Science.gov

Sample records for late rectal toxicity

  1. Early Proctoscopy is a Surrogate Endpoint of Late Rectal Toxicity in Prostate Cancer Treated With Radiotherapy

    SciTech Connect

    Ippolito, Edy; Massaccesi, Mariangela; Digesu, Cinzia; Deodato, Francesco; Macchia, Gabriella; Pirozzi, Giuseppe Antonio; Cilla, Savino; Cuscuna, Daniele; Di Lallo, Alessandra; Mattiucci, Gian Carlo; Mantini, Giovanna; Pacelli, Fabio; Valentini, Vincenzo; Cellini, Numa; Ingrosso, Marcello; Morganti, Alessio Giuseppe

    2012-06-01

    Purpose: To predict the grade and incidence of late clinical rectal toxicity through short-term (1 year) mucosal alterations. Methods and Materials: Patients with prostate adenocarcinoma treated with curative or adjuvant radiotherapy underwent proctoscopy a year after the course of radiotherapy. Mucosal changes were classified by the Vienna Rectoscopy Score (VRS). Late toxicity data were analyzed according to the Kaplan-Meier method. Comparison between prognosis groups was performed by log-rank analysis. Results: After a median follow-up time of 45 months (range, 18-99), the 3-year incidence of grade {>=}2 rectal late toxicity according to the criteria of the European Organization for Research and Treatment of Cancer and the Radiation Therapy Oncology Group was 24%, with all patients (24/24; 100%) experiencing rectal bleeding. The occurrence of grade {>=}2 clinical rectal late toxicity was higher in patients with grade {>=}2 (32% vs. 15 %, p = 0.02) or grade {>=}3 VRS telangiectasia (47% vs. 17%, p {<=} 0.01) and an overall VRS score of {>=}2 (31% vs. 16 %, p = 0.04) or {>=}3 (48% vs. 17%, p = 0.01) at the 1-year proctoscopy. Conclusions: Early proctoscopy (1 year) predicts late rectal bleeding and therefore can be used as a surrogate endpoint for late rectal toxicity in studies aimed at reducing this frequent complication.

  2. Late Rectal Toxicity on RTOG 94-06: Analysis Using a Mixture Lyman Model

    SciTech Connect

    Tucker, Susan L.; Dong Lei; Bosch, Walter R.; Michalski, Jeff; Winter, Kathryn; Mohan, Radhe; Purdy, James A.; Kuban, Deborah; Lee, Andrew K.; Cheung, M. Rex; Thames, Howard D.; Cox, James D.

    2010-11-15

    Purpose: To estimate the parameters of the Lyman normal-tissue complication probability model using censored time-to-event data for Grade {>=}2 late rectal toxicity among patients treated on Radiation Therapy Oncology Group 94-06, a dose-escalation trial designed to determine the maximum tolerated dose for three-dimensional conformal radiotherapy of prostate cancer. Methods and Materials: The Lyman normal-tissue complication probability model was fitted to data from 1,010 of the 1,084 patients accrued on Radiation Therapy Oncology Group 94-06 using an approach that accounts for censored observations. Separate fits were obtained using dose-volume histograms for whole rectum and dose-wall histograms for rectal wall. Results: With a median follow-up of 7.2 years, the crude incidence of Grade {>=}2 late rectal toxicity was 15% (n = 148). The parameters of the Lyman model fitted to dose-volume histograms data, with 95% profile-likelihood confidence intervals, were TD{sub 50} = 79.1 Gy (75.3 Gy, 84.3 Gy), m = 0.146 (0.107, 0.225), and n = 0.077 (0.041, 0.156). The fit based on dose-wall histogram data was not significantly different. Patients with cardiovascular disease had a significantly higher incidence of late rectal toxicity (p = 0.015), corresponding to a dose-modifying factor of 5.3%. No significant association with late rectal toxicity was found for diabetes, hypertension, rectal volume, rectal length, neoadjuvant hormone therapy, or prescribed dose per fraction (1.8 Gy vs. 2 Gy). Conclusions: These results, based on a large cohort of patients from a multi-institutional trial, are expected to be widely representative of the ability of the Lyman model to describe the long-term risk of Grade {>=}2 late rectal toxicity after three-dimensional conformal radiotherapy of prostate cancer.

  3. Consolidating Risk Estimates for Radiation-Induced Complications in Individual Patient: Late Rectal Toxicity

    SciTech Connect

    Prior, Phillip; Devisetty, Kiran; Tarima, Sergey S.; Lawton, Colleen A.F.; Semenenko, Vladimir A.

    2012-05-01

    Purpose: To test the feasibility of a new approach to synthesize published normal tissue complication data using late rectal toxicity in prostate cancer as an example. Methods and Materials: A data survey was performed to identify the published reports on the dose-response relationships for late rectal toxicity. The risk estimates for Grade 1 or greater, Grade 2 or greater, and Grade 3 or greater toxicity were obtained for a test cohort of patients treated at our institution. The influence of the potential factors that might have affected the reported toxicity levels was investigated. The studies that did not conform to the general data trends were excluded, and single, combined risk estimates were derived for each patient and toxicity level. Results: A total of 21 studies of nonoverlapping patient populations were identified. Three studies provided dose-response models for more than one level of toxicity. Of these 21 studies, 6, 14, and 5 were used to derive the initial risk estimates for Grade 1, 2, and 3 or greater toxicity, respectively. A comparison of risk estimates between the studies reporting rectal bleeding and rectal toxicity (bleeding plus other symptoms) or between studies with follow-up <36 months and {>=}36 months did not reveal significant differences (p {>=} .29 for all comparisons). After excluding three reports that did not conform to the general data trends, the combined risk estimates were derived from 5 reports (647 patients), 11 reports (3,369 patients), and 5 reports (1,330 patients) for Grade 1, 2, and 3 or greater toxicity, respectively. Conclusions: The proposed approach is feasible and allows for more systematic use of published dose-response data to estimate the complication risks for the individual patient.

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

    SciTech Connect

    Peeters, Stephanie T.H.; Lebesque, Joos V. . E-mail: j.lebesque@nki.nl; Heemsbergen, Wilma D.; Putten, Wim L.J. van; Slot, Annerie; Dielwart, Michel F.H.; Koper, Peter C.M.

    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}). 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.

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

    SciTech Connect

    Hamstra, Daniel A.; Stenmark, Matt H.; Ritter, Tim; Litzenberg, Dale; Jackson, William; Johnson, Skyler; Albrecht-Unger, Liesel; Donaghy, Alex; Phelps, Laura; Blas, Kevin; Halverson, Schuyler; Marsh, Robin; Olson, Karin; Feng, Felix Y.

    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 Cox 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.

  6. Validation of Normal Tissue Complication Probability Predictions in Individual Patient: Late Rectal Toxicity

    SciTech Connect

    Semenenko, Vladimir A.; Tarima, Sergey S.; Devisetty, Kiran; Pelizzari, Charles A.; Liauw, Stanley L.

    2013-03-15

    Purpose: To perform validation of risk predictions for late rectal toxicity (LRT) in prostate cancer obtained using a new approach to synthesize published normal tissue complication data. Methods and Materials: A published study survey was performed to identify the dose-response relationships for LRT derived from nonoverlapping patient populations. To avoid mixing models based on different symptoms, the emphasis was placed on rectal bleeding. The selected models were used to compute the risk estimates of grade 2+ and grade 3+ LRT for an independent validation cohort composed of 269 prostate cancer patients with known toxicity outcomes. Risk estimates from single studies were combined to produce consolidated risk estimates. An agreement between the actuarial toxicity incidence 3 years after radiation therapy completion and single-study or consolidated risk estimates was evaluated using the concordance correlation coefficient. Goodness of fit for the consolidated risk estimates was assessed using the Hosmer-Lemeshow test. Results: A total of 16 studies of grade 2+ and 5 studies of grade 3+ LRT met the inclusion criteria. The consolidated risk estimates of grade 2+ and 3+ LRT were constructed using 3 studies each. For grade 2+ LRT, the concordance correlation coefficient for the consolidated risk estimates was 0.537 compared with 0.431 for the best-fit single study. For grade 3+ LRT, the concordance correlation coefficient for the consolidated risk estimates was 0.477 compared with 0.448 for the best-fit single study. No evidence was found for a lack of fit for the consolidated risk estimates using the Hosmer-Lemeshow test (P=.531 and P=.397 for grade 2+ and 3+ LRT, respectively). Conclusions: In a large cohort of prostate cancer patients, selected sets of consolidated risk estimates were found to be more accurate predictors of LRT than risk estimates derived from any single study.

  7. 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

    SciTech Connect

    Valdagni, Riccardo; Kattan, Michael W.; Rancati, Tiziana; Yu Changhong; Vavassori, Vittorio; Fellin, Giovanni; Cagna, Elena; Gabriele, Pietro; Mauro, Flora Anna; Baccolini, Micaela; Bianchi, Carla; Menegotti, Loris; Monti, Angelo F.; Stasi, Michele; Giganti, Maria Olga; and others

    2012-04-01

    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 the 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.

  8. Late toxicity and quality of life after definitive treatment of prostate cancer: redefining optimal rectal sparing constraints for intensity-modulated radiation therapy

    PubMed Central

    Chennupati, Sravana K; Pelizzari, Charles A; Kunnavakkam, Rangesh; Liauw, Stanley L

    2014-01-01

    The objective of this study was to assess late toxicity and quality of life (QOL) for patients receiving definitive intensity-modulated radiotherapy (IMRT) and image-guided radiation therapy (IGRT) with regard to normal tissue sparing objectives. Three hundred and seventy-two consecutive men treated with definitive IMRT for prostate adenocarcinoma. Toxicity was graded by CTC v3.0 genitourinary (GU) and gastrointestinal (GI) toxicity at each follow-up visit. Patient-reported QOL (EPIC-26) was prospectively collected for a subset of men. Dosimetric data for bladder and rectum were compared to toxicity and QOL global domain scores, specifically analyzing outcomes for men who met ideal rectal constraints (V70 <10%, V65 <20%, V40 <40%). The median age and prescription dose was 69 years and 76 Gy, respectively. Median follow-up was 47 months. At 4 years, freedom from Grade 2 (FFG2) GI toxicity was 92% and FFG2 GU toxicity was 76%. On univariate analysis, current smoking, larger bladder volume, and higher RT dose were associated with decreased FFG2 GU toxicity, while use of anticoagulation, increasing age, and not meeting ideal rectal constraints were associated with decreased FFG2 GI toxicity (all P ≤ 0.05). Bowel QOL remained stable over the 2-year follow-up period and was higher for patients who met ideal rectal constraints (P = 0.05). IMRT with IGRT is associated with low rates of severe toxicity and a high GI and GU QOL. The use of strict rectal constraints can further improve GI QOL and reduce GI toxicity. PMID:24803087

  9. Multi-Institutional Phase II Study of Proton Beam Therapy for Organ-Confined Prostate Cancer Focusing on the Incidence of Late Rectal Toxicities

    SciTech Connect

    Nihei, Keiji; Ogino, Takashi; Onozawa, Masakatsu; Murayama, Shigeyuki; Fuji, Hiroshi; Murakami, Masao; Hishikawa, Yoshio

    2011-10-01

    Purpose: Proton beam therapy (PBT) is theoretically an excellent modality for external beam radiotherapy, providing an ideal dose distribution. However, it is not clear whether PBT for prostate cancer can clinically control toxicities. The purpose of the present study was to estimate prospectively the incidence of late rectal toxicities after PBT for organ-confined prostate cancer. Methods and Materials: The major eligibility criteria included clinical Stage T1-T2N0M0; initial prostate-specific antigen level of {<=}20 ng/mL and Gleason score {<=}7; no hormonal therapy or hormonal therapy within 12 months before registration; and written informed consent. The primary endpoint was the incidence of late Grade 2 or greater rectal toxicity at 2 years. Three institutions in Japan participated in the present study after institutional review board approval from each. PBT was delivered to a total dose of 74 GyE in 37 fractions. The patients were prospectively followed up to collect the data on toxicities using the National Cancer Institute-Common Toxicity Criteria, version 2.0. Results: Between 2004 and 2007, 151 patients were enrolled in the present study. Of the 151 patients, 75, 49, 9, 17, and 1 had Stage T1c, T2a, T2b, T2c, and T3a, respectively. The Gleason score was 4, 5, 6, and 7 in 5, 15, 80 and 51 patients, respectively. The initial prostate-specific antigen level was <10 or 10-20 ng/mL in 102 and 49 patients, respectively, and 42 patients had received hormonal therapy and 109 had not. The median follow-up period was 43.4 months. Acute Grade 2 rectal and bladder toxicity temporarily developed in 0.7% and 12%, respectively. Of the 147 patients who had been followed up for >2 years, the incidence of late Grade 2 or greater rectal and bladder toxicity was 2.0% (95% confidence interval, 0-4.3%) and 4.1% (95% confidence interval, 0.9-7.3%) at 2 years, respectively. Conclusion: The results of the present prospective study have revealed a valuable piece of evidence that

  10. Late rectal toxicity after image-based high-dose-rate interstitial brachytherapy for postoperative recurrent and/or residual cervical cancers: EQD2 predictors for Grade ≥II toxicity.

    PubMed

    Chopra, Supriya; Dora, Tapas; Engineer, Reena; Mechanery, Siji; Agarwal, Priyanka; Kannan, Sadhna; Ghadi, Yogesh; Swamidas, Jamema; Mahantshetty, Umesh; Shrivastava, Shyam Kishore

    2015-01-01

    To investigate the correlation of rectal dose volume metrics with late rectal toxicity after high-dose-rate pelvic interstitial brachytherapy. From October 2009 to November 2012, 50 patients with residual or recurrent cervical cancer were included. Patients received external radiation 50 Gy in 25 fractions over 5 weeks with weekly cisplatin. Rectum and rectal mucosal (RM) contours were delineated retrospectively. RM was defined as the outer surface of the flatus tube inserted at brachytherapy. The dose received by 0.1, 1, 2, 5 cc of rectum, RM, and sigmoid was recorded. Cumulative equivalent dose in 2 Gy (EQD2) for organs at risk was calculated assuming α/β of 3. Univariate analysis was performed to identify predictors of rectal toxicity. At a median follow-up of 34 months (12-51 months), Grade II and III late rectal toxicity was observed in 9 (18%) and 2 (4%) patients, respectively. On univariate analysis, rectal doses were not significant predictors; however, D 0.1-cc RM dose >72 Gy (p = 0.04), D 1-cc RM dose >65 Gy (p = 0.004), D 2-cc RM dose >62.3 Gy (p = 0.004), and D 5-cc RM dose >60 Gy (p = 0.007) correlated with Grade ≥II toxicity. On probit analysis, the estimated dose in EQD2 for a 10% and 20% risk of rectal toxicity was D 2-cc rectum of 55 and 66 Gy, and RM <55 and 63 Gy, respectively. Limiting 2-cc RM and rectal doses within the proposed thresholds can minimize Grade ≥II toxicity for gynecologic high-dose-rate interstitial brachytherapy. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  11. Late Patient-Reported Toxicity After Preoperative Radiotherapy or Chemoradiotherapy in Nonresectable Rectal Cancer: Results From a Randomized Phase III Study

    SciTech Connect

    Braendengen, Morten; Tveit, Kjell Magne; Bruheim, Kjersti; Cvancarova, Milada; Berglund, Ake; Glimelius, Bengt

    2011-11-15

    Purpose: Preoperative chemoradiotherapy (CRT) is superior to radiotherapy (RT) in locally advanced rectal cancer, but the survival gain is limited. Late toxicity is, therefore, important. The aim was to compare late bowel, urinary, and sexual functions after CRT or RT. Methods and Materials: Patients (N = 207) with nonresectable rectal cancer were randomized to preoperative CRT or RT (2 Gy Multiplication-Sign 25 {+-} 5-fluorouracil/leucovorin). Extended surgery was often required. Self-reported late toxicity was scored according to the LENT SOMA criteria in a structured telephone interview and with questionnaires European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30), International Index of Erectile Function (IIEF), and sexual function -vaginal changes questionnaire (SVQ). Results: Of the 105 patients alive in Norway and Sweden after 4 to 12 years of follow-up, 78 (74%) responded. More patients in the CRT group had received a stoma (73% vs. 52%, p = 0.09). Most patients without a stoma (7 of 12 in CRT group and 9 of 16 in RT group) had incontinence for liquid stools or gas. No stoma and good anal function were seen in 5 patients (11%) in the CRT group and in 11 (30%) in the RT group (p = 0.046). Of 44 patients in the CRT group, 12 (28%) had had bowel obstruction compared with 5 of 33 (15%) in the RT group (p = 0.27). One-quarter of the patients reported urinary incontinence. The majority of men had severe erectile dysfunction. Few women reported sexual activity during the previous month. However, the majority did not have concerns about their sex life. Conclusions: Fecal incontinence and erectile dysfunction are frequent after combined treatment for locally advanced rectal cancer. There was a clear tendency for the problems to be more common after CRT than after RT.

  12. Rectal planning risk volume correlation with acute and late toxicity in 3-dimensional conformal radiation therapy for prostate cancer.

    PubMed

    Dias, R S; Giordani, A J; Souhami, L; Segreto, R A; Segreto, H R C

    2011-12-01

    The purpose of this study was to evaluate rectum motion during 3-Dimensional conformal radiation therapy (3D-CRT) in prostate cancer patients, to derive a planning volume at risk (PRV) and to correlate the PRV dose-volume histograms (DVH) with treatment complications.This study was conducted in two phases. Initially, the PRV was defined prospectively in 50 consecutive prostate cancer patients (Group 1) who received a radical course of 3-D CRT. Then, the obtained PRV was used in the radiotherapy planning of these same 50 patients plus another 59 prostate cancer patients (Group 2) previously treated between 2004 and 2008. All these patients' data, including the rectum and PRV DVHs, were correlated to acute and late complications, according to the Common Toxicity Criteria (CTC) v4.0.The largest displacement occurred in the anterior axis. Long-term gastrointestinal (GI) complications grade ≥ 2 were seen in 9.2% of the cases. Factors that influenced acute GI reactions were: doses at 25% (p 5 0.011) and 40% (p 5 0.005) of the rectum volume and at 40% of the PRV (p 5 0.012). The dose at 25% of the rectum volume (p 5 0.033) and acute complications ≥ grade 2 (p 5 0.018) were prognostic factors for long-term complications. The PRV DVH did not correlate with late toxicity. The rectum showed a significant inter-fraction motion during 3D-CRT for prostate cancer. PRV dose correlated with acute gastrointestinal complications and may be a useful tool to predict and reduce their occurrence.

  13. Nomogram to predict rectal toxicity following prostate cancer radiotherapy

    PubMed Central

    Delobel, Jean-Bernard; Ospina, Juan David; Beckendorf, Véronique; Chira, Ciprian; Zhu, Jian; Bossi, Alberto; Messai, Taha; Acosta, Oscar; Castelli, Joël; de Crevoisier, Renaud

    2017-01-01

    Background To identify predictors of acute and late rectal toxicity following prostate cancer radiotherapy (RT), while integrating the potential impact of RT technique, dose escalation, and moderate hypofractionation, thus enabling us to generate a nomogram for individual prediction. Methods In total, 972 patients underwent RT for localized prostate cancer, to a total dose of 70 Gy or 80 Gy, using two different fractionations (2 Gy or 2.5 Gy/day), by means of several RT techniques (3D conformal RT [3DCRT], intensity-modulated RT [IMRT], or image-guided RT [IGRT]). Multivariate analyses were performed to identify predictors of acute and late rectal toxicity. A nomogram was generated based on the logistic regression model used to predict the 3-year rectal toxicity risk, with its accuracy assessed by dividing the cohort into training and validation subgroups. Results Mean follow-up for the entire cohort was 62 months, ranging from 6 to 235. The rate of acute Grade ≥2 rectal toxicity was 22.2%, decreasing when combining IMRT and IGRT, compared to 3DCRT (RR = 0.4, 95%CI: 0.3–0.6, p<0.01). The 5-year Grade ≥2 risks for rectal bleeding, urgency/tenesmus, diarrhea, and fecal incontinence were 9.9%, 4.5%, 2.8%, and 0.4%, respectively. The 3-year Grade ≥2 risk for overall rectal toxicity increased with total dose (p<0.01, RR = 1.1, 95%CI: 1.0–1.1) and dose per fraction (2Gy vs. 2.5Gy) (p = 0.03, RR = 3.3, 95%CI: 1.1–10.0), and decreased when combining IMRT and IGRT (RR = 0.50, 95% CI: 0.3–0.8, p<0.01). Based on these three parameters, a nomogram was generated. Conclusions Dose escalation and moderate hypofractionation increase late rectal toxicity. IMRT combined with IGRT markedly decreases acute and late rectal toxicity. Performing combined IMRT and IGRT can thus be envisaged for dose escalation and moderate hypofractionation. Our nomogram predicts the 3-year rectal toxicity risk by integrating total dose, fraction dose, and RT technique. PMID:28640871

  14. 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

    2017-09-01

    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

  15. Risk factors of late rectal bleeding after carbon ion therapy for prostate cancer

    SciTech Connect

    Ishikawa, Hitoshi; Tsuji, Hiroshi . E-mail: h_tsuji@nirs.go.jp; Kamada, Tadashi; Hirasawa, Naoki; Yanagi, Takeshi; Mizoe, Jun-Etsu; Akakura, Koichiro; Suzuki, Hiroyoshi; Shimazaki, Jun; Tsujii, Hirohiko

    2006-11-15

    Purpose: The aim of this study was to determine the risk factors for late gastrointestinal (GI) morbidity after hypofractionated carbon ion radiotherapy (C-ion RT) for prostate cancer. Methods and Materials: Between April 2000 and November 2003, a Phase II clinical trial of C-ion RT with a total dose of 66 GyE in 20 fractions was performed on 175 patients with prostate cancer, and the correlations of clinical and dosimetric parameters with the incidence of late GI toxicity in 172 patients who survived for more than 18 months were investigated. Results: Although no Grade 3-4 late morbidities of the rectum were observed, Grade 1 and 2 morbidities developed in 23 (13%) and 4 (2%) patients, respectively. Dose-volume histogram analysis revealed that the percentage of rectal volume receiving 50% of the prescribed dose (V50) was significantly higher in patients with rectal toxicity than without toxicity (13.2 {+-} 5.6% with toxicity; 11.4 {+-} 4.0% without toxicity, p = 0.046). Multivariate analysis demonstrated that the use of anticoagulation therapy (p = 0.010) and rectal V50 (p = 0.012) were significant risk factors for the occurrence of Grade 1-2 late GI toxicity. Conclusions: Although C-ion RT with hypofractionation yielded favorable results regarding late GI complication, dosimetric parameter was a very important factor in the occurrence of rectal bleeding after C-ion RT as well as photon beam RT. Our results provide useful information for physicians applying charged particle RT in the treatment of prostate cancer.

  16. Random forests to predict rectal toxicity following prostate cancer radiation therapy.

    PubMed

    Ospina, Juan D; Zhu, Jian; Chira, Ciprian; Bossi, Alberto; Delobel, Jean B; Beckendorf, Véronique; Dubray, Bernard; Lagrange, Jean-Léon; Correa, Juan C; Simon, Antoine; Acosta, Oscar; de Crevoisier, Renaud

    2014-08-01

    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. 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 model was fit. The performance of all the models was assessed by computing the area under the receiving operating characteristic curve (AUC). 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. 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. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Random Forests to Predict Rectal Toxicity Following Prostate Cancer Radiation Therapy

    SciTech Connect

    Ospina, Juan D.; Zhu, Jian; Chira, Ciprian; Bossi, Alberto; Delobel, Jean B.; Beckendorf, Véronique; Dubray, Bernard; Lagrange, Jean-Léon; Correa, Juan C.; and others

    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 model 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.

  18. Clinical effect of multileaf collimator width on the incidence of late rectal bleeding after high-dose intensity-modulated radiotherapy for localized prostate carcinoma.

    PubMed

    Inokuchi, Haruo; Mizowaki, Takashi; Norihisa, Yoshiki; Takayama, Kenji; Ikeda, Itaru; Nakamura, Kiyonao; Nakamura, Mitsuhiro; Hiraoka, Masahiro

    2016-02-01

    Several studies have confirmed a dosimetric advantage associated with use of a smaller leaf in intensity-modulated radiation therapy (IMRT). However, no studies have identified any clinical benefits. We investigated the effect of a smaller multileaf collimator (MLC) width on the onset of late rectal bleeding after high-dose prostate IMRT. Two hundred and five prostate cancer patients were treated with a total dose of 78 Gy in 39 fractions by use of a dynamic MLC technique; however, two different MLC were used: a 10-mm-wide device and a 5-mm-wide device. Gastrointestinal toxicity and several clinical factors were assessed. The 5-year actuarial risk of grade 2 or higher rectal bleeding was 6.9 % for the 10-mm-wide group (n = 132) and 1.8 % for the 5-mm-wide group (n = 73) (p = 0.04). The median estimated rectal doses for the two groups were 55.1 and 50.6 Gy (p < 0.001), respectively. Univariate analysis showed that acute toxicity, rectal V30-60, median rectal dose, normal tissue complication probability (NTCP), and MLC type were significant predictive factors for late rectal toxicity. In multivariate analysis, acute toxicity and NTCP remained significant. In our planning approach for prostate IMRT, a decrease in MLC width from 10 to 5 mm contributed to further rectal dose reduction, which was the most important predictor of late rectal toxicity.

  19. Reduced late rectal mucosal changes after prostate three-dimensional conformal radiotherapy with endorectal balloon as observed in repeated endoscopy

    SciTech Connect

    Lin, Emile van . E-mail: E.vanLin@rther.umcn.nl; Kristinsson, Jon; Philippens, Marielle E.P.; Jong, Dirk J. de; Vight, Lisette P. van der; Kaanders, Johannes; Leer, Jan Willem; Visser, Andries G.

    2007-03-01

    Purpose: The aim of this study was to investigate prospectively the rectal wall (Rwall) spatial dose distribution, toxicity, and mucosal changes after prostate cancer radiotherapy with or without an endorectal balloon (ERB). Methods and Materials: A total of 24 patients with ERB and 24 without ERB (No-ERB) were treated with three-dimensional conformal radiotherapy (3D-CRT) to a dose of 67.5 Gy. The Rwall was divided into 16 mucosal areas and Rwall dose surface maps were constructed. After 3 months, 6 months, 1 year, and 2 years a rectosigmoidoscopy was performed, and each mucosal area was scored on telangiectasia, congestion, ulceration, stricture, and necrosis. Late rectal toxicity was correlated with the endoscopic findings. Results: The ERB significantly reduced the Rwall volume exposed to doses >40 Gy. Late rectal toxicity (grade {>=}1, including excess of bowel movements and slight rectal discharge) was reduced significantly in the ERB group. A total of 146 endoscopies and 2,336 mucosal areas were analyzed. Telangiectases were most frequently seen and appeared after 6 months. At 1 and 2 years, significantly less high-grade telangiectasia (T 2-3) was observed in the ERB group at the lateral and posterior part of the Rwall. In mucosal areas exposed to doses >40 Gy, less high-grade telangiectases (T 2-3) were seen in the ERB group compared with the No-ERB group. Conclusions: An ERB reduced the Rwall volume exposed to doses >40 Gy, resulting in reduction of late rectal mucosal changes and reduced late rectal toxicity. Although further analysis is needed, these data suggest an ERB-induced increased tolerance for late Rwall damage.

  20. Reduced Acute Bowel Toxicity in Patients Treated With Intensity-Modulated Radiotherapy for Rectal Cancer

    SciTech Connect

    Samuelian, Jason M.; Callister, Matthew D.; Ashman, Jonathan B.; Young-Fadok, Tonia M.; Borad, Mitesh J.; Gunderson, Leonard L.

    2012-04-01

    Purpose: We have previously shown that intensity-modulated radiotherapy (IMRT) can reduce dose to small bowel, bladder, and bone marrow compared with three-field conventional radiotherapy (CRT) technique in the treatment of rectal cancer. The purpose of this study was to review our experience using IMRT to treat rectal cancer and report patient clinical outcomes. Methods and Materials: A retrospective review was conducted of patients with rectal cancer who were treated at Mayo Clinic Arizona with pelvic radiotherapy (RT). Data regarding patient and tumor characteristics, treatment, acute toxicity according to the Common Terminology Criteria for Adverse Events v 3.0, tumor response, and perioperative morbidity were collected. Results: From 2004 to August 2009, 92 consecutive patients were treated. Sixty-one (66%) patients were treated with CRT, and 31 (34%) patients were treated with IMRT. All but 2 patients received concurrent chemotherapy. There was no significant difference in median dose (50.4 Gy, CRT; 50 Gy, IMRT), preoperative vs. postoperative treatment, type of concurrent chemotherapy, or history of previous pelvic RT between the CRT and IMRT patient groups. Patients who received IMRT had significantly less gastrointestinal (GI) toxicity. Sixty-two percent of patients undergoing CRT experienced {>=}Grade 2 acute GI side effects, compared with 32% among IMRT patients (p = 0.006). The reduction in overall GI toxicity was attributable to fewer symptoms from the lower GI tract. Among CRT patients, {>=}Grade 2 diarrhea and enteritis was experienced among 48% and 30% of patients, respectively, compared with 23% (p = 0.02) and 10% (p = 0.015) among IMRT patients. There was no significant difference in hematologic or genitourinary acute toxicity between groups. In addition, pathologic complete response rates and postoperative morbidity between treatment groups did not differ significantly. Conclusions: In the management of rectal cancer, IMRT is associated with a

  1. Low interrater reliability in grading of rectal bleeding using National Cancer Institute Common Toxicity Criteria and Radiation Therapy Oncology Group Toxicity scales: a survey of radiation oncologists.

    PubMed

    Huynh-Le, Minh-Phuong; Zhang, Zhe; Tran, Phuoc T; DeWeese, Theodore L; Song, Daniel Y

    2014-12-01

    To measure concordance among genitourinary radiation oncologists in using the National Cancer Institute Common Toxicity Criteria (NCI CTC) and Radiation Therapy Oncology Group (RTOG) grading scales to grade rectal bleeding. From June 2013 to January 2014, a Web-based survey was sent to 250 American and Canadian academic radiation oncologists who treat prostate cancer. Participants were provided 4 case vignettes in which patients received radiation therapy and developed rectal bleeding and were asked for management plans and to rate the bleeding according to NCI CTC v.4 and RTOG late toxicity grading (scales provided). In 2 cases, participants were also asked whether they would send the patient for colonoscopy. A multilevel, random intercept modeling approach was used to assess sources of variation (case, respondent) in toxicity grading to calculate the intraclass correlation coefficient (ICC). Agreement on a dichotomous grading scale (low grades 1-2 vs high grades 3-4) was also assessed, using the κ statistic for multiple respondents. Seventy-two radiation oncologists (28%) completed the survey. Forty-seven (65%) reported having either written or been principal investigator on a study using these scales. Agreement between respondents was moderate (ICC 0.52, 95% confidence interval [CI] 0.47-0.58) when using NCI CTC and fair using the RTOG scale (ICC 0.28, 95% CI 0.20-0.40). Respondents who chose an invasive management were more likely to select a higher toxicity grade (P<.0001). Using the dichotomous scale, we observed moderate agreement (κ = 0.42, 95% CI 0.40-0.44) with the NCI CTC scale, but only slight agreement with the RTOG scale (κ = 0.19, 95% CI 0.17-0.21). Low interrater reliability was observed among radiation oncologists grading rectal bleeding using 2 common scales. Clearer definitions of late rectal bleeding toxicity should be constructed to reduce this variability and avoid ambiguity in both reporting and interpretation. Copyright © 2014 Elsevier

  2. 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

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

    PubMed

    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

    2012-03-07

    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

  4. Reduced rectal toxicity with ultrasound-based image guided radiotherapy using BAT (B-mode acquisition and targeting system) for prostate cancer.

    PubMed

    Bohrer, Markus; Schröder, Peter; Welzel, Grit; Wertz, Hansjörg; Lohr, Frank; Wenz, Frederik; Mai, Sabine Kathrin

    2008-12-01

    To evaluate the effect of image guided radiotherapy with stereotactic ultrasound BAT (B-mode acquisition and targeting system) on rectal toxicity in conformal radiotherapy of prostate cancer. 42 sequential patients with prostate cancer undergoing radiotherapy before and after the introduction of BAT were included. Planning computed tomography (CT) was performed with empty rectum and moderately filled bladder. The planning target volume (PTV) included the prostate and seminal vesicles with a safety margin of 1.5 cm in anterior and lateral direction. In posterior direction the anterior 1/3 of the rectum circumference were included. Total dose was 66 Gy and a boost of 4 Gy excluding the seminal vesicles. 22 patients (BAT group) were treated with daily stereotactic ultrasound positioning, for the other 20 patients (NoBAT group) an EPID (electronic portal imaging device) was performed once a week. Acute and late genito-urinary (GU) and rectal toxicity and PSA values were evaluated after 1.5, 3, 6, 9 and 12 months. The total median follow up of toxicity was 3 years in the BAT group and 4 years in the NoBAT group. In the NoBAT group significant more rectal toxicity occurred, while in GU toxicity no difference was seen. Two patients in the NoBAT group showed late rectal toxicity grade 3, no toxicity>grade 2 occurred in the BAT group. There was no significant difference in PSA reduction between the groups. Without BAT significant more acute and a trend to more late rectal toxicity was found. With regard to dose escalation this aspect is currently evaluated with a larger number of patients using intensity-modulated radiotherapy (IMRT).

  5. Systematic Review of Radiation Therapy Toxicity Reporting in Randomized Controlled Trials of Rectal Cancer: A Comparison of Patient-Reported Outcomes and Clinician Toxicity Reporting

    SciTech Connect

    Gilbert, Alexandra; Ziegler, Lucy; Martland, Maisie; Davidson, Susan; Efficace, Fabio; Sebag-Montefiore, David; Velikova, Galina

    2015-07-01

    The use of multimodal treatments for rectal cancer has improved cancer-related outcomes but makes monitoring toxicity challenging. Optimizing future radiation therapy regimens requires collection and publication of detailed toxicity data. This review evaluated the quality of toxicity information provided in randomized controlled trials (RCTs) of radiation therapy in rectal cancer and focused on the difference between clinician-reported and patient-reported toxicity. Medline, EMBASE, and the Cochrane Library were searched (January 1995-July 2013) for RCTs reporting late toxicity in patients treated with regimens including preoperative (chemo)radiation therapy. Data on toxicity measures and information on toxicity reported were extracted using Quantitative Analyses of Normal Tissue Effects in the Clinic recommendations. International Society for Quality of Life Research standards on patient-reported outcomes (PROs) were used to evaluate the quality of patient-reported toxicity. Twenty-one RCT publications met inclusion criteria out of 4144 articles screened. All PRO studies reported higher rates of toxicity symptoms than clinician-reported studies and reported on a wider range and milder symptoms. No clinician-reported study published data on sexual dysfunction. Of the clinician-reported studies, 55% grouped toxicity data related to an organ system together (eg “Bowel”), and 45% presented data only on more-severe (grade ≥3) toxicity. In comparison, all toxicity grades were reported in 79% of PRO publications, and all studies (100%) presented individual symptom toxicity data (eg bowel urgency). However, PRO reporting quality was variable. Only 43% of PRO studies presented baseline data, 28% did not use any psychometrically validated instruments, and only 29% of studies described statistical methods for managing missing data. Analysis of these trials highlights the lack of reporting standards for adverse events and reveals the differences between clinician and

  6. Urinary and Rectal Toxicity Profiles After Permanent Iodine-125 Implant Brachytherapy in Japanese Men: Nationwide J-POPS Multi-institutional Prospective Cohort Study

    SciTech Connect

    Ohashi, Toshio; Yorozu, Atsunori; Saito, Shiro; Tanaka, Nobumichi; Katayama, Norihisa; Kojima, Shinsuke; Maruo, Shinichiro; Kikuchi, Takashi; Dokiya, Takushi; Fukushima, Masanori; Yamanaka, Hidetoshi

    2015-09-01

    Purpose: To assess, in a nationwide multi-institutional cohort study begun in 2005 and in which 6927 subjects were enrolled by 2010, the urinary and rectal toxicity profiles of subjects who enrolled during the first 2 years, and evaluate the toxicity profiles for permanent seed implantation (PI) and a combination therapy with PI and external beam radiation therapy (EBRT). Methods and Materials: Baseline data for 2339 subjects out of 2354 patients were available for the analyses. Toxicities were evaluated using the National Cancer Institute's Common Terminology Criteria for Adverse Events, and the International Prostate Symptom Scores were recorded prospectively until 36 months after radiation therapy. Results: Grade 2+ acute urinary toxicities developed in 7.36% (172 of 2337) and grade 2+ acute rectal toxicities developed in 1.03% (24 of 2336) of the patients. Grade 2+ late urinary and rectal toxicities developed in 5.75% (133 of 2312) and 1.86% (43 of 2312) of the patients, respectively. A higher incidence of grade 2+ acute urinary toxicity occurred in the PI group than in the EBRT group (8.49% vs 3.66%; P<.01). Acute rectal toxicity outcomes were similar between the treatment groups. The 3-year cumulative incidence rates for grade 2+ late urinary toxicities were 6.04% versus 4.82% for the PI and the EBRT groups, respectively, with no significant differences between the treatment groups. The 3-year cumulative incidence rates for grade 2+ late rectal toxicities were 0.90% versus 5.01% (P<.01) for the PI and the EBRT groups, respectively. The mean of the postimplant International Prostate Symptom Score peaked at 3 months, but it decreased to a range that was within 2 points of the baseline score, which was observed in 1625 subjects (69.47%) at the 1-year follow-up assessment. Conclusions: The acute urinary toxicities observed were acceptable given the frequency and retention, and the late rectal toxicities were more favorable than those of other studies.

  7. Rectal Dose and Source Strength of the High-Dose-Rate Iridium-192 Both Affect Late Rectal Bleeding After Intracavitary Radiation Therapy for Uterine Cervical Carcinoma

    SciTech Connect

    Isohashi, Fumiaki; Yoshioka, Yasuo; Koizumi, Masahiko

    2010-07-01

    Purpose: The purpose of this study was to reconfirm our previous findings that the rectal dose and source strength both affect late rectal bleeding after high-dose-rate intracavitary brachytherapy (HDR-ICBT), by using a rectal dose calculated in accordance with the definitions of the International Commission on Radiation Units and Measurements Report 38 (ICRU{sub RP}) or of dose-volume histogram (DVH) parameters by the Groupe Europeen de Curietherapie of the European Society for Therapeutic Radiology and Oncology. Methods and Materials: Sixty-two patients who underwent HDR-ICBT and were followed up for 1 year or more were studied. The rectal dose for ICBT was calculated by using the ICRP{sub RP} based on orthogonal radiographs or the DVH parameters based on computed tomography (CT). The total dose was calculated as the biologically equivalent dose expressed in 2-Gy fractions (EQD{sub 2}). The relationship between averaged source strength or the EQD{sub 2} and late rectal bleeding was then analyzed. Results: When patients were divided into four groups according to rectal EQD{sub 2} ({>=} or =} or <2.4 cGy.m{sup 2}.h{sup -1}), the group with both a high EQD{sub 2} and a high source strength showed a significantly greater probability of rectal bleeding for ICRU{sub RP}, D{sub 2cc}, and D{sub 1cc}. The patients with a median rectal dose above the threshold level did not show a greater frequency of rectal bleeding unless the source strength exceeded 2.4 cGy.m{sup 2}.h{sup -1}. Conclusions: Our results obtained with data based on ICRU{sub RP} and CT-based DVH parameters indicate that rectal dose and source strength both affect rectal bleeding after HDR-ICBT.

  8. Rectal dose and source strength of the high-dose-rate iridium-192 both affect late rectal bleeding after intracavitary radiation therapy for uterine cervical carcinoma.

    PubMed

    Isohashi, Fumiaki; Yoshioka, Yasuo; Koizumi, Masahiko; Suzuki, Osamu; Konishi, Koji; Sumida, Iori; Takahashi, Yutaka; Ogata, Toshiyuki; Kotsuma, Tadayuki; Inoue, Takehiro

    2010-07-01

    The purpose of this study was to reconfirm our previous findings that the rectal dose and source strength both affect late rectal bleeding after high-dose-rate intracavitary brachytherapy (HDR-ICBT), by using a rectal dose calculated in accordance with the definitions of the International Commission on Radiation Units and Measurements Report 38 (ICRU(RP)) or of dose-volume histogram (DVH) parameters by the Groupe Européen de Curietherapie of the European Society for Therapeutic Radiology and Oncology. Sixty-two patients who underwent HDR-ICBT and were followed up for 1 year or more were studied. The rectal dose for ICBT was calculated by using the ICRP(RP) based on orthogonal radiographs or the DVH parameters based on computed tomography (CT). The total dose was calculated as the biologically equivalent dose expressed in 2-Gy fractions (EQD(2)). The relationship between averaged source strength or the EQD(2) and late rectal bleeding was then analyzed. When patients were divided into four groups according to rectal EQD(2) (>or= or or= or <2.4 cGy.m(2).h(-1)), the group with both a high EQD(2) and a high source strength showed a significantly greater probability of rectal bleeding for ICRU(RP), D(2cc), and D(1cc). The patients with a median rectal dose above the threshold level did not show a greater frequency of rectal bleeding unless the source strength exceeded 2.4 cGy.m(2).h(-1). Our results obtained with data based on ICRU(RP) and CT-based DVH parameters indicate that rectal dose and source strength both affect rectal bleeding after HDR-ICBT. (c) 2010 Elsevier Inc. All rights reserved.

  9. Cross-Linked Hyaluronan Gel Reduces the Acute Rectal Toxicity of Radiotherapy for Prostate Cancer

    SciTech Connect

    Wilder, Richard B.; Barme, Greg A.; Gilbert, Ronald F.; Holevas, Richard E.; Kobashi, Luis I.; Reed, Richard R.; Solomon, Ronald S.; Walter, Nancy L.; Chittenden, Lucy; Mesa, Albert V.; Agustin, Jeffrey; Lizarde, Jessica; Macedo, Jorge; Ravera, John; Tokita, Kenneth M.

    2010-07-01

    Purpose: To prospectively analyze whether cross-linked hyaluronan gel reduces the mean rectal dose and acute rectal toxicity of radiotherapy for prostate cancer. Methods and Materials: Between September 2008 and March 2009, we transperitoneally injected 9mL of cross-linked hyaluronan gel (Hylaform; Genzyme Corporation, Cambridge, MA) into the anterior perirectal fat of 10 early-stage prostate cancer patients to increase the separation between the prostate and rectum by 8 to 18mm at the start of radiotherapy. Patients then underwent high-dose rate brachytherapy to 2,200cGy followed by intensity-modulated radiation therapy to 5,040cGy. We assessed acute rectal toxicity using the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 grading scheme. Results: Median follow-up was 3 months. The anteroposterior dimensions of Hylaform at the start and end of radiotherapy were 13 {+-} 3mm (mean {+-} SD) and 10 {+-} 4mm, respectively. At the start of intensity-modulated radiation therapy, daily mean rectal doses were 73 {+-} 13cGy with Hylaform vs. 106 {+-} 20cGy without Hylaform (p = 0.005). There was a 0% incidence of National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 Grade 1, 2, or 3 acute diarrhea in 10 patients who received Hylaform vs. a 29.7% incidence (n = 71) in 239 historical controls who did not receive Hylaform (p = 0.04). Conclusions: By increasing the separation between the prostate and rectum, Hylaform decreased the mean rectal dose. This led to a significant reduction in the acute rectal toxicity of radiotherapy for prostate cancer.

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

    SciTech Connect

    Tho, Lye Mun . E-mail: l.tho@beatson.gla.ac.uk; Glegg, Martin; Paterson, Jennifer; Yap, Christina; MacLeod, Alice; McCabe, Marie; McDonald, Alexander C.

    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 intervals (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

  11. Late Toxicity After Intensity-Modulated Radiation Therapy for Localized Prostate Cancer: An Exploration of Dose-Volume Histogram Parameters to Limit Genitourinary and Gastrointestinal Toxicity

    SciTech Connect

    Pederson, Aaron W.; Fricano, Janine; Correa, David; Pelizzari, Charles A.; Liauw, Stanley L.

    2012-01-01

    Purpose: To characterize the late genitourinary (GU) and gastrointestinal (GI) toxicity for prostate cancer patients treated with intensity-modulated radiation therapy (IMRT) and propose dose-volume histogram (DVH) guidelines to limit late treatment-related toxicity. Methods and Materials: In this study 296 consecutive men were treated with IMRT for adenocarcinoma of the prostate. Most patients received treatment to the prostate with or without proximal seminal vesicles (90%), to a median dose of 76 Gy. Concurrent androgen deprivation therapy was given to 150 men (51%) for a median of 4 months. Late toxicity was defined by Common Toxicity Criteria version 3.0 as greater than 3 months after radiation therapy completion. Four groupings of DVH parameters were defined, based on the percentage of rectal or bladder tissue receiving 70 Gy (V{sub 70}), 65 Gy (V{sub 65}), and 40 Gy (V{sub 40}). These DVH groupings, as well as clinical and treatment characteristics, were correlated to maximal Grade 2+ GU and GI toxicity. Results: With a median follow-up of 41 months, the 4-year freedom from maximal Grade 2+ late toxicity was 81% and 91% for GU and GI systems, respectively, and by last follow-up, the rates of Grade 2+ GU and GI toxicity were 9% and 5%, respectively. On multivariate analysis, whole-pelvic IMRT was associated with Grade 2+ GU toxicity and age was associated with Grade 2+ GI toxicity. Freedom from Grade 2+ GI toxicity at 4 years was 100% for men with rectal V{sub 70} {<=}10%, V{sub 65} {<=}20%, and V{sub 40} {<=}40%; 92% for men with rectal V{sub 70} {<=}20%, V{sub 65} {<=}40%, and V{sub 40} {<=}80%; and 85% for men exceeding these criteria (p = 0.13). These criteria were more highly associated with GI toxicity in men aged {>=}70 years (p = 0.07). No bladder dose-volume relationships were associated with the risk of GU toxicity. Conclusions: IMRT is associated with low rates of severe GU or GI toxicity after treatment for prostate cancer. Rectal dose constraints

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

    SciTech Connect

    Peterson, Jennifer L.; Buskirk, Steven J.; Heckman, Michael G.; Diehl, Nancy N.; Bernard, Johnny R.; Tzou, Katherine S.; Casale, Henry E.; Bellefontaine, Louis P.; Serago, Christopher; Kim, Siyong; Vallow, Laura A.; Daugherty, Larry C.; Ko, Stephen J.

    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 Terminology 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.

  13. Increasing the risk of late rectal bleeding after high-dose radiotherapy for prostate cancer: the case of previous abdominal surgery. Results from a prospective trial.

    PubMed

    Valdagni, Riccardo; Vavassori, Vittorio; Rancati, Tiziana; Fellin, Gianni; Baccolini, Micaela; Bianchi, Carla; Cagna, Emanuela; Gabriele, Pietro; Mauro, Floranna; Menegotti, Loris; Monti, Angelo Filippo; Stasi, Michele; Fiorino, Claudio

    2012-05-01

    To evaluate and discuss the role of specific types of abdominal surgery (SURG) before radical radiation therapy as a risk factor for late rectal toxicity in prostate cancer patients. Results concerning questionnaire-based scored late bleeding and faecal incontinence in 718 patients with a complete follow-up of 36 months were analysed, focusing on the impact of specific pre-radiotherapy abdominal/pelvic surgery procedures. Patients were accrued in the prospective study AIROPROS 0102. Different types of surgery (rectum-sigma resection, kidney resection, cholecystectomy or appendectomy) were considered as covariates together with a number of different parameters previously found to be predictive of late toxicity and including clinical as well as dosimetric parameters. Univariate (UVA) and multivariate (MVA) logistic analyses were carried out. In total 69/718 patients were previously submitted to one or more surgical procedures, mostly cholecystectomy (n=21) and appendectomy (n=27). Actuarial incidences of G2-G3 and G3 bleeding were 52 (7.2%) and 24 (3.3%) respectively; 19 (2.6%) chronic incontinence events were registered. Cholecystectomy was found to be highly correlated with late rectal bleeding at UVA: OR=4.3 and p=0.006 for G2-G3 and OR=5.4 and p=0.01 for G3. Considering MVA (including dosimetric and clinical factors), G2-G3 bleeding was significantly correlated to cholecystectomy (OR=6.5, p=0.002), V75 Gy (OR=1.074, p=0.003) and secondarily with appendectomy (OR=2.7, p=0.10), presence of acute radioinduced rectal bleeding (OR=1.70, p=0.21) and androgen deprivation (OR=0.67, p=0.25). Appendectomy (OR=5.9, p=0.004) and cholecystectomy (OR=5.5, p=0.016) were very strong predictors of G3 bleeding with V75 Gy playing a less significant role (OR=1.037, p=0.26). Conversely, no specific surgery was correlated with actuarial or chronic incontinence. This analysis highlights previous SURG as the best predictor of late rectal bleeding. Among the different types of abdominal

  14. Acute and late gastrointestinal toxicity after radiotherapy in prostate cancer patients: Consequential late damage

    SciTech Connect

    Heemsbergen, Wilma D. . E-mail: w.heemsbergen@nki.nl; Peeters, Stephanie T.H.; Koper, Peter; Hoogeman, Mischa S.; Lebesque, Joos V.

    2006-09-01

    Purpose: Late gastrointestinal (GI) toxicity after radiotherapy can be partly explained by late effects of acute toxicity (consequential late damage). We studied whether there is a direct relationship between acute and late GI toxicity. Patients and Methods: A total of 553 evaluable patients from the Dutch dose escalation trial (68 Gy vs. 78 Gy) were included. We defined three outcomes for acute reactions: 1) maximum Radiation Therapy Oncology Group acute toxicity, 2) maximum acute mucous discharge (AMD), and 3) maximum acute proctitis. Within a multivariable model, late endpoints (overall toxicity and five toxicity indicators) were studied as a function of acute toxicity, pretreatment symptoms, and relevant dose parameters. Results: At multivariable analysis, AMD and acute proctitis were strong predictors for overall toxicity, 'intermittent bleeding,' and 'incontinence pads' (p {<=} 0.01). For 'stools {>=}6/day' all three were strong predictors. No significant associations were found for 'severe bleeding' and 'use of steroids.' The predictive power of the dose parameters remained at the same level or became weaker for most late endpoints. Conclusions: Acute GI toxicity is an independent significant predictor of late GI toxicity. This suggests a significant consequential component in the development of late GI toxicity.

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

    PubMed Central

    Acosta, Oscar; Drean, Gael; Ospina, Juan David; Simon, Antoine; Haigron, Pascal; Lafond, Caroline; De Crevoisier, Renaud

    2013-01-01

    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 80Gy to the prostate by IMRT. Within the patients presenting bleeding, a significant dose excess (6Gy on average, p<0.01) was found in a region of the anterior rectal wall. This region, close to the prostate (1cm), 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. PMID:23528429

  16. Late Side Effects and Quality of Life After Radiotherapy for Rectal Cancer

    SciTech Connect

    Bruheim, Kjersti; Guren, Marianne G.; Skovlund, Eva; Hjermstad, Marianne J.; Dahl, Olav; Frykholm, Gunilla; Carlsen, Erik; Tveit, Kjell Magne

    2010-03-15

    Purpose: There is little knowledge on long-term morbidity after radiotherapy (50 Gy) and total mesorectal excision for rectal cancer. Therefore, late effects on bowel, anorectal, and urinary function, and health-related quality of life (QoL), were studied in a national cohort (n = 535). Methods and Materials: All Norwegian patients who received pre- or postoperative (chemo-)radiotherapy for rectal cancer from 1993 to 2003 were identified. Patients treated with surgery alone served as controls. Patients were without recurrence or metastases. Bowel and urinary function was scored with the LENT SOMA scale and the St. Marks Score for fecal incontinence and QoL with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). Results: Median time since surgery was 4.8 years. Radiation-treated (RT+) patients (n = 199) had increased bowel frequency compared with non-radiation-treated (RT-) patients (n = 336); 19% vs. 6% had more than eight daily bowel movements (p < 0.001). In patients without stoma, a higher proportion of RT+ (n = 69) compared with RT- patients (n = 240), were incontinent for liquid stools (49% vs. 15%, p < 0.001), needed a sanitary pad (52% vs. 13%, p < 0.001), and lacked the ability to defer defecation (44% vs. 16%, p < 0.001). Daily urinary incontinence occurred more frequently after radiotherapy (9% vs. 2%, p = 0.001). Radiation-treated patients had worse social function than RT- patients, and patients with fecal or urinary incontinence had impaired scores for global quality of life and social function (p < 0.001). Conclusions: Radiotherapy for rectal cancer is associated with considerable long-term effects on anorectal function, especially in terms of bowel frequency and fecal incontinence. RT+ patients have worse social function, and fecal incontinence has a negative impact on QoL.

  17. Low inter-rater reliability in grading of rectal bleeding using NCI CTC and RTOG toxicity scales: a survey of radiation oncologists

    PubMed Central

    Huynh-Le, Minh-Phuong; Zhang, Zhe; Tran, Phuoc T.; DeWeese, Theodore L.; Song, Danny Y.

    2014-01-01

    Purpose/Objective(s) Rectal bleeding is one of the most common toxicities following prostate radiotherapy (RT), and both NCI CTC and RTOG grading scales are frequently used to report outcomes. We measured concordance among genitourinary radiation oncologists in using these scales to grade rectal bleeding. Methods and Materials From 6/2013–1/2014, a web-based survey was sent to 250 American and Canadian academic radiation oncologists who treat prostate cancer. Participants were provided 4 case vignettes where patients received RT and developed rectal bleeding and were asked for management plans and to rate the bleeding according to NCI CTC v.4 and RTOG late toxicity grading (scales provided). In 2 cases, participants were also asked if they would send the patient for colonoscopy. A multilevel, random intercept modeling approach was used to assess sources of variation (case, respondent) in toxicity grading to calculate the intraclass correlation coefficient (ICC). Agreement on a dichotomous grading scale (low grades 1–2 vs. high grades 3–4) was also assessed, using kappa statistic for multiple respondents. Results Seventy-two radiation oncologists (28%) completed the survey. Forty-seven (65%) reported having either written or been principal investigator on a study using these scales. Agreement between respondents was moderate (ICC=0.52, 95% CI 0.47–0.58) when using NCI CTC and fair using the RTOG scale (ICC=0.28, 95% CI 0.20–0.40). Respondents who chose an invasive management were more likely to select a higher toxicity grade (p<0.0001). Using the dichotomous scale, we observed moderate agreement (kappa=0.42, 95% CI 0.40–0.44) with the NCI CTC scale, but only slight agreement with the RTOG scale (kappa=0.19, 95% CI 0.17–0.21). Conclusion Low inter-rater reliability was observed among radiation oncologists grading rectal bleeding using two common scales. Clearer definitions of late rectal bleeding toxicity should be constructed to reduce this variability

  18. USE OF FRACTIONAL DOSE-VOLUME HISTOGRAMS TO MODEL RISK OF ACUTE RECTAL TOXICITY AMONG PATIENTS TREATED ON RTOG 94-06

    PubMed Central

    Tucker, Susan L.; Michalski, Jeff M.; Bosch, Walter R.; Mohan, Radhe; Dong, Lei; Winter, Kathryn; Purdy, James A.; Cox, James D.

    2012-01-01

    Background and Purpose For toxicities occurring during the course of radiotherapy, it is conceptually inaccurate to perform normal-tissue complication probability analyses using the complete dose-volume histogram. The goal of this study was to analyze acute rectal toxicity using a novel approach in which the fit of the Lyman-Kutcher-Burman (LKB) model is based on the fractional rectal dose-volume histogram (DVH). Materials and Methods Grade ≥2 acute rectal toxicity was analyzed in 509 patients treated on Radiation Therapy Oncology Group (RTOG) protocol 94-06. These patients had no field reductions or treatment-plan revisions during therapy, allowing the fractional rectal DVH to be estimated from the complete rectal DVH based on the total number of dose fractions delivered. Results The majority of patients experiencing Grade ≥2 acute rectal toxicity did so before completion of radiotherapy (70/80=88%). Acute rectal toxicity depends on fractional mean rectal dose, with no significant improvement in the LKB model fit when the volume parameter differs from n=1. The incidence of toxicity was significantly lower for patients who received hormone therapy (P=0.024). Conclusions Variations in fractional mean dose explain the differences in incidence of acute rectal toxicity, with no detectable effect seen here for differences in numbers of dose fractions delivered. PMID:22673726

  19. Rectal temperature changes and oxygen toxicity in dogs treated in a monoplace chamber.

    PubMed

    Shmalberg, Justin; Davies, Wendy; Lopez, Stacy; Shmalberg, Danielle; Zilberschtein, Jose

    2015-01-01

    Hyperbaric oxygen treatments are increasingly administered to pet dogs, using veterinary-specific monoplace chambers. The basic physiologic responses, chamber performance and oxygen toxicity rates have not yet been evaluated in dogs in a clinical setting. As a result, a series of consecutive 45-minute, 2-atmospheres absolute (atm abs) hyperbaric treatments with 100% oxygen were evaluated in a veterinary rehabilitation center (n = 285). 65 dogs with a mean body weight of 21 ± 15 kg (1.4-71 kg) were treated with an average of four sessions each. The mean rectal temperature of canine patients decreased 0.07 degrees C (0.1 degrees F) during treatments (p = 0.04). Intra-chamber temperature and humidity both increased: +1.0 degrees C (1.7 degrees F, p < 0.0001) and +5.7% (p < 0.0001), respectively. The mean maximal oxygen concentration measured before depressurization of the veterinary-specific commercial chamber was 98.0 ± 0.9%. No strong correlations (r > 0.75) were identified between body weights, body condition scores, maximal oxygen concentrations, starting or ending rectal temperature, chamber humidity and chamber temperature. Oxygen toxicity was not observed during the observational period. Patients were most commonly treated for intervertebral disc disease (n = 16 dogs) and extensive traumatic wounds (n = 10 dogs), which represented a large number of the total study sessions (19% and 16%, respectively).

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

    PubMed

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

    2013-04-21

    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.

  1. 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.

  2. Quantifying cell migration distance as a contributing factor to the development of rectal toxicity after prostate radiotherapy

    SciTech Connect

    Munbodh, Reshma; Jackson, Andrew

    2014-02-15

    Purpose: Spatial information is usually neglected in mathematical models of radiation-induced toxicity. In the presence of inhomogeneous dose distributions produced by intensity modulated radiation therapy (IMRT) and volumetric arc therapy, this may be a limitation. We present a model to quantify the spatial characteristics of the dose distribution on the rectum through the quantification of the distribution of distances between dose points on the surface of the rectum in three-dimensions. The method allows us to evaluate the hypothesis that distances between lower and higher dose regions on the rectum influence radiation damage repair due to the migration of normal cells into damaged areas, and consequently, the development of radiation-induced toxicity in patients treated with radiation for prostate cancer. Methods: We present a method to compute distances between dose points on the surface of the rectum in three dimensions (3D) and to generate distance maps representing the distances between specific dose regions on the rectum. We introduce the concept of the distance dose surface histogram (DDSH), which is computed from the distance maps. The DDSH is a 2D histogram of rectum area on a grid defined by pairwise combinations of dose and distance. Each bin in the DDSH quantifies the area of the rectum exposed to a given dose and at a given distance from other another dose region on the rectum. By summing across the columns and rows of the DDSH, we can generate the dose surface histogram (DSH) and distance surface histogram (DiSH) for a particular dose region. The DiSH is a marginal histogram showing the distribution of distances for the dose points in a specific dose region from another region. We computed the DDSH, DiSH, and DSH for 33 patients treated with IMRT for prostate cancer, nine of whom developed late Grade 2 or higher late rectal toxicity. Results: We show how even though the total area of the rectum exposed to a given dose may be the same for different

  3. Relation between Ku80 and microRNA-99a expression and late rectal bleeding after radiotherapy for prostate cancer.

    PubMed

    Someya, Masanori; Yamamoto, Hiroyuki; Nojima, Masanori; Hori, Masakazu; Tateoka, Kunihiko; Nakata, Kensei; Takagi, Masaru; Saito, Masato; Hirokawa, Naoki; Tokino, Takashi; Sakata, Koh-Ichi

    2015-05-01

    Late rectal bleeding is one of the severe adverse events after radiotherapy for prostate cancer. New biomarkers are needed to allow a personalized treatment. Four patients each with grade 0-1 or grade 2-3 rectal bleeding were randomly selected for miRNA array to examine miRNA expression in peripheral blood lymphocytes (PBLs). Based on results of miRNA array, 1 of 348 miRNAs was selected for microRNA assays. Then, expression of DNA-dependent protein kinase mRNA and miR-99a was analyzed in the PBLs of 97 patients. PBLs were exposed to 4Gy of X-ray ex-vivo. In the discovery cohort, grade 2-3 rectal bleeding was significantly higher in the Ku80 <1.09 expression group compared with ⩾1.09 group (P=0.011). In radiation-induced expression of miR-99a, grade 2-3 rectal bleeding was significantly higher in the miR-99a IR(+)/IR(-) >0.93 group compared with ⩽0.93 group (P=0.013). Most patients with grade 2-3 rectal bleeding were in the group with low Ku80 and high miR-99a expression. In the validation cohort, similar results were obtained. A combination of low Ku80 expression and highly-induced miR-99a expression could be a promising marker for predicting rectal bleeding after radiotherapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Low Interrater Reliability in Grading of Rectal Bleeding Using National Cancer Institute Common Toxicity Criteria and Radiation Therapy Oncology Group Toxicity Scales: A Survey of Radiation Oncologists

    SciTech Connect

    Huynh-Le, Minh-Phuong; Zhang, Zhe; Tran, Phuoc T.; DeWeese, Theodore L.; Song, Daniel Y.

    2014-12-01

    Purpose: To measure concordance among genitourinary radiation oncologists in using the National Cancer Institute Common Toxicity Criteria (NCI CTC) and Radiation Therapy Oncology Group (RTOG) grading scales to grade rectal bleeding. Methods and Materials: From June 2013 to January 2014, a Web-based survey was sent to 250 American and Canadian academic radiation oncologists who treat prostate cancer. Participants were provided 4 case vignettes in which patients received radiation therapy and developed rectal bleeding and were asked for management plans and to rate the bleeding according to NCI CTC v.4 and RTOG late toxicity grading (scales provided). In 2 cases, participants were also asked whether they would send the patient for colonoscopy. A multilevel, random intercept modeling approach was used to assess sources of variation (case, respondent) in toxicity grading to calculate the intraclass correlation coefficient (ICC). Agreement on a dichotomous grading scale (low grades 1-2 vs high grades 3-4) was also assessed, using the κ statistic for multiple respondents. Results: Seventy-two radiation oncologists (28%) completed the survey. Forty-seven (65%) reported having either written or been principal investigator on a study using these scales. Agreement between respondents was moderate (ICC 0.52, 95% confidence interval [CI] 0.47-0.58) when using NCI CTC and fair using the RTOG scale (ICC 0.28, 95% CI 0.20-0.40). Respondents who chose an invasive management were more likely to select a higher toxicity grade (P<.0001). Using the dichotomous scale, we observed moderate agreement (κ = 0.42, 95% CI 0.40-0.44) with the NCI CTC scale, but only slight agreement with the RTOG scale (κ = 0.19, 95% CI 0.17-0.21). Conclusion: Low interrater reliability was observed among radiation oncologists grading rectal bleeding using 2 common scales. Clearer definitions of late rectal bleeding toxicity should be constructed to reduce this variability and avoid ambiguity in both

  5. 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.

  6. Predictors of urinary and rectal toxicity after external conformed radiation therapy in prostate cancer: Correlation between clinical, tumour and dosimetric parameters and radical and postoperative radiation therapy.

    PubMed

    Martínez-Arribas, C M; González-San Segundo, C; Cuesta-Álvaro, P; Calvo-Manuel, F A

    2017-06-15

    To determine rectal and urinary toxicity after external beam radiation therapy (EBRT), assessing the results of patients who undergo radical or postoperative therapy for prostate cancer (pancreatic cancer) and their correlation with potential risk factors. A total of 333 patients were treated with EBRT. Of these, 285 underwent radical therapy and 48 underwent postoperative therapy (39 cases of rescue and 9 of adjuvant therapy). We collected clinical, tumour and dosimetric variable to correlate with toxicity parameters. We developed decision trees based on the degree of statistical significance. The rate of severe acute toxicity, both urinary and rectal, was 5.4% and 1.5%, respectively. The rate of chronic toxicity was 4.5% and 2.7%, respectively. Twenty-seven patients presented haematuria, and 9 presented haemorrhagic rectitis. Twenty-five patients (7.5%) presented permanent limiting sequela. The patients with lower urinary tract symptoms prior to the radiation therapy presented poorer tolerance, with greater acute bladder toxicity (P=0.041). In terms of acute rectal toxicity, 63% of the patients with mean rectal doses >45Gy and anticoagulant/antiplatelet therapy developed mild toxicity compared with 37% of the patients with mean rectal doses <45 Gy and without anticoagulant therapy. We were unable to establish predictors of chronic toxicity in the multivariate analysis. The long-term sequelae were greater in the patients who underwent urological operations prior to the radiation therapy and who were undergoing anticoagulant therapy. The tolerance to EBRT was good, and severe toxicity was uncommon. Baseline urinary symptoms constitute the predictor that most influenced the acute urinary toxicity. Rectal toxicity is related to the mean rectal dose and with anticoagulant/antiplatelet therapy. There were no significant differences in severe toxicity between radical versus postoperative radiation therapy. Copyright © 2017 AEU. Publicado por Elsevier España, S

  7. Clinical and Dosimetric Predictors of Late Rectal Syndrome After 3D-CRT for Localized Prostate Cancer: Preliminary Results of a Multicenter Prospective Study

    SciTech Connect

    Fiorino, Claudio Fellin, Gianni; Rancati, Tiziana; Vavassori, Vittorio; Bianchi, Carla; Borca, Valeria Casanova; Girelli, Giuseppe; Mapelli, Marco; Menegotti, Loris; Nava, Simona; Valdagni, Riccardo

    2008-03-15

    Purpose: To assess the predictors of late rectal toxicity in a prospectively investigated group of patients treated at 70-80 Gy for prostate cancer (1.8-2 Gy fractions) with three-dimensional conformal radiotherapy. Methods and Materials: A total of 1,132 patients were entered into the study between 2002 and 2004. Three types of rectal toxicity, evaluated by a self-administered questionnaire, mainly based on the subjective objective management, analytic late effects of normal tissue system, were considered: stool frequency/tenesmus/pain, fecal incontinence, and bleeding. The data from 506 patients with a follow-up of 24 months were analyzed. The correlation between a number of clinical and dosimetric parameters and Grade 2 or greater toxicity was investigated by univariate and multivariate (MVA) logistic analyses. Results: Of the 1,132 patients, 21, 15, and 30 developed stool frequency/tenesmus/pain, fecal incontinence, and bleeding, respectively. Stool frequency/tenesmus/pain correlated with previous abdominal/pelvic surgery (MVA, p = 0.05, odds ratio [OR], 3.3). With regard to incontinence, MVA showed the volume receiving {>=}40 Gy (V{sub 40}) (p = 0.035, OR, 1.037) and surgery (p = 0.02, OR, 4.4) to be the strongest predictors. V{sub 40} to V{sub 70} were highly predictive of bleeding; V{sub 70} showed the strongest impact on MVA (p = 0.03), together with surgery (p = 0.06, OR, 2.5), which was also the main predictor of Grade 3 bleeding (p = 0.02, OR, 4.2). Conclusions: The predictive value of the dose-volume histogram was confirmed for bleeding, consistent with previously suggested constraints (V{sub 50} <55%, V{sub 60} <40%, V{sub 70} <25%, and V{sub 75} <5%). A dose-volume histogram constraint for incontinence can be suggested (V{sub 40} <65-70%). Previous abdominal/pelvic surgery correlated with all toxicity types; thus, a modified constraint for bleeding (V{sub 70} <15%) can be suggested for patients with a history of abdominal/pelvis surgery, although

  8. Effect of High-Dose-Rate {sup 192}Ir Source Activity on Late Rectal Bleeding After Intracavitary Radiation Therapy for Uterine Cervix Cancer

    SciTech Connect

    Suzuki, Osamu Yoshioka, Yasuo; Isohashi, Fumiaki; Morimoto, Masahiro; Kotsuma, Tadayuki; Kawaguchi, Yoshifumi; Konishi, Koji; Nakamura, Satoaki; Shiomi, Hiroya; Inoue, Takehiro

    2008-08-01

    Purpose: This retrospective study analyzed the effect of the activity of high-dose-rate (HDR) {sup 192}Ir source on late rectal bleeding after HDR intracavitary radiotherapy (ICRT) in patients with uterine cervix cancer. Methods and Materials: One hundred thirty-two patients who underwent HDR-ICRT and external beam radiotherapy (EBRT) were analyzed. The rectal point dose in ICRT was calculated by inserting a lead wire into the rectal lumen and summed with the whole-pelvic EBRT dose. The rectal biologic effective dose (BED) was calculated. The relationship between averaged source activity or the BED and late rectal bleeding were analyzed. Results: Three-year actuarial rectal bleeding probabilities were 46% ({>=}100 Gy{sub 3}) and 18% ({<=} 100 Gy{sub 3}), respectively (p < 0.005). When patients were divided into four groups according to rectal BED ({>=} or {<=}100 Gy{sub 3}) and source activity ({>=} or {<=}2.4 cGy.m{sup 2}.h{sup -1}), the group with both a high BED and high activity showed significantly greater probability (58% at 3 years; p < 0.005). It was noted that the probability of the group with BED of 100 Gy{sub 3} or greater was high, but that was not the case with 2.4 cGy.m{sup 2}.h{sup -1} or less. Conclusion: This is the first clinical report concerning the source activity effect of HDR {sup 192}Ir on late rectal bleeding in patients undergoing HDR-ICRT. This suggests that when source activity is higher than 2.4 cGy.m{sup 2}.h{sup -1}, ICRT should be performed with more caution not to exceed 100 Gy{sub 3} in total.

  9. Late Toxicity After Definitive Concurrent Chemoradiotherapy for Thoracic Esophageal Carcinoma

    SciTech Connect

    Morota, Madoka Gomi, Kotaro; Kozuka, Takuyo; Chin, Keisho; Matsuura, Masaaki; Oguchi, Masahiko; Ito, Hisao; Yamashita, Takashi

    2009-09-01

    Purpose: To evaluate late cardiopulmonary toxicities after concurrent chemoradiotherapy (CCRT) for esophageal carcinomas. Methods and Materials: From February 2002 through April 2005, 74 patients with clinical Stage I-IVB carcinoma of the esophagus were treated with CCRT. Sixty-nine patients with thoracic squamous cell carcinoma were the core of this analysis. Patients received 60 Gy of radiation therapy in 30 fractions over 8 weeks, including a 2-week break, and received 2 cycles of fluorouracil/cisplatin chemotherapy concomitantly. Initial radiation fields included primary tumors, metastatic lymph nodes, and supraclavicular, mediastinal, and celiac nodes areas. Late toxicities were assessed with the late radiation morbidity scoring scheme of the Radiation Therapy Oncology Group/European Organiation for Research and Treatment of Cancer. Results: The median age was 67 years (range, 45-83 years). The median follow-up time was 26.1 months for all patients and 51.4 months for patients still alive at the time of analysis. Five cardiopulmonary toxic events of Grade 3 or greater were observed in 4 patients, Grade 5 heart failure and Grade 3 pericarditis in 1 patient, and Grade 3 myocardial infarction, Grade 3 radiation pneumonitis, and Grade 3 pleural effusion. The 2-year cumulative incidence of late cardiopulmonary toxicities of Grade 3 or greater for patients 75 years or older was 29% compared with 3% for younger patients (p = 0.005). Conclusion: The CCRT used in this study with an extensive radiation field is acceptable for younger patients but is not tolerated by patients older than 75 years.

  10. Cancer of the uterine cervix: dosimetric guidelines for prevention of late rectal and rectosigmoid complications as a result of radiotherapeutic treatment

    SciTech Connect

    Pourquier, H.; Dubois, J.B.; Delard, R.

    1982-11-01

    This paper is the report of a dosimetric study of 41 rectal and rectosigmoid complications after radiotherapeutic treatment (1974-1978) of 287 cervical uterine tumors. Treatment consisted of external irradiation (25 MeV linear accelerator) and intracavitary irradiation (Fletcher-Suit applicator) at different doses depending on tumor stage. Dosimetric measurements were expressed as the maximum rectal dose and mean rectal dose on the anterior surface of the rectum, as proposed by the Groupe Europeen de Curietherapie. Rectal doses were also studied as a function of intracavitary irradiation and intracavitary + external irradiation (maximum rectal and mean cummulative doses for each). The results show a significant difference in the state of the patients with and without complications, based on the dose reaching the rectum. The maximum and the mean cumulative rectal doses serve as one of the primary indicators for predicting complications. These values should therefore be determined before placement of intracavitary sources or, at the latest, before the second intracavitary applications. We have shown that there is no fixed threshold dose, but that it varies from one region to another, depending on level of external irradiation. Our results argue in favor of adapting individual patient therapy based on simple precautions, which are adjustable to all treatment modalities. This method could lead to complete elimination of late rectal and rectosigmoid complications arising from radiotherapeutic treatment of cervical uterine cancer.

  11. Cancer of the uterine cervix: dosimetric guidelines for prevention of late rectal and rectosigmoid complications as a result of radiotherapeutic treatment

    SciTech Connect

    Pourquier, H.; Dubois, J.B.; Delard, R.

    1982-11-01

    This paper is the report of a dosimetric study of 41 rectal and rectosigmoid complications after radiotherapeutic treatment (1974-1978) of 287 cervical uterine tumors. Treatment consisted of external irradiation (25 MeV linear accelerator) and intracavitary irradiation (Fletcher-Suit applicator) at different doses depending on tumor stage. Dosimetric measurements were expressed as the maximum rectal dose and mean rectal dose on the anterior surface of the rectum, as proposed by the Groupe Europeen de Curietherapie. Rectal doses were also studied as a function of intracavitary irradiation + external irradiation (maximum rectal and mean cumulative doses for each).The results show a significant difference in the state of the patients with and without complications, based on the dose reaching the rectum. The maximum and the mean cumulative rectal doses serve as one of the primary indicators for predicting complications. These values should therefore be determined before placement of intracavitary sources or, at the latest, before the second intracavitary application. We have shown that there is no fixed threshold dose, but that it varies from one region to another, depending on level of external irradiation. Our results argue in favor of adapting individual patient therapy based on simple precautions, which are applicable to all treatment modalities. This method could lead to complete elimination of late rectal and rectosigmoid complications arising from radiotherapeutic treatment of cervical uterine cancer.

  12. [Quality radiotherapy in rectal cancer].

    PubMed

    Capirci, C; Amichetti, M; De Renzis, C

    2001-01-01

    The quality of radiotherapy significantly impacts on the results of treatment, in patients with rectal carcinoma, especially in terms of acute and late toxicity. Based on this assumption, the Italian Association of Radiation Oncology (AIRO) formulated a document aimed to define the standards of radiation treatment for rectal carcinomas. Two different levels of standard were described: a first level, considered as "minimal requirement", and a second level, considered as "optimal treatment". A retrospective evaluation, based on a questionnaire, revealed that in 1996, in most Italian Centers, patients affected by rectal carcinoma received radiation treatment within the first level of proposed standards. A subsequent analysis concerned the evaluation of the level of treatments applied in 2000. In this paper the radiotherapy standards proposed by the AIRO are described in the different phases of the radiation treatment.

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

    SciTech Connect

    Colaco, Rovel J.; Hoppe, Bradford S.; Flampouri, Stella; McKibben, Brian T.; Henderson, Randal H.; Bryant, Curtis; Nichols, Romaine C.; Mendenhall, William M.; Li, Zuofeng; Su, Zhong; Morris, Christopher G.; Mendenhall, Nancy P.

    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, 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.

  14. TNF rs1799964 as a Predictive Factor of Acute Toxicities in Chinese Rectal Cancer Patients Treated With Chemoradiotherapy

    PubMed Central

    Zhang, Hui; Wang, Mengyun; Shi, Tingyan; Shen, Lijun; Liang, Liping; Deng, Yun; Li, Guichao; Zhu, Ji; Wu, Yongxin; Fan, Ming; Deng, Weijuan; Wei, Qingyi; Zhang, Zhen

    2015-01-01

    Abstract Acute toxicity is the main dose-limiting factor in the chemoradiotherapy of rectal cancer patients and depends on several pro-inflammatory factors, including interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-α). It is unknown whether genetic factors, such as single-nucleotide polymorphisms (SNPs) in the IL-1, IL-6, and TNF genes, are also associated with acute toxicity in the process. We genotyped 5 potentially functional SNPs in these 3 genes (TNF rs1799964, TNF rs1800629, IL-6 rs1800796, and IL-1 rs1143623, IL-1 rs1143627) and estimated their associations with severe acute radiation injury (grade ≥2) in 356 rectal cancer patients. We found a predictive role of the TNF rs1799964 T variant allele in the development of acute injury (for CT vs CC: adjusted odds ratio [OR] = 4.718, 95% confidence interval [CI] = 1.152–19.328, P = 0.031; for TT vs CC: adjusted OR = 4.443, 95% CI = 1.123–17.581, P = 0.034). In the dominant model, for CT/TT vs CC, the adjusted OR = 4.132, 95% CI = 1.069–15.966, and P = 0.04. Our results suggested that genetic variants in the TNF gene may influence acute injury in rectal cancer patients treated with chemoradiotherapy and may be a predictor for personalized treatment. Additional larger and independent studies are needed to confirm our findings. PMID:26559268

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

    SciTech Connect

    Vavassori, Vittorio; Fiorino, Claudio . E-mail: fiorino.claudio@hsr.it; Rancati, Tiziana; Magli, Alessandro; Fellin, Gianni; Baccolini, Michela; Bianchi, Carla; Cagna, Emanuela; Mauro, Flora A.; Monti, Angelo F.; Munoz, Fernando; Stasi, Michele; Franzone, Paola; Valdagni, Riccardo

    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 1,132 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

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

    SciTech Connect

    Song, T; Zhou, L; Li, Y; Jiang, S; Gu, X

    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 CRW24 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.

  17. Treatment and prognosis of patients with late rectal bleeding after intensity-modulated radiation therapy for prostate cancer.

    PubMed

    Takemoto, Shinya; Shibamoto, Yuta; Ayakawa, Shiho; Nagai, Aiko; Hayashi, Akihiro; Ogino, Hiroyuki; Baba, Fumiya; Yanagi, Takeshi; Sugie, Chikao; Kataoka, Hiromi; Mimura, Mikio

    2012-06-12

    Radiation proctitis after intensity-modulated radiation therapy (IMRT) differs from that seen after pelvic irradiation in that this adverse event is a result of high-dose radiation to a very small area in the rectum. We evaluated the results of treatment for hemorrhagic proctitis after IMRT for prostate cancer. Between November 2004 and February 2010, 403 patients with prostate cancer were treated with IMRT at 2 institutions. Among these patients, 64 patients who developed late rectal bleeding were evaluated. Forty patients had received IMRT using a linear accelerator and 24 by tomotherapy. Their median age was 72 years. Each patient was assessed clinically and/or endoscopically. Depending on the severity, steroid suppositories or enemas were administered up to twice daily and Argon plasma coagulation (APC) was performed up to 3 times. Response to treatment was evaluated using the Rectal Bleeding Score (RBS), which is the sum of Frequency Score (graded from 1 to 3 by frequency of bleeding) and Amount Score (graded from 1 to 3 by amount of bleeding). Stoppage of bleeding over 3 months was scored as RBS 1. The median follow-up period for treatment of rectal bleeding was 35 months (range, 12-69 months). Grade of bleeding was 1 in 31 patients, 2 in 26, and 3 in 7. Nineteen of 45 patients (42%) observed without treatment showed improvement and bleeding stopped in 17 (38%), although mean RBS did not change significantly. Eighteen of 29 patients (62%) treated with steroid suppositories or enemas showed improvement (mean RBS, from 4.1 ± 1.0 to 3.0 ± 1.8, p = 0.003) and bleeding stopped in 9 (31%). One patient treated with steroid enema 0.5-2 times a day for 12 months developed septic shock and died of multiple organ failure. All 12 patients treated with APC showed improvement (mean RBS, 4.7 ± 1.2 to 2.3 ± 1.4, p < 0.001) and bleeding stopped in 5 (42%). After adequate periods of observation, steroid suppositories/enemas are expected to be

  18. Management of late radiation-induced rectal injury after treatment of carcinoma of the uterus

    SciTech Connect

    Allen-Mersh, T.G.; Wilson, E.J.; Hope-Stone, H.F.; Mann, C.V.

    1987-06-01

    Sixty-one of 1418 (4.3 per cent) patients treated with radiation for carcinoma of the uterus from 1963 to 1983 had significant radiation-induced complications of the intestine develop which required a surgical opinion considering further management. Ninety-three per cent of these complications involved the rectum. Florid proctitis resolved within two years of onset in 33 per cent of the patients who were managed conservatively while 22 per cent of the patients died of disseminated disease within the same time period. Surgical treatment was eventually necessary in 39 per cent of the patients who were initially treated conservatively for radiation induced proctitis. Rectal excision with coloanal sleeve anastomosis produced a satisfactory result in eight of 11 patients with severe radiation injury involving the rectum. The incidence of radiation-induced and malignant rectovaginal fistula were similar (1 per cent), but disease-induced symptoms tended to occur earlier after primary treatment (a median of eight months) compared with radiation-induced symptoms (a median of 16 months).

  19. Systematic Review of the Relationship between Acute and Late Gastrointestinal Toxicity after Radiotherapy for Prostate Cancer

    PubMed Central

    Peach, Matthew Sean; Showalter, Timothy N.; Ohri, Nitin

    2015-01-01

    A small but meaningful percentage of men who are treated with external beam radiation therapy for prostate cancer will develop late gastrointestinal toxicity. While numerous strategies to prevent gastrointestinal injury have been studied, clinical trials concentrating on late toxicity have been difficult to carry out. Identification of subjects at high risk for late gastrointestinal injury could allow toxicity prevention trials to be performed using reasonable sample sizes. Acute radiation therapy toxicity has been shown to predict late toxicity in several organ systems. Late toxicities may occur as a consequential effect of acute injury. In this systematic review of published reports, we found that late gastrointestinal toxicity following prostate radiotherapy seems to be statistically and potentially causally related to acute gastrointestinal morbidity as a consequential effect. We submit that acute gastrointestinal toxicity may be used to identify at-risk patients who may benefit from additional attention for medical interventions and close follow-up to prevent late toxicity. Acute gastrointestinal toxicity could also be explored as a surrogate endpoint for late effects in prospective trials. PMID:26697225

  20. Absolute volume of the rectum and AUC from rectal DVH between 25Gy and 50Gy predict acute gastrointestinal toxicity with IG-IMRT in prostate cancer.

    PubMed

    Mirjolet, Céline; Walker, Paul M; Gauthier, Mélanie; Dalban, Cécile; Naudy, Suzanne; Mazoyer, Frédéric; Martin, Etienne; Maingon, Philippe; Créhange, Gilles

    2016-11-04

    To determine whether dose/volume specific endpoints (DVSE) or Area under the rectal DVH curve (rAUC) better predict acute gastrointestinal (GI) toxicity in prostate cancer patients treated with IMRT in the era of daily image guidance (IG-IMRT). A set of DVSE was recorded from V25 to V75 (increments of 5Gy) (both in % and in cc) for 180 men. The rAUC was calculated for doses ranging between 25Gy and 50Gy (rAUC25-50). Univariate and multivariate logistic regressions were performed to determine the relationship between DVSE or rAUC25-50 and the appearance of any acute GI toxicity. The rates of acute grade 1 (G1), G2 and G3 GI toxicities were 53.3 %, 10.6 % and 1.1 %, respectively. No G4+ toxicity was observed. Rectal V25 to V75 expressed in % were not predictive of G ≥ 1 GI toxicity (p ≥ 0.12) whereas rectal V25 to V50 expressed in cc did correlate with GI toxicity G ≥ 1 (p ≤ 0.04). rAUC25-50 expressed in cc. Gy correlated significantly with the occurrence of any acute GI toxicity G ≥ 1 (p = 0.027). The absolute volume of the rectum between 25Gy and 50Gy and rAUC25-50 could significantly predict any acute rectal toxicity in prostate cancer patients treated with daily IG-IMRT.

  1. Mathematical Model for Evaluating Incidence of Acute Rectal Toxicity During Conventional or Hypofractionated Radiotherapy Courses for Prostate Cancer

    SciTech Connect

    Strigari, Lidia Arcangeli, Giorgio; Arcangeli, Stefano; Benassi, Marcello

    2009-04-01

    Purpose: To describe the radiation-induced acute rectal toxicity (ART) using a modified Lyman-Kutcher-Burman normal tissue complication probability model and parameters set, taking into account the overall treatment time. Methods and Materials: A total of 160 patients underwent three-dimensional conformal radiotherapy to the prostate and seminal vesicles and were randomized to receive 80 Gy in 40 fractions within 8 weeks (Group A) or 62 Gy in 20 fractions within 5 weeks, 4 d/wk (Group B). An additional 52 patients (Group C) underwent intensity-modulated radiotherapy with a hypofractionation schedule consisting of 56 Gy, delivered in 16 fractions (4/wk) of 3.5 Gy. Patients were followed for ART weekly during treatment. The overall treatment time, rectal dose-volume histograms, and ART status, defined as Radiation Therapy Oncology Group Grade 2 or greater gastrointestinal toxicity, were used to determine the modified Lyman-Kutcher-Burman model parameters. The m and n values were obtained from the cohort, and the tolerance doses for 50% complication probability for uniform irradiation [TD{sub 50}(1){sub k}] were obtained for each fractionation schedule indicated with k. Results: Of 212 patients treated with localized prostate radiotherapy, 65 developed Grade for {>=}1 week during treatment. The m and n value was 0.17 and 0.08, respectively. The TD{sub 50}(1){sub k} parameter was 79, 62.5, and 53 Gy, respectively for Group A, B, and C. Conclusion: The optimized modified Lyman-Kutcher-Burman normal tissue complication probability model allowed us to describe the ART data from conventional and hypofractionated regimens, using the dose-volume histograms and overall treatment time. This model could prove useful in designing hypofractionation schedules to reduce the incidence of ART.

  2. Results and DVH analysis of late rectal bleeding in patients treated with 3D-CRT or IMRT for localized prostate cancer

    PubMed Central

    Someya, Masanori; Hori, Masakazu; Tateoka, Kunihiko; Nakata, Kensei; Takagi, Masaru; Saito, Masato; Hirokawa, Naoki; Hareyama, Masato; Sakata, Koh-ichi

    2015-01-01

    In patients undergoing radiotherapy for localized prostate cancer, dose–volume histograms and clinical variables were examined to search for correlations between radiation treatment planning parameters and late rectal bleeding. We analyzed 129 patients with localized prostate cancer who were managed from 2002 to 2010 at our institution. They were treated with 3D conformal radiation therapy (3D-CRT, 70 Gy/35 fractions, 55 patients) or intensity-modulated radiation therapy (IMRT, 76 Gy/38 fractions, 74 patients). All radiation treatment plans were retrospectively reconstructed, dose–volume histograms of the rectum were generated, and the doses delivered to the rectum were calculated. Time to rectal bleeding ranged from 9–53 months, with a median of 18.7 months. Of the 129 patients, 33 patients had Grade 1 bleeding and were treated with steroid suppositories, while 25 patients with Grade 2 bleeding received argon plasma laser coagulation therapy (APC). Three patients with Grade 3 bleeding required both APC and blood transfusion. The 5-year incidence rate of Grade 2 or 3 rectal bleeding was 21.8% for the 3D-CRT group and 21.6% for the IMRT group. Univariate analysis showed significant differences in the average values from V65 to V10 between Grades 0–1 and Grades 2–3. Multivariate analysis demonstrated that patients with V65 ≥ 17% had a significantly increased risk (P = 0.032) of Grade 2 or 3 rectal bleeding. Of the 28 patients of Grade 2 or 3 rectal bleeding, 17 patients (60.7%) were cured by a single session of APC, while the other 11 patients required two sessions. Thus, none of the patients had any further rectal bleeding after the second APC session. PMID:25212601

  3. Risk of Late Toxicity in Men Receiving Dose-Escalated Hypofractionated Intensity Modulated Prostate Radiation Therapy: Results From a Randomized Trial

    SciTech Connect

    Hoffman, Karen E. Voong, K. Ranh; Pugh, Thomas J.; Skinner, Heath; Levy, Lawrence B.; Takiar, Vinita; Choi, Seungtaek; Du, Weiliang; Frank, Steven J.; Johnson, Jennifer; Kanke, James; Kudchadker, Rajat J.; Lee, Andrew K.; Mahmood, Usama; McGuire, Sean E.; Kuban, Deborah A.

    2014-04-01

    Objective: To report late toxicity outcomes from a randomized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment. Methods and Materials: Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy fractions). Late (≥90 days after completion of radiation therapy) genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored according to modified Radiation Therapy Oncology Group criteria. Results: 101 men received CIMRT and 102 men received HIMRT. The median age was 68, and the median follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had intermediate-risk, and 1% had high-risk disease. There was no difference in late GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade ≥2 GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT. The actuarial 5-year grade ≥2 GI toxicity was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was associated with the development of late GI toxicity (P<.05). The 5-year actuarial grade ≥2 GI toxicity was 27.3% in men with R64.6Gy ≥ 20% but only 6.0% in men with R64.6Gy < 20% (P=.016). Conclusions: Dose-escalated IMRT using a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this

  4. Non-surgical interventions for late rectal problems (proctopathy) of radiotherapy in people who have received radiotherapy to the pelvis.

    PubMed

    van de Wetering, Fleur T; Verleye, Leen; Andreyev, H Jervoise N; Maher, Jane; Vlayen, Joan; Pieters, Bradley R; van Tienhoven, Geertjan; Scholten, Rob J P M

    2016-04-25

    This is an update of a Cochrane review first published in 2002, and previously updated in 2007. Late radiation rectal problems (proctopathy) include bleeding, pain, faecal urgency, and incontinence and may develop after pelvic radiotherapy treatment for cancer. To assess the effectiveness and safety of non-surgical interventions for managing late radiation proctopathy. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 11, 2015); MEDLINE (Ovid); EMBASE (Ovid); CANCERCD; Science Citation Index; and CINAHL from inception to November 2015. We included randomised controlled trials (RCTs) comparing non-surgical interventions for the management of late radiation proctopathy in people with cancer who have undergone pelvic radiotherapy for cancer. Primary outcomes considered were: episodes of bowel activity, bleeding, pain, tenesmus, urgency, and sphincter dysfunction. Study selection, 'Risk of bias' assessment, and data extraction were performed in duplicate, and any disagreements were resolved by involving a third review author. We identified 1221 unique references and 16 studies including 993 participants that met our inclusion criteria. One study found through the last update was moved to the 'Studies awaiting classification' section. We did not pool outcomes for a meta-analysis due to variation in study characteristics and endpoints across included studies.Since radiation proctopathy is a condition with various symptoms or combinations of symptoms, the studies were heterogeneous in their intended effect. Some studies investigated treatments targeted at bleeding only (group 1), some investigated treatments targeted at a combination of anorectal symptoms, but not a single treatment (group 2). The third group focused on the treatment of the collection of symptoms referred to as pelvic radiation disease. In order to enable some comparison of this heterogeneous collection of studies, we describe the effects in these three groups separately

  5. Psychometric properties of a prostate cancer radiation late toxicity questionnaire

    PubMed Central

    Rodrigues, George; Bauman, Glenn; Lock, Michael; D'Souza, David; Mahon, Jeff

    2007-01-01

    Background To construct a short prostate cancer radiation late toxicity (PCRT) questionnaire with health-related quality-of-life (HRQoL) domains. Methods The PCRT was developed by item generation, questionnaire construction (n = 7 experts, n = 8 focus group patients), pilot testing (n = 37), item reduction (n = 100), reliability testing (n = 237), and validity testing (n = 274). Results Reliability of the three item-reduced subscales demonstrated intraclass correlation coefficients (CC) of 0.811 (GU), 0.842 (GI), and 0.740 (sexual). Discriminant validity demonstrated Pearson CC of 0.449 (GU-GI), 0.200 (sexual-GU), and 0.09 (sexual-GI). Content validity correlations between PCRT-PCQoL were 0.35–0.78, PCRT-FACT-G© were 0.19–0.39, and PCRT-SF-36® were 0.03–0.34. Conclusion We successfully generated a PCRT HRQoL questionnaire including subscales with very good psychometric properties. PMID:17540022

  6. Meta-analysis of Genome Wide Association Studies Identifies Genetic Markers of Late Toxicity Following Radiotherapy for Prostate Cancer.

    PubMed

    Kerns, Sarah L; Dorling, Leila; Fachal, Laura; Bentzen, Søren; Pharoah, Paul D P; Barnes, Daniel R; Gómez-Caamaño, Antonio; Carballo, Ana M; Dearnaley, David P; Peleteiro, Paula; Gulliford, Sarah L; Hall, Emma; Michailidou, Kyriaki; Carracedo, Ángel; Sia, Michael; Stock, Richard; Stone, Nelson N; Sydes, Matthew R; Tyrer, Jonathan P; Ahmed, Shahana; Parliament, Matthew; Ostrer, Harry; Rosenstein, Barry S; Vega, Ana; Burnet, Neil G; Dunning, Alison M; Barnett, Gillian C; West, Catharine M L

    2016-08-01

    Nearly 50% of cancer patients undergo radiotherapy. Late radiotherapy toxicity affects quality-of-life in long-term cancer survivors and risk of side-effects in a minority limits doses prescribed to the majority of patients. Development of a test predicting risk of toxicity could benefit many cancer patients. We aimed to meta-analyze individual level data from four genome-wide association studies from prostate cancer radiotherapy cohorts including 1564 men to identify genetic markers of toxicity. Prospectively assessed two-year toxicity endpoints (urinary frequency, decreased urine stream, rectal bleeding, overall toxicity) and single nucleotide polymorphism (SNP) associations were tested using multivariable regression, adjusting for clinical and patient-related risk factors. A fixed-effects meta-analysis identified two SNPs: rs17599026 on 5q31.2 with urinary frequency (odds ratio [OR] 3.12, 95% confidence interval [CI] 2.08-4.69, p-value 4.16×10(-8)) and rs7720298 on 5p15.2 with decreased urine stream (OR 2.71, 95% CI 1.90-3.86, p-value=3.21×10(-8)). These SNPs lie within genes that are expressed in tissues adversely affected by pelvic radiotherapy including bladder, kidney, rectum and small intestine. The results show that heterogeneous radiotherapy cohorts can be combined to identify new moderate-penetrance genetic variants associated with radiotherapy toxicity. The work provides a basis for larger collaborative efforts to identify enough variants for a future test involving polygenic risk profiling.

  7. Acute Toxicity of Radiochemotherapy in Rectal Cancer Patients: A Risk Particularly for Carriers of the TGFB1 Pro25 variant

    SciTech Connect

    Schirmer, Markus Anton; Mergler, Caroline Patricia Nadine; Rave-Fraenk, Margret; Herrmann, Markus Karl; Hennies, Steffen; Gaedcke, Jochen; Conradi, Lena-Christin; Jo, Peter; Beissbarth, Tim; Hess, Clemens Friedrich; Becker, Heinz; Ghadimi, Michael; Brockmoeller, Juergen; Christiansen, Hans; Wolff, Hendrik Andreas

    2012-05-01

    Purpose: Transforming growth factor-beta1 is related to adverse events in radiochemotherapy. We investigated TGFB1 genetic variability in relation to quality of life-impairing acute organ toxicity (QAOT) of neoadjuvant radiochemotherapy under clinical trial conditions. Methods and Materials: Two independent patient cohorts (n = 88 and n = 75) diagnosed with International Union Against Cancer stage II/III rectal cancer received neoadjuvant radiation doses of 50.4 Gy combined with 5-fluorouracil-based chemotherapy. Toxicity was monitored according to Common Terminology Criteria for Adverse Events. QAOT was defined as a CTCAE grade {>=}2 for at least one case of enteritis, proctitis, cystitis, or dermatitis. Nine germline polymorphisms covering the common genetic diversity in the TGFB1 gene were genotyped. Results: In both cohorts, all patients carrying the TGFB1 Pro25 variant experienced QAOT (positive predictive value of 100%, adjusted p = 0.0006). In a multivariate logistic regression model, gender, age, body mass index, type of chemotherapy, or disease state had no significant impact on QAOT. Conclusion: The TGFB1 Pro25 variant could be a relevant marker for individual treatment stratification and carriers may benefit from adaptive clinical care or specific radiation techniques.

  8. Increasing late stage colorectal cancer and rectal cancer mortality demonstrates the need for screening: a population based study in Ireland, 1994-2010.

    PubMed

    Clarke, Nicholas; McDevitt, Joseph; Kearney, Patricia M; Sharp, Linda

    2014-05-13

    This paper describes trends in colorectal cancer incidence, survival and mortality from 1994 to 2010 in Ireland prior to the introduction of population-based screening. We examined incidence (National Cancer Registry Ireland (NCRI) and mortality (Central Statistics Office) from 1994 to 2010. Age standardised rates (ASR) for incidence and mortality have been calculated, weighted by the European standard population. Annual percentage change was calculated in addition to testing for linear trends in treatment and case fraction of early and late stage disease. Relative survival was calculated considering deaths from all causes. The colorectal cancer ASR was 63.7 per 100,000 in males and 38.7 per 100,000 in females in 2010. There was little change in the ASR over time in either sex, or when colon and rectal cancers were considered separately; however the number of incident cancers increased significantly during 1994-2010 (1752 to 2298). The case fractions of late stage (III/IV) colon and rectal cancers rose significantly over time. One and 5 year relative survival improved for both sexes between the periods 1994-2008. Colorectal cancer mortality ASRs decreased annually from 1994-2009 by 1.8% (95% CI -2.2, -1.4). Rectal cancer mortality ASRs rose annually by 2.4% (95% CI 1.1, 3.6) and 2.8% (95% CI 1.2, 4.4) in males and females respectively. Increases in late-stage disease and rectal cancer mortality demonstrate an urgent need for colorectal cancer screening. However, the narrow age range at which screening is initially being rolled-out in Ireland means that the full potential for reductions in late-stage cancers and incidence and mortality are unlikely to be achieved. While it is possible that the observed increase in rectal cancer mortality may be partly an artefact of cause of death misclassification, it could also be explained by variations in treatment and adherence to best practice guidelines; further investigation is warranted.

  9. Comparison of Acute and Late Toxicities for Three Modern High-Dose Radiation Treatment Techniques for Localized Prostate Cancer

    SciTech Connect

    Mohammed, Nasiruddin; Kestin, Larry; Ghilezan, Mihai; Krauss, Daniel; Vicini, Frank; Brabbins, Donald; Gustafson, Gary; Ye Hong; Martinez, Alavaro

    2012-01-01

    Purpose: We compared acute and late genitourinary (GU) and gastrointestinal (GI) toxicities in prostate cancer patients treated with three different high-dose radiation techniques. Methods and Materials: A total of 1,903 patients with localized prostate cancer were treated with definitive RT at William Beaumont Hospital from 1992 to 2006: 22% with brachytherapy alone (BT), 55% with image-guided external beam (EB-IGRT), and 23% external beam with high-dose-rate brachytherapy boost (EBRT+HDR). Median dose with BT was 120 Gy for LDR and 38 Gy for HDR (9.5 Gy Multiplication-Sign 4). Median dose with EB-IGRT was 75.6 Gy (PTV) to prostate with or without seminal vesicles. For EBRT+HDR, the pelvis was treated to 46 Gy with an additional 19 Gy (9.5 Gy Multiplication-Sign 2) delivered via HDR. GI and GU toxicity was evaluated utilizing the NCI-CTC criteria (v.3.0). Median follow-up was 4.8 years. Results: The incidences of any acute {>=} Grade 2 GI or GU toxicities were 35%, 49%, and 55% for BT, EB-IGRT, and EBRT+HDR (p < 0.001). Any late GU toxicities {>=} Grade 2 were present in 22%, 21%, and 28% for BT, EB-IGRT, and EBRT+HDR (p = 0.01), respectively. Patients receiving EBRT+HDR had a higher incidence of urethral stricture and retention, whereas dysuria was most common in patients receiving BT. Any Grade {>=}2 late GI toxicities were 2%, 20%, and 9% for BT, EB-IGRT, and EBRT+HDR (p < 0.001). Differences were most pronounced for rectal bleeding, with 3-year rates of 0.9%, 20%, and 6% (p < 0.001) for BT, EB-IGRT, and EBRT+HDR respectively. Conclusions: Each of the three modern high-dose radiation techniques for localized prostate cancer offers a different toxicity profile. These data can help patients and physicians to make informed decisions regarding radiotherapy for prostate andenocarcinoma.

  10. Radiation-Induced Lymphocyte Apoptosis to Predict Radiation Therapy Late Toxicity in Prostate Cancer Patients

    SciTech Connect

    Schnarr, Kara; Boreham, Douglas; Sathya, Jinka; Julian, Jim; Dayes, Ian S.

    2009-08-01

    Purpose: To examine a potential correlation between the in vitro apoptotic response of lymphocytes to radiation and the risk of developing late gastrointestinal (GI)/genitourinary (GU) toxicity from radiotherapy for prostate cancer. Methods and Materials: Prostate cancer patients formerly enrolled in a randomized study were tested for radiosensitivity by using a radiation-induced lymphocyte apoptosis assay. Apoptosis was measured using flow cytometry-based Annexin-FITC/7AAD and DiOC{sub 6}/7AAD assays in subpopulations of lymphocytes (total lymphocytes, CD4+, CD8+ and CD4-/CD8-) after exposure to an in vitro dose of 0, 2, 4, or 8 Gy. Results: Patients with late toxicity after radiotherapy showed lower lymphocyte apoptotic responses to 8 Gy than patients who had not developed late toxicity (p = 0.01). All patients with late toxicity had apoptosis levels that were at or below the group mean. The negative predictive value in both apoptosis assays ranged from 95% to 100%, with sensitivity values of 83% to 100%. Apoptosis at lower dose points and in lymphocyte subpopulations had a weaker correlation with the occurrence of late toxicity. Conclusions: Lymphocyte apoptosis after 8 Gy of radiation has the potential to predict which patients will be spared late toxicity after radiation therapy. Further research should be performed to identify the specific subset of lymphocytes that correlates with late toxicity, followed by a corresponding prospective study.

  11. Toward Restored Bowel Health in Rectal Cancer Survivors.

    PubMed

    Steineck, Gunnar; Schmidt, Heike; Alevronta, Eleftheria; Sjöberg, Fei; Bull, Cecilia Magdalena; Vordermark, Dirk

    2016-07-01

    As technology gets better and better, and as clinical research provides more and more knowledge, we can extend our ambition to cure patients from cancer with restored physical health among the survivors. This increased ambition requires attention to grade 1 toxicity that decreases quality of life. It forces us to document the details of grade 1 toxicity and improve our understanding of the mechanisms. Long-term toxicity scores, or adverse events as documented during clinical trials, may be regarded as symptoms or signs of underlying survivorship diseases. However, we lack a survivorship nosology for rectal cancer survivors. Primarily focusing on radiation-induced side effects, we highlight some important observations concerning late toxicity among rectal cancer survivors. With that and other data, we searched for a preliminary survivorship-disease nosology for rectal cancer survivors. We disentangled the following survivorship diseases among rectal cancer survivors: low anterior resection syndrome, radiation-induced anal sphincter dysfunction, gut wall inflammation and fibrosis, blood discharge, excessive gas discharge, excessive mucus discharge, constipation, bacterial overgrowth, and aberrant anatomical structures. The suggested survivorship nosology may form the basis for new instruments capturing long-term symptoms (patient-reported outcomes) and professional-reported signs. For some of the diseases, we can search for animal models. As an end result, the suggested survivorship nosology may accelerate our understanding on how to prevent, ameliorate, or eliminate manifestations of treatment-induced diseases among rectal cancer survivors.

  12. Analysis of late toxicity associated with external beam radiation therapy for prostate cancer with uniform setting of classical 4-field 70 Gy in 35 fractions: a survey study by the Osaka Urological Tumor Radiotherapy Study Group

    PubMed Central

    Yoshioka, Yasuo; Suzuki, Osamu; Nishimura, Kazuo; Inoue, Hitoshi; Hara, Tsuneo; Yoshida, Ken; Imai, Atsushi; Tsujimura, Akira; Nonomura, Norio; Ogawa, Kazuhiko

    2013-01-01

    We aimed to analyse late toxicity associated with external beam radiation therapy (EBRT) for prostate cancer using uniform dose-fractionation and beam arrangement, with the focus on the effect of 3D (CT) simulation and portal field size. We collected data concerning patients with localized prostate adenocarcinoma who had been treated with EBRT at five institutions in Osaka, Japan, between 1998 and 2006. All had been treated with 70 Gy in 35 fractions, using the classical 4-field technique with gantry angles of 0°, 90°, 180° and 270°. Late toxicity was evaluated strictly in terms of the Common Terminology Criteria for Adverse Events Version 4.0. In total, 362 patients were analysed, with a median follow-up of 4.5 years (range 1.0–11.6). The 5-year overall and cause-specific survival rates were 93% and 96%, respectively. The mean ± SD portal field size in the right–left, superior–inferior, and anterior–posterior directions was, respectively, 10.8 ± 1.1, 10.2 ± 1.0 and 8.8 ± 0.9 cm for 2D simulation, and 8.4 ± 1.2, 8.2 ± 1.0 and 7.7 ± 1.0 cm for 3D simulation (P < 0.001). No Grade 4 or 5 late toxicity was observed. The actuarial 5-year Grade 2–3 genitourinary and gastrointestinal (GI) late toxicity rates were 6% and 14%, respectively, while the corresponding late rectal bleeding rate was 23% for 2D simulation and 7% for 3D simulation (P < 0.001). With a uniform setting of classical 4-field 70 Gy/35 fractions, the use of CT simulation and the resultant reduction in portal field size were significantly associated with reduced late GI toxicity, especially with less rectal bleeding. PMID:22988284

  13. XRCC1 Polymorphism Associated With Late Toxicity After Radiation Therapy in Breast Cancer Patients

    SciTech Connect

    Seibold, Petra; Behrens, Sabine; Schmezer, Peter; Helmbold, Irmgard; Barnett, Gillian; Coles, Charlotte; Yarnold, John; Talbot, Christopher J.; Imai, Takashi; Azria, David; Koch, C. Anne; Dunning, Alison M.; Burnet, Neil; Bliss, Judith M.; Symonds, R. Paul; Rattay, Tim; Suga, Tomo; Kerns, Sarah L.; and others

    2015-08-01

    Purpose: To identify single-nucleotide polymorphisms (SNPs) in oxidative stress–related genes associated with risk of late toxicities in breast cancer patients receiving radiation therapy. Methods and Materials: Using a 2-stage design, 305 SNPs in 59 candidate genes were investigated in the discovery phase in 753 breast cancer patients from 2 prospective cohorts from Germany. The 10 most promising SNPs in 4 genes were evaluated in the replication phase in up to 1883 breast cancer patients from 6 cohorts identified through the Radiogenomics Consortium. Outcomes of interest were late skin toxicity and fibrosis of the breast, as well as an overall toxicity score (Standardized Total Average Toxicity). Multivariable logistic and linear regression models were used to assess associations between SNPs and late toxicity. A meta-analysis approach was used to summarize evidence. Results: The association of a genetic variant in the base excision repair gene XRCC1, rs2682585, with normal tissue late radiation toxicity was replicated in all tested studies. In the combined analysis of discovery and replication cohorts, carrying the rare allele was associated with a significantly lower risk of skin toxicities (multivariate odds ratio 0.77, 95% confidence interval 0.61-0.96, P=.02) and a decrease in Standardized Total Average Toxicity scores (−0.08, 95% confidence interval −0.15 to −0.02, P=.016). Conclusions: Using a stage design with replication, we identified a variant allele in the base excision repair gene XRCC1 that could be used in combination with additional variants for developing a test to predict late toxicities after radiation therapy in breast cancer patients.

  14. XRCC1 Polymorphism Associated With Late Toxicity After Radiation Therapy in Breast Cancer Patients.

    PubMed

    Seibold, Petra; Behrens, Sabine; Schmezer, Peter; Helmbold, Irmgard; Barnett, Gillian; Coles, Charlotte; Yarnold, John; Talbot, Christopher J; Imai, Takashi; Azria, David; Koch, C Anne; Dunning, Alison M; Burnet, Neil; Bliss, Judith M; Symonds, R Paul; Rattay, Tim; Suga, Tomo; Kerns, Sarah L; Bourgier, Celine; Vallis, Katherine A; Sautter-Bihl, Marie-Luise; Claßen, Johannes; Debus, Juergen; Schnabel, Thomas; Rosenstein, Barry S; Wenz, Frederik; West, Catharine M; Popanda, Odilia; Chang-Claude, Jenny

    2015-08-01

    To identify single-nucleotide polymorphisms (SNPs) in oxidative stress-related genes associated with risk of late toxicities in breast cancer patients receiving radiation therapy. Using a 2-stage design, 305 SNPs in 59 candidate genes were investigated in the discovery phase in 753 breast cancer patients from 2 prospective cohorts from Germany. The 10 most promising SNPs in 4 genes were evaluated in the replication phase in up to 1883 breast cancer patients from 6 cohorts identified through the Radiogenomics Consortium. Outcomes of interest were late skin toxicity and fibrosis of the breast, as well as an overall toxicity score (Standardized Total Average Toxicity). Multivariable logistic and linear regression models were used to assess associations between SNPs and late toxicity. A meta-analysis approach was used to summarize evidence. The association of a genetic variant in the base excision repair gene XRCC1, rs2682585, with normal tissue late radiation toxicity was replicated in all tested studies. In the combined analysis of discovery and replication cohorts, carrying the rare allele was associated with a significantly lower risk of skin toxicities (multivariate odds ratio 0.77, 95% confidence interval 0.61-0.96, P=.02) and a decrease in Standardized Total Average Toxicity scores (-0.08, 95% confidence interval -0.15 to -0.02, P=.016). Using a stage design with replication, we identified a variant allele in the base excision repair gene XRCC1 that could be used in combination with additional variants for developing a test to predict late toxicities after radiation therapy in breast cancer patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. 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

  16. Comparative analysis of late functional outcome following preoperative radiation therapy or chemoradiotherapy and surgery or surgery alone in rectal cancer.

    PubMed

    Contin, Pietro; Kulu, Yakup; Bruckner, Thomas; Sturm, Martin; Welsch, Thilo; Müller-Stich, Beat P; Huber, Johannes; Büchler, Markus W; Ulrich, Alexis

    2014-02-01

    This study evaluates the anorectal and genitourinary function of patients treated by preoperative short-term radiotherapy (RT) or chemoradiotherapy (CRT) followed by surgery and surgery alone for rectal cancer. For this study, a total of 613 patients, who were identified from a prospective rectal cancer database, underwent anterior resection of the rectum between October 2001 and December 2007. Standardized questionnaires were used to determine fecal incontinence, urinary, and sexual function. Relevant clinical variables were evaluated using univariate and multivariate analyses. Independent predictors of functional outcome were identified by a binary logistic regression analysis. The data of 263 (43 %) patients were available for analysis. On multivariate analysis, neoadjuvant RT (P < 0.01) and low anterior resection (LAR) (P = 0.049) were associated with fecal incontinence. In univariate analysis, fecal incontinence was linked to preoperative neoadjuvant treatment (RT and/or CRT vs. LAR) (P < 0.01). The hazard ratio for developing fecal incontinence was 3.3 (1.6-6.8) for patients who received RT. One hundred twenty-five patients (51.2 %) experienced urinary incontinence following surgery, the majority of whom were female (P < 0.01). On univariate analysis, male sexual function was associated with age (P < 0.01), ASA class (P = 0.01) and LAR (P = 0.01). Multimodal therapy of low rectal cancer increases the incidence of fecal incontinence and negatively affects sexual function. The potential benefits of RT or CRT need to be balanced against the risk of increased bowel dysfunction when determining the appropriate treatment for individual patients with rectal cancer.

  17. Severe Late Toxicities Following Concomitant Chemoradiotherapy Compared to Radiotherapy Alone in Cervical Cancer: An Inter-era Analysis

    SciTech Connect

    Gondi, Vinai; Bentzen, Soren M.; Sklenar, Kathryn L.; Dunn, Emily F.; Petereit, Daniel G.; Tannehill, Scott P.; Straub, Margaret; Bradley, Kristin A.

    2012-11-15

    Purpose: To compare rates of severe late toxicities following concomitant chemoradiotherapy and radiotherapy alone for cervical cancer. Methods and Materials: Patients with cervical cancer were treated at a single institution with radiotherapy alone or concomitant chemoradiotherapy for curative intent. Severe late toxicity was defined as grade {>=}3 vaginal, urologic, or gastrointestinal toxicity or any pelvic fracture, using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE), occurring {>=}6 months from treatment completion and predating any salvage therapy. Severe late toxicity rates were compared after adjusting for pertinent covariates. Results: At 3 years, probability of vaginal severe late toxicity was 20.2% for radiotherapy alone and 35.1% for concomitant chemoradiotherapy (P=.026). At 3 years, probability of skeletal severe late toxicity was 1.6% for radiotherapy alone and 7.5% for concomitant chemoradiotherapy (P=.010). After adjustment for case mix, concomitant chemoradiotherapy was associated with higher vaginal (hazard ratio [HR] 3.0, 95% confidence interval [CI], 1.7-5.2, P<.001), and skeletal (HR 7.0, 95% CI 1.4-34.1, P=.016) severe late toxicity. Compared to high dilator compliance, moderate (HR 3.6, 95% CI 2.0-6.5, P<.001) and poor (HR 8.5, 95% CI 4.3-16.9, P<.001) dilator compliance was associated with higher vaginal severe late toxicity. Age >50 was associated with higher vaginal (HR 1.8, 95% CI 1.1-3.0, P=.013) and skeletal (HR 5.7, 95% CI 1.2-27.0, P=.028) severe late toxicity. Concomitant chemoradiotherapy was not associated with higher gastrointestinal (P=.886) or urologic (unadjusted, P=.053; adjusted, P=.063) severe late toxicity. Conclusion: Compared to radiotherapy alone, concomitant chemoradiotherapy is associated with higher rates of severe vaginal and skeletal late toxicities. Other predictive factors include dilator compliance for severe vaginal late toxicity and age for severe vaginal and skeletal late toxicities.

  18. Potential Role of Single Nucleotide Polymorphisms of XRCC1, XRCC3, and RAD51 in Predicting Acute Toxicity in Rectal Cancer Patients Treated With Preoperative Radiochemotherapy.

    PubMed

    Osti, Mattia F; Nicosia, Luca; Agolli, Linda; Gentile, Giovanna; Falco, Teresa; Bracci, Stefano; Di Nardo, Francesco; Minniti, Giuseppe; De Sanctis, Vitaliana; Valeriani, Maurizio; Maglio, Marianna; Borro, Marina; Simmaco, Maurizio; Enrici, Riccardo M

    2015-03-24

    To investigate the association between polymorphisms of DNA repair genes and xenobiotic with acute adverse effects in locally advanced rectal cancer patients treated with neoadjuvant radiochemotherapy. Sixty-seven patients were analyzed for the current study. Genotypes in DNA repair genes XRCC1 (G28152A), XRCC3 (A4541G), XRCC3 (C18067T), RAD51 (G315C), and GSTP1 (A313G) were determined by pyrosequencing technology. The observed grade ≥3 acute toxicity rates were 23.8%. Chemotherapy and radiotherapy were interrupted for 46 and 14 days, respectively, due to critical complications. Four patients were hospitalized, 6 patients had been admitted to the ER, and 5 patients received invasive procedures (2 bladder catheters, 2 blood transfusions, and 1 growth factor therapy).RAD51 correlated with acute severe gastrointestinal toxicity in heterozygosity (Aa) and homozygosity (AA) (P=0.036). Grade ≥3 abdominal/pelvis pain toxicity was higher in the Aa group (P=0.017) and in the Aa+AA group (P=0.027) compared with homozygous (aa) patients. Acute skin toxicity of any grade occurred in 55.6% of the mutated patients versus 22.8% in the wild-type group (P=0.04) for RAD51. XRCC1 correlated with skin toxicity of any grade in the Aa+AA group (P=0.03) and in the Aa group alone (P=0.044). Grade ≥3 urinary frequency/urgency was significantly higher in patients with AA (P=0.01), Aa (P=0.022), and Aa+AA (P=0.031) for XRCC3 compared with aa group. Our study suggested that RAD51, XRCC1, and XRCC3 polymorphisms may be predictive factors for radiation-induced acute toxicity in rectal cancer patients treated with preoperative combined therapy.

  19. Transperineal Injection of Hyaluronic Acid in Anterior Perirectal Fat to Decrease Rectal Toxicity From Radiation Delivered With Intensity Modulated Brachytherapy or EBRT for Prostate Cancer Patients

    SciTech Connect

    Prada, Pedro J. Fernandez, Jose; Martinez, Alvaro A.; Rua, Angeles de la; Gonzalez, Jose M.; Fernandez, Jose M.; Juan, German

    2007-09-01

    Purpose: Rectal toxicity remains a serious complication affecting quality of life for prostate cancer patients treated with radiotherapy. We began an investigational trial injecting hyaluronic acid (HA) in the perirectal fat to increase the distance between the prostate and the anterior rectal wall. This is the first report using HA injection in oncology. Methods and Materials: This is a trial of external beam radiation therapy with HDR brachytherapy boosts in prostate cancer. During the two high-dose-rate (HDR) fractions, thermoluminescent dosimeter dosimeters were placed in the urethra and in the rectum. Before the second HDR fraction, 3-7 mL (mean, 6 mL) of HA was injected under transrectal ultrasound guidance in the perirectal fat to systematically create a 1.5-cm space. Urethral and rectal HDR doses were calculated and measured. Computed tomography and magnetic resonance imaging were used to assess the stability of the new space. Results: Twenty-seven patients enrolled in the study. No toxicity was produced from the HA or the injection. In follow-up computed tomography and magnetic resonance imaging, the HA injection did not migrate or change in mass/shape for close to 1 year. The mean distance between rectum and prostate was 2.0 cm along the entire length of the prostate. The median measured rectal dose, when normalized to the median urethral dose, demonstrated a decrease in dose from 47.1% to 39.2% (p < 0.001) with or without injection. For an HDR boost dose of 1150 cGy, the rectum mean Dmax reduction was from 708 cGy to 507 cGy, p < 0.001, and the rectum mean Dmean drop was from 608 to 442 cGy, p < 0.001 post-HA injection. Conclusion: The new 2-cm distance derived from the HA injection significantly decreased rectal dose in HDR brachytherapy. Because of the several-month duration of stability, the same distance was maintained during the course of external beam radiation therapy.

  20. Hypofractionated Concomitant Intensity-Modulated Radiotherapy Boost for High-Risk Prostate Cancer: Late Toxicity

    SciTech Connect

    Quon, Harvey; Cheung, Patrick C.F.; Loblaw, D. Andrew; Morton, Gerard; Pang, Geordi; Szumacher, Ewa; Danjoux, Cyril; Choo, Richard; Thomas, Gillian; Kiss, Alex; Mamedov, Alexandre; Deabreu, Andrea

    2012-02-01

    Purpose: To report the acute and late toxicities of patients with high-risk localized prostate cancer treated using a concomitant hypofractionated, intensity-modulated radiotherapy boost combined with long-term androgen deprivation therapy. Methods and Materials: A prospective Phase I-II study of patients with any of the following: clinical Stage T3 disease, prostate-specific antigen level {>=}20 ng/mL, or Gleason score 8-10. A dose of 45 Gy (1.8 Gy/fraction) was delivered to the pelvic lymph nodes with a concomitant 22.5 Gy prostate intensity-modulated radiotherapy boost, to a total of 67.5 Gy (2.7 Gy/fraction) in 25 fractions within 5 weeks. Image guidance was performed using three gold seed fiducials. The National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, and Radiation Therapy Oncology Group late morbidity scores were used to assess the acute and late toxicities, respectively. Biochemical failure was determined using the Phoenix definition. Results: A total of 97 patients were treated and followed up for a median of 39 months, with 88% having a minimum of 24 months of follow-up. The maximal toxicity scores were recorded. The grade of acute gastrointestinal toxicity was Grade 0 in 4%, 1 in 59%, and 2 in 37%. The grade of acute urinary toxicity was Grade 0 in 8%, 1 in 50%, 2 in 39%, and 3 in 4%. The grade of late gastrointestinal toxicity was Grade 0 in 54%, 1 in 40%, and 2 in 7%. No Grade 3 or greater late gastrointestinal toxicities developed. The grade of late urinary toxicity was Grade 0 in 82%, 1 in 9%, 2 in 5%, 3 in 3%, and 4 in 1% (1 patient). All severe toxicities (Grade 3 or greater) had resolved at the last follow-up visit. The 4-year biochemical disease-free survival rate was 90.5%. Conclusions: A hypofractionated intensity-modulated radiotherapy boost delivering 67.5 Gy in 25 fractions within 5 weeks combined with pelvic nodal radiotherapy and long-term androgen deprivation therapy was well tolerated, with low rates

  1. Carcinogenesis: a late effect of irreversible toxic damage during development

    PubMed Central

    Rice, Jerry M.

    1976-01-01

    Intrauterine and early postnatal life are periods of exceptionally high susceptibility to certain kinds of chemical carcinogens. The most potent known transplacental carcinogens are direct acting alkylating agents. Most nonreactive compounds, which require enzymes for metabolic conversion into chemically reactive “proximate carcinogens,” are less effective because the required enzymes are present at low levels in the fetus, and many proximate carcinogens are too reactive to reach the fetus when formed in maternal tissues. Despite this, many carcinogens which require metabolic activation are very active transplancentally, as the intrinsic susceptibility of rapidly dividing fetal cells compensates effectively for comparatively low tissue levels of reactive metabolites. Transplacental carcinogens of all kinds are most effective late in gestation, generally after organogenesis has begun and after the period of greatest susceptibility to teratogens. Only a small number of known carcinogens have been tested for transplacental carcinogenic activity. The great majority of tumors induced transplacentally in the well-studied rodent and lagomorph species (mouse, rat, Syrian hamster, and rabbit) have morphologic features of adult, rather than embryonal, tissues. A given agent tends to induce in a given species largely the same types of tumor when given transplacentally as when administered directly to postweaning animals, unless its carcinogenic effect in the latter is ascribable to some peculiarity of distribution, metabolism, or physiology. In a second species, the spectrum of tumors induced either before of after birth may be quite different. For bioassay of suspected carcinogens, the significance of perinatal carcinogenesis lies in the facts that the fetal and preweaning rodent is an extremely sensitive indicator of carcinogenic activity, and that the facile adaptibility of fetal cells to tissue culture and their rapid expression in vitro of properties of neoplastic

  2. TERT alleviates irradiation-induced late rectal injury by reducing hypoxia-induced ROS levels through the activation of NF-κB and autophagy

    PubMed Central

    Liu, Qi; Sun, Yong; Lv, Yuefeng; Le, Ziyu; Xin, Yuhu; Zhang, Ping; Liu, Yong

    2016-01-01

    The hypoxic microenvironment which is present following irradiation has been proven to promote radiation-induced injury to normal tissues. Previous studies have demonstrated that telomerase reverse transcriptase (TERT) is regulated by hypoxia, and that it plays a protective role in the process of wound repair. However, its effects on radiation-induced injury remain unclear. In this study, we examined the effects of human TERT on irradiation-induced late rectal injury in fibroblasts under hypoxic conditions. We also performed in vivo experiments. The rectums of 5-week-old female C57BL/6N mice were irradiated locally with a single dose of 25 Gy. We then examined the fibrotic changes using hematoxylin and eosin staining, and Masson's staining. The expression of hypoxia inducible factor-1α (HIF-1α) and TERT was analyzed by immunohistochemistry. In in vitro experiments, apoptosis, reactive oxygen species (ROS) production and the autophagy level induced by exposure to hypoxia were assayed in fibroblasts. The association between TERT, nuclear factor-κB (NF-κB) and the autophagy level was examined by western blot analysis. The antioxidant effects of TERT were examined on the basis of the ratio of glutathione to glutathione disulfide (GSH/GSSG) and mitochondrial membrane potential. Rectal fibrosis was induced significantly at 12 weeks following irradiation. The HIF-1α and TERT expression levels increased in the fibrotic region. The TERT-overexpressing fibroblasts (transfected with an hTERT-expressing lentiviral vector) exhibited reduced apoptosis, reduced ROS production, a higher autophagy level, a higher GSH/GSSG ratio and stable mitochondrial membrane potential compared with the fibroblasts in which TERT had been silenced by siRNA. NF-κB was activated by TERT, and the inhibition of TERT reduced the autophagy level in the fibroblasts. These results demonstrate that TERT decreases cellular ROS production, while maintaining mitochondrial function and protecting the

  3. Late hematologic toxicity following treatment of rattlesnake envenomation with crotalidae polyvalent immune Fab antivenom.

    PubMed

    Ruha, Anne-Michelle; Curry, Steven C; Albrecht, Clay; Riley, Brad; Pizon, Anthony

    2011-01-01

    North American rattlesnake envenomations commonly produce defibrination, coagulopathy and/or thrombocytopenia, which may be reversed following treatment with Crotalidae Polyvalent Immune Fab Ovine (FabAV). Despite initial resolution with FabAV, late onset or recurrence of venom-induced hematologic effects may occur. Time at which onset of late hematotoxicity may first be detected is unknown. The purpose of this study was to identify the incidence and time of onset of recurrent or new late hypofibrinogenemia, coagulopathy, or thrombocytopenia in a cohort of rattlesnake envenomation patients seen in outpatient follow-up after treatment with FabAV, and to report hematologic outcomes in these patients. Review of 66 charts of patients with rattlesnake envenomation who were treated with FabAV, and subsequently had outpatient follow-up evaluation at least 48 h after last FabAV, was performed. Demographic information, rattlesnake and bite characteristics, dose and timing of antivenom administration, adverse events, in-patient laboratory values, length of hospital stay, and follow-up laboratory values were collected. The primary outcome parameters were recurrent or delayed onset coagulopathy, hypofibrinogenemia, or thrombocytopenia identified no sooner than 48 h after last dose of FabAV. Prior to control of the envenomation with FabAV, 42 patients (63.6%) experienced hematologic toxicity. At follow-up, 21 patients (32%) were found to have late coagulopathy, hypofibrinogenemia, or thrombocytopenia. Of twenty-three patients (35%) with more than one follow-up visit, fifteen had normal laboratory findings at the first follow-up visit. Five of these 15 patients (8% of total study group; 33% of this subgroup) with normal hematologic studies at first follow-up exhibited late hematologic toxicity at second follow-up. Severe late hematologic toxicity developed in five of 66 (8%) patients. One patient was retreated with FabAV for late severe thrombocytopenia. Recurrent and delayed

  4. Dose-Volume Constraints to Reduce Rectal Side Effects From Prostate Radiotherapy: Evidence From MRC RT01 Trial ISRCTN 47772397

    SciTech Connect

    Gulliford, Sarah L.; Foo, Kerwyn; Morgan, Rachel C.; Aird, Edwin G.; Bidmead, A. Margaret; Critchley, Helen; Evans, Philip M. D.Phil.; Gianolini, Stefano; Mayles, W. Philip; Moore, A. Rollo; Sanchez-Nieto, Beatriz; Partridge, Mike; Sydes, Matthew R. C.Stat; Webb, Steve; Dearnaley, David P.

    2010-03-01

    Purpose: Radical radiotherapy for prostate cancer is effective but dose limited because of the proximity of normal tissues. Comprehensive dose-volume analysis of the incidence of clinically relevant late rectal toxicities could indicate how the dose to the rectum should be constrained. Previous emphasis has been on constraining the mid-to-high dose range (>=50 Gy). Evidence is emerging that lower doses could also be important. Methods and Materials: Data from a large multicenter randomized trial were used to investigate the correlation between seven clinically relevant rectal toxicity endpoints (including patient- and clinician-reported outcomes) and an absolute 5% increase in the volume of rectum receiving the specified doses. The results were quantified using odds ratios. Rectal dose-volume constraints were applied retrospectively to investigate the association of constraints with the incidence of late rectal toxicity. Results: A statistically significant dose-volume response was observed for six of the seven endpoints for at least one of the dose levels tested in the range of 30-70 Gy. Statistically significant reductions in the incidence of these late rectal toxicities were observed for the group of patients whose treatment plans met specific proposed dose-volume constraints. The incidence of moderate/severe toxicity (any endpoint) decreased incrementally for patients whose treatment plans met increasing numbers of dose-volume constraints from the set of V30<=80%, V40<=65%, V50<=55%, V60<=40%, V65<=30%, V70<=15%, and V75<=3%. Conclusion: Considering the entire dose distribution to the rectum by applying dose-volume constraints such as those tested here in the present will reduce the incidence of late rectal toxicity.

  5. Factors influencing acute and late toxicity in the era of adjuvant hypofractionated breast radiotherapy.

    PubMed

    De Santis, M C; Bonfantini, F; Di Salvo, F; Dispinzieri, M; Mantero, E; Soncini, F; Baili, P; Sant, M; Bianchi, G; Maggi, C; Di Cosimo, S; Agresti, R; Pignoli, E; Valdagni, R; Lozza, L

    2016-10-01

    To evaluate toxicity in breast cancer patients treated with anthracycline and taxane based chemotherapy and whole breast hypofractionated radiotherapy, and to identify the risk factors for toxicity. 537 early breast cancer patients receiving hypofractionated radiotherapy after conservative surgery were enrolled from April 2009 to December 2014, in an Italian cancer institute. The dose was 42.4 Gy in 16 daily fractions, 2.65 Gy per fraction. The boost to the tumor bed was administered only in grade III breast cancer patients and in patients with close or positive margins. Acute and late toxicity were prospectively assessed during and after radiotherapy according to RTOG scale. The impact of patients clinical characteristics, performed treatments and dose inhomogeneities on the occurrence of an higher level of acute skin toxicity and late fibrosis has been evaluated by univariate and multivariate analysis. The mean age was 74 (range 46-91 yrs). 27% of patients received boost. 22% of cases (n = 119) received also chemotherapy. The median follow-up was 32 months. G1 and G2/G3 acute skin toxicity were 61.3% and 20.5% and G1 and G2/G3 late fibrosis 12.6% and 4.3% respectively. Chemotherapy (p = 0.04), diabetes (p = 0.04) and boost administration (p < 0.01) were found to be statistically significant on the occurrence of late fibrosis, but a multivariate analysis did not show any factors connected. The boost administration (p < 0.01), the breast volume (p = 0.05), dose inhomogeneities (p < 0.01) and boost volume (p = 0.04) were found to be statistically significant as concerns the occurrence of acute skin reaction at the univariate analysis, but only the boost administration (p = 0.02), at multivariate analysis. The results of our study, according to the large randomized trials, confirmed that hypofractionated whole breast irradiation is safe, and only the boost administration seems to be an important predictor for toxicity. Chemotherapy does not

  6. Rectal dose to prostate cancer patients treated with proton therapy with or without rectal spacer.

    PubMed

    Chung, Heeteak; Polf, Jerimy; Badiyan, Shahed; Biagioli, Matthew; Fernandez, Daniel; Latifi, Kujtim; Wilder, Richard; Mehta, Minesh; Chuong, Michael

    2017-01-01

    The purpose of this study was to evaluate whether a spacer inserted in the prerectal space could reduce modeled rectal dose and toxicity rates for patients with prostate cancer treated in silico with pencil beam scanning (PBS) proton therapy. A total of 20 patients were included in this study who received photon therapy (12 with rectal spacer (DuraSeal™ gel) and 8 without). Two PBS treatment plans were retrospectively created for each patient using the following beam arrangements: (1) lateral-opposed (LAT) fields and (2) left and right anterior oblique (LAO/RAO) fields. Dose volume histograms (DVH) were generated for the prostate, rectum, bladder, and right and left femoral heads. The normal tissue complication probability (NTCP) for ≥grade 2 rectal toxicity was calculated using the Lyman-Kutcher-Burman model and compared between patients with and without the rectal spacer. A significantly lower mean rectal DVH was achieved in patients with rectal spacer compared to those without. For LAT plans, the mean rectal V70 with and without rectal spacer was 4.19 and 13.5%, respectively. For LAO/RAO plans, the mean rectal V70 with and without rectal spacer was 5.07 and 13.5%, respectively. No significant differences were found in any rectal dosimetric parameters between the LAT and the LAO/RAO plans generated with the rectal spacers. We found that ≥ 9 mm space resulted in a significant decrease in NTCP modeled for ≥grade 2 rectal toxicity. Rectal spacers can significantly decrease modeled rectal dose and predicted ≥grade 2 rectal toxicity in prostate cancer patients treated in silico with PBS. A minimum of 9 mm separation between the prostate and anterior rectal wall yields the largest benefit.

  7. Diazepam Rectal

    MedlinePlus

    Diazepam rectal gel is used in emergency situations to stop cluster seizures (episodes of increased seizure activity) in people who are ... Diazepam comes as a gel to instill rectally using a prefilled syringe with a special plastic tip. Follow the directions on your prescription label carefully, ...

  8. Late Gastrointestinal Toxicity After Dose-Escalated Conformal Radiotherapy for Early Prostate Cancer: Results From the UK Medical Research Council RT01 Trial (ISRCTN47772397)

    SciTech Connect

    Syndikus, Isabel; Morgan, Rachel C.; Sydes, Matthew R.; Graham, John D.; Dearnaley, David P.

    2010-07-01

    Purpose: In men with localized prostate cancer, dose-escalated conformal radiotherapy (CFRT) improves efficacy outcomes at the cost of increased toxicity. We present a detailed analysis to provide further information about the incidence and prevalence of late gastrointestinal side effects. Methods and Materials: The UK Medical Research Council RT01 trial included 843 men with localized prostate cancer, who were treated for 6 months with neoadjuvant radiotherapy and were randomly assigned to either 64-Gy or 74-Gy CFRT. Toxicity was evaluated before CFRT and during long-term follow-up using Radiation Therapy Oncology Group (RTOG) grading, the Late Effects on Normal Tissue: Subjective, Objective, Management (LENT/SOM) scale, and Royal Marsden Hospital assessment scores. Patients regularly completed Functional Assessment of Cancer Therapy--Prostate (FACT-P) and University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) questionnaires. Results: In the dose-escalated group, the hazard ratio (HR) for rectal bleeding (LENT/SOM grade {>=}2) was 1.55 (95% CI, 1.17-2.04); for diarrhea (LENT/SOM grade {>=}2), the HR was 1.79 (95% CI, 1.10-2.94); and for proctitis (RTOG grade {>=}2), the HR was 1.64 (95% CI, 1.20-2.25). Compared to baseline scores, the prevalence of moderate and severe toxicities generally increased up to 3 years and than lessened. At 5 years, the cumulative incidence of patient-reported severe bowel problems was 6% vs. 8% (standard vs. escalated, respectively) and severe distress was 4% vs. 5%, respectively. Conclusions: There is a statistically significant increased risk of various adverse gastrointestinal events with dose-escalated CFRT. This remains at clinically acceptable levels, and overall prevalence ultimately decreases with duration of follow-up.

  9. Evidence from a breast cancer hypofractionated schedule: late skin toxicity assessed by ultrasound.

    PubMed

    Landoni, Valeria; Giordano, Carolina; Marsella, Annelisa; Saracino, Biancamaria; Petrongari, Maria; Ferraro, Anna; Strigari, Lidia; Pinnarò, Paola

    2013-10-24

    Feasibility of whole breast hypofractionated radiotherapy schedules in breast conserving therapy is recognized however concerns remain about the role of the boost dose on the overall treatment's potential toxicity. In this study we report on the possibility to quantitatively evaluate radiation induced toxicity in patients treated with an abbreviated course with major concern in the irradiated boost region. Eighty-nine patients who underwent conservative surgery for early-stage breast cancer followed by adjuvant accelerated hypofractionated whole breast radiotherapy were included in this study to assess skin and subcutaneous tissue late toxicity by means of ultrasonographic quantitative examination. For each patient the skin thickness was measured at four positions: on the irradiated breast, in the boost region and in the corresponding positions in the contra-lateral not treated breast. All patients were scanned by the same radiologist to reduce potential inter-operator variability, the operator was blind to the scoring of the patient CTCv3 late toxicity as well as patient treatment characteristics. Ultrasound assessment and clinical evaluation were compared. The median time between the end of adjuvant radiotherapy and ultrasound examination was 20.5 months. The measured mean skin thickness in the irradiated breast was 2.13 ± 0.72 mm while in the mirror region of the contra-lateral healthy breast was 1.61 ± 0.29 mm. The measured mean skin thickness in the irradiated boost region was 2.25 ± 0.79 mm versus 1.63 ± 0.33 mm in the corresponding region of contra-lateral healthy breast. The mean increment in skin thickness respect to the counterpart in the healthy breast was 0.52 ± 0.67 mm and 0.62 ± 0.74 mm for the breast and the boost region respectively. A significant direct correlation was found between the increment in skin thickness in the irradiated breast and in the boost region with fibrosis (G ≥ 1). In this study results from a breast cancer

  10. Hypopharyngeal Dose Is Associated With Severe Late Toxicity in Locally Advanced Head-and-Neck Cancer: An RTOG Analysis

    SciTech Connect

    Machtay, Mitchell; Moughan, Jennifer; Farach, Andrew; Galvin, James; Garden, Adam S.; Weber, Randal S.; Cooper, Jay S.; Forastiere, Arlene; Ang, K. Kian

    2012-11-15

    Purpose: Concurrent chemoradiation therapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN) increases local tumor control but at the expense of increased toxicity. We recently showed that several clinical/pretreatment factors were associated with the occurrence of severe late toxicity. This study evaluated the potential relationship between radiation dose delivered to the pharyngeal wall and toxicity. Methods and Materials: This was an analysis of long-term survivors from 3 previously reported Radiation Therapy Oncology Group (RTOG) trials of CCRT for locally advanced SCCHN (RTOG trials 91-11, 97-03, and 99-14). Severe late toxicity was defined in this secondary analysis as chronic grade 3-4 pharyngeal/laryngeal toxicity and/or requirement for a feeding tube {>=}2 years after registration and/or potential treatment-related death (eg, pneumonia) within 3 years. Radiation dosimetry (2-dimensional) analysis was performed centrally at RTOG headquarters to estimate doses to 4 regions of interest along the pharyngeal wall (superior oropharynx, inferior oropharynx, superior hypopharynx, and inferior hypopharynx). Case-control analysis was performed with a multivariate logistic regression model that included pretreatment and treatment potential factors. Results: A total of 154 patients were evaluable for this analysis, 71 cases (patients with severe late toxicities) and 83 controls; thus, 46% of evaluable patients had a severe late toxicity. On multivariate analysis, significant variables correlated with the development of severe late toxicity, including older age (odds ratio, 1.062 per year; P=.0021) and radiation dose received by the inferior hypopharynx (odds ratio, 1.023 per Gy; P=.016). The subgroup of patients receiving {<=}60 Gy to the inferior hypopharynx had a 40% rate of severe late toxicity compared with 56% for patients receiving >60 Gy. Oropharyngeal dose was not associated with this outcome. Conclusions: Severe late toxicity following CCRT is

  11. 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

  12. The impact of body mass index on rectal dose in locally advanced cervical cancer treated with high-dose-rate brachytherapy.

    PubMed

    Lim, Jihoon; Durbin-Johnson, Blythe; Valicenti, Richard; Mathai, Matthew; Stern, Robin L; Mayadev, Jyoti

    2013-01-01

    The impact of body mass index (BMI) on rectal dose in brachytherapy for cervical cancer is unknown. We assessed the association of BMI on rectal dose and lower gastrointestinal (GI) toxicity. Between 2007 and 2010, 51 patients with 97 brachytherapy planning images were reviewed. Volumetric measurements of the maximum percentage, mean percentage, dose to 2cc (D2cc), and dose to 1cc (D1cc) of the rectum, and the Internal Commission on Radiation Units and Measurement (ICRU) rectal point were recorded. Linear mixed effect models, analysis of variance, and regression analyses were used to determine the correlation between multiple observations or to detect a difference in the mean. The GI acute and late toxicity were prospectively recorded and retrospectively analyzed. The average BMI (kg/m(2)) was 27.7 with a range of 17.4-46.6. Among the patients, 8% were morbidly obese, 25% obese, 25% overweight, 40% normal weight, and 2% underweight. The mean D1cc, D2cc, mean rectal dose (%), maximum rectal dose (%), and ICRU rectum was 3.03 Gy, 2.78 Gy, 20%, 60%, and 2.99 Gy, respectively. On multivariate analysis, there was a significant decrease in the D1cc and D2cc rectal dose (p=0.016), ICRU rectal point dose (p=0.022), and mean rectal dose percentage (p=0.021) with an increase in BMI. There was, however, no statistically significant relationship between BMI and GI toxicity. Obesity decreases the rectal dose given in high-dose-rate brachytherapy for locally advanced cervical cancer because of an increase in fatty tissue in the recto-uterine space. There is no significant correlation between BMI and acute or late GI toxicity. Published by Elsevier Inc.

  13. IMRT for Sinonasal Tumors Minimizes Severe Late Ocular Toxicity and Preserves Disease Control and Survival

    SciTech Connect

    Duprez, Frederic; Madani, Indira; Morbee, Lieve; Bonte, Katrien; Deron, Philippe; Domjan, Vilmos; Boterberg, Tom; De Gersem, Werner; De Neve, Wilfried

    2012-05-01

    Purpose: To report late ocular (primary endpoint) and other toxicity, disease control, and survival (secondary endpoints) after intensity-modulated radiotherapy (IMRT) for sinonasal tumors. Methods and Materials: Between 1998 and 2009, 130 patients with nonmetastatic sinonasal tumors were treated with IMRT at Ghent University Hospital. Prescription doses were 70 Gy (n = 117) and 60-66 Gy (n = 13) at 2 Gy per fraction over 6-7 weeks. Most patients had adenocarcinoma (n = 82) and squamous cell carcinoma (n = 23). One hundred and one (101) patients were treated postoperatively. Of 17 patients with recurrent tumors, 9 were reirradiated. T-stages were T1-2 (n = 39), T3 (n = 21), T4a (n = 38), and T4b (n = 22). Esthesioneuroblastoma was staged as Kadish A, B, and C in 1, 3, and 6 cases, respectively. Results: Median follow-up was 52, range 15-121 months. There was no radiation-induced blindness in 86 patients available for late toxicity assessment ({>=}6 month follow-up). We observed late Grade 3 tearing in 10 patients, which reduced to Grade 1-2 in 5 patients and Grade 3 visual impairment because of radiation-induced ipsilateral retinopathy and neovascular glaucoma in 1 patient. There was no severe dry eye syndrome. The worst grade of late ocular toxicity was Grade 3 (n = 11), Grade 2 (n = 31), Grade 1 (n = 33), and Grade 0 (n = 11). Brain necrosis and osteoradionecrosis occurred in 6 and 1 patients, respectively. Actuarial 5-year local control and overall survival were 59% and 52%, respectively. On multivariate analysis local control was negatively affected by cribriform plate and brain invasion (p = 0.044 and 0.029, respectively) and absence of surgery (p = 0.009); overall survival was negatively affected by cribriform plate and orbit invasion (p = 0.04 and <0.001, respectively) and absence of surgery (p = 0.001). Conclusions: IMRT for sinonasal tumors allowed delivering high doses to targets at minimized ocular toxicity, while maintaining disease control and survival

  14. Optical Coherence Tomography for Quantitative Assessment of Microstructural and Microvascular Alterations in Late Oral Radiation Toxicity

    NASA Astrophysics Data System (ADS)

    Davoudi, Bahar

    More than half of head-and-neck cancer patients undergo radiotherapy at some point during their treatment. Even though the use of conformed therapeutic beams has increased radiation dose localization to the tumor, resulting in more normal tissue sparing, still, in many head-and-neck cancer patients, the healthy tissue of the oral cavity still receives a sizeable amount of radiation. This causes acute and / or late complications in these patients. The latter occur as late as several months or even years after the completion of treatment and are typically associated with severe symptoms. Currently, the clinical method for diagnosing these complications is visual examination of the oral tissue surface. However, it has been well established that such complications originate in subsurface oral tissue layers including its microvasculature. Therefore, to better understand the mechanism of these complications and to be able to diagnose them earlier, there exists a need for subsurface monitoring of the irradiated oral tissue. Histology has been used as such a tool for research purposes; however, its use in clinical diagnosis is limited due to its invasive and hazardous nature. Therefore, in this thesis, I propose to use optical coherence tomography (OCT) as a subsurface, micron-scale resolution optical imaging tool that can provide images of oral tissue subsurface layers down to a depth of 1-2 mm (structural OCT), as well as images demonstrating vessel morphology (speckle variance OCT) and blood flow information (Doppler OCT). This thesis explains the development of an OCT setup and an oral probe to acquire images in-vivo. Moreover, it introduces a software-based quantification platform for extracting specific biologically-meaningful metrics from the structural and vascular OCT images. It then describes the application of the developed imaging and quantification platform in a feasibility clinical study that was performed on 15 late oral radiation toxicity patients and 5 age

  15. Effects of salinity and pre-exposure on acute cadmium toxicity to seabass, Lates calcarifer

    SciTech Connect

    Shazili, N.A.M.

    1995-01-01

    In recent years in Malaysia, aquaculture activities have expanded into coastal areas. One of the species gaining importance is the seabass, Lates caclarifer. It is a marine fish tolerant to a wide range of salinities down to almost freshwater, although they are normally cultured in floating cages in estuaries with a salinity range of 10 to 25 ppt. The adults spawn in the sea, and upon hatching, the young move into mangrove areas and upstream where the salinity regime fluctuates. The seabass is commonly reared in floating cages in estuaries where the salinity may approach freshwater. However, there is increasing concern for heavy metal pollution in estuaries and coastal areas in Malaysia. The toxicity of heavy metals to marine organisms increases with decreasing salinity; probably due to an increase in free ion concentration and, hence, metal accumulation. There is then the possibility that seabass cultured in estuaries where low salinities are frequently encountered, especially during rainy seasons, would be more susceptible to the effects of metal pollution. There is also a paucity of data on toxicity studies with the seabass. Due to these reasons, an investigation was carried out to establish the toxicity of cadmium to the seabass at two stages of development and the influence of salinity n its toxicity. 20 refs., 5 tabs.

  16. 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

  17. SU-E-J-93: Parametrisation of Dose to the Mucosa of the Anterior Rectal Wall in Transrectal Ultrasound Guided High-Dose-Rate Brachytherapy of the Prostate

    SciTech Connect

    Aitkenhead, A; Hamlett, L; Wood, D; Choudhury, A

    2014-06-01

    Purpose: In high-dose-rate (HDR) brachytherapy of the prostate, radiation is delivered from a number of radioactive sources which are inserted via catheter into the target volume. The rectal mucosa also receives dose during the treatment, which may lead to late toxicity effects. To allow possible links between rectal dose and toxicity to be investigated, suitable methods of parametrising the rectal dose are needed. Methods: During treatment of a series of 95 patients, anatomy and catheter locations were monitored by transrectal ultrasound, and target volume positions were contoured on the ultrasound scan by the therapist. The anterior rectal mucosal wall was identified by contouring the transrectal ultrasound balloon within the ultrasound scan. Source positions and dwell times, along with the dose delivered to the patient were computed using the Oncentra Prostate treatment planning system (TPS). Data for the series of patients were exported from the TPS in Dicom format, and a series of parametrisation methods were developed in a Matlab environment to assess the rectal dose. Results: Contours of the anterior rectal mucosa were voxelised within Matlab to allow the dose to the rectal mucosa to be analysed directly from the 3D dose grid. Dose parametrisations based on dose-surface (DSH) and dose-line (DLH) histograms were obtained. Both lateral and longitudinal extents of the mucosal dose were parametrised using dose-line histograms in the relevant directions. Conclusion: We have developed a series of dose parametrisations for quantifying the dose to the rectal mucosa during HDR prostate brachytherapy which are suitable for future studies investigating potential associations between mucosal dose and late toxicity effects. The geometry of the transrectal probe standardises the rectal anatomy, making this treatment technique particularly suited to studies of this nature.

  18. WE-D-BRE-03: Late Toxicity Following Photon Or Proton Radiotherapy in Patients with Brain Tumors

    SciTech Connect

    Munbodh, R; Ding, X; Yin, L; Anamalayil, S; Dorsey, J; Lustig, R; Alonso-Basanta, M

    2014-06-15

    Purpose: To identify indicators of Late Grade 3 (LG3) toxicity, late vision and hearing changes in patients treated for primary brain tumors with photon (XRT) or proton radiotherapy (PRT). Methods: We retrospectively reviewed 102 patients who received brain XRT or PRT to doses of 54 or 59.6 Gy in daily fractions of 1.8–2 Gy. Of the 80 patients (34 XRT, 39 PRT and 7 both modalities) reviewed for indicators of LG3 toxicity, 25 developed LG3 toxicity 90 to 500 days after radiotherapy completion. 55 patients had less than LG3 toxicity > 500 days after treatment. In that time, late vision and hearing changes were seen in 44 of 75 and 25 of 78 patients, respectively. The correlation between late toxicity and prescription dose, planning target volume (PTV) size, and doses to the brainstem, brain, optic chiasm, optic nerves, eyes and cochlea was evaluated. A two-tailed Fisher's exact test and Wilcoxon rank sum test were used for the statistical analysis for XRT, PRT and all patients combined. Results: Exceeding the 54 Gy-5% dose-volume brainstem constraint, but not the optic structure constraints, was significantly correlated (p < 0.05) with late vision changes in all three groups. Exceeding maximum and mean cochlear doses of 45 and 30 Gy, respectively, was a significant indicator of hearing changes (p < 0.05) in PRT patients and all patients combined. In a sub-group of 52 patients in whom the brain was contoured, the absolute brain volume receiving ≤ 50 Gy and > 60 Gy was significantly larger in patients with LG3 toxicity for all patients combined (p < 0.05). Prescription dose, brainstem dose and PTV volume were not correlated to LG3 toxicity. Conclusion: Our results indicate the importance of minimizing the brain volume irradiated, and brainstem and cochlea doses to reduce the risk of late toxicities following brain radiotherapy.

  19. Predictors of Severe Acute and Late Toxicities in Patients With Localized Head-and-Neck Cancer Treated With Radiation Therapy

    SciTech Connect

    Meyer, Francois; Fortin, Andre; Wang, Chang Shu; Liu, Geoffrey

    2012-03-15

    Purpose: Radiation therapy (RT) causes acute and late toxicities that affect various organs and functions. In a large cohort of patients treated with RT for localized head and neck cancer (HNC), we prospectively assessed the occurrence of RT-induced acute and late toxicities and identified characteristics that predicted these toxicities. Methods and Materials: We conducted a randomized trial among 540 patients treated with RT for localized HNC to assess whether vitamin E supplementation could improve disease outcomes. Adverse effects of RT were assessed using the Radiation Therapy Oncology Group Acute Radiation Morbidity Criteria during RT and one month after RT, and the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme at six and 12 months after RT. The most severe adverse effect among the organs/tissues was selected as an overall measure of either acute or late toxicity. Grade 3 and 4 toxicities were considered as severe. Stepwise multivariate logistic regression models were used to identify all independent predictors (p < 0.05) of acute or late toxicity and to estimate odds ratios (OR) for severe toxicity with their 95% confidence intervals (CI). Results: Grade 3 or 4 toxicity was observed in 23% and 4% of patients, respectively, for acute and late toxicity. Four independent predictors of severe acute toxicity were identified: sex (female vs. male: OR = 1.72, 95% confidence interval [CI]: 1.06-2.80), Karnofsky Performance Status (OR = 0.67 for a 10-point increment, 95% CI: 0.52-0.88), body mass index (above 25 vs. below: OR = 1.88, 95% CI: 1.22-2.90), TNM stage (Stage II vs. I: OR = 1.91, 95% CI: 1.25-2.92). Two independent predictors were found for severe late toxicity: female sex (OR = 3.96, 95% CI: 1.41-11.08) and weight loss during RT (OR = 1.26 for a 1 kg increment, 95% CI: 1.12-1.41). Conclusions: Knowledge of these predictors easily collected in a clinical setting could help

  20. External Beam Radiotherapy With Endocavitary Boost for Nasopharyngeal Cancer: Treatment Results and Late Toxicity After Extended Follow-Up

    SciTech Connect

    Schinagl, Dominic A.X.; Marres, Henri A.M.; Kappelle, Arnoud C.; Merkx, Matthias A.W.; Pop, Lucas A.M.; Verstappen, Suzan M.M.; Kaanders, Johannes H.A.M.

    2010-11-01

    Purpose: To evaluate the long-term outcome after treatment of nasopharyngeal carcinoma and assess late toxicity in a multidisciplinary clinic. Methods and Materials: A retrospective analysis of 117 patients treated for nasopharyngeal cancer in a single institute between 1985 and 2002 was performed. Fifty-one long-term survivors were evaluated for late toxicity by a multidisciplinary team comprising a radiation oncologist, otolaryngologist, neurologist, and oral and maxillofacial surgeon. Results: The 5-year local control rate for T1 to T2 and T3 to T4 tumors was 97% and 76%, respectively. Five-year disease-free survival and overall survival were 82% and 88% for Stage I to IIb disease and 46% and 52% for Stage III to IVb, respectively. Late morbidity evaluation revealed Radiation Therapy Oncology Group (RTOG) Grade III to IV toxicity in 71% of patients. A high incidence of cranial nerve palsies (47%) and mandibular osteolysis (82%) was found, although these complications had limited clinical impact. Conclusions: The multidisciplinary late morbidity clinic revealed an unexpected high incidence of cranial nerve palsies and mandibular osteolysis and overall an RTOG Grade III to IV toxicity in 71% of patients treated for nasopharyngeal cancer. External beam radiotherapy with endocavitary brachytherapy produces excellent rates of local control for T1 to T2 tumors, but the high incidence of late toxicity suggests an overtreatment.

  1. Standardized Total Average Toxicity Score: A Scale- and Grade-Independent Measure of Late Radiotherapy Toxicity to Facilitate Pooling of Data From Different Studies

    SciTech Connect

    Barnett, Gillian C.; West, Catharine M.L.; Coles, Charlotte E.; Pharoah, Paul D.P.; Talbot, Christopher J.; Elliott, Rebecca M.; Tanteles, George A.; Symonds, R. Paul; Wilkinson, Jennifer S.; Dunning, Alison M.; Burnet, Neil G.; Bentzen, Soren M.

    2012-03-01

    Purpose: The search for clinical and biologic biomarkers associated with late radiotherapy toxicity is hindered by the use of multiple and different endpoints from a variety of scoring systems, hampering comparisons across studies and pooling of data. We propose a novel metric, the Standardized Total Average Toxicity (STAT) score, to try to overcome these difficulties. Methods and Materials: STAT scores were derived for 1010 patients from the Cambridge breast intensity-modulated radiotherapy trial and 493 women from University Hospitals of Leicester. The sensitivity of the STAT score to detect differences between patient groups, stratified by factors known to influence late toxicity, was compared with that of individual endpoints. Analysis of residuals was used to quantify the effect of these covariates. Results: In the Cambridge cohort, STAT scores detected differences (p < 0.00005) between patients attributable to breast volume, surgical specimen weight, dosimetry, acute toxicity, radiation boost to tumor bed, postoperative infection, and smoking (p < 0.0002), with no loss of sensitivity over individual toxicity endpoints. Diabetes (p = 0.017), poor postoperative surgical cosmesis (p = 0.0036), use of chemotherapy (p = 0.0054), and increasing age (p = 0.041) were also associated with increased STAT score. When the Cambridge and Leicester datasets were combined, STAT was associated with smoking status (p < 0.00005), diabetes (p = 0.041), chemotherapy (p = 0.0008), and radiotherapy boost (p = 0.0001). STAT was independent of the toxicity scale used and was able to deal with missing data. There were correlations between residuals of the STAT score obtained using different toxicity scales (r > 0.86, p < 0.00005 for both datasets). Conclusions: The STAT score may be used to facilitate the analysis of overall late radiation toxicity, from multiple trials or centers, in studies of possible genetic and nongenetic determinants of radiotherapy toxicity.

  2. Acute and Late Toxicity in a Randomized Trial of Conventional Versus Hypofractionated Three-Dimensional Conformal Radiotherapy for Prostate Cancer

    SciTech Connect

    Arcangeli, Giorgio; Fowler, Jack; Gomellini, Sara; Arcangeli, Stefano; Saracino, Biancamaria; Petrongari, Maria Grazia; Benassi, Marcello; Strigari, Lidia

    2011-03-15

    Purpose: To compare the toxicity between hypofractionation vs. conventional fractionation schedules in patients with high-risk prostate cancer. Methods and Materials: Between January 2003 and December 2007, 168 patients were randomized to receive either hypofractionated (62 Gy in 20 fractions within 5 weeks, 4 fractions/wk) or conventionally fractionated (80 Gy in 40 fractions within 8 weeks) three-dimensional conformal radiotherapy to the prostate and seminal vesicles. All patients had undergone a 9-month course of total androgen deprivation, with radiotherapy starting 2 months after initiation of the total androgen deprivation. Results: The median follow-up was 32 and 35 months in the hypofractionation and conventional fractionation arms, respectively. For the patients developing acute toxicity, no difference between the two fractionation groups was found in either severity or duration of gastrointestinal or genitourinary toxicity. Also, no difference was found in the incidence and severity of late gastrointestinal and genitourinary toxicity between the two treatment schedules, with a 3-year rate of Grade 2 or greater toxicity of 17% and 16% for the hypofractionation arm and 14% and 11% for the conventional fractionation arm, respectively. A statistically significant correlation between acute and late gastrointestinal toxicity was found only in the conventional fractionation group. Conclusion: Our findings suggest that the hypofractionation regimen used in our study is safe, with only a slight, nonsignificant increase in tolerable and temporary acute toxicity compared with the conventional fractionation schedule. The severity and frequency of late complications was equivalent between the two treatment groups.

  3. SU-D-204-03: Comparison of Patient Positioning Methods Through Modeling of Acute Rectal Toxicity in Intensity Modulated Radiation Therapy for Prostate Cancer. Does Quality of Data Matter More Than the Quantity?

    SciTech Connect

    Liu, X; Fatyga, M; Vora, S; Wong, W; Schild, S; Schild, M; Herman, M; Li, J; Wu, T

    2016-06-15

    Purpose: To determine if differences in patient positioning methods have an impact on the incidence and modeling of grade >=2 acute rectal toxicity in prostate cancer patients who were treated with Intensity Modulated Radiation Therapy (IMRT). Methods: We compared two databases of patients treated with radiation therapy for prostate cancer: a database of 79 patients who were treated with 7 field IMRT and daily image guided positioning based on implanted gold markers (IGRTdb), and a database of 302 patients who were treated with 5 field IMRT and daily positioning using a trans-abdominal ultrasound system (USdb). Complete planning dosimetry was available for IGRTdb patients while limited planning dosimetry, recorded at the time of planning, was available for USdb patients. We fit Lyman-Kutcher-Burman (LKB) model to IGRTdb only, and Univariate Logistic Regression (ULR) NTCP model to both databases. We perform Receiver Operating Characteristics analysis to determine the predictive power of NTCP models. Results: The incidence of grade >= 2 acute rectal toxicity in IGRTdb was 20%, while the incidence in USdb was 54%. Fits of both LKB and ULR models yielded predictive NTCP models for IGRTdb patients with Area Under the Curve (AUC) in the 0.63 – 0.67 range. Extrapolation of the ULR model from IGRTdb to planning dosimetry in USdb predicts that the incidence of acute rectal toxicity in USdb should not exceed 40%. Fits of the ULR model to the USdb do not yield predictive NTCP models and their AUC is consistent with AUC = 0.5. Conclusion: Accuracy of a patient positioning system affects clinically observed toxicity rates and the quality of NTCP models that can be derived from toxicity data. Poor correlation between planned and clinically delivered dosimetry may lead to erroneous or poorly performing NTCP models, even if the number of patients in a database is large.

  4. Prospective study on late renal toxicity following postoperative chemoradiotherapy in gastric cancer

    SciTech Connect

    Jansen, Edwin; Boot, Henk; Cats, Annemieke

    2007-03-01

    Purpose: Postoperative chemoradiotherapy in gastric cancer improves locoregional control and survival. Reports on late toxicity, however, have been scarce thus far. Because renal toxicity is one of the most serious late complications in upper abdominal radiotherapy, we prospectively analyzed kidney function in patients who underwent postoperative chemoradiotherapy for gastric cancer. Patients and Methods: In 44 patients, Tc{sup 99m}-thiatide renography was performed before and at regular intervals after postoperative chemoradiotherapy. The left-to-right (L/R) ratio was used as an index of the relative kidney function. Mean L/R values were calculated for four follow-up time intervals. For all patients, kidney V{sub 20} (percentage of the volume of the kidney that received more than 20 Gy) and mean dose of both kidneys were retrieved from the three-dimensional dose-volume histograms. Results: We observed a progressive decrease in left renal function of 11% (p = 0.012) after 6 months, up to 52% (p < 0.001) after >18 months. The V{sub 20} (left kidney) and mean left kidney dose were identified as parameters associated with decreased kidney function. Mean serum creatinine was increased from 74.6 {mu}mol/L before treatment to 86.1 {mu}mol/L at 1 year after chemoradiotherapy (p < 0.001). In patients with a follow-up of 18-28 months, one case of severe renovascular hypertension was observed. Conclusion: A progressive relative functional impairment of the left kidney in patients after postoperative chemoradiotherapy for gastric cancer is demonstrated. To optimize the survival benefit that can be established with adjuvant regimens, strategies to minimize the dose to the kidneys and other critical organs should be explored.

  5. Receiver operating curves and dose-volume analysis of late toxicity with stereotactic body radiation therapy for prostate cancer.

    PubMed

    Zhang, Li; Johnson, Julian; Gottschalk, Alexander R; Chang, Albert J; Hsu, I-Chow; Roach, Mack; Seymour, Zachary A

    The purpose of this study was to evaluate a receiver operating characteristic (ROC) curve method to determine dose thresholds with late genitourinary (GU) toxicity after stereotactic body radiation therapy for prostate cancer. Seventy-eight patients diagnosed with low- to intermediate-risk prostate cancer and treated with stereotactic body radiation therapy alone were reviewed retrospectively. All patients received a total dose of 38 Gy in 4 fractions with a planning target volume expansion of 2 mm. GU toxicity was documented according to the Common Terminology Criteria for Adverse Events, version 4. ROC analysis applied on a logistic regression model was used to determine optimal dosimetric parameters for GU toxicity. The median age at treatment was 69 years with a median prostate volume of 46.2 mL. The median prescription isodose line was 67% (interquartile range, 65, 70). The median clinical follow-up was 35.49 months. Late grade 1, 2, and 3 GU toxicity occurred in 21.8%, 19.2%, and 2.6% of cases, respectively. Late grade 2+ GU toxicity was associated with prescription to isodose line (P = .009) and normalized volumes for heterogeneity ≥46 Gy. The ROC method successfully produced thresholds for dose-volume recommendations for both prostate and urethra, including normalized prostate volumes from 46 to 50 Gy, such as volume of target tissue receiving 46% of the prescribed dose (V46) Gy of 36.7% (sensitivity, 71%; specificity, 61%; area under the curve, 0.67) with an associated probability of late GU grade 2+ toxicity of 21%. Intraprostatic heterogeneity should be controlled with potential thresholds at V46 Gy <36.7%, V48 Gy <21%, and V50 Gy <9.5% of the normalized prostate volume to keep late grade 2+ GU toxicity ≤20% with 4-fraction schemes. This may be facilitated with a higher prescription isodose line (>69%). Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

  6. Impact of tumour bed boost integration on acute and late toxicity in patients with breast cancer: A systematic review.

    PubMed

    Hamilton, Daniel George; Bale, Rebecca; Jones, Claire; Fitzgerald, Emma; Khor, Richard; Knight, Kellie; Wasiak, Jason

    2016-06-01

    The purpose of this systematic review was to summarise the evidence from studies investigating the integration of tumour bed boosts into whole breast irradiation for patients with Stage 0-III breast cancer, with a focus on its impact on acute and late toxicities. A comprehensive systematic electronic search through the Ovid MEDLINE, EMBASE and PubMed databases from January 2000 to January 2015 was conducted. Studies were considered eligible if they investigated the efficacy of hypo- or normofractionated whole breast irradiation with the inclusion of a daily concurrent boost. The primary outcomes of interest were the degree of observed acute and late toxicity following radiotherapy treatment. Methodological quality assessment was performed on all included studies using either the Newcastle-Ottawa Scale or a previously published investigator-derived quality instrument. The search identified 35 articles, of which 17 satisfied our eligibility criteria. Thirteen and eleven studies reported on acute and late toxicities respectively. Grade 3 acute skin toxicity ranged from 1 to 7% whilst moderate to severe fibrosis and telangiectasia were both limited to 9%. Reported toxicity profiles were comparable to historical data at similar time-points. Studies investigating the delivery of concurrent boosts with whole breast radiotherapy courses report safe short to medium-term toxicity profiles and cosmesis rates. Whilst the quality of evidence and length of follow-up supporting these findings is low, sufficient evidence has been generated to consider concurrent boost techniques as an alternative to conventional sequential techniques.

  7. [A case of long-term survival in rectal cancer with late lung and kidney metastases treated with combined multimodality therapy].

    PubMed

    Ikenaga, Masakazu; Kim, Ho Min; Hitora, Toshiki; Hirota, Masaki; Murakami, Masahiro; Oda, Naofumi; Yoshikawa, Masato; Morishima, Hirotaka; Shimizu, Junzo; Mikata, Shoki; Matsunami, Nobuki; Miwa, Hideaki; Hasegawa, Junichi

    2014-11-01

    A 59-year-old man was diagnosed with rectal cancer and a low anterior resection was performed. Bilateral lung metastases appeared 4 years and 4 months after the primary surgery. The lung metastases were resected and FOLFOX6 neoadjuvant chemotherapy was administered. An abdominal computed tomography (CT) scan 7 years and 11 months after the primary surgery revealed bilateral multiple lung metastases, a left renal tumor, and swelling in the surrounding lymph node. A left nephrectomy and lymph node dissection were performed. A diagnosis of renal tumor from rectal cancer metastasis was made. For the lung metastases, chemotherapy (sLV/5FU2+Bmab) was administered in 26 courses and stable disease was achieved. It is important to combine adequate surgical resection and systemic chemotherapy for long survival.

  8. Tumor histology and location predict deep nuclei toxicity: Implications for late effects from focal brain irradiation.

    PubMed

    Plaga, Alexis; Shields, Lisa B E; Sun, David A; Vitaz, Todd W; Spalding, Aaron C

    2012-01-01

    Normal tissue toxicity resulting from both disease and treatment is an adverse side effect in the management of patients with central nervous system malignancies. We tested the hypothesis that despite these improvements, certain tumors place patients at risk for neurocognitive, neuroendocrine, and neurosensory late effects. Defining patient groups at risk for these effects could allow for development of preventive strategies. Fifty patients with primary brain tumors underwent radiation planning with magnetic resonance imaging scan and computed tomography datasets. Organs at risk (OAR) responsible for neurocognitive, neuroendocrine, and neurosensory function were defined. Inverse-planned intensity-modulated radiation therapy was optimized with priority given to target coverage while penalties were assigned to exceeding normal tissue tolerances. Tumor laterality, location, and histology were compared with OAR doses, and analysis of variance was performed to determine the significance of any observed correlation. The ipsilateral hippocampus exceeded dose limits in frontal (74%), temporal (94%), and parietal (100%) lobe tumor locations. The contralateral hippocampus was at risk in the following tumor locations: frontal (53%), temporal (83%), or parietal (50%) lobe. Patients with high-grade glioma were at risk for ipsilateral (88%) and contralateral (73%) hippocampal damage (P <0.05 compared with other histologies). The pituitary gland and hypothalamus exceeded dose tolerances in patients with pituitary tumors (both 100%) and high-grade gliomas (50% and 75%, P <0.05 compared with other histologies), respectively. Despite application of modern radiation therapy, certain tumor locations and histologies continue to place patients at risk for morbidity. Patients with high-grade gliomas or tumors located in the frontal, temporal, or parietal lobes are at risk for neurocognitive decline, likely because of larger target volumes and higher radiation doses. Data from this study

  9. Tumor histology and location predict deep nuclei toxicity: Implications for late effects from focal brain irradiation

    SciTech Connect

    Plaga, Alexis; Shields, Lisa B.E.; Sun, David A.; Vitaz, Todd W.; Spalding, Aaron C.

    2012-10-01

    Normal tissue toxicity resulting from both disease and treatment is an adverse side effect in the management of patients with central nervous system malignancies. We tested the hypothesis that despite these improvements, certain tumors place patients at risk for neurocognitive, neuroendocrine, and neurosensory late effects. Defining patient groups at risk for these effects could allow for development of preventive strategies. Fifty patients with primary brain tumors underwent radiation planning with magnetic resonance imaging scan and computed tomography datasets. Organs at risk (OAR) responsible for neurocognitive, neuroendocrine, and neurosensory function were defined. Inverse-planned intensity-modulated radiation therapy was optimized with priority given to target coverage while penalties were assigned to exceeding normal tissue tolerances. Tumor laterality, location, and histology were compared with OAR doses, and analysis of variance was performed to determine the significance of any observed correlation. The ipsilateral hippocampus exceeded dose limits in frontal (74%), temporal (94%), and parietal (100%) lobe tumor locations. The contralateral hippocampus was at risk in the following tumor locations: frontal (53%), temporal (83%), or parietal (50%) lobe. Patients with high-grade glioma were at risk for ipsilateral (88%) and contralateral (73%) hippocampal damage (P <0.05 compared with other histologies). The pituitary gland and hypothalamus exceeded dose tolerances in patients with pituitary tumors (both 100%) and high-grade gliomas (50% and 75%, P <0.05 compared with other histologies), respectively. Despite application of modern radiation therapy, certain tumor locations and histologies continue to place patients at risk for morbidity. Patients with high-grade gliomas or tumors located in the frontal, temporal, or parietal lobes are at risk for neurocognitive decline, likely because of larger target volumes and higher radiation doses. Data from this study

  10. Reduced Activity of Double-Strand Break Repair Genes in Prostate Cancer Patients With Late Normal Tissue Radiation Toxicity

    SciTech Connect

    Oorschot, Bregje van; Hovingh, Suzanne E.; Moerland, Perry D.; Medema, Jan Paul; Stalpers, Lukas J.A.; Vrieling, Harry; Franken, Nicolaas A.P.

    2014-03-01

    Purpose: To investigate clinical parameters and DNA damage response as possible risk factors for radiation toxicity in the setting of prostate cancer. Methods and Materials: Clinical parameters of 61 prostate cancer patients, 34 with (overresponding, OR) and 27 without (non-responding, NR) severe late radiation toxicity were assembled. In addition, for a matched subset the DNA damage repair kinetics (γ-H2AX assay) and expression profiles of DNA repair genes were determined in ex vivo irradiated lymphocytes. Results: Examination of clinical data indicated none of the considered clinical parameters to be correlated with the susceptibility of patients to develop late radiation toxicity. Although frequencies of γ-H2AX foci induced immediately after irradiation were similar (P=.32), significantly higher numbers of γ-H2AX foci were found 24 hours after irradiation in OR compared with NR patients (P=.03). Patient-specific γ-H2AX foci decay ratios were significantly higher in NR patients than in OR patients (P<.0001). Consequently, NR patients seem to repair DNA double-strand breaks (DSBs) more efficiently than OR patients. Moreover, gene expression analysis indicated several genes of the homologous recombination pathway to be stronger induced in NR compared with OR patients (P<.05). A similar trend was observed in genes of the nonhomologous end-joining repair pathway (P=.09). This is congruent with more proficient repair of DNA DSBs in patients without late radiation toxicity. Conclusions: Both gene expression profiling and DNA DSB repair kinetics data imply that less-efficient repair of radiation-induced DSBs may contribute to the development of late normal tissue damage. Induction levels of DSB repair genes (eg, RAD51) may potentially be used to assess the risk for late radiation toxicity.

  11. Quantitative Ultrasonic Evaluation of Radiation-Induced Late Tissue Toxicity: Pilot Study of Breast Cancer Radiotherapy

    SciTech Connect

    Liu Tian; Zhou Jun; Yoshida, Emi J.; Woodhouse, Shermian A.; Schiff, Peter B.; Wang, Tony J.C.; Lu Zhengfeng; Pile-Spellman, Eliza; Zhang Pengpeng; Kutcher, Gerald J.

    2010-11-01

    Purpose: To investigate the use of advanced ultrasonic imaging to quantitatively evaluate normal-tissue toxicity in breast-cancer radiation treatment. Methods and Materials: Eighteen breast cancer patients who received radiation treatment were enrolled in an institutional review board-approved clinical study. Radiotherapy involved a radiation dose of 50.0 to 50.4 Gy delivered to the entire breast, followed by an electron boost of 10.0 to 16.0 Gy delivered to the tumor bed. Patients underwent scanning with ultrasound during follow-up, which ranged from 6 to 94 months (median, 22 months) postradiotherapy. Conventional ultrasound images and radio-frequency (RF) echo signals were acquired from treated and untreated breasts. Three ultrasound parameters, namely, skin thickness, Pearson coefficient, and spectral midband fit, were computed from RF signals to measure radiation-induced changes in dermis, hypodermis, and subcutaneous tissue, respectively. Ultrasound parameter values of the treated breast were compared with those of the untreated breast. Ultrasound findings were compared with clinical assessment using Radiation Therapy Oncology Group (RTOG) late-toxicity scores. Results: Significant changes were observed in ultrasonic parameter values of the treated vs. untreated breasts. Average skin thickness increased by 27.3%, from 2.05 {+-} 0.22mm to 2.61 {+-} 0.52mm; Pearson coefficient decreased by 31.7%, from 0.41 {+-} 0.07 to 0.28 {+-} 0.05; and midband fit increased by 94.6%, from -0.92 {+-} 7.35 dB to 0.87 {+-} 6.70 dB. Ultrasound evaluations were consistent with RTOG scores. Conclusions: Quantitative ultrasound provides a noninvasive, objective means of assessing radiation-induced changes to the skin and subcutaneous tissue. This imaging tool will become increasingly valuable as we continue to improve radiation therapy technique.

  12. Exposure to ultraviolet radiation late in development increases the toxicity of oil to mahi-mahi (Coryphaena hippurus) embryos.

    PubMed

    Sweet, Lauren E; Magnuson, Jason; Garner, T Ross; Alloy, Matthew M; Stieglitz, John D; Benetti, Daniel; Grosell, Martin; Roberts, Aaron P

    2017-06-01

    The Deepwater Horizon oil spill in 2010 overlapped with the spawning of many pelagic fish species in the Gulf of Mexico, including mahi-mahi (Coryphaena hippurus). Polycyclic aromatic hydrocarbons (PAHs) released during the spill have been shown to cause photo-induced toxicity under ultraviolet (UV) radiation. In the present study, mahi-mahi embryos were exposed to high-energy water accommodated fractions of source and naturally weathered oils for up to 48 h. The timing of co-exposure with UV radiation varied between an early development exposure for 8 h or a late development exposure for 8 h. The UV co-exposure had a photo-induced toxic effect on hatching success for all oil types and exposure scenarios. A more sensitive developmental window to photo-induced toxicity was observed when UV exposure occurred late in development. Source Oil B was over 6-fold more toxic, and Massachusetts source oil was 1.6-fold more toxic when the embryos were co-exposed to UV light late in development. Furthermore, weathered oil from the surface co-exposure with UV late in development resulted in bradycardia in the mahi-mahi. The present study provides evidence that the developmental window when UV co-exposure occurs has a significant effect on the degree of photo-induced toxicity of oil and that UV co-exposure may exacerbate long-term cardiac effects in developing fish. Environ Toxicol Chem 2017;36:1592-1598. © 2016 SETAC. © 2016 SETAC.

  13. Hyperfractionated Accelerated Radiotherapy for Rectal Cancer in Patients With Prior Pelvic Irradiation

    SciTech Connect

    Das, Prajnan; Delclos, Marc E.; Skibber, John M.; Rodriguez-Bigas, Miguel A.; Feig, Barry W.; Chang, George J.; Eng, Cathy; Bedi, Manpreet; Krishnan, Sunil; Crane, Christopher H.

    2010-05-01

    Purpose: To retrospectively determine rates of toxicity, freedom from local progression, and survival in rectal cancer patients treated with reirradiation. Methods and Materials: Between February 2001 and February 2005, 50 patients with a history of pelvic radiotherapy were treated with hyperfractionated accelerated radiotherapy for primary (n = 2 patients) or recurrent (n = 48 patients) rectal adenocarcinoma. Patients were treated with 150-cGy fractions twice daily, with a total dose of 39 Gy (n = 47 patients) if the retreatment interval was >=1 year or 30 Gy (n = 3) if the retreatment interval was <1 year. Concurrent chemotherapy was administered to 48 (96%) patients. Eighteen (36%) patients underwent surgical resection following radiotherapy. Results: Two patients had grade 3 acute toxicity and 13 patients had grade 3 to 4 late toxicity. The 3-year rate of grade 3 to 4 late toxicity was 35%. The 3-year rate of freedom from local progression was 33%. The 3-year freedom from local progression rate was 47% in patients undergoing surgery and 21% in those not undergoing surgery (p = 0.057). The 3-year overall survival rate was 39%. The 3-year overall survival rate was 66% in patients undergoing surgery and 27% in those not undergoing surgery (p = 0.003). The 3-year overall survival rate was 53% in patients with a retreatment interval of >2 years and 21% in those with a retreatment interval of <=2 years (p = 0.001). Conclusions: Hyperfractionated, accelerated reirradiation was well tolerated, with low rates of acute toxicity and moderate rates of late toxicity. Reirradiation may help improve pelvic control in rectal cancer patients with a history of pelvic radiotherapy.

  14. Acute encephalopathy with biphasic seizures and late reduced diffusion associated with staphylococcal toxic shock syndrome caused by burns.

    PubMed

    Yokochi, Takaoki; Sakanishi, Shinpei; Ishidou, Yuuki; Kawano, Go; Matsuishi, Toyojiro; Akita, Yukihiro; Obu, Keizo

    2016-10-01

    We report a case of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) associated with toxic shock syndrome caused by burns. A one-year-old girl was admitted to our hospital for treatment of severe burns. On day 3, she exhibited a fever, generalized rash and multiple organ failure. She was diagnosed with toxic shock syndrome after burns. She had seizures with fever twice on the same day, followed by secondary seizures on day 8 and transient deterioration of the gross motor functions involved in sitting alone and rolling over. On day 9, MRI diffusion-weighted images showed bright tree appearance (BTA). We conclude that she developed AESD.

  15. Modelling the Impact of Fractionation on Late Urinary Toxicity After Postprostatectomy Radiation Therapy

    SciTech Connect

    Fiorino, Claudio; Cozzarini, Cesare; Rancati, Tiziana; Briganti, Alberto; Cattaneo, Giovanni Mauro; Mangili, Paola; Di Muzio, Nadia Gisella; Calandrino, Riccardo

    2014-12-01

    Purpose: To fit urinary toxicity data of patients treated with postprostatectomy radiation therapy with the linear quadratic (LQ) model with/without introducing a time factor. Methods and Materials: Between 1993 and 2010, 1176 patients were treated with conventional fractionation (1.8 Gy per fraction, median 70.2 Gy, n=929) or hypofractionation (2.35-2.90 Gy per fraction, n=247). Data referred to 2004-2010 (when all schemes were in use, n=563; conventional fractionation: 316; hypofractionation: 247) were fitted as a logit function of biological equivalent dose (BED), according to the LQ model with/without including a time factor γ (fixing α/β = 5 Gy). The 3-year risks of severe urethral stenosis, incontinence, and hematuria were considered as endpoints. Best-fit parameters were derived, and the resulting BEDs were taken in multivariable backward logistic models, including relevant clinical variables, considering the whole population. Results: The 3-year incidences of severe stenosis, incontinence, and hematuria were, respectively, 6.6%, 4.8%, and 3.3% in the group treated in 2004-2010. The best-fitted α/β values were 0.81 Gy and 0.74 Gy for incontinence and hematuria, respectively, with the classic LQ formula. When fixing α/β = 5 Gy, best-fit values for γ were, respectively, 0.66 Gy/d and 0.85 Gy/d. Sensitivity analyses showed reasonable values for γ (0.6-1.0 Gy/d), with comparable goodness of fit for α/β values between 3.5 and 6.5 Gy. Likelihood ratio tests showed that the fits with/without including γ were equivalent. The resulting multivariable backward logistic models in the whole population included BED, pT4, and use of antihypertensives (area under the curve [AUC] = 0.72) for incontinence and BED, pT4, and year of surgery (AUC = 0.80) for hematuria. Stenosis data could not be fitted: a 4-variable model including only clinical factors (acute urinary toxicity, pT4, year of surgery, and use of antihypertensives) was suggested (AUC

  16. Increased rectal wall stiffness after prostate radiotherapy: relation with fecal urgency.

    PubMed

    Krol, R; Hopman, W P M; Smeenk, R J; Van Lin, E N J T

    2012-04-01

    Late anorectal toxicity is a frequent adverse event of external beam radiotherapy (EBRT) for prostate cancer. The pathophysiology of anorectal toxicity remains unknown, but we speculate that rectal distensibility is impaired due to fibrosis. Our goal was to determine whether EBRT induces changes of rectal distensibility as measured by an electronic barostat and to explore whether anorectal complaints are related to specific changes of anorectal function.   Thirty-two men, irradiated for localized prostate carcinoma, underwent barostat measurements, anorectal manometry, and completed a questionnaire prior to and 1 year after radiotherapy. The primary outcome measure was rectal distensibility in response to stepwise isobaric distensions. In addition, we assessed sensory thresholds, anal pressures, and anorectal complaints.   External beam radiotherapy reduced maximal rectal capacity (227 ± 14 mL vs 277 ± 15 mL; P < 0.001), area under the pressure-volume curve (3212 ± 352 mL mmHg vs 3969 ± 413 mL mmHg; P < 0.005), and rectal compliance (15.7 ± 1.2 mL mmHg(-1) vs 17.6 ± 0.9 mL mmHg(-1) ; P = 0.12). Sensory pressure thresholds did not significantly change. Sixteen of the 32 patients (50%) had one or more anorectal complaints. Patients with urgency (n = 10) had a more reduced anal squeeze and maximum pressure (decrease 29 ± 11 mmHg vs 1 ± 7 mmHg; P < 0.05 and 31 ± 12 mmHg vs 2 ± 8 mmHg; P < 0.05 respectively) compared with patients without complaints, indicating a deteriorated external anal sphincter function.   Irradiation for prostate cancer leads to reduced rectal distensibility. In patients with urgency symptoms, anal sphincter function was also impaired. © 2012 Blackwell Publishing Ltd.

  17. Spectrophotometer and ultrasound evaluation of late toxicity following breast-cancer radiotherapy.

    PubMed

    Yoshida, E J; Chen, H; Torres, M A; Curran, W J; Liu, T

    2011-10-01

    Radiation-induced normal-tissue toxicities are common, complex, and distressing side effects that affect 90% of patients receiving breast-cancer radiotherapy and 40% of patients post radiotherapy. In this study, the authors investigated the use of spectrophotometry and ultrasound to quantitatively measure radiation-induced skin discoloration and subcutaneous-tissue fibrosis. The study's purpose is to determine whether skin discoloration correlates with the development of fibrosis in breast-cancer radiotherapy. Eighteen breast-cancer patients were enrolled in our initial study. All patients were previously treated with a standard course of radiation, and the median follow-up time was 22 months. The treated and untreated breasts were scanned with a spectrophotometer and an ultrasound. Two spectrophotometer parameters-melanin and erythema indices-were used to quantitatively assess skin discoloration. Two ultrasound parameters-skin thickness and Pearson coefficient of the hypodermis-were used to quantitatively assess severity of fibrosis. These measurements were correlated with clinical assessments (RTOG late morbidity scores). Significant measurement differences between the treated and contralateral breasts were observed among all patients: 27.3% mean increase in skin thickness (p < 0.001), 34.1% mean decrease in Pearson coefficient (p < 0.001), 27.3% mean increase in melanin (p < 0.001), and 22.6% mean increase in erythema (p < 0.001). All parameters except skin thickness correlated with RTOG scores. A moderate correlation exists between melanin and erythema; however, spectrophotometer parameters do not correlate with ultrasound parameters. Spectrophotometry and quantitative ultrasound are objective tools that assess radiation-induced tissue injury. Spectrophotometer parameters did not correlate with those of quantitative ultrasound suggesting that skin discoloration cannot be used as a marker for subcutaneous fibrosis. These tools may prove useful

  18. Spectrophotometer and ultrasound evaluation of late toxicity following breast-cancer radiotherapy

    PubMed Central

    Yoshida, E. J.; Chen, H.; Torres, M. A.; Curran, W. J.; Liu, T.

    2011-01-01

    Purpose: Radiation-induced normal-tissue toxicities are common, complex, and distressing side effects that affect 90% of patients receiving breast-cancer radiotherapy and 40% of patients post radiotherapy. In this study, the authors investigated the use of spectrophotometry and ultrasound to quantitatively measure radiation-induced skin discoloration and subcutaneous-tissue fibrosis. The study’s purpose is to determine whether skin discoloration correlates with the development of fibrosis in breast-cancer radiotherapy.Methods : Eighteen breast-cancer patients were enrolled in our initial study. All patients were previously treated with a standard course of radiation, and the median follow-up time was 22 months. The treated and untreated breasts were scanned with a spectrophotometer and an ultrasound. Two spectrophotometer parameters—melanin and erythema indices—were used to quantitatively assess skin discoloration. Two ultrasound parameters—skin thickness and Pearson coefficient of the hypodermis—were used to quantitatively assess severity of fibrosis. These measurements were correlated with clinical assessments (RTOG late morbidity scores).Results: Significant measurement differences between the treated and contralateral breasts were observed among all patients: 27.3% mean increase in skin thickness (p < 0.001), 34.1% mean decrease in Pearson coefficient (p < 0.001), 27.3% mean increase in melanin (p < 0.001), and 22.6% mean increase in erythema (p < 0.001). All parameters except skin thickness correlated with RTOG scores. A moderate correlation exists between melanin and erythema; however, spectrophotometer parameters do not correlate with ultrasound parameters.Conclusions: Spectrophotometry and quantitative ultrasound are objective tools that assess radiation-induced tissue injury. Spectrophotometer parameters did not correlate with those of quantitative ultrasound suggesting that skin discoloration cannot be used as a marker for

  19. Locally advanced rectal cancer: The importance of a multidisciplinary approach

    PubMed Central

    Berardi, Rossana; Maccaroni, Elena; Onofri, Azzurra; Morgese, Francesca; Torniai, Mariangela; Tiberi, Michela; Ferrini, Consuelo; Cascinu, Stefano

    2014-01-01

    Rectal cancer accounts for a relevant part of colorectal cancer cases, with a mortality of 4-10/100000 per year. The development of locoregional recurrences and the occurrence of distant metastases both influences the prognosis of these patients. In the last two decades, new multimodality strategies have improved the prognosis of locally advanced rectal cancer with a significant reduction of local relapse and an increase in terms of overall survival. Radical surgery still remains the principal curative treatment and the introduction of total mesorectal excision has significantly achieved a reduction in terms of local recurrence rates. The employment of neoadjuvant treatment, delivered before surgery, also achieved an improved local control and an increased sphincter preservation rate in low-lying tumors, with an acceptable acute and late toxicity. This review describes the multidisciplinary management of rectal cancer, focusing on the effectiveness of neoadjuvant chemoradiotherapy and of post-operative adjuvant chemotherapy both in the standard combined modality treatment programs and in the ongoing research to improve these regimens. PMID:25516638

  20. Locally advanced rectal cancer: the importance of a multidisciplinary approach.

    PubMed

    Berardi, Rossana; Maccaroni, Elena; Onofri, Azzurra; Morgese, Francesca; Torniai, Mariangela; Tiberi, Michela; Ferrini, Consuelo; Cascinu, Stefano

    2014-12-14

    Rectal cancer accounts for a relevant part of colorectal cancer cases, with a mortality of 4-10/100000 per year. The development of locoregional recurrences and the occurrence of distant metastases both influences the prognosis of these patients. In the last two decades, new multimodality strategies have improved the prognosis of locally advanced rectal cancer with a significant reduction of local relapse and an increase in terms of overall survival. Radical surgery still remains the principal curative treatment and the introduction of total mesorectal excision has significantly achieved a reduction in terms of local recurrence rates. The employment of neoadjuvant treatment, delivered before surgery, also achieved an improved local control and an increased sphincter preservation rate in low-lying tumors, with an acceptable acute and late toxicity. This review describes the multidisciplinary management of rectal cancer, focusing on the effectiveness of neoadjuvant chemoradiotherapy and of post-operative adjuvant chemotherapy both in the standard combined modality treatment programs and in the ongoing research to improve these regimens.

  1. Esophageal Dose Tolerance to Hypofractionated Stereotactic Body Radiation Therapy: Risk Factors for Late Toxicity

    SciTech Connect

    Stephans, Kevin L.; Djemil, Toufik; Diaconu, Claudiu; Reddy, Chandana A.; Xia, Ping; Woody, Neil M.; Greskovich, John; Makkar, Vinit; Videtic, Gregory M.M.

    2014-09-01

    Purpose: To identify factors associated with grade ≥3 treatment related late esophageal toxicity after lung or liver stereotactic body radiation therapy (SBRT). Methods and Materials: This was a retrospective review of 52 patients with a planning target volume within 2 cm of the esophagus from a prospective registry of 607 lung and liver SBRT patients treated between 2005 and 2011. Patients were treated using a risk-adapted dose regimen to a median dose of 50 Gy in 5 fractions (range, 37.5-60 Gy in 3-10 fractions). Normal structures were contoured using Radiation Therapy Oncology Group (RTOG) defined criteria. Results: The median esophageal point dose and 1-cc dose were 32.3 Gy (range, 8.9-55.4 Gy) and 24.0 Gy (range, 7.8-50.9 Gy), respectively. Two patients had an esophageal fistula at a median of 8.4 months after SBRT, with maximum esophageal point doses of 51.5 and 52 Gy, and 1-cc doses of 48.1 and 50 Gy, respectively. These point and 1-cc doses were exceeded by 9 and 2 patients, respectively, without a fistula. The risk of a fistula for point doses exceeding 40, 45, and 50 Gy was 9.5% (n=2/21), 10.5% (n=2/19), and 12.5% (n=2/16), respectively. The risk of fistula for 1-cc doses exceeding 40, 45, and 50 Gy was 25% (n=2/9), 50% (n=2/4), and 50% (n=2/4), respectively. Eighteen patients received systemic therapy after SBRT (11 systemic chemotherapy, and 6 biologic agents, and 1 both). Both patients with fistulas had received adjuvant anti-angiogenic (vascular endothelial growth factor) agents within 2 months of completing SBRT. No patient had a fistula in the absence of adjuvant VEGF-modulating agents. Conclusions: Esophageal fistula is a rare complication of SBRT. In this series, fistula was seen with esophageal point doses exceeding 51 Gy and 1-cc doses greater than 48 Gy. Notably, however, fistula was seen only in those patients who also received adjuvant VEGF-modulating agents after SBRT. The potential interaction of dose and adjuvant therapy

  2. Intrarectal application of amifostine for the prevention of radiation-induced rectal injury.

    PubMed

    Ben-Josef, Edgar; Han, Sue; Tobi, Martin; Vargas, Barbara J; Stamos, Beth; Kelly, Laura; Biggar, Sandra; Kaplan, Irving

    2002-01-01

    Clinically symptomatic late injury to the rectal wall occurs in about one third of patients with prostate cancer treated with external beam irradiation. Reducing the physical dose to the anterior rectal wall without a similar reduction in the posterior peripheral zone is difficult because of the proximity of these structures. Based on our previous observations that intrarectal application of amifostine resulted in very high concentrations of amifostine and its active metabolite WR-1065 in the rectal wall of Copenhagen rats, the authors initiated a phase I clinical trial in 1998. Twenty-nine patients with localized prostate cancer were accrued. Eligibility criteria included histologically confirmed adenocarcinoma, a Karnofsky performance status of > or =70, and no pelvic lymphadenopathy or distant metastases. The total dose to the prostate was 70.2 Gy (20 patients) and 73.8 Gy (9 patients). Therapy was delivered using a 4-field axial technique and 3-dimensional conformal planning. Amifostine was administered intrarectally as an aqueous solution 30 minutes before irradiation on the first 15 days of therapy. Amifostine dose was escalated, in cohorts, from 500 mg to 2,500 mg. Toxicity was evaluated using the Radiation Therapy Oncology Group late morbidity scale. All patients completed therapy with no amifostine-related toxicity at any dose level. The application was feasible and well tolerated. With a median follow-up time of 21 months, 9 patients (33%) had rectal bleeding (8 grade 1, 1 grade 2). Four patients (14%) had symptoms suggestive of radiation injury, which proved to be secondary to nonrelated processes. These included preexisting nonspecific proctitis (1 patient), diverticular disease of the sigmoid colon, rectal polyp (1 patient), and ulcerative colitis (1 patient). Symptoms developed significantly more often in patients receiving 500 to 1,000 mg than in patients receiving 1,500 to 2,500 mg amifostine (7 of 14 [50%] versus 2 of 13 [15%]; P =.0325, 1-sided

  3. Apoptosis for prediction of radiotherapy late toxicity: lymphocyte subset sensitivity and potential effect of TP53 Arg72Pro polymorphism.

    PubMed

    Fuentes-Raspall, María J; Caragol, Isabel; Alonso, Carmen; Ramón y Cajal, Teresa; Fisas, David; Seoane, Alejandro; Carvajal, Nerea; Bonache, Sandra; Díez, Orland; Gutiérrez-Enríquez, Sara

    2015-03-01

    We tested apoptosis levels in in vitro irradiated T-lymphocytes from breast cancer (BC) patients with radiotherapy-induced late effects. Previous results reported in the literature were revised. We also examined the effect of TP53 Arg72Pro polymorphism on irradiation-induced apoptosis (IA). Twenty BC patients, ten with fibrosis and/or telangiectasias and ten matched controls with no late reactions, were selected from those receiving radiotherapy between 1993 and 2007. All patients were followed-up at least 6 years after radiotherapy. Using the combination of both CD3 and CD8 antibodies the in vitro IA was measured in CD3, CD8 and CD4 T-lymphocytes, and CD8 natural killer lymphocytes (CD8 NK) by flow cytometry. The TP53 Arg72Pro genotype was determined by sequencing. Patients with late radiotherapy toxicity showed less IA for all T-lymphocytes except for the CD8 NK. CD8 NK showed the highest spontaneous apoptosis and the lowest IA. IA in patients with toxicity appears to be lower than the control patients only in TP53 Arg/Arg patients (P = 0.077). This difference was not present in patients carrying at least one Pro allele (P = 0.8266). Our data indicate that late side effects induced by radiotherapy of BC are associated to low levels of IA. CD8 NK cells have a different response to in vitro irradiation compared to CD8 T-lymphocytes. It would be advisable to distinguish the CD8 NK lymphocytes from the pool of CD8+ lymphocytes in IA assays using CD8+ cells. Our data suggest that the 72Pro TP53 allele may influence the IA of patients with radiotherapy toxicity.

  4. Dosimetric and late radiation toxicity comparison between iodine-125 brachytherapy and stereotactic radiation therapy for juxtapapillary choroidal melanoma.

    PubMed

    Krema, Hatem; Heydarian, Mostafa; Beiki-Ardakani, Akbar; Weisbrod, Daniel; Xu, Wei; Laperriere, Normand J; Sahgal, Arjun

    2013-07-01

    To compare the dose distributions and late radiation toxicities for (125)I brachytherapy (IBT) and stereotactic radiation therapy (SRT) in the treatment of juxtapapillary choroidal melanoma. Ninety-four consecutive patients with juxtapapillary melanoma were reviewed: 30 have been treated with IBT and 64 with SRT. Iodine-125 brachytherapy cases were modeled with plaque simulator software for dosimetric analysis. The SRT dosimetric data were obtained from the Radionics XKnife RT3 software. Mean doses at predetermined intraocular points were calculated. Kaplan-Meier estimates determined the actuarial rates of late toxicities, and the log-rank test compared the estimates. The median follow-up was 46 months in both cohorts. The 2 cohorts were balanced with respect to pretreatment clinical and tumor characteristics. Comparisons of radiation toxicity rates between the IBT and SRT cohorts yielded actuarial rates at 50 months for cataracts of 62% and 75% (P=.1), for neovascular glaucoma 8% and 47% (P=.002), for radiation retinopathy 59% and 89% (P=.0001), and for radiation papillopathy 39% and 74% (P=.003), respectively. Dosimetric comparisons between the IBT and SRT cohorts yielded mean doses of 12.8 and 14.1 Gy (P=.56) for the lens center, 17.6 and 19.7 Gy (P=.44) for the lens posterior pole, 13.9 and 10.8 Gy (P=.30) for the ciliary body, 61.9 and 69.7 Gy (P=.03) for optic disc center, and 48.9 and 60.1 Gy (P<.0001) for retina at 5-mm distance from tumor margin, respectively. Late radiation-induced toxicities were greater with SRT, which is secondary to the high-dose exposure inherent to the technique as compared with IBT. When technically feasible, IBT is preferred to treat juxtapapillary choroidal melanoma. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Dosimetric and Late Radiation Toxicity Comparison Between Iodine-125 Brachytherapy and Stereotactic Radiation Therapy for Juxtapapillary Choroidal Melanoma

    SciTech Connect

    Krema, Hatem

    2013-07-01

    Purpose: To compare the dose distributions and late radiation toxicities for {sup 125}I brachytherapy (IBT) and stereotactic radiation therapy (SRT) in the treatment of juxtapapillary choroidal melanoma. Methods: Ninety-four consecutive patients with juxtapapillary melanoma were reviewed: 30 have been treated with IBT and 64 with SRT. Iodine-125 brachytherapy cases were modeled with plaque simulator software for dosimetric analysis. The SRT dosimetric data were obtained from the Radionics XKnife RT3 software. Mean doses at predetermined intraocular points were calculated. Kaplan-Meier estimates determined the actuarial rates of late toxicities, and the log–rank test compared the estimates. Results: The median follow-up was 46 months in both cohorts. The 2 cohorts were balanced with respect to pretreatment clinical and tumor characteristics. Comparisons of radiation toxicity rates between the IBT and SRT cohorts yielded actuarial rates at 50 months for cataracts of 62% and 75% (P=.1), for neovascular glaucoma 8% and 47% (P=.002), for radiation retinopathy 59% and 89% (P=.0001), and for radiation papillopathy 39% and 74% (P=.003), respectively. Dosimetric comparisons between the IBT and SRT cohorts yielded mean doses of 12.8 and 14.1 Gy (P=.56) for the lens center, 17.6 and 19.7 Gy (P=.44) for the lens posterior pole, 13.9 and 10.8 Gy (P=.30) for the ciliary body, 61.9 and 69.7 Gy (P=.03) for optic disc center, and 48.9 and 60.1 Gy (P<.0001) for retina at 5-mm distance from tumor margin, respectively. Conclusions: Late radiation-induced toxicities were greater with SRT, which is secondary to the high-dose exposure inherent to the technique as compared with IBT. When technically feasible, IBT is preferred to treat juxtapapillary choroidal melanoma.

  6. Prospective Study of Local Control and Late Radiation Toxicity After Intraoperative Radiation Therapy Boost for Early Breast Cancer

    SciTech Connect

    Chang, David W.; Marvelde, Luc te; Chua, Boon H.

    2014-01-01

    Purpose: To report the local recurrence rate and late toxicity of intraoperative radiation therapy (IORT) boost to the tumor bed using the Intrabeam System followed by external-beam whole-breast irradiation (WBI) in women with early-stage breast cancer in a prospective single-institution study. Methods and Materials: Women with breast cancer ≤3 cm were recruited between February 2003 and May 2005. After breast-conserving surgery, a single dose of 5 Gy IORT boost was delivered using 50-kV x-rays to a depth of 10 mm from the applicator surface. This was followed by WBI to a total dose of 50 Gy in 25 fractions. Patients were reviewed at regular, predefined intervals. Late toxicities were recorded using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring systems. Results: Fifty-five patients completed both IORT boost and external-beam WBI. Median follow-up was 3.3 years (range, 1.4-4.1 years). There was no reported locoregional recurrence or death. One patient developed distant metastases. Grade 2 and 3 subcutaneous fibrosis was detected in 29 (53%) and 8 patients (15%), respectively. Conclusions: The use of IORT as a tumor bed boost using kV x-rays in breast-conserving therapy was associated with good local control but a clinically significant rate of grade 2 and 3 subcutaneous fibrosis.

  7. 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

  8. Radiation Dose-Volume Effects in Radiation-Induced Rectal Injury

    SciTech Connect

    Michalski, Jeff M.; Gay, Hiram; Jackson, Andrew; Tucker, Susan L.; Deasy, Joseph O.

    2010-03-01

    The available dose/volume/outcome data for rectal injury were reviewed. The volume of rectum receiving >=60Gy is consistently associated with the risk of Grade >=2 rectal toxicity or rectal bleeding. Parameters for the Lyman-Kutcher-Burman normal tissue complication probability model from four clinical series are remarkably consistent, suggesting that high doses are predominant in determining the risk of toxicity. The best overall estimates (95% confidence interval) of the Lyman-Kutcher-Burman model parameters are n = 0.09 (0.04-0.14); m = 0.13 (0.10-0.17); and TD{sub 50} = 76.9 (73.7-80.1) Gy. Most of the models of late radiation toxicity come from three-dimensional conformal radiotherapy dose-escalation studies of early-stage prostate cancer. It is possible that intensity-modulated radiotherapy or proton beam dose distributions require modification of these models because of the inherent differences in low and intermediate dose distributions.

  9. Digital rectal exam

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/007069.htm Digital rectal exam To use the sharing features on this page, please enable JavaScript. A digital rectal exam is an examination of the lower ...

  10. Light-dependent toxicity of α-terthienyl and anthracene toward late embryonic stages ofRana pipiens.

    PubMed

    Kagan, J; Kagan, P A; Buhse, H E

    1984-07-01

    Alpha-terthienyl is toxic to late embryonic stages ofRana pipiens in the presence of sunlight. Neither α-terthienyl alone in the dark nor a previously photolyzed solution of α-terthienyl has comparable activity. The LC50 was 0.11 ppm with 30 min of exposure and 0.018 ppm with 2 hr of exposure to sunlight. Anthracene, a representative example of polycyclic aromatic hydrocarbons widely distributed in the environment, also showed similar phototoxicity, with an LC50 of 0.065 ppm after 30 min of exposure and 0.025 ppm after 5 hr.

  11. Additional rectal and sigmoid mucosal points and doses in high dose rate intracavitary brachytherapy for carcinoma cervix: a dosimetric study.

    PubMed

    Mahantshetty, Umesh; Tiwana, Manpreet Singh; Jamema, Swamidas; Mishra, Sanjib; Engineer, Reena; Deshpande, Deepak; Shrivastava, Shyamkishore

    2011-01-01

    Late rectal and sigmoid toxicities seen in cervical cancer patients are attributed to brachytherapy despite rectal doses within tolerance limits. The purpose of this study was to identify additional dosimetric points which may better forecast rectal complications. Fifteen high dose rate intracavitary brachytherapy (ICA-HDR) applications with conventional X-ray and computed tomography (CT) based planning were studied. In addition to International Commission on Radiation Units and Measurement (ICRU) rectal and bladder points, proximal and distal rectal and sigmoid points were digitized on CT scans and dose volume histograms' (DVHs') parameters were computed and correlated. The mean ICRU, additional distal, proximal and sigmoid point doses were 486 ± 152 cGy, 527 ± 156 cGy, 401 ± 149 cGy and 838 ± 254 cGy, respectively, for a prescription of 700 cGy to point A. The mean sigmoid point dose was significantly higher than the ICRU rectal point doses (P=0.001). The high-dose sigmoid points were situated at a mean -8 mm (range -22.95 to 10.43 mm) lateral, 10 mm posterior (range -15.87 to 27.82 mm) and 31 mm (range 8.08-62.91 mm) cranial to the intracavitary applicator flange of central tandem. Our dosimetric study suggests that sigmoid points and 0.1 cm 3 receive significantly higher doses than rectal points during ICA-HDR in carcinoma of the uterine cervix. No definite conclusion on reproducible spatial distribution on orthogonal X-rays could be achieved. To document and reduce sigmoid doses, some form of 3D image-based planning is necessary.

  12. 76 FR 72952 - Guidance for Industry on Nonclinical Evaluation of Late Radiation Toxicity of Therapeutic...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-28

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry on Nonclinical Evaluation of Late... commonly associated with XRT (e.g., brain necrosis, paralysis, pulmonary fibrosis, liver or kidney failure... tolerance doses of most human organs for conventional fractionated XRT are known, and are routinely used...

  13. THE CYANOBACTERIAL TOXIN, CYLINDROSPERMOPSIN, INDUCES FETAL TOXICITY IN THE MOUSE AFTER EXPOSURE LATE IN GESTATION

    EPA Science Inventory

    Cylindrospermopsin (cyn) is a cyanobacterial toxin implicated in human and wildlife poisonings. We have completed studies investigating the potential of purified cyn to induce developmental toxicity in mammals. The teratology study involved intraperitoneal injections (8.0¿128ug/k...

  14. THE CYANOBACTERIAL TOXIN, CYLINDROSPERMOPSIN, INDUCES FETAL TOXICITY IN THE MOUSE AFTER EXPOSURE LATE IN GESTATION

    EPA Science Inventory

    Cylindrospermopsin (cyn) is a cyanobacterial toxin implicated in human and wildlife poisonings. We have completed studies investigating the potential of purified cyn to induce developmental toxicity in mammals. The teratology study involved intraperitoneal injections (8.0¿128ug/k...

  15. Toxic Shock Syndrome Toxin-1-Mediated Toxicity Inhibited by Neutralizing Antibodies Late in the Course of Continual in Vivo and in Vitro Exposure

    PubMed Central

    Stich, Norbert; Model, Nina; Samstag, Aysen; Gruener, Corina S.; Wolf, Hermann M.; Eibl, Martha M.

    2014-01-01

    Toxic shock syndrome (TSS) results from the host’s overwhelming inflammatory response and cytokine storm mainly due to superantigens (SAgs). There is no effective specific therapy. Application of immunoglobulins has been shown to improve the outcome of the disease and to neutralize SAgs both in vivo and in vitro. However, in most experiments that have been performed, antiserum was either pre-incubated with SAg, or both were applied simultaneously. To mirror more closely the clinical situation, we applied a multiple dose (over five days) lethal challenge in a rabbit model. Treatment with toxic shock syndrome toxin 1 (TSST-1) neutralizing antibody was fully protective, even when administered late in the course of the challenge. Kinetic studies on the effect of superantigen toxins are scarce. We performed in vitro kinetic studies by neutralizing the toxin with antibodies at well-defined time points. T-cell activation was determined by assessing T-cell proliferation (3H-thymidine incorporation), determination of IL-2 release in the cell supernatant (ELISA), and IL-2 gene activation (real-time PCR (RT-PCR)). Here we show that T-cell activation occurs continuously. The application of TSST-1 neutralizing antiserum reduced IL-2 and TNFα release into the cell supernatant, even if added at later time points. Interference with the prolonged stimulation of proinflammatory cytokines is likely to be in vivo relevant, as postexposure treatment protected rabbits against the multiple dose lethal SAg challenge. Our results shed new light on the treatment of TSS by specific antibodies even at late stages of exposure. PMID:24887085

  16. Toxic shock syndrome toxin-1-mediated toxicity inhibited by neutralizing antibodies late in the course of continual in vivo and in vitro exposure.

    PubMed

    Stich, Norbert; Model, Nina; Samstag, Aysen; Gruener, Corina S; Wolf, Hermann M; Eibl, Martha M

    2014-05-30

    Toxic shock syndrome (TSS) results from the host's overwhelming inflammatory response and cytokine storm mainly due to superantigens (SAgs). There is no effective specific therapy. Application of immunoglobulins has been shown to improve the outcome of the disease and to neutralize SAgs both in vivo and in vitro. However, in most experiments that have been performed, antiserum was either pre-incubated with SAg, or both were applied simultaneously. To mirror more closely the clinical situation, we applied a multiple dose (over five days) lethal challenge in a rabbit model. Treatment with toxic shock syndrome toxin 1 (TSST-1) neutralizing antibody was fully protective, even when administered late in the course of the challenge. Kinetic studies on the effect of superantigen toxins are scarce. We performed in vitro kinetic studies by neutralizing the toxin with antibodies at well-defined time points. T-cell activation was determined by assessing T-cell proliferation (3H-thymidine incorporation), determination of IL-2 release in the cell supernatant (ELISA), and IL-2 gene activation (real-time PCR (RT-PCR)). Here we show that T-cell activation occurs continuously. The application of TSST-1 neutralizing antiserum reduced IL-2 and TNFα release into the cell supernatant, even if added at later time points. Interference with the prolonged stimulation of proinflammatory cytokines is likely to be in vivo relevant, as postexposure treatment protected rabbits against the multiple dose lethal SAg challenge. Our results shed new light on the treatment of TSS by specific antibodies even at late stages of exposure.

  17. Current concepts in rectal cancer.

    PubMed

    Fleshman, James W; Smallwood, Nathan

    2015-03-01

    The history of rectal cancer management informs current therapy and points us in the direction of future improvements. Multidisciplinary team management of rectal cancer will move us to personalized treatment for individuals with rectal cancer in all stages.

  18. A Preliminary Study on Racial Differences in HMOX1, NFE2L2 and TGFβ1 Gene Polymorphisms and Radiation Induced Late Normal Tissue Toxicity

    PubMed Central

    Alam, Asim; Mukhopadhyay, Nitai D.; Ning, Yi; Reshko, Leonid B.; Cardnell, Robert J.G.; Alam, Omair; Rabender, Christopher S.; Yakovlev, Vasily A.; Walker, Linda; Anscher, Mitchell S.; Mikkelsen, Ross B.

    2015-01-01

    Purpose This study tests whether racial differences in genetic polymorphisms of four genes involved in wound repair and response to radiation can be used to predict the occurrence of normal tissue late effects of radiotherapy and indicate potential therapeutic targets. Methods and Materials This prospective study examines genetic polymorphisms that modulate the expression of four genes involved in inflammation and fibrosis and response to radiation (HMOX1, NFE2L2, NOS3 and TGFβ1). DNA from blood samples of 179 patients (~80% breast and head and neck) collected at the time of diagnosis by their radiation oncologist as exhibiting late normal tissue toxicity was used for the analysis. Patient demographics were: 56% Caucasian, 43% African-American, 1% other. Allelic frequencies of the different polymorphisms of the participants were compared to those of the general American population stratified by race. Twenty-six additional patients treated with radiation, but without toxicity at 3 months or later post-therapy, were also analyzed. Results Increased frequency of a long GT repeat in the HMOX1 promoter was associated with late effects in both African-American and Caucasian populations. The single nucleotide polymorphisms (SNP) rs1800469 in the TGFβ1 promoter and the rs6721961 SNP in the NFE2L2 promoter were also found to significantly associate with late effects in African-Americans but not Caucasians. A combined analysis of these polymorphisms revealed that >90% of African-American patients with late effects had at least one and 58% two or more of these minor alleles. No statistical significance was found relating the studied NOS3 polymorphisms and normal tissue toxicity. Conclusions These results support a strong association between wound repair and late toxicities of radiation. The presence of these genetic risk factors can vary significantly among different ethnic groups, as demonstrated for some of the SNPs. Future studies should account for the possibility of

  19. A Preliminary Study on Racial Differences in HMOX1, NFE2L2, and TGFβ1 Gene Polymorphisms and Radiation-Induced Late Normal Tissue Toxicity

    SciTech Connect

    Alam, Asim; Mukhopadhyay, Nitai D.; Ning, Yi; Reshko, Leonid B.; Cardnell, Robert J.G.; Alam, Omair; Rabender, Christopher S.; Yakovlev, Vasily A.; Walker, Linda; Anscher, Mitchell S.; Mikkelsen, Ross B.

    2015-10-01

    Purpose: This study tested whether racial differences in genetic polymorphisms of 4 genes involved in wound repair and response to radiation can be used to predict the occurrence of normal tissue late effects of radiation therapy and indicate potential therapeutic targets. Methods and Materials: This prospective study examined genetic polymorphisms that modulate the expression of 4 genes involved in inflammation and fibrosis and response to radiation (HMOX1, NFE2L2, NOS3, and TGFβ1). DNA from blood samples of 179 patients (∼80% breast and head and neck) collected at the time of diagnosis by their radiation oncologist as exhibiting late normal tissue toxicity was used for the analysis. Patient demographics were as follows: 56% white, 43% African American, 1% other. Allelic frequencies of the different polymorphisms of the participants were compared with those of the general American population stratified by race. Twenty-six additional patients treated with radiation, but without toxicity at 3 months or later after therapy, were also analyzed. Results: Increased frequency of a long GT repeat in the HMOX1 promoter was associated with late effects in both African American and white populations. The single nucleotide polymorphisms (SNP) rs1800469 in the TGFβ1 promoter and the rs6721961 SNP in the NFE2L2 promoter were also found to significantly associate with late effects in African Americans but not whites. A combined analysis of these polymorphisms revealed that >90% of African American patients with late effects had at least 1 of these minor alleles, and 58% had 2 or more. No statistical significance was found relating the studied NOS3 polymorphisms and normal tissue toxicity. Conclusions: These results support a strong association between wound repair and late toxicities of radiation. The presence of these genetic risk factors can vary significantly among different ethnic groups, as demonstrated for some of the SNPs. Future studies should account for the

  20. Neoadjuvant Treatment in Rectal Cancer: Actual Status

    PubMed Central

    Garajová, Ingrid; Di Girolamo, Stefania; de Rosa, Francesco; Corbelli, Jody; Agostini, Valentina; Biasco, Guido; Brandi, Giovanni

    2011-01-01

    Neoadjuvant (preoperative) concomitant chemoradiotherapy (CRT) has become a standard treatment of locally advanced rectal adenocarcinomas. The clinical stages II (cT3-4, N0, M0) and III (cT1-4, N+, M0) according to International Union Against Cancer (IUCC) are concerned. It can reduce tumor volume and subsequently lead to an increase in complete resections (R0 resections), shows less toxicity, and improves local control rate. The aim of this review is to summarize actual approaches, main problems, and discrepancies in the treatment of locally advanced rectal adenocarcinomas. PMID:22295206

  1. Chemoradiation of rectal cancer.

    PubMed

    Arrazubi, V; Suárez, J; Novas, P; Pérez-Hoyos, M T; Vera, R; Martínez Del Prado, P

    2013-02-01

    The treatment of locally advanced rectal cancer is a challenge. Surgery, chemotherapy and radiotherapy comprise the multimodal therapy that is administered in most cases. Therefore, a multidisciplinary approach is required. Because this cancer has a high rate of local recurrence, efforts have been made to improve clinical outcomes while minimizing toxicity and maintaining quality of life. Thus, total mesorectal excision technique was developed as the standard surgery, and chemotherapy and radiotherapy have been established as neoadjuvant treatment. Both approaches reduce locoregional relapse. Two neoadjuvant treatments have emerged as standards of care: short-course radiotherapy and long-course chemoradiotherapy with fluoropyrimidines; however, long-course chemoradiotherapy might be more appropriate for low-lying neoplasias, bulky tumours or tumours with near-circumferential margins. If neoadjuvant treatment is not administered and locally advanced stage is demonstrated in surgical specimens, adjuvant chemoradiotherapy is recommended. The addition of chemotherapy to the treatment regimen confers a significant benefit. Adjuvant chemotherapy is widely accepted despite scarce evidence of its benefit. The optimal time for surgery after neoadjuvant therapy, the treatment of low-risk T3N0 neoplasms, the convenience of avoiding radiotherapy in some cases and tailoring treatment to pathological response have been recurrent subjects of debate that warrant more extensive research. Adding new drugs, changing the treatment sequence and selecting the treatment based on prognostic or predictive factors other than stage remain experimental.

  2. Major Late Toxicities After Conformal Radiotherapy for Nasopharyngeal Carcinoma-Patient- and Treatment-Related Risk Factors

    SciTech Connect

    Lee, Anne W.M. Ng, W.T.; Hung, W.M.; Choi, C.W.; Tung, Raymond; Ling, Y.H.; Cheng, Peter T.C.; Yau, T.K.; Chang, Amy T.Y.; Leung, Samuel K.C.; Lee, Michael C.H.; Bentzen, Soren M.

    2009-03-15

    Purpose: To retrospectively analyze the factors affecting late toxicity for nasopharyngeal carcinoma. Methods and Materials: Between 1998 and 2003, 422 patients were treated with a conformal technique with 2-Gy daily fractions to a total dose of 70 Gy. Conventional fractionation (5 fractions weekly) was used in 232 patients and accelerated fractionation (6 fractions weekly) in 190 patients. One hundred seventy-one patients were treated with the basic radiotherapy course alone (Group 1), 55 patients had an additional boost of 5 Gy in 2 fractions (Group 2), and 196 patients underwent concurrent cisplatin-based chemotherapy (Group 3). Results: The 5-year overall toxicity rate was significantly greater in Group 3 than in Group 1 (37% vs. 27%, p = 0.009). Although the overall rate in Group 2 was not elevated (28% vs. 27%, p = 0.697), a significant increase in temporal lobe necrosis was observed (4.8% vs. 0%, p = 0.015). Multivariate analyses showed that age and concurrent chemotherapy were significant factors. The hazard ratio of overall toxicity attributed to chemotherapy was 1.99 (95% confidence interval, 1.32-2.99, p = 0.001). The mean radiation dose to the cochlea was another significant factor affecting deafness, with a hazard ratio of 1.03 (95% confidence interval, 1.01-1.05, p = 0.005) per 1-Gy increase. The cochlea that received >50 Gy had a significantly greater deaf rate (Group 1, 18% vs. 7%; and Group 3, 22% vs. 14%). Conclusion: The therapeutic margin for nasopharyngeal carcinoma is extremely narrow, and a significant increase in brain necrosis could result from dose escalation. The significant factors affecting the risk of deafness included age, concurrent chemoradiotherapy, and greater radiation dose to the cochlea.

  3. Predictors of late bowel toxicity using three different methods of contouring in patients undergoing post-operative radiation for cervical cancer.

    PubMed

    Chopra, Supriya; Krishnatry, Rahul; Dora, Tapas; Kannan, Sadhna; Thomas, Biji; Sonawone, Supriya; Engineer, Reena; Paul, Siji; Phurailatpam, Reena; Mahantshetty, Umesh; Shrivastava, Shyam

    2015-01-01

    This study investigates the correlation between dose-volume histogram derived from three bowel contouring methods and late toxicity in patients undergoing post-operative radiation therapy (PORT) for cervical cancer. From June 2010 to May 2013, 103 patients undergoing PORT were included. Three different contouring methods were used: (a) individual small bowel (SB) and large bowel (LB) loops, (b) total bowel (TB; including SB and LB) and (c) peritoneal cavity (PC). The volume of SB, LB, TB and PC receiving 15, 30 and 40 Gy was calculated. Acute and late bowel toxicities were scored using Common Terminology Criteria for Adverse events v. 3.0. Receiver operating characteristic curve identified thresholds predicting late toxicity with the highest specificity. All data were dichotomized across these thresholds. Univariate and multivariate analyses were performed using SPSS(®) v. 20 (IBM Corporation, Armonk, NY; formerly SPSS Inc., Chicago, IL). On univariate analysis, V30 PC ≥ 900 cm(3) (p = 0.01), V40 PC ≥ 750 cm(3) (p = 0.03) and V40 TB ≥ 280 cm(3) (p = 0.03) and use of concurrent chemotherapy (p = 0.03) predicted grade ≥II acute toxicity. On multivariate analysis, use of concurrent chemotherapy [odds ratio (OR) 3.5, 95% confidence interval (CI) 1.1-11.1, p = 0.03] and V30 PC ≥ 900 cm(3) (OR 2.3, 95% CI 1-5.5, p = 0.05) predicted acute grade ≥II toxicity. On univariate analysis for late toxicity, SB (V30 ≥ 190 cm(3), p = 0.009; V40 ≥ 150 cm(3), p = 0.03), LB (V15 ≥ 250 cm(3), p = 0.04), V40 PC (V40 ≥ 750 cm(3), p = 0.001) and presence of acute grade ≥III toxicity (p = 0.006), treatment technique (three-dimensional conformal radiation or intensity modulated radiotherapy, p = 0.02) predicted more than or equal to grade ll late bowel toxicity. On multivariate analysis, only body mass index ≥25 kg m(-2) (OR 7.3, 95% CI 1.6-31.6, p = 0.008) and

  4. Predictors of late bowel toxicity using three different methods of contouring in patients undergoing post-operative radiation for cervical cancer

    PubMed Central

    Krishnatry, Rahul; Dora, Tapas; Kannan, Sadhna; Thomas, Biji; Sonawone, Supriya; Engineer, Reena; Paul, Siji; Phurailatpam, Reena; Mahantshetty, Umesh; Shrivastava, Shyam

    2015-01-01

    Objective: This study investigates the correlation between dose–volume histogram derived from three bowel contouring methods and late toxicity in patients undergoing post-operative radiation therapy (PORT) for cervical cancer. Methods: From June 2010 to May 2013, 103 patients undergoing PORT were included. Three different contouring methods were used: (a) individual small bowel (SB) and large bowel (LB) loops, (b) total bowel (TB; including SB and LB) and (c) peritoneal cavity (PC). The volume of SB, LB, TB and PC receiving 15, 30 and 40 Gy was calculated. Acute and late bowel toxicities were scored using Common Terminology Criteria for Adverse events v. 3.0. Receiver operating characteristic curve identified thresholds predicting late toxicity with the highest specificity. All data were dichotomized across these thresholds. Univariate and multivariate analyses were performed using SPSS® v. 20 (IBM Corporation, Armonk, NY; formerly SPSS Inc., Chicago, IL). Results: On univariate analysis, V30 PC ≥ 900 cm3 (p = 0.01), V40 PC ≥ 750 cm3 (p = 0.03) and V40 TB ≥ 280 cm3 (p = 0.03) and use of concurrent chemotherapy (p = 0.03) predicted grade ≥II acute toxicity. On multivariate analysis, use of concurrent chemotherapy [odds ratio (OR) 3.5, 95% confidence interval (CI) 1.1–11.1, p = 0.03] and V30 PC ≥ 900 cm3 (OR 2.3, 95% CI 1–5.5, p = 0.05) predicted acute grade ≥II toxicity. On univariate analysis for late toxicity, SB (V30 ≥ 190 cm3, p = 0.009; V40 ≥ 150 cm3, p = 0.03), LB (V15 ≥ 250 cm3, p = 0.04), V40 PC (V40 ≥ 750 cm3, p = 0.001) and presence of acute grade ≥III toxicity (p = 0.006), treatment technique (three-dimensional conformal radiation or intensity modulated radiotherapy, p = 0.02) predicted more than or equal to grade ll late bowel toxicity. On multivariate analysis, only body mass index ≥25 kg m−2 (OR 7.3, 95% CI 1.6–31

  5. Influence of Rough Hair Coats and Steroidal Implants on Hair Growth, Rectal Temperatures, and Sweating by Steers Grazed on Toxic Tall Fescue During the Summer

    USDA-ARS?s Scientific Manuscript database

    Cattle grazing toxic tall fescue months [Schedonorus arundinaceus (Schreb.)] typically retain their rough hair coats into the summer, which can exacerbate heat stress induced by fescue toxicosis. Further, previous research has indicated that progesterone and estradiol implants may increase body tem...

  6. Phase II Study of Preoperative Helical Tomotherapy With a Simultaneous Integrated Boost for Rectal Cancer

    SciTech Connect

    Engels, Benedikt; Tournel, Koen; Everaert, Hendrik; Hoorens, Anne; Sermeus, Alexandra; Christian, Nicolas; Storme, Guy; Verellen, Dirk; De Ridder, Mark

    2012-05-01

    Purpose: The addition of concomitant chemotherapy to preoperative radiotherapy is considered the standard of care for patients with cT3-4 rectal cancer. The combined treatment modality increases the complete response rate and local control (LC), but has no impact on survival or the incidence of distant metastases. In addition, it is associated with considerable toxicity. As an alternative strategy, we explored prospectively, preoperative helical tomotherapy with a simultaneous integrated boost (SIB). Methods and Materials: A total of 108 patients were treated with intensity-modulated and image-guided radiotherapy using the Tomotherapy Hi-Art II system. A dose of 46 Gy, in daily fractions of 2 Gy, was delivered to the mesorectum and draining lymph nodes, without concomitant chemotherapy. Patients with an anticipated circumferential resection margin (CRM) of less than 2 mm, based on magnetic resonance imaging, received a SIB to the tumor up to a total dose of 55.2 Gy. Acute and late side effects were scored using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Results: A total of 102 patients presented with cT3-4 tumors; 57 patients entered the boost group and 51 the no-boost group. One patient in the no-boost group developed a radio-hypersensitivity reaction, resulting in a complete tumor remission, a Grade 3 acute and Grade 5 late enteritis. No other Grade {>=}3 acute toxicities occurred. With a median follow-up of 32 months, Grade {>=}3 late gastrointestinal and urinary toxicity were observed in 6% and 4% of the patients, respectively. The actuarial 2-year LC, progression-free survival and overall survival were 98%, 79%, and 93%. Conclusions: Preoperative helical tomotherapy displays a favorable acute toxicity profile in patients with cT3-4 rectal cancer. A SIB can be safely administered in patients with a narrow CRM and resulted in a promising LC.

  7. Late renal toxicity of treatment for childhood malignancy: risk factors, long-term outcomes, and surveillance.

    PubMed

    Skinner, Roderick

    2017-04-22

    Chronic glomerular and tubular nephrotoxicity is reported in 20-50% and 20-25%, respectively, of children and adolescents treated with ifosfamide and 60-80% and 10-30%, respectively, of those given cisplatin. Up to 20% of children display evidence of chronic glomerular damage after unilateral nephrectomy for a renal tumour. Overall, childhood cancer survivors have a ninefold higher risk of developing renal failure compared with their siblings. Such chronic nephrotoxicity may have multiple causes, including chemotherapy, radiotherapy exposure to kidneys, renal surgery, supportive care drugs and tumour-related factors. These cause a wide range of chronic glomerular and tubular toxicities, often with potentially severe clinical sequelae. Many risk factors for developing nephrotoxicity, mostly patient and treatment related, have been described, but we remain unable to predict all episodes of renal damage. This implies that other factors may be involved, such as genetic polymorphisms influencing drug metabolism. Although our knowledge of the long-term outcomes of chronic nephrotoxicity is increasing, there is still much to learn, including how we can optimally predict or achieve early detection of nephrotoxicity. Greater understanding of the pathogenesis of nephrotoxicity is needed before its occurrence can be prevented.

  8. Dosimetric Implications of an Injection of Hyaluronic Acid for Preserving the Rectal Wall in Prostate Stereotactic Body Radiation Therapy

    SciTech Connect

    Chapet, Olivier; Udrescu, Corina; Tanguy, Ronan; Ruffion, Alain; Fenoglietto, Pascal; Sotton, Marie-Pierre; Devonec, Marian; Colombel, Marc; Jalade, Patrice; Azria, David

    2014-02-01

    Purpose: This study assessed the contribution of ahyaluronic acid (HA) injection between the rectum and the prostate to reducing the dose to the rectal wall in stereotactic body radiation therapy (SBRT). Methods and Materials: As part of a phase 2 study of hypofractionated radiation therapy (62 Gy in 20 fractions), the patients received a transperineal injection of 10 cc HA between the rectum and the prostate. A dosimetric computed tomographic (CT) scan was systematically performed before (CT1) and after (CT2) the injection. Two 9-beam intensity modulated radiation therapy-SBRT plans were optimized for the first 10 patients on both CTs according to 2 dosage levels: 5 × 6.5 Gy (PlanA) and 5 × 8.5 Gy (PlanB). Rectal wall parameters were compared with a dose–volume histogram, and the prostate–rectum separation was measured at 7 levels of the prostate on the center line of the organ. Results: For both plans, the average volume of the rectal wall receiving the 90% isodose line (V90%) was reduced up to 90% after injection. There was no significant difference (P=.32) between doses received by the rectal wall on CT1 and CT2 at the base of the prostate. This variation became significant from the median plane to the apex of the prostate (P=.002). No significant differences were found between PlanA without HA and PlanB with HA for each level of the prostate (P=.77, at the isocenter of the prostate). Conclusions: HA injection significantly reduced the dose to the rectal wall and allowed a dose escalation from 6.5 Gy to 8.5 Gy without increasing the dose to the rectum. A phase 2 study is under way in our department to assess the rate of acute and late rectal toxicities when SBRT (5 × 8.5 Gy) is combined with an injection of HA.

  9. A Novel Method for Predicting Late Genitourinary Toxicity After Prostate Radiation Therapy and the Need for Age-Based Risk-Adapted Dose Constraints

    SciTech Connect

    Ahmed, Awad A.; Egleston, Brian; Alcantara, Pino; Li, Linna; Pollack, Alan; Horwitz, Eric M.; Buyyounouski, Mark K.

    2013-07-15

    Background: There are no well-established normal tissue sparing dose–volume histogram (DVH) criteria that limit the risk of urinary toxicity from prostate radiation therapy (RT). The aim of this study was to determine which criteria predict late toxicity among various DVH parameters when contouring the entire solid bladder and its contents versus the bladder wall. The area under the histogram curve (AUHC) was also analyzed. Methods and Materials: From 1993 to 2000, 503 men with prostate cancer received 3-dimensional conformal RT (median follow-up time, 71 months). The whole bladder and the bladder wall were contoured in all patients. The primary endpoint was grade ≥2 genitourinary (GU) toxicity occurring ≥3 months after completion of RT. Cox regressions of time to grade ≥2 toxicity were estimated separately for the entire bladder and bladder wall. Concordance probability estimates (CPE) assessed model discriminative ability. Before training the models, an external random test group of 100 men was set aside for testing. Separate analyses were performed based on the mean age (≤ 68 vs >68 years). Results: Age, pretreatment urinary symptoms, mean dose (entire bladder and bladder wall), and AUHC (entire bladder and bladder wall) were significant (P<.05) in multivariable analysis. Overall, bladder wall CPE values were higher than solid bladder values. The AUHC for bladder wall provided the greatest discrimination for late bladder toxicity when compared with alternative DVH points, with CPE values of 0.68 for age ≤68 years and 0.81 for age >68 years. Conclusion: The AUHC method based on bladder wall volumes was superior for predicting late GU toxicity. Age >68 years was associated with late grade ≥2 GU toxicity, which suggests that risk-adapted dose constraints based on age should be explored.

  10. Rectal diverticulitis mimicking rectal carcinoma with intestinal obstruction: case report.

    PubMed

    Özçelik, Ümit; Bircan, Hüseyin Yüce; Eren, Eryiğit; Demiralay, Ebru; Işıklar, İclal; Demirağ, Alp; Moray, Gökhan

    2015-01-01

    Although diverticular disease of the colon is common, the occurrence of rectal diverticula is extremely rare with only sporadic reports in the literature since 1911. Symptomatic rectal diverticula are seen even less frequently, and surgical intervention is needed for only complicated cases. Here we report the case of a 63-year-old woman presenting with rectal diverticulitis mimicking rectal carcinoma with intestinal obstruction.

  11. Ultrastructural alterations in allylamine cardiovascular toxicity. Late myocardial and vascular lesions.

    PubMed Central

    Boor, P. J.; Ferrans, V. J.

    1985-01-01

    The late myocardial and vascular ultrastructural changes in rat hearts following consumption of the cardiovascular toxin allylamine were studied. Rats were given 0.1% allylamine HCl in drinking water for 10-104 days. From 10 to 21 days, there was organization of acute myocardial necrosis by macrophages and scattered polymorphonuclear leukocytes with prominent interstitial-cell proliferation. Alterations at 21-104 days included extensive scarring with formation of dense mature collagen with scattered fibroblasts present, grossly evident left-ventricular aneurysm, and gross and microscopic changes similar to those observed in the secondary form of endocardial fibroelastosis. Areas of scar contained highly cellular foci of smooth-muscle cells, myofibroblasts, and abundant extracellular elastin. Cardiac myocytes frequently showed markedly disorganized myofilaments, bizarrely distorted mitochondria with condensed cristae, and other severe degenerative changes. Small vessels within and adjacent to scar showed proliferation of intimal smooth-muscle cells. Endothelial lesions or recent or organized thrombi were not seen. Focal endocardial metaplasia, consisting of both chondroid and osseous tissue, was found in areas of transmural scarring, or ventricular aneurysm. Chondrocytes had the overall nuclear and cellular morphology, abundant rough endoplasmic reticulum, and surrounding lacunae typical of mature fibrocartilage. In some areas, the collagen matrix was undergoing calcification with the typical cross-banded pattern of calcifying connective tissue. Osteocytes were located in a densely calcified bone matrix and displayed characteristic cellular extensions into surrounding canaliculi. These findings indicate a severe myocardial, small-vessel, and endocardial injury during the course of chronic allylamine intoxication. Images Figure 13 Figure 14 Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 15 Figure

  12. Clinical Factors Predicting Late Severe Urinary Toxicity After Postoperative Radiotherapy for Prostate Carcinoma: A Single-Institute Analysis of 742 Patients

    SciTech Connect

    Cozzarini, Cesare; Fiorino, Claudio; Da Pozzo, Luigi Filippo; Alongi, Filippo; Berardi, Genoveffa; Bolognesi, Angelo; Briganti, Alberto; Broggi, Sara; Deli, Aniko; Guazzoni, Giorgio; Perna, Lucia; Pasetti, Marcella; Salvadori, Giovannella; Montorsi, Francesco; Rigatti, Patrizio; Di Muzio, Nadia

    2012-01-01

    Purpose: To investigate the clinical factors independently predictive of long-term severe urinary sequelae after postprostatectomy radiotherapy. Patients and Methods: Between 1993 and 2005, 742 consecutive patients underwent postoperative radiotherapy with either adjuvant (n = 556; median radiation dose, 70.2 Gy) or salvage (n = 186; median radiation dose, 72 Gy) intent. Results: After a median follow-up of 99 months, the 8-year risk of Grade 2 or greater and Grade 3 late urinary toxicity was almost identical (23.9% vs. 23.7% and 12% vs. 10%) in the adjuvant and salvage cohorts, respectively. On univariate analysis, acute toxicity was significantly predictive of late Grade 2 or greater sequelae in both subgroups (p <.0001 in both cases), and hypertension (p = .02) and whole-pelvis radiotherapy (p = .02) correlated significantly in the adjuvant cohort only. The variables predictive of late Grade 3 sequelae were acute Grade 2 or greater toxicity in both groups and whole-pelvis radiotherapy (8-year risk of Grade 3 events, 21% vs. 11%, p = .007), hypertension (8-year risk, 18% vs. 10%, p = .005), age {<=} 62 years at RT (8-year risk, 16% vs. 11%, p = .04) in the adjuvant subset, and radiation dose >72 Gy (8-year risk, 19% vs. 6%, p = .007) and age >71 years (8-year risk, 16% vs. 6%, p = .006) in the salvage subgroup. Multivariate analysis confirmed the independent predictive role of all the covariates indicated as statistically significant on univariate analysis. Conclusions: The risk of late Grade 2 or greater and Grade 3 urinary toxicity was almost identical, regardless of the RT intent. In the salvage cohort, older age and greater radiation doses resulted in a worse toxicity profile, and younger, hypertensive patients experienced a greater rate of severe late sequelae in the adjuvant setting. The causes of this latter correlation and apparently different etiopathogenesis of chronic damage in the two subgroups were unclear and deserve additional investigation.

  13. Management of Rectal Cancer: Short- vs. Long-Course Preoperative Radiation

    SciTech Connect

    Mohiuddin, Mohammed Marks, John; Marks, Gerald

    2008-11-01

    There is considerable debate on the optimum approach to neoadjuvant therapy in rectal cancer. This review of major published studies of short-course preoperative radiation and the more conventional approach of long-course neoadjuvant chemoradiation was undertaken in an effort to understand the potential advantages and disadvantages of each of these approaches. Studies were evaluated with regard to patient selection, clinical outcomes, and toxicities. Short-course preoperative radiation has shown a clear advantage over surgery alone in reducing local recurrence rates and improving survival of patients with rectal cancer. However, studies using short-course preoperative treatment have included a significant number of early (30%; Stage I/II) and more proximal cancers yet appear to have higher positive margin rates, higher abdominoperineal resection rates, and lower aggregate survival than patients treated with long-course neoadjuvant chemoradiation. Although long-course preoperative chemoradiation is associated with higher rates of reversible acute toxicity, there appears to be more significant and a higher rate of late gastrointestinal toxicity observed in short-course preoperative radiation studies. Patient convenience and lower cost of treatment, however, can be a significant advantage in using a short-course treatment schedule. Selective utilization of either of these approaches should be based on extent of disease and goals of treatment. Patients with distal cancers or more advanced disease (T3/T4) appear to have better outcomes with neoadjuvant chemoradiation, especially where downstaging of disease is critical for more complete surgical resection and sphincter preservation.

  14. Rectal cancer: a review

    PubMed Central

    Fazeli, Mohammad Sadegh; Keramati, Mohammad Reza

    2015-01-01

    Rectal cancer is the second most common cancer in large intestine. The prevalence and the number of young patients diagnosed with rectal cancer have made it as one of the major health problems in the world. With regard to the improved access to and use of modern screening tools, a number of new cases are diagnosed each year. Considering the location of the rectum and its adjacent organs, management and treatment of rectal tumor is different from tumors located in other parts of the gastrointestinal tract or even the colon. In this article, we will review the current updates on rectal cancer including epidemiology, risk factors, clinical presentations, screening, and staging. Diagnostic methods and latest treatment modalities and approaches will also be discussed in detail. PMID:26034724

  15. A rectal neuroendocrine neoplasm.

    PubMed

    Varas Lorenzo, Modesto J; Muñoz Agel, Fernando

    2017-08-01

    The incidence of gastric and rectal carcinoids is increasing. This is probably due to endoscopic screening. The prognosis is primarily dependent upon tumor size, aggressiveness (pathology, Ki-67), metastatic disease and stage. However, neuroendocrine carcinoma usually behaves as an adenocarcinoma.

  16. Rectal imaging and cancer.

    PubMed

    Vining, D J

    1998-09-01

    Rectal imaging has evolved substantially during the past 25 years and now offers surgeons exquisite anatomic detail and physiologic information. Dynamic cystoproctography, helical computed tomography, endoscopic ultrasonography, endorectal magnetic resonance imaging, and immunoscintigraphy have become standards for the diagnosis of rectal disease, staging of neoplasia, and survey of therapeutic results. The indications, limitations, and relative costs of current imaging methods are reviewed, and advances in imaging technology that promise future benefits to colorectal surgeons are introduced.

  17. Postoperative radiochemotherapy in rectal cancer comparison of two combination schemes: alternating versus concomitant.

    PubMed

    Valencia, Javier; Escó, Ricardo; Polo, Sofía; Bascón, Natividad; Escudero, Pilar; Alonso, Vicente

    2004-01-01

    To compare the results on disease control and toxicity of two different schedules of adjuvant combined treatment in advanced rectal cancer. From January 1995 to September 1998, 127 patients with stage B2-C rectal cancer were treated with postoperative chemotherapy and radiotherapy with two different schemes: three cycles of 5-fluorouracil and leucovorin followed by pelvic radiotherapy and three weeks after radiation therapy was completed, another three cycles of chemotherapy were administered (alternating arm), or two cycles of 5-fluorouracil and leucovorin followed by concurrent radiochemotherapy and three weeks after ending another two cycles of 5-fluorouracil and leucovorin were administered (concomitant arm). Grade 3 acute toxicity was more frequent in the concomitant schedule group (33% vs 13%, P = 0.014). In the alternating schedule group, the acute adverse effects were observed after an average radiation dose of 28.4 Gy and in the concomitant schedule group after an average dose of 22.7 Gy (P = 0.012). In the arm of concomitant treatment, 37.8% of patients had to interrupt the irradiation for severe toxicity compared to 10.4% in the arm of alternating treatment (P = 0.001). There was no difference in the rate of late toxicity. The actuarial overall survival rates at 3 and 5 years were, respectively, 68.8% and 56.6% in the alternating arm and 75.5% and 61.8% in the concomitant arm (P = 0.4599). There were no differences between the two arms in the 5-year actuarial rates of overall recurrence (47% vs 51.3%, P = 0.722), local recurrence (34.6% vs 35.7%, P = 0.935) or distant recurrence (32.7% vs 31.8%, P = 0.983). For patients with B2-C rectal cancer, postoperative treatment with an alternating scheme of chemoradiotherapy is as effective as a concomitant scheme in control of the disease. The concomitant scheme had a higher incidence, earlier appearance and higher severity of intestinal acute toxicity than the alternating scheme, with a lower completion rate of

  18. Californium-252 neutron intracavity brachytherapy alone for T1N0 low-lying rectal adenocarcinoma: A definitive anal sphincter-preserving radiotherapy.

    PubMed

    Xiong, Yanli; Shan, Jinlu; Liu, Jia; Zhao, Kewei; Chen, Shu; Xu, Wenjing; Zhou, Qian; Yang, Mei; Lei, Xin

    2017-01-17

    This study evaluated the 4-year results of 32 patients with T1N0 low-lying rectal adenocarcinoma treated solely with californium-252 (Cf-252) neutron intracavity brachytherapy (ICBT). Patients were solicited into the study from January 2008 to June 2011. All the patients had refused surgery or surgery was contraindicated. The patients were treated with Cf-252 neutron ICBT using a novel 3.5-cm diameter off-axis 4-channel intrarectal applicator designed by the authors. The dose reference point was defined on the mucosa surface, with a total dose of 55-62 Gy-eq/4 f (13-16 Gy-eq/f/wk). All the patients completed the radiotherapy in accordance with our protocol. The rectal lesions regressed completely, and the acute rectal toxicity was mild (≤G2). The 4-year local control, overall survival, disease-free survival, and late complication (≥G2) rates were 96.9%, 90.6%, 87.5% and 15.6%, respectively. No severe late complication (≥G3) occurred. The mean follow-up was 56.1 ± 16.0 months. At the end of last follow-up, 29 patients remained alive. The mean survival time was 82.1 ± 2.7 months. Cf-252 neutron ICBT administered as the sole treatment (without surgery) for patients with T1N0 low-lying rectal adenocarcinoma is effective with acceptable late complications. Our study and method offers a definitive anal sphincter-preserving radiotherapy for T1N0 low-lying rectal adenocarcinoma patients.

  19. Californium-252 neutron intracavity brachytherapy alone for T1N0 low-lying rectal adenocarcinoma: A definitive anal sphincter-preserving radiotherapy

    PubMed Central

    Xiong, Yanli; Shan, Jinlu; Liu, Jia; Zhao, Kewei; Chen, Shu; Xu, Wenjing; Zhou, Qian; Yang, Mei; Lei, Xin

    2017-01-01

    This study evaluated the 4-year results of 32 patients with T1N0 low-lying rectal adenocarcinoma treated solely with californium-252 (Cf-252) neutron intracavity brachytherapy (ICBT). Patients were solicited into the study from January 2008 to June 2011. All the patients had refused surgery or surgery was contraindicated. The patients were treated with Cf-252 neutron ICBT using a novel 3.5-cm diameter off-axis 4-channel intrarectal applicator designed by the authors. The dose reference point was defined on the mucosa surface, with a total dose of 55–62 Gy-eq/4 f (13–16 Gy-eq/f/wk). All the patients completed the radiotherapy in accordance with our protocol. The rectal lesions regressed completely, and the acute rectal toxicity was mild (≤G2). The 4-year local control, overall survival, disease-free survival, and late complication (≥G2) rates were 96.9%, 90.6%, 87.5% and 15.6%, respectively. No severe late complication (≥G3) occurred. The mean follow-up was 56.1 ± 16.0 months. At the end of last follow-up, 29 patients remained alive. The mean survival time was 82.1 ± 2.7 months. Cf-252 neutron ICBT administered as the sole treatment (without surgery) for patients with T1N0 low-lying rectal adenocarcinoma is effective with acceptable late complications. Our study and method offers a definitive anal sphincter-preserving radiotherapy for T1N0 low-lying rectal adenocarcinoma patients. PMID:28094790

  20. Preliminary Toxicity Analysis of 3DCRT versus IMRT on the High Dose Arm of the RTOG 0126 Prostate Cancer Trial

    PubMed Central

    Michalski, Jeff M.; Yan, Yan; Watkins-Bruner, Deborah; Bosch, Walter; Winter, Kathryn; Galvin, James M.; Bahary, Jean-Paul; Morton, Gerard C.; Parliament, Matthew B.; Sandler, Howard M.

    2013-01-01

    Purpose A Preliminary report of clinical and treatment factors associated with toxicity in men receiving high dose radiation (RT) on a phase III dose escalation trial. Methods and Materials Trial was initiated with 3 dimensional RT (3DCRT) and amended after 1 year to allow intensity modulated RT (IMRT). Patients treated with 3DCRT received 55.8Gy to a planning target volume that included the prostate and seminal vesicles then 23.4Gy to prostate only. IMRT patients were treated to the prostate and proximal seminal vesicles to 79.2Gy. CTC v2.0 and RTOG/EORTC late morbidity scores were used for acute and late effects. Results 748 of 763 patients randomized to the 79.2 Gy arm of RTOG 0126 were eligible and evaluable. 491 and 257 were treated with 3DCRT and IMRT, respectively. For both bladder and rectum, the volumes receiving 65, 70, and 75Gy were significantly lower with IMRT (all p<0.0001). For G2+ acute GI/GU toxicity, both univariate and multivariate analyses show a statistically significant decrease in G2+ acute collective GI/GU toxicity for IMRT. There are no significant differences with 3DCRT or IMRT for acute or late, G2+ or 3+ GU toxicities. Univariate analysis shows a statistically significant decrease in late G2+ GI toxicity for IMRT (p=0.039). On multivariate analysis, IMRT shows a 26% reduction in G2+ late GI toxicity (p=0.099). Acute G3+ toxicity was associated with late G3+ toxicity (p=0.005). With DVH data in the multivariate analysis, RT modality is not significant whereas white race (p=0.001) and rectal V70 >=15% are associated with G2+ rectal toxicity (p=0.034). Conclusions IMRT is associated with a significant reduction in acute G2+ GI/GU toxicity. There is a trend for a clinically meaningful reduction in late G2+ GI toxicity with IMRT. The occurrence of acute GI toxicity and large (>15%) volumes of rectum >70Gy are associated with late rectal toxicity. PMID:24113055

  1. Periodical assessment of genitourinary and gastrointestinal toxicity in patients who underwent prostate low-dose-rate brachytherapy

    PubMed Central

    2013-01-01

    Background To compare the periodical incidence rates of genitourinary (GU) and gastrointestinal (GI) toxicity in patients who underwent prostate low-dose-rate brachytherapy between the monotherapy group (seed implantation alone) and the boost group (in combination with external beam radiation therapy (EBRT)). Methods A total of 218 patients with a median follow-up of 42.5 months were enrolled. The patients were divided into 2 groups by treatment modality, namely, the monotherapy group (155 patients) and the boost group (63 patients). The periodical incidence rates of GU and GI toxicity were separately evaluated and compared between the monotherapy group and the boost group using the National Cancer Institute - Common Terminology Criteria for Adverse Events, version 3.0. To elucidate an independent factor among clinical and postdosimetric parameters to predict grade 2 or higher GU and GI toxicity in the acute and late phases, univariate and multivariate logistic regression analyses were carried out. Results Of all patients, 78.0% showed acute GU toxicity, and 7.8% showed acute GI toxicity, while 63.8% showed late GU toxicity, and 21.1% showed late GI toxicity. The incidence rates of late GU and GI toxicity were significantly higher in the boost group. Multivariate analysis showed that the International Prostate Symptom Score (IPSS) before seed implantation was a significant parameter to predict acute GU toxicity, while there were no significant predictive parameters for acute GI toxicity. On the other hand, combination with EBRT was a significant predictive parameter for late GU toxicity, and rectal volume (mL) receiving 100% of the prescribed dose (R100) was a significant predictive parameter for late GI toxicity. Conclusions The boost group showed higher incidence rates of both GU and GI toxicity. Higher IPSS before seed implantation, combination with EBRT and a higher R100 were significant predictors for acute GU, late GU and late GI toxicity. PMID:23363647

  2. Periodical assessment of genitourinary and gastrointestinal toxicity in patients who underwent prostate low-dose-rate brachytherapy.

    PubMed

    Tanaka, Nobumichi; Asakawa, Isao; Anai, Satoshi; Hirayama, Akihide; Hasegawa, Masatoshi; Konishi, Noboru; Fujimoto, Kiyohide

    2013-01-30

    To compare the periodical incidence rates of genitourinary (GU) and gastrointestinal (GI) toxicity in patients who underwent prostate low-dose-rate brachytherapy between the monotherapy group (seed implantation alone) and the boost group (in combination with external beam radiation therapy (EBRT)). A total of 218 patients with a median follow-up of 42.5 months were enrolled. The patients were divided into 2 groups by treatment modality, namely, the monotherapy group (155 patients) and the boost group (63 patients). The periodical incidence rates of GU and GI toxicity were separately evaluated and compared between the monotherapy group and the boost group using the National Cancer Institute - Common Terminology Criteria for Adverse Events, version 3.0. To elucidate an independent factor among clinical and postdosimetric parameters to predict grade 2 or higher GU and GI toxicity in the acute and late phases, univariate and multivariate logistic regression analyses were carried out. Of all patients, 78.0% showed acute GU toxicity, and 7.8% showed acute GI toxicity, while 63.8% showed late GU toxicity, and 21.1% showed late GI toxicity. The incidence rates of late GU and GI toxicity were significantly higher in the boost group. Multivariate analysis showed that the International Prostate Symptom Score (IPSS) before seed implantation was a significant parameter to predict acute GU toxicity, while there were no significant predictive parameters for acute GI toxicity. On the other hand, combination with EBRT was a significant predictive parameter for late GU toxicity, and rectal volume (mL) receiving 100% of the prescribed dose (R100) was a significant predictive parameter for late GI toxicity. The boost group showed higher incidence rates of both GU and GI toxicity. Higher IPSS before seed implantation, combination with EBRT and a higher R100 were significant predictors for acute GU, late GU and late GI toxicity.

  3. Hyperbaric oxygen therapy for late radiation-induced tissue toxicity: prospectively patient-reported outcome measures in breast cancer patients.

    PubMed

    Teguh, David N; Bol Raap, René; Struikmans, Henk; Verhoef, Cees; Koppert, Linetta B; Koole, Arne; Huang, Yadi; van Hulst, Rob A

    2016-09-29

    This study examines patient reported outcome measures of women undergoing hyperbaric oxygen treatment (HBOT) after breast-conserving therapy. Included were 57 women treated with HBOT for late radiation-induced tissue toxicity (LRITT) referred in the period January 2014-December 2015. HBOT consisted of (on average) 47 sessions. In total, 80 min of 100 % O2 was administered under increased pressure of 2.4 ATA. Quality of life was assessed before and after treatment using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-BR23, and a NRS pain score. Fifty-seven women were available for evaluation before and after treatment. Before HBOT, patients had severe complaints of pain in the arm/shoulder (46 %), swollen arm/hand (14 %), difficulty to raise arm or move it sideways (45 %), pain in the area of the affected breast (67 %), swollen area of the affected breast (45 %), oversensitivity of the affected breast (54 %), and skin problems on/in the area of the affected breast (32 %); post HBOT, severe complaints were still experienced in 17, 7, 22, 15, 13, 15, and 11 % of the women, respectively. Differences were all significant. The NRS pain score improved at least 1 point (range 0-10) in 81 % of the patients (p < 0.05). In these breast cancer patients treated with HBOT for LRITT, the patient-reported outcomes were positive and improvements were observed. HBOT was a well-tolerated treatment for LRITT and its side-effects were both minimal and reversible.

  4. Comparative Toxicity and Dosimetric Profile of Whole-Pelvis Versus Prostate Bed-Only Intensity-Modulated Radiation Therapy After Prostatectomy

    SciTech Connect

    Deville, Curtiland; Vapiwala, Neha; Hwang, Wei-Ting; Lin Haibo; Bar Ad, Voichita; Tochner, Zelig; Both, Stefan

    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 evaluated 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.

  5. Development of Late Toxicity and International Prostate Symptom Score Resolution After External-Beam Radiotherapy Combined With Pulsed Dose Rate Brachytherapy for Prostate Cancer

    SciTech Connect

    Pieters, Bradley R.; Rezaie, Elisa; Geijsen, Elisabeth D.; Koedooder, Kees; Grient, Johan N.B. van der; Blank, Leo E.C.M.; Reijke, Theo M. de; Koning, Caro C.E.

    2011-11-01

    Purpose: To investigate the development of gastrointestinal (GI) toxicity, genitourinary (GU) toxicity, erectile dysfunction, and International Prostate Symptom Score (IPSS) resolution in a cohort of patients treated with external-beam radiotherapy (EBRT) followed by a brachytherapy pulsed dose rate (PDR) boost. Methods and Materials: Between 2002 and 2008, 110 patients were treated with 46-Gy EBRT followed by PDR brachytherapy (24.96-28.80 Gy). The investigated outcome variables, GI toxicity, GU toxicity, erectile dysfunction, and IPSS were prospectively scored at several time points during follow-up. Association between time (as continuous and categorical variable) and the outcome variables was assessed using generalized linear models. Results: No statistically significant association was found between time (continuous) and GI toxicity (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.89-1.06), GU toxicity (OR, 0.97; 95% CI, 0.91-1.03), erectile dysfunction (OR, 1.06; 95% CI, 0.99-1.11), and IPSS (-0.11; 95% CI, -0.41-0.20). Also, no statistically significant association was found between these variables and time as a categorical variable. GU toxicity was associated with IPSS resolution (OR, 1.16; 95% CI, 1.09-1.24). Posttreatment IPSS was associated with pretreatment IPSS (0.52; 95% CI, 0.25-0.79). Conclusions: No accumulation of high-grade toxicity over time could be established for a group of patients treated with EBRT and PDR brachytherapy for prostate cancer, probably because high-grade late toxicity resolves with time. Also, differences in IPSS values among patients are smaller after treatment than before treatment.

  6. Transitioning from conventional radiotherapy to intensity-modulated radiotherapy for localized prostate cancer: changing focus from rectal bleeding to detailed quality of life analysis

    PubMed Central

    Yamazaki, Hideya; Nakamura, Satoaki; Nishimura, Takuya; Yoshida, Ken; Yoshioka, Yasuo; Koizumi, Masahiko; Ogawa, Kazuhiko

    2014-01-01

    With the advent of modern radiation techniques, we have been able to deliver a higher prescribed radiotherapy dose for localized prostate cancer without severe adverse reactions. We reviewed and analyzed the change of toxicity profiles of external beam radiation therapy (EBRT) from the literature. Late rectal bleeding is the main adverse effect, and an incidence of >20% of Grade ≥2 adverse events was reported for 2D conventional radiotherapy of up to 70 Gy. 3D conformal radiation therapy (3D-CRT) was found to reduce the incidence to ∼10%. Furthermore, intensity-modulated radiation therapy (IMRT) reduced it further to a few percentage points. However, simultaneously, urological toxicities were enhanced by dose escalation using highly precise external radiotherapy. We should pay more attention to detailed quality of life (QOL) analysis, not only with respect to rectal bleeding but also other specific symptoms (such as urinary incontinence and impotence), for two reasons: (i) because of the increasing number of patients aged >80 years, and (ii) because of improved survival with elevated doses of radiotherapy and/or hormonal therapy; age is an important prognostic factor not only for prostate-specific antigen (PSA) control but also for adverse reactions. Those factors shift the main focus of treatment purpose from survival and avoidance of PSA failure to maintaining good QOL, particularly in older patients. In conclusion, the focus of toxicity analysis after radiotherapy for prostate cancer patients is changing from rectal bleeding to total elaborate quality of life assessment. PMID:25204643

  7. Fixed Drug Eruption Late in the Course of Capecitabine Therapy.

    PubMed

    Del Rosario, Michael; Tsai, Henry; Dasanu, Constantin A

    2016-04-01

    A fixed drug eruption (FDE) is a toxic skin effect thought to be caused by delayed cell-mediated hypersensitivity to a pharmaceutical agent. We report herein the first known patient with capecitabine-induced FDE that appeared relatively late in the course of adjuvant therapy for rectal cancer. The temporal association with capecitabine use and prompt disappearance after capecitabine discontinuation make this relationship probable. Knowledge about this dermatologic skin effect seen with oral fluoropyrimidines should avoid unnecessary diagnostic workup and provide the necessary patient reassurance.

  8. The effect of obesity on rectal dosimetry after permanent prostate brachytherapy.

    PubMed

    Patil, Nikhilesh; Crook, Juanita; Saibishkumar, Elantholi P; Aneja, Manipdip; Borg, Jette; Pond, Greg; Ma, Clement

    2009-01-01

    Men with higher body mass index (BMI) tend to have more fatty tissue in prostate-rectum interface, which may reduce the rectal wall dose by the inverse square law. We hypothesized that men with higher BMI will have a lower dose to the rectal wall and less rectal toxicity after permanent prostate implant. Prospectively collected data on rectal dosimetry/toxicity and BMI of 407 patients who underwent iodine-125 ((125)I) prostate implant were analyzed. Postimplant dosimetry used CT-MRI fusion on Day 30. Rectal wall was contoured on all slices where seeds were seen. The volume of rectal wall receiving the prescribed dose (RV(100) in cm(3)) and the dose to 1cc of rectal wall (RD(1cc)) were reported. Other factors evaluated for association with rectal dosimetry and toxicity included age, diabetes, hypertension, smoking, use of neoadjuvant hormones, T stage, baseline prostate volume, 1 month prostate edema, seed type and activity, and prostate dosimetry factors (the isodose enclosing 90% of the prostate volume [D(90)], the percentage of the prostate volume enclosed by the prescription [V(100)], and the percentage of the prostate volume enclosed by the 150% isodose [V(150)]). Rectal toxicity was reported as per Radiation Therapy Oncology Group criteria. BMIs ranged from 15.9 to 46.8 (mean+/-standard deviation [SD]: 27.8+/-4.2). The mean+/-SD values for RV(100) and RD(1cc) were 0.79+/-0.49cm(3) and 128.2+/-27.8Gy, respectively. There was a significant negative association of BMI with RV(100) (p=0.007) and RD(1cc) (p=0.01) on univariate analysis. The mean RV(100) and RD(1cc) for men with higher BMI (>27.8) were lower compared with their slimmer counterparts (0.70 vs. 0.86cm(3) and 123.4 vs. 132.4Gy, respectively). On multivariate analysis for RV(100) and RD(1cc), BMI remained significant (p-values 0.004 and 0.01, respectively) along with prostate volume and V(150), suggesting that anatomic factors are important in rectal dosimetry in prostate brachytherapy. Overall the

  9. Accelerated partial breast irradiation: An analysis of variables associated with late toxicity and long-term cosmetic outcome after high-dose-rate interstitial brachytherapy

    SciTech Connect

    Wazer, David E. . E-mail: dwazer@tufts-nemc.org; Kaufman, Seth; Cuttino, Laurie; Di Petrillo, Thomas; Arthur, Douglas W.

    2006-02-01

    Purpose: To perform a detailed analysis of variables associated with late tissue effects of high-dose-rate (HDR) interstitial brachytherapy accelerated partial breast irradiation (APBI) in a large cohort of patients with prolonged follow-up. Methods and Materials: Beginning in 1995, 75 women with Stage I/II breast cancer were enrolled in identical institutional trials evaluating APBI as monotherapy after lumpectomy. Patients eligible included those with T1-2, N0-1 ({<=}3 nodes positive), M0 tumors of nonlobular histology with negative surgical margins, no extracapsular nodal extension, and negative results on postexcision mammogram. All patients underwent surgical excision and postoperative irradiation with HDR interstitial brachytherapy. The planning target volume was defined as the excision cavity plus a 2-cm margin. Treatment was delivered with a high-activity Ir-192 source at 3.4 Gy per fraction twice daily for 5 days to a total dose of 34 Gy. Dosimetric analyses were performed with three-dimensional postimplant dose and volume reconstructions. All patients were evaluated at 3-6-month intervals and assessed with a standardized cosmetic rating scale and according to Radiation Therapy Oncology Group late normal tissue toxicity scoring criteria. Clinical and therapy-related features were analyzed for their relationship to cosmetic outcome and toxicity rating. Clinical features analyzed included age, volume of resection, history of diabetes or hypertension, extent of axillary surgery, and systemic therapies. Therapy-related features analyzed included volume of tissue encompassed by the 100%, 150%, and 200% isodose lines (V100, V150, and V200, respectively), the dose homogeneity index (DHI), number of source dwell positions, and planar separation. Results: The median follow-up of all patients was 73 months (range, 43-118 months). The cosmetic outcome at last follow-up was rated as excellent, good, and fair/poor in 67%, 24%, and 9% of patients, respectively

  10. High-dose-rate intraluminal brachytherapy during preoperative chemoradiation for locally advanced rectal cancers

    PubMed Central

    Tunio, Mutahir Ali; Rafi, Mansoor; Hashmi, Altaf; Mohsin, Rehan; Qayyum, Abdul; Hasan, Mujahid; Sattar, Amjad; Mubarak, Muhammad

    2010-01-01

    AIM: To determine the feasibility and safety of high dose rate intraluminal brachytherapy (HDR-ILBT) boost during preoperative chemoradiation for rectal cancer. METHODS: Between 2008 and 2009, thirty-six patients with locally advanced rectal cancer (≥ T3 or N+), were treated initially with concurrent capecitabine (825 mg/m2 oral twice daily) and pelvic external beam radiotherapy (EBRT) (45 Gy in 25 fractions), then were randomized to group A; HDR-ILBT group (n = 17) to receive 5.5-7 Gy × 2 to gross tumor volume (GTV) and group B; EBRT group (n = 19) to receive 5.4 Gy × 3 fractions to GTV with EBRT. All patients underwent total mesorectal excision. RESULTS: Grade 3 acute toxicities were registered in 12 patients (70.6%) in group A and in 8 (42.1%) in group B. Complete pathologic response of T stage (ypT0) in group A was registered in 10 patients (58.8%) and in group B, 3 patients (15.8%) had ypT0 (P < 0.0001). Sphincter preservation was reported in 6/9 patients (66.7%) in group A and in 5/10 patients (50%) in group B (P < 0.01). Overall radiological response was 68.15% and 66.04% in Group A and B, respectively. During a median follow up of 18 mo, late grade 1 and 2 sequelae were registered in 3 patients (17.6%) and 4 patients (21.1%) in the groups A and B, respectively. CONCLUSION: HDR-ILBT was found to be effective dose escalation technique in preoperative chemoradiation for rectal cancers, with higher response rates, downstaging and with manageable acute toxicities. PMID:20845511

  11. Concurrent administration of adjuvant chemotherapy and radiotherapy after breast-conserving surgery enhances late toxicities: Long-term results of the ARCOSEIN multicenter randomized study

    SciTech Connect

    Toledano, Alain . E-mail: alain.toledano@gmail.com; Garaud, Pascal; Serin, Daniel; Fourquet, Alain; Bosset, Jean-Francois; Breteau, Noel; Body, Gilles; Azria, David; Le Floch, Olivier; Calais, Gilles

    2006-06-01

    Purpose: In 1996, a multicenter randomized study was initiated that compared sequential vs. concurrent adjuvant chemotherapy (CT) with radiation therapy (RT) after breast-conserving surgery (ARCOSEIN study). After a median follow-up of 6.7 years (range, 4.3-9 years), we decided to prospectively evaluate the late effects of these 2 strategies. Methods and Materials: A total of 297 patients from the 5 larger participating institutions were asked to report for a follow-up examination. Seventy-two percent (214 patients) were eligible for evaluation of late toxicity. After breast-conserving surgery, patients were treated either with sequential treatment with CT first followed by RT (Arm A) or CT administered concurrently with RT (Arm B). In all patients, CT regimen consisted of mitoxantrone (12 mg/m{sup 2}), 5-FU (500 mg/m{sup 2}), and cyclophosphamide (500 mg/m{sup 2}), 6 cycles (Day 1 to Day 21). Conventional RT was delivered to the whole breast by administration of a 2 Gy per fraction protocol to a total dose of 50 Gy ({+-} boost to the primary tumor bed). The assessment of toxicity was blinded to treatment and was graded by the radiation oncologist, according to the LENT/SOMA scale. Skin pigmentation was also evaluated according to a personal 5-points scoring system (excellent, good, moderate, poor, very poor). Results: Among the 214 evaluable patients, 107 were treated in each arm. The 2 populations were homogeneous for patient, tumor, and treatment characteristics. Subcutaneous fibrosis (SF), telangectasia (T), skin pigmentation (SP), and breast atrophy (BA) were significantly increased in Arm B. No statistical difference was observed between the 2 arms of the study concerning Grade 2 or higher pain, breast edema, or lymphedema. No deaths were caused by late toxicity. Conclusion: After breast-conserving surgery, the concurrent use of CT with RT is significantly associated with an increase incidence of Grade 2 or greater late side effects.

  12. Late toxicities and outcomes of adjuvant radiotherapy combined with concurrent bevacizumab in patients with triple-negative non-metastatic breast cancer

    PubMed Central

    Pernin, V; Belin, L; Cottu, P; Bontemps, P; Lemanski, C; De La Lande, B; Baumann, P; Missohou, F; Levy, C; Peignaux, K; Reynaud-Bougnoux, A; Denis, F; Gobillion, A; Bollet, M; Vago, N A; Dendale, R; Campana, F; Fourquet, A

    2015-01-01

    Objective: To evaluate the safety of the concurrent combination of bevacizumab with adjuvant radiotherapy (B-RT) in breast cancer (BC). Methods: Multicentre, prospective study, of the toxicity of adjuvant radiotherapy (RT) alone or B-RT in patients with non-metastatic BC enrolled in randomized Phase 3 BEATRICE trial. Early and late toxicities were assessed by the Common Terminology Criteria for Adverse Events v. 3.0 during and 12 months after the completion of RT. Results: From 2007 to 2012, 39 females received adjuvant B-RT and 45 received adjuvant RT alone. Median follow-up was 21.5 months. All patients had triple-negative non-metastatic BC and received adjuvant chemotherapy followed by RT. 90% of the 39 females treated by concurrent B-RT received whole breast irradiation (WBI) with a boost and 4 (10%) received post-mastectomy RT. Lymph node RT was delivered in 49% of the females with internal mammary chain irradiation. The mean duration of bevacizumab was 11.7 months. 38 (84%) females treated by RT alone received WBI with a boost and 16% of the females received post-mastectomy RT. Lymph node RT was delivered in 47% of the females with internal mammary chain RT in 31%. Grade 3 acute dermatitis was observed in 9% of patients receiving B-RT and 5% of patients receiving RT alone with no significant difference. 1 year after the completion of RT, the most common late grade 1–2 toxicities in the B-RT group were pain (18%), fibrosis (8%) and telangiectasia (5%). Conclusion: The concurrent bevacizumab with locoregional RT is associated with acceptable early and late 1-year toxicities in patients with BC. Advances in knowledge: The largest series of this association. PMID:25645108

  13. Late toxicities and outcomes of adjuvant radiotherapy combined with concurrent bevacizumab in patients with triple-negative non-metastatic breast cancer.

    PubMed

    Pernin, V; Belin, L; Cottu, P; Bontemps, P; Lemanski, C; De La Lande, B; Baumann, P; Missohou, F; Levy, C; Peignaux, K; Reynaud-Bougnoux, A; Denis, F; Gobillion, A; Bollet, M; Vago, N A; Dendale, R; Campana, F; Fourquet, A; Kirova, Y M

    2015-04-01

    To evaluate the safety of the concurrent combination of bevacizumab with adjuvant radiotherapy (B-RT) in breast cancer (BC). Multicentre, prospective study, of the toxicity of adjuvant radiotherapy (RT) alone or B-RT in patients with non-metastatic BC enrolled in randomized Phase 3 BEATRICE trial. Early and late toxicities were assessed by the Common Terminology Criteria for Adverse Events v. 3.0 during and 12 months after the completion of RT. From 2007 to 2012, 39 females received adjuvant B-RT and 45 received adjuvant RT alone. Median follow-up was 21.5 months. All patients had triple-negative non-metastatic BC and received adjuvant chemotherapy followed by RT. 90% of the 39 females treated by concurrent B-RT received whole breast irradiation (WBI) with a boost and 4 (10%) received post-mastectomy RT. Lymph node RT was delivered in 49% of the females with internal mammary chain irradiation. The mean duration of bevacizumab was 11.7 months. 38 (84%) females treated by RT alone received WBI with a boost and 16% of the females received post-mastectomy RT. Lymph node RT was delivered in 47% of the females with internal mammary chain RT in 31%. Grade 3 acute dermatitis was observed in 9% of patients receiving B-RT and 5% of patients receiving RT alone with no significant difference. 1 year after the completion of RT, the most common late grade 1-2 toxicities in the B-RT group were pain (18%), fibrosis (8%) and telangiectasia (5%). The concurrent bevacizumab with locoregional RT is associated with acceptable early and late 1-year toxicities in patients with BC. The largest series of this association.

  14. Efficacy of orgotein in prevention of late side effects of pelvic irradiation: a randomized study.

    PubMed

    Esco, Ricardo; Valencia, Javier; Coronel, Pilar; Carceller, Jose Antonio; Gimeno, Mercedes; Bascón, Natividad

    2004-11-15

    To study whether orgotein is effective in preventing late radiation-induced effects. Patients >18 years old who were diagnosed with rectal cancer, had an indication for pelvic irradiation (RT) after surgery, and complied with the selection criteria were randomly assigned at the end of RT to receive orgotein for 7 weeks or no treatment (control). The Radiation Therapy Oncology Group toxicity scale was used to evaluate the RT-induced side effects for up to 2 years. Interruptions due to toxicity, concomitant medication, and non-RT adverse events were also recorded. A total of 100 patients were included, with 50 in each group. The groups were comparable in terms of the demographic and baseline characteristics. The orgotein group had statistically significant less late toxicity than the control group (p = 0.036) and nontreated patients had a 66% greater chance of developing late toxicity at 2 years. Grouping toxicity as nonrelevant (Radiation Therapy Oncology Group Grade 0-1) and relevant (Grade 2 or worse), patients given orgotein had a lower incidence of late relevant toxicity than did controls, with statistical significance reached at all follow-up visits. After 2 years, patients not treated with orgotein had, in general, a 37% greater chance of developing late relevant toxicity; this risk was 26% when referring specifically to GI toxicity. No adverse events attributable to orgotein were recorded at any time during the study. Orgotein is a safe treatment that significantly prevents the overall occurrence of late toxicity, with toxicity reduction particularly evident in the lower GI tract.

  15. Rectal absorption of propylthiouracil.

    PubMed

    Bartle, W R; Walker, S E; Silverberg, J D

    1988-06-01

    The rectal absorption of propylthiouracil (PTU) was studied and compared to oral absorption in normal volunteers. Plasma levels of PTU after administration of suppositories of PTU base and PTU diethanolamine were significantly lower compared to the oral route. Elevated plasma reverse T3 levels were demonstrated after each treatment, however, suggesting a desirable therapeutic effect at this dosage level for all preparations.

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

    SciTech Connect

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

    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, 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. 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

  17. 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

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

    PubMed Central

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

    2016-01-01

    Background 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. Objectives This study was designed to compare the antipyretic effectiveness of the rectal form of Paracetamol and Diclofenac. Patients and Methods 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. Results 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). Conclusions In the first one hour, Diclofenac suppository is able to control the fever more efficient than Paracetamol suppositories. PMID:26889398

  19. Rectal contrast increases rectal dose during vaginal cuff brachytherapy.

    PubMed

    Sabater, Sebastia; Andres, Ignacio; Jimenez-Jimenez, Esther; Berenguer, Roberto; Sevillano, Marimar; Lopez-Honrubia, Veronica; Rovirosa, Angeles; Sanchez-Prieto, Ricardo; Arenas, Meritxell

    2016-01-01

    To evaluate the impact of rectal dose on rectal contrast use during vaginal cuff brachytherapy (VCB). A retrospective review of gynecology patients who received some brachytherapy fractions with and without rectal contrast was carried out. Rectal contrast was instilled at the clinician's discretion to increase rectal visibility. Thirty-six pairs of CT scans in preparation for brachytherapy were analyzed. Pairs of CTs were segmented and planned using the same parameters. The rectum was always defined from 1 cm above the cylinder tip up to 1.5 cm below the last activated dwell source position. An individual plan was computed at every VCB fraction. A set of values (Dmax, D(0.1cc), D(1cc), and D(2cc)) derived from dose-volume histograms were extracted and compared according to the rectal status. Rectal volume was 26.7% larger in the fractions with rectal contrast. Such an increase in volume represented a significant increase from 7.7% to 10.4% in all parameters analyzed except Dmax dose-volume histogram. Avoiding rectal contrast is a simple way of decreasing the rectal dose parameters of VCB, which would mean a better therapeutic ratio. Results also suggest that action directed at maintaining the rectum empty might have the same effect. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  20. Comparison of Acute and Late Toxicity of Two Regimens of 3- and 5-Week Concomitant Boost Prone IMRT to Standard 6-Week Breast Radiotherapy

    PubMed Central

    Raza, Shahzad; Lymberis, Stella C.; Ciervide, Raquel; Axelrod, Deborah; Fenton-Kerimian, Maria; Magnolfi, Chiara; Rosenstein, Barry; DeWyngaert, J. Keith; Formenti, Silvia C.

    2012-01-01

    Purpose: Limited information is available comparing toxicity of accelerated radiotherapy (RT) to that of standard fractionation RT for early stage breast cancer. We report early and late toxicities of two prone regimens of accelerated intensity-modulated radiation therapy (IMRT) with a concomitant boost (CB) to the tumor bed delivered over 3 or 5 weeks as compared to standard 6 week RT with a sequential electron boost. Methods: From 2/2003 to 12/2007, 169 consecutive patients with Stage I–II breast cancer were offered the choice to undergo prone RT with either: a 6-week standard RT regimen of 46 Gy/23 fractions (fx) to the whole breast (WB), followed by a14 Gy sequential boost (SB) to the tumor bed (6wSB), a 5-week regimen of 50 Gy to WB with an IMRT CB of 6.25 Gy in 25 fx (5wCB); or a 3-week protocol of 40.5 Gy to WB with an IMRT CB of 7.5 Gy in 15 fx (3wCB). These regimens were estimated as biologically equivalent, based on alpha/beta = 4 for tumor control. Toxicities were reported using RTOG and LENT/SOMA scoring. Results: 51/169 patients chose standard 6wSB, 28 selected 5wCB, and 90 enrolled in 3wCB protocol. Maximum acute toxicity was Grade 3 dermatitis in 4% of the patients in the 6wSB compared 1% in 3wCB. In general, acute complications (breast pain, fatigue, and dermatitis) were significantly less in the 3wCB than in the other schedules (P < 0.05). With a median follow-up of 61 months, the only Grade 3 late toxicity was telangiectasia in two patients: one in 3wCB and one in 5wCB group. Notably, fibrosis was comparable among the three groups (P = NS). Conclusion: These preliminary data suggest that accelerated regimens of breast RT over 3 or 5 weeks in the prone position, with an IMRT tumor bed CB, result in comparable late toxicity to standard fractionation with a sequential tumor boost delivered over 6 weeks. As predicted by radiobiological modeling the shorter regimen was associated with less acute effects. PMID:22649788

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

    SciTech Connect

    Lee, Larissa J.; Viswanathan, Akila N.

    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 Adverse 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

  2. SU-D-204-06: Integration of Machine Learning and Bioinformatics Methods to Analyze Genome-Wide Association Study Data for Rectal Bleeding and Erectile Dysfunction Following Radiotherapy in Prostate Cancer

    SciTech Connect

    Oh, J; Deasy, J; Kerns, S; Ostrer, H; Rosenstein, B

    2016-06-15

    Purpose: We investigated whether integration of machine learning and bioinformatics techniques on genome-wide association study (GWAS) data can improve the performance of predictive models in predicting the risk of developing radiation-induced late rectal bleeding and erectile dysfunction in prostate cancer patients. Methods: We analyzed a GWAS dataset generated from 385 prostate cancer patients treated with radiotherapy. Using genotype information from these patients, we designed a machine learning-based predictive model of late radiation-induced toxicities: rectal bleeding and erectile dysfunction. The model building process was performed using 2/3 of samples (training) and the predictive model was tested with 1/3 of samples (validation). To identify important single nucleotide polymorphisms (SNPs), we computed the SNP importance score, resulting from our random forest regression model. We performed gene ontology (GO) enrichment analysis for nearby genes of the important SNPs. Results: After univariate analysis on the training dataset, we filtered out many SNPs with p>0.001, resulting in 749 and 367 SNPs that were used in the model building process for rectal bleeding and erectile dysfunction, respectively. On the validation dataset, our random forest regression model achieved the area under the curve (AUC)=0.70 and 0.62 for rectal bleeding and erectile dysfunction, respectively. We performed GO enrichment analysis for the top 25%, 50%, 75%, and 100% SNPs out of the select SNPs in the univariate analysis. When we used the top 50% SNPs, more plausible biological processes were obtained for both toxicities. An additional test with the top 50% SNPs improved predictive power with AUC=0.71 and 0.65 for rectal bleeding and erectile dysfunction. A better performance was achieved with AUC=0.67 when age and androgen deprivation therapy were added to the model for erectile dysfunction. Conclusion: Our approach that combines machine learning and bioinformatics techniques

  3. ¹³¹I treatment of toxic nodular goiter under combined thyrostatic-thyromimetic medication is at low risk of late hypothyroidism.

    PubMed

    Paghera, B; Panarotto, M B; Maira, G; Magri, G C; Bertagna, F; Bosio, G; Rossini, P; De Agostini, A; Savelli, G; Lucchini, S; Giubbini, R

    2010-06-01

    Treatment of toxic nodular goiter with ¹³¹I is a first-line therapy for hyperthyroidism. To avoid a thyrotoxic storm, ¹³¹I is usually administered after pretreatment with antithyroid drugs, with thyroid-stimulating hormone (TSH) increase and functional recruitment of inhibited normal tissue. Therefore, both autonomous nodule(s) and normal tissue are irradiated. This may be a reason for late hypothyroidism occurring in 15-25% of patients. This study aimed at assessing different pretreatment modalities with combined methymazole and triiodothyronine, achieving euthyroidism with suppressed TSH. After diagnosis of autonomously functioning toxic nodule, patients were subjected to thyrostatic medication. Two months later, TSH was checked; if >0.5 mU/L triiodothyronine treatment was associated. After 2 more months, if the TSH level was suppressed, patients received ¹³¹I-therapy. A total of 149 patients were consecutively enrolled, 41 of whom with uninodular and 108 with multinodular goiter. They were evaluated at diagnosis, pretreatment, 3 and 6 months after therapy and at late follow-up (6.8+/-4.2 years; range: 1-22 years). Administered activity was calculated according to ¹³¹I uptake and gland weight. Methymazole was discontinued 6 days before treatment and T3 was maintained until administration of ¹³¹I-therapy. Euthyroidism was achieved in 88% of patients. At late follow-up, subclinical hypothyroidism was observed in 10 patients (6.7%) and overt hypothyroidism in 5 patients (3.3%). No pathological consequences or side effects of ¹³¹I-therapy were found during the 6.8+/-4.2 year follow-up period. Treatment of toxic nodular goiter with ¹³¹I-therapy, under combined thyrostatic-thyromimetic treatment is a simple, safe, well-tolerated, and effective procedure.

  4. Optimizing the Benefit of CNS Radiation Therapy in the Pediatric Population-PART 1: Understanding and Managing Acute and Late Toxicities.

    PubMed

    Rowe, Lindsay S; Krauze, Andra V; Ning, Holly; Camphausen, Kevin A; Kaushal, Aradhana

    2017-03-15

    Radiation therapy continues to be a key component in the management of pediatric malignancies. Increasing the likelihood of cure while minimizing late treatment toxicity in these young patients remains the primary goal. Within the realm of central nervous system neoplasms, efforts to further improve the efficacy of radiation therapy continue, while balancing risks of damage to uninvolved tissue. Radiation therapy can result in second malignancies, as well as cerebrovascular, neurotoxic, neurocognitive, endocrine, psychosocial, and quality-of-life effects. In this article we describe these acute and late effects and their implications, and we highlight strategies that have emerged to reduce both the volume of tissue that is irradiated and the radiation dose delivered. The feasibility, efficacy, and risks of these newer approaches to radiation therapy continue to be evaluated and monitored; robust outcome data are needed.

  5. Prostate Hypofractionated Radiation Therapy With Injection of Hyaluronic Acid: Acute Toxicities in a Phase 2 Study

    SciTech Connect

    Chapet, Olivier; Decullier, Evelyne; Bin, Sylvie; Faix, Antoine; Ruffion, Alain; Jalade, Patrice; Fenoglietto, Pascal; Udrescu, Corina; Enachescu, Ciprian; Azria, David

    2015-03-15

    Purpose: Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. Methods and Materials: The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Events version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. Results: From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. Conclusions: The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity.

  6. Geant4 simulation of the Elekta XVI kV CBCT unit for accurate description of potential late toxicity effects of image-guided radiotherapy.

    PubMed

    Brochu, F M; Burnet, N G; Jena, R; Plaistow, R; Parker, M A; Thomas, S J

    2014-12-21

    This paper describes the modelisation of the Elekta XVI Cone Beam Computed Tomography (CBCT) machine components with Geant4 and its validation against calibration data taken for two commonly used machine setups. Preliminary dose maps of simulated CBCTs coming from this modelisation work are presented. This study is the first step of a research project, GHOST, aiming to improve the understanding of late toxicity risk in external beam radiotherapy patients by simulating dose depositions integrated from different sources (imaging, treatment beam) over the entire treatment plan. The second cancer risk will then be derived from different models relating irradiation dose and second cancer risk.

  7. Geant4 simulation of the Elekta XVI kV CBCT unit for accurate description of potential late toxicity effects of image-guided radiotherapy

    NASA Astrophysics Data System (ADS)

    Brochu, F. M.; Burnet, N. G.; Jena, R.; Plaistow, R.; Parker, M. A.; Thomas, S. J.

    2014-12-01

    This paper describes the modelisation of the Elekta XVI Cone Beam Computed Tomography (CBCT) machine components with Geant4 and its validation against calibration data taken for two commonly used machine setups. Preliminary dose maps of simulated CBCTs coming from this modelisation work are presented. This study is the first step of a research project, GHOST, aiming to improve the understanding of late toxicity risk in external beam radiotherapy patients by simulating dose depositions integrated from different sources (imaging, treatment beam) over the entire treatment plan. The second cancer risk will then be derived from different models relating irradiation dose and second cancer risk.

  8. Increasing the rate of late toxicity by changing the score? A comparison of RTOG/EORTC and LENT/SOMA scores.

    PubMed

    Hoeller, Ulrike; Tribius, Silke; Kuhlmey, Antje; Grader, Kai; Fehlauer, Fabian; Alberti, Winfried

    2003-03-15

    The Radiation Therapy Oncology Group (RTOG) and Late Effects Normal Tissue Task Force subjective, objective, management, and analytic (LENT/SOMA) scores were compared in a group of breast cancer patients. The impact of the classification system on grading late effects was evaluated. Telangiectasia, skin pigmentation, and fibrosis were scored according to both LENT/SOMA and RTOG criteria. The results were compared with respect to up- or downgrading and correlated (Spearman's rho). Other side effects were recorded using LENT/SOMA criteria. Interobserver variability was calculated with Cohen's kappa. Two hundred fifty-nine subsequent relapse-free patients who underwent breast-conserving therapy between 1981 and 1995 were examined. The median dose of radiotherapy to the breast was 55 Gy. Adjuvant chemotherapy was given to 31 patients and tamoxifen to 52 patients. The median follow-up was 8 years. RTOG skin and s.c. tissue scales and LENT/SOMA breast and pigmentation scales were used. Two doctors examined 45 patients jointly. Of all patients, 20% had telangiectasia, 22% pigmentation, 43% fibrosis, 4% breast edema, 77% retraction/atrophy, and 54% pain. In comparison, when LENT/SOMA criteria were used, telangiectasia and pigmentation were upgraded in 34% and 36%, respectively, and telangiectasia was downgraded in 45%. Fibrosis correlated well (Spearman's rho 0.78, p = 0.01). An additional 356 side effects, mainly retraction/atrophy were observed in 226 patients using LENT/SOMA criteria. Interobserver variability was similar for both classification systems and ranged from Cohen's kappa 0.3 (retraction) to 0.91 (telangiectasia). LENT/SOMA criteria seem to be the better tool in grading and recording late radiation toxicity compared with the RTOG scale. There was some upgrading with the RTOG score when skin toxicity is evaluated. In contrast, fibrosis scores correlated very well. Adjustments of the LENT/SOMA scoring system should be considered to standardize reporting of late

  9. Preliminary Toxicity Analysis of 3-Dimensional Conformal Radiation Therapy Versus Intensity Modulated Radiation Therapy on the High-Dose Arm of the Radiation Therapy Oncology Group 0126 Prostate Cancer Trial

    SciTech Connect

    Michalski, Jeff M.; Yan, Yan; Watkins-Bruner, Deborah; Bosch, Walter R.; Winter, Kathryn; Galvin, James M.; Bahary, Jean-Paul; Morton, Gerard C.; Parliament, Matthew B.; Sandler, Howard M.

    2013-12-01

    Purpose: To give a preliminary report of clinical and treatment factors associated with toxicity in men receiving high-dose radiation therapy (RT) on a phase 3 dose-escalation trial. Methods and Materials: The trial was initiated with 3-dimensional conformal RT (3D-CRT) and amended after 1 year to allow intensity modulated RT (IMRT). Patients treated with 3D-CRT received 55.8 Gy to a planning target volume that included the prostate and seminal vesicles, then 23.4 Gy to prostate only. The IMRT patients were treated to the prostate and proximal seminal vesicles to 79.2 Gy. Common Toxicity Criteria, version 2.0, and Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late morbidity scores were used for acute and late effects. Results: Of 763 patients randomized to the 79.2-Gy arm of Radiation Therapy Oncology Group 0126 protocol, 748 were eligible and evaluable: 491 and 257 were treated with 3D-CRT and IMRT, respectively. For both bladder and rectum, the volumes receiving 65, 70, and 75 Gy were significantly lower with IMRT (all P<.0001). For grade (G) 2+ acute gastrointestinal/genitourinary (GI/GU) toxicity, both univariate and multivariate analyses showed a statistically significant decrease in G2+ acute collective GI/GU toxicity for IMRT. There were no significant differences with 3D-CRT or IMRT for acute or late G2+ or 3+ GU toxicities. Univariate analysis showed a statistically significant decrease in late G2+ GI toxicity for IMRT (P=.039). On multivariate analysis, IMRT showed a 26% reduction in G2+ late GI toxicity (P=.099). Acute G2+ toxicity was associated with late G3+ toxicity (P=.005). With dose–volume histogram data in the multivariate analysis, RT modality was not significant, whereas white race (P=.001) and rectal V70 ≥15% were associated with G2+ rectal toxicity (P=.034). Conclusions: Intensity modulated RT is associated with a significant reduction in acute G2+ GI/GU toxicity. There is a trend for a

  10. Practical modifications to the Time-to-Event Continual Reassessment Method for phase I cancer trials with fast patient accrual and late-onset toxicities

    PubMed Central

    Polley, Mei-Yin C.

    2014-01-01

    The goal of phase I cancer trials is to determine the highest dose of a treatment regimen with an acceptable toxicity rate. Traditional designs for phase I trials, such as the Continual Reassessment Method (CRM) and the 3+3 design, require each patient or a cohort of patients to be fully evaluated for the dose-limiting toxicity (DLT) before new patients can be enrolled. As such, the trial duration may be prohibitively long. The Time-to-Event Continual Reassessment Method (TITE-CRM, Cheung and Chappell, 2000) circumvents this limitation by allowing staggered patient accrual without the need for complete DLT follow-up of previously treated patients. However, in the setting of fast patient accrual and late-onset toxicities, the TITE-CRM results in overly aggressive dose escalation and exposes a considerable number of patients to toxic doses. We examine a modification to the TITE-CRM proposed by the original TITE-CRM creator and propose an alternative approach useful in this setting by incorporating an accrual suspension rule. A simulation study designed based on a neuro-oncology trial indicates that the modified methods provide a much improved degree of safety than the TITE-CRM while maintaining desirable design accuracy. The practical aspects of the proposed designs are discussed. The modifications presented are useful when planning phase I trials involving chemoradiation therapy. PMID:21590790

  11. Acute and late vaginal toxicity after adjuvant high-dose-rate vaginal brachytherapy in patients with intermediate risk endometrial cancer: is local therapy with hyaluronic acid of clinical benefit?

    PubMed Central

    Delishaj, Durim; Fabrini, Maria Grazia; Gonnelli, Alessandra; Morganti, Riccardo; Perrone, Franco; Tana, Roberta; Paiar, Fabiola; Gadducci, Angiolo

    2016-01-01

    Purpose The aim of the present study was to evaluate the effectiveness of hyaluronic acid (HA) in the prevention of acute and late vaginal toxicities after high-dose-rate (HDR) vaginal brachytherapy (BT). Material and methods Between January 2011 and January 2015, we retrospectively analyzed 126 patients with endometrial cancer who underwent extrafascial hysterectomy with or without lymphadenectomy and adjuvant HDR-vaginal BT +/– adjuvant chemotherapy. The total dose prescription was 21 Gy in 3 fractions (one fraction for week). Vaginal ovules containing 5 mg of HA were given for whole duration of vaginal BT and for the two following weeks. Acute and late toxicities were evaluated according to CTCAE vs 4.02. Results According to the revised FIGO 2009 classification, most tumors were in stage IA (30.9%) and in stage IB (57.9%). Thirty-three patients (26.2%) received adjuvant chemotherapy before vaginal BT. Five-year disease-free survival (DFS) and five-year overall survival (OS) were 88% and 93%, respectively. The most common grade 1-2 acute toxicities were vaginal inflammation (18 patients, 14.3%) and dyspareunia (7 patients, 5.5%). Two patients (1.6%) had more than one toxicity. Late toxicity occurred in 20 patients (15.9%). Grade 1-2 late toxicities were fibrosis (14 patients, 11.1%) and telangiectasias (7 patients, 5.5%). Six patients (4.8%) had more than one late toxicity. No grade 3 or higher acute or late toxicities were observed. Conclusions These results appear to suggest that the local therapy with HA is of clinical benefit for intermediate risk endometrial cancer patients who receive adjuvant HDR-vaginal BT after surgery. A randomized trial comparing HA treatment vs. no local treatment in this clinical setting is warranted to further evaluate the efficacy of HA in preventing vaginal BT-related vaginal toxicity. PMID:28115957

  12. 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

  13. Radiation-induced Vulvar Angiokeratoma Along with Other Late Radiation Toxicities after Carcinoma Cervix: A Rare Case Report

    PubMed Central

    Bhandari, Virendra; Naik, Ayush; Gupta, K L; Kausar, Mehlam

    2016-01-01

    Angiokeratoma including vulvar angiokeratoma is a very rare complication of radiation. Exact incidence is still unknown, we report a case that developed radiation-induced angiokeratoma of skin in the vulvar region along with other late radiation sequelae in the form of bone fracture, new bone formation, bone marrow widening, muscle hypertrophy, and subcutaneous fibrosis, 18 years after radiotherapy to the pelvic region for the treatment of carcinoma cervix. All these late radiation sequel are rare to be seen in a single patient, and none of the case reports could be found in the world literature. PMID:27057045

  14. Predictors of Grade 3 or Higher Late Bowel Toxicity in Patients Undergoing Pelvic Radiation for Cervical Cancer: Results From a Prospective Study

    SciTech Connect

    Chopra, Supriya; Dora, Tapas; Chinnachamy, Anand N.; Thomas, Biji; Kannan, Sadhna; Engineer, Reena; Mahantshetty, Umesh; Phurailatpam, Reena; Paul, Siji N.; Shrivastava, Shyam Kishore

    2014-03-01

    Purpose: The present study investigates relationship between dose–volume parameters and severe bowel toxicity after postoperative radiation treatment (PORT) for cervical cancer. Methods and Materials: From June 2010 to December 2012, a total of 71 patients undergoing PORT were included. Small bowel (SB) and large bowel (LB) loops were contoured 2 cm above the target volume. The volume of SB and LB that received 15 Gy, 30 Gy, and 40 Gy was calculated (V15 SB, V15 LB, V30 SB, V30 LB, V40 SB, V 40 LB). On follow-up, bowel toxicity was scored using Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. A reciever operating characteristic (ROC) curve identified volume thresholds that predicted for grade 3 or higher toxicity with highest specificity. All data was dichotomized across these identified cut-off values. Univariate and multivariate analysis was performed using SPSS, version 15. Results: The median patient age was 47 years (range, 35-65 years). Of the 71 patients, 46 received image-guided intensity modulated radiation therapy, and 25 received conformal radiation (50 Gy in 25 fractions for 5 weeks). Overall, 63 of 71 patients received concurrent chemotherapy. On a median follow-up of 18 months (range, 8-29 months), grade 2 or higher bowel toxicity was seen in 22 of 71 patients (30.9%) and grade 3 or higher bowel toxicity was seen in 9 patients (12.6%). On univariate analysis, V15 SB <275 cc (P=.01), V30 SB <190 cc (P=.02), V40 SB <150 cc (P=.01), and V15 LB <250 cc (P=.03), and V40 LB <90 cc (P=.04) predicted for absence of grade 3 or higher toxicity. No other patient- or treatment-related factors were statistically significant. On multivariate analysis, only V15 SB (P=.002) and V15 LB (P=.03) were statistically significant. Conclusions: V 15 Gy SB and LB are independent predictors of late grade 3 or higher toxicity. Restricting V15 SB and V15 LB to <275 cc and <250 cc can reduce grade 3 or higher toxicity to less than 5%.

  15. Predictors of grade 3 or higher late bowel toxicity in patients undergoing pelvic radiation for cervical cancer: results from a prospective study.

    PubMed

    Chopra, Supriya; Dora, Tapas; Chinnachamy, Anand N; Thomas, Biji; Kannan, Sadhna; Engineer, Reena; Mahantshetty, Umesh; Phurailatpam, Reena; Paul, Siji N; Shrivastava, Shyam Kishore

    2014-03-01

    The present study investigates relationship between dose-volume parameters and severe bowel toxicity after postoperative radiation treatment (PORT) for cervical cancer. From June 2010 to December 2012, a total of 71 patients undergoing PORT were included. Small bowel (SB) and large bowel (LB) loops were contoured 2 cm above the target volume. The volume of SB and LB that received 15 Gy, 30 Gy, and 40 Gy was calculated (V15 SB, V15 LB, V30 SB, V30 LB, V40 SB, V 40 LB). On follow-up, bowel toxicity was scored using Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. A reciever operating characteristic (ROC) curve identified volume thresholds that predicted for grade 3 or higher toxicity with highest specificity. All data was dichotomized across these identified cut-off values. Univariate and multivariate analysis was performed using SPSS, version 15. The median patient age was 47 years (range, 35-65 years). Of the 71 patients, 46 received image-guided intensity modulated radiation therapy, and 25 received conformal radiation (50 Gy in 25 fractions for 5 weeks). Overall, 63 of 71 patients received concurrent chemotherapy. On a median follow-up of 18 months (range, 8-29 months), grade 2 or higher bowel toxicity was seen in 22 of 71 patients (30.9%) and grade 3 or higher bowel toxicity was seen in 9 patients (12.6%). On univariate analysis, V15 SB <275 cc (P=.01), V30 SB <190 cc (P=.02), V40 SB <150 cc (P=.01), and V15 LB <250 cc (P=.03), and V40 LB <90 cc (P=.04) predicted for absence of grade 3 or higher toxicity. No other patient- or treatment-related factors were statistically significant. On multivariate analysis, only V15 SB (P=.002) and V15 LB (P=.03) were statistically significant. V 15 Gy SB and LB are independent predictors of late grade 3 or higher toxicity. Restricting V15 SB and V15 LB to <275 cc and <250 cc can reduce grade 3 or higher toxicity to less than 5%. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Adjuvant therapy of resectable rectal cancer.

    PubMed

    Minsky, Bruce D

    2002-08-01

    The two conventional treatments for clinically resectable rectal cancer are surgery followed by postoperative combined modality therapy and preoperative combined modality therapy followed by surgery and postoperative chemotherapy. Preoperative therapy (most commonly combined modality therapy) has gained acceptance as a standard adjuvant therapy. The potential advantages of the preoperative approach include decreased tumor seeding, less acute toxicity, increased radiosensitivity due to more oxygenated cells, and enhanced sphincter preservation. There are a number of new chemotherapeutic agents that have been developed for the treatment of patients with colorectal cancer. Phase I/II trials examining the use of new chemotherapeutic agents in combination with pelvic radiation therapy are in progress.

  17. Co-administration of betulinic acid and methamphetamine causes toxicity to dopaminergic and serotonergic nerve terminals in the striatum of late adolescent rats

    PubMed Central

    Killinger, Bryan; Shah, Mrudang; Moszczynska, Anna

    2013-01-01

    Psychostimulant methamphetamine (METH) is toxic to dopaminergic and serotonergic striatal nerve terminals in adult, but not in adolescent, brain. Betulinic acid (BA) and its derivatives are promising anti-HIV agents with some toxic properties. Many METH users, particularly young men, are HIV-positive; therefore, they might be treated with BA or its derivative for HIV infection. It is not known whether BA, or any of its derivatives, is neurotoxic in combination with METH in adolescent brain. The present study investigated the effects of BA and binge METH in the striatum in late adolescent rats. BA or METH alone did not decrease the levels of dopaminergic or serotonergic markers in the striatum whereas BA and METH together decreased these markers in a BA dose-dependent manner. BA and METH combination also caused decreases in the levels of mitochondrial complex I in the same manner; BA alone only slightly decreased the levels of the enzyme in striatal synaptosomes. BA or METH alone increased cytochrome c. METH alone decreased parkin, increased complex II and striatal BA levels. These results suggest that METH in combination with BA can be neurotoxic to dopaminergic and serotonergic striatal nerve terminals in late adolescent brain via mitochondrial dysfunction and parkin deficit. PMID:24151877

  18. Final results of local-regional control and late toxicity of RTOG 9003: a randomized trial of altered fractionation radiation for locally advanced head and neck cancer.

    PubMed

    Beitler, Jonathan J; Zhang, Qiang; Fu, Karen K; Trotti, Andy; Spencer, Sharon A; Jones, Christopher U; Garden, Adam S; Shenouda, George; Harris, Jonathan; Ang, Kian K

    2014-05-01

    To test whether altered radiation fractionation schemes (hyperfractionation [HFX], accelerated fractionation, continuous [AFX-C], and accelerated fractionation with split [AFX-S]) improved local-regional control (LRC) rates for patients with squamous cell cancers (SCC) of the head and neck when compared with standard fractionation (SFX) of 70 Gy. Patients with stage III or IV (or stage II base of tongue) SCC (n=1076) were randomized to 4 treatment arms: (1) SFX, 70 Gy/35 daily fractions/7 weeks; (2) HFX, 81.6 Gy/68 twice-daily fractions/7 weeks; (3) AFX-S, 67.2 Gy/42 fractions/6 weeks with a 2-week rest after 38.4 Gy; and (4) AFX-C, 72 Gy/42 fractions/6 weeks. The 3 experimental arms were to be compared with SFX. With patients censored for LRC at 5 years, only the comparison of HFX with SFX was significantly different: HFX, hazard ratio (HR) 0.79 (95% confidence interval 0.62-1.00), P=.05; AFX-C, 0.82 (95% confidence interval 0.65-1.05), P=.11. With patients censored at 5 years, HFX improved overall survival (HR 0.81, P=.05). Prevalence of any grade 3, 4, or 5 toxicity at 5 years; any feeding tube use after 180 days; or feeding tube use at 1 year did not differ significantly when the experimental arms were compared with SFX. When 7-week treatments were compared with 6-week treatments, accelerated fractionation appeared to increase grade 3, 4 or 5 toxicity at 5 years (P=.06). When the worst toxicity per patient was considered by treatment only, the AFX-C arm seemed to trend worse than the SFX arm when grade 0-2 was compared with grade 3-5 toxicity (P=.09). At 5 years, only HFX improved LRC and overall survival for patients with locally advanced SCC without increasing late toxicity. Published by Elsevier Inc.

  19. Preoperative radiotherapy in rectal cancer treatment -- is it really a gold standard?

    PubMed

    Pătraşcu, Tr; Doran, H; Mihalache, O

    2014-01-01

    Preoperative radiotherapy in the treatment of rectal cancer was thought to be an achievement of similar importance to total mesorectal excision (TME), for the therapeutic management of rectal malignancies. However, numerous criticisms have been discussed in this field lately. We have analysed the two main purposes of preoperative radiation: possible sphincter preservation and the conversion of a non-resectable tumor into a resectable one in a series of 31 consecutive patients, operated in our clinic. In 20 of them, preoperative radio chemoradiotherapy was applied, while 11 patients were firstly operated and then irradiated. The surgical procedure included total mesorectal excision in 30 patients, as part of a low anterior resection,in 13 cases and of an abdominal perineal resection, in the other 17 cases. We have found that preoperative radiotherapy improves the local recurrence rate but has no influence on the overall survival rate. However, we should not overlook the adverse effects of this method: toxicity of radiotherapy on the small bowel and the urinary bladder, the healing of the perineal wounds and the risk of anastomotic leaks. We concluded in favor of elective preoperative radiotherapy in selected cases: any T4 tumors, T3 tumors which threaten the mesorectal fascia on MRI, whenever there is a suspicion of nodal involvement and also for very low tumors. Celsius.

  20. Progress in the treatment of locally advanced clinically resectable rectal cancer.

    PubMed

    Minsky, Bruce D

    2011-12-01

    There have been significant developments in the adjuvant treatment of locally advanced clinically resectable (T3 and/or N+) rectal cancer. Postoperative systemic chemotherapy plus concurrent pelvic irradiation (chemoradiation) significantly improves local control and survival compared with surgery alone. The German Rectal Cancer Trial confirmed that when chemoradiation is delivered preoperatively there is a significant decrease in acute and late toxicity and a corresponding increase in local control and sphincter preservation. Despite these advances, controversies remain. Among these controversies are the role of short-course radiation, whether postoperative adjuvant chemotherapy is necessary for all patients, and if the type of surgery after chemoradiation can be modified based on tumor response. Are there more accurate imaging techniques and/or molecular markers to help identify patients with positive pelvic nodes with the goal of reducing the chance of overtreatment with preoperative therapy. Will more effective systemic agents both improve outcome and modify the need for pelvic irradiation? This review examines the advances in chemoradiation as well as addresses these and other opportunities for improvement.

  1. Limited toxicity of NH(x) pulses on an early and late successional tropical seagrass species: interactions with pH and light level.

    PubMed

    Christianen, M J A; van der Heide, T; Bouma, T J; Roelofs, J G M; van Katwijk, M M; Lamers, L P M

    2011-07-01

    Seagrasses have declined at a global scale due to light reduction and toxicity events, caused by eutrophication and increased sediment loading. Although several studies have tested effects of light reduction and toxicants on seagrasses, there is at present no information available on their interacting effects. In a full-factorial 5-day laboratory experiment, we studied short-term interactive effects of light conditions, pH and reduced nitrogen (NH(x)) in the water layer, mimicking pulses of river discharge, on the tropical early successional species Halodule uninervis and the late successional species Thalassia hemprichii. In contrast to recent results reported for the temperate species Zostera marina, increased NH(x) supply did not affect leaf mortality or photochemical efficiency in H. uninervis and in 7 out of 8 treatments for T. hemprichii. However, both tropical species demonstrated striking differences in nitrogen accumulation, free amino acid composition and free NH₃ accumulation. The increase in tissue nitrogen content was two times higher for H. uninervis than for T. hemprichii. Nitrogen stored as free amino acids (especially asparagine) only increased in H. uninervis. High pH only affected T. hemprichii, but only when not shaded, by doubling its free NH₃ concentrations, concomitantly decreasing its photosynthetic efficiency. Our results indicate that the early successional H. uninervis has higher tolerance to high NH(x) loads as compared to the late successional T. hemprichii. H. uninervis was better able to avoid toxic internal NH(x) levels by further assimilating glutamine into asparagine in contrast to T. hemprichii. Moreover, both tropical species seem to cope much better with high NH(x) than the temperate Z. marina. The implications for the distribution and succession of seagrass species under high nutrient loads are discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Late tissue-specific toxicity of total body irradiation and busulfan in a murine bone marrow transplant model.

    PubMed

    Down, J D; Berman, A J; Warhol, M; Van Dijken, P J; Ferrara, J L; Yeap, B; Hellman, S; Mauch, P M

    1989-07-01

    Total body irradiation (TBI) and busulfan were compared for late effects in a murine model of bone marrow transplantation (BMT). Male C57BL/6 mice were given fractionated TBI or busulfan given in 4 equal daily doses followed by infusion of 10(7) syngeneic bone marrow cells. Total doses of 16.4 Gy TBI and 3.4 mg busulfan were chosen for their equivalence in inducing near complete engraftment of allogeneic marrow from donor mice of the LP strain. The two treatment groups had a late wave of mortality starting at about 80 weeks after transplantation. Specific tissue damage was manifested in bone marrow stem cells, splenic T-cell precursors, hair greying and cataract formation for both TBI and busulfan but to varying degrees. Severe nephrotoxicity and anemia were observed only after TBI. Although both busulfan and TBI kill early marrow stem cells and are effective preparative agents in bone marrow transplantation, their effects on other stem cell and organ systems are not similar. In addition, many of the injuries seen are late to occur. The delayed expression of injury deserves careful long-term evaluation of BMT recipients before the therapeutic potential of effective preparative regimens can be fully appreciated.

  3. Comparing the RTOG/EORTC and LENT-SOMA scoring systems for the evaluation of late skin toxicity after (125)I seed brachytherapy for parotid gland cancer.

    PubMed

    Mao, Ming-Hui; Feng, Zhien; Li, Hua; Qin, Li-Zheng; Li, Jian-Hua; Huang, Xin; Xing, Ru-Dong; Zhang, Jie; Zhang, Jian-Guo; Han, Zheng-Xue

    The Radiation Therapy Oncology Group (RTOG) and Late Effects Normal Tissue Task Force-Subjective, Objective, Management and Analytic (LENT-SOMA) scoring systems were compared for grading late skin effects after iodine-125 seed brachytherapy in parotid gland cancer patients. A total of 109 patients diagnosed with parotid gland carcinoma were treated postoperatively with iodine-125 seed brachytherapy at a dose of 100-120 Gy. After 6-24 months of followup, telangiectasia, skin pigmentation, atrophy, fibrosis, and ulceration were scored according to both RTOG and LENT-SOMA scale criteria. The strength of correlation between the scores and the interobserver variability were calculated. Of 109 patients, 22.9% had telangiectasia; 78.9%, pigmentation; 28.4%, fibrosis; 4.6%, edema; 0.9%, ulceration; 37.6%, retraction and/or atrophy; 22.9%, sensation change; and 11%, scaliness and/or roughness. Compared with RTOG, LENT-SOMA criteria resulted in the upgrading of pigmentation in 17% of cases, the downgrading of all instances of telangiectasia and the downgrading of one instance of Grade 4 ulceration to Grade 3. Between the two scales, fibrosis and atrophy correlated well (Spearman ρ, 0.992, 0.986). An additional 229 side effects were observed using LENT-SOMA criteria. The LENT-SOMA scale was more accurate than the RTOG scale for the evaluation of late skin and subcutaneous toxicity. The downgrading of telangiectasia and upgrading of pigmentation with the LENT-SOMA scale reflected the patients' conditions better than the scores obtained with the RTOG scale. The assessment of fibrosis and atrophy correlated well between the two scales. The use of the sum of the individual scores of the LENT-SOMA is therefore advocated. The addition of decreased sweating and the removal of the alopecia (scalp) metric should be considered to standardize the reporting of late radiation morbidity. Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  4. 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

    SciTech Connect

    Hrycushko, B; Chopra, R; Futch, C; Bing, C; Wodzak, M; Stojadinovic, S; Jiang, S; Medin, P

    2015-06-15

    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 intake 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

  5. Dose escalation to the dominant intraprostatic lesion defined by sextant biopsy in a permanent prostate I-125 implant: a prospective comparative toxicity analysis.

    PubMed

    Gaudet, Marc; Vigneault, Eric; Aubin, Sylviane; Varfalvy, Nicolas; Harel, François; Beaulieu, L; Martin, André-Guy

    2010-05-01

    Using real-time intraoperative inverse-planned permanent seed prostate implant (RTIOP/PSI), multiple core biopsy maps, and three-dimensional ultrasound guidance, we planned a boost volume (BV) within the prostate to which hyperdosage was delivered selectively. The aim of this study was to investigate the potential negative effects of such a procedure. Patients treated with RTIOP/PSI for localized prostate cancer with topographic biopsy results received an intraprostatic boost (boost group [BG]). They were compared with patients treated with a standard plan (reference group [RG]). Plans were generated using a simulated annealing inverse planning algorithm. Prospectively recorded urinary, rectal, and sexual toxicities and dosimetric parameters were compared between groups. The study included 120 patients treated with boost technique who were compared with 70 patients treated with a standard plan. Boost technique did not significantly change the number of seeds (55.1/RG vs. 53.6/BG). The intraoperative prostate V150 was slightly higher in BG (75.2/RG vs. 77.2/BG, p = 0.039). Urethra V100, urethra D90, and rectal D50 were significantly lower in the BG. No significant differences were seen in acute or late urinary, rectal, or sexual toxicities. Because there were no differences between the groups in acute and late toxicities, we believe that BV can be planned and delivered to the dominant intraprostatic lesion without increasing toxicity. It is too soon to say whether a boost technique will ultimately increase local control.

  6. Bevacizumab, Capecitabine, Amifostine, and Preoperative Hypofractionated Accelerated Radiotherapy (HypoArc) for Rectal Cancer: A Phase II Study

    SciTech Connect

    Koukourakis, Michael I.; Tsoutsou, Pelagia; Chloropoulou, Pelagia A.; Manolas, Kostantinos; Sivridis, Efthimios

    2011-06-01

    Purpose: Bevacizumab has established therapeutic activity in patients with metastatic colorectal cancer, and anti-vascular endothelial growth factor therapy enhances the activity of radiotherapy in experimental models. We assessed the feasibility and efficacy of preoperative radiochemotherapy combined with bevacizumab in patients with rectal cancer. Methods and Materials: Nineteen patients with radiologic T3 and/or N+ rectal carcinoma were treated with preoperative conformal hypofractionated accelerated radiotherapy (3.4 Gy in 10 consecutive fractions) supported with amifostine (500-1,000 mg daily), capecitabine (600 mg/m{sup 2} twice daily, 5 days per week), and bevacizumab (5 mg/kg every 2 weeks for 2 cycles). Surgery followed 6 weeks after the end of radiotherapy. A cohort of 14 sequential patients treated with the same regimen without bevacizumab was available for comparison. Results: Grade 2 or 3 diarrhea was noted in 7 of 19 patients (36.8%), which was statistically worse than patients receiving the same regimen without bevacizumab (p = 0.01). A higher incidence of Grade 2 or 3 proctalgia was also noted (21.1%) (p = 0.03). Bladder and skin toxicity was negligible. All toxicities regressed completely within 2 weeks after the end of therapy. Pathologic complete and partial response was noted in 7 of 19 cases (36.8%) and 8 of 19 cases (42.1%). Within a median follow-up of 21 months, none of the patients has had late complications develop and only 1 of 18 evaluable cases (5.5%) has had locoregional relapse. Conclusions: Bevacizumab can be safely combined with hypofractionated radiotherapy and capecitabine as a preoperative radiochemotherapy regimen for patients with rectal cancer. The high pathologic complete response rates urges the testing of bevacizumab in randomized studies.

  7. Bladder and rectal complications following radiotherapy for cervix cancer

    SciTech Connect

    Stryker, J.A.; Bartholomew, M.; Velkley, D.E.; Cunningham, D.E.; Mortel, R.; Craycraft, G.; Shafer, J.

    1988-01-01

    One-hundred and thirty-two patients with cervix carcinoma who were treated with whole pelvis irradiation and two intracavitary applications had bladder and rectal dosimetry during brachytherapy with contrast agents placed into the bladder and rectum prior to orthogonal simulator radiographs. Doses were computer calculated at points A and B, F (bladder), R1 (rectum), and R2 (rectosigmoid). Late occurring bladder and rectal complications were graded on a severity scale of 1 to 3, and 14% had grade 2 or 3 injuries (9% developed fistulas). Statistical evaluation of the data showed that severe bladder and rectal injuries occur more commonly in stage IIIA and IIIB disease and in those receiving high external beam doses (5000 rad +). Analysis of variance tests revealed a significant correlation of brachytherapy dose to points R1 and R2 with severe rectal injuries but there was not a correlation of dose to F with bladder injuries. Nor was there correlation of injuries with dose to point A or the milligram-hour dose. We conclude that our technique for rectal dosimetry is adequate but that an improved technique of bladder dosimetry is needed. Also, when combining whole pelvis irradiation with two intracavitary applications (4000 rad to point A), the whole pelvis dose should probably not exceed 4000-4500 rad.

  8. Human Collagen Injections to Reduce Rectal Dose During Radiotherapy

    SciTech Connect

    Noyes, William R.; Hosford, Charles C.; Schultz, Steven E.

    2012-04-01

    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 perirectal 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.

  9. Human collagen injections to reduce rectal dose during radiotherapy.

    PubMed

    Noyes, William R; Hosford, Charles C; Schultz, Steven E

    2012-04-01

    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. 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 perirectal 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. 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. 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. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. SCID patients with ARTEMIS vs RAG deficiencies following HCT: increased risk of late toxicity in ARTEMIS-deficient SCID

    PubMed Central

    Leroy, Sandrine; Ege, Markus J.; Pannicke, Ulrich; Schwarz, Klaus; Schulz, Ansgar S.; Hoenig, Manfred; Sparber-Sauer, Monika; Gatz, Susanne A.; Denzer, Christian; Blanche, Stephane; Moshous, Despina; Picard, Capucine; Horn, Biljana N.; de Villartay, Jean-Pierre; Cavazzana, Marina; Debatin, Klaus-Michael; Friedrich, Wilhelm; Fischer, Alain; Cowan, Morton J.

    2014-01-01

    A subgroup of severe combined immunodeficiencies (SCID) is characterized by lack of T and B cells and is caused by defects in genes required for T- and B-cell receptor gene rearrangement. Several of these genes are also involved in nonhomologous end joining of DNA double-strand break repair, the largest subgroup consisting of patients with T−B−NK+SCID due to DCLRE1C/ARTEMIS defects. We postulated that in patients with ARTEMIS deficiency, early and late complications following hematopoietic cell transplantation might be more prominent compared with patients with T−B−NK+SCID caused by recombination activating gene 1/2 (RAG1/2) deficiencies. We analyzed 69 patients with ARTEMIS and 76 patients with RAG1/2 deficiencies who received transplants from either HLA-identical donors without conditioning or from HLA-nonidentical donors without or with conditioning. There was no difference in survival or in the incidence or severity of acute graft-versus-host disease regardless of exposure to alkylating agents. Secondary malignancies were not observed. Immune reconstitution was comparable in both groups, however, ARTEMIS-deficient patients had a significantly higher occurrence of infections in long-term follow-up. There is a highly significant association between poor growth in ARTEMIS deficiency and use of alkylating agents. Furthermore, abnormalities in dental development and endocrine late effects were associated with alkylation therapy in ARTEMIS deficiency. PMID:24144642

  11. SCID patients with ARTEMIS vs RAG deficiencies following HCT: increased risk of late toxicity in ARTEMIS-deficient SCID.

    PubMed

    Schuetz, Catharina; Neven, Benedicte; Dvorak, Christopher C; Leroy, Sandrine; Ege, Markus J; Pannicke, Ulrich; Schwarz, Klaus; Schulz, Ansgar S; Hoenig, Manfred; Sparber-Sauer, Monika; Gatz, Susanne A; Denzer, Christian; Blanche, Stephane; Moshous, Despina; Picard, Capucine; Horn, Biljana N; de Villartay, Jean-Pierre; Cavazzana, Marina; Debatin, Klaus-Michael; Friedrich, Wilhelm; Fischer, Alain; Cowan, Morton J

    2014-01-09

    A subgroup of severe combined immunodeficiencies (SCID) is characterized by lack of T and B cells and is caused by defects in genes required for T- and B-cell receptor gene rearrangement. Several of these genes are also involved in nonhomologous end joining of DNA double-strand break repair, the largest subgroup consisting of patients with T(-)B(-)NK(+)SCID due to DCLRE1C/ARTEMIS defects. We postulated that in patients with ARTEMIS deficiency, early and late complications following hematopoietic cell transplantation might be more prominent compared with patients with T(-)B(-)NK(+)SCID caused by recombination activating gene 1/2 (RAG1/2) deficiencies. We analyzed 69 patients with ARTEMIS and 76 patients with RAG1/2 deficiencies who received transplants from either HLA-identical donors without conditioning or from HLA-nonidentical donors without or with conditioning. There was no difference in survival or in the incidence or severity of acute graft-versus-host disease regardless of exposure to alkylating agents. Secondary malignancies were not observed. Immune reconstitution was comparable in both groups, however, ARTEMIS-deficient patients had a significantly higher occurrence of infections in long-term follow-up. There is a highly significant association between poor growth in ARTEMIS deficiency and use of alkylating agents. Furthermore, abnormalities in dental development and endocrine late effects were associated with alkylation therapy in ARTEMIS deficiency.

  12. Hodgkin's disease in children: Treatment with MOPP and low-dose, extended field irradiation without laparotomy. Late results and toxicity

    SciTech Connect

    Jenkin, D.; Doyle, J.; Berry, M.; Blanchette, V.; Chan, H.; Doherty, M.; Freedman, M.; Greenberg, M.; Panzarella, T.; Saunders, F. )

    1990-01-01

    The 10 year results of a trial of bimodal treatment of Hodgkin's disease in children with 6 cycles of MOPP and low-dose extended field irradiation, without staging laparotomy, were for 57 children in all stages as follows: survival 85%, relapse-free survival 80%, and survival-free of second relapse 86%. There were three fatal toxic events, two due to viral infection and one to a second malignant tumor (NHL). Three other patients developed a second malignant tumour, and one developed a thyroid adenoma. No patient developed acute leukemia. These results are compared with the results of treatment of surgically staged children by extended field irradiation alone, with bimodal treatment reserved for relapse or advanced disease at diagnosis. Initial bimodal treatment improved the overall 10 year survival free from a second relapse rate by 20% (86% vs. 66%). No major difference in treatment toxicity between these two groups has emerged during the first 10 years of follow-up. We conclude that, except for favourable CS-1 presentations, children with Hodgkin's disease confined to the lymphatic system should be given bimodal treatment, but that the least morbid effective combination remains to be determined.

  13. Acute and Late Toxicity After Dose Escalation to 82 GyE Using Conformal Proton Radiation for Localized Prostate Cancer: Initial Report of American College of Radiology Phase II Study 03-12

    SciTech Connect

    Coen, John J.; Bae, Kyounghwa; Zietman, Anthony L.; Patel, Baldev; Shipley, William U.; Slater, Jerry D.; Rossi, Carl J.

    2011-11-15

    Purpose: Several randomized trials have shown a benefit of dose escalation to 78 to 79 Gy for men treated with external radiation for localized prostate cancer. Single-institution data suggest a benefit with even higher doses. American College of Radiology 03-12 is a Phase II trial testing the safety and efficacy of 82 GyE (Gray equivalent) delivered with conformal proton radiation. Methods and Materials: From 2003-2006, 85 men with localized prostate cancer were accrued to American College of Radiology 03-12. Eighty-four were eligible for analysis. They were treated with conformal proton radiation alone to a total dose of 82 GyE. The study was designed to test whether the rate of 18-month Grade 3+ late toxicity was greater than 10%. Results: The median follow-up was 31.6 months. Regarding treatment-related acute toxicity, there were 39 Grade 1 cases (46%), 19 Grade 2 cases (23%) and 2 Grade 3 cases (2%). Regarding genitourinary/gastrointestinal toxicity, there were 42 Grade 1 cases (50%), 12 Grade 2 cases (14%) and 1 Grade 3 case (1%). Regarding late toxicity, there were 28 Grade 1 cases (33%), 22 Grade 2 cases (26%), 6 Grade 3 cases (7%), and 1 Grade 4 case (1%). The late genitourinary/gastrointestinal rates were the same. The estimated rate of Grade 3+ late toxicity at 18 months was 6.08%. Conclusions: Although not free of late toxicity, 82 GyE at 2 GyE per fraction delivered with conformal proton radiation did not exceed the late morbidity target tested in this trial. There was sufficient morbidity, however, that this may be the maximal dose that can be delivered safely with this technique and fractionation.

  14. Second cancers and late toxicities after treatment of aggressive non-Hodgkin lymphoma with the ACVBP regimen: a GELA cohort study on 2837 patients.

    PubMed

    André, Marc; Mounier, Nicolas; Leleu, Xavier; Sonet, Anne; Brice, Pauline; Henry-Amar, Michel; Tilly, Hervé; Coiffier, Bertrand; Bosly, André; Morel, Pierre; Haioun, Corinne; Gaulard, Philippe; Reyes, Felix; Gisselbrecht, Christian

    2004-02-15

    The survival of patients with aggressive non-Hodgkin lymphoma (NHL) is increasing, but the incidence of secondary cancer and late toxicity is poorly defined for those treated with cyclophosphamide-hydroxydaunomycin/doxorubicin-Oncovin-prednisone (CHOP)-like chemotherapy. From February 1984 to January 1998, 2837 patients with aggressive NHL received the control-arm chemotherapy adriamycin-cyclophosphamide-vindesine-bleomycin-prednisone (ACVBP) in 3 consecutive Groupe d'Etude des Lymphomes de l'Adulte (GELA) studies. With a median follow-up time of 74 months, the 5-year overall and event-free survival rates were 60% and 52%. Two hundred two occurrences of nonneoplastic late toxicity were reported, resulting in a 5.35% cumulative probability of incidence at 7 years. Eighty-one second tumors developed, for which the 7-year cumulative incidence rate was 2.75%; 64 were solid tumors, and 17 were hematologic malignancies. In multivariate analysis, age was the only risk factor for the second development of cancer. Epidemiologic analysis allowed a comparison of this NHL group with the general population. Considering all tumors, no excess of second cancer was observed. In the male population, however, there was an excess of lung cancer (standardized incidence ratio [SIR], 2.45; P <.001) and myelodysplastic syndrome/acute myelocytic leukemia (MDS/AML) (SIR, 5.65; P =.006), and in the female population there was an excess of MDS/AML (SIR, 19.9; P <.001). With a long follow-up, the ACVBP regimen was highly effective for the treatment of aggressive NHL. Increases occurred in secondary MDS/AML and in lung cancer among men.

  15. Final Results of Local-Regional Control and Late Toxicity of RTOG 9003: A Randomized Trial of Altered Fractionation Radiation for Locally Advanced Head and Neck Cancer

    SciTech Connect

    Beitler, Jonathan J.; Zhang, Qiang; Fu, Karen K.; Trotti, Andy; Spencer, Sharon A.; Jones, Christopher U.; Garden, Adam S.; Shenouda, George; Harris, Jonathan; Ang, Kian K.

    2014-05-01

    Purpose: To test whether altered radiation fractionation schemes (hyperfractionation [HFX], accelerated fractionation, continuous [AFX-C], and accelerated fractionation with split [AFX-S]) improved local-regional control (LRC) rates for patients with squamous cell cancers (SCC) of the head and neck when compared with standard fractionation (SFX) of 70 Gy. Methods and Materials: Patients with stage III or IV (or stage II base of tongue) SCC (n=1076) were randomized to 4 treatment arms: (1) SFX, 70 Gy/35 daily fractions/7 weeks; (2) HFX, 81.6 Gy/68 twice-daily fractions/7 weeks; (3) AFX-S, 67.2 Gy/42 fractions/6 weeks with a 2-week rest after 38.4 Gy; and (4) AFX-C, 72 Gy/42 fractions/6 weeks. The 3 experimental arms were to be compared with SFX. Results: With patients censored for LRC at 5 years, only the comparison of HFX with SFX was significantly different: HFX, hazard ratio (HR) 0.79 (95% confidence interval 0.62-1.00), P=.05; AFX-C, 0.82 (95% confidence interval 0.65-1.05), P=.11. With patients censored at 5 years, HFX improved overall survival (HR 0.81, P=.05). Prevalence of any grade 3, 4, or 5 toxicity at 5 years; any feeding tube use after 180 days; or feeding tube use at 1 year did not differ significantly when the experimental arms were compared with SFX. When 7-week treatments were compared with 6-week treatments, accelerated fractionation appeared to increase grade 3, 4 or 5 toxicity at 5 years (P=.06). When the worst toxicity per patient was considered by treatment only, the AFX-C arm seemed to trend worse than the SFX arm when grade 0-2 was compared with grade 3-5 toxicity (P=.09). Conclusions: At 5 years, only HFX improved LRC and overall survival for patients with locally advanced SCC without increasing late toxicity.

  16. 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.

  17. Diverse developmental toxicity of di-n-butyl phthalate in both sexes of rat offspring after maternal exposure during the period from late gestation through lactation.

    PubMed

    Lee, Kyoung-Youl; Shibutani, Makoto; Takagi, Hironori; Kato, Natsumi; Takigami, Shu; Uneyama, Chikako; Hirose, Masao

    2004-10-15

    To evaluate developmental toxicity of di-n-butyl phthalate (DBP) with exposure during the period from late gestation to following lactation, maternal rats were given DBP at dietary concentrations of 0, 20, 200, 2000 and 10,000 ppm from gestational day 15 to postnatal day (PND) 21. At 10,000 ppm, male offspring showed a decreased neonatal anogenital distance and retention of nipples (PND 14), while females showed a slight non-significant delay in the onset of puberty. At PND 21, reduction of testicular spermatocyte development was evident from 20 ppm, as well as mammary gland changes at low incidence in both sexes. At this time point, population changes of pituitary hormone-immunoreactive cells were observed at 10,000 ppm with a similar pattern of increase in the percentages of luteinizing hormone (LH)-positive and decrease in follicle-stimulating hormone (FSH) and prolactin producing cells in both sexes, effects also being evident on FSH from 200 ppm and LH from 2000 ppm in females. During postnatal week (PNW) 8-11, marginal increase of the number of cases with extended diestrus was found at 10,000 ppm. At adult stage necropsy, testicular lesions appeared to be very faint in most cases, but degeneration and atrophy of mammary gland alveoli were observed in males from 20 ppm. Although without clear monotonic dose-dependence, relative pituitary weights were increased with the intermediate doses in males at PNW 11. In females, relative pituitary weights were decreased after 10,000 ppm at PNW 11, and from 200 ppm at PNW 20. The proportion of FSH-positive cells in the pituitaries at PNW 11 was increased in both sexes at 10,000 ppm. Thus, developmental exposure to DBP affected female sexual development involving pituitary function, while in males testicular toxicity was mostly reversible but mammary gland toxicity was persistent at a dose level as low as 20 ppm.

  18. Late-Course Adaptive Adjustment Based on Metabolic Tumor Volume Changes during Radiotherapy May Reduce Radiation Toxicity in Patients with Non-Small Cell Lung Cancer.

    PubMed

    Xiao, Linlin; Liu, Ning; Zhang, Guifang; Zhang, Hui; Gao, Song; Fu, Zheng; Wang, Suzhen; Yu, Qingxi; Yu, Jinming; Yuan, Shuanghu

    2017-01-01

    To reduce the high risk of radiation toxicity and enhance the quality of life of patients with non-small cell lung cancer (NSCLC), we quantified the metabolic tumor volumes (MTVs) from baseline to the late-course of radiotherapy (RT) by fluorodeoxyglucose positron emission tomography computerized tomography (FDG PET-CT) and discussed the potential benefit of late-course adaptive plans rather than original plans by dose volume histogram (DVH) comparisons. Seventeen patients with stage II-III NSCLC who were treated with definitive conventionally fractionated RT were eligible for this prospective study. FDG PET-CT scans were acquired within 1 week before RT (pre-RT) and at approximately two-thirds of the total dose during-RT (approximately 40 Gy). MTVs were taken as gross tumor volumes (GTVs) that included the primary tumor and any involved hilar or mediastinal lymph nodes. An original plan based on the baseline MTVs and adaptive plans based on observations during-RT MTVs were generated for each patient. The DVHs for lung, heart, esophagus and spinal cord were compared between the original plans and composite plans at 66 Gy. At the time of approximately 40 Gy during-RT, MTVs were significantly reduced in patients with NSCLC (pre-RT 136.2±82.3 ml vs. during-RT 64.7±68.0 ml, p = 0.001). The composite plan of the original plan at 40 Gy plus the adaptive plan at 26 Gy resulted in better DVHs for all the organs at risk that were evaluated compared to the original plan at 66 Gy (p<0.05), including V5, V10, V15, V20, V25, V30 and the mean dose of total lung, V10, V20, V30, V40, V50, V60 and the mean dose of heart, V35, V40, V50, V55, V60, the maximum dose and mean dose of the esophagus, and the maximum dose of the spinal-cord. PET-MTVs were reduced significantly at the time of approximately 40 Gy during-RT. Late course adaptive radiotherapy may be an effective way to reduce the dose volume to the organs at risk, thus reducing radiation toxicity in patients with NSCLC.

  19. Late-Course Adaptive Adjustment Based on Metabolic Tumor Volume Changes during Radiotherapy May Reduce Radiation Toxicity in Patients with Non-Small Cell Lung Cancer

    PubMed Central

    Zhang, Guifang; Zhang, Hui; Gao, Song; Fu, Zheng; Wang, Suzhen; Yu, Qingxi; Yu, Jinming; Yuan, Shuanghu

    2017-01-01

    To reduce the high risk of radiation toxicity and enhance the quality of life of patients with non-small cell lung cancer (NSCLC), we quantified the metabolic tumor volumes (MTVs) from baseline to the late-course of radiotherapy (RT) by fluorodeoxyglucose positron emission tomography computerized tomography (FDG PET-CT) and discussed the potential benefit of late-course adaptive plans rather than original plans by dose volume histogram (DVH) comparisons. Seventeen patients with stage II-III NSCLC who were treated with definitive conventionally fractionated RT were eligible for this prospective study. FDG PET-CT scans were acquired within 1 week before RT (pre-RT) and at approximately two-thirds of the total dose during-RT (approximately 40 Gy). MTVs were taken as gross tumor volumes (GTVs) that included the primary tumor and any involved hilar or mediastinal lymph nodes. An original plan based on the baseline MTVs and adaptive plans based on observations during-RT MTVs were generated for each patient. The DVHs for lung, heart, esophagus and spinal cord were compared between the original plans and composite plans at 66 Gy. At the time of approximately 40 Gy during-RT, MTVs were significantly reduced in patients with NSCLC (pre-RT 136.2±82.3 ml vs. during-RT 64.7±68.0 ml, p = 0.001). The composite plan of the original plan at 40 Gy plus the adaptive plan at 26 Gy resulted in better DVHs for all the organs at risk that were evaluated compared to the original plan at 66 Gy (p<0.05), including V5, V10, V15, V20, V25, V30 and the mean dose of total lung, V10, V20, V30, V40, V50, V60 and the mean dose of heart, V35, V40, V50, V55, V60, the maximum dose and mean dose of the esophagus, and the maximum dose of the spinal-cord. PET-MTVs were reduced significantly at the time of approximately 40 Gy during-RT. Late course adaptive radiotherapy may be an effective way to reduce the dose volume to the organs at risk, thus reducing radiation toxicity in patients with NSCLC. PMID

  20. Systematic review: anal and rectal changes after radiotherapy for prostate cancer.

    PubMed

    Krol, Robin; Smeenk, Robert Jan; van Lin, Emile N J T; Yeoh, Eric E K; Hopman, Wim P M

    2014-03-01

    Pelvic radiotherapy may lead to changes of anorectal function resulting in incontinence-related complaints. The aim of this study was to systematically review objective findings of late anorectal physiology and mucosal appearance after irradiation for prostate cancer. MEDLINE, EMBASE, and the Cochrane library were searched. Original articles in which anal function, rectal function, or rectal mucosa were examined ≥3 months after EBRT for prostate cancer were included. Twenty-one studies were included with low to moderate quality. Anal resting pressures significantly decreased in 6 of the 9 studies including 277 patients. Changes of squeeze pressure and rectoanal inhibitory reflex were less uniform. Rectal distensibility was significantly impaired after EBRT in 7 of 9 studies (277 patients). In 4 of 9 studies on anal and in 5 of 9 on rectal function, disturbances were associated with urgency, frequent bowel movements or fecal incontinence. Mucosal changes as assessed by the Vienna Rectoscopy Score revealed telangiectasias in 73 %, congestion in 33 %, and ulceration in 4 % of patients in 8 studies including 346 patients, but no strictures or necrosis. Three studies reported mucosal improvement during follow-up. Telangiectasias, particularly multiple, were associated with rectal bleeding. Not all bowel complaints (30 %) were related to radiotherapy. Low to moderate quality evidence indicates that EBRT reduces anal resting pressure, decreases rectal distensibility, and frequently induces telangiectasias of rectal mucosa. Objective changes may be associated with fecal incontinence, urgency, frequent bowel movements, and rectal bleeding, but these symptoms are not always related to radiation damage.

  1. Using dose-surface maps to predict radiation-induced rectal bleeding: a neural network approach

    NASA Astrophysics Data System (ADS)

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

    2009-09-01

    The incidence of late-toxicities after radiotherapy can be modelled based on the dose delivered to the organ under consideration. Most predictive models reduce the dose distribution to a set of dose-volume parameters and do not take the spatial distribution of the dose into account. The aim of this study was to develop a classifier predicting radiation-induced rectal bleeding using all available information on the dose to the rectal wall. The dose was projected on a two-dimensional dose-surface map (DSM) by virtual rectum-unfolding. These DSMs were used as inputs for a classification method based on locally connected neural networks. In contrast to fully connected conventional neural nets, locally connected nets take the topology of the input into account. In order to train the nets, data from 329 patients from the RT01 trial (ISRCTN 47772397) were split into ten roughly equal parts. By using nine of these parts as a training set and the remaining part as an independent test set, a ten-fold cross-validation was performed. Ensemble learning was used and 250 nets were built from randomly selected patients from the training set. Out of these 250 nets, an ensemble of expert nets was chosen. The performances of the full ensemble and of the expert ensemble were quantified by using receiver-operator-characteristic (ROC) curves. In order to quantify the predictive power of the shape, ensembles of fully connected conventional neural nets based on dose-surface histograms (DSHs) were generated and their performances were quantified. The expert ensembles performed better than or equally as well as the full ensembles. The area under the ROC curve for the DSM-based expert ensemble was 0.64. The area under the ROC curve for the DSH-based expert ensemble equalled 0.59. This difference in performance indicates that not only volumetric, but also morphological aspects of the dose distribution are correlated to rectal bleeding after radiotherapy. Thus, the shape of the dose

  2. Protocol for a phase III randomised trial of image-guided intensity modulated radiotherapy (IG-IMRT) and conventional radiotherapy for late small bowel toxicity reduction after postoperative adjuvant radiation in Ca cervix

    PubMed Central

    Chopra, Supriya; Engineer, Reena; Mahantshetty, Umesh; Misra, Shagun; Phurailatpam, Reena; Paul, Siji N; Kannan, Sadhna; Kerkar, Rajendra; Maheshwari, Amita; Shylasree, TS; Ghosh, Jaya; Gupta, Sudeep; Thomas, Biji; Singh, Shalini; Sharma, Sanjiv; Chilikuri, Srinivas; Shrivastava, Shyam Kishore

    2012-01-01

    Introduction External beam radiation followed by vaginal brachytherapy (±chemotherapy) leads to reduction in the risk of local recurrence and improves progression-free survival in patients with adverse risk factors following Wertheim's hysterectomy albeit at the risk of late bowel toxicity. Intensity Modulated Radiotherapy (IMRT) results in reduction in bowel doses and has potential to reduce late morbidity, however, needs to be confirmed prospectively in a randomised trial. The present randomised trial tests reduction if any in late small bowel toxicity with the use of IMRT in postoperative setting. Methods and analysis Patients more than 18 years of age who need adjuvant (chemo) radiation will be eligible. Patients with residual pelvic or para-aortic nodal disease, history of multiple abdominal surgeries or any other medical bowel condition will be excluded. The trial will randomise patients into standard radiation or IMRT. The primary aim is to compare differences in late grades II–IV bowel toxicity between the two arms. The secondary aims of the study focus on evaluating correlation of dose–volume parameters and late toxicity and quality of life. The trial is planned as a multicentre randomised study. The trial is designed to detect a 13% difference in late grades II–IV bowel toxicity with an α of 0.05 and β of 0.80. A total of 240 patients will be required to demonstrate the aforesaid difference. Ethics and dissemination The trial is approved by institutional ethics review board and will be routinely monitored as per standard guidelines. The study results will be disseminated via peer reviewed scientific journals, conference presentations and submission to regulatory authorities. Registration The trial is registered with clinicaltrials.gov (NCT 01279135). PMID:23242243

  3. Predicting Mechanical Ventilation and Mortality: Early and Late Indicators in Steven-Johnson Syndrome and Toxic Epidermal Necrolysis.

    PubMed

    Beck, Anna; Cooney, Ryan; Gamelli, Richard L; Mosier, Michael J

    2016-01-01

    Steven-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are characterized by loss of the epidermis, often accompanied by sloughing of the oral mucosa and airway, which may be associated with the need for mechanical ventilation. We retrospectively examined our SJS and TEN population for factors predictive of the need for mechanical ventilation and mortality. Over more than a 7-year period, 74 subjects of ≥18 years old with biopsy-confirmed SJS-TEN were identified. Variables within the first 3 days of admission and throughout the entire hospital stay were analyzed for their value in predicting the need for mechanical ventilation and mortality. Predictive variables were examined using univariate and multivariate logistic regression analyses. Of our 74 subjects, 28 (37.8%) required mechanical ventilation and 11 (13.9%) died, all of whom were intubated. Patients requiring ventilation had a significantly higher %TBSA loss of epidermis on admission and progressive epidermal loss after admission. On multivariate analysis, acute kidney injury within the first 3 days of admission and fewer days from symptom onset to admission were statistically significant in predicting need for mechanical ventilation. In addition, the early need for mechanical ventilation, early serum bicarbonate <20 mm/L, and older age were all associated with higher mortality on multivariate analysis. In conclusion, the need for mechanical ventilation in adult TEN subjects is associated with higher mortality. This is the first time that mechanical ventilation has been specifically examined in the recent U.S. SJS and TEN population. The early recognition of patients at risk for ventilation may help guide management, especially in those patients admitted early after symptom development with acute kidney injury and extensive, progressing epidermal loss.

  4. Clinical Toxicities and Dosimetric Parameters After Whole-Pelvis Versus Prostate-Only Intensity-Modulated Radiation Therapy for Prostate Cancer

    SciTech Connect

    Deville, Curtiland; Both, Stefan; Hwang, Wei-Ting; Tochner, Zelig; Vapiwala, Neha

    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 gastrointestinal (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.

  5. Cuprizone decreases intermediate and late-stage progenitor cells in hippocampal neurogenesis of rats in a framework of 28-day oral dose toxicity study

    SciTech Connect

    Abe, Hajime; Tanaka, Takeshi; Kimura, Masayuki; Mizukami, Sayaka; Saito, Fumiyo; Imatanaka, Nobuya; Akahori, Yumi; Yoshida, Toshinori; Shibutani, Makoto

    2015-09-15

    Developmental exposure to cuprizone (CPZ), a demyelinating agent, impairs intermediate-stage neurogenesis in the hippocampal dentate gyrus of rat offspring. To investigate the possibility of alterations in adult neurogenesis following postpubertal exposure to CPZ in a framework of general toxicity studies, CPZ was orally administered to 5-week-old male rats at 0, 120, or 600 mg/kg body weight/day for 28 days. In the subgranular zone (SGZ), 600 mg/kg CPZ increased the number of cleaved caspase-3{sup +} apoptotic cells. At ≥ 120 mg/kg, the number of SGZ cells immunoreactive for TBR2, doublecortin, or PCNA was decreased, while that for SOX2 was increased. In the granule cell layer, CPZ at ≥ 120 mg/kg decreased the number of postmitotic granule cells immunoreactive for NEUN, CHRNA7, ARC or FOS. In the dentate hilus, CPZ at ≥ 120 mg/kg decreased phosphorylated TRKB{sup +} interneurons, although the number of reelin{sup +} interneurons was unchanged. At 600 mg/kg, mRNA levels of Bdnf and Chrna7 were decreased, while those of Casp4, Casp12 and Trib3 were increased in the dentate gyrus. These data suggest that CPZ in a scheme of 28-day toxicity study causes endoplasmic reticulum stress-mediated apoptosis of granule cell lineages, resulting in aberrations of intermediate neurogenesis and late-stage neurogenesis and following suppression of immediate early gene-mediated neuronal plasticity. Suppression of BDNF signals to interneurons caused by decreased cholinergic signaling may play a role in these effects of CPZ. The effects of postpubertal CPZ on neurogenesis were similar to those observed with developmental exposure, except for the lack of reelin response, which may contribute to a greater decrease in SGZ cells. - Highlights: • Effect of 28-day CPZ exposure on hippocampal neurogenesis was examined in rats. • CPZ suppressed intermediate neurogenesis and late-stage neurogenesis in the dentate gyrus. • CPZ suppressed BDNF signals to interneurons by decrease of

  6. 4π Noncoplanar Stereotactic Body Radiation Therapy for Head-and-Neck Cancer: Potential to Improve Tumor Control and Late Toxicity

    SciTech Connect

    Rwigema, Jean-Claude M.; Nguyen, Dan; Heron, Dwight E.; Chen, Allen M.; Lee, Percy; Wang, Pin-Chieh; Vargo, John A.; Low, Daniel A.; Huq, M. Saiful; Tenn, Stephen; Steinberg, Michael L.; Kupelian, Patrick; Sheng, Ke

    2015-02-01

    Purpose: To evaluate the potential benefit of 4π radiation therapy in recurrent, locally advanced, or metastatic head-and-neck cancer treated with stereotactic body radiation therapy (SBRT). Methods and Materials: Twenty-seven patients with 29 tumors who were treated using SBRT were included. In recurrent disease (n=26), SBRT was delivered with a median 44 Gy (range, 35-44 Gy) in 5 fractions. Three patients with sinonasal mucosal melanoma, metastatic breast cancer, and primary undifferentiated carcinoma received 35 Gy, 22.5 Gy, and 40 Gy in 5 fractions, respectively. Novel 4π treatment plans were created for each patient to meet the objective that 95% of the planning target volume was covered by 100% of the prescription dose. Doses to organs at risk (OARs) and 50% dose spillage volumes were compared against the delivered clinical SBRT plans. Local control (LC), late toxicity, tumor control probability (TCP), and normal tissue complication probability were determined. Results: Using 4π plans, mean/maximum doses to all OARs were reduced by 22% to 89%/10% to 86%. With 4π plans, the 50% dose spillage volume was decreased by 33%. Planning target volume prescription dose escalation by 10 Gy and 20 Gy were achieved while keeping doses to OARs significantly improved or unchanged from clinical plans, except for the carotid artery maximum dose at 20-Gy escalation. At a median follow-up of 10 months (range, 1-41 months), crude LC was 52%. The 2-year LC of 39.2% approximated the predicted mean TCP of 42.2%, which increased to 45.9% with 4π plans. For 10-Gy and 20-Gy dose escalation, 4π plans increased TCP from 80.1% and 88.1% to 85.5% and 91.4%, respectively. The 7.4% rate of grade ≥3 late toxicity was comparable to the predicted 5.6% mean normal tissue complication probability for OARs, which was significantly reduced by 4π planning at the prescribed and escalated doses. Conclusions: 4π plans may allow dose escalation with significant and consistent

  7. Rectal microbicides: clinically relevant approach to the design of rectal specific placebo formulations

    PubMed Central

    2011-01-01

    Background The objective of this study is to identify the critical formulation parameters controlling distribution and function for the rectal administration of microbicides in humans. Four placebo formulations were designed with a wide range of hydrophilic characteristics (aqueous to lipid) and rheological properties (Newtonian, shear thinning, thermal sensitive and thixotropic). Aqueous formulations using typical polymers to control viscosity were iso-osmotic and buffered to pH 7. Lipid formulations were developed from lipid solvent/lipid gelling agent binary mixtures. Testing included pharmaceutical function and stability as well as in vitro and in vivo toxicity. Results The aqueous fluid placebo, based on poloxamer, was fluid at room temperature, thickened and became shear thinning at 37°C. The aqueous gel placebo used carbopol as the gelling agent, was shear thinning at room temperature and showed a typical decrease in viscosity with an increase in temperature. The lipid fluid placebo, myristyl myristate in isopropyl myristate, was relatively thin and temperature independent. The lipid gel placebo, glyceryl stearate and PEG-75 stearate in caprylic/capric triglycerides, was also shear thinning at both room temperature and 37°C but with significant time dependency or thixotropy. All formulations showed no rectal irritation in rabbits and were non-toxic using an ex vivo rectal explant model. Conclusions Four placebo formulations ranging from fluid to gel in aqueous and lipid formats with a range of rheological properties were developed, tested, scaled-up, manufactured under cGMP conditions and enrolled in a formal stability program. Clinical testing of these formulations as placebos will serve as the basis for further microbicide formulation development with drug-containing products. PMID:21385339

  8. Cuprizone decreases intermediate and late-stage progenitor cells in hippocampal neurogenesis of rats in a framework of 28-day oral dose toxicity study.

    PubMed

    Abe, Hajime; Tanaka, Takeshi; Kimura, Masayuki; Mizukami, Sayaka; Saito, Fumiyo; Imatanaka, Nobuya; Akahori, Yumi; Yoshida, Toshinori; Shibutani, Makoto

    2015-09-15

    Developmental exposure to cuprizone (CPZ), a demyelinating agent, impairs intermediate-stage neurogenesis in the hippocampal dentate gyrus of rat offspring. To investigate the possibility of alterations in adult neurogenesis following postpubertal exposure to CPZ in a framework of general toxicity studies, CPZ was orally administered to 5-week-old male rats at 0, 120, or 600mg/kg body weight/day for 28days. In the subgranular zone (SGZ), 600mg/kg CPZ increased the number of cleaved caspase-3(+) apoptotic cells. At ≥120mg/kg, the number of SGZ cells immunoreactive for TBR2, doublecortin, or PCNA was decreased, while that for SOX2 was increased. In the granule cell layer, CPZ at ≥120mg/kg decreased the number of postmitotic granule cells immunoreactive for NEUN, CHRNA7, ARC or FOS. In the dentate hilus, CPZ at ≥120mg/kg decreased phosphorylated TRKB(+) interneurons, although the number of reelin(+) interneurons was unchanged. At 600mg/kg, mRNA levels of Bdnf and Chrna7 were decreased, while those of Casp4, Casp12 and Trib3 were increased in the dentate gyrus. These data suggest that CPZ in a scheme of 28-day toxicity study causes endoplasmic reticulum stress-mediated apoptosis of granule cell lineages, resulting in aberrations of intermediate neurogenesis and late-stage neurogenesis and following suppression of immediate early gene-mediated neuronal plasticity. Suppression of BDNF signals to interneurons caused by decreased cholinergic signaling may play a role in these effects of CPZ. The effects of postpubertal CPZ on neurogenesis were similar to those observed with developmental exposure, except for the lack of reelin response, which may contribute to a greater decrease in SGZ cells.

  9. Comparison of patient-reported late treatment toxicity (LENT-SOMA) with quality of life (EORTC QLQ-C30 and QLQ-H&N35) assessment after head and neck radiotherapy.

    PubMed

    Ho, Kean Fatt; Farnell, Damien J J; Routledge, Jacqueline A; Burns, Meriel P; Sykes, Andrew J; Slevin, Nick J; Davidson, Susan E

    2010-11-01

    The patient's role in toxicity reporting is increasingly acknowledged but requires the adaptation and validation of toxicity reporting instruments for patient use as most toxicity scales are designed for physician use. Recording of radiotherapy related late toxicity is important and needs to be improved. A patient-scored symptom questionnaire of late treatment effects using LENT-SOMA was compared with a recognised quality of life tool (EORTC QLQ-C30/H&N35). LENT-SOMA and EORTC QLQ-C30 patient questionnaires were prospectively completed by 220 head and neck cancer patients over 3 years and 72 completed EORTC QLQ-H&N35 questionnaires at 2 years post-radiotherapy. Endpoints common to both questionnaires (pain, swallowing, dental pain, dry mouth, opening mouth, analgesics) were matched. Spearman rank correlation coefficients with ρ>0.6 (P<0.001) were obtained for all "matched" scales except for analgesics scale, ρ=0.267 (P<0.05). There was good agreement between LENT-SOMA and EORTC QLQ-H&N35 except for analgesic endpoints. Global quality of life scores correlated negatively with average LENT-SOMA scores (P<0.001). Significant differences in average LENT-SOMA scores between treatment modalities were found. The LENT-SOMA questionnaire has demonstrated a high Cronbach's α value (0.786) indicating good reliability. LENT-SOMA patient questionnaire results agreed well with those from the EORTC QLQ-H&N35 questionnaire for toxicity items where they could be compared explicitly, particularly for subjective endpoints. Patient-reported late toxicity had a negative impact on quality of life. The LENT-SOMA patient questionnaire is both reliable and sensitive to differences between patients treated with different modalities. A patient-based questionnaire is an important contributor to capturing late radiotherapy effects. Copyright © 2010. Published by Elsevier Ireland Ltd.

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

    SciTech Connect

    Kim, D.W. Nathan; Cho, L. Chinsoo; Straka, Christopher; Christie, Alana; Lotan, Yair; Pistenmaa, David; Kavanagh, Brian D.; Nanda, Akash; Kueplian, Patrick; Brindle, Jeffrey; Cooley, Susan; Perkins, Alida; Raben, David; Xie, Xian-Jin; Timmerman, Robert D.

    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% of 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.

  11. [Clinical research for rectal carcinoma: State of the art and objectives].

    PubMed

    Maingon, P; Simon, J-M; Canova, C-H; Troussier, I; Besson, N; Caillot, É; Huguet, F

    2017-10-01

    The treatment of rectal carcinoma is based on multidisciplinary strategy and multimodal approaches including gastrointestinal tract specialists, medical oncologists, radiation oncologists and surgery. The different objectives should be declined according to the characteristics of the tumours. The aim of the therapist would be to select the best strategy offering to the patient to be cured with as less as possible late adverse toxicity. The challenge of the treatment of small tumours is to maintain a functional anal sphincter while minimizing the risk of local recurrence. The standard treatment of locally advanced disease is aiming firstly to cure the patient and secondly to prevent late complications. Each of these clinical presentations of the disease has to be considered as a whole taking into account the new surgical techniques and a personalized approach adapted to the tumour. Nowadays they should be studied with dedicated clinical trials. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  12. Hypofractionated irradiation of infra-supraclavicular lymph nodes after axillary dissection in patients with breast cancer post-conservative surgery: impact on late toxicity.

    PubMed

    Guenzi, Marina; Blandino, Gladys; Vidili, Maria Giuseppina; Aloi, Deborah; Configliacco, Elena; Verzanini, Elisa; Tornari, Elena; Cavagnetto, Francesca; Corvò, Renzo

    2015-08-20

    The aim of the present work was to analyse the impact of mild hypofractionated radiotherapy (RT) of infra-supraclavicular lymph nodes after axillary dissection on late toxicity. From 2007 to 2012, 100 females affected by breast cancer (pT1- T4, pN1-3, pMx) were treated with conservative surgery, Axillary Node Dissection (AND) and loco-regional radiotherapy (whole breast plus infra-supraclavicular fossa). Axillary lymph nodes metastases were confirmed in all women. The median age at diagnosis was 60 years (range 34-83). Tumors were classified according to molecular characteristics: luminal-A 59 pts (59%), luminal-B 24 pts (24%), basal-like 10 pts (10%), Her-2 like 7 pts (7%). 82 pts (82%) received hormonal therapy, 9 pts (9%) neo-adjuvant chemotherapy, 81pts (81%) adjuvant chemotherapy. All patients received a mild hypofractionated RT: 46 Gy in 20 fractions 4 times a week to whole breast and infra-supraclavicular fossa plus an additional weekly dose of 1,2 Gy to the lumpectomy area. The disease control and treatment related toxicity were analysed in follow-up visits. The extent of lymphedema was analysed by experts in Oncological Rehabilitation. Within a median follow-up of 50 months (range 19-82), 6 (6%) pts died, 1 pt (1%) had local progression disease, 2 pts (2%) developed distant metastasis and 1 subject (1%) presented both. In all patients the acute toxicity was mainly represented by erythema and patchy moist desquamation. At the end of radiotherapy 27 pts (27%) presented lymphedema, but only 10 cases (10%) seemed to be correlated to radiotherapy. None of the patients showed a severe damage to the brachial plexus, and the described cases of paresthesias could not definitely be attributed to RT. We did not observe symptomatic pneumonitis. Irradiation of infra-supraclavicular nodes with a mild hypofractionated schedule can be a safe and effective treatment without evidence of a significant increase of lymphedema appearance radiotherapy related.

  13. A unique hypofractionated radiotherapy schedule with 51.3 Gy in 18 fractions three times per week for early breast cancer: outcomes including local control, acute and late skin toxicity.

    PubMed

    Vassilis, Kouloulias; Ioannis, Gogalis; Anna, Zygogianni; Christina, Armpilia; Christos, Antypas; John, Kokakis; Porfyrios, Koromperlis; Vassiliki, Gennimata; John, Kouvaris

    2017-03-01

    Evaluation of local control and acute and late toxicity regarding a hypofractionated RT schedule for breast cancer patients. Between October 2007 and October 2009, 80 women with early breast cancer were treated by 42.75 Gy in 15 fractions over 5 weeks. This treatment involved three fractions per week (Monday-Wednesday-Friday). All patients received an additional boost dose to the tumor bed of 8.55 Gy in 3 fractions using 6 MV photons. The primary endpoint included any local recurrence in the treated breast. Secondary endpoint included acute and late radiation skin toxicity. The median follow-up time was 63 months (range 60-72). Radiation toxicity was graded according the RTOG/EORTC criteria. Neither local nor distant recurrence was noted in any patient during this 3-year follow-up. Grade 0, 1, 2 acute skin toxicity was observed in 56/80 (70.0 %), in 19/80 (23.8 %) and in 5/80 (6.3 %), respectively. Three months post-RT, toxicity grades 0, 1, 2 skin toxicity were 64/80 (80 %), 14/80 (17.5 %) and 2/80 (2.5 %), respectively. Late toxicity as grade 0, 1 was observed in 72/80 (90.0 %) and in 8/80 (10.0 %), respectively, 6 months post-RT, whereas after 1 year they were 78/80 (97.5 %) and 2/80 (2.5 %), respectively. Preliminary results regarding skin reactions, cosmetic appearance and local control are consistent with published data that support the use of shorter fractionation schedules in early breast cancer patients after breast conservative surgery. Longer follow-up and a randomized prospective study stand in need for the extraction of safe conclusions.

  14. Multidisciplinary management of resectable rectal cancer. New developments and controversies.

    PubMed

    Minsky, Bruce D; Guillem, Jose G

    2008-11-15

    Until 2004, initial surgery and, in cases of pT3 and/or node-positive disease, postoperative chemoradiotherapy (radiation plus concurrent chemotherapy) was the conventional approach for patients with clinical T3 and/or node-positive rectal cancer. The German CAO/ARO/AIO 94 trial confirmed that, compared with preoperative chemoradiotherapy, postoperative chemoradiotherapy is associated with significantly higher local failure and toxicity rates as well as a decrease in the incidence of sphincter preservation. These data resulted in a change from postoperative to preoperative chemoradiotherapy. This shift to preoperative therapy has prompted a series of new questions regarding the multidisciplinary management of rectal cancer, including: What is the ideal neoadjuvant approach (short-course vs. combined-modality therapy)? Is postoperative adjuvant chemotherapy necessary for all patients following preoperative chemoradiotherapy? Do patients with node-negative rectal cancer require pelvic radiation? What is the ideal combined-modality regimen? Does an increase in response rate translate into improved local control and survival? And lastly, what is the benefit of novel radiation sensitization and delivery techniques? This review will address these and other questions surrounding the multidisciplinary management of rectal cancer.

  15. American Society of Colon and Rectal Surgeons

    MedlinePlus

    ... Educational Resources ASCRS Textbook, 3rd Edition CARSEP® CREST® Case Study Listserv International Colon and Rectal Societies and Organizations ... Board of Colon and Rectal Surgery CARSEP® Members Case Study Listserv CREST® Young Surgeons Listserv Quality Assessment and ...

  16. ACR Appropriateness Criteria on Resectable Rectal Cancer

    SciTech Connect

    Suh, W. Warren; Konski, Andre A.; Mohiuddin, Mohammed; Poggi, Matthew M.; Regine, William F.; Cosman, Bard C.; Saltz, Leonard; Johnstone, Peter A.S.

    2008-04-01

    The American College of Radiology (ACR) Appropriateness Criteria on Resectable Rectal Cancer was updated by the Expert Panel on Radiation Oncology-Rectal/Anal Cancer, based on a literature review completed in 2007.

  17. Preoperative radio-chemotherapy (RT-CT) in rectal cancer. Prospective study with postoperative RT-CT control group.

    PubMed

    Cambray i Amenós, M; Navarro García, M; Martí Ragué, J; Pareja Fernández, L; Pera Fábregas, J

    2007-03-01

    of comparing either pre- or postoperative groups. There were, however, differences with regard to late toxicity; they showed less toxicity when RT-CT was administered preoperatively; no case of radiation enteritis that required surgery was seen in this group, whereas in the postoperative RT-CT it was 4.2%, p=0.022. Preoperative treatment of locally advanced rectal cancer is recommended, for it yields a high level of response to treatment; it allows preservation surgery of the anal sphincter in one third of patients showing low rectal tumours. There is also a clear diminution of late toxicity with pre-op treatment. On the other hand, response to pre-op treatment selects patients with a better prognosis.

  18. Rectal cancer: An evidence-based update for primary care providers

    PubMed Central

    Gaertner, Wolfgang B; Kwaan, Mary R; Madoff, Robert D; Melton, Genevieve B

    2015-01-01

    Rectal adenocarcinoma is an important cause of cancer-related deaths worldwide, and key anatomic differences between the rectum and the colon have significant implications for management of rectal cancer. Many advances have been made in the diagnosis and management of rectal cancer. These include clinical staging with imaging studies such as endorectal ultrasound and pelvic magnetic resonance imaging, operative approaches such as transanal endoscopic microsurgery and laparoscopic and robotic assisted proctectomy, as well as refined neoadjuvant and adjuvant therapies. For stage II and III rectal cancers, combined chemoradiotherapy offers the lowest rates of local and distant relapse, and is delivered neoadjuvantly to improve tolerability and optimize surgical outcomes, particularly when sphincter-sparing surgery is an endpoint. The goal in rectal cancer treatment is to optimize disease-free and overall survival while minimizing the risk of local recurrence and toxicity from both radiation and systemic therapy. Optimal patient outcomes depend on multidisciplinary involvement for tailored therapy. The successful management of rectal cancer requires a multidisciplinary approach, with the involvement of enterostomal nurses, gastroenterologists, medical and radiation oncologists, radiologists, pathologists and surgeons. The identification of patients who are candidates for combined modality treatment is particularly useful to optimize outcomes. This article provides an overview of the diagnosis, staging and multimodal therapy of patients with rectal cancer for primary care providers. PMID:26167068

  19. SU-E-T-280: Reconstructed Rectal Wall Dose Map-Based Verification of Rectal Dose Sparing Effect According to Rectum Definition Methods and Dose Perturbation by Air Cavity in Endo-Rectal Balloon

    SciTech Connect

    Park, J; Park, H; Lee, J; Kang, S; Lee, M; Suh, T; Lee, B

    2014-06-01

    Purpose: Dosimetric effect and discrepancy according to the rectum definition methods and dose perturbation by air cavity in an endo-rectal balloon (ERB) were verified using rectal-wall (Rwall) dose maps considering systematic errors in dose optimization and calculation accuracy in intensity-modulated radiation treatment (IMRT) for prostate cancer patients. Methods: When the inflated ERB having average diameter of 4.5 cm and air volume of 100 cc is used for patient, Rwall doses were predicted by pencil-beam convolution (PBC), anisotropic analytic algorithm (AAA), and AcurosXB (AXB) with material assignment function. The errors of dose optimization and calculation by separating air cavity from the whole rectum (Rwhole) were verified with measured rectal doses. The Rwall doses affected by the dose perturbation of air cavity were evaluated using a featured rectal phantom allowing insert of rolled-up gafchromic films and glass rod detectors placed along the rectum perimeter. Inner and outer Rwall doses were verified with reconstructed predicted rectal wall dose maps. Dose errors and extent at dose levels were evaluated with estimated rectal toxicity. Results: While AXB showed insignificant difference of target dose coverage, Rwall doses underestimated by up to 20% in dose optimization for the Rwhole than Rwall at all dose range except for the maximum dose. As dose optimization for Rwall was applied, the Rwall doses presented dose error less than 3% between dose calculation algorithm except for overestimation of maximum rectal dose up to 5% in PBC. Dose optimization for Rwhole caused dose difference of Rwall especially at intermediate doses. Conclusion: Dose optimization for Rwall could be suggested for more accurate prediction of rectal wall dose prediction and dose perturbation effect by air cavity in IMRT for prostate cancer. This research was supported by the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea

  20. Local management of rectal neoplasia.

    PubMed

    Touzios, John; Ludwig, Kirk A

    2008-11-01

    The treatment of rectal neoplasia, whether benign or malignant, challenges the surgeon. The challenge in treating rectal cancer is selecting the proper approach for the appropriate patient. In a small number of rectal cancer patients local excision may be the best approach. In an attempt to achieve two goals-cure of disease with a low rate of local failure and maintenance of function and quality of life-multiple approaches can be utilized. The key to obtaining a good outcome for any one patient is balancing the competing factors that impact on these goals. Any effective treatment aimed at controlling rectal cancer in the pelvis must take into account the disease in the bowel wall itself and the disease, or potential disease, in the mesorectum. The major downside of local excision techniques is the potential of leaving untreated disease in the mesorectum. Local management techniques avoid the potential morbidity, mortality, and functional consequences of a major abdominal radical resection and are thus quite effective in achieving the maintenance of function and quality of life goal. The issue for the transanal techniques is how they fare in achieving the first goal-cure of the cancer while keeping local recurrence rates to an absolute minimum. Without removing both the rectum and the mesorectum there is no completely accurate way to determine whether a rectal cancer has moved outside the bowel wall, so any decision on local management of a rectal neoplasm is a calculated risk. For benign neoplasia, the challenge is removing the lesion without having to resort to a major abdominal procedure.

  1. Significant Reduction of Late Toxicities in Patients With Extremity Sarcoma Treated With Image-Guided Radiation Therapy to a Reduced Target Volume: Results of Radiation Therapy Oncology Group RTOG-0630 Trial

    PubMed Central

    Wang, Dian; Zhang, Qiang; Eisenberg, Burton L.; Kane, John M.; Li, X. Allen; Lucas, David; Petersen, Ivy A.; DeLaney, Thomas F.; Freeman, Carolyn R.; Finkelstein, Steven E.; Hitchcock, Ying J.; Bedi, Manpreet; Singh, Anurag K.; Dundas, George; Kirsch, David G.

    2015-01-01

    Purpose We performed a multi-institutional prospective phase II trial to assess late toxicities in patients with extremity soft tissue sarcoma (STS) treated with preoperative image-guided radiation therapy (IGRT) to a reduced target volume. Patients and Methods Patients with extremity STS received IGRT with (cohort A) or without (cohort B) chemotherapy followed by limb-sparing resection. Daily pretreatment images were coregistered with digitally reconstructed radiographs so that the patient position could be adjusted before each treatment. All patients received IGRT to reduced tumor volumes according to strict protocol guidelines. Late toxicities were assessed at 2 years. Results In all, 98 patients were accrued (cohort A, 12; cohort B, 86). Cohort A was closed prematurely because of poor accrual and is not reported. Seventy-nine eligible patients from cohort B form the basis of this report. At a median follow-up of 3.6 years, five patients did not have surgery because of disease progression. There were five local treatment failures, all of which were in field. Of the 57 patients assessed for late toxicities at 2 years, 10.5% experienced at least one grade ≥ 2 toxicity as compared with 37% of patients in the National Cancer Institute of Canada SR2 (CAN-NCIC-SR2: Phase III Randomized Study of Pre- vs Postoperative Radiotherapy in Curable Extremity Soft Tissue Sarcoma) trial receiving preoperative radiation therapy without IGRT (P < .001). Conclusion The significant reduction of late toxicities in patients with extremity STS who were treated with preoperative IGRT and absence of marginal-field recurrences suggest that the target volumes used in the Radiation Therapy Oncology Group RTOG-0630 (A Phase II Trial of Image-Guided Preoperative Radiotherapy for Primary Soft Tissue Sarcomas of the Extremity) study are appropriate for preoperative IGRT for extremity STS. PMID:25667281

  2. Ozone Therapy in the Management of Persistent Radiation-Induced Rectal Bleeding in Prostate Cancer Patients.

    PubMed

    Clavo, Bernardino; Santana-Rodriguez, Norberto; Llontop, Pedro; Gutierrez, Dominga; Ceballos, Daniel; Méndez, Charlin; Rovira, Gloria; Suarez, Gerardo; Rey-Baltar, Dolores; Garcia-Cabrera, Laura; Martínez-Sánchez, Gregorio; Fiuza, Dolores

    2015-01-01

    Introduction. Persistent radiation-induced proctitis and rectal bleeding are debilitating complications with limited therapeutic options. We present our experience with ozone therapy in the management of such refractory rectal bleeding. Methods. Patients (n = 12) previously irradiated for prostate cancer with persistent or severe rectal bleeding without response to conventional treatment were enrolled to receive ozone therapy via rectal insufflations and/or topical application of ozonized-oil. Ten (83%) patients had Grade 3 or Grade 4 toxicity. Median follow-up after ozone therapy was 104 months (range: 52-119). Results. Following ozone therapy, the median grade of toxicity improved from 3 to 1 (p < 0.001) and the number of endoscopy treatments from 37 to 4 (p = 0.032). Hemoglobin levels changed from 11.1 (7-14) g/dL to 13 (10-15) g/dL, before and after ozone therapy, respectively (p = 0.008). Ozone therapy was well tolerated and no adverse effects were noted, except soft and temporary flatulence for some hours after each session. Conclusions. Ozone therapy was effective in radiation-induced rectal bleeding in prostate cancer patients without serious adverse events. It proved useful in the management of rectal bleeding and merits further evaluation.

  3. Ozone Therapy in the Management of Persistent Radiation-Induced Rectal Bleeding in Prostate Cancer Patients

    PubMed Central

    Clavo, Bernardino; Santana-Rodriguez, Norberto; Llontop, Pedro; Gutierrez, Dominga; Ceballos, Daniel; Méndez, Charlin; Rovira, Gloria; Suarez, Gerardo; Rey-Baltar, Dolores; Garcia-Cabrera, Laura; Martínez-Sánchez, Gregorio; Fiuza, Dolores

    2015-01-01

    Introduction. Persistent radiation-induced proctitis and rectal bleeding are debilitating complications with limited therapeutic options. We present our experience with ozone therapy in the management of such refractory rectal bleeding. Methods. Patients (n = 12) previously irradiated for prostate cancer with persistent or severe rectal bleeding without response to conventional treatment were enrolled to receive ozone therapy via rectal insufflations and/or topical application of ozonized-oil. Ten (83%) patients had Grade 3 or Grade 4 toxicity. Median follow-up after ozone therapy was 104 months (range: 52–119). Results. Following ozone therapy, the median grade of toxicity improved from 3 to 1 (p < 0.001) and the number of endoscopy treatments from 37 to 4 (p = 0.032). Hemoglobin levels changed from 11.1 (7–14) g/dL to 13 (10–15) g/dL, before and after ozone therapy, respectively (p = 0.008). Ozone therapy was well tolerated and no adverse effects were noted, except soft and temporary flatulence for some hours after each session. Conclusions. Ozone therapy was effective in radiation-induced rectal bleeding in prostate cancer patients without serious adverse events. It proved useful in the management of rectal bleeding and merits further evaluation. PMID:26357522

  4. 21 CFR 876.5450 - Rectal dilator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Rectal dilator. 876.5450 Section 876.5450 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5450 Rectal dilator. (a) Identification. A rectal...

  5. 21 CFR 876.5450 - Rectal dilator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Rectal dilator. 876.5450 Section 876.5450 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5450 Rectal dilator. (a) Identification. A rectal...

  6. Chemotherapy, Radiation Therapy, and Surgery in Treating Patients With Locally Advanced Rectal Cancer

    ClinicalTrials.gov

    2013-01-09

    Adenocarcinoma of the Rectum; Mucinous Adenocarcinoma of the Rectum; 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

  7. Rectal dose-volume constraints in high-dose radiotherapy of localized prostate cancer.

    PubMed

    Fiorino, Claudio; Sanguineti, Giuseppe; Cozzarini, Cesare; Fellin, Gianni; Foppiano, Franca; Menegotti, Loris; Piazzolla, Anna; Vavassori, Vittorio; Valdagni, Riccardo

    2003-11-15

    To investigate the relationship between rectal bleeding and dosimetric-clinical parameters in patients receiving three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer. In a retrospective national study (AIROPROS01-01, AIRO: Associazione Italiana Radioterapia Oncologica), planning/clinical data for 245 consecutive patients with stage T1-4N0-x prostate carcinoma who underwent 3D-CRT to 70-78 Gy (ICRU point) were pooled from four Italian institutions. The correlation between late rectal bleeding and rectal dose-volume data (the percentage of rectum receiving more than 50, 55, 60, 65, 70, and 75 Gy [V(50-70)]) and other dosimetric and clinical parameters were investigated in univariate (log-rank) and multivariate (Cox regression model) analyses. Median follow-up was 2 years. Twenty-three patients were scored as late bleeders according to a modified RTOG definition (Grade 2: 16; Grade 3: 7); the actuarial 2-year rate was 9.2%. Excepting V75, all median and third quartile V(50-70) values were found to be significantly correlated with late bleeding at univariate analysis. The smallest p value was seen for V(50) below/above the third quartile value (66%). The V70 (cut-off value: 30%) was found to be also predictive for late bleeding. In the high-dose subgroup (74-78 Gy), Grade 3 bleeding was highly correlated with this constraint. The predictive value of both V(50) and V(70) was confirmed by multivariate analyses. The present article provides evidence for correlation between rectal DVH parameters and late rectal bleeding in patients treated with curative intent with 3D-CRT. To keep the rate of moderate/severe rectal bleeding below 5-10%, it seems advisable to limit V(50) to 60-65%, V(60) to 45-50%, and V70 to 25-30%.

  8. Individualized 3D Reconstruction of Normal Tissue Dose for Patients With Long-term Follow-up: A Step Toward Understanding Dose Risk for Late Toxicity

    SciTech Connect

    Ng, Angela; Brock, Kristy K.; Sharpe, Michael B.; Moseley, Joanne L.; Craig, Tim; Hodgson, David C.

    2012-11-15

    Purpose: Understanding the relationship between normal tissue dose and delayed radiation toxicity is an important component of developing more effective radiation therapy. Late outcome data are generally available only for patients who have undergone 2-dimensional (2D) treatment plans. The purpose of this study was to evaluate the accuracy of 3D normal tissue dosimetry derived from reconstructed 2D treatment plans in Hodgkin's lymphoma (HL) patients. Methods and Materials: Three-dimensional lung, heart, and breast volumes were reconstructed from 2D planning radiographs for HL patients who received mediastinal radiation therapy. For each organ, a reference 3D organ was modified with patient-specific structural information, using deformable image processing software. Radiation therapy plans were reconstructed by applying treatment parameters obtained from patient records to the reconstructed 3D volumes. For each reconstructed organ mean dose (D{sub mean}) and volumes covered by at least 5 Gy (V{sub 5}) and 20Gy (V{sub 20}) were calculated. This process was performed for 15 patients who had both 2D and 3D planning data available to compare the reconstructed normal tissue doses with those derived from the primary CT planning data and also for 10 historically treated patients with only 2D imaging available. Results: For patients with 3D planning data, the normal tissue doses could be reconstructed accurately using 2D planning data. Median differences in D{sub mean} between reconstructed and actual plans were 0.18 Gy (lungs), -0.15 Gy (heart), and 0.30 Gy (breasts). Median difference in V{sub 5} and V{sub 20} were less than 2% for each organ. Reconstructed 3D dosimetry was substantially higher in historical mantle-field treatments than contemporary involved-field mediastinal treatments: average D{sub mean} values were 15.2 Gy vs 10.6 Gy (lungs), 27.0 Gy vs 14.3 Gy (heart), and 8.0 Gy vs 3.2 Gy (breasts). Conclusions: Three-dimensional reconstruction of absorbed dose to

  9. Individualized 3D reconstruction of normal tissue dose for patients with long-term follow-up: a step toward understanding dose risk for late toxicity.

    PubMed

    Ng, Angela; Brock, Kristy K; Sharpe, Michael B; Moseley, Joanne L; Craig, Tim; Hodgson, David C

    2012-11-15

    Understanding the relationship between normal tissue dose and delayed radiation toxicity is an important component of developing more effective radiation therapy. Late outcome data are generally available only for patients who have undergone 2-dimensional (2D) treatment plans. The purpose of this study was to evaluate the accuracy of 3D normal tissue dosimetry derived from reconstructed 2D treatment plans in Hodgkin's lymphoma (HL) patients. Three-dimensional lung, heart, and breast volumes were reconstructed from 2D planning radiographs for HL patients who received mediastinal radiation therapy. For each organ, a reference 3D organ was modified with patient-specific structural information, using deformable image processing software. Radiation therapy plans were reconstructed by applying treatment parameters obtained from patient records to the reconstructed 3D volumes. For each reconstructed organ mean dose (Dmean) and volumes covered by at least 5 Gy (V5) and 20 Gy (V20) were calculated. This process was performed for 15 patients who had both 2D and 3D planning data available to compare the reconstructed normal tissue doses with those derived from the primary CT planning data and also for 10 historically treated patients with only 2D imaging available. For patients with 3D planning data, the normal tissue doses could be reconstructed accurately using 2D planning data. Median differences in Dmean between reconstructed and actual plans were 0.18 Gy (lungs), -0.15 Gy (heart), and 0.30 Gy (breasts). Median difference in V5 and V20 were less than 2% for each organ. Reconstructed 3D dosimetry was substantially higher in historical mantle-field treatments than contemporary involved-field mediastinal treatments: average Dmean values were 15.2 Gy vs 10.6 Gy (lungs), 27.0 Gy vs 14.3 Gy (heart), and 8.0 Gy vs 3.2 Gy (breasts). Three-dimensional reconstruction of absorbed dose to organs at risk can be estimated accurately many years after exposure by using limited 2D data

  10. Extended (5-year) Outcomes of Accelerated Partial Breast Irradiation Using MammoSite Balloon Brachytherapy: Patterns of Failure, Patient Selection, and Dosimetric Correlates for Late Toxicity

    SciTech Connect

    Vargo, John A.; Verma, Vivek; Kim, Hayeon; Kalash, Ronny; Heron, Dwight E.; Johnson, Ronald; Beriwal, Sushil

    2014-02-01

    Purpose: Accelerated partial breast irradiation (APBI) with balloon and catheter-based brachytherapy has gained increasing popularity in recent years and is the subject of ongoing phase III trials. Initial data suggest promising local control and cosmetic results in appropriately selected patients. Long-term data continue to evolve but are limited outside of the context of the American Society of Breast Surgeons Registry Trial. Methods and Materials: A retrospective review of 157 patients completing APBI after breast-conserving surgery and axillary staging via high-dose-rate {sup 192}Ir brachytherapy from June 2002 to December 2007 was made. APBI was delivered with a single-lumen MammoSite balloon-based applicator to a median dose of 34 Gy in 10 fractions over a 5-day period. Tumor coverage and critical organ dosimetry were retrospectively collected on the basis of computed tomography completed for conformance and symmetry. Results: At a median follow-up time of 5.5 years (range, 0-10.0 years), the 5-year and 7-year actuarial incidences of ipsilateral breast control were 98%/98%, of nodal control 99%/98%, and of distant control 99%/99%, respectively. The crude rate of ipsilateral breast recurrence was 2.5% (n=4); of nodal failure, 1.9% (n=3); and of distant failure, 0.6% (n=1). The 5-year and 7-year actuarial overall survival rates were 89%/86%, with breast cancer–specific survival of 100%/99%, respectively. Good to excellent cosmetic outcomes were achieved in 93.4% of patients. Telangiectasia developed in 27% of patients, with 1-year, 3-year, and 5-year actuarial incidence of 7%/24%/33%; skin dose >100% significantly predicted for the development of telangiectasia (50% vs 14%, P<.0001). Conclusions: Long-term single-institution outcomes suggest excellent tumor control, breast cosmesis, and minimal late toxicity. Skin toxicity is a function of skin dose, which may be ameliorated with dosimetric optimization afforded by newer multicatheter brachytherapy

  11. 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.

  12. 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.

  13. A phase III randomized, placebo-controlled, double-blind study of misoprostol rectal suppositories to prevent acute radiation proctitis in patients with prostate cancer

    SciTech Connect

    Hille, Andrea . E-mail: ahille@med.uni-goettingen.de; Schmidberger, Heinz; Hermann, Robert M.; Christiansen, Hans; Saile, Bernhard; Pradier, Olivier; Hess, Clemens F.

    2005-12-01

    Purpose: Acute radiation proctitis is the most relevant complication of pelvic radiation and is still mainly treated supportively. Considering the negative impact of acute proctitis symptoms on patients' daily activities and the potential relationship between the severity of acute radiation injury and late damage, misoprostol was tested in the prevention of acute radiation-induced proctitis. Methods and Materials: A total of 100 patients who underwent radiotherapy for prostate cancer were entered into this phase III randomized, placebo-controlled, double-blind study with misoprostol or placebo suppositories. Radiation-induced toxicity was evaluated weekly during radiotherapy using the Common Toxicity Criteria. Results: Between the placebo and the misoprostol groups, no significant differences in proctitis symptoms occurred: 76% of patients in each group had Grade 1 toxicity, and 26% in the placebo group and 36% in the misoprostol group had Grade 2 toxicity. No differences were found in onset or symptom duration. Comparing the peak incidence of patients' toxicity symptoms, significantly more patients experienced rectal bleeding in the misoprostol group (p = 0.03). Conclusion: Misoprostol given as a once-daily suppository did not decrease the incidence and severity of radiation-induced acute proctitis and may increase the incidence of acute bleeding.

  14. Magnetic resonance imaging of rectal cancer.

    PubMed

    Dewhurst, Catherine E; Mortele, Koenraad J

    2013-01-01

    This article aims to discuss the anatomy of the anorectum, the MRI protocol parameters required to optimize diagnosis of rectal cancer, and the diagnostic MRI criteria essential to stage rectal cancer accurately, using the TNM staging classification. A brief review of more emerging important aspects of rectal cancer staging, such as the circumferential resection margin, extramural vascular invasion, and the staging of low rectal cancers, will also be provided. Finally, the authors will touch upon the evaluation of tumor response to neoadjuvant chemoradiation therapy in the setting of locally advanced rectal cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Update and Debate Issues in Surgical Treatment of Middle and Low Rectal Cancer

    PubMed Central

    Kim, Min Sung; AL-Asari, Sami F.

    2012-01-01

    Based on a review of the literature, this paper provides an update on surgical treatment of middle and low rectal cancer and discusses issues of debate surrounding that treatment. The main goal of the surgical treatment of rectal cancer is radical resection of the tumor and surrounding lymphatic tissue. Local excision of early rectal cancer can be another treatment option, in which the patient can avoid possible complications related to radical surgery. Neoadjuvant chemoradiation therapy (CRT) has been recommended for patients with cT3-4N0 or any T N+ rectal cancer because CRT shows better local control and less toxicity than adjuvant CRT. However, recent clinical trials showed promising results for local excision after neoadjuvant CRT in selected patients with low rectal cancer. In addition, the "wait and see" concept is another modality that has been reported for the management of tumors that show complete clinical remission after neoadjuvant CRT. Although radical surgery for middle and low rectal cancer is the cornerstone therapy, an ultralow anterior resection with or without intersphincteric resection (ISR) has become an alternative standard surgical method for selected patients. Many studies have reported on the oncological safety of the ISR, but few of them have addressed the issue the functional outcome. Furthermore, an abdominoperineal resection (APR) has problems with high rates of tumor perforations and positive circumferential resection margins, and those factors have contributed to its having a high rate of local recurrence and a poor survival rate for rectal cancer compared with sphincter-saving procedures. Recently, great efforts have been made to reduce these problems, and the total levator excision or the extended APR concept has emerged. Surgical management for low rectal cancer should aim to radically excise the tumor and to preserve as much of the sphincter function as possible by using multidisciplinary approaches. However, further prospective

  16. Rectal-wall dose dependence on postplan timing after permanent-seed prostate brachytherapy

    SciTech Connect

    Taussky, Daniel; Yeung, Ivan; Williams, Theresa; Pearson, Shannon; McLean, Michael; Pond, Gregory; Crook, Juanita . E-mail: Juanita.crook@rmp.uhn.on.ca

    2006-06-01

    Purpose: Dose to rectal wall after permanent-seed prostate brachytherapy is dependent on distance between posterior prostatic seeds and anterior rectal wall and is influenced by postimplant periprostatic edema. We analyzed the effect of postplan timing on anterior rectal-wall dose. Methods and Materials: Twenty patients received permanent seed {sup 125}I brachytherapy as monotherapy (145 Gy). Implants were preplanned by use of transrectal ultrasound (TRUS) and carried out by use of preloaded needles. Postimplant dosimetry was calculated by use of magnetic resonance imaging-computed tomography fusion on Days 1, 8, and 30. The anterior rectal-wall dose is reported as the isodose enclosing 1.0 or 2.0 cc of rectal wall and as the RV100 in cc. Results: The dose to rectal wall increased progressively over time. The median increase in dose to 1.0 cc of rectal wall (RD [1 cc]) from Day 1 to 30 was 39.2 Gy (p < 0.001). RV100 increased from a median of 0.07 cc on Day 1 to 0.67 cc on Day 30. The most significant predictor of rectal-wall dose (RD [1 cc], RD [2 cc], or RV100) was the time of evaluation (p < 0.001). Conclusion: Although periprostatic edema cannot be quantified by postimplant imaging, the dose to the anterior rectal wall increases significantly over time as prostatic and periprostatic edema resolve. Critical-organ dose reporting and guidelines for minimizing toxicity must take into account the time of the assessment.

  17. Ultrasonic Nakagami-parameter characterization of parotid-gland injury following head-and-neck radiotherapy: A feasibility study of late toxicity

    SciTech Connect

    Yang, Xiaofeng; Wu, Ning; Wang, Yuefeng; Tridandapani, Srini; Beitler, Jonathan J.; Yu, David S.; Curran, Walter J.; Liu, Tian; Bruner, Deborah W.

    2014-02-15

    Purpose: The study aims to investigate whether Nakagami parameters—estimated from the statistical distribution of the backscattered ultrasound radio-frequency (RF) signals—could provide a means for quantitative characterization of parotid-gland injury resulting from head-and-neck radiotherapy. Methods: A preliminary clinical study was conducted with 12 postradiotherapy patients and 12 healthy volunteers. Each participant underwent one ultrasound study in which ultrasound scans were performed in the longitudinal, i.e., vertical orientation on the bilateral parotids. For the 12 patients, the mean radiation dose to the parotid glands was 37.7 ± 9.5 Gy, and the mean follow-up time was 16.3 ± 4.8 months. All enrolled patients experienced grade 1 or 2 late salivary-gland toxicity (RTOG/EORTC morbidity scale). The normal parotid glands served as the control group. The Nakagami-scaling and Nakagami-shape parameters were computed from the RF data to quantify radiation-induced parotid-gland changes. Results: Significant differences in Nakagami parameters were observed between the normal and postradiotherapy parotid glands. Compared with the control group, the Nakagami-scaling parameter of the postradiotherapy group decreased by 25.8% (p < 0.001), and the Nakagami-shape parameter decreased by 31.3% (p < 0.001). The area under the receiver operating characteristic curve was 0.85 for the Nakagami-scaling parameter and was 0.95 for the Nakagami-shape parameter, which further demonstrated the diagnostic efficiency of the Nakagami parameters. Conclusions: Nakagami parameters could be used to quantitatively measure parotid-gland injury following head-and-neck radiotherapy. Moreover, the clinical feasibility was demonstrated and this study provides meaningful preliminary data for future clinical investigation.

  18. [Rectosacropexy in rectal prolapse management].

    PubMed

    Titov, A Iu; Biriukov, O M; Fomenko, O Iu; Zarodniuk, I V; Voĭnov, M A

    2016-01-01

    To compare results of rectosacropexy and posterior-loop rectopexy in rectal prolapse management. Study included 122 patients operated for rectal prolapse for the period January 2007 to August 2014. Patients' age ranged from 19 to 85 years (mean 47.3±16.1). Main group consisted of 60 (49.2%) patients who underwent rectosacropexy (D'Hoore's procedure). Control group included 62 (50.8%) patients in whom posterior-loop rectopexy was applied (Wells's procedure). Long-term results were followed-up in 94 (77.0%) patients including 48 and 46 from main and control group respectively. Recurrent prolaple incidence after rectosacropexy and posterior-loop rectopexy was 2% and 8.7% respectively. Multivariant analysis statistically confirmed that postoperative impaired colon motility was independent risk factor of recurrence. Recurrent disease is observed 5.7 times more often in this case. Rectosacropexy does not significantly impair colon motility because of ileus occurs in 8.3% of operated patients. Impovement of anal continence does not depend on rectopexy method and occurs in all patients with degree 1-2 of anal sphincter failure. Rectosacropexy may be preferred in rectal prolapse. However, further highly significant studies are necessary to optimize rectal prolapse management.

  19. Incidence and risk factors for rectal pain after laparoscopic rectal cancer surgery

    PubMed Central

    Lee, Jin Young; Kim, Hee Cheol; Huh, Jung Wook; Lim, Hyun Young; Lee, Eun Kyung; Park, Hui Gyeong; Bang, Yu Jeong

    2017-01-01

    Objective This study was performed to investigate the incidence of and potential risk factors for rectal pain after laparoscopic rectal cancer surgery. Methods We retrospectively analyzed data from 300 patients who underwent laparoscopic rectal cancer surgery. We assessed the presence of rectal pain and categorized patients into Group N (no rectal pain) or Group P (rectal pain). Results In total, 288 patients were included. Of these patients, 39 (13.5%) reported rectal pain and 14 (4.9%) had rectal pain that persisted for >3 months. Univariate analysis revealed that patients in Group P had more preoperative chemoradiotherapy, more ileostomies, longer operation times, more anastomotic margins of <2 cm from the anal verge, more anastomotic leakage, and longer hospital stays. Multivariate analysis identified an anastomotic margin of <2 cm from the anal verge and a long operation time as risk factors. The presence of diabetes mellitus was a negative predictor of rectal pain. Conclusions In this study, the incidence of rectal pain after laparoscopic rectal cancer surgery was 13.5%. An anastomotic margin of <2 cm from the anal verge and a long operation time were risk factors for rectal pain. The presence of diabetes mellitus was a negative predictor of rectal pain. Thus, the possibility of postoperative rectal pain should be discussed preoperatively with patients with these risk factors. PMID:28415928

  20. Late Side Effects After Image Guided Intensity Modulated Radiation Therapy Compared to 3D-Conformal Radiation Therapy for Prostate Cancer: Results From 2 Prospective Cohorts.

    PubMed

    Wortel, Ruud C; Incrocci, Luca; Pos, Floris J; van der Heide, Uulke A; Lebesque, Joos V; Aluwini, Shafak; Witte, Marnix G; Heemsbergen, Wilma D

    2016-06-01

    Technical developments in the field of external beam radiation therapy (RT) enabled the clinical introduction of image guided intensity modulated radiation therapy (IG-IMRT), which improved target conformity and allowed reduction of safety margins. Whether this had an impact on late toxicity levels compared to previously applied three-dimensional conformal radiation therapy (3D-CRT) is currently unknown. We analyzed late side effects after treatment with IG-IMRT or 3D-CRT, evaluating 2 prospective cohorts of men treated for localized prostate cancer to investigate the hypothesized reductions in toxicity. Patients treated with 3D-CRT (n=189) or IG-IMRT (n=242) to 78 Gy in 39 fractions were recruited from 2 Dutch randomized trials with identical toxicity scoring protocols. Late toxicity (>90 days after treatment) was derived from self-assessment questionnaires and case report forms, according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG-EORTC) scoring criteria. Grade ≥2 endpoints included gastrointestinal (GI) rectal bleeding, increased stool frequency, discomfort, rectal incontinence, proctitis, and genitourinary (GU) obstruction, increased urinary frequency, nocturia, urinary incontinence, and dysuria. The Cox proportional hazards regression model was used to compare grade ≥2 toxicities between both techniques, adjusting for other modifying factors. The 5-year cumulative incidence of grade ≥2 GI toxicity was 24.9% for IG-IMRT and 37.6% following 3D-CRT (adjusted hazard ratio [HR]: 0.59, P=.005), with significant reductions in proctitis (HR: 0.37, P=.047) and increased stool frequency (HR: 0.23, P<.001). GU grade ≥2 toxicity levels at 5 years were comparable with 46.2% and 36.4% following IG-IMRT and 3D-CRT, respectively (adjusted HR: 1.19, P=.33). Other strong predictors (P<.01) of grade ≥2 late toxicity were baseline complaints, acute toxicity, and age. Treatment with IG-IMRT reduced the risk of

  1. Dose/volume-response relations for rectal morbidity using planned and simulated motion-inclusive dose distributions.

    PubMed

    Thor, Maria; Apte, Aditya; Deasy, Joseph O; Karlsdóttir, Àsa; Moiseenko, Vitali; Liu, Mitchell; Muren, Ludvig Paul

    2013-12-01

    Many dose-limiting normal tissues in radiotherapy (RT) display considerable internal motion between fractions over a course of treatment, potentially reducing the appropriateness of using planned dose distributions to predict morbidity. Accounting explicitly for rectal motion could improve the predictive power of modelling rectal morbidity. To test this, we simulated the effect of motion in two cohorts. The included patients (232 and 159 cases) received RT for prostate cancer to 70 and 74 Gy. Motion-inclusive dose distributions were introduced as simulations of random or systematic motion to the planned dose distributions. Six rectal morbidity endpoints were analysed. A probit model using the QUANTEC recommended parameters was also applied to the cohorts. The differences in associations using the planned over the motion-inclusive dose distributions were modest. Statistically significant associations were obtained with four of the endpoints, mainly at high doses (55-70 Gy), using both the planned and the motion-inclusive dose distributions, primarily when simulating random motion. The strongest associations were observed for GI toxicity and rectal bleeding (Rs=0.12-0.21; Rs=0.11-0.20). Applying the probit model, significant associations were found for tenesmus and rectal bleeding (Rs=0.13, p=0.02). Equally strong associations with rectal morbidity were observed at high doses (>55 Gy), for the planned and the simulated dose distributions including in particular random rectal motion. Future studies should explore patient-specific descriptions of rectal motion to achieve improved predictive power. Published by Elsevier Ireland Ltd.

  2. Poloxamer 188 and propylene glycol-based rectal suppository enhances anticancer effect of 5-fluorouracil in mice.

    PubMed

    Paek, Seung-Hwan; Xuan, Jing-Ji; Choi, Han-Gon; Park, Byung Chul; Lee, Yoon-Seok; Jeong, Tae-Cheon; Jin, Chun Hua; Oh, Yu-Kyoung; Kim, Jung-Ae

    2006-05-01

    The tumoricidal and apoptosis-inducing activities of 5-fluorouracil (5-FU) have been demonstrated in experimental and clinical investigations. Clinically, the 5-FU suppository form has been widely adopted for its advantages of less systemic toxicity, higher local tissue concentrations, and reduced first-pass effect. In this study, we investigated the feasibility of rectal administration of 5-FU suppository based on poloxamer 188 (P188) and propylene glycol (PG) and its anticancer effect on the murine experimental cancer models. The rectal suppository was made with 70% P188 and 30% PG, which was a solid phase at room temperature and instantly melted at physiological temperature. The treatment with the 5-FU suppository was more effective than the oral route in decreasing the volume of rectal cancer in mice. In addition, the survival rate of the mice with rectal cancer was higher in the group treated with the 5-FU suppository than in the group treated with 5-FU orally. Furthermore, in mice skin cancers induced by inoculation of murine CT-26 colon carcinoma cells, the anticancer effect of 5-FU was significantly enhanced by the rectal administration of the suppository than by oral treatment. Taken together, the results suggest that a poloxamer gel system with 5-FU/P188/PG is an effective rectal dosage form for the treatment of both rectal and non-rectal cancers.

  3. Does initial 45Gy of pelvic intensity-modulated radiotherapy reduce late complications in patients with locally advanced cervical cancer? A cohort control study using definitive chemoradiotherapy with high-dose rate brachytherapy

    PubMed Central

    Chen, Shang-Wen; Liang, Ji-An; Hung, Yao-Ching; Yeh, Lian-Shung; Chang, Wei-Chun; Lin, Wu-Chou; Chien, Chun-Ru

    2013-01-01

    Background Comparing initial 45 Gy of pelvic intensity-modulated radiation therapy (IMRT) and non-IMRT in terms of the late toxicities associated with advanced cervical cancer that has also been treated with definitive concurrent chemoradiotherapy and high-dose rate intracavitary brachytherapy (HDRICB). Patients and methods This retrospective study included 320 stage IB2-IIIB cervical cancer patients treated with CCRT (83 IMRT and 237 non-IMRT). The two groups had similar stage and HDRICB ratings. Following 45 Gy to the pelvis, HDRICB of 24 Gy in four courses was prescribed. Late toxicities, including rectal complications (RC), bladder complications (BC) and non-rectal intestinal injury (NRRII), were scored by the Common Terminology Criteria for Adverse Events. A logistic regression was used to estimate the odds ratio (OR) of the complications. Results With a median follow-up duration of 33 and 77 months for IMRT and non-IMRT, 33 patients had Grade 2 or higher late RC (7.2% IMRT, 11.4% non-IMRT), whereas that for BC was 40 (9.6% IMRT, 13.5% non-IMRT) and for NRRII was 48 (12.0% IMRT, 16.0% non-IMRT). The cumulative rate for total grade 3 or higher gastrointestinal or genitourinary toxicities was 8.4% and 11.8% (p = 0.33). IMRT did not reduce the OR for all endpoints; however, the ORs for rectum and bladder reference doses to Point A were associated with RC and BC. Conclusions Locally advanced cervical cancer patients treated with initial 45Gy of pelvic IMRT and HDRICB have similar treatment-related late toxicities as those treated with non-IMRT. Optimization of the brachytherapy scheme is essential to minimize late toxicities. PMID:23801915

  4. Correlation between tumor regression grade and rectal volume in neoadjuvant concurrent chemoradiotherapy for rectal cancer

    PubMed Central

    Lee, Hong Seok; Choi, Doo Ho; Park, Hee Chul; Park, Won; Yu, Jeong Il; Chung, Kwangzoo

    2016-01-01

    Purpose To determine whether large rectal volume on planning computed tomography (CT) results in lower tumor regression grade (TRG) after neoadjuvant concurrent chemoradiotherapy (CCRT) in rectal cancer patients. Materials and Methods We reviewed medical records of 113 patients treated with surgery following neoadjuvant CCRT for rectal cancer between January and December 2012. Rectal volume was contoured on axial images in which gross tumor volume was included. Average axial rectal area (ARA) was defined as rectal volume divided by longitudinal tumor length. The impact of rectal volume and ARA on TRG was assessed. Results Average rectal volume and ARA were 11.3 mL and 2.9 cm². After completion of neoadjuvant CCRT in 113 patients, pathologic results revealed total regression (TRG 4) in 28 patients (25%), good regression (TRG 3) in 25 patients (22%), moderate regression (TRG 2) in 34 patients (30%), minor regression (TRG 1) in 24 patients (21%), and no regression (TRG0) in 2 patients (2%). No difference of rectal volume and ARA was found between each TRG groups. Linear correlation existed between rectal volume and TRG (p = 0.036) but not between ARA and TRG (p = 0.058). Conclusion Rectal volume on planning CT has no significance on TRG in patients receiving neoadjuvant CCRT for rectal cancer. These results indicate that maintaining minimal rectal volume before each treatment may not be necessary. PMID:27592514

  5. Phase II dose escalation study of image-guided adaptive radiotherapy for prostate cancer: Use of dose-volume constraints to achieve rectal isotoxicity

    SciTech Connect

    Vargas, Carlos; Yan Di; Kestin, Larry L.; Krauss, Daniel; Lockman, David M.; Brabbins, Donald S.; Martinez, Alvaro A. . E-mail: amartinez@beaumont.edu

    2005-09-01

    Purpose: In our Phase II prostate cancer Adaptive Radiation Therapy (ART) study, the highest possible dose was selected on the basis of normal tissue tolerance constraints. We analyzed rectal toxicity rates in different dose levels and treatment groups to determine whether equivalent toxicity rates were achieved as hypothesized when the protocol was started. Methods and Materials: From 1999 to 2002, 331 patients with clinical stage T1 to T3, node-negative prostate cancer were prospectively treated with three-dimensional conformal adaptive RT. A patient-specific confidence-limited planning target volume was constructed on the basis of 5 CT scans and 4 sets of electronic portal images after the first 4 days of treatment. For each case, the rectum (rectal solid) was contoured in its entirety. The rectal wall was defined by use of a 3-mm wall thickness (median volume: 29.8 cc). The prescribed dose level was chosen using the following rectal wall dose constraints: (1) Less than 30% of the rectal wall volume can receive more than 75.6 Gy. (2) Less than 5% of the rectal wall can receive more than 82 Gy. Low-risk patients (PSA < 10, Stage {<=} T2a, Gleason score < 7) were treated to the prostate alone (Group 1). All other patients, intermediate and high risk, where treated to the prostate and seminal vesicles (Group 2). The risk of chronic toxicity (NCI Common Toxicity Criteria 2.0) was assessed for the different dose levels prescribed. HIC approval was acquired for all patients. Median follow-up was 1.6 years. Results: Grade 2 chronic rectal toxicity was experienced by 34 patients (10%) (9% experienced rectal bleeding, 6% experienced proctitis, 3% experienced diarrhea, and 1% experienced rectal pain) at a median interval of 1.1 year. Nine patients (3%) experienced grade 3 or higher chronic rectal toxicity (1 Grade 4) at a median interval of 1.2 years. The 2-year rates of Grade 2 or higher and Grade 3 or higher chronic rectal toxicity were 17% and 3%, respectively. No

  6. [Surgical treatment of rectal cancer].

    PubMed

    Vergara-Fernández, O; Salinas-Aragón, L E; Camacho-Mauries, D; Medina-Franco, H

    2010-01-01

    Rectal affection accounts for 30% of colorectal cancer. The standard of treatment is surgical resection, which often is curative. For superior and middle-rectal involvement, low anterior resection (LAR) is the preferred procedure. For tumors involving the lower portion of the rectum, abdominoperineal resection (APR) or LAR are the options of treatment, depending on sphincter involvement. The main surgical objective is to achieve a R0 resection with an appropriated total mesorrectal excision, greater number of lymph nodes and negative distal and radial margins. These surgical parameters have been used as quality indicators and have prognostic implications in terms of overall and disease-free survival. Total mesorectal excision with preservation of hypogastric nerves has shown a reduction in rates of sexual and bladder dysfunction as well as lower local recurrence. At specialized centers such procedures are performed by minimal invasive surgery; however the number of meta-analysis is scarce.

  7. Low Toxicity in Inflammatory Bowel Disease Patients Treated With Abdominal and Pelvic Radiation Therapy.

    PubMed

    White, Evan C; Murphy, James D; Chang, Daniel T; Koong, Albert C

    2015-12-01

    To determine the short-term and long-term toxicity of abdominal and pelvic radiation therapy in a cohort of patients with inflammatory bowel disease (IBD). We hypothesize that with newer techniques, such as intensity-modulated radiation therapy (IMRT) and 3-dimensional conformal radiotherapy (3D-CRT), patients with IBD can safely undergo abdominal and pelvic radiation, with low risk for major acute or late toxicity. Nineteen consecutive patients with IBD (14 with ulcerative colitis, 5 with Crohn disease) who were treated with abdominal or pelvic external beam radiation therapy at Stanford University from 1997 to 2011 were identified. Fourteen patients were treated with IMRT and 5 were treated with 3D-CRT. Treated sites included prostate (n=8), gastric/esophageal (n=5), rectal/anal (n=3), and liver (n=3) tumors. Charts were reviewed and toxicity was graded according to the Common Terminology Criteria for Acute Events version 4.0. Median follow-up was 32.5 months. Fisher exact test was used to determine if any clinical and/or treatment factors were associated with toxicity outcomes. Acute grade ≥3 toxicity occurred in 2 patients (11%). Late grade ≥3 toxicity occurred in 1 patient (6%). Acute grade ≥2 toxicity occurred in 28% of patients treated with IMRT versus 100% of patients treated with 3D-CRT (P=0.01). Acute grade ≥2 gastrointestinal toxicity was lower in patients treated with IMRT versus 3D-CRT (14% vs. 100%, respectively, P=0.002). Late grade ≥2 toxicity occurred in 21% of patients. Higher total dose (Gy) and biologically effective dose (Gy) were associated with increased rates of late grade ≥2 toxicity (P=0.02 and 0.03, respectively). These data suggest that select patients with IBD can safely undergo abdominal and pelvic radiation therapy. The use of IMRT was associated with decreased acute toxicity. Acute and late severe toxicity rates were low in this patient population with the use of modern radiation techniques.

  8. Robotic surgery for rectal cancer.

    PubMed

    Nozawa, Hiroaki; Watanabe, Toshiaki

    2017-09-26

    Laparoscopic surgery has gained acceptance as a less invasive approach in the treatment of colon cancer. However, laparoscopic surgery for rectal cancer, particularly cancer of the lower rectum, is still challenging because of limited accessibility. Robotic surgery overcomes the limitations of laparoscopy associated with anatomy and offers certain advantages, including 3-D imaging, dexterity and ambidextrous capability, lack of tremors, motion scaling, and a short learning curve. Robotic rectal surgery has been reported to reduce conversion rates, particularly in low anterior resection, but it is associated with longer operative times than the conventional laparoscopic approach. Postoperative morbidities are similar between the robotic and conventional laparoscopic approaches, and oncological outcomes such as the quality of the mesorectum and the status of resection margins are also equivalent. The possible superiority of robotic surgery in terms of the preservation of autonomic function has yet to be established in research based on larger numbers of patients. Although robotic rectal surgery is safe, feasible, and appears to overcome some of the technical limitations associated with conventional laparoscopic surgery, the advantages provided by this technical innovation are currently limited. To justify its expensive cost, robotic surgery is more suitable for select patients, such as obese patients, men, those with cancer of the lower rectum, and those receiving preoperative chemoradiotherapy. © 2017 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.

  9. Stubborn rectal prolapse in systemic sclerosis.

    PubMed

    Petersen, Sven; Tobisch, Alexander; Puhl, Gero; Kötter, Ina; Wollina, Uwe

    2017-01-01

    Systemic sclerosis (SSc) is an autoimmune connective tissue disorder. Anorectal involvement might typically cause fecal incontinence and rarely rectal prolapse. Here we report three female patients, who were admitted with a mean history of 10 years suffering from SSc. All patients presented with the initial symptom of anal incontinence, in all cases this was associated with rectal intussusception or rectal prolapse. The three women faced prolapse recurrence, independent of the initial procedure. After surgical removal of the prolapse, the incontinence remained. In SSc rectal prolapse syndrome might occur at an earlier age, and a primary prolapse of the ventral aspect of the rectal wall seems to be typical for this disease. If patients with prior diagnosis of SSc appear with third degree of fecal incontinence, it is suspected to be associated with rectal prolapse. The prolapse recurrence rate after surgery in SSc patients is high.

  10. Effects of Prostate-Rectum Separation on Rectal Dose From External Beam Radiotherapy

    SciTech Connect

    Susil, Robert C.; McNutt, Todd R.; DeWeese, Theodore L.; Song, Danny

    2010-03-15

    Purpose: In radiotherapy for prostate cancer, the rectum is the major dose-limiting structure. Physically separating the rectum from the prostate (e.g., by injecting a spacer) can reduce the rectal radiation dose. Despite pilot clinical studies, no careful analysis has been done of the risks, benefits, and dosimetric effects of this practice. Methods and Materials: Using cadaveric specimens, 20 mL of a hydrogel was injected between the prostate and rectum using a transperineal approach. Imaging was performed before and after spacer placement, and the cadavers were subsequently dissected. Ten intensity-modulated radiotherapy plans were generated (five before and five after separation), allowing for characterization of the rectal dose reduction. To quantify the amount of prostate-rectum separation needed for effective rectal dose reduction, simulations were performed using nine clinically generated intensity-modulated radiotherapy plans. Results: In the cadaveric studies, an average of 12.5 mm of prostate-rectum separation was generated with the 20-mL hydrogel injections (the seminal vesicles were also separated from the rectum). The average rectal volume receiving 70 Gy decreased from 19.9% to 4.5% (p < .05). In the simulation studies, a prostate-rectum separation of 10 mm was sufficient to reduce the mean rectal volume receiving 70 Gy by 83.1% (p <.05). No additional reduction in the average rectal volume receiving 70 Gy was noted after 15 mm of separation. In addition, spacer placement allowed for increased planning target volume margins without exceeding the rectal dose tolerance. Conclusion: Prostate-rectum spacers can allow for reduced rectal toxicity rates, treatment intensification, and/or reduced dependence on complex planning and treatment delivery techniques.

  11. Preoperative Chemoradiotherapy in Elderly Patients with Locally Advanced Rectal Cancer

    PubMed Central

    Musio, Daniela; Izzo, Luciano; Pugliese, Federico; Izzo, Paolo; Bolognese, Antonio

    2013-01-01

    Purpose. To evaluate the treatment tolerance and clinical outcomes in patients aged 70 and older with locally advanced rectal carcinoma treated with multimodality approach. Methods and Materials. We retrospectively analysed 20 consecutive elderly patients, with histologically proven rectal adenocarcinoma, staged T3-4, and/or node-positive tumour, who received chemoradiotherapy and proceeded to surgical approach. Performance status score and adult comorbidity evaluation-27 score were calculated, and their influence on treatment tolerance and clinical outcomes was analysed. Results. All patients completed programmed chemoradiotherapy treatment. Gastrointestinal toxicity was the most common acute side effects: proctitis in 70% of patients and diarrhoea in 55%, classified as Grade 3 in 3 patients only. Radiation dermatitis was reported in 7 patients (35%) and it was graded G3 in one patient. There was no haematological toxicity. Eighteen patients out of 20 underwent surgery. Sphincter preservation was assured in 13 patients. Comorbidity index was related to higher severe acute toxicity (P = 0.015) but no influenced treatment outcomes. Conclusion. Treatment tolerance with combined modality is good in elderly patients. Due to age, no dose reduction for radiation therapy and chemotherapy should be considered. PMID:24392453

  12. Penile metastases of rectal adenocarcinoma.

    PubMed

    Persec, Z; Persec, J; Sovic, T; Rako, D; Savic, I; Marinic, D K

    2014-02-01

    Penile metastases are very rare and arise most frequently from genitourinary cancers. Penile metastases from rectal adenocarcinoma are less common and only 50 or so cases have been reported. We present a 43-year-old man with penile metastases from a rectal adenocarcinoma. Two years before admittance to our department, abdomino-perineal resection of the rectum (Miles operation) was performed for a Dukes B (T3N0M0) rectal adenocarcinoma; the surgical resection margins wee negative. Adjuvant chemotherapy and radiotherapy treatment were administered. One year after initial management, excision of a local recurrence was performed followed by further chemotherapy. The patient subsequently noticed lesions of the penis measuring up to 1.2 cm in diameter. Biopsy revealed metastatic adenocarcinoma. Computed tomography showed normal structure of penis with subcutaneous nodular thickening. Soon thereafter, the entire shaft of the penis becomes indurated and the patient developed urinary obstruction. A suprapubic cystostomy was performed. The patient died within 6 months. Penile metastases arise most frequently from genitourinary cancers, primarily from the bladder and the prostate gland. Metastasis to the penis from a rectal adenocarcinoma occurs much less commonly. Other reported primary origins of penile metastases include malignancies of the lung, nasopharynx and melanoma. The major symptoms are penile nodular mass, malignant priapism, penile pain and tenderness, difficulty in micturition, and urinary retention. Possible routes of metastasis are arterial, retrograde venous spread, retrograde lymphatic spread, but direct tumor infiltration/extension is also possible. Penile metastases from rectal adenocarcinoma usually occur within 2 years after diagnosis of the primary tumor. The prognosis is very poor regardless of treatment modality. Treatment is more often palliative than curative. Survival usually varies from 7 months to 2 years. Long-term survival (9 years) has been

  13. Robotic rectal surgery: what are the benefits?

    PubMed

    Kim, C W; Baik, S H

    2013-10-01

    Robotic rectal surgery is not a rare event for colorectal surgeons any more. Even patients with colorectal diseases obtain information through the mass media and are asking surgeons about robotic surgery. Since laparoscopic rectal surgery has proved to have some benefits compared to open rectal surgery, many surgeons became interested in robotic rectal surgery. Some of them have reported the advantages and disadvantages of robotic rectal surgery over the last decade. This review will report on the outcomes of robotic rectal surgery. Robotic rectal surgery requires a longer operation time than laparoscopic or open surgery, but many authors reduced the gap as they were accustomed to the robotic system and used various additional techniques. The high cost for purchasing and maintaining the robotic system is still a problem, though. However, except for this reason, robotic rectal surgery shows comparable and even superior results in some parameters than laparoscopic or open surgery. They include pathologic and functional outcomes as well as short-term outcomes such as complication rates, length of hospital stay, time to recover normal bowel function or first flatus, time to start diet, and postoperative pain. Moreover, studies on oncologic outcomes show acceptable results. Robotic rectal surgery is safe and feasible and has a number of benefits. Therefore, it can be an alternative option to conventional laparoscopic and open surgery with strict indications.

  14. Rectal neuroendocrine neoplasms: a case report

    PubMed Central

    Su, Hao

    2016-01-01

    The gastrointestinal neuroendocrine neoplasms (GI-NENs) are very rare, among which second most common type is the rectal NENs in China. Patients with rectal NENs may experience non-specific symptoms such as pain, perianal bulge, anemia, and bloody stools, and surgery is considered as the first treatment for rectal NENs. We report a case of rectal NENs in a 68-year-old male patient with bloody stools, who received surgery and postoperative pathology revealed an elevated well-differentiated neuroendocrine carcinoma. PMID:28138616

  15. Multivariate normal tissue complication probability modeling of gastrointestinal toxicity after external beam radiotherapy for localized prostate cancer

    PubMed Central

    2013-01-01

    Background The risk of radio-induced gastrointestinal (GI) complications is affected by several factors other than the dose to the rectum such as patient characteristics, hormonal or antihypertensive therapy, and acute rectal toxicity. Purpose of this work is to study clinical and dosimetric parameters impacting on late GI toxicity after prostate external beam radiotherapy (RT) and to establish multivariate normal tissue complication probability (NTCP) model for radiation-induced GI complications. Methods A total of 57 men who had undergone definitive RT for prostate cancer were evaluated for GI events classified using the RTOG/EORTC scoring system. Their median age was 73 years (range 53–85). The patients were assessed for GI toxicity before, during, and periodically after RT completion. Several clinical variables along with rectum dose-volume parameters (Vx) were collected and their correlation to GI toxicity was analyzed by Spearman’s rank correlation coefficient (Rs). Multivariate logistic regression method using resampling techniques was applied to select model order and parameters for NTCP modeling. Model performance was evaluated through the area under the receiver operating characteristic curve (AUC). Results At a median follow-up of 30 months, 37% (21/57) patients developed G1-2 acute GI events while 33% (19/57) were diagnosed with G1-2 late GI events. An NTCP model for late mild/moderate GI toxicity based on three variables including V65 (OR = 1.03), antihypertensive and/or anticoagulant (AH/AC) drugs (OR = 0.24), and acute GI toxicity (OR = 4.3) was selected as the most predictive model (Rs = 0.47, p < 0.001; AUC = 0.79). This three-variable model outperforms the logistic model based on V65 only (Rs = 0.28, p < 0.001; AUC = 0.69). Conclusions We propose a logistic NTCP model for late GI toxicity considering not only rectal irradiation dose but also clinical patient-specific factors. Accordingly, the risk of G1

  16. Magnamosis: a novel technique for the management of rectal atresia

    PubMed Central

    Russell, Katie W; Rollins, Michael D; Feola, G Peter; Scaife, Eric R

    2014-01-01

    We report a case of rectal atresia treated using magnets to create a rectal anastomosis. This minimally invasive technique is straightforward and effective for the treatment of rectal atresia in children. PMID:25096648

  17. 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

  18. Natural history of late radiation proctosigmoiditis treated with topical sucralfate suspension.

    PubMed

    Kochhar, R; Sriram, P V; Sharma, S C; Goel, R C; Patel, F

    1999-05-01

    Rectal bleeding due to radiation proctosigmoiditis is often difficult to manage. We had earlier shown the efficacy of short-term therapy with topical sucralfate in controlling bleeding in the radiation proctosigmoiditis. We now report our long-term results with this form of therapy. The study comprised 26 patients with radiation proctosigmoiditis. Sigmoidoscopically, 9 (34.6%) patients had severe changes, 15 (57.69%) had moderate, and 2 (7.69%) had mild changes. Severity of bleeding was graded as severe (> 15 episodes per week), moderate (8-14 episodes per week), mild (2-7 episodes per week), negligible (< or = 1 episode per week), or nil (no bleeding). Ten patients had moderate rectal bleeding, while 16 had severe bleeding. All patients were treated with 20 ml of 10% rectal sucralfate suspension enemas twice a day until bleeding per rectum ceased or failure of therapy was acknowledged. Response to therapy was considered good whenever the severity of bleeding showed improvement by a change of two grades. Rectally administered sucralfate achieved good response in 20 (76.9%) patients at 4 weeks, 22 (84.6%) patients at 8 weeks, and 24 (92.3%) patients at 16 weeks. This change was significant by Wilcoxon matched-pairs signed-ranks test. Two patients required surgery due to poor response. Over a median follow-up of 45.5 months (range 5-73 months) after cessation of bleeding, 17 (70.8%) patients had no further bleeding while 7 (22.2%) had recurrence of bleeding. All recurrences responded to short-term reinstitution of therapy. No treatment-related complications were observed. Ten patients had other associated late toxicity due to pelvic irradiation in the form of asymptomatic rectal stricture (N = 3), rectovaginal fistula (N = 1), intestinal stricture (N = 1), vaginal stenosis (N = 1), and hematuria (N = 6). Three patients had progression of the primary disease in the form of pelvic recurrence (N = 2) and hepatic metastases (N = 1). We conclude that topical sucralfate

  19. Dose Escalation to the Dominant Intraprostatic Lesion Defined by Sextant Biopsy in a Permanent Prostate I-125 Implant: A Prospective Comparative Toxicity Analysis

    SciTech Connect

    Gaudet, Marc; Vigneault, Eric; Aubin, Sylviane; Varfalvy, Nicolas; Harel, Francois; Beaulieu, L.; Martin, Andre-Guy

    2010-05-01

    Purpose: Using real-time intraoperative inverse-planned permanent seed prostate implant (RTIOP/PSI), multiple core biopsy maps, and three-dimensional ultrasound guidance, we planned a boost volume (BV) within the prostate to which hyperdosage was delivered selectively. The aim of this study was to investigate the potential negative effects of such a procedure. Methods and Materials: Patients treated with RTIOP/PSI for localized prostate cancer with topographic biopsy results received an intraprostatic boost (boost group [BG]). They were compared with patients treated with a standard plan (reference group [RG]). Plans were generated using a simulated annealing inverse planning algorithm. Prospectively recorded urinary, rectal, and sexual toxicities and dosimetric parameters were compared between groups. Results: The study included 120 patients treated with boost technique who were compared with 70 patients treated with a standard plan. Boost technique did not significantly change the number of seeds (55.1/RG vs. 53.6/BG). The intraoperative prostate V150 was slightly higher in BG (75.2/RG vs. 77.2/BG, p = 0.039). Urethra V100, urethra D90, and rectal D50 were significantly lower in the BG. No significant differences were seen in acute or late urinary, rectal, or sexual toxicities. Conclusions: Because there were no differences between the groups in acute and late toxicities, we believe that BV can be planned and delivered to the dominant intraprostatic lesion without increasing toxicity. It is too soon to say whether a boost technique will ultimately increase local control.

  20. Multidisciplinary management in rectal cancer.

    PubMed

    Hervás Morón, Asunción; García de Paredes, María Luisa; Lobo Martínez, Eduardo

    2010-12-01

    The treatment of rectal cancer has evolved over the last few decades from surgery alone to treatments with trimodal therapy for high-risk patients. The involvement of a multidisciplinary team of radiologists, pathologists, surgeons, radiotherapists and medical oncologists is now fundamental for decision-making and outcomes. The evolution of different diagnostic and therapeutic techniques has optimised the therapeutic rate. Future studies will determine the optimal regimen for inducing complete responses in locally advanced disease and whether the intensification of local treatments could enable the use of more conservative treatments, as for other tumour locations. The study of biomarkers will be essential in this respect.

  1. Multiple rectal carcinoid tumors in monozygotic twins.

    PubMed

    Doi, Momoko; Ikawa, Osamu; Taniguchi, Hiroki; Kawamura, Takuji; Katsura, Kanade

    2016-08-01

    We report multiple rectal carcinoid tumors in monozygotic twins who, respectively, had 42 and 36 carcinoid tumors in the lower rectum. This is the first report about carcinoid tumors in monozygotic twins. Both twins developed a similar number of rectal carcinoids with a similar distribution. Investigation of their genetic background may provide information about the origin of these tumors.

  2. Fournier gangrene: rare complication of rectal cancer.

    PubMed

    Ossibi, Pierlesky Elion; Souiki, Tarik; Ibn Majdoub, Karim; Toughrai, Imane; Laalim, Said Ait; Mazaz, Khalid; Tenkorang, Somuah; Farih, My Hassan

    2015-01-01

    Fournier's Gangrene is a rare complication of rectal cancer. Its discovery is often delayed. It's incidence is about 0.3/100,000 populations in Western countries. We report a patient with peritoneal perforation of rectal cancer revealed by scrotal and perineal necrotizing fasciitis.

  3. Late toxicity and patient self-assessment of breast appearance/satisfaction on RTOG 0319: a phase 2 trial of 3-dimensional conformal radiation therapy-accelerated partial breast irradiation following lumpectomy for stages I and II breast cancer.

    PubMed

    Chafe, Susan; Moughan, Jennifer; McCormick, Beryl; Wong, John; Pass, Helen; Rabinovitch, Rachel; Arthur, Douglas W; Petersen, Ivy; White, Julia; Vicini, Frank A

    2013-08-01

    Late toxicities and cosmetic analyses of patients treated with accelerated partial breast irradiation (APBI) on RTOG 0319 are presented. Patients with stages I to II breast cancer ≤3 cm, negative margins, and ≤3 positive nodes were eligible. Patients received three-dimensional conformal external beam radiation therapy (3D-CRT; 38.5 Gy in 10 fractions twice daily over 5 days). Toxicity and cosmesis were assessed by the patient (P), the radiation oncologist (RO), and the surgical oncologist (SO) at 3, 6, and 12 months from the completion of treatment and then annually. National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, was used to grade toxicity. Fifty-two patients were evaluable. Median follow-up was 5.3 years (range, 1.7-6.4 years). Eighty-two percent of patients rated their cosmesis as good/excellent at 1 year, with rates of 64% at 3 years. At 3 years, 31 patients were satisfied with the treatment, 5 were not satisfied but would choose 3D-CRT again, and none would choose standard radiation therapy. The worst adverse event (AE) per patient reported as definitely, probably, or possibly related to radiation therapy was 36.5% grade 1, 50% grade 2, and 5.8% grade 3 events. Grade 3 AEs were all skin or musculoskeletal-related. Treatment-related factors were evaluated to potentially establish an association with observed toxicity. Surgical bed volume, target volume, the number of beams used, and the use of bolus were not associated with late cosmesis. Most patients enrolled in RTOG 0319 were satisfied with their treatment, and all would choose to have the 3D-CRT APBI again. Copyright © 2013. Published by Elsevier Inc.

  4. Late Toxicity and Patient Self-Assessment of Breast Appearance/Satisfaction on RTOG 0319: A Phase 2 Trial of 3-Dimensional Conformal Radiation Therapy-Accelerated Partial Breast Irradiation Following Lumpectomy for Stages I and II Breast Cancer

    SciTech Connect

    Chafe, Susan; Moughan, Jennifer; McCormick, Beryl; Wong, John; Pass, Helen; Rabinovitch, Rachel; Arthur, Douglas W.; Petersen, Ivy; White, Julia; Vicini, Frank A.

    2013-08-01

    Purpose: Late toxicities and cosmetic analyses of patients treated with accelerated partial breast irradiation (APBI) on RTOG 0319 are presented. Methods and Materials: Patients with stages I to II breast cancer ≤3 cm, negative margins, and ≤3 positive nodes were eligible. Patients received three-dimensional conformal external beam radiation therapy (3D-CRT; 38.5 Gy in 10 fractions twice daily over 5 days). Toxicity and cosmesis were assessed by the patient (P), the radiation oncologist (RO), and the surgical oncologist (SO) at 3, 6, and 12 months from the completion of treatment and then annually. National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, was used to grade toxicity. Results: Fifty-two patients were evaluable. Median follow-up was 5.3 years (range, 1.7-6.4 years). Eighty-two percent of patients rated their cosmesis as good/excellent at 1 year, with rates of 64% at 3 years. At 3 years, 31 patients were satisfied with the treatment, 5 were not satisfied but would choose 3D-CRT again, and none would choose standard radiation therapy. The worst adverse event (AE) per patient reported as definitely, probably, or possibly related to radiation therapy was 36.5% grade 1, 50% grade 2, and 5.8% grade 3 events. Grade 3 AEs were all skin or musculoskeletal-related. Treatment-related factors were evaluated to potentially establish an association with observed toxicity. Surgical bed volume, target volume, the number of beams used, and the use of bolus were not associated with late cosmesis. Conclusions: Most patients enrolled in RTOG 0319 were satisfied with their treatment, and all would choose to have the 3D-CRT APBI again.

  5. Bevacizumab, Fluorouracil, Leucovorin Calcium, and Oxaliplatin Before Surgery in Treating Patients With Stage II-III Rectal Cancer

    ClinicalTrials.gov

    2017-04-11

    Mucinous Adenocarcinoma of the Rectum; 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

  6. [Rectal administration of anesthetic agents].

    PubMed

    Ceriana, P; Maurelli, M

    1995-05-01

    To collect data in the current literature dealing with the diffusion, the reliability and the effectiveness of the rectal administration of anaesthetic drugs. To evaluate differences with parenteral administration. Pharmacokinetics and clinical studies published in recent years in indexed journals. Based on the study methodology, drugs employed and pharmacokinetic parameters evaluated. Factors involved in absorption of drugs from the rectal mucosa, clinical effect and pharmacokinetic data of the following drugs: diazepam, flunitrazepam, midazolam, ketamin and methohexital, then a brief evaluation of other drugs: thiopental, etomidate, morphine and chloral hydrate. The most widely used drugs are benzodiazepines: they are safe, easy to manage and highly effective; among them midazolam has the best kinetic and dynamic pattern. Ketamin is useful during painful diagnostic procedures; with the use of barbiturates there is a greater risk of respiratory depression and more caution must be employed. Wide intervariability of rate of absorption, achievement of plasma levels and clinical effect is a relevant drawback of this technique, such to make it not preferable to the parenteral route, when both are feasible. It deserves, anyway, more consideration, and maintains its validity for the preparation of the paediatric patient to general anaesthesia.

  7. Progress in Rectal Cancer Treatment

    PubMed Central

    Ceelen, Wim P.

    2012-01-01

    The dramatic improvement in local control of rectal cancer observed during the last decades is to be attributed to attention to surgical technique and to the introduction of neoadjuvant therapy regimens. Nevertheless, systemic relapse remains frequent and is currently insufficiently addressed. Intensification of neoadjuvant therapy by incorporating chemotherapy with or without targeted agents before the start of (chemo)radiation or during the waiting period to surgery may present an opportunity to improve overall survival. An increasing number of patients can nowadays undergo sphincter preserving surgery. In selected patients, local excision or even a “wait and see” approach may be feasible following active neoadjuvant therapy. Molecular and genetic biomarkers as well as innovative imaging techniques may in the future allow better selection of patients for this treatment option. Controversy persists concerning the selection of patients for adjuvant chemotherapy and/or targeted therapy after neoadjuvant regimens. The currently available evidence suggests that in complete pathological responders long-term outcome is excellent and adjuvant therapy may be omitted. The results of ongoing trials will help to establish the ideal tailored approach in resectable rectal cancer. PMID:22970381

  8. 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.

  9. Induction chemotherapy with paclitaxel and cisplatin followed by radiotherapy for larynx organ preservation in advanced laryngeal and hypopharyngeal cancer offers moderate late toxicity outcome (DeLOS-I-trial).

    PubMed

    Dietz, Andreas; Rudat, Volker; Dreyhaupt, Jens; Pritsch, Maria; Hoppe, Florian; Hagen, Rudolph; Pfreundner, Leo; Schröder, Ursula; Eckel, Hans; Hess, Markus; Schröder, Michael; Schneider, Petra; Jens, Bünzel; Zenner, Hans P; Werner, Jochen A; Engenhardt-Cabillic, Rita; Vanselow, Bernhard; Plinkert, Peter; Niewald, Marcus; Kuhnt, Thomas; Budach, Wilfried; Flentje, Michael

    2009-08-01

    A prospective multicenter phase-II trial (12 centers) was performed by the German larynx organ preservation group (DeLOS) to evaluate the effect of induction chemotherapy (ICHT) with paclitaxel/cisplatin (TP), followed by accelerated-hyperfractionated (concomitant boost) radiotherapy (RT) in responders. The trial was focused on larynx preservation, tumor control, survival, salvage surgery and late toxicity in patients with advanced larynx/hypopharynx carcinoma eligible for total laryngectomy (LE). Seventy-one patients (40 larynx, 87.5% St. III, IV; 31 hypopharynx, 93.4% St. III, IV) were enrolled into the study and treated with ICHT (200 mg/m(2) paclitaxel, 100 mg/m(2) cisplatin; day 1, 22) according to the DeLOS protocol. Patients with complete or partial tumor response proceeded to RT (69.9 Gy in 5.5 weeks). Non-responders received a LE followed by postoperative RT (56-70 Gy in 5.5-7 weeks). The response rate to ICHT for larynx cancer was 69.6% (7.1% complete, 62.5% partial response) and for hypopharyngeal cancer was 84.3% (6.9% complete, 77.4% partial response). Overall survival after 36 months was 60.3% (95% CI, 48.4-72.2%), after 42 months was 56.5% (95% CI, 44.2-68.8%). Laryngectomy-free survival was as follows: after 36 months, 43.0% (95% CI, 30.9-55.0%); after 42 months, 41.3% (95% CI, 29.3-53.3%). Both parameters did not show different outcomes after distinguishing larynx from hypopharynx. LE was indicated in 15 non-responders after ICHT. Five of the 15 non-responders refused the laryngectomy. Two of the five received RT instead and had no evidence of disease 42 months after RT. Late toxicity (dysphagia III, IV LENT SOMA score in laryngectomy-free survivors: after 6 months, 1.8%; 12 months, 11.4%; 18 months, 14.5%; 24 months, 8.1%; 36 months, 16%) and salvage surgery (4 pharyngocutaneous fistulas in 27 operations) were tolerable. In a large portion of patients eligible for LE, the larynx could be preserved with satisfying functional outcome. Good

  10. Transanal endoscopic surgery in rectal cancer.

    PubMed

    Serra-Aracil, Xavier; Mora-Lopez, Laura; Alcantara-Moral, Manel; Caro-Tarrago, Aleidis; Gomez-Diaz, Carlos Javier; Navarro-Soto, Salvador

    2014-09-07

    Total mesorectal excision (TME) is the standard treatment for rectal cancer, but complications are frequent and rates of morbidity, mortality and genitourinary alterations are high. Transanal endoscopic microsurgery (TEM) allows preservation of the anal sphincters and, via its vision system through a rectoscope, allows access to rectal tumors located as far as 20 cm from the anal verge. The capacity of local surgery to cure rectal cancer depends on the risk of lymph node invasion. This means that correct preoperative staging of the rectal tumor is necessary. Currently, local surgery is indicated for rectal adenomas and adenocarcinomas invading the submucosa, but not beyond (T1). Here we describe the standard technique for TEM, the different types of equipment used, and the technical limitations of this approach. TEM to remove rectal adenoma should be performed in the same way as if the lesion were an adenocarcinoma, due to the high percentage of infiltrating adenocarcinomas in these lesions. In spite of the generally good results with T1, some authors have published surprisingly high recurrence rates; this is due to the existence of two types of lesions, tumors with good and poor prognosis, divided according to histological and surgical factors. The standard treatment for rectal adenocarcinoma T2N0M0 is TME without adjuvant therapy. In this type of adenocarcinoma, local surgery obtains the best results when complete pathological response has been achieved with previous chemoradiotherapy. The results with chemoradiotherapy and TEM are encouraging, but the scientific evidence remains limited at present.

  11. 11C choline PET guided salvage radiotherapy with volumetric modulation arc therapy and hypofractionation for recurrent prostate cancer after HIFU failure: preliminary results of tolerability and acute toxicity.

    PubMed

    Alongi, Filippo; Liardo, Rocco L E; Iftode, Cristina; Lopci, Egesta; Villa, Elisa; Comito, Tiziana; Tozzi, Angelo; Navarria, Pierina; Ascolese, Anna M; Mancosu, Pietro; Tomatis, Stefano; Bellorofonte, Carlo; Arturo, Chiti; Scorsetti, Marta

    2014-10-01

    The purpose of this work was to evaluate tolerance, feasibility and acute toxicity in patients undergoing salvage radiotherapy after high-intensity focused ultrasound (HIFU) failure. From 2005 to 2011 a total of 15 patients were treated with HIFU as primary radical treatment. Between July 2011 and February 2013, all 15 patients presented biochemical relapse after HIFU and 11C choline PET documenting intrapostatic-only failure. Salvage EBRT was performed with moderate hypofractionation schedule in 28 fractions with volumetric modulation arc therapy (VMAT). Genito-urinary (GU) and rectal and bowel toxicity were scored by common terminology criteria for adverse events version 4 (CTCAE V.4) scale. Biochemical response was assessed by ASTRO Phoenix criteria. Median age of patients was 67 years (range: 53-85). The median Gleason score was 7 (range: 6-9). The median prostate specific antigen (PSA) at the time of biochemical relapse after HIFU was 5.2 ng/mL (range: 2-64.2). Seven of the 15 patients received androgen deprivation therapy (ADT) started after HIFU failure, interrupted before 11C choline PET and radiotherapy. Median prescribed dose was 71.4 Gy (range: 71.4-74.2 Gy) in 28 fractions. No radiation related major upper gastrointestinal (GI), rectal and GU toxicity were experienced. GU, acute grade 1 and grade 2 toxicities were recorded in 7/15 and 4/15 respectively; bowel acute grade 1 and grade 2 toxicities in 4/15 and 1/15; rectal acute grade 1 and grade 2 toxicities in 3/15 and 2/15 respectively. No grade 3 or greater acute or late toxicities occurred. Biochemical control was assessed in 12/15 (80%) patients. With a median follow up of 12 months, three out of 15 patients, with biochemical relapse, showed lymph-nodal recurrence. Our early clinical results and biochemical data confirm the feasibility and show a good tolerance of the 11C choline PET guided salvage radiation therapy after HIFU failure. The findings of low acute toxicity is encouraging, but longer

  12. Photodynamic therapy with motexafin lutetium for rectal cancer: a preclinical model in the dog.

    PubMed

    Ross, H M; Smelstoys, J A; Davis, G J; Kapatkin, A S; Del Piero, F; Reineke, E; Wang, H; Zhu, T C; Busch, T M; Yodh, A G; Hahn, S M

    2006-10-01

    Local recurrence of rectal cancer remains a significant clinical problem despite multi-modality therapy. Photodynamic Therapy (PDT) is a cancer treatment which generates tumor kill through the production of singlet oxygen in cells containing a photosensitizing drug when exposed to laser light of a specific wavelength. PDT is a promising modality for prevention of local recurrence of rectal cancer for several reasons: tumor cells may selectively retain photosensitizer at higher levels than normal tissues, the pelvis after mesorectal excision is a fixed space amenable to intra-operative illumination, and PDT can generate toxicity in tissues up to 1 cm thick. This study evaluated the safety, tissue penetration of 730 nm light, normal tissue toxicity and surgical outcome in a dog model of rectal resection after motexafin lutetium-mediated photodynamic therapy. Ten mixed breed dogs were used. Eight dogs underwent proctectomy and low rectal end to end stapled anastomosis. Six dogs received the photosensitizing agent motexafin lutetium (MLu, Pharmacyclics, Inc., Sunnyvale, CA) of 2 mg/kg preoperatively and underwent subsequent pelvic illumination of the transected distal rectum of 730 nm light with light doses ranging from 0.5 J/cm(2) to 10 J/cm(2) three hours after drug delivery. Two dogs received light, but no drug, and underwent proctectomy and low-rectal stapled anastomosis. Two dogs underwent midline laparotomy and pelvic illumination. Light penetration in tissues was determined for small bowel, rectum, pelvic sidewall, and skin. Clinical outcomes were recorded. Animals were sacrificed at 14 days and histological evaluation was performed. All dogs recovered uneventfully. No dog suffered an anastomotic leak. Severe tissue toxicity was not seen. Histological findings at necropsy revealed mild enteritis in all dogs. The excitation light penetration depths were 0.46 +/- 0.18, 0.46 +/- 0.15, and 0.69 +/- 0.39 cm, respectively, for rectum, small bowel, and peritoneum in

  13. Toxicity associated with adjuvant postoperative therapy for adenocarcinoma of the rectum

    SciTech Connect

    Thomas, P.R.; Lindblad, A.S.; Stablein, D.M.; Knowlton, A.H.; Bruckner, H.W.; Childs, D.S.; Mittelman, A.

    1986-03-15

    An adjuvant rectal carcinoma study compared four postoperative treatment regimens: (1) control (no adjuvant therapy); (2) chemotherapy alone consisting of pulses of 5-fluorouracil and methyl CCNU for 18 months; (3) pelvic and perineal radiotherapy using parallel opposed fields with 4000 rad in 4.5 to 5 weeks or 4800 rad in 5 to 5.5 weeks; and (4) a combination of both modalities. The results of this study are published elsewhere and show a significantly reduced recurrence rate and prolonged disease-free survival time for the combined modality arm compared with the no therapy arm. Severe toxicity in the combined therapy arm was significantly worse (P less than 0.001) than in either single modality arm. Most of the differences in toxicity experienced between the three regimens involved diarrhea, thrombocytopenia, and leukopenia. Analysis of all parameters of radiotherapy quality assurance data was not significantly associated with toxicity. Radiation enteritis was noted in 5 patients of 96 (5.2%) in the two arms containing irradiation. All five required laparotomy. The two enteritis fatalities occurred late at 605 and 1000 days after start of combined modality treatment, respectively. One other patient on the chemotherapy arm died of acute nonlymphocytic leukemia. The authors conclude that combined radiotherapy and chemotherapy, although significantly more effective in reducing recurrence than no therapy, is significantly more toxic than single-modality therapy in many parameters, although most of the toxicity is transient and therefore not limiting. Late complications, which are less reversible and therefore much more important than early reactions, and radiation enteritis in this study were relatively uncommon. This schedule of combined modality therapy is not only effective but appears to have tolerable toxicity, because of the relative lack of late effects.

  14. Development of the American Society of Colon & Rectal Surgeons (ASCRS) Rectal Cancer Surgery Checklist

    PubMed Central

    Glasgow, Sean C.; Morris, Arden M.; Baxter, Nancy N.; Fleshman, James W.; Alavi, Karim S.; Luchtefeld, Martin A.; Monson, John R. T.; Chang, George J.; Temple, Larissa K.

    2016-01-01

    Background There is excellent evidence that surgical safety checklists contribute to decreased morbidity and mortality. Objective To develop a surgical checklist comprising the key phases of care for rectal cancer patients. Design Consensus-oriented decision-making model involving iterative input from subject matter experts under the auspices of the American Society of Colon and Rectal Surgeons. Results The process generated a 25-item checklist covering the spectrum of care for rectal cancer patients undergoing surgery. Limitations Lack of prospective validation. Conclusions The American Society of Colon and Rectal Surgeons Rectal Cancer Surgery checklist comprises the essential elements of pre-, intra- and postoperative care that must be addressed during the surgical treatment of patients with rectal cancer. PMID:27270511

  15. Future of therapy for rectal cancer.

    PubMed

    Minsky, Bruce D

    2013-06-01

    Since 2004, the standard of care for patients with cT3 and/or N+ rectal cancer has been preoperative chemoradiation followed by surgery and postoperative adjuvant chemotherapy. A number of advances have occurred and are defining the future of rectal cancer therapy. Among these are short course radiation, the impact of postoperative adjuvant chemotherapy, selective radiation and selective surgery, and new chemoradiation regimens with novel agents. This review will examine these developments and assess their impact on the future therapy of rectal cancer.

  16. 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

  17. Treatment outcomes and late toxicities of 869 patients with nasopharyngeal carcinoma treated with definitive intensity modulated radiation therapy: new insight into the value of total dose of cisplatin and radiation boost

    PubMed Central

    Ou, Xiaomin; Zhou, Xin; Shi, Qi; Xing, Xing; Yang, Youqi; Xu, Tingting; Shen, Chunying; Wang, Xiaoshen; He, Xiayun; Kong, Lin; Ying, Hongmei; Hu, Chaosu

    2015-01-01

    This study was to report the long-term outcomes and toxicities of nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). From 2009 to 2010, 869 non-metastatic NPC patients treated with IMRT were retrospectively enrolled. With a median follow-up of 54.3 months, the 5-year estimated local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) were 89.7%, 94.5%, 85.6%, 76.3%, 84.0%, respectively. In locally advanced NPC, gender, T, N, total dose of cisplatin more than 300 mg/m2 and radiation boost were independent prognostic factors for DMFS and DFS. Age, T, N and total dose of cisplatin were independent prognostic factors for OS. Radiation boost was an adverse factor for LRFS, RRFS, DMFS and DFS. Concurrent chemotherapy was not an independent prognostic factor for survival, despite marginally significant for DMFS in univariate analysis. Concurrent chemotherapy increased xerostomia and trismus, while higher total dose of cisplatin increased xerostomia and otologic toxicities. In conclusion, IMRT provided satisfactory long-term outcome for NPC, with acceptable late toxicities. Total dose of cisplatin was a prognostic factor for distant metastasis and overall survival. The role of concurrent chemotherapy and radiation boost in the setting of IMRT warrants further investigation. PMID:26485757

  18. Paediatric rectal prolapse in Rwanda.

    PubMed Central

    Chaloner, E J; Duckett, J; Lewin, J

    1996-01-01

    During the 1994 crisis in Rwanda, a high incidence of full-thickness rectal prolapse was noted among the refugee children in the south-west of the country. The prolapses arose as a result of acute diarrhoeal illness superimposed on malnutrition and worm infestation. We used a modification of the Thiersch wire technique in 40 of these cases during two months working in a refugee camp. A catgut pursestring was tied around the anal margin under local, regional or general anaesthesia. This was effective in achieving short-term control of full-thickness prolapse until the underlying illness was corrected. Under the circumstances, no formal follow-up could be arranged; however, no complications were reported and only one patient presented with recurrence. Images Figure 1 PMID:9014879

  19. Mechanical suture in rectal cancer.

    PubMed

    Cheregi, Cornel Dragos; Simon, Ioan; Fabian, Ovidiu; Maghiar, Adrian

    2017-01-01

    Colorectal cancer is one of the most frequent digestive malignancies, being the third cause of death by cancer, despite early diagnosis and therapeutic progress made over the past years. Standard treatment in these patients is to preserve the anal sphincter with restoration of intestinal function by mechanical colorectal anastomosis or coloanal anastomosis, and to maintain genitourinary function by preservation of hypogastric nerves. In order to emphasize the importance of this surgical technique in the Fourth Surgical Clinic of the CF Clinical Hospital Cluj-Napoca, we conducted a prospective observational interventional study over a 3-year period (2013-2016) in 165 patients hospitalized for rectal and rectosigmoid adenocarcinoma in various disease stages, who underwent Dixon surgery using the two techniques of manual and mechanical end-to-end anastomosis. For mechanical anastomosis, we used Covidien and Panther circular staplers. The patients were assigned to two groups, group A in which Dixon surgery with manual end-to-end anastomosis was performed (116 patients), and group B in which Dixon surgery with mechanical end-to-end anastomosis was carried out (49 patients). Mechanical anastomosis allowed to restore intestinal continuity following low anterior resection in 21 patients with lower rectal adenocarcinoma compared to 2 patients in whom intestinal continuity was restored by manual anastomosis, with a statistically significant difference (p<0.000001). The double-row mechanical suture technique is associated with a reduced duration of surgery (121.67 minutes for Dixon surgery with mechanical anastomosis, compared to 165.931 minutes for Dixon surgery with manual anastomosis, p<0.0001). The use of circular transanal staplers facilitates end-to-end anastomosis by double-row mechanical suture, allowing to perform low anterior resection in situations when the restoration of intestinal continuity by manual anastomosis is technically not possible, with the aim to

  20. A rare cause of chronic rectal bleeding in children; solitary rectal ulcer: case report.

    PubMed

    Temiz, Abdulkerim; Tander, Burak; Temiz, Muhyittin; Barış, Sancar; Arıtürk, Ender

    2011-03-01

    Solitary rectal ulcer causing lower gastrointestinal bleeding is extremely rare in children. Rare presentation, non-specific symptoms, insufficient experience, and characteristics mimicking other rectal diseases may cause misdiagnosis or delay of diagnosis in some pediatric patients. Here, we report a 10-year-old boy with solitary rectal ulcer diagnosed two years after onset of the symptoms who responded well to the conservative therapy, including high-fiber diet, laxatives, defecation training, and sucralfate enema.

  1. PET-MRI in Diagnosing Patients With Colon or Rectal Cancer

    ClinicalTrials.gov

    2015-11-25

    Recurrent Colon Cancer; Recurrent 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; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  2. Influence of image slice thickness on rectal dose-response relationships following radiotherapy of prostate cancer

    NASA Astrophysics Data System (ADS)

    Olsson, C.; Thor, M.; Liu, M.; Moissenko, V.; Petersen, S. E.; Høyer, M.; Apte, A.; Deasy, J. O.

    2014-07-01

    When pooling retrospective data from different cohorts, slice thicknesses of acquired computed tomography (CT) images used for treatment planning may vary between cohorts. It is, however, not known if varying slice thickness influences derived dose-response relationships. We investigated this for rectal bleeding using dose-volume histograms (DVHs) of the rectum and rectal wall for dose distributions superimposed on images with varying CT slice thicknesses. We used dose and endpoint data from two prostate cancer cohorts treated with three-dimensional conformal radiotherapy to either 74 Gy (N = 159) or 78 Gy (N = 159) at 2 Gy per fraction. The rectum was defined as the whole organ with content, and the morbidity cut-off was Grade ≥2 late rectal bleeding. Rectal walls were defined as 3 mm inner margins added to the rectum. DVHs for simulated slice thicknesses from 3 to 13 mm were compared to DVHs for the originally acquired slice thicknesses at 3 and 5 mm. Volumes, mean, and maximum doses were assessed from the DVHs, and generalized equivalent uniform dose (gEUD) values were calculated. For each organ and each of the simulated slice thicknesses, we performed predictive modeling of late rectal bleeding using the Lyman-Kutcher-Burman (LKB) model. For the most coarse slice thickness, rectal volumes increased (≤18%), whereas maximum and mean doses decreased (≤0.8 and ≤4.2 Gy, respectively). For all a values, the gEUD for the simulated DVHs were ≤1.9 Gy different than the gEUD for the original DVHs. The best-fitting LKB model parameter values with 95% CIs were consistent between all DVHs. In conclusion, we found that the investigated slice thickness variations had minimal impact on rectal dose-response estimations. From the perspective of predictive modeling, our results suggest that variations within 10 mm in slice thickness between cohorts are unlikely to be a limiting factor when pooling multi-institutional rectal dose data that include slice thickness

  3. Rectal gastrointestinal stromal tumor as an incidental finding in a patient with rectal polyps.

    PubMed

    Zhou, Yong; Wu, Xu-Dong; Fan, Ren-Gen; zha, Wen-Zhang; Xu, Yong-Hua; Qing, Cheng-Lin; Jia, Jing

    2015-01-01

    A patient who was diagnosed as rectal polyps in the local hospital went to our hospital for surgical treatment. Abdominal CT demonstrated a large irregular extra-luminal tumor of at least 5 cm cross-section on the ventral side of the lower rectal wall. Intraoperatively, a large irregular extra-luminal tumor (about 5×4.5×4 cm) was found. Anterior resection with end colostomy and rectal stump (Hartmann's procedure) was performed. Postoperative histological examination showed simultaneous development of rectal GIST and polyps.

  4. Drugs Approved for Colon and Rectal Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for use in colon cancer and rectal cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  5. Low Rectal Cancer Study (MERCURY II)

    ClinicalTrials.gov

    2016-03-11

    Adenocarcinoma; Adenocarcinoma, Mucinous; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Cystic, Mucinous, and Serous; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

  6. How to Use Rectal Suppositories Properly

    MedlinePlus

    ... Lubricate the suppository tip with a water-soluble lubricant such as K-Y Jelly, not petroleum jelly (Vaseline). If you do not have this lubricant, moisten your rectal area with cool tap water. ...

  7. Predictive models of toxicity with external radiotherapy for prostate cancer: clinical issues.

    PubMed

    Valdagni, Riccardo; Rancati, Tiziana; Fiorino, Claudio

    2009-07-01

    The objective of the current study was to analyze the state of the art and present limitations of available predictive clinical models (when available) estimating the risk of genitourinary tract and small bowel complications, erectile dysfunction, and acute and late symptoms of the rectal syndrome caused by prostate cancer external irradiation. An analysis of the literature indicated that very limited attention has been devoted to the development of "integrated," patient-tailored, user-friendly, and clinically usable tools for the prediction of external beam radiotoxicity. In this article, the authors reported on the multivariate correlation between late genitourinary and gastrointestinal toxicities and clinical/dosimetric risk factors, as well as on the first set of nomograms developed to predict acute and late rectal side effects. At the present state of knowledge, the use of nomograms as predictive instruments of radiotoxicity appears to be particularly attractive for several main reasons. They are "user friendly" and easily developed using the results of multivariate analyses, as they weigh the combined effects of multiple independent factors found to be correlated with the selected clinical endpoint. The integrated evaluation of clinical and dosimetric parameters in the single patient can help to provide a tailored probability of the specific outcome considered. Predicting a high probability of toxicity could avoid unnecessary daily costs for the individual patient in terms of quality of life modification during and after treatment, helping patients in the decision-making process of choosing the best individual, quality of life-related treatment, and clinicians in better tailoring the treatment to patient's characteristics. Cancer 2009;115(13 suppl):3141-9. (c) 2009 American Cancer Society.

  8. Robotic rectal surgery: State of the art.

    PubMed

    Staderini, Fabio; Foppa, Caterina; Minuzzo, Alessio; Badii, Benedetta; Qirici, Etleva; Trallori, Giacomo; Mallardi, Beatrice; Lami, Gabriele; Macrì, Giuseppe; Bonanomi, Andrea; Bagnoli, Siro; Perigli, Giuliano; Cianchi, Fabio

    2016-11-15

    Laparoscopic rectal surgery has demonstrated its superiority over the open approach, however it still has some technical limitations that lead to the development of robotic platforms. Nevertheless the literature on this topic is rapidly expanding there is still no consensus about benefits of robotic rectal cancer surgery over the laparoscopic one. For this reason a review of all the literature examining robotic surgery for rectal cancer was performed. Two reviewers independently conducted a search of electronic databases (PubMed and EMBASE) using the key words "rectum", "rectal", "cancer", "laparoscopy", "robot". After the initial screen of 266 articles, 43 papers were selected for review. A total of 3013 patients were included in the review. The most commonly performed intervention was low anterior resection (1450 patients, 48.1%), followed by anterior resections (997 patients, 33%), ultra-low anterior resections (393 patients, 13%) and abdominoperineal resections (173 patients, 5.7%). Robotic rectal surgery seems to offer potential advantages especially in low anterior resections with lower conversions rates and better preservation of the autonomic function. Quality of mesorectum and status of and circumferential resection margins are similar to those obtained with conventional laparoscopy even if robotic rectal surgery is undoubtedly associated with longer operative times. This review demonstrated that robotic rectal surgery is both safe and feasible but there is no evidence of its superiority over laparoscopy in terms of postoperative, clinical outcomes and incidence of complications. In conclusion robotic rectal surgery seems to overcome some of technical limitations of conventional laparoscopic surgery especially for tumors requiring low and ultra-low anterior resections but this technical improvement seems not to provide, until now, any significant clinical advantages to the patients.

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

    SciTech Connect

    Shiraishi, Yutaka; Hanada, Takashi; Ohashi, Toshio; Yorozu, Atsunori; Toya, Kazuhito; Saito, Shiro; Shigematsu, Naoyuki

    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 of 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.

  10. Vaginal-cuff control and toxicity results of a daily HDR brachytherapy schedule in endometrial cancer patients.

    PubMed

    Ríos, I; Rovirosa, A; Ascaso, C; Valduvieco, I; Herreros, A; Castilla, L; Sabater, S; Holub, K; Pahisa, J; Biete, A; Arenas, M

    2016-09-01

    To analyze the vaginal-cuff local control (VCC) and toxicity in postoperative endometrial carcinoma patients (EC) underwent high-dose-rate brachytherapy (HDR-BT) administered daily. 154 consecutive patients received postoperative HDR-BT for EC from January 2007 to September 2011. FIGO-staging I-IIIC2 patients were divided into two groups according to risk classification: Group 1 (94/154) included high-risk or advanced disease patients and Group 2 (60/154) included intermediate-risk EC patients. Group 1 underwent external beam irradiation (EBI) plus HDR-BT (2 fractions of 5 Gy) and Group 2 underwent HDR-BT alone (4 fractions of 5 Gy). Toxicity evaluation was done with RTOG scores for bladder and rectum, and the objective criteria of LENT-SOMA for vagina. With a median follow-up of 46.7 months (36.6-61 months) only two patients developed vaginal-cuff recurrence in Group 1 (2.1 %) and none in group 2 (0 %). Early toxicity in Group 1 appeared 5.3 % in rectum, 7.5 % in bladder (G1-G2) and 2.1 % in vagina (G1); late toxicity was present in 7.3 % in rectum (all G1-G2 but 1 G3) and in 27.7 % in vagina (all G1-G2 but one G4). In Group 2, 6.7 % developed acute G1-G2 bladder and 6.6 % acute vaginal (G1-G2) toxicity. No late rectal or bladder toxicity was observed; 21.7 % of G1-G2 presented late problems in vagina. The present HDR-BT schedule of 2 fractions of 5 Gy after EBI and 4 fractions of 5 Gy administered daily showed excellent results in terms of VCC and toxicity.

  11. Locally advanced rectal cancer: management challenges

    PubMed Central

    Kokelaar, RF; Evans, MD; Davies, M; Harris, DA; Beynon, J

    2016-01-01

    Between 5% and 10% of patients with rectal cancer present with locally advanced rectal cancer (LARC), and 10% of rectal cancers recur after surgery, of which half are limited to locoregional disease only (locally recurrent rectal cancer). Exenterative surgery offers the best long-term outcomes for patients with LARC and locally recurrent rectal cancer so long as a complete (R0) resection is achieved. Accurate preoperative multimodal staging is crucial in assessing the potential operability of advanced rectal tumors, and resectability may be enhanced with neoadjuvant therapies. Unfortunately, surgical options are limited when the tumor involves the lateral pelvic sidewall or high sacrum due to the technical challenges of achieving histological clearance, and must be balanced against the high morbidity associated with resection of the bony pelvis and significant lymphovascular structures. This group of patients is usually treated palliatively and subsequently survival is poor, which has led surgeons to seek innovative new solutions, as well as revisit previously discarded radical approaches. A small number of centers are pioneering new techniques for resection of beyond-total mesorectal excision tumors, including en bloc resections of the sciatic notch and composite resections of the first two sacral vertebrae. Despite limited experience, these new techniques offer the potential for radical treatment of previously inoperable tumors. This narrative review sets out the challenges facing the management of LARCs and discusses evolving management options. PMID:27785074

  12. Management of rectal varices in portal hypertension

    PubMed Central

    Al Khalloufi, Kawtar; Laiyemo, Adeyinka O

    2015-01-01

    Rectal varices are portosystemic collaterals that form as a complication of portal hypertension, their prevalence has been reported as high as 94% in patients with extrahepatic portal vein obstruction. The diagnosis is typically based on lower endoscopy (colonoscopy or sigmoidoscopy). However, endoscopic ultrasonography has been shown to be superior to endoscopy in diagnosing rectal varices. Color Doppler ultrasonography is a better method because it allows the calculation of the velocity of blood flow in the varices and can be used to predict the bleeding risk in the varices. Although rare, bleeding from rectal varices can be life threatening. The management of patients with rectal variceal bleeding is not well established. It is important to ensure hemodynamic stability with blood transfusion and to correct any coagulopathy prior to treating the bleeding varices. Endoscopic injection sclerotherapy has been reported to be more effective in the management of active bleeding from rectal varices with less rebleeding rate as compared to endoscopic band ligation. Transjugular intrahepatic portsystemic shunt alone or in combination with embolization is another method used successfully in control of bleeding. Balloon-occluded retrograde transvenous obliteration is an emerging procedure for management of gastric varices that has also been successfully used to treat bleeding rectal varices. Surgical procedures including suture ligation and porto-caval shunts are considered when other methods have failed. PMID:26730278

  13. Hodgkin’s lymphoma emerging radiation treatment techniques: trade-offs between late radio-induced toxicities and secondary malignant neoplasms

    PubMed Central

    2013-01-01

    Background Purpose of this study is to explore the trade-offs between radio-induced toxicities and second malignant neoplasm (SMN) induction risk of different emerging radiotherapy techniques for Hodgkin’s lymphoma (HL) through a comprehensive dosimetric analysis on a representative clinical model. Methods Three different planning target volume (PTVi) scenarios of a female patient with supradiaphragmatic HL were used as models for the purpose of this study. Five treatment radiation techniques were simulated: an anterior-posterior parallel-opposed (AP-PA), a forward intensity modulated (FIMRT), an inverse intensity modulated (IMRT), a Tomotherapy (TOMO), a proton (PRO) technique. A radiation dose of 30 Gy or CGE was prescribed. Dose-volume histograms of PTVs and organs-at-risk (OARs) were calculated and related to available dose-volume constraints. SMN risk for breasts, thyroid, and lungs was estimated through the Organ Equivalent Dose model considering cell repopulation and inhomogeneous organ doses. Results With similar level of PTVi coverage, IMRT, TOMO and PRO plans generally reduced the OARs’ dose and accordingly the related radio-induced toxicities. However, only TOMO and PRO plans were compliant with all constraints in all scenarios. For the IMRT and TOMO plans an increased risk of development of breast, and lung SMN compared with AP-PA and FIMRT techniques was estimated. Only PRO plans seemed to reduce the risk of predicted SMN compared with AP-PA technique. Conclusions Our model–based study supports the use of advanced RT techniques to successfully spare OARs and to reduce the risk of radio-induced toxicities in HL patients. However, the estimated increase of SMNs’ risk inherent to TOMO and IMRT techniques should be carefully considered in the evaluation of a risk-adapted therapeutic strategy. PMID:23360559

  14. Development of a Set of Nomograms to Predict Acute Lower Gastrointestinal Toxicity for Prostate Cancer 3D-CRT

    SciTech Connect

    Valdagni, Riccardo; Rancati, Tiziana Fiorino, Claudio; Fellin, Gianni; Magli, Alessandro; Baccolini, Michela; Bianchi, Carla; Cagna, Emanuela; Greco, Carlo; Mauro, Flora A.; Monti, Angelo F.; Munoz, Fernando; Stasi, Michele; Franzone, Paola; Vavassori, Vittorio

    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. 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

  15. Chromosome Damage and Cell Proliferation Rates in In Vitro Irradiated Whole Blood as Markers of Late Radiation Toxicity After Radiation Therapy to the Prostate

    SciTech Connect

    Beaton, Lindsay A.; Ferrarotto, Catherine; Marro, Leonora; Samiee, Sara; Malone, Shawn; Grimes, Scott; Malone, Kyle; Wilkins, Ruth C.

    2013-04-01

    Purpose: In vitro irradiated blood samples from prostate cancer patients showing late normal tissue damage were examined for lymphocyte response by measuring chromosomal aberrations and proliferation rate. Methods and Materials: Patients were selected from a randomized trial evaluating the optimal timing of dose-escalated radiation and short-course androgen deprivation therapy. Of 438 patients, 3% experienced grade 3 late radiation proctitis and were considered to be radiosensitive. Blood samples were taken from 10 of these patients along with 20 matched samples from patients with grade 0 proctitis. The samples were irradiated at 6 Gy and, along with control samples, were analyzed for dicentric chromosomes and excess fragments per cell. Cells in first and second metaphase were also enumerated to determine the lymphocyte proliferation rate. Results: At 6 Gy, there were statistically significant differences between the radiosensitive and control cohorts for 3 endpoints: the mean number of dicentric chromosomes per cell (3.26 ± 0.31, 2.91 ± 0.32; P=.0258), the mean number of excess fragments per cell (2.27 ± 0.23, 1.43 ± 0.37; P<.0001), and the proportion of cells in second metaphase (0.27 ± 0.10, 0.46 ± 0.09; P=.0007). Conclusions: These results may be a valuable indicator for identifying radiosensitive patients and for tailoring radiation therapy.

  16. Argon Plasma Coagulation Therapy Versus Topical Formalin for Intractable Rectal Bleeding and Anorectal Dysfunction After Radiation Therapy for Prostate Carcinoma

    SciTech Connect

    Yeoh, Eric; Tam, William; Schoeman, Mark; Moore, James; Thomas, Michelle; Botten, Rochelle; Di Matteo, Addolorata

    2013-12-01

    Purpose: To evaluate and compare the effect of argon plasma coagulation (APC) and topical formalin for intractable rectal bleeding and anorectal dysfunction associated with chronic radiation proctitis. Methods and Materials: Thirty men (median age, 72 years; range, 49-87 years) with intractable rectal bleeding (defined as ≥1× per week and/or requiring blood transfusions) after radiation therapy for prostate carcinoma were randomized to treatment with APC (n=17) or topical formalin (n=13). Each patient underwent evaluations of (1) anorectal symptoms (validated questionnaires, including modified Late Effects in Normal Tissues–Subjective, Objective, Management, and Analytic and visual analogue scales for rectal bleeding); (2) anorectal motor and sensory function (manometry and graded rectal balloon distension); and (3) anal sphincteric morphology (endoanal ultrasound) before and after the treatment endpoint (defined as reduction in rectal bleeding to 1× per month or better, reduction in visual analogue scales to ≤25 mm, and no longer needing blood transfusions). Results: The treatment endpoint was achieved in 94% of the APC group and 100% of the topical formalin group after a median (range) of 2 (1-5) sessions of either treatment. After a follow-up duration of 111 (29-170) months, only 1 patient in each group needed further treatment. Reductions in rectal compliance and volumes of sensory perception occurred after APC, but no effect on anorectal symptoms other than rectal bleeding was observed. There were no differences between APC and topical formalin for anorectal symptoms and function, nor for anal sphincteric morphology. Conclusions: Argon plasma coagulation and topical formalin had comparable efficacy in the durable control of rectal bleeding associated with chronic radiation proctitis but had no beneficial effect on anorectal dysfunction.

  17. Surgical management of rectal prolapse.

    PubMed

    Madiba, Thandinkosi E; Baig, Mirza K; Wexner, Steven D

    2005-01-01

    The problem of complete rectal prolapse is formidable, with no clear predominant treatment of choice. Surgical management is aimed at restoring physiology by correcting the prolapse and improving continence and constipation with acceptable mortality and recurrence rates. Abdominal procedures are ideal for young fit patients, whereas perineal procedures are reserved for older frail patients with significant comorbidity. Laparoscopic procedures with their advantages of early recovery, less pain, and possibly lower morbidity are recently added options. Regardless of the therapy chosen, matching the surgical selection to the patient is essential. To review the present status of the surgical treatment of rectal prolapse. Literature review using MEDLINE. All articles reporting on rectopexy were included. Articles reporting on prospective and retrospective comparisons were included. Case reports were excluded, as were studies comparing data with historical controls. The results were tabulated to show outcomes of different studies and were compared. Studies that did not report some of the outcomes were noted as "not stated." Abdominal operations offer not only lower recurrence but also greater chance for functional improvements. Suture and mesh rectopexy produce equivalent results. However, the polyvinyl alcohol (Ivalon) sponge rectopexy is associated with an increased risk of infectious complications and has largely been abandoned. The advantage of adding a resection to the rectopexy seems to be related to less constipation. Laparoscopic rectopexy has similar results to open rectopexy but has all of the advantages related to laparoscopy. Perineal procedures are better suited to frail elderly patients with extensive comorbidity. Abdominal procedures are generally better for young fit patients; the results of all abdominal procedures are comparable. Suture and mesh rectopexy are still popular with many surgeons-the choice depends on the surgeon's experience and preference

  18. Definition and delineation of the clinical target volume for rectal cancer

    SciTech Connect

    Roels, Sarah; Duthoy, Wim; Haustermans, Karin . E-mail: Karin.Haustermans@uzleuven.be; Penninckx, Freddy; Vandecaveye, Vincent; Boterberg, Tom; Neve, Wilfried de

    2006-07-15

    Purpose: Optimization of radiation techniques to maximize local tumor control and to minimize small bowel toxicity in locally advanced rectal cancer requires proper definition and delineation guidelines for the clinical target volume (CTV). The purpose of this investigation was to analyze reported data on the predominant locations and frequency of local recurrences and lymph node involvement in rectal cancer, to propose a definition of the CTV for rectal cancer and guidelines for its delineation. Methods and Materials: Seven reports were analyzed to assess the incidence and predominant location of local recurrences in rectal cancer. The distribution of lymphatic spread was analyzed in another 10 reports to record the relative frequency and location of metastatic lymph nodes in rectal cancer, according to the stage and level of the primary tumor. Results: The mesorectal, posterior, and inferior pelvic subsites are most at risk for local recurrences, whereas lymphatic tumor spread occurs mainly in three directions: upward into the inferior mesenteric nodes; lateral into the internal iliac lymph nodes; and, in a few cases, downward into the external iliac and inguinal lymph nodes. The risk for recurrence or lymph node involvement is related to the stage and the level of the primary lesion. Conclusion: Based on a review of articles reporting on the incidence and predominant location of local recurrences and the distribution of lymphatic spread in rectal cancer, we defined guidelines for CTV delineation including the pelvic subsites and lymph node groups at risk for microscopic involvement. We propose to include the primary tumor, the mesorectal subsite, and the posterior pelvic subsite in the CTV in all patients. Moreover, the lateral lymph nodes are at high risk for microscopic involvement and should also be added in the CTV.

  19. Self-Administered Home Series Fecal "Minitransplants" for Recurrent Clostridium difficile Infection on a Rectal Remnant.

    PubMed

    Popa, Daniel; Laszlo, Mihaela; Ciobanu, Lidia; Ucenic, Elena; Mihalache, Manuela; Pascu, Oliviu

    2015-12-01

    A fecal microbiota transplant has proved to be an extremely effective method for patients with recurrent infections with Clostridium difficile. We present the case of a 65-year-old female patient with multiple Clostridium difficile infection (CDI) relapses on the rectal remnant, post-colectomy for a CDI-related toxic megacolon. The patient also evidenced associated symptomatic Clostridium difficile vaginal infection. She was successfully treated with serial fecal "minitransplants" (self-administered at home) and metronidazole ovules.

  20. Differences in microbial signatures between rectal mucosal biopsies and rectal swabs.

    PubMed

    Araújo-Pérez, Félix; McCoy, Amber N; Okechukwu, Charles; Carroll, Ian M; Smith, Kevin M; Jeremiah, Kim; Sandler, Robert S; Asher, Gary N; Keku, Temitope O

    2012-01-01

    There is growing evidence the microbiota of the large bowel may influence the risk of developing colorectal cancer as well as other diseases including type-1 diabetes, inflammatory bowel diseases and irritable bowel syndrome. Current sampling methods to obtain microbial specimens, such as feces and mucosal biopsies, are inconvenient and unappealing to patients. Obtaining samples through rectal swabs could prove to be a quicker and relatively easier method, but it is unclear if swabs are an adequate substitute. We compared bacterial diversity and composition from rectal swabs and rectal mucosal biopsies in order to examine the viability of rectal swabs as an alternative to biopsies. Paired rectal swabs and mucosal biopsy samples were collected in un-prepped participants (n = 11) and microbial diversity was characterized by Terminal Restriction Fragment Length polymorphism (T-RFLP) analysis and quantitative polymerase chain reaction (qPCR) of the 16S rRNA gene. Microbial community composition from swab samples was different from rectal mucosal biopsies (p = 0.001). Overall the bacterial diversity was higher in swab samples than in biopsies as assessed by diversity indexes such as: richness (p = 0.01), evenness (p = 0.06) and Shannon's diversity (p = 0.04). Analysis of specific bacterial groups by qPCR showed higher copy number of Lactobacillus (p < 0.0001) and Eubacteria (p = 0.0003) in swab samples compared with biopsies. Our findings suggest that rectal swabs and rectal mucosal samples provide different views of the microbiota in the large intestine.

  1. Late Cardiac Toxicity After Mediastinal Radiation Therapy for Hodgkin Lymphoma: Contributions of Coronary Artery and Whole Heart Dose-Volume Variables to Risk Prediction.

    PubMed

    Hahn, Ezra; Jiang, Haiyan; Ng, Angela; Bashir, Shaheena; Ahmed, Sameera; Tsang, Richard; Sun, Alexander; Gospodarowicz, Mary; Hodgson, David

    2017-08-01

    Mediastinal radiation therapy (RT) for Hodgkin lymphoma (HL) is associated with late cardiotoxicity, but there are limited data to indicate which dosimetric parameters are most valuable for predicting this risk. This study investigated which whole heart dosimetric measurements provide the most information regarding late cardiotoxicity, and whether coronary artery dosimetry was more predictive of this outcome than whole heart dosimetry. A random sample of 125 HL patients treated with mediastinal RT was selected, and 3-dimensional cardiac dose-volume data were generated from historical plans using validated methods. Cardiac events were determined by linking patients to population-based datasets of inpatient and same-day hospitalizations and same-day procedures. Variables collected for the whole heart and 3 coronary arteries included the following: Dmean, Dmax, Dmin, dose homogeneity, V5, V10, V20, and V30. Multivariable competing risk regression models were generated for the whole heart and coronary arteries. There were 44 cardiac events documented, of which 70% were ischemic. The best multivariable model included the following covariates: whole heart Dmean (hazard ratio [HR] 1.09, P=.0083), dose homogeneity (HR 0.94, P=.0034), male sex (HR 2.31, P=.014), and age (HR 1.03, P=.0049). When any adverse cardiac event was the outcome, models using coronary artery variables did not perform better than models using whole heart variables. However, in a subanalysis of ischemic cardiac events only, the model using coronary artery variables was superior to the whole heart model and included the following covariates: age (HR 1.05, P<.001), volume of left anterior descending artery receiving 5 Gy (HR 0.98, P=.003), and volume of left circumflex artery receiving 20 Gy (HR 1.03, P<.001). In addition to higher mean heart dose, increasing inhomogeneity in cardiac dose was associated with a greater risk of late cardiac effects. When all types of cardiotoxicity were evaluated, the

  2. Preoperative hyperfractionated chemoradiation for locally recurrent rectal cancer in patients previously irradiated to the pelvis: A multicentric phase II study

    SciTech Connect

    Valentini, Vincenzo . E-mail: vvalentini@rm.unicatt.it; Morganti, Alessio G.; Gambacorta, M. Antonietta; Mohiuddin, Mohammed; Doglietto, G. Battista; Coco, Claudio; De Paoli, Antonino; Rossi, Carlo; Di Russo, Annamaria; Valvo, Francesca; Bolzicco, Giampaolo; Dalla Palma, Maurizio

    2006-03-15

    Purpose: The combination of irradiation and total mesorectal excision for rectal carcinoma has significantly lowered the incidence of local recurrence. However, a new problem is represented by the patient with locally recurrent cancer who has received previous irradiation to the pelvis. In these patients, local recurrence is very often not easily resectable and reirradiation is expected to be associated with a high risk of late toxicity. The aim of this multicenter phase II study is to evaluate the response rate, resectability rate, local control, and treatment-related toxicity of preoperative hyperfractionated chemoradiation for locally recurrent rectal cancer in patients previously irradiated to the pelvis. Methods and Materials: Patients with histologically proven pelvic recurrence of rectal carcinoma, with the absence of extrapelvic disease or bony involvement and previous pelvic irradiation with doses {<=}55 Gy; age {>=}18 years; performance status (PS) (Karnofsky) {>=}60, and who gave institutional review board-approved written informed consent were treated by preoperative chemoradiation. Radiotherapy was delivered to a planning target volume (PTV2) including the gross tumor volume (GTV) plus a 4-cm margin, with a dose of 30 Gy (1.2 Gy twice daily with a minimum 6-h interval). A boost was delivered, with the same fractionation schedule, to a PTV1 including the GTV plus a 2-cm margin (10.8 Gy). During the radiation treatment, concurrent chemotherapy was delivered (5-fluorouracil, protracted intravenous infusion, 225 mg/m{sup 2}/day, 7 days per week). Four to 6 weeks after the end of chemoradiation, patients were evaluated for tumor resectability, and, when feasible, surgical resection of recurrence was performed between 6-8 weeks from the end of chemoradiation. Adjuvant chemotherapy was prescribed to all patients, using Raltitrexed, 3 mg/square meter (sm), every 3 weeks, for a total of 5 cycles. Patients were staged using the computed tomography (CT)-based F

  3. Laparoscopic versus robotic rectal resection for rectal cancer in a veteran population.

    PubMed

    Fernandez, Ramiro; Anaya, Daniel A; Li, Linda T; Orcutt, Sonia T; Balentine, Courtney J; Awad, Samir A; Berger, David H; Albo, Daniel A; Artinyan, Avo

    2013-10-01

    Robotic rectal cancer resection remains controversial. We compared the safety and efficacy of laparoscopic vs robotic rectal cancer resection in a high-risk Veterans Health Administration population. Patients who underwent minimally invasive rectal cancer resection were identified from an institutional colorectal cancer database. Baseline characteristics and outcomes were compared between robotic and laparoscopic groups. The robotic group (n = 13) did not differ significantly from the laparoscopic group (n = 59) with respect to baseline characteristics except for a higher rate of previous abdominal surgery. Robotic patients had significantly lower tumors, more advanced disease, a higher rate of preoperative chemoradiation, and were more likely to undergo abdominoperineal resection. Robotic rectal resection was associated with longer operative time. There were no differences in blood loss, conversion rates, postoperative morbidity, lymph nodes harvested, margin positivity, or specimen quality between groups. The robotic approach for rectal cancer resection is safe with similar postoperative and oncologic outcomes compared with laparoscopy. Published by Elsevier Inc.

  4. Neoadjuvant Bevacizumab, Oxaliplatin, 5-Fluorouracil, and Radiation for Rectal Cancer

    SciTech Connect

    Dipetrillo, Tom; Pricolo, Victor; Lagares-Garcia, Jorge; Vrees, Matt; Klipfel, Adam; Cataldo, Tom; Sikov, William; McNulty, Brendan; Shipley, Joshua; Anderson, Elliot; Khurshid, Humera; Oconnor, Brigid; Oldenburg, Nicklas B.E.; Radie-Keane, Kathy; Husain, Syed; Safran, Howard

    2012-01-01

    Purpose: To evaluate the feasibility and pathologic complete response rate of induction bevacizumab + modified infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) 6 regimen followed by concurrent bevacizumab, oxaliplatin, continuous infusion 5-fluorouracil (5-FU), and radiation for patients with rectal cancer. Methods and Materials: Eligible patients received 1 month of induction bevacizumab and mFOLFOX6. Patients then received 50.4 Gy of radiation and concurrent bevacizumab (5 mg/kg on Days 1, 15, and 29), oxaliplatin (50 mg/m{sup 2}/week for 6 weeks), and continuous infusion 5-FU (200 mg/m{sup 2}/day). Because of gastrointestinal toxicity, the oxaliplatin dose was reduced to 40 mg/m{sup 2}/week. Resection was performed 4-8 weeks after the completion of chemoradiation. Results: The trial was terminated early because of toxicity after 26 eligible patients were treated. Only 1 patient had significant toxicity (arrhythmia) during induction treatment and was removed from the study. During chemoradiation, Grade 3/4 toxicity was experienced by 19 of 25 patients (76%). The most common Grade 3/4 toxicities were diarrhea, neutropenia, and pain. Five of 25 patients (20%) had a complete pathologic response. Nine of 25 patients (36%) developed postoperative complications including infection (n = 4), delayed healing (n = 3), leak/abscess (n = 2), sterile fluid collection (n = 2), ischemic colonic reservoir (n = 1), and fistula (n = 1). Conclusions: Concurrent oxaliplatin, bevacizumab, continuous infusion 5-FU, and radiation causes significant gastrointestinal toxicity. The pathologic complete response rate of this regimen was similar to other fluorouracil chemoradiation regimens. The high incidence of postoperative wound complications is concerning and consistent with other reports utilizing bevacizumab with chemoradiation before major surgical resections.

  5. Robotic rectal surgery: State of the art

    PubMed Central

    Staderini, Fabio; Foppa, Caterina; Minuzzo, Alessio; Badii, Benedetta; Qirici, Etleva; Trallori, Giacomo; Mallardi, Beatrice; Lami, Gabriele; Macrì, Giuseppe; Bonanomi, Andrea; Bagnoli, Siro; Perigli, Giuliano; Cianchi, Fabio

    2016-01-01

    Laparoscopic rectal surgery has demonstrated its superiority over the open approach, however it still has some technical limitations that lead to the development of robotic platforms. Nevertheless the literature on this topic is rapidly expanding there is still no consensus about benefits of robotic rectal cancer surgery over the laparoscopic one. For this reason a review of all the literature examining robotic surgery for rectal cancer was performed. Two reviewers independently conducted a search of electronic databases (PubMed and EMBASE) using the key words “rectum”, “rectal”, “cancer”, “laparoscopy”, “robot”. After the initial screen of 266 articles, 43 papers were selected for review. A total of 3013 patients were included in the review. The most commonly performed intervention was low anterior resection (1450 patients, 48.1%), followed by anterior resections (997 patients, 33%), ultra-low anterior resections (393 patients, 13%) and abdominoperineal resections (173 patients, 5.7%). Robotic rectal surgery seems to offer potential advantages especially in low anterior resections with lower conversions rates and better preservation of the autonomic function. Quality of mesorectum and status of and circumferential resection margins are similar to those obtained with conventional laparoscopy even if robotic rectal surgery is undoubtedly associated with longer operative times. This review demonstrated that robotic rectal surgery is both safe and feasible but there is no evidence of its superiority over laparoscopy in terms of postoperative, clinical outcomes and incidence of complications. In conclusion robotic rectal surgery seems to overcome some of technical limitations of conventional laparoscopic surgery especially for tumors requiring low and ultra-low anterior resections but this technical improvement seems not to provide, until now, any significant clinical advantages to the patients. PMID:27895814

  6. [Neoadjuvant radiochemotherapy treatment in locally advanced rectal adenocarcinoma].

    PubMed

    Carau, B; Orrù, P; Orrù, S; Dessì, M; Nagliati, M; Lay, G; Maxia, V; Casula, G; Amichetti, M

    2003-01-01

    A prospective phase II study was conducted to evacuate toxicity and results of preoperative radiochemotherapy in locoregionally advanced rectal cancer (LARC). A total of 33 patients entered the study and received 45 Gy to the pelvis plus a supplemental boost of 5.4-9 Gy concurrently with 5 FU c.i. at a dose of 225-275 mg/m2. Thirty patients were operated after 5-7 weeks (20 anterior resection and 10 abdominoperineal excision). In 14 patients (47%) a downstaging was observed, 5 patients experienced a complete clearance of the primary tumor. After a median of 14 months (range, 5-27), 23 patients, are alive and well. And 8 patients experienced a disease progression (4 local-regional and 4 distant). Our results provide further evidence of the utility and effectiveness of preoperative radiochemotherapy in LARC.

  7. Effects of cows grazing toxic endophyte-infected tall fescue or novel endophyte-infected tall fescue in late gestation on cow performance, reproduction, and progeny growth performance and carcass characteristics.

    PubMed

    Shoup, L M; Miller, L M; Srinivasan, M; Ireland, F A; Shike, D W

    2016-12-01

    Very little is known regarding the effects of cow exposure to toxic ergot alkaloids in late gestation and the subsequent, long-term effects on progeny. Therefore, the objectives were to determine the effects of grazing toxic endophyte-infected tall fescue () or novel endophyte-infected tall fescue during late gestation on cow BW, BCS, hair coat score (HCS), respiration rates, milk production, and reproduction and on growth performance and carcass characteristics of progeny. Eighty gestating, Angus × Simmental cows (age = 6.68 ± 0.32 yr; 588 ± 16 kg initial BW; initial BCS = 5.66 ± 0.28) were stratified by initial BW and allocated into 8 pasture groups (10 cows/group) with 4 groups per treatment. Each group was allotted to 1 of 2 grazing treatments: toxic endophyte-infected tall fescue ('Kentucky-31'; E+) or novel endophyte-infected tall fescue ('Jesup MaxQ'; NOV). Cows were placed on grazing treatments at 110 ± 6 d prepartum (May 28, 2014) and remained on treatment until the end of the calving period (October 8, 2014; 23 ± 6 d postpartum). Cow BW and BCS did not diverge ( ≥ 0.15) at any time point among grazing treatments. However, cows grazing E+ had increased ( < 0.05) respiration rates and HCS and reduced ( < 0.05) prolactin concentration compared with cows grazing NOV. Calf birth BW, Julian calving date, milk production, AI conception rate, and overall pregnancy rate did not differ ( ≥ 0.23) by grazing treatment. In a subsequent grazing period of the progeny, dam grazing treatment did not affect ( ≥ 0.14) respiration rates, HCS, or prolactin concentration of the progeny when all progeny grazed E+ pastures. However, progeny born to dams grazing NOV tended ( > 0.06 to ≤0.10) to have increased BW at 70 ± 6 d of age, 205 d (adjusted weaning BW), and throughout the postweaning calf grazing period. Despite a tendency for BW to differ throughout the postweaning calf grazing period, finishing phase performance and carcass characteristics of progeny did

  8. Histopathological and scintigraphic comparisons of the protective effects of L-carnitine and amifostine against radiation-induced late renal toxicity in rats.

    PubMed

    Caloglu, Murat; Yurut-Caloglu, Vuslat; Durmus-Altun, Gulay; Oz-Puyan, Fulya; Ustun, Funda; Cosar-Alas, Rusen; Saynak, Mert; Parlar, Sule; Turan, Fatma N; Uzal, Cem

    2009-05-01

    1. The aim of the present study was to compare the protective effects of L-carnitine and amifostine against radiation-induced late nephrotoxicity using technetium-99m diethylenetriaminepentaacetic acid scintigraphy and histopathological examination. 2. Seventy-one Albino rats were randomly divided into six groups as follows: (i) AMI + RAD (n = 15), 200 mg/kg, i.p., amifostine 30 min prior to irradiation (a single dose of 9 Gy); (ii) LC + RAD (n = 15), 300 mg/kg, i.p., L-carnitine 30 min prior to irradiation; (iii) LC (n = 10), 300 mg/kg, i.p., L-carnitine 30 min prior to sham irradiation; (iv) AMI (n = 10), 200 mg/kg, i.p., amifostine 30 min prior to sham irradiation; RAD (n = 11), 1 mL/kg, i.p., normal saline 30 min prior to irradiation; and (vi) control (n = 10), 1 mL/kg, i.p., normal saline 30 min prior to sham irradiation. Scintigraphy was performed before treatment and again 6 months after treatment. Kidneys were examined by light microscopy and a histopathological scoring system was used to assess the degree of renal damage. 3. The main histopathological findings were proximal tubular damage and interstitial fibrosis. Glomerular injury was similar in all groups. Tubular degeneration and atrophy were less common in the AMI + RAD group than in the RAD group (P = 0.011 and P = 0.015, respectively), as well as in the LC + RAD group compared with the RAD group (P = 0.028 and P = 0.036, respectively). Interstitial fibrosis in the AMI + RAD and LC + RAD groups was significantly less than that in the RAD group (P = 0.015 and P = 0.015, respectively). The highest total renal injury score (9) was seen in the RAD group. On scintigraphy, there were significant differences in post-treatment time to peak count (T(max)) and time from peak count to half count (T((1/2))) values (P = 0.01 and 0.02, respectively) between groups in the right kidney. In the control and RAD groups, the T((1/2)) of the right kidney was 8 +/- 2 and 21 +/- 2 min, respectively. The T(max) values for

  9. Prospective evaluation of a hydrogel spacer for rectal separation in dose-escalated intensity-modulated radiotherapy for clinically localized prostate cancer

    PubMed Central

    2013-01-01

    Background As dose-escalation in prostate cancer radiotherapy improves cure rates, a major concern is rectal toxicity. We prospectively assessed an innovative approach of hydrogel injection between prostate and rectum to reduce the radiation dose to the rectum and thus side effects in dose-escalated prostate radiotherapy. Methods Acute toxicity and planning parameters were prospectively evaluated in patients with T1-2 N0 M0 prostate cancer receiving dose-escalated radiotherapy after injection of a hydrogel spacer. Before and after hydrogel injection, we performed MRI scans for anatomical assessment of rectal separation. Radiotherapy was planned and administered to 78 Gy in 39 fractions. Results From eleven patients scheduled for spacer injection the procedure could be performed in ten. In one patient hydrodissection of the Denonvillier space was not possible. Radiation treatment planning showed low rectal doses despite dose-escalation to the target. In accordance with this, acute rectal toxicity was mild without grade 2 events and there was complete resolution within four to twelve weeks. Conclusions This prospective study suggests that hydrogel injection is feasible and may prevent rectal toxicity in dose-escalated radiotherapy of prostate cancer. Further evaluation is necessary including the definition of patients who might benefit from this approach. Trial registration: German Clinical Trials Register DRKS00003273. PMID:23336502

  10. Intensity-Modulated Radiotherapy Reduces Gastrointestinal Toxicity in Patients Treated With Androgen Deprivation Therapy for Prostate Cancer

    SciTech Connect

    Sharma, Navesh K.; Li Tianyu; Chen, David Y.; Pollack, Alan; Horwitz, Eric M.; Buyyounouski, Mark K.

    2011-06-01

    Purpose: Androgen deprivation therapy (AD) has been shown to increase late Grade 2 or greater rectal toxicity when used concurrently with three-dimensional conformal radiotherapy (3D-CRT). Intensity-modulated radiotherapy (IMRT) has the potential to reduce toxicity by limiting the radiation dose received by the bowel and bladder. The present study compared the genitourinary and gastrointestinal (GI) toxicity in men treated with 3D-CRT+AD vs. IMRT+AD. Methods and Materials: Between July 1992 and July 2004, 293 men underwent 3D-CRT (n = 170) or IMRT (n = 123) with concurrent AD (<6 months, n = 123; {>=}6 months, n = 170). The median radiation dose was 76 Gy for 3D-CRT (International Commission on Radiation Units and Measurements) and 76 Gy for IMRT (95% to the planning target volume). Toxicity was assessed by a patient symptom questionnaire that was completed at each visit and recorded using a Fox Chase Modified Late Effects Normal Tissue Task radiation morbidity scale. Results: The mean follow-up was 86 months (standard deviation, 29.3) for the 3D-CRT group and 40 months (standard deviation, 9.7) for the IMRT group. Acute GI toxicity (odds ratio, 4; 95% confidence interval, 1.6-11.7; p = .005) was significantly greater with 3D-CRT than with IMRT and was independent of the AD duration (i.e., <6 vs. {>=}6 months). The interval to the development of late GI toxicity was significantly longer in the IMRT group. The 5-year Kaplan-Meier estimate for Grade 2 or greater GI toxicity was 20% for 3D-CRT and 8% for IMRT (p = .01). On multivariate analysis, Grade 2 or greater late GI toxicity (hazard ratio, 2.1; 95% confidence interval, 1.1-4.3; p = .04) was more prevalent in the 3D-CRT patients. Conclusion: Compared with 3D-CRT, IMRT significantly decreased the acute and late GI toxicity in patients treated with AD.

  11. Preoperative staging of rectal cancer.

    PubMed

    Smith, Neil; Brown, Gina

    2008-01-01

    Detailed preoperative staging using high resolution magnetic resonance imaging (MRI) enables the selection of patients that require preoperative therapy for tumour regression. This information can be used to instigate neoadjuvant therapy in those patients with poor prognostic features prior to disturbing the tumour bed and potentially disseminating disease. The design of trials incorporating MR assessment of prognostic factors prior to therapy has been found to be of value in assessing treatment modalities and outcomes that are targeted to these preoperative prognostic subgroups and in providing a quantifiable assessment of the efficacy of particular chemoradiation treatment protocols by comparing pre-treatment MR staging with post therapy histology assessment. At present, we are focused on achieving clear surgical margins of excision (CRM) to avoid local recurrence. We recommend that all patients with rectal cancer should undergo pre-operative MRI staging. Of these, about half will have good prognosis features (T1-T3b, N0, EMVI negative, CRM clear) and may safely undergo primary total mesorectal excision. Of the remainder, those with threatened or involved margins will certainly benefit from pre-operative chemoradiotherapy with the aim of downstaging to permit safe surgical excision. In the future, our ability to recognise features predicting distant failure, such as extramural vascular invasion (EMVI) may be used to stratify patients for neo-adjuvant systemic chemotherapy in an effort to prevent distant relapse. The optimal pre-operative treatment regimes for these patients (radiotherapy alone, systemic chemotherapy alone or combination chemo-radiotherapy) is the subject of current and future trials.

  12. A watch-and-wait approach to the management of rectal cancer.

    PubMed

    Das, Prajnan; Minsky, Bruce D

    2013-10-01

    There has been increasing interest in whether a watch-and-wait strategy can be pursued instead of routine surgery in selected rectal cancer patients who have a clinical complete response (cCR) after chemoradiation. The watch-and-wait approach could potentially reduce treatment-related toxicity in selected rectal cancer patients. A large study from Brazil and a prospective trial from the Netherlands appear to support this approach, although multiple other studies have raised concerns about the high rate of local recurrence with this strategy. This article reviews current evidence in support of a watch-and-wait approach to rectal cancer management, and discusses the challenges and limitations of this approach. Among these are the facts that current methods of assessing tumor response have limited accuracy, and that a cCR does not necessarily imply pathologic complete response. Careful patient selection and systematic methods of response assessment and follow-up will be critical to the success of nonoperative approaches. Based on the available evidence, ideally a watch-and-wait approach for patients with rectal cancer should be pursued within the context of a prospective clinical trial.

  13. Limitation of surgical radicality in rectal cancer responding to neoadjuvant therapy.

    PubMed

    Troja, Achim; Hempen, Hans-Günther; Raab, Hans-Rudolf

    2009-05-01

    The basic principle in the treatment of rectal cancer is the complete surgical removal of the tumor together with the lymphatic drainage region, i.e. the mesorectum encased by the mesorectal 'fascia pelvis visceralis' according to Westhues. It was shown in the 1990s that the results of surgery alone could be improved by additional adjuvant and neoadjuvant therapy. Because of less toxicity and a lower rate of local recurrence, neoadjuvant therapies in International Union Against Cancer (UICC) stage II and III disease are now preferred over adjuvant strategies. The German Rectal Cancer study CAO/ARO/AIO-94 showed a full remission rate of 8% after a 5-fluorouracil (5-FU)based chemotherapy added to a conventional fractional radiation therapy (50.4 Gy). This figure, together with similar results of others, leads to the question whether surgical radicality in rectal cancer treatment could be limited in case of a good remission after neoadjuvant therapy. There are several promising possibilities under investigation, e.g. local excision instead of radical resection, or even no resection at all. Nevertheless, up to now these strategies did not prove to give comparable results to standard surgical procedures. Therefore, reduction of radicality in curable rectal cancer should be limited to accurately designed randomized clinical trials. Copyright (c) 2009 S. Karger AG, Basel.

  14. Preoperative chemoradiotherapy followed by transanal local excision for T3 distal rectal cancer: A case report

    PubMed Central

    YEO, SEUNG-GU

    2016-01-01

    Local excision (LE) for rectal cancer is currently indicated for selected T1 stage tumors. However, preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer not only improves local disease control, but also leads to a decrease in the stage and size of the primary mural tumor, along with a decrease in the risk of regional lymphadenopathy. The present study reports the outcome of a patient with T3N0M0 rectal cancer who was treated with LE following preoperative CRT. The distal pole of the tumor was located 2 cm from the anal verge. Preoperative pelvic radiotherapy of 50.4 Gy was administered in 28 fractions. Chemotherapy using 5-fluorouracil and leucovorin was administered during the first and last weeks of radiotherapy. The tumor response to CRT, was found to be marked at 7 weeks after CRT completion, and a complete response was presumed clinically. Transanal full-thickness LE was performed, and pathological examination revealed the absence of residual cancer cells. After 30 months of close follow-up, the patient was alive with no evidence of disease, and treatment-associated severe toxicities were not observed. Although a longer follow-up period is required, this case report suggests that LE may also be a feasible alternative treatment for T3 rectal cancer, which exhibits a marked response to preoperative CRT, particularly in elderly and comorbid patients contraindicated for radical surgery, or patients who are reluctant to undergo sphincter-ablation surgery. PMID:27073466

  15. Preoperative bi-fractionated accelerated radiation therapy for combined treatment of locally advanced rectal cancer in a consectutive series of unselected patients

    PubMed Central

    Biffi, Roberto; Marsiglia, Hugo; Fossa, Barbara Jereczek; Leonardi, Maria Cristina; Cante, Domenico; Lazzari, Roberta; Chiappa, Antonio; Cenciarelli, Sabine; Andreoni, Bruno; Zampino, Maria Giulia; Orecchia, Roberto

    2007-01-01

    preoperative setting to patients bearing locally advanced rectal cancer is reliable and safe, as its immediate and late toxicity (mainly infectious) is acceptably low and long-term survivals are achievable. These findings support the increasing use of preoperative RT for treatment of this malignancy in experienced centres. Ongoing multicentric trials are expected to address still unsolved issues, including the benefit of CT adjunct to preoperative RT. PMID:17883838

  16. Novel radiation techniques for rectal cancer

    PubMed Central

    2014-01-01

    The concepts for management of rectal cancer have changed drastically over the past few years. Through national bowel cancer screening programmes in the Western countries and the increasing use of endoscopic procedures as diagnostic tool, there is increase in detection of rectal cancer in early stages. There is increase in ageing population worldwide but more so in Western countries. In addition, there is realisation of harm from extirpative surgical procedures which are directed towards managing advanced rectal cancer in the past. Increase in cost of health care burden has also led the investigators to seek alternative treatment options which are effective, safe and cost effective. There are several modern radiation techniques which fits this bill and we need to be aware of newer novel radiation techniques to fulfil this gap. PMID:24982769

  17. Rectal mucosa in cows' milk allergy.

    PubMed Central

    Iyngkaran, N; Yadav, M; Boey, C G

    1989-01-01

    Eleven infants who were suspected clinically of having cows' milk protein sensitive enteropathy were fed with a protein hydrolysate formula for six to eight weeks, after which they had jejunal and rectal biopsies taken before and 24 hours after challenge with cows' milk protein. When challenged six infants (group 1) developed clinical symptoms and five did not (group 2). In group 1 the lesions developed in both the jejunal mucosa (four infants at 24 hours and one at three days), and the rectal mucosa, and the injury was associated with depletion of alkaline phosphatase activity. Infants in group 2 were normal. It seems that rectal injury that develops as a direct consequence of oral challenge with the protein in reactive infants may be used as one of the measurements to confirm the diagnosis of cows' milk protein sensitive enteropathy. Moreover, ingestion of such food proteins may injure the distal colonic mucosa without affecting the proximal small gut in some infants. PMID:2817945

  18. Workshop summary: phosgene-induced pulmonary toxicity revisited: appraisal of early and late markers of pulmonary injury from animal models with emphasis on human significance.

    PubMed

    Pauluhn, J; Carson, A; Costa, D L; Gordon, T; Kodavanti, U; Last, J A; Matthay, M A; Pinkerton, K E; Sciuto, A M

    2007-08-01

    pulmonary threshold dose. Exposure concentrations high enough to elicit an increased acute extravasation of plasma constituents into the alveolus may also be associated with surfactant dysfunction, intra-alveolar accumulation of fibrin and collagen, and increased recruitment and activation of inflammatory cells. Although the exact mechanisms of toxicity have not yet been completely elucidated, consensus was reached that the acute pulmonary toxicity of phosgene gas is consistent with a simple, irritant mode of action at the site of its initial deposition/retention. The acute concentration x time mortality relationship of phosgene gas in rats is extremely steep, which is typical for a local, directly acting pulmonary irritant gas. Due to the high lipophilicity of phosgene gas, it efficiently penetrates the lower respiratory tract. Indeed, more recent published evidence from animals or humans has not revealed appreciable irritant responses in central and upper airways, unless exposure was to almost lethal concentrations. The comparison of acute inhalation studies in rats and dogs with focus on changes in BAL fluid constituents demonstrates that dogs are approximately three to four times less susceptible to phosgene than rats under methodologically similar conditions. There are data to suggest that the dog may be useful particularly for the study of mechanisms associated with the acute extravasation of plasma constituents because of its size and general morphology and physiology of the lung as well as its oronasal breathing patterns. However, the study of the long-term sequelae of acute effects is experimentally markedly more demanding in dogs as compared to rats, precluding the dog model to be applied on a routine base. The striking similarity of threshold concentrations from single exposure (increased protein in BAL fluid) and repeated-exposure 3-mo inhalation studies (increased pulmonary collagen deposition) in rats supports the notion that chronic changes depend on acute

  19. Primary Transanal Management of Rectal Atresia in a Neonate

    PubMed Central

    M, Braiek; A, Ksia; I, Krichen; S, Belhassen; K, Maazoun; S, Ben youssef; N, Kechiche; M, Mekki; A, Nouri

    2016-01-01

    Rectal atresia (RA) with a normal anus is a rare anomaly. We describe a case of rectal atresia in a newborn male presenting with an abdominal distension and failure of passing meconium. The rectal atresia was primarily operated by transanal route. PMID:27123404

  20. Primary Transanal Management of Rectal Atresia in a Neonate.

    PubMed

    M, Braiek; A, Ksia; I, Krichen; S, Belhassen; K, Maazoun; S, Ben Youssef; N, Kechiche; M, Mekki; A, Nouri

    2016-01-01

    Rectal atresia (RA) with a normal anus is a rare anomaly. We describe a case of rectal atresia in a newborn male presenting with an abdominal distension and failure of passing meconium. The rectal atresia was primarily operated by transanal route.

  1. Massive zosteriform cutaneous metastasis from rectal carcinoma.

    PubMed

    Damin, D C; Lazzaron, A R; Tarta, C; Cartel, A; Rosito, M A

    2003-07-01

    A 44-year-old man presented with a large and rapidly growing skin lesion approximately six months after resection of a rectal carcinoma. The lesion measured 40 cm in size, extended from the suprapubic area to the proximal half of the left groin, and showed a particular zosteriform aspect. Biopsy confirmed a metastatic skin adenocarcinoma. Cutaneous metastases from rectal cancer are very uncommon. Their gross appearance is not distinctive, although the skin tumors are usually solid, small (less than 5 cm) and painless nodules or papules. Early biopsies for suspicious skin lesions are needed in patients with a history of colorectal cancer.

  2. Transanal Approach to Rectal Polyps and Cancer

    PubMed Central

    Rai, Vinay; Mishra, Nitin

    2016-01-01

    A transanal approach to rectal polyp and cancer excision is often an appropriate alternative to conventional rectal resection, and has a lower associated morbidity. There has been a steady evolution in the techniques of transanal surgery over the past 30 years. It started with traditional transanal excision and was revolutionized by introduction of transanal endoscopic microsurgery in early 1980s. Introduction of transanal minimally invasive surgery made it more accessible to surgeons around the world. Now robotic platforms are being tried in certain institutions. Concerns have been raised about recurrence rates of cancers with transanal approach and success of subsequent salvage operations. PMID:26929754

  3. [Adjuvant chemotherapy for patients with rectal cancer].

    PubMed

    Qvortrup, Camilla; Mortensen, John Pløen; Pfeiffer, Per

    2013-09-09

    A new Cochrane meta-analysis evaluated adjuvant chemotherapy (5-fluorouracil (5FU)-based, not modern combination chemotherapy) in almost 10,000 patients with rectal cancer and showed a 17% reduction in mortality corresponding well to the efficacy observed in recent studies, which reported a reduction in mortality just about 20%. The authors recommend adjuvant chemotherapy which is in accordance with the Danish national guidelines where 5-FU-based chemotherapy is recommended for stage III and high-risk stage II rectal cancer.

  4. Study between axillary and rectal temperature measurements in children.

    PubMed

    Haddadin, R B; Shamo'on, H I

    2007-01-01

    We compared axillary and rectal temperatures in 216 patients to assess the reliability of axillary temperature for determining fever in children under 14 years of age. Beyond the neonatal period, the mean rectal temperature was significantly higher than the axillary temperature. The sensitivity of axillary temperature in detecting fever was 87.5% among neonates but only 46% among older children. Axillary temperature correlated well with rectal temperature in neonates but not older children. There was no direct mathematical relationship between axillary and rectal temperature. Axillary temperature should be taken in neonates as it is less hazardous; rectal temperature should be used beyond this age.

  5. Molecular Genetic Changes Associated With Colorectal Carcinogenesis Are Not Prognostic for Tumor Regression Following Preoperative Chemoradiation of Rectal Carcinoma

    SciTech Connect

    Zauber, N. Peter Marotta, Steven P.; Berman, Errol; Grann, Alison; Rao, Maithili; Komati, Naga; Ribiero, Kezia; Bishop, D. Timothy

    2009-06-01

    Purpose: Preoperative chemotherapy and radiation has become the standard of care for many patients with rectal cancer. The therapy may have toxicity and delays definitive surgery. It would therefore be desirable to identify those cancers that will not regress with preoperative therapy. We assessed a series of rectal cancers for the molecular changes of loss of heterozygosity of the APC and DCC genes, K-ras mutations, and microsatellite instability, changes that have clearly been associated with rectal carcinogenesis. Methods and Materials: Diagnostic colonoscopic biopsies from 53 patients who received preoperative chemotherapy and radiation were assayed using polymerase chain reaction techniques followed by single-stranded conformation polymorphism and DNA sequencing. Regression of the primary tumor was evaluated using the surgically removed specimen. Results: Twenty-three lesions (45%) were found to have a high degree of regression. None of the molecular changes were useful as indicators of regression. Conclusions: Recognized molecular changes critical for rectal carcinogenesis including APC and DCC loss of heterozygosity, K-ras mutations, and microsatellite instability are not useful as indicators of tumor regression following chemoradiation for rectal carcinoma.

  6. Distribution of fibronectin in the rectal mucosa.

    PubMed

    Scott, D L; Morris, C J; Blake, A E; Low-Beer, T S; Walton, K W

    1981-07-01

    Fibronectin is a glycoprotein of high molecular weight present in tissues, plasma, and tissue fluids. Its distribution in the rectal mucosa was studied by immunofluorescent and immunoperoxidase techniques using a monospecific antiserum. Immunofluorescent reactivity for fibronectin was present in the normal rectal mucosa of control subjects in epithelial cells, on basement membranes, and as a loose cribriform network of extracellular reactivity in the lamina propria that codistributed with histochemically demonstrable reticulin. Fibronectin was demonstrated immunoelectromicroscopically on collagen fibres, on smooth muscle cells and within and between columnar epithelial cells. In the rectal mucosa of patients with colitis with marked inflammatory changes, fibronectin appeared thickened and more prominent when present on basement membranes and as sparse strands between inflammatory cells infiltrating the lamina propria. In patients with longstanding colitis and less inflammatory cell infiltration there was a diffuse increase in fibronectin which was densely and uniformly present throughout the lamina propria. Fibronectin is a structural component of the rectal mucosa and changes in its distribution may form an important part of the local reaction to inflammatory bowel disease.

  7. Rectal bezoars due to pumpkin seeds.

    PubMed

    Mirza, Mohammad Salman; Al-Wahibi, Khalifa; Baloch, Shafiq; Al-Qadhi, Hani

    2009-01-01

    Rectal bezoars commonly occur due to seeds, especially in children living in countries south of the Mediterranean and in the Middle-East. Dried seeds are considered a delicacy and consumed widely. Inadequate chewing or hastily eating without removing the hull may lead to their impaction as bezoars, which may require manual removal under general anaesthesia.

  8. Combined radical retropubic prostatectomy and rectal resection.

    PubMed

    Klee, L W; Grmoljez, P

    1999-10-01

    To present our experience with a small series of men who underwent simultaneous radical retropubic prostatectomy and rectal resection. Three men with newly diagnosed prostate cancer were found to have concurrent rectal tumors requiring resection. All three men underwent non-nerve-sparing radical retropubic prostatectomy and abdominoperineal resection (APR) or low anterior resection (LAR) of the rectum at the same operation. In the 2 patients undergoing APR, the levators were approximated posterior to the urethra, and the bladder was secured to the pubis. The patient undergoing LAR had urinary diversion stents placed and a diverting transverse loop colostomy. All 3 patients had excellent return of urinary continence. One patient required reoperation in the early postoperative period for small bowel adhesiolysis and stoma revision. Another patient had a mild rectal anastomotic stricture and a bladder neck stricture; both were successfully treated with a single dilation. No other significant complications occurred in these patients. Radical retropubic prostatectomy can safely be performed with partial or complete rectal resection in a single operation. A few minor modifications of the standard radical retropubic prostatectomy in this setting are suggested.

  9. [Rectal cancer: diagnosis, screening and treatment].

    PubMed

    Decanini-Terán, César Oscar; González-Acosta, Jorge; Obregón-Méndez, Jorge; Vega-de Jesús, Martín

    2011-01-01

    Rectal cancer is one of the primary malignant neoplasms occurring in Mexican patients of reproductive age. Unfortunately, randomized studies in rectal cancer do not exist as they do with well-recognized colon cancer. We must individualize the epidemiology, risk factors, diagnostic approach, staging and treatment because management is different in rectal cancers affecting the mid- and lower third of the rectum than in the upper third and in colon cancers. Histological staging is the primary prognostic factor. TNM staging (tumor, node, and metastasis) is used internationally by the American Joint Committee on Cancer (AJCC). Staging is done with the assistance of endorectal ultrasound, which is best used in early-stage cancer; however, there are certain disadvantages in detecting node involvement. Magnetic resonance, on the other hand, allows for the evaluation of stenotic tumors and node involvement. Once the correct diagnosis and staging have been made, the next step is correct treatment. Neoadjuvant treatment has demonstrated to be better than adjuvant treatment. Abdominoperineal resection is rarely practiced currently, with sphincter preservation being the preferred procedure. Laparoscopic approach has conferred the advantages of the approach itself when performed by experts in the procedure but there is insufficient evidence to make it the "gold standard." Rectal cancer is a complex pathology that must be considered totally different from colon cancer for diagnosis and treatment. The patient must be staged completely and appropriately for individualizing correct treatment. More long-term studies are needed for optimizing treatment modalities.

  10. [Electronic rectal temperature measurement. A clinical trial].

    PubMed

    Ottesen, S; Nielsen, F T; Lund, H

    1993-05-24

    Rectal measurement of body temperature with an electronic device (Ivac) was compared to measurement with mercury thermometers in 157 adult patients on a medical ward. The electronic thermometers were less accurate, giving 3.6 times as many febrile patients. This was reduced to 1.6 after thermometer calibration. It is necessary to make regular calibrations of Ivac thermometers.

  11. Comparison of Adjuvant Chemotherapy Regimens in Treating Patients With Stage II or Stage III Rectal Cancer Who Are Receiving Radiation Therapy and Fluorouracil Before or After Surgery

    ClinicalTrials.gov

    2013-02-26

    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; Stage IVA Rectal Cancer; Stage IVB Rectal Cancer

  12. Dose to the Bladder Neck Is the Most Important Predictor for Acute and Late Toxicity After Low-Dose-Rate Prostate Brachytherapy: Implications for Establishing New Dose Constraints for Treatment Planning

    SciTech Connect

    Hathout, Lara; Folkert, Michael R.; Kollmeier, Marisa A.; Yamada, Yoshiya; Cohen, Gil'ad N.; Zelefsky, Michael J.

    2014-10-01

    Purpose: To identify an anatomic structure predictive for acute (AUT) and late (LUT) urinary toxicity in patients with prostate cancer treated with low-dose-rate brachytherapy (LDR) with or without external beam radiation therapy (EBRT). Methods and Materials: From July 2002 to January 2013, 927 patients with prostate cancer (median age, 66 years) underwent LDR brachytherapy with Iodine 125 (n=753) or Palladium 103 (n=174) as definitive treatment (n=478) and as a boost (n=449) followed by supplemental EBRT (median dose, 50.4 Gy). Structures contoured on the computed tomographic (CT) scan on day 0 after implantation included prostate, urethra, bladder, and the bladder neck, defined as 5 mm around the urethra between the catheter balloon and the prostatic urethra. AUT and LUT were assessed with the Common Terminology Criteria for Adverse Events, version4. Clinical and dosimetric factors associated with AUT and LUT were analyzed with Cox regression and receiver operating characteristic analysis to calculate area under the receiver operator curve (ROC) (AUC). Results: Grade ≥2 AUT and grade ≥2 LUT occurred in 520 patients (56%) and 154 patients (20%), respectively. No grade 4 toxicities were observed. Bladder neck D2cc retained a significant association with AUT (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.03-1.04; P<.0001) and LUT (HR, 1.01; 95% CI, 1.00-1.03; P=.014) on multivariable analysis. In a comparison of bladder neck with the standard dosimetric variables by use of ROC analysis (prostate V100 >90%, D90 >100%, V150 >60%, urethra D20 >130%), bladder neck D2cc >50% was shown to have the strongest prognostic power for AUT (AUC, 0.697; P<.0001) and LUT (AUC, 0.620; P<.001). Conclusions: Bladder neck D2cc >50% was the strongest predictor for grade ≥2 AUT and LUT in patients treated with LDR brachytherapy. These data support inclusion of bladder neck constraints into brachytherapy planning to decrease urinary toxicity.

  13. Toxic megacolon

    MedlinePlus

    ... disease - toxic megacolon; Crohn disease - toxic megacolon; Ulcerative colitis - toxic megacolon ... people with an inflamed colon due to: Ulcerative colitis , or Crohn disease that is not well controlled ...

  14. Protocol for a multicentre randomised feasibility trial evaluating early Surgery Alone In LOw Rectal cancer (SAILOR)

    PubMed Central

    Thorne, Kymberley; Hutchings, Hayley; Islam, Saiful; Holland, Gail; Hatcher, Olivia; Gwynne, Sarah; Jenkins, Ian; Coyne, Peter; Duff, Michael; Feldman, Melanie; Winter, Des C; Gollins, Simon; Quirke, Phil; West, Nick; Brown, Gina; Fitzsimmons, Deborah; Brown, Alan; Beynon, John

    2016-01-01

    Introduction There are 11 500 rectal cancers diagnosed annually in the UK. Although surgery remains the primary treatment, there is evidence that preoperative radiotherapy (RT) improves local recurrence rates. High-quality surgery in rectal cancer is equally important in minimising local recurrence. Advances in MRI-guided prediction of resection margin status and improvements in abdominoperineal excision of the rectum (APER) technique supports a reassessment of the contribution of preoperative RT. A more selective approach to RT may be appropriate given the associated toxicity. Methods and analysis This trial will explore the feasibility of a definitive trial evaluating the omission of RT in resectable low rectal cancer requiring APER. It will test the feasibility of randomising patients to (1) standard care (neoadjuvant long course RT±chemotherapy and APER, or (2) APER surgery alone for cT2/T3ab N0/1 low rectal cancer with clear predicted resection margins on MRI. RT schedule will be 45 Gy over 5 weeks as current standard, with restaging and surgery after 8–12 weeks. Recruitment will be for 24 months with a minimum 12-month follow-up. Objectives Objectives include testing the ability to recruit, consent and retain patients, to quantify the number of patients eligible for a definitive trial and to test feasibility of outcomes measures. These include locoregional recurrence rates, distance to circumferential resection margin, toxicity and surgical complications including perineal wound healing, quality of life and economic analysis. The quality of MRI staging, RT delivery and surgical specimen quality will be closely monitored. Ethics and dissemination The trial is approved by the Regional Ethics Committee and Health Research Authority (HRA) or equivalent. Written informed consent will be obtained. Serious adverse events will be reported to Swansea Trials Unit (STU), the ethics committee and trial sites. Trial results will be submitted for peer review

  15. Bladder urothelial carcinoma extending to rectal mucosa and presenting with rectal bleeding

    PubMed Central

    Aneese, Andrew M; Manuballa, Vinayata; Amin, Mitual; Cappell, Mitchell S

    2017-01-01

    An 87-year-old-man with prostate-cancer-stage-T1c-Gleason-6 treated with radiotherapy in 1996, recurrent prostate cancer treated with leuprolide hormonal therapy in 2009, and bladder-urothelial-carcinoma in situ treated with Bacillus-Calmette-Guerin and adriamycin in 2010, presented in 2015 with painless, bright red blood per rectum coating stools daily for 5 mo. Rectal examination revealed bright red blood per rectum; and a hard, fixed, 2.5 cm × 2.5 cm mass at the normal prostate location. The hemoglobin was 7.6 g/dL (iron saturation = 8.4%, indicating iron-deficiency-anemia). Abdominopelvic-CT-angiography revealed focal wall thickening at the bladder neck; a mass containing an air cavity replacing the normal prostate; and adjacent rectal invasion. Colonoscopy demonstrated an ulcerated, oozing, multinodular, friable, 2.5 cm × 2.5 cm mass in anterior rectal wall, at the usual prostate location. Histologic and immunohistochemical analysis of colonoscopic biopsies of the mass revealed poorly-differentiated-carcinoma of urothelial origin. At visceral angiography, the right-superior-rectal-artery was embolized to achieve hemostasis. The patient subsequently developed multiple new metastases and expired 13 mo post-embolization. Comprehensive literature review revealed 16 previously reported cases of rectal involvement from bladder urothelial carcinoma, including 11 cases from direct extension and 5 cases from metastases. Patient age averaged 63.7 ± 9.6 years (all patients male). Rectal involvement was diagnosed on average 13.5 ± 11.8 mo after initial diagnosis of bladder urothelial carcinoma. Symptoms included constipation/gastrointestinal obstruction-6, weight loss-5, diarrhea-3, anorexia-3, pencil thin stools-3, tenesmus-2, anorectal pain-2, and other-5. Rectal examination in 9 patients revealed annular rectal constriction-6, and rectal mass-3. The current patient had the novel presentation of daily bright red blood per rectum coating the stools simulating

  16. Complications and outcomes following rectal pull-through surgery in dogs with rectal masses: 74 cases (2000-2013).

    PubMed

    Nucci, Daniel J; Liptak, Julius M; Selmic, Laura E; Culp, William T N; Durant, April M; Worley, Deanna; Maritato, Karl C; Thomson, Maurine; Annoni, Maurizio; Singh, Ameet; Matz, Brad; Benson, John; Buracco, Paolo

    2014-09-15

    To evaluate the incidence of and factors associated with complications following rectal pull-through (RPT) surgery and the outcome for dogs with rectal tumors. Retrospective case series. 74 dogs with rectal masses. Information regarding signalment, history, diagnostic testing, type of rectal disease, surgical details, and postoperative complications, treatments, and outcomes was obtained from medical records and follow-up communications. Survival times were calculated. Descriptive statistics were generated. Regression analyses were used to evaluate the effect of various variables on the development of postsurgical complications and survival time. 58 (78.4%) dogs developed postsurgical complications, the most common of which was fecal incontinence with 42 (56.8%) dogs affected, of which 23 (54.8%) developed permanent incontinence. Other complications included diarrhea (n = 32), tenesmus (23), stricture formation (16), rectal bleeding (8), constipation (7), dehiscence (6), and infection (4). The rectal tumor recurred in 10 dogs. The median survival time was 1,150 days for all dogs and 726 days for dogs with malignant tumors. The 2 most common rectal masses were rectal carcinoma and rectal carcinoma in situ, and the dogs with these tumors had median survival times of 696 and 1,006 days, respectively. Dogs with rectal diseases that underwent RPT surgery had a high incidence of complications; however, those dogs had good local tumor control and survival times. The risk and impact of postsurgical complications on the quality of life and oncological outcomes should be discussed with owners before RPT surgery is performed in dogs with rectal masses.

  17. Toxic Synovitis

    MedlinePlus

    ... Feeding Your 1- to 2-Year-Old Toxic Synovitis KidsHealth > For Parents > Toxic Synovitis A A A ... and causes no long-term problems. About Toxic Synovitis Toxic synovitis (also known as transient synovitis ) is ...

  18. Transanal local excision of rectal cancer.

    PubMed

    Read, D R; Sokil, S; Ruiz-Salas, G

    1995-01-01

    Twenty-five patients with invasive rectal cancer treated by transanal excision between 1978-1989 are presented. Two patients had poorly differentiated tumours and were converted to abdominoperineal resection and one patient had extensive liver metastases documented preoperatively. The remaining twenty-two, mean age 64 years, fulfilled the criteria for local treatment. Eighty-two percent of tumours were T1 or T2 stage. There was no operative mortality. Six complications in five patients occurred, none requiring surgical intervention. Five patients died of unrelated causes without evidence of recurrence at 4, 4, 14, 26 and 58 months. The length of follow-up for the surviving group (17 patients) was 16 to 115 months (mean 63 months). Two patients developed local recurrence at 32 and 60 months. Transanal excision can be curative for selected rectal cancers.

  19. [Fatal intoxication following rectal instillation of alcohol].

    PubMed

    Nadjem, H; Ropohl, D; Werp, J

    1990-01-01

    A 62-year old man who had been living on a remote farm was found dead in his bed. Inserted in his rectum was a synthetic flexible tube filled with brandy (43 vol. %) and connected to a bicycle pump. Samples taken during autopsy from 3 different parts of the body showed ethanol concentrations from 4.87% to 5.35% in the blood and 6.73% in the urine. The ethanol concentrations in the small and large intestine were considerably higher (more than 29%) than in the stomach (9%). The decreased had a tumor as large as a tennis ball on the base of his tongue, almost completely filling the oropharynx, making swallowing very difficult, which probably was the reason of the rectal instillation of alcohol. The report deals with this unusual case of rectal alcohol instillation, and with the different ethanol and congener alcohol concentrations in the body fluids.

  20. Management of radiation-induced rectal bleeding.

    PubMed

    Laterza, Liboria; Cecinato, Paolo; Guido, Alessandra; Mussetto, Alessandro; Fuccio, Lorenzo

    2013-11-01

    Pelvic radiation disease is one of the major complication after radiotherapy for pelvic cancers. The most commonly reported symptom is rectal bleeding which affects patients' quality of life. Therapeutic strategies for rectal bleeding are generally ignored and include medical, endoscopic, and hyperbaric oxygen treatments. Most cases of radiation-induced bleeding are mild and self-limiting, and treatment is normally not indicated. In cases of clinically significant bleeding (i.e. anaemia), medical therapies, including stool softeners, sucralfate enemas, and metronidazole, should be considered as first-line treatment options. In cases of failure, endoscopic therapy, mainly represented by argon plasma coagulation and hyperbaric oxygen treatments, are valid and complementary second-line treatment strategies. Although current treatment options are not always supported by high-quality studies, patients should be reassured that treatment options exist and success is achieved in most cases if the patient is referred to a dedicated centre.

  1. Long-term disease-free survival after surgical resection for multiple bone metastases from rectal cancer.

    PubMed

    Choi, Seok Jin; Kim, Jong Hun; Lee, Min Ro; Lee, Chang Ho; Kuh, Ja Hong; Kim, Jung Ryul

    2011-08-10

    Bone metastasis of primary colorectal cancer is uncommon. When it occurs, it is usually a late manifestation of disease and is indicative of poor prognosis. We describe a patient with multiple metachronous bone metastases from lower rectal cancer who was successfully treated with multimodal treatment including surgical resections and has shown 32 mo disease-free survival. Surgical resection of metastatic bone lesion(s) from colorectal cancer may be a good treatment option in selected patients.

  2. ACR Appropriateness Criteria®  Resectable Rectal Cancer

    PubMed Central

    2012-01-01

    The management of resectable rectal cancer continues to be guided by clinical trials and advances in technique. Although surgical advances including total mesorectal excision continue to decrease rates of local recurrence, the management of locally advanced disease (T3-T4 or N+) benefits from a multimodality approach including neoadjuvant concomitant chemotherapy and radiation. Circumferential resection margin, which can be determined preoperatively via MRI, is prognostic. Toxicity associated with radiation therapy is decreased by placing the patient in the prone position on a belly board, however for patients who cannot tolerate prone positioning, IMRT decreases the volume of normal tissue irradiated. The use of IMRT requires knowledge of the patterns of spreads and anatomy. Clinical trials demonstrate high variability in target delineation without specific guidance demonstrating the need for peer review and the use of a consensus atlas. Concomitant with radiation, fluorouracil based chemotherapy remains the standard, and although toxicity is decreased with continuous infusion fluorouracil, oral capecitabine is non-inferior to the continuous infusion regimen. Additional chemotherapeutic agents, including oxaliplatin, continue to be investigated, however currently should only be utilized on clinical trials as increased toxicity and no definitive benefit has been demonstrated in clinical trials. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment

  3. Altemeier operation for gangrenous rectal prolapse.

    PubMed

    Abdelhedi, Cherif; Frikha, F; Bardaa, S; Kchaw, A; Mzali, R

    2014-08-08

    A stranguled rectal prolapse is a rare cause of intestinal occlusion. It requires emergency surgery. A patient who underwent emergency perineal proctectomy, the Altemeier operation, combined with diverting loop sigmoid colostomy is described. The postoperative course was uneventful, with an excellent final result after colostomy closure. The successful treatment of this patient illustrates the value of the Altemeier procedure in the difficult and unusual scenario of bowel incarceration.

  4. Acute toxicity of hypofractionated intensity-modulated radiotherapy for prostate cancer

    PubMed Central

    Drodge, C.S.; Boychak, O.; Patel, S.; Usmani, N.; Amanie, J.; Parliament, M.B.; Murtha, A.; Field, C.; Ghosh, S.; Pervez, N.

    2015-01-01

    Background Dose-escalated hypofractionated radiotherapy (hfrt) using intensity-modulated radiotherapy (imrt), with inclusion of the pelvic lymph nodes (plns), plus androgen suppression therapy (ast) in high-risk prostate cancer patients should improve patient outcomes, but acute toxicity could limit its feasibility. Methods Our single-centre phase ii prospective study enrolled 40 high-risk prostate cancer patients. All patients received hfrt using imrt with daily mega-voltage computed tomography imaging guidance, with 95% of planning target volumes (ptv68 and ptv50) receiving 68 Gy and 50 Gy (respectively) in 25 daily fractions. The boost volume was targeted to the involved plns and the prostate (minus the urethra plus 3 mm and minus 3 mm from adjacent rectal wall) and totalled up to 75 Gy in 25 fractions. Acute toxicity scores were recorded weekly during and 3 months after radiotherapy (rt) administration. Results For the 37 patients who completed rt and the 3-month follow-up, median age was 65.5 years (range: 50–76 years). Disease was organ-confined (T1c–T2c) in 23 patients (62.1%), and node-positive in 5 patients (13.5%). All patients received long-term ast. Maximum acute genitourinary (gu) and gastrointestinal (gi) toxicity peaked at grade 2 in 6 of 36 evaluated patients (16.6%) and in 4 of 31 evaluated patients (12.9%) respectively. Diarrhea and urinary frequency were the chief complaints. Dose–volume parameters demonstrated no correlation with toxicity. The ptv treatment objectives were met in 36 of the 37 patients. Conclusions This hfrt dose-escalation trial in high-risk prostate cancer has demonstrated the feasibility of administering 75 Gy in 25 fractions with minimal acute gi and gu toxicities. Further follow-up will report late toxicities and outcomes. PMID:25908924

  5. Increasing trend in retained rectal foreign bodies

    PubMed Central

    Ayantunde, Abraham A; Unluer, Zynep

    2016-01-01

    AIM To highlight the rising trend in hospital presentation of foreign bodies retained in the rectum over a 5-year period. METHODS Retrospective review of the cases of retained rectal foreign bodies between 2008 and 2012 was performed. Patients’ clinical data and yearly case presentation with data relating to hospital episodes were collected. Data analysis was by SPSS Inc. Chicago, IL, United States. RESULTS Twenty-five patients presented over a 5-year period with a mean age of 39 (17-62) years and M: F ratio of 2:1. A progressive rise in cases was noted from 2008 to 2012 with 3, 4, 4, 6, 8 recorded patients per year respectively. The majority of the impacted rectal objects were used for self-/partner-eroticism. The commonest retained foreign bodies were sex vibrators and dildos. Ninty-six percent of the patients required extraction while one passed spontaneously. Two and three patients had retrieval in the Emergency Department and on the ward respectively while 19 patients needed examination under anaesthesia for extraction. The mean hospital stay was 19 (2-38) h. Associated psychosocial issues included depression, deliberate self-harm, illicit drug abuse, anxiety and alcoholism. There were no psychosocial problems identified in 15 patients. CONCLUSION There is a progressive rise in hospital presentation of impacted rectal foreign bodies with increasing use of different objects for sexual arousal. PMID:27830039

  6. Long-term results of intersphincteric resection for low rectal cancer.

    PubMed

    Yamada, Kazutaka; Ogata, Shunji; Saiki, Yasumitsu; Fukunaga, Mitsuko; Tsuji, Yoriyuki; Takano, Masahiro

    2009-06-01

    Intersphincteric resection has been performed as an alternative to abdominoperineal resection for low rectal cancer. The purpose of this study was to assess the long-term results after intersphincteric resection in terms of the morbidity, oncologic safety, and defecatory function. Between 1994 and 2006, 107 consecutive patients with low rectal cancer had curative intersphincteric resection, categorized as total, subtotal, or partial resection of the internal anal sphincter. There were no mortalities. Neorectal mucosal prolapse in patients with total intersphincteric resection and coloanal anastomotic stenosis in patients with subtotal or partial intersphincteric resection were observed as characteristic late complications. The five-year disease-free survival rates classified according to the TNM stage were 100 percent for stage I, 83.5 percent for stage II, and 72.0 percent for stage III cases. The five-year cumulative local recurrence rate after intersphincteric resection was 2.5 percent. Defecatory function, which was evaluated by bowel movement in a 24-hour period, and continence after intersphincteric resection were objectively good. The results of the multivariate analysis revealed that age was the only factor associated with a risk of fecal incontinence. Provided strict selection criteria are used, intersphincteric resection may be the optimal sphincter-preserving surgery for low rectal cancer.

  7. Preoperative chemoradiotherapy followed by local excision in clinical T2N0 rectal cancer

    PubMed Central

    Shin, Young Seob; Yoon, Yong sik; Lim, Seok-Byung; Yu, Chang Sik; Kim, Tae Won; Chang, Heung Moon; Park, Jin-hong; Ahn, Seung Do; Lee, Sang-Wook; Choi, Eun Kyung; Kim, Jin Cheon; Kim, Jong Hoon

    2016-01-01

    Purpose To investigate whether preoperative chemoradiotherapy (PCRT) followed by local excision (LE) is feasible approach in clinical T2N0 rectal cancer patients. Materials and Methods Patients who received PCRT and LE because of clinical T2 rectal cancer within 7 cm from anal verge between January 2006 and June 2014 were retrospectively analyzed. LE was performed in case of a good clinical response after PCRT. Patients’ characteristics, treatment record, tumor recurrence, and treatment-related complications were reviewed at a median follow-up of 49 months. Results All patients received transanal excision or transanal minimally invasive surgery. Of 34 patients, 19 patients (55.9%) presented pathologic complete response (pCR). The 3-year local recurrence-free survival and disease free-survival were 100.0% and 97.1%, respectively. There was no recurrence among the patients with pCR. Except for 1 case of grade 4 enterovesical fistula, all other late complications were mild and self-limiting. Conclusion PCRT followed by an LE might be feasible as an alternative to total mesorectal excision in good responders with clinical T2N0 distal rectal cancer. PMID:27730804

  8. Statistical simulations to estimate motion-inclusive dose-volume histograms for prediction of rectal morbidity following radiotherapy

    PubMed Central

    THOR, MARIA; APTE, ADITYA; DEASY, JOSEPH O.; MUREN, LUDVIG PAUL

    2016-01-01

    Background and purpose Internal organ motion over a course of radiotherapy (RT) leads to uncertainties in the actual delivered dose distributions. In studies predicting RT morbidity, the single estimate of the delivered dose provided by the treatment planning computed tomography (pCT) is typically assumed to be representative of the dose distribution throughout the course of RT. In this paper, a simple model for describing organ motion is introduced, and is associated to late rectal morbidity data, with the aim of improving morbidity prediction. Material and methods Organ motion was described by normally distributed translational motion, with its magnitude characterised by the standard deviation (SD) of this distribution. Simulations of both isotropic and anisotropic (anterior-posterior only) motion patterns were performed, as were random, systematic or combined random and systematic motion. The associations between late rectal morbidity and motion-inclusive delivered dose-volume histograms (dDVHs) were quantified using Spearman's rank correlation coefficient (Rs) in a series of 232 prostate cancer patients, and were compared to the associations obtained with the static/planned DVH (pDVH). Results For both isotropic and anisotropic motion, different associations with rectal morbidity were seen with the dDVHs relative to the pDVHs. The differences were most pronounced in the mid-dose region (40–60 Gy). The associations were dependent on the applied motion patterns, with the strongest association with morbidity obtained by applying random motion with an SD in the range 0.2–0.8 cm. Conclusion In this study we have introduced a simple model for describing organ motion occurring during RT. Differing and, for some cases, stronger dose-volume dependencies were found between the motion-inclusive dose distributions and rectal morbidity as compared to the associations with the planned dose distributions. This indicates that rectal organ motion during RT influences the

  9. Statistical simulations to estimate motion-inclusive dose-volume histograms for prediction of rectal morbidity following radiotherapy.

    PubMed

    Thor, Maria; Apte, Aditya; Deasy, Joseph O; Muren, Ludvig Paul

    2013-04-01

    Internal organ motion over a course of radiotherapy (RT) leads to uncertainties in the actual delivered dose distributions. In studies predicting RT morbidity, the single estimate of the delivered dose provided by the treatment planning computed tomography (pCT) is typically assumed to be representative of the dose distribution throughout the course of RT. In this paper, a simple model for describing organ motion is introduced, and is associated to late rectal morbidity data, with the aim of improving morbidity prediction. Organ motion was described by normally distributed translational motion, with its magnitude characterised by the standard deviation (SD) of this distribution. Simulations of both isotropic and anisotropic (anterior-posterior only) motion patterns were performed, as were random, systematic or combined random and systematic motion. The associations between late rectal morbidity and motion-inclusive delivered dose-volume histograms (dDVHs) were quantified using Spearman's rank correlation coefficient (Rs) in a series of 232 prostate cancer patients, and were compared to the associations obtained with the static/planned DVH (pDVH). For both isotropic and anisotropic motion, different associations with rectal morbidity were seen with the dDVHs relative to the pDVHs. The differences were most pronounced in the mid-dose region (40-60 Gy). The associations were dependent on the applied motion patterns, with the strongest association with morbidity obtained by applying random motion with an SD in the range 0.2-0.8 cm. In this study we have introduced a simple model for describing organ motion occurring during RT. Differing and, for some cases, stronger dose-volume dependencies were found between the motion-inclusive dose distributions and rectal morbidity as compared to the associations with the planned dose distributions. This indicates that rectal organ motion during RT influences the efforts to model the risk of morbidity using planning distributions

  10. Giant rectal gastrointestinal stromal tumours: a diagnostic and therapeutic challenge

    PubMed Central

    Alder, L.S.; Elver, G.; Foo, F.J.; Dobson, M.

    2013-01-01

    Gastrointestinal stromal tumour (GIST are the most common mesenchymal tumours; however, rectal GISTs account for <5%. In the pelvis they represent a diagnostic challenge with giant GISTs likely to be malignant. They may present with urological, gynaecological or rectal symptoms. Sphincter-preserving surgery can be aided by neoadjuvant therapy. We present an uncommon case of giant rectal GIST masquerading as acute urinary retention. PMID:24968434

  11. Endoscopic Ultrasound-Guided Management of Bleeding Rectal Varices.

    PubMed

    Philips, Cyriac Abby; Augustine, Philip

    2017-01-01

    Rectal variceal bleeding, though rare, can pose significant morbidity and mortality in the wake of treatment failure. Conventional treatment utilizing endoscopic glue injection might not be feasible in all cases due to poor visualization and inadvertent missing of variceal source of bleed. Endoscopic ultrasound (EUS)-guided rectal variceal management is a promising and effective modality. We provide real-time images and a video of EUS-guided precision management of rectal variceal bleed using coiling and glue in a cirrhotic.

  12. [Ventral rectal sacropexy (colpo-perineal) in the treatment of rectal and rectogenital prolapse].

    PubMed

    Enríquez-Navascués, José M; Elósegui, José L; Apeztegui, Francisco J; Placer, Carlos; Borda, Nerea; Irazusta, Martín; Múgica, José A; Murgoitio, Javier

    2009-11-01

    Ventral sacral-rectopexy with mesh corrects rectal prolapse and minimises rectal dissection. Subsequent colpopexy corrects apical and posterior prolapses of the vagina. The combination of both procedures can lead to the simultaneous correction of pelvic organ prolapses (POP). To present the results of a patient series with several types of POP treated using the same approach and operation. A total of 57 patients diagnosed with any type of POP were operated on between January 2005 and August 2008 using ventral rectal-colpo-sacropexy, who were grouped into three types: A, total rectal prolapse isolated or combined with a hysterocele or colpocele (11 patients); B, rectoenterocele with internal rectal invagination and/or descending perineum (4 patients); and C, middle and posterior genital compartment prolapse (42 patients). The laparoscopic approach was used in the 15 patients of groups A and B and 11 from group C. A biological mesh was used in 41 patients and a macroporous synthetic one in the rest. The mean age of the patients in the series was 66 (19-81) years, with 55 females and 2 males. The median follow up was 25 (4-48) months. There were no major post-surgical complications. A recurrence of prolapse was recorded in one patient in group A (1/11); the 7 patients who suffered from incontinence improved after the surgery, no case of de novo constipation being recorded and an improvement in 8 of the 9 patients from groups A and B with obstructive defaecation. There were 9 (21%) recurrences detected in group C, but only 4 (9%) required reintervention. In all the recurrences a biological mesh had been used. Laparoscopic ventral rectal-colpo-pexy is an effective technique to correct POP. Although safe and innocuous, the results with biological meshes did not last as long.

  13. Comparison of the preventive analgesic effect of rectal ketamine and rectal acetaminophen after pediatric tonsillectomy.

    PubMed

    Heidari, S Morteza; Mirlohi, S Zahra; Hashemi, S Jalal

    2012-03-01

    There is a little data about rectal administration of Ketamine as a postoperative analgesic, so we compared the efficacy of rectal ketamine with rectal acetaminophen, which is applied routinely for analgesia after painful surgeries like tonsillectomy. In this single-blinded comparative trial, we enrolled 70 children undergoing elective tonsillectomy, and divided them randomly in two groups. Patients received rectal ketamine (2 mg / kg) or rectal acetaminophen (20 mg / kg) at the end of surgery. The children's Hospital of Eastern Ontario Pain scale was used to estimate pain in children. Also the vital signs, Wilson sedation scale, and side effects in each group were noted and compared for 24 hours. The ketamine group had a lower pain score at 15 minutes and 60 minutes after surgery in Recovery (6.4 ± 0.8, 7.4 ± 1 vs. 7.1 ± 1.2, 7.8 ± 1.2 in the acetaminophen group, P < 0.05) and one hour and two hours in the ward (7.2 ± 0.7, 7 ± 0.5 vs. 7.9 ± 1.2, 7.5 ± 1.2 in the acetaminophen group, P < 0.05), with no significant differences till 24 hours. Dreams and hallucinations were not reported in the ketamine group. Systolic blood pressure was seen to be higher in the ketamine group (104.4 ± 7.9 vs. 99.8 ± 7.7 in the acetaminophen group) and nystagmus was reported only in the ketamine group (14.2%). Other side effects were equivalent in both the groups. With low complications, rectal ketamine has analgesic effects, especially in the first hours after surgery in comparison with acetaminophen, and it can be an alternative analgesic with easy administration in children after tonsillectomy.

  14. Laparoscopic intersphincteric resection for low rectal cancer.

    PubMed

    Lim, Sang Woo; Huh, Jung Wook; Kim, Young Jin; Kim, Hyeong Rok

    2011-12-01

    Laparoscopic intersphincteric resection (ISR) after neoadjuvant chemoradiation is helpful in the management of patients with low rectal cancer. With the advent of this technique, the need for performance of abdominoperineal resection seems to have decreased in patients with very low rectal tumors. The aim of the present study was to evaluate the feasibility, the functional outcome, and the short-term oncologic outcomes of laparoscopic ISR for low rectal adenocarcinoma at our institution. We retrospectively reviewed the data of 111 consecutive patients who underwent laparoscopic ISR for low rectal adenocarcinoma between July 2005 and December 2009. Demographic status, surgical outcomes, functional outcome data, and oncologic outcome data were collected. The mean distance of the tumor from the anal verge was 3.4 cm (range: 1-5 cm). The mean operative time was 214.7 min (range, 150-450 min). The mean distal resection margin was 1.3 ± 1.1 cm. Morbidity occurred in 24 patients (21.6%), including anastomotic leakage in 2 patients (1.8%). The mean Wexner continence score after stoma repair was 7.5 ± 2.7 (range: 2 ~ 19), and 9.8 in total ISR, 7.3 in partial ISR (P = 0.071). The 3-year overall survival rate was 92.8%, and the 3-year disease-free survival rate was 73.0%. Local recurrence was noted in 6 of the 111 patients with TNM stage I to III (5.4%). The patients with lesions at 2 cm to the dentate line had a 7.07-fold greater risk of local recurrence, including a 13.42-fold greater risk of lateral pelvic wall recurrence and perineal recurrence (95% Confidence interval [CI], 1.141-158.006; P = 0.009) than in those who had lesions more than 2 cm from the anal verge (95% CI, 1.290-38.832; P = 0.011). Laparoscopic ISR after neoadjuvant chemoradiation can be recommended as a technically feasible, minimally invasive, and a sphincter-saving procedure with acceptable functional and short-term oncologic outcomes in patients with very low rectal cancer.

  15. [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.

  16. Tegafur-uracil (UFT) plus folinic acid in advanced rectal cancer.

    PubMed

    Sanchiz, F; Milla, A

    1994-12-01

    We previously reported positive results to Tegafur-Uracil (UFT) chemotherapy in a group of patients with advanced rectal cancer. We have continued the study and now report the effectiveness of UFT plus folinic acid (FA) in 52 patients with advanced rectal cancer. The therapeutic schedule was UFT, 600 mg/m2/day x 14 days p.o. + FA, 90 mg/m2/day x 14 days p.o. Fifty-two out of a total of 56 patients were evaluated for response and toxicity. A higher incidence of positive responses in patients without previous chemotherapy was appreciated. Twenty-one of the 52 evaluated patients showed a partial response (PR). Responses were strongly correlated with previous chemotherapy (14/20; 70% PR of cases without previous chemotherapy vs 7/32; 22% of cases with previous chemotherapy). All responding patients came forward with a median time to progression of 8.2 months (19.6 months for patients without previous chemotherapy vs 7.7 months for patients with previous chemotherapy, P < 0.01). We concluded that the UFT plus FA could be a treatment of choice for patients with advanced rectal cancer.

  17. 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

  18. Transanal endoscopic microsurgery for the treatment of uncommon rectal lesions.

    PubMed

    Ferrer-Márquez, Manuel; Rubio-Gil, Francisco; Ortega-Ruiz, Sofía; Blesa-Sierra, Isabel; Álvarez-García, Antonio; Jorge-Cerrudo, Jaime; Vidaña-Márquez, Elisabet; Belda-Lozano, Ricardo; Reina-Duarte, Ángel

    Transanal endoscopic microsurgery (TEM) was developed as a less aggressive alternative treatment for rectal lesions (mainly adenomas and adenocarcinomas). However, its use for other rectal lesions has become more frequent, trying to reduce the morbidity associated with more invasive techniques. The aim of this study is to describe our experience in the use of TEM in other rectal lesions. Retrospective and descriptive study including patients operated with TEM (from June 2008 to December 2016) for the treatment of rectal lesions different from adenomas or adenocarcinomas. Among the 138 patients treated by TEM in our department, 10 patients were operated on for rectal lesions other than adenomas or adenocarcinomas. Rectal lesions were 3neuroendocrine tumours, a neuroendocrine tumour metastasis, a rectal stenosis, a cloacogenic polyp, an endometrioma, a retrorrectal tumour, a presacral abscess and a lesion in the rectovaginal septum. Mean operative time was 72min and postoperative stay was 4.2 days. Only one patient needed a reoperation, due to rectal bleeding. TEM could be a useful tool for the treatment of rectal lesions different from adenomas or adenocarcinomas, potentially decreasing the morbidity associated with more aggressive surgical techniques. Copyright © 2017 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Rectal transmission of bovine leukemia virus in cattle and sheep.

    PubMed

    Henry, E T; Levine, J F; Coggins, L

    1987-04-01

    Bovine leukemia virus (BLV) was transmitted by rectal inoculation of BLV-infective whole blood into cattle and sheep. Two cows and 2 sheep each were given 500 ml and 50 ml of blood, respectively, by rectal infusion. Two sheep which served as positive controls each were given 1 ml of the same blood, IV. All animals became seropositive to BLV by postinoculation week 5. Although relatively large volumes of blood were used for rectal inoculation, a base line for infectivity was established for the rectal route.

  20. Three-Dimensional Analysis of Recurrence Patterns in Rectal Cancer: The Cranial Border in Hypofractionated Preoperative Radiotherapy Can Be Lowered

    SciTech Connect

    Nijkamp, Jasper; Kusters, Miranda; Beets-Tan, Regina G.H.; Martijn, Hendrik; Beets, Geerard L.; Velde, Cornelis J.H. van de; Marijnen, Corrie A.M.

    2011-05-01

    Purpose: The aim of this study was to determine whether and where the radiotherapy (RT) clinical target volume (CTV) could be reduced in short-course preoperative treatment of rectal cancer patients. Methods and Materials: Patients treated in the Dutch total mesorectal excision trial, with a local recurrence were analyzed. For 94 (25 who underwent radiation therapy 69 who did not) of 114 patients with a local recurrence, the location of the recurrence was placed in a three-dimensionalthree (3D) model. The data in the 3D model were correlated to the clinical trial data to distinguish a group of patients eligible for CTV reduction. Effects of CTV reduction on dose to the small bowel was tested retrospectively in a dataset of 8 patients with three-field conformal plans and intensity-modulated RT (IMRT). Results: The use of preoperative RT mainly reduces anastomotic, lateral, and perineal recurrences. In patients without primary nodal involvement, no recurrences were found cranially of the S2-S3 interspace, irrespective of the delivery of RT. In patients without primary nodal involvement and a negative circumferential resection margin (CRM), only one recurrence was found cranial to the S2-S3 interspace. With a cranially reduced CTV to the S2-S3 interspace, over 60% reduction in absolute small bowel exposure at dose levels from 15 to 35 Gy could be achieved with three-field conventional RT, increasing to 80% when IMRT is also added. Conclusions: The cranial border of the CTV can safely be lowered for patients without expected nodal or CRM involvement, yielding a significant reduction of dose to the small bowel. Therefore, a significant reduction of acute and late toxicity can be expected.

  1. Dose escalation using contact x-ray brachytherapy (Papillon) for rectal cancer. Does it improve the chance of organ preservation?

    PubMed

    Sun Myint, Arthur; Smith, Fraser McLean; Gollins, Simon William; Wong, Helen; Rao, Christopher; Whitmarsh, Karen; Sripadam, Raj; Rooney, Paul; Hershman, Michael Jeremy; Fekete, Zsolt; Perkins, Kate; Pritchard, D Mark

    2017-09-20

    A watch and wait policy for patients with a complete clinical response (cCR) after external beam chemoradiotherapy (EBCRT) for rectal cancer is an attractive option. However, approximately a third of tumours will regrow, which requires surgical salvage for cure. We assessed whether contact x-ray brachytherapy (CXB) can improve organ preservation by avoiding surgery for local regrowth. From our institutional database, we identified 200 of 573 patients treated by CXB from 2003 to 2012. Median age was 74 years (range 32-94), and 134 (67%) patients were men. Histology was confirmed in all patients and was staged using CT scan, MRI, or endorectal ultrasound. All patients received combined CXB and EBCRT, except 17 (8.5%) who had CXB alone. Initial cCR was achieved in 144/200 (72%) patients. 38/56 (68%) patients who had residual tumour received immediate salvage surgery. 16/144 (11%) patients developed local relapse after cCR, and 124/144 (86%) maintained cCR. At median follow up of 2.7 years, 161 (80.5%) patients were free of cancer. The main late toxicity was bleeding (28%). Organ preservation was achieved in 124/200 (62%) patients. Our data suggest that CXB can reduce local regrowth to 11% compared with around 30% after EBCRT alone. Organ preservation of 62% achieved was higher than reported in most published watch and wait studies. Advances in knowledge: CXB is a promising treatment option to avoid salvage surgery for local regrowth, which can improve the chance of organ preservation in patients who are not suitable for or refuse surgery.

  2. Case report: Sigmoid strangulation from evisceration through a perforated rectal prolapse ulcer – An unusual complication of rectal prolapse

    PubMed Central

    Li, Jennifer Z.; Kittmer, Tiffaney; Forbes, Shawn; Ruo, Leyo

    2015-01-01

    Introduction Rectal prolapse occurs particularly in elder females and presentation can sometimes lead to complications such as strangulation and evisceration of other organs through the necrotic mucosa. Presentation of case This is a case of a 61 year-old female with rectal prolapse complicated by rectal perforation through which a segment of sigmoid colon eviscerated and became strangulated. This patient initially presented with sepsis requiring ICU admission, but fully recovered following a Hartmann’s procedure with a sacral rectopexy. Discussion Complications of rectal prolapse include incarceration, strangulation, and rarely, perforation with evisceration of other viscera requiring urgent operation. This report provides a brief overview of complications associated with rectal prolapse, reviews similar cases of transrectal evisceration, and discusses the management of chronic rectal prolapse. Conclusion Prompt surgical consult is warranted if any signs or symptoms suggestive of complications from prolapse are present. PMID:25680532

  3. Akt Inhibitor MK2206 in Treating Patients With Previously Treated Colon or Rectal Cancer That is Metastatic or Locally Advanced and Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2016-12-13

    Colon Mucinous Adenocarcinoma; Colon Signet Ring Cell Adenocarcinoma; Rectal Mucinous Adenocarcinoma; Rectal Signet Ring Cell Adenocarcinoma; Recurrent Colon Carcinoma; Recurrent Rectal Carcinoma; 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

  4. Rectal sensation test helps avoid pain of apical prostate biopsy.

    PubMed

    Jones, J Stephen; Zippe, Craig D

    2003-12-01

    Apical cores obtained during transrectal prostate biopsy are associated with greater pain than cores obtained from the remainder of the gland. We present a method to minimize this pain. During 30 consecutive apical biopsies the needle was purposefully placed above all rectal pain fibers, which are anatomically present only below the dentate line. All patients received a periprostatic nerve block prior to biopsy. The patient was asked if he felt the sharp sensation of the needle as it was placed lightly against the rectal mucosa when the needle was aimed at apex (the rectal sensation test). If so, the needle was advanced cranially 2 to 3 mm or until he could no longer detect its light touch. The probe handle was then rotated dorsally, pulling the rectal mucosa downward until the needle was again aimed at the apex. Patients were asked to report a visual analog pain score for each biopsy. These results were compared to those obtained when doing 30 consecutive apical biopsies without the rectal sensation test. The average visual analog pain score for apical biopsy was 1.25 (range 0 to 2.2) for patients in whom the rectal sensation test was used to bypass rectal pain sensory fibers. The average score in control patients in whom the rectal sensation test was not used was higher at 2.28 (range 0.3-6.2). These results were statistically significant (p > 0.0005). Increased sensitivity to apical prostate biopsy is due to rectal pain fibers located below the dentate line. These fibers and the associated pain may be safely avoided by passing through the rectal wall above the dentate line. The rectal sensation test easily identifies the sensate area below the dentate line. Painless apical biopsy can then be achieved by rotating the ultrasound probe to aim the biopsy needle in the desired path.

  5. [Photochemotherapy with indocyanine green in cutaneous metastases of rectal carcinoma].

    PubMed

    Karrer, S; Abels, C; Bäumler, W; Steinbauer, M; Landthaler, M; Szeimies, R M

    1997-09-12

    Six weeks before admission of a 47-year-old man with known rectal carcinoma, small nodular metastases had occurred over the front of both his thighs. Examination showed many aggregatet cuti-color or livid nodes, diameter 0.5 cm. The patient's poor general condition excluded the usual palliative measures. Photochemotherapy of the skin metastases with indocyanine green (ICG; absorption maximum 805 nm), a non-toxic dye approved for diagnostic purposes, was undertaken on a trial basis. The dye, being bound to plasma proteins, is retained in the intravacular space. Immediately after administration of the dye (2.5 mg/kg intravenously) the skin metastases were irradiated by diode laser (lambda = 805 nm, 100 J/cm2, 3 W/cm2, radiation diameter 2 cm). This necrosed the metastases and clinically as well as histologically resulted in their complete disappearance with scarring of the treated area. This case illustrates the effectiveness of photochemotherapy with ICG against solid skin tumours of increased microvascular density.

  6. Bevacizumab, Oxaliplatin, and Capecitabine With Radiation Therapy in Rectal Cancer: Phase I Trial Results

    SciTech Connect

    Czito, Brian G. . E-mail: czito001@mc.duke.edu; Bendell, Johanna C.; Willett, Christopher G.; Morse, Michael A.; Blobe, Gerard C.; Tyler, Douglas S.; Thomas, John; Ludwig, Kirk A.; Mantyh, Christopher R.; Ashton, Jill; Yu Daohai; Hurwitz, Herbert I.

    2007-06-01

    Purpose: The overexpression of vascular endothelial growth factor (VEGF) is associated with poor outcomes in colorectal cancer patients. Bevacizumab, a VEGF inhibitor, enhances the effects of chemotherapy and radiation therapy on tumor cytotoxicity in preclinical models, including colorectal cancer. A Phase I trial was undertaken to evaluate the combination of bevacizumab, capecitabine, oxaliplatin, and radiation therapy in patients with rectal cancer. Methods and Materials: Patients with pathologically confirmed adenocarcinoma of the rectum were eligible. Pretreatment staging included computerized tomography, endoscopic ultrasound, and surgical evaluation. Patients received 50.4 Gy of external beam radiation therapy (EBRT) to the tumor in 28 fractions. Capecitabine, oxaliplatin, and bevacizumab were administered concurrently with radiation therapy. After EBRT completion, patients were restaged and evaluated for surgery. Primary endpoints included the determination of dose-limiting toxicity and a recommended Phase II dose, non dose-limiting toxicity, and preliminary radiographic and pathologic response rates. Results: Eleven patients were enrolled. All were evaluable for toxicity and efficacy. Dose level 2 was associated with unacceptable toxicity (primarily diarrhea). Dose level 1 had an acceptable toxicity profile. The recommended Phase II dose in our study was bevacizumab 15 mg/kg Day 1 + 10 mg/kg Days 8 and 22, oxaliplatin 50 mg/m{sup 2} weekly, and capecitabine 625 mg/m{sup 2} bid during radiation days. Six patients had clinical responses. Two patients had a pathologic complete response, and 3 had microscopic disease only. One patient experienced a postoperative abscess, one a syncopal episode during adjuvant chemotherapy, and one a subclinical myocardial infarction during adjuvant chemotherapy. Conclusions: The combination of bevacizumab, capecitabine, oxaliplatin, and radiation therapy in rectal cancer was tolerable, with encouraging response rates. Further

  7. Lubricant Provides Poor Rectal Mucosal HIV Coverage.

    PubMed

    Shieh, Eugenie C; Weld, Ethel D; Fuchs, Edward J; Hiruy, Hiwot; Buckheit, Karen W; Buckheit, Robert W; Breakey, Jennifer; Hendrix, Craig W

    2017-08-01

    Given the rising HIV incidence in men who have sex with men (MSM) despite repeatedly proven effectiveness of oral HIV pre-exposure prophylaxis, behaviorally congruent periodic dosing strategies, such as dosing microbicides as lubricants, are now in demand. Rectal microbicide gel studies largely administer gels using vaginal applicators, which have not been well received and do not mimic lubricant use. We compared rectal gel manually dosed as lubricant with applicator dosing in five healthy, HIV-negative MSM who received 10 or 3.5 ml of (99m)Tc-DTPA-radiolabeled hydroxyethyl cellulose universal placebo gel intrarectally. After washout, participants received 10 ml of radiolabeled Wet(®) Original(®) lubricant to apply to the anus with fingers and/or a phallus in a manner typical of sexual lubricant use with a partner, followed by simulated receptive anal intercourse. Single-photon emission computed tomography with transmission computed tomography was performed 4 h after each gel administration. Manual dosing was associated with more variable rectosigmoid distribution, 4.4-15.3 cm from the anorectal junction, compared with more uniform distribution, 5.9-7.4 and 5.3-7.6 cm after 10 and 3.5 ml applicator dosing, respectively. A significantly smaller fraction of the initial 10 ml dose was retained within the colon after manual dosing, 3.4%, compared with 94.9% and 88.4% after 10 and 3.5 ml applicator dosing, respectively (both p < .001). Manual dosing of a sexual lubricant delivered a small, variable fraction of the dose with variable rectosigmoid distribution compared with applicator dosing. These results raise concern that dosing a rectal microbicide gel as a sexual lubricant may not provide adequate or predictable mucosal coverage for HIV protection.

  8. Abdominosacral resection for locally recurring rectal cancer

    PubMed Central

    Belli, Filiberto; Gronchi, Alessandro; Corbellini, Carlo; Milione, Massimo; Leo, Ermanno

    2016-01-01

    AIM To investigate feasibility and outcome of abdominal-sacral resection for treatment of locally recurrent rectal adenocarcinoma. METHODS A population of patients who underwent an abdominal-sacral resection for posterior recurrent adenocarcinoma of the rectum at the National Cancer Institute of Milano, between 2005 and 2013, is considered. Retrospectively collected data includes patient characteristics, treatment and pathology details regarding the primary and the recurrent rectal tumor surgical resection. A clinical and instrumental follow-up was performed. Surgical and oncological outcome were investigated. Furthermore an analytical review of literature was conducted in order to compare our case series with other reported experiences. RESULTS At the time of abdomino-sacral resection, the mean age of patients was 55 (range, 38-64). The median operating time was 380 min (range, 270-480). Sacral resection was performed at S2/S3 level in 3 patients, S3/S4 in 3 patients and S4/S5 in 4 patients. The median operating time was 380 ± 58 min. Mean intraoperative blood loss was 1750 mL (range, 200-680). The median hospital stay was 22 d. Overall morbidity was 80%, mainly type II complication according to the Clavien-Dindo classification. Microscopically negative margins (R0) is obtained in all patients. Overall 5-year survival after first surgical procedure is 60%, with a median survival from the first surgery of 88 ± 56 mo. The most common site of re-recurrence was intrapelvic. CONCLUSION Sacral resection represents a feasible approach to posterior rectal cancer recurrence without evidence of distant spreading. An accurate staging is essential for planning the best therapy. PMID:28070232

  9. [Robotic total mesorectal excision for rectal cancer].

    PubMed

    Rossi, Gustavo; Alvarez, Fernando A; Mentz, Ricardo; Vaccaro, Carlos A; Im, Víctor; Quintana, Guillermo Ojea

    2013-06-01

    Laparoscopic total mesorectal excision (TME) has proven to be feasible and safe. However, it represents a major technical challenge, since it involves the dissection of the rectum in a confined space such as the bony pelvis using un-ergonomic surgical devices. This difficulty is accentuated in patients with distal tumors and high body mass index (BMI), in which the surgical margins and the hypogastric nerves may be affected. Therefore, robotic surgery aims to overcome these limitations that conspire against the mininvasive surgical approach of rectal cancer. We present an obese (BMI = 32 kg/m2) 82-year-old man with a history of smoking and prostate cancer that was recently diagnosed with a middle rectal adenocarcinoma at 9 cm from the anal verge. Rectal examination evidenced a mobile lesion. Computed tomography scan ruled out metastases and at the local staging by MRI, the tumor was considered as T3-N0 with free circumferential margins. Surgical treatment was decided and a hybrid technique was used combining an initial laparoscopic approach followed by the robotic TME. The patient had a full recovery and was discharged three days after surgery without complications. Pathological examination revealed a low-grade adenocarcinoma with mesorectal invasion, free circumferential and distal margins, and 24 negative lymph nodes (pT3-pN0-pM0/Stage II). Robotic TME was performed safely in an obese patient. It facilitated dissection maneuvers in a confined space with proper identification and preservation of the hypogastric nerves, allowing retrieving an intact mesorectum. Prospective randomized trials will define the role of this new technology.

  10. A new 'enterocompressor' to facilitate rectal anastomosis.

    PubMed

    Barraza, R P

    1990-02-01

    A newly devised enterocompressor facilitates low rectal anastomosis in children with Hirschsprung's disease. This simple surgical instrument, composed of two semicylindrical valves, a hinge, and a regulating screw, maintains intestinal anastomoses properly placed and produces spur crushing. In addition, it is inexpensive and reusable. The enterocompressor, used in 33 primary and 15 secondary Duhamel operations, and applied to normalize intestinal transit in 10 colectomies, provided adequate anastomosis and prevented leakage of intestinal contents. This enterocompressor can be used safely in children as young as six months of age.

  11. Combined modality therapy for rectal cancer.

    PubMed

    Minsky, Bruce D; Röedel, Claus; Valentini, Vincenzo

    2010-01-01

    The standard adjuvant treatment for cT3 and/or N+ rectal cancer is preoperative chemoradiation. However, there are many controversies regarding this approach. These include the role of short course radiation, whether postoperative adjuvant chemotherapy necessary for all patients and whether the type of surgery after chemoradiation should be based on the response rate. More accurate imaging techniques and/or molecular markers may help identify patients with positive pelvic nodes to reduce the chance of overtreatment with preoperative therapy. Will more effective systemic agents both improve the results of radiation as well as modify the need for pelvic radiation? These questions and others remain active areas of clinical investigation.

  12. Rectal and appendiceal inflammatory myofibroblastic tumors.

    PubMed

    Khoddami, Maliheh; Sanae, Shahram; Nikkhoo, Bahram

    2006-07-01

    Inflammatory myofibroblastic tumors are neoplasms characterized by spindle cell proliferation and a fiboinflammatory vascular stroma. Herein, we presented the successful treatment of a rectal inflammatory myofibroblastic tumor in an 11-year-old boy who presented with diarrhea and abdominal pain of 1(1/2) months duration and an appendiceal inflammatory myofibroblastic tumor in a 29-year-old man presented with recurrent abdominal pain of two months duration with associated tenderness and rebound tenderness in the right lower abdomen. Histologically, our cases had inflammatory myofibroblastic tumors very similar to that of other sites; the spindle cells were positive for vimentin and muscle-specific actin.

  13. A tertiary care hospital's 10 years' experience with rectal ultrasound in early rectal cancer.

    PubMed

    Akhter, Ahmed; Walker, Andrew; Heise, Charles P; Kennedy, Gregory D; Benson, Mark E; Pfau, Patrick R; Johnson, Eric A; Frick, Terrence J; Gopal, Deepak V

    2017-08-24

    Rectal endoscopic ultrasound (RUS) has become an essential tool in the management of rectal adenocarcinoma because of the ability to accurately stage lesions. The aim of this study was to identify the staging agreement of early RUS-staged rectal adenocarcinoma with surgical resected pathology and ultimately determine how this impacts the management of early rectal cancer (T1-T2). Retrospective chart review was performed from November 2002 to November 2013 to identify procedure indication, RUS staging data, surgical management, and postoperative surgical pathology data. There were a total of 693 RUS examinations available for review and 282 of these were performed for a new diagnosis of rectal adenocarcinoma. There was staging agreement between RUS and surgical pathology in 19 out of 20 (95%) RUS-staged T1 cases. There was staging agreement between RUS and surgical pathology in 3 out of 9 (33%) RUS-staged T2 cases. There was significantly better staging agreement for RUS-staged T1 lesions compared to RUS staged T2 lesions (P = 0.002). Nearly 60% of T1N0 cancers were referred for transanal excisions (TAEs), and 78% of T2N0 cancers underwent low anterior resection. This study identified only a small number of T1-T2 adenocarcinomas. There was good staging agreement between RUS and surgical pathology among RUS-staged T1 lesions whereas poor staging agreement among RUS-staged T2 lesions. Although TAE is largely indicated by the staging of a T1 lesion, this approach may be less appropriate for T2 lesions due to high reported local recurrence.

  14. Locally advanced rectal cancer: Preliminary results of rectal preservation after neoadjuvant chemoradiotherapy.

    PubMed

    Vaccaro, Carlos Alberto; Yazyi, Federico Julio; Ojra Quintana, Guillermo; Santino, Juan Pablo; Sardi, Mabel Edith; Beder, Damián; Tognelli, Joaquin; Bonadeo, Fernando; Lastiri, José María; Rossi, Gustavo Leandro

    2016-05-01

    The standard treatment for locally advanced rectal cancer is total mesorectal excision. However, organ preservation has been proposed for tumors with good response to neoadjuvant treatment. The aim of this study was to evaluate the oncologic results of this strategy. This is a retrospective cohort study (2005-2014) including a consecutive series of patients with rectal adenocarcinoma with complete or almost complete clinical response after preoperative chemo-radiotherapy, that were treated according to a strategy of preservation of the rectum. A total of 204 patients with rectal cancer received neoadjuvant therapy. Thirty (14.7%) had a good response and were treated with rectal preservation (23 «Watch and Wait» and 7 local resections). Median follow-up was 46 months (interquartile range: 30-68). In the group of «Watch & Wait», 4 patients had local recurrence before 12 months (actuarial local recurrence rate=18.5%). All of them underwent salvage surgery (2 with radical surgery and 2 local resections) without any further recurrence. Disease-free survival actuarial rate at 3 years follow-up was 94.1% (95% CI 82.9-100). None of the 7 patients that were treated by local excision had local recurrence. The organ preservation rate for the whole group was 93%. The strategy of organ preservation in locally advanced rectal cancer is feasible in cases with good response to neoadjuvant therapy. When implemented in a highly selected group of patients this strategy is associated with satisfactory oncologic results. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Is rectal MRI beneficial for determining the location of rectal cancer with respect to the peritoneal reflection?

    PubMed

    Jung, Eun Joo; Ryu, Chun Geun; Kim, Gangmi; Kim, Su Ran; Nam, Sang Eun; Park, Hee Sun; Kim, Young Jun; Hwang, Dae-Yong

    2012-12-01

    An objective method for determining the location of the cancer with respect to peritoneal reflection would be helpful to decide the treatment modality for rectal cancer. This study was designed to evaluate the accuracy and usefulness of rectal MRI to determine spatial relations between the peritoneal reflection and rectal cancer and to compare these with operative findings. Patients that underwent a rectal cancer operation after a rectal MRI check between November 2008 and June 2010 were considered for the study. The patients that received preoperative concurrent chemoradiation or trans-anal local excision were excluded. Fifty-four patients constituted the study cohort. By comparing surgical and radiologic findings, the accuracy for predicting tumour location in relation to the peritoneal reflection by rectal MRI in all patients was 90.7%. In terms of tumour location in relation to peritoneal reflection, the accuracy of rectal MRI was 93.5% in patients with a tumour located above the peritoneal reflection, 90.0% in patients with a tumour located on the peritoneal reflection, and 84.6% in patients with a tumour located below the peritoneal reflection (p=0.061). When the cohort was subdivided by gender, body mass index (BMI), operative findings, or tumour size, no significant difference was observed among subgroups. Rectal MRI could be a useful tool for evaluating the relation between rectal cancer and peritoneal reflection especially when tumour size is less than 8cm. Rectal MRI can provide information regarding the location of rectal cancer in relation to the peritoneal reflection for treatment planning purposes.

  16. Rectal gonorrhoea in male homosexuals. Presentation and therapy.

    PubMed

    Fluker, J L; Deherogoda, P; Platt, D J; Gerken, A

    1980-12-01

    In a review of rectal gonorrhoea 73 episodes were studied in 65 homosexual men. The presenting signs and symptoms were carefully noted. Treatment with a single injection of spectinomycin hydrochloride 2 g resulted in a cure rate of 94.5%. The relatively high treatment failure rate associated with rectal gonorrhoea may possibly be due to microbial mechanisms.

  17. Rectal chlamydia - should screening be recommended in women?

    PubMed

    Andersson, Nirina; Boman, Jens; Nylander, Elisabet

    2017-04-01

    Chlamydia trachomatis is the most common bacterial sexually transmitted infection in Europe and has large impacts on patients' physical and emotional health. Unidentified asymptomatic rectal Chlamydia trachomatis could be a partial explanation for the high Chlamydia trachomatis prevalence. In this study, we evaluated rectal Chlamydia trachomatis testing in relation to symptoms and sexual habits in women and men who have sex with men. Rectal Chlamydia trachomatis prevalence was 9.1% in women and 0.9% in men who have sex with men. None of the patients reported any rectal symptoms; 59.0% of the women with a rectal Chlamydia trachomatis infection denied anal intercourse and 18.8% did not have a urogenital infection; 9.4% did neither have a urogenital infection nor reported anal sex. We suggest that rectal sampling should be considered in women visiting sexually transmitted infection clinics regardless of rectal symptoms and irrespective of anal intercourse, since our data suggest that several cases of rectal Chlamydia trachomatis otherwise would be missed, thus enabling further disease transmission.

  18. Predictive Biomarkers to Chemoradiation in Locally Advanced Rectal Cancer

    PubMed Central

    Conde-Muíño, Raquel; Cuadros, Marta; Zambudio, Natalia; Segura-Jiménez, Inmaculada; Cano, Carlos; Palma, Pablo

    2015-01-01

    There has been a high local recurrence rate in rectal cancer. Besides improvements in surgical techniques, both neoadjuvant short-course radiotherapy and long-course chemoradiation improve oncological results. Approximately 40–60% of rectal cancer patients treated with neoadjuvant chemoradiation achieve some degree of pathologic response. However, there is no effective method of predicting which patients will respond to neoadjuvant treatment. Recent studies have evaluated the potential of genetic biomarkers to predict outcome in locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation. The articles produced by the PubMed search were reviewed for those specifically addressing a genetic profile's ability to predict response to neoadjuvant treatment in rectal cancer. Although tissue gene microarray profiling has led to promising data in cancer, to date, none of the identified signatures or molecular markers in locally advanced rectal cancer has been successfully validated as a diagnostic or prognostic tool applicable to routine clinical practice. PMID:26504848

  19. Predictive Biomarkers to Chemoradiation in Locally Advanced Rectal Cancer.

    PubMed

    Conde-Muíño, Raquel; Cuadros, Marta; Zambudio, Natalia; Segura-Jiménez, Inmaculada; Cano, Carlos; Palma, Pablo

    2015-01-01

    There has been a high local recurrence rate in rectal cancer. Besides improvements in surgical techniques, both neoadjuvant short-course radiotherapy and long-course chemoradiation improve oncological results. Approximately 40-60% of rectal cancer patients treated with neoadjuvant chemoradiation achieve some degree of pathologic response. However, there is no effective method of predicting which patients will respond to neoadjuvant treatment. Recent studies have evaluated the potential of genetic biomarkers to predict outcome in locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation. The articles produced by the PubMed search were reviewed for those specifically addressing a genetic profile's ability to predict response to neoadjuvant treatment in rectal cancer. Although tissue gene microarray profiling has led to promising data in cancer, to date, none of the identified signatures or molecular markers in locally advanced rectal cancer has been successfully validated as a diagnostic or prognostic tool applicable to routine clinical practice.

  20. Immunological Landscape and Clinical Management of Rectal Cancer

    PubMed Central

    Pérez-Ruiz, Elísabeth; Berraondo, Pedro

    2016-01-01

    The clinical management of rectal cancer and colon cancer differs due to increased local relapses in rectal cancer. However, the current molecular classification does not differentiate rectal cancer and colon cancer as two different entities. In recent years, the impact of the specific immune microenvironment in cancer has attracted renewed interest and is currently recognized as one of the major determinants of clinical progression in a wide range of tumors. In colorectal cancer, the density of lymphocytic infiltration is associated with better overall survival. Due to the need for biomarkers of response to conventional treatment with chemoradiotherapy in rectal tumors, the immune status of rectal cancer emerges as a useful tool to improve the management of patients. PMID:26941741

  1. MRI in local staging of rectal cancer: an update

    PubMed Central

    Tapan, Ümit; Özbayrak, Mustafa; Tatlı, Servet

    2014-01-01

    Preoperative imaging for staging of rectal cancer has become an important aspect of current approach to rectal cancer management, because it helps to select suitable patients for neoadjuvant chemoradiotherapy and determine the appropriate surgical technique. Imaging modalities such as endoscopic ultrasonography, computed tomography, and magnetic resonance imaging (MRI) play an important role in assessing the depth of tumor penetration, lymph node involvement, mesorectal fascia and anal sphincter invasion, and presence of distant metastatic diseases. Currently, there is no consensus on a preferred imaging technique for preoperative staging of rectal cancer. However, high-resolution phased-array MRI is recommended as a standard imaging modality for preoperative local staging of rectal cancer, with excellent soft tissue contrast, multiplanar capability, and absence of ionizing radiation. This review will mainly focus on the role of MRI in preoperative local staging of rectal cancer and discuss recent advancements in MRI technique such as diffusion-weighted imaging and dynamic contrast-enhanced MRI. PMID:25010367

  2. Rectal prolapse as initial clinical manifestation of colon cancer.

    PubMed

    Chen, C-W; Hsiao, C-W; Wu, C-C; Jao, S-W

    2008-04-01

    Rectal prolapse as the initial clinical manifestation of colorectal cancer is uncommon. We describe the case of a 75-year-old woman who was diagnosed as having adenocarcinoma of the sigmoid colon after presenting with complete rectal prolapse. The tumor caused rectosigmoid intussusception and then it prolapsed out through the anus. She underwent rectosigmoidectomy and rectopexy. The postoperative course was uneventful. The relationship between colorectal cancer and rectal prolapse has not been clearly established. This case report describes an unusual presentation of colorectal cancer. It suggests that rectal prolapse can present as the initial symptom of colorectal cancer and may also be a presenting feature of the occult intra-abdominal pathology. The importance of adequate investigation such as colonoscopy should be emphasized in patients who develop a new onset of rectal prolapse.

  3. [Local diagnostics for rectal cancer. What is realistic?].

    PubMed

    Ptok, H; Gastinger, I; Lippert, H

    2012-05-01

    Accurate pretherapeutic staging of rectal cancer is crucial for further therapeutic management and important for prognosis. The most accurate diagnostic tools in the assessment of T and N categories of rectal cancer are endorectal ultrasound (EUS) and magnetic resonance imaging (MRI). Furthermore, MRI can accurately predict the distance of the tumor to the colorectal membrane (CRM) and computed tomography (CT) is more suitable for detecting distant metastases. In the routine care of rectal cancer EUS is the most frequently used diagnostic tool for local staging. The achieved accuracy for determining T category by EUS in routine clinical staging is lower than results reported in the literature. Furthermore, the accuracy of EUS depends on the experience of the examiner. Currently the frequency of using MRI for routine clinical staging of rectal cancer is low and in one out of five cases the local staging of rectal cancer is exclusively carried out by CT.

  4. The Quality-of-Life Effects of Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer

    SciTech Connect

    Herman, Joseph M.; Narang, Amol K.; Griffith, Kent A.; Zalupski, Mark M.; Reese, Jennifer B.; Gearhart, Susan L.; Azad, Nolifer S.; Chan, June; Olsen, Leah; Efron, Jonathan E.; Lawrence, Theodore S.; Ben-Josef, Edgar

    2013-01-01

    Purpose: Existing studies that examine the effect of neoadjuvant chemoradiation (CRT) for locally advanced rectal cancer on patient quality of life (QOL) are limited. Our goals were to prospectively explore acute changes in patient-reported QOL endpoints during and after treatment and to establish a distribution of scores that could be used for comparison as new treatment modalities emerge. Methods and Materials: Fifty patients with locally advanced rectal cancer were prospectively enrolled at 2 institutions. Validated cancer-specific European Organization for Research and Treatment of Cancer (EORTC QLQ-CR30) and colorectal cancer-specific (EORTC QLQ-CR38 and EORTC QLQ-CR 29) QOL questionnaires were administered to patients 1 month before they began CRT, at week 4 of CRT, and 1 month after they had finished CRT. The questionnaires included multiple symptom scales, functional domains, and a composite global QOL score. Additionally, a toxicity scale was completed by providers 1 month before the beginning of CRT, weekly during treatment, and 1 month after the end of CRT. Results: Global QOL showed a statistically significant and borderline clinically significant decrease during CRT (-9.50, P=.0024) but returned to baseline 1 month after the end of treatment (-0.33, P=.9205). Symptoms during treatment were mostly gastrointestinal (nausea/vomiting +9.94, P<.0001; and diarrhea +16.67, P=.0022), urinary (dysuria +13.33, P<.0001; and frequency +11.82, P=.0006) or fatigue (+16.22, P<.0001). These symptoms returned to baseline after therapy. However, sexual enjoyment (P=.0236) and sexual function (P=.0047) remained persistently diminished after therapy. Conclusions: Rectal cancer patients undergoing neoadjuvant CRT may experience a reduction in global QOL along with significant gastrointestinal and genitourinary symptoms during treatment. Moreover, provider-rated toxicity scales may not fully capture this decrease in patient-reported QOL. Although most symptoms are transient

  5. Neoadjuvant chemoradiation with concomitant boost radiotherapy associated to capecitabine in rectal cancer patients.

    PubMed

    Osti, Mattia F; Agolli, Linda; Bracci, Stefano; Masoni, Luigi; Valeriani, Maurizio; Falco, Teresa; De Sanctis, Vitaliana; Maurizi Enrici, Riccardo

    2014-07-01

    The primary end-points were complete pathological response and local control. Secondary end-points were survivals, anal sphincter preservation, and toxicity profile. Patients with T3/T4 and or N+ rectal cancer (n = 65) were treated with preoperative concomitant boost radiotherapy (55 Gy/25 fractions) associated to concurrent chemotherapy with oral capecitabine. All patients completed the programmed treatment. The complete pathological response was achieved by 17 % of the patients. Anal sphincter preservation surgery was possible for 86 % of the patients with low rectal cancer (≤ 5 cm from the anal verge). The T-stage and N-stage downstaging were achieved by 40 and 58 % of the patients, respectively. Circumferential radial margin was involved (close/positive) in eight patients. After a median follow-up of 26 months, local and distant recurrence occurred in two and 11 patients, respectively. The 3-year overall survival and disease-free survival were 86.8 and 81 %, respectively. Non-hematological ≥ grade 3 toxicities were observed in 15 % of the patients. On univariate analysis N-downstaging and positive circumferential radial margin were significantly associated with worse overall survival (p = 0.003 and p = 0.023, respectively), disease-free survival (p = 0.001 and p = 0.036, respectively), and metastasis-free survival (MFS) (p = 0.001 and p = 0.038, respectively).On multivariate analysis, the N-downstaging were significantly associated with better overall survival (OS) (p = 0.022). Our data support the efficacy of preoperative treatment for rectal cancer in terms of local outcomes. Radiation treatment intensification may have a biological rationale; longer follow-up is needed.

  6. Comparison of rectal and axillary temperatures in dogs and cats.

    PubMed

    Goic, Joana B; Reineke, Erica L; Drobatz, Kenneth J

    2014-05-15

    To compare rectal versus axillary temperatures in dogs and cats. Prospective observational study. 94 dogs and 31 cats. Paired axillary and rectal temperatures were measured in random order with a standardized method. Animal signalment, initial complaint, blood pressure, blood lactate concentration, and variables associated with vascular perfusion and coat were evaluated for associations with axillary and rectal temperatures. Axillary temperature was positively correlated with rectal temperature (ρ = 0.75 in both species). Median axillary temperature (38.4°C [101.1°F] in dogs, and 38.4°C [101.2°F] in cats) was significantly different from median rectal temperature in dogs (38.9°C [102.0°F]) but not in cats (38.6°C [101.5°F]). Median rectal-axillary gradient (difference) was 0.4°C (0.7°F; range, -1.3° to 2.3°C [-2.4° to 4.1°F]) in dogs and 0.17°C (0.3°F; range -1.1° to 1.6°C [-1.9° to 3°F]) in cats. Sensitivity and specificity for detection of hyperthermia with axillary temperature were 57% and 100%, respectively, in dogs and 33% and 100%, respectively, in cats; sensitivity and specificity for detection of hypothermia were 86% and 87%, respectively, in dogs and 80% and 96%, respectively, in cats. Body weight (ρ = 0.514) and body condition score (ρ = 0.431) were correlated with rectal-axillary gradient in cats. Although axillary and rectal temperatures were correlated in dogs and cats, a large gradient was present between rectal temperature and axillary temperature, suggesting that axillary temperature should not be used as a substitute for rectal temperature.

  7. An isolated vaginal metastasis from rectal cancer.

    PubMed

    Sadatomo, Ai; Koinuma, Koji; Horie, Hisanaga; Lefor, Alan K; Sata, Naohiro

    2016-02-01

    Isolated vaginal metastases from colorectal cancer are extremely rare. There are only a few reported cases in the English literature, and the characteristics of such cases of metastasis remain relatively unknown. We present a case of isolated vaginal metastasis from rectal cancer in a 78-year-old female patient. The patient had no symptoms related to vaginal tumor. Magnetic resonance imaging (MRI) showed thickening of the middle rectum and a vaginal tumor. Biopsy from the vaginal tumor showed adenocarcinoma, similar to the rectal lesion. Low anterior resection with ileostomy, hystero-oophorectomy, and transvaginal tumor resection was performed. After nineteen months, computed tomography scan revealed multiple lung metastases and recurrent tumor in the pelvis. The patient refused chemotherapy and is alive three months after developing recurrent disease. Most cases of primary vaginal carcinoma are squamous cell carcinoma. Other histologic types such as adenocarcinoma are usually metastatic lesions. Primary lesions associated with metastatic vaginal adenocarcinoma are most often the uterus, and are very rarely from the colon or rectum. We review previous case reports of isolated vaginal metastases from colorectal cancer and discuss their symptoms, treatments, and outcomes. We should keep the vagina within the field of view of pelvic MRI, which is one of the preoperative diagnostic tools for colorectal cancer. If female patients show gynecological symptoms, gynecological examination should be recommended. Isolated vaginal metastases are an indication for surgical resection, and adjuvant chemotherapy is also recommended.

  8. [Radiotherapy in pelvic recurrences of rectal cancer].

    PubMed

    Morganti, A G; Santoni, R; Osti, M F

    2001-01-01

    Patients with locally recurrent rectal carcinoma have an unfavourable prognosis for the high incidence of distant metastases, the infrequent feasibility of radical surgical resection, and, in these last cases, the high incidence of re-recurrences. Based on the low resectability rate of pelvic recurrences, the clear impact of tumor diameter on resectability and outcome, and the documented possibility to achieve a significant tumor downstaging and downsizing with the use of concurrent chemoradiation, it is evident that the most promising treatment several authors have considered concurrent chemoradiation followed, if feasible, by radical resection. Furthermore, based on the high local and distant failure rate after surgery, the utilization of intraoperative radiation therapy (IORT) and adjuvant chemotherapy seems justified. Some published comparisons between patients treated with and without IORT seems to suggest the possible improvement in both local control and survival in these patients. Particularly interesting issues in this field are: 1) the definition of the most effective treatment modality (both in terms of radiation dose, fractionation and techniques, and drugs to be used concurrently to radiotherapy); 2) the analysis of the prognostic impact of several factors, with the aim of designing and validating staging systems of local rectal recurrences; 3) the possibility to treat with relatively high doses also patients previously irradiated on the pelvis.

  9. Focusing the management of rectal cancer

    PubMed Central

    Dbeis, Rachel; Smart, Neil J.

    2016-01-01

    Rectal cancer treatment has undergone major changes over the last 15 years with a focus on individualized care based around MRI assessment of the relationship of the tumour to the mesorectal fascia, improved surgical techniques and targeted use of pre-operative oncological therapies in patients with locally advanced disease. The recognition that some tumours responded completely to pre-operative chemoradiotherapy, and the selective use of a non-operative policy has led to a quest to further identify those patients and their tumour in whom this approach could be used, irrespective of MRI stage. With no clear patient factors identified, the tumour and its gene expression has become a target for research to identify individual single-nucleotide polymorphisms, which may indicate a response to specific treatment, or not. To date some agents have been identified and trialed, such as cetuximab, with individual tumours being assessed for response allowing directed treatment. The reviewed paper by Sebio and colleagues report a study that links polymorphisms in the DNA repair gene XRCC1 with response to neoadjuvant 5-Fluorouracil treatment in rectal cancer patients. However, genetic heterogeneity alone may not explain the variations of drug response and environmental factors may lead to epigenetic effects and therefore alter responses. Therefore whilst this study demonstrates the impact of different single nucleotide polymorphisms (SNPs), it is only one step forward, but perhaps a step in the right direction. PMID:28149883

  10. Late results.

    PubMed

    Daly, B D

    1999-08-01

    Pneumonectomy is performed for a number of benign and malignant conditions. It is most commonly performed for lung cancer. Adjuvant and neoadjuvant protocols have increased the number of these operations being performed and the long-term results are improving. Pneumonectomy may also be performed for metastases to lung and for mesothelioma with encouraging results. Some bronchial adenomas require pneumonectomy. Treatment of resistant mycobacteria or the complications of tuberculosis frequently require pneumonectomy. Late bronchopleural fistulae, esophagopleural fistulae, and empyema may occur.

  11. Laparoscopic rectopexy for solitary rectal ulcer syndrome without overt rectal prolapse: a case report and review of the literature.

    PubMed

    Menekse, Ebru; Ozdogan, Mehmet; Karateke, Faruk; Ozyazici, Sefa; Demirturk, Pelin; Kuvvetli, Adnan

    2014-02-20

    Solitary rectal ulcer syndrome is a rare clinical entity. Several treatment options has been described. However, there is no consensus yet on treatment algorithm and standard surgical procedure. Rectopexy is one of the surgical options and it is generally performed in patients with solitary rectal ulcer accompanied with overt prolapse. Various outcomes have been reported for rectopexy in the patients with occult prolapse or rectal intussusception. In the literature; outcomes of laparoscopic non-resection rectopexy procedure have been reported in the limited number of case or case series. No study has emphasized the outcomes of laparoscopic non-resection rectopexy procedure in the patients with solitary rectal ulcer without overt prolapse. In this report we aimed to present clinical outcomes of laparoscopic non-resection posterior suture rectopexy procedure in a 21-year-old female patient with solitary rectal ulcer without overt prolapse.

  12. Laparoscopic rectopexy for solitary rectal ulcer syndrome without overt rectal prolapse. A case report and review of the literature.

    PubMed

    Menekse, Ebru; Ozdogan, Mehmet; Karateke, Faruk; Ozyazici, Sefa; Demirturk, Pelin; Kuvvetli, Adnan

    2014-01-01

    Solitary rectal ulcer syndrome is a rare clinical entity. Several treatment options has been described. However, there is no consensus yet on treatment algorithm and standard surgical procedure. Rectopexy is one of the surgical options and it is generally performed in patients with solitary rectal ulcer accompanied with overt prolapse. Various outcomes have been reported for rectopexy in the patients with occult prolapse or rectal intussusception. In the literature; outcomes of laparoscopic non-resection rectopexy procedure have been reported in the limited number of case or case series. No study has emphasized the outcomes of laparoscopic non-resection rectopexy procedure in the patients with solitary rectal ulcer without overt prolapse. In this report we aimed to present clinical outcomes of laparoscopic non-resection posterior suture rectopexy procedure in a 21-year-old female patient with solitary rectal ulcer without overt prolapse.

  13. Rectal HSV-2 Infection May Increase Rectal SIV Acquisition Even in the Context of SIVΔnef Vaccination.

    PubMed

    Guerra-Pérez, Natalia; Aravantinou, Meropi; Veglia, Filippo; Goode, Diana; Truong, Rosaline; Derby, Nina; Blanchard, James; Grasperge, Brooke; Gettie, Agegnehu; Robbiani, Melissa; Martinelli, Elena

    2016-01-01

    Prevalent HSV-2 infection increases the risk of HIV acquisition both in men and women even in asymptomatic subjects. Understanding the impact of HSV-2 on the mucosal microenvironment may help to identify determinants of susceptibility to HIV. Vaginal HSV-2 infection increases the frequency of cells highly susceptible to HIV in the vaginal tissue of women and macaques and this correlates with increased susceptibility to vaginal SHIV infection in macaques. However, the effect of rectal HSV-2 infection on HIV acquisition remains understudied. We developed a model of rectal HSV-2 infection in macaques in combination with rectal SIVmac239Δnef (SIVΔnef) vaccination and our results suggest that rectal HSV-2 infection may increase the susceptibility of macaques to rectal SIVmac239 wild-type (wt) infection even in SIVΔnef-infected animals. Rectal SIVΔnef infection/vaccination protected 7 out of 7 SIVΔnef-infected macaques from SIVmac239wt rectal infection (vs 12 out of 16 SIVΔnef-negative macaques), while 1 out of 3 animals co-infected with SIVΔnef and HSV-2 acquired SIVmac239wt infection. HSV-2/SIVmac239wt co-infected animals had increased concentrations of inflammatory factors in their plasma and rectal fluids and a tendency toward higher acute SIVmac239wt plasma viral load. However, they had higher blood CD4 counts and reduced depletion of CCR5+ CD4+ T cells compared to SIVmac239wt-only infected animals. Thus, rectal HSV-2 infection generates a pro-inflammatory environment that may increase susceptibility to rectal SIV infection and may impact immunological and virological parameters during acute SIV infection. Studies with larger number of animals are needed to confirm these findings.

  14. Focal adhesion kinase: predictor of tumour response and risk factor for recurrence after neoadjuvant chemoradiation in rectal cancer.

    PubMed

    Gómez Del Pulgar, Teresa; Cebrián, Arancha; Fernández-Aceñero, Maria Jesús; Borrero-Palacios, Aurea; Del Puerto-Nevado, Laura; Martínez-Useros, Javier; Marín-Arango, Juan Pablo; Caramés, Cristina; Vega-Bravo, Ricardo; Rodríguez-Remírez, María; Cruz-Ramos, Marlid; Manzarbeitia, Félix; García-Foncillas, Jesús

    2016-09-01

    Rectal cancer represents about 30% of colorectal cancers, being around 50% locally advanced at presentation. Chemoradiation (CRT) followed by total mesorectal excision is the standard of care for these locally advanced stages. However, it is not free of adverse effects and toxicity and the complete pathologic response rate is between 10% and 30%. This makes it extremely important to define factors that can predict response to this therapy. Focal adhesion kinase (FAK) expression has been correlated with worse prognosis in several tumours and its possible involvement in cancer radio- and chemosensitivity has been suggested; however, its role in rectal cancer has not been analysed yet. To analyse the association of FAK expression with tumour response to CRT in locally advanced rectal cancer. This study includes 73 patients with locally advanced rectal cancer receiving standard neoadjuvant CRT followed by total mesorectal excision. Focal adhesion kinase protein levels were immunohistochemically analysed in the pre-treatment biopsies of these patients and correlated with tumour response to CRT and patients survival. Low FAK expression was significantly correlated with local and distant recurrence (P = 0.013). Low FAK expression was found to be a predictive marker of tumour response to neoadjuvant therapy (P = 0.007) and patients whose tumours did not express FAK showed a strong association with lower disease-free survival (P = 0.01). Focal adhesion kinase expression predicts neoadjuvant CRT response in rectal cancer patients and it is a clinically relevant risk factor for local and distant recurrence. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  15. Rectal 1% Tenofovir Gel Use Associates with Altered Epidermal Protein Expression

    PubMed Central

    Romas, Laura; Birse, Kenzie; Mayer, Kenneth H.; Abou, Max; Westmacott, Garrett; Giguere, Rebecca; Febo, Irma; Cranston, Ross D.; Carballo-Diéguez, Alex; McGowan, Ian

    2016-01-01

    Abstract Rectal use of a 1% tenofovir (TFV) gel is currently being evaluated for HIV prevention. While careful assessment of mucosal safety of candidate microbicides is a primary concern, tools to assess mucosal toxicity are limited. Mass spectrometry-based proteomics is a sensitive and high-throughput technique that can provide in-depth information on inflammation processes in biological systems. In this study, we utilized a proteomics approach to characterize mucosal responses in study participants involved in a phase 1 clinical trial of a rectal TFV-based gel. Project Gel was a phase 1 randomized (1:1), double-blind, multisite, placebo-controlled trial in which 24 participants received rectal TFV or a universal placebo [hydroxyethyl cellulose (HEC)] over a course of 8 daily doses. Rectal mucosal swabs were collected after 0, 1, and 8 doses and were analyzed by label-free tandem mass spectrometry. Differential protein expression was evaluated using a combination of paired (time-effects) and unpaired (across study arm) t-tests, and multivariate [least absolute shrinkage and selection operator (LASSO)] modeling. Within the TFV arm, 7% (17/249, p < .05) and 10% (25/249, p < .05) of total proteins changed after 1 and 8 daily applications of TFV gel, respectively, compared to 3% (7/249, p < .05) and 6% (16/249, p < .05) in the HEC arm. Biofunctional analysis associated TFV use with a decrease in epidermal barrier proteins (adj. p = 1.21 × 10−10). Multivariate modeling identified 13 proteins that confidently separated TFV gel users (100% calibration and 96% cross-validation accuracy), including the epithelial integrity factors (FLMNB, CRNN, CALM), serpins (SPB13, SPB5), and cytoskeletal proteins (VILI, VIME, WRD1). This study suggested that daily rectal applications of a 1% TFV gel may be associated with mucosal proteome changes involving epidermal development. Further assessment of more extended use of TFV-gel is recommended to validate

  16. Rectal and colon cancer: Not just a different anatomic site.

    PubMed

    Tamas, K; Walenkamp, A M E; de Vries, E G E; van Vugt, M A T M; Beets-Tan, R G; van Etten, B; de Groot, D J A; Hospers, G A P

    2015-09-01

    Due to differences in anatomy, primary rectal and colon cancer require different staging procedures, different neo-adjuvant treatment and different surgical approaches. For example, neoadjuvant radiotherapy or chemoradiotherapy is administered solely for rectal cancer. Neoadjuvant therapy and total mesorectal excision for rectal cancer might be responsible in part for the differing effect of adjuvant systemic treatment on overall survival, which is more evident in colon cancer than in rectal cancer. Apart from anatomic divergences, rectal and colon cancer also differ in their embryological origin and metastatic patterns. Moreover, they harbor a different composition of drug targets, such as v-raf murine sarcoma viral oncogene homolog B (BRAF), which is preferentially mutated in proximal colon cancers, and the epidermal growth factor receptor (EGFR), which is prevalently amplified or overexpressed in distal colorectal cancers. Despite their differences in metastatic pattern, composition of drug targets and earlier local treatment, metastatic rectal and colon cancer are, however, commonly regarded as one entity and are treated alike. In this review, we focused on rectal cancer and its biological and clinical differences and similarities relative to colon cancer. These aspects are crucial because they influence the current staging and treatment of these cancers, and might influence the design of future trials with targeted drugs.

  17. Microscopy detection of rectal gonorrhoea in asymptomatic men.

    PubMed

    Forni, J; Miles, K; Hamill, M

    2009-11-01

    This audit