateral (SB) proton beam arrangements. Additionally, AO proton beams targeted at the prostate avoid the femoral heads and so form a particularly appealing option for patients with hip prostheses. This study investigates LET enhancement at the distal edge of AO SOBPs, applying RBE models to consider the extent to which AO beams lead to hotspots in rectummore » biological dose. Methods: Eight patients were selected, all treated with passively scattered, SB proton beams to 79.2Gy(E) within the prostate and 50.4Gy(E) within the proximal 5–15mm of seminal vesicles. Additional plans utilizing AO beams (±35°) were created in XiO (Elekta) assuming a fixed RBE of 1.1. Voxelised dose and LET distributions were calculated using Monte Carlo (TOPAS). Three different LET/RBE models were applied (Carabe 2012, Wedenberg 2013, McNamara 2015). Results: Across the eight patients, the mean LET within the rectal wall was found to be 3.5(3.2–4.0)keV/µm for the SB plans compared to 10.5(8.6–13.0)keV/µm for the AO plans. Application of the median LET/RBE model to the AO plans, rather than a fixed RBE of 1.1, resulted in an increase of 13.6(11.9–14.7)GyRBE in maximum rectal wall (1cc) RBEw dose, leading to values of 90.4(90.0–91.3)GyRBE. Conclusion: relative to SB proton beams, AO proton beams exhibit substantially increased mean LET values within the rectal wall. For the passively scattered AO beams, modeling indicates that this enhancement is likely to translate into unacceptable RBEw dose hotspots. Whilst no RBE- LET model has yet been fully validated in-vivo, caution must be applied if AO beams are to be considered for prostate patients.« less

A clinical trial of single dose rectal and oral administration of diazepam for the prevention of serial seizures in adult epileptic patients.

PubMed Central

Milligan, N M; Dhillon, S; Griffiths, A; Oxley, J; Richens, A

1984-01-01

The clinical anticonvulsant efficacy of single dose rectal and oral administration of diazepam 20 mg was examined in two double-blind placebo-controlled trials in adult epileptic patients. All subjects suffered from drug resistant epilepsy and frequently experienced serial seizures. Diazepam was administered rectally as a new experimental suppository formulation immediately after a seizure and was highly effective in preventing recurrent fits within a 24 h observation period (p less than 0.001). Pharmacokinetic studies revealed a wide range of serum diazepam concentrations 60 min after administration of the suppository (mean serum diazepam level 190 +/- 73 (SD ng/ml). In a similar study oral administration of diazepam 20 mg significantly reduced the incidence of serial seizures compared with a placebo (p less than 0.01) and the mean 60 min serum diazepam level was 273 +/- 190 (SD) ng/ml. PMID:6368753

Comparative study of late rectal toxicity in prostate cancer patients treated with low-dose-rate brachytherapy: With or without supplemental external beam radiotherapy.

PubMed

Serrano, Nicholas; Moghanaki, Drew; Asher, David; Karlin, Jeremy; Schutzer, Matthew; Chang, Michael; Hagan, Michael P

2016-01-01

Supplemental external beam radiation therapy (sEBRT) is often prescribed in men undergoing low-dose-rate (LDR) brachytherapy. A population of patients was analyzed to assess the effect of sEBRT on late rectal toxicity. It was hypothesized that sEBRT + LDR would be associated with a higher risk of late rectal toxicity. This retrospective cohort study examined LDR brachytherapy patients, treated with or without sEBRT, with a minimum of 5-year followup. Longitudinal assessments were evaluated using the computerized patient record system. The Kaplan-Meier method was used for analysis. Median followup was 7.5 years for 245 patients from 2004 to 2007. sEBRT was administered to 33.5%. Followup beyond 5 years was available for 89%. Overall rates of Grade ≥2 and ≥3 rectal toxicities were 6.9% and 2.9%, respectively. The risk of Grade ≥2 rectal toxicity was 2.8-fold higher for patients receiving sEBRT (95% confidence interval: 1.1-7.2; p = 0.02). The risk of Grade ≥3 rectal toxicity was 11.9-fold higher for patients who received sEBRT (1.5-97.4, 95% confidence interval; p = 0.003). Six of seven patients with a Grade ≥3 rectal toxicity received sEBRT, including one who required an abdominoperineal resection. Median post-LDR D90, V150, V200, and R100 values were 103.3%, 59.4%, 30.1%, and 0.5 cc. In a cohort of LDR brachytherapy patients with high rates of followup, sEBRT + LDR was associated with significantly higher risk of Grade ≥2 and ≥3 late rectal toxicity. This analysis supports previous findings and maintains concern about the supplemental use of external beam radiation therapy with LDR brachytherapy while its benefit for tumor control has yet to be prospectively validated. Published by Elsevier Inc.

Anti-inflammatory and anti-pyretic properties of Spirulina platensis and Spirulina lonar: a comparative study.

PubMed

Somchit, Muhammad Nazrul; Mohamed, Nor Azura; Ahmad, Zuraini; Zakaria, Zainul Amiruddin; Shamsuddin, Lokman; Omar-Fauzee, Mohd Sofian; Kadir, Arifah Abdul

2014-09-01

Spirulina spp. is a blue-green algae belongs to the family of Oscillatoriaceae, which having diverse biological activity. The aim of this current study was to evaluate and compare the anti-pyretic and anti-inflammatory activity of Spirulina platensis/SP and Spirulina lonar/SL extracts. In the anti-pyretic study, the ability to reduce the rectal temperature of rats induced pyrexia with 2g/kg Brewer's Yeast (BY) was performed. Rats were dosed either 2 or 4 mg/kg SP or SL. Rectal temperature was taken every hour for 8 hours. Results shown that there were significant dose-dependent (p<0.05) reduction of both treatments. However, SP treatment revealed faster reduction in rectal temperature. For anti-inflammatory activity, the reduction in the volume of paw edema induced by Prostaglandin E2 (100 IU/rat intraplantar) was measured. Rats were dosed orally with 2 or 4 mg/kg SP or SL. The paw edema was measured every 30 minutes for 4 hours using plethysmometer. Results had shown a significant dose dependent reduction in diameter of paw edema (p<0.05). The finding suggests that SP and SL extracts have anti-pyretic and anti-inflammatory properties. However, SP was found to be more effective than SL as anti-pyretic and anti-inflammatory agent.

Radiation Dose-Response Model for Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Appelt, Ane L., E-mail: ane.lindegaard.appelt@slb.regionsyddanmark.dk; University of Southern Denmark, Odense; Ploen, John

2013-01-01

Purpose: Preoperative chemoradiation therapy (CRT) is part of the standard treatment of locally advanced rectal cancers. Tumor regression at the time of operation is desirable, but not much is known about the relationship between radiation dose and tumor regression. In the present study we estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from themore » histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect of including clinical parameters in the model was examined. The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50% response, D{sub 50,i}, and the normalized dose-response gradient, {gamma}{sub 50,i}. Results: A highly significant dose-response relationship was found (P=.002). For complete response (TRG1), the dose-response parameters were D{sub 50,TRG1} = 92.0 Gy (95% confidence interval [CI] 79.3-144.9 Gy), {gamma}{sub 50,TRG1} = 0.982 (CI 0.533-1.429), and for major response (TRG1-2) D{sub 50,TRG1} and {sub 2} = 72.1 Gy (CI 65.3-94.0 Gy), {gamma}{sub 50,TRG1} and {sub 2} = 0.770 (CI 0.338-1.201). Tumor size and N category both had a significant effect on the dose-response relationships. Conclusions: This study demonstrated a significant dose-response relationship for tumor regression after preoperative CRT for locally advanced rectal cancer for tumor dose levels in the range of 50.4-70 Gy, which is higher than the dose range usually considered.« less

Image-guided method for TLD-based in vivo rectal dose verification with endorectal balloon in proton therapy for prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsi, Wen C.; Fagundes, Marcio; Zeidan, Omar

Purpose: To present a practical image-guided method to position an endorectal balloon that improves in vivo thermoluminiscent dosimeter (TLD) measurements of rectal doses in proton therapy for prostate cancer. Methods: TLDs were combined with endorectal balloons to measure dose at the anterior rectal wall during daily proton treatment delivery. Radiopaque metallic markers were employed as surrogates for balloon position reproducibility in rotation and translation. The markers were utilized to guide the balloon orientation during daily treatment employing orthogonal x-ray image-guided patient positioning. TLDs were placed at the 12 o'clock position on the anterior balloon surface at the midprostatic plane. Markersmore » were placed at the 3 and 9 o'clock positions on the balloon to align it with respect to the planned orientation. The balloon rotation along its stem axis, referred to as roll, causes TLD displacement along the anterior-posterior direction. The magnitude of TLD displacement is revealed by the separation distance between markers at opposite sides of the balloon on sagittal x-ray images. Results: A total of 81 in vivo TLD measurements were performed on six patients. Eighty-three percent of all measurements (65 TLD readings) were within +5% and -10% of the planning dose with a mean of -2.1% and a standard deviation of 3.5%. Examination of marker positions with in-room x-ray images of measured doses between -10% and -20% of the planned dose revealed a strong correlation between balloon roll and TLD displacement posteriorly from the planned position. The magnitude of the roll was confirmed by separations of 10-20 mm between the markers which could be corrected by manually adjusting the balloon position and verified by a repeat x-ray image prior to proton delivery. This approach could properly correct the balloon roll, resulting in TLD positioning within 2 mm along the anterior-posterior direction. Conclusions: Our results show that image-guided TLD-based in vivo dosimetry for rectal dose verification can be perfomed reliably and reproducibly for proton therapy in prostate cancer.« less

Image-guided method for TLD-based in vivo rectal dose verification with endorectal balloon in proton therapy for prostate cancer.

PubMed

Hsi, Wen C; Fagundes, Marcio; Zeidan, Omar; Hug, Eugen; Schreuder, Niek

2013-05-01

To present a practical image-guided method to position an endorectal balloon that improves in vivo thermoluminiscent dosimeter (TLD) measurements of rectal doses in proton therapy for prostate cancer. TLDs were combined with endorectal balloons to measure dose at the anterior rectal wall during daily proton treatment delivery. Radiopaque metallic markers were employed as surrogates for balloon position reproducibility in rotation and translation. The markers were utilized to guide the balloon orientation during daily treatment employing orthogonal x-ray image-guided patient positioning. TLDs were placed at the 12 o'clock position on the anterior balloon surface at the midprostatic plane. Markers were placed at the 3 and 9 o'clock positions on the balloon to align it with respect to the planned orientation. The balloon rotation along its stem axis, referred to as roll, causes TLD displacement along the anterior-posterior direction. The magnitude of TLD displacement is revealed by the separation distance between markers at opposite sides of the balloon on sagittal x-ray images. A total of 81 in vivo TLD measurements were performed on six patients. Eighty-three percent of all measurements (65 TLD readings) were within +5% and -10% of the planning dose with a mean of -2.1% and a standard deviation of 3.5%. Examination of marker positions with in-room x-ray images of measured doses between -10% and -20% of the planned dose revealed a strong correlation between balloon roll and TLD displacement posteriorly from the planned position. The magnitude of the roll was confirmed by separations of 10-20 mm between the markers which could be corrected by manually adjusting the balloon position and verified by a repeat x-ray image prior to proton delivery. This approach could properly correct the balloon roll, resulting in TLD positioning within 2 mm along the anterior-posterior direction. Our results show that image-guided TLD-based in vivo dosimetry for rectal dose verification can be perfomed reliably and reproducibly for proton therapy in prostate cancer.

Predicting Grade 3 Acute Diarrhea During Radiation Therapy for Rectal Cancer Using a Cutoff-Dose Logistic Regression Normal Tissue Complication Probability Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robertson, John M., E-mail: jrobertson@beaumont.ed; Soehn, Matthias; Yan Di

Purpose: Understanding the dose-volume relationship of small bowel irradiation and severe acute diarrhea may help reduce the incidence of this side effect during adjuvant treatment for rectal cancer. Methods and Materials: Consecutive patients treated curatively for rectal cancer were reviewed, and the maximum grade of acute diarrhea was determined. The small bowel was outlined on the treatment planning CT scan, and a dose-volume histogram was calculated for the initial pelvic treatment (45 Gy). Logistic regression models were fitted for varying cutoff-dose levels from 5 to 45 Gy in 5-Gy increments. The model with the highest LogLikelihood was used to developmore » a cutoff-dose normal tissue complication probability (NTCP) model. Results: There were a total of 152 patients (48% preoperative, 47% postoperative, 5% other), predominantly treated prone (95%) with a three-field technique (94%) and a protracted venous infusion of 5-fluorouracil (78%). Acute Grade 3 diarrhea occurred in 21%. The largest LogLikelihood was found for the cutoff-dose logistic regression model with 15 Gy as the cutoff-dose, although the models for 20 Gy and 25 Gy had similar significance. According to this model, highly significant correlations (p <0.001) between small bowel volumes receiving at least 15 Gy and toxicity exist in the considered patient population. Similar findings applied to both the preoperatively (p = 0.001) and postoperatively irradiated groups (p = 0.001). Conclusion: The incidence of Grade 3 diarrhea was significantly correlated with the volume of small bowel receiving at least 15 Gy using a cutoff-dose NTCP model.« less

Predictors of Toxicity After Image-guided High-dose-rate Interstitial Brachytherapy for Gynecologic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Larissa J.; Viswanathan, Akila N., E-mail: aviswanathan@lroc.harvard.edu

2012-12-01

Purpose: To identify predictors of grade 3-4 complications and grade 2-4 rectal toxicity after three-dimensional image-guided high-dose-rate (HDR) interstitial brachytherapy for gynecologic cancer. Methods and Materials: Records were reviewed for 51 women (22 with primary disease and 29 with recurrence) treated with HDR interstitial brachytherapy. A single interstitial insertion was performed with image guidance by computed tomography (n = 43) or magnetic resonance imaging (n = 8). The median delivered dose in equivalent 2-Gy fractions was 72.0 Gy (45 Gy for external-beam radiation therapy and 24 Gy for brachytherapy). Toxicity was reported according to the Common Toxicity Criteria for Adversemore » Events. Actuarial toxicity estimates were calculated by the Kaplan-Meier method. Results: At diagnosis, the median patient age was 62 years and the median tumor size was 3.8 cm. The median D90 and V100 were 71.4 Gy and 89.5%; the median D2cc for the bladder, rectum, and sigmoid were 64.6 Gy, 61.0 Gy, and 52.7 Gy, respectively. The actuarial rates of all grade 3-4 complications at 2 years were 20% gastrointestinal, 9% vaginal, 6% skin, 3% musculoskeletal, and 2% lymphatic. There were no grade 3-4 genitourinary complications and no grade 5 toxicities. Grade 2-4 rectal toxicity was observed in 10 patients, and grade 3-4 complications in 4; all cases were proctitis with the exception of 1 rectal fistula. D2cc for rectum was higher for patients with grade 2-4 (68 Gy vs 57 Gy for grade 0-1, P=.03) and grade 3-4 (73 Gy vs 58 Gy for grade 0-2, P=.02) rectal toxicity. The estimated dose that resulted in a 10% risk of grade 2-4 rectal toxicity was 61.8 Gy (95% confidence interval, 51.5-72.2 Gy). Discussion: Image-guided HDR interstitial brachytherapy results in acceptable toxicity for women with primary or recurrent gynecologic cancer. D2cc for the rectum is a reliable predictor of late rectal complications. Three-dimensional-based treatment planning should be performed to ensure adequate tumor coverage while minimizing the D2cc to the rectum.« less

Rectal 5-aminosalicylic acid for maintenance of remission in ulcerative colitis.

PubMed

Marshall, John K; Thabane, Marroon; Steinhart, A Hillary; Newman, Jamie R; Anand, Anju; Irvine, E Jan

2012-11-14

5-Aminosalicylic acid (5-ASA) is a first-line therapy for inducing and maintaining remission of mild and moderately active ulcerative colitis (UC). When the proximal margin of inflammation is distal to the splenic flexure, 5-ASA therapy can be delivered as a rectal suppository, foam or liquid enema. The primary objective was to assess the efficacy and safety of rectal 5-ASA for maintaining remission of distal UC. We searched MEDLINE (1966 to August 2012), the Cochrane Library (August 2012), abstracts from major gastroenterology meetings (1997-2011) and bibliographies of relevant publications to identify relevant studies. Eligible studies were randomized controlled trials comparing rectal 5-ASA to placebo or another active treatment for a minimum duration of six months. Symptom scores needed to be assessed in at least one study outcome. Patients had to be at least 12 years of age with disease extent less than 60 cm from the anal verge or distal to the splenic flexure, as determined by barium enema, colonoscopy or sigmoidoscopy. Patients were expected to be in remission prior to the treatment trial. Study eligibility was independently assessed by three authors. Data were extracted using standardized forms by two independent reviewers, with inter-rater agreement assessed using Cohen's Kappa and disagreements resolved by consensus. In cases where clarification of study results or methodology was needed, corresponding authors were contacted. The methodological quality of each trial was assessed by the Cochrane risk of bias tool and by a 30-point scale developed and used previously by the authors. Pooled risk ratios (RR) and corresponding 95% confidence intervals (CI) for continued clinical, endoscopic and histologic remission were estimated for comparisons between rectal 5-ASA and placebo or oral 5-ASA, and for comparisons among 5-ASA doses. Heterogeneity was assessed using the Chi(2) test and visual inspection of forest plots. If no significant heterogeneity was identified (P > 0.10 for Chi(2)) a fixed-effect model (Mantel-Haenstzel) was used. If heterogeneity was significant, a random-effects model was used. Nine studies (484 patients) met the pre-specified inclusion criteria (Kappa 1.00). Six studies were rated as low risk of bias. Three studies were rated as high risk of bias due to blinding (two open label and one single-blind). The total daily dose of rectal 5-ASA ranged from 0.5 g to 4 g, and dose frequency ranged from once to three times daily. 5-ASA was delivered as liquid enema in five studies or as a suppository in four studies. Follow-up ranged from 6 to 24 months. Rectal 5-ASA was significantly superior to placebo for maintenance of symptomatic remission over a period of 12 months.Sixty-two per cent of patients in the rectal 5-ASA group maintained symptomatic remission compared to 30% of patients in the placebo group (4 studies; 301 patients; RR 2.22, 95% CI 1.26 to 3.90; I(2) = 67%; P < 0.01). A GRADE analysis indicated that the overall quality of the evidence for the primary outcome was low due to imprecision (i.e. sparse data 144 events) and inconsistency (i.e. unexplained heterogeneity). Rectal 5-ASA was significantly superior to placebo for maintenance of endoscopic remission over a 12 month period. Seventy-five per cent of patients in the rectal 5-ASA group maintained endoscopic remission compared to 15% of patients in the placebo group (1 study; 25 patients; RR 4.88, 95% CI 1.31 to 18.18; P < 0.05). There was no statistically significant difference in the proportion of patients who experienced at least one adverse event. Sixteen per cent of patients in the rectal 5-ASA group experienced at least one adverse compared to 12% of placebo patients (2 studies; 160 patients; RR 1.35, 95% CI 0.63 to 2.89; I(2) = 0%; P = 0.44). The most commonly reported adverse events were anal irritation and abdominal pain. No statistically significant differences between rectal and oral 5-ASA were identified for either symptomatic or endoscopic remission over a period of six months. Eighty per cent of patients in the rectal 5-ASA group maintained symptomatic remission compared to 65% of patients in the oral 5-ASA group (2 studies; 69 patients; RR 1.24, 95% CI 0.92 to 1.66; I(2) = 0%; P = 0.15). A GRADE analysis indicated that the overall quality of the evidence for the primary outcome was low due to imprecision (i.e. sparse data 50 events) and high risk of bias (i.e. both studies in the pooled analysis were open label). Eighty per cent of patients in the rectal 5-ASA group maintained endoscopic remission compared to 70% of patients in the oral 5-ASA group (2 studies; 91 patients; RR 1.14, 95% CI 0.90 to 1.45; I(2) = 0%; P = 0.26). In two small trials, one comparing 2 g/day 5-ASA enemas to 4 g/day 5-ASA enemas and the other comparing 0.5 g/day 5-ASA suppositories to 1 g/day 5-ASA suppositories no dose response relationship was observed. The limited data available suggest that rectal 5-ASA is effective and safe for maintenance of remission of mild to moderately active distal UC. Well designed randomized trials are needed to establish the optimal dosing regimen for rectal 5-ASA, to compare rectal 5-ASA with rectal corticosteroids and to identify subgroups of patients who are more or less responsive to specific rectal 5-ASA regimens. The combination of oral and rectal 5-ASA appears to be more effective than either oral or rectal monotherapy for induction of remission. The efficacy of combination therapy for maintenance of remission has not been assessed and could be evaluated in future trials.

Bladder filling variation during conformal radiotherapy for rectal cancer

NASA Astrophysics Data System (ADS)

Sithamparam, S.; Ahmad, R.; Sabarudin, A.; Othman, Z.; Ismail, M.

2017-05-01

Conformal radiotherapy for rectal cancer is associated with small bowel toxicity mainly diarrhea. Treating patients with a full bladder is one of the practical solutions to reduce small bowel toxicity. Previous studies on prostate and cervix cancer patients revealed that maintaining consistent bladder volume throughout radiotherapy treatment is challenging. The aim of this study was to measure bladder volume variation throughout radiotherapy treatment. This study also measured the association between bladder volume changes and diarrhea. Twenty two rectal cancer patients were recruited prospectively. Patients were planned for treatment with full bladder following departmental bladder filling protocol and the planning bladder volume was measured during CT-simulation. During radiotherapy, the bladder volume was measured weekly using cone-beam computed tomography (CBCT) and compared to planning bladder volume. Incidence and severity of diarrhea were recorded during the weekly patient review. There was a negative time trend for bladder volume throughout five weeks treatment. The mean bladder volume decreased 18 % from 123 mL (SD 54 mL) during CT-simulation to 101 mL (SD 71 mL) on the 5th week of radiotherapy, but the decrease is not statistically significant. However, there was a large variation of bladder volume within each patient during treatment. This study showed an association between changes of bladder volume and diarrhea (P = 0.045). In conclusion bladder volume reduced throughout radiotherapy treatment for conformal radiotherapy for rectal cancer and there was a large variation of bladder volume within patients.

Comparison of 2D and 3D Imaging and Treatment Planning for Postoperative Vaginal Apex High-Dose Rate Brachytherapy for Endometrial Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Russo, James K.; Armeson, Kent E.; Richardson, Susan, E-mail: srichardson@radonc.wustl.edu

2012-05-01

Purpose: To evaluate bladder and rectal doses using two-dimensional (2D) and 3D treatment planning for vaginal cuff high-dose rate (HDR) in endometrial cancer. Methods and Materials: Ninety-one consecutive patients treated between 2000 and 2007 were evaluated. Seventy-one and 20 patients underwent 2D and 3D planning, respectively. Each patient received six fractions prescribed at 0.5 cm to the superior 3 cm of the vagina. International Commission on Radiation Units and Measurements (ICRU) doses were calculated for 2D patients. Maximum and 2-cc doses were calculated for 3D patients. Organ doses were normalized to prescription dose. Results: Bladder maximum doses were 178% ofmore » ICRU doses (p < 0.0001). Two-cubic centimeter doses were no different than ICRU doses (p = 0.22). Two-cubic centimeter doses were 59% of maximum doses (p < 0.0001). Rectal maximum doses were 137% of ICRU doses (p < 0.0001). Two-cubic centimeter doses were 87% of ICRU doses (p < 0.0001). Two-cubic centimeter doses were 64% of maximum doses (p < 0.0001). Using the first 1, 2, 3, 4 or 5 fractions, we predicted the final bladder dose to within 10% for 44%, 59%, 83%, 82%, and 89% of patients by using the ICRU dose, and for 45%, 55%, 80%, 85%, and 85% of patients by using the maximum dose, and for 37%, 68%, 79%, 79%, and 84% of patients by using the 2-cc dose. Using the first 1, 2, 3, 4 or 5 fractions, we predicted the final rectal dose to within 10% for 100%, 100%, 100%, 100%, and 100% of patients by using the ICRU dose, and for 60%, 65%, 70%, 75%, and 75% of patients by using the maximum dose, and for 68%, 95%, 84%, 84%, and 84% of patients by using the 2-cc dose. Conclusions: Doses to organs at risk vary depending on the calculation method. In some cases, final dose accuracy appears to plateau after the third fraction, indicating that simulation and planning may not be necessary in all fractions. A clinically relevant level of accuracy should be determined and further research conducted to address this issue.« less

Alterations in Hormone Levels After Adjuvant Chemoradiation in Male Rectal Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoon, Frederick H.; Perera, Francisco; Fisher, Barbara

Purpose: To evaluate follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels after postoperative chemoradiation in men with rectal cancer. Methods and Materials: Forty-three men with rectal cancer had baseline and postchemoradiation FSH, LH, and testosterone measured. Adjuvant chemoradiation consisted of two 5-day cycles of bolus 5-fluorouracil (5-FU) every 4 weeks at a dose of 500 mg/m{sup 2}/d followed by concurrent chemoradiation followed by two additional 5-day cycles of 5-FU at a dose of 450 mg/m{sup 2}/d. Continuous-infusion 5-FU at 225 mg/m{sup 2}/d was given during radiation. Pelvic radiation consisted of a three- or four-field technique with a median dosemore » of 54.0 Gy in 30 fractions. Results: Median follow-up was 6.1 years. Mean baseline FSH levels increased from 5.3 to a peak of 23.9 IU/L (p < 0.001) 13-24 months after chemoradiation. Mean baseline LH levels increased from 4.3 to a peak of 8.5 IU/L (p < 0.001) within 6 months after chemoradiation. Mean testosterone levels decreased from 15.4 nmol/L at baseline to 8.0 nmol/L more than 4 years after chemoradiation. Mean testosterone to mean LH ratio decreased from 4.4 at baseline to 1.1 after 48 months posttreatment, suggesting a continued decrease in Leydig cell function with time. Testicular dose was measured in 5 patients. Median dose was 4 Gy (range, 1.5-8.9 Gy). Conclusions: Chemoradiation in men with rectal cancer causes persistent increases in FSH and LH levels and decreases in testosterone levels.« less

Dosimetric effects of endorectal balloons on intensity-modulated radiation therapy plans for prostate cancer

NASA Astrophysics Data System (ADS)

Kim, Jae-Sung; Chung, Jin-Beom; Kim, In-Ah; Eom, Keun-Yong

2013-10-01

We used an endorectal balloon (ERB) for prostate immobilization during intensity-modulated radiotherapy (IMRT) for prostate cancer treatment. To investigate the dosimetric effects of ERB-filling materials, we changed the ERB Hounsfield unit (HU) from 0 to 1000 HU in 200-HU intervals to simulate the various ERB fillings; 0 HU simulated a water-filled ERB, and 1000 HU simulated the densest material-filled ERB. Dosimetric data (coverage, homogeneity, conformity, maximal dose, and typical volume dose) for the tumor and the organs at risk (OARs) were evaluated in prostate IMRT treatment plans with 6-MV and 15-MV beams. The tumor coverage appeared to differ by approximately 1%, except for the clinical target volume (CTV) V100% and the planning target volume (PTV) V100%. The largest difference for the various ERB fillings was observed in the PTV V100%. In spite of increasing HU, the prostate IMRT plans at both energies had relatively low dosimetric effects on the PTV and the CTV. However, the maximal and the typical volume doses (D25%, D30%, and D50%) to the rectal wall and the bladder increased with increasing HU. For an air-filled ERB, the maximal doses to the rectal wall and the monitor units were lower than the corresponding values for the water-filled and the densest material-filled ERBs. An air-filled ERB spared the rectal wall because of its dosimetric effect. Thus, we conclude that the use of an air-filled ERB provides a dosimetric benefit to the rectal wall without a loss of target coverage and is an effective option for prostate IMRT treatment.

Failure of evidence-based cancer care in the United States: the association between rectal cancer treatment, cancer center volume, and geography.

PubMed

Monson, John R T; Probst, Christian P; Wexner, Steven D; Remzi, Feza H; Fleshman, James W; Garcia-Aguilar, Julio; Chang, George J; Dietz, David W

2014-10-01

This study examines recent adherence to recommended neoadjuvant chemoradiotherapy guidelines for patients with rectal cancer across geographic regions and institution volume and assesses trends over time. A recent report by the Institute of Medicine described US cancer care as chaotic. Cited deficiencies included wide variation in adherence to evidence-based guidelines even where clear consensus exists. Patients operated on for clinical stage II and III rectal cancer were selected from the 2006-2011 National Cancer Data Base. Multivariable logistic regressions were used to assess variation in chemotherapy and radiation use by cancer center type, geographical location, and hospital volume. The analysis controlled for patient age at diagnosis, sex, race/ethnicity, primary payer, average household income, average education, urban/rural classification of patient residence, comorbidity, and oncologic stage. There were 30,994 patients who met the inclusion criteria. Use of neoadjuvant radiation therapy and chemotherapy varied significantly by type of cancer center. The highest rates of adherence were observed in high-volume centers compared with low-volume centers (78% vs 69%; adjusted odds ratio = 1.46; P < 0.001). This variation is mirrored by hospital geographic location. Primary payer and year of diagnosis were not predictive of rates of neoadjuvant chemoradiotherapy. Adherence to evidence-based treatment guidelines in rectal cancer is suboptimal in the United States, with significant differences based on hospital volume and geographic regions. Little improvement has occurred in the last 5 years. These results support the implementation of standardized care pathways and a Centers of Excellence program for US patients with rectal cancer.

Iterative dataset optimization in automated planning: Implementation for breast and rectal cancer radiotherapy.

PubMed

Fan, Jiawei; Wang, Jiazhou; Zhang, Zhen; Hu, Weigang

2017-06-01

To develop a new automated treatment planning solution for breast and rectal cancer radiotherapy. The automated treatment planning solution developed in this study includes selection of the iterative optimized training dataset, dose volume histogram (DVH) prediction for the organs at risk (OARs), and automatic generation of clinically acceptable treatment plans. The iterative optimized training dataset is selected by an iterative optimization from 40 treatment plans for left-breast and rectal cancer patients who received radiation therapy. A two-dimensional kernel density estimation algorithm (noted as two parameters KDE) which incorporated two predictive features was implemented to produce the predicted DVHs. Finally, 10 additional new left-breast treatment plans are re-planned using the Pinnacle 3 Auto-Planning (AP) module (version 9.10, Philips Medical Systems) with the objective functions derived from the predicted DVH curves. Automatically generated re-optimized treatment plans are compared with the original manually optimized plans. By combining the iterative optimized training dataset methodology and two parameters KDE prediction algorithm, our proposed automated planning strategy improves the accuracy of the DVH prediction. The automatically generated treatment plans using the dose derived from the predicted DVHs can achieve better dose sparing for some OARs without compromising other metrics of plan quality. The proposed new automated treatment planning solution can be used to efficiently evaluate and improve the quality and consistency of the treatment plans for intensity-modulated breast and rectal cancer radiation therapy. © 2017 American Association of Physicists in Medicine.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chapet, Olivier, E-mail: olivier.chapet@chu-lyon.fr; Udrescu, Corina; Department of Medical Physics, Centre Hospitalier Lyon Sud, Pierre Benite

Purpose: The aim of this study was to evaluate the contribution of an injection of hyaluronic acid (HA) between the rectum and the prostate for reducing the dose to the rectal wall in a hypofractionated irradiation for prostate cancer. Methods and Materials: In a phase 2 study, 10 cc of HA was injected between the rectum and prostate. For 16 patients, the same intensity modulated radiation therapy plan (62 Gy in 20 fractions) was optimized on 2 computed tomography scans: CT1 (before injection) and CT2 (after injection). Rectal parameters were compared: dose to 2.5 cc (D2.5), 5 cc (D5), 10more » cc (D10), 15 cc (D15), and 20 cc (D20) of rectal wall and volume of rectum covered by the 90% isodose line (V90), 80% (V80), 70% (V70), 60% (V60), and 50% (V50). Results: The mean V90, V80, V70, V60, and V50 values were reduced by 73.8% (P<.0001), 55.7% (P=.0003), 43.0% (P=.007), 34% (P=.002), and 25% (P=.036), respectively. The average values of D2.5, D5, D10, D15, and D20 were reduced by 8.5 Gy (P<.0001), 12.3 Gy (P<.0001), 8.4 Gy (P=.005), 3.7 Gy (P=.026), and 1.2 Gy (P=.25), respectively. Conclusions: The injection of HA significantly limited radiation doses to the rectal wall.« less

Intensity modulated radiation therapy (IMRT): differences in target volumes and improvement in clinically relevant doses to small bowel in rectal carcinoma.

PubMed

Mok, Henry; Crane, Christopher H; Palmer, Matthew B; Briere, Tina M; Beddar, Sam; Delclos, Marc E; Krishnan, Sunil; Das, Prajnan

2011-06-08

A strong dose-volume relationship exists between the amount of small bowel receiving low- to intermediate-doses of radiation and the rates of acute, severe gastrointestinal toxicity, principally diarrhea. There is considerable interest in the application of highly conformal treatment approaches, such as intensity-modulated radiation therapy (IMRT), to reduce dose to adjacent organs-at-risk in the treatment of carcinoma of the rectum. Therefore, we performed a comprehensive dosimetric evaluation of IMRT compared to 3-dimensional conformal radiation therapy (3DCRT) in standard, preoperative treatment for rectal cancer. Using RTOG consensus anorectal contouring guidelines, treatment volumes were generated for ten patients treated preoperatively at our institution for rectal carcinoma, with IMRT plans compared to plans derived from classic anatomic landmarks, as well as 3DCRT plans treating the RTOG consensus volume. The patients were all T3, were node-negative (N = 1) or node-positive (N = 9), and were planned to a total dose of 45-Gy. Pairwise comparisons were made between IMRT and 3DCRT plans with respect to dose-volume histogram parameters. IMRT plans had superior PTV coverage, dose homogeneity, and conformality in treatment of the gross disease and at-risk nodal volume, in comparison to 3DCRT. Additionally, in comparison to the 3DCRT plans, IMRT achieved a concomitant reduction in doses to the bowel (small bowel mean dose: 18.6-Gy IMRT versus 25.2-Gy 3DCRT; p = 0.005), bladder (V40Gy: 56.8% IMRT versus 75.4% 3DCRT; p = 0.005), pelvic bones (V40Gy: 47.0% IMRT versus 56.9% 3DCRT; p = 0.005), and femoral heads (V40Gy: 3.4% IMRT versus 9.1% 3DCRT; p = 0.005), with an improvement in absolute volumes of small bowel receiving dose levels known to induce clinically-relevant acute toxicity (small bowel V15Gy: 138-cc IMRT versus 157-cc 3DCRT; p = 0.005). We found that the IMRT treatment volumes were typically larger than that covered by classic bony landmark-derived fields, without incurring penalty with respect to adjacent organs-at-risk. For rectal carcinoma, IMRT, compared to 3DCRT, yielded plans superior with respect to target coverage, homogeneity, and conformality, while lowering dose to adjacent organs-at-risk. This is achieved despite treating larger volumes, raising the possibility of a clinically-relevant improvement in the therapeutic ratio through the use of IMRT with a belly-board apparatus.

TU-AB-201-07: Image Guided Endorectal HDR Brachytherapy Using a Compliant Balloon Applicator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cohen, G; Goodman, K

2015-06-15

Purpose: High dose rate endorectal brachytherapy is an option to deliver a focal, high-dose radiotherapy to rectal tumors for patients undergoing non-operative management. We investigate a new multichannel, MR compatible applicator with a novel balloon-based design to provide improved treatment geometry. We report on the initial clinical experience using this applicator. Methods: Patients were enrolled on an IRB-approved, dose-escalation protocol evaluating the use of the anorectal (AR-1) applicator (Ancer Medical, Hialeah, FL), a multichannel applicator with two concentric balloons. The inner balloon supports 8 source lumens; the compliant outer balloon expands to separate the normal rectal wall and the sourcemore » lumens, yet deforms around a firm, exophytic rectal mass, leading to dose escalation to tumor while sparing normal rectum. Under general anesthesia, gold fiducial markers were inserted above and below the tumor, and the AR applicator was placed in the rectum. MRI-based treatment plans were prepared to deliver 15 Gy in 3 weekly fractions to the target volume while sparing healthy rectal tissue, bladder, bowel and anal muscles. Prior to each treatment, CBCT/Fluoroscopy were used to place the applicator in the treatment position and confirm the treatment geometry using rigid registration of the CBCT and planning MRI. After registration of the applicator images, positioning was evaluated based on the match of the gold markers. Results: Highly conformal treatment plans were achieved. MR compatibility of the applicator enabled good tumor visualization. In spite of the non-rigid nature of the applicators and the fact that a new applicator was used at each treatment session, treatment geometry was reproducible to within 2.5 mm. Conclusions: This is the first report on using the AR applicator in patients. Highly conformal plans, confidence in MRI target delineation, in combination with reproducible treatment geometry provide encouraging feedback for continuation with dose escalation in these patients.« less

Accuracy of Monte Carlo simulations compared to in-vivo MDCT dosimetry.

PubMed

Bostani, Maryam; Mueller, Jonathon W; McMillan, Kyle; Cody, Dianna D; Cagnon, Chris H; DeMarco, John J; McNitt-Gray, Michael F

2015-02-01

The purpose of this study was to assess the accuracy of a Monte Carlo simulation-based method for estimating radiation dose from multidetector computed tomography (MDCT) by comparing simulated doses in ten patients to in-vivo dose measurements. MD Anderson Cancer Center Institutional Review Board approved the acquisition of in-vivo rectal dose measurements in a pilot study of ten patients undergoing virtual colonoscopy. The dose measurements were obtained by affixing TLD capsules to the inner lumen of rectal catheters. Voxelized patient models were generated from the MDCT images of the ten patients, and the dose to the TLD for all exposures was estimated using Monte Carlo based simulations. The Monte Carlo simulation results were compared to the in-vivo dose measurements to determine accuracy. The calculated mean percent difference between TLD measurements and Monte Carlo simulations was -4.9% with standard deviation of 8.7% and a range of -22.7% to 5.7%. The results of this study demonstrate very good agreement between simulated and measured doses in-vivo. Taken together with previous validation efforts, this work demonstrates that the Monte Carlo simulation methods can provide accurate estimates of radiation dose in patients undergoing CT examinations.

The curative management of synchronous rectal and prostate cancer

PubMed Central

Kavanagh, Dara O; Martin, Joseph; Small, Cormac; Joyce, Myles R; Faul, Clare M; Kelly, Paul J; O'Riordain, Michael; Gillham, Charles M; Armstrong, John G; Salib, Osama; McNamara, Deborah A; McVey, Gerard; O'Neill, Brian D P

2016-01-01

Objective: Neoadjuvant “long-course” chemoradiation is considered a standard of care in locally advanced rectal cancer. In addition to prostatectomy, external beam radiotherapy and brachytherapy with or without androgen suppression (AS) are well established in prostate cancer management. A retrospective review of ten cases was completed to explore the feasibility and safety of applying these standards in patients with dual pathology. To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. Methods: Eligible patients had synchronous histologically proven locally advanced rectal cancer (defined as cT3-4Nx; cTxN1-2) and non-metastatic prostate cancer (pelvic nodal disease permissible). Curative treatment was delivered to both sites simultaneously. Follow-up was as per institutional guidelines. Acute and late toxicities were reviewed, and a literature search performed. Results: Pelvic external beam radiotherapy (RT) 45–50.4 Gy was delivered concurrent with 5-fluorouracil (5FU). Prostate total dose ranged from 70.0 to 79.2 Gy. No acute toxicities occurred, excluding AS-induced erectile dysfunction. Nine patients proceeded to surgery, and one was managed expectantly. Three relapsed with metastatic colorectal cancer, two with metastatic prostate cancer. Five patients have no evidence of recurrence, and four remain alive with metastatic disease. With a median follow-up of 2.2 years (range 1.2–6.3 years), two significant late toxicities occurred; G3 proctitis in a patient receiving palliative bevacizumab and a G3 anastomotic stricture precluding stoma reversal. Conclusion: Patients proceeding to synchronous radical treatment of both primary sites should receive 45–50.4 Gy pelvic RT with infusional 5FU. Prostate dose escalation should be given with due consideration to the potential impact of prostate cancer on patient survival, as increasing dose may result in significant late morbidity. Review of published series explores the possibility of prostate brachytherapy as an alternative method of boost delivery. Frequent use of bevacizumab in metastatic rectal cancer may compound late rectal morbidity in this cohort. Advances in knowledge: To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. This article contributes to the understanding of how best to approach definitive treatment in these patients. PMID:26539631

Localized volume effects for late rectal and anal toxicity after radiotherapy for prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peeters, Stephanie T.H.; Lebesque, Joos V.; Heemsbergen, Wilma D.

2006-03-15

Purpose: To identify dosimetric parameters derived from anorectal, rectal, and anal wall dose distributions that correlate with different late gastrointestinal (GI) complications after three-dimensional conformal radiotherapy for prostate cancer. Methods and Materials: In this analysis, 641 patients from a randomized trial (68 Gy vs. 78 Gy) were included. Toxicity was scored with adapted Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer (RTOG/EORTC) criteria and five specific complications. The variables derived from dose-volume histogram of anorectal, rectal, and anal wall were as follows: % receiving {>=}5-70 Gy (V5-V70), maximum dose (D{sub max}), and mean dose (D{sub mean}).more » The anus was defined as the most caudal 3 cm of the anorectum. Statistics were done with multivariate Cox regression models. Median follow-up was 44 months. Results: Anal dosimetric variables were associated with RTOG/EORTC Grade {>=}2 (V5-V40, D{sub mean}) and incontinence (V5-V70, D{sub mean}). Bleeding correlated most strongly with anorectal V55-V65, and stool frequency with anorectal V40 and D{sub mean}. Use of steroids was weakly related to anal variables. No volume effect was seen for RTOG/EORTC Grade {>=}3 and pain/cramps/tenesmus. Conclusion: Different volume effects were found for various late GI complications. Therefore, to evaluate the risk of late GI toxicity, not only intermediate and high doses to the anorectal wall volume should be taken into account, but also the dose to the anal wall.« less

Evaluating the prophylactic potential of zafirlukast against the toxic effects of acetic acid on the rat colon.

PubMed

Mahgoub, Afaf A; El-Medany, Azza A; Hager, Hanan H; Mustafa, Ali A; El-Sabah, Doryia M

2003-11-01

The present work was conducted to assess the possible protective effects of zafirlukast against the toxic damage induced by acetic acid in rat colon. Zafirlukast is a potent and selective cysteinyl leukotriene receptor antagonist which is used mainly in the prophylaxis of bronchial asthma. Two doses of zafirlukast were used (40 and 80 mg/kg) dissolved in gum acacia and given either orally or rectally (0.5 ml/kg). Several parameters including, macroscopic score, histopathological and biochemical such as malondialdehyde (MDA), myeloperoxidase (MPO), catalase and reduced glutathione (GSH) levels were measured using standard assay procedures. The study showed that pretreatment with zafirlukast in a dose of 80 mg/kg orally produced a significant decrease in tissue malondialdehyde, myeloperoxidase, and an increase in both reduced glutathione and catalase levels, while there was no significant changes with the rectal route. The 40 mg/kg dose had no significant protective effects when given either orally or rectally. The available data indicate that the inhibition of leukotriene synthesis or action may have a role in inflammatory bowel disease (IBD) as they are considered as important mediators in this condition.

Vaccine-induced T cells Provide Partial Protection Against High-dose Rectal SIVmac239 Challenge of Rhesus Macaques

PubMed Central

Lasaro, Marcio O; Haut, Larissa H; Zhou, Xiangyang; Xiang, Zhiquan; Zhou, Dongming; Li, Yan; Giles-Davis, Wynetta; Li, Hua; Engram, Jessica C; DiMenna, Lauren J; Bian, Ang; Sazanovich, Marina; Parzych, Elizabeth M; Kurupati, Raj; Small, Juliana C; Wu, Te-Lang; Leskowitz, Rachel M; Klatt, Nicole R; Brenchley, Jason M; Garber, David A; Lewis, Mark; Ratcliffe, Sarah J; Betts, Michael R; Silvestri, Guido; Ertl, Hildegund C

2011-01-01

Despite enormous efforts by the scientific community, an effective HIV vaccine remains elusive. To further address to what degree T cells in absence of antibodies may protect against simian immunodeficiency virus (SIV) disease progression, rhesus macaques were vaccinated intramuscularly with a chimpanzee-derived Ad vector (AdC) serotype 6 and then boosted intramuscularly with a serologically distinct AdC vector of serotype 7 both expressing Gag of SIVmac239. Animals were subsequently boosted intramuscularly with a modified vaccinia Ankara (MVA) virus expressing Gag and Tat of the homologous SIV before mucosal challenge with a high dose of SIVmac239 given rectally. Whereas vaccinated animals showed only a modest reduction of viral loads, their overall survival was improved, in association with a substantial protection from the loss of CD4+ T cells. In addition, the two vaccinated Mamu-A*01+ macaques controlled viral loads to levels below detection within weeks after challenge. These data strongly suggest that T cells, while unable to affect SIV acquisition upon high-dose rectal infection, can reduce disease progression. Induction of potent T-cell responses should thus remain a component of our efforts to develop an efficacious vaccine to HIV-1. PMID:21081905

Vaccine-induced T cells provide partial protection against high-dose rectal SIVmac239 challenge of rhesus macaques.

PubMed

Lasaro, Marcio O; Haut, Larissa H; Zhou, Xiangyang; Xiang, Zhiquan; Zhou, Dongming; Li, Yan; Giles-Davis, Wynetta; Li, Hua; Engram, Jessica C; Dimenna, Lauren J; Bian, Ang; Sazanovich, Marina; Parzych, Elizabeth M; Kurupati, Raj; Small, Juliana C; Wu, Te-Lang; Leskowitz, Rachel M; Klatt, Nicole R; Brenchley, Jason M; Garber, David A; Lewis, Mark; Ratcliffe, Sarah J; Betts, Michael R; Silvestri, Guido; Ertl, Hildegund C

2011-02-01

Despite enormous efforts by the scientific community, an effective HIV vaccine remains elusive. To further address to what degree T cells in absence of antibodies may protect against simian immunodeficiency virus (SIV) disease progression, rhesus macaques were vaccinated intramuscularly with a chimpanzee-derived Ad vector (AdC) serotype 6 and then boosted intramuscularly with a serologically distinct AdC vector of serotype 7 both expressing Gag of SIVmac239. Animals were subsequently boosted intramuscularly with a modified vaccinia Ankara (MVA) virus expressing Gag and Tat of the homologous SIV before mucosal challenge with a high dose of SIVmac239 given rectally. Whereas vaccinated animals showed only a modest reduction of viral loads, their overall survival was improved, in association with a substantial protection from the loss of CD4(+) T cells. In addition, the two vaccinated Mamu-A*01(+) macaques controlled viral loads to levels below detection within weeks after challenge. These data strongly suggest that T cells, while unable to affect SIV acquisition upon high-dose rectal infection, can reduce disease progression. Induction of potent T-cell responses should thus remain a component of our efforts to develop an efficacious vaccine to HIV-1.

Dosimetric comparison of IMRT rectal and anal canal plans generated using an anterior dose avoidance structure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leicher, Brian, E-mail: bleicher@wpahs.org; Day, Ellen; Colonias, Athanasios

2014-10-01

To describe a dosimetric method using an anterior dose avoidance structure (ADAS) during the treatment planning process for intensity-modulated radiation therapy (IMRT) for patients with anal canal and rectal carcinomas. A total of 20 patients were planned on the Elekta/CMS XiO treatment planning system, version 4.5.1 (Maryland Heights MO) with a superposition algorithm. For each patient, 2 plans were created: one employing an ADAS (ADAS plan) and the other replanned without an ADAS (non-ADAS plan). The ADAS was defined to occupy the volume between the inguinal nodes and primary target providing a single organ at risk that is completely outsidemore » of the target volume. Each plan used the same beam parameters and was analyzed by comparing target coverage, overall plan dose conformity using a conformity number (CN) equation, bowel dose-volume histograms, and the number of segments, daily treatment duration, and global maximum dose. The ADAS and non-ADAS plans were equivalent in target coverage, mean global maximum dose, and sparing of small bowel in low-dose regions (5, 10, 15, and 20 Gy). The mean difference between the CN value for the non-ADAS plans and ADAS plans was 0.04 ± 0.03 (p < 0.001). The mean difference in the number of segments was 15.7 ± 12.7 (p < 0.001) in favor of ADAS plans. The ADAS plan delivery time was shorter by 2.0 ± 1.5 minutes (p < 0.001) than the non-ADAS one. The ADAS has proven to be a powerful tool when planning rectal and anal canal IMRT cases with critical structures partially contained inside the target volume.« less

Phase I Trial of Neoadjuvant Preoperative Chemotherapy With S-1 and Irinotecan Plus Radiation in Patients With Locally Advanced Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sato, Takeo; Kokuba, Yukihito; Koizumi, Wasaburo

Purpose: To determine the maximum tolerated dose (MTD) and recommended dose (RD) of irinotecan combined with preoperative chemoradiotherapy with S-1 in patients with locally advanced rectal cancer. Patients and Methods: We gave preoperative radiotherapy (total dose, 45 Gy) to 23 patients with locally advanced (T3/T4) rectal cancer. Concurrently, S-1 was given orally at a fixed dose of 80 mg/m{sup 2}/day on Days 1-5, 8-12, 22-26, and 29-33, and irinotecan was given as a 90-min continuous i.v. infusion on Days 1, 8, 22, and 29. The dose of irinotecan was initially 40 mg/m{sup 2}/day and gradually increased to determine the MTDmore » and RD of this regimen. Results: Among the 4 patients who received 90 mg/m{sup 2} irinotecan, 2 had Grade 4 neutropenia and 1 had Grade 3 diarrhea. Because dose-limiting toxicity (DLT) occurred in 3 of the 4 patients, 90 mg/m{sup 2} irinotecan was designated as the MTD. Consequently, 80 mg/m{sup 2} irinotecan was given to 7 additional patients, with no DLT, and this was considered the RD. Of the patients who received irinotecan at the RD or lower doses, 6 (31.6%) had a complete pathologic response (Grade 3) and 9 (47.4%) underwent sphincter-preserving surgery. Conclusions: With our new regimen, the MTD of irinotecan was 90 mg/m{sup 2}, and the RD of irinotecan for Phase II studies was 80 mg/m{sup 2}. Although our results are preliminary, this new neoadjuvant chemoradiotherapy was considered safe and active, meriting further investigation in Phase II studies.« less

A comparative study of set up variations and bowel volumes in supine versus prone positions of patients treated with external beam radiation for carcinoma rectum.

PubMed

Rajeev, K R; Menon, Smrithy S; Beena, K; Holla, Raghavendra; Kumar, R Rajaneesh; Dinesh, M

2014-01-01

A prospective study was undertaken to evaluate the influence of patient positioning on the set up variations to determine the planning target volume (PTV) margins and to evaluate the clinical relevance volume assessment of the small bowel (SB) within the irradiated volume. During the period of months from December 2011 to April 2012, a computed tomography (CT) scan was done either in supine position or in prone position using a belly board (BB) for 20 consecutive patients. All the patients had histologically proven rectal cancer and received either post- or pre-operative pelvic irradiation. Using a three-dimensional planning system, the dose-volume histogram for SB was defined in each axial CT slice. Total dose was 46-50 Gy (2 Gy/fraction), delivered using the 4-field box technique. The set up variation of the study group was assessed from the data received from the electronic portal imaging device in the linear accelerator. The shift along X, Y, and Z directions were noted. Both systematic and random errors were calculated and using both these values the PTV margin was calculated. The systematic errors of patients treated in the supine position were 0.87 (X-mm), 0.66 (Y-mm), 1.6 (Z-mm) and in the prone position were 1.3 (X-mm), 0.59 (Y-mm), 1.17 (Z-mm). The random errors of patients treated in the supine positions were 1.81 (X-mm), 1.73 (Y-mm), 1.83 (Z-mm) and in prone position were 2.02 (X-mm), 1.21 (Y-mm), 3.05 (Z-mm). The calculated PTV margins in the supine position were 3.45 (X-mm), 2.87 (Y-mm), 5.31 (Z-mm) and in the prone position were 4.91 (X-mm), 2.32 (Y-mm), 5.08 (Z-mm). The mean volume of the peritoneal cavity was 648.65 cm 3 in the prone position and 1197.37 cm 3 in the supine position. The prone position using BB device was more effective in reducing irradiated SB volume in rectal cancer patients. There were no significant variations in the daily set up for patients treated in both supine and prone positions.

The Benefits of Including Clinical Factors in Rectal Normal Tissue Complication Probability Modeling After Radiotherapy for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Defraene, Gilles, E-mail: gilles.defraene@uzleuven.be; Van den Bergh, Laura; Al-Mamgani, Abrahim

2012-03-01

Purpose: To study the impact of clinical predisposing factors on rectal normal tissue complication probability modeling using the updated results of the Dutch prostate dose-escalation trial. Methods and Materials: Toxicity data of 512 patients (conformally treated to 68 Gy [n = 284] and 78 Gy [n = 228]) with complete follow-up at 3 years after radiotherapy were studied. Scored end points were rectal bleeding, high stool frequency, and fecal incontinence. Two traditional dose-based models (Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) and a logistic model were fitted using a maximum likelihood approach. Furthermore, these model fits were improved by including themore » most significant clinical factors. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminating ability of all fits. Results: Including clinical factors significantly increased the predictive power of the models for all end points. In the optimal LKB, RS, and logistic models for rectal bleeding and fecal incontinence, the first significant (p = 0.011-0.013) clinical factor was 'previous abdominal surgery.' As second significant (p = 0.012-0.016) factor, 'cardiac history' was included in all three rectal bleeding fits, whereas including 'diabetes' was significant (p = 0.039-0.048) in fecal incontinence modeling but only in the LKB and logistic models. High stool frequency fits only benefitted significantly (p = 0.003-0.006) from the inclusion of the baseline toxicity score. For all models rectal bleeding fits had the highest AUC (0.77) where it was 0.63 and 0.68 for high stool frequency and fecal incontinence, respectively. LKB and logistic model fits resulted in similar values for the volume parameter. The steepness parameter was somewhat higher in the logistic model, also resulting in a slightly lower D{sub 50}. Anal wall DVHs were used for fecal incontinence, whereas anorectal wall dose best described the other two endpoints. Conclusions: Comparable prediction models were obtained with LKB, RS, and logistic NTCP models. Including clinical factors improved the predictive power of all models significantly.« less

Estimates of the pharmacokinetics of famciclovir and its active metabolite penciclovir in young Asian elephants (Elephas maximus).

PubMed

Brock, A Paige; Isaza, Ramiro; Hunter, Robert P; Richman, Laura K; Montali, Richard J; Schmitt, Dennis L; Koch, David E; Lindsay, William A

2012-12-01

To determine plasma pharmacokinetics of penciclovir following oral and rectal administration of famciclovir to young Asian elephants (Elephas maximus). 6 healthy Asian elephants (5 females and 1 male), 4.5 to 9 years old and weighing 1,646 to 2,438 kg. Famciclovir was administered orally or rectally in accordance with an incomplete crossover design. Three treatment groups, each comprising 4 elephants, received single doses of famciclovir (5 mg/kg, PO, or 5 or 15 mg/kg, rectally); there was a minimum 12-week washout period between subsequent famciclovir administrations. Serial blood samples were collected after each administration. Samples were analyzed for famciclovir and penciclovir with a validated liquid chromatography-mass spectroscopy assay. Famciclovir was tolerated well for both routes of administration and underwent complete biotransformation to the active metabolite, penciclovir. Mean maximum plasma concentration of penciclovir was 1.3 μg/mL at 1.1 hours after oral administration of 5 mg/kg. Similar results were detected after rectal administration of 5 mg/kg. Mean maximum plasma concentration was 3.6 μg/mL at 0.66 hours after rectal administration of 15 mg/kg; this concentration was similar to results reported for humans receiving 7 mg/kg orally. Juvenile Asian elephants are susceptible to elephant endotheliotropic herpesvirus. Although most infections are fatal, case reports indicate administration of famciclovir has been associated with survival of 3 elephants. In Asian elephants, a dose of 8 to 15 mg of famciclovir/kg given orally or rectally at least every 8 hours may result in penciclovir concentrations that are considered therapeutic in humans.

SU-F-T-09: In Phantom Full-Implant Validation of Plastic Scintillation Detectors for in Vivo Dosimetry During Low Dose Rate Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Therriault-Proulx, F; Bruno, T; Beddar, S

Purpose: To validate in a water phantom the use of plastic scintillation detectors to measure dose to the urethra and the rectal wall during a clinically realistic low dose rate (LDR) brachytherapy implant. Methods: A template was designed to replicate a clinically realistic LDR brachytherapy prostate implant inside a water phantom. Twenty-two catheters were inserted, including one mimicking the urethra and another the rectal wall. The needles inserted in the remaining 20 catheters were composed of thin-walled nylon tubes in which I-125 radioactive seeds (Air Kerma Strengths of (0.328±0.020)U) were abutted together with plastic spacers to replicate a typical loading.more » A plastic scintillation detector (PSD) with a 5-mm long × 1-mm diameter sensitive element was first placed inside the urethra and 1-second measurements were performed for 60s after each needle implant. Measurements were also performed at multiple positions along the urethra once all the needles were inserted. The procedure was then repeated with the PSD placed at the rectal wall. Results: Individual dose-rates ranging from 0.07µGy/s to 1.5µGy/s were measured after each needle implant. The average absolute relative differences were (6.2±3.6)% and (6.9±6.5)% to the values calculated with the TG-43 formalism, for the urethra and rectal wall respectively. These results are within expectations from the error uncertainty budget once accounting for uncertainties in seeds’ strength and positioning. Interestingly, the PSD allowed for unplanned error detection as the study was performed. Finally, the measured dose after the full implant at different positions along the mimicked organs at risk were in agreement with TG-43 values for all of the positions tested. Conclusion: Plastic scintillation detectors could be used as in vivo detectors for LDR brachytherapy as they would provide accurate dose information after each needle implant as well as along the organs at risk at the end of the implant.« less

Microstructure imaging of human rectal mucosa using multiphoton microscopy

NASA Astrophysics Data System (ADS)

Liu, N. R.; Chen, G.; Chen, J. X.; Yan, J.; Zhuo, S. M.; Zheng, L. Q.; Jiang, X. S.

2011-01-01

Multiphoton microscopy (MPM) has high resolution and sensitivity. In this study, MPM was used to image microstructure of human rectal mucosa. The morphology and distribution of the main components in mucosa layer, absorptive cells and goblet cells in the epithelium, abundant intestinal glands in the lamina propria and smooth muscle fibers in the muscularis mucosa were clearly monitored. The variations of these components were tightly relevant to the pathology in gastrointestine system, especially early rectal cancer. The obtained images will be helpful for the diagnosis of early colorectal cancer.

Sumatriptan (rectal route of administration) for acute migraine attacks in adults

PubMed Central

Derry, Christopher J; Derry, Sheena; Moore, R Andrew

2014-01-01

Background Migraine is a highly disabling condition for the individual and also has wide-reaching implications for society, healthcare services, and the economy. Sumatriptan is an abortive medication for migraine attacks, belonging to the triptan family. Rectal administration may be preferable to oral for individuals experiencing nausea and/or vomiting. Objectives To determine the efficacy and tolerability of rectal sumatriptan compared to placebo and other active interventions in the treatment of acute migraine attacks in adults. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, online databases, and reference lists for studies through 13 October 2011. Selection criteria We included randomised, double-blind, placebo- and/or active-controlled studies using rectally administered sumatriptan to treat a migraine headache episode, with at least 10 participants per treatment arm. Data collection and analysis Two review authors independently assessed trial quality and extracted data. We used numbers of participants achieving each outcome to calculate relative risk (or ‘risk ratio’) and numbers needed to treat to benefit (NNT) or harm (NNH) compared to placebo or a different active treatment. Main results Three studies (866 participants) compared rectally administered sumatriptan with placebo or an active comparator. Most of the data were for the 12.5 mg and 25 mg doses. For the majority of efficacy outcomes, sumatriptan surpassed placebo. For sumatriptan 12.5 mg versus placebo the NNTs were 5.2 and 3.2 for headache relief at one and two hours, respectively. Results for the 25 mg dose were similar to the 12.5 mg dose, and there were no significant differences between the two doses for any of the outcomes analysed. The NNTs for sumatriptan 25 mg versus placebo were 4.2, 3.2, and 2.4 for pain-free at two hours, headache relief at one hour, and headache relief at two hours, respectively. Relief of functional disability was greater with sumatriptan than with placebo, with NNTs of 8.0 and 4.0 for the 12.5 mg and 25 mg doses, respectively. For the most part, adverse events were transient and mild and were more common with sumatriptan than with placebo, but there were insufficient data to perform any analyses. Direct comparison of sumatriptan with active treatments was limited to one study comparing sumatriptan 25 mg with ergotamine tartrate 2 mg + caffeine 100 mg. Authors’ conclusions Based on limited amounts of data, sumatriptan 25 mg, administered rectally, is an effective treatment for acute migraine attacks, with participants in these studies experiencing a significant reduction in headache pain and functional disability within two hours of treatment. The lack of data on relief of headache-associated symptoms or incidence of adverse events limits any conclusions that can be drawn. PMID:22336868

Rectal misoprostol in management of retained placenta: a contradictory result.

PubMed

Pongsatha, Saipin; Tongsong, Theera

2011-05-01

Retained placenta is one of the common problems in obstetric practice. The most common procedure to manage cases with retained placenta is manual removal of placenta (MROP) under general anesthesia. Recent data indicates that misoprostol may be helpful in decreasing the rate of MROP. To assess the efficacy of rectal misoprostol in women with delayed placental separation. A descriptive, retrospective cohort was conducted. All pregnant women with retained placenta longer than 30 minutes after fetal delivery, either in second or third trimester that received 800 mcg rectal misoprostol were included in the present study. Successful treatment was defined as spontaneous placental expulsion within 30 minutes after rectal misoprostol administration. The rate of spontaneous placental expulsion within 30 minutes after misoprostol administration was very low, only three out of 20 cases (15%). High dose rectal misoprostol does not give a promising result in cases of retained placenta. It is ineffective to facilitate placental separation in cases of retained placenta and does not seem to decrease the rate of MROP.

Acute Toxicity and Tumor Response in Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy With Shortening of the Overall Treatment Time Using Intensity-Modulated Radiation Therapy With Simultaneous Integrated Boost: A Phase 2 Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

But-Hadzic, Jasna, E-mail: jbut@onko-i.si; Anderluh, Franc; Brecelj, Erik

Background and Purpose: This phase 2 study investigated the efficacy and safety of preoperative intensity modulated radiation therapy with a simultaneous integrated boost (IMRT-SIB) without dose escalation, concomitant with standard capecitabine chemotherapy in locally advanced rectal cancer. Methods and Materials: Between January 2014 and March 2015, 51 patients with operable stage II-III rectal adenocarcinoma received preoperative IMRT with pelvic dose of 41.8 Gy and simultaneously delivered 46.2 Gy to T2/3 and 48.4 Gy to T4 tumor in 22 fractions, concomitant with capecitabine, 825 mg/m{sup 2}/12 hours, including weekends. The primary endpoint was pathologic complete response (pCR). Results: Fifty patients completed preoperative treatment according to themore » protocol, and 47 underwent surgical resection. The sphincter preservation rate for the low rectal tumors was 62%, and the resection margins were free in all but 1 patient. Decrease in tumor and nodal stage was observed in 32 (68%) and 39 (83%) patients, respectively, with pCR achieved in 12 (25.5%) patients. There were only 2 G ≥ 3 acute toxicities, with infectious enterocolitis in 1 patient and dermatitis over the sacral area caused by the bolus effect of the treatment table in the second patient. Conclusions: Preoperative IMRT-SIB without dose escalation is well tolerated, with a low acute toxicity profile, and can achieve a high rate of pCR and downstaging.« less

Can a peri-rectal hydrogel spaceOAR programme for prostate cancer intensity-modulated radiotherapy be successfully implemented in a regional setting?

PubMed

Te Velde, Bridget L; Westhuyzen, Justin; Awad, Nader; Wood, Maree; Shakespeare, Thomas P

2017-08-01

The aim of this study was to investigate whether the implementation of a hydrogel spacer (SpaceOAR) programme for patients treated with 81 Gy prostate intensity-modulated radiotherapy (IMRT) in a regional setting can reduce rectal doses and toxicity. In this retrospective study, 125 patients with localised prostate cancer treated between April 2014 (programme commencement) and June 2015 were compared: 65 with SpaceOAR (inserted by five different urologists) and 60 patients treated over the same time period without SpaceOAR. Patients were treated with 81 Gy in 45Fx of IMRT over 9 weeks. Planning aims included restricting rectal doses to V40 Gy < 35%, V65 Gy < 17%, V75 Gy < 10%. Acute toxicity was assessed weekly during radiotherapy and at 12 weeks. Rectal volume parameters were all significantly lower in the SpaceOAR group, with an associated reduction in acute diarrhoea (13.8% vs 31.7%). There were no significant differences in the very low rates of acute and late faecal incontinence or proctitis, however, there was a trend towards increased haemorrhoid rate in the SpaceOAR group (11.7% vs 3.1%, P = 0.09). A SpaceOAR programme in a regional setting with urologists performing low volumes of insertions (<1 per month on average) is of clinical benefit, and was associated with significantly lower radiation doses to the rectum and lower rates of acute diarrhoea. © 2017 The Royal Australian and New Zealand College of Radiologists.

Acute Toxicity and Tumor Response in Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy With Shortening of the Overall Treatment Time Using Intensity-Modulated Radiation Therapy With Simultaneous Integrated Boost: A Phase 2 Trial.

PubMed

But-Hadzic, Jasna; Anderluh, Franc; Brecelj, Erik; Edhemovic, Ibrahim; Secerov-Ermenc, Ajra; Hudej, Rihard; Jeromen, Ana; Kozelj, Miran; Krebs, Bojan; Oblak, Irena; Omejc, Mirko; Vogrin, Andrej; Velenik, Vaneja

2016-12-01

This phase 2 study investigated the efficacy and safety of preoperative intensity modulated radiation therapy with a simultaneous integrated boost (IMRT-SIB) without dose escalation, concomitant with standard capecitabine chemotherapy in locally advanced rectal cancer. Between January 2014 and March 2015, 51 patients with operable stage II-III rectal adenocarcinoma received preoperative IMRT with pelvic dose of 41.8 Gy and simultaneously delivered 46.2 Gy to T2/3 and 48.4 Gy to T4 tumor in 22 fractions, concomitant with capecitabine, 825 mg/m 2 /12 hours, including weekends. The primary endpoint was pathologic complete response (pCR). Fifty patients completed preoperative treatment according to the protocol, and 47 underwent surgical resection. The sphincter preservation rate for the low rectal tumors was 62%, and the resection margins were free in all but 1 patient. Decrease in tumor and nodal stage was observed in 32 (68%) and 39 (83%) patients, respectively, with pCR achieved in 12 (25.5%) patients. There were only 2 G ≥ 3 acute toxicities, with infectious enterocolitis in 1 patient and dermatitis over the sacral area caused by the bolus effect of the treatment table in the second patient. Preoperative IMRT-SIB without dose escalation is well tolerated, with a low acute toxicity profile, and can achieve a high rate of pCR and downstaging. Copyright © 2016 Elsevier Inc. All rights reserved.

Rectal 5-aminosalicylic acid for induction of remission in ulcerative colitis.

PubMed

Marshall, John K; Thabane, Marroon; Steinhart, A Hillary; Newman, Jamie R; Anand, Anju; Irvine, E Jan

2010-01-20

5-Aminosalicylates (5-ASA) are considered a first-line therapy for inducing and maintaining remission of mild to moderately active ulcerative colitis (UC). When inflammation in UC is limited to the distal colon, 5-ASA can also be administered rectally as a suppository, enema or foam. A systematic review was undertaken to evaluate the efficacy of rectal 5-ASA for treating active distal UC. Electronic searches of the MEDLINE database (1966-2008), the Cochrane Central Register of Controlled Trials and the Cochrane IBD/FBD Group Specialized Trials Register were supplemented by manual reviews of reference listings and conference proceedings. Randomized trials comparing rectal 5-ASA to placebo or another active therapy were eligible for inclusion. Eligible trials enrolled patients with a distal disease margin less than 60 cm from the anal verge or distal to the splenic flexure. Trials that enrolled subjects less than 12 years of age were excluded. Eligibility was assessed by three authors. Data were extracted by two authors using standardized forms. Pooled odds ratios (POR) for inducing improvement and remission by symptomatic, endoscopic and histologic criteria were calculated using an intention to treat principle. Fixed effects models were used unless heterogeneity was encountered within groups (P < 0.10), where random effects models were used. All statistical analyses were performed using RevMan 5. Where sufficient data were available, subgroup analyses were performed for disease extent, total daily 5-ASA dose, 5-ASA formulation (enema,suppository, foam) and the type of control intervention (placebo or another active therapy). Thirty-eight studies fulfilled the inclusion criteria. Rectal 5-ASA was superior to placebo for inducing symptomatic, endoscopic and histological improvement and remission, with POR for symptomatic improvement 8.87 (8 trials, 95% CI: 5.30 to 14.83; P < 0.00001), endoscopic improvement 11.18 (5 trials, 95% CI 5.99 to 20.88; P < 0.00001), histologic improvement 7.69 (6 trials, 95% CI 3.26 to 18.12; P < 0.00001), symptomatic remission 8.30 (8 trials, 95% CI 4.28 to 16.12; P < 0.00001), endoscopic remission 5.31 (7 trials, 95% CI 3.15 to 8.92; P < 0.00001), and histologic remission 6.28 (5 trials, 95% CI 2.74 to 14.40; P < 0.0001). Rectal 5-ASA was superior to rectal corticosteroids for inducing symptomatic improvement and remission with POR 1.56 (6 trials, 95% CI 1.15 to 2.11; P = 0.004) and 1.65 (6 trials, 95% CI 1.11 to 2.45; P = 0.01), respectively. Rectal 5-ASA was not superior to oral 5-ASA for symptomatic improvement (POR 2.25; 95% CI 0.53 to 19.54; P = 0.27). Neither total daily dose nor 5-ASA formulation affected treatment response. Rectal 5-ASA should be considered a first-line therapy for patients with mild to moderately active distal UC. The optimal total daily dose and dose frequency of 5-ASA remain to be determined. Future research should define differences in efficacy among patient subgroups defined by proximal disease margin and disease activity. There is a strong need for consensus standardization of outcome measurements for clinical trials in ulcerative colitis.

``In Vivo'' Dosimetry in High Dose Rate Brachytherapy for Cervical Cancer Treatments

NASA Astrophysics Data System (ADS)

González-Azcorra, S. A.; Mota-García, A.; Poitevín-Chacón, M. A.; Santamaría-Torruco, B. J.; Rodríguez-Ponce, M.; Herrera-Martínez, F. P.; Gamboa de Buen, I.; Ruíz-Trejo, C.; Buenfil, A. E.

2008-08-01

In this prospective study, rectal dose was measured "in vivo" using TLD-100 crystals (3×3×1 mm3), and it has been compared to the prescribed dose. Measurements were performed in patients with cervical cancer classified in FIGO stages IB-IIIB and treated with high dose rate brachytherapy (HDR BT) at the Instituto Nacional de Cancerología (INCan).

Synchronous prostate and rectal adenocarcinomas irradiation utilising volumetric modulated arc therapy.

PubMed

Ng, Sweet Ping; Tran, Thu; Moloney, Philip; Sale, Charlotte; Mathlum, Maitham; Ong, Grace; Lynch, Rod

2015-12-01

Cases of synchronous prostate and colorectal adenocarcinomas have been sporadically reported. There are case reports on patients with synchronous prostate and rectal cancers treated with external beam radiotherapy alone or combined with high-dose rate brachytherapy boost to the prostate. Here, we illustrate a patient with synchronous prostate and rectal cancers treated using the volumetric arc therapy (VMAT) technique. The patient was treated with radical radiotherapy to 50.4 Gy in 28 fractions to the pelvis, incorporating the involved internal iliac node and the prostate. A boost of 24 Gy in 12 fractions was delivered to the prostate only, using VMAT. Treatment-related toxicities and follow-up prostate-specific antigen and carcinoembryonic antigen were collected for data analysis. At 12 months, the patient achieved complete response for both rectal and prostate cancers without significant treatment-related toxicities.

Clinical commissioning of an in vivo range verification system for prostate cancer treatment with anterior and anterior oblique proton beams

NASA Astrophysics Data System (ADS)

Hoesl, M.; Deepak, S.; Moteabbed, M.; Jassens, G.; Orban, J.; Park, Y. K.; Parodi, K.; Bentefour, E. H.; Lu, H. M.

2016-04-01

The purpose of this work is the clinical commissioning of a recently developed in vivo range verification system (IRVS) for treatment of prostate cancer by anterior and anterior oblique proton beams. The IRVS is designed to perform a complete workflow for pre-treatment range verification and adjustment. It contains specifically designed dosimetry and electronic hardware and a specific software for workflow control with database connection to the treatment and imaging systems. An essential part of the IRVS system is an array of Si-diode detectors, designed to be mounted to the endorectal water balloon routinely used for prostate immobilization. The diodes can measure dose rate as function of time from which the water equivalent path length (WEPL) and the dose received are extracted. The former is used for pre-treatment beam range verification and correction, if necessary, while the latter is to monitor the dose delivered to patient rectum during the treatment and serves as an additional verification. The entire IRVS workflow was tested for anterior and 30 degree inclined proton beam in both solid water and anthropomorphic pelvic phantoms, with the measured WEPL and rectal doses compared to the treatment plan. Gafchromic films were also used for measurement of the rectal dose and compared to IRVS results. The WEPL measurement accuracy was in the order of 1 mm and after beam range correction, the dose received by the rectal wall were 1.6% and 0.4% from treatment planning, respectively, for the anterior and anterior oblique field. We believe the implementation of IRVS would make the treatment of prostate with anterior proton beams more accurate and reliable.

Accuracy of Monte Carlo simulations compared to in-vivo MDCT dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bostani, Maryam, E-mail: mbostani@mednet.ucla.edu; McMillan, Kyle; Cagnon, Chris H.

Purpose: The purpose of this study was to assess the accuracy of a Monte Carlo simulation-based method for estimating radiation dose from multidetector computed tomography (MDCT) by comparing simulated doses in ten patients to in-vivo dose measurements. Methods: MD Anderson Cancer Center Institutional Review Board approved the acquisition of in-vivo rectal dose measurements in a pilot study of ten patients undergoing virtual colonoscopy. The dose measurements were obtained by affixing TLD capsules to the inner lumen of rectal catheters. Voxelized patient models were generated from the MDCT images of the ten patients, and the dose to the TLD for allmore » exposures was estimated using Monte Carlo based simulations. The Monte Carlo simulation results were compared to the in-vivo dose measurements to determine accuracy. Results: The calculated mean percent difference between TLD measurements and Monte Carlo simulations was −4.9% with standard deviation of 8.7% and a range of −22.7% to 5.7%. Conclusions: The results of this study demonstrate very good agreement between simulated and measured doses in-vivo. Taken together with previous validation efforts, this work demonstrates that the Monte Carlo simulation methods can provide accurate estimates of radiation dose in patients undergoing CT examinations.« less

SU-E-T-457: Impact of Interfractional Variations On Anterior Vs. Lateral-Field Proton Therapy of Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moteabbed, M; Trofimov, A; Sharp, G C

2015-06-15

Purpose: To investigate the effects of interfractional anatomy and setup variations on plans with anterior-oblique vs. lateral beams for prostate cancer pencil beam scanning (PBS) and passive scattered (PS) proton therapy. Methods: Six patients with low/intermediate risk prostate cancer treated with PS proton therapy at our institution were selected. All patients underwent weekly verification CT scans. Implanted fiducials were used for localization, and endorectal balloons for prostate immobilization. New PBS plans with lateral beams, as well as PBS and PS plans with anterior-oblique beams (±35 deg) were created. PBS plans used two different spot sizes: ∼10mm (large) and ∼5mm (medium)more » sigma at 25cm range and optimized as single-field-uniform-dose with ∼8% non-uniformity. No range uncertainty margins were applied in PBS plans to maximize rectal sparing. Field-specific apertures were used when planning with large spots to sharpen the penumbrae. The planned dose was recomputed on each weekly CT with fiducials aligned to the simulation CT, scaled and accumulated via deformable image registration. Results: The dose volume analysis showed that although difference between planned and accumulated dose remains negligible for plans with conventional lateral beams using both PS and PBS, this is not the case for plans with anterior beams. The target coverage in anterior plans was largely degraded due to the variations in the beam path length and the absence of range margins. The average prostate D95 was reduced by 7.5/15.9% (using PS/PBS) after accumulation for anterior plans, compared with 0/0.4% for lateral plans. The average mean dose in organs-at-risk decreased by 1% for lateral and 2% for anterior plans, similarly for PS and PBS. Spot size did not affect the dose changes. Conclusion: Prostate plans using anterior beams may undergo clinically relevant interfractional dose degradation. Corrective strategies guided by in-vivo range measurements should be studied before clinical application of this technique.« less

Analysis and Management of Rectal Gas with Kampo Formulas During Intensity-Modulated Radiotherapy of Prostate Cancer: A Case Series Study.

PubMed

Nagai, Aiko; Shibamoto, Yuta; Ogawa, Keiko; Inoda, Koji; Yoshida, Masanori; Kikuchi, Yuzo

2016-06-01

During intensity-modulated radiation therapy (IMRT) for prostate cancer, the target, bladder, and rectum positions should be kept constant to reduce adverse events, such as radiation proctitis, and to increase local tumor control. For this purpose, decreasing the rectal contents as much as possible is important. Daisaikoto (DST) and bukuryoingohangekobokuto (BIHKT) are traditional Japanese herbal (Kampo) formulas that have been used to treat patients with abdominal bloating or constipation. This study investigated the effect of DST and BIHKT on the rectal gas volume during prostate IMRT according to Kampo diagnosis. Five patients were treated with DST or BIHKT at a dose of 5.0 or 7.5 g/d. The volume of rectal gas in 189 megavoltage computed tomographic images taken before each treatment session and the frequency of rectal gas drainage were evaluated before and after DST or BIHKT administration. After DST or BIHKT treatment, the mean volume of rectal gas was reduced from 6.4 to 2.1 mL, and the mean frequency of gas drainage decreased from 43% to 9%. DST and BIHKT appear to be useful in reducing rectal gas, which would help prevent radiation proctitis and improve the local control of prostate cancer with IMRT.

Acute small bowel toxicity and preoperative chemoradiotherapy for rectal cancer: Investigating dose-volume relationships and role for inverse planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tho, Lye Mun; Glegg, Martin; Paterson, Jennifer

2006-10-01

Purpose: The relationship between volume of irradiated small bowel (VSB) and acute toxicity in rectal cancer radiotherapy is poorly quantified, particularly in patients receiving concurrent preoperative chemoradiotherapy. Using treatment planning data, we studied a series of such patients. Methods and Materials: Details of 41 patients with locally advanced rectal cancer were reviewed. All received 45 Gy in 25 fractions over 5 weeks, 3-4 fields three-dimensional conformal radiotherapy with daily 5-fluorouracil and folinic acid during Weeks 1 and 5. Toxicity was assessed prospectively in a weekly clinic. Using computed tomography planning software, the VSB was determined at 5 Gy dose intervalsmore » (V{sub 5}, V{sub 1}, etc.). Eight patients with maximal VSB had dosimetry and radiobiological modeling outcomes compared between inverse and conformal three-dimensional planning. Results: VSB correlated strongly with diarrheal severity at every dose level (p < 0.03), with strongest correlation at lowest doses. Median VSB differed significantly between patients experiencing Grade 0-1 and Grade 2-4 diarrhea (p {<=} 0.05). No correlation was found with anorexia, nausea, vomiting, abdominal cramps, age, body mass index, sex, tumor position, or number of fields. Analysis of 8 patients showed that inverse planning reduced median dose to small bowel by 5.1 Gy (p = 0.008) and calculated late normal tissue complication probability (NTCP) by 67% (p = 0.016). We constructed a model using mathematical analysis to predict for acute diarrhea occurring at V{sub 5} and V{sub 15}. Conclusions: A strong dose-volume relationship exists between VSB and acute diarrhea at all dose levels during preoperative chemoradiotherapy. Our constructed model may be useful in predicting toxicity, and this has been derived without the confounding influence of surgical excision on bowel function. Inverse planning can reduce calculated dose to small bowel and late NTCP, and its clinical role warrants further investigation.« less

Phase I Study of Oxaliplatin in Combination With Capecitabine and Radiotherapy as Postoperative Treatment for Stage II and III Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jin Jing; Li Yexiong; Wang Jinwan

Purpose: A Phase I study was conducted to determine the maximal tolerated dose and the dose-limiting toxicity (DLT) of oxaliplatin (OXA) combined with capecitabine and radiotherapy as adjuvant treatment in patients with operable rectal cancer. Patients and Methods: A total of 21 patients with Stage II or III rectal adenocarcinoma after curative surgery were treated with radiotherapy to a total dose of 50 Gy in 5 weeks. OXA was administered at a dosage of 40 (n = 6), 50 (n = 3),60 (n = 3), 70 (n = 3), or 80 mg/m{sup 2} (n = 6) once a week formore » 2 weeks (first cycle) followed by a second cycle after a 7-day break. Capecitabine at a fixed dose of 1,300 mg/m{sup 2}/d was administered orally at the same schedule as for OXA. DLT was defined as Grade 3 or 4 hematologic and nonhematologic toxicity. Results: Grade 1-3 leukopenia, diarrhea, and nausea/vomiting were the most common toxic side effects, and most were Grade 1-2. A DLT was first observed in 1 of 3 patients at 40 mg/m{sup 2} (Grade 3 diarrhea) but was not observed in the next 3 patients at the same level or in patients who received a dose level of 50-70 mg/m{sup 2}. At 80 mg/m{sup 2}, DLT occurred in 3 of 6 patients (1 Grade 4 leukopenia and 2 Grade 3 diarrhea). Conclusions: OXA combined with a fixed dose of capecitabine at 625 mg/m{sup 2} twice daily by mouth plus radiotherapy in the adjuvant setting was tolerable and clinically feasible. The maximal tolerated dose of OXA in this setting was 80 mg/m{sup 2}, comparable to the maximal tolerated dose of OXA in the neoadjuvant setting.« less

Rectal sac distention is induced by 20-hydroxyecdysone in the pupa of Bombyx mori.

PubMed

Suzuki, Takumi; Sakurai, Sho; Iwami, Masafumi

2009-03-01

Holometabolous insects do not excrete but store metabolic wastes during the pupal period. The waste is called meconium and is purged after adult emergence. Although the contents of meconium are well-studied, the developmental and physiological regulation of meconium accumulation is poorly understood. In Bombyx mori, meconium is accumulated in the rectal sac; thereby, the rectal sac distends at the late pupal stage. Here, we show that rectal sac distention occurs between 4 and 5 days after pupation. The distention is halted by brain-removal just after larval-pupal ecdysis but not by brain-removal 1 day after pupation. In the pupae, brain-removal just after ecdysis kept the hemolymph ecdysteroid titer low during early and mid-pupal stages. An injection of 20-hydroxyecdysone (20E) evoked the distention that was halted by brain-removal in a dose-dependent manner. Therefore, brain-removal caused the lack of ecdysteroid, and rectal sac distention did not appear in the brain-removed pupae because of the lack of ecdysteroid. We conclude that rectal sac distention is one of the developmental events regulated by 20E during the pupal period in B. mori.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Margalit, Danielle N.; Mamon, Harvey J.; Ancukiewicz, Marek

Purpose: To determine the rate of treatment deviations during combined modality therapy for rectal cancer in elderly patients aged 75 years and older. Methods and Materials: We reviewed the records of consecutively treated patients with rectal cancer aged 75 years and older treated with combined modality therapy at Massachusetts General Hospital and Brigham and Women's Hospital from 2002 to 2007. The primary endpoint was the rate of treatment deviation, defined as a treatment break, dose reduction, early discontinuation of therapy, or hospitalization during combined modality therapy. Patient comorbidity was rated using the validated Adult Comorbidity Evaluation 27 Test (ACE-27) comorbiditymore » index. Fisher's exact test and the Mantel-Haenszel trend test were used to identify predictors of treatment tolerability. Results: Thirty-six eligible patients had a median age of 79.0 years (range, 75-87 years); 53% (19/36) had no or mild comorbidity and 47% (17/36) had moderate or severe comorbidity. In all, 58% of patients (21/36) were treated with preoperative chemoradiotherapy (CRT) and 33% (12/36) with postoperative CRT. Although 92% patients (33/36) completed the planned radiotherapy (RT) dose, 25% (9/36) required an RT-treatment break, 11% (4/36) were hospitalized, and 33% (12/36) had a dose reduction, break, or discontinuation of concurrent chemotherapy. In all, 39% of patients (14/36) completed {>=}4 months of adjuvant chemotherapy, and 17% (6/36) completed therapy without a treatment deviation. More patients with no to mild comorbidity completed treatment than did patients with moderate to severe comorbidity (21% vs. 12%, p = 0.66). The rate of deviation did not differ between patients who had preoperative or postoperative CRT (19% vs. 17%, p = 1.0). Conclusions: The majority of elderly patients with rectal cancer in this series required early termination of treatment, treatment interruptions, or dose reductions. These data suggest that further intensification of combined modality therapy for rectal cancer should be performed with caution in elderly patients, who require aggressive supportive care to complete treatment.« less

High doses of granulocyte-macrophage colony stimulating factor inhibit antibody responses in rectal secretions and diminish MVA/SIV vaccine protection in TRIM5α restrictive macaques

PubMed Central

Kannanganat, Sunil; Wyatt, Linda S; Gangadhara, Sailaja; Chamcha, Venkateswarlu; Chea, Lynette S.; Kozlowski, Pamela A; LaBranche, Celia C; Chennareddi, Lakshmi; Lawson, Benton; Reddy, Pradeep B. J.; Styles, Tiffany M.; Vanderford, Thomas H; Montefiori, David C; Moss, Bernard; Robinson, Harriet L; Amara, Rama Rao

2016-01-01

Here, we test in rhesus macaques the effects of a 500-fold range of an admixed recombinant modified vaccinia Ankara (MVA) expressing rhesus GM-CSF (MVA/GM-CSF) on the immunogenicity and protection elicited by an MVA/simian immunodeficiency macaque 239 (SIVmac239) vaccine. High doses of the MVA/GM-CSF did not affect the levels of systemic Env-specific Ab but did decrease the expression of the gut homing receptor α4β7 on plasmacytoid dendritic cells (p<0.01) and the magnitudes of Env-specific IgA (p=0.01) and IgG (p<0.05) in rectal secretions. The protective effect of the vaccine was evaluated using 12 weekly rectal challenges in rhesus subgrouped by tripartite motif-containing protein 5α (TRIM5α) genotypes that are restrictive or permissive for infection by the challenge virus, SIVsmE660. Eight of 9 TRIM5α-restrictive animals receiving no, or the lowest dose [1×105 plaque forming units (pfu)] of MVA/GM-CSF resisted all 12 challenges. In the comparable TRIM5α-permissive group only 1 of 12 animals resisted all 12 challenges. In the TRIM5α restrictive, but not permissive animals, the number of challenges to infection directly correlated with the magnitudes of Env-specific rectal IgG (r=0.6) and IgA (r=0.6), the avidity of Env-specific serum IgG (r=0.5), and antibody dependent cell-mediated virus inhibition (r=0.6). Titers of neutralizing Ab did not correlate with protection. We conclude that (i) protection elicited by MVA/SIVmac239 is strongly dependent on the presence of the TRIM5α restriction, (ii) in TRIM5α restrictive animals, non-neutralizing Ab responses contribute to protection against SIVsmE660, and (iii) high doses of co-expressed MVA/GM-CSF inhibit mucosal Ab responses and MVA/SIV239-elicited protection. PMID:27683750

Influence des conditions climatiques saisonnières sur quelques paramètres physiologiques dès boucs Créoles alimentés avec de l'ensilage de banane

NASA Astrophysics Data System (ADS)

Fauconneau, B.; Xande, A.

1986-06-01

Response of three groups of 12 male creole goats (weighing about 10 kg) to environmental variations was tested in Guadeloupe (French West Indies) respectively at three times in the year: end of humid season (October November), dry season (February March) and beginning of humid season (July August). Voluntary free intake of banana silage (silage of mixed green banana, bagassa, wheat bran and urea complemented with molasse) was not significantly affected by climatic variations. Three physiological parameters: rectal temperature, respiratory frequency and cardiac frequency were measured. These parameters were correlated with heat production dependent factors such as metabolic body weight, body weight gain and voluntary free intake. Rectal temperature increased all through the day until sunset and then decreased during the night. Both minimal rectal temperature and daily increase of rectal temperature were correlated with ambient temperature. Cardiac frequency increased during feeding. Generally cardiac frequency seemed to be correlated with activity of animals and so with behavioural response to environmental variations. Respiratory frequency was the most sensitive index of goat response to climate. The daily increase of respiratory frequency was important at the end of the humid season but was not observed in dry season. This increase was dependent on ambient temperature increase but also on air humidity characteristics and air velocity. These points are discussed according to integration of those physiological parameters in thermoregulation.

Functional anatomy of the prostate: implications for treatment planning.

PubMed

McLaughlin, Patrick W; Troyer, Sara; Berri, Sally; Narayana, Vrinda; Meirowitz, Amichay; Roberson, Peter L; Montie, James

2005-10-01

To summarize the functional anatomy relevant to prostate cancer treatment planning. Coronal, axial, and sagittal T2 magnetic resonance imaging (MRI) and MRI angiography were fused by mutual information and registered with computed tomography (CT) scan data sets to improve definition of zonal anatomy of the prostate and critical adjacent structures. The three major prostate zones (inner, outer, and anterior fibromuscular) are visible by T2 MRI imaging. The bladder, bladder neck, and internal (preprostatic) sphincter are a continuous muscular structure and clear definition of the preprostatic sphincter is difficult by MRI. Transition zone hypertrophy may efface the bladder neck and internal sphincter. The external "lower" sphincter is clearly visible by T2 MRI with wide variations in length. The critical erectile structures are the internal pudendal artery (defined by MRI angiogram or T2 MRI), corpus cavernosum, and neurovascular bundle. The neurovascular bundle is visible along the posterior lateral surface of the prostate on CT and MRI, but its terminal branches (cavernosal nerves) are not visible and must be defined by their relationship to the urethra within the genitourinary diaphragm. Visualization of the ejaculatory ducts within the prostate is possible on sagittal MRI. The anatomy of the prostate-rectum interface is clarified by MRI, as is the potentially important distinction of rectal muscle and rectal mucosa. Improved understanding of functional anatomy and imaging of the prostate and critical adjacent structures will improve prostate radiation therapy by improvement of dose and toxicity correlation, limitation of dose to critical structures, and potential improvement in post therapy quality of life.

Discrimination of rectal cancer through human serum using surface-enhanced Raman spectroscopy

NASA Astrophysics Data System (ADS)

Li, Xiaozhou; Yang, Tianyue; Li, Siqi; Zhang, Su; Jin, Lili

2015-05-01

In this paper, surface-enhanced Raman spectroscopy (SERS) was used to detect the changes in blood serum components that accompany rectal cancer. The differences in serum SERS data between rectal cancer patients and healthy controls were examined. Postoperative rectal cancer patients also participated in the comparison to monitor the effects of cancer treatments. The results show that there are significant variations at certain wavenumbers which indicates alteration of corresponding biological substances. Principal component analysis (PCA) and parameters of intensity ratios were used on the original SERS spectra for the extraction of featured variables. These featured variables then underwent linear discriminant analysis (LDA) and classification and regression tree (CART) for the discrimination analysis. Accuracies of 93.5 and 92.4 % were obtained for PCA-LDA and parameter-CART, respectively.

Is Dose Deformation–Invariance Hypothesis Verified in Prostate IGRT?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Simon, Antoine, E-mail: antoine.simon@univ-rennes1.fr; Laboratoire Traitement du Signal et de l'Image, Université de Rennes 1, 35000 Rennes; Le Maitre, Amandine

Purpose: To assess dose uncertainties resulting from the dose deformation–invariance hypothesis in prostate cone beam computed tomography (CT)–based image guided radiation therapy (IGRT), namely to evaluate whether rigidly propagated planned dose distribution enables good estimation of fraction dose distributions. Methods and Materials: Twenty patients underwent a CT scan for planning intensity modulated radiation therapy–IGRT delivering 80 Gy to the prostate, followed by weekly CT scans. Two methods were used to obtain the dose distributions on the weekly CT scans: (1) recalculating the dose using the original treatment plan; and (2) rigidly propagating the planned dose distribution. The cumulative doses were then estimatedmore » in the organs at risk for each dose distribution by deformable image registration. The differences between recalculated and propagated doses were finally calculated for the fraction and the cumulative dose distributions, by use of per-voxel and dose-volume histogram (DVH) metrics. Results: For the fraction dose, the mean per-voxel absolute dose difference was <1 Gy for 98% and 95% of the fractions for the rectum and bladder, respectively. The maximum dose difference within 1 voxel reached, however, 7.4 Gy in the bladder and 8.0 Gy in the rectum. The mean dose differences were correlated with gas volume for the rectum and patient external contour variations for the bladder. The mean absolute differences for the considered volume receiving greater than or equal to dose x (V{sub x}) of the DVH were between 0.37% and 0.70% for the rectum and between 0.53% and 1.22% for the bladder. For the cumulative dose, the mean differences in the DVH were between 0.23% and 1.11% for the rectum and between 0.55% and 1.66% for the bladder. The largest dose difference was 6.86%, for bladder V{sub 80Gy}. The mean dose differences were <1.1 Gy for the rectum and <1 Gy for the bladder. Conclusions: The deformation–invariance hypothesis was corroborated for the organs at risk in prostate IGRT except in cases of a large disappearance or appearance of rectal gas for the rectum and large external contour variations for the bladder.« less

Trial Comparing a Combined Regimen of Amikacin and Ciprofloxacin to Ciprofloxacin Alone as Transrectal Prostate Biopsy Prophylaxis in the Era of High Fluoroquinolone-Resistant Rectal Flora.

PubMed

Son, Kyung Chul; Chung, Ho Seok; Jung, Seung Il; Kim, Myung Soo; Hwang, Eu Chang; Kim, Jin Woong; Kwon, Dong Deuk

2018-04-09

To investigate whether addition of amikacin to fluoroquinolone (FQ) antimicrobial prophylaxis reduces infections after transrectal ultrasound-guided prostate biopsy (TRUSPB). A total of 503 patients undergoing rectal swab were divided into three groups. Patients with FQ-sensitive rectal flora (group 1, n = 248) were administered ciprofloxacin before TRUSPB, and patients with FQ-resistant rectal flora were either administered ciprofloxacin (group 2, n = 97) or amikacin and ciprofloxacin (group 3, n = 158) before TRUSPB. Based on the rectal swab, FQ resistance was 54.9%, and extended-spectrum β-lactamase (ESBL) positivity was 17.2%. The incidence of infectious complication in group 1 was 1.6%. Groups 2 and 3, with FQ-resistant rectal flora, tended to have increased infectious complications (5.2% and 4.4%, respectively) but the difference between those results is not statistically significant. The most common pathogens of infectious complications in patients with FQ-resistant rectal flora were FQ-resistant and ESBL-producing Escherichia coli. E. coli pathogens isolated in Group 3 were amikacin-susceptible species. The operation history and ESBL positivity of rectal flora increased the incidence of infectious complications (odds ratio [OR] = 3.68; P = 0.035 and OR = 4.02; P = 0.008, respectively). DM and antibiotics exposure were risk factors for FQ resistance (OR = 2.19; P = 0.002) and ESBL positivity of rectal flora (OR = 2.96; P = 0.005), respectively. Addition of amikacin to ciprofloxacin prophylaxis could not reduce infectious complications in patients with FQ-resistant rectal flora. Despite the amikacin sensitivity of infectious complications, single-dose amikacin addition to ciprofloxacin prophylaxis has limitations. © 2018 The Korean Academy of Medical Sciences.

Technical Note: System for evaluating local hypothermia as a radioprotector of the rectum in a small animal model.

PubMed

Hrycushko, Brian A; Bing, Chenchen; Futch, Cecil; Wodzak, Michelle; Stojadinovic, Strahinja; Medin, Paul M; Chopra, Rajiv

2017-08-01

The protective effects of induced or even accidental hypothermia on the human body are widespread with several medical uses currently under active research. In vitro experiments using human cell lines have shown hypothermia provides a radioprotective effect that becomes more pronounced at large, single-fraction doses common to stereotactic body radiotherapy (SBRT) and stereotactic radiosurgery (SRS) treatments. This work describes the development of a system to evaluate local hypothermia for a radioprotective effect of the rat rectum during a large dose of radiation relevant to prostate SBRT. This includes the evaluation of a 3D-printed small animal rectal cooling device and the integration with a small animal irradiator. A 3-cm long, dual-lumen rectal temperature control apparatus (RTCA) was designed in SOLIDWORKS CAD for 3D printing. The RTCA was capable of recirculating flow in a device small enough for insertion into the rat rectum, with a metal support rod for strength as well as visibility during radiation treatment planning. The outer walls of the RTCA comprised of thin heat shrink plastic, achieving efficient heat transfer into adjacent tissues. Following leak-proof testing, fiber optic temperature probes were used to evaluate the temperature over time when placed adjacent to the cooling device within the rat rectum. MRI thermometry characterized the relative temperature distribution in concentric ROIs surrounding the probe. Integration with an image-guided small animal irradiator and associated treatment planning system included evaluation for imaging artifacts and effect of brass tubing on dose calculation. The rectal temperature adjacent to the cooling device decreased from body temperature to 15°C within 10-20 min from device insertion and was maintained at 15 ± 3°C during active cooling for the evaluated time of one hour. MR thermometry revealed a steep temperature gradient with increasing distance from the cooling device with the desired temperature range maintained within the surrounding few millimeters. A 3D-printed rectal cooling device was fabricated for the purpose of inducing local hypothermia in the rat rectum. The RTCA was simply integrated with an image-guided small animal irradiator and Monte Carlo-based treatment planning system to facilitate an in vivo investigation of the radioprotective effect of hypothermia for late rectal toxicity following a single large dose of radiation. © 2017 American Association of Physicists in Medicine.

Genetic Modeling of Radiation Injury in Prostate Cancer Patients Treated with Radiotherapy

DTIC Science & Technology

2016-10-01

nucleotide polymorphisms, prostate cancer, radiation therapy, adverse effects, urinary morbidity, rectal injury, sexual dysfunction 16. SECURITY...prostate cancer, radiation therapy, adverse effects, urinary morbidity, rectal injury, sexual dysfunction 3. ACCOMPLISHMENTS: What were the...Significant results: As shown in Table 1A, the mean age of patients across the eight studies ranged from 65 to 72 years with some moderate variation

Dose-Volume Effects on Patient-Reported Acute Gastrointestinal Symptoms During Chemoradiation Therapy for Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Ronald C.; Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

2012-07-15

Purpose: Research on patient-reported outcomes (PROs) in rectal cancer is limited. We examined whether dose-volume parameters of the small bowel and large bowel were associated with patient-reported gastrointestinal (GI) symptoms during 5-fluorouracil (5-FU)-based chemoradiation treatment for rectal cancer. Methods and Materials: 66 patients treated at the Brigham and Women's Hospital or Massachusetts General Hospital between 2006 and 2008 were included. Weekly during treatment, patients completed a questionnaire assessing severity of diarrhea, urgency, pain, cramping, mucus, and tenesmus. The association between dosimetric parameters and changes in overall GI symptoms from baseline through treatment was examined by using Spearman's correlation. Potential associationsmore » between these parameters and individual GI symptoms were also explored. Results: The amount of small bowel receiving at least 15 Gy (V15) was significantly associated with acute symptoms (p = 0.01), and other dosimetric parameters ranging from V5 to V45 also trended toward association. For the large bowel, correlations between dosimetric parameters and overall GI symptoms at the higher dose levels from V25 to V45 did not reach statistical significance (p = 0.1), and a significant association was seen with rectal pain from V15 to V45 (p < 0.01). Other individual symptoms did not correlate with small bowel or large bowel dosimetric parameters. Conclusions: The results of this study using PROs are consistent with prior studies with physician-assessed acute toxicity, and they identify small bowel V15 as an important predictor of acute GI symptoms during 5-FU-based chemoradiation treatment. A better understanding of the relationship between radiation dosimetric parameters and PROs may allow physicians to improve radiation planning to optimize patient outcomes.« less

PHARMACOKINETICS OF A SINGLE DOSE OF METRONIDAZOLE AFTER RECTAL ADMINISTRATION IN CAPTIVE ASIAN ELEPHANTS (ELEPHAS MAXIMUS).

PubMed

Sander, Samantha J; Siegal-Willott, Jessica L; Ziegler, Jessie; Lee, Elizabeth; Tell, Lisa; Murray, Suzan

2016-03-01

Metronidazole is a nitroimidazole antibacterial and antiprotozoal drug with bacteriocidal activity against a broad range of anaerobic bacteria. It is a recognized treatment for elephants diagnosed with anaerobic bacterial infection or protozoal disease or exhibiting signs of colonic impaction, diarrhea, and colic. This study evaluated the pharmacokinetics of rectally administered metronidazole (15 mg/kg) in five adult female Asian elephants (Elephas maximus). Serum samples were collected from each animal for 96 hr after rectal administration of metronidazole. Serum concentrations of metronidazole and its primary metabolite, hydroxymetronidazole, were measured via ultraperformance liquid chromatography. Data were analyzed via a noncompartmental pharmacokinetic approach. Results indicated that serum levels of metronidazole were quantifiable at the 0.25 hr time point and absent in all elephants by the 96 hr time point. The serum peak concentration (mean ± SD, 13.15 ± 2.59 μg/ml) and area under the curve from time 0 to infinity (mean ± SD, 108.79 ± 24.77 hr × μg/ml) were higher than that reported in domestic horses after similar usage. Concurrently, the time of maximum serum concentration (mean ± SD, 1.2 ± 0.45 hr) and terminal elimination half-life (harmonic mean ± pseudo-SD, 7.85 ± 0.93 hr) were longer when compared to equine reports. Rectal administration of metronidazole was well tolerated and rapidly absorbed in all study elephants. Based on the findings in this study, metronidazole administered at a single dose of 15 mg/kg per rectum in the Asian elephant is likely to result in serum concentrations above 4 μg/ml for 8 hr and above 2 μg/ml for 24 hr after treatment is administered. Dosing recommendations should reflect the mean inhibitory concentration of metronidazole for each pathogen.

Variability and Reproducibility of 3rd-generation dual-source dynamic volume perfusion CT Parameters in Comparison to MR-perfusion Parameters in Rectal Cancer.

PubMed

Sudarski, Sonja; Henzler, Thomas; Floss, Teresa; Gaa, Tanja; Meyer, Mathias; Haubenreisser, Holger; Schoenberg, Stefan O; Attenberger, Ulrike I

2018-05-02

To compare in patients with untreated rectal cancer quantitative perfusion parameters calculated from 3 rd -generation dual-source dynamic volume perfusion CT (dVPCT) with 3-Tesla-MR-perfusion with regard to data variability and tumour differentiation. In MR-perfusion, plasma flow (PF), plasma volume (PV) and mean transit time (MTT) were assessed in two measurements (M1 and M2) by the same reader. In dVPCT, blood flow (BF), blood volume (BV), MTT and permeability (PERM) were assessed respectively. CT dose values were calculated. 20 patients (60 ± 13 years) were analysed. Intra-individual and intra-reader variability of duplicate MR-perfusion measurements was higher compared to duplicate dVPCT measurements. dVPCT-derived BF, BV and PERM could differentiate between tumour and normal rectal wall (significance level for M1 and M2, respectively, regarding BF: p < 0.0001*/0.0001*; BV: p < 0.0001*/0.0001*; MTT: p = 0.93/0.39; PERM: p < 0.0001*/0.0001*), with MR-perfusion this was true for PF and PV (p-values M1/M2 for PF: p = 0.04*/0.01*; PV: p = 0.002*/0.003*; MTT: p = 0.70/0.27*). Mean effective dose of CT-staging incl. dVPCT was 29 ± 6 mSv (20 ± 5 mSv for dVPCT alone). In conclusion, dVPCT has a lower data variability than MR-perfusion while both dVPCT and MR-perfusion could differentiate tumour tissue from normal rectal wall. With 3 rd -generation dual-source CT dVPCT could be included in a standard CT-staging without exceeding national dose reference values.

Treatment-Related Morbidity in Prostate Cancer: A Comparison of 3-Dimensional Conformal Radiation Therapy With and Without Image Guidance Using Implanted Fiducial Markers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, Jasmeet, E-mail: drsingh.j@gmail.com; Greer, Peter B.; White, Martin A.

Purpose: To estimate the prevalence of rectal and urinary dysfunctional symptoms using image guided radiation therapy (IGRT) with fiducials and magnetic resonance planning for prostate cancer. Methods and Materials: During the implementation stages of IGRT between September 2008 and March 2010, 367 consecutive patients were treated with prostatic irradiation using 3-dimensional conformal radiation therapy with and without IGRT (non-IGRT). In November 2010, these men were asked to report their bowel and bladder symptoms using a postal questionnaire. The proportions of patients with moderate to severe symptoms in these groups were compared using logistic regression models adjusted for tumor and treatmentmore » characteristic variables. Results: Of the 282 respondents, the 154 selected for IGRT had higher stage tumors, received higher prescribed doses, and had larger volumes of rectum receiving high dosage than did the 128 selected for non-IGRT. The follow-up duration was 8 to 26 months. Compared with the non-IGRT group, improvement was noted in all dysfunctional rectal symptoms using IGRT. In multivariable analyses, IGRT improved rectal pain (odds ratio [OR] 0.07 [0.009-0.7], P=.02), urgency (OR 0.27 [0.11-0.63], P=<.01), diarrhea (OR 0.009 [0.02-0.35], P<.01), and change in bowel habits (OR 0.18 [0.06-0.52], P<.010). No correlation was observed between rectal symptom levels and dose-volume histogram data. Urinary dysfunctional symptoms were similar in both treatment groups. Conclusions: In comparison with men selected for non-IGRT, a significant reduction of bowel dysfunctional symptoms was confirmed in men selected for IGRT, even though they had larger volumes of rectum treated to higher doses.« less

Small Bowel Dose Parameters Predicting Grade ≥3 Acute Toxicity in Rectal Cancer Patients Treated With Neoadjuvant Chemoradiation: An Independent Validation Study Comparing Peritoneal Space Versus Small Bowel Loop Contouring Techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Banerjee, Robyn, E-mail: robynbanerjee@gmail.com; Chakraborty, Santam; Nygren, Ian

Purpose: To determine whether volumes based on contours of the peritoneal space can be used instead of individual small bowel loops to predict for grade ≥3 acute small bowel toxicity in patients with rectal cancer treated with neoadjuvant chemoradiation therapy. Methods and Materials: A standardized contouring method was developed for the peritoneal space and retrospectively applied to the radiation treatment plans of 67 patients treated with neoadjuvant chemoradiation therapy for rectal cancer. Dose-volume histogram (DVH) data were extracted and analyzed against patient toxicity. Receiver operating characteristic analysis and logistic regression were carried out for both contouring methods. Results: Grade ≥3more » small bowel toxicity occurred in 16% (11/67) of patients in the study. A highly significant dose-volume relationship between small bowel irradiation and acute small bowel toxicity was supported by the use of both small bowel loop and peritoneal space contouring techniques. Receiver operating characteristic analysis demonstrated that, for both contouring methods, the greatest sensitivity for predicting toxicity was associated with the volume receiving between 15 and 25 Gy. Conclusion: DVH analysis of peritoneal space volumes accurately predicts grade ≥3 small bowel toxicity in patients with rectal cancer receiving neoadjuvant chemoradiation therapy, suggesting that the contours of the peritoneal space provide a reasonable surrogate for the contours of individual small bowel loops. The study finds that a small bowel V15 less than 275 cc and a peritoneal space V15 less than 830 cc are associated with a less than 10% risk of grade ≥3 acute toxicity.« less

Nonintravenous rescue medications for pediatric status epilepticus: A cost-effectiveness analysis.

PubMed

Sánchez Fernández, Iván; Gaínza-Lein, Marina; Loddenkemper, Tobias

2017-08-01

To quantify the cost-effectiveness of rescue medications for pediatric status epilepticus: rectal diazepam, nasal midazolam, buccal midazolam, intramuscular midazolam, and nasal lorazepam. Decision analysis model populated with effectiveness data from the literature and cost data from publicly available market prices. The primary outcome was cost per seizure stopped ($/SS). One-way sensitivity analyses and second-order Monte Carlo simulations evaluated the robustness of the results across wide variations of the input parameters. The most cost-effective rescue medication was buccal midazolam (incremental cost-effectiveness ratio ([ICER]: $13.16/SS) followed by nasal midazolam (ICER: $38.19/SS). Nasal lorazepam (ICER: -$3.8/SS), intramuscular midazolam (ICER: -$64/SS), and rectal diazepam (ICER: -$2,246.21/SS) are never more cost-effective than the other options at any willingness to pay. One-way sensitivity analysis showed the following: (1) at its current effectiveness, rectal diazepam would become the most cost-effective option only if its cost was $6 or less, and (2) at its current cost, rectal diazepam would become the most cost-effective option only if effectiveness was higher than 0.89 (and only with very high willingness to pay of $2,859/SS to $31,447/SS). Second-order Monte Carlo simulations showed the following: (1) nasal midazolam and intramuscular midazolam were the more effective options; (2) the more cost-effective option was buccal midazolam for a willingness to pay from $14/SS to $41/SS and nasal midazolam for a willingness to pay above $41/SS; (3) cost-effectiveness overlapped for buccal midazolam, nasal lorazepam, intramuscular midazolam, and nasal midazolam; and (4) rectal diazepam was not cost-effective at any willingness to pay, and this conclusion remained extremely robust to wide variations of the input parameters. For pediatric status epilepticus, buccal midazolam and nasal midazolam are the most cost-effective nonintravenous rescue medications in the United States. Rectal diazepam is not a cost-effective alternative, and this conclusion remains extremely robust to wide variations of the input parameters. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Single nucleotide polymorphisms associated with thermoregulation in lactating dairy cows exposed to heat stress.

PubMed

Dikmen, S; Wang, X-z; Ortega, M S; Cole, J B; Null, D J; Hansen, P J

2015-12-01

Dairy cows with increased rectal temperature experience lower milk yield and fertility. Rectal temperature during heat stress is heritable, so genetic selection for body temperature regulation could reduce effects of heat stress on production. One aim of the study was to validate the relationship between genotype and heat tolerance for single nucleotide polymorphisms (SNPs) previously associated with resistance to heat stress. A second aim was to identify new SNPs associated with heat stress resistance. Thermotolerance was assessed in lactating Holsteins during the summer by measuring rectal temperature (a direct measurement of body temperature regulation; n = 435), respiration rate (an indirect measurement of body temperature regulation, n = 450) and sweating rate (the major evaporative cooling mechanism in cattle, n = 455). The association between genotype and thermotolerance was evaluated for 19 SNPs previously associated with rectal temperature from a genomewide analysis study (GWAS), four SNPs previously associated with change in milk yield during heat stress from GWAS, 2 candidate gene SNPs previously associated with rectal temperature and respiration rate during heat stress (ATPA1A and HSP70A) and 66 SNPs in genes previously shown to be associated with reproduction, production or health traits in Holsteins. For SNPs previously associated with heat tolerance, regions of BTA4, BTA6 and BTA24 were associated with rectal temperature; regions of BTA6 and BTA24 were associated with respiration rate; and regions of BTA5, BTA26 and BTA29 were associated with sweating rate. New SNPs were identified for rectal temperature (n = 12), respiration rate (n = 8) and sweating rate (n = 3) from among those previously associated with production, reproduction or health traits. The SNP that explained the most variation were PGR and ASL for rectal temperature, ACAT2 and HSD17B7 for respiration rate, and ARL6IP1 and SERPINE2 for sweating rate. ARL6IP1 was associated with all three thermotolerance traits. In conclusion, specific genetic markers responsible for genetic variation in thermoregulation during heat stress in Holsteins were identified. These markers may prove useful in genetic selection for heat tolerance in Holstein cattle. © 2015 Blackwell Verlag GmbH.

Treatment of trichomoniasis with metronidazole rectal suppositories

PubMed Central

Panja, S K

1982-01-01

Since a single dose of metronidazole in suppository form is very effective in the prevention of postoperative Gram-negative anaerobic infections, 84 patients with vaginal trichomoniasis were treated with metronidazole suppositories (two 1-g suppositories in a single dose). The cure rate in this series was 94%. PMID:7104657

SU-F-J-145: MRI-Guided Interventional Boost Radiotherapy for Rectal Cancer: Investigating the Feasibility of Adapting the Anatomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kleijnen, J J E; Couwenberg, A M; Asselen, B van

Purpose: The recent development of an MRI-linac allows adaptation of treatments to the anatomy of the moment. This anatomy, in turn, could be altered into a more favorable situation for radiotherapy purposes. The purpose of this study is to investigate the potential dosimetric benefits of manipulating rectal anatomy in MRI-guided interventional external-beam radiotherapy for rectal cancer. Methods: For this retrospective analysis, four patients (1M/3F) diagnosed with rectal cancer were included. These underwent MR-imaging using sonography transmission gel as endorectal contrast at time of diagnosis and standard, non-contrast, MR-imaging prior to radiotherapy planning. In the contrast scan, the rectum is inflatedmore » by the inserted contrast gel, thereby potentially increasing the distance between tumor and the organs-at-risk (OAR). Both anatomies were delineated and 7- beam IMRT-plans were calculated for both situations (RT-standard and RT-inflated), using in-house developed treatment planning software. Each plan was aimed to deliver 15Gy to the planning target volume (PTV; tumor+3mm margin) with a D99>95% and Dmax<120% of the planned dose. The D2cc dose to the OAR were then compared for both situations. Results: At equal (or better) target coverage, we found a mean reduction in D2cc of 4.1Gy/237% [range 2.6Gy–6.3Gy/70%–621%] for the bladder and of 2.0Gy/145% [range −0.7Gy–7.9Gy/−73%–442%] for the small-bowel, for the RT-inflated compared to the RT-standard plans. For the three female patients, a reduction in D2cc of 5.2Gy/191% [range 3.2Gy–9.2Gy/44%–475%] for the gynecological organs was found. We found all D2cc doses to be better for the RT-inflated plans, except for one patient for whom the bladder D2cc dose was slightly increased. Conclusion: Reduction of OAR dose by manipulation of anatomy is feasible. Inflation of the rectum results in more distance between OAR and PTV. This leads to a substantial reduction in dose to OAR at equal or better target coverage.« less

A 1.5 T transverse magnetic field in radiotherapy of rectal cancer: Impact on the dose distribution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uilkema, Sander, E-mail: s.uilkema@nki.nl; Heide, Uulke van der; Sonke, Jan-Jakob

2015-12-15

Purpose: MRI guidance during radiotherapy has the potential to enable more accurate dose delivery, optimizing the balance between local control and treatment related toxicity. However, the presence of a permanent magnetic field influences the dose delivery, especially around air cavities. Here, electrons are able to return to the surface through which they entered the air cavity (electron return effect, ERE) locally resulting in dose hot- and cold-spots. Where RT of rectal cancer patients might benefit from MRI guidance for margin reduction, air cavities in and around the target volume are frequently present. The purpose of this research is to evaluatemore » the impact of the presence of a 1.5 T transverse magnetic field on dose delivery in patients with rectal cancer. Methods: Ten patients treated with 5 × 5 Gy RT having large changes in pelvic air content were selected out of a cohort of 33 patients. On the planning CT, a 1.5 T, 6 MV, 7-field intensity modulated radiotherapy (IMRT) plan was created. This plan was subsequently recalculated on daily CT scans. For each daily CT, the CTV V{sub 95%} and V{sub 107%} and bowel area V{sub 5Gy}, V{sub 10Gy}, V{sub 15Gy}, V{sub 20Gy}, and V{sub 25Gy} were calculated to evaluate the changes in dose distribution from fraction to fraction. For comparison, the authors repeated this procedure for the 0 T situation. To study the effect of changing air cavities separate from other anatomical changes, the authors also generated artificial air cavities in the CTV of one patient (2 and 5 cm diameter), in the high dose gradient region (2 cm), and in the low dose area (2 cm). Treatment plans were optimized without and with each simulated air cavity. For appearing and disappearing air cavities, the CTV V{sub 95%} and V{sub 107%} were evaluated. The authors also evaluated the ERE separate from attenuation changes locally around appearing gas pockets. Results: For the ten patients, at 1.5 T, the V{sub 95%} was influenced by both appearing and disappearing air, and dropped to <98% in 2 out of 50 fractions due a disappearing air cavity of 150 cm{sup 3}. V{sub 95%} differences between 0 and 1.5 T were all within 2%. The V{sub 107%} was below 1% in 46 out of 50 fractions, and increased to 3% in the remaining fractions due to appearing air of around 120 cm{sup 3}. For comparison, V{sub 107%} was <1% at 0 T for all fractions. In the bowel area, the V{sub 15Gy} varied strongest from fraction to fraction, but differences between 1.5 and 0 T were minimal with an average difference of 2.3 cm{sup 3} (SD = 18.7 cm{sup 3}, p = 0.38). For the simulated air cavities, the ERE resulted in cold-spots maximally 5% lower than prescribed and hot-spots maximally 6% higher than prescribed. Conclusions: The presence of a 1.5 T magnetic field has an impact on the dose distribution when the air content changes of within a few percent in these selected rectal cancer patients. The authors consider this influence of the transverse magnetic field on the dose distribution in IMRT for rectal cancer patients clinically acceptable.« less

Dosimetric and radiobiologic comparison of 3D conformal versus intensity modulated planning techniques for prostate bed radiotherapy.

PubMed

Koontz, Bridget F; Das, Shiva; Temple, Kathy; Bynum, Sigrun; Catalano, Suzanne; Koontz, Jason I; Montana, Gustavo S; Oleson, James R

2009-01-01

Adjuvant radiotherapy for locally advanced prostate cancer improves biochemical and clinical disease-free survival. While comparisons in intact prostate cancer show a benefit for intensity modulated radiation therapy (IMRT) over 3D conformal planning, this has not been studied for post-prostatectomy radiotherapy (RT). This study compares normal tissue and target dosimetry and radiobiological modeling of IMRT vs. 3D conformal planning in the postoperative setting. 3D conformal plans were designed for 15 patients who had been treated with IMRT planning for salvage post-prostatectomy RT. The same computed tomography (CT) and target/normal structure contours, as well as prescription dose, was used for both IMRT and 3D plans. Normal tissue complication probabilities (NTCPs) were calculated based on the dose given to the bladder and rectum by both plans. Dose-volume histogram and NTCP data were compared by paired t-test. Bladder and rectal sparing were improved with IMRT planning compared to 3D conformal planning. The volume of the bladder receiving at least 75% (V75) and 50% (V50) of the dose was significantly reduced by 28% and 17%, respectively (p = 0.002 and 0.037). Rectal dose was similarly reduced, V75 by 33% and V50 by 17% (p = 0.001 and 0.004). While there was no difference in the volume of rectum receiving at least 65 Gy (V65), IMRT planning significant reduced the volume receiving 40 Gy or more (V40, p = 0.009). Bladder V40 and V65 were not significantly different between planning modalities. Despite these dosimetric differences, there was no significant difference in the NTCP for either bladder or rectal injury. IMRT planning reduces the volume of bladder and rectum receiving high doses during post-prostatectomy RT. Because of relatively low doses given to the bladder and rectum, there was no statistically significant improvement in NTCP between the 3D conformal and IMRT plans.

Impact of a commercially available model-based dose calculation algorithm on treatment planning of high-dose-rate brachytherapy in patients with cervical cancer.

PubMed

Abe, Kota; Kadoya, Noriyuki; Sato, Shinya; Hashimoto, Shimpei; Nakajima, Yujiro; Miyasaka, Yuya; Ito, Kengo; Umezawa, Rei; Yamamoto, Takaya; Takahashi, Noriyoshi; Takeda, Ken; Jingu, Keiichi

2018-03-01

We evaluated the impact of model-based dose calculation algorithms (MBDCAs) on high-dose-rate brachytherapy (HDR-BT) treatment planning for patients with cervical cancer. Seven patients with cervical cancer treated using HDR-BT were studied. Tandem and ovoid applicators were used in four patients, a vaginal cylinder in one, and interstitial needles in the remaining two patients. MBDCAs were applied to the Advanced Collapsed cone Engine (ACE; Elekta, Stockholm, Sweden). All plans, which were originally calculated using TG-43, were re-calculated using both ACE and Monte Carlo (MC) simulations. Air was used as the rectal material. The mean difference in the rectum D2cm3 between ACErec-air and MCrec-air was 8.60 ± 4.64%, whereas that in the bladder D2cm3 was -2.80 ± 1.21%. Conversely, in the small group analysis (n = 4) using water instead of air as the rectal material, the mean difference in the rectum D2cm3 between TG-43 and ACErec-air was 11.87 ± 2.65%, whereas that between TG-43 and ACErec-water was 0.81 ± 2.04%, indicating that the use of water as the rectal material reduced the difference in D2cm3 between TG-43 and ACE. Our results suggested that the differences in the dose-volume histogram (DVH) parameters of TG-43 and ACE were large for the rectum when considerable air (gas) volume was present in it, and that this difference was reduced when the air (gas) volume was reduced. Also, ACE exhibited better dose calculation accuracy than that of TG-43 in this situation. Thus, ACE may be able to calculate the dose more accurately than TG-43 for HDR-BT in treating cervical cancers, particularly for patients with considerable air (gas) volume in the rectum.

Role of belly board device in the age of intensity modulated radiotherapy for pelvic irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Estabrook, Neil C.; Bartlett, Gregory K.; Compton, Julia J.

Small bowel dose often represents a limiting factor for radiation treatment of pelvic malignancies. To reduce small bowel toxicity, a belly board device (BBD) with a prone position is often recommended. Intensity modulated radiotherapy (IMRT) could reduce dose to small bowel based on the desired dose-volume constraints. We investigated the efficacy of BBD in conjunction with IMRT. A total of 11 consecutive patients with the diagnosis of rectal cancer, who were candidates for definitive therapy, were selected. Patients were immobilized with BBD in prone position for simulation and treatment. Supine position computed tomography (CT) data were either acquired at themore » same time or during a diagnostic scan, and if existed was used. Target volumes (TV) as well as organs at risk (OAR) were delineated in both studies. Three-dimensional conformal treatment (3DCRT) and IMRT plans were made for both scans. Thus for each patient, 4 plans were generated. Statistical analysis was conducted for maximum, minimum, and mean dose to each structure. When comparing the normalized mean Gross TV dose for the different plans, there was no statistical difference found between the planning types. There was a significant difference in small bowel sparing when using prone position on BBD comparing 3DCRT and IMRT plans, favoring IMRT with a 29.6% reduction in dose (p = 0.007). There was also a statistically significant difference in small bowel sparing when comparing supine position IMRT to prone-BBD IMRT favoring prone-BBD IMRT with a reduction of 30.3% (p = 0.002). For rectal cancer when small bowel could be a limiting factor, prone position using BBD along with IMRT provides the best sparing. We conclude that whenever a dose escalation in rectal cancer is desired where small bowel could be limiting factor, IMRT in conjunction with BBD should be selected.« less

Tympanic ear thermometer assessment of body temperature among patients with cognitive disturbances. An acceptable and ethically desirable alternative?

PubMed

Aadal, Lena; Fog, Lisbet; Pedersen, Asger Roer

2016-12-01

Investigation of a possible relation between body temperature measurements by the current generation of tympanic ear and rectal thermometers. In Denmark, a national guideline recommends the rectal measurement. Subsequently, the rectal thermometers and tympanic ear devices are the most frequently used and first choice in Danish hospital wards. Cognitive changes constitute challenges with cooperating in rectal temperature assessments. With regard to diagnosing, ethics, safety and the patients' dignity, the tympanic ear thermometer might comprise a desirable alternative to rectal noninvasive measurement of body temperature during in-hospital-based neurorehabilitation. A prospective, descriptive cohort study. Consecutive inclusion of 27 patients. Linear regression models were used to analyse 284 simultaneous temperature measurements. Ethical approval for this study was granted by the Danish Data Protection Agency, and the study was completed in accordance with the Helsinki Declaration 2008. About 284 simultaneous rectal and ear temperature measurements on 27 patients were analysed. The patient-wise variability of measured temperatures was significantly higher for the ear measurements. Patient-wise linear regressions for the 25 patients with at least three pairs of simultaneous ear and rectal temperature measurements showed large interpatient variability of the association. A linear relationship between the rectal body temperature assessment and the temperature assessment employing the tympanic thermometer is weak. Both measuring methods reflect variance in temperature, but ear measurements showed larger variation. © 2016 Nordic College of Caring Science.

Pharmacokinetics and pharmacodynamics of human chorionic gonadotropin (hCG) after rectal administration of hollow-type suppositories containing hCG.

PubMed

Kowari, Kouji; Hirosawa, Iori; Kurai, Hirono; Utoguchi, Naoki; Fujii, Makiko; Watanabe, Yoshiteru

2002-05-01

To determine the effectiveness of human chorionic gonadotropin (hCG) administered rectally, we studied the pharmacokinetics and pharmacodynamics of hCG using a hollow-type suppository. HCG was not detected in plasma when only hCG was administered rectally, even at a higher dose (4,000 IU/kg body weight) than intravenous injection, because of its low bioavailability due to high molecular weight or degradation by proteolytic activity. To enhance the rectal absorption of hCG, the effectiveness of its coadministration with alpha-cyclodextrin (alpha-CyD), an absorption-enhancing agent, was investigated in male rabbits. HCG was detected in plasma following coadministration of hCG and alpha-CyD (10 mg/kg body weight) into the rectum. The plasma hCG concentration increased with increasing dose of alpha-CyD. The AUC(0-48) observed after coadministration of hCG and alpha-CyD at 30 mg/kg body weight was approximately four times higher than that of hCG and alpha-CyD at 10mg/kg body weight. HCG at a high concentration induced a rapid increase in the plasma testosterone concentration (74.2 +/- 3.4 ng/ml) 2 h after intravenous administration. However, the testosterone concentration 24 h after intravenous administration decreased to the physiological level (approximately 20 ng/ml) which had been observed before such administration. On the other hand, the maximum level of testosterone concentration (40.0 +/- 12.6 ng/ml) was observed 24 h after rectal administration of hCG (400 IU/kg body weight) in combination with alpha-CyD (30 mg/kg body weight). Moreover, the plasma testosterone concentration (31.0 +/- 11.4 ng/ml) obtained 72 h after rectal administration tended to be maintained at a higher level than that (14.4 +/- 0.9ng/ml) observed before the administration. These results suggest that the hollow-type suppository as a rectal delivery system of hCG is promising as a new mode of hCG therapy.

Genotype-guided Dosing of mFOLFIRINOX Chemotherapy in Patients With Previously Untreated Advanced Gastrointestinal Malignancies

ClinicalTrials.gov

2018-03-08

Acinar Cell Adenocarcinoma of the Pancreas; Adenocarcinoma of the Gallbladder; Adenocarcinoma of Unknown Primary; Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Diffuse Adenocarcinoma of the Stomach; Duct Cell Adenocarcinoma of the Pancreas; Intestinal Adenocarcinoma of the Stomach; Localized Unresectable Adult Primary Liver Cancer; Metastatic Carcinoma of Unknown Primary; Metastatic Extrahepatic Bile Duct Cancer; Mixed Adenocarcinoma of the Stomach; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Newly Diagnosed Carcinoma of Unknown Primary; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage III Pancreatic Cancer; Stage IIIA Colon Cancer; Stage IIIA Gallbladder Cancer; Stage IIIA Gastric Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Gallbladder Cancer; Stage IIIB Gastric Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Gastric Cancer; Stage IIIC Rectal Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IVA Colon Cancer; Stage IVA Gallbladder Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Gallbladder Cancer; Stage IVB Rectal Cancer; Unresectable Extrahepatic Bile Duct Cancer

Infants and young children metabolise codeine to morphine. A study after single and repeated rectal administration.

PubMed Central

Quiding, H; Olsson, G L; Boreus, L O; Bondesson, U

1992-01-01

1. Codeine was administered rectally to thirteen infants and young children undergoing elective surgery. Nine infants (6-10 months old) received a 4 mg suppository and four children (3-4 years old) an 8 mg suppository. Codeine and its metabolite morphine were measured in plasma by GC/MS. 2. The mean concentrations of codeine at 3, 4 and 5 h after administration were 240, 163 and 123 nmol l-1 in the younger and 309, 251 and 169 nmol l-1 in the older patients. The corresponding concentrations of morphine were 8.3, 7.4 and 4.5 nmol l-1 and 6.8, 5.5 and 2.8 nmol l-1 respectively. One patient in each age group had no detectable amounts of morphine. 3. In the four children, the rectal dose was repeated 6-hourly for four doses. The plasma concentrations of codeine and morphine following the fifth dose were similar to those after the first dose. The mean AUC(0,5 h) of morphine was 1.6% that of codeine. 4. In the infants the mean plasma half-lives of codeine and morphine were 2.6 and 2.5 h. The two infants with the lowest body weights had the longest half-lives. 5. The mean morphine/codeine concentration ratio was 4.3% in the infants and 1.6% in the children, suggesting impaired glucuronidation of morphine in the former group. The hourly concentration ratios were almost identical following the first and fifth dose in the children. 6. We conclude that at the age of 6 months infants are capable of O-demethylating codeine to morphine. PMID:1540490

The Dose-Volume Relationship of Small Bowel Irradiation and Acute Grade 3 Diarrhea During Chemoradiotherapy for Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robertson, John M.; Lockman, David; Yan Di

Purpose: Previous work has found a highly significant relationship between the irradiated small-bowel volume and development of Grade 3 small-bowel toxicity in patients with rectal cancer. This study tested the previously defined parameters in a much larger group of patients. Methods and Materials: A total of 96 consecutive patients receiving pelvic radiation therapy for rectal cancer had treatment planning computed tomographic scans with small-bowel contrast that allowed the small bowel to be outlined with calculation of a small-bowel dose-volume histogram for the initial intended pelvic treatment to 45 Gy. Patients with at least one parameter above the previously determined dose-volumemore » parameters were considered high risk, whereas those with all parameters below these levels were low risk. The grade of diarrhea and presence of liquid stool was determined prospectively. Results: There was a highly significant association with small-bowel dose-volume and Grade 3 diarrhea (p {<=} 0.008). The high-risk and low-risk parameters were predictive with Grade 3 diarrhea in 16 of 51 high-risk patients and in 4 of 45 low-risk patients (p = 0.01). Patients who had undergone irradiation preoperatively had a lower incidence of Grade 3 diarrhea than those treated postoperatively (18% vs. 28%; p = 0.31); however, the predictive ability of the high-risk/low-risk parameters was better for preoperatively (p = 0.03) than for postoperatively treated patients (p = 0.15). Revised risk parameters were derived that improved the overall predictive ability (p = 0.004). Conclusions: The highly significant dose-volume relationship and validity of the high-risk and low-risk parameters were confirmed in a large group of patients. The risk parameters provided better modeling for the preoperative patients than for the postoperative patients.« less

Non-daily pre-exposure prophylaxis for HIV prevention

PubMed Central

Anderson, Peter L.; García-Lerma, J. Gerardo; Heneine, Walid

2015-01-01

Purpose of review To discuss non-daily pre-exposure prophylaxis (PrEP) modalities that may provide advantages compared with daily PrEP in cost and cumulative toxicity, but may have lower adherence forgiveness. Recent Findings Animal models have informed our understanding of early viral transmission events, which help guide event-driven PrEP dosing strategies. These models indicate early establishment of viral replication in rectal or cervicovaginal tissues, so event-driven PrEP should rapidly deliver high mucosal drug concentrations within hours of the potential exposure event. Macaque models have demonstrated the high biological efficacy for event-driven dosing of oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) against both vaginal and rectal virus transmission. In humans, the IPERGAY study demonstrated 86% efficacy for event-driven oral TDF/FTC dosing among men who have sex with men (MSM), while no similar efficacy data are available on women or heterosexual men. The HPTN 067 study showed that certain MSM populations adhere well to non-daily PrEP while other populations of women adhere more poorly to non-daily versus daily regimens. Pharmacokinetic studies following oral TDF/FTC dosing in humans, indicate that TFV-diphosphate (the active form of TFV) accumulates to higher concentrations in rectal versus cervicovaginal tissue but non-adherence in trials complicates the interpretation of differential mucosal drug concentrations. Summary Event-driven dosing for TFV-based PrEP has promise for HIV prevention in MSM. Future research of event-driven PrEP in women and heterosexual men should be guided by a better understanding of the importance of mucosal drug concentrations for PrEP efficacy and its sensitivity to adherence. PMID:26633641

Variations in pelvic dimensions do not predict the risk of circumferential resection margin (CRM) involvement in rectal cancer.

PubMed

Salerno, G; Daniels, I R; Brown, G; Norman, A R; Moran, B J; Heald, R J

2007-06-01

The objective of this study was to assess the value of preoperative pelvimetry, using magnetic resonance imaging (MRI), in predicting the risk of an involved circumferential resection margin (CRM) in a group of patients with operable rectal cancer. A cohort of 186 patients from the MERCURY study was selected. These patients' histological CRM status was compared against 14 pelvimetry parameters measured from the preoperative MRI. These measurements were taken by one of the investigators (G.S.), who was blinded to the final CRM status. There was no correlation between the pelvimetry and the CRM status. However, there was a difference in the height of the rectal cancer and the positive CRM rate (p = 0.011). Of 61 patients with low rectal cancer, 10 had positive CRM at histology (16.4% with CI 8.2%-22.1%) compared with 5 of 110 patients with mid/upper rectal cancers (4.5% with CI 0.7%-8.4%). Magnetic resonance imaging can predict clear margins in most cases of rectal cancer. Circumferential resection margin positivity cannot be predicted from pelvimetry in patients with rectal cancer selected for curative surgery. The only predictive factor for a positive CRM in the patients studied was tumor height.

Impact of knee support and shape of tabletop on rectum and prostate position

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steenbakkers, Roel; Duppen, Joop C.; Betgen, Anja

2004-12-01

Purpose: To evaluate the impact of different tabletops with or without a knee support on the position of the rectum, prostate, and bulb of the penis; and to evaluate the effect of these patient-positioning devices on treatment planning. Methods and materials: For 10 male volunteers, five MRI scans were made in four different positions: on a flat tabletop with knee support, on a flat tabletop without knee support, on a rounded tabletop with knee support, and on a rounded tabletop without knee support. The fifth scan was in the same position as the first. With image registration, the position differencesmore » of the rectum, prostate, and bulb of the penis were measured at several points in a sagittal plane through the central axis of the prostate. A planning target volume was generated from the delineated prostates with a margin of 10 mm in three dimensions. A three-field treatment plan with a prescribed dose of 78 Gy to the International Commission on Radiation Units and Measurements point was automatically generated from each planning target volume. Dose-volume histograms were calculated for all rectal walls. Results: The shape of the tabletop did not affect the rectum and prostate position. Addition of a knee support shifted the anterior and posterior rectal walls dorsally. For the anterior rectal wall, the maximum dorsal shift was 9.9 mm (standard error of the mean [SEM] 1.7 mm) at the top of the prostate. For the posterior rectal wall, the maximum dorsal shift was 10.2 mm (SEM 1.5 mm) at the middle of the prostate. Therefore, the rectal filling was pushed caudally when a knee support was added. The knee support caused a rotation of the prostate around the left-right axis at the apex (i.e., a dorsal rotation) by 5.6 deg (SEM 0.8 deg ) and shifts in the caudal and dorsal directions of 2.6 mm (SEM 0.4 cm) and 1.4 mm (SEM 0.6 mm), respectively. The position of the bulb of the penis was not influenced by the use of a knee support or rounded tabletop. The volume of the rectal wall receiving the same dose range (e.g., 40-75 Gy) was reduced by 3.5% (SEM 0.9%) when a knee support was added. No significant differences were observed between the first and fifth scan (flat tabletop with knee support) for all measured points, thereby excluding time trends. Conclusions: The rectum and prostate were significantly shifted dorsally by the use of a knee support. The rectum shifted more than the prostate, resulting in a dose benefit compared with irradiation without knee support. The shape of the tabletop did not influence the rectum or prostate position.« less

Predicting Rectal and Bladder Overdose During the Course of Prostate Radiotherapy Using Dose-Volume Data From Initial Treatment Fractions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murthy, Vedang, E-mail: vmurthy@actrec.gov.in; Shukla, Pragya; Adurkar, Pranjal

2012-09-01

Purpose: To evaluate whether information from the initial fractions can determine which patients are likely to consistently exceed their planning dose-volume constraints during the course of radiotherapy for prostate cancer. Methods and Materials: Ten patients with high-risk prostate cancer were treated with helical tomotherapy to a dose of 60 Gy in 20 fractions. The prostate, rectum, and bladder were recontoured on their daily megavoltage computed tomography scans and the dose was recalculated. The bladder and rectal volumes (in mL) receiving {>=}100% and {>=}70% of the prescribed dose in each fraction and in the original plans were recorded. A fraction formore » which the difference between planned and delivered was more than 2 mL was considered a volume failure. Similarly if the difference in the planned and delivered maximum dose (D{sub max}) was {>=}1% for the rectum and bladder, the fraction was considered a dose failure. Each patient's first 3 to 5 fractions were analyzed to determine if they correctly identified those patients who would consistently fail (i.e., {>=}20% of fractions) during the course of their radiotherapy. Results: Six parameters were studied; the rectal volume (RV) and bladder volumes (BV) (in mL) received {>=}100% and {>=}70% of the prescribed dose and maximum dose to 2 mL of the rectum and bladder. This was given by RV{sub 100}, RV{sub 70}, BV{sub 100}, BV{sub 70}, RD{sub max}, and BD{sub max}, respectively. When more than 1 of the first 3 fractions exceed the planning constraint as defined, it accurately predicts consistent failures through the course of the treatment. This method is able to correctly identify the consistent failures about 80% (RV{sub 70}, BV{sub 100}, and RV{sub 100}), 90% (BV{sub 70}), and 100% (RD{sub max} and BD{sub max}) of the times. Conclusions: This study demonstrates the feasibility of a method accurately identifying patients who are likely to consistently exceed the planning constraints during the course of their treatment, using information from the first 3 to 5 fractions.« less

The efficacy of azithromycin and doxycycline for the treatment of rectal chlamydia infection: a systematic review and meta-analysis.

PubMed

Kong, Fabian Yuh Shiong; Tabrizi, Sepehr N; Fairley, Christopher Kincaid; Vodstrcil, Lenka A; Huston, Wilhelmina M; Chen, Marcus; Bradshaw, Catriona; Hocking, Jane S

2015-05-01

There are increasing concerns about treatment failure following treatment for rectal chlamydia with 1 g of azithromycin. A systematic review and meta-analysis was conducted to investigate the efficacy of 1 g of azithromycin as a single dose or 100 mg of doxycycline twice daily for 7 days for the treatment of rectal chlamydia. Medline, Embase, PubMed, Cochrane Controlled Trials Register, Australia New Zealand Clinical Trial Register and ClinicalTrials.gov were searched to the end of April 2014. Studies using 1 g of azithromycin or 7 days of doxycycline for the treatment of rectal chlamydia were eligible. Gender, diagnostic test, serovar, symptomatic status, other sexually transmitted infections, follow-up time, attrition and microbial cure were extracted. Meta-analysis was used to calculate pooled (i) azithromycin and doxycycline efficacy and (ii) efficacy difference. All eight included studies were observational. The random-effects pooled efficacy for azithromycin (based on eight studies) was 82.9% (95% CI 76.0%-89.8%; I(2) = 71.0%; P < 0.01) and for doxycycline (based on five studies) was 99.6% (95% CI 98.6%-100%; I(2) = 0%; P = 0.571), resulting in a random-effects pooled efficacy difference (based on five studies) of 19.9% (95% CI 11.4%-28.3%; I(2) = 48.5%; P = 0.101) in favour of doxycycline. The efficacy of single-dose azithromycin may be considerably lower than 1 week of doxycycline for treating rectal chlamydia. However, the available evidence is very poor. Robust randomized controlled trials are urgently required. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Two-week course of preoperative chemoradiotherapy followed by delayed surgery for rectal cancer: a phase II multi-institutional clinical trial (KROG 11-02).

PubMed

Lee, Jong Hoon; Kim, Jun-Gi; Oh, Seong Taek; Lee, Myung Ah; Chun, Hoo Geun; Kim, Dae Yong; Kim, Tae Hyun; Kim, Sun Young; Baek, Ji Yeon; Park, Ji Won; Oh, Jae Hwan; Park, Hee Chul; Choi, Doo Ho; Park, Young Suk; Kim, Hee Cheol; Chie, Eui Kyu; Jang, Hong Seok

2014-01-01

The aim of this study was to evaluate the efficacy and safety of a two-week schedule of radiotherapy with oral capecitabine in locally advanced rectal cancer. Eighty patients with rectal cancer located in the mid to low rectum, staged cT3-4N0-2M0, were prospectively enrolled. They underwent preoperative chemoradiotherapy and delayed surgery 6-8 weeks after the completion of radiation therapy. A radiation dose of 33 Gy in 10 fractions was delivered to the pelvis for 2 weeks. One cycle of oral capecitabine was administered at a dose of 1650 mg/m(2)/day during radiotherapy. Tumor response and toxicity were the study endpoints. This study was registered at ClinicalTrials.gov (number, NCT01431599). All included patients underwent total mesorectal excisions including 12 cases of robot assisted surgery and 50 cases of laparoscopic surgery. Of the 80 patients, 27 (33.8%) achieved downstaging (ypT0-2N0) of a rectal tumor and 11 (13.8%) had a pathologically complete response (ypCR). Downstaging rates were 45% for T classification and 65% for N classification. Sphincter saving was achieved in 73 (91.3%) of the 80 patients. Of the 80 patients, 3 (3.8%) experienced grade 3 hematologic toxicity, and 2 (2.5%) had grade 3 postoperative complications such as ileus and wound dehiscence. There was no grade 4 toxicity. A two-week schedule of radiotherapy with oral capecitabine in locally advanced rectal cancer patients showed low toxicity profiles and promising results in terms of tumor response. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Comparison of Intravenous Infusion of Tramadol Alone with Combination of Tramadol and Paracetamol for Postoperative Pain after Major Abdominal Surgery in Children.

PubMed

Ali, Shayesta; Sofi, Khalid; Dar, Abdul Qayoom

2017-01-01

Pain is a common complaint after surgery and seems to be difficult to manage in children because of fear of complications of pain treatment or misconception that infants and small children do not feel pain at all or feel less pain. A survey reported that 40% of pediatric surgical patients experienced moderate or severe postoperative pain and that more than 75% had insufficient analgesia. Our study was carried to provide continuous infusion of intravenous (i.v.) tramadol alone using a dedicated infusion device Graseby 2100 syringe pump and compared it to a combination of i.v. tramadol infusion and per rectal paracetamol. A total of 124 children aged 1-8 years selected for the study were randomized into two groups using a table of random numbers. Power calculation had suggested a sample size of 62 in each group with a power of 80% and significance level of 5%. Group A comprising 62 children, received i.v. infusion of tramadol in a dose of 0.25 mg/kg/h for 24 h postoperatively. Group B comprising 62 children, received i.v. infusion of tramadol in a dose of 0.25 mg/kg/h for 24 h postoperatively in addition to per rectal suppository of paracetamol in a dose of 90 mg/kg in 24 h (30 mg/kg as first dose followed by 20 mg/kg every 6 hourly for the next 18 h). Postoperatively, patients were observed for 24 h. A statistically significant difference ( P ≤ 0.001) in Face, Legs, Activity, Cry, Consolability pain scores was seen between two groups at 4, 6, and 8 h. Pain scores being less in Group B patients who had received infusion of tramadol and per rectal suppositories of paracetamol compared to Group A patients who received only infusion of tramadol. A statistically significant difference ( P < 0.05) was found in mean analgesic consumption during the first 24 h between the groups. Consumption was more in Group A as compared to Group B. In Group A, 13 patients (21%) required rescue analgesia as compared to only 4 patients (6.5%) in Group B. We recommend use of an infusion of tramadol in a dose of 0.25 mg/kg/h in the first 24 h after surgery, in combination with a regular per rectal paracetamol in a daily dose of 90 mg/kg/day in four divided doses for children after major abdominal surgery. However, a close nursing supervision is essential to increase the safety profile.

Safety and efficacy of E coli enterotoxin adjuvant for urease-based rectal immunization against Helicobacter pylori.

PubMed

Sougioultzis, Stavros; Lee, Cynthia K; Alsahli, Mazen; Banerjee, Subhas; Cadoz, Michel; Schrader, Robert; Guy, Bruno; Bedford, Philip; Monath, Thomas P; Kelly, Ciaran P; Michetti, Pierre

2002-12-13

Low dose E. coli heat-labile enterotoxin (LT), delivered orally or enterically, has been used as an adjuvant for Helicobacter pylori (H. pylori) urease in healthy adults. In this study we aim to test the safety and adjuvant efficacy of LT delivered rectally together with recombinant H. pylori urease. Eighteen healthy adults without present or past H. pylori infection were enrolled in a double blind, randomized, ascending dose study to receive either urease (60 mg), or urease (60 mg) + LT (5 or 25 microg). The immunization preparation was administered per rectum on days 0, 14 and 28. Serum, stool and saliva anti-urease and anti-LT IgG and IgA antibodies (Abs) were measured and urease-specific and LT-specific antigen secreting cells (ASCs) were counted in peripheral blood at baseline and 7 (ASC counts) or 14 days (antibody levels) after each dosing. Peripheral blood lymphoproliferation assays were also performed at baseline and at the end of the study. Rectally delivered urease and LT were well tolerated. Among the 12 subjects assigned to urease+LT, 2 (16.7%) developed anti-urease IgG Abs, 1 (8.3%) developed anti-urease IgA Abs, and 3 (25%) showed urease-specific IgA(+) ASCs. Immune responses to LT were more vigorous, especially in subjects exposed to 5 microg LT. In the urease+ 5 microg LT group, anti-LT IgG and IgA Abs developed in 60 and 80% of the subjects, respectively, while LT-specific IgG(+) and IgA(+) ASCs were detected in all subjects. The magnitude of the anti-LT response was much higher than the response to urease. No IgA anti-urease or anti-LT Abs were detected in stool or saliva and lymphocyte proliferative responses to urease were unsatisfactory. In conclusion, rectal delivery of 5 microg LT is safe and induces vigorous systemic anti-LT immune responses. Further studies are needed to determine if LT can be an effective adjuvant for rectally delivered antigens.

GSK1265744 pharmacokinetics in plasma and tissue after single-dose long-acting injectable administration in healthy subjects.

PubMed

Spreen, William; Ford, Susan L; Chen, Shuguang; Wilfret, David; Margolis, David; Gould, Elizabeth; Piscitelli, Stephen

2014-12-15

GSK1265744 (744) is an HIV-1 integrase inhibitor in clinical development as a long-acting (LA) injectable formulation. This study evaluated plasma and tissue pharmacokinetics after single-dose administration of 744 LA administered by intramuscular (IM) or subcutaneous injections. This was a phase I, open-label, 9-cohort, parallel study of 744 in healthy subjects. 744 was administered as a 200 mg/mL nanosuspension at doses of 100-800 mg IM and 100-400 mg subcutaneous. Eight (6 active and 2 placebo) male and female subjects participated in each of the first 7 cohorts. All 8 subjects, 4 males and 4 females, received active 744 LA in cohorts 8 and 9 and underwent rectal and cervicovaginal tissue sampling, respectively. Plasma pharmacokinetic sampling was performed for a minimum of 12 weeks or until 744 concentrations were ≤0.1 μg/mL. Rectal and cervicovaginal tissue biopsies were performed at weeks 2 and 8 (cohort 8) and weeks 4 and 12 (cohort 9). 744 LA was generally safe and well tolerated after single injections. A majority of subjects reported injection site reactions, all graded as mild in intensity. Plasma concentration-time profiles were prolonged with measureable concentrations up to 52 weeks after dosing. 744 LA 800 mg IM achieved mean concentrations above protein adjusted-IC90 for approximately 16 weeks. Rectal and cervicovaginal tissue concentrations ranged from <8% to 28% of corresponding plasma concentrations. These data suggest 744 LA injection has potential application as a monthly or less frequent HIV treatment or prevention agent.

The importance of applicator design for intraluminal brachytherapy of rectal cancer.

PubMed

Hansen, Johnny Witterseh; Jakobsen, Anders

2006-09-01

An important aspect of designing an applicator for radiation treatment of rectal cancer is the ability to minimize dose to the mucosa and noninvolved parts of the rectum wall. For this reason we investigated a construction of a flexible multichannel applicator with several channels placed along the periphery of a cylinder and a construction of a rigid cylinder with a central channel and interchangeable shields. Calculations of the dose gradient, dose homogeneity in the tumor, and shielding ability were performed for the two applicators in question. Furthermore, the influence on dose distribution around a flexible multichannel applicator from an unintended off-axis positioning of the source inside a bent channel was investigated by film measurements on a single bent catheter. Calculations showed that a single-channel applicator with interchangeable shields yields a higher degree of shielding and has a better dose homogeneity in the tumor volume than that of a multi-channel applicator. A single-channel applicator with interchangeable shields was manufactured, and the influence of different size of shield angle on dose rate in front of and behind the shields was measured. While dose rate in front of the shield and shielding ability are closely independent of the size of the shield angle when measured 1 cm from the applicator surface, dose rate in more distant volumes will to some extent be influenced by shield angle due to volume scatter conditions.

The importance of applicator design for intraluminal brachytherapy of rectal cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hansen, Johnny Witterseh; Jakobsen, Anders; Department of Oncology, Hospital of Vejle, DK-7100 Vejle

2006-09-15

An important aspect of designing an applicator for radiation treatment of rectal cancer is the ability to minimize dose to the mucosa and noninvolved parts of the rectum wall. For this reason we investigated a construction of a flexible multichannel applicator with several channels placed along the periphery of a cylinder and a construction of a rigid cylinder with a central channel and interchangeable shields. Calculations of the dose gradient, dose homogeneity in the tumor, and shielding ability were performed for the two applicators in question. Furthermore, the influence on dose distribution around a flexible multichannel applicator from an unintendedmore » off-axis positioning of the source inside a bent channel was investigated by film measurements on a single bent catheter. Calculations showed that a single-channel applicator with interchangeable shields yields a higher degree of shielding and has a better dose homogeneity in the tumor volume than that of a multichannel applicator. A single-channel applicator with interchangeable shields was manufactured, and the influence of different size of shield angle on dose rate in front of and behind the shields was measured. While dose rate in front of the shield and shielding ability are closely independent of the size of the shield angle when measured 1 cm from the applicator surface, dose rate in more distant volumes will to some extent be influenced by shield angle due to volume scatter conditions.« less

Rectal Diclofenac Versus Rectal Paracetamol: Comparison of Antipyretic Effectiveness in Children.

PubMed

Sharif, Mohammad Reza; Haji Rezaei, Mostafa; Aalinezhad, Marzieh; Sarami, Golbahareh; Rangraz, Masoud

2016-01-01

Fever is the most common complaint in pediatric medicine and its treatment is recommended in some situations. Paracetamol is the most common antipyretic drug, which has serious side effects such as toxicity along with its positive effects. Diclofenac is one of the strongest non-steroidal anti-inflammatory (NSAID) drugs, which has received little attention as an antipyretic drug. This study was designed to compare the antipyretic effectiveness of the rectal form of Paracetamol and Diclofenac. This double-blind controlled clinical trial was conducted on 80 children aged six months to six years old. One group was treated with rectal Paracetamol suppositories at 15 mg/kg dose and the other group received Diclofenac at 1 mg/kg by rectal administration (n = 40). Rectal temperature was measured before and one hour after the intervention. Temperature changes in the two groups were compared. The average rectal temperature in the Paracetamol group was 39.6 ± 1.13°C, and 39.82 ± 1.07°C in the Diclofenac group (P = 0.37). The average rectal temperature, one hour after the intervention, in the Paracetamol and the Diclofenac group was 38.39 ± 0.89°C and 38.95 ± 1.09°C, respectively (P = 0.02). Average temperature changes were 0.65 ± 0.17°C in the Paracetamol group and 1.73 ± 0.69°C in the Diclofenac group (P < 0.001). In the first one hour, Diclofenac suppository is able to control the fever more efficient than Paracetamol suppositories.

Interleukin genes and associations with colon and rectal cancer risk and overall survival

PubMed Central

Bondurant, Kristina L.; Lundgreen, Abbie; Herrick, Jennifer S.; Kadlubar, Susan; Wolff, Roger K.; Slattery, Martha L.

2012-01-01

Interleukins are a group of cytokines that contribute to growth and differentiation, cell migration, and inflammatory and anti-inflammatory responses by the immune system. In this study we examined genetic variation in genes from various anti-inflammatory and pro-inflammatory interleukins to determine association with colon and rectal cancer risk and overall survival. Data from two population-based incident studies of colon cancer (1555 cases and 1956 controls) and rectal cancer (754 cases and 954 controls) were utilized. After controlling for multiple comparisons, single nucleotide polymorphisms (SNPs) from four genes, IL3, IL6R, IL8, IL15, were associated with increased colon cancer risk and CXCR1, and CXCR2 were significantly associated with increased rectal cancer risk. Only SNPs from genes within the IL-8 pathway (IL8, CXCR1, and CXCR2) showed a significant association with both colon and rectal cancer risk. Several SNPs interacted significantly with IL8 and IFNG SNPs and with aspirin/NSAID, cigarette smoking, estrogen use and BMI. For both colon and rectal cancer, increasing numbers of risk alleles were associated with increased hazard of death from cancer; the estimated hazard of death for colon cancer for the highest category of risk alleles was 1.74 (95% CI 1.18–2.56) and 1.96 (95% CI 1.28–2.99) for rectal cancer. These data suggest interleukin genes play a role in risk and overall survival for colon and rectal cancer. PMID:22674296

Evaluation of Biologic Effective Dose and Schedule of Fractionation for Preoperative Radiotherapy for Rectal Cancer: Meta-Analyses and Meta-Regression;Rectal cancer; Preoperative radiotherapy; Biologic effective dose; Meta-analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arruda Viani, Gustavo, E-mail: gusviani@gmail.com; Stefano, Eduardo Jose; Vendito Soares, Francisco

2011-07-15

Purpose: To evaluate whether the risk of local recurrence depends on the biologic effective dose (BED) or fractionation dose in patients with resectable rectal cancer undergoing preoperative radiotherapy (RT) compared with surgery alone. Methods and Materials: A meta-analysis of randomized controlled trials (RCTs) was performed. The MEDLINE, Embase, CancerLit, and Cochrane Library databases were systematically searched for evidence. To evaluate the dose-response relationship, we conducted a meta-regression analysis. Four subgroups were created: Group 1, RCTs with a BED >30 Gy{sub 10} and a short RT schedule; Group 2, RCTs with BED >30 Gy{sub 10} and a long RT schedule; Groupmore » 3, RCTs with BED {<=}30 Gy{sub 10} and a short RT schedule; and Group 4, RCTs with BED {<=}30 Gy{sub 10} and a long RT schedule. Results: Our review identified 21 RCTs, yielding 9,097 patients. The pooled results from these 21 randomized trials of preoperative RT showed a significant reduction in mortality for groups 1 (p = .004) and 2 (p = .03). For local recurrence, the results were also significant in groups 1 (p = .00001) and 2 (p = .00001).The only subgroup that showed a greater sphincter preservation (SP) rate than surgery was group 2 (p = .03). The dose-response curve was linear (p = .006), and RT decreased the risk of local recurrence by about 1.7% for each Gy{sub 10} of BED. Conclusion: Our data have shown that RT with a BED of >30 Gy{sub 10} is more efficient in reducing local recurrence and mortality rates than a BED of {<=}30 Gy{sub 10}, independent of the schedule of fractionation used. A long RT schedule with a BED of >30 Gy{sub 10} should be recommended for sphincter preservation.« less

Favorable toxicity and biochemical control using real-time inverse optimization technique for prostate brachytherapy.

PubMed

Raben, Adam; Rusthoven, Kyle E; Sarkar, Abrihup; Glick, Andrew; Benge, Bruce; Jacobs, Dayee; Raben, David

2009-01-01

Favorable dosimetric results have been reported using intraoperative inverse optimization (IO) for permanent prostate brachytherapy. The clinical implications of these improvements in dosimetry are unclear. We review toxicity and early biochemical outcomes for patients implanted using IO technique. Between 2001 and 2007, 165 patients received permanent prostate implants using real-time IO and had >/=3 months of followup. Dose constraints for inverse planning were: the prostate volume receiving 100% of the prescription dose [prostate V(100)] was >95%; the dose received by 90% of the gland [prostate D(90)] was within the 140-180 by dose range; the volume of urethra receiving 150% of the prescription dose [urethra V(150)] was <30%; and the volume of rectal wall receiving 110% of the prescription dose [rectal V(110)] was <1.0 cc. Toxicity was prospectively scored using the Radiation Therapy Oncology Group toxicity scale and the International Prostate Symptom Score questionnaire. Biochemical control was determined using the nadir + 2 ng/mL definition. Mean followup was 30 months (range, 6-63 months). Risk classification was low risk in 89% and intermediate risk in 11%. Iodine-125 sources were used for 161 implants and palladium-103 sources for four implants. The median number of seeds and total activity implanted were 61 and 999 MBq, respectively, for a median prostate volume of 33.6 cc. Late GU and GI morbidity was uncommon. Among patients with at least 24 months followup, 16% had persistent Grade 2-3 urinary morbidity. Grade 2 rectal bleeding occurred in 1 patient (0.6%). Biochemical failure has occurred in only 4 patients at last followup. IO technique for prostate brachytherapy is associated with low rates of late morbidity and excellent early biochemical control. Additionally, the number of seeds and total implanted activity required to achieve a high-quality implant are lower compared with historical controls.

Impact of a commercially available model-based dose calculation algorithm on treatment planning of high-dose-rate brachytherapy in patients with cervical cancer

PubMed Central

Abe, Kota; Kadoya, Noriyuki; Sato, Shinya; Hashimoto, Shimpei; Nakajima, Yujiro; Miyasaka, Yuya; Ito, Kengo; Umezawa, Rei; Yamamoto, Takaya; Takahashi, Noriyoshi; Takeda, Ken; Jingu, Keiichi

2018-01-01

Abstract We evaluated the impact of model-based dose calculation algorithms (MBDCAs) on high-dose-rate brachytherapy (HDR-BT) treatment planning for patients with cervical cancer. Seven patients with cervical cancer treated using HDR-BT were studied. Tandem and ovoid applicators were used in four patients, a vaginal cylinder in one, and interstitial needles in the remaining two patients. MBDCAs were applied to the Advanced Collapsed cone Engine (ACE; Elekta, Stockholm, Sweden). All plans, which were originally calculated using TG-43, were re-calculated using both ACE and Monte Carlo (MC) simulations. Air was used as the rectal material. The mean difference in the rectum D2cm3 between ACErec-air and MCrec-air was 8.60 ± 4.64%, whereas that in the bladder D2cm3 was −2.80 ± 1.21%. Conversely, in the small group analysis (n = 4) using water instead of air as the rectal material, the mean difference in the rectum D2cm3 between TG-43 and ACErec-air was 11.87 ± 2.65%, whereas that between TG-43 and ACErec-water was 0.81 ± 2.04%, indicating that the use of water as the rectal material reduced the difference in D2cm3 between TG-43 and ACE. Our results suggested that the differences in the dose–volume histogram (DVH) parameters of TG-43 and ACE were large for the rectum when considerable air (gas) volume was present in it, and that this difference was reduced when the air (gas) volume was reduced. Also, ACE exhibited better dose calculation accuracy than that of TG-43 in this situation. Thus, ACE may be able to calculate the dose more accurately than TG-43 for HDR-BT in treating cervical cancers, particularly for patients with considerable air (gas) volume in the rectum. PMID:29378024

A dosimetric analysis of intensity-modulated radiation therapy (IMRT) as an alternative to adjuvant high-dose-rate (HDR) brachytherapy in early endometrial cancer patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aydogan, Bulent; Mundt, Arno J.; Department of Radiation Oncology, University of Illinois at Chicago, Chicago, IL

2006-05-01

Purpose: To evaluate the role of intensity-modulated radiation treatment (IMRT) as an alternative to high-dose-rate (HDR) brachytherapy in the treatment of the vagina in postoperative early endometrial cancer patients after surgery. Methods and Materials: Planning computed tomography (CT) scans of 10 patients previously treated with HDR were used in this study. In all cases, a dose of 700 cGy/fraction was prescribed at a distance of 0.5 cm from the cylinder surface. The same CT scans were then used in IMRT planning. In this paradigm, the vaginal cylinder represents a component of a hypothetical immobilization system that would be indexed tomore » the linac treatment table. Results: Our study showed that IMRT provided relatively lower rectal doses than HDR when treatment was prescribed at a distance of 0.5 cm away from the cylinder surface. Maximum rectal doses were lower with IMRT compared with HDR (average: 89.0% vs. 142.6%, respectively, p < 0.05). Moreover, the mean rectal dose was lower in IMRT plans compared with HDR plans with treatment prescribed either to the surface (average: 14.8% vs. 21.4%, respectively, p < 0.05) or to 0.5 cm (average: 19.6% vs. 33.5%, respectively, p < 0.05). IMRT plans had planning target volume (PTV) coverage comparable with HDR (average PTV minimum for treatment prescribed to 0.5 cm: 93.9% vs. 92.1%, p = 0.71, respectively) with less inhomogeneity (average PTV maximum: 110.8% vs. 381.6%, p < 0.05). Conclusion: Our dosimetric analysis suggests that when used in conjunction with a suitable immobilization system, IMRT may provide an alternative to HDR brachytherapy in women with early endometrial cancer after hysterectomy. However, more studies are needed to evaluate the clinical merit of the IMRT in these patients.« less

Clinical analysis of speculum-based vaginal packing for high-dose-rate intracavitary tandem and ovoid brachytherapy in cervical cancer

PubMed Central

Sud, Shivani; Roth, Toni

2018-01-01

Purpose Intra-vaginal packing is used to fix the applicator and displace organs at risk (OAR) during high-dose-rate intracavitary tandem and ovoid brachytherapy (HDR-ICB). We retain the speculum from applicator placement as a dual-function bladder and rectum retractor during treatment. Our objective is to review salient techniques for OAR displacement, share our packing technique, and determine the reduction in dose to OAR and inter-fraction variability of dose to OAR, associated with speculum-based vaginal packing (SBVP) in comparison to conventional gauze packing during HDR-ICB. Material and methods We reviewed HDR-ICB treatment plans for 45 patients, including 10 who underwent both conventional gauze packing and SBVP. Due to institutional inter-provider practice differences, patients non-selectively received either packing procedure. Packing was performed under conscious sedation, followed by cone beam computed tomography used for dosimetric planning. Maximum absolute and percent-of-prescription dose to the International Commission of Radiation Units bladder and rectal points in addition to D0.1cc, D1.0cc, and D2.0cc volumes of the bladder and rectum were analyzed and compared for each packing method using an independent sample t-test. Results Of the 179 fractions included, 73% and 27% used SBVP and gauze packing, respectively. For patients prescribed 6 Gy to point A, SBVP was associated with reduced mean D0.1cc bladder dose, inter-fraction variability in D0.1cc bladder dose by 9.3% (p = 0.026) and 9.0%, respectively, and statistically equivalent rectal D0.1cc, D1.0cc, and D2.0cc. Patients prescribed 5.5 Gy or 5 Gy to point A after dose optimization, were less likely to benefit from SBVP. In the intra-patient comparison, 80% of patients had reduction in at least one rectum or bladder parameter. Conclusions In patients with conducive anatomy, SBVP is a cost-efficient packing method that is associated with improved bladder sparing and comparable rectal sparing relative to gauze packing during HDR-ICB without general anesthesia. PMID:29619054

Study on rectal administration of azithromycin by suppository for pediatric use.

PubMed

Maeda, Miyuki; Nakano, Yukitaka; Aoyama, Takahiko; Matsumoto, Yoshiaki; Fujito, Hiroshi

2016-04-01

Azithromycin (AZM) is widely used as a first-line treatment option for children with mycoplasma pneumonia. Although pharmacists perform medication counseling in the pediatric ward, children often experience vomiting as a result of oral AZM administration. Drugs that are administered rectally are generally considered to enter the circulation system without passing through the liver first. The aim of our study was to prepare an AZM suppository and investigate the pharmaceutical properties and well as pharmacokinetics of the rectal administration route in humans. Five healthy volunteers were enrolled in the study. All subjects provided written informed consent before participating in the study. Subjects were randomly assigned to either oral administration of oral AZM 500-mg tablet or rectal administration of 125-mg, 250-mg, or 500-mg AZM suppository. Blood samples for preparation of serum were collected predose as well as at 1, 2, 3, 4, 6, 12, and 24 hours following the first rectal dose. Serum concentrations of AZM were determined by high-performance liquid chromatography (HPLC) with electrochemical detection. The bioavailability of the AZM suppository through rectal administration was 20.3% compared to oral administration. We hypothesize that the surface area where AZM is absorbed also affects the absorption by rectal administration. Although further investigation is necessary to improve the absorption of AZM by the rectum and to ensure safety in children, the AZM suppository may be an effective preparation in cases where oral administration is not tolerated.

Nicotinamide pharmacokinetics in humans: effect of gastric acid inhibition, comparison of rectal vs oral administration and the use of saliva for drug monitoring.

PubMed Central

Stratford, M. R.; Dennis, M. F.; Hoskin, P.; Phillips, H.; Hodgkiss, R. J.; Rojas, A.

1996-01-01

The effect of inhibiting gastric acid secretion on nicotinamide pharmacokinetics was studied in five volunteers with the intent of reducing the large variations observed previously in the time to and magnitude of peak plasma concentrations. Plasma levels were determined using a standard high-performance liquid chromatography (HPLC) method after an oral dose of 3 g of nicotinamide either alone or preceded by pretreatment with omeprazole. Suppression of gastric acid production had no significant effect on the rate of uptake or on the peak levels achieved. To bypass gastric acidity, the rectal route was also assessed using a suppository in four volunteers and one patient undergoing radiotherapy. Absorption was slow and variable and much lower plasma levels were observed than after oral dosing. Thus, no improvement in the pharmacokinetics of nicotinamide was observed using either of these two approaches. Parallel estimations were made using a novel and non-invasive method for monitoring nicotinamide pharmacokinetics in saliva. A large and variable fraction of the total amount of nicotinamide-related material in saliva was found to be nicotinic acid, a metabolite not normally found in human plasma. This conversion was inhibited by the use of a chlorhexidine mouthwash, indicating that the oral flora was responsible for its production. The time to peak levels of nicotinamide or of nicotinamide plus nicotinic acid in saliva correlated well with that in plasma. However, peak concentrations for nicotinamide alone were significantly lower than in plasma, and very variable, whereas for nicotinamide plus nicotinic acid saliva levels were 20-30% higher, but more consistent. Although there are some practical difficulties in quantitatively handling saliva, the method is very useful for monitoring nicotinamide pharmacokinetics and for assessment of compliance with nicotinamide treatment. PMID:8679452

Rectal methadone in cancer patients with pain. A preliminary clinical and pharmacokinetic study.

PubMed

Ripamonti, C; Zecca, E; Brunelli, C; Rizzio, E; Saita, L; Lodi, F; De Conno, F

1995-10-01

Cancer pain can be treated in most cases with oral analgesics. However, during their clinical history, 53% to 70% of patients will need alternative routes of opioid administration. The rectal administration of opioids is a simple alternative route for many patients. There are no data in the literature regarding the pharmacodynamics and pharmacokinetics of rectal methadone. We evaluated the analgesia, tolerability and absorption profile of methadone hydrochloride in six opioid-naive cancer patients with pain. A blood sample was collected before administration of a single dose of drug (10 mg) and then again after fixed times. At these fixed times the patients were asked about pain, nausea and drowsiness by means of a visual analogue scale of 0-100 mm (VAS). Pain relief was statistically significant as early as 30 minutes and up to eight hours after methadone administration. None of the patients reported significant side effects. The pharmacokinetics of rectal methadone showed rapid and extensive distribution phases followed by a slow elimination phase. Rectal methadone can be considered an effective analgesic therapy for patients with cancer pain for whom oral and/or parenteral opioids are not indicated or available.

Helicobacter pylori-Negative Primary Rectal MALT Lymphoma: Complete Remission after Radiotherapy

PubMed Central

Okamura, Takuma; Suga, Tomoaki; Iwaya, Yugo; Ito, Tetsuya; Yokosawa, Shuichi; Arakura, Norikazu; Ota, Hiroyoshi; Tanaka, Eiji

2012-01-01

Rectal mucosa-associated lymphoid tissue (MALT) lymphoma is a rare condition. Although the majority of patients undergo surgical resection, a definitive treatment for rectal MALT lymphoma has not yet been established. In the present study, we report the outcome of radiotherapy in 3 patients with rectal MALT lymphoma. Our cohort ranged from 56 to 65 years of age. The male/female ratio was 1:2, and all patients were in stage I (Lugano classification) of the disease. Endoscopic findings revealed elevated lesions resembling submucosal tumors in 2 patients, and a sessile elevated lesion with a nodular surface in 1 patient. One of the 3 patients underwent magnifying endoscopy with crystal violet staining that demonstrated a type I pit pattern (Kudo's classification) lesion with a broad intervening area caused by the upthrust of the tumor from the submucosa. All patients tolerated radiotherapy at doses of 30 Gy without major complications and achieved complete remission. Follow-up ranged from 13 to 75 months (mean 51.0 months), revealing no recurrence of MALT lymphoma. As such, we propose radiotherapy to be a safe and effective means for treating rectal MALT lymphoma. PMID:22754493

Clinical efficacy of Spasmofen® suppository in the emergency treatment of renal colic: a randomized, double-blind, double-dummy comparative trial.

PubMed

Yakoot, Mostafa; Salem, Amel; Yousef, Sameh; Helmy, Sherine

2014-01-01

Renal colic is typically characterized by the sudden onset of severe pain radiating from the flank to the groin and its acute management in emergency departments essentially aims at rapid pain relief. Spasmofen(®) is a brand of Amriya Pharmaceutical Industries in the form of rectal suppositories containing ketoprofen 100 mg and hyoscine butylbromide 10 mg. This combination is intended for the rapid relief of severe colicky pain in the renal system, hepatobiliary system, or gastrointestinal tract. This trial aims to compare a single-dose of Spasmofen rectal suppository to a single intravenous (IV) ketorolac tromethamine 30 mg/2 mL dose in patients with acute renal colic. A total of 80 eligible consecutive patients presenting to the emergency departments of two medical centers with acute renal colic were included in the study. Eligible patients who signed the informed consent were randomly assigned into two treatment groups: an experimental group (Spasmofen group) who received one Spasmofen rectal suppository plus an IV injection of 2 mL of normal saline solution; and a control group (ketorolac group) who received one ketorolac 30 mg/2 mL ampoule IV plus one placebo suppository. Treatment success, defined as a change in the verbal rating score from severe or moderate pain to none or mild at 60 minutes after the dose, was compared between groups using the chi-square/Fisher's exact test. Percentage reductions in visual pain analog scale (VPAS) scores at 15 and 60 minutes after the dose were compared between groups using the Z-test for proportions. Successful treatment at 60 minutes occurred in 35 of 40 (87.5%) of Spasmofen-treated patients and in 33 of 40 (82.5%) of ketorolac-treated patients. The difference was not statistically significant by Fisher's exact test (P=0.755). The mean percentage reduction of VPAS after 15 minutes was 61.82% in the Spasmofen-treated group and 64.76% in the ketorolac-treated group. The difference was also not statistically significant by the Z-test for proportions (P=0.795). Sixty minutes after being treated, Spasmofen was associated with a statistically significant greater reduction in VPAS (mean% reduction =92.36%) than ketorolac (75.06%; P=0.0466). Single-dose Spasmofen rectal suppository might be a safe and effective first-aid treatment for the emergency department relief of acute renal colic.

Pharmacokinetics of promethazine hydrochloride after administration of rectal suppositories and oral syrup to healthy subjects.

PubMed

Strenkoski-Nix, L C; Ermer, J; DeCleene, S; Cevallos, W; Mayer, P R

2000-08-15

The pharmacokinetics of promethazine hydrochloride after administration of rectal suppositories at three dosage strengths and oral syrup were studied. The study had an open-label, randomized, crossover design. At intervals of five to nine days, healthy volunteers were given two 12.5-mg promethazine rectal suppositories, one 25-mg suppository, one 50-mg suppository, or 50 mg (10 mL) of promethazine oral syrup. Blood samples were collected before each dose and at intervals from 0.5 to 48 hours afterward. Promethazine concentration was determined by high-performance liquid chromatography, and pharmacokinetic values were calculated with noncompartmental methods. Thirty-six subjects (18 men and 18 women) completed the study. Absorption was highly variable for all the formulations. On average, absorption was more rapid and the maximum plasma concentration (Cmax) higher for the syrup than for the suppositories. Cmax was significantly lower for the 50-mg suppository (mean, 9.04 ng/mL) than for the syrup (19.3 ng/mL). The time to Cmax (tmax) was significantly shorter for the syrup (mean, 4.4 hours) than for the suppositories (6.7-8.6 hours). There were no significant differences in dose-normalized Cmax among the three suppository treatments. Area under the concentration-versus-time curve (AUC) was comparable between the syrup and the 50-mg suppository and between the treatments with two 12.5-mg suppositories and the 25-mg suppository. Elimination profiles were similar among all treatments (mean half-life [t1/2], 16-19 hours). There were no significant differences in pharmacokinetics on the basis of sex or race. The mean relative bioavailability for the three suppository treatments ranged from 70% to 97%. Individual relative bioavailabilities ranged from 4% to 343%. The pharmacokinetics of promethazine administered in oral syrup and rectal suppositories were highly variable, but, in general, the suppositories produced a lower Cmax and later tmax than the syrup. All formulations were comparable in terms of dose-normalized AUC and t1/2, and the three suppository treatments were comparable in terms of dose-normalized Cmax.

High Doses of GM-CSF Inhibit Antibody Responses in Rectal Secretions and Diminish Modified Vaccinia Ankara/Simian Immunodeficiency Virus Vaccine Protection in TRIM5α-Restrictive Macaques.

PubMed

Kannanganat, Sunil; Wyatt, Linda S; Gangadhara, Sailaja; Chamcha, Venkatesarlu; Chea, Lynette S; Kozlowski, Pamela A; LaBranche, Celia C; Chennareddi, Lakshmi; Lawson, Benton; Reddy, Pradeep B J; Styles, Tiffany M; Vanderford, Thomas H; Montefiori, David C; Moss, Bernard; Robinson, Harriet L; Amara, Rama Rao

2016-11-01

We tested, in rhesus macaques, the effects of a 500-fold range of an admixed recombinant modified vaccinia Ankara (MVA) expressing rhesus GM-CSF (MVA/GM-CSF) on the immunogenicity and protection elicited by an MVA/SIV macaque 239 vaccine. High doses of MVA/GM-CSF did not affect the levels of systemic envelope (Env)-specific Ab, but it did decrease the expression of the gut-homing receptor α4β7 on plasmacytoid dendritic cells (p < 0.01) and the magnitudes of Env-specific IgA (p = 0.01) and IgG (p < 0.05) in rectal secretions. The protective effect of the vaccine was evaluated using 12 weekly rectal challenges in rhesus macaques subgrouped by tripartite motif-containing protein 5α (TRIM5α) genotypes that are restrictive or permissive for infection by the challenge virus SIVsmE660. Eight of nine TRIM5α-restrictive animals receiving no or the lowest dose (1 × 10 5 PFU) of MVA/GM-CSF resisted all 12 challenges. In the comparable TRIM5α-permissive group, only 1 of 12 animals resisted all 12 challenges. In the TRIM5α-restrictive animals, but not in the TRIM5α-permissive animals, the number of challenges to infection directly correlated with the magnitudes of Env-specific rectal IgG (r = +0.6) and IgA (r = +0.6), the avidity of Env-specific serum IgG (r = +0.5), and Ab dependent cell-mediated virus inhibition (r = +0.6). Titers of neutralizing Ab did not correlate with protection. We conclude that 1) protection elicited by MVA/SIVmac239 is strongly dependent on the presence of TRIM5α restriction, 2) nonneutralizing Ab responses contribute to protection against SIVsmE660 in TRIM5α-restrictive animals, and 3) high doses of codelivered MVA/GM-CSF inhibit mucosal Ab responses and the protection elicited by MVA expressing noninfectious SIV macaque 239 virus-like particles. Copyright © 2016 by The American Association of Immunologists, Inc.

Additional 4-week capecitabine during the resting periods after 6-week neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer: long-term oncologic outcomes.

PubMed

Park, Sang Woo; Kim, Jin Soo; Kim, Ji Yeon; Lee, Kyung Ha

2018-06-01

The aim of this study was to evaluate the long-term outcome of additional 4-week chemotherapy with capecitabine during the resting periods following a 6-week neoadjuvant chemoradiotherapy (NCRT) regimen, in patients with locally advanced rectal cancer. Radiotherapy was delivered to the whole pelvis at a total dose of 50.4 Gy for 6 weeks. Oral capecitabine was administered at a dose of 825 mg/m 2 twice daily for 10 weeks. Surgery was performed 2-4 weeks following the completion of chemotherapy. Between January 2010 and September 2011, 41 patients completed the scheduled neoadjuvant therapy and surgery. The pathologic complete response rate, 5-year overall survival, and 5-year disease-free survival rates were 22%, 85.4%, and 78.0%, respectively. The 5-year systemic recurrence and 5-year local recurrence rates were 22% and 0%, respectively. Additional 4-week chemotherapy with capecitabine, during the resting periods following a 6-week NCRT regimen, has favorable long-term oncologic outcomes. Further randomized controlled trials are however necessary to evaluate if substantial improvement in local control is achieved with this additional chemotherapy modality for locally advanced rectal cancer.

Genetic Variation in Selenoprotein Genes, Lifestyle, and Risk of Colon and Rectal Cancer

PubMed Central

Slattery, Martha L.; Lundgreen, Abbie; Welbourn, Bill; Corcoran, Christopher; Wolff, Roger K.

2012-01-01

Background Associations between selenium and cancer have directed attention to role of selenoproteins in the carcinogenic process. Methods We used data from two population-based case-control studies of colon (n = 1555 cases, 1956 controls) and rectal (n = 754 cases, 959 controls) cancer. We evaluated the association between genetic variation in TXNRD1, TXNRD2, TXNRD3, C11orf31 (SelH), SelW, SelN1, SelS, SepX, and SeP15 with colorectal cancer risk. Results After adjustment for multiple comparisons, several associations were observed. Two SNPs in TXNRD3 were associated with rectal cancer (rs11718498 dominant OR 1.42 95% CI 1.16,1.74 pACT 0.0036 and rs9637365 recessive 0.70 95% CI 0.55,0.90 pACT 0.0208). Four SNPs in SepN1 were associated with rectal cancer (rs11247735 recessive OR 1.30 95% CI 1.04,1.63 pACT 0.0410; rs2072749 GGvsAA OR 0.53 95% CI 0.36,0.80 pACT 0.0159; rs4659382 recessive OR 0.58 95% CI 0.39,0.86 pACT 0.0247; rs718391 dominant OR 0.76 95% CI 0.62,0.94 pACT 0.0300). Interaction between these genes and exposures that could influence these genes showed numerous significant associations after adjustment for multiple comparisons. Two SNPs in TXNRD1 and four SNPs in TXNRD2 interacted with aspirin/NSAID to influence colon cancer; one SNP in TXNRD1, two SNPs in TXNRD2, and one SNP in TXNRD3 interacted with aspirin/NSAIDs to influence rectal cancer. Five SNPs in TXNRD2 and one in SelS, SeP15, and SelW1 interacted with estrogen to modify colon cancer risk; one SNP in SelW1 interacted with estrogen to alter rectal cancer risk. Several SNPs in this candidate pathway influenced survival after diagnosis with colon cancer (SeP15 and SepX1 increased HRR) and rectal cancer (SepX1 increased HRR). Conclusions Findings support an association between selenoprotein genes and colon and rectal cancer development and survival after diagnosis. Given the interactions observed, it is likely that the impact of cancer susceptibility from genotype is modified by lifestyle. PMID:22615972

VMAT vs. 7-Field-IMRT: Assessing the Dosimetric Parameters of Prostate Cancer Treatment with a 292-Patient Sample

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kopp, Robert W.; Duff, Michael, E-mail: mduff@cancercarewny.com; Catalfamo, Frank

2011-01-01

We compared normal tissue radiation dose for the treatment of prostate cancer using 2 different radiation therapy delivery methods: volumetric modulated arc therapy (VMAT) vs. fixed-field intensity-modulated radiation therapy (IMRT). Radiotherapy plans for 292 prostate cancer patients treated with VMAT to a total dose of 7740 cGy were analyzed retrospectively. Fixed-angle, 7-field IMRT plans were created using the same computed tomography datasets and contours. Radiation doses to the planning target volume (PTV) and organs at risk (bladder, rectum, penile bulb, and femoral heads) were measured, means were calculated for both treatment methods, and dose-volume comparisons were made with 2-tailed, pairedmore » t-tests. The mean dose to the bladder was lower with VMAT at all measured volumes: 5, 10, 15, 25, 35, and 50% (p < 0.05). The mean doses to 5 and 10% of the rectum, the high-dose regions, were lower with VMAT (p < 0.05). The mean dose to 15% of the rectal volume was not significantly different (p = 0.95). VMAT exposed larger rectal volumes (25, 35, and 50%) to more radiation than fixed-field IMRT (p < 0.05). Average mean dose to the penile bulb (p < 0.05) and mean dose to 10% of the femoral heads (p < 0.05) were lower with VMAT. VMAT therapy for prostate cancer has dosimetric advantages for critical structures, notably for high-dose regions compared with fixed-field IMRT, without compromising PTV coverage. This may translate into reduced acute and chronic toxicity.« less

Phase I Study of Preoperative Chemoradiation With S-1 and Oxaliplatin in Patients With Locally Advanced Resectable Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hong, Yong Sang; Lee, Jae-Lyun; Park, Jin Hong

Purpose: To perform a Phase I study of preoperative chemoradiation (CRT) with S-1, a novel oral fluoropyrimidine, plus oxaliplatin in patients with locally advanced rectal cancer, to determine the maximum tolerated dose and the recommended dose. Methods and Materials: Radiotherapy was delivered to a total of 45 Gy in 25 fractions and followed by a coned-down boost of 5.4 Gy in 3 fractions. Concurrent chemotherapy consisted of a fixed dose of oxaliplatin (50 mg/m{sup 2}/week) on Days 1, 8, 22, and 29 and escalated doses of S-1 on Days 1-14 and 22-35. The initial dose of S-1 was 50 mg/m{supmore » 2}/day, gradually increasing to 60, 70, and 80 mg/m{sup 2}/day. Surgery was performed within 6 {+-} 2 weeks. Results: Twelve patients were enrolled and tolerated up to Dose Level 4 (3 patients at each dose level) without dose-limiting toxicity. An additional 3 patients were enrolled at Dose Level 4, with 1 experiencing a dose-limiting toxicity of Grade 3 diarrhea. Although maximum tolerated dose was not attained, Dose Level 4 (S-1 80 mg/m{sup 2}/day) was chosen as the recommended dose for further Phase II studies. No Grade 4 toxicity was observed, and Grade 3 toxicities of leukopenia and diarrhea occurred in the same patient (1 of 15, 6.7%). Pathologic complete responses were observed in 2 of 15 patients (13.3%). Conclusions: The recommended dose of S-1 was determined to be 80 mg/m{sup 2}/day when combined with oxaliplatin in preoperative CRT, and a Phase II trial is now ongoing.« less

Long-acting rilpivirine as potential pre-exposure prophylaxis for HIV-1 prevention (the MWRI-01 study): an open-label, phase 1, compartmental, pharmacokinetic and pharmacodynamic assessment.

PubMed

McGowan, Ian; Dezzutti, Charlene S; Siegel, Aaron; Engstrom, Jarret; Nikiforov, Alexiy; Duffill, Kathryn; Shetler, Cory; Richardson-Harman, Nicola; Abebe, Kaleab; Back, David; Else, Laura; Egan, Deidre; Khoo, Saye; Egan, James E; Stall, Ronald; Williams, Peter E; Rehman, Khaleel K; Adler, Amy; Brand, Rhonda M; Chen, Beatrice; Achilles, Sharon; Cranston, Ross D

2016-12-01

Long-acting injectable antiretroviral agents are being developed for HIV-1 prevention. The MWRI-01 study was done to characterise the safety, acceptability, and pharmacokinetic and pharmacodynamic profile of long-acting rilpivirine. We did a phase 1 open-label study at the University of Pittsburgh. We enrolled healthy individuals (aged 18-45 years) who were seronegative for HIV-1. Participants were assigned alternately one intramuscular dose of either 1200 mg or 600 mg long-acting rilpivirine, beginning with the 1200 mg dose. We obtained plasma specimens, genital and rectal fluids, and tissue samples (rectal, cervical, and vaginal) before and after exposure to long-acting rilpivirine for assessment of pharmacokinetics and ex-vivo biopsy challenge with HIV-1. Our primary objective was to characterise product safety, and the analysis included all enrolled participants. This trial is registered with ClinicalTrials.gov, number NCT01656018. 36 participants were enrolled into the study, of whom 24 were women and 12 men. 12 women and six men received each dose. 204 adverse events were reported among the 36 participants, of which 200 (98%) were grade 1-2. The most common adverse event was injection site reaction. All grade 3 and 4 adverse events were deemed not related to rilpivirine. Geometric mean (90% CI) concentrations in plasma of rilpivirine at day 28 post dose were 53 ng/mL (38-67) in women and 43 ng/mL (23-63) in men for the 1200 mg dose and 28 ng/mL (19-37) in women and 17 ng/mL (9-24) in men for the 600 mg dose. The tissue-to-plasma ratio for rilpivirine in rectal tissue was about two-fold higher than in vaginal and cervical tissue (1·10-1·53 vs 0·61-0·72 and 0·50-0·71, respectively). Exposure to long-acting rilpivirine suppressed viral replication significantly in rectal tissue (p<0·0001), and this suppression persisted for up to 4 months. By contrast, no viral suppression was seen in cervical or vaginal tissue. Ongoing research will characterise longer term safety and acceptability of multiple injections and help ascertain whether long-acting rilpivirine should advance to assessment of efficacy in preventing HIV-1 infection. Bill & Melinda Gates Foundation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Adherence to Rectal Mesalamine in Patients with Ulcerative Colitis.

PubMed

Boyle, Marie; Ting, Amanda; Cury, Didia B; Nanda, Kavinderjit; Cheifetz, Adam S; Moss, Alan

2015-12-01

Rectal mesalamine is an effective induction and maintenance therapy for ulcerative colitis. Little is known about the adherence rates to rectal mesalamine or barriers to its use. The aim was to quantify the prevalence of nonadherence to rectal mesalamine and to identify patient-reported barriers to adherence. A cohort of patients with ulcerative colitis was prospectively enrolled in this observational study and followed for 12 months. Adherence was assessed by tracking pharmacy refills (medication possession ratio). Individual interviews were undertaken in a subset of subjects. Transcripts from the focus groups and interviews were analyzed to identify themes and links between these themes using qualitative data software (MaxQDA). Seventy patients prescribed rectal mesalamine were prospectively enrolled in the study. At enrollment, 39 of 70 subjects (55%) self-reported "occasional nonadherence" to rectal mesalamine. Over the 12-month follow-up period, only 20 subjects (26%) completed 3 or more refills. Males, or subjects prescribed a once-a-day suppository, were significantly more likely to refill than females (odds ratio = 3.3, 95% confidence interval, 1.1-10.9) or those prescribed suppositories more than once a day (odds ratio = 1.3, 95% confidence interval, 1.1-1.7). By medication possession ratio criteria, 71% of all subjects were nonadherent with their prescribed regimen (medication possession ratio <0.6). Nonadherers were significantly older than adherent subjects: mean age 48 years in nonadherers, versus 37 in adherers, P = 0.04. Patients who were nonadherent to rectal mesalamine frequently cited the mode of administration (65%) and busy lifestyle (40%) as reasons for nonadherence. Intentional nonadherence is common in patients who have been prescribed rectal mesalamine. Gender, age, frequency of dosing, and lifestyle factors may impact adherence.

Mercury toxicity in the shark (Squalus acanthias) rectal gland: apical CFTR chloride channels are inhibited by mercuric chloride.

PubMed

Ratner, Martha A; Decker, Sarah E; Aller, Stephen G; Weber, Gerhard; Forrest, John N

2006-03-01

In the shark rectal gland, basolateral membrane proteins have been suggested as targets for mercury. To examine the membrane polarity of mercury toxicity, we performed experiments in three preparations: isolated perfused rectal glands, primary monolayer cultures of rectal gland epithelial cells, and Xenopus oocytes expressing the shark cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. In perfused rectal glands we observed: (1) a dose-dependent inhibition by mercury of forskolin/3-isobutyl-1-methylxanthine (IBMX)-stimulated chloride secretion; (2) inhibition was maximal when mercury was added before stimulation with forskolin/IBMX; (3) dithiothrietol (DTT) and glutathione (GSH) completely prevented inhibition of chloride secretion. Short-circuit current (Isc) measurements in monolayers of rectal gland epithelial cells were performed to examine the membrane polarity of this effect. Mercuric chloride inhibited Isc more potently when applied to the solution bathing the apical vs. the basolateral membrane (23 +/- 5% and 68 +/- 5% inhibition at 1 and 10 microM HgCl2 in the apical solution vs. 2 +/- 0.9% and 14 +/- 5% in the basolateral solution). This inhibition was prevented by pre-treatment with apical DTT or GSH; however, only the permeant reducing agent DTT reversed mercury inhibition when added after exposure. When the shark rectal gland CFTR channel was expressed in Xenopus oocytes and chloride conductance was measured by two-electrode voltage clamping, we found that 1 microM HgCl2 inhibited forskolin/IBMX conductance by 69.2 +/- 2.0%. We conclude that in the shark rectal gland, mercury inhibits chloride secretion by interacting with the apical membrane and that CFTR is the likely site of this action. Copyright 2006 Wiley-Liss, Inc.

Rectal Toxicity After Proton Therapy For Prostate Cancer: An Analysis of Outcomes of Prospective Studies Conducted at the University of Florida Proton Therapy Institute

DOE Office of Scientific and Technical Information (OSTI.GOV)

Colaco, Rovel J.; Hoppe, Bradford S.; Flampouri, Stella

2015-01-01

Purpose: Study goals were to characterize gastrointestinal effects of proton therapy (PT) in a large cohort of patients treated for prostate cancer, identify factors associated with rectal bleeding (RB), and compare RB between patients receiving investigational protocols versus those in outcome-tracking protocols. Methods and Materials: A total of 1285 consecutive patients were treated with PT between August 2006 and May 2010. Potential pre-existing clinical and treatment-related risk factors for rectal toxicity were recorded. Common Terminology Criteria for Adverse Events version 3.0 was used to score toxicity. Results: Transient RB was the predominant grade 2 or higher (GR2+) toxicity after PT,more » accounting for 95% of gastrointestinal events. GR1 RB occurred in 217 patients (16.9%), GR2 RB in 187 patients (14.5%), and GR3 in 11 (0.9%) patients. There were no GR4 or GR5 events. Univariate analyses showed correlations between GR2+ RB and anticoagulation therapy (P=.008) and rectal and rectal wall dose-volume histogram (DVH) parameters (P<.001). On multivariate analysis, anticoagulation therapy (P=.0034), relative volume of rectum receiving 75 Gy (V75; P=.0102), and relative rectal wall V75 (P=.0017) were significant predictors for G2+ RB. Patients treated with investigational protocols had toxicity rates similar to those receiving outcome-tracking protocols. Conclusions: PT was associated with a low rate of GR2+ gastrointestinal toxicity, predominantly transient RB, which was highly correlated with anticoagulation and rectal DVH parameters. Techniques that limit rectal exposure should be used when possible.« less

[A Case of Effective Chemoradiotherapy Using mFOLFOX6 for Locally Advanced Rectal Cancer].

PubMed

Kuga, Yoshio; Kitamura, Shosuke; Mouri, Teruo; Miwata, Tomohiro; Hirata, Yuzoh; Ishizaki, Yasuyo; Hashimoto, Yasutoshi

2017-05-01

We report a case of locally advanced rectal cancer, treated effectively with chemotherapy consisting of mFOLFOX6 combined with radiotherapy. A 63-year-old man was admitted to our hospital in March 2012 for diarrhea and anal and perineal pain. Advanced rectal cancer with invasion ofthe right perineum was diagnosed based on computer tomography(CT) findings. Surgery was performed; however, the rectal cancer was unresectable. A sigmoid colostomy was performed, and a central venous port was implanted. In April 2012, the patient was treated with chemotherapy using 3 courses ofmFOLFOX6 and concurrent radiotherapy. Radiotherapy at 2 Gy/day was administered 25 times(total dose, 50 Gy). After chemoradiotherapy, the patient underwent 3 courses ofmFOLFOX6 as an additional therapy. By June 2012, CT showed resolution ofthe tumor in the right perineum and a marked decrease in the size ofthe primary rectal cancer. Because the patient refused surgery, we started treatment with combination chemotherapy using oral S-1 and intravenous CPT-11 in August 2012. After 18 courses, the treatment was changed to oral administration ofS -1 alone, which was continued for 1 year. The patient remained well without recurrence for 54 months since the original diagnosis. Therefore, chemoradiotherapy with mFOLFOX6 is a possible option for the management of advanced rectal cancer.

SU-D-BRB-02: Patient-Specific Rectal Toxicity Predictor Based Plan Quality Control for Prostate Stereotactic Body Radiation Therapy (SBRT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, T; Zhou, L; Li, Y

2015-06-15

Purpose: To develop a patient-specific rectal toxicity predictor guided plan quality control tool for prostate SBRT plans. Methods: For prostate SBRT cases, four segments of rectal walls including peri-prostatic anterior rectal wall, peri-prostatic lateral rectal walls, peri-prostatic posterior rectal wall and rectum superior to prostate are identified as organs at risk and the circumference of rectal wall receiving more than 39 Gy (CRW39) and 24 Gy (CRW24) are rectal toxicity predictors. In this new geometry-dosimetry model, a patient geometry descriptor, differential circumference of rectal wall (dCRW) is used as model input geometry parameters and plan dosimetric endpoints CRW39 and CRW24more » are output dosimetric parameters. Linear models are built to correlate dCRW to both CRW39 and CRW24 and established with both a linear regression method and a modified bagging ensemble machine learning method. 27 SBRT prostate cases are retrospectively studied from a dose-escalated clinical trial research. 20 prescribed 50 Gy SBRT cases are recruited to train the model and the other rescaled 7 cases are used to evaluated model feasibility and accuracy. Results: Each solved linear coefficient sequence related to CRW39 or CRW24 is a one-dimensional decreasing function of the distance from the PTV boundary, indicating that the different locations of each rectal circumference have different contributions to each particular dosimetric endpoint. The fitting errors for those trained 20 prostate SBRT cases are small with mean values of 2.39%, 2.45% relative to the endpoint values for SBRT rectal toxicity predictor CRW39 and CRW24 respectively. 1 out of 7 evaluation plans is identified as poor quality plan. After re-planning, the CRW39 and CRW24 can be reduced by 3.34% and 3%, without sacrificing PTV coverage. Conclusion: The proposed patient geometry-plan toxicity predictor model for SBRT plans can be successfully applied to plan quality control for prostate SBRT cases.« less

Age and Comorbid Illness Are Associated With Late Rectal Toxicity Following Dose-Escalated Radiation Therapy for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamstra, Daniel A.; Stenmark, Matt H.; Ritter, Tim

2013-04-01

Purpose: To assess the impacts of patient age and comorbid illness on rectal toxicity following external beam radiation therapy (EBRT) for prostate cancer and to assess the Qualitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) normal tissue complication probability (NTCP) model in this context. Methods and Materials: Rectal toxicity was analyzed in 718 men previously treated for prostate cancer with EBRT (≥75 Gy). Comorbid illness was scored using the Charlson Comorbidity Index (CCMI), and the NTCP was evaluated with the QUANTEC model. The influence of clinical and treatment-related parameters on rectal toxicity was assessed by Kaplan-Meier and Coxmore » proportional hazards models. Results: The cumulative incidence of rectal toxicity grade ≥2 was 9.5% and 11.6% at 3 and 5 years and 3.3% and 3.9% at 3 and 5 years for grade ≥3 toxicity, respectively. Each year of age predicted an increasing relative risk of grade ≥2 (P<.03; hazard ratio [HR], 1.04 [95% confidence interval (CI), 1.01-1.06]) and ≥3 rectal toxicity (P<.0001; HR, 1.14 [95% CI,1.07-1.22]). Increasing CCMI predicted rectal toxicity where a history of either myocardial infarction (MI) (P<.0001; HR, 5.1 [95% CI, 1.9-13.7]) or congestive heart failure (CHF) (P<.0006; HR, 5.4 [95% CI, 0.6-47.5]) predicted grade ≥3 rectal toxicity, with lesser correlation with grade ≥2 toxicity (P<.02 for MI, and P<.09 for CHF). An age comorbidity model to predict rectal toxicity was developed and confirmed in a validation cohort. The use of anticoagulants increased toxicity independent of age and comorbidity. NTCP was prognostic for grade ≥3 (P=.015) but not grade ≥2 (P=.49) toxicity. On multivariate analysis, age, MI, CHF, and an NTCP >20% all correlated with late rectal toxicity. Conclusions: Patient age and a history of MI or CHF significantly impact rectal toxicity following EBRT for the treatment of prostate cancer, even after controlling for NTCP.« less

[Haemorrhagic proctocolitis as primary manifestation of lymphogranuloma venereum in an HIV-positive male].

PubMed

Gormsen, Andreas Brandt; Diernæs, Jon Erik-Fraes; Jensen, Jørgen Skov; Koppelhus, Uffe

2018-03-12

This is a case report of lymphogranuloma venereum (LGV) manifesting as haemorrhagic proctocolitis in a homosexual HIV-positive male. The primary symptom was a rectal abscess, which was initially surgically treated and subsequently insufficiently treated with single-dose tablet azithromycin. The patient's symptoms were successfully treated after a 21-day doxycycline regime. LGV is a sexually transmitted infection with a rising incidence among persons with risk behaviour. This case report underlines the importance, that all positive rectal screenings for Chlamydia trachomatis should be routinely serotyped.

[Haemorrhagic proctocolitis as primary manifestation of lymphogranuloma venereum in an HIV-positive male].

PubMed

Gormsen, Andreas Brandt; Fraes Diernæs, Jon Erik; Jensen, Jørgen Skov; Koppelhus, Uffe

2018-05-14

This is a case report of lymphogranuloma venereum (LGV) manifesting as haemorrhagic proctocolitis in a homosexual HIV-positive male. The primary symptom was a rectal abscess, which was initially surgically treated and subsequently insufficiently treated with single-dose tablet azithromycin. The patient's symptoms were successfully treated after a 21-day doxycycline regime. LGV is a se xually transmitted infection with a rising incidence among persons with risk behaviour. This case report underlines the importance, that all positive rectal screenings for Chlamydia trachomatis should be routinely serotyped.

Prognostic factors in prostate cancer patients treated by radical external beam radiotherapy.

PubMed

Garibaldi, Elisabetta; Gabriele, Domenico; Maggio, Angelo; Delmastro, Elena; Garibaldi, Monica; Russo, Filippo; Bresciani, Sara; Stasi, Michele; Gabriele, Pietro

2017-09-01

The aim of this paper was to analyze, retrospectively, in prostate cancer patients treated in our Centre with external beam radiotherapy, the prognostic factors and their impact on the outcome in terms of cancer-specific survival (CSS), biochemical disease-free survival (BDFS) and clinical disease-free survival (CDFS). From October 1999 and March 2012, 1080 patients were treated with radiotherapy at our Institution: 87% of them were classified as ≤cT2, 83% had a Gleason Score (GS) ≤7, their mean of iPSA was 18 ng/mL, and the rate of clinical positive nodes was 1%. The mean follow-up was 81 months. The statistically significant prognostic factors for all groups of patients at both, univariate and multivariate analysis, were the GS and the iPSA. In intermediate- and high- or very-high-risk patients at multivariate analysis other prognostic factors for CSS were positive nodes on computed tomography (CT) scan and rectal preparation during the treatment; for BDFS, the prognostic factors were patient risk classification, positive lymph nodes on CT scan and rectal/bladder preparation; for CDFS, the prognostic factors were the number of positive core on biopsy (P=0.003), positive lymph nodes on CT scan, and radiotherapy (RT) dose. In high/very-high risk patient group at multivariate analysis other prognostic factors for CSS were clinical/radiological stage and RT dose, for BDFS they were adjuvant hormone therapy, clinical/radiological stage, and RT dose >77.7 Gy, and for CDFS they were clinical/radiological stage and RT dose >77.7 Gy. The results of this study confirm the prognostic factors described in the recent literature, with the addition of rectal/bladder preparation, generally known for its effect on toxicity but not yet on outcome.

Comparison of Intravenous Infusion of Tramadol Alone with Combination of Tramadol and Paracetamol for Postoperative Pain after Major Abdominal Surgery in Children

PubMed Central

Ali, Shayesta; Sofi, Khalid; Dar, Abdul Qayoom

2017-01-01

Background: Pain is a common complaint after surgery and seems to be difficult to manage in children because of fear of complications of pain treatment or misconception that infants and small children do not feel pain at all or feel less pain. A survey reported that 40% of pediatric surgical patients experienced moderate or severe postoperative pain and that more than 75% had insufficient analgesia. Our study was carried to provide continuous infusion of intravenous (i.v.) tramadol alone using a dedicated infusion device Graseby 2100 syringe pump and compared it to a combination of i.v. tramadol infusion and per rectal paracetamol. Subjects and Methods: A total of 124 children aged 1–8 years selected for the study were randomized into two groups using a table of random numbers. Power calculation had suggested a sample size of 62 in each group with a power of 80% and significance level of 5%. Group A comprising 62 children, received i.v. infusion of tramadol in a dose of 0.25 mg/kg/h for 24 h postoperatively. Group B comprising 62 children, received i.v. infusion of tramadol in a dose of 0.25 mg/kg/h for 24 h postoperatively in addition to per rectal suppository of paracetamol in a dose of 90 mg/kg in 24 h (30 mg/kg as first dose followed by 20 mg/kg every 6 hourly for the next 18 h). Postoperatively, patients were observed for 24 h. Results: A statistically significant difference (P ≤ 0.001) in Face, Legs, Activity, Cry, Consolability pain scores was seen between two groups at 4, 6, and 8 h. Pain scores being less in Group B patients who had received infusion of tramadol and per rectal suppositories of paracetamol compared to Group A patients who received only infusion of tramadol. A statistically significant difference (P < 0.05) was found in mean analgesic consumption during the first 24 h between the groups. Consumption was more in Group A as compared to Group B. In Group A, 13 patients (21%) required rescue analgesia as compared to only 4 patients (6.5%) in Group B. Conclusion: We recommend use of an infusion of tramadol in a dose of 0.25 mg/kg/h in the first 24 h after surgery, in combination with a regular per rectal paracetamol in a daily dose of 90 mg/kg/day in four divided doses for children after major abdominal surgery. However, a close nursing supervision is essential to increase the safety profile. PMID:28663644

Random Forests to Predict Rectal Toxicity Following Prostate Cancer Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ospina, Juan D.; INSERM, U1099, Rennes; Escuela de Estadística, Universidad Nacional de Colombia Sede Medellín, Medellín

2014-08-01

Purpose: To propose a random forest normal tissue complication probability (RF-NTCP) model to predict late rectal toxicity following prostate cancer radiation therapy, and to compare its performance to that of classic NTCP models. Methods and Materials: Clinical data and dose-volume histograms (DVH) were collected from 261 patients who received 3-dimensional conformal radiation therapy for prostate cancer with at least 5 years of follow-up. The series was split 1000 times into training and validation cohorts. A RF was trained to predict the risk of 5-year overall rectal toxicity and bleeding. Parameters of the Lyman-Kutcher-Burman (LKB) model were identified and a logistic regression modelmore » was fit. The performance of all the models was assessed by computing the area under the receiving operating characteristic curve (AUC). Results: The 5-year grade ≥2 overall rectal toxicity and grade ≥1 and grade ≥2 rectal bleeding rates were 16%, 25%, and 10%, respectively. Predictive capabilities were obtained using the RF-NTCP model for all 3 toxicity endpoints, including both the training and validation cohorts. The age and use of anticoagulants were found to be predictors of rectal bleeding. The AUC for RF-NTCP ranged from 0.66 to 0.76, depending on the toxicity endpoint. The AUC values for the LKB-NTCP were statistically significantly inferior, ranging from 0.62 to 0.69. Conclusions: The RF-NTCP model may be a useful new tool in predicting late rectal toxicity, including variables other than DVH, and thus appears as a strong competitor to classic NTCP models.« less

Normal values for high-resolution anorectal manometry in healthy women: effects of age and significance of rectoanal gradient.

PubMed

Noelting, Jessica; Ratuapli, Shiva K; Bharucha, Adil E; Harvey, Doris M; Ravi, Karthik; Zinsmeister, Alan R

2012-10-01

High-resolution manometry (HRM) is used to measure anal pressures in clinical practice but normal values have not been available. Although rectal evacuation is assessed by the rectoanal gradient during simulated evacuation, there is substantial overlap between healthy people and defecatory disorders, and the effects of age are unknown. We evaluated the effects of age on anorectal pressures and rectal balloon expulsion in healthy women. Anorectal pressures (HRM), rectal sensation, and balloon expulsion time (BET) were evaluated in 62 asymptomatic women ranging in age from 21 to 80 years (median age 44 years) without risk factors for anorectal trauma. In total, 30 women were aged <50 years. Age is associated with lower (r=-0.47, P<0.01) anal resting (63 (5) (≥50 years), 88 (3) (<50 years), mean (s.e.m.)) but not squeeze pressures; higher rectal pressure and rectoanal gradient during simulated evacuation (r=0.3, P<0.05); and a shorter (r=-0.4, P<0.01) rectal BET (17 (9) s (≥50 years) vs. 31 (10) s (<50 years)). Only 5 women had a prolonged (>60 s) rectal BET but 52 had higher anal than rectal pressures (i.e., negative gradient) during simulated evacuation. The gradient was more negative in younger (-41 (6) mm Hg) than older (-12 (6) mm Hg) women and negatively (r=-0.51, P<0.0001) correlated with rectal BET but only explained 16% of the variation in rectal BET. These observations provide normal values for anorectal pressures by HRM. Increasing age is associated with lower anal resting pressure, a more positive rectoanal gradient during simulated evacuation, and a shorter BET in asymptomatic women. Although the rectoanal gradient is negatively correlated with rectal BET, this gradient is negative even in a majority of asymptomatic women, undermining the utility of a negative gradient for diagnosing defecatory disorders by HRM.

Irradiation with and without razoxane in the treatment of incompletely resected or inoperable recurrent rectal cancer. Results of a small randomized multicenter study.

PubMed

Rhomberg, Walter; Hammer, Josef; Sedlmayer, Felix; Eiter, Helmut; Seewald, Dieter; Schneider, Barbara

2007-07-01

In an earlier phase II study, irradiation together with razoxane was shown to improve local control in recurrent rectal cancer. Therefore, the Austrian Society of Radiooncology (OGRO) initiated a randomized controlled trial in 1992 to compare this combined treatment versus radiation therapy alone. Between 1992 and 1999, 36 patients with localized recurrences of rectal cancer were randomized to receive radiotherapy without (group A) or with razoxane (group B). The prognostic variables of the two groups were similar except for a longer median latency period from initial surgery to local recurrence in group A. High-energy photons with daily fractions between 170 and 200 cGy were used. The median total radiation dose was 60 Gy in each group. The patients in group B received a median razoxane dose of 9.6 g (range, 5-12 g). Main outcome measures were local control, overall survival, and toxicity. The combined treatment with razoxane increased the local control rate compared to radiotherapy alone (39% vs. 8%; p = 0.05). The median survival time was not different between the groups (20 months each). No patient in arm A but four of 18 patients in arm B survived 5 years. Acute toxic effects were of moderate degree in both groups. There were no substantial differences as to late side effects. Radiotherapy together with razoxane is superior to radiation treatment alone in recurrent rectal cancer as far as local control is concerned. In some patients, long-term survival was achieved with razoxane and radiotherapy.

Effects of omeprazole in improving concurrent chemoradiotherapy efficacy in rectal cancer.

PubMed

Zhang, Jin-Liang; Liu, Min; Yang, Qing; Lin, Shi-Yong; Shan, Hong-Bo; Wang, Hui-Yun; Xu, Guo-Liang

2017-04-14

To explore the effects of omeprazole on chemoradiotherapy efficacy and tumor recurrence in rectal cancer. The medical data of 125 rectal cancer patients who received the same neoadjuvant chemoradiotherapy (CRT) followed by surgery were retrospectively collected. Patients who received omeprazole (OME) orally at a dose of 20 mg at least once daily for six days and/or intravenously at 40 mg a day were recognized as eligible OME users (EOU). Otherwise, patients were regarded as non-eligible OME users (non-EOU). Moreover, a preferred OME dose cut-off of 200 mg on tumor recurrence was obtained by receiver operating characteristic (ROC) curves. Patients were divided into two groups: the effective OME group (EOG, OME ≥ 200 mg) and the non-effective OME group (non-EOG, OME < 200 mg). The good response rate of CRT efficacy (50.8%) in EOU was significantly increased compared with non-EOU (30.6%) ( P = 0.02). The recurrence rate in the EOG was 10.3%, which was significantly lower compared with 31.3% in non-EOG ( P = 0.025). The good response rate of CRT efficacy in EOG was 55.2%, which was obviously higher compared with 36.5% in non-EOG, with a significant difference ( P = 0.072). Multivariate Cox analysis demonstrated that OME (non-EOG and EOG) was an independent and significant impact factor for DFS ( P = 0.048, HR = 0.30, 95%CI: 0.09-0.99). When applied as an adjuvant drug in cancer treatment for relieving common side effects of chemotherapy, omeprazole has a synergetic effect in improving CRT efficacy and decreasing rectal cancer recurrence.

Thermosensitive In Situ Gel Based on Solid Dispersion for Rectal Delivery of Ibuprofen.

PubMed

Liu, Yangdan; Wang, Xin; Liu, Youping; Di, Xin

2018-01-01

The objective of this study was to develop a thermosensitive in situ gel based on solid dispersions (SDs) for rectal delivery of ibuprofen (IBU). Thermosensitive (poloxamer 407) and mucoadhesive (hydroxypropylmethyl cellulose E5 and sodium alginate) polymers were used to prepare the in situ gel and the sol-gel transition temperature (T sol-gel ) and gel strength were optimized. The in vitro release performance and in vivo pharmacokinetic properties of the in situ gel after their rectal administration to rabbits were investigated. Compared with the solid suppository, the cumulative release of the IBU SDs loaded in situ gel was significantly increased. The in vivo pharmacokinetics indicated that in situ gel had a higher peak plasma concentration (C max ) and area under the curve (AUC (0-∞) ) in plasma than the solid suppositories. Histopathology results showed that the IBU in situ gel given at a dose of 15 mg/kg did not produce any irritation. In conclusion, this study suggested that the in situ gel could be an effective rectal formulation for IBU.

Rectal hydrocortisone during stress in patients with adrenal insufficiency

PubMed Central

De Vroede, M; Beukering, R; Spit, M; Jansen, M

1998-01-01

OBJECTIVE—Patients with glucocorticoid deficiency need lifelong glucocorticoid replacement treatment. During acute stressful events, steroid dosage must be increased several times, which is often problematical in children. This study investigated the reliability of rectal hydrocortisone administration as an alternative to the intramuscular route.
STUDY DESIGN—Serum cortisol was assessed during stress in normal children to determine the concentration that should be achieved after rectal hydrocortisone. Subsequently, serum cortisol concentrations were measured three hours after administering a suppository containing hydrocortisone 100 mg/m2 to 57 patients with adrenocortical insufficiency. In eight patients, the time dependency of the cortisol rise after rectal administration was established.
RESULTS—In 51 previously healthy children admitted to hospital with an acute stressful condition, the mean serum cortisol concentration was 1092 nmol/l. Rectal hydrocortisone in patients with adrenocortical insufficiency resulted in a mean serum cortisol concentration of 1212 nmol/l three hours after insertion of the suppository containing hydrocortisone. In 14 of 57 children, serum cortisol was < 1000 nmol/l and in eight children it was below 600 nmol/l. One hour after administration, the mean cortisol concentration had reached 1000 nmol/l. This was sustained for more than four hours.
CONCLUSION—Rectal hydrocortisone is a safe alternative to parenteral administration in the self management of Addisonian prone conditions. However, because eight of 57 children did not achieve concentrations > 600 nmol/l, its use is recommended only after previously documenting an adequate serum cortisol concentration three hours after receiving a test dose.

 PMID:9713011

Normal tissue complication probability (NTCP) models for late rectal bleeding, stool frequency and fecal incontinence after radiotherapy in prostate cancer patients.

PubMed

Schaake, Wouter; van der Schaaf, Arjen; van Dijk, Lisanne V; Bongaerts, Alfons H H; van den Bergh, Alfons C M; Langendijk, Johannes A

2016-06-01

Curative radiotherapy for prostate cancer may lead to anorectal side effects, including rectal bleeding, fecal incontinence, increased stool frequency and rectal pain. The main objective of this study was to develop multivariable NTCP models for these side effects. The study sample was composed of 262 patients with localized or locally advanced prostate cancer (stage T1-3). Anorectal toxicity was prospectively assessed using a standardized follow-up program. Different anatomical subregions within and around the anorectum were delineated. A LASSO logistic regression analysis was used to analyze dose volume effects on toxicity. In the univariable analysis, rectal bleeding, increase in stool frequency and fecal incontinence were significantly associated with a large number of dosimetric parameters. The collinearity between these predictors was high (VIF>5). In the multivariable model, rectal bleeding was associated with the anorectum (V70) and anticoagulant use, fecal incontinence was associated with the external sphincter (V15) and the iliococcygeal muscle (V55). Finally, increase in stool frequency was associated with the iliococcygeal muscle (V45) and the levator ani (V40). No significant associations were found for rectal pain. Different anorectal side effects are associated with different anatomical substructures within and around the anorectum. The dosimetric variables associated with these side effects can be used to optimize radiotherapy treatment planning aiming at prevention of specific side effects and to estimate the benefit of new radiation technologies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Preoperative downstaging chemoradiation with concurrent irinotecan and capecitabine in MRI-defined locally advanced rectal cancer: a phase I trial (NWCOG-2).

PubMed

Gollins, S W; Myint, S; Susnerwala, S; Haylock, B; Wise, M; Topham, C; Samuel, L; Swindell, R; Morris, J; Mason, L; Levine, E

2009-09-15

The aim of this study was to investigate the safety of neoadjuvant chemoradiation using radiotherapy (RT) combined with concurrent capecitabine and irinotecan for locally advanced rectal cancer before surgery. Forty-six patients were recruited and treated on the basis that MRI scanning had shown poor-risk tumours with threatening (< or =1 mm) or involvement of the mesorectal fascia. Conformal RT was given using 3 or 4 fields at daily fractions of 1.8 Gy on 5 days per week to a total dose of 45 Gy. Concurrently oral capecitabine was given twice daily throughout radiotherapy continuously from days 1 to 35 and intravenous irinotecan was given once per week during weeks 1 to 4 of RT. Dose levels were gradually escalated as follows. Dose level 1: capecitabine 650 mg m(-2) b.i.d. and irinotecan 50 mg m(-2); Dose level 2: capecitabine 650 mg m(-2) b.i.d. and irinotecan 60 mg m(-2); Dose level 3: capecitabine 825 mg m(-2) b.i.d. and irinotecan 60 mg m(2); Dose level 4: capecitabine 825 mg m(-2) b.i.d. and irinotecan 70 mg m(-2). Diarrhoea (grade 3, no grade 4) was the main serious acute toxicity with lesser degrees of fatigue, neutropenia, anorexia and palmar-plantar erythrodysesthesia. The recommended dose for future study was dose level 2 at which 3 of 14 patients (21%) developed grade 3 diarrhoea. Postoperative complications included seven pelvic or wound infections and two anastomotic and two perineal wound dehiscences. There were no deaths in the first 30 days postoperatively. Of 41 resected specimens, 11 (27%) showed a pathological complete response (pCR) and five (12%) showed an involved circumferential resection margin (defined as < or =1 mm). The 3-year disease-free survival (intent-to-treat) was 53.2%. In patients with poor-risk MRI-defined locally advanced rectal cancer threatening or involving the mesorectal fascia, preoperative chemoradiation based on RT at 45 Gy in 25 daily fractions over 5 weeks with continuous daily oral capecitabine at 650 mg m(-2) b.i.d. days 1-35 and weekly IV irinotecan at 60 mg m(-2) weeks 1-4, provides acceptable acute toxicity and postoperative morbidity with encouraging response and curative resection rates.

A mini-review of non-parenteral clonidine preparations for paediatric sedation.

PubMed

Hanning, Sara M; Orlu Gul, Mine; Toni, Irmgard; Neubert, Antje; Tuleu, Catherine

2017-04-01

To provide an overview of non-parenteral clonidine formulations and assess the feasibility of their use for paediatric sedation. A literature search was conducted using electronic databases and a combination of search terms. Forty articles met the inclusion criteria. Publications were grouped into different dosage forms and assessed for their potential application for sedation of children in intensive care. Several routes of clonidine administration have been investigated for numerous indications in children, including perioperative sedation and analgesia. These include oral liquids, tablets, oral transmucosal systems, nasal sprays and rectal suspensions. Conflicting studies on oral transmucosal clonidine formulations suggest that further research is required to fully establish efficacy. Nasal sprays and rectal suspensions have the advantages of rapid onset of action and potential for dose flexibility, but predictable absorption is difficult to obtain. Provided age-appropriate strengths are available, intravenous formulations remain the most predictable in terms of bioavailability and flexible in terms of dose adjustment. However, as with all routes, down-titration is difficult given the long half-life of clonidine. Oral transmucosal systems, nasal sprays and rectal suspensions have potential in a less acute setting, but significant clinical work is required to elucidate a full pharmacokinetic and pharmacodynamic profile. © 2016 Royal Pharmaceutical Society.

Successful treatment for ulcerative proctitis with rectal tacrolimus in an 8-year-old girl with intolerance to mesalamine.

PubMed

Navas-López, Víctor Manuel; Blasco-Alonso, Javier; Girón Fernández-Crehuet, Francisco; Serrano Nieto, Maria Juliana; Gallego-Gutiérrez, Silvia; Luque Pérez, Silvia; Sierra Salinas, Carlos

2014-08-01

Ulcerative colitis (UC) is defined as a chronic inflammatory condition causing continuous mucosal inflammation of the colon without granulomas on biopsy. It affects the rectum, and, to a variable extent, the colon in continuity and is characterized by a relapsing and remitting course. Oral 5-aminosalicylic acid (5-ASA) regimens are recommended as first-line induction therapy for mild to moderately active pediatric UC and for maintenance of remission regardless of other initial treatments. In large clinical trials in adults, mesalamine intolerance was found in 2-5 % of the patients. We present a case of an 8-year-old female patient with intolerance to mesalamine and proctitis resistant to conventional therapy who responded to rectal tacrolimus treatment. The patient started with a dose of 2 mg/day at night with an excellent response. She reported feeling better than any of the previously prescribed treatments and without feeling the discomfort of previously administered enemas. After four weeks of treatment, the dose was reduced to 2 mg/week with no relapses. Tacrolimus suppositories were very well tolerated, and no adverse effects have been reported. Although only very little data has been published, rectal tacrolimus seems to be safe and of efficacy in ulcerative proctitis resistant to standard therapy.

Thermoluminescence dosimetry for in-vivo verification of high dose rate brachytherapy for prostate cancer.

PubMed

Das, R; Toye, W; Kron, T; Williams, S; Duchesne, G

2007-09-01

It was the aim of the study to verify dose delivered in urethra and rectum during High Dose Rate brachytherapy boost (HDRBB) of prostate cancer patients. During the first fraction of HDRBB measurement catheters were placed in the urethra and rectum of prostate cancer patients. These contained LiF:Mg,Ti Thermoluminescence Dosimetry (TLD) rods of 1 mm diameter, with up to 11 detectors positioned every 16 mm separated by radio-opaque markers. A Lorentzian peak function was used to fit the data. Measurements from 50 patients were evaluated and measured doses were compared with predictions from the treatment planning system (Plato Vs 13.5 to 14.1). Prospective urinary and rectal toxicity scores were collected following treatment. In more than 90% of cases, the Lorentzian peak function provided a good fit to both experimental and planning urethral data (r2 > 0.9). In general there was good agreement between measured and predicted doses with the average difference between measured and planned maximum dose being 0.1 Gy. No significant association between dose and any clinical endpoints was observed in 43 patients available for clinical evaluation. An average inferior shift of 2 mm between the plan and the measurement performed approximately 1 hour after the planning CT scan was found for the dose distribution in the cohort of patients for the urethra measurements. Rectal measurements proved to be more difficult to interpret as there is more variability of TLD position between planning and treatment. TLD in-vivo measurements are easily performed in urethra and rectum during HDR brachytherapy of prostate patients. They verify the delivery and provide information about the dose delivered to critical structures. The latter may be of particular interest if higher doses are to be given per fraction such as in HDR monotherapy.

Rectal administration of metronidazole in severely ill patients.

PubMed Central

Barker, E M; Aitchison, J M; Cridland, J S; Baker, L W

1983-01-01

Ten severely ill patients with life threatening sepsis received metronidazole as suppositories and blood concentrations of the drug were measured twice daily over five days. Therapeutic blood concentrations of metronidazole were maintained at all times in all patients. Rectal administration of metronidazole is accepted as effective prophylaxis against infection associated with surgery and as treatment of established infection. This study shows that in gravely ill patients metronidazole administered as suppositories gives perfectly adequate therapeutic serum concentrations of the drug, but that to achieve these concentrations rapidly the first suppository should be given with an intravenous loading dose. PMID:6409287

Evidence that enforced sunlight exposure can cause hyperthermia in cattle ingesting low levels of ergot of rye (Claviceps purpurea), when air temperature and humidity conditions are only moderate.

PubMed

Bourke, C A

2003-09-01

To determine the rectal temperature response of cattle, following the oral administration of ergot of rye (Claviceps purpurea), under pen conditions of enforced sunlight compared with those of enforced shade. Hereford cross steers were divided into two groups of 18. One group was dosed once, on a Monday morning, with finely ground rye grass ergots at a rate of 180 mg/kg body weight and held in the sun for 7 h each day until Friday afternoon. The other group was not dosed but was similarly held in the sun during the same period. Their rectal temperatures were measured early morning and mid afternoon, from Monday to Friday inclusive. The process was repeated for each group, but this time they were held in the shade. The four treatment options were run concurrently by conducting the experiments over 6 weeks and using 3 animals in each treatment group, each week. The thermic response over all weeks, of the ergot treated, sunlight exposed cattle, was deemed greater than for the other groups, based on the following four parameters. The increase in rectal temperature between early morning and mid afternoon, the size of the mid afternoon rectal temperature rise, the difference between the maximum mid afternoon rectal temperature recorded by an animal in the sun compared with that recorded by the same animal in the shade, and finally the number of animals in a treatment group that recorded rectal temperatures > 40.00 degrees C. The difference in the daily increase in body temperature between the ergot treated, sun exposed cattle and the ergot treated, shaded cattle, was greater than that observed between the sun exposed and shade restricted control cattle. Nine of 18 ergot treated and sun exposed cattle developed hyperthermia; no cattle in the other three groups did. Some sunlight exposed cattle, dosed with a low amount of ergot of rye, can experience a body temperature elevation above the normal range, even under mild ambient temperature and humidity conditions. Sunlight exposure causes an increase in body temperature in normal cattle that is probably attributable to solar radiant heat. Ergot ingestion causes an increase in body temperature in shaded cattle that is probably attributable to ambient temperature and humidity effects. This response can be increased by sun exposure and this increase is attributable to solar radiant heat effects and possibly also solar radiation. A response to radiant heat is consistent with the known physiological effects of ingested ergot alkaloids, but a response to solar radiation is not.

Gastrointestinal Dose-Histogram Effects in the Context of Dose-Volume–Constrained Prostate Radiation Therapy: Analysis of Data From the RADAR Prostate Radiation Therapy Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ebert, Martin A., E-mail: Martin.Ebert@health.wa.gov.au; School of Physics, University of Western Australia, Perth, Western Australia; Foo, Kerwyn

Purpose: To use a high-quality multicenter trial dataset to determine dose-volume effects for gastrointestinal (GI) toxicity following radiation therapy for prostate carcinoma. Influential dose-volume histogram regions were to be determined as functions of dose, anatomical location, toxicity, and clinical endpoint. Methods and Materials: Planning datasets for 754 participants in the TROG 03.04 RADAR trial were available, with Late Effects of Normal Tissues (LENT) Subjective, Objective, Management, and Analytic (SOMA) toxicity assessment to a median of 72 months. A rank sum method was used to define dose-volume cut-points as near-continuous functions of dose to 3 GI anatomical regions, together with amore » comprehensive assessment of significance. Univariate and multivariate ordinal regression was used to assess the importance of cut-points at each dose. Results: Dose ranges providing significant cut-points tended to be consistent with those showing significant univariate regression odds-ratios (representing the probability of a unitary increase in toxicity grade per percent relative volume). Ranges of significant cut-points for rectal bleeding validated previously published results. Separation of the lower GI anatomy into complete anorectum, rectum, and anal canal showed the impact of mid-low doses to the anal canal on urgency and tenesmus, completeness of evacuation and stool frequency, and mid-high doses to the anorectum on bleeding and stool frequency. Derived multivariate models emphasized the importance of the high-dose region of the anorectum and rectum for rectal bleeding and mid- to low-dose regions for diarrhea and urgency and tenesmus, and low-to-mid doses to the anal canal for stool frequency, diarrhea, evacuation, and bleeding. Conclusions: Results confirm anatomical dependence of specific GI toxicities. They provide an atlas summarizing dose-histogram effects and derived constraints as functions of anatomical region, dose, toxicity, and endpoint for informing future radiation therapy planning.« less

3D-segmentation of the 18F-choline PET signal for target volume definition in radiation therapy of the prostate.

PubMed

Ciernik, I Frank; Brown, Derek W; Schmid, Daniel; Hany, Thomas; Egli, Peter; Davis, J Bernard

2007-02-01

Volumetric assessment of PET signals becomes increasingly relevant for radiotherapy (RT) planning. Here, we investigate the utility of 18F-choline PET signals to serve as a structure for semi-automatic segmentation for forward treatment planning of prostate cancer. 18F-choline PET and CT scans of ten patients with histologically proven prostate cancer without extracapsular growth were acquired using a combined PET/CT scanner. Target volumes were manually delineated on CT images using standard software. Volumes were also obtained from 18F-choline PET images using an asymmetrical segmentation algorithm. PTVs were derived from CT 18F-choline PET based clinical target volumes (CTVs) by automatic expansion and comparative planning was performed. As a read-out for dose given to non-target structures, dose to the rectal wall was assessed. Planning target volumes (PTVs) derived from CT and 18F-choline PET yielded comparable results. Optimal matching of CT and 18F-choline PET derived volumes in the lateral and cranial-caudal directions was obtained using a background-subtracted signal thresholds of 23.0+/-2.6%. In antero-posterior direction, where adaptation compensating for rectal signal overflow was required, optimal matching was achieved with a threshold of 49.5+/-4.6%. 3D-conformal planning with CT or 18F-choline PET resulted in comparable doses to the rectal wall. Choline PET signals of the prostate provide adequate spatial information amendable to standardized asymmetrical region growing algorithms for PET-based target volume definition for external beam RT.

[The effects of selective 5HT3 receptor blockade on physiological markers of abdominal pain in awake dogs].

PubMed

Panteleev, S S; Busygina, I I; Liubashina, O A

2013-04-01

In awake dogs, the visceromotor and cardioautonomic responses to the rectal balloon distension were studied before and after intravenous administration of a selective 5HT3 receptor antagonist granisetron. It was shown that balloon distension level up to 60 mmHg caused neither noticeable muscle responses nor substantial changes in heart rate. In turn, distending pressures of 80 mmHg and higher induced vigorous abdominal muscle contractions and tachycardia that were graded with increasing intensities of stimulation. Thus, the rectal stimulation with pressures 80 mmHg and more produced the changes in visceromotor and cardiovascular indices which could be considered as suitable indicators of visceral nociception in conscious animals. Based on monitoring of these physiological markers in a model of abdominal pain the dose-dependent antinociceptive effect of granisetron in awake dogs has been demonstrated for the first time. It was determined that granisetron in doses of 0.25, 0.5 or 1.0 mg/kg induced correspondingly 33.6 +/- 9.2, 58.0+/- 8.6 [see text] 76.7 +/- 5.5 % decrease in visceromotor response of dogs to nociceptive visceral stimulation. The effect occurred immediately after the drug administration and was lasting more than 90 min. In turn, the dose-dependent suppression of the rectal distension-induced tachycardia was less prominent and only observed during the initial period of granisetron action. The described model of abdominal pain in awake dogs might be useful for preclinical screening of new pharmacological substances, whereas the obtained data could contribute to the development of more efficient analgesics aimed in patients with irritable bowel syndrome.

Hydrogel Spacer Prospective Multicenter Randomized Controlled Pivotal Trial: Dosimetric and Clinical Effects of Perirectal Spacer Application in Men Undergoing Prostate Image Guided Intensity Modulated Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mariados, Neil, E-mail: nmariados@ampofny.com; Sylvester, John; Shah, Dhiren

2015-08-01

Purpose: Perirectal spacing, whereby biomaterials are placed between the prostate and rectum, shows promise in reducing rectal dose during prostate cancer radiation therapy. A prospective multicenter randomized controlled pivotal trial was performed to assess outcomes following absorbable spacer (SpaceOAR system) implantation. Methods and Materials: Overall, 222 patients with clinical stage T1 or T2 prostate cancer underwent computed tomography (CT) and magnetic resonance imaging (MRI) scans for treatment planning, followed with fiducial marker placement, and were randomized to receive spacer injection or no injection (control). Patients received postprocedure CT and MRI planning scans and underwent image guided intensity modulated radiation therapymore » (79.2 Gy in 1.8-Gy fractions). Spacer safety and impact on rectal irradiation, toxicity, and quality of life were assessed throughout 15 months. Results: Spacer application was rated as “easy” or “very easy” 98.7% of the time, with a 99% hydrogel placement success rate. Perirectal spaces were 12.6 ± 3.9 mm and 1.6 ± 2.0 mm in the spacer and control groups, respectively. There were no device-related adverse events, rectal perforations, serious bleeding, or infections within either group. Pre-to postspacer plans had a significant reduction in mean rectal V70 (12.4% to 3.3%, P<.0001). Overall acute rectal adverse event rates were similar between groups, with fewer spacer patients experiencing rectal pain (P=.02). A significant reduction in late (3-15 months) rectal toxicity severity in the spacer group was observed (P=.04), with a 2.0% and 7.0% late rectal toxicity incidence in the spacer and control groups, respectively. There was no late rectal toxicity greater than grade 1 in the spacer group. At 15 months 11.6% and 21.4% of spacer and control patients, respectively, experienced 10-point declines in bowel quality of life. MRI scans at 12 months verified spacer absorption. Conclusions: Spacer application was well tolerated. Increased perirectal space reduced rectal irradiation, reduced rectal toxicity severity, and decreased rates of patients experiencing declines in bowel quality of life. The spacer appears to be an effective tool, potentially enabling advanced prostate RT protocols.« less

Hydrogel Spacer Prospective Multicenter Randomized Controlled Pivotal Trial: Dosimetric and Clinical Effects of Perirectal Spacer Application in Men Undergoing Prostate Image Guided Intensity Modulated Radiation Therapy.

PubMed

Mariados, Neil; Sylvester, John; Shah, Dhiren; Karsh, Lawrence; Hudes, Richard; Beyer, David; Kurtzman, Steven; Bogart, Jeffrey; Hsi, R Alex; Kos, Michael; Ellis, Rodney; Logsdon, Mark; Zimberg, Shawn; Forsythe, Kevin; Zhang, Hong; Soffen, Edward; Francke, Patrick; Mantz, Constantine; Rossi, Peter; DeWeese, Theodore; Hamstra, Daniel A; Bosch, Walter; Gay, Hiram; Michalski, Jeff

2015-08-01

Perirectal spacing, whereby biomaterials are placed between the prostate and rectum, shows promise in reducing rectal dose during prostate cancer radiation therapy. A prospective multicenter randomized controlled pivotal trial was performed to assess outcomes following absorbable spacer (SpaceOAR system) implantation. Overall, 222 patients with clinical stage T1 or T2 prostate cancer underwent computed tomography (CT) and magnetic resonance imaging (MRI) scans for treatment planning, followed with fiducial marker placement, and were randomized to receive spacer injection or no injection (control). Patients received postprocedure CT and MRI planning scans and underwent image guided intensity modulated radiation therapy (79.2 Gy in 1.8-Gy fractions). Spacer safety and impact on rectal irradiation, toxicity, and quality of life were assessed throughout 15 months. Spacer application was rated as "easy" or "very easy" 98.7% of the time, with a 99% hydrogel placement success rate. Perirectal spaces were 12.6 ± 3.9 mm and 1.6 ± 2.0 mm in the spacer and control groups, respectively. There were no device-related adverse events, rectal perforations, serious bleeding, or infections within either group. Pre-to postspacer plans had a significant reduction in mean rectal V70 (12.4% to 3.3%, P<.0001). Overall acute rectal adverse event rates were similar between groups, with fewer spacer patients experiencing rectal pain (P=.02). A significant reduction in late (3-15 months) rectal toxicity severity in the spacer group was observed (P=.04), with a 2.0% and 7.0% late rectal toxicity incidence in the spacer and control groups, respectively. There was no late rectal toxicity greater than grade 1 in the spacer group. At 15 months 11.6% and 21.4% of spacer and control patients, respectively, experienced 10-point declines in bowel quality of life. MRI scans at 12 months verified spacer absorption. Spacer application was well tolerated. Increased perirectal space reduced rectal irradiation, reduced rectal toxicity severity, and decreased rates of patients experiencing declines in bowel quality of life. The spacer appears to be an effective tool, potentially enabling advanced prostate RT protocols. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Effects of organ motion on proton prostate treatments, as determined from analysis of daily CT imaging for patient positioning.

PubMed

Maeda, Yoshikazu; Sato, Yoshitaka; Shibata, Satoshi; Bou, Sayuri; Yamamoto, Kazutaka; Tamamura, Hiroyasu; Fuwa, Nobukazu; Takamatsu, Shigeyuki; Sasaki, Makoto; Tameshige, Yuji; Kume, Kyo; Minami, Hiroki; Saga, Yusuke; Saito, Makoto

2018-05-01

We quantified interfractional movements of the prostate, seminal vesicles (SVs), and rectum during computed tomography (CT) image-guided proton therapy for prostate cancer and studied the range variation in opposed lateral proton beams. We analyzed 375 sets of daily CT images acquired throughout the proton therapy treatment of ten patients. We analyzed daily movements of the prostate, SVs, and rectum by simulating three image-matching strategies: bone matching, prostate center (PC) matching, and prostate-rectum boundary (PRB) matching. In the PC matching, translational movements of the prostate center were corrected after bone matching. In the PRB matching, we performed PC matching and correction along the anterior-posterior direction to match the boundary between the prostate and the rectum's anterior region. In each strategy, we evaluated systematic errors (Σ) and random errors (σ) by measuring the daily movements of certain points on each anatomic structure. The average positional deviations in millimeter of each point were determined by the Van Herk formula of 2.5Σ + 0.7σ. Using these positional deviations, we created planning target volumes of the prostate and SVs and analyzed the daily variation in the water equivalent length (WEL) from the skin surface to the target along the lateral beam directions using the density converted from the daily CT number. Based on this analysis, we designed prostate cancer treatment planning and evaluated the dose volume histograms (DVHs) for these strategies. The SVs' daily movements showed large variations over the superior-inferior direction, as did the rectum's anterior region. The average positional deviations of the prostate in the anterior, posterior, superior, inferior, and lateral sides (mm) in bone matching, PC matching, and PRB matching were (8.9, 9.8, 7.5, 3.6, 1.6), (5.6, 6.1, 3.5, 4.5, 1.9), and (8.6, 3.2, 3.5, 4.5, 1.9) (mm), respectively. Moreover, the ones of the SV tip were similarly (22.5, 15.5, 11.0, 7.6, 6.0), (11.8, 8.4, 7.8, 5.2, 6.3), and (9.9, 7.5, 7.8, 5.2, 6.3). PRB matching showed the smallest positional deviations at all portions except for the anterior portion of the prostate and was able to markedly reduce the positional deviations at the posterior portion. The averaged WEL variations at the distal and proximal sides of planning target volumes were estimated 7-9 mm and 4-6 mm, respectively, and showed the increasing of a few millimeters in PC and PRB matching compared to bone matching. In the treatment planning simulation, the DVH values of the rectum in PRB matching were reduced compared to those obtained with other matching strategies. The positional deviations for the prostate on the posterior side and the SVs were smaller by PRB matching than the other strategies and effectively reduced the rectal dose. 3D dose calculations indicate that PRB matching with CT image guidance may do a better job relative to other positioning methods to effectively reduce the rectal complications. The WEL variation was quite large, and the appropriate margin (approx. 10 mm) must be adapted to the proton range in an initial planning to maintain the coverage of target volumes throughout entire treatment. © 2018 American Association of Physicists in Medicine.

Dose-Effect Relationships for Individual Pelvic Floor Muscles and Anorectal Complaints After Prostate Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smeenk, Robert Jan, E-mail: r.smeenk@rther.umcn.nl; Hoffmann, Aswin L.; Hopman, Wim P.M.

2012-06-01

Purpose: To delineate the individual pelvic floor muscles considered to be involved in anorectal toxicity and to investigate dose-effect relationships for fecal incontinence-related complaints after prostate radiotherapy (RT). Methods and Materials: In 48 patients treated for localized prostate cancer, the internal anal sphincter (IAS) muscle, the external anal sphincter (EAS) muscle, the puborectalis muscle (PRM), and the levator ani muscles (LAM) in addition to the anal wall (Awall) and rectal wall (Rwall) were retrospectively delineated on planning computed tomography scans. Dose parameters were obtained and compared between patients with and without fecal urgency, incontinence, and frequency. Dose-effect curves were constructed.more » Finally, the effect of an endorectal balloon, which was applied in 28 patients, was investigated. Results: The total volume of the pelvic floor muscles together was about three times that of the Awall. The PRM was exposed to the highest RT dose, whereas the EAS received the lowest dose. Several anal and rectal dose parameters, as well as doses to all separate pelvic floor muscles, were associated with urgency, while incontinence was associated mainly with doses to the EAS and PRM. Based on the dose-effect curves, the following constraints regarding mean doses could be deduced to reduce the risk of urgency: {<=}30 Gy to the IAS; {<=}10 Gy to the EAS; {<=}50 Gy to the PRM; and {<=}40 Gy to the LAM. No dose-effect relationships for frequency were observed. Patients treated with an endorectal balloon reported significantly less urgency and incontinence, while their treatment plans showed significantly lower doses to the Awall, Rwall, and all pelvic floor muscles. Conclusions: Incontinence-related complaints show specific dose-effect relationships to individual pelvic floor muscles. Dose constraints for each muscle can be identified for RT planning. When only the Awall is delineated, substantial components of the continence apparatus are excluded.« less

Dose-effect relationships for individual pelvic floor muscles and anorectal complaints after prostate radiotherapy.

PubMed

Smeenk, Robert Jan; Hoffmann, Aswin L; Hopman, Wim P M; van Lin, Emile N J Th; Kaanders, Johannes H A M

2012-06-01

To delineate the individual pelvic floor muscles considered to be involved in anorectal toxicity and to investigate dose-effect relationships for fecal incontinence-related complaints after prostate radiotherapy (RT). In 48 patients treated for localized prostate cancer, the internal anal sphincter (IAS) muscle, the external anal sphincter (EAS) muscle, the puborectalis muscle (PRM), and the levator ani muscles (LAM) in addition to the anal wall (Awall) and rectal wall (Rwall) were retrospectively delineated on planning computed tomography scans. Dose parameters were obtained and compared between patients with and without fecal urgency, incontinence, and frequency. Dose-effect curves were constructed. Finally, the effect of an endorectal balloon, which was applied in 28 patients, was investigated. The total volume of the pelvic floor muscles together was about three times that of the Awall. The PRM was exposed to the highest RT dose, whereas the EAS received the lowest dose. Several anal and rectal dose parameters, as well as doses to all separate pelvic floor muscles, were associated with urgency, while incontinence was associated mainly with doses to the EAS and PRM. Based on the dose-effect curves, the following constraints regarding mean doses could be deduced to reduce the risk of urgency: ≤ 30 Gy to the IAS; ≤ 10 Gy to the EAS; ≤ 50 Gy to the PRM; and ≤ 40 Gy to the LAM. No dose-effect relationships for frequency were observed. Patients treated with an endorectal balloon reported significantly less urgency and incontinence, while their treatment plans showed significantly lower doses to the Awall, Rwall, and all pelvic floor muscles. Incontinence-related complaints show specific dose-effect relationships to individual pelvic floor muscles. Dose constraints for each muscle can be identified for RT planning. When only the Awall is delineated, substantial components of the continence apparatus are excluded. Copyright © 2012 Elsevier Inc. All rights reserved.

Is It Time to Tailor the Prediction of Radio-Induced Toxicity in Prostate Cancer Patients? Building the First Set of Nomograms for Late Rectal Syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valdagni, Riccardo; Radiotherapy, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan; Kattan, Michael W.

Purpose: Development of user-friendly tools for the prediction of single-patient probability of late rectal toxicity after conformal radiotherapy for prostate cancer. Methods and Materials: This multicenter protocol was characterized by the prospective evaluation of rectal toxicity through self-assessed questionnaires (minimum follow-up, 36 months) by 718 adult men in the AIROPROS 0102 trial. Doses were between 70 and 80 Gy. Nomograms were created based on multivariable logistic regression analysis. Three endpoints were considered: G2 to G3 late rectal bleeding (52/718 events), G3 late rectal bleeding (24/718 events), and G2 to G3 late fecal incontinence (LINC, 19/718 events). Results: Inputs for themore » nomogram for G2 to G3 late rectal bleeding estimation were as follows: presence of abdominal surgery before RT, percentage volume of rectum receiving >75 Gy (V75Gy), and nomogram-based estimation of the probability of G2 to G3 acute gastrointestinal toxicity (continuous variable, which was estimated using a previously published nomogram). G3 late rectal bleeding estimation was based on abdominal surgery before RT, V75Gy, and NOMACU. Prediction of G2 to G3 late fecal incontinence was based on abdominal surgery before RT, presence of hemorrhoids, use of antihypertensive medications (protective factor), and percentage volume of rectum receiving >40 Gy. Conclusions: We developed and internally validated the first set of nomograms available in the literature for the prediction of radio-induced toxicity in prostate cancer patients. Calculations included dosimetric as well as clinical variables to help radiation oncologists predict late rectal morbidity, thus introducing the possibility of RT plan corrections to better tailor treatment to the patient's characteristics, to avoid unnecessary worsening of quality of life, and to provide support to the patient in selecting the best therapeutic approach.« less

Role of the parameters involved in the plan optimization based on the generalized equivalent uniform dose and radiobiological implications

NASA Astrophysics Data System (ADS)

Widesott, L.; Strigari, L.; Pressello, M. C.; Benassi, M.; Landoni, V.

2008-03-01

We investigated the role and the weight of the parameters involved in the intensity modulated radiation therapy (IMRT) optimization based on the generalized equivalent uniform dose (gEUD) method, for prostate and head-and-neck plans. We systematically varied the parameters (gEUDmax and weight) involved in the gEUD-based optimization of rectal wall and parotid glands. We found that the proper value of weight factor, still guaranteeing planning treatment volumes coverage, produced similar organs at risks dose-volume (DV) histograms for different gEUDmax with fixed a = 1. Most of all, we formulated a simple relation that links the reference gEUDmax and the associated weight factor. As secondary objective, we evaluated plans obtained with the gEUD-based optimization and ones based on DV criteria, using the normal tissue complication probability (NTCP) models. gEUD criteria seemed to improve sparing of rectum and parotid glands with respect to DV-based optimization: the mean dose, the V40 and V50 values to the rectal wall were decreased of about 10%, the mean dose to parotids decreased of about 20-30%. But more than the OARs sparing, we underlined the halving of the OARs optimization time with the implementation of the gEUD-based cost function. Using NTCP models we enhanced differences between the two optimization criteria for parotid glands, but no for rectum wall.

Toward a real-time in vivo dosimetry system using plastic scintillation detectors

PubMed Central

Archambault, Louis; Briere, Tina M.; Pönisch, Falk; Beaulieu, Luc; Kuban, Deborah A.; Lee, Andrew; Beddar, Sam

2010-01-01

Purpose In this work, we present and validate a plastic scintillation detector (PSD) system designed for real-time multi-probe in vivo measurements. Methods and Materials The PSDs were built with a dose-sensitive volume of 0.4 mm3. PSDs were assembled into modular detector patches, each containing 5 closely packed PSDs. Continuous dose readings were performed every 150 ms, with a gap between consecutive readings of less than 0.3 ms. We first studied the effect of electron multiplication. We then assessed system performance in acrylic and anthropomorphic pelvic phantoms. Results The PSDs are compatible with clinical rectal balloons and are easily inserted into the anthropomorphic phantom. With an electron multiplication average gain factor of 40, a twofold increase in the signal-to-noise ratio was observed, making near real-time dosimetry feasible. Under calibration conditions, the PSDs agreed with ion chamber measurements to 0.08%. Precision, evaluated as a function of the total dose delivered, ranged from 2.3% at 2 cGy to 0.4% at 200 cGy. Conclusion Real-time PSD measurements are highly accurate and precise. These PSDs can be mounted onto rectal balloons, transforming these clinical devices into in vivo dose detectors without modifying current clinical practice. Real-time monitoring of the dose delivered near the rectum during prostate radiation therapy should help radiation oncologists protect this sensitive normal structure. PMID:20231074

Pre-operative combined 5-FU, low dose leucovorin, and sequential radiation therapy for unresectable rectal cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Minsky, B.D.; Cohen, A.M.; Kemeny, N.

1993-04-02

The authors performed a Phase 1 trial to determine the maximum tolerated dose of combined pre-operative radiation (5040 cGy) and 2 cycles (bolus daily [times] 5) of 5-FU and low dose LV (20 mg/m2), followed by surgery and 10 cycles of post-operative LV/5-FU in patients with unresectable primary or recurrent rectal cancer. Twelve patients were entered. The initial dose of 5-FU was 325 mg/m2. 5-FU was to be escalated while the LV remained constant at 20 mg/m2. Chemotherapy began on day 1 and radiation on day 8. The post-operative chemotherapy was not dose escalated; 5-FU: 425 mg/m2 and LV: 20more » mg/m2. The median follow-up was 14 months (7--16 months). Following pre-operative therapy, the resectability rate with negative margins was 91% and the pathologic complete response rate was 9%. For the combined modality segment (preoperative) the incidence of any grade 3+ toxicity was diarrhea: 17%, dysuria: 8%, mucositis: 8%, and erythema: 8%. The median nadir counts were WBC: 3.1, HGB: 8.8, and PLT: 153000. The maximum tolerated dose of 5-FU for pre-operative combined LV/5-FU/RT was 325 mg/m2 with no escalation possible. Therefore, the recommended dose was less than 325 mg/m2. Since adequate doses of 5-FU to treat systemic disease could not be delivered until at least 3 months (cycle 3) following the start of therapy, the authors do not recommend that this 5-FU, low dose LV, and sequential radiation therapy regimen be used as presently designed. However, given the 91% resectability rate they remain encouraged with this approach. 31 refs., 1 fig., 2 tabs.« less

A standard dose of radiation for microscopic disease is not appropriate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marks, L.B.

1990-12-15

Elective irradiation of sites of potential occult tumor spread is often part of a patient's radiation therapy program. The required radiation dose (D) depends on the probability that occult disease exists (P(occ)), the number of sites at risk (A), the number of tumor clonogens present (Ni), their radiation sensitivity, and the desired control rate. An exponential model of cell survival is used to quantify the importance of these factors. Control Probability = (1 - Pocc x (1 - e-Ni x (SF2)D/2))A; SF2 = surviving fraction after 2 Gy. Implications for clinical radiation therapy include: 1. Since the number of clonogensmore » in an occult site may vary from 10 degrees to 10(8), Ni is the major determinant of the required dose. The intrinsic radiation sensitivity of the clonogens (SF2) is also extremely important in determining the dose. Other factors are less influential since they vary less. 2. The variability of Ni (8 logs) is larger than the variation in cell number seen with gross disease (1 cm3 versus 1000 cm3, 3 logs). When Ni approximately 10(8), the required dose approaches that needed for small volume gross disease (10(9) cells, 1 cm3). 3. The dose prescribed to elective sites should reflect the risk of occult disease based on the primary tumor site, stage, and grade. 4. Regions where clinicoradiologic evaluation is difficult (e.g., pelvis and obese neck) require higher doses because macroscopic tumor deposits may exist. 5. Relatively low doses (10 to 30 Gy) are often thought to be inadequate for microscopic tumor. However, similar doses have been reported to sterilize microscopic tumor in ovarian, rectal, bladder, breast, and head and neck carcinomas. Relatively low doses should not be discounted since they may be useful in select cases when normal tissue tolerances and/or previous irradiation treatment limit the radiation dose.« less

Physicochemical characterization of diclofenac sodium-loaded poloxamer gel as a rectal delivery system with fast absorption.

PubMed

Yong, Chul Soon; Sah, Hongkee; Jahng, Yurngdong; Chang, Hyeun Wook; Son, Jong-Keun; Lee, Seung Ho; Jeong, Tae Cheon; Rhee, Jong-Dal; Baek, Suk Hwan; Kim, Chong-Kook; Choi, Han-Gon

2003-05-01

Rectal poloxamer gel systems composed of poloxamers and bioadhesive polymers were easy to administer to the anus and were mucoadhesive to the rectal tissues without leakage after the dose. However, a poloxamer gel containing diclofenac sodium could not be developed using bioadhesive polymers, since the drug was precipitated in this preparation. To develop a poloxamer gel using sodium chloride instead of bioadhesive polymers, the physicochemical properties such as gelation temperature, gel strength, and bioadhesive force of various formulations composed of diclofenac sodium, poloxamers, and sodium chloride were investigated. Furthermore, the pharmacokinetic study of diclofenac sodium delivered by the poloxamer gel was performed. Diclofenac sodium significantly increased the gelation temperature and weakened the gel strength and bioadhesive force, while sodium chloride did the opposite. The poloxamer gels with less than 1.0% sodium chloride, in which the drug was not precipitated, were inserted into the rectum without difficulty and leakage, and were retained in the rectum of rats for at least 6 hr. Furthermore, poloxamer gel gave significantly higher initial plasma concentrations and faster Tmax of diclofenac sodium than did solid suppository, indicating that drug from poloxamer gel could be absorbed faster than that from the solid one in rats. Our results suggested that a rectal poloxamer gel system with sodium chloride and poloxamers was a more physically stable, convenient, and effective rectal dosage form for diclofenac sodium.

Per rectal endoscopic myotomy for the treatment of adult Hirschsprung's disease: First human case (with video).

PubMed

Bapaye, Amol; Wagholikar, Gajanan; Jog, Sameer; Kothurkar, Aditi; Purandare, Shefali; Dubale, Nachiket; Pujari, Rajendra; Mahadik, Mahesh; Vyas, Viral; Bapaye, Jay

2016-09-01

Hirschsprung's disease (HD) is a congenital disorder characterized by the absence of intrinsic ganglion cells in submucosal and myenteric plexuses of the hindgut; and presents with constipation, intestinal obstruction and/or megacolon. HD commonly involves the rectosigmoid region (short segment HD), although shorter and longer variants of the disease are described. Standard treatment involves pull-through surgery for short segment HD or posterior anorectal myotomy in selected ultrashort segment candidates. Third space endoscopy has evolved during the past few years. Per oral endoscopic myotomy and per oral pyloromyotomy are described for treatment of achalasia cardia and refractory gastroparesis, respectively. Using the same philosophy of muscle/sphincter disruption for spastic bowel segments, per rectal endoscopic myotomy could be considered as a treatment option for short segment HD. A 24-year-old male patient presented with refractory constipation since childhood, and habituated to high-dose laxative combinations. Diagnosis was confirmed as adult short segment HD by barium enema, colonoscopic deep suction mucosal biopsies and anorectal manometry. Histopathology confirmed aganglionosis in the distal 15 cm. By implementing principles of third space endoscopy, per rectal endoscopic myotomy 20 cm in length was successfully carried out. At 24-week follow up, the patient reported significant relief of constipation and associated symptoms. Sigmoidoscopy, anorectal manometry and barium enema confirm improved rectal distensibility and reduced rectal pressures. The present case report describes the first human experience of per rectal endoscopic myotomy for successful treatment of adult short segment HD. © 2016 Japan Gastroenterological Endoscopy Society.

Hospital variability in postoperative mortality after rectal cancer surgery in the Spanish Association of Surgeons project: The impact of hospital volume.

PubMed

Ortiz, Héctor; Biondo, Sebastiano; Codina, Antonio; Ciga, Miguel Á; Enríquez-Navascués, José M; Espín, Eloy; García-Granero, Eduardo; Roig, José Vicente

2016-01-01

This multicentre observational study examines variation between hospitals in postoperative mortality after elective surgery in the Rectal Cancer Project of the Spanish Society of Surgeons and explores whether hospital volume and patient characteristics contribute to any variation between hospitals. Hospital variation was quantified using a multilevel approach on prospective data derived from the multicentre database of all rectal adenocarcinomas operated by an anterior resection or an abdominoperineal excision at 84 surgical departments from 2006 to 2013. The following variables were included in the analysis; demographics, American Society of Anaesthesiologists classification, tumour location and stage, administration of neoadjuvant treatment, and annual volume of surgical procedures. A total of 9809 consecutive patients were included. The rate of 30-day postoperative mortality was 1.8% Stratified by annual surgical volume hospitals varied from 1.4 to 2.0 in 30-day mortality. In the multilevel regression analysis, male gender (OR 1.623 [1.143; 2.348]; P<.008), increased age (OR: 5.811 [3.479; 10.087]; P<.001), and ASA score (OR 10.046 [3.390; 43.185]; P<.001) were associated with 30-day mortality. However, annual surgical volume was not associated with mortality (OR 1.309 [0.483; 4.238]; P=.619). Besides, there was a statistically significant variation in mortality between all departments (MOR 1.588 [1.293; 2.015]; P<.001). Postoperative mortality varies significantly among hospitals included in the project and this difference cannot be attributed to the annual surgical volume. Copyright © 2015 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

KRAS Mutation Status and Clinical Outcome of Preoperative Chemoradiation With Cetuximab in Locally Advanced Rectal Cancer: A Pooled Analysis of 2 Phase II Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Sun Young; Shim, Eun Kyung; Yeo, Hyun Yang

2013-01-01

Purpose: Cetuximab-containing chemotherapy is known to be effective for KRAS wild-type metastatic colorectal cancer; however, it is not clear whether cetuximab-based preoperative chemoradiation confers an additional benefit compared with chemoradiation without cetuximab in patients with locally advanced rectal cancer. Methods and Materials: We analyzed EGFR, KRAS, BRAF, and PIK3CA mutation status with direct sequencing and epidermal growth factor receptor (EGFR) and Phosphatase and tensin homolog (PTEN) expression status with immunohistochemistry in tumor samples of 82 patients with locally advanced rectal cancer who were enrolled in the IRIX trial (preoperative chemoradiation with irinotecan and capecitabine; n=44) or the ERBIRIX trial (preoperativemore » chemoradiation with irinotecan and capecitabine plus cetuximab; n=38). Both trials were similarly designed except for the administration of cetuximab; radiation therapy was administered at a dose of 50.4 Gy/28 fractions and irinotecan and capecitabine were given at doses of 40 mg/m{sup 2} weekly and 1650 mg/m{sup 2}/day, respectively, for 5 days per week. In the ERBIRIX trial, cetuximab was additionally given with a loading dose of 400 mg/m{sup 2} on 1 week before radiation, and 250 mg/m{sup 2} weekly thereafter. Results: Baseline characteristics before chemoradiation were similar between the 2 trial cohorts. A KRAS mutation in codon 12, 13, and 61 was noted in 15 (34%) patients in the IRIX cohort and 5 (13%) in the ERBIRIX cohort (P=.028). Among 62 KRAS wild-type cancer patients, major pathologic response rate, disease-free survival and pathologic stage did not differ significantly between the 2 cohorts. No mutations were detected in BRAF exon 11 and 15, PIK3CA exon 9 and 20, or EGFR exon 18-24 in any of the 82 patients, and PTEN and EGFR expression were not predictive of clinical outcome. Conclusions: In patients with KRAS wild-type locally advanced rectal cancer, the addition of cetuximab to the chemoradiation with irinotecan plus capecitabine regimen was not associated with improved clinical outcome compared with chemoradiation without cetuximab.« less

Is neoadjuvant chemoradiation with dose-escalation and consolidation chemotherapy sufficient to increase surgery-free and distant metastases-free survival in baseline cT3 rectal cancer?

PubMed

São Julião, Guilherme Pagin; Habr-Gama, Angelita; Vailati, Bruna Borba; Aguilar, Patricia Bailão; Sabbaga, Jorge; Araújo, Sérgio Eduardo Alonso; Mattacheo, Adrian; Alexandre, Flavia Andrea; Fernandez, Laura Melina; Gomes, Diogo Bugano; Gama-Rodrigues, Joaquim; Perez, Rodrigo Oliva

2018-01-01

Patients with cT3 rectal cancer are less likely to develop complete response to neoadjuvant chemoradiation (nCRT) and still face significant risk for systemic relapse. In this setting, radiation (RT) dose-escalation and consolidation chemotherapy in "extended" nCRT regimens have been suggested to improve primary tumor response and decrease the risks of systemic recurrences. For these reasons we compared surgery-free and distant-metastases free survival among cT3 patients undergoing standard or extended nCRT. Patients with distal and non-metastatic T3 rectal cancer managed by nCRT were retrospectively reviewed. Patients undergoing standard CRT (50.4 Gy and 2 cycles of 5FU-based chemotherapy) were compared to those undergoing extended CRT (54 Gy and 6 cycles of 5FU-based chemotherapy). Patients were assessed for tumor response at 8-10 weeks. Patients with complete clinical response (cCR) underwent organ-preservation strategy (Watch & Wait). Patients were referred to salvage surgery in the event of local recurrence during follow-up. Cox's logistic regression was performed to identify independent features associated with improved surgery-free survival after cCR and distant-metastases-free survival. 155 patients underwent standard and 66 patients extended CRT. Patients undergoing extended CRT were more likely to harbor larger initial tumor size (p = 0.04), baseline nodal metastases (cN+; p < 0.001) and higher tumor location (p = 0.02). Cox-regression analysis revealed that the type of nCRT regimen was not independently associated with distinct surgery-free survival after cCR or distant-metastases-free survival (p > 0.05). Dose-escalation and consolidation chemotherapy are insufficient to increase long-term surgery-free survival among cT3 rectal cancer patients and provides no advantage in distant metastases-free survival. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Germline and somatic genetic predictors of pathological response in neoadjuvant settings of rectal and esophageal cancers: systematic review and meta-analysis.

PubMed

Salnikova, L E; Kolobkov, D S

2016-06-01

Oncologists have pointed out an urgent need for biomarkers that can be useful for clinical application to predict the susceptibility of patients to preoperative therapy. This review collects, evaluates and combines data on the influence of reported somatic and germline genetic variations on histological tumor regression in neoadjuvant settings of rectal and esophageal cancers. Five hundred and twenty-seven articles were identified, 204 retrieved and 61 studies included. Among 24 and 14 genetic markers reported for rectal and esophageal cancers, respectively, significant associations in meta-analyses were demonstrated for the following markers. In rectal cancer, major response was more frequent in carriers of the TYMS genotype 2 R/2 R-2 R/3 R (rs34743033), MTHFR genotype 677C/C (rs1801133), wild-type TP53 and KRAS genes. In esophageal cancer, successful therapy appeared to correlate with wild-type TP53. These results may be useful for future research directions to translate reported data into practical clinical use.

SU-E-T-311: Dosimetric Comparison of Volumetric Modulated Arc Therapy Plans for Preoperative Radiotherapy Rectal Cancer Using Flattening Filter-Free and Flattening Filter Modes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, W; Zhang, J; Lu, J

Purpose: To compare the dosimetric difference of volumetric modulated arc therapy(VMAT) for preoperative radiotherapy rectal cancer using 6MV X-ray flattening filter free(FFF) and flattening filter(FF) modes. Methods: FF-VMAT and FFF-VMAT plans were designed to 15 rectal cancer patients with preoperative radiotherapy by planning treatment system(Eclipse 10.0),respectively. Dose prescription was 50 Gy in 25 fractions. All plans were normalized to 50 Gy to 95% of PTV. The Dose Volume Histogram (DVH), target and risk organ doses, conformity indexes (CI), homogeneity indexes (HI), low dose volume of normal tissue(BP), monitor units(MU) and treatment time (TT) were compared between the two kinds ofmore » plans. Results: FF-VMAT provided the lower Dmean, V105, HI, and higher CI as compared with FFF-VMAT. The small intestine of D5, Bladder of D5, Dmean, V40, V50, L-femoral head of V40, R-femoral head of Dmean were lower in FF-VMAT than in FFF-VMAT. FF-VMAT had higher BP of V5, but no significantly different of V10, V15, V20, V30 as compared with FFF-VMAT. FF-VMAT reduceed the monitor units(MU) by 21%(P<0.05), as well as the treatment time(TT) was no significantly different(P>0.05), as compared with FFF-VMAT. Conclusion: The plan qualities of FF and FFF VMAT plans were comparable and both clinically acceptable. FF-VMAT as compared with FFF-VMAT, showing better target coverage, some of OARs sparing, the MUs of FFF-VMAT were higher than FF-VMAT, yet were delivered within the same time. This work was supported by the Medical Scientific Research Foundation of Guangdong Procvince (A2014455 to Changchun Ma)« less

A phase 1 study of heat/phenol-killed, E. coli-encapsulated, recombinant modified peanut proteins Ara h 1, Ara h 2, and Ara h 3 (EMP-123) for the treatment of peanut allergy.

PubMed

Wood, R A; Sicherer, S H; Burks, A W; Grishin, A; Henning, A K; Lindblad, R; Stablein, D; Sampson, H A

2013-06-01

Immunotherapy for peanut allergy may be limited by the risk of adverse reactions. To investigate the safety and immunologic effects of a vaccine containing modified peanut proteins. This was a phase 1 trial of EMP-123, a rectally administered suspension of recombinant Ara h 1, Ara h 2, and Ara h 3, modified by amino acid substitutions at major IgE-binding epitopes, encapsulated in heat/phenol-killed E. coli. Five healthy adults were treated with 4 weekly escalating doses after which 10 peanut-allergic adults received weekly dose escalations over 10 weeks from 10 mcg to 3063 mcg, followed by three biweekly doses of 3063 mcg. There were no significant adverse effects in the healthy volunteers. Of the 10 peanut-allergic subjects [4 with intermittent asthma, median peanut IgE 33.3 kUA /l (7.2-120.2), and median peanut skin prick test wheal 11.3 mm (6.5-18)]; four experienced no symptoms; one had mild rectal symptoms; and the remaining five experienced adverse reactions preventing completion of dosing. Two were categorized as mild, but the remaining three were more severe, including one moderate reaction and two anaphylactic reactions. Baseline peanut IgE was significantly higher in the five reactive subjects (median 82.4 vs 17.2 kUA /l, P = 0.032), as was baseline anti-Ara h 2 IgE (43.3 versus 8.3, P = 0.036). Peanut skin test titration and basophil activation (at a single dilution) were significantly reduced after treatment, but no significant changes were detected for total IgE, peanut IgE, or peanut IgG4. Rectal administration of EMP-123 resulted in frequent adverse reactions, including severe allergic reactions in 20%. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dose-Effect Relationship in Chemoradiotherapy for Locally Advanced Rectal Cancer: A Randomized Trial Comparing Two Radiation Doses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jakobsen, Anders, E-mail: anders.jakobsen@slb.regionsyddanmark.dk; University of Southern Denmark, Odense; Ploen, John

2012-11-15

Purpose: Locally advanced rectal cancer represents a major therapeutic challenge. Preoperative chemoradiation therapy is considered standard, but little is known about the dose-effect relationship. The present study represents a dose-escalation phase III trial comparing 2 doses of radiation. Methods and Materials: The inclusion criteria were resectable T3 and T4 tumors with a circumferential margin of {<=}5 mm on magnetic resonance imaging. The patients were randomized to receive 50.4 Gy in 28 fractions to the tumor and pelvic lymph nodes (arm A) or the same treatment supplemented with an endorectal boost given as high-dose-rate brachytherapy (10 Gy in 2 fractions; armmore » B). Concomitant chemotherapy, uftoral 300 mg/m{sup 2} and L-leucovorin 22.5 mg/d, was added to both arms on treatment days. The primary endpoint was complete pathologic remission. The secondary endpoints included tumor response and rate of complete resection (R0). Results: The study included 248 patients. No significant difference was found in toxicity or surgical complications between the 2 groups. Based on intention to treat, no significant difference was found in the complete pathologic remission rate between the 2 arms (18% and 18%). The rate of R0 resection was different in T3 tumors (90% and 99%; P=.03). The same applied to the rate of major response (tumor regression grade, 1+2), 29% and 44%, respectively (P=.04). Conclusions: This first randomized trial comparing 2 radiation doses indicated that the higher dose increased the rate of major response by 50% in T3 tumors. The endorectal boost is feasible, with no significant increase in toxicity or surgical complications.« less

Population Pharmacokinetics of Artesunate and Dihydroartemisinin following Intra-Rectal Dosing of Artesunate in Malaria Patients

PubMed Central

Simpson, Julie A; Agbenyega, Tsiri; Barnes, Karen I; Perri, Gianni Di; Folb, Peter; Gomes, Melba; Krishna, Sanjeev; Krudsood, Srivicha; Looareesuwan, Sornchai; Mansor, Sharif; McIlleron, Helen; Miller, Raymond; Molyneux, Malcolm; Mwenechanya, James; Navaratnam, Visweswaran; Nosten, Francois; Olliaro, Piero; Pang, Lorrin; Ribeiro, Isabela; Tembo, Madalitso; van Vugt, Michele; Ward, Steve; Weerasuriya, Kris; Win, Kyaw; White, Nicholas J

2006-01-01

Background Intra-rectal artesunate has been developed as a potentially life-saving treatment of severe malaria in rural village settings where administration of parenteral antimalarial drugs is not possible. We studied the population pharmacokinetics of intra-rectal artesunate and the relationship with parasitological responses in patients with moderately severe falciparum malaria. Methods and Findings Adults and children in Africa and Southeast Asia with moderately severe malaria were recruited in two Phase II studies (12 adults from Southeast Asia and 11 children from Africa) with intensive sampling protocols, and three Phase III studies (44 children from Southeast Asia, and 86 children and 26 adults from Africa) with sparse sampling. All patients received 10 mg/kg artesunate as a single intra-rectal dose of suppositories. Venous blood samples were taken during a period of 24 h following dosing. Plasma artesunate and dihydroartemisinin (DHA, the main biologically active metabolite) concentrations were measured by high-performance liquid chromatography with electrochemical detection. The pharmacokinetic properties of DHA were determined using nonlinear mixed-effects modelling. Artesunate is rapidly hydrolysed in vivo to DHA, and this contributes the majority of antimalarial activity. For DHA, a one-compartment model assuming complete conversion from artesunate and first-order appearance and elimination kinetics gave the best fit to the data. The mean population estimate of apparent clearance (CL/F) was 2.64 (l/kg/h) with 66% inter-individual variability. The apparent volume of distribution (V/F) was 2.75 (l/kg) with 96% inter-individual variability. The estimated DHA population mean elimination half-life was 43 min. Gender was associated with increased mean CL/F by 1.14 (95% CI: 0.36–1.92) (l/kg/h) for a male compared with a female, and weight was positively associated with V/F. Larger V/Fs were observed for the patients requiring early rescue treatment compared with the remainder, independent of any confounders. No associations between the parasitological responses and the posterior individual estimates of V/F, CL/F, and AUC0–6h were observed. Conclusions The pharmacokinetic properties of DHA were affected only by gender and body weight. Patients with the lowest area under the DHA concentration curve did not have slower parasite clearance, suggesting that rectal artesunate is well absorbed in most patients with moderately severe malaria. However, a number of modelling assumptions were required due to the large intra- and inter-individual variability of the DHA concentrations. PMID:17132053

Tranexamic acid therapy in ulcerative colitis

PubMed Central

Hollanders, D.; Thomson, Jean M.; Schofield, Phillip F.

1982-01-01

The antifibrinolytic drug tranexamic acid was assessed in controlling bleeding in 12 patients with left-sided proctocolitis. The study was designed as a double-blind cross-over trial employing a dose of 4·5 g of tranexamic acid/day together with identical placebo. A statistically significant reduction in rectal bleeding was achieved in 50% of cases with a minimum of side effects. Sigmoidoscopic grading of rectal mucosal appearances was improved. Frequency of diarrhoea and stool consistency were not altered. Tranexamic acid may have a part to play in the management of selected patients with ulcerative colitis in whom bleeding is difficult to control with orthodox treatment. PMID:6980404

Rectal Cancer in Asian vs. Western Countries: Why the Variation in Incidence?

PubMed

Deng, Yanhong

2017-09-25

Colorectal cancer (CRC) is the third most common cancer worldwide. CRC has been thought to be less common in Asia compared to Western countries. However, the incidence rates of CRC in Asia are high and there is an increasing trend in the Asian population. Furthermore, colorectal cancer accounts for the greatest number of all incidences of CRC in Asia. The increasing adoption of a Western lifestyle, particularly in dietary habits, is likely the most important factor contributing to the rapid increase in colon cancer incidence; it is noteworthy that trends for rectal cancer were flat. The etiology of colon and rectal cancer is a bit different. The risks of distal colon and rectal cancers are more likely to be related to environmental factors, such as polluted surface water sources, alcohol consumption, and habitual smoking. The lack of great change in the incidence of rectal cancer might be due to weaker associations with such lifestyle factors. Therefore, it has been hypothesized that proximal and distal sections of the colon and rectum are two different organs in terms of function and genetic background. It may mean differences in differential sensitivities and exposures to carcinogens. However, despite the decrease in whole incidence, the CRC incidence in young adults in Western countries are reversely increasing, especially in rectal cancer, due to reasons largely unknown. Although the treatment algorithm is different between Asia and western countries, globally, the survival rate for patients with rectal cancer has risen during the past 10 years. Screening contributes a great deal to reducing the incidence and improving survival. Most countries in Asia, such as China, need nationwide registration and screening systems to provide better data.

Preoperative chemoradiation of locally advanced T3 rectal cancer combined with an endorectal boost

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jakobsen, Anders; Mortensen, John P.; Bisgaard, Claus

2006-02-01

Purpose: To investigate the effect and feasibility of concurrent radiation and chemotherapy combined with endorectal brachytherapy in T3 rectal cancer with complete pathologic remission as end point. Methods and Materials: The study included 50 patients with rectal adenocarcinoma. All patients had T3 tumor with a circumferential margin 0-5 mm on a magnetic resonance imaging scan. The radiotherapy was delivered by a technique including two planning target volumes. Clinical target volume 1 (CTV1) received 60 Gy/30 fractions, and CTV2 received 48.6 Gy/27 fractions. The tumor dose was raised to 65 Gy with endorectal brachytherapy 5 Gy/1 fraction to the tumor bed.more » On treatment days, the patients received uracil and tegafur 300 mg/m2 concurrently with radiotherapy. Results: Forty-eight patients underwent operation. Histopathologic tumor regression was assessed by the Tumor Regression Grade (TRG) system. TRG1 was recorded in 27% of the patients, and a further 27% were classified as TRG2. TRG3 was found in 40%, and 6% had TRG4. The toxicity was low. Conclusion: The results indicate that high-dose radiation with concurrent chemotherapy and endorectal brachytherapy is feasible with a high rate of complete response, but further trials are needed to define its possible role as treatment option.« less

An assessment of PTV margin based on actual accumulated dose for prostate cancer radiotherapy

NASA Astrophysics Data System (ADS)

Wen, Ning; Kumarasiri, Akila; Nurushev, Teamour; Burmeister, Jay; Xing, Lei; Liu, Dezhi; Glide-Hurst, Carri; Kim, Jinkoo; Zhong, Hualiang; Movsas, Benjamin; Chetty, Indrin J.

2013-11-01

The purpose of this work is to present the results of a margin reduction study involving dosimetric and radiobiologic assessment of cumulative dose distributions, computed using an image guided adaptive radiotherapy based framework. Eight prostate cancer patients, treated with 7-9, 6 MV, intensity modulated radiation therapy (IMRT) fields, were included in this study. The workflow consists of cone beam CT (CBCT) based localization, deformable image registration of the CBCT to simulation CT image datasets (SIM-CT), dose reconstruction and dose accumulation on the SIM-CT, and plan evaluation using radiobiological models. For each patient, three IMRT plans were generated with different margins applied to the CTV. The PTV margin for the original plan was 10 mm and 6 mm at the prostate/anterior rectal wall interface (10/6 mm) and was reduced to: (a) 5/3 mm, and (b) 3 mm uniformly. The average percent reductions in predicted tumor control probability (TCP) in the accumulated (actual) plans in comparison to the original plans over eight patients were 0.4%, 0.7% and 11.0% with 10/6 mm, 5/3 mm and 3 mm uniform margin respectively. The mean increase in predicted normal tissue complication probability (NTCP) for grades 2/3 rectal bleeding for the actual plans in comparison to the static plans with margins of 10/6, 5/3 and 3 mm uniformly was 3.5%, 2.8% and 2.4% respectively. For the actual dose distributions, predicted NTCP for late rectal bleeding was reduced by 3.6% on average when the margin was reduced from 10/6 mm to 5/3 mm, and further reduced by 1.0% on average when the margin was reduced to 3 mm. The average reduction in complication free tumor control probability (P+) in the actual plans in comparison to the original plans with margins of 10/6, 5/3 and 3 mm was 3.7%, 2.4% and 13.6% correspondingly. The significant reduction of TCP and P+ in the actual plan with 3 mm margin came from one outlier, where individualizing patient treatment plans through margin adaptation based on biological models, might yield higher quality treatments.

Medical audit of rectal biopsy diagnosis of inflammatory bowel disease.

PubMed

Frei, J V; Morson, B C

1982-03-01

The records of the rectal biopsy diagnoses of ulcerative colitis and Crohn's disease in the Department of Pathology, St Mark's Hospital, London, were reviewed. The biopsy diagnoses were compared to subsequent resection diagnoses on the same patients, and annual and seasonal variations in the frequency of these and related diagnoses were studied. The accuracy rate for the biopsy diagnosis of ulcerative colitis was about 70% and for Crohn's disease about 40% each time a biopsy was read. The low figure for the accuracy rate for Crohn's disease could be attributed to sampling error inherent in the diagnosis of a disease which is essentially patchy, showing discontinuous pathology. Also, many patients with Crohn's disease have a normal rectum which is biopsied to demonstrate the distinction from ulcerative colitis. In practical terms therefore a 40% accuracy rate in Crohn's disease is probably adequate. The rate of "false-positive" diagnoses was about 5%. There was a seasonal variation in the frequency of these two diagnoses, but no variation attributable to changes in observers, as pathology trainees in the Department change regularly. The frequency of diagnoses of non-specific inflammation and of normal colon did show such non-random variations.

Anesthetic and pathological changes following high doses of ketamine and xylazine in Sprague Dawley rats

PubMed Central

GIROUX, Marie-Chantal; HÉLIE, Pierre; BURNS, Patrick; VACHON, Pascal

2015-01-01

The main objective of this study was to compare the effects of ketamine and xylazine in aging rats when coadministered intraperitoneally at high anesthetic doses. Three groups (n=6 rats/group) consisting of rats at 3, 6 and 12 months of age were used. During anesthesia, animals were monitored for heart rate, respiratory frequency, blood oxygen saturation, and rectal temperature. The corneal and paw withdrawal reflex were also examined during anesthesia. During anesthesia, withdrawal and corneal reflexes were absent for progressively longer durations with increasing age. Significant decreases in cardiac and respiratory frequency and, blood oxygen saturation occurred for the 6- and 12-month-old animals. Respiratory frequency and blood oxygen saturation returned to normal at the end of the anesthesia; however, the significant decrease in cardiac frequency persisted in the 6- and 12-month-old animals. Rectal temperature was decreased significantly only in the 3-month-old animals. Pulmonary edema and effusion occurred in 50% of the 12-month-old animals. In conclusion, if ketamine-xylazine are used for anesthesia, the doses should be optimized for the age of the subjects prior to initiation of the research project. PMID:25818316

A double-blind, placebo-controlled, randomised, parallel-group, dose-escalating, repeat dose study in healthy volunteers to evaluate the safety, tolerability, pharmacodynamic effects and pharmacokinetics of the once daily rectal application of NRL001 suppositories for 14 days.

PubMed

Bell, D; Duffin, A; Jacobs, A; Pediconi, C; Gruss, H J

2014-03-01

The 1R,2S stereoisomer of methoxamine hydrochloride, NRL001, is a highly selective α1-adrenoceptor agonist being developed for the local treatment of non-structural faecal incontinence caused by weak internal anal sphincter tone. This study investigated the steady state pharmacokinetics (PK) and safety of 2 g rectal suppositories containing NRL001 in different strengths (7.5, 10, 12.5 or 15 mg). Healthy volunteers aged 18-45 years received 14 daily doses of NRL001 2 g suppositories or matching placebo. In each dose group nine participants received NRL001 and three received placebo. Blood samples to determine NRL001 concentrations were taken on Days 1, 7 and 14. Cardiovascular parameters were collected via electrocardiograms, Holter monitoring (three lead Holter monitor) and vital signs. Forty-eight volunteers were enrolled; 43 completed the study and were included in the PK analysis population. AUC and Cmax broadly increased with increasing dose, Tmax generally occurred between 4.0 and 5.0 h. Although the data did not appear strongly dose proportional, dose proportionality analysis did not provide evidence against dose proportionality as the log(dose) coefficients were not significantly < 1. NRL001 did not accumulate over time for any dose. Increasing NRL001 concentrations were related to changes in vital sign variables, most notably decreased heart rate. The most commonly reported adverse events (AEs) in the active treatment groups were paraesthesia and piloerection. Treatment with NRL001 was generally well tolerated over 14 days once daily dosing and plasma NRL001 did not accumulate over time. Treatment was associated with changes in vital sign variables, most notably decreased heart rate. AEs commonly reported with NRL001 treatment were events indicative of a systemic α-adrenergic effect. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

Management of colorectal cancer in three South Thames District Health Authorities.

PubMed

Pollock, A M; Vickers, N

1997-05-01

This study describes the management of colorectal cancer, diagnosed in 1988, of residents in three South Thames Districts. Of the 328 cases identified as having being diagnosed in 1988, case notes were retrieved on 263 (80%) including 62 registered by death certificate only. There were 159 cases (61%) of colon cancer and 104 cases (39%) of rectal cancer. Of these, 172 cases (68%) were admitted electively and 90 (32%) as emergencies. Patients subsequently diagnosed with colon cancer had a relative risk of being admitted through emergency (relative to rectal cancer patients) of 1.39 (95% C.I.: 1.16, 1.67). Elective admissions varied significantly by district of residence (P < 0.0001) ranging from 36-65% for colon cancers and from 63-92% for rectal cancers across the three districts. Dukes' stage was recorded in only 143 (54%) sets of case notes, with significant variation by district of residence in the proportion of elective patients for whom a Dukes' stage was indicated (P < 0.01). Two-hundred and thirty-six (90%) cases received treatment. Of the treated cases, 233 patients received surgery with 29 cases of colon cancer (18%) and 32 cases of rectal cancer (31%) receiving adjuvant therapy. The proportions of anterior resection, AP resection and colostomies given, varied by district. Patients presenting for elective surgery were more likely to be treated by a consultant than patients presenting on emergency: the relative risks were 2.58 (95% C.I.: 1.74, 3.82) for colon cancer patients and 4.93 (95% C.I.: 2.20, 11.06) for rectal cancer patients. In 44 (26%) colon cancer cases and 21 (22%) rectal cancer cases it was explicitly stated that the tumour had not been fully resected. For colon tumours the five year relative survival rates were 35% (95% C.I.: 21%, 50%), 52% (95% C.I.: 34%, 70%), and 14% (95% C.I.: -2%, 30%) in districts A, B and C respectively. The corresponding figures for rectal tumours were 45% (95% C.I.: 27%, 64%), 62% (95% C.I.: 41%, 83%) and 24% (95% C.I.: -1%, 50%). There were wide variations in the representation, management of and survival from colorectal cancers across the three districts. Differences were significant at the level of district of residence, mode of presentation and surgical grade. More assiduous recording of Dukes' stage is imperative if consensus is to be achieved on effective management. Further work is also warranted on district differences in diagnostic and referral protocols.

Proteogenomic characterization of human colon and rectal cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Bing; Wang, Jing; Wang, Xiaojing

2014-09-18

We analyzed proteomes of colon and rectal tumors previously characterized by the Cancer Genome Atlas (TCGA) and performed integrated proteogenomic analyses. Protein sequence variants encoded by somatic genomic variations displayed reduced expression compared to protein variants encoded by germline variations. mRNA transcript abundance did not reliably predict protein expression differences between tumors. Proteomics identified five protein expression subtypes, two of which were associated with the TCGA "MSI/CIMP" transcriptional subtype, but had distinct mutation and methylation patterns and associated with different clinical outcomes. Although CNAs showed strong cis- and trans-effects on mRNA expression, relatively few of these extend to the proteinmore » level. Thus, proteomics data enabled prioritization of candidate driver genes. Our analyses identified HNF4A, a novel candidate driver gene in tumors with chromosome 20q amplifications. Integrated proteogenomic analysis provides functional context to interpret genomic abnormalities and affords novel insights into cancer biology.« less

Image-guided high dose rate endorectal brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Devic, Slobodan; Vuong, Te; Moftah, Belal

2007-11-15

Fractionated high dose rate endorectal brachytherapy (HDR-EBT) using CT-based treatment planning is an alternative method for preoperative down-sizing and down-staging of advanced rectal adeno-carcinomas. The authors present an image guidance procedure that was developed to ensure daily dose reproducibility for the four brachytherapy treatment fractions. Since the applicator might not be placed before each treatment fraction inside the rectal lumen in the same manner as it was placed during the 3D CT volume acquisition used for treatment planning, there is a shift along the catheter axis that may have to be performed. The required shift is determined by comparison ofmore » a daily radiograph with the treatment planning digitally-reconstructed radiograph (DRR). A procedure is developed for DRR reconstruction from the 3D data set used for the treatment planning, and two possible daily longitudinal shifts are illustrated: above and below the planning dose distribution. The authors also describe the procedure for rotational alignment illustrated on a clinical case. Reproduction of the treatment planned dose distribution on a daily basis is crucial for the success of fractionated 3D based brachytherapy treatments. Due to the cylindrical symmetry of the applicator used for preoperative HDR-EBT, two types of adjustments are necessary: applicator rotation and dwell position shift along the applicator's longitudinal axis. The impact of the longitudinal applicator shift prior to treatment delivery for 62 patients treated in our institution is also assessed.« less

Rectal bleeding, fecal incontinence, and high stool frequency after conformal radiotherapy for prostate cancer: Normal tissue complication probability modeling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peeters, Stephanie; Hoogeman, Mischa S.; Heemsbergen, Wilma D.

2006-09-01

Purpose: To analyze whether inclusion of predisposing clinical features in the Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model improves the estimation of late gastrointestinal toxicity. Methods and Materials: This study includes 468 prostate cancer patients participating in a randomized trial comparing 68 with 78 Gy. We fitted the probability of developing late toxicity within 3 years (rectal bleeding, high stool frequency, and fecal incontinence) with the original, and a modified LKB model, in which a clinical feature (e.g., history of abdominal surgery) was taken into account by fitting subset specific TD50s. The ratio of these TD50s is the dose-modifyingmore » factor for that clinical feature. Dose distributions of anorectal (bleeding and frequency) and anal wall (fecal incontinence) were used. Results: The modified LKB model gave significantly better fits than the original LKB model. Patients with a history of abdominal surgery had a lower tolerance to radiation than did patients without previous surgery, with a dose-modifying factor of 1.1 for bleeding and of 2.5 for fecal incontinence. The dose-response curve for bleeding was approximately two times steeper than that for frequency and three times steeper than that for fecal incontinence. Conclusions: Inclusion of predisposing clinical features significantly improved the estimation of the NTCP. For patients with a history of abdominal surgery, more severe dose constraints should therefore be used during treatment plan optimization.« less

Anorectal physiology is not changed following transanal haemorrhoidal dearterialization for haemorrhoidal disease: clinical, manometric and endosonographic features.

PubMed

Ratto, C; Parello, A; Donisi, L; Litta, F; Doglietto, G B

2011-08-01

The effect of transanal haemorrhoidal dearterialization (THD) on continence and anorectal physiology has not yet been demonstrated. Twenty patients suffering from 3rd degree haemorrhoids were enrolled and underwent THD, including both dearterialization and mucopexy. Clinical assessment, anorectal manometry, rectal volumetry and endoanal ultrasound were performed preoperatively and at 6 months postoperatively. Postoperatively two and six patients had transient rectal pain and tenesmus, respectively. No patient reported faecal urgency or minor or major incontinence. All patients remained able to discriminate gas from faeces. No significant variation of the mean values of anal manometric and rectal volumetric parameters was recorded at 6 months of follow-up compared with preoperative values. At 6 months both internal and external sphincters were endosonographically intact. THD does not cause trauma to the anal canal and rectum. © 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.

A Comparison of Surface Infrared with Rectal Thermometry in Dogs.

PubMed

Omóbòwálé, T O; Ogunro, B N; Odigie, E A; Otuh, P I; Olugasa, B O

2017-12-30

Accurate determination of temperature is crucial in the diagnosis of febrile conditions. Although fewer techniques have proven as useful and reliable a predictor of core body temperature as the rectal thermometry, the process of obtaining the rectal temperature could be stressful in dogs. The infrared thermometry is a noncontact device used for measuring body temperature, with advantages which include speed, convenience, and reduced stress to the animals and reduced occupational risks to the animal handler. Therefore, there is the need to assess the consistency and agreement between non-contact infrared thermometry and traditional rectal thermometry in body temperature estimation. This study compared and assessed the sensitivity of non-contact infrared thermometer used on the forehead and nasal regions respectively with that of a rectal thermometer in dogs for body temperature estimation. One hundred and thirty (130) dogs presented for veterinary attention at the Veterinary Teaching Hospital (VTH), University of Ibadan, Nigeria were enrolled in this study during August to September 2014, irrespective of sex, age, breed or health status. Temperatures of dogs presented at the clinic were obtained using both multiple non-contact infrared thermometric measures obtained in the nasal and frontal head regions; and by rectal temperature. A multivariate cross-matrix analysis was used to assess the difference in measurements between the rectal thermometry and non-contact infrared thermometry. Descriptive statistics was used to compare variation and trend regularity of the nasal and fore-head infrared thermometry. A logistic regression of the difference in measurements was computed at 95% confidence interval and P<0.05. The mean difference revealed that the rectal temperature was 5.330C higher than the non-contact infrared forehead-based temperature and 7.570C higher than nasal-based temperature measurements respectively. The Bland-Altman (B-A) plot showed that the 95% limits of agreement between the frontal and nasal obtained infrared laser thermometry methods. Temperature measure obtained using non-contact infrared thermometry (forehead and nasal region of the head) was poor in consistency and agreement compared to rectal thermometry. Usefulness of non-contact forehead infrared thermometry in routine clinical practice as a close estimate of core body temperature depends on accurate calibration and therefore not recommended.

Excellent response rate of anismus to botulinum toxin if rectal prolapse misdiagnosed as anismus ('pseudoanismus') is excluded.

PubMed

Hompes, R; Harmston, C; Wijffels, N; Jones, O M; Cunningham, C; Lindsey, I

2012-02-01

Anismus causes obstructed defecation as a result of inappropriate contraction of the puborectalis/external sphincter. Proctographic failure to empty after 30 s is used as a simple surrogate for simultaneous electromyography/proctography. Botulinum toxin is theoretically attractive but efficacy is variable. We aimed to evaluate the efficacy of botulinum toxin to treat obstructed defecation caused by anismus. Botulinum toxin was administered, under local anaesthetic, into the puborectalis/external sphincter of patients with proctographic anismus. Responders (resolution followed by recurrence of obstructed defecation over a 1- to 2-month period) underwent repeat injection. Nonresponders underwent rectal examination under anaesthetic (EUA). EUA-diagnosed rectal prolapse was graded using the Oxford Prolapse Grade 1-5. Fifty-six patients were treated with botulinum toxin. Twenty-two (39%) responded initially and 21/22 (95%) underwent repeat treatment. At a median follow up of 19.2 (range, 7.0-30.4) months, 20/21 (95%) had a sustained response and required no further treatment. Isolated obstructed defecation symptoms (OR = 7.8, P = 0.008), but not proctographic or physiological factors, predicted response on logistic regression analysis. In 33 (97%) of 34 nonresponders, significant abnormalities were demonstrated at EUA: 31 (94%) had a grade 3-5 rectal prolapse, one had internal anal sphincter myopathy and one had a fissure. Exclusion of these alternative diagnoses revised the initial response rate to 96%. Simple proctographic criteria overdiagnose anismus and underdiagnose rectal prolapse. This explains the published variable response to botulinum toxin. Failure to respond should prompt EUA seeking undiagnosed rectal prolapse. A response to an initial dose of botulinum toxin might be considered a more reliable diagnosis of anismus than proctography. © 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.

Does ITV vaginal procedure ensure dosimetric coverage during IMRT of post-operative gynaecological tumours without instructions concerning rectal filling?

PubMed

Verges, Ramona; Giraldo, Alexandra; Seoane, Alejandro; Toral, Elisabet; Ruiz, M Carmen; Pons, Ariadna; Giralt, Jordi

2018-01-01

To find out whether the internal target volume (ITV) vaginal procedure ensures dosimetric coverage during intensity-modulated radiation therapy (IMRT) of post-operative gynaecological tumours without instructions on rectal filling. The ITV vaginal procedure does not necessarily include all movements of the bladder, and does not include changes in the rectal volume. We should know if the vaginal ITV is a useful tool in maintaining CTV coverage during treatment. A retrospective analysis of 24 patients treated between July 2012 and July 2014 with adjuvant IMRT for gynaecological cancer. All patients underwent empty and full bladder CT on simulation (CT-planning) and three weeks later (CT-control). ITV displacement was measured and the 3D vector was calculated. ITV coverage was then evaluated by comparing the volume covered by the prescription isodose on both CT's. Patients were asked to have full bladder but they did not follow recommendations for the rectum. The mean 3D vector was 0.64 ± 0.32 cm (0.09-1.30). The mean ITV coverage loss was 5.8 ± 5.7% (0-20.2). We found a significant positive correlation between the 3D vector and the loss of coverage (Pearson correlation, r  = 0.493, 95% CI: 0.111-0.748, p  = 0.0144). We did not find any significant correlation between the bladder and rectal parameters with the 3D vector and loss of dosimetric coverage. We found a trend between the maximum rectal diameter in CT-planning and 3D vector ( r  = 0.400, 95% CI: -0.004 to 0.692, p  = 0.0529). ITV vaginal procedure contributed to ensuring a good dose coverage without instructions on rectal filling.

The first clinical implementation of electromagnetic transponder-guided MLC tracking.

PubMed

Keall, Paul J; Colvill, Emma; O'Brien, Ricky; Ng, Jin Aun; Poulsen, Per Rugaard; Eade, Thomas; Kneebone, Andrew; Booth, Jeremy T

2014-02-01

We report on the clinical process, quality assurance, and geometric and dosimetric results of the first clinical implementation of electromagnetic transponder-guided MLC tracking which occurred on 28 November 2013 at the Northern Sydney Cancer Centre. An electromagnetic transponder-based positioning system (Calypso) was modified to send the target position output to in-house-developed MLC tracking code, which adjusts the leaf positions to optimally align the treatment beam with the real-time target position. Clinical process and quality assurance procedures were developed and performed. The first clinical implementation of electromagnetic transponder-guided MLC tracking was for a prostate cancer patient being treated with dual-arc VMAT (RapidArc). For the first fraction of the first patient treatment of electromagnetic transponder-guided MLC tracking we recorded the in-room time and transponder positions, and performed dose reconstruction to estimate the delivered dose and also the dose received had MLC tracking not been used. The total in-room time was 21 min with 2 min of beam delivery. No additional time was needed for MLC tracking and there were no beam holds. The average prostate position from the initial setup was 1.2 mm, mostly an anterior shift. Dose reconstruction analysis of the delivered dose with MLC tracking showed similar isodose and target dose volume histograms to the planned treatment and a 4.6% increase in the fractional rectal V60. Dose reconstruction without motion compensation showed a 30% increase in the fractional rectal V60 from that planned, even for the small motion. The real-time beam-target correction method, electromagnetic transponder-guided MLC tracking, has been translated to the clinic. This achievement represents a milestone in improving geometric and dosimetric accuracy, and by inference treatment outcomes, in cancer radiotherapy.

The first clinical implementation of electromagnetic transponder-guided MLC tracking

PubMed Central

Keall, Paul J.; Colvill, Emma; O’Brien, Ricky; Ng, Jin Aun; Poulsen, Per Rugaard; Eade, Thomas; Kneebone, Andrew; Booth, Jeremy T.

2014-01-01

Purpose: We report on the clinical process, quality assurance, and geometric and dosimetric results of the first clinical implementation of electromagnetic transponder-guided MLC tracking which occurred on 28 November 2013 at the Northern Sydney Cancer Centre. Methods: An electromagnetic transponder-based positioning system (Calypso) was modified to send the target position output to in-house-developed MLC tracking code, which adjusts the leaf positions to optimally align the treatment beam with the real-time target position. Clinical process and quality assurance procedures were developed and performed. The first clinical implementation of electromagnetic transponder-guided MLC tracking was for a prostate cancer patient being treated with dual-arc VMAT (RapidArc). For the first fraction of the first patient treatment of electromagnetic transponder-guided MLC tracking we recorded the in-room time and transponder positions, and performed dose reconstruction to estimate the delivered dose and also the dose received had MLC tracking not been used. Results: The total in-room time was 21 min with 2 min of beam delivery. No additional time was needed for MLC tracking and there were no beam holds. The average prostate position from the initial setup was 1.2 mm, mostly an anterior shift. Dose reconstruction analysis of the delivered dose with MLC tracking showed similar isodose and target dose volume histograms to the planned treatment and a 4.6% increase in the fractional rectal V60. Dose reconstruction without motion compensation showed a 30% increase in the fractional rectal V60 from that planned, even for the small motion. Conclusions: The real-time beam-target correction method, electromagnetic transponder-guided MLC tracking, has been translated to the clinic. This achievement represents a milestone in improving geometric and dosimetric accuracy, and by inference treatment outcomes, in cancer radiotherapy. PMID:24506591

Comparison of three methods of temperature measurement in hypothermic, euthermic, and hyperthermic dogs.

PubMed

Greer, Rebecca J; Cohn, Leah A; Dodam, John R; Wagner-Mann, Colette C; Mann, F A

2007-06-15

To assess the reliability and accuracy of a predictive rectal thermometer, an infrared auricular thermometer designed for veterinary use, and a subcutaneous temperature-sensing microchip for measurement of core body temperature over various temperature conditions in dogs. Prospective study. 8 purpose-bred dogs. A minimum of 7 days prior to study commencement, a subcutaneous temperature-sensing microchip was implanted in 1 of 3 locations (interscapular, lateral aspect of shoulder, or sacral region) in each dog. For comparison with temperatures measured via rectal thermometer, infrared auricular thermometer, and microchip, core body temperature was measured via a thermistor-tipped pulmonary artery (TTPA) catheter. Hypothermia was induced during anesthesia at the time of TTPA catheter placement; on 3 occasions after placement of the catheter, hyperthermia was induced via administration of a low dose of endotoxin. Near-simultaneous duplicate temperature measurements were recorded from the TTPA catheter, the rectal thermometer, auricular thermometer, and subcutaneous microchips during hypothermia, euthermia, and hyperthermia. Reliability (variability) of temperature measurement for each device and agreement between each device measurement and core body temperature were assessed. Variability between duplicate near-simultaneous temperature measurements was greatest for the auricular thermometer and least for the TTPA catheter. Measurements obtained by use of the rectal thermometer were in closest agreement with core body temperature; for all other devices, temperature readings typically underestimated core body temperature. Among the 3 methods of temperature measurement, rectal thermometry provided the most accurate estimation of core body temperature in dogs.

[Trimigren in stopping migraine attacks: an open prospective multicenter comparative study of rectal suppository and tablet forms of sumatriptan].

PubMed

Azimova, Iu E; Tabeeva, G R

2009-01-01

Efficacy and safety of sumatriptan in rectal suppository (50 mg) and tablet forms (50 mg) in stopping migraine attacks has been studied in 80 patients with migraine with or without aura. Dynamics of migraine pain intensity measured with the VAS 30 min, 1, 2, 6 and 24 h after the first dose of drug was a primary index of efficacy. Secondary indices were the VAS intensity of nausea, vomiting, photophobia, phonophobia, duration of each migraine attack, quality of life parameters of a patient during the migraine attack assessed with the 24-hour questionnaire, severity of migraine course on the MIDAS, percentage of patients with complete regression of migraine pain, at least in 2 out of 3 attacks. To assess drug safety, any adverse effects, data of instrumental methods (clinical and biochemical blood tests, clinical urine test), EKG were taken into account. Rectal suppository had the more rapid effect on headache reduction compared to tablets. Changes of intensity of concomitant symptoms (nausea, vomiting, photophobia, phonophobia) as well as other secondary indices of drug efficacy were similar in both groups. In the group treated with rectal suppository, 9 (22.5%) patients had 12 adverse effects. In the group treated with tablets, 22 adverse effects were noted in 15 (37.5%) patients. Adverse effects related to the cardio-vascular system were observed less often in the group treated with rectal suppository (6.6 and 32%, respectively, p=0,004).

Amitriptyline reduces rectal pain related activation of the anterior cingulate cortex in patients with irritable bowel syndrome.

PubMed

Morgan, V; Pickens, D; Gautam, S; Kessler, R; Mertz, H

2005-05-01

Irritable bowel syndrome (IBS) is a disorder of intestinal hypersensitivity and altered motility, exacerbated by stress. Functional magnetic resonance imaging (fMRI) during painful rectal distension in IBS has demonstrated greater activation of the anterior cingulate cortex (ACC), an area relevant to pain and emotions. Tricyclic antidepressants are effective for IBS. The aim of this study was to determine if low dose amitriptyline reduces ACC activation during painful rectal distension in IBS to confer clinical benefits. Secondary aims were to identify other brain regions altered by amitriptyline, and to determine if reductions in cerebral activation are greater during mental stress. Nineteen women with painful IBS were randomised to amitriptyline 50 mg or placebo for one month and then crossed over to the alternate treatment after washout. Cerebral activation during rectal distension was compared between placebo and amitriptyline groups by fMRI. Distensions were performed alternately during auditory stress and relaxing music. Rectal pain induced significant activation of the perigenual ACC, right insula, and right prefrontal cortex. Amitriptyline was associated with reduced pain related cerebral activations in the perigenual ACC and the left posterior parietal cortex, but only during stress. The tricyclic antidepressant amitriptyline reduces brain activation during pain in the perigenual (limbic) anterior cingulated cortex and parietal association cortex. These reductions are only seen during stress. Amitriptyline is likely to work in the central nervous system rather than peripherally to blunt pain and other symptoms exacerbated by stress in IBS.

Treatment of Gonorrhea with Spectinomycin Hydrochloride: Comparison with Standard Penicillin Schedules

PubMed Central

Duncan, W. Christopher; Holder, William R.; Roberts, David P.; Knox, John M.

1972-01-01

Spectinomycin hydrochloride, a new parenteral antibiotic prepared from Streptomyces spectabilis, was compared with standard U.S. Public Health Service-recommended dosages of aqueous procaine penicillin G in the treatment of uncomplicated gonorrhea in 353 men and 314 women. Of the 314 women, 130 had a pretreatment positive rectal culture. All diagnoses were proven by culture on Thayer-Martin selective medium. Minimal inhibitory concentrations of both drugs were determined. Single doses of 2 and 4 g of spectinomycin were compared with 2.4 million units of procaine penicillin in males and with both 2.4 and 4.8 million units of procaine penicillin in females. Both spectinomycin schedules, 2.4 million units of penicillin in males and 4.8 million units of penicillin in females, resulted in cure rates in excess of 90%. There were no failures at the rectal site only in those women with positive rectal cultures. There was no advantage to using the larger amount of spectinomycin in either sex. PMID:4261553

SU-F-T-348: The Impact of Model Library Population On RapidPlan Based Dose-Volume Histograms (DVHs) Prediction for Rectal Cancer Patients Treated with Volumetric-Modulated Radiotherapy (VMAT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, K; Zhou, L; Chen, Z

Purpose: RapidPlan uses a library consisting of expert plans from different patients to create a model that can predict achievable dose-volume histograms (DVHs) for new patients. The goal of this study is to investigate the impacts of model library population (plan numbers) on the DVH prediction for rectal cancer patients treated with volumetric-modulated radiotherapy (VMAT) Methods: Ninety clinically accepted rectal cancer patients’ VMAT plans were selected to establish 3 models, named as Model30, Model60 and Model90, with 30,60, and 90 plans in the model training. All plans had sufficient target coverage and bladder and femora sparings. Additional 10 patients weremore » enrolled to test the DVH prediction differences with these 3 models. The predicted DVHs from these 3 models were compared and analyzed. Results: Predicted V40 (Vx, percent of volume that received x Gy for the organs at risk) and Dmean (mean dose, cGy) of the bladder were 39.84±13.38 and 2029.4±141.6 for the Model30,37.52±16.00 and 2012.5±152.2 for the Model60, and 36.33±18.35 and 2066.5±174.3 for the Model90. Predicted V30 and Dmean of the left femur were 23.33±9.96 and 1443.3±114.5 for the Model30, 21.83±5.75 and 1436.6±61.9 for the Model60, and 20.31±4.6 and 1415.0±52.4 for the Model90.There were no significant differences among the 3 models for the bladder and left femur predictions. Predicted V40 and Dmean of the right femur were 19.86±10.00 and 1403.6±115.6 (Model30),18.97±6.19 and 1401.9±68.78 (Model60), and 21.08±7.82 and 1424.0±85.3 (Model90). Although a slight lower DVH prediction of the right femur was found on the Model60, the mean differences for V30 and mean dose were less than 2% and 1%, respectively. Conclusion: There were no significant differences among Model30, Model60 and Model90 for predicting DVHs on rectal patients treated with VMAT. The impact of plan numbers for model library might be limited for cancers with similar target shape.« less

Intramuscular and rectal therapies of acute seizures.

PubMed

Leppik, Ilo E; Patel, Sima I

2015-08-01

The intramuscular (IM) and rectal routes are alternative routes of delivery for antiepileptic drugs (AEDs) when the intravenous route is not practical or possible. For treatment of acute seizures, the AED used should have a short time to maximum concentration (Tmax). Some AEDs have preparations that may be given intramuscularly. These include the benzodiazepines (diazepam, lorazepam, and midazolam) and others (fosphenytoin, levetiracetam). Although phenytoin and valproate have parenteral preparations, these should not be given intramuscularly. A recent study of prehospital treatment of status epilepticus evaluated a midazolam (MDZ) autoinjector delivering IM drug compared to IV lorazepam (LZP). Seizures were absent on arrival to the emergency department in 73.4% of the IM MDZ compared to a 63.4% response in LZP-treated subjects (p < 0.001 for superiority). Almost all AEDs have been evaluated for rectal administration as solutions, gels, and suppositories. In a placebo-controlled study, diazepam (DZP) was administered at home by caregivers in doses that ranged from 0.2 to 0.5 mg/kg. Diazepam was superior to placebo in reduced seizure frequency in children (p < 0.001) and in adults (p = 0.02) and time to recurrent seizures after an initial treatment (p < 0.001). Thus, at this time, only MZD given intramuscularly and DZP given rectally appear to have the properties required for rapid enough absorption to be useful when intravenous routes are not possible. Some drugs cannot be administered rectally owing to factors such as poor absorption or poor solubility in aqueous solutions. The relative rectal bioavailability of gabapentin, oxcarbazepine, and phenytoin is so low that the current formulations are not considered to be suitable for administration by this route. When administered as a solution, diazepam is rapidly absorbed rectally, reaching the Tmax within 5-20 min in children. By contrast, rectal administration of lorazepam is relatively slow, with a Tmax of 1-2h. The dependence of gabapentin on an active transport system, and the much-reduced surface area of the rectum compared with the small intestine, may be responsible for its lack of absorption from the rectum. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Son, Christina H.; Law, Ethel; Oh, Jung Hun

Purpose: Although vaginal stenosis (VS) is a recognized toxicity in women who receive pelvic radiation therapy (RT), the relationship between RT dose and the volume and extent of toxicity has not been analyzed. We modeled this relationship to identify predictors of VS. Methods and Materials: We evaluated 54 women, aged 29 to 78 years, who underwent pelvic RT for rectal or anal cancer during 2008 to 2011 and were enrolled in a prospective study evaluating vaginal dilator use. Maximum dilator size was measured before RT (baseline) and 1 month and 12 months after RT. Dilator use was initiated at 1 month. The difference (D)more » in dilator size before and after RT was recorded. Those with D ≤−1 were classified as having VS (n=35); those with D ≥0 were classified as having no VS (n=19 at 1 month). Dose-volume parameters were extracted, and the generalized equivalent uniform dose (gEUD) was used to build a predictive model. Results: The mean vaginal doses were 50.0 Gy and 36.8 Gy for anal and rectal cancer patients, respectively. One month after RT, a gEUD model using a wide range of a values suggests that sparing of vaginal volume to a low dose may be important. When gEUD (a = −1) was <35 Gy and the mean vaginal dose was <43 Gy, severe VS was reduced (P=.02). A 1-year analysis suggests increasingly negative D values with increasing mean dose. However, patients with compliance <40% were more likely to have toxicity. Conclusions: Vaginal stenosis is influenced by multiple RT dose-volume characteristics. Mean dose and gEUD constraints together may reduce the risk of severe VS. Patients receiving higher mean vaginal doses should have greater compliance with dilator therapy to minimize risk of toxicity. Further validation with independent datasets is needed.« less

Reversible anaesthesia of free-ranging lions (Panthera leo) in Zimbabwe.

PubMed

Fahlman, A; Loveridge, A; Wenham, C; Foggin, C; Arnemo, J M; Nyman, G

2005-12-01

The combination of medetomidine-zolazepam-tiletamine with subsequent antagonism by atipamezole was evaluated for reversible anaesthesia of free-ranging lions (Panthera leo). Twenty-one anaesthetic events of 17 free-ranging lions (5 males and 12 females, body weight 105-211 kg) were studied in Zimbabwe. Medetomidine at 0.027-0.055 mg/kg (total dose 4-11 mg) and zolazepam-tiletamine at 0.38-1.32 mg/kg (total dose 50-275 mg) were administered i.m. by dart injection. The doses were gradually decreased to improve recovery. Respiratory and heart rates, rectal temperature and relative haemoglobin oxygen saturation (SpO2) were recorded every 15 min. Arterial blood samples were collected from 5 lions for analysis of blood gases and acid-base status. For anaesthetic reversal, atipamezole was administered i.m. at 2.5 or 5 times the medetomidine dose. Induction was smooth and all lions were anaesthetised with good muscle relaxation within 3.4-9.5 min after darting. The predictable working time was a minimum of 1 h and no additional drug doses were needed. Respiratory and heart rates and SpO2 were stable throughout anaesthesia, whereas rectal temperature changed significantly over time. Atipamezole at 2.5 times the medetomidine dose was sufficient for reversal and recoveries were smooth and calm in all lions independent of the atipamezole dose. First sign of recovery was observed 3-27 min after reversal. The animals were up walking 8-26 min after reversal when zolazepam-tiletamine doses < 1 mg/kg were used. In practice, a total dose of 6 mg medetomidine and 80 mg zolazepam-tiletamine and reversal with 15 mg atipamezole can be used for either sex of an adult or subadult lion. The drugs and doses used in this study provided a reliable, safe and reversible anaesthesia protocol for free-ranging lions.

Bupivacaine administered intrathecally versus rectally in the management of intractable rectal cancer pain in palliative care

PubMed Central

Zaporowska-Stachowiak, Iwona; Kowalski, Grzegorz; Łuczak, Jacek; Kosicka, Katarzyna; Kotlinska-Lemieszek, Aleksandra; Sopata, Maciej; Główka, Franciszek

2014-01-01

Background Unacceptable adverse effects, contraindications to and/or ineffectiveness of World Health Organization step III “pain ladder” drugs causes needless suffering among a population of cancer patients. Successful management of severe cancer pain may require invasive treatment. However, a patient’s refusal of an invasive procedure necessitates that clinicians consider alternative options. Objective Intrathecal bupivacaine delivery as a viable treatment of intractable pain is well documented. There are no data on rectal bupivacaine use in cancer patients or in the treatment of cancer tenesmoid pain. This study aims to demonstrate that bupivacaine administered rectally could be a step in between the current treatment options for intractable cancer pain (conventional/conservative analgesia or invasive procedures), and to evaluate the effect of the mode of administration (intrathecal versus rectal) on the bupivacaine plasma concentration. Cases We present two Caucasian, elderly inpatients admitted to hospice due to intractable rectal/tenesmoid pain. The first case is a female with vulvar cancer, and malignant infiltration of the rectum/vagina. Bupivacaine was used intrathecally (0.25–0.5%, 1–2 mL every 6 hours). The second case is a female with ovarian cancer and malignant rectal infiltration. Bupivacaine was adminstered rectally (0.05–0.1%, 100 mL every 4.5–11 hours). Methods Total bupivacaine plasma concentrations were determined using the high-performance liquid chromatography-ultraviolet method. Results Effective pain control was achieved with intrathecal bupivacaine (0.077–0.154 mg·kg−1) and bupivacaine in enema (1.820 mg·kg−1). Intrathecal bupivacaine (0.5%, 2 mL) caused a drop in blood pressure; other side effects were absent in both cases. Total plasma bupivacaine concentrations following intrathecal and rectal bupivacaine application did not exceed 317.2 ng·mL−1 and 235.7 ng·mL−1, respectively. Bupivacaine elimination was slower after rectal than after intrathecal administration (t½= 5.50 versus 2.02 hours, respectively). Limitations This study reports two cases only, and there could be inter-patient variation. Conclusion Bupivacaine in boluses administered intrathecally (0.25%, 2 mL) provided effective, safe analgesia in advanced cancer patients. Bupivacaine enema (100 mg·100 mL−1) was shown to be a valuable option for control of end-of-life tenesmoid cancer pain. PMID:25336967

Comparison of doses to the rectum derived from treatment planning system with in-vivo dose values in vaginal vault brachytherapy using cylinder applicators

PubMed Central

Obed, Rachel Ibhade; Akinlade, Bidemi Idayat; Ntekim, Atara

2015-01-01

Purpose In-vivo measurements to determine doses to organs-at-risk can be an essential part of brachytherapy quality assurance (QA). This study compares calculated doses to the rectum with measured dose values as a means of QA in vaginal vault brachytherapy using cylinder applicators. Material and methods At the Department of Radiotherapy, University College Hospital (UCH), Ibadan, Nigeria, intracavitary brachytherapy (ICBT) was delivered by a GyneSource high-dose-rate (HDR) unit with 60Co. Standard 2D treatment plans were created with HDR basic 2.6 software for prescription doses 5-7 Gy at points 5 mm away from the posterior surface of vaginal cylinder applicators (20, 25, and 30 mm diameters). The LiF:Mg, Ti thermoluminescent dosimeter rods (1 x 6 mm) were irradiated to a dose of 7 Gy on Theratron 60Co machine for calibration purpose prior to clinical use. Measurements in each of 34 insertions involving fourteen patients were performed with 5 TLD-100 rods placed along a re-usable rectal marker positioned in the rectum. The dosimeters were read in Harshaw 3500 TLD reader and compared with doses derived from the treatment planning system (TPS) at 1 cm away from the dose prescription points. Results The mean calculated and measured doses ranged from 2.1-3.8 Gy and 1.2-5.6 Gy with averages of 3.0 ± 0.5 Gy and 3.1 ± 1.1 Gy, respectively, for treatment lengths 2-8 cm along the cylinder-applicators. The mean values correspond to 48.9% and 50.8% of the prescribed doses, respectively. The deviations of the mean in-vivo doses from the TPS values ranged from –1.9 to 2.1 Gy with a p-value of 0.427. Conclusions This study was part of efforts to verify rectal dose obtained from the TPS during vaginal vault brachytherapy. There was no significant difference in the dose to the rectum from the two methods of measurements. PMID:26816506

Genetic Variation in the Transforming Growth Factor-β Signaling Pathway and Survival After Diagnosis With Colon and Rectal Cancer

PubMed Central

Slattery, Martha L.; Lundgreen, Abbie; Herrick, Jennifer S.; Wolff, Roger K.; Caan, Bette J.

2012-01-01

BACKGROUND The transforming growth factor-β (TGF-β) signaling pathway is involved in many aspects of tumori-genesis, including angiogenesis and metastasis. The authors evaluated this pathway in association with survival after a diagnosis of colon or rectal cancer. METHODS The study included 1553 patients with colon cancer and 754 patients with rectal cancer who had incident first primary disease and were followed for a minimum of 7 years after diagnosis. Genetic variations were evaluated in the genes TGF-β1 (2 single nucleotide polymorphisms [SNPs]), TGF-β receptor 1 (TGF-βR1) (3 SNPs), smooth muscle actin/mothers against decapentaplegic homolog 1 (Smad1) (5 SNPs), Smad2 (4 SNPs), Smad3 (37 SNPs), Smad4 (2 SNPs), Smad7 (11 SNPs), bone morphogenetic protein 1 (BMP1) (11 SNPs), BMP2 (5 SNPs), BMP4 (3 SNPs), bone morphogenetic protein receptor 1A (BMPR1A) (9 SNPs), BMPR1B (21 SNPs), BMPR2 (11 SNPs), growth differentiation factor 10 (GDF10) (7 SNPs), Runt-related transcription factor 1 (RUNX1) (40 SNPs), RUNX2 (19 SNPs), RUNX3 (9 SNPs), eukaryotic translation initiation factor 4E (eiF4E) (3 SNPs), eukaryotic translation initiation factor 4E-binding protein 3 (eiF4EBP2) (2 SNPs), eiF4EBP3 (2 SNPs), and mitogen-activated protein kinase 1 (MAPK1) (6 SNPs). RESULTS After adjusting for American Joint Committee on Cancer stage and tumor molecular phenotype, 12 genes and 18 SNPs were associated with survival in patients with colon cancer, and 7 genes and 15 tagSNPs were associated with survival after a diagnosis of rectal cancer. A summary score based on “at-risk” genotypes revealed a hazard rate ratio of 5.10 (95% confidence interval, 2.56-10.15) for the group with the greatest number of “at-risk” genotypes; for rectal cancer, the hazard rate ratio was 6.03 (95% confidence interval, 2.83-12.75). CONCLUSIONS The current findings suggest that the presence of several higher risk alleles in the TGF-β signaling pathway increase the likelihood of dying after a diagnosis of colon or rectal cancer. PMID:21365634

Quality of life in rectal cancer patients with permanent colostomy in Xi'an.

PubMed

Yang, Xiuxiu; Li, Qin; Zhao, Haihong; Li, Junhua; Duan, Jiaobo; Wang, Dandan; Fang, Ningning; Zhu, Ping; Fu, Jufang

2014-03-01

To observe the quality of life (QOL) in rectal cancer patients with permanent colostomy in different periods after operation. A 1-,3-,6-month prospective study of QOL in 51 rectal cancer patients with permanent colostomy and 50 without permanent colostomy was assessed using European Organization for Research and Treatment of Cancer (EORTC) QOL-30 and CR38 questionnaires. The variation of QOL in different periods was "v" type. In the 1st postoperative month, these patients had the lowest quality of life scores, accompanied significantly varied functions and severe symptoms. Almost of all indexes of these patients had improved consistently in the postoperative period. The scores of global QOL even better than pre-operative level at 6th months post-operation, but the social function, body image, chemotherapy side effects and financial difficulties had not restored to the baseline level. Patients without permanent colostomy had a better score in most of categories of QOL-30 and CR38. The 1st postoperative month was crucial for patients' recovery, in which we should pay great attention to these problems which relate to the recovery of rectal cancer patients with permanent colostomy.

Clinicopathologic Comparison of High-Dose-Rate Endorectal Brachytherapy versus Conventional Chemoradiotherapy in the Neoadjuvant Setting for Resectable Stages II and III Low Rectal Cancer

PubMed Central

Smith, Jessica A.; Wild, Aaron T.; Singhi, Aatur; Raman, Siva P.; Qiu, Haoming; Kumar, Rachit; Hacker-Prietz, Amy; Hruban, Ralph H.; Kamel, Ihab R.; Efron, Jonathan; Wick, Elizabeth C.; Azad, Nilofer S.; Diaz, Luis A.; Le, Yi; Armour, Elwood P.; Gearhart, Susan L.; Herman, Joseph M.

2012-01-01

Purpose. To assess for differences in clinical, radiologic, and pathologic outcomes between patients with stage II-III rectal adenocarcinoma treated neoadjuvantly with conventional external beam radiotherapy (3D conformal radiotherapy (3DRT) or intensity-modulated radiotherapy (IMRT)) versus high-dose-rate endorectal brachytherapy (EBT). Methods. Patients undergoing neoadjuvant EBT received 4 consecutive daily 6.5 Gy fractions without chemotherapy, while those undergoing 3DRT or IMRT received 28 daily 1.8 Gy fractions with concurrent 5-fluorouracil. Data was collected prospectively for 7 EBT patients and retrospectively for 25 historical 3DRT/IMRT controls. Results. Time to surgery was less for EBT compared to 3DRT and IMRT (P < 0.001). There was a trend towards higher rate of pathologic CR for EBT (P = 0.06). Rates of margin and lymph node positivity at resection were similar for all groups. Acute toxicity was less for EBT compared to 3DRT and IMRT (P = 0.025). Overall and progression-free survival were noninferior for EBT. On MRI, EBT achieved similar complete response rate and reduction in tumor volume as 3DRT and IMRT. Histopathologic comparison showed that EBT resulted in more localized treatment effects and fewer serosal adhesions. Conclusions. EBT offers several practical benefits over conventional radiotherapy techniques and appears to be at least as effective against low rectal cancer as measured by short-term outcomes. PMID:22830003

Ozone therapy as add-on treatment in fibromyalgia management by rectal insufflation: an open-label pilot study.

PubMed

Hidalgo-Tallón, Javier; Menéndez-Cepero, Silvia; Vilchez, Juan S; Rodríguez-López, Carmen M; Calandre, Elena P

2013-03-01

The objectives of this study were to evaluate the effectiveness and tolerability of ozone therapy by rectal insufflation as add-on therapy in fibromyalgia management. Patients with fibromyalgia received 24 sessions of ozone therapy during a 12-week period. At each session, the administered dose of ozone was 8 mg (200 mL of gas, at a concentration of 40 μg/mL). Ozone sessions were given 5 days a week during the first 2 weeks, twice a week from weeks 3-6, and weekly from weeks 7-12. Fibromyalgia Impact Questionnaire (FIQ) was the main outcome measure, and was administered at baseline and at weeks 4, 8, and 12. Secondary outcome measures, administered at baseline and at endpoint, were the Pittsburgh Sleep Quality Index, the Beck Depression Inventory, the State and Trait Anxiety Inventory, and the SF-12, the abbreviated form of the Short Form Health Survey. Emergent adverse reactions to treatment were recorded. FIQ total scores decreased significantly during the study period, with the decrease being observed in the first 4 weeks of the study. Significant improvement was also seen both in depression scores and in the Physical Summary Score of the SF-12. Transient meteorism after ozone therapy sessions was the most frequently reported side-effect. At the dose and number of sessions used in this study, ozone therapy by rectal insufflation seems to be beneficial for physical symptoms and depression of fibromyalgia.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, D; Chi, Z; Yang, H

Purpose: To investigate the performances of three commercial treatment planning systems (TPS) for intensity modulated radiotherapy (IMRT) optimization regarding cervical cancer. Methods: For twenty cervical cancer patients, three IMRT plans were retrospectively re-planned: one with Pinnacle TPS,one with Oncentra TPS and on with Eclipse TPS. The total prescribed dose was 50.4 Gy delivered for PTV and 58.8 Gy for PTVnd by simultaneous integrated boost technique. The treatments were delivered using the Varian 23EX accelerator. All optimization schemes generated clinically acceptable plans. They were evaluated based on target coverage, homogeneity (HI) and conformity (CI). The organs at risk (OARs) were analyzedmore » according to the percent volume under some doses and the maximum doses. The statistical method of the collected data of variance analysis was used to compare the difference among the quality of plans. Results: IMRT with Eclipse provided significant better HI, CI and all the parameters of PTV. However, the trend was not extension to the PTVnd, it was still significant better at mean dose, D50% and D98%, but plans with Oncentra showed significant better in the hight dosage volume, such as maximum dose and D2%. For the bladder wall, there were not notable difference among three groups, although Pinnacle and Oncentra systems provided a little lower dose sparing at V50Gy of bladder and rectal wall and V40Gy of bladder wall, respectively. V40Gy of rectal wall (p=0.037), small intestine (p=0.001 for V30Gy, p=0.010 for maximum dose) and V50Gy of right-femoral head (p=0.019) from Eclipse plans showed significant better than other groups. Conclusion: All SIB-IMRT plans were clinically acceptable which were generated by three commercial TPSs. The plans with Eclipse system showed advantages over the plans with Oncentra and Pinnacle system in the overwhelming majority of the dose coverage for targets and dose sparing of OARs in cervical cancer.« less

Clinical Toxicities and Dosimetric Parameters After Whole-Pelvis Versus Prostate-Only Intensity-Modulated Radiation Therapy for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deville, Curtiland, E-mail: deville@uphs.upenn.ed; Both, Stefan; Hwang, Wei-Ting

2010-11-01

Purpose: To assess whether whole-pelvis (WP) intensity-modulated radiation therapy (IMRT) is associated with increased toxicity compared with prostate-only (PO) IMRT. Methods and Materials: We retrospectively analyzed all patients with prostate cancer undergoing definitive IMRT to 79.2 Gy with concurrent androgen deprivation at our institution from November 2005 to May 2007 with a minimum follow-up of 12 months. Thirty patients received initial WP IMRT to 45 Gy in 1.8-Gy fractions, and thirty patients received PO IMRT. Study patients underwent computed tomography simulation and treatment planning by use of predefined dose constraints. Bladder and rectal dose-volume histograms, maximum genitourinary (GU) and gastrointestinalmore » (GI) Radiation Therapy Oncology Group toxicity grade, and late Grade 2 or greater toxicity-free survival curves were compared between the two groups by use of the Student t test, Fisher exact test, and Kaplan-Meier curve, respectively. Results: Bladder minimum dose, mean dose, median dose, volume receiving 5 Gy, volume receiving 20 Gy, volume receiving 40 Gy, and volume receiving 45 Gy and rectal minimum dose, median dose, and volume receiving 20 Gy were significantly increased in the WP group (all p values < 0.01). Maximum acute GI toxicity was limited to Grade 2 and was significantly increased in the WP group at 50% vs. 13% the PO group (p = 0.006). With a median follow-up of 24 months (range, 12-35 months), there was no difference in late GI toxicity (p = 0.884) or in acute or late GU toxicity. Conclusions: Despite dosimetric differences in the volume of bowel, bladder, and rectum irradiated in the low-dose and median-dose regions, WP IMRT results only in a clinically significant increase in acute GI toxicity, in comparison to PO IMRT, with no difference in GU or late GI toxicity.« less

Late Radiation and Cardiovascular Adverse Effects After Androgen Deprivation and High-Dose Radiation Therapy in Prostate Cancer: Results From the DART 01/05 Randomized Phase 3 Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zapatero, Almudena, E-mail: almudena.zapatero@salud.madrid.org; Guerrero, Araceli; Maldonado, Xavier

Purpose: To present data on the late toxicity endpoints of a randomized trial (DART 01/05) conducted to determine whether long-term androgen deprivation (LTAD) was superior to short-term AD (STAD) when combined with high-dose radiation therapy (HDRT) in patients with prostate cancer (PCa). Patients and Methods: Between November 2005 and December 2010, 355 eligible men with cT1c-T3aN0M0 PCa and intermediate-risk and high-risk factors (2005 National Comprehensive Cancer Network criteria) were randomized to 4 months of AD combined with HDRT (median dose, 78 Gy) (STAD) or the same treatment followed by 24 months of AD (LTAD). Treatment-related complications were assessed using European Organization for Research andmore » Treatment of Cancer–Radiation Therapy Oncology Group and Common Terminology Criteria for Adverse Events v3.0 scoring schemes. Multivariate analyses for late toxicity were done using the Fine-Gray method. Results: The 5-year incidence of grade ≥2 rectal and urinary toxicity was 11.1% and 8.2% for LTAD and 7.6% and 7.3% for STAD, respectively. Compared with STAD, LTAD was not significantly associated with a higher risk of late grade ≥2 rectal toxicity (hazard ratio [HR] 1.360, 95% confidence interval [CI] 0.660-2.790, P=.410) or urinary toxicity (HR 1.028, 95% CI 0.495-2.130, P=.940). The multivariate analysis showed that a baseline history of intestinal comorbidity (HR 3.510, 95% CI 1.560-7.930, P=.025) and the rectal volume receiving >60 Gy (Vr60) (HR 1.030, 95% CI 1.001-1.060, P=.043) were the only factors significantly correlated with the risk of late grade ≥2 rectal complications. A history of previous surgical prostate manipulations was significantly associated with a higher risk of grade ≥2 urinary complications (HR 2.427, 95% CI 1.051-5.600, P=.038). Long-term AD (HR 2.090; 95% CI 1.170-3.720, P=.012) and a history of myocardial infarction (HR 2.080; 95% CI 1.130-3.810, P=.018) were significantly correlated with a higher probability of cardiovascular events. Conclusion: Long-term AD did not significantly impact urinary or rectal radiation-induced toxicity, although it was associated with a higher risk of cardiovascular events. Longer follow-up is needed to measure the impact of AD on late morbidity and non-PCa mortality.« less

Rectal cancer delivery of radiotherapy in adequate time and with adequate dose is influenced by treatment center, treatment schedule, and gender and is prognostic parameter for local control: Results of study CAO/ARO/AIO-94

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fietkau, Rainer; Roedel, Claus; Hohenberger, Werner

2007-03-15

Purpose: The impact of the delivery of radiotherapy (RT) on treatment results in rectal cancer patients is unknown. Methods and Materials: The data from 788 patients with rectal cancer treated within the German CAO/AIO/ARO-94 phase III trial were analyzed concerning the impact of the delivery of RT (adequate RT: minimal radiation RT dose delivered, 4300 cGy for neoadjuvant RT or 4700 cGy for adjuvant RT; completion of RT in <44 days for neoadjuvant RT or <49 days for adjuvant RT) in different centers on the locoregional recurrence rate (LRR) and disease-free survival (DFS) at 5 years. The LRR, DFS, andmore » delivery of RT were analyzed as endpoints in multivariate analysis. Results: A significant difference was found between the centers and the delivery of RT. The overall delivery of RT was a prognostic factor for the LRR (no RT, 29.6% {+-} 7.8%; inadequate RT, 21.2% {+-} 5.6%; adequate RT, 6.8% {+-} 1.4%; p = 0.0001) and DFS (no RT, 55.1% {+-} 9.1%; inadequate RT, 57.4% {+-} 6.3%; adequate RT, 69.1% {+-} 2.3%; p = 0.02). Postoperatively, delivery of RT was a prognostic factor for LRR on multivariate analysis (together with pathologic stage) but not for DFS (independent parameters, pathologic stage and age). Preoperatively, on multivariate analysis, pathologic stage, but not delivery of RT, was an independent prognostic parameter for LRR and DFS (together with adequate chemotherapy). On multivariate analysis, the treatment center, treatment schedule (neoadjuvant vs. adjuvant RT), and gender were prognostic parameters for adequate RT. Conclusion: Delivery of RT should be regarded as a prognostic factor for LRR in rectal cancer and is influenced by the treatment center, treatment schedule, and patient gender.« less

Potential risk of alpha-glucosidase inhibitor administration in prostate cancer external radiotherapy by exceptional rectal gas production: a case report.

PubMed

Nishimura, Takuya; Yamazaki, Hideya; Iwama, Kazuki; Oota, Yoshitaka; Aibe, Norihiro; Nakamura, Satoaki; Yoshida, Ken; Okabe, Haruumi; Yamada, Kei

2014-05-05

Radiotherapy is a standard treatment for prostate cancer, and image-guided radiotherapy is increasingly being used to aid precision of dose delivery to targeted tissues. However, precision during radiotherapy cannot be maintained when unexpected intrafraction organ motion occurs. We report our experience of internal organ motion caused by persistent gas production in a patient taking an alpha-glucosidase inhibitor. A 68-year-old Japanese man with prostate cancer visited our institution for treatment with helical tomotherapy. He suffered from diabetes mellitus and took an alpha-glucosidase inhibitor. Routine treatment planning computed tomography showed a large volume of rectal gas; an enema was given to void the rectum. Subsequent treatment planning computed tomography again showed a large volume of gas. After exercise (walking) to remove the intestinal gas, a third scan was performed as a test scan without tight fixation, which showed a sufficiently empty rectum for planning. However, after only a few minutes, treatment planning computed tomography again showed extreme accumulation of gas. Therefore, we postponed treatment planning computed tomography and consulted his doctor to suspend the alpha-glucosidase inhibitor, which was the expected cause of his persistent gas. Four days after the alpha-glucosidase inhibitor regimen was suspended, we took a fourth treatment planning computed tomography and made a treatment plan without gas accumulation. Thereafter, the absence of rectal gas accumulation was confirmed using daily megavolt computed tomography before treatment, and the patient received 37 fractions of intensity-modified radiotherapy at 74 Gy without rectal gas complications. In this case study, the alpha-glucosidase inhibitor induced the accumulation of intestinal gas, which may have caused unexpected organ motion, untoward reactions, and insufficient doses to clinical targets. We suggest that patients who are taking an alpha-glucosidase inhibitor for diabetes should discontinue use of that particular medicine prior to beginning radiotherapy.

Prognostic Factors Affecting Locally Recurrent Rectal Cancer and Clinical Significance of Hemoglobin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rades, Dirk; Kuhn, Hildegard; Schultze, Juergen

2008-03-15

Purpose: To investigate potential prognostic factors, including hemoglobin levels before and during radiotherapy, for associations with survival and local control in patients with unirradiated locally recurrent rectal cancer. Patients and Methods: Ten potential prognostic factors were investigated in 94 patients receiving radiotherapy for recurrent rectal cancer: age ({<=}68 vs. {>=}69 years), gender, Eastern Cooperative Oncology Group performance status (0-1 vs. 2-3), American Joint Committee on Cancer (AJCC) stage ({<=}II vs. III vs. IV), grading (G1-2 vs. G3), surgery, administration of chemotherapy, radiation dose (equivalent dose in 2-Gy fractions: {<=}50 vs. >50 Gy), and hemoglobin levels before (<12 vs. {>=}12 g/dL)more » and during (majority of levels: <12 vs. {>=}12 g/dL) radiotherapy. Multivariate analyses were performed, including hemoglobin levels, either before or during radiotherapy (not both) because these are confounding variables. Results: Improved survival was associated with better performance status (p < 0.001), lower AJCC stage (p = 0.023), surgery (p = 0.011), chemotherapy (p = 0.003), and hemoglobin levels {>=}12 g/dL both before (p = 0.031) and during (p < 0.001) radiotherapy. On multivariate analyses, performance status, AJCC stage, and hemoglobin levels during radiotherapy maintained significance. Improved local control was associated with better performance status (p = 0.040), lower AJCC stage (p = 0.010), lower grading (p = 0.012), surgery (p < 0.001), chemotherapy (p < 0.001), and hemoglobin levels {>=}12 g/dL before (p < 0.001) and during (p < 0.001) radiotherapy. On multivariate analyses, chemotherapy, grading, and hemoglobin levels before and during radiotherapy remained significant. Subgroup analyses of the patients having surgery demonstrated the extent of resection to be significantly associated with local control (p = 0.011) but not with survival (p = 0.45). Conclusion: Predictors for outcome in patients who received radiotherapy for locally recurrent rectal cancer were performance status, AJCC stage, chemotherapy, surgery, extent of resection, histologic grading, and hemoglobin levels both before and during radiotherapy.« less

Lymph node retrieval in abdominoperineal surgical specimen is radiation time-dependent

PubMed Central

Sermier, Alain; Gervaz, Pascal; Egger, Jean F; Dao, My; Allal, Abdelkarim S; Bonet, Marta; Morel, Philippe

2006-01-01

Background A low yield of lymph nodes (LN) in abdominoperineal resection (APR) specimen has been associated with preoperative radiation therapy (XRT) in population-based studies, which may preclude adequate staging of anorectal carcinomas. We hypothesized that the number of LN retrieved in APR specimen was correlated with the dose and the timing of pelvic irradiation. Patients and methods We performed a retrospective study of 102 patients who underwent APR in a single institution between 1980 and 2004. Pathological reports were reviewed and the number of lymph nodes retrieved in APR specimens was correlated with: 1) Preoperative radiation; 2) Dose of pelvic irradiation; and 3) Time interval between the end of XRT and surgery. Results There were 61 men and 41 women, with a median age of 66 (range 25–89) years. There were 12 patients operated for squamous cell carcinoma of the anal canal (SCCA) and 90 for rectal cancer. 83% and 46% of patients with anal and rectal cancer respectively underwent radical/neoadjuvant radiotherapy. The mean ± SD number of LN in APR specimen was 9.2 ± 5.9. The mean number of LN in APR specimen was significantly lower in patients who underwent preoperative XRT (8 ± 5.5 vs. 10.5 ± 6.1, Mann-Whitney U test, p = 0.02). The mean number of LN was not significantly different after XRT in patients with SCCA than in patients with rectal cancer (6.2 ± 5.3 vs. 7.8 ± 5.3, p = 0.33). Finally, there was an inverse correlation between the yield of LN and the time elapsed between XRT and surgery (linear regression coefficient r = -0.32, p = 0.03). Conclusion Our data indicate that: 1) radiation therapy affects the yield of LN retrieval in APR specimen; 2) this impact is time-dependent. These findings have important implications with regard to anatomic-pathological staging of anal and rectal cancers and subsequent decision-making regarding adjuvant chemotherapy. PMID:16749931

Poster - 56: Preliminary comparison of FF- and FFF-VMAT for prostate plans with higher rectal dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Baochang; Darko, Johnson; Osei, Ernest

2016-08-15

Purpose: A recent retrospective study found 53 patients previously treated to 78Gy/39 using flattened filtered (FF) 6X-VMAT at GRRCC had rectal DVH more than one standard deviation higher than the average. This study was to investigate if using 6FFFor10FFF beams could reduce these DVHs without compromising target coverage. Methods: Twenty patients’ plans were re-planed with 2-arc 6X-VMAT, 6FFF-VMAT and 10FFF-VMAT using the Eclipse TPS following departmental protocol. All plans had the same optimization and normalization, and were evaluated against the acceptance criteria from the QUANTEC and Emami. Statistical differences in the mean dose to OARs (D{sub m}) and PTV homogeneitymore » index (HI) between energies were tested using the paired sample Wilcoxon signed rank statistical method (p<0.05). Beam delivery accuracy was checked on five patients using portal dosimetry (PD). Results: The PTV HI for the 10FFF shows no statistical difference from the 6X. All the OARs, except left femoral head with 6FFF, have significantly lower Dm using 6FFF and 10FFF .There is no difference in the maximum doses to rectum and bladder and are limited by the prescribed doses. Measurements show good agreements in the gamma evaluation (3%/3mm) for all energies. Conclusion: This preliminary study shows that doses to the OARs are reduced using 10FFF for the same target coverage. The plans using 6FFF result in lower doses to some OARs, and statistically different PTV HI. All plans showed very good agreement with measurements.« less

Analysis of results of radiation therapy for Stage II carcinoma of the cervix.

PubMed

Montana, G S; Fowler, W C; Varia, M A; Walton, L A; Mack, Y

1985-03-01

From April 1969 through December 1980, 251 patients with invasive, epidermoid carcinoma of the cervix received radical radiation therapy consisting of a combination of external beam and intracavitary therapy designed to deliver 7000 to 8000 rad to Point A and 6000 to 6500 rad to the pelvic lymph nodes. The disease-free survival at 2, 5, and 10 years for patients with Stage IIA disease was 90%, 76%, and 76%, respectively, whereas for patients with Stage IIB disease it was 77%, 62%, and 59%, respectively. The survival for the entire group at 2, 5, and 10 years was 80%, 65%, and 62%, respectively. Sixty-eight patients had a recurrence within the irradiated volume, for a locoregional recurrence rate of 27% (68/251). In 49 patients complications developed for an overall complication rate of 19.5% (49/251). An analysis of the complications and their degree of severity revealed a correlation with the dose of intracavitary plus external beam therapy given to Point A and to the rectum. The mean dose to Point A for patients with and without complications were 7877 rad (standard error [SE] +/- 95) and 7593 rad (SE +/- 67), respectively. The mean rectal dose for patients with and without intestinal complications were 6767 rad (SE +/- 157) and 6426 rad (SE +/- 78), respectively. The dose difference between patients with and without complications was statistically significant for Point A (P = to 0.0163) but not for the rectal dose (P = to 0.0887). There was no correlation between the bladder dose and urinary complications. Other treatment methods as well as patient and tumor parameters, are being currently analyzed to identify which factors, singly or in combination, may contribute to the development of treatment failures or complications.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yi, Sun K., E-mail: sun.yi@ucdmc.ucdavis.edu; Mak, Walter; Yang, Claus C.

Purpose: To generate a reproducible step-wise guideline for the delineation of the lumbosacral plexus (LSP) on axial computed tomography (CT) planning images and to provide a preliminary dosimetric analysis on 15 representative patients with rectal or anal cancers treated with an intensity-modulated radiotherapy (IMRT) technique. Methods and Materials: A standardized method for contouring the LSP on axial CT images was devised. The LSP was referenced to identifiable anatomic structures from the L4-5 interspace to the level of the sciatic nerve. It was then contoured retrospectively on 15 patients treated with IMRT for rectal or anal cancer. No dose limitations weremore » placed on this organ at risk during initial treatment planning. Dosimetric parameters were evaluated. The incidence of radiation-induced lumbosacral plexopathy (RILSP) was calculated. Results: Total prescribed dose to 95% of the planned target volume ranged from 50.4 to 59.4 Gy (median 54 Gy). The mean ({+-}standard deviation [SD]) LSP volume for the 15 patients was 100 {+-} 22 cm{sup 3} (range, 71-138 cm{sup 3}). The mean maximal dose to the LSP was 52.6 {+-} 3.9 Gy (range, 44.5-58.6 Gy). The mean irradiated volumes of the LSP were V40Gy = 58% {+-} 19%, V50Gy = 22% {+-} 23%, and V55Gy = 0.5% {+-} 0.9%. One patient (7%) was found to have developed RILSP at 13 months after treatment. Conclusions: The true incidence of RILSP in the literature is likely underreported and is not a toxicity commonly assessed by radiation oncologists. In our analysis the LSP commonly received doses approaching the prescribed target dose, and 1 patient developed RILSP. Identification of the LSP during IMRT planning may reduce RILSP. We have provided a reproducible method for delineation of the LSP on CT images and a preliminary dosimetric analysis for potential future dose constraints.« less

Development of a Set of Nomograms to Predict Acute Lower Gastrointestinal Toxicity for Prostate Cancer 3D-CRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valdagni, Riccardo; Rancati, Tiziana; Fiorino, Claudio

2008-07-15

Purpose: To predict acute Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) and Subjective Objective Signs Management and Analysis/Late Effect of Normal Tissue (SOMA/LENT) toxicities of the lower gastrointestinal (LGI) syndrome in patients with prostate cancer undergoing three-dimensional conformal radiotherapy using a tool (nomogram) that takes into account clinical and dosimetric variables that proved to be significant in the Italian Association for Radiation Oncology (AIRO) Group on Prostate Cancer (AIROPROS) 0102 trial. Methods and Materials: Acute rectal toxicity was scored in 1,132 patients by using both the RTOG/EORTC scoring system and a 10-item self-assessed questionnaire.more » Correlation between clinical variables/dose-volume histogram constraints and rectal toxicity was investigated by means of multivariate logistic analyses. Multivariate logistic analyses results were used to create nomograms predicting the symptoms of acute LGI syndrome. Results: Mean rectal dose was a strong predictor of Grade 2-3 RTOG/EORTC acute LGI toxicity (p 0.0004; odds ratio (OR) = 1.035), together with hemorrhoids (p = 0.02; OR 1.51), use of anticoagulants/antiaggregants (p = 0.02; OR = 0.63), and androgen deprivation (AD) (p = 0.04; OR = 0.65). Diabetes (p = 0.34; OR 1.28) and pelvic node irradiation (p = 0.11; OR = 1.56) were significant variables to adjust toxicity prediction. Bleeding was related to hemorrhoids (p = 0.02; OR = 173), AD (p = 0.17; OR = 0.67), and mean rectal dose (p 0.009; OR = 1.024). Stool frequency was related to seminal vesicle irradiation (p = 0.07; OR = 6.46), AD administered for more than 3 months (p = 0.002; OR = 0.32), and the percent volume of rectum receiving more than 60 Gy (V60Gy) V60 (p = 0.02; OR = 1.02). Severe fecal incontinence depended on seminal vesicle irradiation (p = 0.14; OR = 4.5) and V70 (p = 0.033; OR 1.029). Conclusions: To the best of our knowledge, this work presents the first set of nomograms available in the literature specific to symptoms of LGI syndrome and provides clinicians with a tailored probability of the specific outcome. Validation of the tool is in progress.« less

Evaluation of online/offline image guidance/adaptation approaches for prostate cancer radiation therapy.

PubMed

Qin, An; Sun, Ying; Liang, Jian; Yan, Di

2015-04-01

To evaluate online/offline image-guided/adaptive treatment techniques for prostate cancer radiation therapy with daily cone-beam CT (CBCT) imaging. Three treatment techniques were evaluated retrospectively using daily pre- and posttreatment CBCT images on 22 prostate cancer patients. Prostate, seminal vesicles (SV), rectal wall, and bladder were delineated on all CBCT images. For each patient, a pretreatment intensity modulated radiation therapy plan with clinical target volume (CTV) = prostate + SV and planning target volume (PTV) = CTV + 3 mm was created. The 3 treatment techniques were as follows: (1) Daily Correction: The pretreatment intensity modulated radiation therapy plan was delivered after online CBCT imaging, and position correction; (2) Online Planning: Daily online inverse plans with 3-mm CTV-to-PTV margin were created using online CBCT images, and delivered; and (3) Hybrid Adaption: Daily Correction plus an offline adaptive inverse planning performed after the first week of treatment. The adaptive plan was delivered for all remaining 15 fractions. Treatment dose for each technique was constructed using the daily posttreatment CBCT images via deformable image registration. Evaluation was performed using treatment dose distribution in target and critical organs. Treatment equivalent uniform dose (EUD) for the CTV was within [85.6%, 100.8%] of the pretreatment planned target EUD for Daily Correction; [98.7%, 103.0%] for Online Planning; and [99.2%, 103.4%] for Hybrid Adaptation. Eighteen percent of the 22 patients in Daily Correction had a target dose deficiency >5%. For rectal wall, the mean ± SD of the normalized EUD was 102.6% ± 2.7% for Daily Correction, 99.9% ± 2.5% for Online Planning, and 100.6% ± 2.1% for Hybrid Adaptation. The mean ± SD of the normalized bladder EUD was 108.7% ± 8.2% for Daily Correction, 92.7% ± 8.6% for Online Planning, and 89.4% ± 10.8% for Hybrid Adaptation. Both Online Planning and Hybrid Adaptation can achieve comparable target coverage and normal tissue sparing and are superior to the Daily Correction technique. The Daily Correction technique using a 3-mm target margin in the pretreatment plan is not appropriate to compensate for residual variations in CBCT image-guided prostate cancer radiation therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of Online/Offline Image Guidance/Adaptation Approaches for Prostate Cancer Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qin, An; Sun, Ying; Liang, Jian

Purpose: To evaluate online/offline image-guided/adaptive treatment techniques for prostate cancer radiation therapy with daily cone-beam CT (CBCT) imaging. Methods and Materials: Three treatment techniques were evaluated retrospectively using daily pre- and posttreatment CBCT images on 22 prostate cancer patients. Prostate, seminal vesicles (SV), rectal wall, and bladder were delineated on all CBCT images. For each patient, a pretreatment intensity modulated radiation therapy plan with clinical target volume (CTV) = prostate + SV and planning target volume (PTV) = CTV + 3 mm was created. The 3 treatment techniques were as follows: (1) Daily Correction: The pretreatment intensity modulated radiation therapy plan was delivered after online CBCT imaging, and positionmore » correction; (2) Online Planning: Daily online inverse plans with 3-mm CTV-to-PTV margin were created using online CBCT images, and delivered; and (3) Hybrid Adaption: Daily Correction plus an offline adaptive inverse planning performed after the first week of treatment. The adaptive plan was delivered for all remaining 15 fractions. Treatment dose for each technique was constructed using the daily posttreatment CBCT images via deformable image registration. Evaluation was performed using treatment dose distribution in target and critical organs. Results: Treatment equivalent uniform dose (EUD) for the CTV was within [85.6%, 100.8%] of the pretreatment planned target EUD for Daily Correction; [98.7%, 103.0%] for Online Planning; and [99.2%, 103.4%] for Hybrid Adaptation. Eighteen percent of the 22 patients in Daily Correction had a target dose deficiency >5%. For rectal wall, the mean ± SD of the normalized EUD was 102.6% ± 2.7% for Daily Correction, 99.9% ± 2.5% for Online Planning, and 100.6% ± 2.1% for Hybrid Adaptation. The mean ± SD of the normalized bladder EUD was 108.7% ± 8.2% for Daily Correction, 92.7% ± 8.6% for Online Planning, and 89.4% ± 10.8% for Hybrid Adaptation. Conclusions: Both Online Planning and Hybrid Adaptation can achieve comparable target coverage and normal tissue sparing and are superior to the Daily Correction technique. The Daily Correction technique using a 3-mm target margin in the pretreatment plan is not appropriate to compensate for residual variations in CBCT image-guided prostate cancer radiation therapy.« less

Integral radiation dose to normal structures with conformal external beam radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aoyama, Hidefumi; Westerly, David Clark; Mackie, Thomas Rockwell

2006-03-01

Background: This study was designed to evaluate the integral dose (ID) received by normal tissue from intensity-modulated radiotherapy (IMRT) for prostate cancer. Methods and Materials: Twenty-five radiation treatment plans including IMRT using a conventional linac with both 6 MV (6MV-IMRT) and 20 MV (20MV-IMRT), as well as three-dimensional conformal radiotherapy (3DCRT) using 6 MV (6MV-3DCRT) and 20 MV (20MV-3DCRT) and IMRT using tomotherapy (6MV) (Tomo-IMRT), were created for 5 patients with localized prostate cancer. The ID (mean dose x tissue volume) received by normal tissue (NTID) was calculated from dose-volume histograms. Results: The 6MV-IMRT resulted in 5.0% lower NTID thanmore » 6MV-3DCRT; 20 MV beam plans resulted in 7.7%-11.2% lower NTID than 6MV-3DCRT. Tomo-IMRT NTID was comparable to 6MV-IMRT. Compared with 6MV-3DCRT, 6MV-IMRT reduced IDs to the rectal wall and penile bulb by 6.1% and 2.7%, respectively. Tomo-IMRT further reduced these IDs by 11.9% and 16.5%, respectively. The 20 MV did not reduce IDs to those structures. Conclusions: The difference in NTID between 3DCRT and IMRT is small. The 20 MV plans somewhat reduced NTID compared with 6 MV plans. The advantage of tomotherapy over conventional IMRT and 3DCRT for localized prostate cancer was demonstrated in regard to dose sparing of rectal wall and penile bulb while slightly decreasing NTID as compared with 6MV-3DCRT.« less

Phase 1 Study of Preoperative Chemoradiation Therapy With Temozolomide and Capecitabine in Patients With Locally Advanced Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jeong, Jae Ho; Hong, Yong Sang; Park, Yangsoon

Purpose: Preoperative chemoradiation therapy (CRT) with capecitabine is a standard treatment strategy in patients with locally advanced rectal cancer (LARC). Temozolomide improves the survival of patients with glioblastoma with hypermethylated O{sup 6}-methylguanine DNA methyltransferase (MGMT); MGMT hypermethylation is one of the colorectal carcinogenesis pathways. We aimed to determine the dose-limiting toxicity (DLT) and recommended dose (RD) of temolozomide in combination with capecitabine-based preoperative CRT for LARC. Methods and Materials: Radiation therapy was delivered with 45 Gy/25 daily fractions with coned-down boost of 5.4 Gy/3 fractions. Concurrent chemotherapy comprised fixed and escalated doses of capecitabine and temozolomide, respectively. The MGMT hypermethylation was evaluatedmore » in pretreatment tumor samples. This trial is registered with (ClinicalTrials.gov) with the number (NCT01781403). Results: Twenty-two patients with LARC of cT3-4N0 or cT{sub any}N1-2 were accrued. Dose level 3 was chosen as the RD because DLT was noticeably absent in 10 patients treated up to dose level 3. An additional 12 patients were recruited in this group. Grade III adverse events were noted, and pathologic complete response (pCR) was observed in 7 patients (31.8%); MGMT hypermethylation was detected in 16. The pCR rate was 37.5% and 16.7% in the hypermethylated and unmethylated MGMT groups, respectively (P=.616). Conclusions: There was a tendency toward higher pCR rates in patients with hypermethylated MGMT. Future randomized studies are therefore warranted.« less

Quality indicators for colorectal cancer surgery and care according to patient-, tumor-, and hospital-related factors.

PubMed

Mathoulin-Pélissier, Simone; Bécouarn, Yves; Belleannée, Geneviève; Pinon, Elodie; Jaffré, Anne; Coureau, Gaëlle; Auby, Dominique; Renaud-Salis, Jean-Louis; Rullier, Eric

2012-07-19

Colorectal cancer (CRC) care has improved considerably, particularly since the implementation of a quality of care program centered on national evidence-based guidelines. Formal quality assessment is however still needed. The aim of this research was to identify factors associated with practice variation in CRC patient care. CRC patients identified from all cancer centers in South-West France were included. We investigated variations in practices (from diagnosis to surgery), and compliance with recommended guidelines for colon and rectal cancer. We identified factors associated with three colon cancer practice variations potentially linked to better survival: examination of ≥ 12 lymph nodes (LN), non-use and use of adjuvant chemotherapy for stage II and stage III patients, respectively. We included 1,206 patients, 825 (68%) with colon and 381 (32%) with rectal cancer, from 53 hospitals. Compliance was high for resection, pathology report, LN examination, and chemotherapy use for stage III patients. In colon cancer, 26% of stage II patients received adjuvant chemotherapy and 71% of stage III patients. 84% of stage US T3T4 rectal cancer patients received pre-operative radiotherapy. In colon cancer, factors associated with examination of ≥ 12 LNs were: lower ECOG score, advanced stage and larger hospital volume; factors negatively associated were: left sided tumor location and one hospital district. Use of chemotherapy in stage II patients was associated with younger age, advanced stage, emergency setting and care structure (private and location); whereas under-use in stage III patients was associated with advanced age, presence of comorbidities and private hospitals. Although some changes in practices may have occurred since this observational study, these findings represent the most recent report on practices in CRC in this region, and offer a useful methodological approach for assessing quality of care. Guideline compliance was high, although some organizational factors such as hospital size or location influence practice variation. These factors should be the focus of any future guideline implementation.

Pharmacokinetics and bioavailability of denaverine hydrochloride in healthy subjects following intravenous, oral and rectal single doses.

PubMed

Staab, Alexander; Schug, Barbara S; Larsimont, Véronique; Elze, Martina; Thümmler, Daniela; Mutschler, Ernst; Blume, Henning

2003-02-01

The neurotropic-musculotropic spasmolytic agent denaverine hydrochloride is used mainly in the treatment of smooth muscle spasms of the gastrointestinal and urogenital tract. Despite its commercial availability as a solution for intravenous or intramuscular administration (ampoule) and as a suppository formulation, no pharmacokinetic data in man was available to date. Therefore, the objectives of this clinical trial were to determine the basic pharmacokinetic parameters of denaverine after intravenous administration, to assess the feasibility of using the oral route of administration and to characterise the bioavailability of the suppository formulation. To achieve this, healthy subjects received 50 mg denaverine hydrochloride intravenously, orally and rectally in aqueous solutions and rectally as suppository in an open, randomised crossover design. Total body clearance, volume of distribution at steady-state and half-life of denaverine are 5.7 ml/min per kg, 7.1 l/kg and 33.8 h, respectively. The absolute bioavailability after oral administration of an aqueous solution is 37%. First-pass metabolism leading to the formation of N-monodemethyl denaverine was found to be one reason for the incomplete bioavailability after oral administration. Rectal administration of an aqueous solution of denaverine hydrochloride resulted in a decreased rate (median of C(max) ratios: 26%, difference in median t(max) values: 1.9 h) and extent (31%) of bioavailability compared to oral administration. Using the suppository formulation led to a further reduction in rate (median of C(max) ratios: 30%, difference in median t(max) values: 3 h) and extent (42%) of bioavailability compared to the rectal solution.

Disturbed Colonic Motility Contributes to Anorectal Symptoms and Dysfunction After Radiotherapy for Carcinoma of the Prostate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yeoh, Eric K., E-mail: eric.yeoh@health.sa.gov.a; Bartholomeusz, Dylan L.; Holloway, Richard H.

2010-11-01

Purpose: To evaluate the role of colonic motility in the pathogenesis of anorectal symptoms and dysfunction after radiotherapy (RT) for carcinoma of the prostate. Patients and Methods: Thirty-eight patients, median age 71 (range, 50-81) years with localized prostate carcinoma randomized to one of two radiation dose schedules underwent colonic transit scintigraphy and assessment of anorectal symptoms (questionnaire), anorectal function (manometry), and anal sphincteric morphology (endoanal ultrasound) before and at 1 month and 1 year after RT. Results: Whole and distal colonic transit increased 1 month after RT, with faster distal colonic transit only persisting at 1 year. Frequency and urgencymore » of defecation, fecal incontinence, and rectal bleeding increased 1 month after RT and persisted at 1 year. Basal anal pressures remained unchanged, but progressive reductions occurred in anal squeeze pressures and responses to increased intra-abdominal pressure. Rectal compliance decreased progressively in the patients, although no changes in anorectal sensory function ensued. Radiotherapy had no effect on the morphology of the internal and external anal sphincters. Distal colonic retention was weakly related to rectal compliance at 1 month, but both faster colonic transit and reduced rectal compliance were more frequent with increased fecal urgency. At 1 year, a weak inverse relationship existed between colonic half-clearance time and frequency of defecation, although both faster whole-colonic transit and reduced rectal compliance occurred more often with increased stool frequency. Conclusion: Colonic dysmotility contributes to anorectal dysfunction after RT for carcinoma of the prostate. This has implications for improving the management of anorectal radiation sequelae.« less

Prospective study of neoadjuvant chemoradiotherapy using intensity-modulated radiotherapy and 5 fluorouracil for locally advanced rectal cancer - toxicities and response assessment.

PubMed

Simson, David K; Mitra, Swarupa; Ahlawat, Parveen; Saxena, Upasna; Sharma, Manoj Kumar; Rawat, Sheh; Singh, Harpreet; Bansal, Babita; Sripathi, Lalitha Kameshwari; Tanwar, Aditi

2018-01-01

The past 2 decades witnessed the strengthening of evidence favoring the role of neoadjuvant chemoradiation (CHRT) in the treatment of locally advanced rectal cancer. The study aims to evaluate the response and acute toxicities to neoadjuvant CHRT using intensity-modulated radiotherapy (IMRT) in the treatment of rectal cancer. Predictive factors to achieve pathological complete response (pCR) were analyzed, as a secondary endpoint. All consecutive patients who underwent IMRT as part of neoadjuvant CHRT in the treatment of rectal cancer between August 2014 and December 2016 at a tertiary cancer care center were accrued for the study. The cohort underwent CHRT with IMRT technique at a dose of 50.4 Gy in 28 fractions concurrent with continuous infusion of 5 fluorouracil during the first and the last 4 days of CHRT. Surgery was performed 6 weeks later and the pathological response to CHRT was noted. Forty-three subjects were accrued for the study. Radiation dermatitis and diarrhea were the only observed grade ≥3 acute toxicities. Sphincter preservation rate (SPR) was 43.3%. pCR was observed in 32.6%. Univariate and multivariate logistic regression showed that carcinoembryonic antigen was the only independent predictive factor to achieve pCR. IMRT as part of neoadjuvant CHRT in the treatment of locally advanced rectal cancer is well tolerated and gives comparable results with respect to earlier studies in terms of pathological response and SPR. Further randomized controlled studies are needed to firmly state that IMRT is superior to 3-dimensional conformal radiotherapy.

A Phase II study of preoperative radiotherapy and concomitant weekly irinotecan in combination with protracted venous infusion 5-fluorouracil, for resectable locally advanced rectal cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Navarro, Matilde; Dotor, Emma; Rivera, Fernando

Purpose: The aim of this study was to evaluate the efficacy and tolerance of preoperative chemoradiotherapy (CRT) with irinotecan (CPT-11) and 5-fluorouracil (5-FU) in patients with resectable rectal cancer. Methods and Materials: Patients with resectable T3-T4 rectal cancer and Eastern Cooperative Oncology Group performance status <2 were included. CPT-11 (50 mg/m{sup 2} weekly) and 5-FU (225 mg/m{sup 2}/day continuous infusion, 5 days/week) were concurrently administered with radiation therapy (RT) (45 Gy, 1.8 Gy/day, 5 days/week), during 5 weeks. Results: A total of 74 patients were enrolled: mean age, 59 years (20-74 years; SD, 11.7). Planned treatment was delivered to mostmore » patients (median relative dose intensity for both drugs was 100%). Grade 3/4 lymphocytopenia occurred in 35 patients (47%), neutropenia in 5 (7%), and anemia in 2 (3%). Main Grade 3 nonhematologic toxicities were diarrhea (14%), asthenia (9%), rectal mucositis (8%), and abdominal pain (8%). Of the 73 resected specimens, 13.7% (95% confidence interval [CI], 6.8-23.7) had a pathologic complete response and 49.3% (95% CI, 37.4-61.3) were downstaged. Additionally, 66.7% (95% CI, 51.1-80.0) of patients with ultrasound staged N1/N2 disease had no pathologic evidence of nodal involvement after CRT. Conclusions: This preoperative CRT schedule has been shown to be effective and feasible in a large population of patients with resectable rectal cancer.« less

Complete Neoadjuvant Treatment for Rectal Cancer: The Brown University Oncology Group CONTRE Study.

PubMed

Perez, Kimberly; Safran, Howard; Sikov, William; Vrees, Matthew; Klipfel, Adam; Shah, Nishit; Schechter, Steven; Oldenburg, Nicklas; Pricolo, Victor; Rosati, Kayla; Dipetrillo, Thomas

2017-06-01

Following preoperative chemoradiation and surgery, many patients with stage II to III rectal cancer are unable to tolerate full-dose adjuvant chemotherapy. BrUOG R-224 was designed to assess the impact of COmplete Neoadjuvant Treatment for REctal cancer (CONTRE), primary chemotherapy followed by chemoradiation and surgery, on treatment delivery, toxicities, and pathologic response at surgery. Patients with clinical stage II to III (T3 to T4 and/or N1 to N2) rectal cancer received 8 cycles of modified FOLFOX6 followed by capecitabine 825 mg/m bid concurrent with 50.4 Gy intensity-modulated radiation therapy. Surgery was performed 6 to 10 weeks after chemoradiation. Thirty-nine patients were enrolled between August 2010 and June 2013. Median age was 61 years (30 to 79 y); 7 patients (18%) were clinical stage II and 32 (82%) stage III. Thirty-six patients (92%) received all 8 cycles of mFOLFOX6, of whom 35 completed subsequent chemoradiation; thus 89% of patients received CONTRE as planned. No unexpected toxicities were reported. All patients had resolution of bleeding and improvement of obstructive symptoms, with no complications requiring surgical intervention. Pathologic complete response (ypT0N0) was demonstrated in 13 patients (33%; 95% CI, 18.24%-47.76%). CONTRE seems to be a well-tolerated alternative to the current standard treatment sequence. Evaluating its impact on long-term outcomes would require a large randomized trial, but using pathologic response as an endpoint, it could serve as a platform for assessing the addition of novel agents to preoperative treatment in stage II to III rectal cancer.

EURECCA colorectal: multidisciplinary management: European consensus conference colon & rectum.

PubMed

van de Velde, Cornelis J H; Boelens, Petra G; Borras, Josep M; Coebergh, Jan-Willem; Cervantes, Andres; Blomqvist, Lennart; Beets-Tan, Regina G H; van den Broek, Colette B M; Brown, Gina; Van Cutsem, Eric; Espin, Eloy; Haustermans, Karin; Glimelius, Bengt; Iversen, Lene H; van Krieken, J Han; Marijnen, Corrie A M; Henning, Geoffrey; Gore-Booth, Jola; Meldolesi, Elisa; Mroczkowski, Pawel; Nagtegaal, Iris; Naredi, Peter; Ortiz, Hector; Påhlman, Lars; Quirke, Philip; Rödel, Claus; Roth, Arnaud; Rutten, Harm; Schmoll, Hans J; Smith, Jason J; Tanis, Pieter J; Taylor, Claire; Wibe, Arne; Wiggers, Theo; Gambacorta, Maria A; Aristei, Cynthia; Valentini, Vincenzo

2014-01-01

Care for patients with colon and rectal cancer has improved in the last 20years; however considerable variation still exists in cancer management and outcome between European countries. Large variation is also apparent between national guidelines and patterns of cancer care in Europe. Therefore, EURECCA, which is the acronym of European Registration of Cancer Care, is aiming at defining core treatment strategies and developing a European audit structure in order to improve the quality of care for all patients with colon and rectal cancer. In December 2012, the first multidisciplinary consensus conference about cancer of the colon and rectum was held. The expert panel consisted of representatives of European scientific organisations involved in cancer care of patients with colon and rectal cancer and representatives of national colorectal registries. The expert panel had delegates of the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy & Oncology (ESTRO), European Society of Pathology (ESP), European Society for Medical Oncology (ESMO), European Society of Radiology (ESR), European Society of Coloproctology (ESCP), European CanCer Organisation (ECCO), European Oncology Nursing Society (EONS) and the European Colorectal Cancer Patient Organisation (EuropaColon), as well as delegates from national registries or audits. Consensus was achieved using the Delphi method. For the Delphi process, multidisciplinary experts were invited to comment and vote three web-based online voting rounds and to lecture on the subjects during the meeting (13th-15th December 2012). The sentences in the consensus document were available during the meeting and a televoting round during the conference by all participants was performed. This manuscript covers all sentences of the consensus document with the result of the voting. The consensus document represents sections on diagnostics, pathology, surgery, medical oncology, radiotherapy, and follow-up where applicable for treatment of colon cancer, rectal cancer and metastatic colorectal disease separately. Moreover, evidence based algorithms for diagnostics and treatment were composed which were also submitted to the Delphi process. The total number of the voted sentences was 465. All chapters were voted on by at least 75% of the experts. Of the 465 sentences, 84% achieved large consensus, 6% achieved moderate consensus, and 7% resulted in minimum consensus. Only 3% was disagreed by more than 50% of the members. Multidisciplinary consensus on key diagnostic and treatment issues for colon and rectal cancer management using the Delphi method was successful. This consensus document embodies the expertise of professionals from all disciplines involved in the care for patients with colon and rectal cancer. Diagnostic and treatment algorithms were developed to implement the current evidence and to define core treatment guidance for multidisciplinary team management of colon and rectal cancer throughout Europe. Copyright © 2013 Elsevier Ltd. All rights reserved.

A Cross-Sectional Review of Reporting Variation in Postoperative Bowel Dysfunction After Rectal Cancer Surgery.

PubMed

Chapman, Stephen J; Bolton, William S; Corrigan, Neil; Young, Neville; Jayne, David G

2017-02-01

Postoperative bowel dysfunction affects quality of life after sphincter-preserving rectal cancer surgery, but the extent of the problem is not clearly defined because of inconsistent outcome measures used to characterize the condition. The purpose of this study was to assess variation in the reporting of postoperative bowel dysfunction and to make recommendations for standardization in future studies. If possible, a quantitative synthesis of bowel dysfunction symptoms was planned. MEDLINE and EMBASE databases, as well as the Cochrane Library, were queried systematically between 2004 and 2015. The studies selected reported at least 1 component of bowel dysfunction after resection of rectal cancer. The main outcome measures were reporting, measurement, and definition of postoperative bowel dysfunction. Of 5428 studies identified, 234 met inclusion criteria. Widely reported components of bowel dysfunction were incontinence to stool (227/234 (97.0%)), frequency (168/234 (71.8%)), and incontinence to flatus (158/234 (67.5%)). Urgency and stool clustering were reported less commonly, with rates of 106 (45.3%) of 234 and 61 (26.1%) of 234. Bowel dysfunction measured as a primary outcome was associated with better reporting (OR = 3.49 (95% CI, 1.99-6.23); p < 0.001). Less than half of the outcomes were assessed using a dedicated research tool (337/720 (46.8%)), and the remaining descriptive measures were infrequently defined (56/383 (14.6%)). Heterogeneity in the reporting, measurement, and definition of postoperative bowel dysfunction precluded pooling of results and limited interpretation. Considerable variation exists in the reporting, measurement, and definition of postoperative bowel dysfunction. These inconsistencies preclude reliable estimates of incidence and meta-analysis. A broadly accepted outcome measure may address this deficit in future studies.

Oxidative stress in rat kidneys due to 3,4-methylenedioxymetamphetamine (ecstasy) toxicity.

PubMed

Ninković, Milica; Selaković, Vesna; Dukić, Mirjana; Milosavljević, Petar; Vasiljević, Ivana; Jovanović, Marina; Malicević, Zivorad

2008-02-01

The mechanism of MDMA (3,4-methylenedioxymethamphetamine)-induced toxicity is believed to be, in part, due to enhanced oxidative stress. As MDMA is eliminated via the kidney, the aim of this study was to investigate whether MDMA created conditions of oxidative stress within rat kidney. Adult male Wistar rats were divided into three groups, control treatment (water), acute MDMA administration (single oral dose: 5, 10, 20 or 40 mg/kg body weight) and subacute MDMA administration (5, 10, or 20 mg/kg body weight per day during 14 days). Animals were sacrificed 8 h after the single oral MDMA administration in the acute MDMA administration group and after the last MDMA administration in the subacute MDMA administration group. Rectal temperature measurements, oxidative stress status parameters and histological examinations were performed. In all MDMA-administered rats, rectal temperature markedly increased peaking approximately 1 h after MDMA ingestion. Superoxide dismutase activity and thiobarbituric acid reactive substances increased after MDMA administration. Histological examinations of the kidney revealed dose-dependent disruption of tissue structure in subacute MDMA-administered rats. The latter was not observed in acute MDMA-administered rats.

Minimal dose interferon suppository treatment suppresses viral replication with platelet counts and serum albumin levels increased in chronically hepatitis C virus-infected patients: a phase 1b, placebo-controlled, randomized study.

PubMed

Haruna, Yoshimichi; Inoue, Atsuo

2014-02-01

Animal studies have shown that rectally administrated interferon (IFN) is transferred into the lymphatic system via the rectal mucous membrane, suggesting that an IFN suppository could serve as another drug delivery method. We developed an IFN suppository and administered it to patients with chronic hepatitis C to evaluate its efficacy and safety. Twenty-eight patients with chronic hepatitis C participated in the study. The low-dose IFN suppository containing 1,000 international units (IU) of lymphoblastoid IFNα was administered to 14 patients daily for 24 weeks. Others had a placebo dosing. In 13 of the 14 IFN suppository-treated patients, viral load decreased at week 4. The serum hepatitis C virus (HCV) RNA levels (Log IU/mL, mean±standard error) were 5.65±0.18 before the treatment and 5.17±0.27 at week 4 (P=0.01). The 2'-5' oligoadenylate synthetase activity increased, while the CD4/CD8 ratio decreased significantly. Interestingly, platelet counts and serum albumin levels were significantly increased during and after the treatment. No serious adverse events were observed. The low-dose IFN suppository treatment suppressed HCV replication, modifying host immunity, with increased platelet counts and serum albumin levels. The IFN suppository could be considered a new drug delivery method to preserve the quality of life of patients.

First clinical implementation of the Capri applicator

PubMed Central

2014-01-01

This study was to assess the Capri applicator for patients with endometrial cancer undergoing high‐radiation dose treatments following external‐beam radiation therapy. The Capri applicator is an inflatable vaginal cylinder with multiple channels. It is used to tailor the dose distribution to an asymmetric vaginal disease, and better spare organs at risk. Five patients with high‐risk endometrial cancer were selected for this study. The patients were treated with a high dose of radiation using the Capri applicator: daily fraction of 7 Gy was prescribed for a total dose of 21 Gy. The treatment plans included radiobiological parameters such as equivalent uniform dose (EUD), normal tissue complication probability (NTCP), and tumor control probability (TCP). Based on the dose‐volume histograms (DVH), we also calculated four quality factors: conformity index (CI), dose homogeneity index (DHI), dose nonuniformity index (DNR), and overdose index (OI). The TCP values range from 82.26% to 95.92%. Very low values of NTCP were observed for the bladder and rectum. The EUDs to organs at risk ranged from 4.65 Gy to 18.22 Gy for the bladder, and from 3.41 Gy from to 6.56 Gy for the rectum. The mean CI was 1.05(SD=0.0008). The mean DNR was 0.10(range0.0−0.295,SD=0.100). The mean OI was 0.019(SD=0.028). The DHIs were in the range of 1.0−0.754(mean0.886,SD=0.116). The use of a multichannel vaginal cylinder may not only help cover extensive vaginal disease, but also reduce the dose to the rectum. This dosimetric analysis shows that rectal doses could be reduced using a multichannel cylinder. However, the dose delivered to the bladder based on EUD calculation may be higher than that obtained with other methods. Each patient must be evaluated independently to determine if a multichannel treatment is appropriate. Clinical followup will show whether this rectal dose sparing translates into a real toxicity improvement. PACS number: 3.6.96.0 PMID:24423857

SU-E-T-616: Comparison of Plan Dose Accuracy for Anterior Vs. Lateral Fields in Proton Therapy of Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moteabbed, M; Trofimov, A; Testa, M

2014-06-01

Purpose: With the anticipated introduction of in vivo range verification methods, the use of anterior fields for proton therapy of prostate cancer may become an attractive treatment option, and improve upon the dose distributions achievable with conventional lateral-opposed fields. This study aimed to evaluate and compare the planned dose accuracy for lateral versus anterior oblique field arrangements. Methods: Four patients with low/intermediate risk prostate cancer, participating in a clinical trial at our institution, were selected for this study. All patients were treated using lateral-opposed fields (LAT). The clinical target volume (CTV) received a total dose of 79.2 Gy in 44more » fractions. Anterior oblique research plans (ANT) were created using the clinical planning system, and featured beams with ±35-degree gantry angle, 1.2 cm aperture margins, 3-mm range compensator smearing and no range uncertainty margins. Monte Carlo (MC) simulations were performed for both beam arrangements using TOPAS. Dose volume histograms were analyzed and compared for planned and MC dose distributions. Differences between MC and planned DVH parameters were computed as a percentage of the total prescribed dose. Results: For all patients, CTV dose was systematically lower (∼2–2.5%) for MC than the plan. This discrepancy was slightly larger (∼0.5%) for LAT compared to ANT plans for all cases. Although the dose differences for bladder and anterior rectal wall remained within 0.7% for all LAT cases, they were slightly larger for ANT plans, especially for case 3 due to larger patient size and MC-plan range difference. The EUD difference for femoral heads was within 0.6% for both LAT and ANT cases. Conclusion: The dose calculated by the treatment planning system using pencil beam algorithm agrees with MC to within 2.5% and is comparable for lateral and anterior scenarios. The dose agreement in the anterior rectal wall is range- and hence, patient-dependent for ANT treatments.« less

Dosimetric evaluation of planning target volume margin reduction for prostate cancer via image-guided intensity-modulated radiation therapy

NASA Astrophysics Data System (ADS)

Hwang, Taejin; Kang, Sei-Kwon; Cheong, Kwang-Ho; Park, Soah; Yoon, Jai-Woong; Han, Taejin; Kim, Haeyoung; Lee, Meyeon; Kim, Kyoung-Joo; Bae, Hoonsik; Suh, Tae-Suk

2015-07-01

The aim of this study was to quantitatively estimate the dosimetric benefits of the image-guided radiation therapy (IGRT) system for the prostate intensity-modulated radiation therapy (IMRT) delivery. The cases of eleven patients who underwent IMRT for prostate cancer without a prostatectomy at our institution between October 2012 and April 2014 were retrospectively analyzed. For every patient, clinical target volume (CTV) to planning target volume (PTV) margins were uniformly used: 3 mm, 5 mm, 7 mm, 10 mm, 12 mm, and 15 mm. For each margin size, the IMRT plans were independently optimized by one medical physicist using Pinnalce3 (ver. 8.0.d, Philips Medical System, Madison, WI) in order to maintain the plan quality. The maximum geometrical margin (MGM) for every CT image set, defined as the smallest margin encompassing the rectum at least at one slice, was between 13 mm and 26 mm. The percentage rectum overlapping PTV (%V ROV ), the rectal normal tissue complication probability (NTCP) and the mean rectal dose (%RD mean ) increased in proportion to the increase of PTV margin. However the bladder NTCP remained around zero to some extent regardless of the increase of PTV margin while the percentage bladder overlapping PTV (%V BOV ) and the mean bladder dose (%BD mean ) increased in proportion to the increase of PTV margin. Without relatively large rectum or small bladder, the increase observed for rectal NTCP, %RDmean and %BD mean per 1-mm PTV margin size were 1.84%, 2.44% and 2.90%, respectively. Unlike the behavior of the rectum or the bladder, the maximum dose on each femoral head had little effect on PTV margin. This quantitative study of the PTV margin reduction supported that IG-IMRT has enhanced the clinical effects over prostate cancer with the reduction of normal organ complications under the similar level of PTV control.

Efficacy of ABT-116, an antagonist of transient receptor potential vanilloid type 1, in providing analgesia for dogs with chemically induced synovitis.

PubMed

Cathcart, Curtis J; Johnston, Spencer A; Reynolds, Lisa R; Al-Nadaf, Sami; Budsberg, Steven C

2012-01-01

To investigate the ability of ABT-116 (a proprietary antagonist of transient receptor potential vanilloid type 1) administered at 2 doses to attenuate lameness in dogs with experimentally induced urate synovitis. 8 purpose-bred mixed-breed dogs. In a 4-way crossover study, dogs orally received each of low-dose ABT-116 treatment (LDA; 10 mg/kg), high-dose ABT-116 treatment (HDA; 30 mg/kg), firocoxib (5 mg/kg), and no treatment (nontreatment) once a day for 2 days, in a randomly assigned order. Synovitis was induced on the second day of each treatment period by intra-articular injection of either stifle joint with sodium urate, alternating between joints for each treatment period, beginning with the left stifle joint. Ground reaction forces, clinical lameness scores, and rectal temperature were assessed before the injection (baseline) and at various points afterward. Lameness scores at the 2-, 6-, and 12-hour assessment points were higher than baseline scores for HDA and nontreatment, whereas scores at the 2- and 6-hour points were higher than baseline scores for LDA. For firocoxib, there was no difference from baseline scores in lameness scores at any point. Compared with baseline values, peak vertical force and vertical impulse were lower at 2 and 6 hours for HDA and nontreatment and at 2 hours for LDA. No changes in these values were evident for firocoxib. The HDA or LDA resulted in higher rectal temperatures than did treatment with firocoxib or nothing, but those temperatures did not differ among treatments. HDA had no apparent effect on sodium urate-induced lameness; LDA did attenuate the lameness but not as completely as firocoxib treatment. High rectal temperature is an adverse effect of oral ABT-116 administration that may be of clinical concern.

Different rectal toxicity tolerance with and without simultaneous conventionally-fractionated pelvic lymph node treatment in patients receiving hypofractionated prostate radiotherapy.

PubMed

McDonald, Andrew M; Baker, Christopher B; Popple, Richard A; Shekar, Kiran; Yang, Eddy S; Jacob, Rojymon; Cardan, Rex; Kim, Robert Y; Fiveash, John B

2014-06-03

To investigate added morbidity associated with the addition of pelvic elective nodal irradiation (ENI) to hypofractionated radiotherapy to the prostate. Two-hundred twelve patients, treated with hypofractionated radiotherapy to the prostate between 2004 and 2011, met the inclusion criteria for the analysis. All patients received 70 Gy to the prostate delivered over 28 fractions and 103 (49%) received ENI consisting of 50.4 Gy to the pelvic lymphatics delivered simultaneously in 1.8 Gy fractions. The mean dose-volume histograms were compared between the two subgroups defined by use of ENI, and various dose-volume parameters were analyzed for effect on late lower gastrointestinal (GI) and genitourinary (GU) toxicity. Acute grade 2 lower GI toxicity occurred in 38 (37%) patients receiving ENI versus 19 (17%) in those who did not (p = 0.001). The Kaplan-Meier estimate of grade ≥ 2 lower GI toxicity at 3 years was 15.3% for patients receiving ENI versus 5.3% for those who did not (p = 0.026). Each rectal isodose volume was increased for patients receiving ENI up to 50 Gy (p ≤ 0.021 for each 5 Gy increment). Across all patients, the absolute V70 of the rectum was the only predictor of late GI toxicity. When subgroups, defined by the use of ENI, were analyzed separately, rectal V70 was only predictive of late GI toxicity for patients who received ENI. For patients receiving ENI, V70 > 3 cc was associated with an increased risk of late GI events. Elective nodal irradiation increases the rates of acute and late GI toxicity when delivered simultaneously with hypofractioanted prostate radiotherapy. The use of ENI appears to sensitize the rectum to hot spots, therefore we recommend added caution to minimize the volume of rectum receiving 100% of the prescription dose in these patients.

Different rectal toxicity tolerance with and without simultaneous conventionally-fractionated pelvic lymph node treatment in patients receiving hypofractionated prostate radiotherapy

PubMed Central

2014-01-01

Purpose To investigate added morbidity associated with the addition of pelvic elective nodal irradiation (ENI) to hypofractionated radiotherapy to the prostate. Methods and materials Two-hundred twelve patients, treated with hypofractionated radiotherapy to the prostate between 2004 and 2011, met the inclusion criteria for the analysis. All patients received 70 Gy to the prostate delivered over 28 fractions and 103 (49%) received ENI consisting of 50.4 Gy to the pelvic lymphatics delivered simultaneously in 1.8 Gy fractions. The mean dose-volume histograms were compared between the two subgroups defined by use of ENI, and various dose-volume parameters were analyzed for effect on late lower gastrointestinal (GI) and genitourinary (GU) toxicity. Results Acute grade 2 lower GI toxicity occurred in 38 (37%) patients receiving ENI versus 19 (17%) in those who did not (p = 0.001). The Kaplan-Meier estimate of grade ≥ 2 lower GI toxicity at 3 years was 15.3% for patients receiving ENI versus 5.3% for those who did not (p = 0.026). Each rectal isodose volume was increased for patients receiving ENI up to 50 Gy (p ≤ 0.021 for each 5 Gy increment). Across all patients, the absolute V70 of the rectum was the only predictor of late GI toxicity. When subgroups, defined by the use of ENI, were analyzed separately, rectal V70 was only predictive of late GI toxicity for patients who received ENI. For patients receiving ENI, V70 > 3 cc was associated with an increased risk of late GI events. Conclusions Elective nodal irradiation increases the rates of acute and late GI toxicity when delivered simultaneously with hypofractioanted prostate radiotherapy. The use of ENI appears to sensitize the rectum to hot spots, therefore we recommend added caution to minimize the volume of rectum receiving 100% of the prescription dose in these patients. PMID:24893842

Formulation and Evaluation of Irinotecan Suppository for Rectal Administration

PubMed Central

Feng, Haiyang; Zhu, Yuping; Li, Dechuan

2014-01-01

Irinotecan suppository was prepared using the moulding method with a homogeneous blend. A sensitive and specific fluorescence method was developed and validated for the determination of irinotecan in plasma using HPLC. The pharmacokinetics of intravenous administered and rectal administered in rabbits was investigated. Following a single intravenous dose of irinotecan (50 mg/kg), the plasma irinotecan concentration demonstrated a bi-exponential decay, with a rapid decline over 15 min. Cmax, t1/2, AUC0–30h and AUC0-∞ were 16.1 ± 2.7 g/ml, 7.6 ± 1.2 h, 71.3 ± 8.8 μg·h/ml and 82.3 ± 9.5 μg·h/ml, respectively. Following rectal administration of 100 mg/kg irinotecan, the plasma irinotecan concentration reached a peak of 5.3 ± 2.5 μg/ml at 4 h. The AUC0–30h and AUC0-∞ were 32.2 ± 6.2 μg·h/ml and 41.6 ± 7.2 μg·h/ml, respectively. It representing ∼50.6% of the absolute bioavailability. PMID:24596626

Formulation and evaluation of irinotecan suppository for rectal administration.

PubMed

Feng, Haiyang; Zhu, Yuping; Li, Dechuan

2014-01-01

Irinotecan suppository was prepared using the moulding method with a homogeneous blend. A sensitive and specific fluorescence method was developed and validated for the determination of irinotecan in plasma using HPLC. The pharmacokinetics of intravenous administered and rectal administered in rabbits was investigated. Following a single intravenous dose of irinotecan (50 mg/kg), the plasma irinotecan concentration demonstrated a bi-exponential decay, with a rapid decline over 15 min. Cmax, t1/2, AUC0-30h and AUC0-∞ were 16.1 ± 2.7 g/ml, 7.6 ± 1.2 h, 71.3 ± 8.8 μg·h/ml and 82.3 ± 9.5 μg·h/ml, respectively. Following rectal administration of 100 mg/kg irinotecan, the plasma irinotecan concentration reached a peak of 5.3 ± 2.5 μg/ml at 4 h. The AUC0-30h and AUC0-∞ were 32.2 ± 6.2 μg·h/ml and 41.6 ± 7.2 μg·h/ml, respectively. It representing ∼50.6% of the absolute bioavailability.

Systematic review of prognostic importance of extramural venous invasion in rectal cancer

PubMed Central

Chand, Manish; Siddiqui, Muhammed RS; Swift, Ian; Brown, Gina

2016-01-01

AIM: To systematically review the survival outcomes relating to extramural venous invasion in rectal cancer. METHODS: A systematic review was conducted using PRISMA guidelines. An electronic search was carried out using MEDLINE, EMBASE, CINAHL, Cochrane library databases, Google scholar and PubMed until October 2014. Search terms were used in combination to yield articles on extramural venous invasion in rectal cancer. Outcome measures included prevalence and 5-year survival rates. These were graphically displayed using Forest plots. Statistical analysis of the data was carried out. RESULTS: Fourteen studies reported the prevalence of extramural venous invasion (EMVI) positive patients. Prevalence ranged from 9%-61%. The pooled prevalence of EMVI positivity was 26% [Random effects: Event rate 0.26 (0.18, 0.36)]. Most studies showed that EMVI related to worse oncological outcomes. The pooled overall survival was 39.5% [Random effects: Event rate 0.395 (0.29, 0.51)]. CONCLUSION: Historically, there has been huge variation in the prevalence of EMVI through inconsistent reporting. However the presence of EMVI clearly leads to worse survival outcomes. As detection rates become more consistent, EMVI may be considered as part of risk-stratification in rectal cancer. Standardised histopathological definitions and the use of magnetic resonance imaging to identify EMVI will improve detection rates in the future. PMID:26819536

Safety, tolerability, and pharmacokinetics of sumatriptan suppositories following single and multiple doses in healthy volunteers.

PubMed

Kunka, R L; Hussey, E K; Shaw, S; Warner, P; Aubert, B; Richard, I; Fowler, P A; Pakes, G E

1997-06-01

A suppository formulation of the 5HT1 agonist sumatriptan could prove an important therapeutic option in migraine patients who dislike or poorly tolerate injectable therapy and where oral tablet administration is unsuitable because of severe migraine-related vomiting. Two independent double-blind, randomized clinical studies were conducted to evaluate the safety, tolerability and pharmacokinetics of sumatriptan suppositories following ascending single doses (four different dose levels) and multiple doses. In the four-period, crossover, single-dose study, 24 healthy male subjects were randomized to receive a suppository containing 12.5, 25, 50, or 100 mg on separate occasions 3-14 days apart. The suppositories were generally well tolerated; transient asthenia, drowsiness, and headache were the most frequently reported adverse events, and these were not dose-related. Peak plasma concentrations (Cmax) of sumatriptan were proportional to dose from 25 to 100 mg; area under the plasma concentration-time curve (AUC infinity) values were proportional to dose except at the highest doses, when they were greater than those predicted from lower doses. For all doses, the tmax of sumatriptan occurred within 2.5 h, and the t1/2 was approximately 2 h. In the two-period, placebo-controlled, crossover, repeat-dose study, 12 healthy adult male subjects were randomized to receive either a 50-mg sumatriptan suppository or placebo suppository, administered rectally twice a day, for 11 doses (5 1/2 days). Adverse events were no more frequent with sumatriptan than with placebo, and stool guaiac, rectal examinations, and physical examinations remained normal. No significant differences were noted between Day 1 and Day 6 values in the AUC, Cmax, time of peak serum concentration (tmax), elimination half-life (t 1/2), fraction of the dose excreted in the urine (fe), or renal clearance (Clr) of sumatriptan or its pharmacologically inactive indole acetic acid metabolite. Serum metabolite concentrations were two to three-fold higher than corresponding sumatriptan concentrations. No clinically significant accumulation of sumatriptan or its metabolite occurred. Overall, these studies show that sumatriptan administration via a suppository formulation is well tolerated, allows rapid absorption of sumatriptan, results in sumatriptan Cmax values that are proportional to dose from 25 to 100 mg, and is not associated with accumulation of sumatriptan or its metabolite.

[Rectal squamous cell carcinoma treatment: Retrospective experience in two French university hospitals, review and proposals].

PubMed

Schernberg, A; Servagi-Vernat, S; Loganadane, G; Touboul, E; Bosset, J-F; Huguet, F

2016-12-01

After publishing a retrospective series of 23 patients treated for a rectal squamous cell carcinoma with exclusive curative and conservative intent chemoradiation, we aim to propose a review of the literature about this rare tumour. We identified 11 retrospective studies, on 106 patients, treated between 2007 and 2016. Treatment of rectal squamous cell carcinoma should be similar to anal carcinoma, based on exclusive chemoradiation, displaying a 5-year overall survival rate over 80%, while it was 32% in surgical series. Baseline explorations should be similar as for anal carcinoma, with an interest in PET-CT at diagnosis and monitoring, after a delay over 6 weeks after chemoradiation. Intensity-modulated radiotherapy is legitimate, to a prophylactic dose between 36 and 45Gy, and over 54Gy to the tumour. Concomitant chemotherapy should combine an antimetabolite (5-fluorouracil or capecitabine) and mitomycin C, or cisplatin. This treatment seems well tolerated, associated with grade 2 or above toxicity below 30%. Follow-up should be established on anal squamous cell carcinoma schedule, with endoscopic ultrasonography and PET-CT. Rectal squamous cell carcinoma is a rare tumour; it management should be based on anal curative and conservative intent chemoradiation. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

A randomized trial of rectal indomethacin to prevent post-ERCP pancreatitis.

PubMed

Elmunzer, B Joseph; Scheiman, James M; Lehman, Glen A; Chak, Amitabh; Mosler, Patrick; Higgins, Peter D R; Hayward, Rodney A; Romagnuolo, Joseph; Elta, Grace H; Sherman, Stuart; Waljee, Akbar K; Repaka, Aparna; Atkinson, Matthew R; Cote, Gregory A; Kwon, Richard S; McHenry, Lee; Piraka, Cyrus R; Wamsteker, Erik J; Watkins, James L; Korsnes, Sheryl J; Schmidt, Suzette E; Turner, Sarah M; Nicholson, Sylvia; Fogel, Evan L

2012-04-12

Preliminary research suggests that rectally administered nonsteroidal antiinflammatory drugs may reduce the incidence of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). In this multicenter, randomized, placebo-controlled, double-blind clinical trial, we assigned patients at elevated risk for post-ERCP pancreatitis to receive a single dose of rectal indomethacin or placebo immediately after ERCP. Patients were determined to be at high risk on the basis of validated patient- and procedure-related risk factors. The primary outcome was post-ERCP pancreatitis, which was defined as new upper abdominal pain, an elevation in pancreatic enzymes to at least three times the upper limit of the normal range 24 hours after the procedure, and hospitalization for at least 2 nights. A total of 602 patients were enrolled and completed follow-up. The majority of patients (82%) had a clinical suspicion of sphincter of Oddi dysfunction. Post-ERCP pancreatitis developed in 27 of 295 patients (9.2%) in the indomethacin group and in 52 of 307 patients (16.9%) in the placebo group (P=0.005). Moderate-to-severe pancreatitis developed in 13 patients (4.4%) in the indomethacin group and in 27 patients (8.8%) in the placebo group (P=0.03). Among patients at high risk for post-ERCP pancreatitis, rectal indomethacin significantly reduced the incidence of the condition. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00820612.).

Comparing azithromycin and doxycycline for the treatment of rectal chlamydial infection: a retrospective cohort study

PubMed Central

Khosropour, Christine M.; Dombrowski, Julia C.; Barbee, Lindley A.; Manhart, Lisa E.; Golden, Matthew R.

2015-01-01

Background Centers for Disease Control and Prevention (CDC) guidelines recommend azithromycin or doxycycline for treatment of rectal chlamydial infection. Methods We created a retrospective cohort of male patients diagnosed with rectal chlamydia 1993-2012 at a sexually transmitted disease clinic in Seattle, Washington. Men were included in the analysis if they were treated with azithromycin (1g single dose) or doxycycline (100mg BID x 7 days) within 60 days of chlamydia diagnosis and returned for repeat testing 14-180 days post-treatment. We compared the risk of persistent/recurrent rectal chlamydial infection among recipients of the two drug regimens using four follow-up testing time intervals (14 to 30, 60, 90, and 180 days). Results Of 1,835 cases of rectal chlamydia diagnosed in the study period, 1,480 (81%) were treated with azithromycin or doxycycline without a second drug active against C. trachomatis. Of these, 407 (33%) of 1231 azithromycin-treated men and 95 (38%) of 249 doxycycline-treated men were re-tested 14-180 days after treatment (P=0.12); 88 (22%) and 8 (8%), respectively, had persistent/recurrent infection (P=0.002). Persistent/recurrent infection was higher among men treated with azithromycin compared to doxycycline at 14-30 days (4/53 (8%) vs. 0/20 (0%)), 14-60 days (23/136 (17%) vs. 0/36 (0%)), and 14-90 days (50/230 (22%) vs. 2/56 (4%)). In multivariate analysis, azithromycin-treated men had a significantly higher risk of persistent/recurrent infection in the 14-90 days (aRR=5.2, 95% CI=1.3-21.0) and 14-180 days (aRR=2.4, 95% CI=1.2-4.8) after treatment. Conclusions These data suggest that doxycycline may be more effective than azithromycin in the treatment of rectal chlamydial infections. PMID:24413484

Oxaliplatin-containing Preoperative Therapy in Locally Advanced Rectal Cancer: Local Response, Toxicity and Long-term Outcome.

PubMed

Dueland, S; Ree, A H; Grøholt, K K; Saelen, M G; Folkvord, S; Hole, K H; Seierstad, T; Larsen, S G; Giercksky, K E; Wiig, J N; Boye, K; Flatmark, K

2016-08-01

This non-randomised study was undertaken to examine oxaliplatin as possibly an intensifying component of sequential neoadjuvant therapy in locally advanced rectal cancer for improved local and metastatic outcome. Ninety-seven patients (57 T2-3 cases, 40 T4 cases) received two cycles of the Nordic FLOX regimen (oxaliplatin 85 mg/m(2) day 1 and bolus 5-fluorouracil 500 mg/m(2) and folinic acid 100 mg days 1 and 2) before long-course chemoradiotherapy with concomitant oxaliplatin and capecitabine, followed by pelvic surgery. Treatment toxicity, local tumour response and long-term outcome were recorded. Good histologic tumour regression was obtained in 72% of patients. Implementing protocol-specific dose adjustments, tolerance was acceptable and 95% of patients received the total prescribed radiation dose. Estimated 5 year progression-free and overall survival were 61% and 83%, respectively. T4 stage was associated with an inferior local response rate, which again was highly associated with impaired long-term outcome. In this cohort of rectal cancer patients dominated by T4 and advanced T3 cases given sequential oxaliplatin-containing preoperative therapy with acceptable toxicity, high tumour response rates and overall survival were obtained, consistent with both local and systemic effects. However, tumour response and long-term outcome remained inferior for a significant number of T4 cases, suggesting that the T4 entity is biologically heterogeneous with subgroups of patients eligible for further individualisation of therapy. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

The Impact of the Grid Size on TomoTherapy for Prostate Cancer

PubMed Central

Kawashima, Motohiro; Kawamura, Hidemasa; Onishi, Masahiro; Takakusagi, Yosuke; Okonogi, Noriyuki; Okazaki, Atsushi; Sekihara, Tetsuo; Ando, Yoshitaka; Nakano, Takashi

2017-01-01

Discretization errors due to the digitization of computed tomography images and the calculation grid are a significant issue in radiation therapy. Such errors have been quantitatively reported for a fixed multifield intensity-modulated radiation therapy using traditional linear accelerators. The aim of this study is to quantify the influence of the calculation grid size on the dose distribution in TomoTherapy. This study used ten treatment plans for prostate cancer. The final dose calculation was performed with “fine” (2.73 mm) and “normal” (5.46 mm) grid sizes. The dose distributions were compared from different points of view: the dose-volume histogram (DVH) parameters for planning target volume (PTV) and organ at risk (OAR), the various indices, and dose differences. The DVH parameters were used Dmax, D2%, D2cc, Dmean, D95%, D98%, and Dmin for PTV and Dmax, D2%, and D2cc for OARs. The various indices used were homogeneity index and equivalent uniform dose for plan evaluation. Almost all of DVH parameters for the “fine” calculations tended to be higher than those for the “normal” calculations. The largest difference of DVH parameters for PTV was Dmax and that for OARs was rectal D2cc. The mean difference of Dmax was 3.5%, and the rectal D2cc was increased up to 6% at the maximum and 2.9% on average. The mean difference of D95% for PTV was the smallest among the differences of the other DVH parameters. For each index, whether there was a significant difference between the two grid sizes was determined through a paired t-test. There were significant differences for most of the indices. The dose difference between the “fine” and “normal” calculations was evaluated. Some points around high-dose regions had differences exceeding 5% of the prescription dose. The influence of the calculation grid size in TomoTherapy is smaller than traditional linear accelerators. However, there was a significant difference. We recommend calculating the final dose using the “fine” grid size. PMID:28974860

SU-E-T-178: Clinical Feasibility of Multi-Leaf Collimator Based Dynamic Wedge

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jeong, C; Kwak, J; Ahn, S

2015-06-15

Purpose: A multi-leaf collimator (MLC) based dynamic wedge (MDW), which provide similar dose profile of physical wedge (PW) along x-jaw direction while significant monitor unit (MU) reduction, was developed and investigated for clinical use. Methods: A novel technique was used to create the wedge profile using MLC. A modification was applied to the DICOM-RT format file of the plan made with the PW to replace PW with MDW. The Varian enhanced dynamic wedge profile was used to produce MLC sequence, while the MU of the wedged field was recalculated using PW factor and fluence map. The profiles for all possiblemore » MDWs to substitute PWs were verified in 6/15 MV x-ray irradiations. New plans with MDWs were compared with the original plans in 5 rectal, 5 RT breast and 5 liver cases. Results: The wedge profile of the MDW fields were well matched with those of PWs inside the fields while less scatter than PW out of the fields. For plan comparisons of the clinical cases no significant dose discrepancy was observed between MDW plan and PW’s with the dose volume histograms. The maximum and mean doses in PTVs are agreed within 1.0%. The Result of OARs of MDW plans are slightly improved in the maximum doses (3.22 ∼ 150.4 cGy) and the mean doses (17.18 ∼ 85.52 cGy) on average for all cases while the prescribed doses are 45 Gy for rectal cases, 40 or 45 Gy for liver cases and 50 Gy for breast cases. The MUs of the fields which replace PW with MDW are reduced to 68% of those of PW. Conclusion: We developed a novel dynamic wedge technique with MLC that shows clinical advantage compared to PW.« less

Lower or Standard Dose Regorafenib in Treating Patients With Refractory Metastatic Colorectal Cancer

ClinicalTrials.gov

2018-03-22

Colon Adenocarcinoma; Rectal Adenocarcinoma; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IV Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7

Bovine acute-phase response following different doses of corticotrophin-releasing hormone (CRH) challenge

USDA-ARS?s Scientific Manuscript database

Fourteen weaned, halter-trained Angus steers (BW = 191 ± 2.1 kg) were fitted with indwelling jugular catheter and rectal temperature monitoring device on d -1 of the study. On d 0, steers were ranked by body weight and randomly assigned to receive 1 of 3 infusion treatments (i.v.): 1) 0.1 micrograms...

A Phase 2 Trial of Oral Solithromycin 1200 mg or 1000 mg as Single-Dose Oral Therapy for Uncomplicated Gonorrhea.

PubMed

Hook, Edward W; Golden, Matthew; Jamieson, Brian D; Dixon, Paula B; Harbison, Hanne S; Lowens, Sylvan; Fernandes, Prabhavathi

2015-10-01

Progressive resistance to antimicrobial agents has reduced options for gonorrhea therapy worldwide. Solithromycin (CEM-101) is a novel oral fluoroketolide antimicrobial with substantial in vitro activity against Neisseria gonorrhoeae. We conducted a phase 2 trial of 2 oral doses of solithromycin (1200 and 1000 mg) for treatment of uncomplicated gonorrhea. A total of 59 participants were enrolled and treated in this trial; 28 participants received 1200 mg of solithromycin and 31 received 1000 mg. Forty-six (78%) participants had positive cultures for N. gonorrhoeae at the time of enrollment: 24 of the 28 persons (86%) who received 1200 mg of oral solithromycin, and 22 of 31 (71%) who received 1000 mg. In addition, 8 participants had positive pharyngeal gonococcal cultures, and 4 had positive rectal cultures. All patients with positive cultures for N. gonorrhoeae were cured at all sites of infection. Chlamydia trachomatis and Mycoplasma genitalium coinfections were evaluated using nucleic acid amplification tests and were negative at 1 week of follow-up in 9 of 11 (82%) participants positive for C. trachomatis and 7 of 10 (70%) participants positive for M. genitalium. Mild dose-related gastrointestinal side effects (nausea, loose stools, vomiting) were common but did not limit therapy. Oral single-dose solithromycin, in doses of 1000 mg and 1200 mg, was 100% effective for treatment of culture-proven gonorrhea at genital, oral, and rectal sites of infection and is a promising new agent for gonorrhea treatment. NCT01591447. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Low abdominoperineal excision rates are associated with high-workload surgeons and lower tumour height. Is further specialization needed?

PubMed

Morris, E J A; Birch, R; West, N P; Finan, P J; Forman, D; Fairley, L; Quirke, P

2011-07-01

Wide variation, independent of disease extent and case mix, has been observed in the rate of use of abdominoperineal excision (APE) for rectal cancer. Previous analyses have, however, been confounded by failure to adjust for the location of the tumour within the rectum. This population-based study sought to examine whether variations in tumour height explained differences in APE use. Information was obtained on all individuals who underwent a major resection for a rectal tumour diagnosed between 1998 and 2005 across the Northern and Yorkshire regions of the UK. Median distances from the dentate line were calculated for all tumours excised by APE and compared with rates of use of APE between specialists and nonspecialist surgeons and across hospital trusts. The completeness of pathological reporting of height of tumour within the rectum was variable. A low rate of APE use was associated with a lower median distance of tumours from the dentate line. Specialist colorectal cancer surgeons performed fewer APEs on patients with a tumour located lower in the rectum than nonspecialist surgeons. Variations in the height of tumour did not explain the variation in APE use. Specialist high-volume surgeons undertook fewer APEs and those they performed were closer to the dentate line than low-volume nonspecialist surgeons. © 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.

MTN-017: A Rectal Phase 2 Extended Safety and Acceptability Study of Tenofovir Reduced-Glycerin 1% Gel

PubMed Central

Lama, Javier R.; Richardson, Barbra A.; Carballo-Diéguez, Alex; Kunjara Na Ayudhya, Ratiya Pamela; Liu, Karen; Patterson, Karen B.; Leu, Cheng-Shiun; Galaska, Beth; Jacobson, Cindy E.; Parikh, Urvi M.; Marzinke, Mark A.; Hendrix, Craig W.; Johnson, Sherri; Piper, Jeanna M.; Grossman, Cynthia; Ho, Ken S.; Lucas, Jonathan; Pickett, Jim; Bekker, Linda-Gail; Chariyalertsak, Suwat; Chitwarakorn, Anupong; Gonzales, Pedro; Holtz, Timothy H.; Liu, Albert Y.; Mayer, Kenneth H.; Zorrilla, Carmen; Schwartz, Jill L.; Rooney, James; McGowan, Ian

2017-01-01

Abstract Background. Human immunodeficiency virus (HIV) disproportionately affects men who have sex with men (MSM) and transgender women (TGW). Safe and acceptable topical HIV prevention methods that target the rectum are needed. Methods. MTN-017 was a phase 2, 3-period, randomized sequence, open-label, expanded safety and acceptability crossover study comparing rectally applied reduced-glycerin (RG) 1% tenofovir (TFV) and oral emtricitabine/TFV disoproxil fumarate (FTC/TDF). In each 8-week study period participants were randomized to RG-TFV rectal gel daily, or RG-TFV rectal gel before and after receptive anal intercourse (RAI; or at least twice weekly in the event of no RAI), or daily oral FTC/TDF. Results. MSM and TGW (n = 195) were enrolled from 8 sites in the United States, Thailand, Peru, and South Africa with mean age of 31.1 years (range 18-64). There were no differences in ≥grade 2 adverse event rates between daily gel (incidence rate ratio [IRR], 1.09; P = .59) or RAI gel (IRR, 0.90; P = .51) compared to FTC/TDF. High adherence (≥80% of prescribed doses assessed by unused product return and Short Message System reports) was less likely in the daily gel regimen (odds ratio [OR], 0.35; P < .001), and participants reported less likelihood of future daily gel use for HIV protection compared to FTC/TDF (OR, 0.38; P < .001). Conclusions. Rectal application of RG TFV gel was safe in MSM and TGW. Adherence and product use likelihood were similar for the intermittent gel and daily oral FTC/TDF regimens, but lower for the daily gel regimen. Clinical Trials Registration: NCT01687218. PMID:27986684

Barium proctography vs magnetic resonance proctography for pelvic floor disorders: a comparative study.

PubMed

Pilkington, S A; Nugent, K P; Brenner, J; Harris, S; Clarke, A; Lamparelli, M; Thomas, C; Tarver, D

2012-10-01

Accurate and reliable imaging of pelvic floor dynamics is important for tailoring treatment in pelvic floor disorders; however, two imaging modalities are available. Barium proctography (BaP) is widely used, but involves a significant radiation dose. Magnetic resonance (MR) proctography allows visualization of all pelvic midline structures but patients are supine. This project investigates whether there are measurable differences between BaP and MR proctography. Patient preference for the tests was also investigated. Consecutive patients referred for BaP were invited to participate (National Research Ethics Service approved). Participants underwent BaP in Poole and MR proctography in Dorchester. Proctograms were reported by a consultant radiologist with pelvic floor subspecialization. A total of 71 patients were recruited. Both tests were carried out on 42 patients. Complete rectal emptying was observed in 29% (12/42) on BaP and in 2% (1/42) on MR proctography. Anismus was reported in 29% (12/42) on BaP and 43% (18/42) on MR proctography. MR proctography missed 31% (11/35) of rectal intussusception detected on BaP. In 10 of these cases no rectal evacuation was achieved during MR proctography. The measure of agreement between grade of rectal intussusception was fair (κ=0.260) although MR proctography tended to underestimate the grade. Rectoceles were extremely common but clinically relevant differences in size were evident. Patients reported that they found MR proctography less embarrassing but harder to empty their bowel. The results demonstrate that MR proctography under-reports pelvic floor abnormalities especially where there has been poor rectal evacuation. © 2012 The Authors. Colorectal Disease © 2012 The Association of Coloproctology of Great Britain and Ireland.

Prospective study of neoadjuvant chemoradiotherapy using intensity-modulated radiotherapy and 5 fluorouracil for locally advanced rectal cancer – toxicities and response assessment

PubMed Central

Simson, David K; Mitra, Swarupa; Ahlawat, Parveen; Saxena, Upasna; Sharma, Manoj Kumar; Rawat, Sheh; Singh, Harpreet; Bansal, Babita; Sripathi, Lalitha Kameshwari; Tanwar, Aditi

2018-01-01

Aims and objectives The past 2 decades witnessed the strengthening of evidence favoring the role of neoadjuvant chemoradiation (CHRT) in the treatment of locally advanced rectal cancer. The study aims to evaluate the response and acute toxicities to neoadjuvant CHRT using intensity-modulated radiotherapy (IMRT) in the treatment of rectal cancer. Predictive factors to achieve pathological complete response (pCR) were analyzed, as a secondary endpoint. Materials and methods All consecutive patients who underwent IMRT as part of neoadjuvant CHRT in the treatment of rectal cancer between August 2014 and December 2016 at a tertiary cancer care center were accrued for the study. The cohort underwent CHRT with IMRT technique at a dose of 50.4 Gy in 28 fractions concurrent with continuous infusion of 5 fluorouracil during the first and the last 4 days of CHRT. Surgery was performed 6 weeks later and the pathological response to CHRT was noted. Results Forty-three subjects were accrued for the study. Radiation dermatitis and diarrhea were the only observed grade ≥3 acute toxicities. Sphincter preservation rate (SPR) was 43.3%. pCR was observed in 32.6%. Univariate and multivariate logistic regression showed that carcinoembryonic antigen was the only independent predictive factor to achieve pCR. Conclusion IMRT as part of neoadjuvant CHRT in the treatment of locally advanced rectal cancer is well tolerated and gives comparable results with respect to earlier studies in terms of pathological response and SPR. Further randomized controlled studies are needed to firmly state that IMRT is superior to 3-dimensional conformal radiotherapy. PMID:29593430

Preoperative Chemoradiotherapy for Rectal Cancer in Patients Aged 75 Years and Older: Acute Toxicity, Compliance with Treatment, and Early Results.

PubMed

Guimas, Valentine; Boustani, Jihane; Schipman, Benjamin; Lescut, Nicolas; Puyraveau, Marc; Bosset, Jean François; Servagi-Vernat, Stéphanie

2016-06-01

Treatment of locally advanced rectal cancer (T3-T4 or N+) is based on short-course radiotherapy (RT) or chemoradiotherapy (CRT) followed by surgery. It is estimated that 30-40 % of rectal cancer occurs in patients aged 75 years or more. Data on adherence to neoadjuvant CRT and its safety remain poor owing to the under-representation of older patients in randomized clinical trials and the discordance in the results from retrospective studies. The aim of this study was to assess adherence with preoperative CRT and tolerability in older patients with a stage II/III unresectable rectal cancer. Patients aged 75 years or more with stage II/III rectal cancer treated with preoperative CRT at the University Hospital of Besancon from 1993 to 2011 were included. Feasibility, toxicities, overall survival, and local recurrence rates were studied. Fifty-six patients with a Charlson score from 2 to 6 were included. The mean age was 78 years. The compliance rates for RT and chemotherapy were 91 and 41.1 %, respectively. Two patients stopped CRT; one for hemostatic surgery, and one for severe sepsis. For CRT, the rate of grade ≥3 toxicity was 14.29 %, mainly the digestive type. Fifty-two patients underwent tumor resection, including 76.79 % total mesorectal excision resection with 84.6 % complete resection, and a rate of postoperative complications of 39.6 %. At 2 years, the overall survival and local recurrences rates were 87.3 and 7.8 %, respectively. In older patients, selected preoperative CRT, with an adapted chemotherapy dose, is well tolerated. The main toxicity was gastrointestinal. Adherence to RT is comparable to that of younger patients.

Continuous Effect of Radial Resection Margin on Recurrence and Survival in Rectal Cancer Patients Who Receive Preoperative Chemoradiation and Curative Surgery: A Multicenter Retrospective Analysis.

PubMed

Sung, SooYoon; Kim, Sung Hwan; Lee, Joo Hwan; Nam, Taek Keun; Jeong, Songmi; Jang, Hong Seok; Song, Jin Ho; Lee, Jeong Won; Bae, Jung Min; Lee, Jong Hoon

2017-07-01

To elucidate the proper length and prognostic value of resection margins in rectal cancer patients who received preoperative chemoradiotherapy (CRT) followed by curative total mesorectal excision (TME). A total of 1476 rectal cancer patients staging cT3-4N0-2M0 were analyzed. All patients received radiation dose of 50.4 Gy in 28 fractions with concurrent 5-fluorouracil or capecitabine. Total mesorectal excision was performed 4 to 8 weeks after radiation therapy. The recurrence-free survival (RFS) at 5 years showed a significant difference between 3 groups: patients with circumferential resection margin (CRM) ≤1 mm, CRM 1.1 to 5 mm, and CRM >5 mm (46.2% vs 68.6% vs 77.5%, P<.001). Patients with CRM ≤1 mm showed a significantly higher cumulative incidence of locoregional recurrence (P<.001) and distant metastasis (P<.001) at 5 years compared with the other 2 groups. Patients with CRM 1.1 to 5 mm showed a significantly higher cumulative incidence of distant metastasis (P<.001), but not locoregional recurrence (P=.192), compared with those with CRM >5 mm. Distal resection margin (≤5 vs >5 mm) did not show any significant difference in cumulative incidence of locoregional recurrence (P=.310) and distant metastasis (P=.926). Rectal cancer patients with CRM ≤1 mm are a high-risk group, with the lowest RFS. Patients with CRM 1.1 to 5 mm may be at intermediate risk, with moderately increased distant recurrence. Distal resection margin was not significantly associated with RFS in rectal cancer after neoadjuvant CRT and total mesorectal excision. Copyright © 2017 Elsevier Inc. All rights reserved.

Severe myositis of the hip flexors after pre-operative chemoradiation therapy for locally advanced rectal cancer: case report.

PubMed

Florczynski, Matthew M; Sanatani, Michael S; Mai, Lauren; Fisher, Barbara; Moulin, Dwight E; Cao, Jeffrey; Louie, Alexander V; Pope, Janet E; Leung, Eric

2016-03-22

The use of neoadjuvant radiation therapy and chemotherapy in the treatment of locally advanced rectal adenocarcinoma has been shown to reduce disease recurrence when combined with surgery and adjuvant chemotherapy. We report a case of a patient who developed a debilitating bilateral myopathy of the hip flexors after successful treatment for rectal cancer. To the best of our knowledge, this is the first such complication from radiation therapy reported in a patient with colorectal cancer. The disproportionate severity of our patient's myopathy relative to the dose of radiation used also makes this case unique among reports of neuromuscular complications from radiation therapy. The patient is a 65-year-old male with node negative, high-grade adenocarcinoma of the rectum penetrating through the distal rectal wall. He underwent neoadjuvant concurrent pelvic radiation therapy and capecitabine-based chemotherapy, followed by abdominoperineal resection and post-operative FOLFOX chemotherapy. Five months post-completion of pelvic radiotherapy and 2 months after the completion of adjuvant chemotherapy, he presented with bilateral weakness of the iliopsoas muscles and severe pain radiating to the groin. The patient improved with 40 mg/d of prednisone, which was gradually tapered to 2 mg/d over 6 months, with substantial recovery of muscle strength and elimination of pain. The timing, presentation and response of our patient's symptoms to corticosteroids are most consistent with a radiation recall reaction. Radiation recall is a phenomenon whereby previously irradiated tissue becomes vulnerable to toxicity by subsequent systemic therapy and is rarely associated with myopathies. Radiation recall should be considered a potential complication of neoadjuvant radiation therapy for rectal cancer, and for ongoing research into the optimization of treatment for these patients. Severe myopathies caused by radiation recall may be fully reversible with corticosteroid treatment.

Comparison of microbial populations in the small intestine, large intestine and feces of healthy horses using terminal restriction fragment length polymorphism

PubMed Central

2013-01-01

Background The composition of the microbiota of the equine intestinal tract is complex. Determining whether the microbial composition of fecal samples is representative of proximal compartments of the digestive tract could greatly simplify future studies. The objectives of this study were to compare the microbial populations of the duodenum, ileum, cecum, colon and rectum (feces) within and between healthy horses, and to determine whether rectal (fecal) samples are representative of proximal segments of the gastrointestinal tract. Intestinal samples were collected from ten euthanized horses. 16S rRNA gene PCR-based TRFLP was used to investigate microbiota richness in various segments of the gastrointestinal tract, and dice similarity indices were calculated to compare the samples. Results Within horses large variations of microbial populations along the gastrointestinal tract were seen. The microbiota in rectal samples was only partially representative of other intestinal compartments. The highest similarity was obtained when feces were compared to the cecum. Large compartmental variations were also seen when microbial populations were compared between six horses with similar dietary and housing management. Conclusion Rectal samples were not entirely representative of intestinal compartments in the small or large intestine. This should be taken into account when designing studies using fecal sampling to assess other intestinal compartments. Similarity between horses with similar dietary and husbandry management was also limited, suggesting that parts of the intestinal microbiota were unique to each animal in this study. PMID:23497580

Diet and Colorectal Cancer: Analysis of a Candidate Pathway Using SNPS, Haplotypes, and Multi-Gene Assessment

PubMed Central

Slattery, Martha L.; Lundgreen, Abbie; Herrick, Jennifer S.; Caan, Bette J.; Potter, John D.; Wolff, Roger K.

2012-01-01

There is considerable biologic plausibility to the hypothesis that genetic variability in pathways involved in insulin signaling and energy homeostasis may modulate dietary risk associated with colorectal cancer. We utilized data from 2 population-based case-control studies of colon (n = 1,574 cases, 1,970 controls) and rectal (n = 791 cases, 999 controls) cancer to evaluate genetic variation in candidate SNPs identified from 9 genes in a candidate pathway: PDK1, RP6KA1, RPS6KA2, RPS6KB1, RPS6KB2, PTEN, FRAP1 (mTOR), TSC1, TSC2, Akt1, PIK3CA, and PRKAG2 with dietary intake of total energy, carbohydrates, fat, and fiber. We employed SNP, haplotype, and multiple-gene analysis to evaluate associations. PDK1 interacted with dietary fat for both colon and rectal cancer and with dietary carbohydrates for colon cancer. Statistically significant interaction with dietary carbohydrates and rectal cancer was detected by haplotype analysis of PDK1. Evaluation of dietary interactions with multiple genes in this candidate pathway showed several interactions with pairs of genes: Akt1 and PDK1, PDK1 and PTEN, PDK1 and TSC1, and PRKAG2 and PTEN. Analyses show that genetic variation influences risk of colorectal cancer associated with diet and illustrate the importance of evaluating dietary interactions beyond the level of single SNPs or haplotypes when a biologically relevant candidate pathway is examined. PMID:21999454

Pharmacokinetic comparison of acetaminophen elixir versus suppositories in vaccinated infants (aged 3 to 36 months): a single-dose, open-label, randomized, parallel-group design.

PubMed

Walson, Philip D; Halvorsen, Mark; Edge, James; Casavant, Marcel J; Kelley, Michael T

2013-02-01

Because of practical problems and ethical concerns, few studies of the pharmacokinetics (PK) of acetaminophen (ACET) in infants have been published. The goal of this study was to compare the PK of an ACET rectal suppository with a commercially available ACET elixir to complete a regulatory obligation to market the suppository. This study was not submitted previously because of numerous obstacles related to both the investigators and the commercial entities associated with the tested product. Thirty infants (age 3-36 months) prescribed ACET for either fever, pain, or postimmunization prophylaxis of fever and discomfort were randomized to receive a single 10- to 15-mg/kg ACET dose either as the rectal suppository or oral elixir. Blood was collected at selected times for up to 8 hours after administration. ACET concentrations were measured by using a validated HPLC method, and PK behavior and bioavailability were compared for the 2 preparations. All 30 infants enrolled were prescribed ACET for postimmunization prophylaxis. PK samples were available in 27 of the 30 enrolled infants. Subject enrollment (completed in January 1995) was rapid (8.3 months) and drawn entirely from a vaccinated infant clinic population. There were no statistically significant differences between the subjects (elixir, n = 12; suppository, n = 15) in either mean (SD) age (10.0 [6.3] vs 12.4 [8.1] months), weight (8.6 [2.3] vs 9.4 [2.4] kg), sex (7 of 12 males vs 7 of 15 males), or racial distribution (5 white, 5 black, and 2 biracial vs 4 white and 11 black) between the 2 dosing groups (oral vs rectal, respectively). The oral and rectal preparations produced similar, rapid peak concentrations (T(max), 1.16 vs 1.17 hours; P = 0.98) and elimination t(½) (1.84 vs 2.10 hours; P = 0.14), respectively. No statistically significant differences were found between either C(max) (7.65 vs 5.68 μg/mL) or total drug exposure (AUC(0-∞), 23.36 vs 20.45 μg-h/mL) for the oral versus rectal preparations. There were no serious treatment-related effects noted. Delays in submitting this work for publication were the result of a number of investigator and sponsor issues despite the study's positive outcome. No statistically significant differences were found between the rates or extent of absorption of the suppository and elixir preparations in this small, infant population. Both preparations were well tolerated. Vaccinated infants were a useful population in which to conduct a PK study of this antipyretic, analgesic product. Delays in publishing pediatric trials can occur as a result of a number of issues even when results are positive. Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.

Solid state TL detectors for in vivo dosimetry in brachytherapy.

PubMed

Gambarini, G; Borroni, M; Grisotto, S; Maucione, A; Cerrotta, A; Fallai, C; Carrara, M

2012-12-01

In vivo dosimetry provides information about the actual dose delivered to the patient treated with radiotherapy and can be adopted within a routinary treatment quality assurance protocol. Aim of this study was to evaluate the feasibility of performing in vivo rectal dosimetry by placing thermoluminescence detectors directly on the transrectal ultrasound probe adopted for on-line treatment planning of high dose rate brachytherapy boosts of prostate cancer patients. A suitable protocol for TLD calibration has been set up. In vivo measurements resulted to be in good agreement with the calculated doses, showing that the proposed method is feasible and returns accurate results. Copyright © 2012 Elsevier Ltd. All rights reserved.

Radiobiological Impact of Reduced Margins and Treatment Technique for Prostate Cancer in Terms of Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jensen, Ingelise, E-mail: inje@rn.d; Carl, Jesper; Lund, Bente

2011-07-01

Dose escalation in prostate radiotherapy is limited by normal tissue toxicities. The aim of this study was to assess the impact of margin size on tumor control and side effects for intensity-modulated radiation therapy (IMRT) and 3D conformal radiotherapy (3DCRT) treatment plans with increased dose. Eighteen patients with localized prostate cancer were enrolled. 3DCRT and IMRT plans were compared for a variety of margin sizes. A marker detectable on daily portal images was presupposed for narrow margins. Prescribed dose was 82 Gy within 41 fractions to the prostate clinical target volume (CTV). Tumor control probability (TCP) calculations based on themore » Poisson model including the linear quadratic approach were performed. Normal tissue complication probability (NTCP) was calculated for bladder, rectum and femoral heads according to the Lyman-Kutcher-Burman method. All plan types presented essentially identical TCP values and very low NTCP for bladder and femoral heads. Mean doses for these critical structures reached a minimum for IMRT with reduced margins. Two endpoints for rectal complications were analyzed. A marked decrease in NTCP for IMRT plans with narrow margins was seen for mild RTOG grade 2/3 as well as for proctitis/necrosis/stenosis/fistula, for which NTCP <7% was obtained. For equivalent TCP values, sparing of normal tissue was demonstrated with the narrow margin approach. The effect was more pronounced for IMRT than 3DCRT, with respect to NTCP for mild, as well as severe, rectal complications.« less

Association Between Incomplete Neoadjuvant Radiotherapy and Survival for Patients With Locally Advanced Rectal Cancer

PubMed Central

Sun, Zhifei; Adam, Mohamed A.; Kim, Jina; Palta, Manisha; Czito, Brian G.; Migaly, John; Mantyh, Christopher R.

2017-01-01

Importance Failing to complete chemotherapy adversely affects survival in patients with colorectal cancer. However, the effect of incomplete delivery of neoadjuvant radiotherapy is unclear. Objective To determine whether incomplete radiotherapy delivery is associated with worse clinical outcomes and survival. Design, Setting, and Participants Data on 17 600 patients with stage II to III rectal adenocarcinoma from the 2006-2012 National Cancer Database who received neoadjuvant chemoradiotherapy followed by surgical resection were included. Multivariable regression methods were used to compare resection margin positivity, permanent colostomy rate, 30-day readmission, 90-day mortality, and overall survival between patients who received complete (45.0-50.4 Gy) and incomplete (<45.0 Gy) doses of radiation as preoperative therapy. Main Outcomes and Measures The primary outcome measure was overall survival; short-term perioperative and oncologic outcomes encompassing margin positivity, permanent ostomy rate, postoperative readmission, and postoperative mortality were also assessed. Results Among 17 600 patients included, 10 862 were men, with an overall median age of 59 years (range, 51-68 years). Of these, 874 patients (5.0%) received incomplete doses of neoadjuvant radiation. The median radiation dose received among those who did not achieve complete dosing was 34.2 Gy (interquartile range, 19.8-40.0 Gy). Female sex (adjusted odds ratio [OR] 0.69; 95% CI, 0.59-0.81; P < .001) and receiving radiotherapy at a different hospital than the one where surgery was performed (OR, 0.72; 95% CI, 0.62-0.85; P < .001) were independent predictors of failing to achieve complete dosing; private insurance status was predictive of completing radiotherapy (OR, 1.60; 95% CI, 1.16-2.21; P = .004). At 5-year follow-up, overall survival was improved among patients who received a complete course of radiotherapy (3086 [estimated survival probability, 73.2%] vs 133 [63.0%]; P < .001). After adjustment for demographic, clinical, and tumor characteristics, patients receiving a complete vs incomplete radiation dose had a similar resection margin positivity (OR, 0.99; 95% CI, 0.72-1.35; P = .92), permanent colostomy rate (OR, 0.96; 95% CI, 0.70-1.32; P = .81), 30-day readmission rate (OR, 0.92; 95% CI, 0.67-1.27; P = .62), and 90-day mortality (OR, 0.72; 95% CI, 0.33-1.54; P = .41). However, a complete radiation dose had a significantly lower risk of long-term mortality (adjusted hazard ratio, 0.70; 95% CI, 0.59-0.84; P < .001). Conclusions and Relevance Achieving a target radiation dose of 45.0 to 50.4 Gy is associated with a survival benefit in patients with locally advanced rectal cancer. Aligning all aspects of multimodal oncology care may increase the probability of completing neoadjuvant therapy. PMID:28273303

Multi-institutional Prospective Evaluation of Bowel Quality of Life After Prostate External Beam Radiation Therapy Identifies Patient and Treatment Factors Associated With Patient-Reported Outcomes: The PROSTQA Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamstra, Daniel A., E-mail: dhamm@med.umich.edu; Conlon, Anna S.C.; Daignault, Stephanie

Purpose: To evaluate patients treated with external beam radiation therapy as part of the multicenter Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment (PROSTQA), to identify factors associated with posttreatment patient-reported bowel health-related quality of life (HRQOL). Methods and Materials: Pretreatment characteristics and treatment details among 292 men were evaluated using a general linear mixed model for their association with measured HRQOL by the Expanded Prostate Cancer Index Composite instrument through 2 years after enrollment. Results: Bowel HRQOL had a median score of 100 (interquartile range 91.7-100) pretreatment and 95.8 (interquartile range 83.3-100) at 2 years, representing new moderate/bigmore » problems in 11% for urgency, 7% for frequency, 4% for bloody stools, and 8% for an overall bowel problems. Baseline bowel score was the strongest predictor for all 2-year endpoints. In multivariable models, a volume of rectum ≥25% treated to 70 Gy (V70) yielded a clinically significant 9.3-point lower bowel score (95% confidence interval [CI] 16.8-1.7, P=.015) and predicted increased risks for moderate to big fecal incontinence (P=.0008). No other radiation therapy treatment-related variables influenced moderate to big changes in rectal HRQOL. However, on multivariate analyses V70 ≥25% was associated with increases in small, moderate, or big problems with the following: incontinence (3.9-fold; 95% CI 1.1-13.4, P=.03), rectal bleeding (3.6-fold; 95% CI 1.3-10.2, P=.018), and bowel urgency (2.9-fold; 95% CI 1.1-7.6, P=.026). Aspirin use correlated with a clinically significant 4.7-point lower bowel summary score (95% CI 9.0-0.4, P=.03) and an increase in small, moderate, or big problems with bloody stools (2.8-fold; 95% CI 1.2-6.4, P=.018). Intensity modulated radiation therapy was associated with higher radiation therapy doses to the prostate and lower doses to the rectum but did not independently correlate with bowel HRQOL. Conclusion: After contemporary dose-escalated external beam radiation therapy up to 11% of patients have newly identified moderate/big problems with bowel HRQOL 2 years after treatment. Bowel HRQOL is related to baseline function, rectal V70, and aspirin use. Finally, our findings validate the commonly utilized cut-point of rectal V70 ≥25% as having significant impact on patient-reported outcomes.« less

High levels of adherence to a rectal microbicide gel and to oral Pre-Exposure Prophylaxis (PrEP) achieved in MTN-017 among men who have sex with men (MSM) and transgender women.

PubMed

Carballo-Diéguez, Alex; Balán, Ivan C; Brown, William; Giguere, Rebecca; Dolezal, Curtis; Leu, Cheng-Shiun; Marzinke, Mark A; Hendrix, Craig W; Piper, Jeanna M; Richardson, Barbra A; Grossman, Cynthia; Johnson, Sherri; Gomez, Kailazarid; Horn, Stephanie; Kunjara Na Ayudhya, Ratiya Pamela; Patterson, Karen; Jacobson, Cindy; Bekker, Linda-Gail; Chariyalertsak, Suwat; Chitwarakorn, Anupong; Gonzales, Pedro; Holtz, Timothy H; Liu, Albert; Mayer, Kenneth H; Zorrilla, Carmen; Lama, Javier; McGowan, Ian; Cranston, Ross D

2017-01-01

Trials to assess microbicide safety require strict adherence to prescribed regimens. If adherence is suboptimal, safety cannot be adequately assessed. MTN-017 was a phase 2, randomized sequence, open-label, expanded safety and acceptability crossover study comparing 1) daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), 2) daily use of reduced-glycerin 1% tenofovir (RG-TFV) gel applied rectally, and 3) RG-TFV gel applied before and after receptive anal intercourse (RAI)-if participants had no RAI in a week, they were asked to use two doses of gel within 24 hours. Product use was assessed by mixed methods including unused product return count, text messaging reports, and qualitative plasma TFV pharmacokinetic (PK) results. Convergence interviews engaged participants in determining the most accurate number of doses used based on product count and text messaging reports. Client-centered adherence counseling was also used. Participants (N = 187) were men who have sex with men and transgender women enrolled in the United States (42%), Thailand (29%), Peru (19%) and South Africa (10%). Mean age was 31.4 years (range 18-64 years). Based on convergence interviews, over an 8-week period, 94% of participants had ≥80% adherence to daily tablet, 41% having perfect adherence; 83% had ≥80% adherence to daily gel, 29% having perfect adherence; and 93% had ≥80% adherence to twice-weekly use during the RAI-associated gel regimen, 75% having perfect adherence and 77% having ≥80% adherence to gel use before and after RAI. Only 4.4% of all daily product PK results were undetectable and unexpected (TFV concentrations <0.31 ng/mL) given self-reported product use near sampling date. The mixed methods adherence measurement indicated high adherence to product use in all three regimens. Adherence to RAI-associated rectal gel use was as high as adherence to daily oral PrEP. A rectal microbicide gel, if efficacious, could be an alternative for individuals uninterested in daily oral PrEP.

Pelvic abscess following preoperative radiation and abdominoperineal resection: management with a free flap

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kraybill, W.G.; Reinsch, J.; Puckett, C.L.

1984-01-01

The case of a woman treated for a large rectal cancer with high-dose radiation therapy and abdominoperineal resection followed by a large pelvic abscess is presented. Wound healing, reconstruction, and rehabilitation were achieved with a free latissimus dorsi myocutaneous flap. The importance of providing well-vascularized tissue for wound healing in the infected irradiated wound is emphasized.

Pharmacokinetics and anti-hypertensive effect of metoprolol tartrate rectal delivery system.

PubMed

Abou el Ela, Amal El Sayeh F; Allam, Ayat A; Ibrahim, Ehsan H

2016-01-01

The main aim of this work was to develop rectal suppositories for better delivery of metoprolol tartrate (MT). The various bases used were fatty, water soluble and emulsion bases. The physical properties of the prepared suppositories were characterized such as weight variation, hardness, disintegration time, melting range and the drug content uniformity. The in vitro release of MT from the prepared suppositories was carried out. The evaluation of the pharmacological effects of MT on the blood pressure and heart rate of the healthy rabbits after the rectal administration compared to the oral tablets was studied. Moreover, the formulation with the highest in vitro release and the highest pharmacological effects would be selected for a further pharmacokinetics study compared to the oral tablets. The results revealed that the emulsion bases gave the highest rate of the drug release than the other bases used. The reduction effect of the emulsion MT suppository base on the blood pressure and heart rate was found to be faster and greater than that administered orally. The selected emulsion suppository base (F11) showed a significant increase in the AUC (1.88-fold) in rabbits as compared to the oral tablets. From the above results we can conclude that rectal route can serve as an efficient alternative route to the oral one for systemic delivery of MT which may be due to the avoidance of first-pass effect in the liver.

Neoadjuvant chemoradiation therapy and pathological complete response in rectal cancer

PubMed Central

Ferrari, Linda; Fichera, Alessandro

2015-01-01

The management of rectal cancer has evolved significantly in the last few decades. Significant improvements in local disease control were achieved in the 1990s, with the introduction of total mesorectal excision and neoadjuvant radiotherapy. Level 1 evidence has shown that, with neoadjuvant chemoradiation therapy (CRT) the rates of local recurrence can be lower than 6% and, as a result, neoadjuvant CRT currently represents the accepted standard of care. This approach has led to reliable tumor down-staging, with 15–27% patients with a pathological complete response (pCR)—defined as no residual cancer found on histological examination of the specimen. Patients who achieve pCR after CRT have better long-term outcomes, less risk of developing local or distal recurrence and improved survival. For all these reasons, sphincter-preserving procedures or organ-preserving options have been suggested, such as local excision of residual tumor or the omission of surgery altogether. Although local recurrence rate has been stable at 5–6% with this multidisciplinary management method, distal recurrence rates for locally-advanced rectal cancers remain in excess of 25% and represent the main cause of death in these patients. For this reason, more recent trials have been looking at the administration of full-dose systemic chemotherapy in the neoadjuvant setting (in order to offer early treatment of disseminated micrometastases, thus improving control of systemic disease) and selective use of radiotherapy only in non-responders or for low rectal tumors smaller than 5 cm. PMID:26290512

A study of the variability in the febrile responses of rabbits to endogenous pyrogen.

PubMed

Stitt, J T

1985-10-01

The range of body temperature increases elicited by a standard dose of endogenous pyrogen (0.5 ml/kg iv) was examined in a population of 26 male New Zealand White rabbits. Although the mean maximum increase in rectal temperature was 0.88 +/- 0.06 degree C (SE), individual responses varied from 0.4 degree to 1.5 degree C. Three representative animals that responded to the standard dose of pyrogen with small, intermediate, and large febrile responses were selected and challenged with the same dose of pyrogen on eight separate occasions, and the variability of these responses was examined. There was little variability within the characteristic responses of any particular animal to the repeated challenges. The variability of the febrile responses elicited by both intravenous and intracerebroventricular administration of the same pyrogen was examined and compared using another group of 11 rabbits. The variability in response to the intravenous route was similar to that found in the larger population, whereas the variation in response to the intracerebroventricular route was smaller, and all 11 animals had fevers that were greater than 1 degrees C. It is concluded that the variability of the febrile responses of rabbits to intravenous pyrogen was due to differences between individual sensitivities of animals to the intravenously administered pyrogen. This difference in sensitivity may be due to a difference in the amount of pyrogen that reaches the putative receptor sites, or to a difference in the density or effectiveness of receptor sites in translating the pyrogenic stimulus into a fever response.

Sarcosine attenuates toluene-induced motor incoordination, memory impairment, and hypothermia but not brain stimulation reward enhancement in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chan, Ming-Huan; Institute of Neuroscience, National Changchi University, Taipei, Taiwan; Chung, Shiang-Sheng

Toluene, a widely used and commonly abused organic solvent, produces various behavioral disturbances, including motor incoordination and cognitive impairment. Toluene alters the function of a large number of receptors and ion channels. Blockade of N-methyl-D-aspartate (NMDA) receptors has been suggested to play a critical role in toluene-induced behavioral manifestations. The present study determined the effects of various toluene doses on motor coordination, recognition memory, body temperature, and intracranial self-stimulation (ICSS) thresholds in mice. Additionally, the effects of sarcosine on the behavioral and physiological effects induced by toluene were evaluated. Sarcosine may reverse toluene-induced behavioral manifestations by acting as an NMDAmore » receptor co-agonist and by inhibiting the effects of the type I glycine transporter (GlyT1). Mice were treated with toluene alone or combined with sarcosine pretreatment and assessed for rotarod performance, object recognition memory, rectal temperature, and ICSS thresholds. Toluene dose-dependently induced motor incoordination, recognition memory impairment, and hypothermia and lowered ICSS thresholds. Sarcosine pretreatment reversed toluene-induced changes in rotarod performance, novel object recognition, and rectal temperature but not ICSS thresholds. These findings suggest that the sarcosine-induced potentiation of NMDA receptors may reverse motor incoordination, memory impairment, and hypothermia but not the enhancement of brain stimulation reward function associated with toluene exposure. Sarcosine may be a promising compound to prevent acute toluene intoxications by occupational or intentional exposure. -- Highlights: ► Toluene induces impairments in Rotarod test and novel object recognition test. ► Toluene lowers rectal temperature and ICSS thresholds in mice. ► Sarcosine reverses toluene-induced changes in motor, memory and body temperature. ► Sarcosine pretreatment does not affect toluene-induced reward enhancement.« less

Blood levels do not predict behavioral or physiological effects of Δ9-tetrahydrocannabinol in rhesus monkeys with different patterns of exposure

PubMed Central

Ginsburg, Brett C.; Hruba, Lenka; Zaki, Armia; Javors, Martin; McMahon, Lance R.

2014-01-01

Background Recent changes in the legality of cannabis have prompted evaluation of whether blood levels of Δ9-tetrahydrocannabinol (THC) or its metabolites could be used to substantiate impairment, particularly related to behavioral tasks such as driving. However, because marked tolerance develops to behavioral effects of THC, the applicability of a particular threshold of blood THC as an index of impairment in people with different patterns of use remains unclear. Studies relevant to this issue are difficult to accomplish in humans, as prior drug exposure is difficult to control. Methods Here, effects of THC to decrease rectal temperature and operant response rate compared to levels of THC and its metabolites were studied in blood in two groups of monkeys: one received intermittent treatment with THC (0.1 mg/kg i.v.) and another received chronic THC (1 mg/kg/12 h s.c.) for several years. Results In monkeys with intermittent THC exposure, a single dose of THC (3.2 mg/kg s.c.) decreased rectal temperature and response rate. The same dose did not affect response rate or rectal temperature in chronically exposed monkeys, indicative of greater tolerance. In both groups, blood levels of THC peaked 20–60 min post-injection and had a similar half life of elimination, indicating no tolerance to the pharmacokinetics of THC. Notably, in both groups, the behavioral effects of THC were not apparent when blood levels were maximal (20-min post-administration). Conclusion These data indicate that thresholds for blood levels of THC do not provide a consistent index of behavioral impairment across individuals with different patterns of THC exposure. PMID:24703610

Preoperative Chemoradiation With Cetuximab, Irinotecan, and Capecitabine in Patients With Locally Advanced Resectable Rectal Cancer: A Multicenter Phase II Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Sun Young; Hong, Yong Sang; Kim, Dae Yong

Purpose: To evaluate the efficacy and safety of preoperative chemoradiation with cetuximab, irinotecan, and capecitabine in patients with rectal cancer. Methods and Materials: Forty patients with locally advanced, nonmetastatic, and mid- to lower rectal cancer were enrolled. Radiotherapy was delivered at a dose of 50.4 Gy/28 fractions. Concurrent chemotherapy consisted of an initial dose of cetuximab of 400 mg/m{sup 2} 1 week before radiotherapy, and then cetuximab 250 mg/m{sup 2}/week, irinotecan 40 mg/m{sup 2}/week for 5 consecutive weeks and capecitabine 1,650 mg/m{sup 2}/day for 5 days a week (weekdays only) from the first day during radiotherapy. Total mesorectal excision wasmore » performed within 6 {+-} 2 weeks. The pathologic responses and survival outcomes were evaluated as study endpoints, and an additional KRAS mutation analysis was performed. Results: In total, 39 patients completed their planned preoperative chemoradiation and underwent R0 resection. The pathologic complete response rate was 23.1% (9/39), and 3 patients (7.7%) showed near total regression of tumor. The 3-year disease-free and overall survival rates were 80.0% and 94.7%, respectively. Grade 3/4 toxicities included leukopenia (4, 10.3%), neutropenia (2, 5.1%), anemia (1, 2.6%), diarrhea (2, 5.1%), fatigue (1, 2.6%), skin rash (1, 2.6%), and ileus (1, 2.6%). KRAS mutations were found in 5 (13.2%) of 38 patients who had available tissue for testing. Clinical outcomes were not significantly correlated with KRAS mutation status. Conclusions: Preoperative chemoradiation with cetuximab, irinotecan, and capecitabine was active and well tolerated. KRAS mutation status was not a predictive factor for pathologic response in this study.« less

Risk of Hypogonadism From Scatter Radiation During Pelvic Radiation in Male Patients With Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yau, Ivan; Vuong, Te; Garant, Aurelie

Purpose: Recent studies have reported fluctuations in sex hormones during pelvic irradiation. The objective of this study was to observe the effects of radiation on hormonal profiles for two treatment modalities: conventional external beam radiotherapy (EBRT) and high-dose-rate brachytherapy (HDRBT) given neoadjuvantly for patients with rectal cancer. Methods and Materials: Routine serum follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were collected from 119 consecutive male patients receiving either EBRT, using 45.0-50.4 Gy in 25-28 fractions with concurrent 5-fluorouracil chemotherapy or HDRBT using 26 Gy in 4 fractions. Results: Thirty patients with initially abnormal profiles were excluded. Profilesmore » included in this study were collected from 51 patients treated with EBRT and 38 patients treated with HDRBT, all of whom had normal hormonal profiles before treatment. Mean follow-up times were 17 months for the entire patient cohort-14 and 20 months, respectively-for the EBRT and HDRBT arms. Dosimetry results revealed a mean cumulative testicular dose of 1.24 Gy received in EBRT patients compared with 0.27 Gy in the HDRBT group. After treatment, FSH and LH were elevated in all patients but were more pronounced in the EBRT group. The testosterone-to-LH ratio was significantly lower (p = 0.0036) in EBRT patients for tumors in the lower third of the rectum. The 2-year hypogonadism rate observed was 2.6% for HDRBT compared with 17.6% for EBRT (p = 0.09) for tumors in the lower two thirds of the rectum. Conclusion: HDRBT allows better hormonal sparing than EBRT during neoadjuvant treatment of patients with rectal cancer.« less

Prostate Stereotactic Ablative Radiation Therapy Using Volumetric Modulated Arc Therapy to Dominant Intraprostatic Lesions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murray, Louise J.; University of Leeds, Leeds; Lilley, John

2014-06-01

Purpose: To investigate boosting dominant intraprostatic lesions (DILs) in the context of stereotactic ablative radiation therapy (SABR) and to examine the impact on tumor control probability (TCP) and normal tissue complication probability (NTCP). Methods and Materials: Ten prostate datasets were selected. DILs were defined using T2-weighted, dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging. Four plans were produced for each dataset: (1) no boost to DILs; (2) boost to DILs, no seminal vesicles in prescription; (3) boost to DILs, proximal seminal vesicles (proxSV) prescribed intermediate dose; and (4) boost to DILs, proxSV prescribed higher dose. The prostate planning target volume (PTV)more » prescription was 42.7 Gy in 7 fractions. DILs were initially prescribed 115% of the PTV{sub Prostate} prescription, and PTV{sub DIL} prescriptions were increased in 5% increments until organ-at-risk constraints were reached. TCP and NTCP calculations used the LQ-Poisson Marsden, and Lyman-Kutcher-Burman models respectively. Results: When treating the prostate alone, the median PTV{sub DIL} prescription was 125% (range: 110%-140%) of the PTV{sub Prostate} prescription. Median PTV{sub DIL} D50% was 55.1 Gy (range: 49.6-62.6 Gy). The same PTV{sub DIL} prescriptions and similar PTV{sub DIL} median doses were possible when including the proxSV within the prescription. TCP depended on prostate α/β ratio and was highest with an α/β ratio = 1.5 Gy, where the additional TCP benefit of DIL boosting was least. Rectal NTCP increased with DIL boosting and was considered unacceptably high in 5 cases, which, when replanned with an emphasis on reducing maximum dose to 0.5 cm{sup 3} of rectum (Dmax{sub 0.5cc}), as well as meeting existing constraints, resulted in considerable rectal NTCP reductions. Conclusions: Boosting DILs in the context of SABR is technically feasible but should be approached with caution. If this therapy is adopted, strict rectal constraints are required including Dmax{sub 0.5cc}. If the α/β ratio of prostate cancer is 1.5 Gy or less, then high TCP and low NTCP can be achieved by prescribing SABR to the whole prostate, without the need for DIL boosting.« less

Anaphylaxis to gelatin-containing rectal suppositories.

PubMed

Sakaguchi, M; Inouye, S

2001-12-01

Some children--though the number is few-have been sensitized with gelatin. To investigate the relationship between the presence of antigelatin IgE and anaphylaxis to gelatin-containing rectal suppository, we measured antigelatin IgE in the sera of the children with anaphylaxis. Ten children showed systemic allergic reactions, including anaphylaxis, to a chloral hydrate rectal suppository containing gelatin (231 mg/dose) that had been used as a sedative. These children's clinical histories and serum samples were submitted from physicians to the National Institute of Infectious Diseases during a 2-year period from 1996 to 1997. Of the 10 children, 5 showed apparent anaphylaxis, including hypotension and/or cyanosis, along with urticaria or wheezing; 2 showed both urticaria and wheezing without hypotension or cyanosis; the other 3 showed only urticaria. All of the children had antigelatin IgE (mean value +/- SD, 7.9 +/- 8.4 Ua/mL). As a control, samples from 250 randomly selected children had no antigelatin IgE. These findings suggest that the 10 children's systemic allergic reactions to this suppository were caused by the gelatin component. Gelatin-containing suppositories must be used with the same caution as gelatin-containing vaccines and other medications.

A novel curvilinear approach for prostate seed implantation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Podder, Tarun K.; Dicker, Adam P.; Hutapea, Parsaoran

Purpose: A new technique called ''curvilinear approach'' for prostate seed implantation has been proposed. The purpose of this study is to evaluate the dosimetric benefit of curvilinear distribution of seeds for low-dose-rate (LDR) prostate brachytherapy. Methods: Twenty LDR prostate brachytherapy cases planned intraoperatively with VariSeed planning system and I-125 seeds were randomly selected as reference rectilinear cases. All the cases were replanned by using curved-needle approach keeping the same individual source strength and the volume receiving 100% of prescribed dose 145 Gy (V{sub 100}). Parameters such as number of needles, seeds, and the dose coverage of the prostate (D{sub 90},more » V{sub 150}, V{sub 200}), urethra (D{sub 30}, D{sub 10}) and rectum (D{sub 5}, V{sub 100}) were compared for the rectilinear and the curvilinear methods. Statistical significance was assessed using two-tailed student's t-test. Results: Reduction of the required number of needles and seeds in curvilinear method were 30.5% (p < 0.001) and 11.8% (p < 0.49), respectively. Dose to the urethra was reduced significantly; D{sub 30} reduced by 10.1% (p < 0.01) and D{sub 10} reduced by 9.9% (p < 0.02). Reduction in rectum dose D{sub 5} was 18.5% (p < 0.03) and V{sub 100} was also reduced from 0.93 cc in rectilinear to 0.21 cc in curvilinear (p < 0.001). Also the V{sub 150} and V{sub 200} coverage of prostate reduced by 18.8% (p < 0.01) and 33.9% (p < 0.001), respectively. Conclusions: Significant improvement in the relevant dosimetric parameters was observed in curvilinear needle approach. Prostate dose homogeneity (V{sub 150}, V{sub 200}) improved while urethral dose was reduced, which might potentially result in better treatment outcome. Reduction in rectal dose could potentially reduce rectal toxicity and complications. Reduction in number of needles would minimize edema and thereby could improve postimplant urinary incontinence. This study indicates that the curvilinear implantation approach is dosimetrically superior to conventional rectilinear implantation technique.« less

Effect of hospital caseload on long-term outcome after standardization of rectal cancer surgery in the Spanish Rectal Cancer Project.

PubMed

Ortiz, Héctor; Codina, Antonio; Ciga, Miguel Á; Biondo, Sebastiano; Enríquez-Navascués, José M; Espín, Eloy; García-Granero, Eduardo; Roig, José V

2016-10-01

INTRODUCCIóN: The purpose of this prospective multicentre multilevel study was to investigate the influence of hospital caseload on long-term outcomes following standardization of rectal cancer surgery in the Rectal Cancer Project of the Spanish Society of Surgeons. Data relating to 2910 consecutive patients with rectal cancer treated for cure between March 2006 and March 2010 were recorded in a prospective database. Hospitals were classified according to number of patients treated per year as low-volume, intermediate-volume, or high volume hospitals (12-23, 24-35, or ≥36 procedures per year). After a median follow-up of 5 years, cumulative rates of local recurrence, metastatic recurrence and overall survival were 6.6 (CI95% 5.6-7.6), 20.3 (CI95% 18.8-21.9) and 73.0 (CI95% 74.7 - 71.3) respectively. In the multilevel regression analysis overall survival was higher for patients treated at hospitals with an annual caseload of 36 or more patients (HR 0,727 [CI95% 0,556-0,951]; P=.02). The risk of local recurrence and metastases were not related to the caseload. Moreover, there was a statistically significant variation in overall survival (median hazard ratio [MHR] 1.184 [CI95% 1.071-1,333]), local recurrence (MHR 1.308 [CI95% 1.010-1.668]) and metastases (MHR 1.300 [CI95% 1.181; 1.476]) between all hospitals. Overall survival was higher for patients treated at hospitals with an annual caseload of 36 or more patients. However, local recurrence was not influenced by caseload. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Lubiprostone induced ischemic colitis.

PubMed

Sherid, Muhammed; Sifuentes, Humberto; Samo, Salih; Deepak, Parakkal; Sridhar, Subbaramiah

2013-01-14

Ischemic colitis accounts for 6%-18% of the causes of acute lower gastrointestinal bleeding. It is often multifactorial and more commonly encountered in the elderly. Several medications have been implicated in the development of colonic ischemia. We report a case of a 54-year old woman who presented with a two-hour history of nausea, vomiting, abdominal pain, and bloody stool. The patient had recently used lubiprostone with close temporal relationship between the increase in the dose and her symptoms of rectal bleeding. The radiologic, colonoscopic and histopathologic findings were all consistent with ischemic colitis. Her condition improved without any serious complications after the cessation of lubiprostone. This is the first reported case of ischemic colitis with a clear relationship with lubiprostone (Naranjo score of 10). Clinical vigilance for ischemic colitis is recommended for patients receiving lubiprostone who are presenting with abdominal pain and rectal bleeding.

Prospective multicenter registration study of colorectal cancer: significant variations in radicality and oncosurgical quality-Swiss Group for Clinical Cancer Research Protocol SAKK 40/00.

PubMed

Maurer, Christoph A; Dietrich, Daniel; Schilling, Martin K; Metzger, Urs; Laffer, Urban; Buchmann, Peter; Lerf, Bruno; Villiger, Peter; Melcher, Gian; Klaiber, Christian; Bilat, Christian; Brauchli, Peter; Terracciano, Luigi; Kessler, Katharina

2017-01-01

This study aimed to investigate in a multicenter cohort study the radicality of colorectal cancer resections, to assess the oncosurgical quality of colorectal specimens, and to compare the performance between centers. One German and nine Swiss hospitals agreed to prospectively register all patients with primary colorectal cancer resected between September 2001 and June 2005. The median number of eligible patients with one primary tumor included per center was 95 (range 12-204). The following variations of median values or percentages between centers were found: length of bowel specimen 20-39 cm (25.8 cm), maximum height of mesocolon 6.5-12.5 cm (9.0 cm), number of examined lymph nodes 9-24 (16), distance to nearer bowel resection margin in colon cancer 4.8-12 cm (7 cm), and in rectal cancer 2-3 cm (2.5 cm), central ligation of major artery 40-97 % (71 %), blood loss 200-500 ml (300 ml), need for perioperative blood transfusion 5-40 % (19 %), tumor opened during mobilization 0-11 % (5 %), T4-tumors not en-bloc resected 0-33 % (4 %), inadvertent perforation of mesocolon/mesorectum 0-8 % (4 %), no-touch isolation technique 36-86 % (67 %), abdominoperineal resection for rectal cancer 0-30 % (17 %), rectal cancer specimen with circumferential margin ≤1 mm 0-19 % (10 %), in-hospital mortality 0-6 % (2 %), anastomotic leak or intra-abdominal abscess 0-17 % (7 %), re-operation 0-17 % (8 %). In colorectal cancer, surgery considerable variations between different centers were found with regard to radicality and oncosurgical quality, suggesting a potential for targeted improvement of surgical technique.

Reduced Circumferential Resection Margin Involvement in Rectal Cancer Surgery: Results of the Dutch Surgical Colorectal Audit.

PubMed

Gietelink, Lieke; Wouters, Michel W J M; Tanis, Pieter J; Deken, Marion M; Ten Berge, Martijn G; Tollenaar, Rob A E M; van Krieken, J Han; de Noo, Mirre E

2015-09-01

The circumferential resection margin (CRM) is a significant prognostic factor for local recurrence, distant metastasis, and survival after rectal cancer surgery. Therefore, availability of this parameter is essential. Although the Dutch total mesorectal excision trial raised awareness about CRM in the late 1990s, quality assurance on pathologic reporting was not available until the Dutch Surgical Colorectal Audit (DSCA) started in 2009. The present study describes the rates of CRM reporting and involvement since the start of the DSCA and analyzes whether improvement of these parameters can be attributed to the audit. Data from the DSCA (2009-2013) were analyzed. Reporting of CRM and CRM involvement was plotted for successive years, and variations of these parameters were analyzed in a funnelplot. Predictors of CRM involvement were determined in univariable analysis and the independent influence of year of registration on CRM involvement was analyzed in multivariable analysis. A total of 12,669 patients were included for analysis. The mean percentage of patients with a reported CRM increased from 52.7% to 94.2% (2009-2013) and interhospital variation decreased. The percentage of patients with CRM involvement decreased from 14.2% to 5.6%. In multivariable analysis, the year of DSCA registration remained a significant predictor of CRM involvement. After the introduction of the DSCA, a dramatic improvement in CRM reporting and a major decrease of CRM involvement after rectal cancer surgery have occurred. This study suggests that a national quality assurance program has been the driving force behind these achievements. Copyright © 2015 by the National Comprehensive Cancer Network.

An ecologic study of cancer mortality rates in Spain with respect to indices of solar UVB irradiance and smoking.

PubMed

Grant, William B

2007-03-01

There is increasing evidence that vitamin D reduces the risk of many types of cancer. Geographic variations in cancer mortality rates in Spain are apparently linked to variations in solar ultraviolet (UV) irradiances and other factors. Cancer mortality rates for 48 continental Spanish provinces for 1978-1992 were used in linear regression analyses with respect to mortality rates for latitude (an index of solar UVB levels), skin cancer (an index of high cumulative UVB irradiance), melanoma (an index related to solar UV irradiance and several other factors) and lung cancer (an index of cumulative effects of smoking). The 9 cancers with mortality rates significantly correlated with latitude for 1 or both sexes were brain, gastric, melanoma, nonmelanoma skin cancer (NMSC), non-Hodgkin's lymphoma (NHL), pancreatic, pleural, rectal and thyroid cancer. Inverse correlations with latitude were found for laryngeal, lung and uterine corpus cancer. The 17 cancers inversely correlated with NMSC are bladder, brain, breast, colon, esophageal, gallbladder, Hodgkin's lymphoma, lung, melanoma, multiple myeloma, NHL, ovarian, pancreatic, pleural, rectal, thyroid and uterine corpus cancer. The 16 correlated with melanoma are bladder, brain, breast, colon, gallbladder, leukemia, lung, multiple myeloma, NHL, ovarian, pancreatic, pleural, prostate, rectal, renal and uterine corpus cancer. The results for lung cancer were in accordance with the literature. These results provide more support for the UVB/vitamin D/cancer hypothesis and indicate a new way to investigate the role of solar UV irradiance on cancer risk. They also provide more evidence that melanoma and NMSC have different etiologies. Copyright 2006 Wiley-Liss, Inc.

Consensus statement on the multidisciplinary management of patients with recurrent and primary rectal cancer beyond total mesorectal excision planes.

PubMed

2013-07-01

The management of primary rectal cancer beyond total mesorectal excision planes (PRC-bTME) and recurrent rectal cancer (RRC) is challenging. There is global variation in standards and no guidelines exist. To achieve cure most patients require extended, multivisceral, exenterative surgery, beyond conventional total mesorectal excision planes. The aim of the Beyond TME Group was to achieve consensus on the definitions and principles of management, and to identify areas of research priority. Delphi methodology was used to achieve consensus. The Group consisted of invited experts from surgery, radiology, oncology and pathology. The process included two international dedicated discussion conferences, formal feedback, three rounds of editing and two rounds of anonymized web-based voting. Consensus was achieved with more than 80 per cent agreement; less than 80 per cent agreement indicated low consensus. During conferences held in September 2011 and March 2012, open discussion took place on areas in which there is a low level of consensus. The final consensus document included 51 voted statements, making recommendations on ten key areas of PRC-bTME and RRC. Consensus agreement was achieved on the recommendations of 49 statements, with 34 achieving consensus in over 95 per cent. The lowest level of consensus obtained was 76 per cent. There was clear identification of the need for referral to a specialist multidisciplinary team for diagnosis, assessment and further management. The consensus process has provided guidance for the management of patients with PRC-bTME or RRC, taking into account global variations in surgical techniques and technology. It has further identified areas of research priority.

Phase I Study of Neoadjuvant Radiotherapy With 5-Fluorouracil for Rectal Cancer

ClinicalTrials.gov

2017-09-14

Mucinous Adenocarcinoma of the Rectum; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Rectum; Rectal Adenocarcinoma; Stage IIA Rectal Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage IIIA Rectal Cancer; Stage IIIB Rectal Cancer; Stage IIIC Rectal Cancer

Functional Data Analysis in NTCP Modeling: A New Method to Explore the Radiation Dose-Volume Effects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benadjaoud, Mohamed Amine, E-mail: mohamedamine.benadjaoud@gustaveroussy.fr; Université Paris sud, Le Kremlin-Bicêtre; Institut Gustave Roussy, Villejuif

2014-11-01

Purpose/Objective(s): To describe a novel method to explore radiation dose-volume effects. Functional data analysis is used to investigate the information contained in differential dose-volume histograms. The method is applied to the normal tissue complication probability modeling of rectal bleeding (RB) for patients irradiated in the prostatic bed by 3-dimensional conformal radiation therapy. Methods and Materials: Kernel density estimation was used to estimate the individual probability density functions from each of the 141 rectum differential dose-volume histograms. Functional principal component analysis was performed on the estimated probability density functions to explore the variation modes in the dose distribution. The functional principalmore » components were then tested for association with RB using logistic regression adapted to functional covariates (FLR). For comparison, 3 other normal tissue complication probability models were considered: the Lyman-Kutcher-Burman model, logistic model based on standard dosimetric parameters (LM), and logistic model based on multivariate principal component analysis (PCA). Results: The incidence rate of grade ≥2 RB was 14%. V{sub 65Gy} was the most predictive factor for the LM (P=.058). The best fit for the Lyman-Kutcher-Burman model was obtained with n=0.12, m = 0.17, and TD50 = 72.6 Gy. In PCA and FLR, the components that describe the interdependence between the relative volumes exposed at intermediate and high doses were the most correlated to the complication. The FLR parameter function leads to a better understanding of the volume effect by including the treatment specificity in the delivered mechanistic information. For RB grade ≥2, patients with advanced age are significantly at risk (odds ratio, 1.123; 95% confidence interval, 1.03-1.22), and the fits of the LM, PCA, and functional principal component analysis models are significantly improved by including this clinical factor. Conclusion: Functional data analysis provides an attractive method for flexibly estimating the dose-volume effect for normal tissues in external radiation therapy.« less

Radiobiological impact of reduced margins and treatment technique for prostate cancer in terms of tumor control probability (TCP) and normal tissue complication probability (NTCP).

PubMed

Jensen, Ingelise; Carl, Jesper; Lund, Bente; Larsen, Erik H; Nielsen, Jane

2011-01-01

Dose escalation in prostate radiotherapy is limited by normal tissue toxicities. The aim of this study was to assess the impact of margin size on tumor control and side effects for intensity-modulated radiation therapy (IMRT) and 3D conformal radiotherapy (3DCRT) treatment plans with increased dose. Eighteen patients with localized prostate cancer were enrolled. 3DCRT and IMRT plans were compared for a variety of margin sizes. A marker detectable on daily portal images was presupposed for narrow margins. Prescribed dose was 82 Gy within 41 fractions to the prostate clinical target volume (CTV). Tumor control probability (TCP) calculations based on the Poisson model including the linear quadratic approach were performed. Normal tissue complication probability (NTCP) was calculated for bladder, rectum and femoral heads according to the Lyman-Kutcher-Burman method. All plan types presented essentially identical TCP values and very low NTCP for bladder and femoral heads. Mean doses for these critical structures reached a minimum for IMRT with reduced margins. Two endpoints for rectal complications were analyzed. A marked decrease in NTCP for IMRT plans with narrow margins was seen for mild RTOG grade 2/3 as well as for proctitis/necrosis/stenosis/fistula, for which NTCP <7% was obtained. For equivalent TCP values, sparing of normal tissue was demonstrated with the narrow margin approach. The effect was more pronounced for IMRT than 3DCRT, with respect to NTCP for mild, as well as severe, rectal complications. Copyright © 2011 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

High-dose chemoradiotherapy and watchful waiting for distal rectal cancer: a prospective observational study.

PubMed

Appelt, Ane L; Pløen, John; Harling, Henrik; Jensen, Frank S; Jensen, Lars H; Jørgensen, Jens C R; Lindebjerg, Jan; Rafaelsen, Søren R; Jakobsen, Anders

2015-08-01

Abdominoperineal resection is the standard treatment for patients with distal T2 or T3 rectal cancers; however, the procedure is extensive and mutilating, and alternative treatment strategies are being investigated. We did a prospective observational trial to assess whether high-dose radiotherapy with concomitant chemotherapy followed by observation (watchful waiting) was successful for non-surgical management of low rectal cancer. Patients with primary, resectable, T2 or T3, N0-N1 adenocarcinoma in the lower 6 cm of the rectum were given chemoradiotherapy (60 Gy in 30 fractions to tumour, 50 Gy in 30 fractions to elective lymph node volumes, 5 Gy endorectal brachytherapy boost, and oral tegafur-uracil 300 mg/m(2)) every weekday for 6 weeks. Endoscopies and biopsies of the tumour were done at baseline, throughout the course of treatment (weeks 2, 4, and 6), and 6 weeks after the end of treatment. We allocated patients with complete clinical tumour regression, negative tumour site biopsies, and no nodal or distant metastases on CT and MRI 6 weeks after treatment to the observation group (watchful waiting). We referred all other patients to standard surgery. Patients under observation were followed up closely with endoscopies and selected-site biopsies, with surgical resection given for local recurrence. The primary endpoint was local tumour recurrence 1 year after allocation to the observation group. This study is registered with ClinicalTrials.gov, number NCT00952926. Enrolment is closed, but follow-up continues for secondary endpoints. Between Oct 20, 2009, and Dec 23, 2013, we enrolled 55 patients. Patients were recruited from three surgical units throughout Denmark and treated in one tertiary cancer centre (Vejle Hospital, Vejle, Denmark). Of 51 patients who were eligible, 40 had clinical complete response and were allocated to observation. Median follow-up for local recurrence in the observation group was 23·9 months (IQR 15·3-31·0). Local recurrence in the observation group at 1 year was 15·5% (95% CI 3·3-26·3). The most common acute grade 3 adverse event during treatment was diarrhoea, which affected four (8%) of 51 patients. Sphincter function in the observation group was excellent, with 18 (72%) of 25 patients at 1 year and 11 (69%) of 16 patients at 2 years reporting no faecal incontinence at all and a median Jorge-Wexner score of 0 (IQR 0-0) at all timepoints. The most common late toxicity was bleeding from the rectal mucosa; grade 3 bleeding was reported in two (7%) in 30 patients at 1 year and one (6%) of 17 patients at 2 years. There were no unexpected serious adverse reactions or treatment-related deaths. High-dose chemoradiotherapy and watchful waiting might be a safe alternative to abdominoperineal resection for patients with distal rectal cancer. CIRRO-The Lundbeck Foundation Center for Interventional Research in Radiation Oncology and The Danish Council for Strategic Research. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of three methadone doses combined with acepromazine on sedation and some cardiopulmonary variables in dogs.

PubMed

Bitti, Flavia S; Campagnol, Daniela; Rangel, Julia Pp; Nunes Junior, Juarez S; Loureiro, Bárbara; Monteiro, Eduardo R

2017-03-01

To evaluate the sedative and cardiopulmonary effects of three methadone doses, combined with acepromazine, in dogs. Prospective, randomized, complete block study. Six healthy, adult, cross-bred dogs weighing 17.2±4.4 kg (mean±standard deviation). Each dog was administered four treatments: acepromazine (0.05 mg kg -1 ) alone or acepromazine (same dose) in combination with methadone (0.25, 0.50 or 0.75 mg kg -1 ). All drugs were administered intramuscularly. Sedation was scored by a numeric descriptive scale (NDS, range 0-3) and a simple numerical scale (SNS, range 0-10). Heart rate, invasive blood pressure, arterial blood gases and rectal temperature were measured at 15 to 30 minute intervals for 120 minutes. According to NDS scores, mild to moderate sedation (NDS=1-2) was observed in most dogs in the acepromazine treatment, with only one out of six dogs scored as exhibiting intense sedation (NDS=3). All treatments with methadone resulted in significantly higher SNS scores compared with acepromazine alone. In these treatments, most dogs exhibited intense sedation (NDS=3). Increasing the dose of methadone from 0.25 to 0.50 or 0.75 mg kg -1 prolonged sedation in a dose-related manner, but did not influence the degree of sedation. The main adverse effects following administration of acepromazine-methadone treatments were decreased blood pressure, mild respiratory acidosis and decreased rectal temperature. These effects were well tolerated and resolved without treatment. In this study in six dogs, acepromazine-methadone administration resulted in intense sedation in most dogs. The results are interpreted to indicate that a low dose of methadone (0.25 mg kg -1 ) administered in combination with acepromazine (0.05 mg kg -1 ) will induce short-term sedation in dogs, whereas higher doses of methadone should be administered when prolonged sedation is desired. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

Intranasal Administration of a Therapeutic HIV Vaccine (Vacc-4x) Induces Dose-Dependent Systemic and Mucosal Immune Responses in a Randomized Controlled Trial

PubMed Central

Brekke, Kristin; Lind, Andreas; Holm-Hansen, Carol; Haugen, Inger Lise; Sørensen, Birger; Sommerfelt, Maja; Kvale, Dag

2014-01-01

Background Vacc-4x, a Gag p24-based therapeutic HIV vaccine, has been shown to reduce viral load set-points after intradermal administration. In this randomized controlled pilot study we investigate intranasal administration of Vacc-4x with Endocine as adjuvant. Methods Safety and immunogenicity were tested in patients on effective ART. They were randomized to low, medium or high dose Vacc-4x or adjuvant alone, administered four times at weekly intervals with no booster. Vacc-4x-specific T cell responses were measured in vitro by proliferation and in vivo by a single DTH skin test at the end of study. Nasal and rectal mucosal secretions were analyzed for Vacc-4x-specific antibodies by ELISA. Immune regulation induced by Vacc-4x was assessed by functional blockade of the regulatory cytokines IL-10 and TGF-β. Results Vacc-4x proliferative T cell responses increased only among the vaccinated (p≤0.031). The low dose group showed the greatest increase in Vacc-4x CD8+T cell responses (p = 0.037) and developed larger DTH (p = 0.005) than the adjuvant group. Rectal (distal) Vacc-4x IgA and IgG antibodies also increased (p = 0.043) in this group. In contrast, the high dose generated higher nasal (local) Vacc-4x IgA (p = 0.028) and serum IgG (p = 0.030) antibodies than the adjuvant. Irrespective of dose, increased Vacc-4x CD4+T cell responses were associated with low proliferation (r = −0.82, p<0.001) and high regulation (r = 0.61, p = 0.010) at baseline. Conclusion Intranasal administration of Vacc-4x with Endocine was safe and induced dose-dependent vaccine-specific T cell responses and both mucosal and systemic humoral responses. The clinical significance of dose, immune regulation and mucosal immunity warrants further investigation. Trial Registration ClinicalTrials.gov NCT01473810 PMID:25398137

Thermoregulation of alpacas bred in Italy

NASA Astrophysics Data System (ADS)

Mattiello, Silvana; Formis, Elena; Barbieri, Sara

2011-03-01

The present study monitored daily and seasonal variations of rectal temperature in response to different environmental temperatures in alpacas bred in the Italian Apennines at 300 m a.s.l. In each season, the rectal temperature of 33 clinically healthy alpacas was measured three times/day (morning, midday, afternoon). Ambient temperatures were also recorded. Rectal temperatures ranged from a minimum value of 35.1 to a maximum of 39.4°C, with a maximum daily thermal excursion (ΔTrec) of 3.2°C. Temperatures increased throughout the day, with highly significant differences recorded in both young and adult animals between all the time bands ( P < 0.001). These differences were particularly dramatic for adults in summer, when the mean rectal temperature in the morning was 36.3 ± 0.13°C, probably as a consequence of recent shearing. Significant ΔTrec differences were recorded depending on the season in both young and adult animals ( P < 0.001), with the highest ΔTrec values recorded in summer (although the highest daily ambient excursion value was recorded in winter). In conclusion, similarly to alpacas bred in their natural environment, alpacas bred in Italy show a wide thermal neutrality zone, which is probably an adaptive response, that allows the animals to save energy. In the Italian Apennines, in order to prevent situations of hypothermia, with possible detrimental effects on alpacas' health and welfare, shearing should be carried out only in warm seasons.

Anorectal Cancer: Critical Anatomic and Staging Distinctions That Affect Use of Radiation Therapy

PubMed Central

Mamon, Harvey J.; Fuchs, Charles S.; Doyle, Leona A.; Tirumani, Sree Harsha; Ramaiya, Nikhil H.; Rosenthal, Michael H.

2015-01-01

Although rectal and anal cancers are anatomically close, they are distinct entities with different histologic features, risk factors, staging systems, and treatment pathways. Imaging is at the core of initial clinical staging of these cancers and most commonly includes magnetic resonance imaging for local-regional staging and computed tomography for evaluation of metastatic disease. The details of the primary tumor and involvement of regional lymph nodes are crucial in determining if and how radiation therapy should be used in treatment of these cancers. Unfortunately, available imaging modalities have been shown to have imperfect accuracy for identification of nodal metastases and imaging features other than size. Staging of nonmetastatic rectal cancers is dependent on the depth of invasion (T stage) and the number of involved regional lymph nodes (N stage). Staging of nonmetastatic anal cancers is determined according to the size of the primary mass and the combination of regional nodal sites involved; the number of positive nodes at each site is not a consideration for staging. Patients with T3 rectal tumors and/or involvement of perirectal, mesenteric, and internal iliac lymph nodes receive radiation therapy. Almost all anal cancers warrant use of radiation therapy, but the extent and dose of the radiation fields is altered on the basis of both the size of the primary lesion and the presence and extent of nodal involvement. The radiologist must recognize and report these critical anatomic and staging distinctions, which affect use of radiation therapy in patients with anal and rectal cancers. ©RSNA, 2015 PMID:26562239

Clinical use of endovenous indocyanine green during rectosigmoid segmental resection for endometriosis.

PubMed

Seracchioli, Renato; Raimondo, Diego; Arena, Alessandro; Zanello, Margherita; Mabrouk, Mohamed

2018-06-01

To describe a new use of endovenous indocyanine green (ICG) to allow real-time visualization of bowel perfusion in women with recto-sigmoid endometriosis who may be candidates for segmental resection. Step-by-step explanation of this method using descriptive text and educational video. Tertiary level referral academic center. A nulliparous 36-year-old woman affected by a large rectal endometriotic nodule was referred for severe dysmenorrhea, dyspareunia, hematochezia, and dyschezia, despite progestinic therapy. An intravenous injection of 1.5 mL solution containing 3.75 mg dose of ICG for intraoperative fluorescence imaging. Evaluation of blood perfusion of bowel and rectal endometriosis nodule. Evaluation of neoanastomosis vascularization after bowel resection. The procedure of endometriosis removal was performed using the daVinciXi surgical platform (Intuitive Surgical, Sunnyvale, CA). After ovarian endometriosis removal and adhesiolysis, we identified the endometriosis nodule on the anterior surface of the rectum. Pararectal, rectovaginal, and retrorectal spaces were dissected with a nerve-sparing technique. Indocyanine green was administered through a peripheral line. A near-infrared camera head enabled vision of the colorant after latency of a few seconds. We observed the ischemic area around the rectal nodule and perfusion areas upstream and downstream from the lesion. We selected the transecting line for rectal resection, taking account of this objective evaluation, beyond the limits of macroscopic disease. After direct mechanical anastomosis, we checked the rectal vascularization with ICG. To the best of our knowledge, this is the first reported use of endovenous ICG during a bowel resection for deep endometriosis. Endovenous ICG is proposed during surgery for rectosigmoid endometriosis to assess the perfusion of the bowel and select the transecting line. With ICG fluorescence imaging, we can objectively evaluate whether blood supply to the anastomosis is adequate. Endovenous ICG for objective vascular assessment is simple and rapid to use, and no complications related to ICG use were recorded. Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Curative effect of Amorphophallus paeoniifolius tuber on experimental hemorrhoids in rats.

PubMed

Dey, Yadu Nandan; Wanjari, Manish M; Kumar, Dharmendra; Lomash, Vinay; Jadhav, Ankush D

2016-11-04

Amorphophallus paeoniifolius (Dennst.) Nicolson (Family- Araceae) is a crop of south East Asian origin. In India, its tuber is widely used in ethnomedicinal practices by different tribes for the treatment of piles (hemorrhoids). The present study evaluated the effect of methanolic and aqueous extract of Amorphophallus paeoniifolius tuber on croton oil induced hemorrhoids in rats. The methanolic extract was standardized with the major phenolic compound, betulinic acid, by HPLC. The hemorrhoids were induced by applying 6% croton oil preparation in the ano-rectal region. Rats were orally administered methanolic and aqueous extract at doses of 250 and 500mg/kg, each for 7 days. Pilex (200mg/kg) was used as reference anti-hemorrhoidal drug. Hemorrhoids were assessed on eighth day by measuring hemorrhoidal and biochemical parameters along with histology of ano-rectal tissue. Croton oil application caused induction of hemorrhoids as indicated by significant (p<0.001) increase in plasma exudation of Evans blue in ano-rectal tissue, macroscopic severity score and ano-rectal coefficient as compared to normal rats. It significantly (p<0.001) elevated lactate dehydrogenase and cytokines (TNF-α and IL-6) levels in serum and increased myeloperoxidase activity and lipid peroxidation in ano-rectal tissue along with marked histological damage as compared to normal rats. Treatment with tuber extracts and pilex significantly (p<0.05-p<0.001) ameliorated Evans blue exudation, hemorrhoidal parameters and other biochemical parameters with attenuation of tissue damage compared to hemorrhoid control rats. The results indicate that tuber extracts exhibited curative action on hemorrhoids. The aqueous extract showed more pronounced effect than methanolic extract. The effects may be attributed to anti-inflammatory and antioxidant properties. Results indicate that tuber of Amorphophallus paeoniifolius exhibited curative action on hemorrhoids through anti-inflammatory and antioxidant properties. The study validates the ethnomedicinal use of tuber in hemorrhoids and implicates its therapeutic potential as an anti-hemorrhoidal agent. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Prospective single-arm study of intraoperative radiotherapy for locally advanced or recurrent rectal cancer.

PubMed

Tan, Jennifer; Heriot, Alexander G; Mackay, Jack; Van Dyk, Sylvia; Bressel, Mathias Ab; Fox, Chris D; Hui, Andrew C; Lynch, A Craig; Leong, Trevor; Ngan, Samuel Y

2013-10-01

This study aims to evaluate the feasibility and outcomes of intraoperative radiotherapy (IORT) using high-dose-rate (HDR) brachytherapy for locally advanced or recurrent rectal cancers. Despite preoperative chemoradiation, patients with locally advanced or recurrent rectal cancers undergoing surgery remain at high risk of local recurrence. Intensification of radiation with IORT may improve local control. This is a prospective non-randomised study. Eligible patients were those with T4 rectal cancer or pelvic recurrence, deemed suitable for radical surgery but at high risk of positive resection margins, without evidence of metastasis. Chemoradiation was followed by radical surgery. Ten gray (Gy) was delivered to tumour bed via an IORT applicator at time of surgery. There were 15% primary and 85% recurrent cancers. The 71% received preoperative chemoradiation. R0, R1 and R2 resections were 70%, 22% and 7%, respectively. IORT was successfully delivered in 27 of 30 registered patients (90% (95% confidence interval (CI) = 73-98) ) at a median reported time of 12 weeks (interquartile range (IQR) = 10-16) after chemoradiation. Mean IORT procedure and delivery times were 63 minutes (range 22-105 minutes). Ten patients (37% (95% CI = 19-58) ) experienced grade 3 or 4 toxicities (three wound, four abscesses, three soft tissue, three bowel obstructions, three ureteric obstructions and two sensory neuropathies). Local recurrence-free, failure-free and overall survival rates at 2.5 years were 68% (95% CI = 52-89), 37% (95% CI = 23-61) and 82% (95% CI = 68-98), respectively. The addition of IORT to radical surgery for T4 or recurrent rectal cancer is feasible. It can be delivered safely with low morbidity and good tumour outcomes. © 2013 The Authors. Journal of Medical Imaging and Radiation Oncology © 2013 The Royal Australian and New Zealand College of Radiologists.

Effect of preoperative treatment strategies on the outcome of patients with clinical T3, non-metastasized rectal cancer: A comparison between Dutch and Canadian expert centers.

PubMed

Breugom, A J; Vermeer, T A; van den Broek, C B M; Vuong, T; Bastiaannet, E; Azoulay, L; Dekkers, O M; Niazi, T; van den Berg, H A; Rutten, H J T; van de Velde, C J H

2015-08-01

High-dose-rate brachytherapy (HDRBT) appears to be associated with less treatment-related toxicity compared with external beam radiotherapy in patients with rectal cancer. The present study compared the effect of preoperative treatment strategies on overall survival, cancer-specific deaths, and local recurrences between a Dutch and Canadian expert center with different preoperative treatment strategies. We included 145 Dutch and 141 Canadian patients with cT3, non-metastasized rectal cancer. All patients from Canada were preoperatively treated with HDRBT. The preoperative treatment strategy for Dutch patients consisted of either no preoperative treatment, short-course radiotherapy, or chemoradiotherapy. Cox proportional hazards models were used to estimate hazard ratios (HR) with 95% confidence intervals (CIs) comparing overall survival. We adjusted for age, cN stage, (y)pT stage, comorbidity, and type of surgery. Primary endpoint was overall survival. Secondary endpoints were cancer-specific deaths and local recurrences. Five-year overall survival was 70.9% (95% CI 62.6%-77.7%) in Dutch patients compared with 86.9% (80.1%-91.6%) in Canadian patients, resulting in an adjusted HR of 0.70 (95% CI 0.39-1.26; p = 0.233). Of 145 Dutch patients, 6.9% (95% CI 2.8%-11.0%) had a local recurrence and 17.9% (95% CI 11.7%-24.2%) patients died of rectal cancer, compared with 4.3% (95% CI 0.9%-7.5%) local recurrences and 10.6% (95% CI 5.5%-15.7%) rectal cancer deaths out of 141 Canadian patients. We did not detect statistically significant differences in overall survival between a Dutch and Canadian expert center with different treatment strategies. This finding needs to be further investigated in a randomized controlled trial. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prevention of colonic neoplasia with polyethylene glycol: A short term randomized placebo-controlled double-blinded trial.

PubMed

Wali, Ramesh K; Bianchi, Laura; Kupfer, Sonia; De La Cruz, Mart; Jovanovic, Borko; Weber, Christopher; Goldberg, Michael J; Rodriguez, L M; Bergan, Raymond; Rubin, David; Tull, Mary Beth; Richmond, Ellen; Parker, Beth; Khan, Seema; Roy, Hemant K

2018-01-01

Chemoprevention represents an attractive modality against colorectal cancer (CRC) although widespread clinical implementation of promising agents (e.g. aspirin/NSAIDS) have been stymied by both suboptimal efficacy and concerns over toxicity. This highlights the need for better agents. Several groups, including our own, have reported that the over-the-counter laxative polyethylene glycol (PEG) has remarkable efficacy in rodent models of colon carcinogenesis. In this study, we undertook the first randomized human trial to address the role of PEG in prevention of human colonic neoplasia. This was a double-blind, placebo-controlled, three-arm trial where eligible subjects were randomized to 8g PEG-3350 (n = 27) or 17g PEG-3350 (n = 24), or placebo (n = 24; maltodextrin) orally for a duration of six months. Our initial primary endpoint was rectal aberrant crypt foci (ACF) but this was changed during protocol period to rectal mucosal epidermal growth factor receptor (EGFR). Of the 87 patients randomized, 48 completed study primary endpoints and rectal EGFR unchanged PEG treatment. Rectal ACF had a trend suggesting potentially reduction with PEG treatment (pre-post change 1.7 in placebo versus -0.3 in PEG 8+ 17g doses, p = 0.108). Other endpoints (proliferation, apoptosis, expression of SNAIL and E-cadherin), previously noted to be modulated in rodent models, appeared unchanged with PEG treatment in this clinical trial. We conclude that PEG was generally well tolerated with the trial failing to meet primary efficacy endpoints. However, rectal ACFs demonstrated a trend (albeit statistically insignificant) for suppression with PEG. Moreover, all molecular assays including EGFR were unaltered with PEG underscoring issues with lack of translatability of biomarkers from preclinical to clinical trials. This data may provide the impetus for future clinical trials on PEG using more robust biomarkers of chemoprevention. ClinicalTrials.gov NCT00828984.

Prevention of colonic neoplasia with polyethylene glycol: A short term randomized placebo-controlled double-blinded trial

PubMed Central

Wali, Ramesh K.; Bianchi, Laura; Kupfer, Sonia; De La Cruz, Mart; Jovanovic, Borko; Weber, Christopher; Goldberg, Michael J.; Rodriguez, L. M.; Bergan, Raymond; Rubin, David; Tull, Mary Beth; Richmond, Ellen; Parker, Beth; Khan, Seema

2018-01-01

Chemoprevention represents an attractive modality against colorectal cancer (CRC) although widespread clinical implementation of promising agents (e.g. aspirin/NSAIDS) have been stymied by both suboptimal efficacy and concerns over toxicity. This highlights the need for better agents. Several groups, including our own, have reported that the over-the-counter laxative polyethylene glycol (PEG) has remarkable efficacy in rodent models of colon carcinogenesis. In this study, we undertook the first randomized human trial to address the role of PEG in prevention of human colonic neoplasia. This was a double-blind, placebo-controlled, three-arm trial where eligible subjects were randomized to 8g PEG-3350 (n = 27) or 17g PEG-3350 (n = 24), or placebo (n = 24; maltodextrin) orally for a duration of six months. Our initial primary endpoint was rectal aberrant crypt foci (ACF) but this was changed during protocol period to rectal mucosal epidermal growth factor receptor (EGFR). Of the 87 patients randomized, 48 completed study primary endpoints and rectal EGFR unchanged PEG treatment. Rectal ACF had a trend suggesting potentially reduction with PEG treatment (pre-post change 1.7 in placebo versus -0.3 in PEG 8+ 17g doses, p = 0.108). Other endpoints (proliferation, apoptosis, expression of SNAIL and E-cadherin), previously noted to be modulated in rodent models, appeared unchanged with PEG treatment in this clinical trial. We conclude that PEG was generally well tolerated with the trial failing to meet primary efficacy endpoints. However, rectal ACFs demonstrated a trend (albeit statistically insignificant) for suppression with PEG. Moreover, all molecular assays including EGFR were unaltered with PEG underscoring issues with lack of translatability of biomarkers from preclinical to clinical trials. This data may provide the impetus for future clinical trials on PEG using more robust biomarkers of chemoprevention. Trial registration: ClinicalTrials.gov NCT00828984 PMID:29617381

Talimogene Laherparepvec, Capecitabine, and Chemoradiation Before Surgery in Treating Patients With Locally Advanced or Metastatic Rectal Cancer

ClinicalTrials.gov

2018-04-30

Rectal Adenocarcinoma; Stage III Rectal Cancer AJCC v7; Stage IIIA Rectal Cancer AJCC v7; Stage IIIB Rectal Cancer AJCC v7; Stage IIIC Rectal Cancer AJCC v7; Stage IV Rectal Cancer AJCC v7; Stage IVA Rectal Cancer AJCC v7; Stage IVB Rectal Cancer AJCC v7

The use of spatial dose gradients and probability density function to evaluate the effect of internal organ motion for prostate IMRT treatment planning

NASA Astrophysics Data System (ADS)

Jiang, Runqing; Barnett, Rob B.; Chow, James C. L.; Chen, Jeff Z. Y.

2007-03-01

The aim of this study is to investigate the effects of internal organ motion on IMRT treatment planning of prostate patients using a spatial dose gradient and probability density function. Spatial dose distributions were generated from a Pinnacle3 planning system using a co-planar, five-field intensity modulated radiation therapy (IMRT) technique. Five plans were created for each patient using equally spaced beams but shifting the angular displacement of the beam by 15° increments. Dose profiles taken through the isocentre in anterior-posterior (A-P), right-left (R-L) and superior-inferior (S-I) directions for IMRT plans were analysed by exporting RTOG file data from Pinnacle. The convolution of the 'static' dose distribution D0(x, y, z) and probability density function (PDF), denoted as P(x, y, z), was used to analyse the combined effect of repositioning error and internal organ motion. Organ motion leads to an enlarged beam penumbra. The amount of percentage mean dose deviation (PMDD) depends on the dose gradient and organ motion probability density function. Organ motion dose sensitivity was defined by the rate of change in PMDD with standard deviation of motion PDF and was found to increase with the maximum dose gradient in anterior, posterior, left and right directions. Due to common inferior and superior field borders of the field segments, the sharpest dose gradient will occur in the inferior or both superior and inferior penumbrae. Thus, prostate motion in the S-I direction produces the highest dose difference. The PMDD is within 2.5% when standard deviation is less than 5 mm, but the PMDD is over 2.5% in the inferior direction when standard deviation is higher than 5 mm in the inferior direction. Verification of prostate organ motion in the inferior directions is essential. The margin of the planning target volume (PTV) significantly impacts on the confidence of tumour control probability (TCP) and level of normal tissue complication probability (NTCP). Smaller margins help to reduce the dose to normal tissues, but may compromise the dose coverage of the PTV. Lower rectal NTCP can be achieved by either a smaller margin or a steeper dose gradient between PTV and rectum. With the same DVH control points, the rectum has lower complication in the seven-beam technique used in this study because of the steeper dose gradient between the target volume and rectum. The relationship between dose gradient and rectal complication can be used to evaluate IMRT treatment planning. The dose gradient analysis is a powerful tool to improve IMRT treatment plans and can be used for QA checking of treatment plans for prostate patients.

The use of spatial dose gradients and probability density function to evaluate the effect of internal organ motion for prostate IMRT treatment planning.

PubMed

Jiang, Runqing; Barnett, Rob B; Chow, James C L; Chen, Jeff Z Y

2007-03-07

The aim of this study is to investigate the effects of internal organ motion on IMRT treatment planning of prostate patients using a spatial dose gradient and probability density function. Spatial dose distributions were generated from a Pinnacle3 planning system using a co-planar, five-field intensity modulated radiation therapy (IMRT) technique. Five plans were created for each patient using equally spaced beams but shifting the angular displacement of the beam by 15 degree increments. Dose profiles taken through the isocentre in anterior-posterior (A-P), right-left (R-L) and superior-inferior (S-I) directions for IMRT plans were analysed by exporting RTOG file data from Pinnacle. The convolution of the 'static' dose distribution D0(x, y, z) and probability density function (PDF), denoted as P(x, y, z), was used to analyse the combined effect of repositioning error and internal organ motion. Organ motion leads to an enlarged beam penumbra. The amount of percentage mean dose deviation (PMDD) depends on the dose gradient and organ motion probability density function. Organ motion dose sensitivity was defined by the rate of change in PMDD with standard deviation of motion PDF and was found to increase with the maximum dose gradient in anterior, posterior, left and right directions. Due to common inferior and superior field borders of the field segments, the sharpest dose gradient will occur in the inferior or both superior and inferior penumbrae. Thus, prostate motion in the S-I direction produces the highest dose difference. The PMDD is within 2.5% when standard deviation is less than 5 mm, but the PMDD is over 2.5% in the inferior direction when standard deviation is higher than 5 mm in the inferior direction. Verification of prostate organ motion in the inferior directions is essential. The margin of the planning target volume (PTV) significantly impacts on the confidence of tumour control probability (TCP) and level of normal tissue complication probability (NTCP). Smaller margins help to reduce the dose to normal tissues, but may compromise the dose coverage of the PTV. Lower rectal NTCP can be achieved by either a smaller margin or a steeper dose gradient between PTV and rectum. With the same DVH control points, the rectum has lower complication in the seven-beam technique used in this study because of the steeper dose gradient between the target volume and rectum. The relationship between dose gradient and rectal complication can be used to evaluate IMRT treatment planning. The dose gradient analysis is a powerful tool to improve IMRT treatment plans and can be used for QA checking of treatment plans for prostate patients.

Genetic Mutations in Blood and Tissue Samples in Predicting Response to Treatment in Patients With Locally Advanced Rectal Cancer Undergoing Chemoradiation

ClinicalTrials.gov

2017-09-08

Mucinous Adenocarcinoma of the Rectum; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Rectum; Stage IIA Rectal Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage IIIA Rectal Cancer; Stage IIIB Rectal Cancer; Stage IIIC Rectal Cancer

NRG Oncology Radiation Therapy Oncology Group 0822: A Phase 2 Study of Preoperative Chemoradiation Therapy Using Intensity Modulated Radiation Therapy in Combination With Capecitabine and Oxaliplatin for Patients With Locally Advanced Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hong, Theodore S., E-mail: tshong1@mgh.harvard.edu; Moughan, Jennifer; Garofalo, Michael C.

Purpose: To evaluate the rate of gastrointestinal (GI) toxicity of neoadjuvant chemoradiation with capecitabine, oxaliplatin, and intensity modulated radiation therapy (IMRT) in cT3-4 rectal cancer. Methods and Materials: Patients with localized, nonmetastatic T3 or T4 rectal cancer <12 cm from the anal verge were enrolled in a prospective, multi-institutional, single-arm study of preoperative chemoradiation. Patients received 45 Gy with IMRT in 25 fractions, followed by a 3-dimensional conformal boost of 5.4 Gy in 3 fractions with concurrent capecitabine/oxaliplatin (CAPOX). Surgery was performed 4 to 8 weeks after the completion of therapy. Patients were recommended to receive FOLFOX chemotherapy after surgery. The primary endpoint ofmore » the study was acute grade 2 to 5 GI toxicity. Seventy-one patients provided 80% probability to detect at least a 12% reduction in the specified GI toxicity with the treatment of CAPOX and IMRT, at a significance level of .10 (1-sided). Results: Seventy-nine patients were accrued, of whom 68 were evaluable. Sixty-one patients (89.7%) had cT3 disease, and 37 (54.4%) had cN (+) disease. Postoperative chemotherapy was given to 42 of 68 patients. Fifty-eight patients had target contours drawn per protocol, 5 patients with acceptable variation, and 5 patients with unacceptable variations. Thirty-five patients (51.5%) experienced grade ≥2 GI toxicity, 12 patients (17.6%) experienced grade 3 or 4 diarrhea, and pCR was achieved in 10 patients (14.7%). With a median follow-up time of 3.98 years, the 4-year rate of locoregional failure was 7.4% (95% confidence interval [CI]: 1.0%-13.7%). The 4-year rates of OS and DFS were 82.9% (95% CI: 70.1%-90.6%) and 60.6% (95% CI: 47.5%-71.4%), respectively. Conclusion: The use of IMRT in neoadjuvant chemoradiation for rectal cancer did not reduce the rate of GI toxicity.« less

Chlamydial Proctitis in a Young Man Who Has Sex with Men: Misdiagnosed as Inflammatory Bowel Disease.

PubMed

Lee, Kyung Jin; Kim, Jaeyeon; Shin, Dong Hwan; Jung, Jun Oh; Koh, Seokyoung; Kim, Ka Young; Lee, Jae Min

2015-12-01

We report the case of a 20-year-old man with a 2-month history of anal pain and bloody rectal discharge. He was referred to our clinic of gastroenterology for suspected inflammatory bowel disease (IBD). The colonoscopy showed mucosal nodularities on the rectum and an anal tag. Because the colonoscopic findings were not consistent with the typical manifestations of IBD, we took an additional sexual history and performed studies for infectious proctitis, including serologic tests for Chlamydia trachomatis, Neisseria gonorrhoeae, and Treponema pallidum. He had homosexual experience, and the serologic tests and PCR of a rectal swab were positive for C. trachomatis infection. Finally he was diagnosed as having chlamydial proctitis and was treated with intramuscular ceftriaxone 250 mg in a single dose and doxycycline 100 mg orally twice daily for 7 days. After 2 months, he had no lower abdominal symptoms and his endoscopic findings were improved.

Lubiprostone induced ischemic colitis

PubMed Central

Sherid, Muhammed; Sifuentes, Humberto; Samo, Salih; Deepak, Parakkal; Sridhar, Subbaramiah

2013-01-01

Ischemic colitis accounts for 6%-18% of the causes of acute lower gastrointestinal bleeding. It is often multifactorial and more commonly encountered in the elderly. Several medications have been implicated in the development of colonic ischemia. We report a case of a 54-year old woman who presented with a two-hour history of nausea, vomiting, abdominal pain, and bloody stool. The patient had recently used lubiprostone with close temporal relationship between the increase in the dose and her symptoms of rectal bleeding. The radiologic, colonoscopic and histopathologic findings were all consistent with ischemic colitis. Her condition improved without any serious complications after the cessation of lubiprostone. This is the first reported case of ischemic colitis with a clear relationship with lubiprostone (Naranjo score of 10). Clinical vigilance for ischemic colitis is recommended for patients receiving lubiprostone who are presenting with abdominal pain and rectal bleeding. PMID:23345954

Magnetic Resonance-guided Inter-fraction Monitoring Opens Doors to Delivering Safer Reirradiation: An Illustrative Case Report and Discussion

PubMed Central

Cao, Minsong; Lee, Percy; Steinberg, Michael L.; Lamb, James; Raldow, Ann C

2018-01-01

Locoregional recurrence in the pelvis after definitive treatment for rectal cancer can lead to significant morbidity. Furthermore, the toxicity associated with reirradiation may also negatively impact the quality of life and even survival. Here we present the case of a 39-year-old male with locoregionally recurrent rectal cancer in a left pelvic sidewall lymph node, treated with stereotactic magnetic resonance (MR)-guided ablative radiotherapy after previously receiving long-course chemoradiation that had already exceeded ideal bowel dose constraints. We discuss the distinct advantages of MR-guidance in the setting of pelvic reirradiation, particularly with regard to inter- and intra-fraction visualization of the target and neighboring bowel anatomy. In this context, MR-guidance may allow radiation oncologists to increase target precision and accuracy, while simultaneously decreasing toxicity to neighboring tissues. PMID:29922520

A novel transanal tube designed to prevent anastomotic leakage after rectal cancer surgery: the WING DRAIN.

PubMed

Nishigori, Hideaki; Ito, Masaaki; Nishizawa, Yuji

2017-04-01

We introduce a novel transanal tube (TAT), named the "WING DRAIN", designed to prevent anastomotic leakage after rectal cancer surgery, and report the fundamental experiments that led to its development. We performed the basic experiments to evaluate the effect of TATs on intestinal decompression, the changes they make in patterns of watery fluid drainage, the changes in their decompression effect when the extension tube connecting the TAT to the collection bag fills with watery drainage fluid, and the variations in intestinal contact and crushing pressure made by some types of TAT. Any type of TAT contributed to decompression in the intestinal tract. Watery drainage commenced from when the water level first rose to the hole in the tip of drain. The intestinal pressure increased with the length of the vertical twist in an extension tube. The crushing pressures of most types of TAT were high enough to cause injury to the intestine. We resolved the problems using an existing TAT for the purpose of intestinal decompression and by creating the first specialized TAT designed to prevent anastomotic leakage after rectal cancer surgery in Japan.

Understanding post-operative temperature drop in cardiac surgery: a mathematical model.

PubMed

Tindall, M J; Peletier, M A; Severens, N M W; Veldman, D J; de Mol, B A J M

2008-12-01

A mathematical model is presented to understand heat transfer processes during the cooling and re-warming of patients during cardiac surgery. Our compartmental model is able to account for many of the qualitative features observed in the cooling of various regions of the body including the central core containing the majority of organs, the rectal region containing the intestines and the outer peripheral region of skin and muscle. In particular, we focus on the issue of afterdrop: a drop in core temperature following patient re-warming, which can lead to serious post-operative complications. Model results for a typical cooling and re-warming procedure during surgery are in qualitative agreement with experimental data in producing the afterdrop effect and the observed dynamical variation in temperature between the core, rectal and peripheral regions. The influence of heat transfer processes and the volume of each compartmental region on the afterdrop effect is discussed. We find that excess fat on the peripheral and rectal regions leads to an increase in the afterdrop effect. Our model predicts that, by allowing constant re-warming after the core temperature has been raised, the afterdrop effect will be reduced.

Acceptability and Preferences for Hypothetical Rectal Microbicides among a Community Sample of Young Men Who Have Sex with Men and Transgender Women in Thailand: A Discrete Choice Experiment.

PubMed

Newman, Peter A; Cameron, Michael P; Roungprakhon, Surachet; Tepjan, Suchon; Scarpa, Riccardo

2016-11-01

Rectal microbicides (RMs) may offer substantial benefits in expanding HIV prevention options for key populations. From April to August 2013, we conducted Tablet-Assisted Survey Interviewing, including a discrete choice experiment, with participants recruited from gay entertainment venues and community-based organizations in Chiang Mai and Pattaya, Thailand. Among 408 participants, 74.5 % were young men who have sex with men, 25.5 % transgender women, with mean age = 24.3 years. One-third (35.5 %) had ≤9th grade education; 63.4 % engaged in sex work. Overall, 83.4 % reported they would definitely use a RM, with more than 2-fold higher odds of choice of a RM with 99 versus 50 % efficacy, and significantly higher odds of choosing gel versus suppository, intermittent versus daily dosing, and prescription versus over-the-counter. Sex workers were significantly more likely to use a RM immediately upon availability, with greater tolerance for moderate efficacy and daily dosing. Engaging key populations in assessing RM preferences may support biomedical research and evidence-informed interventions to optimize the effectiveness of RMs in HIV prevention.

Rectal mucosal electrosensitivity - what is being tested?

PubMed

Meagher, A P; Kennedy, M L; Lubowski, D Z

1996-01-01

The results of rectal mucosal electrosensitivity (RME) testing have been used to support theories regarding the aetiology of both idiopathic constipation and bowel dysfunction following rectopexy. The aim of this study was to assess the validity of tests of RME. Sixty-eight patients, comprising three groups (group 1: 50 patients undergoing assessment in the Anorectal Physiology Unit, group 2: 10 patients with coloanal or ileoanal anastomosis, group 3: 8 patients with a stoma) underwent mucosal electrosensitivity testing, with the threshold stimulus required to elicit sensation being recorded. In addition the RME was measured in groups 1 and 2 when placing the electrode, mounted on a catheter with a central wire, against the anterior, posterior, right and left rectal or neorectal walls. To asses the influence on this test of loss of mucosal contact due to faeces, a further 8 cases with a normal rectum had RME performed with and without a layer of water soaked gauze around the electrode to stimulate faeces and prevent the electrode from making contact with the rectal mucosa. There was marked variance in the sensitivity of the different regions of rectal wall tested (P < 0.001). In group 1 patients the mean sensitivities were: central 36.6 mA, anterior 27.4 mA, posterior 37.9 mA, right 22.3 mA and left 25.6 mA. This circumferential variation suggests that the pelvic floor rather than rectal mucosa was being stimulated. All patients in group 2 had recordable sensitivities, and the mean sensitivity threshold was significantly higher than group 1 patients in the central (P = 0.03), right (P = 0.03) and left (P = 0.007) positions. In group 3 the sensitivity was greater within the stoma at the level of the abdominal wall muscle than intra-abdominally or subcutaneously, again suggesting an extra-colonic origin of the sensation. The sensitivity threshold was significantly greater with the electrode wrapped in gauze (P < 0.01), and loss of mucosal contact was not detected by the EMG machine. Therefore RME testing would seem not to measure mucosal sensitivity, and is probably influenced by the presence of faeces.

Temporal artery thermometry in children younger than 5 years: a comparison with rectal thermometry.

PubMed

Odinaka, Kelechi K; Edelu, Benedict O; Nwolisa, Charles E; Amamilo, Ifeyinwa B; Okolo, Seline N

2014-12-01

Temporal artery (TA) thermometry has come as one of the new methods for temperature measurement, especially in children in whom accurate temperature monitoring can save lives. The device which is convenient and simple to use is yet to gain popularity in several parts of the world, as there are conflicting reports of its accuracy. This study compares the accuracy of the TA thermometry in children younger than 5 years using the rectal thermometry as the gold standard. Temperature was measured simultaneously in eligible children younger than 5 years from the forehead and rectum using the TA thermometer (TAT-2000C Exergen, USA) and standard mercury in glass rectal thermometer, respectively. The difference between the mean temperatures obtained by the 2 thermometry methods was tested using the paired t test. Pearson correlation coefficient, linear regression, and Bland-Altman plot were also used to test the relationship and agreement between the 2 instruments. The sensitivity, specificity, and positive and negative predictive values were also calculated. Overall, the mean TA temperature (37.80°C ± 1.07°C) was significantly lower than the mean rectal temperature (38.07°C ± 0.95°C), P < 0.001. In neonates, however, the mean difference was not significant, 0.02 ± 0.59 (P = 0.810). There was a significant positive correlation between the rectal and the temporal temperatures (r = 0.80, P < 0.01). The Bland-Altman plot showed wide variation in the limit of agreement between the rectal and the TA temperatures which ranged from -1.02°C to +1.56°C. The sensitivity of the TA thermometer was 64.6% and 83.5%, respectively, at a TA fever cutoff of 38.0°C and 37.7°C. Temporal artery thermometer is not accurate enough for the measurement of core body temperature in children younger than 5 years. However, it may be used as a tool for screening for fever in very busy clinics and emergency room at a fever cutoff of 37.7°C.

Nightly high dose lactulose infusion could be a cost-effective treatment for hepatic encephalopathy, renal insufficiency and heart failure.

PubMed

Alisky, Joseph Martin

2007-01-01

Lactulose is an established remedy for hepatic encephalopathy and shows efficacy for chronic renal insufficiency, reducing volume overload, uremia and hyperkalemia. Potentially lactulose could also be used for non-diuretic treatment of congestive heart failure. However, use of lactulose is limited by diarrhea and flatulence. Chronic lactulose administration might be tolerable if it was accomplished by nocturnal infusion through a percutaneous duodenostomy tube, also placing a rectal foley each night following a clearing enema so that large volumes of liquid stool could be passed while patients sleep. Each morning the duodenostomy would be clamped and the foley removed. For acute patients without duodenostomies, a temporary dobhoff feeding tube with accompanying rectal foley could be employed. Patients who did not want a rectal foley could elect to have a permanent colostomy. Clinical trials could establish the relationship between lactulose infusion and clearance of water, salt, potassium, hydrogen, urea and other wastes, and compare efficacy, cost and tolerability with that of peritoneal dialysis and ultrafiltration. Lactulose could potentially allow inexpensive home-based therapy for hepatic encephalopathy, chronic renal failure and congestive heart failure, and might be life-saving in countries where renal replacement in any form is currently unavailable.

Piperine impairs cell cycle progression and causes reactive oxygen species-dependent apoptosis in rectal cancer cells.

PubMed

Yaffe, Paul B; Doucette, Carolyn D; Walsh, Mark; Hoskin, David W

2013-02-01

Piperine, an alkaloid phytochemical found in the fruit of black and long pepper plants, is reported to inhibit the growth of cancer cells; however, the mechanism of action in human cancer cells is not clear. In this study we investigated the effect of piperine on the growth of HRT-18 human rectal adenocarcinoma cells. MTT assays showed that piperine inhibited the metabolic activity of HRT-18 cells in a dose- and time-dependent fashion, suggesting a cytostatic and/or cytotoxic effect. Flow cytometric analysis of Oregon Green 488-stained and propidium iodide-stained HRT-18 cells showed that piperine inhibited cell cycle progression. Piperine also caused HRT-18 cells to die by apoptosis, as determined by Annexin-V-FLUOS staining and characteristic changes in cell morphology. Flow cytometric analysis of dihydroethidium- and 2',7'-dichlorofluorescein diacetate-stained HRT-18 cells showed increased production of reactive oxygen species in piperine-treated cells. Furthermore, the antioxidant N-acetylcysteine reduced apoptosis in cultures of piperine-treated HRT-18 cells, indicating that piperine-induced cytotoxicity was mediated at least in part by reactive oxygen species. The cytostatic and cytotoxic effects of piperine on rectal cancer cells suggest that this dietary phytochemical may be useful in cancer treatment. Copyright © 2012 Elsevier Inc. All rights reserved.

Irradiation with protons for the individualized treatment of patients with locally advanced rectal cancer: a planning study with clinical implications.

PubMed

Wolff, Hendrik Andreas; Wagner, Daniela Melanie; Conradi, Lena-Christin; Hennies, Steffen; Ghadimi, Michael; Hess, Clemens Friedrich; Christiansen, Hans

2012-01-01

Ongoing clinical trials aim to improve local control and overall survival rates by intensification of therapy regimen for patients with locally advanced rectal cancer. It is well known that whenever treatment is intensified, risk of therapy-related toxicity rises. An irradiation with protons could possibly present an approach to solve this dilemma by lowering the exposure to the organs-at-risk (OAR) without compromising tumor response. Twenty five consecutive patients were treated from 04/2009 to 5/2010. For all patients, four different treatment plans including protons, RapidArc, IMRT and 3D-conformal-technique were retrospectively calculated and analyzed according to dosimetric aspects. Detailed DVH-analyses revealed that protons clearly reduced the dose to the OAR and entire normal tissue when compared to other techniques. Furthermore, the conformity index was significantly better and target volumes were covered consistent with the ICRU guidelines. Planning results suggest that treatment with protons can improve the therapeutic tolerance for the irradiation of rectal cancer, particularly for patients scheduled for an irradiation with an intensified chemotherapy regimen and identified to be at high risk for acute therapy-related toxicity. However, clinical experiences and long-term observation are needed to assess tumor response and related toxicity rates. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

[Hospital variation in anastomotic leakage after rectal cancer surgery in the Spanish Association of Surgeons project: The contribution of hospital volume].

PubMed

Ortiz, Héctor; Biondo, Sebastiano; Codina, Antonio; Ciga, Miguel Á; Enríquez-Navascués, José; Espín, Eloy; García-Granero, Eduardo; Roig, José Vicente

2016-04-01

This multicentre observational study aimed to determine the anastomotic leak rate in the hospitals included in the Rectal Cancer Project of the Spanish Society of Surgeons and examine whether hospital volume may contribute to any variation between hospitals. Hospital variation was quantified using a multilevel approach on prospective data derived from the multicentre database of all adenocarcinomas of the rectum operated by an anterior resection at 84 surgical departments from 2006 to 2013. The following variables were included in the analysis; demographics, American Society of Anaesthesiologists classification, use of defunctioning stoma, tumour location and stage, administration of neoadjuvant treatment, and annual volume of elective surgical procedures. A total of 7231 consecutive patients were included. The rate of anastomotic leak was 10.0%. Stratified by annual surgical volume hospitals varied from 9.9 to 11.3%. In multilevel regression analysis, the risk of anastomotic leak increased in male patients, in patients with tumours located below 12 cm from the anal verge, and advanced tumour stages. However, a defunctioning stoma seemed to prevent this complication. Hospital surgical volume was not associated with anastomotic leak (OR: 0.852, [0.487-1.518]; P=.577). Furthermore, there was a statistically significant variation in anastomotic leak between all departments (MOR: 1.475; [1.321-1.681]; P<0.001). Anastomotic leak varies significantly among hospitals included in the project and this difference cannot be attributed to the annual surgical volume. Copyright © 2015 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Heat-Related Illnesses

DTIC Science & Technology

1988-04-01

factors, thermometry, and fever versus hyper- thernia. ihe review of heat illnesses includes heat "anps, heat edema, heat syncope, heat exhaustiom...clinical situations. For example, fever , the daily circadian rhythm of temperature variation, and the 0.50 C difference in rectal temperature following...thermometry is state of the art. Fever versus Hyperthermia Elevations of body temperature can occur as a result of several different mechanisms. One

Megacystis - microcolon - intestinal hypoperistalsis syndrome.

PubMed

Goldberg, M; Pruchniewski, D; Beale, P G; Da Fonseca, J M; Davies, M R

1996-04-01

Two non-related female neonates with the megacystis-microcolon-intestinal hypoperistalsis syndrome are described. One presented with a family history of a similar condition. In one child no intestinal peristalsis was observed, while in the other decreased peristalsis with occasional rectal evacuation occurred. Both had fatal outcomes. These two cases demonstrate the wide variation in the clinical course of this rare and fatal syndrome.

Late Fecal Incontinence After High-Dose Radiotherapy for Prostate Cancer: Better Prediction Using Longitudinal Definitions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fiorino, Claudio, E-mail: fiorino.claudio@hsr.it; Rancati, Tiziana; Fellin, Gianni

2012-05-01

Purpose: To model late fecal incontinence after high-dose prostate cancer radiotherapy (RT) in patients accrued in the AIROPROS (prostate working group of the Italian Association of Radiation Oncology) 0102 trial using different endpoint definitions. Methods and Materials: The self-reported questionnaires (before RT, 1 month after RT, and every 6 months for {<=}3 years after RT) of 586 patients were available. The peak incontinence (P{sub I}NC) and two longitudinal definitions (chronic incontinence [C{sub I}NC], defined as the persistence of Grade 1 or greater incontinence after any Grade 2-3 event; and mean incontinence score [M{sub I}NC], defined as the average score duringmore » the 3-year period after RT) were considered. The correlation between the clinical/dosimetric parameters (including rectal dose-volume histograms) and P{sub I}NC (Grade 2 or greater), C{sub I}NC, and M{sub I}NC of {>=}1 were investigated using multivariate logistic analyses. Receiver operating characteristic curves and the area under the curve were used to assess the predictive value of the different multivariate models. Results: Of the 586 patients, 36 with a Grade 1 or greater incontinence score before RT were not included in the present analysis. Of the 550 included patients, 197 (35.8%) had at least one control with a Grade 1 or greater incontinence score (M{sub I}NC >0). Of these 197 patients, 37 (6.7%), 22 (4.0%), and 17 (3.1%) were scored as having P{sub I}NC, M{sub I}NC {>=}1, and C{sub I}NC, respectively. On multivariate analysis, Grade 2 or greater acute incontinence was the only predictor of P{sub I}NC (odds ratio [OR], 5.9; p = .0009). Grade 3 acute incontinence was predictive of C{sub I}NC (OR, 9.4; p = .02), and percentage of the rectal volume receiving >40 Gy of {>=}80% was predictive of a M{sub I}NC of {>=}1 (OR, 3.8; p = .008) and of C{sub I}NC (OR, 3.6; p = .03). Previous bowel disease, previous abdominal/pelvic surgery, and the use of antihypertensive (protective factor) correlated highly with both C{sub I}NC and M{sub I}NC {>=}1. The predictive values of the models for C{sub I}NC (area under the curve, 0.83) and M{sub I}NC {>=}1 (area under the curve, 0.73) were greater than the ones for P{sub I}NC (area under the curve, 0.62) and more reliable (p = .0001-.0003 against p = .02). Nomograms for the two longitudinal definitions were derived. Conclusions: The longitudinal definitions of fecal incontinence (C{sub I}NC and M{sub I}NC {>=}1) were helpful in accounting for both the persistence and the severity of the incontinence. A significant fraction of peak events was consequential to acute incontinence, and a longer duration of symptoms mainly depended on the rectal dose bath (percentage of rectal volume receiving >40 Gy), and pretreatment clinical factors.« less

Subchronic (26- and 52-week) toxicity and irritation studies of a novel microbicidal gel formulation containing sodium lauryl sulfate in animal models.

PubMed

Piret, Jocelyne; Laforest, Geneviève; Bussières, Martin; Bergeron, Michel G

2008-03-01

The safety of an ethylene oxide/propylene oxide gel formulation containing sodium lauryl sulfate (2%, w/w), that could be a potent candidate as a topical microbicide, has been evaluated. More specifically, the subchronic (26- and 52-week) toxicity of the formulation when applied intravaginally as well as its irritating potential for the rectal, penile, eye, skin and buccal mucosa have been examined in animal models. The results showed that the vaginal administration of the gel formulation containing sodium lauryl sulfate once and twice daily (with doses 12 +/- 2 h apart) for 26 weeks to rats and for 52 weeks to rabbits induced slight to moderate histopathological alterations. When the formulation was applied intrarectally to male and female rabbits once and twice daily (with doses 12 +/- 2 h apart) for 14 days, no macroscopic or microscopic changes were reported. For both vaginal and rectal dosing, no effect was seen on the haematology, coagulation and serum chemistry parameters as well as on the body weight of animals and the relative organ weights. Other sporadic macroscopic and histopathological findings were incidental in origin and of no toxicological significance. The gel formulation containing sodium lauryl sulfate was considered as mildly irritating for the penile mucosa of rabbits, non-irritating for the eye of rabbits, mildly irritating for the skin in a rabbit model and non-irritating for the hamster cheek pouch. It is suggested that the gel formulation containing sodium lauryl sulfate is safe for most tissues that could be exposed to the product under normal use.

Plasma and cerebrospinal fluid pharmacokinetic parameters after single-dose administration of intravenous, oral, or rectal acetaminophen.

PubMed

Singla, Neil K; Parulan, Cherri; Samson, Roselle; Hutchinson, Joel; Bushnell, Rick; Beja, Evelyn G; Ang, Robert; Royal, Mike A

2012-09-01

This is the first study to compare plasma and cerebrospinal fluid (CSF) pharmacokinetics of intravenous (IV), oral (PO), or rectal (PR) formulations of acetaminophen. Healthy male subjects (N = 6) were randomized to receive a single dose of IV (OFIRMEV(®) ; Cadence) 1,000 mg (15 minute infusion), PO (2 Tylenol(®) 500 mg caplets; McNeil Consumer Healthcare), or PR acetaminophen (2 Feverall(®) 650 mg suppositories; Actavis) with a 1-day washout period between doses. The 1,300 mg PR concentrations were standardized to 1,000 mg. Acetaminophen plasma and CSF levels were obtained at T0, 0.25, 0.5, 0.75, 1, 2, 3, 4, and 6 hours. IV acetaminophen showed earlier and higher plasma and CSF levels compared with PO or PR administration. CSF bioavailability over 6 hours (AUC(0-6)) for IV, PO, and PR 1 g was 24.9, 14.2, and 10.3 μg·h/mL, respectively. No treatment-related adverse events were reported. One subject was replaced because of premature failure of his lumbar spinal catheter. The mean CSF level in the IV group was similar to plasma from 3 to 4 hours and higher from 4 hours on. Absorption phase, variability in plasma, and CSF were greater in PO and PR groups than variability with IV administration. These results demonstrate that earlier and greater CSF penetration occurs as a result of the earlier and higher plasma peak with IV administration compared with PO or PR. © 2012 Lotus Clinical Research, LLC. Pain Practice © 2012 World Institute of Pain.

Erlotinib Hydrochloride in Treating Patients With Stage I-III Colorectal Cancer or Adenoma

ClinicalTrials.gov

2014-12-22

Adenomatous Polyp; Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage I Colon Cancer; Stage I Rectal Cancer; Stage IIA Colon Cancer; Stage IIA Rectal Cancer; Stage IIB Colon Cancer; Stage IIB Rectal Cancer; Stage IIC Colon Cancer; Stage IIC Rectal Cancer; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer

Randomised clinical trial: a phase 1, dose-ranging study of the anti-matrix metalloproteinase-9 monoclonal antibody GS-5745 versus placebo for ulcerative colitis.

PubMed

Sandborn, W J; Bhandari, B R; Fogel, R; Onken, J; Yen, E; Zhao, X; Jiang, Z; Ge, D; Xin, Y; Ye, Z; French, D; Silverman, J A; Kanwar, B; Subramanian, G M; McHutchison, J G; Lee, S D; Shackelton, L M; Pai, R K; Levesque, B G; Feagan, B G

2016-07-01

Matrix metalloproteinase-9 is a proteolytic enzyme whose expression is increased in ulcerative colitis. To evaluate the safety and efficacy of GS-5745, a fully humanised anti-matrix metalloproteinase-9 monoclonal antibody, in moderately-to-severely active ulcerative colitis. We randomised 74 patients with ulcerative colitis to treatment with single or multiple ascending intravenous or subcutaneous doses of GS-5745 or placebo. Multiple-dose cohorts received either IV infusions (0.3, 1.0, 2.5 or 5.0 mg/kg GS-5745 or placebo) every 2 weeks (three total IV infusions) or five weekly SC injections (150 mg GS-5745 or placebo). The primary outcomes were the safety, tolerability and pharmacokinetics of escalating single and multiple doses of GS-5745. Exploratory analyses in the multiple-dose cohorts included clinical response (≥3 points or 30% decrease from baseline in Mayo Clinic score and ≥1 point decrease in the rectal bleeding subscore or a rectal bleeding subscore ≤1) and clinical remission (a complete Mayo Clinic score ≤2 with no subscore >1) at Day 36. Biological effects associated with a clinical response to GS-5745 were explored using histological and molecular approaches. Twenty-three of the 42 patients (55%) receiving multiple doses of GS-5745 had adverse events, compared with 5/8 patients (63%) receiving placebo. GS-5745 showed target-mediated drug disposition, approximately dose-proportional increases in maximum plasma concentration and more than dose-proportional increases in the area under the plasma drug concentration-time curve. Clinical response occurred in 18/42 patients (43%) receiving GS-5745 compared with 1/8 patients (13%) receiving placebo. Clinical remission occurred in 6/42 patients (14%) receiving GS-5745 and 0/8 (0%) receiving placebo. Patients with a clinical response to GS-5745 had reductions in matrix metalloproteinase-9 tissue levels (mean 48.9% decrease from baseline compared with a mean 18.5% increase in nonresponders, P = 0.008) significant improvements in histopathology scores (confirmed with three separate histological disease activity indices), as well as changes in colonic gene expression that were consistent with reduced inflammation. This phase 1 trial provides preliminary evidence for the safety and therapeutic potential of GS-5745 in the treatment of ulcerative colitis. © 2016 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

Intensity Modulated Radiation Therapy Dose Painting for Localized Prostate Cancer Using {sup 11}C-choline Positron Emission Tomography Scans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, Joe H.; University of Melbourne, Victoria; Lim Joon, Daryl

Purpose: To demonstrate the technical feasibility of intensity modulated radiation therapy (IMRT) dose painting using {sup 11}C-choline positron emission tomography PET scans in patients with localized prostate cancer. Methods and Materials: This was an RT planning study of 8 patients with prostate cancer who had {sup 11}C-choline PET scans prior to radical prostatectomy. Two contours were semiautomatically generated on the basis of the PET scans for each patient: 60% and 70% of the maximum standardized uptake values (SUV{sub 60%} and SUV{sub 70%}). Three IMRT plans were generated for each patient: PLAN{sub 78}, which consisted of whole-prostate radiation therapy to 78more » Gy; PLAN{sub 78-90}, which consisted of whole-prostate RT to 78 Gy, a boost to the SUV{sub 60%} to 84 Gy, and a further boost to the SUV{sub 70%} to 90 Gy; and PLAN{sub 72-90}, which consisted of whole-prostate RT to 72 Gy, a boost to the SUV{sub 60%} to 84 Gy, and a further boost to the SUV{sub 70%} to 90 Gy. The feasibility of these plans was judged by their ability to reach prescription doses while adhering to published dose constraints. Tumor control probabilities based on PET scan-defined volumes (TCP{sub PET}) and on prostatectomy-defined volumes (TCP{sub path}), and rectal normal tissue complication probabilities (NTCP) were compared between the plans. Results: All plans for all patients reached prescription doses while adhering to dose constraints. TCP{sub PET} values for PLAN{sub 78}, PLAN{sub 78-90}, and PLAN{sub 72-90} were 65%, 97%, and 96%, respectively. TCP{sub path} values were 71%, 97%, and 89%, respectively. Both PLAN{sub 78-90} and PLAN{sub 72-90} had significantly higher TCP{sub PET} (P=.002 and .001) and TCP{sub path} (P<.001 and .014) values than PLAN{sub 78}. PLAN{sub 78-90} and PLAN{sub 72-90} were not significantly different in terms of TCP{sub PET} or TCP{sub path}. There were no significant differences in rectal NTCPs between the 3 plans. Conclusions: IMRT dose painting for localized prostate cancer using {sup 11}C-choline PET scans is technically feasible. Dose painting results in higher TCPs without higher NTCPs.« less

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions

PubMed Central

Zeng, Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A.; Trofimov, Alexei

2013-01-01

Purpose: Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. Methods: For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor control probability (TCP) and normal tissue complication probability (NTCP). To assess potential local RBE variations, LET distributions were calculated with Monte Carlo, and compared for different plans. The results were assessed in terms of their sensitivity to uncertainties in model parameters and delivery. Results: IFD courses included equal number of fractions boosting either hemisphere, thus, the combined physical dose was close to uniform throughout the prostate. However, for the entire course, the prostate EUD in IFD was higher than in conventional FTP by up to 14%, corresponding to the estimated increase in TCP to 96% from 88%. The extent of gain depended on the mixing factor, i.e., relative weights used to combine FTP and STP spot weights. Increased weighting of STP typically yielded a higher target EUD, but also led to increased sensitivity of dose to variations in the proton's range. Rectal and bladder EUD were same or lower (per normalization), and the NTCP for both remained below 1%. The LET distributions in IFD also depended strongly on the mixing weights: plans using higher weight of STP spots yielded higher LET, indicating a potentially higher local RBE. Conclusions: In proton therapy delivered by pencil beam scanning, improved therapeutic outcome can potentially be expected with delivery of IFD distributions, while administering the prescribed quasi-uniform dose to the target over the entire course. The biological effectiveness of IFD may be further enhanced by optimizing the LET distributions. IFD distributions are characterized by a dose gradient located in proximity of the prostate's midplane, thus, the fidelity of delivery would depend crucially on the precision with which the proton range could be controlled. PMID:23635256

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions.

PubMed

Zeng, Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A; Trofimov, Alexei

2013-05-01

Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor control probability (TCP) and normal tissue complication probability (NTCP). To assess potential local RBE variations, LET distributions were calculated with Monte Carlo, and compared for different plans. The results were assessed in terms of their sensitivity to uncertainties in model parameters and delivery. IFD courses included equal number of fractions boosting either hemisphere, thus, the combined physical dose was close to uniform throughout the prostate. However, for the entire course, the prostate EUD in IFD was higher than in conventional FTP by up to 14%, corresponding to the estimated increase in TCP to 96% from 88%. The extent of gain depended on the mixing factor, i.e., relative weights used to combine FTP and STP spot weights. Increased weighting of STP typically yielded a higher target EUD, but also led to increased sensitivity of dose to variations in the proton's range. Rectal and bladder EUD were same or lower (per normalization), and the NTCP for both remained below 1%. The LET distributions in IFD also depended strongly on the mixing weights: plans using higher weight of STP spots yielded higher LET, indicating a potentially higher local RBE. In proton therapy delivered by pencil beam scanning, improved therapeutic outcome can potentially be expected with delivery of IFD distributions, while administering the prescribed quasi-uniform dose to the target over the entire course. The biological effectiveness of IFD may be further enhanced by optimizing the LET distributions. IFD distributions are characterized by a dose gradient located in proximity of the prostate's midplane, thus, the fidelity of delivery would depend crucially on the precision with which the proton range could be controlled.

Statistical modeling of interfractional tissue deformation and its application in radiation therapy planning

NASA Astrophysics Data System (ADS)

Vile, Douglas J.

In radiation therapy, interfraction organ motion introduces a level of geometric uncertainty into the planning process. Plans, which are typically based upon a single instance of anatomy, must be robust against daily anatomical variations. For this problem, a model of the magnitude, direction, and likelihood of deformation is useful. In this thesis, principal component analysis (PCA) is used to statistically model the 3D organ motion for 19 prostate cancer patients, each with 8-13 fractional computed tomography (CT) images. Deformable image registration and the resultant displacement vector fields (DVFs) are used to quantify the interfraction systematic and random motion. By applying the PCA technique to the random DVFs, principal modes of random tissue deformation were determined for each patient, and a method for sampling synthetic random DVFs was developed. The PCA model was then extended to describe the principal modes of systematic and random organ motion for the population of patients. A leave-one-out study tested both the systematic and random motion model's ability to represent PCA training set DVFs. The random and systematic DVF PCA models allowed the reconstruction of these data with absolute mean errors between 0.5-0.9 mm and 1-2 mm, respectively. To the best of the author's knowledge, this study is the first successful effort to build a fully 3D statistical PCA model of systematic tissue deformation in a population of patients. By sampling synthetic systematic and random errors, organ occupancy maps were created for bony and prostate-centroid patient setup processes. By thresholding these maps, PCA-based planning target volume (PTV) was created and tested against conventional margin recipes (van Herk for bony alignment and 5 mm fixed [3 mm posterior] margin for centroid alignment) in a virtual clinical trial for low-risk prostate cancer. Deformably accumulated delivered dose served as a surrogate for clinical outcome. For the bony landmark setup subtrial, the PCA PTV significantly (p<0.05) reduced D30, D20, and D5 to bladder and D50 to rectum, while increasing rectal D20 and D5. For the centroid-aligned setup, the PCA PTV significantly reduced all bladder DVH metrics and trended to lower rectal toxicity metrics. All PTVs covered the prostate with the prescription dose.

SU-C-BRD-06: Results From a 5 Patient in Vivo Rectal Wall Dosimetry Study Using Plastic Scintillation Detectors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wootton, L; Kudchadker, R; Lee, A

Purpose: To evaluate the performance characteristics of plastic scintillation detectors (PSDs) in an in vivo environment for external beam radiation, and to establish the usefulness and ease of implementation of a PSD based in vivo dosimetry system for routine clinical use. Methods: A five patient IRB approved in vivo dosimetry study was performed. Five patients with prostate cancer were enrolled and PSDs were used to monitor rectal wall dose and verify the delivered dose for approximately two fractions each week over the course of their treatment (approximately fourteen fractions), resulting in a total of 142 in vivo measurements. A setmore » of two PSDs was fabricated for each patient. At each monitored fraction the PSDs were attached to the anterior surface of an endorectal balloon used to immobilize the patient's prostate during treatment. A CT scan was acquired with a CTon- rails linear accelerator to localize the detectors and to calculate the dose expected to be delivered to the detectors. Each PSD acquired data in 10 second intervals for the duration of the treatment. The deviation between expected and measured cumulative dose was calculated for each detector for each fraction, and averaged over each patient and the patient population as a whole. Results: The average difference between expected dose and measured dose ranged from -3.3% to 3.3% for individual patients, with standard deviations between 5.6% and 7.1% for four of the patients. The average difference for the entire population was -0.4% with a standard deviation of 2.8%. The detectors were well tolerated by the patients and the system did not interrupt the clinical workflow. Conclusion: PSDs perform well as in vivo dosimeters, exhibiting good accuracy and precision. This, combined with the practicability of using such a system, positions the PSD as a strong candidate for clinical in vivo dosimetry in the future. This work supported in part by the National Cancer Institute through an R01 grant (CA120198-01A2) and by the American Legion Auxiliary through the American Auxiliary Fellowship in Cancer Research.« less

Programs to Support You During Chemotherapy (Pro-You)

ClinicalTrials.gov

2015-06-19

Depressive Symptoms; Fatigue; Psychosocial Effects of Cancer and Its Treatment; Stage IIA Colon Cancer; Stage IIA Rectal Cancer; Stage IIB Colon Cancer; Stage IIB Rectal Cancer; Stage IIC Colon Cancer; Stage IIC Rectal Cancer; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

European Paediatric Surgeons' Association Survey on the Management of Hirschsprung Disease.

PubMed

Zani, Augusto; Eaton, Simon; Morini, Francesco; Puri, Prem; Rintala, Risto; Heurn, Ernest van; Lukac, Marija; Bagolan, Pietro; Kuebler, Joachim F; Friedmacher, Florian; Wijnen, Rene; Tovar, Juan A; Hoellwarth, Michael E; Pierro, Agostino

2017-02-01

Aim  This study aims to define patterns of Hirschsprung disease (HD) management. Methods  An online questionnaire was sent to all European Paediatric Surgeons' Association (EUPSA) members. Results  A total of 294 members (61 countries) answered (response rate: 61%). All respondents perform rectal biopsies (61% rectal suction [RSBs], 39% open full-thickness), 96% contrast enema, and 31% anorectal manometry. At RSB, 17% take the most distal biopsy 1 cm above the dentate line, 34% take 2 cm, 30% take 3 cm, and 19% take > 3 cm. Rectal biopsy staining's are hematoxylin/eosin (77%), acetylcholinesterase (74%), calretinin (31%), S100 (2%), nicotinamide adenine dinucleotide-tetrazolium reductase (2%), succinate dehydrogenase (1%), and neuron-specific enolase (1%). A total of 85% respondents recognize entities including hypoganglionosis (69%), intestinal neuronal dysplasia (55%), and ultrashort segment HD (50%). Pull-through (PT) is performed at diagnosis by 33% or delayed by 67% (4 months or > 5 kg). Awaiting definitive surgery, 77% perform rectal irrigations, 22% rectal dilatation/stimulations, and 33% perform a stoma. The preferred type of PT is the Soave approach (65%), performed with transanal technique by 70% respondents. If symptoms persist after PT, most opt for conservative approach (enemas/laxatives = 76%; botulinum toxin = 27%), 30% would redo the PT. Total colonic aganglionosis: PT is performed in neonates (4%), at 1 to 6 months (29%), 6 to 12 months (37%) or older (30%). If required, a stoma is sited in the ileum (31%), according to intraoperative biopsies (54%), macroscopic impression (13%), and radiology (2%). Duhamel PT is performed by 52%, Soave by 31%, and Swenson by 17%. Overall, 31% would perform a J-pouch. Conclusions  Most aspects of HD management lack consensus with wide variations in obtaining a diagnosis. Transanal Soave PT is the most common technique in standard segment HD. Guidelines should be developed to avoid such variability in management and to facilitate research studies. Georg Thieme Verlag KG Stuttgart · New York.

Role of genetic polymorphisms in NFKB-mediated inflammatory pathways in response to primary chemoradiation therapy for rectal cancer.

PubMed

Dzhugashvili, Maia; Luengo-Gil, Ginés; García, Teresa; González-Conejero, Rocío; Conesa-Zamora, Pablo; Escolar, Pedro Pablo; Calvo, Felipe; Vicente, Vicente; Ayala de la Peña, Francisco

2014-11-01

To investigate whether polymorphisms of genes related to inflammation are associated with pathologic response (primary endpoint) in patients with rectal cancer treated with primary chemoradiation therapy (PCRT). Genomic DNA of 159 patients with locally advanced rectal cancer treated with PCRT was genotyped for polymorphisms rs28362491 (NFKB1), rs1213266/rs5789 (PTGS1), rs5275 (PTGS2), and rs16944/rs1143627 (IL1B) using TaqMan single nucleotide polymorphism genotyping assays. The association between each genotype and pathologic response (poor response vs complete or partial response) was analyzed using logistic regression models. The NFKB1 DEL/DEL genotype was associated with pathologic response (odds ratio [OR], 6.39; 95% confidence interval [CI], 0.78-52.65; P=.03) after PCRT. No statistically significant associations between other polymorphisms and response to PCRT were observed. Patients with the NFKB1 DEL/DEL genotype showed a trend for longer disease-free survival (log-rank test, P=.096) and overall survival (P=.049), which was not significant in a multivariate analysis that included pathologic response. Analysis for 6 polymorphisms showed that patients carrying the haplotype rs28362491-DEL/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G (13.7% of cases) had a higher response rate to PCRT (OR, 8.86; 95% CI, 1.21-64.98; P=.034) than the reference group (rs28362491-INS/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G). Clinically significant (grade ≥2) acute organ toxicity was also more frequent in patients with that same haplotype (OR, 4.12; 95% CI, 1.11-15.36; P=.037). Our results suggest that genetic variation in NFKB-related inflammatory pathways might influence sensitivity to primary chemoradiation for rectal cancer. If confirmed, an inflammation-related radiogenetic profile might be used to select patients with rectal cancer for preoperative combined-modality treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Performance of endoscopic ultrasound in staging rectal adenocarcinoma appropriate for primary surgical resection.

PubMed

Ahuja, Nitin K; Sauer, Bryan G; Wang, Andrew Y; White, Grace E; Zabolotsky, Andrew; Koons, Ann; Leung, Wesley; Sarkaria, Savreet; Kahaleh, Michel; Waxman, Irving; Siddiqui, Ali A; Shami, Vanessa M

2015-02-01

Endoscopic ultrasound (EUS) often is used to stage rectal cancer and thereby guide treatment. Prior assessments of its accuracy have been limited by small sets of data collected from tumors of varying stages. We aimed to characterize the diagnostic performance of EUS analysis of rectal cancer, paying particular attention to determining whether patients should undergo primary surgical resection. We performed a retrospective observational study using procedural databases and electronic medical records from 4 academic tertiary-care hospitals, collecting data on EUS analyses from 2000 through 2012. Data were analyzed from 86 patients with rectal cancer initially staged as T2N0 by EUS. The negative predictive value (NPV) was calculated by comparing initial stages determined by EUS with those determined by pathology analysis of surgical samples. Logistic regression models were used to assess variation in diagnostic performance with case attributes. EUS excluded advanced tumor depth with an NPV of 0.837 (95% confidence interval [CI], 0.742-0.908), nodal metastasis with an NPV of 0.872 (95% CI, 0.783-0.934), and both together with an NPV of 0.767 (95% CI, 0.664-0.852) compared with pathology analysis. Incorrect staging by EUS affected treatment decision making for 20 of 86 patients (23.3%). Patient age at time of the procedure correlated with the NPV for metastasis to lymph node, but no other patient features were associated significantly with diagnostic performance. Based on a multicenter retrospective study, EUS staging of rectal cancer as T2N0 excludes advanced tumor depth and nodal metastasis, respectively, with an approximate NPV of 85%, similar to that of other modalities. EUS has an error rate of approximately 23% in identifying disease appropriate for surgical resection, which is lower than previously reported. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Effects of VX on Acoustic Startle Response and Acquisition of Operant Behavior in Rats

DTIC Science & Technology

2008-02-01

spontaneous motor activity , fore- and hind-limb grip strength, thermal sensitivity (paw-lick latency), rectal temperature, acoustic startle response, and...whereas spontaneous motor activity and avoidance responding were affected at doses at or above 123 µg/kg, and acoustic startle response was affected...The 60- and 70-dB stimuli were stimulus control conditions presented to ensure that there was not significant activity within the recording chamber

Use of hydrogel spacer for improved rectal dose-sparing in patients undergoing radical radiotherapy for localized prostate cancer: First Canadian experience

PubMed Central

Berlin, Alejandro; Di Tomasso, Anne; Ballantyne, Heather; Patterson, Susan; Lam, Tony; Sundaramurthy, Aravind; Helou, Joelle; Bayley, Andrew; Chung, Peter

2017-01-01

We describe the initial experience using a hydrogel spacer (SpaceOAR) to separate the prostate-rectum interspace in patients planned to undergo radical hypofractionated, image-guided, intensity-modulated radiotherapy (IG-IMRT). We depict and discuss the impact of SpaceOAR in the context of hypofractionated IG-IMRT, and the particular considerations for its applications in the Canadian setting. PMID:29257741

Polysaccharide utilization loci and nutritional specialization in a dominant group of butyrate-producing human colonic Firmicutes.

PubMed

Sheridan, Paul O; Martin, Jennifer C; Lawley, Trevor D; Browne, Hilary P; Harris, Hugh M B; Bernalier-Donadille, Annick; Duncan, Sylvia H; O'Toole, Paul W; Scott, Karen P; Flint, Harry J

2016-02-01

Firmicutes and Bacteroidetes are the predominant bacterial phyla colonizing the healthy human large intestine. Whilst both ferment dietary fibre, genes responsible for this important activity have been analysed only in the Bacteroidetes , with very little known about the Firmicutes . This work investigates the carbohydrate-active enzymes (CAZymes) in a group of Firmicutes , Roseburia spp. and Eubacterium rectale , which play an important role in producing butyrate from dietary carbohydrates and in health maintenance. Genome sequences of 11 strains representing E. rectale and four Roseburia spp. were analysed for carbohydrate-active genes. Following assembly into a pan-genome, core, variable and unique genes were identified. The 1840 CAZyme genes identified in the pan-genome were assigned to 538 orthologous groups, of which only 26 were present in all strains, indicating considerable inter-strain variability. This analysis was used to categorize the 11 strains into four carbohydrate utilization ecotypes (CUEs), which were shown to correspond to utilization of different carbohydrates for growth. Many glycoside hydrolase genes were found linked to genes encoding oligosaccharide transporters and regulatory elements in the genomes of Roseburia spp. and E. rectale , forming distinct polysaccharide utilization loci (PULs). Whilst PULs are also a common feature in Bacteroidetes , key differences were noted in these Firmicutes , including the absence of close homologues of Bacteroides polysaccharide utilization genes, hence we refer to Gram-positive PULs (gpPULs). Most CAZyme genes in the Roseburia / E. rectale group are organized into gpPULs. Variation in gpPULs can explain the high degree of nutritional specialization at the species level within this group.

Polysaccharide utilization loci and nutritional specialization in a dominant group of butyrate-producing human colonic Firmicutes

PubMed Central

O. Sheridan, Paul; Martin, Jennifer C.; Lawley, Trevor D.; Browne, Hilary P.; Harris, Hugh M. B.; Bernalier-Donadille, Annick; Duncan, Sylvia H.; O'Toole, Paul W.; J. Flint, Harry

2016-01-01

Firmicutes and Bacteroidetes are the predominant bacterial phyla colonizing the healthy human large intestine. Whilst both ferment dietary fibre, genes responsible for this important activity have been analysed only in the Bacteroidetes, with very little known about the Firmicutes. This work investigates the carbohydrate-active enzymes (CAZymes) in a group of Firmicutes, Roseburia spp. and Eubacterium rectale, which play an important role in producing butyrate from dietary carbohydrates and in health maintenance. Genome sequences of 11 strains representing E. rectale and four Roseburia spp. were analysed for carbohydrate-active genes. Following assembly into a pan-genome, core, variable and unique genes were identified. The 1840 CAZyme genes identified in the pan-genome were assigned to 538 orthologous groups, of which only 26 were present in all strains, indicating considerable inter-strain variability. This analysis was used to categorize the 11 strains into four carbohydrate utilization ecotypes (CUEs), which were shown to correspond to utilization of different carbohydrates for growth. Many glycoside hydrolase genes were found linked to genes encoding oligosaccharide transporters and regulatory elements in the genomes of Roseburia spp. and E. rectale, forming distinct polysaccharide utilization loci (PULs). Whilst PULs are also a common feature in Bacteroidetes, key differences were noted in these Firmicutes, including the absence of close homologues of Bacteroides polysaccharide utilization genes, hence we refer to Gram-positive PULs (gpPULs). Most CAZyme genes in the Roseburia/E. rectale group are organized into gpPULs. Variation in gpPULs can explain the high degree of nutritional specialization at the species level within this group. PMID:28348841

Self-paced cycling performance and recovery under a hot and highly humid environment after cooling.

PubMed

Gonzales, B R; Hagin, V; Guillot, R; Placet, V; Monnier-Benoit, P; Groslambert, A

2014-02-01

This study investigated the effects of pre- and post-cooling on self-paced time-trial cycling performance and recovery of cyclists exercising under a hot and highly humid environment (29.92 °C-78.52% RH). Ten male cyclists performed a self-paced 20-min time trial test (TT20) on a cyclo-ergometer while being cooled by a cooling vest and a refrigerating headband during the warm-up and the recovery period. Heart rate, power output, perceived exertion, thermal comfort, skin and rectal temperatures were recorded. Compared to control condition (222.78 ± 47 W), a significant increase (P<0.05) in the mean power output during the TT20 (239.07 ± 45 W; +7.31%) was recorded with a significant (P<0.05) decrease in skin temperature without affecting perceived exertion, heart rate, or rectal temperature at the end of the TT20. However, pace changes occurred independently of skin or rectal temperatures variations but a significant difference (P<0.05) in the body's heat storage was observed between both conditions. This result suggests that a central programmer using body's heat storage as an input may influence self-paced time-trial performance. During the recovery period, post-cooling significantly decreased heart rate, skin and rectal temperatures, and improved significantly (P<0.05) thermal comfort. Therefore, in hot and humid environments, wearing a cooling vest and a refrigerating headband during warm-up improves self-paced performance, and appears to be an effective mean of reaching skin rest temperatures more rapidly during recovery.

The Lactobacillus flora in vagina and rectum of fertile and postmenopausal healthy Swedish women

PubMed Central

2011-01-01

Background Lactobacillus species are the most often found inhabitants of vaginal ecosystem of fertile women. In postmenopausal women with low oestrogen levels, Lactobacillus flora is diminishing or absent. However, no studies have been performed to investigate the correlation between oestrogen levels and the lactobacilli in the gut. The aim of the present study was to investigate the relation in healthy women between vaginal and rectal microbial flora as well as possible variations with hormone levels. Methods Vaginal and rectal smears were taken from 20 healthy fertile women, average 40 years (range 28-49 years), in two different phases of the menstrual cycle, and from 20 postmenopausal women, average 60 years (range 52-85 years). Serum sex hormone levels were analyzed. Bacteria from the smears isolated on Rogosa Agar were grouped by Randomly Amplified Polymorphic DNA and identified by multiplex PCR and partial 16S rRNA gene sequencing. Results Lactobacillus crispatus was more often found in the vaginal flora of fertile women than in that of postmenopausal (p = 0.036). Fifteen of 20 fertile women had lactobacilli in their rectal smears compared to 10 postmenopausal women (p = 0.071). There was no correlation between the number of bacteria in vagina and rectum, or between the number of bacteria and hormonal levels. Neither could any association between the presence of rectal lactobacilli and hormonal levels be found. Conclusion Lactobacillus crispatus was more prevalent in the vaginal flora of fertile women, whereas the Lactobacillus flora of rectum did not correlate to the vaginal flora nor to hormonal levels. PMID:21609500

Neoadjuvant conformal chemoradiation with induction chemotherapy for rectal adenocarcinoma. A prospective observational study.

PubMed

Fekete, Zsolt; Muntean, Alina-Simona; Hica, Ştefan; Rancea, Alin; Resiga, Liliana; Csutak, Csaba; Todor, Nicolae; Nagy, Viorica Magdalena

2014-06-01

The purpose of this prospective observational study was to evaluate the rate and the prognostic factors for down-staging and complete response for rectal adenocarcinoma after induction chemotherapy and neoadjuvant chemoradiation followed by surgery, and to analyze the rate of sphincter-saving surgery. We included from March 2011 to October 2013 a number of 88 patients hospitalized with locally advanced rectal adenocarcinoma in the Prof. Dr. Ion Chiricuta Institute of Oncology, Cluj. The treatment schedule included 2-4 cycles of Oxaliplatin plus a fluoropyrimidine followed by concomitant chemoradiation with a dose of 50 Gy in 25 fractions combined with a fluoropyrimidine monotherapy. The rate of T down-staging was 49.4% (40/81 evaluable patients). Independent prognostic factors for T down-staging were: age >57 years (p<0.01), cN0 (p<0.01), distance from anal verge >5 cm (p<0.01), initial CEA <6.2 ng/ml (p<0.01), higher number of chemotherapy cycles with Oxaliplatin (pROC=0.05) and protraction of radiotherapy of >35 days (p<0.01). Nine patients from 81 (11.1%) presented complete response (7 pathological and 2 clinical); the independent prognostic factors were stage cT2 versus cT3-4 (p<0.01), initial tumor size ≤3.5 cm and distance from anal verge >5 cm (p=0.03). Sixty-eight patients (79.1%) underwent radical surgery and among them 35 patients (51.5 %) had a sphincter saving procedure. Induction chemotherapy with neoadjuvant chemoradiation produced important down-staging in rectal adenocarcinoma. Independent prognostic factors for T down-staging were: age, cN0, distance from anal verge, initial CEA, the number of Oxaliplatin cycles and duration of radiotherapy; for complete response: cT2, initial tumor size and distance from the anal verge.

Comparison of different administration of ketamine and intravenous tramadol hydrochloride for postoperative pain relief and sedation after pediatric tonsillectomy.

PubMed

Yenigun, Alper; Et, Tayfun; Aytac, Sirin; Olcay, Betul

2015-01-01

Tonsillectomy is the oldest and most frequently performed surgical procedure practiced by ear, nose, and throat physicians. In this study, our aim was to compare the analgesic effects of peritonsillar, rectal, as well as intravenous infiltration of ketamine and intravenous tramadol hydrochloride infiltration for postoperative pain relief and sedation after tonsillectomy in children. This randomized controlled study evaluated the effects of peritonsillar, intravenous, and rectal infiltration of ketamine in children undergoing adenotonsillectomy. One hundred twenty children who were categorized under American Society of Anesthesiologists classes I to II were randomized to 4 groups of 30 members each. Group 1 received intravenous (IV) ketamine (0.5 mg/kg), group 2 received rectal ketamine (0.5 mg/kg), group 3 received local peritonsillar ketamine (2 mg/kg), and the control group received IV tramadol hydrochloride infiltration (2 mg/kg). Children's Hospital of Eastern Ontario Pain Scale scores and Wilson sedation scale were recorded at minutes 1, 15, 30, 60 as well as hours 2, 12, and 24 postoperatively. The patients were interviewed on the day after the surgery to assess the postoperative pain and sedation. All the routes of infiltration of ketamine were as effective as those of tramadol hydrochloride (P > 0.05). A statistically significant difference was observed between IV infiltrations and all groups during the assessments at hours 6 and 24. The analgesic efficacy of IV ketamine was found especially higher at hours 6 and 24 (P(6) = 0.045, P(24) = 0.011). Perioperative, low-dose IV, rectal, or peritonsillar ketamine infiltration provides efficient pain relief without any adverse effects in children who would undergo adenotonsillectomy.

Prediction of response to chemoradiation in rectal cancer by a gene polymorphism in the epidermal growth factor receptor promoter region

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spindler, Karen-Lise Garm; Nielsen, Jens Nederby; Lindebjerg, Jan

2006-10-01

Purpose: Epidermal growth factor receptor (EGFR) has been associated with radioresistance in solid tumors. Recently a polymorphism in the Sp1 recognition site of the EGFR promoter region was identified. The present study investigated the predictive value of this polymorphism for the outcome of chemoradiation in locally advanced rectal cancer. Methods and Materials: The study included 77 patients with locally advanced T3 rectal tumors. Treatment consisted of preoperative radiation therapy at a total tumor dose of 65 Gy and concomitant chemotherapy with Uftoral. Blood samples from 63 patients were evaluated for Sp1 -216 G/T polymorphism by polymerase chain reaction analysis. Forty-eightmore » primary tumor biopsies were available for EGFR immunostaining. Patients underwent surgery 8 weeks after treatment. Pathologic response evaluation was performed according to the tumor regression grade (TRG) system. Results: Forty-nine percent had major response (TRG1-2) and 51% moderate response (TRG 3-4) to chemoradiation. The rates of major response were 34% (10/29) in GG homozygote patients compared with 65% (22/34) in patients with T containing variants (p = 0.023). Fifty-eight percent of biopsies were positive for EGFR expression (28/48). The major response rates with regard to EGFR immunostaining were not significantly different. EGFR-positive tumors were found in 83% of the GG homozygote patients compared with 38% of patients with TT or GT variants (p = 0.008). Conclusions: There was a significant correlation between EGFR Sp1 -216 G/T polymorphism and treatment response to chemoradiation in locally advanced rectal cancer. Further investigations of a second set of patient and other treatment schedules are warranted.« less

Sacral Insufficiency Fractures After Preoperative Chemoradiation for Rectal Cancer: Incidence, Risk Factors, and Clinical Course

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herman, Michael P.; Kopetz, Scott; Bhosale, Priya R.

2009-07-01

Purpose: Sacral insufficiency (SI) fractures can occur as a late side effect of pelvic radiation therapy. Our goal was to determine the incidence, risk factors, and clinical course of SI fractures in patients treated with preoperative chemoradiation for rectal cancer. Materials and Methods: Between 1989 and 2004, 562 patients with non-metastatic rectal adenocarcinoma were treated with preoperative chemoradiation followed by mesorectal excision. The median radiotherapy dose was 45 Gy. The hospital records and radiology reports of these patients were reviewed to identify those with pelvic fractures. Radiology images of patients with pelvic fractures were then reviewed to identify those withmore » SI fractures. Results: Among the 562 patients, 15 had SI fractures. The 3-year actuarial rate of SI fractures was 3.1%. The median time to SI fractures was 17 months (range, 2-34 months). The risk of SI fractures was significantly higher in women compared to men (5.8% vs. 1.6%, p = 0.014), and in whites compared with non-whites (4% vs. 0%, p = 0.037). On multivariate analysis, gender independently predicted for the risk of SI fractures (hazard ratio, 3.25; p = 0.031). Documentation about the presence or absence of pain was available for 13 patients; of these 7 (54%) had symptoms requiring pain medications. The median duration of pain was 22 months. No patient required hospitalization or invasive intervention for pain control. Conclusions: SI fractures were uncommon in patients treated with preoperative chemoradiation for rectal cancer. The risk of SI fractures was significantly higher in women. Most cases of SI fractures can be managed conservatively with pain medications.« less

Fractures of the Sacrum After Chemoradiation for Rectal Carcinoma: Incidence, Risk Factors, and Radiographic Evaluation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Han Jo; Boland, Patrick J.; Meredith, Dennis S.

Purpose: Sacral insufficiency fractures after adjuvant radiation for rectal carcinoma can present similarly to recurrent disease. As a complication associated with pelvic radiation, it is important to be aware of the incidence and risk factors associated with sacral fractures in the clinical assessment of these patients. Methods and Materials: Between 1998 and 2007, a total of 582 patients with locally advanced rectal carcinoma received adjuvant chemoradiation and surgical excision. Of these, 492 patients had imaging studies available for review. Hospital records and imaging studies from all 492 patients were retrospectively evaluated to identify risk factors associated with developing a sacralmore » insufficiency fracture. Results: With a median follow-up time of 3.5 years, the incidence of sacral fractures was 7.1% (35/492). The 4-year sacral fracture free rate was 0.91. Univariate analysis showed that increasing age ({>=}60 vs. <60 years), female sex, and history of osteoporosis were significantly associated with shorter time to sacral fracture (P=.01, P=.004, P=.001, respectively). There was no significant difference in the time to sacral fracture for patients based on stage, radiotherapy dose, or chemotherapy regimen. Multivariate analysis showed increasing age ({>=}60 vs. <60 years, hazard ratio [HR] = 2.50, 95% confidence interval [CI] = 1.22-5.13, P=.01), female sex (HR = 2.64, CI = 1.29-5.38, P=.008), and history of osteoporosis (HR = 3.23, CI = 1.23-8.50, P=.02) were independent risk factors associated with sacral fracture. Conclusions: Sacral insufficiency fractures after pelvic radiation for rectal carcinoma occur more commonly than previously described. Independent risk factors associated with fracture were osteoporosis, female sex, and age greater than 60 years.« less

Effects of nifedipine on anorectal smooth muscle in vitro.

PubMed

Cook, T A; Brading, A F; Mortensen, N J

1999-06-01

Glyceryl trinitrate reduces anal resting pressure and aids the healing of anal fissures. However, some patients develop tachyphylaxis and the fissure fails to heal, suggesting that other agents are needed. This study assesses the effects of nifedipine (a calcium channel antagonist) in modulating resting tone and agonist-induced contractions in human internal anal sphincter (IAS) and rectal circular muscle. Smooth muscle strips from the IAS and rectal circular muscle from ten patients undergoing surgical resection were mounted for isometric tension recording in a superfusion organ bath. The effects of noradrenaline and carbachol were assessed in the presence of various perfusates. LAS strips developed tone and spontaneous activity. Noradrenaline produced dose-dependent contractions. In calcium-free Krebs solution, tone and activity were abolished and no contractions were elicited in response to noradrenaline. Nifedipine also abolished tone and spontaneous activity, but contractions to noradrenaline were only slightly attenuated. In contrast, rectal smooth muscle strips developed spontaneous activity but no resting tone and contracted in response to carbachol. In calcium-free Krebs solution, the spontaneous activity and carbachol contractions were abolished. Addition of nifedipine to the perfusate abolished spontaneous activity and greatly reduced contractions. These data suggest that spontaneous activity and resting tone are dependent on extracellular calcium and flux across the cells. Agonist-induced contraction in the IAS is attributable mainly to the release of calcium from intracellular stores, whereas rectal circular smooth muscle depends principally on extracellular calcium entering the cell for contraction. The attenuation of contractions in both tissues and the abolition of resting tone in the IAS suggest that nifedipine may be useful in the management of patients with anorectal disorders.

CT-Guided Transgluteal Biopsy for Systematic Random Sampling of the Prostate in Patients Without Rectal Access.

PubMed

Goenka, Ajit H; Remer, Erick M; Veniero, Joseph C; Thupili, Chakradhar R; Klein, Eric A

2015-09-01

The objective of our study was to review our experience with CT-guided transgluteal prostate biopsy in patients without rectal access. Twenty-one CT-guided transgluteal prostate biopsy procedures were performed in 16 men (mean age, 68 years; age range, 60-78 years) who were under conscious sedation. The mean prostate-specific antigen (PSA) value was 11.4 ng/mL (range, 2.3-39.4 ng/mL). Six had seven prior unsuccessful transperineal or transurethral biopsies. Biopsy results, complications, sedation time, and radiation dose were recorded. The mean PSA values and number of core specimens were compared between patients with malignant results and patients with nonmalignant results using the Student t test. The average procedural sedation time was 50.6 minutes (range, 15-90 minutes) (n = 20), and the mean effective radiation dose was 8.2 mSv (median, 6.6 mSv; range 3.6-19.3 mSv) (n = 13). Twenty of the 21 (95%) procedures were technically successful. The only complication was a single episode of gross hematuria and penile pain in one patient, which resolved spontaneously. Of 20 successful biopsies, 8 (40%) yielded adenocarcinoma (Gleason score: mean, 8; range, 7-9). Twelve biopsies yielded nonmalignant results (60%): high-grade prostatic intraepithelial neoplasia (n = 3) or benign prostatic tissue with or without inflammation (n = 9). Three patients had carcinoma diagnosed on subsequent biopsies (second biopsy, n = 2 patients; third biopsy, n = 1 patient). A malignant biopsy result was not significantly associated with the number of core specimens (p = 0.3) or the mean PSA value (p = 0.1). CT-guided transgluteal prostate biopsy is a safe and reliable technique for the systematic random sampling of the prostate in patients without a rectal access. In patients with initial negative biopsy results, repeat biopsy should be considered if there is a persistent rise in the PSA value.

Comparative Toxicity and Dosimetric Profile of Whole-Pelvis Versus Prostate Bed-Only Intensity-Modulated Radiation Therapy After Prostatectomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deville, Curtiland, E-mail: deville@uphs.upenn.edu; Vapiwala, Neha; Hwang, Wei-Ting

2012-03-15

Purpose: To assess whether whole-pelvis (WP) intensity modulated radiation therapy (IMRT) for prostate cancer (PCa) after prostatectomy is associated with increased toxicity compared to prostate-bed only (PB) IMRT. Methods and Materials: All patients (n = 67) undergoing postprostatectomy IMRT to 70.2 Gy at our institution from January 2006 to January 2009 with minimum 12-month follow-up were divided into WP (n = 36) and PB (n = 31) comparison groups. WP patients received initial pelvic nodal IMRT to 45 Gy. Pretreatment demographics, bladder and rectal dose-volume histograms, and maximum genitourinary (GU) and gastrointestinal (GI) toxicities were compared. Logistic regression models evaluatedmore » uni- and multivariate associations between pretreatment demographics and toxicities. Results: Pretreatment demographics including age and comorbidities were similar between groups. WP patients had higher Gleason scores, T stages, and preoperative prostate-specific antigen (PSA) levels, and more WP patients underwent androgen deprivation therapy (ADT). WP minimum (Dmin) and mean bladder doses, bladder volumes receiving more than 5 Gy (V5) and V20, rectal Dmin, and PB bladder and rectal V65 were significantly increased. Maximum acute GI toxicity was Grade 2 and was increased for WP (61%) vs. PB (29%) patients (p = 0.001); there was no significant difference in acute Grade {>=}2 GU toxicity (22% WP vs. 10% PB; p = 0.193), late Grade {>=}2 GI toxicity (3% WP vs. 0% PB; p = 0.678), or late Grade {>=}2 GU toxicity (28% WP vs. 19% PB; p = 0.274) with 25-month median follow-up (range, 12-44 months). On multivariate analysis, long-term ADT use was associated with Grade {>=}2 late GU toxicity (p = 0.02). Conclusion: Despite dosimetric differences in irradiated bowel, bladder, and rectum, WP IMRT resulted only in clinically significant increased acute GI toxicity in comparison to that with PB IMRT, with no differences in GU or late GI toxicity.« less

Positioning accuracy and daily dose assessment for prostate cancer treatment using in-room CT image guidance at a proton therapy facility.

PubMed

Maeda, Yoshikazu; Sato, Yoshitaka; Minami, Hiroki; Yasukawa, Yutaka; Yamamoto, Kazutaka; Tamamura, Hiroyasu; Shibata, Satoshi; Bou, Sayuri; Sasaki, Makoto; Tameshige, Yuji; Kume, Kyo; Ooto, Hiroshi; Kasahara, Shigeru; Shimizu, Yasuhiro; Saga, Yusuke; Omoya, Akira; Saitou, Makoto

2018-05-01

To evaluate the effectiveness of CT image-guided proton radiotherapy for prostate cancer by analyzing the positioning uncertainty and assessing daily dose change due to anatomical variations. Patients with prostate cancer were treated by opposed lateral proton beams based on a passive scattering method using an in-room CT image-guided system. The system employs a single couch for both CT scanning and beam delivery. The patient was positioned by matching the boundary between the prostate and the rectum's anterior region identified in the CT images to the corresponding boundary in the simulator images after bone matching. We acquired orthogonal kV x-ray images after couch movement and confirmed the body position by referring to the bony structure prior to treatment. In offline analyses, we contoured the targeted anatomical structures on 375 sets of daily in-room CT images for 10 patients. The uncertainty of the image-matching procedure was evaluated using the prostate contours and actual couch corrections. We also performed dose calculations using the same set of CT images, and evaluated daily change of dose-volume histograms (DVHs) to compare the effectiveness of the treatment using prostate matching to the bone-matching procedure. The isocenter shifts by prostate matching after bone matching were 0.5 ± 1.8 and -0.8 ± 2.6 mm along the superior-inferior (SI) and anterior-posterior (AP) directions, respectively. The body movement errors (σ) after couch movement were 0.7, 0.5, and 0.3 mm along the lateral, SI and AP direction, respectively, for 30 patients. The estimated errors (σ) in the prostate matching were 1.0 and 1.3 mm, and, in conjunction with the movement errors, the total positioning uncertainty was estimated to be 1.0 and 1.4 mm along the SI and AP directions, respectively. Daily DVH analyses showed that in the prostate matching, 98.7% and 86.1% of the total 375 irradiations maintained a dose condition of V 95%  > 95% for the prostate and a dose constraint of V 77%  < 18% for the rectum, whereas 90.4% and 66.1% of the total irradiations did so when bone matching was used. The dose constraint of the rectum and dose coverage of the prostate were better maintained by prostate matching than bone matching (P < 0.001). The daily variation in the dose to the seminal vesicles (SVs) was large, and only 40% of the total irradiations maintained the initial planned values of V 95% for high-risk treatment. Nevertheless, the deviations from the original value were -4 ± 7% and -5 ± 11% in the prostate and bone matching, respectively, and a better dose coverage of the SV was achieved by the prostate matching. The correction of repositioning along the AP and SI direction from conventional bone matching in CT image-guided proton therapy was found to be effective to maintain the dose constraint of the rectum and the dose coverage of the prostate. This work indicated that prostate cancer treatment by prostate matching using CT image guidance may be effective to reduce the rectal complications and achieve better tumor control of the prostate. However, an adaptive approach is desirable to maintain better dose coverage of the SVs. © 2018 American Association of Physicists in Medicine.

Immunoscore in Rectal Cancer

ClinicalTrials.gov

2017-06-13

Cancer of the Rectum; Neoplasms, Rectal; Rectal Cancer; Rectal Tumors; Rectal Adenocarcinoma; Melanoma; Breast Cancer; Renal Cell Cancer; Lung Cancer; Bladder Cancer; Head and Neck Cancer; Ovarian Cancer; Thyroid Cancer

Financial Burden Assessment in Patients With Stage I-III Colon or Rectal Cancer Undergoing Treatment

ClinicalTrials.gov

2018-06-12

Stage I Colon Cancer AJCC v8; Stage I Rectal Cancer AJCC v8; Stage II Colon Cancer AJCC v8; Stage II Rectal Cancer AJCC v8; Stage IIA Colon Cancer AJCC v8; Stage IIA Rectal Cancer AJCC v8; Stage IIB Colon Cancer AJCC v8; Stage IIB Rectal Cancer AJCC v8; Stage IIC Colon Cancer AJCC v8; Stage IIC Rectal Cancer AJCC v8; Stage III Colon Cancer AJCC v8; Stage III Rectal Cancer AJCC v8; Stage IIIA Colon Cancer AJCC v8; Stage IIIA Rectal Cancer AJCC v8; Stage IIIB Colon Cancer AJCC v8; Stage IIIB Rectal Cancer AJCC v8; Stage IIIC Colon Cancer AJCC v8; Stage IIIC Rectal Cancer AJCC v8

Review of the clinical pharmacokinetics of artesunate and its active metabolite dihydroartemisinin following intravenous, intramuscular, oral or rectal administration

PubMed Central

2011-01-01

Artesunate (AS) is a clinically versatile artemisinin derivative utilized for the treatment of mild to severe malaria infection. Given the therapeutic significance of AS and the necessity of appropriate AS dosing, substantial research has been performed investigating the pharmacokinetics of AS and its active metabolite dihydroartemisinin (DHA). In this article, a comprehensive review is presented of AS clinical pharmacokinetics following administration of AS by the intravenous (IV), intramuscular (IM), oral or rectal routes. Intravenous AS is associated with high initial AS concentrations which subsequently decline rapidly, with typical AS half-life estimates of less than 15 minutes. AS clearance and volume estimates average 2 - 3 L/kg/hr and 0.1 - 0.3 L/kg, respectively. DHA concentrations peak within 25 minutes post-dose, and DHA is eliminated with a half-life of 30 - 60 minutes. DHA clearance and volume average between 0.5 - 1.5 L/kg/hr and 0.5 - 1.0 L/kg, respectively. Compared to IV administration, IM administration produces lower peaks, longer half-life values, and higher volumes of distribution for AS, as well as delayed peaks for DHA; other parameters are generally similar due to the high bioavailability, assessed by exposure to DHA, associated with IM AS administration (> 86%). Similarly high bioavailability of DHA (> 80%) is associated with oral administration. Following oral AS, peak AS concentrations (Cmax) are achieved within one hour, and AS is eliminated with a half-life of 20 - 45 minutes. DHA Cmax values are observed within two hours post-dose; DHA half-life values average 0.5 - 1.5 hours. AUC values reported for AS are often substantially lower than those reported for DHA following oral AS administration. Rectal AS administration yields pharmacokinetic results similar to those obtained from oral administration, with the exceptions of delayed AS Cmax and longer AS half-life. Drug interaction studies conducted with oral AS suggest that AS does not appreciably alter the pharmacokinetics of atovaquone/proguanil, chlorproguanil/dapsone, or sulphadoxine/pyrimethamine, and mefloquine and pyronaridine do not alter the pharmacokinetics of DHA. Finally, there is evidence suggesting that the pharmacokinetics of AS and/or DHA following AS administration may be altered by pregnancy and by acute malaria infection, but further investigation would be required to define those alterations precisely. PMID:21914160

High-Dose-Rate Brachytherapy as a Monotherapy for Favorable-Risk Prostate Cancer: A Phase II Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barkati, Maroie; Williams, Scott G., E-mail: scott.williams@petermac.org; Department of Pathology, University of Melbourne, Melbourne

Purpose: There are multiple treatment options for favorable-risk prostate cancer. High-dose-rate (HDR) brachytherapy as a monotherapy is appealing, but its use is still investigational. A Phase II trial was undertaken to explore the value of such treatment in low-to-intermediate risk prostate cancer. Methods and Materials: This was a single-institution, prospective study. Eligible patients had low-risk prostate cancer features but also Gleason scores of 7 (51% of patients) and stage T2b to T2c cancer. Treatment with HDR brachytherapy with a single implant was administered over 2 days. One of four fractionation schedules was used in a dose escalation study design: 3more » fractions of 10, 10.5, 11, or 11.5 Gy. Patients were assessed with the Common Terminology Criteria for Adverse Events version 2.0 for urinary toxicity, the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scoring schema for rectal toxicity, and the Expanded Prostate Cancer Index Composite (EPIC) questionnaire to measure patient-reported health-related quality of life. Biochemical failure was defined as a prostate-specific antigen (PSA) nadir plus 2 ng/ml. Results: Between 2003 and 2008, 79 patients were enrolled. With a median follow-up of 39.5 months, biochemical relapse occurred in 7 patients. Three- and 5-year actuarial biochemical control rates were 88.4% (95% confidence interval [CI], 78.0-96.2%) and 85.1% (95% CI, 72.5-94.5%), respectively. Acute grade 3 urinary toxicity was seen in only 1 patient. There was no instance of acute grade 3 rectal toxicity. Rates of late grade 3 rectal toxicity, dysuria, hematuria, urinary retention, and urinary incontinence were 0%, 10.3%, 1.3%, 9.0%, and 0%, respectively. No grade 4 or greater toxicity was recorded. Among the four (urinary, bowel, sexual, and hormonal) domains assessed with the EPIC questionnaire, only the sexual domain did not recover with time. Conclusions: HDR brachytherapy as a monotherapy for favorable-risk prostate cancer, administered using a single implant over 2 days, is feasible and has acceptable acute and late toxicities. Further follow-up is still required to better evaluate the efficacy of such treatment.« less

To Bleed or Not to Bleed. A Prediction Based on Individual Gene Profiling Combined With Dose-Volume Histogram Shapes in Prostate Cancer Patients Undergoing Three-Dimensional Conformal Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valdagni, Riccardo; Scientific Directorate, Fondazione IRCCS-Istituto Nazionale dei Tumori, Milano; Rancati, Tiziana

2009-08-01

Purpose: The main purpose of this work was to try to elucidate why, despite excellent rectal dose-volume histograms (DVHs), some patients treated for prostate cancer exhibit late rectal bleeding (LRB) and others with poor DVHs do not. Thirty-five genes involved in DNA repair/radiation response were analyzed in patients accrued in the AIROPROS 0101 trial, which investigated the correlation between LRB and dosimetric parameters. Methods and Materials: Thirty patients undergoing conformal radiotherapy with prescription doses higher than 70 Gy (minimum follow-up, 48 months) were selected: 10 patients in the low-risk group (rectal DVH with the percent volume of rectum receiving moremore » than 70 Gy [V70Gy] < 20% and the percent volume of rectum receiving more than 50 Gy [V50Gy] < 55%) with Grade 2 or Grade 3 (G2-G3) LRB, 10 patients in the high-risk group (V70Gy > 25% and V50Gy > 60%) with G2-G3 LRB, and 10 patients in the high-risk group with no toxicity. Quantitative reverse-transcriptase polymerase chain reaction was performed on RNA from lymphoblastoid cell lines obtained from Epstein-Barr virus-immortalized peripheral-blood mononucleated cells and on peripheral blood mononucleated cells. Interexpression levels were compared by using the Kruskal-Wallis test. Results: Intergroup comparison showed many constitutive differences: nine genes were significantly down-regulated in the low-risk bleeder group vs. the high-risk bleeder and high-risk nonbleeder groups: AKR1B1 (p = 0.019), BAZ1B (p = 0.042), LSM7 (p = 0.0016), MRPL23 (p = 0.015), NUDT1 (p = 0.0031), PSMB4 (p = 0.079), PSMD1 (p = 0.062), SEC22L1 (p = 0.040), and UBB (p = 0.018). Four genes were significantly upregulated in the high-risk nonbleeder group than in the other groups: DDX17 (p = 0.048), DRAP1 (p = 0.0025), RAD23 (p = 0.015), and SRF (p = 0.024). For most of these genes, it was possible to establish a cut-off value that correctly classified most patients. Conclusions: The predictive value of sensitivity and resistance to LRB of the genes identified by the study is promising and should be tested in a larger data set.« less

Quantification of hygiene indicators and Salmonella in the tonsils, oral cavity and rectal content samples of pigs during slaughter.

PubMed

Van Damme, Inge; Mattheus, Wesley; Bertrand, Sophie; De Zutter, Lieven

2018-05-01

The tonsils, oral cavity and faeces of 94 pigs at slaughter were sampled to assess the numbers of total aerobic bacteria, Enterobacteriaceae and Escherichia coli in the rectal content, tonsils and oral cavity of pigs at time of evisceration. Moreover, the prevalence, numbers and types of Salmonella spp. were determined. Mean numbers of Enterobacteriaceae in tonsils and the oral cavity differed between slaughterhouses. The proportion of Enterobacteriaceae relative to total aerobic bacteria differed between the different tissues, though large variations were observed between animals. Salmonella spp. were mostly detected in oral cavity swabs (n = 51, 54%), of which six samples were contaminated in numbers over 2.0 log CFU/100 cm 2 . Salmonella spp. were also recovered from 17 tonsillar tissue samples (18%) and 12 tonsillar swabs (13%). Out of the 29 rectal content samples from which Salmonella was recovered (31%), most were lowly contaminated, in the range between -1 and 0 log CFU/g. The predominant serotypes were S. Typhimurium and its monophasic variant, which were recovered from 33 and 13 pigs, respectively. In most cases, the same serotypes and MLVA profiles were found in pigs slaughtered during the same day, thus suggesting a common source of contamination. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reflux symptoms and side effects among patients with gastroesophageal reflux disease at baseline, during treatment with PPIs, and after Nissen fundoplication.

PubMed

Rantanen, Tuomo; Kiljander, Toni; Salminen, Paulina; Ranta, Arto; Oksala, Niku; Kellokumpu, Ilmo

2013-06-01

There are no prospective studies available on the behavior of extraesophageal and esophageal symptoms and treatment-related side effects in patients without effective antireflux medication, receiving the most effective antireflux medication, and after laparoscopic fundoplication. Extraesophageal and esophageal reflux symptoms and treatment-related side effects were assessed in 60 patients while they were on no effective antireflux medication (three-week washout period), after three month of treatment with double-dose esomeprazole, and 3 months after laparoscopic Nissen fundoplication. Esophageal and extraesophageal reflux symptoms, rectal flatulence, and bloating were analyzed with the visual analog scale. In addition, dysphagia, rectal flatulence, and bloating were recorded as none, mild, moderate, or severe. Both extraesophageal and esophageal reflux symptoms decreased after treatment with esomeprazole and were further reduced after fundoplication. Dysphagia and flatulence did not increase from baseline after surgery. Bloating decreased both after treatment with esomeprazole and after fundoplication. In contrast, dysphagia and increased flatus were found more often after surgery than during treatment with esomeprazole. Dysphagia and rectal flatulence were less common during treatment with esomeprazole than at baseline or after surgery. Both extraesophageal and esophageal reflux symptoms decreased after treatment with esomeprazole and were reduced further after fundoplication. Any treatment-related side effect was not increased after surgery when compared to baseline. However, compared to esomeprazole there was more dysphagia and flatulence after fundoplication.

Design and evaluation of ondansetron liquid suppository for the treatment of emesis.

PubMed

Ban, Eunmi; Kim, Chong-Kook

2013-05-01

The thermosensitive-mucoadhesive ondansetron liquid suppository (tmOLS) was developed to enhance patient compliance and bioavailability in high-risk patients receiving highly emetogenic therapy and having difficulty in swallowing, The thermosensitive-mucoadhesive liquid suppository bases were formulated using poloxamers (P407 and P188) and hydroxypropylmethyl cellulose (HPMC). The physicochemical properties of the liquid suppository bases were characterized by their gelation temperature, mucoadhesive force, rheological properties, and in vitro release. Rectal mucosal damage following rectal administration of tmOLS in rats was assessed using microscopy. Pharmacokinetic analyses were performed to compare tmOLS administered via the rectal route to ondansetron solution administered orally. The liquid suppository base of tmOLS contained P407, P188, and HPMC in the ratio 18:20:0.8, was in the liquid state at room temperature, underwent gelation at body temperature. Area under the curve and half-life (t1/2) of ondansetron were significantly higher in the tmOLS-treated group, indicating that the formulation bypassed the first-pass metabolism and that it was released slowly from the tmOLS because of the formation of mucoadhesive gel state. Furthermore, the t1/2 of tmOLS was two-fold that of the oral solution. Thus, tmOLS could be administered to patients who have difficulty in swallowing; however, adjustments in dosing interval may be needed.

Barostat testing of rectal sensation and compliance in humans: comparison of results across two centres and overall reproducibility.

PubMed

Cremonini, F; Houghton, L A; Camilleri, M; Ferber, I; Fell, C; Cox, V; Castillo, E J; Alpers, D H; Dewit, O E; Gray, E; Lea, R; Zinsmeister, A R; Whorwell, P J

2005-12-01

We assessed reproducibility of measurements of rectal compliance and sensation in health in studies conducted at two centres. We estimated samples size necessary to show clinically meaningful changes in future studies. We performed rectal barostat tests three times (day 1, day 1 after 4 h and 14-17 days later) in 34 healthy participants. We measured compliance and pressure thresholds for first sensation, urgency, discomfort and pain using ascending method of limits and symptom ratings for gas, urgency, discomfort and pain during four phasic distensions (12, 24, 36 and 48 mmHg) in random order. Results obtained at the two centres differed minimally. Reproducibility of sensory end points varies with type of sensation, pressure level and method of distension. Pressure threshold for pain and sensory ratings for non-painful sensations at 36 and 48 mmHg distension were most reproducible in the two centres. Sample size calculations suggested that crossover design is preferable in therapeutic trials: for each dose of medication tested, a sample of 21 should be sufficient to demonstrate 30% changes in all sensory thresholds and almost all sensory ratings. We conclude that reproducibility varies with sensation type, pressure level and distension method, but in a two-centre study, differences in observed results of sensation are minimal and pressure threshold for pain and sensory ratings at 36-48 mmHg of distension are reproducible.

Single and Multiple Dose Pharmacokinetics of Maraviroc in Saliva, Semen, and Rectal Tissue of Healthy HIV-negative Men

PubMed Central

Patterson, Kristine B.; Malone, Stephanie A.; Shaheen, Nicholas J.; Asher Prince, Heather M.; Dumond, Julie B.; Spacek, Melissa B.; Heidt, Paris E.; Cohen, Myron S.; Kashuba, Angela D. M.

2011-01-01

Background. Antiretroviral pharmacology in seminal plasma (SP) and rectal tissue (RT) may provide insight into antiretroviral resistance and the prevention of sexual transmission of human immunodeficiency virus (HIV). Saliva may be of utility for noninvasively measuring adherence. Methods. A pharmacokinetic study was performed in 12 HIV-negative men receiving maraviroc 300 mg twice daily for 8 days. Seven time-matched pairs of blood plasma (BP) and saliva samples were collected over 12 h on day 1 (PK1) and days 7 and 8 (PK2). One RT sample from each subject was collected during PK1 and PK2. Two SP samples were collected from each subject during PK1, and 6 SP samples were collected from each subject during PK2. Results. SP AUCs were ∼50% lower than BP. However, protein binding in SP ranged from 4% to 25%, resulting in protein-free concentrations >2-fold higher than BP. RT AUCs were 7.5- to 26-fold higher than BP. Maraviroc saliva AUCs were ∼70% lower than BP, but saliva concentrations correlated with BP (r2 = 0.58). Conclusions. More pharmacologically available maraviroc was found in SP than BP. High RT concentrations are promising for preventing rectal HIV acquisition. Saliva correlation with BP suggests that this may be useful for monitoring adherence. Clinical Trials Registration. NCT00775294. PMID:21502084

Effect of Acute Administration of Recombinant Human Leptin during the Neonatal Period on Body Temperature and Endocrine Profile of the Piglet.

PubMed

Litten, J C; Mostyn, A; Laws, J; Corson, A M; Symonds, M E; Clarke, L

2008-01-01

Leptin is produced predominantly by white adipocytes; in adults it regulates appetite and energy expenditure but its role in the neonate remains to be fully established. To examine the effects of acute administration of recombinant human leptin on the endocrine profile and thermoregulation of neonatal pigs. 24 pairs of siblings (n = 48) were administered with either a single dose (4 microg ml(-1) kg(-1) body weight) of leptin (L: n = 24) or a placebo (P: n = 24) on day 6 of neonatal life. Rectal temperature was recorded, and tissue samples were taken at 1 (n = 12), 2 (n = 12), 4 (n = 12) or 6 (n = 12) hours post-administration. Plasma concentrations of hormones and metabolites were determined in conjunction with messenger RNA (mRNA) for leptin and uncoupling protein-2. Plasma leptin increased following leptin administration, and differences in concentrations of insulin, thyroxine and non-esterified fatty acids were observed between the two groups. Initially, rectal temperature decreased in L pigs but returned to start values by 1.5 h. This decline in rectal temperature was delayed in placebo animals, resulting in differences between treatments at 1.5 and 2 h. Acute leptin administration alters the endocrine profile of pigs and influences the thermoregulatory ability of the neonate. Copyright (c) 2007 S. Karger AG, Basel.

A Phase 1 Randomized, Blinded Comparison of the Pharmacokinetics and Colonic Distribution of Three Candidate Rectal Microbicide Formulations of Tenofovir 1% Gel with Simulated Unprotected Sex (CHARM-02)

PubMed Central

Hiruy, Hiwot; Fuchs, Edward J.; Marzinke, Mark A.; Bakshi, Rahul P.; Breakey, Jennifer C.; Aung, Wutyi S.; Manohar, Madhuri; Yue, Chen; Caffo, Brian S.; Du, Yong; Abebe, Kaleab Z.; Spiegel, Hans M.L.; Rohan, Lisa C.; McGowan, Ian

2015-01-01

Abstract CHARM-02 is a crossover, double-blind, randomized trial to compare the safety and pharmacokinetics of three rectally applied tenofovir 1% gel candidate rectal microbicides of varying osmolalities: vaginal formulation (VF) (3111 mOsmol/kg), the reduced glycerin vaginal formulation (RGVF) (836 mOsmol/kg), and an isoosmolal rectal-specific formulation (RF) (479 mOsmol/kg). Participants (n = 9) received a single, 4 ml, radiolabeled dose of each gel twice, once with and once without simulated unprotected receptive anal intercourse (RAI). The safety, plasma tenofovir pharmacokinetics, colonic small molecule permeability, and SPECT/CT imaging of lower gastrointestinal distribution of drug and virus surrogate were assessed. There were no Grade 3 or 4 adverse events reported for any of the products. Overall, there were more Grade 2 adverse events in the VF group compared to RF (p = 0.006) and RGVF (p = 0.048). In the absence of simulated unprotected RAI, VF had up to 3.8-fold greater systemic tenofovir exposure, 26- to 234-fold higher colonic permeability of the drug surrogate, and 1.5- to 2-fold greater proximal migration in the colonic lumen, when compared to RF and RGVF. Similar trends were observed with simulated unprotected RAI, but most did not reach statistical significance. SPECT analysis showed 86% (standard deviation 19%) of the drug surrogate colocalized with the virus surrogate in the colonic lumen. There were no significant differences between the RGVF and RF formulation, with the exception of a higher plasma tenofovir concentration of RGVF in the absence of simulated unprotected RAI. VF had the most adverse events, highest plasma tenofovir concentrations, greater mucosal permeability of the drug surrogate, and most proximal colonic luminal migration compared to RF and RGVF formulations. There were no major differences between RF and RGVF formulations. Simultaneous assessment of toxicity, systemic and luminal pharmacokinetics, and colocalization of drug and viral surrogates substantially informs rectal microbicide product development. PMID:26227279

Metronidazole stewardship initiative at Christchurch hospitals-achievable with immediate benefits.

PubMed

Gardiner, Sharon J; Metcalf, Sarah Cl; Chin, Paul Kl; Doogue, Matthew P; Dalton, Simon C; Chambers, Stephen T

2018-04-13

To evaluate an antimicrobial stewardship (AMS) initiative to change hospital prescribing practice for metronidazole. In October 2015, the Canterbury District Health Board (CDHB) AMS committee changed advice for metronidazole to promote two times daily dosing for most indications, prioritisation of the oral route and avoidance of double anaerobic cover. Adoption of the initiative was facilitated via change in prescribing guidelines, education and ongoing pharmacy support. Usage and expenditure on metronidazole for adult inpatients were compared for the five years pre- and two years post-change. Other district health boards (DHBs) were surveyed to determine their dosing recommendation for metronidazole IV. Mean annual metronidazole IV use, as defined daily doses per 1,000 occupied bed days, decreased by 43% post-initiative. Use of non-IV (oral or rectal) formulations increased by 104%. Total savings associated with the initiative were approximately $33,400 in drug costs plus $78,200 per annum in IV giving sets and post-dose flushes. Twelve of 20 (60%) DHBs (including CDHB) endorse twice daily IV dosing. In addition to financial savings, reduction in IV doses has potential benefits, including avoidance of IV catheter-associated complications such as bloodstream infections. Approaches to metronidazole dosing vary across DHBs and could benefit from national coordination.

Volumetric modulated arc therapy planning for primary prostate cancer with selective intraprostatic boost determined by 18F-choline PET/CT.

PubMed

Kuang, Yu; Wu, Lili; Hirata, Emily; Miyazaki, Kyle; Sato, Miles; Kwee, Sandi A

2015-04-01

This study evaluated expected tumor control and normal tissue toxicity for prostate volumetric modulated arc therapy (VMAT) with and without radiation boosts to an intraprostatically dominant lesion (IDL), defined by (18)F-choline positron emission tomography/computed tomography (PET/CT). Thirty patients with localized prostate cancer underwent (18)F-choline PET/CT before treatment. Two VMAT plans, plan79 Gy and plan100-105 Gy, were compared for each patient. The whole-prostate planning target volume (PTVprostate) prescription was 79 Gy in both plans, but plan100-105 Gy added simultaneous boost doses of 100 Gy and 105 Gy to the IDL, defined by 60% and 70% of maximum prostatic uptake on (18)F-choline PET (IDLsuv60% and IDLsuv70%, respectively, with IDLsuv70% nested inside IDLsuv60% to potentially enhance tumor specificity of the maximum point dose). Plan evaluations included histopathological correspondence, isodose distributions, dose-volume histograms, tumor control probability (TCP), and normal tissue complication probability (NTCP). Planning objectives and dose constraints proved feasible in 30 of 30 cases. Prostate sextant histopathology was available for 28 cases, confirming that IDLsuv60% adequately covered all tumor-bearing prostate sextants in 27 cases and provided partial coverage in 1 case. Plan100-105 Gy had significantly higher TCP than plan79 Gy across all prostate regions for α/β ratios ranging from 1.5 Gy to 10 Gy (P<.001 for each case). There were no significant differences in bladder and femoral head NTCP between plans and slightly lower rectal NTCP (endpoint: grade ≥ 2 late toxicity or rectal bleeding) was found for plan100-105 Gy. VMAT can potentially increase the likelihood of tumor control in primary prostate cancer while observing normal tissue tolerances through simultaneous delivery of a steep radiation boost to a (18)F-choline PET-defined IDL. Copyright © 2015 Elsevier Inc. All rights reserved.

Rectal cooling test in the differentiation between constipation due to rectal inertia and anismus.

PubMed

Shafik, A; Shafik, I; El Sibai, O; Shafik, A A

2007-03-01

The differentiation between constipation due to rectal inertia and that due to outlet obstruction from non-relaxing puborectalis muscle (PRM) is problematic and not easily achieved with one diagnostic test. Therefore, we studied the hypothesis that the rectal cooling test (RCT) can effectively be used to differentiate between those two forms of constipation. The study enrolled 28 patients with constipation and abnormal transit study in whom radio-opaque markers accumulated in the rectum; 15 healthy volunteers acted as controls. Electromyographic activity of the external anal sphincter (EAS) and PRM was initially recorded. Subsequently rectal wall tone was assessed by a barostat system during rectal infusion with normal saline at 30 degrees C and at 4 degrees C with simultaneous electromyography (EMG). There was a significant increase in EMG activity of the EAS and PRM on strain- ing (p<0.001), suggestive of anismus, in 10 of 28 patients and 0 of 15 controls. Rectal tone in controls did not respond to saline infusion at 30 degrees C, but it increased at 4 degrees C (p<0.05). Similarly, in constipated patients rectal tone did not respond to rectal saline infusion at 30 degrees C, but infusion at 4 degrees C increased tone in all 10 patients with anismus (p<0.05); EMG activity of the EAS and PRM also increased (p<0.001). In the remaining 18 patients, rectal tone after saline infusion at 4 degrees C remained unchanged. Rectal infusion with iced saline increased rectal tone in healthy controls and constipated patients with anismus while it had no effect in the remaining patients. Lack of increase of rectal tone may be secondary to rectal inertia. According to these preliminary observations, the rectal cooling test may be useful in differentiating between rectal inertia and anismus.

"Like Holding an Umbrella Before It Rains": Acceptability of Future Rectal Microbicides Among Men Who Have Sex With Men in India-A Modified Technology Acceptance Model.

PubMed

Chakrapani, Venkatesan; Newman, Peter A; Shunmugam, Murali; Mengle, Shruta; Nelson, Ruban; Rubincam, Clara; Kumar, Pushpesh

2017-07-01

Topical rectal microbicides (RMs) are a new prevention technology in development that aims to reduce the risk of HIV acquisition from anal sex. We examined RM acceptability among men who have sex with men (MSM) in India. We conducted a qualitative exploratory study guided by a modified Technology Acceptance Model, with 10 focus groups ( n = 61) of MSM and 10 key informant interviews. Data were explored using framework analysis. RM acceptability was influenced by technological contexts: perceived usefulness of RMs, perceived ease of use of RM and applicator, and habits around condom and lubricant use; individual and interpersonal contexts: perceived relevance and preferences for product formulation and dosing frequency; and MSM community/social contexts: perceived social approval, RM-related stigma, social support. Implementation of RMs for MSM in India may be supported by multi-level interventions that engage community-based organizations in destigmatizing and distributing RMs, ideally gel-based products that enable on-demand use before sex.

Potential benefits of dosimetric VMAT tracking verified with 3D film measurements.

PubMed

Crijns, Wouter; Defraene, Gilles; Van Herck, Hans; Depuydt, Tom; Haustermans, Karin; Maes, Frederik; Van den Heuvel, Frank

2016-05-01

To evaluate three different plan adaptation strategies using 3D film-stack dose measurements of both focal boost and hypofractionated prostate VMAT treatments. The adaptation strategies (a couch shift, geometric tracking, and dosimetric tracking) were applied for three realistic intrafraction prostate motions. A focal boost (35 × 2.2 and 35 × 2.7 Gy) and a hypofractionated (5 × 7.25 Gy) prostate VMAT plan were created for a heterogeneous phantom that allows for internal prostate motion. For these plans geometric tracking and dosimetric tracking were evaluated by ionization chamber (IC) point dose measurements (zero-D) and measurements using a stack of EBT3 films (3D). The geometric tracking applied translations, rotations, and scaling of the MLC aperture in response to realistic prostate motions. The dosimetric tracking additionally corrected the monitor units to resolve variations due to difference in depth, tissue heterogeneity, and MLC-aperture. The tracking was based on the positions of four fiducial points only. The film measurements were compared to the gold standard (i.e., IC measurements) and the planned dose distribution. Additionally, the 3D measurements were converted to dose volume histograms, tumor control probability, and normal tissue complication probability parameters (DVH/TCP/NTCP) as a direct estimate of clinical relevance of the proposed tracking. Compared to the planned dose distribution, measurements without prostate motion and tracking showed already a reduced homogeneity of the dose distribution. Adding prostate motion further blurs the DVHs for all treatment approaches. The clinical practice (no tracking) delivered the dose distribution inside the PTV but off target (CTV), resulting in boost dose errors up to 10%. The geometric and dosimetric tracking corrected the dose distribution's position. Moreover, the dosimetric tracking could achieve the planned boost DVH, but not the DVH of the more homogeneously irradiated prostate. A drawback of both the geometric and dosimetric tracking was a reduced MLC blocking caused by the rotational component of the MLC aperture corrections. Because of the used CTV to PTV margins and the high doses in the considered fractionation schemes, the TCP differed less than 0.02 from the planned value for all targets and all correction methods. The rectal NTCP constraints, however, could not be realized using any of these methods. The geometric and dosimetric tracking use only a limited input, but they deposit the dose distribution with higher geometric accuracy than the clinical practice. The latter case has boost dose errors up to 10%. The increased accuracy has a modest impact [Δ(NT)CP < 0.02] because of the applied margins and the high dose levels used. To allow further margin reduction tracking methods are vital. The proposed methodology could further be improved by implementing a rotational correction using collimator rotations.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crijns, Wouter, E-mail: wouter.crijns@uzleuven.be; Depuydt, Tom; Haustermans, Karin

Purpose: To evaluate three different plan adaptation strategies using 3D film-stack dose measurements of both focal boost and hypofractionated prostate VMAT treatments. The adaptation strategies (a couch shift, geometric tracking, and dosimetric tracking) were applied for three realistic intrafraction prostate motions. Methods: A focal boost (35 × 2.2 and 35 × 2.7 Gy) and a hypofractionated (5 × 7.25 Gy) prostate VMAT plan were created for a heterogeneous phantom that allows for internal prostate motion. For these plans geometric tracking and dosimetric tracking were evaluated by ionization chamber (IC) point dose measurements (zero-D) and measurements using a stack of EBT3more » films (3D). The geometric tracking applied translations, rotations, and scaling of the MLC aperture in response to realistic prostate motions. The dosimetric tracking additionally corrected the monitor units to resolve variations due to difference in depth, tissue heterogeneity, and MLC-aperture. The tracking was based on the positions of four fiducial points only. The film measurements were compared to the gold standard (i.e., IC measurements) and the planned dose distribution. Additionally, the 3D measurements were converted to dose volume histograms, tumor control probability, and normal tissue complication probability parameters (DVH/TCP/NTCP) as a direct estimate of clinical relevance of the proposed tracking. Results: Compared to the planned dose distribution, measurements without prostate motion and tracking showed already a reduced homogeneity of the dose distribution. Adding prostate motion further blurs the DVHs for all treatment approaches. The clinical practice (no tracking) delivered the dose distribution inside the PTV but off target (CTV), resulting in boost dose errors up to 10%. The geometric and dosimetric tracking corrected the dose distribution’s position. Moreover, the dosimetric tracking could achieve the planned boost DVH, but not the DVH of the more homogeneously irradiated prostate. A drawback of both the geometric and dosimetric tracking was a reduced MLC blocking caused by the rotational component of the MLC aperture corrections. Because of the used CTV to PTV margins and the high doses in the considered fractionation schemes, the TCP differed less than 0.02 from the planned value for all targets and all correction methods. The rectal NTCP constraints, however, could not be realized using any of these methods. Conclusions: The geometric and dosimetric tracking use only a limited input, but they deposit the dose distribution with higher geometric accuracy than the clinical practice. The latter case has boost dose errors up to 10%. The increased accuracy has a modest impact [Δ(NT)CP < 0.02] because of the applied margins and the high dose levels used. To allow further margin reduction tracking methods are vital. The proposed methodology could further be improved by implementing a rotational correction using collimator rotations.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Underwood, Tracy, E-mail: tunderwood@mgh.harvard.edu; Department of Medical Physics and Bioengineering, University College London, London; Giantsoudi, Drosoula

Purpose: For prostate treatments, robust evidence regarding the superiority of either intensity modulated radiation therapy (IMRT) or proton therapy is currently lacking. In this study we investigated the circumstances under which proton therapy should be expected to outperform IMRT, particularly the proton beam orientations and relative biological effectiveness (RBE) assumptions. Methods and Materials: For 8 patients, 4 treatment planning strategies were considered: (A) IMRT; (B) passively scattered standard bilateral (SB) proton beams; (C) passively scattered anterior oblique (AO) proton beams, and (D) AO intensity modulated proton therapy (IMPT). For modalities (B)-(D) the dose and linear energy transfer (LET) distributions weremore » simulated using the TOPAS Monte Carlo platform and RBE was calculated according to 3 different models. Results: Assuming a fixed RBE of 1.1, our implementation of IMRT outperformed SB proton therapy across most normal tissue metrics. For the scattered AO proton plans, application of the variable RBE models resulted in substantial hotspots in rectal RBE weighted dose. For AO IMPT, it was typically not possible to find a plan that simultaneously met the tumor and rectal constraints for both fixed and variable RBE models. Conclusion: If either a fixed RBE of 1.1 or a variable RBE model could be validated in vivo, then it would always be possible to use AO IMPT to dose-boost the prostate and improve normal tissue sparing relative to IMRT. For a cohort without rectum spacer gels, this study (1) underlines the importance of resolving the question of proton RBE within the framework of an IMRT versus proton debate for the prostate and (2) highlights that without further LET/RBE model validation, great care must be taken if AO proton fields are to be considered for prostate treatments.« less

A novel method for accurate needle-tip identification in trans-rectal ultrasound-based high-dose-rate prostate brachytherapy.

PubMed

Zheng, Dandan; Todor, Dorin A

2011-01-01

In real-time trans-rectal ultrasound (TRUS)-based high-dose-rate prostate brachytherapy, the accurate identification of needle-tip position is critical for treatment planning and delivery. Currently, needle-tip identification on ultrasound images can be subject to large uncertainty and errors because of ultrasound image quality and imaging artifacts. To address this problem, we developed a method based on physical measurements with simple and practical implementation to improve the accuracy and robustness of needle-tip identification. Our method uses measurements of the residual needle length and an off-line pre-established coordinate transformation factor, to calculate the needle-tip position on the TRUS images. The transformation factor was established through a one-time systematic set of measurements of the probe and template holder positions, applicable to all patients. To compare the accuracy and robustness of the proposed method and the conventional method (ultrasound detection), based on the gold-standard X-ray fluoroscopy, extensive measurements were conducted in water and gel phantoms. In water phantom, our method showed an average tip-detection accuracy of 0.7 mm compared with 1.6 mm of the conventional method. In gel phantom (more realistic and tissue-like), our method maintained its level of accuracy while the uncertainty of the conventional method was 3.4mm on average with maximum values of over 10mm because of imaging artifacts. A novel method based on simple physical measurements was developed to accurately detect the needle-tip position for TRUS-based high-dose-rate prostate brachytherapy. The method demonstrated much improved accuracy and robustness over the conventional method. Copyright © 2011 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Moderate hypofractionated radiotherapy with volumetric modulated arc therapy and simultaneous integrated boost for pelvic irradiation in prostate cancer.

PubMed

Franzese, C; Fogliata, A; D'Agostino, G R; Di Brina, L; Comito, T; Navarria, P; Cozzi, L; Scorsetti, M

2017-07-01

The optimal treatment for unfavourable intermediate/high-risk prostate cancer is still debated. In the present study, the pattern of toxicity and early clinical outcome of patients with localized prostate cancer was analyzed. A cohort of 90 patients treated on pelvic lymph nodes from 2010 to 2015 was selected. All patients were treated with Volumetric Modulated Arc Therapy (VMAT), and Simultaneous integrated boost (SIB) in 28 fractions; the prostate, the seminal vesicle and the pelvic lymph node received total doses of 74.2, 65.5, and 51.8 Gy, respectively. End points were the detection of acute and late toxicities graded according to the Common Toxicity Criteria CTCAE version 3, evaluating the rectal, genito-urinary and gastro-intestinal toxicity. Correlation of OARs dose parameters and related toxicities was explored. Preliminary overall survival and Progression-free survival (PFS) were evaluated. With a median follow-up of 25 months, no interruptions for treatment-related toxicity were recorded. Univariate analysis among dosimetric data and acute toxicities showed no correlations. Regarding late toxicity: the dose received by a rectal volume of 90 cm 3 was found to be significant for toxicity prediction (p = 0.024). PFS was 90.6% and 60.2% at 2 and 4 years, respectively. PFS correlates with age (p = 0.011) and Gleason score (p = 0.011). Stratifying the PSA nadir in quartiles, its value was significant (p = 0.016) in predicting PFS, showing a reduction of PFS of 2 months for each PSA-nadir increase of 0.1 ng/ml. HRT with VMAT and SIB on the whole pelvis in unfavourable prostate cancer patients is effective with a mild pattern of toxicity.

Quantification of Organ Motion During Chemoradiotherapy of Rectal Cancer Using Cone-Beam Computed Tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chong, Irene; Hawkins, Maria; Hansen, Vibeke

2011-11-15

Purpose: There has been no previously published data related to the quantification of rectal motion using cone-beam computed tomography (CBCT) during standard conformal long-course chemoradiotherapy. The purpose of the present study was to quantify the interfractional changes in rectal movement and dimensions and rectal and bladder volume using CBCT and to quantify the bony anatomy displacements to calculate the margins required to account for systematic ({Sigma}) and random ({sigma}) setup errors. Methods and Materials: CBCT images were acquired from 16 patients on the first 3 days of treatment and weekly thereafter. The rectum and bladder were outlined on all CBCTmore » images. The interfraction movement was measured using fixed bony landmarks as references to define the rectal location (upper, mid, and low), The maximal rectal diameter at the three rectal locations was also measured. The bony anatomy displacements were quantified, allowing the calculation of systematic ({Sigma}) and random ({sigma}) setup errors. Results: A total of 123 CBCT data sets were analyzed. Analysis of variance for standard deviation from planning scans showed that rectal anterior and lateral wall movement differed significantly by rectal location. Anterior and lateral rectal wall movements were larger in the mid and upper rectum compared with the low rectum. The posterior rectal wall movement did not change significantly with the rectal location. The rectal diameter changed more in the mid and upper than in the low rectum. No consistent relationship was found between the rectal and bladder volume and time, nor was a significant relationship found between the rectal volume and bladder volume. Conclusions: In the present study, the anterior and lateral rectal movement and rectal diameter were found to change most in the upper rectum, followed by the mid rectum, with the smallest changes seen in the low rectum. Asymmetric margins are warranted to ensure phase 2 coverage.« less

S1613, Trastuzumab and Pertuzumab or Cetuximab and Irinotecan Hydrochloride in Treating Patients With Locally Advanced or Metastatic HER2/Neu Amplified Colorectal Cancer That Cannot Be Removed by Surgery

ClinicalTrials.gov

2018-04-09

Colon Adenocarcinoma; ERBB2 Gene Amplification; Rectal Adenocarcinoma; Recurrent Colon Carcinoma; Recurrent Rectal Carcinoma; Stage III Colon Cancer AJCC v7; Stage III Rectal Cancer AJCC v7; Stage IIIA Colon Cancer AJCC v7; Stage IIIA Rectal Cancer AJCC v7; Stage IIIB Colon Cancer AJCC v7; Stage IIIB Rectal Cancer AJCC v7; Stage IIIC Colon Cancer AJCC v7; Stage IIIC Rectal Cancer AJCC v7; Stage IV Colon Cancer AJCC v7; Stage IV Rectal Cancer AJCC v7; Stage IVA Colon Cancer AJCC v7; Stage IVA Rectal Cancer AJCC v7; Stage IVB Colon Cancer AJCC v7; Stage IVB Rectal Cancer AJCC v7

The Need for Consensus and Transparency in Assessing Population-Based Rates of Positive Circumferential Radial Margins in Rectal Cancer: Data from Consecutive Cases in a Large Region of Ontario, Canada.

PubMed

Keng, Christine; Coates, Angela; Grubac, Vanja; Lovrics, Peter; DeNardi, Franco; Thabane, Lehana; Simunovic, Marko

2016-02-01

A positive circumferential radial margin (CRM) after rectal cancer surgery is an important predictor of local recurrence. The definition of a positive CRM differs internationally, and reported rates vary greatly in the literature. This study used time-series population-based data to assess positive CRM rates in a region over time and to inform future methods of CRM analysis in a defined geographic area. Chart reviews provided relevant data from consecutive patients undergoing rectal cancer surgery between 2006 and 2012 in all hospitals of the authors' region. Outcomes included rates for pathologic examination of CRM, CRM distance reporting, and positive CRM. The rate of positive CRM was calculated using various definitions. The variations included positive margin cutoffs of CRM at 1 mm or less versus 2 mm or less and inclusion or exclusion of cases without CRM assessment. In this study, 1222 consecutive rectal cancer cases were analyzed. The rate for pathology reporting of CRM distance increased from 54.7 to 93.2 % during the study. Depending on how the rate of positive CRM was defined, its value varied 8.5 to 19.4 % in 2006 and 6.0 to 12.5 % in 2012. Using a pre-specified definition, the rate of positive CRM decreased over time from 14.0 to 6.3 %. A marked increase in CRM distance reporting was observed, whereas the rates of positive CRM dropped, suggesting improved pathologist and surgeon performance over time. Changing definitions greatly influenced the rates of positive CRM, indicating the need for more transparency when such population-based rates are reported in the literature.