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Sample records for dose-escalated image-guided radiotherapy

  1. Clinical Outcome of Dose-Escalated Image-Guided Radiotherapy for Spinal Metastases

    SciTech Connect

    Guckenberger, Matthias; Goebel, Joachim; Wilbert, Juergen; Baier, Kurt; Richter, Anne; Sweeney, Reinhart A.; Bratengeier, Klaus; Flentje, Michael

    2009-11-01

    Purpose: To evaluate the outcomes after dose-escalated radiotherapy (RT) for spinal metastases and paraspinal tumors. Methods and Materials: A total of 14 patients, 12 with spinal metastases and a long life expectancy and 2 with paraspinal tumors, were treated for 16 lesions with intensity-modulated, image-guided RT. A median biologic effective dose of 74 Gy{sub 10} (range, 55-86) in a median of 20 fractions (range, 3-34) was prescribed to the target volume. The spinal canal was treated to 40 Gy in 20 fractions using a second intensity-modulated RT dose level in the case of epidural involvement. Results: After median follow-up of 17 months, one local recurrence was observed, for an actuarial local control rate of 88% after 2 years. Local control was associated with rapid and long-term pain relief. Of 11 patients treated for a solitary spinal metastasis, 6 developed systemic disease progression. The actuarial overall survival rate for metastatic patients was 85% and 63% after 1 and 2 years, respectively. Acute Grade 2-3 skin toxicity was seen in 2 patients with no late toxicity greater than Grade 2. No radiation-induced myelopathy was observed. Conclusion: Dose-escalated irradiation of spinal metastases was safe and resulted in excellent local control. Oligometastatic patients with a long life expectancy and epidural involvement are considered to benefit the most from fractionated RT.

  2. Long-term outcomes from dose-escalated image-guided intensity-modulated radiotherapy with androgen deprivation: encouraging results for intermediate- and high-risk prostate cancer

    PubMed Central

    Wilcox, Shea W; Aherne, Noel J; Benjamin, Linus C; Wu, Bosco; de Campos Silva, Thomaz; McLachlan, Craig S; McKay, Michael J; Last, Andrew J; Shakespeare, Thomas P

    2014-01-01

    Purpose Dose-escalated (DE) radiotherapy in the setting of localized prostate cancer has been shown to improve biochemical disease-free survival (bDFS) in several studies. In the same group of patients, androgen deprivation therapy (ADT) has been shown to confer a survival benefit when combined with radiotherapy doses of up to 70 Gy; however, there is currently little long-term data on patients who have received high-dose intensity-modulated radiotherapy (IMRT) with ADT. We report the long-term outcomes in a large cohort of patients treated with the combination of DE image-guided IMRT (IG-IMRT) and ADT. Methods and materials Patients with localized prostate cancer were identified from a centralized database across an integrated cancer center. All patients received DE IG-IMRT, combined with ADT, and had a minimum follow up of 12 months post-radiotherapy. All relapse and toxicity data were collected prospectively. Actuarial bDFS, metastasis-free survival, prostate cancer-specific survival, and multivariate analyses were calculated using the SPSS v20.0 statistical package. Results Seven hundred and eighty-two eligible patients were identified with a median follow up of 46 months. Overall, 4.3% of patients relapsed, 2.0% developed distant metastases, and 0.6% died from metastatic prostate cancer. At 5-years, bDFS was 88%, metastasis-free survival was 95%, and prostate cancer-specific survival was 98%. Five-year grade 2 genitourinary and gastrointestinal toxicity was 2.1% and 3.4%, respectively. No grade 3 or 4 late toxicities were reported. Pretreatment prostate specific antigen (P=0.001) and Gleason score (P=0.03) were significant in predicting biochemical failure on multivariate analysis. Conclusion There is a high probability of tumor control with DE IG-IMRT combined with androgen deprivation, and this is a technique with a low probability of significant late toxicity. Our long term results corroborate the safety and efficacy of treating with IG-IMRT to high doses

  3. 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

    significant difference by dose level was seen in the 2-year rate of Grade 2 or higher chronic rectal toxicity. These rates were 27%, 15%, 14%, 17%, and 24% for dose levels equal to or less than 72, 73.8, 75.6, 77.4, and 79.2 Gy, respectively (p = 0.3). Grade 2 or higher chronic rectal bleeding was significantly greater for Group 2 than for Group 1, 17% vs. 8% (p = 0.035). Conclusions: High doses (79.2 Gy) were safely delivered in selected patients by our adaptive radiotherapy process. Under the rectal dose-volume histogram constraints for the dose level selection, the risk of chronic rectal toxicity is similar among patients treated to different dose levels. Therefore, rectal chronic toxicity rates reflect the dose-volume cutoff used and are independent of the actual dose levels. On the other hand, a larger PTV will increase the rectal wall dose and chronic rectal toxicity rates. PTV volume and dose constraints should be defined, considering their potential benefit.

  4. Online image-guided intensity-modulated radiotherapy for prostate cancer: How much improvement can we expect? A theoretical assessment of clinical benefits and potential dose escalation by improving precision and accuracy of radiation delivery

    SciTech Connect

    Ghilezan, Michel; Yan Di . E-mail: dyan@beaumont.edu; Liang Jian; Jaffray, David; Wong, John; Martinez, Alvaro

    2004-12-01

    Purpose: To quantify the theoretical benefit, in terms of improvement in precision and accuracy of treatment delivery and in dose increase, of using online image-guided intensity-modulated radiotherapy (IG-IMRT) performed with onboard cone-beam computed tomography (CT), in an ideal setting of no intrafraction motion/deformation, in the treatment of prostate cancer. Methods and materials: Twenty-two prostate cancer patients treated with conventional radiotherapy underwent multiple serial CT scans (median 18 scans per patient) during their treatment. We assumed that these data sets were equivalent to image sets obtainable by an onboard cone-beam CT. Each patient treatment was simulated with conventional IMRT and online IG-IMRT separately. The conventional IMRT plan was generated on the basis of pretreatment CT, with a clinical target volume to planning target volume (CTV-to-PTV) margin of 1 cm, and the online IG-IMRT plan was created before each treatment fraction on the basis of the CT scan of the day, without CTV-to-PTV margin. The inverse planning process was similar for both conventional IMRT and online IG-IMRT. Treatment dose for each organ of interest was quantified, including patient daily setup error and internal organ motion/deformation. We used generalized equivalent uniform dose (EUD) to compare the two approaches. The generalized EUD (percentage) of each organ of interest was scaled relative to the prescription dose at treatment isocenter for evaluation and comparison. On the basis of bladder wall and rectal wall EUD, a dose-escalation coefficient was calculated, representing the potential increment of the treatment dose achievable with online IG-IMRT as compared with conventional IMRT. Results: With respect to radiosensitive tumor, the average EUD for the target (prostate plus seminal vesicles) was 96.8% for conventional IMRT and 98.9% for online IG-IMRT, with standard deviations (SDs) of 5.6% and 0.7%, respectively (p < 0.0001). The average EUDs of

  5. Efficacy of Dose-Escalated Radiotherapy for Recurrent Colorectal Cancer

    PubMed Central

    Jo, Sunmi; Park, Sung-Kwang; Kim, Jin-Young; Kim, Hyun Jung; Lee, Yun-Han; Oh, Won Yong; Cho, Heunglae; Ahn, Ki Jung

    2016-01-01

    Purpose This study aimed to evaluate the effects of radiotherapy (RT) on progression-free survival (PFS) for patients with recurrent colorectal cancer. Methods We reviewed the records of 22 patients with recurrent colorectal cancer treated with RT between 2008 and 2014. The median radiation dose for recurrent disease was 57.6 Gy (range, 45–75.6 Gy). Patients were divided into 2 groups according to the type of RT: patients underwent RT without previous history of irradiation (n = 14) and those treated with secondary RT (reirradiation: n = 8) at the time of recurrence. Results The median follow-up period was 24.9 months (range, 4.5–66.6 months). Progression was observed in 14 patients (including 8 with loco-regional failure and 9 with distant metastases). Distant metastases were related to the RT dose (<70 Gy, P = 0.031). The 2-year loco-regional control (LRC), PFS, and overall survival (OS) rates were 74.6%, 45.1%, and 82.0%, respectively. The LRC rate was not different between the patients treated with RT for the first time and those treated with reirradiation (P = 0.101, 2-year LRC 79.5% vs. 41.7%). However, reirradiation was related to poor PFS (P = 0.022) and OS (P = 0.002). An escalated RT dose (≥70 Gy) was associated with a higher PFS (P = 0.014, 2-year PFS 63.5% vs. 20.8%). Conclusion Salvage RT for locally recurrent colorectal cancer can be offered when surgery is impossible. Dose-escalated RT shows a possible benefit in reducing the risk of progression. PMID:27218097

  6. Image-guided adaptive radiation therapy (IGART): Radiobiological and dose escalation considerations for localized carcinoma of the prostate.

    PubMed

    Song, William; Schaly, Bryan; Bauman, Glenn; Battista, Jerry; Van Dyk, Jake

    2005-07-01

    The goal of this work was to evaluate the efficacy of various image-guided adaptive radiation therapy (IGART) techniques to deliver and escalate dose to the prostate in the presence of geometric uncertainties. Five prostate patients with 15-16 treatment CT studies each were retrospectively analyzed. All patients were planned with an 18 MV, six-field conformal technique with a 10 mm margin size and an initial prescription of 70 Gy in 35 fractions. The adaptive strategy employed in this work for patient-specific dose escalation was to increase the prescription dose in 2 Gy-per-fraction increments until the rectum normal tissue complication probability (NTCP) reached a level equal to that of the nominal plan NTCP (i.e., iso-NTCP dose escalation). The various target localization techniques simulated were: (1) daily laser-guided alignment to skin tattoo marks that represents treatment without image-guidance, (2) alignment to bony landmarks with daily portal images, and (3) alignment to the clinical target volume (CTV) with daily CT images. Techniques (1) and (3) were resimulated with a reduced margin size of 5 mm to investigate further dose escalation. When delivering the original clinical prescription dose of 70 Gy in 35 fractions, the "CTV registration" technique yielded the highest tumor control probability (TCP) most frequently, followed by the "bone registration" and "tattoo registration" techniques. However, the differences in TCP among the three techniques were minor when the margin size was 10 mm (< or = 1.1 %). Reducing the margin size to 5 mm significantly degraded the TCP values of the "tattoo registration" technique in two of the five patients, where a large difference was found compared to the other techniques (< or = 11.8 %). The "CTV registration" technique, however, did maintain similar TCP values compared to their 10 mm margin counterpart. In terms of normal tissue sparing, the technique producing the lowest NTCP varied from patient to patient. Reducing

  7. The Impact of Dose Escalation on Secondary Cancer Risk After Radiotherapy of Prostate Cancer

    SciTech Connect

    Schneider, Uwe . E-mail: uwe.schneider@psi.ch; Lomax, Antony; Besserer, Juergen; Pemler, Peter; Lombriser, Norbert; Kaser-Hotz, Barbara D.V.M.

    2007-07-01

    Purpose: To estimate secondary cancer risk due to dose escalation in patients treated for prostatic carcinoma with three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated RT (IMRT), and spot-scanned proton RT. Methods and Materials: The organ equivalent dose (OED) concept with a linear-exponential, a plateau, and a linear dose-response curve was applied to dose distributions of 23 patients who received RT of prostate cancer. Conformal RT was used in 7 patients, 8 patients received IMRT with 6- and 15-MV photons, and 8 patients were treated with spot-scanned protons. We applied target doses ranging from 70 Gy to 100 Gy. Cancer risk was estimated as a function of target dose and tumor control probability. Results: At a 100-Gy target dose the secondary cancer risk relative to the 3D treatment plan at 70 Gy was +18.4% (15.0% for a plateau model, 22.3% for a linear model) for the 6-MV IMRT plan, +25.3% (17.0%, 14.1%) for the 15-MV IMRT plan, and -40.7% (-41.3%, -40.0%) for the spot-scanned protons. The increasing risk of developing a radiation-associated malignancy after RT with increasing dose was balanced by the enhanced cure rates at a larger dose. Conclusions: Cancer risk after dose escalation for prostate RT is expected to be equal to or lower than for conventional 3D treatment at 70 Gy, independent of treatment modality or dose-response model. Spot-scanned protons are the treatment of choice for dose escalation because this therapy can halve the risk of secondary cancers.

  8. Intensity-Modulated Radiotherapy for Locally Advanced Non-Small-Cell Lung Cancer: A Dose-Escalation Planning Study

    SciTech Connect

    Lievens, Yolande; Nulens, An; Gaber, Mousa Amr; Defraene, Gilles; De Wever, Walter; Stroobants, Sigrid; Van den Heuvel, Frank

    2011-05-01

    Purpose: To evaluate the potential for dose escalation with intensity-modulated radiotherapy (IMRT) in positron emission tomography-based radiotherapy planning for locally advanced non-small-cell lung cancer (LA-NSCLC). Methods and Materials: For 35 LA-NSCLC patients, three-dimensional conformal radiotherapy and IMRT plans were made to a prescription dose (PD) of 66 Gy in 2-Gy fractions. Dose escalation was performed toward the maximal PD using secondary endpoint constraints for the lung, spinal cord, and heart, with de-escalation according to defined esophageal tolerance. Dose calculation was performed using the Eclipse pencil beam algorithm, and all plans were recalculated using a collapsed cone algorithm. The normal tissue complication probabilities were calculated for the lung (Grade 2 pneumonitis) and esophagus (acute toxicity, grade 2 or greater, and late toxicity). Results: IMRT resulted in statistically significant decreases in the mean lung (p <.0001) and maximal spinal cord (p = .002 and 0005) doses, allowing an average increase in the PD of 8.6-14.2 Gy (p {<=}.0001). This advantage was lost after de-escalation within the defined esophageal dose limits. The lung normal tissue complication probabilities were significantly lower for IMRT (p <.0001), even after dose escalation. For esophageal toxicity, IMRT significantly decreased the acute NTCP values at the low dose levels (p = .0009 and p <.0001). After maximal dose escalation, late esophageal tolerance became critical (p <.0001), especially when using IMRT, owing to the parallel increases in the esophageal dose and PD. Conclusion: In LA-NSCLC, IMRT offers the potential to significantly escalate the PD, dependent on the lung and spinal cord tolerance. However, parallel increases in the esophageal dose abolished the advantage, even when using collapsed cone algorithms. This is important to consider in the context of concomitant chemoradiotherapy schedules using IMRT.

  9. Update of Dutch Multicenter Dose-Escalation Trial of Radiotherapy for Localized Prostate Cancer

    SciTech Connect

    Al-Mamgani, Abrahim Putten, Wim L.J. van; Heemsbergen, Wilma D.; Leenders, Geert J.L.H. van; Slot, Annerie; Dielwart, Michel F.H.; Incrocci, Luca; Lebesque, Joos V.

    2008-11-15

    Purpose: To update the analysis of the Dutch dose-escalation trial of radiotherapy for prostate cancer. Patients and Methods: A total of 669 patients with localized prostate cancer were randomly assigned to receive 68 or 78 Gy. The patients were stratified by age, institution, use of neoadjuvant or adjuvant hormonal therapy, and treatment group. The primary endpoint was freedom from failure (FFF), with failure defined as clinical or biochemical failure. Two definitions of biochemical failure were used: the American Society for Therapeutic Radiology and Oncology definition (three consecutive increases in prostate-specific antigen level) and the Phoenix definition (nadir plus 2 {mu}g/L). The secondary endpoints were freedom from clinical failure, overall survival, and genitourinary and gastrointestinal toxicity. Results: After a median follow-up of 70 months, the FFF using the American Society for Therapeutic Radiology and Oncology definition was significantly better in the 78-Gy arm than in the 68-Gy arm (7-year FFF rate, 54% vs. 47%, respectively; p = 0.04). The FFF using the Phoenix definition was also significantly better in the 78-Gy arm than in the 68-Gy arm (7-year FFF rate, 56% vs. 45%, respectively; p = 0.03). However, no differences in freedom from clinical failure or overall survival were observed. The incidence of late Grade 2 or greater genitourinary toxicity was similar in both arms (40% and 41% at 7 years; p = 0.6). However, the cumulative incidence of late Grade 2 or greater gastrointestinal toxicity was increased in the 78-Gy arm compared with the 68-Gy arm (35% vs. 25% at 7 years; p = 0.04). Conclusion: The results of our study have shown a statistically significant improvement in FFF in prostate cancer patients treated with 78 Gy but with a greater rate of late gastrointestinal toxicity.

  10. Dose Escalation of Whole-Brain Radiotherapy for Brain Metastases From Melanoma

    SciTech Connect

    Rades, Dirk; Heisterkamp, Christine; Huttenlocher, Stefan; Bohlen, Guenther; Dunst, Juergen; Haatanen, Tiina; Schild, Steven E.

    2010-06-01

    Purpose: The majority of patients with brain metastases from melanoma receive whole-brain radiotherapy (WBRT). However, the results are poor. Hypofractionation regimens failed to improve the outcome of these patients. This study investigates a potential benefit from escalation of the WBRT dose beyond the 'standard' regimen 30 Gy in 10 fractions (10x3 Gy). Methods and Materials: Data from 51 melanoma patients receiving WBRT alone were retrospectively analyzed. A dosage of 10x3 Gy (n = 33) was compared with higher doses including 40 Gy/20 fractions (n = 11) and 45 Gy/15 fractions (n = 7) for survival (OS) and local (intracerebral) control (LC). Additional potential prognostic factors were evaluated: age, gender, performance status, number of metastases, extracerebral metastases, and recursive partitioning analysis (RPA) class. Results: At 6 months, OS rates were 27% after 10x3 Gy and 50% after higher doses (p = 0.009). The OS rates at 12 months were 4% and 20%. On multivariate analysis, higher WBRT doses (p = 0.010), fewer than four brain metastases (p = 0.012), no extracerebral metastases (p = 0.006), and RPA class 1 (p = 0.005) were associated with improved OS. The LC rates at 6 months were 23% after 10x3 Gy and 50% after higher doses (p = 0.021). The LC rates at 12 months were 0% and 13%. On multivariate analysis, higher WBRT doses (p = 0.020) and fewer than brain metastases (p = 0.002) were associated with better LC. Conclusions: Given the limitations of a retrospective study, the findings suggest that patients with brain metastases from melanoma receiving WBRT alone may benefit from dose escalation beyond 10x3 Gy. The hypothesis generated by this study must be confirmed in a randomized trial stratifying for significant prognostic factors.

  11. Positron Emission Tomography-Guided, Focal-Dose Escalation Using Intensity-Modulated Radiotherapy for Head and Neck Cancer

    SciTech Connect

    Madani, Indira . E-mail: indira@krtkg1.ugent.be; Duthoy, Wim; Derie, Cristina R.N.; De Gersem, Werner Ir.; Boterberg, Tom; Saerens, Micky; Jacobs, Filip Ir.; Gregoire, Vincent; Lonneux, Max; Vakaet, Luc; Vanderstraeten, Barbara; Bauters, Wouter; Bonte, Katrien; Thierens, Hubert; Neve, Wilfried de

    2007-05-01

    Purpose: To assess the feasibility of intensity-modulated radiotherapy (IMRT) using positron emission tomography (PET)-guided dose escalation, and to determine the maximum tolerated dose in head and neck cancer. Methods and Materials: A Phase I clinical trial was designed to escalate the dose limited to the [{sup 18}-F]fluoro-2-deoxy-D-glucose positron emission tomography ({sup 18}F-FDG-PET)-delineated subvolume within the gross tumor volume. Positron emission tomography scanning was performed in the treatment position. Intensity-modulated radiotherapy with an upfront simultaneously integrated boost was employed. Two dose levels were planned: 25 Gy (level I) and 30 Gy (level II), delivered in 10 fractions. Standard IMRT was applied for the remaining 22 fractions of 2.16 Gy. Results: Between 2003 and 2005, 41 patients were enrolled, with 23 at dose level I, and 18 at dose level II; 39 patients completed the planned therapy. The median follow-up for surviving patients was 14 months. Two cases of dose-limiting toxicity occurred at dose level I (Grade 4 dermitis and Grade 4 dysphagia). One treatment-related death at dose level II halted the study. Complete response was observed in 18 of 21 (86%) and 13 of 16 (81%) evaluated patients at dose levels I and II (p < 0.7), respectively, with actuarial 1-year local control at 85% and 87% (p n.s.), and 1-year overall survival at 82% and 54% (p = 0.06), at dose levels I and II, respectively. In 4 of 9 patients, the site of relapse was in the boosted {sup 18}F-FDG-PET-delineated region. Conclusions: For head and neck cancer, PET-guided dose escalation appears to be well-tolerated. The maximum tolerated dose was not reached at the investigated dose levels.

  12. The role and strategy of IMRT in radiotherapy of pelvic tumors: Dose escalation and critical organ sparing in prostate cancer

    SciTech Connect

    Liu, Y.-M.; Shiau, C.-Y.; Lee, M.-L.; Huang, P.-I.; Hsieh, C.-M.; Chen, P.-H.; Lin, Y.-H.; Wang, L.-W.; Yen, S.-H. . E-mail: shyen@vghtpe.gov.tw

    2007-03-15

    Purpose: To investigate the intensity-modulated radiotherapy (IMRT) strategy in dose escalation of prostate and pelvic lymph nodes. Methods and Materials: Plan dosimetric data of 10 prostate cancer patients were compared with two-dimensional (2D) or IMRT techniques for pelvis (two-dimensional whole pelvic radiation therapy [2D-WPRT] or IM-WPRT) to receive 50 Gy or 54 Gy and additional prostate boost by three-dimensional conformal radiation therapy or IMRT (3D-PBRT or IM-PBRT) techniques up to 72 Gy or 78 Gy. Dose-volume histograms (DVHs), normal tissue complication probabilities (NTCP) of critical organ, and conformity of target volume in various combinations were calculated. Results: In DVH analysis, the plans with IM-WPRT (54 Gy) and additional boost up to 78 Gy had lower rectal and bladder volume percentage at 50 Gy and 60 Gy, compared with those with 2D-WPRT (50 Gy) and additional boost up to 72 Gy or 78 Gy. Those with IM-WPRT (54 Gy) also had better small bowel sparing at 30 Gy and 50 Gy, compared with those with 2D-WPRT (50 Gy). In NTCP, those with IM-WPRT and total dose of 78 Gy achieved lower complication rates in rectum and small bowel, compared with those of 2D-WPRT with total dose of 72 Gy. In conformity, those with IM-WPRT had better conformity compared with those with 2D-WPRT with significance (p < 0.005). No significant difference in DVHs, NTCP, or conformity was found between IM-PBRT and 3D-PBRT after IM-WPRT. Conclusions: Initial pelvic IMRT is the most important strategy in dose escalation and critical organ sparing. IM-WPRT is recommended for patients requiring WPRT. There is not much benefit for critical organ sparing by IMRT after 2D-WPRT.

  13. Radiation dose escalation by simultaneous modulated accelerated radiotherapy combined with chemotherapy for esophageal cancer: a phase II study

    PubMed Central

    Zhai, Tiantian; Chang, Daniel; Chen, Zhijian; Huang, Ruihong; Zhang, Wuzhe; Lin, Kun; Guo, Longjia; Zhou, Mingzhen; Li, Dongsheng; Li, Derui; Chen, Chuangzhen

    2016-01-01

    The outcomes for patients with esophageal cancer (EC) underwent standard-dose radical radiotherapy were still disappointing. This phase II study investigated the feasibility, safety and efficacy of radiation dose escalation using simultaneous modulated accelerated radiotherapy (SMART) combined with chemotherapy in 60 EC patients. Radiotherapy consisted of 66Gy at 2.2 Gy/fraction to the gross tumor and 54Gy at 1.8 Gy/fraction to subclinical diseases simultaneously. Chemotherapy including cisplatin and 5fluorouracil were administered to all patients during and after radiotherapy. The data showed that the majority of patients (98.3%) completed the whole course of radiotherapy and concurrent chemotherapy. The most common ≥ grade 3 acute toxicities were neutropenia (16.7%), followed by esophagitis (6.7%) and thrombopenia (5.0%). With a median follow-up of 24 months (5-38) for all patients and 30 months (18-38) for those still alive, 11 patients (18.3%) developed ≥ Grade 3 late toxicities and 2 (3.3%) of them died subsequently due to esophageal hemorrhage. The 1- and 2-year local-regional control, distant metastasis-free survival, disease-free survival and overall survival rates were 87.6% and 78.6%, 86.0% and 80.5%, 75.6% and 64.4%, 86.7% and 72.7%, respectively. SMART combined with concurrent chemotherapy is feasible in EC patients with tolerable acute toxicities. They showed a trend of significant improvements in local-regional control and overall survival. Further follow-up is needed to evaluate the late toxicities. PMID:26992206

  14. Dose Escalation and Quality of Life in Patients With Localized Prostate Cancer Treated With Radiotherapy: Long-Term Results of the Dutch Randomized Dose-Escalation Trial (CKTO 96-10 Trial)

    SciTech Connect

    Al-Mamgani, Abrahim; Putten, Wim L.J. van; Wielen, Gerard J. van der; Levendag, Peter C.; Incrocci, Luca

    2011-03-15

    Purpose: To assess the impact of dose escalation of radiotherapy on quality of life (QoL) in prostate cancer patients. Patients and Methods: Three hundred prostate cancer patients participating in the Dutch randomized trial (CKTO 69-10) comparing 68 Gy with 78 Gy were the subject of this analysis. These patients filled out the SF-36 QoL questionnaire before radiotherapy (baseline) and 6, 12, 24, and 36 months thereafter. Changes in QoL over time of {>=}10 points were considered clinically relevant. Repeated-measures regression analyses were applied to estimate and test the QoL changes over time, the differences between the two arms, and for association with a number of covariates. Results: At 3-year follow-up, the summary score physical health was 73.2 for the 68-Gy arm vs. 71.6 for the 78-Gy arm (p = 0.81), and the summary score mental health was 76.7 for the 68-Gy arm vs. 76.1 for the 78-Gy arm (p = 0.97). Statistically significant (p < 0.01) deterioration in QoL scores over time was registered in both arms in six scales. The deterioration over time was more pronounced in the high-dose arm for most scales. However, clinically relevant deterioration (>10 points) was seen for only two scales. None of the tested covariates were significantly correlated with QoL scores. Conclusion: Dose escalation did not result in significant deterioration of QoL in prostate cancer patients. In both randomization arms, statistically significant decreases in QoL scores over time were seen in six scales. The deterioration of QoL was more pronounced in the physical than in the mental health domain and in some scales more in the high- than in the low-dose arm, but the differences between arms were not statistically significant.

  15. Sexual Function After Three-Dimensional Conformal Radiotherapy for Prostate Cancer: Results From a Dose-Escalation Trial

    SciTech Connect

    Wielen, Gerard J. van der . E-mail: g.vanderwielen@erasmusmc.nl; Putten, Wim van; Incrocci, Luca

    2007-06-01

    Purpose: The purpose of this study is to provide information about sexual function (SF) after three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer while taking important factors into account that influence SF. Methods and Materials: Between June 1997 and February 2003, a total of 268 patients from a randomized dose-escalation trial comparing 68 Gy and 78 Gy agreed to participate in an additional part of the trial that evaluated SF. Results: At baseline 28% of patients had erectile dysfunction (ED). After 1 year, 27% of the pretreatment potent patients had developed ED. After 2 years this percentage had increased to 36%. After 3 years it almost stabilized at 38%. Satisfaction with sexual life was significantly correlated with ED. After 2 years one third of the pre-treatment potent patients still had considerable to very much sexual desire and found sex (very) important. No significant differences were found between the two dose-arms. Potency aids were used on a regular base by 14% of the patients. Conclusion: By taking adjuvant hormonal therapy (HT), HT during follow-up and potency aids into account, we found a lower percentage of ED after 3D-CRT than reported in previous prospective studies. A large group of patients still had sexual desire, considered sex important and 14% used potency aids after 3D-CRT.

  16. SU-E-T-183: Feasibility of Extreme Dose Escalation for Glioblastoma Multiforme Using 4π Radiotherapy

    SciTech Connect

    Nguyen, D; Rwigema, J; Yu, V; Kaprealian, T; Kupelian, P; Selch, M; Low, D; Sheng, K

    2014-06-01

    Purpose: GBM recurrence primarily occurs inside or near the high-dose radiation field of original tumor site requiring greater than 100 Gy to significantly improve local control. We utilize 4π non-coplanar radiotherapy to test the feasibility of planning target volume (PTV) margin expansions or extreme dose escalations without incurring additional radiation toxicities. Methods: 11 GBM patients treated with VMAT to a prescription dose of 59.4 Gy or 60 Gy were replanned with 4π. Original VMAT plans were created with 2 to 4 coplanar or non-coplanar arcs using 3 mm hi-res MLC. The 4π optimization, using 5 mm MLC, selected and inverse optimized 30 beams from a candidate pool of 1162 beams evenly distributed through 4π steradians. 4π plans were first compared to clinical plans using the same prescription dose. Two more studies were then performed to respectively escalate the GTV and PTV doses to 100 Gy, followed by a fourth plan expanding the PTV by 5 mm and maintaining the prescription dose. Results: The standard 4π plan significantly reduced (p<0.01) max and mean doses to critical structures by a range of 47.0–98.4% and 61.0–99.2%, respectively. The high dose PTV/high dose GTV/expanded PTV studies showed a reduction (p<0.05) or unchanged* (p>0.05) maximum dose of 72.1%/86.7%/77.1% (chiasm), 7.2%*/27.7%*/30.7% (brainstem), 39.8%*/84.2%/51.9%* (spinal cord), 69.0%/87.0%/66.9% (L eye), 76.2%/88.1%/84.1% (R eye), 95.0%/98.6%/97.5% (L lens), 93.9%/98.8%/97.6% (R lens), 74.3%/88.5%/72.4% (L optical nerve), 80.4%/91.3%/75.7% (R optical nerve), 64.8%/84.2%/44.9%* (L cochlea), and 85.2%/93.0%/78.0% (R cochlea), respectively. V30 and V36 for both brain and (brain - PTV) were reduced for all cases except the high dose PTV plan. PTV dose coverage increased for all 4π plans. Conclusion: Extreme dose escalation or further margin expansion is achievable using 4π, maintaining or reducing OAR doses. This study indicates that clinical trials employing 4π delivery using

  17. Role of Intensity-Modulated Radiotherapy in Reducing Toxicity in Dose Escalation for Localized Prostate Cancer

    SciTech Connect

    Al-Mamgani, Abrahim Heemsbergen, Wilma D.; Peeters, Stephanie T.H.; Lebesque, Joos V.

    2009-03-01

    Purpose: To compare the acute and late gastrointestinal (GI) and genitourinary (GU) toxicity in prostate cancer patients treated to a total dose of 78 Gy with either a three-conformal radiotherapy technique with a sequential boost (SEQ) or a simultaneous integrated boost using intensity-modulated radiotherapy (SIB-IMRT). Patients and Methods: A total of 78 prostate cancer patients participating in the randomized Dutch trial comparing 68 Gy and 78 Gy were the subject of this analysis. They were all treated at the same institution to a total dose of 78 Gy. The median follow-up was 76 and 56 months for the SEQ and SIB-IMRT groups, respectively. The primary endpoints were acute and late GI and GU toxicity. Results: A significantly lower incidence of acute Grade 2 or greater GI toxicity occurred in patients treated with SIB-IMRT compared with SEQ (20% vs. 61%, p = 0.001). For acute GU toxicity and late GI and GU toxicity, the incidence was lower after SIB-IMRT, but these differences were not statistically significant. No statistically significant difference were found in the 5-year freedom from biochemical failure rate (Phoenix definition) between the two groups (70% for the SIB-IMRT group vs. 61% for the SEQ group, p = 0.3). The same was true for the 5-year freedom from clinical failure rate (90% vs. 72%, p = 0.07). Conclusion: The results of our study have shown that SIB-IMRT reduced the toxicity without compromising the outcome in patients with localized prostate cancer treated to 78 Gy radiation.

  18. Incorporating Androgen Deprivation With Dose-Escalated External-Beam Radiotherapy for Prostate Cancer.

    PubMed

    Dosoretz, Arie P; Yu, James B

    2016-05-20

    was concerned about the potential for greater urinary incontinence and/or urinary irritation associated with these treatments compared with external-beam radiotherapy (RT).(1,2). PMID:27001587

  19. Lack of Benefit for the Addition of Androgen Deprivation Therapy to Dose-Escalated Radiotherapy in the Treatment of Intermediate- and High-Risk Prostate Cancer

    SciTech Connect

    Krauss, Daniel; Kestin, Larry; Ye, Hong; Brabbins, Donald; Ghilezan, Michel; Gustafson, Gary; Vicini, Frank; Martinez, Alvaro

    2011-07-15

    Purpose: Assessment of androgen deprivation therapy (ADT) benefits for prostate cancer treated with dose-escalated radiotherapy (RT). Methods and Materials: From 1991 to 2004, 1,044 patients with intermediate- (n = 782) or high-risk (n = 262) prostate cancer were treated with dose-escalated RT at William Beaumont Hospital. Patients received external-beam RT (EBRT) alone, brachytherapy (high or low dose rate), or high dose rate brachytherapy plus pelvic EBRT. Intermediate-risk patients had Gleason score 7, prostate-specific antigen (PSA) 10.0-19.9 ng/mL, or Stage T2b-T2c. High-risk patients had Gleason score 8-10, PSA {>=}20, or Stage T3. Patients were additionally divided specifically by Gleason score, presence of palpable disease, and PSA level to further define subgroups benefitting from ADT. Results: Median follow-up was 5 years; 420 patients received ADT + dose-escalated RT, and 624 received dose-escalated RT alone. For all patients, no advantages in any clinical endpoints at 8 years were associated with ADT administration. No differences in any endpoints were associated with ADT administration based on intermediate- vs. high-risk group or RT modality when analyzed separately. Patients with palpable disease plus Gleason {>=}8 demonstrated improved clinical failure rates and a trend toward improved survival with ADT. Intermediate-risk patients treated with brachytherapy alone had improved biochemical control when ADT was given. Conclusion: Benefits of ADT in the setting of dose-escalated RT remain poorly defined. This question must continue to be addressed in prospective study.

  20. Feasibility of dose escalation using intensity-modulated radiotherapy in posthysterectomy cervical carcinoma

    SciTech Connect

    D'Souza, Warren D. . E-mail: wdsou001@umaryland.edu; Ahamad, Anesa A.; Iyer, Revathy B.; Salehpour, Mohammad R.; Jhingran, Anuja; Eifel, Patricia J.

    2005-03-15

    Purpose: To evaluate retrospectively the utility of intensity-modulated radiotherapy (IMRT) in reducing the volume of normal tissues receiving radiation at varying dose levels when the female pelvis after hysterectomy is treated to doses of 50.4 Gy and 54 Gy. Methods and materials: Computed tomography scans from 10 patients who had previously undergone conventional postoperative RT were selected. The clinical tumor volume (vaginal apex and iliac nodes) and organs at risk were contoured. Margins were added to generate the planning tumor volume. The Pinnacle and Corvus planning systems were used to develop conventional and IMRT plans, respectively. Conventional four-field plans were prescribed to deliver 45 Gy (4F{sub 45Gy}) or 50.4 Gy; eight-field IMRT plans were prescribed to deliver 50.4 Gy (IMRT{sub 50.4Gy}) or 54 Gy (IMRT{sub 54Gy}) to the planning tumor volume. All plans were normalized so that {>=}97% of the planning tumor volume received the prescribed dose. Student's t test was used to compare the volumes of organs at risk receiving the same doses with different plans. Results: The mean volume of bowel receiving {>=}45 Gy was lower with the IMRT{sub 50.4Gy} (33% lower) and IMRT{sub 54Gy} (18% lower) plans than with the 4F{sub 45Gy} plan. The mean volume of rectum receiving {>=}45 Gy or {>=}50 Gy was also significantly reduced with the IMRT plans despite an escalation of the prescribed dose from 45 Gy with the conventional plans to 54 Gy with IMRT. The mean volume of bladder treated to 45 Gy was the same or slightly lower with the IMRT{sub 50.4Gy} and IMRT{sub 54Gy} plans compared with the 4F{sub 45Gy} plan. Compared with the 4F{sub 45Gy} plan, the IMRT{sub 50.4Gy} plan resulted in a smaller volume of bowel receiving 35-45 Gy and a larger volume of bowel receiving 50-55 Gy. Compared with the 4F{sub 45Gy} plan, the IMRT{sub 54Gy} plan resulted in smaller volumes of bowel receiving 45-50 Gy; however, small volumes of bowel received 55-60 Gy with the IMRT plan

  1. Dynamic targeting image-guided radiotherapy

    SciTech Connect

    Huntzinger, Calvin; Munro, Peter; Johnson, Scott; Miettinen, Mika; Zankowski, Corey; Ahlstrom, Greg; Glettig, Reto; Filliberti, Reto; Kaissl, Wolfgang; Kamber, Martin; Amstutz, Martin; Bouchet, Lionel; Klebanov, Dan; Mostafavi, Hassan; Stark, Richard

    2006-07-01

    Volumetric imaging and planning for 3-dimensional (3D) conformal radiotherapy and intensity-modulated radiotherapy (IMRT) have highlighted the need to the oncology community to better understand the geometric uncertainties inherent in the radiotherapy delivery process, including setup error (interfraction) as well as organ motion during treatment (intrafraction). This has ushered in the development of emerging technologies and clinical processes, collectively referred to as image-guided radiotherapy (IGRT). The goal of IGRT is to provide the tools needed to manage both inter- and intrafraction motion to improve the accuracy of treatment delivery. Like IMRT, IGRT is a process involving all steps in the radiotherapy treatment process, including patient immobilization, computed tomogaphy (CT) simulation, treatment planning, plan verification, patient setup verification and correction, delivery, and quality assurance. The technology and capability of the Dynamic Targeting{sup TM} IGRT system developed by Varian Medical Systems is presented. The core of this system is a Clinac (registered) or Trilogy{sup TM} accelerator equipped with a gantry-mounted imaging system known as the On-Board Imager{sup TM} (OBI). This includes a kilovoltage (kV) x-ray source, an amorphous silicon kV digital image detector, and 2 robotic arms that independently position the kV source and imager orthogonal to the treatment beam. A similar robotic arm positions the PortalVision{sup TM} megavoltage (MV) portal digital image detector, allowing both to be used in concert. The system is designed to support a variety of imaging modalities. The following applications and how they fit in the overall clinical process are described: kV and MV planar radiographic imaging for patient repositioning, kV volumetric cone beam CT imaging for patient repositioning, and kV planar fluoroscopic imaging for gating verification. Achieving image-guided motion management throughout the radiation oncology process

  2. Five-year prospective patient evaluation of bladder and bowel symptoms after dose-escalated radiotherapy for prostate cancer with the BeamCath (registered) technique

    SciTech Connect

    Fransson, Per . E-mail: Per.Fransson@onkologi.umu.se; Bergstroem, Per; Loefroth, Per-Olov; Widmark, Anders

    2006-10-01

    Purpose: Late side effects were prospectively evaluated up to 5 years after dose-escalated external beam radiotherapy (EBRT) and were compared with a previously treated series with conventional conformal technique. Methods and Materials: Bladder and bowel symptoms were prospectively evaluated with the Prostate Cancer Symptom Scale (PCSS) questionnaire up to 5 years posttreatment. In all, 257 patients completed the questionnaire 5 years posttreatment. A total of 168 patients were treated with the conformal technique at doses <71 Gy, and 195 were treated with the dose-escalated stereotactic BeamCath (registered) technique comprising three dose levels: 74 Gy (n = 68), 76 Gy (n = 74), and 78 Gy (n = 53). Results: For all dose groups analyzed together, 5 years after treatment, urinary starting problems decreased and urinary incontinence increased in comparison to baseline values. No increase in other bladder symptoms or frequency was detected. When comparing dose groups after 5 years, both the 74-Gy and 78-Gy groups reported increased urinary starting problems compared with patients given the conventional dose (<71 Gy). No increased incontinence was seen in the 76-Gy or the 78-Gy groups. Bowel symptoms were slightly increased during the follow-up period in comparison to baseline. Dose escalation with stereotactic EBRT (74-78 Gy) did not increase gastrointestinal late side effects after 5 years in comparison to doses <71 Gy. Conclusion: Dose-escalated EBRT with the BeamCath (registered) technique with doses up to 78 Gy is tolerable, and the toxicity profile is similar to that observed with conventional doses <71 Gy.

  3. 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.

  4. Expression of Bcl-2, p53, and MDM2 in Localized Prostate Cancer With Respect to the Outcome of Radical Radiotherapy Dose Escalation

    SciTech Connect

    Vergis, Roy; Corbishley, Catherine M.; Thomas, Karen

    2010-09-01

    Purpose: Established prognostic factors in localized prostate cancer explain only a moderate proportion of variation in outcome. We analyzed tumor expression of apoptotic markers with respect to outcome in men with localized prostate cancer in two randomized controlled trials of radiotherapy dose escalation. Methods and Materials: Between 1995 and 2001, 308 patients with localized prostate cancer received neoadjuvant androgen deprivation and radical radiotherapy at our institution in one of two dose-escalation trials. The biopsy specimens in 201 cases were used to make a biopsy tissue microarray. We evaluated tumor expression of Bcl-2, p53, and MDM2 by immunohistochemistry with respect to outcome. Results: Median follow-up was 7 years, and 5-year freedom from biochemical failure (FFBF) was 70.4% (95% CI, 63.5-76.3%). On univariate analysis, expression of Bcl-2 (p < 0.001) and p53 (p = 0.017), but not MDM2 (p = 0.224), was significantly associated with FFBF. Expression of Bcl-2 remained significantly associated with FFBF (p = 0.001) on multivariate analysis, independently of T stage, Gleason score, initial prostate-specific antigen level, and radiotherapy dose. Seven-year biochemical control was 61% vs. 41% (p = 0.0122) for 74 Gy vs. 64 Gy, respectively, among patients with Bcl-2-positive tumors and 87% vs. 81% (p = 0.423) for 74 Gy vs. 64 Gy, respectively, among patients with Bcl-2-negative tumors. There was no statistically significant interaction between dose and Bcl-2 expression. Conclusions: Bcl-2 expression was a significant, independent determinant of biochemical control after neoadjuvant androgen deprivation and radical radiotherapy for prostate cancer. These data generate the hypothesis that Bcl-2 expression could be used to inform the choice of radiotherapy dose in individual patients.

  5. Superiority of helical tomotherapy on liver sparing and dose escalation in hepatocellular carcinoma: a comparison study of three-dimensional conformal radiotherapy and intensity-modulated radiotherapy

    PubMed Central

    Zhao, Qianqian; Wang, Renben; Zhu, Jian; Jin, Linzhi; Zhu, Kunli; Xu, Xiaoqing; Feng, Rui; Jiang, Shumei; Qi, Zhonghua; Yin, Yong

    2016-01-01

    Background and purpose To compare the difference of liver sparing and dose escalation between three-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), and helical tomotherapy (HT) for hepatocellular carcinoma. Patients and methods Sixteen unresectable HCC patients were enrolled in this study. First, some evaluation factors of 3DCRT, IMRT, and HT plans were calculated with prescription dose at 50 Gy/25 fractions. Then, the doses were increased using HT or IMRT independently until either the plans reached 70 Gy or any normal tissue reached the dose limit according to quantitative analysis of normal tissue effects in the clinic criteria. Results The conformal index of 3DCRT was lower than that of IMRT (P<0.001) or HT (P<0.001), and the homogeneity index of 3DCRT was higher than that of IMRT (P<0.001) or HT (P<0.001). HT took the longest treatment time (P<0.001). For V50% (fraction of normal liver treated to at least 50% of the isocenter dose) of the normal liver, there was a significant difference: 3DCRT > IMRT > HT (P<0.001). HT had a lower Dmean (mean dose) and V20 (Vn, the percentage of organ volume receiving ≥n Gy) of liver compared with 3DCRT (P=0.005 and P=0.005, respectively) or IMRT (P=0.508 and P=0.007, respectively). Dmean of nontarget normal liver and V30 of liver were higher for 3DCRT than IMRT (P=0.005 and P=0.005, respectively) or HT (P=0.005 and P=0.005, respectively). Seven patients in IMRT (43.75%) and nine patients in HT (56.25%) reached the isodose 70 Gy, meeting the dose limit of the organs at risk. Conclusion HT may provide significantly better liver sparing and allow more patients to achieve higher prescription dose in HCC radiotherapy. PMID:27445485

  6. Hypofractionated Boost to the Dominant Tumor Region With Intensity Modulated Stereotactic Radiotherapy for Prostate Cancer: A Sequential Dose Escalation Pilot Study

    SciTech Connect

    Miralbell, Raymond; Molla, Meritxell; Rouzaud, Michel; Hidalgo, Alberto; Toscas, Jose Ignacio; Lozano, Joan; Sanz, Sergi B.Sc.; Ares, Carmen; Jorcano, Sandra; Linero, Dolors; Escude, Lluis

    2010-09-01

    Purpose: To evaluate the feasibility, tolerability, and preliminary outcomes in patients with prostate cancer treated according to a hypofractionated dose escalation protocol to boost the dominant tumor-bearing region of the prostate. Methods and Materials: After conventional fractionated external radiotherapy to 64 to 64.4Gy, 50 patients with nonmetastatic prostate cancer were treated with an intensity-modulated radiotherapy hypofractionated boost under stereotactic conditions to a reduced prostate volume to the dominant tumor region. A rectal balloon inflated with 60cc of air was used for internal organ immobilization. Five, 8, and 8 patients were sequentially treated with two fractions of 5, 6, or 7Gy, respectively (normalized total dose in 2Gy/fraction [NTD{sub 2Gy}] < 100Gy, low-dose group), whereas 29 patients received two fractions of 8Gy each (NTD{sub 2Gy} > 100Gy, high-dose group). Androgen deprivation was given to 33 patients. Acute and late toxicities were assessed according to the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer (RTOG/EORTC) scoring system. Results: Two patients presented with Grade 3 acute urinary toxicity. The 5-year probabilities of {>=}Grade 2 late urinary and late low gastrointestinal (GI) toxicity-free survival were 82.2% {+-} 7.4% and 72.2% {+-} 7.6%, respectively. The incidence and severity of acute or late toxicities were not correlated with low- vs. high-dose groups, pelvic irradiation, age, or treatment with or without androgen deprivation. The 5-year biochemical disease-free survival (b-DFS) and disease-specific survival were 98% {+-} 1.9% and 100%, respectively. Conclusion: Intensity-modulated radiotherapy hypofractionated boost dose escalation under stereotactic conditions was feasible, and showed excellent outcomes with acceptable long-term toxicity. This approach may well be considered an alternative to high-dose-rate brachytherapy.

  7. Percentage of Cancer Volume in Biopsy Cores Is Prognostic for Prostate Cancer Death and Overall Survival in Patients Treated With Dose-Escalated External Beam Radiotherapy

    SciTech Connect

    Vance, Sean M.; Stenmark, Matthew H.; Blas, Kevin; Halverson, Schulyer; Hamstra, Daniel A.; Feng, Felix Y.

    2012-07-01

    Purpose: To investigate the prognostic utility of the percentage of cancer volume (PCV) in needle biopsy specimens for prostate cancer patients treated with dose-escalated external beam radiotherapy. Methods and Materials: The outcomes were analyzed for 599 men treated for localized prostate cancer with external beam radiotherapy to a minimal planning target volume dose of 75 Gy (range, 75-79.2). We assessed the effect of PCV and the pretreatment and treatment-related factors on the freedom from biochemical failure, freedom from metastasis, cause-specific survival, and overall survival. Results: The median number of biopsy cores was 7 (interquartile range, 6-12), median PCV was 10% (interquartile range, 2.5-25%), and median follow-up was 62 months. The PCV correlated with the National Comprehensive Cancer Network risk group and individual risk features, including T stage, prostate-specific antigen level, Gleason score, and percentage of positive biopsy cores. On log-rank analysis, the PCV stratified by quartile was prognostic for all endpoints, including overall survival. In addition, the PCV was a stronger prognostic factor than the percentage of positive biopsy cores when the two metrics were analyzed together. On multivariate analysis, the PCV predicted a worse outcome for all endpoints, including freedom from biochemical failure, (hazard ratio, 1.9; p = .0035), freedom from metastasis (hazard ratio, 1.7, p = .09), cause-specific survival (hazard ratio, 3.9, p = .014), and overall survival (hazard ratio, 1.8, p = .02). Conclusions: For patients treated with dose-escalated external beam radiotherapy, the volume of cancer in the biopsy specimen adds prognostic value for clinically relevant endpoints, particularly in intermediate- and high-risk patients. Although the PCV determination is more arduous than the percentage of positive biopsy cores, it provides superior risk stratification.

  8. Image-Guided Radiotherapy and -Brachytherapy for Cervical Cancer

    PubMed Central

    Dutta, Suresh; Nguyen, Nam Phong; Vock, Jacqueline; Kerr, Christine; Godinez, Juan; Bose, Satya; Jang, Siyoung; Chi, Alexander; Almeida, Fabio; Woods, William; Desai, Anand; David, Rick; Karlsson, Ulf Lennart; Altdorfer, Gabor

    2015-01-01

    Conventional radiotherapy for cervical cancer relies on clinical examination, 3-dimensional conformal radiotherapy (3D-CRT), and 2-dimensional intracavitary brachytherapy. Excellent local control and survival have been obtained for small early stage cervical cancer with definitive radiotherapy. For bulky and locally advanced disease, the addition of chemotherapy has improved the prognosis but toxicity remains significant. New imaging technology such as positron-emission tomography and magnetic resonance imaging has improved tumor delineation for radiotherapy planning. Image-guided radiotherapy (IGRT) may decrease treatment toxicity of whole pelvic radiation because of its potential for bone marrow, bowel, and bladder sparring. Tumor shrinkage during whole pelvic IGRT may optimize image-guided brachytherapy (IGBT), allowing for better local control and reduced toxicity for patients with cervical cancer. IGRT and IGBT should be integrated in future prospective studies for cervical cancer. PMID:25853092

  9. Image-guided radiotherapy and -brachytherapy for cervical cancer.

    PubMed

    Dutta, Suresh; Nguyen, Nam Phong; Vock, Jacqueline; Kerr, Christine; Godinez, Juan; Bose, Satya; Jang, Siyoung; Chi, Alexander; Almeida, Fabio; Woods, William; Desai, Anand; David, Rick; Karlsson, Ulf Lennart; Altdorfer, Gabor

    2015-01-01

    Conventional radiotherapy for cervical cancer relies on clinical examination, 3-dimensional conformal radiotherapy (3D-CRT), and 2-dimensional intracavitary brachytherapy. Excellent local control and survival have been obtained for small early stage cervical cancer with definitive radiotherapy. For bulky and locally advanced disease, the addition of chemotherapy has improved the prognosis but toxicity remains significant. New imaging technology such as positron-emission tomography and magnetic resonance imaging has improved tumor delineation for radiotherapy planning. Image-guided radiotherapy (IGRT) may decrease treatment toxicity of whole pelvic radiation because of its potential for bone marrow, bowel, and bladder sparring. Tumor shrinkage during whole pelvic IGRT may optimize image-guided brachytherapy (IGBT), allowing for better local control and reduced toxicity for patients with cervical cancer. IGRT and IGBT should be integrated in future prospective studies for cervical cancer. PMID:25853092

  10. Dose-Escalated Intensity-Modulated Radiotherapy Is Feasible and May Improve Locoregional Control and Laryngeal Preservation in Laryngo-Hypopharyngeal Cancers

    SciTech Connect

    Miah, Aisha B.; Bhide, Shreerang A.; Guerrero-Urbano, M. Teresa; Clark, Catharine; Bidmead, A. Margaret; St Rose, Suzanne; Barbachano, Yolanda; A'Hern, Roger; Tanay, Mary; Hickey, Jennifer; Nicol, Robyn; Newbold, Kate L.; Harrington, Kevin J.; Nutting, Christopher M.

    2012-02-01

    Purpose: To determine the safety and outcomes of induction chemotherapy followed by dose-escalated intensity-modulated radiotherapy (IMRT) with concomitant chemotherapy in locally advanced squamous cell cancer of the larynx and hypopharynx (LA-SCCL/H). Methods and Materials: A sequential cohort Phase I/II trial design was used to evaluate moderate acceleration and dose escalation. Patients with LA-SCCL/H received IMRT at two dose levels (DL): DL1, 63 Gy/28 fractions (Fx) to planning target volume 1 (PTV1) and 51.8 Gy/28 Fx to PTV2; DL2, 67.2 Gy/28 Fx and 56 Gy/28 Fx to PTV1 and PTV2, respectively. Patients received induction cisplatin/5-fluorouracil and concomitant cisplatin. Acute and late toxicities and tumor control rates were recorded. Results: Between September 2002 and January 2008, 60 patients (29 DL1, 31 DL2) with Stage III (41% DL1, 52% DL2) and Stage IV (52% DL1, 48% DL2) disease were recruited. Median (range) follow-up for DL1 was 51.2 (12.1-77.3) months and for DL2 was 36.2 (4.2-63.3) months. Acute Grade 3 (G3) dysphagia was higher in DL2 (87% DL2 vs. 59% DL1), but other toxicities were equivalent. One patient in DL1 required dilatation of a pharyngeal stricture (G3 dysphagia). In DL2, 2 patients developed benign pharyngeal strictures at 1 year. One underwent a laryngo-pharyngectomy and the other a dilatation. No other G3/G4 toxicities were reported. Overall complete response was 79% (DL1) and 84% (DL2). Two-year locoregional progression-free survival rates were 64.2% (95% confidence interval, 43.5-78.9%) in DL1 and 78.4% (58.1-89.7%) in DL2. Two-year laryngeal preservation rates were 88.7% (68.5-96.3%) in DL1 and 96.4% (77.7-99.5%) in DL2. Conclusions: At a mean follow-up of 36 months, dose-escalated chemotherapy-IMRT at DL2 has so far been safe to deliver. In this study, DL2 delivered high rates of locoregional control, progression-free survival, and organ preservation and has been selected as the experimental arm in a Cancer Research UK Phase III

  11. Evaluating changes in tumor volume using magnetic resonance imaging during the course of radiotherapy treatment of high-grade gliomas: Implications for conformal dose-escalation studies

    SciTech Connect

    Tsien, Christina . E-mail: ctsien@umich.edu; Gomez-Hassan, Diana; Haken, Randall K. ten; Tatro, Daniel C.; Junck, L.; Chenevert, T.L.; Lawrence, T.

    2005-06-01

    tumors had tumor progression, based on MRI obtained during Week 3 of radiotherapy. Median increase in GTV (Week 3) was 11.7 cc (range, 9.8-21.3). Retrospective DVH analysis of PTV (Pre-Rx) and PTV (Week 3) demonstrated a decrease in V{sub 95%}(PTV volume receiving 95% of the prescribed dose) in those 3 cases. Conclusions: Routine MR imaging during radiotherapy may be essential in ensuring tumor coverage if highly conformal radiotherapy techniques such as stereotactic boost and intensity-modulated radiotherapy are used in dose-escalation trials that utilize smaller treatment margins.

  12. Stereotactic Body Radiotherapy for Recurrent Squamous Cell Carcinoma of the Head and Neck: Results of a Phase I Dose-Escalation Trial

    SciTech Connect

    Heron, Dwight E.; Ferris, Robert L.; Karamouzis, Michalis; Andrade, Regiane S.; Deeb, Erin L.; Burton, Steven; Gooding, William E.; Branstetter, Barton F.; Mountz, James M.; Johnson, Jonas T.; Argiris, Athanassios; Grandis, Jennifer R.; Lai, Stephen Y.

    2009-12-01

    Purpose: To evaluate the safety and efficacy of stereotactic body radiotherapy (SBRT) in previously irradiated patients with squamous cell carcinoma of the head and neck (SCCHN). Patients and Methods: In this Phase I dose-escalation clinical trial, 25 patients were treated in five dose tiers up to 44 Gy, administered in 5 fractions over a 2-week course. Response was assessed according to the Response Evaluation Criteria in Solid Tumors and [{sup 18}F]-fluorodeoxyglucose standardized uptake value change on positron emission tomography-computed tomography (PET-CT). Results: No Grade 3/4 or dose-limiting toxicities occurred. Four patients had Grade 1/2 acute toxicities. Four objective responses were observed, for a response rate of 17% (95% confidence interval 2%-33%). The maximum duration of response was 4 months. Twelve patients had stable disease. Median time to disease progression was 4 months, and median overall survival was 6 months. Self-reported quality of life was not significantly affected by treatment. Fluorodeoxyglucose PET was a more sensitive early-measure response to treatment than CT volume changes. Conclusion: Reirradiation up to 44 Gy using SBRT is well tolerated in the acute setting and warrants further evaluation in combination with conventional and targeted therapies.

  13. Results of the Phase I Dose-Escalating Study of Motexafin Gadolinium With Standard Radiotherapy in Patients With Glioblastoma Multiforme

    SciTech Connect

    Ford, Judith M. Seiferheld, Wendy; Alger, Jeffrey R.; Wu, Genevieve; Endicott, Thyra J.; Mehta, Minesh; Curran, Walter; Phan, See-Chun

    2007-11-01

    Purpose: Motexafin gadolinium (MGd) is a putative radiation enhancer initially evaluated in patients with brain metastases. This Phase I trial studied the safety and tolerability of a 2-6-week course (10-22 doses) of MGd with radiotherapy for glioblastoma multiforme. Methods and Materials: A total of 33 glioblastoma multiforme patients received one of seven MGd regimens starting at 10 doses of 4 mg/kg/d MGd and escalating to 22 doses of 5.3 mg/kg/d MGd (5 or 10 daily doses then three times per week). The National Cancer Institute Cancer Therapy Evaluation Program toxicity and stopping rules were applied. Results: The maximal tolerated dose was 5.0 mg/kg/d MGd (5 d/wk for 2 weeks, then three times per week) for 22 doses. The dose-limiting toxicity was reversible transaminase elevation. Adverse reactions included rash/pruritus (45%), chills/fever (30%), and self-limiting vesiculobullous rash of the thumb and fingers (42%). The median survival of 17.6 months prompted a case-matched analysis. In the case-matched analysis, the MGd patients had a median survival of 16.1 months (n = 31) compared with the matched Radiation Therapy Oncology Group database patients with a median survival of 11.8 months (hazard ratio, 0.43; 95% confidence interval, 0.20-0.94). Conclusion: The maximal tolerated dose of MGd with radiotherapy for glioblastoma multiforme in this study was 5 mg/kg/d for 22 doses (daily for 2 weeks, then three times weekly). The baseline survival calculations suggest progression to Phase II trials is appropriate, with the addition of MGd to radiotherapy with concurrent and adjuvant temozolomide.

  14. A phase I dose escalation study of S-1 with concurrent radiotherapy in elderly patients with esophageal cancer

    PubMed Central

    Ji, Yongling; Qiu, Guoqing; Sheng, Liming; Sun, Xiaojiang; Zheng, Yuanda; Chen, Ming

    2016-01-01

    Background Concurrent chemoradiotherapy (CRT) with 5-fluorouracil (5-FU) and cisplatin (CDDP) are often associated with significant incidence of toxic effects in elderly patients with esophageal cancer. This phase I trial was designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of S-1, an oral 5-FU derivative, when given with radiotherapy in elderly patients. Methods Patients who were age of 70 years or older with histologically confirmed esophageal cancer, and had an Eastern Cooperative Oncology Group (ECOG) score of 0–2 were eligible for this study. Radiotherapy was administered in 1.8 Gy fractions 5 times weekly to a total dose of 54 Gy. S-1 was administered on days 1–14 and 29–42 at the following dosages: 60, 70, and 80 mg/m2/day. Trial registration: NCT01175447 (ClinicalTrials.gov). Results Twelve previously untreated patients were enrolled in this study. No grade 3 or 4 toxicity was observed in six patients treated at the 60 and 70 mg/m2 dose levels. DLT was observed in four of six patients treated at the 80 mg/m2 dose level. Two patients developed grade 3 esophagitis, one patient developed grade 3 esophagitis and pneumonitis, and one patient developed grade 3 thrombocytopaenia. Endoscopic complete response (CR) was observed in eight patients (66.7%). The median progression free survival (PFS) was 20 months and median overall survival was 29 months. Conclusions The MTD of S-1 was 80 mg/m2, and the recommended dose (RD) for phase II studies was 70 mg/m2. This regimen was well tolerated and active in elderly patients with esophageal cancer, meriting further investigation in phase II studies. PMID:27076940

  15. Dose-escalated intensity-modulated radiotherapy and irradiation of subventricular zones in relation to tumor control outcomes of patients with glioblastoma multiforme

    PubMed Central

    Kusumawidjaja, Grace; Gan, Patricia Zhun Hong; Ong, Whee Sze; Teyateeti, Achiraya; Dankulchai, Pittaya; Tan, Daniel Yat Harn; Chua, Eu Tiong; Chua, Kevin Lee Min; Tham, Chee Kian; Wong, Fuh Yong; Chua, Melvin Lee Kiang

    2016-01-01

    Background Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with high relapse rate. In this study, we aimed to determine if dose-escalated (DE) radiotherapy improved tumor control and survival in GBM patients. Methods We conducted a retrospective analysis of 49 and 23 newly-diagnosed histology-proven GBM patients, treated with DE radiotherapy delivered in 70 Gy (2.33 Gy per fraction) and conventional doses (60 Gy), respectively, between 2007 and 2013. Clinical target volumes for 70 and 60 Gy were defined by 0.5 and 2.0 cm expansion of magnetic resonance imaging T1-gadolinium-enhanced tumor/surgical cavity, respectively. Bilateral subventricular zones (SVZ) were contoured on a co-registered pre-treatment magnetic resonance imaging and planning computed tomography dataset as a 5 mm wide structure along the lateral margins of the lateral ventricles. Survival outcomes of both cohorts were compared using log-rank test. Radiation dose to SVZ in the DE cohort was evaluated. Results Median follow-up was 13.6 and 15.1 months for the DE- and conventionally-treated cohorts, respectively. Median overall survival (OS) of patients who received DE radiotherapy was 15.2 months (95% confidence interval [CI] =11.0–18.6), while median OS of the latter cohort was 18.4 months (95% CI =12.5–31.4, P=0.253). Univariate analyses of clinical and dosimetric parameters among the DE cohort demonstrated a trend of longer progression-free survival, but not OS, with incremental radiation doses to the ipsilateral SVZ (hazard ratio [HR] =0.95, 95% CI =0.90–1.00, P=0.052) and proportion of ipsilateral SVZ receiving 50 Gy (HR =0.98, 95% CI =0.97–1.00, P=0.017). Conclusion DE radiotherapy did not improve survival in patients with GBM. Incorporation of ipsilateral SVZ as a radiotherapy target volume for patients with GBM requires prospective validation. PMID:27042103

  16. Twice-Weekly Hypofractionated Intensity-Modulated Radiotherapy for Localized Prostate Cancer With Low-Risk Nodal Involvement: Toxicity and Outcome From a Dose Escalation Pilot Study

    SciTech Connect

    Zilli, Thomas; Jorcano, Sandra; Rouzaud, Michel; Dipasquale, Giovanna; Nouet, Philippe; Toscas, Jose Ignacio; Casanova, Nathalie; Wang, Hui; Escude, Lluis; Molla, Meritxell; Linero, Dolors; Weber, Damien C.; Miralbell, Raymond

    2011-10-01

    Purpose: To evaluate the toxicity and preliminary outcome of patients with localized prostate cancer treated with twice-weekly hypofractionated intensity-modulated radiotherapy (IMRT). Methods and Materials: Between 2003 and 2006, 82 prostate cancer patients with a nodal involvement risk {<=}20% (Roach index) have been treated to the prostate with or without seminal vesicles with 56 Gy (4 Gy/fraction twice weekly) and an overall treatment time of 6.5 weeks. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities were scored according to the Radiation Therapy Oncology Group (RTOG) grading system. Median follow-up was 48 months (range, 9-67 months). Results: All patients completed the treatment without interruptions. No patient presented with Grade {>=}3 acute GU or GI toxicity. Of the patients, 4% presented with Grade 2 GU or GI persistent acute toxicity 6 weeks after treatment completion. The estimated 4-year probability of Grade {>=}2 late GU and GI toxicity-free survival were 94.2% {+-} 2.9% and 96.1% {+-} 2.2%, respectively. One patient presented with Grade 3 GI and another patient with Grade 4 GU late toxicity, which were transitory in both cases. The 4-year actuarial biochemical relapse-free survival was 91.3% {+-} 5.9%, 76.4% {+-} 8.8%, and 77.5% {+-} 8.9% for low-, intermediate-, and high-risk groups, respectively. Conclusions: In patients with localized prostate cancer, acute and late toxicity were minimal after dose-escalation administering twice-weekly 4 Gy to a total dose of 56 Gy, with IMRT. Further prospective trials are warranted to further assess the best fractionation schemes for these patients.

  17. Dose-Volume Parameters of the Corpora Cavernosa Do Not Correlate With Erectile Dysfunction After External Beam Radiotherapy for Prostate Cancer: Results From a Dose-Escalation Trial

    SciTech Connect

    Wielen, Gerard J. van der Hoogeman, Mischa S.; Dohle, Gert R.; Putten, Wim L.J. van; Incrocci, Luca

    2008-07-01

    Purpose: To analyze the correlation between dose-volume parameters of the corpora cavernosa and erectile dysfunction (ED) after external beam radiotherapy (EBRT) for prostate cancer. Methods and Materials: Between June 1997 and February 2003, a randomized dose-escalation trial comparing 68 Gy and 78 Gy was conducted. Patients at our institute were asked to participate in an additional part of the trial evaluating sexual function. After exclusion of patients with less than 2 years of follow-up, ED at baseline, or treatment with hormonal therapy, 96 patients were eligible. The proximal corpora cavernosa (crura), the superiormost 1-cm segment of the crura, and the penile bulb were contoured on the planning computed tomography scan and dose-volume parameters were calculated. Results: Two years after EBRT, 35 of the 96 patients had developed ED. No statistically significant correlations between ED 2 years after EBRT and dose-volume parameters of the crura, the superiormost 1-cm segment of the crura, or the penile bulb were found. The few patients using potency aids typically indicated to have ED. Conclusion: No correlation was found between ED after EBRT for prostate cancer and radiation dose to the crura or penile bulb. The present study is the largest study evaluating the correlation between ED and radiation dose to the corpora cavernosa after EBRT for prostate cancer. Until there is clear evidence that sparing the penile bulb or crura will reduce ED after EBRT, we advise to be careful in sparing these structures, especially when this involves reducing treatment margins.

  18. The Natural History and Predictors of Outcome Following Biochemical Relapse in the Dose Escalation Era for Prostate Cancer Patients Undergoing Definitive External Beam Radiotherapy

    PubMed Central

    Zumsteg, Zachary S.; Spratt, Daniel E.; Romesser, Paul B.; Pei, Xin; Zhang, Zhigang; Polkinghorn, William; McBride, Sean; Kollmeier, Marisa; Yamada, Yoshiya; Zelefsky, Michael J.

    2016-01-01

    Background The management of biochemical failure (BF) following external beam radiotherapy (EBRT) for prostate cancer is controversial, due to both the heterogeneous disease course following a BF and a lack of clinical trials in this setting. Objective We sought to characterize the natural history and predictors of outcome for patients experiencing BF in a large cohort of men with localized prostate cancer undergoing definitive dose-escalated EBRT. Design, setting, and participants This retrospective analysis included 2694 patients with localized prostate cancer treated with EBRT at a large academic center. Of these, 609 experienced BF, defined as prostate-specific antigen (PSA) nadir + 2 ng/ml. The median follow-up was 83 mo for all patients and 122 mo for BF patients. Intervention(s) All patients received EBRT at doses of 75.6–86.4 Gy. Outcome measurements and statistical analysis The primary objective of this study was to determine predictors of distant progression at the time of BF. Cox proportional hazards models were used in univariate and multivariate analyses of distant metastases (DM), and a competing risks method was used to analyze prostate cancer–specific mortality (PCSM). Results and limitations From the date of BF, the median times to DM and PCSM mortality were 5.4 yr and 10.5 yr, respectively. Shorter posttreatment PSA doubling time, a higher initial clinical tumor stage, a higher pretreatment Gleason score, and a shorter interval from the end of radiotherapy to BF were independent predictors for clinical progression following BF. Patients with two of these risk factors had a significantly higher incidence of DM and PCSM following BF than those with zero or one risk factor. The main limitations of this study are its retrospective nature and heterogeneous salvage interventions. Conclusions Clinical and pathologic factors can help identify patients at high risk of clinical progression following BF. Patient summary In this report, we look at

  19. Potential Applications of Imaging and Image-Guided Radiotherapy for Brain Metastases and Glioblastoma to Improve Patient Quality of Life

    PubMed Central

    Nguyen, Nam P.; Nguyen, Mai L.; Vock, Jacqueline; Lemanski, Claire; Kerr, Christine; Vinh-Hung, Vincent; Chi, Alexander; Khan, Rihan; Woods, William; Altdorfer, Gabor; D’Andrea, Mark; Karlsson, Ulf; Hamilton, Russ; Ampil, Fred

    2013-01-01

    Treatment of glioblastoma multiforme (GBM) and brain metastasis remains a challenge because of the poor survival and the potential for brain damage following radiation. Despite concurrent chemotherapy and radiation dose escalation, local recurrence remains the predominant pattern of failure in GBM most likely secondary to repopulation of cancer stem cells. Even though radiotherapy is highly effective for local control of radio-resistant tumors such as melanoma and renal cell cancer, systemic disease progression is the cause of death in most patients with brain metastasis. Preservation of quality of life (QOL) of cancer survivors is the main issue for patients with brain metastasis. Image-guided radiotherapy (IGRT) by virtue of precise radiation dose delivery may reduce treatment time of patients with GBM without excessive toxicity and potentially improve neurocognitive function with preservation of local control in patients with brain metastasis. Future prospective trials for primary brain tumors or brain metastasis should include IGRT to assess its efficacy to improve patient QOL. PMID:24312897

  20. An image guided small animal stereotactic radiotherapy system.

    PubMed

    Sha, Hao; Udayakumar, Thirupandiyur S; Johnson, Perry B; Dogan, Nesrin; Pollack, Alan; Yang, Yidong

    2016-04-01

    Small animal radiotherapy studies should be performed preferably on irradiators capable of focal tumor irradiation and healthy tissue sparing. In this study, an image guided small animal arc radiation treatment system (iSMAART) was developed which can achieve highly precise radiation targeting through the utilization of onboard cone beam computed tomography (CBCT) guidance. The iSMAART employs a unique imaging and radiation geometry where animals are positioned upright. It consists of a stationary x-ray tube, a stationary flat panel detector, and a rotatable and translational animal stage. System performance was evaluated in regards to imaging, image guidance, animal positioning, and radiation targeting using phantoms and tumor bearing animals. The onboard CBCT achieved good signal, contrast, and sub-millimeter spatial resolution. The iodine contrast CBCT accurately delineated orthotopic prostate tumors. Animal positioning was evaluated with ~0.3 mm vertical displacement along superior-inferior direction. The overall targeting precision was within 0.4 mm. Stereotactic radiation beams conformal to tumor targets can be precisely delivered from multiple angles surrounding the animal. The iSMAART allows radiobiology labs to utilize an image guided precision radiation technique that can focally irradiate tumors while sparing healthy tissues at an affordable cost. PMID:26958942

  1. An image guided small animal stereotactic radiotherapy system

    PubMed Central

    Sha, Hao; Udayakumar, Thirupandiyur S.; Johnson, Perry B.; Dogan, Nesrin; Pollack, Alan; Yang, Yidong

    2016-01-01

    Small animal radiotherapy studies should be performed preferably on irradiators capable of focal tumor irradiation and healthy tissue sparing. In this study, an image guided small animal arc radiation treatment system (iSMAART) was developed which can achieve highly precise radiation targeting through the utilization of onboard cone beam computed tomography (CBCT) guidance. The iSMAART employs a unique imaging and radiation geometry where animals are positioned upright. It consists of a stationary x-ray tube, a stationary flat panel detector, and a rotatable and translational animal stage. System performance was evaluated in regards to imaging, image guidance, animal positioning, and radiation targeting using phantoms and tumor bearing animals. The onboard CBCT achieved good signal, contrast, and sub-millimeter spatial resolution. The iodine contrast CBCT accurately delineated orthotopic prostate tumors. Animal positioning was evaluated with ∼0.3 mm vertical displacement along superior-inferior direction. The overall targeting precision was within 0.4 mm. Stereotactic radiation beams conformal to tumor targets can be precisely delivered from multiple angles surrounding the animal. The iSMAART allows radiobiology labs to utilize an image guided precision radiation technique that can focally irradiate tumors while sparing healthy tissues at an affordable cost. PMID:26958942

  2. Volumetric-modulated arc therapy (RapidArc) vs. conventional fixed-field intensity-modulated radiotherapy for {sup 18}F-FDG-PET-guided dose escalation in oropharyngeal cancer: A planning study

    SciTech Connect

    Teoh, May; Beveridge, Sabeena; Wood, Katie; Whitaker, Stephen; Adams, Elizabeth; Rickard, Donna; Jordan, Tom; Nisbet, Andrew; Clark, Catharine H.

    2013-04-01

    Fluorine-18-fluorodeoxyglucose-positron emission tomography ({sup 18}F-FDG-PET)–guided focal dose escalation in oropharyngeal cancer may potentially improve local control. We evaluated the feasibility of this approach using volumetric-modulated arc therapy (RapidArc) and compared these plans with fixed-field intensity-modulated radiotherapy (IMRT) focal dose escalation plans. Materials and methods: An initial study of 20 patients compared RapidArc with fixed-field IMRT using standard dose prescriptions. From this cohort, 10 were included in a dose escalation planning study. Dose escalation was applied to {sup 18}F-FDG-PET–positive regions in the primary tumor at dose levels of 5% (DL1), 10% (DL2), and 15% (DL3) above standard radical dose (65 Gy in 30 fractions). Fixed-field IMRT and double-arc RapidArc plans were generated for each dataset. Dose-volume histograms were used for plan evaluation and comparison. The Paddick conformity index (CI{sub Paddick}) and monitor units (MU) for each plan were recorded and compared. Both IMRT and RapidArc produced clinically acceptable plans and achieved planning objectives for target volumes. Dose conformity was significantly better in the RapidArc plans, with lower CI{sub Paddick} scores in both primary (PTV1) and elective (PTV2) planning target volumes (largest difference in PTV1 at DL3; 0.81 ± 0.03 [RapidArc] vs. 0.77 ± 0.07 [IMRT], p = 0.04). Maximum dose constraints for spinal cord and brainstem were not exceeded in both RapidArc and IMRT plans, but mean doses were higher with RapidArc (by 2.7 ± 1 Gy for spinal cord and 1.9 ± 1 Gy for brainstem). Contralateral parotid mean dose was lower with RapidArc, which was statistically significant at DL1 (29.0 vs. 29.9 Gy, p = 0.01) and DL2 (29.3 vs. 30.3 Gy, p = 0.03). MU were reduced by 39.8–49.2% with RapidArc (largest difference at DL3, 641 ± 94 vs. 1261 ± 118, p < 0.01). {sup 18}F-FDG-PET–guided focal dose escalation in oropharyngeal cancer is feasible with Rapid

  3. Temporary organ displacement coupled with image-guided, intensity-modulated radiotherapy for paraspinal tumors

    PubMed Central

    2013-01-01

    Background To investigate the feasibility and dosimetric improvements of a novel technique to temporarily displace critical structures in the pelvis and abdomen from tumor during high-dose radiotherapy. Methods Between 2010 and 2012, 11 patients received high-dose image-guided intensity-modulated radiotherapy with temporary organ displacement (TOD) at our institution. In all cases, imaging revealed tumor abutting critical structures. An all-purpose drainage catheter was introduced between the gross tumor volume (GTV) and critical organs at risk (OAR) and infused with normal saline (NS) containing 5-10% iohexol. Radiation planning was performed with the displaced OARs and positional reproducibility was confirmed with cone-beam CT (CBCT). Patients were treated within 36 hours of catheter placement. Radiation plans were re-optimized using pre-TOD OARs to the same prescription and dosimetrically compared with post-TOD plans. A two-tailed permutation test was performed on each dosimetric measure. Results The bowel/rectum was displaced in six patients and kidney in four patients. One patient was excluded due to poor visualization of the OAR; thus 10 patients were analyzed. A mean of 229 ml (range, 80–1000) of NS 5-10% iohexol infusion resulted in OAR mean displacement of 17.5 mm (range, 7–32). The median dose prescribed was 2400 cGy in one fraction (range, 2100–3000 in 3 fractions). The mean GTV Dmin and PTV Dmin pre- and post-bowel TOD IG-IMRT dosimetry significantly increased from 1473 cGy to 2086 cGy (p=0.015) and 714 cGy to 1214 cGy (p=0.021), respectively. TOD increased mean PTV D95 by 27.14% of prescription (p=0.014) while the PTV D05 decreased by 9.2% (p=0.011). TOD of the bowel resulted in a 39% decrease in mean bowel Dmax (p=0.008) confirmed by CBCT. TOD of the kidney significantly decreased mean kidney dose and Dmax by 25% (0.022). Conclusions TOD was well tolerated, reproducible, and facilitated dose escalation to previously radioresistant tumors

  4. Fluoroscopic tumor tracking for image-guided lung cancer radiotherapy

    NASA Astrophysics Data System (ADS)

    Lin, Tong; Cerviño, Laura I.; Tang, Xiaoli; Vasconcelos, Nuno; Jiang, Steve B.

    2009-02-01

    Accurate lung tumor tracking in real time is a keystone to image-guided radiotherapy of lung cancers. Existing lung tumor tracking approaches can be roughly grouped into three categories: (1) deriving tumor position from external surrogates; (2) tracking implanted fiducial markers fluoroscopically or electromagnetically; (3) fluoroscopically tracking lung tumor without implanted fiducial markers. The first approach suffers from insufficient accuracy, while the second may not be widely accepted due to the risk of pneumothorax. Previous studies in fluoroscopic markerless tracking are mainly based on template matching methods, which may fail when the tumor boundary is unclear in fluoroscopic images. In this paper we propose a novel markerless tumor tracking algorithm, which employs the correlation between the tumor position and surrogate anatomic features in the image. The positions of the surrogate features are not directly tracked; instead, we use principal component analysis of regions of interest containing them to obtain parametric representations of their motion patterns. Then, the tumor position can be predicted from the parametric representations of surrogates through regression. Four regression methods were tested in this study: linear and two-degree polynomial regression, artificial neural network (ANN) and support vector machine (SVM). The experimental results based on fluoroscopic sequences of ten lung cancer patients demonstrate a mean tracking error of 2.1 pixels and a maximum error at a 95% confidence level of 4.6 pixels (pixel size is about 0.5 mm) for the proposed tracking algorithm.

  5. Testicular Doses in Image-Guided Radiotherapy of Prostate Cancer

    SciTech Connect

    Deng Jun; Chen Zhe; Yu, James B.; Roberts, Kenneth B.; Peschel, Richard E.; Nath, Ravinder

    2012-01-01

    Purpose: To investigate testicular doses contributed by kilovoltage cone-beam computed tomography (kVCBCT) during image-guided radiotherapy (IGRT) of prostate cancer. Methods and Materials: An EGS4 Monte Carlo code was used to calculate three-dimensional dose distributions from kVCBCT on 3 prostate cancer patients. Absorbed doses to various organs were compared between intensity-modulated radiotherapy (IMRT) treatments and kVCBCT scans. The impact of CBCT scanning mode, kilovoltage peak energy (kVp), and CBCT field span on dose deposition to testes and other organs was investigated. Results: In comparison with one 10-MV IMRT treatment, a 125-kV half-fan CBCT scan delivered 3.4, 3.8, 4.1, and 5.7 cGy to the prostate, rectum, bladder, and femoral heads, respectively, accounting for 1.7%, 3.2%, 3.2%, and 8.4% of megavoltage photon dose contributions. However, the testes received 2.9 cGy from the same CBCT scan, a threefold increase as compared with 0.7 cGy received during IMRT. With the same kVp, full-fan mode deposited much less dose to organs than half-fan mode, ranging from 9% less for prostate to 69% less for testes, except for rectum, where full-fan mode delivered 34% more dose. As photon beam energy increased from 60 to 125 kV, kVCBCT-contributed doses increased exponentially for all organs, irrespective of scanning mode. Reducing CBCT field span from 30 to 10 cm in the superior-inferior direction cut testicular doses from 5.7 to 0.2 cGy in half-fan mode and from 1.5 to 0.1 cGy in full-fan mode. Conclusions: Compared with IMRT, kVCBCT-contributed doses to the prostate, rectum, bladder, and femoral heads are clinically insignificant, whereas dose to the testes is threefold more. Full-fan CBCT usually deposits much less dose to organs (except for rectum) than half-fan mode in prostate patients. Kilovoltage CBCT-contributed doses increase exponentially with photon beam energy. Reducing CBCT field significantly cuts doses to testes and other organs.

  6. The Percent of Positive Biopsy Cores Improves Prediction of Prostate Cancer-Specific Death in Patients Treated With Dose-Escalated Radiotherapy

    SciTech Connect

    Qian Yushen; Feng, Felix Y.; Halverson, Schuyler; Blas, Kevin; Sandler, Howard M.; Hamstra, Daniel A.

    2011-11-01

    Purpose: To examine the prognostic utility of the percentage of positive cores (PPC) at the time of prostate biopsy for patients treated with dose-escalated external beam radiation therapy. Methods and Materials: We performed a retrospective analysis of patients treated at University of Michigan Medical Center to at least 75 Gy. Patients were stratified according to PPC by quartile, and freedom from biochemical failure (nadir + 2 ng/mL), freedom from metastasis (FFM), cause-specific survival (CSS), and overall survival (OS) were assessed by log-rank test. Receiver operator characteristic (ROC) curve analysis was used to determine the optimal cut point for PPC stratification. Finally, Cox proportional hazards multivariate regression was used to assess the impact of PPC on clinical outcome when adjusting for National Comprehensive Cancer Network (NCCN) risk group and androgen deprivation therapy. Results: PPC information was available for 651 patients. Increasing-risk features including T stage, prostate-specific antigen, Gleason score, and NCCN risk group were all directly correlated with increasing PPC. On log-rank evaluation, all clinical endpoints, except for OS, were associated with PPC by quartile, with worse clinical outcomes as PPC increased, with the greatest impact seen in the highest quartile (>66.7% of cores positive). ROC curve analysis confirmed that a cut point using two-thirds positive cores was most closely associated with CSS (p = 0.002; area under ROC curve, 0.71). On univariate analysis, stratifying patients according to PPC less than or equal to 66.7% vs. PPC greater than 66.7% was prognostic for freedom from biochemical failure (p = 0.0001), FFM (p = 0.0002), and CSS (p = 0.0003) and marginally prognostic for OS (p = 0.055). On multivariate analysis, after adjustment for NCCN risk group and androgen deprivation therapy use, PPC greater than 66.7% increased the risk for biochemical failure (p = 0.0001; hazard ratio [HR], 2.1 [95% confidence

  7. [Image-guided radiotherapy and partial delegation to radiotherapy technicians: Clermont-Ferrand experience].

    PubMed

    Loos, G; Moreau, J; Miroir, J; Benhaïm, C; Biau, J; Caillé, C; Bellière, A; Lapeyre, M

    2013-10-01

    The various image-guided radiotherapy techniques raise the question of how to achieve the control of patient positioning before irradiation session and sharing of tasks between radiation oncologists and radiotherapy technicians. We have put in place procedures and operating methods to make a partial delegation of tasks to radiotherapy technicians and secure the process in three situations: control by orthogonal kV imaging (kV-kV) of bony landmarks, control by kV-kV imaging of intraprostatic fiducial goldmarkers and control by cone beam CT (CBCT) imaging for prostate cancer. Significant medical overtime is required to control these three IGRT techniques. Because of their competence in imaging, these daily controls can be delegated to radiotherapy technicians. However, to secure the process, initial training and regular evaluation are essential. The analysis of the comparison of the use of kV/kV on bone structures allowed us to achieve a partial delegation of control to radiotherapy technicians. Controlling the positioning of the prostate through the use and automatic registration of fiducial goldmarkers allows better tracking of the prostate and can be easily delegated to radiotherapy technicians. The analysis of the use of daily cone beam CT for patients treated with intensity modulated irradiation is underway, and a comparison of practices between radiotherapy technicians and radiation oncologists is ongoing to know if a partial delegation of this control is possible. PMID:24011600

  8. SU-C-BRA-01: 18F-NaF PET/CT-Directed Dose Escalation in Stereotactic Body Radiotherapy for Spine Oligometastases From Prostate Cancer

    SciTech Connect

    Wu, L; Zhang, W; Li, M; Peng, X; Xie, L; Lin, Z; Kwee, S; Wang, H; Kuang, Y

    2015-06-15

    Purpose: To investigate the technical feasibility of SBRT dose painting using {sup 18}F-NaF positron emission tomography (PET) scans guidance in patients with spine oligometastases from prostate cancer. Methods: As a proof of concept, six patients with 14 spine oligometastatic lesions from prostate cancer who had {sup 18}F-NaF PET/CT scan prior to treatment were retrospectively included. GTV{sub reg} was delineated according to the regular tumor boundary shown on PET and/or CT images; and GTV{sub MATV} was contoured based on a net metabolically active tumor volume (MATV) defined by 60% of the SUV{sub max} values on {sup 18}F-NaF PET images. The PTVs (PTV{sub reg} and PTV{sub MATV}) were defined as respective GTVs (plus involved entire vertebral body for PTV{sub reg}) with a 3-mm isotropic expansion margin. Three 1-fraction SBRT plans using VMAT technique along with 10 MV FFF beams (Plan{sub 24Gy}, Plan{sub 24–27Gy}, and Plan{sub 24–30Gy}) were generated for each patient. All plans included a dose of 24 Gy prescribed to PTV{sub reg}. The Plan{sub 24–27Gy} and Plan{sub 24–30Gy} also included a simultaneous boost dose of 27 Gy or 30 Gy prescribed to the PTV{sub MATV}, respectively. The feasibility of 18F-NaF PET-guided SBRT dose escalation was evaluated by its ability to achieve the prescription dose objectives while adhering to organ-at-risk (OAR) dose constraints. The normal tissue complication probabilities (NTCP) calculated by radiological models were also compared between the plans. Results: In all 33 SBRT plans generated, the planning objectives and dose constraints were met without exception. Plan{sub 24–27Gy} and Plan{sub 24–30Gy} had a significantly higher dose in PTV{sub MATV} than Plan{sub 24Gy} (p < 0.05), respectively, while maintaining a similar OAR sparing profile and NTCP values. Conclusion: Using VMAT with FFF beams to incorporate a simultaneous {sup 18}F-NaF PET-guided radiation boost dose up to 30 Gy into a SBRT plan is technically

  9. Recent Advances in Image-Guided Radiotherapy for Head and Neck Carcinoma

    PubMed Central

    Nath, Sameer K.; Simpson, Daniel R.; Rose, Brent S.; Sandhu, Ajay P.

    2009-01-01

    Radiotherapy has a well-established role in the management of head and neck cancers. Over the past decade, a variety of new imaging modalities have been incorporated into the radiotherapy planning and delivery process. These technologies are collectively referred to as image-guided radiotherapy and may lead to significant gains in tumor control and radiation side effect profiles. In the following review, these techniques as they are applied to head and neck cancer patients are described, and clinical studies analyzing their use in target delineation, patient positioning, and adaptive radiotherapy are highlighted. Finally, we conclude with a brief discussion of potential areas of further radiotherapy advancement. PMID:19644564

  10. Phase II Trial of Radiation Dose Escalation With Conformal External Beam Radiotherapy and High-Dose-Rate Brachytherapy Combined With Long-Term Androgen Suppression in Unfavorable Prostate Cancer: Feasibility Report

    SciTech Connect

    Valero, Jeanette; Cambeiro, Mauricio; Galan, Carlos; Teijeira, Mercedes; Romero, Pilar; Zudaire, Javier; Moreno, Marta; Ciervide, Raquel; Aristu, Jose Javier; Martinez-Monge, Rafael

    2010-02-01

    Purpose: To determine the feasibility of combined long-term luteinizing hormone-releasing hormone agonist-based androgen suppressive therapy (AST) and dose escalation with high-dose-rate (HDR) brachytherapy for high-risk (HRPC) or very-high-risk prostate cancer (VHRPC). Methods and Materials: Between January 2001 and October 2006, 134 patients (median age, 70 years) with either National Comprehensive Cancer Network criteria-defined HRPC (n = 47, 35.1%) or VHRPC (n = 87, 64.9%) were prospectively enrolled in this Phase II trial. Tumor characteristics included a median pretreatment prostate-specific antigen level of 14.6 ng/mL, a median clinical stage of T2c, and a median Gleason score of 7. Three-dimensional conformal radiotherapy (54 Gy in 30 fractions) was followed by HDR brachytherapy (19 Gy in 4 b.i.d. treatments). Androgen suppressive therapy started 0-3 months before three-dimensional conformal radiotherapy and continued for 2 years. Results: One implant was repositioned with a new procedure (0.7%). Five patients (3.7%) discontinued AST at a median of 13 months (range, 6-18 months) because of disease progression (n = 1), hot flashes (n = 2), fatigue (n = 1), and impotence (n = 1). After a median follow-up of 37.4 months (range, 24-90 months), the highest Radiation Therapy Oncology Group-defined late urinary toxicities were Grade 0 in 47.8%, Grade 1 in 38.1%, Grade 2 in 7.5%, and Grade 3 in 6.7% of patients. Maximal late gastrointestinal toxicities were Grade 0 in 73.1%, Grade 1 in 16.4%, Grade 2 in 7.5%, and Grade 3 in 2.9% of patients. There were no Grade 4 or 5 events. Conclusions: Intermediate-term results show that dose escalation with HDR brachytherapy combined with long-term AST is feasible and has a toxicity profile similar to that reported by previous HDR brachytherapy studies.

  11. Intensity-Modulated Radiotherapy as Primary Therapy for Prostate Cancer: Report on Acute Toxicity After Dose Escalation With Simultaneous Integrated Boost to Intraprostatic Lesion

    SciTech Connect

    Fonteyne, Valerie Villeirs, Geert; Speleers, Bruno; Neve, Wilfried de; Wagter, Carlos de; Lumen, Nicolas; Meerleer, Gert de

    2008-11-01

    Purpose: To report on the acute toxicity of a third escalation level using intensity-modulated radiotherapy for prostate cancer (PCa) and the acute toxicity resulting from delivery of a simultaneous integrated boost (SIB) to an intraprostatic lesion (IPL) detected on magnetic resonance imaging (MRI), with or without spectroscopy. Methods and Materials: Between January 2002 and March 2007, we treated 230 patients with intensity-modulated radiotherapy to a third escalation level as primary therapy for prostate cancer. If an IPL (defined by MRI or MRI plus spectroscopy) was present, a SIB was delivered to the IPL. To report on acute toxicity, patients were seen weekly during treatment and 1 and 3 months after treatment. Toxicity was scored using the Radiation Therapy Oncology Group toxicity scale, supplemented by an in-house-developed scoring system. Results: The median dose to the planning target volume was 78 Gy. An IPL was found in 118 patients. The median dose to the MRI-detected IPL and MRI plus spectroscopy-detected IPL was 81 Gy and 82 Gy, respectively. No Grade 3 or 4 acute gastrointestinal toxicity developed. Grade 2 acute gastrointestinal toxicity was present in 26 patients (11%). Grade 3 genitourinary toxicity was present in 15 patients (7%), and 95 patients developed Grade 2 acute genitourinary toxicity (41%). No statistically significant increase was found in Grade 2-3 acute gastrointestinal or genitourinary toxicity after a SIB to an IPL. Conclusion: The results of our study have shown that treatment-induced acute toxicity remains low when intensity-modulated radiotherapy to 80 Gy as primary therapy for prostate cancer is used. In addition, a SIB to an IPL did not increase the severity or incidence of acute toxicity.

  12. Carbon-ion radiotherapy for locally advanced or unfavorably located choroidal melanoma: A Phase I/II dose-escalation study

    SciTech Connect

    Tsuji, Hiroshi . E-mail: h_tsuji@nirs.go.jp; Ishikawa, Hitoshi; Yanagi, Takeshi; Hirasawa, Naoki; Kamada, Tadashi; Mizoe, Jun-Etsu; Kanai, Tatsuaki; Tsujii, Hirohiko; Ohnishi, Yoshitaka

    2007-03-01

    Purpose: To evaluate the applicability of carbon ion beams for the treatment of choroidal melanoma with regard to normal tissue morbidity and local tumor control. Methods and Materials: Between January 2001 and February 2006, 59 patients with locally advanced or unfavorably located choroidal melanoma were enrolled in a Phase I/II clinical trial of carbon-ion radiotherapy at the National Institute of Radiologic Sciences. The primary endpoint of this study was normal tissue morbidity, and secondary endpoints were local tumor control and patient survival. Of the 59 subjects enrolled, 57 were followed >6 months and analyzed. Results: Twenty-three patients (40%) developed neovascular glaucoma, and three underwent enucleation for eye pain due to elevated intraocular pressure. Incidence of neovascular glaucoma was dependent on tumor size and site. Five patients had died at analysis, three of distant metastasis and two of concurrent disease. All but one patient, who developed marginal recurrence, were controlled locally. Six patients developed distant metastasis, five in the liver and one in the lung. Three-year overall survival, disease-free survival, and local control rates were 88.2%, 84.8%, and 97.4%, respectively. No apparent dose-response relationship was observed in either tumor control or normal tissue morbidity at the dose range applied. Conclusion: Carbon-ion radiotherapy can be applied to choroidal melanoma with an acceptable morbidity and sufficient antitumor effect, even with tumors of unfavorable size or site.

  13. Clinical Application of High-Dose, Image-Guided Intensity-Modulated Radiotherapy in High-Risk Prostate Cancer

    SciTech Connect

    Bayley, Andrew; Rosewall, Tara; Craig, Tim; Bristow, Rob; Chung, Peter; Gospodarowicz, Mary; Menard, Cynthia; Milosevic, Michael; Warde, Padraig; Catton, Charles

    2010-06-01

    Purpose: To report the feasibility and early toxicity of dose-escalated image-guided IMRT to the pelvic lymph nodes (LN), prostate (P), and seminal vesicles (SV). Methods and Materials: A total of 103 high-risk prostate cancer patients received two-phase, dose-escalated, image-guided IMRT with 3 years of androgen deprivation therapy. Clinical target volumes (CTVs) were delineated using computed tomography/magnetic resonance co-registration and included the prostate, portions of the SV, and the LN. Planning target volume margins (PTV) used were as follows: P (10 mm, 7 mm posteriorly), SV (10 mm), and LN (5 mm). Organs at risk (OaR) were the rectal and bladder walls, femoral heads, and large and small bowel. The IMRT was planned with an intended dose of 55.1 Gy in 29 fractions to all CTVs (Phase 1), with P+SV consecutive boost of 24.7 Gy in 13 fractions. Daily online image guidance was performed using bony landmarks and intraprostatic markers. Feasibility criteria included delivery of intended doses in 80% of patients, 95% of CTV displacements incorporated within PTV during Phase 1, and acute toxicity rate comparable to that of lower-dose pelvic techniques. Results: A total of 91 patients (88%) received the total prescription dose. All patients received at least 72 Gy. In Phase 1, 63 patients (61%) received the intended 55.1 Gy, whereas 87% of patients received at least 50 Gy. Dose reductions were caused by small bowel and rectal wall constraints. All CTVs received the planned dose in >95% of treatment fractions. There were no Radiation Therapy Oncology Group acute toxicities greater than Grade 3, although there were five incidences equivalent to Grade 3 within a median follow-up of 23 months. Conclusion: These results suggest that dose escalation to the PLN+P+SV using IMRT is feasible, with acceptable rates of acute toxicity.

  14. 70 Gy Versus 80 Gy in Localized Prostate Cancer: 5-Year Results of GETUG 06 Randomized Trial;Prostate cancer; Dose escalation; Conformal radiotherapy; Randomized trial

    SciTech Connect

    Beckendorf, Veronique; Guerif, Stephane; Le Prise, Elisabeth; Cosset, Jean-Marc; Bougnoux, Agnes; Chauvet, Bruno; Salem, Naji; Chapet, Olivier; Bourdain, Sylvain; Bachaud, Jean-Marc; Maingon, Philippe; Hannoun-Levi, Jean-Michel; Malissard, Luc; Simon, Jean-Marc; Pommier, Pascal; Hay, Men; Dubray, Bernard; Lagrange, Jean-Leon; Luporsi, Elisabeth; Bey, Pierre

    2011-07-15

    Purpose: To perform a randomized trial comparing 70 and 80 Gy radiotherapy for prostate cancer. Patients and Methods: A total of 306 patients with localized prostate cancer were randomized. No androgen deprivation was allowed. The primary endpoint was biochemical relapse according to the modified 1997-American Society for Therapeutic Radiology and Oncology and Phoenix definitions. Toxicity was graded using the Radiation Therapy Oncology Group 1991 criteria and the late effects on normal tissues-subjective, objective, management, analytic scales (LENT-SOMA) scales. The patients' quality of life was scored using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item cancer-specific and 25-item prostate-specific modules. Results: The median follow-up was 61 months. According to the 1997-American Society for Therapeutic Radiology and Oncology definition, the 5-year biochemical relapse rate was 39% and 28% in the 70- and 80-Gy arms, respectively (p = .036). Using the Phoenix definition, the 5-year biochemical relapse rate was 32% and 23.5%, respectively (p = .09). The subgroup analysis showed a better biochemical outcome for the higher dose group with an initial prostate-specific antigen level >15 ng/mL. At the last follow-up date, 26 patients had died, 10 of their disease and none of toxicity, with no differences between the two arms. According to the Radiation Therapy Oncology Group scale, the Grade 2 or greater rectal toxicity rate was 14% and 19.5% for the 70- and 80-Gy arms (p = .22), respectively. The Grade 2 or greater urinary toxicity was 10% at 70 Gy and 17.5% at 80 Gy (p = .046). Similar results were observed using the LENT-SOMA scale. Bladder toxicity was more frequent at 80 Gy than at 70 Gy (p = .039). The quality-of-life questionnaire results before and 5 years after treatment were available for 103 patients with no differences found between the 70- and 80-Gy arms. Conclusion: High-dose radiotherapy provided a

  15. Dose-Escalated Radiotherapy for High-Risk Prostate Cancer: Outcomes in Modern Era With Short-Term Androgen Deprivation Therapy

    SciTech Connect

    Liauw, Stanley L.; Stadler, Walter M.; Correa, David B.S.; Weichselbaum, Ralph R.; Jani, Ashesh B.

    2010-05-01

    Purpose: Randomized data have supported the use of long-term androgen deprivation therapy (ADT) combined with radiotherapy (RT) for men with high-risk prostate cancer. The present study reviewed the outcomes of intermediate- and high-risk men treated with RT and short-term ADT. Materials and Methods: A total of 184 men with any single risk factor of prostate-specific antigen >=10 ng/mL, clinical Stage T2b or greater, or Gleason score >=7 were treated with primary external beam RT for nonmetastatic adenocarcinoma of the prostate. The median radiation dose was 74 Gy; 55% were treated with intensity-modulated RT. All patients received ADT for 1 to 6 months (median, 4), consisting of a gonadotropin-releasing hormone analog. Univariate and multivariable analyses were performed for risk factors, including T stage, Gleason score, radiation dose, and prostate-specific antigen level. Results: With a median follow-up of 51 months, the 4-year freedom from biochemical failure (FFBF) using the nadir plus 2 ng/mL definition was 83% for all patients. Clinical Stage T3 disease was the only variable tested associated with FFBF on univariate (4-year FFBF rate, 46% vs. 87% for Stage T1-T2c disease; p = .0303) and multivariable analysis (hazard ratio, 3.9; p = .0016). On a subset analysis of high-risk patients (National Comprehensive Cancer Network criteria), those with clinical Stage T3 disease (4-year FFBF rate, 46% vs. 80%; p = .0303) and a radiation dose <74 Gy (4-year FFBF rate, 64% vs. 80%) had a poorer outcome on univariate analysis. However, clinical Stage T3 disease and radiation dose were not significant on multivariable analysis, although a statistical multivariable trend was seen for both (p = .0650 and p = .0597, respectively). Conclusion: Short-term ADT and RT might be acceptable for men with intermediate- and high-risk prostate cancer, especially for clinically localized disease treated with doses of >=74 Gy.

  16. Image-guided radiotherapy and motion management in lung cancer

    PubMed Central

    2015-01-01

    In this review, image guidance and motion management in radiotherapy for lung cancer is discussed. Motion characteristics of lung tumours and image guidance techniques to obtain motion information are elaborated. Possibilities for management of image guidance and motion in the various steps of the treatment chain are explained, including imaging techniques and beam delivery techniques. Clinical studies using different motion management techniques are reviewed, and finally future directions for image guidance and motion management are outlined. PMID:25955231

  17. Health technology assessment of image-guided radiotherapy (IGRT): A systematic review of current evidence

    PubMed Central

    Arabloo, Jalal; Hamouzadeh, Pejman; Mousavinezhad, Seyedeh Maryam; Mobinizadeh, Mohammadreza; Olyaeemanesh, Alireza; Pooyandjoo, Morvarid

    2016-01-01

    Background: Image-guided radiotherapy used multiple imaging during the radiation therapy course to improve the precision and accuracy of health care provider's treatment. Objectives: This study aims to assess the safety, effectiveness and economic aspects of image-guided radiation therapy for decision-making about this technology in Iran. Methods: In this study, the most important medical databases such as PubMed and Cochrane Library were searched until November 2014. The systematic reviews, health technology assessment reports and economic evaluation studies were included. The results of included studies were analyzed via the thematic synthesis. Results: Seven articles were included in the study. The results showed that image-guided radiation therapy, regardless of the imaging technique used in it, is associated with no major toxicity and has the potential to reduce the symptoms of poisoning. Using image-guided radiation therapy for prostate cancer resulted in substantial improvement in the quality of the received dose and optimal therapeutic dose of radiation to the targeted tumor while the radiation dose to the surrounding healthy tissues was minimal. Additionally, image-guided radiation therapy facilitated the diagnosis and management of exception deviations, including immediate changes and gross errors, weight loss, significant limbs deformity, systematic changes in the internal organs and changes in respiratory movements. Usage of image-guided radiation therapy for prostate cancer was associated with increased costs. Conclusion: Current available evidence suggests that the image-guided radiation therapy can reduce the amount of radiation to healthy tissue around the tumor and the toxicity associated with it. This can enhance the safe dose of radiation to the tumor and increase the likelihood of destruction of tumor. The current level of evidence required conducting further studies on the costs and effectiveness of this technology compared with conventional

  18. Automatic localization of the prostate for on-line or off-line image-guided radiotherapy

    SciTech Connect

    Smitsmans, Monique H.P.; Wolthaus, Jochem W.H.; Artignan, Xavier; Bois, Josien de; Jaffray, David A.; Lebesque, Joos V.; Herk, Marcel van . E-mail: portal@nki.nl

    2004-10-01

    Purpose: With higher radiation dose, higher cure rates have been reported in prostate cancer patients. The extra margin needed to account for prostate motion, however, limits the level of dose escalation, because of the presence of surrounding organs at risk. Knowledge of the precise position of the prostate would allow significant reduction of the treatment field. Better localization of the prostate at the time of treatment is therefore needed, e.g. using a cone-beam computed tomography (CT) system integrated with the linear accelerator. Localization of the prostate relies upon manual delineation of contours in successive axial CT slices or interactive alignment and is fairly time-consuming. A faster method is required for on-line or off-line image-guided radiotherapy, because of prostate motion, for patient throughput and efficiency. Therefore, we developed an automatic method to localize the prostate, based on 3D gray value registration. Methods and materials: A study was performed on conventional repeat CT scans of 19 prostate cancer patients to develop the methodology to localize the prostate. For each patient, 8-13 repeat CT scans were made during the course of treatment. First, the planning CT scan and the repeat CT scan were registered onto the rigid bony structures. Then, the delineated prostate in the planning CT scan was enlarged by an optimum margin of 5 mm to define a region of interest in the planning CT scan that contained enough gray value information for registration. Subsequently, this region was automatically registered to a repeat CT scan using 3D gray value registration to localize the prostate. The performance of automatic prostate localization was compared to prostate localization using contours. Therefore, a reference set was generated by registering the delineated contours of the prostates in all scans of all patients. Gray value registrations that showed large differences with respect to contour registrations were detected with a {chi

  19. Moderate dose escalation for advanced stage Hodgkin's disease using the bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone scheme and adjuvant radiotherapy: a study of the German Hodgkin's Lymphoma Study Group.

    PubMed

    Tesch, H; Diehl, V; Lathan, B; Hasenclever, D; Sieber, M; Rüffer, U; Engert, A; Franklin, J; Pfreundschuh, M; Schalk, K P; Schwieder, G; Wulf, G; Dölken, G; Worst, P; Koch, P; Schmitz, N; Bruntsch, U; Tirier, C; Müller, U; Loeffler, M

    1998-12-15

    The BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) regimen, a rearranged and accelerated version of the standard COPP/adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy, has been shown to be effective and safe in a previous pilot study for advanced stage Hodgkin's disease (HD). The present study aimed to determine a maximum practicable dose of three drugs, ie, etoposide, adriamycin, and cyclophosphamide, for which acute toxicities were acceptable and to assess the feasibility of the escalated scheme. Sixty untreated patients with advanced stage HD were enrolled in this study. Radiotherapy was given in 44 patients (73%) after chemotherapy to initial bulk lesions and residual disease. Granulocyte-colony stimulating factor (G-CSF) was given from day 8 to prevent prolonged neutrocytopenia and severe infections. The intended doses of adriamycin, etoposide, and cyclophosphamide in the BEACOPP schedule could be substantially escalated: adriamycin from 25 to 35, cyclophosphamide from 650 to 1,200, and etoposide from 100 to 200 mg/m2. The major toxicities were leukocytopenia and thrombocytopenia with considerable heterogeneity between individual patients. Of 60 patients, 56 (93%) achieved a complete remission (CR). At a median observation of 32 months, the rates of survival and freedom from treatment failure (FFTF) were estimated to be 91% (95% confidence interval 83% to 99%) and 90% (82% to 98%). These results show that a moderate dose escalation of adriamycin, cyclophosphamide, and etoposide of the baseline BEACOPP regimen is feasible. The escalated BEACOPP regimen shows very encouraging results in advanced stage HD and is now being compared in a randomized phase III study with BEACOPP at baseline dose level. PMID:9845521

  20. Effect of image-guided hypofractionated stereotactic radiotherapy on peripheral non-small-cell lung cancer

    PubMed Central

    Wang, Shu-wen; Ren, Juan; Yan, Yan-li; Xue, Chao-fan; Tan, Li; Ma, Xiao-wei

    2016-01-01

    The objective of this study was to compare the effects of image-guided hypofractionated radiotherapy and conventional fractionated radiotherapy on non-small-cell lung cancer (NSCLC). Fifty stage- and age-matched cases with NSCLC were randomly divided into two groups (A and B). There were 23 cases in group A and 27 cases in group B. Image-guided radiotherapy (IGRT) and stereotactic radiotherapy were conjugately applied to the patients in group A. Group A patients underwent hypofractionated radiotherapy (6–8 Gy/time) three times per week, with a total dose of 64–66 Gy; group B received conventional fractionated radiotherapy, with a total dose of 68–70 Gy five times per week. In group A, 1-year and 2-year local failure survival rate and 1-year local failure-free survival rate were significantly higher than in group B (P<0.05). The local failure rate (P<0.05) and distant metastasis rate (P>0.05) were lower in group A than in group B. The overall survival rate of group A was significantly higher than that of group B (P=0.03), and the survival rate at 1 year was 87% vs 63%, (P<0.05). The median survival time of group A was longer than that of group B. There was no significant difference in the incidence of complications between the two groups (P>0.05). Compared with conventional fractionated radiation therapy, image-guided hypofractionated stereotactic radiotherapy in NSCLC received better treatment efficacy and showed good tolerability. PMID:27574441

  1. Monte Carlo modeling of ultrasound probes for image guided radiotherapy

    SciTech Connect

    Bazalova-Carter, Magdalena; Schlosser, Jeffrey; Chen, Josephine; Hristov, Dimitre

    2015-10-15

    X6-1 probe in vertical orientation caused the highest attenuation of the 6 and 15 MV beams, which at 10 cm depth accounted for 33% and 43% decrease compared to the respective (15 × 15) cm{sup 2} open fields. The C5-2 probe in horizontal orientation, on the other hand, caused a dose increase of 10% and 53% for the 6 and 15 MV beams, respectively, in the buildup region at 0.5 cm depth. For the X6-1 probe in vertical orientation, the dose at 5 cm depth for the 3-cm diameter 6 MV and 5-cm diameter 15 MV beams was attenuated compared to the corresponding open fields to a greater degree by 65% and 43%, respectively. Conclusions: MC models of two US probes used for real-time image guidance during radiotherapy have been built. Due to the high beam attenuation of the US probes, the authors generally recommend avoiding delivery of treatment beams that intersect the probe. However, the presented MC models can be effectively integrated into US-guided radiotherapy treatment planning in cases for which beam avoidance is not practical due to anatomy geometry.

  2. Rationale and development of image-guided intensity-modulated radiotherapy post-prostatectomy: the present standard of care?

    PubMed Central

    Murray, Julia R; McNair, Helen A; Dearnaley, David P

    2015-01-01

    The indications for post-prostatectomy radiotherapy have evolved over the last decade, although the optimal timing, dose, and target volume remain to be well defined. The target volume is susceptible to anatomical variations with its borders interfacing with the rectum and bladder. Image-guided intensity-modulated radiotherapy has become the gold standard for radical prostate radiotherapy. Here we review the current evidence for image-guided techniques with intensity-modulated radiotherapy to the prostate bed and describe current strategies to reduce or account for interfraction and intrafraction motion. PMID:26635484

  3. Development of a MicroCT-Based Image-Guided Conformal Radiotherapy System for Small Animals

    PubMed Central

    Zhou, Hu; Rodriguez, Manuel; van den Haak, Fred; Nelson, Geoffrey; Jogani, Rahil; Xu, Jiali; Zhu, Xinzhi; Xian, Yongjiang; Tran, Phuoc T.; Felsher, Dean W.; Keall, Paul J.; Graves, Edward E.

    2009-01-01

    Purpose The need for clinically-relevant radiation therapy technology for the treatment of preclinical models of disease has spurred the development of a variety of dedicated platforms for small animal irradiation. Our group has taken the approach of adding the ability to deliver conformal radiotherapy to an existing 120 kVp micro-computed tomography (microCT) scanner. Methods A GE eXplore RS120 microCT scanner was modified by the addition of a two-dimensional subject translation stage and a variable aperture collimator. Quality assurance protocols for these devices, including measurement of translation stage positioning accuracy, collimator aperture accuracy, and collimator alignment with the x-ray beam, were devised. Use of this system for image-guided radiotherapy was assessed by irradiation of a solid water phantom as well as of two mice bearing spontaneous MYC-induced lung tumors. Radiation damage was assessed ex vivo by immunohistochemical detection of γH2AX foci. Results The positioning error of the translation stage was found to be less than 0.05 mm, while after alignment of the collimator with the x-ray axis through adjustment of its displacement and rotation, the collimator aperture error was less than 0.1 mm measured at isocenter. CT image-guided treatment of a solid water phantom demonstrated target localization accuracy to within 0.1 mm. γH2AX foci were detected within irradiated lung tumors in mice, with contralateral lung tissue displaying background staining. Conclusions Addition of radiotherapy functionality to a microCT scanner is an effective means of introducing image-guided radiation treatments into the preclinical setting. This approach has been shown to facilitate small animal conformal radiotherapy while leveraging existing technology. PMID:20395069

  4. Primary Cardiac Angiosarcoma Treated With Positron Emission Tomography/Magnetic Resonance Imaging-Guided Adaptive Radiotherapy.

    PubMed

    Elsayad, Khaled; Lehrich, Philipp; Yppaerilae-Wolters, Heidi; Dieckmann, Chantal; Kriz, Jan; Haverkamp, Uwe; Eich, Hans Theodor

    2016-06-01

    Radiotherapy (RT) for inoperable patients with primary cardiac sarcomas or residual tumor is often limited by the sensitivity of the heart and lung to radiation injury. We describe a novel treatment modality with adaptive radiotherapy (ART) using tumor volume tracking in a 37-year-old woman who presented with unresectable primary cardiac angiosarcoma. The patient was treated using positron emission tomography/magnetic resonance imaging-guided ART with 55.8 Gy concomitant with paclitaxel chemotherapy. In conclusion, the treatment was well tolerated, and a significant tumor volume reduction of ∼ 57% was achieved during radiotherapy, suggesting the effectiveness and tolerability of ART in combination with paclitaxel-based chemotherapy. PMID:26514752

  5. Stereotactic Image-Guided Intensity Modulated Radiotherapy Using the HI-ART II Helical Tomotherapy System

    SciTech Connect

    Holmes, Timothy W. Hudes, Richard; Dziuba, Sylwester; Kazi, Abdul; Hall, Mark; Dawson, Dana

    2008-07-01

    The highly integrated adaptive radiation therapy (HI-ART II) helical tomotherapy unit is a new radiotherapy machine designed to achieve highly precise and accurate treatments at all body sites. The precision and accuracy of the HI-ART II is similar to that provided by stereotactic radiosurgery systems, hence the historical distinction between external beam radiotherapy and stereotactic procedures based on differing precision requirements is removed for this device. The objectives of this work are: (1) to describe stereotactic helical tomotherapy processes (SRS, SBRT); (2) to show that the precision and accuracy of the HI-ART meet the requirements defined for SRS and SBRT; and (3) to describe the clinical implementation of a stereotactic image-guided intensity modulated radiation therapy (IG-IMRT) system that incorporates optical motion management.

  6. Computed tomography imaging-guided radiotherapy by targeting upconversion nanocubes with significant imaging and radiosensitization enhancements

    PubMed Central

    Xing, Huaiyong; Zheng, Xiangpeng; Ren, Qingguo; Bu, Wenbo; Ge, Weiqiang; Xiao, Qingfeng; Zhang, Shengjian; Wei, Chenyang; Qu, Haiyun; Wang, Zheng; Hua, Yanqing; Zhou, Liangping; Peng, Weijun; Zhao, Kuaile; Shi, Jianlin

    2013-01-01

    The clinical potentials of radiotherapy could not be achieved completely because of the inaccurate positioning and inherent radioresistance of tumours. In this study, a novel active-targeting upconversion theranostic agent (arginine-glycine-aspartic acid-labelled BaYbF5: 2% Er3+ nanocube) was developed for the first time to address these clinical demands. Heavy metal-based nanocubes (~10 nm) are potential theranostic agents with bifunctional features: computed tomography (CT) contrast agents for targeted tumour imaging and irradiation dose enhancers in tumours during radiotherapy. Remarkably, they showed low toxicity and excellent performance in active-targeting CT imaging and CT imaging-guided radiosensitizing therapy, which could greatly concentrate and enlarge the irradiation dose deposition in tumours to enhance therapeutic efficacy and minimize the damage to surrounding tissues. PMID:23624542

  7. Feasibility of intensity-modulated and image-guided radiotherapy for locally advanced esophageal cancer

    PubMed Central

    2014-01-01

    Background In this study the feasibility of intensity-modulated radiotherapy (IMRT) and tomotherapy-based image-guided radiotherapy (IGRT) for locally advanced esophageal cancer was assessed. Methods A retrospective study of ten patients with locally advanced esophageal cancer who underwent concurrent chemotherapy with IMRT (1) and IGRT (9) was conducted. The gross tumor volume was treated to a median dose of 70 Gy (62.4-75 Gy). Results At a median follow-up of 14 months (1-39 months), three patients developed local failures, six patients developed distant metastases, and complications occurred in two patients (1 tracheoesophageal fistula, 1 esophageal stricture requiring repeated dilatations). No patients developed grade 3-4 pneumonitis or cardiac complications. Conclusions IMRT and IGRT may be effective for the treatment of locally advanced esophageal cancer with acceptable complications. PMID:24742268

  8. Accurate calibration of a stereo-vision system in image-guided radiotherapy.

    PubMed

    Liu, Dezhi; Li, Shidong

    2006-11-01

    Image-guided radiotherapy using a three-dimensional (3D) camera as the on-board surface imaging system requires precise and accurate registration of the 3D surface images in the treatment machine coordinate system. Two simple calibration methods, an analytical solution as three-point matching and a least-squares estimation method as multipoint registration, were introduced to correlate the stereo-vision surface imaging frame with the machine coordinate system. Both types of calibrations utilized 3D surface images of a calibration template placed on the top of the treatment couch. Image transformational parameters were derived from corresponding 3D marked points on the surface images to their given coordinates in the treatment room coordinate system. Our experimental results demonstrated that both methods had provided the desired calibration accuracy of 0.5 mm. The multipoint registration method is more robust particularly for noisy 3D surface images. Both calibration methods have been used as our weekly QA tools for a 3D image-guided radiotherapy system. PMID:17153416

  9. Accurate calibration of a stereo-vision system in image-guided radiotherapy

    SciTech Connect

    Liu Dezhi; Li Shidong

    2006-11-15

    Image-guided radiotherapy using a three-dimensional (3D) camera as the on-board surface imaging system requires precise and accurate registration of the 3D surface images in the treatment machine coordinate system. Two simple calibration methods, an analytical solution as three-point matching and a least-squares estimation method as multipoint registration, were introduced to correlate the stereo-vision surface imaging frame with the machine coordinate system. Both types of calibrations utilized 3D surface images of a calibration template placed on the top of the treatment couch. Image transformational parameters were derived from corresponding 3D marked points on the surface images to their given coordinates in the treatment room coordinate system. Our experimental results demonstrated that both methods had provided the desired calibration accuracy of 0.5 mm. The multipoint registration method is more robust particularly for noisy 3D surface images. Both calibration methods have been used as our weekly QA tools for a 3D image-guided radiotherapy system.

  10. Reliability of the Bony Anatomy in Image-Guided Stereotactic Radiotherapy of Brain Metastases

    SciTech Connect

    Guckenberger, Matthias Baier, Kurt; Guenther, Iris; Richter, Anne; Wilbert, Juergen; Sauer, Otto; Vordermark, Dirk; Flentje, Michael

    2007-09-01

    Purpose: To evaluate whether the position of brain metastases remains stable between planning and treatment in cranial stereotactic radiotherapy (SRT). Methods and Materials: Eighteen patients with 20 brain metastases were treated with single-fraction (17 lesions) or hypofractionated (3 lesions) image-guided SRT. Median time interval between planning and treatment was 8 days. Before treatment a cone-beam CT (CBCT) and a conventional CT after application of i.v. contrast were acquired. Setup errors using automatic bone registration (CBCT) and manual soft-tissue registration of the brain metastases (conventional CT) were compared. Results: Tumor size was not significantly different between planning and treatment. The three-dimensional setup error (mean {+-} SD) was 4.0 {+-} 2.1 mm and 3.5 {+-} 2.2 mm according to the bony anatomy and the lesion itself, respectively. A highly significant correlation between automatic bone match and soft-tissue registration was seen in all three directions (r {>=} 0.88). The three-dimensional distance between the isocenter according to bone match and soft-tissue registration was 1.7 {+-} 0.7 mm, maximum 2.8 mm. Treatment of intracranial pressure with steroids did not influence the position of the lesion relative to the bony anatomy. Conclusion: With a time interval of approximately 1 week between planning and treatment, the bony anatomy of the skull proved to be an excellent surrogate for the target position in image-guided SRT.

  11. Image-guided radiotherapy platform using single nodule conditional lung cancer mouse models

    PubMed Central

    Herter-Sprie, Grit S.; Korideck, Houari; Christensen, Camilla L.; Herter, Jan M.; Rhee, Kevin; Berbeco, Ross I.; Bennett, David G.; Akbay, Esra A.; Kozono, David; Mak, Raymond H.; Makrigiorgos, G. Mike; Kimmelman, Alec C.; Wong, Kwok-Kin

    2014-01-01

    Close resemblance of murine and human trials is essential to achieve the best predictive value of animal-based translational cancer research. Kras-driven genetically engineered mouse models of non-small cell lung cancer faithfully predict the response of human lung cancers to systemic chemotherapy. Due to development of multifocal disease, however, these models have not been usable in studies of outcomes following focal radiotherapy (RT). We report the development of a preclinical platform to deliver state-of-the-art image-guided RT in these models. Presence of a single tumour as usually diagnosed in patients is modelled by confined injection of adenoviral Cre recombinase. Furthermore, three-dimensional conformal planning and state-of-the-art image-guided dose delivery are performed as in humans. We evaluate treatment efficacies of two different radiation regimens and find that Kras-driven tumours can temporarily be stabilized upon RT, whereas additional loss of either Lkb1 or p53 renders these lesions less responsive to RT. PMID:25519892

  12. Phase I Trial of Pelvic Nodal Dose Escalation With Hypofractionated IMRT for High-Risk Prostate Cancer

    SciTech Connect

    Adkison, Jarrod B.; McHaffie, Derek R.; Bentzen, Soren M.; Patel, Rakesh R.; Khuntia, Deepak; Petereit, Daniel G.; Hong, Theodore S.; Tome, Wolfgang; Ritter, Mark A.

    2012-01-01

    Purpose: Toxicity concerns have limited pelvic nodal prescriptions to doses that may be suboptimal for controlling microscopic disease. In a prospective trial, we tested whether image-guided intensity-modulated radiation therapy (IMRT) can safely deliver escalated nodal doses while treating the prostate with hypofractionated radiotherapy in 5 Vulgar-Fraction-One-Half weeks. Methods and Materials: Pelvic nodal and prostatic image-guided IMRT was delivered to 53 National Comprehensive Cancer Network (NCCN) high-risk patients to a nodal dose of 56 Gy in 2-Gy fractions with concomitant treatment of the prostate to 70 Gy in 28 fractions of 2.5 Gy, and 50 of 53 patients received androgen deprivation for a median duration of 12 months. Results: The median follow-up time was 25.4 months (range, 4.2-57.2). No early Grade 3 Radiation Therapy Oncology Group or Common Terminology Criteria for Adverse Events v.3.0 genitourinary (GU) or gastrointestinal (GI) toxicities were seen. The cumulative actuarial incidence of Grade 2 early GU toxicity (primarily alpha blocker initiation) was 38%. The rate was 32% for Grade 2 early GI toxicity. None of the dose-volume descriptors correlated with GU toxicity, and only the volume of bowel receiving {>=}30 Gy correlated with early GI toxicity (p = 0.029). Maximum late Grades 1, 2, and 3 GU toxicities were seen in 30%, 25%, and 2% of patients, respectively. Maximum late Grades 1 and 2 GI toxicities were seen in 30% and 8% (rectal bleeding requiring cautery) of patients, respectively. The estimated 3-year biochemical control (nadir + 2) was 81.2 {+-} 6.6%. No patient manifested pelvic nodal failure, whereas 2 experienced paraaortic nodal failure outside the field. The six other clinical failures were distant only. Conclusions: Pelvic IMRT nodal dose escalation to 56 Gy was delivered concurrently with 70 Gy of hypofractionated prostate radiotherapy in a convenient, resource-efficient, and well-tolerated 28-fraction schedule. Pelvic nodal dose

  13. SU-E-J-191: Motion Prediction Using Extreme Learning Machine in Image Guided Radiotherapy

    SciTech Connect

    Jia, J; Cao, R; Pei, X; Wang, H; Hu, L

    2015-06-15

    Purpose: Real-time motion tracking is a critical issue in image guided radiotherapy due to the time latency caused by image processing and system response. It is of great necessity to fast and accurately predict the future position of the respiratory motion and the tumor location. Methods: The prediction of respiratory position was done based on the positioning and tracking module in ARTS-IGRT system which was developed by FDS Team (www.fds.org.cn). An approach involving with the extreme learning machine (ELM) was adopted to predict the future respiratory position as well as the tumor’s location by training the past trajectories. For the training process, a feed-forward neural network with one single hidden layer was used for the learning. First, the number of hidden nodes was figured out for the single layered feed forward network (SLFN). Then the input weights and hidden layer biases of the SLFN were randomly assigned to calculate the hidden neuron output matrix. Finally, the predicted movement were obtained by applying the output weights and compared with the actual movement. Breathing movement acquired from the external infrared markers was used to test the prediction accuracy. And the implanted marker movement for the prostate cancer was used to test the implementation of the tumor motion prediction. Results: The accuracy of the predicted motion and the actual motion was tested. Five volunteers with different breathing patterns were tested. The average prediction time was 0.281s. And the standard deviation of prediction accuracy was 0.002 for the respiratory motion and 0.001 for the tumor motion. Conclusion: The extreme learning machine method can provide an accurate and fast prediction of the respiratory motion and the tumor location and therefore can meet the requirements of real-time tumor-tracking in image guided radiotherapy.

  14. Clinical Experience With Image-Guided Radiotherapy in an Accelerated Partial Breast Intensity-Modulated Radiotherapy Protocol

    SciTech Connect

    Leonard, Charles E.; Tallhamer, Michael M.S.; Johnson, Tim; Hunter, Kari C.M.D.; Howell, Kathryn; Kercher, Jane; Widener, Jodi; Kaske, Terese; Paul, Devchand; Sedlacek, Scot; Carter, Dennis L.

    2010-02-01

    Purpose: To explore the feasibility of fiducial markers for the use of image-guided radiotherapy (IGRT) in an accelerated partial breast intensity modulated radiotherapy protocol. Methods and Materials: Nineteen patients consented to an institutional review board approved protocol of accelerated partial breast intensity-modulated radiotherapy with fiducial marker placement and treatment with IGRT. Patients (1 patient with bilateral breast cancer; 20 total breasts) underwent ultrasound guided implantation of three 1.2- x 3-mm gold markers placed around the surgical cavity. For each patient, table shifts (inferior/superior, right/left lateral, and anterior/posterior) and minimum, maximum, mean error with standard deviation were recorded for each of the 10 BID treatments. The dose contribution of daily orthogonal films was also examined. Results: All IGRT patients underwent successful marker placement. In all, 200 IGRT treatment sessions were performed. The average vector displacement was 4 mm (range, 2-7 mm). The average superior/inferior shift was 2 mm (range, 0-5 mm), the average lateral shift was 2 mm (range, 1-4 mm), and the average anterior/posterior shift was 3 mm (range, 1 5 mm). Conclusions: This study shows that the use of IGRT can be successfully used in an accelerated partial breast intensity-modulated radiotherapy protocol. The authors believe that this technique has increased daily treatment accuracy and permitted reduction in the margin added to the clinical target volume to form the planning target volume.

  15. Phase II Trial of Concurrent Sunitinib and Image-Guided Radiotherapy for Oligometastases

    PubMed Central

    Tong, Charles C. L.; Ko, Eric C.; Sung, Max W.; Cesaretti, Jamie A.; Stock, Richard G.; Packer, Stuart H.; Forsythe, Kevin; Genden, Eric M.; Schwartz, Myron; Lau, K. H. Vincent; Galsky, Matthew; Ozao-Choy, Junko; Chen, Shu-hsia; Kao, Johnny

    2012-01-01

    Background Preclinical data suggest that sunitinib enhances the efficacy of radiotherapy. We tested the combination of sunitinib and hypofractionated image-guided radiotherapy (IGRT) in a cohort of patients with historically incurable distant metastases. Methods Twenty five patients with oligometastases, defined as 1–5 sites of active disease on whole body imaging, were enrolled in a phase II trial from 2/08 to 9/10. The most common tumor types treated were head and neck, liver, lung, kidney and prostate cancers. Patients were treated with the recommended phase II dose of 37.5 mg daily sunitinib (days 1–28) and IGRT 50 Gy (days 8–12 and 15–19). Maintenance sunitinib was used in 33% of patients. Median follow up was 17.5 months (range, 0.7 to 37.4 months). Results The 18-month local control, distant control, progression-free survival (PFS) and overall survival (OS) were 75%, 52%, 56% and 71%, respectively. At last follow-up, 11 (44%) patients were alive without evidence of disease, 7 (28%) were alive with distant metastases, 3 (12%) were dead from distant metastases, 3 (12%) were dead from comorbid illness, and 1 (4%) was dead from treatment-related toxicities. The incidence of acute grade ≥ 3 toxicities was 28%, most commonly myelosuppression, bleeding and abnormal liver function tests. Conclusions Concurrent sunitinib and IGRT achieves major clinical responses in a subset of patients with oligometastases. Trial Registration ClinicalTrials.gov NCT00463060 PMID:22761653

  16. NBN gain is predictive for adverse outcome following image-guided radiotherapy for localized prostate cancer.

    PubMed

    Berlin, Alejandro; Lalonde, Emilie; Sykes, Jenna; Zafarana, Gaetano; Chu, Kenneth C; Ramnarine, Varune R; Ishkanian, Adrian; Sendorek, Dorota H S; Pasic, Ivan; Lam, Wan L; Jurisica, Igor; van der Kwast, Theo; Milosevic, Michael; Boutros, Paul C; Bristow, Robert G

    2014-11-30

    Despite the use of clinical prognostic factors (PSA, T-category and Gleason score), 20-60% of localized prostate cancers (PCa) fail primary local treatment. Herein, we determined the prognostic importance of main sensors of the DNA damage response (DDR): MRE11A, RAD50, NBN, ATM, ATR and PRKDC. We studied copy number alterations in DDR genes in localized PCa treated with image-guided radiotherapy (IGRT; n=139) versus radical prostatectomy (RadP; n=154). In both cohorts, NBN gains were the most frequent genomic alteration (14.4 and 11% of cases, respectively), and were associated with overall tumour genomic instability (p<0.0001). NBN gains were the only significant predictor of 5yrs biochemical relapse-free rate (bRFR) following IGRT (46% versus 77%; p=0.00067). On multivariate analysis, NBN gain remained a significant independent predictor of bRFR after adjusting for known clinical prognostic variables (HR=3.28, 95% CI 1.56-6.89, Wald p-value=0.0017). No DDR-sensing gene was prognostic in the RadP cohort. In vitro studies correlated NBN gene overexpression with PCa cells radioresistance. In conclusion, NBN gain predicts for decreased bRFR in IGRT, but not in RadP patients. If validated independently, Nibrin gains may be the first PCa predictive biomarker to facilitate local treatment decisions using precision medicine approaches with surgery or radiotherapy. PMID:25415046

  17. Dose Escalation Improves Cancer-Related Events at 10 Years for Intermediate- and High-Risk Prostate Cancer Patients Treated With Hypofractionated High-Dose-Rate Boost and External Beam Radiotherapy

    SciTech Connect

    Martinez, Alvaro A.; Gonzalez, Jose; Ye Hong; Ghilezan, Mihai; Shetty, Sugandh; Kernen, Kenneth; Gustafson, Gary; Krauss, Daniel; Vicini, Frank; Kestin, Larry

    2011-02-01

    Purpose: To evaluate the 10-year outcomes of intermediate- and high-risk prostate cancer patients treated with a prospective dose escalation hypofractionated trial of pelvic external beam radiation therapy (P-EBRT) with a high-dose-rate (HDR) brachytherapy boost. Methods and Materials: From 1992 to 2007, 472 patients were treated with a HDR boost at William Beaumont Hospital. They had at least one of the following: a prostate-specific antigen (PSA) level of >10 ng/ml, a Gleason score of {>=}7, or clinical stage {>=}T2b. Patients received 46-Gy P-EBRT and an HDR boost. The HDR dose fractionation was divided into two dose levels. The prostate biologically equivalent dose (BED) low-dose-level group received <268 Gy, and the high-dose group received >268 Gy . Phoenix biochemical failure (BF) definition was used. Results: Median follow-up was 8.2 years (range, 0.4-17 years). The 10-year biochemical failure rate of 43.1% vs. 18.9%, (p < 0.001), the clinical failure rate of 23.4% vs. 7.7%, (p < 0.001), and the distant metastasis of 12.4% vs. 5.7%, (p = 0.028) were all significantly better for the high-dose level group. On Cox multivariate analysis, higher BED levels (p = 0.017; hazard ratio [HR]= 0.586), pretreatment PSA assays (p < 0.001, HR = 1.022), and Gleason scores (p = 0.004) were significant variables for reduced biochemical failure. Higher dose levels (p, 0.002; HR, 0.397) and Gleason scores (p < 0.001) were significant for clinical failure. Grade 3 genitourinary complications were 2% and 3%, respectively, and grade 3 gastrointestinal complication was <0.5%. Conclusions: This prospective trial using P-EBRT with HDR boost and hypofractionated dose escalation demonstrates a strong dose-response relationship for intermediate- and high-risk prostate cancer patients. The improvement at 10 years for locoregional control with higher radiation doses (BED, > 268Gy) has significantly decreased biochemical and clinical failures as well as distant metastasis.

  18. Integral test phantom for dosimetric quality assurance of image guided and intensity modulated stereotactic radiotherapy

    SciTech Connect

    Letourneau, Daniel; Keller, Harald; Sharpe, Michael B.; Jaffray, David A.

    2007-05-15

    The objective of this work is to develop a dosimetric phantom quality assurance (QA) of linear accelerators capable of cone-beam CT (CBCT) image guided and intensity-modulated radiotherapy (IG-IMRT). This phantom is to be used in an integral test to quantify in real-time both the performance of the image guidance and the dose delivery systems in terms of dose localization. The prototype IG-IMRT QA phantom consisted of a cylindrical imaging phantom (CatPhan) combined with an array of 11 radiation diodes mounted on a 10 cm diameter disk, oriented perpendicular to the phantom axis. Basic diode response characterization was performed for 6 and 18 MV photons. The diode response was compared to planning system calculations in the open and penumbrae regions of simple and complex beam arrangements. The clinical use of the QA phantom was illustrated in an integral test of an IG-IMRT treatment designed for a clinical spinal radiosurgery case. The sensitivity of the phantom to multileaf collimator (MLC) calibration and setup errors in the clinical setting was assessed by introducing errors in the IMRT plan or by displacing the phantom. The diodes offered good response linearity and long-term reproducibility for both 6 and 18 MV. Axial dosimetry of coplanar beams (in a plane containing the beam axes) was made possible with the nearly isoplanatic response of the diodes over 360 deg. of gantry (usually within {+-}1%). For single beam geometry, errors in phantom placement as small as 0.5 mm could be accurately detected (in gradient {>=}1%/mm). In clinical setting, MLC systematic errors of 1 mm on a single MLC bank introduced in the IMRT plan were easily detectable with the QA phantom. The QA phantom demonstrated also sufficient sensitivity for the detection of setup errors as small as 1 mm for the IMRT delivery. These results demonstrated that the prototype can accurately and efficiently verify the entire IG-IMRT process. This tool, in conjunction with image guidance capabilities

  19. Image-guided adaptive gating of lung cancer radiotherapy: a computer simulation study

    NASA Astrophysics Data System (ADS)

    Aristophanous, Michalis; Rottmann, Joerg; Park, Sang-June; Nishioka, Seiko; Shirato, Hiroki; Berbeco, Ross I.

    2010-08-01

    The purpose of this study is to investigate the effect that image-guided adaptation of the gating window during treatment could have on the residual tumor motion, by simulating different gated radiotherapy techniques. There are three separate components of this simulation: (1) the 'Hokkaido Data', which are previously measured 3D data of lung tumor motion tracks and the corresponding 1D respiratory signals obtained during the entire ungated radiotherapy treatments of eight patients, (2) the respiratory gating protocol at our institution and the imaging performed under that protocol and (3) the actual simulation in which the Hokkaido Data are used to select tumor position information that could have been collected based on the imaging performed under our gating protocol. We simulated treatments with a fixed gating window and a gating window that is updated during treatment. The patient data were divided into different fractions, each with continuous acquisitions longer than 2 min. In accordance to the imaging performed under our gating protocol, we assume that we have tumor position information for the first 15 s of treatment, obtained from kV fluoroscopy, and for the rest of the fractions the tumor position is only available during the beam-on time from MV imaging. The gating window was set according to the information obtained from the first 15 s such that the residual motion was less than 3 mm. For the fixed gating window technique the gate remained the same for the entire treatment, while for the adaptive technique the range of the tumor motion during beam-on time was measured and used to adapt the gating window to keep the residual motion below 3 mm. The algorithm used to adapt the gating window is described. The residual tumor motion inside the gating window was reduced on average by 24% for the patients with regular breathing patterns and the difference was statistically significant (p-value = 0.01). The magnitude of the residual tumor motion depended on the

  20. Penile bulb dose and impotence after three-dimensional conformal radiotherapy for prostate cancer on RTOG 9406: Findings from a prospective, multi-institutional, phase I/II dose-escalation study

    SciTech Connect

    Roach, Mack . E-mail: roach@radonc17.ucsf.edu; Winter, Kathryn; Michalski, Jeffrey M.; Cox, James D.; Purdy, James A.; Bosch, Walter; Lin Xiao; Shipley, William S.

    2004-12-01

    Purpose: To assess the relationship between the dose to the bulb of the penis and the risk of impotence in men treated on Radiation Therapy Oncology Group (RTOG) 9406. Methods and materials: Men enrolled on a Phase I/II dose-escalation study, RTOG 9406, who were reported to be potent at entry and evaluable (n = 158) were selected for inclusion. Follow-up evaluations were scheduled every 3, 4, and 6 months for the first, second, and the third through fifth years, then annually. At each follow-up visit an assessment of potency status was made. Penile structures were defined by a single observer blinded to the potency status, using Web-based, on-line software. The dosimetry for penile structures was calculated at the Quality Assurance Center at Washington University and provided to RTOG Statistical Headquarters to determine whether there was a relationship between dose and impotence. Results: Patients whose median penile dose was {>=}52.5 Gy had a greater risk of impotence compared with those receiving <52.5 Gy (p = 0.039). In a multivariate analysis neither age, the dose to the prostate, nor the use of hormonal therapy correlated with the risk of impotence. Conclusions: Dose to the bulb of the penis seems to be associated with the risk of radiation-induced impotence.

  1. Image-guided radiation therapy: Physician's perspectives

    PubMed Central

    Gupta, T.; Narayan, C. Anand

    2012-01-01

    The evolution of radiotherapy has been ontogenetically linked to medical imaging. Over the years, major technological innovations have resulted in substantial improvements in radiotherapy planning, delivery, and verification. The increasing use of computed tomography imaging for target volume delineation coupled with availability of computer-controlled treatment planning and delivery systems have progressively led to conformation of radiation dose to the target tissues while sparing surrounding normal tissues. Recent advances in imaging technology coupled with improved treatment delivery allow near-simultaneous soft-tissue localization of tumor and repositioning of patient. The integration of various imaging modalities within the treatment room for guiding radiation delivery has vastly improved the management of geometric uncertainties in contemporary radiotherapy practice ushering in the paradigm of image-guided radiation therapy (IGRT). Image-guidance should be considered a necessary and natural corollary to high-precision radiotherapy that was long overdue. Image-guided radiation therapy not only provides accurate information on patient and tumor position on a quantitative scale, it also gives an opportunity to verify consistency of planned and actual treatment geometry including adaptation to daily variations resulting in improved dose delivery. The two main concerns with IGRT are resource-intensive nature of delivery and increasing dose from additional imaging. However, increasing the precision and accuracy of radiation delivery through IGRT is likely to reduce toxicity with potential for dose escalation and improved tumor control resulting in favourable therapeutic index. The radiation oncology community needs to leverage this technology to generate high-quality evidence to support widespread adoption of IGRT in contemporary radiotherapy practice. PMID:23293448

  2. Real-time 3D surface-image-guided beam setup in radiotherapy of breast cancer

    SciTech Connect

    Djajaputra, David; Li Shidong

    2005-01-01

    We describe an approach for external beam radiotherapy of breast cancer that utilizes the three-dimensional (3D) surface information of the breast. The surface data of the breast are obtained from a 3D optical camera that is rigidly mounted on the ceiling of the treatment vault. This 3D camera utilizes light in the visible range therefore it introduces no ionization radiation to the patient. In addition to the surface topographical information of the treated area, the camera also captures gray-scale information that is overlaid on the 3D surface image. This allows us to visualize the skin markers and automatically determine the isocenter position and the beam angles in the breast tangential fields. The field sizes and shapes of the tangential, supraclavicular, and internal mammary gland fields can all be determined according to the 3D surface image of the target. A least-squares method is first introduced for the tangential-field setup that is useful for compensation of the target shape changes. The entire process of capturing the 3D surface data and subsequent calculation of beam parameters typically requires less than 1 min. Our tests on phantom experiments and patient images have achieved the accuracy of 1 mm in shift and 0.5 deg. in rotation. Importantly, the target shape and position changes in each treatment session can both be corrected through this real-time image-guided system.

  3. Calcifications Are Potential Surrogates for Prostate Localization in Image-Guided Radiotherapy

    SciTech Connect

    Zeng, Grace G. McGowan, Tom S.; Larsen, Tessa M.; Bruce, Lisa M.; Moran, Natasha K.; Tsao, Jonathan R.; MacPherson, Miller S.

    2008-11-15

    Purpose: To investigate the feasibility of using calcifications as surrogates for the prostate position during cone-beam computed tomography (CBCT) image-guided radiotherapy. Methods and Materials: The twice-weekly CBCT images taken during the treatment course of 4 patients were retrospectively studied for the stability of the calcifications. The geometric center of three fiducial markers was used as the reference. The planning CT images of 131 prostate patients recently treated with external beam radiotherapy at our center were reviewed to estimate the calcification occurrence rate. Analysis was conducted using the Varian Eclipse treatment planning system. Two patients were treated using prostate calcifications as the landmark in on-line registration. Both the Varian standard and the low-dose CBCT modes were used for imaging. Results: The calcifications were found to be stable during the treatment course. At the 95% confidence interval, the difference between the distance from an identified calcification to the fiducial markers on CBCT and the distance on the planning CT scans was 0.2 {+-} 2.0 mm, 0.8 {+-} 2.2 mm, and 0.4 {+-} 2.4 mm in the left-right, anteroposterior, and superoinferior direction, respectively. Of the 131 patients, 46 (35%) had well-defined calcifications either inside the prostate or near the borders. Our experience in treating the first 2 patients demonstrated that the calcifications are easily distinguished on low-dose scans and that calcification registration can be precisely performed. Conclusion: The results of our study have shown that calcifications can be reliable markers of prostate position and allow for precise image guidance with a low-imaging dose. With this approach, potentially about one-third of prostate patients could benefit from precise image guidance without the invasive use of markers.

  4. Biological Image-Guided Radiotherapy in Rectal Cancer: Challenges and Pitfalls

    SciTech Connect

    Roels, Sarah; Slagmolen, Pieter; Lee, John A.; Loeckx, Dirk; Maes, Frederik; Stroobants, Sigrid; Ectors, Nadine; Penninckx, Freddy; Haustermans, Karin

    2009-11-01

    Purpose: To investigate the feasibility of integrating multiple imaging modalities for image-guided radiotherapy in rectal cancer. Patients and Methods: Magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) were performed before, during, and after preoperative chemoradiotherapy (CRT) in patients with resectable rectal cancer. The FDG-PET signals were segmented with an adaptive threshold-based and a gradient-based method. Magnetic resonance tumor volumes (TVs) were manually delineated. A nonrigid registration algorithm was applied to register the images, and mismatch analyses were carried out between MR and FDG-PET TVs and between TVs over time. Tumor volumes delineated on the images after CRT were compared with the pathologic TV. Results: Forty-five FDG-PET/CT and 45 MR images were analyzed from 15 patients. The mean MRI and FDG-PET TVs showed a tendency to shrink during and after CRT. In general, MRI showed larger TVs than FDG-PET. There was an approximately 50% mismatch between the FDG-PET TV and the MRI TV at baseline and during CRT. Sixty-one percent of the FDG-PET TV and 76% of the MRI TV obtained after 10 fractions of CRT remained inside the corresponding baseline TV. On MRI, residual tumor was still suspected in all 6 patients with a pathologic complete response, whereas FDG-PET showed a metabolic complete response in 3 of them. The FDG-PET TVs delineated with the gradient-based method matched closest with pathologic findings. Conclusions: Integration of MRI and FDG-PET into radiotherapy seems feasible. Gradient-based segmentation is recommended for FDG-PET. Spatial variance between MRI and FDG-PET TVs should be taken into account for target definition.

  5. Incremental Learning With Selective Memory (ILSM): Towards Fast Prostate Localization for Image Guided Radiotherapy

    PubMed Central

    Gao, Yaozong; Zhan, Yiqiang

    2015-01-01

    Image-guided radiotherapy (IGRT) requires fast and accurate localization of the prostate in 3-D treatment-guided radiotherapy, which is challenging due to low tissue contrast and large anatomical variation across patients. On the other hand, the IGRT workflow involves collecting a series of computed tomography (CT) images from the same patient under treatment. These images contain valuable patient-specific information yet are often neglected by previous works. In this paper, we propose a novel learning framework, namely incremental learning with selective memory (ILSM), to effectively learn the patient-specific appearance characteristics from these patient-specific images. Specifically, starting with a population-based discriminative appearance model, ILSM aims to “personalize” the model to fit patient-specific appearance characteristics. The model is personalized with two steps: backward pruning that discards obsolete population-based knowledge and forward learning that incorporates patient-specific characteristics. By effectively combining the patient-specific characteristics with the general population statistics, the incrementally learned appearance model can localize the prostate of a specific patient much more accurately. This work has three contributions: 1) the proposed incremental learning framework can capture patient-specific characteristics more effectively, compared to traditional learning schemes, such as pure patient-specific learning, population-based learning, and mixture learning with patient-specific and population data; 2) this learning framework does not have any parametric model assumption, hence, allowing the adoption of any discriminative classifier; and 3) using ILSM, we can localize the prostate in treatment CTs accurately (DSC ∼0.89) and fast (∼4 s), which satisfies the real-world clinical requirements of IGRT. PMID:24495983

  6. Automatic block-matching registration to improve lung tumor localization during image-guided radiotherapy

    NASA Astrophysics Data System (ADS)

    Robertson, Scott Patrick

    To improve relatively poor outcomes for locally-advanced lung cancer patients, many current efforts are dedicated to minimizing uncertainties in radiotherapy. This enables the isotoxic delivery of escalated tumor doses, leading to better local tumor control. The current dissertation specifically addresses inter-fractional uncertainties resulting from patient setup variability. An automatic block-matching registration (BMR) algorithm is implemented and evaluated for the purpose of directly localizing advanced-stage lung tumors during image-guided radiation therapy. In this algorithm, small image sub-volumes, termed "blocks", are automatically identified on the tumor surface in an initial planning computed tomography (CT) image. Each block is independently and automatically registered to daily images acquired immediately prior to each treatment fraction. To improve the accuracy and robustness of BMR, this algorithm incorporates multi-resolution pyramid registration, regularization with a median filter, and a new multiple-candidate-registrations technique. The result of block-matching is a sparse displacement vector field that models local tissue deformations near the tumor surface. The distribution of displacement vectors is aggregated to obtain the final tumor registration, corresponding to the treatment couch shift for patient setup correction. Compared to existing rigid and deformable registration algorithms, the final BMR algorithm significantly improves the overlap between target volumes from the planning CT and registered daily images. Furthermore, BMR results in the smallest treatment margins for the given study population. However, despite these improvements, large residual target localization errors were noted, indicating that purely rigid couch shifts cannot correct for all sources of inter-fractional variability. Further reductions in treatment uncertainties may require the combination of high-quality target localization and adaptive radiotherapy.

  7. Inter- and Intrafraction Uncertainty in Prostate Bed Image-Guided Radiotherapy

    SciTech Connect

    Huang, Kitty; Palma, David A.; Scott, Danielle; McGregor, Danielle; Gaede, Stewart; Yartsev, Slav; Bauman, Glenn; Louie, Alexander V.; Rodrigues, George

    2012-10-01

    Purpose: The goals of this study were to measure inter- and intrafraction setup error and prostate bed motion (PBM) in patients undergoing post-prostatectomy image-guided radiotherapy (IGRT) and to propose appropriate population-based three-dimensional clinical target volume to planning target volume (CTV-PTV) margins in both non-IGRT and IGRT scenarios. Methods and Materials: In this prospective study, 14 patients underwent adjuvant or salvage radiotherapy to the prostate bed under image guidance using linac-based kilovoltage cone-beam CT (kV-CBCT). Inter- and intrafraction uncertainty/motion was assessed by offline analysis of three consecutive daily kV-CBCT images of each patient: (1) after initial setup to skin marks, (2) after correction for positional error/immediately before radiation treatment, and (3) immediately after treatment. Results: The magnitude of interfraction PBM was 2.1 mm, and intrafraction PBM was 0.4 mm. The maximum inter- and intrafraction prostate bed motion was primarily in the anterior-posterior direction. Margins of at least 3-5 mm with IGRT and 4-7 mm without IGRT (aligning to skin marks) will ensure 95% of the prescribed dose to the clinical target volume in 90% of patients. Conclusions: PBM is a predominant source of intrafraction error compared with setup error and has implications for appropriate PTV margins. Based on inter- and estimated intrafraction motion of the prostate bed using pre- and post-kV-CBCT images, CBCT IGRT to correct for day-to-day variances can potentially reduce CTV-PTV margins by 1-2 mm. CTV-PTV margins for prostate bed treatment in the IGRT and non-IGRT scenarios are proposed; however, in cases with more uncertainty of target delineation and image guidance accuracy, larger margins are recommended.

  8. Dual source and dual detector arrays tetrahedron beam computed tomography for image guided radiotherapy

    NASA Astrophysics Data System (ADS)

    Kim, Joshua; Lu, Weiguo; Zhang, Tiezhi

    2014-02-01

    Cone-beam computed tomography (CBCT) is an important online imaging modality for image guided radiotherapy. But suboptimal image quality and the lack of a real-time stereoscopic imaging function limit its implementation in advanced treatment techniques, such as online adaptive and 4D radiotherapy. Tetrahedron beam computed tomography (TBCT) is a novel online imaging modality designed to improve on the image quality provided by CBCT. TBCT geometry is flexible, and multiple detector and source arrays can be used for different applications. In this paper, we describe a novel dual source-dual detector TBCT system that is specially designed for LINAC radiation treatment machines. The imaging system is positioned in-line with the MV beam and is composed of two linear array x-ray sources mounted aside the electrical portal imaging device and two linear arrays of x-ray detectors mounted below the machine head. The detector and x-ray source arrays are orthogonal to each other, and each pair of source and detector arrays forms a tetrahedral volume. Four planer images can be obtained from different view angles at each gantry position at a frame rate as high as 20 frames per second. The overlapped regions provide a stereoscopic field of view of approximately 10-15 cm. With a half gantry rotation, a volumetric CT image can be reconstructed having a 45 cm field of view. Due to the scatter rejecting design of the TBCT geometry, the system can potentially produce high quality 2D and 3D images with less radiation exposure. The design of the dual source-dual detector system is described, and preliminary results of studies performed on numerical phantoms and simulated patient data are presented.

  9. Image-guided radiotherapy for prostate cancer by CT-linear accelerator combination: Prostate movements and dosimetric considerations

    SciTech Connect

    Wong, James R.; Grimm, Lisa; Oren, Reva

    2005-02-01

    Purpose: Multiple studies have indicated that the prostate is not stationary and can move as much as 2 cm. Such prostate movements are problematic for intensity-modulated radiotherapy, with its associated tight margins and dose escalation. Because of these intrinsic daily uncertainties, a relative generous 'margin' is necessary to avoid marginal misses. Using the CT-linear accelerator combination in the treatment suite (Primatom, Siemens), we found that the daily intrinsic prostate movements can be easily corrected before each radiotherapy session. Dosimetric calculations were performed to evaluate the amount of discrepancy of dose to the target if no correction was done for prostate movement. Methods and materials: The Primatom consists of a Siemens Somatom CT scanner and a Siemens Primus linear accelerator installed in the same treatment suite and sharing a common table/couch. The patient is scanned by the CT scanner, which is movable on a pair of horizontal rails. During scanning, the couch does not move. The exact location of the prostate, seminal vesicles, and rectum are identified and localized. These positions are then compared with the planned positions. The daily movement of the prostate and rectum were corrected for and a new isocenter derived. The patient was treated immediately using the new isocenter. Results: Of the 108 patients with primary prostate cancer studied, 540 consecutive daily CT scans were performed during the last part of the cone down treatment. Of the 540 scans, 46% required no isocenter adjustments for the AP-PA direction, 54% required a shift of {>=}3 mm, 44% required a shift of >5 mm, and 15% required a shift of >10 mm. In the superoinferior direction, 27% required a shift of >3 mm, 25% required a shift of >5 mm, and 4% required a shift of >10 mm. In the right-left direction, 34% required a shift of >3 mm, 24% required a shift of >5 mm, and 5% required a shift of >10 mm. Dosimetric calculations for a typical case of prostate cancer

  10. Multi-System Verification of Registrations for Image-Guided Radiotherapy in Clinical Trials

    SciTech Connect

    Cui Yunfeng; Galvin, James M.; Straube, William L.; Bosch, Walter R.; Purdy, James A.; Li, X. Allen; Xiao Ying

    2011-09-01

    Purpose: To provide quantitative information on the image registration differences from multiple systems for image-guided radiotherapy (IGRT) credentialing and margin reduction in clinical trials. Methods and Materials: Images and IGRT shift results from three different treatment systems (Tomotherapy Hi-Art, Elekta Synergy, Varian Trilogy) have been sent from various institutions to the Image-Guided Therapy QA Center (ITC) for evaluation for the Radiation Therapy Oncology Group (RTOG) trials. Nine patient datasets (five head-and-neck and four prostate) were included in the comparison, with each patient having 1-4 daily individual IGRT studies. In all cases, daily shifts were re-calculated by re-registration of the planning CT with the daily IGRT data using three independent software systems (MIMvista, FocalSim, VelocityAI). Automatic fusion was used in all calculations. The results were compared with those submitted from institutions. Similar regions of interest (ROIs) and same initial positions were used in registrations for inter-system comparison. Different slice spacings for CBCT sampling and different ROIs for registration were used in some cases to observe the variation of registration due to these factors. Results: For the 54 comparisons with head-and-neck datasets, the absolute values of differences of the registration results between different systems were 2.6 {+-} 2.1 mm (mean {+-} SD; range 0.1-8.6 mm, left-right [LR]), 1.7 {+-} 1.3 mm (0.0-4.9 mm, superior-inferior [SI]), and 1.8 {+-} 1.1 mm (0.1-4.0 mm, anterior-posterior [AP]). For the 66 comparisons in prostate cases, the differences were 1.1 {+-} 1.0 mm (0.0-4.6 mm, LR), 2.1 {+-} 1.7 mm (0.0-6.6 mm, SI), and 2.0 {+-} 1.8 mm (0.1-6.9 mm, AP). The differences caused by the slice spacing variation were relatively small, and the different ROI selections in FocalSim and MIMvista also had limited impact. Conclusion: The extent of differences was reported when different systems were used for image

  11. Dose escalation for unresectable locally advanced non-small cell lung cancer: end of the line?

    PubMed

    Hong, Julian C; Salama, Joseph K

    2016-02-01

    Radiation Therapy Oncology Group (RTOG) 0617 was a randomized trial that investigated both the impact of radiation dose-escalation and the addition of cetuximab on the treatment of non-small cell lung cancer (NSCLC). The results of RTOG 0617 were surprising, with the dose escalation randomization being closed prematurely due to futility stopping rules, and cetuximab ultimately showing no overall survival benefit. Locally advanced unresectable NSCLC has conventionally been treated with concurrent chemoradiation. Though advances in treatment technology have improved the ability to deliver adequate treatment dose, the foundation for radiotherapy (RT) has remained the same since the 1980s. Since then, progressive studies have sought to establish the safety and efficacy of escalating radiation dose to loco-regional disease. Though RTOG 0617 did not produce the anticipated result, much interest remains in dose escalation and establishing an explanation for the findings of this study. Cetuximab was also not found to provide a survival benefit when applied to an unselected population. However, planned retrospective analysis suggests that those patients with high epidermal growth factor receptor (EGFR) expression may benefit, suggesting that cetuximab should be applied in a targeted fashion. We discuss the results of RTOG 0617 and additional findings from post-hoc analysis that suggest that dose escalation may be limited by normal tissue toxicity. We also present ongoing studies that aim to address potential causes for mortality in the dose escalation arm through adaptive or proton therapy, and are also leveraging additional concurrent systemic agents such as tyrosine kinase inhibitors (TKIs) for EGFR-activating mutations or EML4-ALK rearrangements, and poly (ADP-ribose) polymerase (PARP) inhibitors. PMID:26958507

  12. Inverse Relationship Between Biochemical Outcome and Acute Toxicity After Image-Guided Radiotherapy for Prostate Cancer

    SciTech Connect

    Vesprini, Danny; Catton, Charles; Jacks, Lindsay; Lockwood, Gina; Rosewall, Tara; Bayley, Andrew; Chung, Peter; Gospodarowicz, Mary; Menard, Cynthia; Milosevic, Michael; Nichol, Alan; Skala, Marketa; Warde, Padraig; Bristow, Robert G.

    2012-06-01

    Purpose: Prostate cancer patients exhibit variability in normal tissue reactions and biochemical failure. With the use of image-guided radiotherapy (IGRT), there is a greater likelihood that the differences in normal tissue and tumor response are due to biological rather than physical factors. We tested the hypothesis that prospectively scored acute toxicity is associated with biochemical failure-free rate (BFFR) in prostate cancer patients treated with IGRT. Methods and Materials: We retrospectively analyzed BFFR in 362 patients with localized prostate cancer treated with IGRT. We compared BFFR with prospectively collected Radiation Therapy Oncology Group (RTOG) maximum acute gastrointestinal (GI) and genitourinary (GU) toxicity scores. Median follow-up for all patients was 58.3 months after total radiotherapy doses of 75.6-79.8 Gy. Results: Patients reporting RTOG acute GU or GI toxicity scores of {>=}2 were considered 'sensitive' (n = 141, 39%) and patients reporting scores <2 were considered 'nonsensitive' (n = 221, 61%). When calculating biochemical failure (BF) using the American Society for Therapeutic Radiology and Oncology definition at 5 years, 76% (CI 70-82%) of the 'nonsensitive' patients were failure free, compared with only 53% (CI 43-62%) of the 'sensitive' patients (log-rank test, p < 0.0001). This difference was also observed using the Phoenix definition; 'nonsensitive' 5-year BFFR was 81% (CI 74-86%) vs. 'sensitive' BFFR was 68% (CI 58-76%; log-rank test p = 0.0012). The difference in BF between cohorts remained significant when controlled for radiation dose (75.6 vs. 79.8 Gy), prognostic stratification (T category, prostate-specific antigen, and Gleason score), and prostate volume. Conclusions: This study unexpectedly shows that prostate cancer patients who develop {>=}Grade 2 RTOG acute toxicity during radiotherapy are less likely to remain BFF at 5 years. These results deserve further study and, if validated in other large IGRT cohorts

  13. [18F]fluoroethylcholine-PET/CT imaging for radiation treatment planning of recurrent and primary prostate cancer with dose escalation to PET/CT-positive lymph nodes

    PubMed Central

    2011-01-01

    Background At present there is no consensus on irradiation treatment volumes for intermediate to high-risk primary cancers or recurrent disease. Conventional imaging modalities, such as CT, MRI and transrectal ultrasound, are considered suboptimal for treatment decisions. Choline-PET/CT might be considered as the imaging modality in radiooncology to select and delineate clinical target volumes extending the prostate gland or prostate fossa. In conjunction with intensity modulated radiotherapy (IMRT) and imaged guided radiotherapy (IGRT), it might offer the opportunity of dose escalation to selected sites while avoiding unnecessary irradiation of healthy tissues. Methods Twenty-six patients with primary (n = 7) or recurrent (n = 19) prostate cancer received Choline-PET/CT planned 3D conformal or intensity modulated radiotherapy. The median age of the patients was 65 yrs (range 45 to 78 yrs). PET/CT-scans with F18-fluoroethylcholine (FEC) were performed on a combined PET/CT-scanner equipped for radiation therapy planning. The majority of patients had intermediate to high risk prostate cancer. All patients received 3D conformal or intensity modulated and imaged guided radiotherapy with megavoltage cone beam CT. The median dose to primary tumours was 75.6 Gy and to FEC-positive recurrent lymph nodal sites 66,6 Gy. The median follow-up time was 28.8 months. Results The mean SUVmax in primary cancer was 5,97 in the prostate gland and 3,2 in pelvic lymph nodes. Patients with recurrent cancer had a mean SUVmax of 4,38. Two patients had negative PET/CT scans. At 28 months the overall survival rate is 94%. Biochemical relapse free survival is 83% for primary cancer and 49% for recurrent tumours. Distant disease free survival is 100% and 75% for primary and recurrent cancer, respectively. Acute normal tissue toxicity was mild in 85% and moderate (grade 2) in 15%. No or mild late side effects were observed in the majority of patients (84%). One patient had a severe bladder

  14. Toward efficient biomechanical-based deformable image registration of lungs for image-guided radiotherapy

    NASA Astrophysics Data System (ADS)

    Al-Mayah, Adil; Moseley, Joanne; Velec, Mike; Brock, Kristy

    2011-08-01

    Both accuracy and efficiency are critical for the implementation of biomechanical model-based deformable registration in clinical practice. The focus of this investigation is to evaluate the potential of improving the efficiency of the deformable image registration of the human lungs without loss of accuracy. Three-dimensional finite element models have been developed using image data of 14 lung cancer patients. Each model consists of two lungs, tumor and external body. Sliding of the lungs inside the chest cavity is modeled using a frictionless surface-based contact model. The effect of the type of element, finite deformation and elasticity on the accuracy and computing time is investigated. Linear and quadrilateral tetrahedral elements are used with linear and nonlinear geometric analysis. Two types of material properties are applied namely: elastic and hyperelastic. The accuracy of each of the four models is examined using a number of anatomical landmarks representing the vessels bifurcation points distributed across the lungs. The registration error is not significantly affected by the element type or linearity of analysis, with an average vector error of around 2.8 mm. The displacement differences between linear and nonlinear analysis methods are calculated for all lungs nodes and a maximum value of 3.6 mm is found in one of the nodes near the entrance of the bronchial tree into the lungs. The 95 percentile of displacement difference ranges between 0.4 and 0.8 mm. However, the time required for the analysis is reduced from 95 min in the quadratic elements nonlinear geometry model to 3.4 min in the linear element linear geometry model. Therefore using linear tetrahedral elements with linear elastic materials and linear geometry is preferable for modeling the breathing motion of lungs for image-guided radiotherapy applications.

  15. Radiation Dose From Kilovoltage Cone Beam Computed Tomography in an Image-Guided Radiotherapy Procedure

    SciTech Connect

    Ding, George X. Coffey, Charles W.

    2009-02-01

    Purpose: Image-guided radiation therapy has emerged as the new paradigm in radiotherapy. This work is to provide detailed information concerning the additional imaging doses to patients' radiosensitive organs from a kilovoltage cone beam computed tomography (kV CBCT) scan procedure. Methods and Materials: The Vanderbilt-Monte-Carlo-Beam-Calibration (VMCBC; Vanderbilt University, Nashville, TN) algorithm was used to calculate radiation dose to organs resulting from a kV CBCT imaging guidance procedure. Eight patients, including 3 pediatric and 5 adult patients, were investigated. The CBCT scans in both full- and half-fan modes were studied. Results: For a head-and-neck scan in half-fan mode, dose-volume histogram analyses show mean doses of 7 and 8 cGy to the eyes, 5 and 6 cGy to the spinal cord, 5 and 6 cGy to the brain, and 18 and 23 cGy to the cervical vertebrae for an adult and a 29-month-old child, respectively. The dose from a scan in full-fan mode is 10-20% lower than that in half-fan mode. For an abdominal scan, mean doses are 3 and 7 cGy to prostate and 7 and 17 cGy to femoral heads for a large adult patient and a 31-month-old pediatric patient, respectively. Conclusions: Doses to radiosensitive organs can total 300 cGy accrued over an entire treatment course if kV CBCT scans are acquired daily. These findings provide needed data for clinicians to make informed decisions concerning additional imaging doses. The dose to bone is two to four times greater than dose to soft tissue for kV x-rays, which should be considered, especially for pediatric patients.

  16. Target Coverage in Image-Guided Stereotactic Body Radiotherapy of Liver Tumors

    SciTech Connect

    Wunderink, Wouter . E-mail: w.wunderink@erasmusmc.nl; Romero, Alejandra Mendez; Osorio, Eliana M. Vasquez; Boer, Hans C.J. de; Brandwijk, Rene P.; Levendag, Peter C.; Heijmen, Ben

    2007-05-01

    Purpose: To determine the effect of image-guided procedures (with computed tomography [CT] and electronic portal images before each treatment fraction) on target coverage in stereotactic body radiotherapy for liver patients using a stereotactic body frame (SBF) and abdominal compression. CT guidance was used to correct for day-to-day variations in the tumor's mean position in the SBF. Methods and Materials: By retrospectively evaluating 57 treatment sessions, tumor coverage, as obtained with the clinically applied CT-guided protocol, was compared with that of alternative procedures. The internal target volume-plus (ITV{sup +}) was introduced to explicitly include uncertainties in tumor delineations resulting from CT-imaging artifacts caused by residual respiratory motion. Tumor coverage was defined as the volume overlap of the ITV{sup +}, derived from a tumor delineated in a treatment CT scan, and the planning target volume. Patient stability in the SBF, after acquisition of the treatment CT scan, was evaluated by measuring the displacement of the bony anatomy in the electronic portal images relative to CT. Results: Application of our clinical protocol (with setup corrections following from manual measurements of the distances between the contours of the planning target volume and the daily clinical target volume in three orthogonal planes, multiple two-dimensional) increased the frequency of nearly full ({>=}99%) ITV{sup +} coverage to 77% compared with 63% without setup correction. An automated three-dimensional method further improved the frequency to 96%. Patient displacements in the SBF were generally small ({<=}2 mm, 1 standard deviation), but large craniocaudal displacements (maximal 7.2 mm) were occasionally observed. Conclusion: Daily, CT-assisted patient setup may substantially improve tumor coverage, especially with the automated three-dimensional procedure. In the present treatment design, patient stability in the SBF should be verified with portal

  17. Investigation of Linac-Based Image-Guided Hypofractionated Prostate Radiotherapy

    SciTech Connect

    Pawlicki, Todd . E-mail: tpaw@stanford.edu; Kim, Gwe-Ya; Hsu, Annie; Cotrutz, Cristian; Boyer, Arthur L.; Xing Lei; King, Christopher R.; Luxton, Gary

    2007-07-01

    A hypofractionation treatment protocol for prostate cancer was initiated in our department in December 2003. The treatment regimen consists of a total dose of 36.25 Gy delivered at 7.25 Gy per fraction over 10 days. We discuss the rationale for such a prostate hypofractionation protocol and the need for frequent prostate imaging during treatment. The CyberKnife (Accuray Inc., Sunnyvale, CA), a linear accelerator mounted on a robotic arm, is currently being used as the radiation delivery device for this protocol, due to its incorporation of near real-time kV imaging of the prostate via 3 gold fiducial seeds. Recently introduced conventional linac kV imaging with intensity modulated planning and delivery may add a new option for these hypofractionated treatments. The purpose of this work is to investigate the use of intensity modulated radiotherapy (IMRT) and the Varian Trilogy Accelerator with on-board kV imaging (Varian Medical Systems Inc., Palo Alto, CA) for treatment of our hypofractionated prostate patients. The dose-volume histograms and dose statistics of 2 patients previously treated on the CyberKnife were compared to 7-field IMRT plans. A process of acquiring images to observe intrafraction prostate motion was achieved in an average time of about 1 minute and 40 seconds, and IMRT beam delivery takes about 40 seconds per field. A complete 7-field IMRT plan can therefore be imaged and delivered in 10 to 17 minutes. The Varian Trilogy Accelerator with on-board imaging and IMRT is well suited for image-guided hypofractionated prostate treatments. During this study, we have also uncovered opportunities for improvement of the on-board imaging hardware/software implementation that would further enhance performance in this regard.

  18. Markerless tumor tracking using short kilovoltage imaging arcs for lung image-guided radiotherapy

    NASA Astrophysics Data System (ADS)

    Shieh, Chun-Chien; Keall, Paul J.; Kuncic, Zdenka; Huang, Chen-Yu; Feain, Ilana

    2015-12-01

    The ability to monitor tumor motion without implanted markers is clinically advantageous for lung image-guided radiotherapy (IGRT). Existing markerless tracking methods often suffer from overlapping structures and low visibility of tumors on kV projection images. We introduce the short arc tumor tracking (SATT) method to overcome these issues. The proposed method utilizes multiple kV projection images selected from a nine-degree imaging arc to improve tumor localization, and respiratory-correlated 4D cone-beam CT (CBCT) prior knowledge to minimize the effects of overlapping anatomies. The 3D tumor position is solved as an optimization problem with prior knowledge incorporated via regularization. We retrospectively validated SATT on 11 clinical scans from four patients with central tumors. These patients represent challenging scenarios for markerless tumor tracking due to the inferior adjacent contrast. The 3D trajectories of implanted fiducial markers were used as the ground truth for tracking accuracy evaluation. In all cases, the tumors were successfully tracked at all gantry angles. Compared to standard pre-treatment CBCT guidance alone, trajectory errors were significantly smaller with tracking in all cases, and the improvements were the most prominent in the superior-inferior direction. The mean 3D tracking error ranged from 2.2-9.9 mm, which was 0.4-2.6 mm smaller compared to pre-treatment CBCT. In conclusion, we were able to directly track tumors with inferior visibility on kV projection images using SATT. Tumor localization accuracies are significantly better with tracking compared to the current standard of care of lung IGRT. Future work involves the prospective evaluation and clinical implementation of SATT.

  19. Role of Intra- or Periprostatic Calcifications in Image-Guided Radiotherapy for Prostate Cancer

    SciTech Connect

    Hanna, Samir Abdallah; Neves-Junior, Wellington Furtado Pimenta; Marta, Gustavo Nader; Haddad, Cecilia Maria Kalil; Fernandes da Silva, Joao Luis

    2012-03-01

    Purpose: Image-guided radiotherapy (IGRT) allows more precise localization of the prostate, thus minimizing errors resulting from organ motion and set-up during treatment of prostate cancer. Using megavoltage cone-beam computed tomography (MVCBCT), references such as bones, the prostate itself or implanted fiducial markers can be used as surrogates to correct patient positioning immediately before each treatment fraction. However, the use of fiducials requires an invasive procedure and may increase costs. We aimed to assess whether intra- or periprostatic calcifications (IPC) could be used as natural fiducials. Methods and Materials: Data on patients treated with IGRT for prostate cancer with clearly visible IPC and implanted fiducials in both planning CT and MVCBCT images were reviewed. IPC were classified as central when inside the prostate and peripheral when within the planning target volume. Daily deviations in lateral, longitudinal, and vertical directions from baseline positioning using fiducials and using IPC were compared. Results: A total of 287 MVCBCT images were obtained and analyzed from 10 patients. The mean {+-} standard deviation daily deviation (mm) in the lateral, longitudinal, and vertical coordinates were 0.55 {+-} 3.11, 0.58 {+-} 3.45, and -0.54 {+-} 4.03, respectively, for fiducials, and 0.72 {+-} 3.22, 0.63 {+-} 3.58, and -0.69 {+-} 4.26, for IPC. The p values for comparisons (fiducials vs. IPC) were 0.003, 0.653, and 0.078 for lateral, longitudinal, and vertical coordinates, respectively. When cases with central IPC were analyzed (n = 7), no significant difference was found in such comparisons. Central IPC and fiducials exhibited a similar pattern of displacement during treatment, with equal values for daily displacements in the three directions for more than 90% of measurements. Conclusions: Our data suggest that centrally located IPC may be used as natural fiducials for treatment positioning during IGRT for prostate cancer, with potential

  20. Image-Guided Radiotherapy in Near Real Time With Intensity-Modulated Radiotherapy Megavoltage Treatment Beam Imaging

    SciTech Connect

    Mao Weihua Hsu, Annie; Riaz, Nadeem; Lee, Louis; Wiersma, Rodney; Luxton, Gary; King, Christopher; Xing Lei; Solberg, Timothy

    2009-10-01

    Purpose: To utilize image-guided radiotherapy (IGRT) in near real time by obtaining and evaluating the online positions of implanted fiducials from continuous electronic portal imaging device (EPID) imaging of prostate intensity-modulated radiotherapy (IMRT) delivery. Methods and Materials: Upon initial setup using two orthogonal images, the three-dimensional (3D) positions of all implanted fiducial markers are obtained, and their expected two-dimensional (2D) locations in the beam's-eye-view (BEV) projection are calculated for each treatment field. During IMRT beam delivery, EPID images of the megavoltage treatment beam are acquired in cine mode and subsequently analyzed to locate 2D locations of fiducials in the BEV. Simultaneously, 3D positions are estimated according to the current EPID image, information from the setup portal images, and images acquired at other gantry angles (the completed treatment fields). The measured 2D and 3D positions of each fiducial are compared with their expected 2D and 3D setup positions, respectively. Any displacements larger than a predefined tolerance may cause the treatment system to suspend the beam delivery and direct the therapists to reposition the patient. Results: Phantom studies indicate that the accuracy of 2D BEV and 3D tracking are better than 1 mm and 1.4 mm, respectively. A total of 7330 images from prostate treatments were acquired and analyzed, showing a maximum 2D displacement of 6.7 mm and a maximum 3D displacement of 6.9 mm over 34 fractions. Conclusions: This EPID-based, real-time IGRT method can be implemented on any external beam machine with portal imaging capabilities without purchasing any additional equipment, and there is no extra dose delivered to the patient.

  1. Image-guided radiotherapy using a mobile kilovoltage x-ray device

    SciTech Connect

    Sorensen, Stephen P. . E-mail: tsolberg@unmc.edu; Chow, Phillip E.; Kriminski, Sergey; Medin, Paul M.; Solberg, Timothy D.

    2006-04-01

    Abstract-: A mobile isocentric C-arm kilovoltage imager has been evaluated as a potential tool for image-guided radiotherapy. The C-arm is equipped with an amorphous silicon flat panel for high-quality image acquisition. Additionally, the device is capable of cone beam computed tomography (CT) and volumetric reconstruction. This is achieved through the application of a modified Feldkamp algorithm with acquisition over a 180 deg. scan arc. The number of projections can be varied from 100 to 1000, resulting in a reconstructed volume 20 cm in diameter by 15-cm long. While acquisition time depends upon number of projections, acceptable quality images can be obtained in less than 60 seconds. Image resolution and contrast of cone-beam phantom images have been compared with images from a conventional CT scanner. The system has a spatial resolution of {>=} 10 lp/cm and resolution is approximately equal in all 3 dimensions. Conversely, subject contrast is poorer than conventional CT, compromised by the increased scatter and underlying noise inherent in cone beam reconstruction, as well as the absence of filtering prior to reconstruction. The mobility of the C-arm makes it necessary to determine the C-arm position relative to the linear accelerator isocenter. Two solutions have been investigated: (1) the use of fiducial markers, embedded in the linac couch, that can subsequently be registered in the image sets; and (2), a navigation approach for infrared tracking of the C-arm relative to the linac isocenter. Observed accuracy in phantom positioning ranged from 1.0 to 1.5 mm using the navigation approach and 1.5 to 2.5 mm using the fiducial-based approach. As part of this work, the impact of respiratory motion on cone-beam image quality was evaluated, and a scheme for retrospective gating was devised. Results demonstrated that kilovoltage cone beam CT provides spatial integrity and resolution comparable to conventional CT. Cone-beam CT studies of patients undergoing

  2. Individualized Tamoxifen Dose Escalation: Confirmation of Feasibility, Question of Utility.

    PubMed

    Hertz, Daniel L; Rae, James M

    2016-07-01

    Tamoxifen may require metabolic activation to endoxifen for efficacy in treating hormone receptor-positive breast cancer. Dose escalation in patients with low endoxifen concentrations could enhance treatment efficacy. This approach is clinically feasible, and successfully increases endoxifen concentrations; however, it is unknown whether patients benefit from individualized tamoxifen dose escalation. Clin Cancer Res; 22(13); 3121-3. ©2016 AACRSee related article by Fox et al., p. 3164. PMID:27012810

  3. Development of a Micro-Computed Tomography-Based Image-Guided Conformal Radiotherapy System for Small Animals

    SciTech Connect

    Zhou Hu; Rodriguez, Manuel; Haak, Fred van den; Nelson, Geoffrey; Jogani, Rahil

    2010-09-01

    Purpose: To report on the physical aspects of a system in which radiotherapy functionality was added to a micro-computed tomography (microCT) scanner, to evaluate the accuracy of this instrument, and to and demonstrate the application of this technology for irradiating tumors growing within the lungs of mice. Methods and Materials: A GE eXplore RS120 microCT scanner was modified by the addition of a two-dimensional subject translation stage and a variable aperture collimator. Quality assurance protocols for these devices, including measurement of translation stage positioning accuracy, collimator aperture accuracy, and collimator alignment with the X-ray beam, were devised. Use of this system for image-guided radiotherapy was assessed by irradiation of a solid water phantom as well as of two mice bearing spontaneous MYC-induced lung tumors. Radiation damage was assessed ex vivo by immunohistochemical detection of {gamma}H2AX foci. Results: The positioning error of the translation stage was found to be <0.05 mm, whereas after alignment of the collimator with the X-ray axis through adjustment of its displacement and rotation, the collimator aperture error was <0.1 mm measured at isocenter. Computed tomography image-guided treatment of a solid water phantom demonstrated target localization accuracy to within 0.1 mm. Gamma-H2AX foci were detected within irradiated lung tumors in mice, with contralateral lung tissue displaying background staining. Conclusions: Addition of radiotherapy functionality to a microCT scanner is an effective means of introducing image-guided radiation treatments into the preclinical setting. This approach has been shown to facilitate small-animal conformal radiotherapy while leveraging existing technology.

  4. Image-Guided Intensity-Modulated Photon Radiotherapy Using Multifractionated Regimen to Paraspinal Chordomas and Rare Sarcomas

    SciTech Connect

    Terezakis, Stephanie A. Lovelock, D. Michael; Bilsky, Mark H.; Hunt, Margaret A.; Zatcky, Joan N.P.; Yamada, Yoshiya

    2007-12-01

    Purpose: Image-guided intensity-modulated radiotherapy enables delivery of high-dose radiation to tumors close to the spinal cord. We report our experience with multifractionated regimens using image-guided intensity-modulated radiotherapy to treat gross paraspinal disease to doses beyond cord tolerance. Methods and Materials: We performed a retrospective review of 27 consecutive patients with partially resected or unresectable paraspinal tumors irradiated to >5,300 cGy in standard fractionation. Results: The median follow-up was 17.4 months (range, 2.1-47.3). Eighteen sarcomas, seven chordomas, and two ependymomas were treated. The median dose to the planning target volume was 6,600 cGy (range, 5,396-7,080) in 180- or 200-cGy fractions. The median planning target volume was 164 cm{sup 3} (range, 29-1,116). Seven patients developed recurrence at the treatment site (26%), and 6 of these patients had high-grade tumors. Three patients with recurrence had metastatic disease at the time of radiotherapy. The 2-year local control rate was 65%, and the 2-year overall survival rate was 79%. Of the 5 patients who died, 4 had metastatic disease at death. Twenty-three patients (84%) reported either no pain or improved pain at the last follow-up visit. Sixteen patients discontinued narcotic use after treatment (62.5%). Twenty-three patients (89%) had a stable or improved American Spine Injury Association score at the last follow-up visit. No patient experienced radiation-induced myelopathy. Conclusions: The dose to paraspinal tumors has traditionally been limited to respect cord tolerance. With image-guided intensity-modulated radiotherapy, greater doses of radiation delivered in multiple fractions can be prescribed with excellent target coverage, effective palliation, and acceptable toxicity and local control.

  5. Phantom validation of coregistration of PET and CT for image-guided radiotherapy.

    PubMed

    Lavely, William C; Scarfone, Christopher; Cevikalp, Hakan; Li, Rui; Byrne, Daniel W; Cmelak, Anthony J; Dawant, Benoit; Price, Ronald R; Hallahan, Dennis E; Fitzpatrick, J Michael

    2004-05-01

    /PET Fusion = 1.66 +/- 0.53 mm, AMIR = 1.15 +/- 0.48 mm. Precision (repeatability by a single user) measured for CT/PET Fusion: IAEA phantom = 1.59 +/- 0.67 mm and anthropomorphic head phantom = 1.63 +/- 0.52 mm. (AMIR has exact precision and so no measurements are necessary.) One sample patient demonstrated the following accuracy results: CT/PET Fusion = 3.89 +/- 1.61 mm, AMIR = 2.86 +/- 0.60 mm. Semi-automatic and automatic image registration methods may be used to facilitate incorporation of PET data into radiotherapy treatment planning in relatively rigid anatomic sites, such as head and neck. The overall accuracies in phantom and patient images are < 2 mm and < 4 mm, respectively, using either registration algorithm. Registration accuracy may decrease, however, as distance from the initial registration points (CT/PET fusion) or center of the image (AMIR) increases. Additional information provided by PET may improve dose coverage to active tumor subregions and hence tumor control. This study shows that the accuracy obtained by image registration with these two methods is well suited for image-guided radiotherapy. PMID:15191296

  6. A strategy to objectively evaluate the necessity of correcting detected target deviations in image guided radiotherapy

    SciTech Connect

    Yue, Ning J.; Kim, Sung; Jabbour, Salma; Narra, Venkat; Haffty, Bruce G.

    2007-11-15

    Image guided radiotherapy technologies are being increasingly utilized in the treatment of various cancers. These technologies have enhanced the ability to detect temporal and spatial deviations of the target volume relative to planned radiation beams. Correcting these detected deviations may, in principle, improve the accuracy of dose delivery to the target. However, in many situations, a clinical decision has to be made as to whether it is necessary to correct some of the deviations since the relevant dosimetric impact may or may not be significant, and the corresponding corrective action may be either impractical or time consuming. Ideally this decision should be based on objective and reproducible criteria rather than subjective judgment. In this study, a strategy is proposed for the objective evaluation of the necessity of deviation correction during the treatment verification process. At the treatment stage, without any alteration from the planned beams, the treatment beams should provide the desired dose coverage to the geometric volume identical to the planning target volume (PTV). Given this fact, the planned dose distribution and PTV geometry were used to compute the dose coverage and PTV enclosure of the clinical target volume (CTV) that was detected from imaging during the treatment setup verification. The spatial differences between the detected CTV and the planning CTV are essentially the target deviations. The extent of the PTV enclosure of the detected CTV as well as its dose coverage were used as criteria to evaluate the necessity of correcting any of the target deviations. This strategy, in principle, should be applicable to any type of target deviations, including both target deformable and positional changes and should be independent of how the deviations are detected. The proposed strategy was used on two clinical prostate cancer cases. In both cases, gold markers were implanted inside the prostate for the purpose of treatment setup

  7. Dose Escalation of Gemcitabine Is Possible With Concurrent Chest Three-Dimensional Rather Than Two-Dimensional Radiotherapy: A Phase I Trial in Patients With Stage III Non-Small-Cell Lung Cancer

    SciTech Connect

    Zinner, Ralph G. Cox, James D.; Glisson, Bonnie S.; Pisters, Katherine M.W.; Herbst, Roy S.; Kies, Merril; Hong, Waun K.; Fossella, Frank V.

    2009-01-01

    Purpose: To determine in a Phase I study the maximum tolerated dose of weekly gemcitabine concurrent with radiotherapy in locally advanced non-small-cell lung cancer (NSCLC), as well as the relationship between the volume of the esophagus irradiated and severe esophagitis. Methods and Materials: Twenty-one patients with Stage III NSCLC received gemcitabine initially at 150 mg/m{sup 2}/wk over 7 weeks concurrently with chest radiotherapy to 63 Gy in 34 fractions. The first 9 patients underwent treatment with two-dimensional (2D) radiotherapy; the remaining 12 patients, with three-dimensional conformal radiotherapy (3D-CRT) and target volume reduced to clinically apparent disease. Consolidation was 4 cycles of gemcitabine at 1000 mg/m{sup 2}/wk and cisplatin 60 mg/m{sup 2}. Results: In the 2D group, the dose-limiting toxicity, Grade 3 esophagitis, occurred in 3 of 6 patients in the 150-mg/m{sup 2}/wk cohort and 2 of 3 patients in the 125-mg/m{sup 2}/wk cohort. No cases of Grade 3 esophagitis occurred at these doses in the 3D group. At gemcitabine 190 mg/m{sup 2}/wk, 2 of 6 patients in the 3D cohort had Grade 3 esophagitis. The mean percentages of esophagus irradiated to 60 Gy were 68% in the 2D cohort and 18% in the 3D cohort. Conclusions: We could not escalate the dose of gemcitabine with concurrent radiotherapy when using 2D planning because of severe acute esophagitis. However, we could escalate the dose of gemcitabine to 190 mg/m{sup 2}/wk when using 3D planning. The Phase II dose is 150 mg/m{sup 2}/wk. Three-dimensional CRT permitted the use of higher doses of gemcitabine.

  8. Evaluation of volume change in rectum and bladder during application of image-guided radiotherapy for prostate carcinoma

    NASA Astrophysics Data System (ADS)

    Luna, J. A.; Rojas, J. I.

    2016-07-01

    All prostate cancer patients from Centro Médico Radioterapia Siglo XXI receive Volumetric Modulated Arc Therapy (VMAT). This therapy uses image-guided radiotherapy (IGRT) with the Cone Beam Computed Tomography (CBCT). This study compares the planned dose in the reference CT image against the delivered dose recalculate in the CBCT image. The purpose of this study is to evaluate the anatomic changes and related dosimetric effect based on weekly CBCT directly for patients with prostate cancer undergoing volumetric modulated arc therapy (VMAT) treatment. The collected data were analyzed using one-way ANOVA.

  9. Evaluation of different fiducial markers for image-guided radiotherapy and particle therapy.

    PubMed

    Habermehl, Daniel; Henkner, Katrin; Ecker, Swantje; Jäkel, Oliver; Debus, Jürgen; Combs, Stephanie E

    2013-07-01

    Modern radiotherapy (RT) techniques are widely used in the irradiation of moving organs. A crucial step in ensuring the correct position of a target structure directly before or during treatment is daily image guidance by computed tomography (CT) or X-ray radiography (image-guided radiotherapy, IGRT). Therefore, combinations of modern irradiation devices and imaging, such as on-board imaging (OBI) with X-rays, or in-room CT such as the tomotherapy system, have been developed. Moreover, combinations of linear accelerators and in-room CT-scanners have been designed. IGRT is of special interest in hypofractionated and radiosurgical treatments where high single doses are applied in the proximity of critical organs at risk. Radiographically visible markers in or in close proximity to the target structure may help to reproduce the position during RT and could therefore be used as external surrogates for motion monitoring. Criteria sought for fiducial markers are (i) visibility in the radiologic modalities involved in radiotherapeutic treatment planning and image guidance, such as CT and kilovoltage (kV) OBI), (ii) low production of imaging artifacts, and (iii) low perturbation of the therapeutic dose to the target volume. Photon interaction with interstitial markers has been shown to be not as important as in particle therapy, where interaction of the particle beam, especially with metal markers, can have a significant impact on treatment. This applies especially with a scanned ion beam. Recently we commenced patient recruitment at our institution within the PROMETHEUS trial, which evaluates a hypofractionation regime, starting with 4 x 10 Gy (RBE), for patients with hepatocellular carcinoma. The aim of this work is, therefore, to evaluate potential implantable fiducial markers for enabling precise patient and thus organ positioning in scanned ion beams. To transfer existing knowledge of marker application from photon to particle therapy, we used a range of commercially

  10. First Clinical Release of an Online, Adaptive, Aperture-Based Image-Guided Radiotherapy Strategy in Intensity-Modulated Radiotherapy to Correct for Inter- and Intrafractional Rotations of the Prostate

    SciTech Connect

    Deutschmann, Heinz; Kametriser, Gerhard; Steininger, Philipp; Scherer, Philipp; Schoeller, Helmut; Gaisberger, Christoph; Mooslechner, Michaela; Mitterlechner, Bernhard; Weichenberger, Harald; Fastner, Gert; Wurstbauer, Karl; Jeschke, Stephan; Forstner, Rosemarie; Sedlmayer, Felix

    2012-08-01

    adaptive image-guided, intensity-modulated prostate protocol on a standard linear accelerator to correct 6 degrees of freedom of internal organ motion, allowing safe and straightforward implementation of margin reduction and dose escalation.

  11. The management of imaging dose during image-guided radiotherapy: Report of the AAPM Task Group 75

    SciTech Connect

    Murphy, Martin J.; Balter, James; Balter, Stephen; BenComo, Jose A. Jr.; Das, Indra J.; Jiang, Steve B.; Ma, C.-M.; Olivera, Gustavo H.; Rodebaugh, Raymond F.; Ruchala, Kenneth J.; Shirato, Hiroki; Yin, Fang-Fang

    2007-10-15

    Radiographic image guidance has emerged as the new paradigm for patient positioning, target localization, and external beam alignment in radiotherapy. Although widely varied in modality and method, all radiographic guidance techniques have one thing in common--they can give a significant radiation dose to the patient. As with all medical uses of ionizing radiation, the general view is that this exposure should be carefully managed. The philosophy for dose management adopted by the diagnostic imaging community is summarized by the acronym ALARA, i.e., as low as reasonably achievable. But unlike the general situation with diagnostic imaging and image-guided surgery, image-guided radiotherapy (IGRT) adds the imaging dose to an already high level of therapeutic radiation. There is furthermore an interplay between increased imaging and improved therapeutic dose conformity that suggests the possibility of optimizing rather than simply minimizing the imaging dose. For this reason, the management of imaging dose during radiotherapy is a different problem than its management during routine diagnostic or image-guided surgical procedures. The imaging dose received as part of a radiotherapy treatment has long been regarded as negligible and thus has been quantified in a fairly loose manner. On the other hand, radiation oncologists examine the therapy dose distribution in minute detail. The introduction of more intensive imaging procedures for IGRT now obligates the clinician to evaluate therapeutic and imaging doses in a more balanced manner. This task group is charged with addressing the issue of radiation dose delivered via image guidance techniques during radiotherapy. The group has developed this charge into three objectives: (1) Compile an overview of image-guidance techniques and their associated radiation dose levels, to provide the clinician using a particular set of image guidance techniques with enough data to estimate the total diagnostic dose for a specific

  12. Evaluation of image guided motion management methods in lung cancer radiotherapy

    SciTech Connect

    Zhuang, Ling; Yan, Di; Liang, Jian; Ionascu, Dan; Mangona, Victor; Yang, Kai; Zhou, Jun

    2014-03-15

    Purpose: To evaluate the accuracy and reliability of three target localization methods for image guided motion management in lung cancer radiotherapy. Methods: Three online image localization methods, including (1) 2D method based on 2D cone beam (CB) projection images, (2) 3D method using 3D cone beam CT (CBCT) imaging, and (3) 4D method using 4D CBCT imaging, have been evaluated using a moving phantom controlled by (a) 1D theoretical breathing motion curves and (b) 3D target motion patterns obtained from daily treatment of 3 lung cancer patients. While all methods are able to provide target mean position (MP), the 2D and 4D methods can also provide target motion standard deviation (SD) and excursion (EX). For each method, the detected MP/SD/EX values are compared to the analytically calculated actual values to calculate the errors. The MP errors are compared among three methods and the SD/EX errors are compared between the 2D and 4D methods. In the theoretical motion study (a), the dependency of MP/SD/EX error on EX is investigated with EX varying from 2.0 cm to 3.0 cm with an increment step of 0.2 cm. In the patient motion study (b), the dependency of MP error on target sizes (2.0 cm and 3.0 cm), motion patterns (four motions per patient) and EX variations is investigated using multivariant linear regression analysis. Results: In the theoretical motion study (a), the MP detection errors are −0.2 ± 0.2, −1.5 ± 1.1, and −0.2 ± 0.2 mm for 2D, 3D, and 4D methods, respectively. Both the 2D and 4D methods could accurately detect motion pattern EX (error < 1.2 mm) and SD (error < 1.0 mm). In the patient motion study (b), MP detection error vector (mm) with the 2D method (0.7 ± 0.4) is found to be significantly less than with the 3D method (1.7 ± 0.8,p < 0.001) and the 4D method (1.4 ± 1.0, p < 0.001) using paired t-test. However, no significant difference is found between the 4D method and the 3D method. Based on multivariant linear regression analysis, the

  13. High-Dose, Single-Fraction Image-Guided Intensity-Modulated Radiotherapy for Metastatic Spinal Lesions

    SciTech Connect

    Yamada, Yoshiya Bilsky, Mark H.; Lovelock, D. Michael; Venkatraman, Ennapadam S.; Toner, Sean; Johnson, Jared; Zatcky, Joan N.P.; Zelefsky, Michael J.; Fuks, Zvi

    2008-06-01

    Purpose: To report tumor control and toxicity for patients treated with image-guided intensity-modulated radiotherapy (RT) for spinal metastases with high-dose single-fraction RT. Methods and Materials: A total of 103 consecutive spinal metastases in 93 patients without high-grade epidural spinal cord compression were treated with image-guided intensity-modulated RT to doses of 18-24 Gy (median, 24 Gy) in a single fraction between 2003 and 2006. The spinal cord dose was limited to a 14-Gy maximal dose. The patients were prospectively examined every 3-4 months with clinical assessment and cross-sectional imaging. Results: The overall actuarial local control rate was 90% (local failure developed in 7 patients) at a median follow-up of 15 months (range, 2-45 months). The median time to local failure was 9 months (range, 2-15 months) from the time of treatment. Of the 93 patients, 37 died. The median overall survival was 15 months. In all cases, death was from progression of systemic disease and not local failure. The histologic type was not a statistically significant predictor of survival or local control. The radiation dose was a significant predictor of local control (p = 0.03). All patients without local failure also reported durable symptom palliation. Acute toxicity was mild (Grade 1-2). No case of radiculopathy or myelopathy has developed. Conclusion: High-dose, single-fraction image-guided intensity-modulated RT is a noninvasive intervention that appears to be safe and very effective palliation for patients with spinal metastases, with minimal negative effects on quality of life and a high probability of tumor control.

  14. Development of a four-dimensional image-guided radiotherapy system with a gimbaled X-ray head

    SciTech Connect

    Kamino, Yuichiro . E-mail: daisaku_horiuchi@mhi.co.jp; Takayama, Kenji; Kokubo, Masaki; Narita, Yuichiro; Hirai, Etsuro; Kawawda, Noriyuki; Mizowaki, Takashi; Nagata, Yasushi; Nishidai, Takehiro; Hiraoka, Masahiro

    2006-09-01

    Purpose: To develop and evaluate a new four-dimensional image-guided radiotherapy system, which enables precise setup, real-time tumor tracking, and pursuit irradiation. Methods and Materials: The system has an innovative gimbaled X-ray head that enables small-angle ({+-}2.4{sup o}) rotations (pan and tilt) along the two orthogonal gimbals. This design provides for both accurate beam positioning at the isocenter by actively compensating for mechanical distortion and quick pursuit of the target. The X-ray head is composed of an ultralight C-band linear accelerator and a multileaf collimator. The gimbaled X-ray head is mounted on a rigid O-ring structure with an on-board imaging subsystem composed of two sets of kilovoltage X-ray tubes and flat panel detectors, which provides a pair of radiographs, cone beam computed tomography images useful for image guided setup, and real-time fluoroscopic monitoring for pursuit irradiation. Results: The root mean square accuracy of the static beam positioning was 0.1 mm for 360{sup o} of O-ring rotation. The dynamic beam response and positioning accuracy was {+-}0.6 mm for a 0.75 Hz, 40-mm stroke and {+-}0.4 mm for a 2.0 Hz, 8-mm stroke. The quality of the images was encouraging for using the tomography-based setup. Fluoroscopic images were sufficient for monitoring and tracking lung tumors. Conclusions: Key functions and capabilities of our new system are very promising for precise image-guided setup and for tracking and pursuit irradiation of a moving target.

  15. Can we avoid high levels of dose escalation for high-risk prostate cancer in the setting of androgen deprivation?

    PubMed Central

    Shakespeare, Thomas P; Wilcox, Shea W; Aherne, Noel J

    2016-01-01

    Aim Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve outcomes in patients with high-risk prostate cancer. However, there is little evidence specifically evaluating DE-EBRT for patients with high-risk prostate cancer receiving ADT, particularly for EBRT doses >74 Gy. We aimed to determine whether DE-EBRT >74 Gy improves outcomes for patients with high-risk prostate cancer receiving long-term ADT. Patients and methods Patients with high-risk prostate cancer were treated on an institutional protocol prescribing 3–6 months neoadjuvant ADT and DE-EBRT, followed by 2 years of adjuvant ADT. Between 2006 and 2012, EBRT doses were escalated from 74 Gy to 76 Gy and then to 78 Gy. We interrogated our electronic medical record to identify these patients and analyzed our results by comparing dose levels. Results In all, 479 patients were treated with a 68-month median follow-up. The 5-year biochemical disease-free survivals for the 74 Gy, 76 Gy, and 78 Gy groups were 87.8%, 86.9%, and 91.6%, respectively. The metastasis-free survivals were 95.5%, 94.5%, and 93.9%, respectively, and the prostate cancer-specific survivals were 100%, 94.4%, and 98.1%, respectively. Dose escalation had no impact on any outcome in either univariate or multivariate analysis. Conclusion There was no benefit of DE-EBRT >74 Gy in our cohort of high-risk prostate patients treated with long-term ADT. As dose escalation has higher risks of radiotherapy-induced toxicity, it may be feasible to omit dose escalation beyond 74 Gy in this group of patients. Randomized studies evaluating dose escalation for high-risk patients receiving ADT should be considered. PMID:27274277

  16. Dose escalation in brachytherapy for cervical cancer: impact on (or increased need for) MRI-guided plan optimisation

    PubMed Central

    Paton, A M; Chalmers, K E; Coomber, H; Cameron, A L

    2012-01-01

    Objective The aim of this study was to assess the impact of dose escalation on the proportion of patients requiring MR image-guided optimisation rather than standard Manchester-based CT-guided planning, and the level of escalation achievable. Methods 30 patients with cervical cancer treated with external beam radiotherapy and image-guided brachytherapy (IGBT) had MR images acquired at the first fraction of IGBT. Gross tumour volume and high-risk clinical target volume (HR CTV) were contoured and treatment plans retrospectively produced for a range of total 2-Gy equivalent (EQD2) prescription doses from 66 Gyα/β=10 to 90 Gyα/β=10 (HR CTV D90). Standard Manchester system-style plans were produced, prescribed to point A and then optimised where necessary with the aim of delivering at least the prescription dose to the HR CTV D90 while respecting organ-at-risk (OAR) tolerances. Results Increasing the total EQD2 from 66 Gyα/β=10 to 90 Gyα/β=10 increased the number of plans requiring optimisation from 13.3% to 90%. After optimisation, the number of plans achieving the prescription dose ranged from 93.3% (66 Gyα/β=10) to 63.3% (90 Gyα/β=10) with the mean±standard deviation for HR CTV D90 EQD2 from 78.4±12.4 Gyα/β=10 (66 Gyα/β=10) to 94.1±19.9 Gyα/β=10 (90 Gyα/β=10). Conclusion As doses are escalated, the need for non-standard optimised planning increases, while benefits in terms of increased target doses actually achieved diminish. The maximum achievable target dose is ultimately limited by proximity of OARs. Advances in knowledge This work represents a guide for other centres in determining the highest practicable prescription doses while considering patient throughput and maintaining acceptable OAR doses. PMID:23175490

  17. A Study of Image-Guided Intensity-Modulated Radiotherapy With Fiducials for Localized Prostate Cancer Including Pelvic Lymph Nodes

    SciTech Connect

    Hsu, Annie; Pawlicki, Todd; Luxton, Gary; Hara, Wendy; King, Christopher R. . E-mail: crking@stanford.edu

    2007-07-01

    Purpose: To study the impact on nodal coverage and dose to fixed organs at risk when using daily fiducial localization of the prostate to deliver intensity-modulated radiotherapy (IMRT). Methods and Materials: Five patients with prostate cancer in whom prostate and pelvic nodes were irradiated with IMRT were studied. Dose was prescribed such that 95% of the prostate planning target volume (PTV) and 90% of the nodal PTV were covered. Random and systematic prostate displacements in the anterior-posterior, superior-inferior, and left-right directions were simulated to shift the original isocenter of the IMRT plan. The composite dose during the course of treatment was calculated. Results: Compared with a static setup, simulating random shifts reduced dose by less than 1.5% for nodal hotspot (i.e., dose to 1 cm{sup 3}), by less than 1% for the 90% nodal PTV coverage, and by less than 0.5% for the nodal mean dose. Bowel and femoral head hotspots were reduced by less than 1.5% and 2%, respectively. A 10-mm systematic offset reduced nodal coverage by up to 10%. Conclusion: The use of prostate fiducials for daily localization during IMRT treatment results in negligible changes in dose coverage of pelvic nodes or normal tissue sparing in the absence of a significant systematic offset. This offers a simple and practical solution to the problem of image-guided radiotherapy for prostate cancer when including pelvic nodes.

  18. Use of the BrainLAB ExacTrac X-Ray 6D system in image-guided radiotherapy.

    PubMed

    Jin, Jian-Yue; Yin, Fang-Fang; Tenn, Stephen E; Medin, Paul M; Solberg, Timothy D

    2008-01-01

    The ExacTrac X-Ray 6D image-guided radiotherapy (IGRT) system will be described and its performance evaluated. The system is mainly an integration of 2 subsystems: (1) an infrared (IR)-based optical positioning system (ExacTrac) and (2) a radiographic kV x-ray imaging system (X-Ray 6D). The infrared system consists of 2 IR cameras, which are used to monitor reflective body markers placed on the patient's skin to assist in patient initial setup, and an IR reflective reference star, which is attached to the treatment couch and can assist in couch movement with spatial resolution to better than 0.3 mm. The radiographic kV devices consist of 2 oblique x-ray imagers to obtain high-quality radiographs for patient position verification and adjustment. The position verification is made by fusing the radiographs with the simulation CT images using either 3 degree-of-freedom (3D) or 6 degree-of-freedom (6D) fusion algorithms. The position adjustment is performed using the infrared system according to the verification results. The reliability of the fusion algorithm will be described based on phantom and patient studies. The results indicated that the 6D fusion method is better compared to the 3D method if there are rotational deviations between the simulation and setup positions. Recently, the system has been augmented with the capabilities for image-guided positioning of targets in motion due to respiration and for gated treatment of those targets. The infrared markers provide a respiratory signal for tracking and gating of the treatment beam, with the x-ray system providing periodic confirmation of patient position relative to the gating window throughout the duration of the gated delivery. PMID:18456164

  19. Use of the BrainLAB ExacTrac X-Ray 6D System in Image-Guided Radiotherapy

    SciTech Connect

    Jin, J.-Y. Yin Fangfang; Tenn, Stephen E.; Medin, Paul M.; Solberg, Timothy D.

    2008-07-01

    The ExacTrac X-Ray 6D image-guided radiotherapy (IGRT) system will be described and its performance evaluated. The system is mainly an integration of 2 subsystems: (1) an infrared (IR)-based optical positioning system (ExacTrac) and (2) a radiographic kV x-ray imaging system (X-Ray 6D). The infrared system consists of 2 IR cameras, which are used to monitor reflective body markers placed on the patient's skin to assist in patient initial setup, and an IR reflective reference star, which is attached to the treatment couch and can assist in couch movement with spatial resolution to better than 0.3 mm. The radiographic kV devices consist of 2 oblique x-ray imagers to obtain high-quality radiographs for patient position verification and adjustment. The position verification is made by fusing the radiographs with the simulation CT images using either 3 degree-of-freedom (3D) or 6 degree-of-freedom (6D) fusion algorithms. The position adjustment is performed using the infrared system according to the verification results. The reliability of the fusion algorithm will be described based on phantom and patient studies. The results indicated that the 6D fusion method is better compared to the 3D method if there are rotational deviations between the simulation and setup positions. Recently, the system has been augmented with the capabilities for image-guided positioning of targets in motion due to respiration and for gated treatment of those targets. The infrared markers provide a respiratory signal for tracking and gating of the treatment beam, with the x-ray system providing periodic confirmation of patient position relative to the gating window throughout the duration of the gated delivery.

  20. Image-guided stereotactic radiotherapy in 4 dogs with intracranial neoplasia.

    PubMed

    Moon, Alaina Burkard; Heller, Heidi Barnes; Forrest, Lisa

    2016-05-01

    The purpose of this study was to describe the use, and side effects, of a novel stereotactic radiotherapy protocol using TomoTherapy(®) in 4 dogs with confirmed or suspected primary extra-axial intracranial neoplasia. Three fractions of 8 Gy were prescribed. Acute side effects were noted in 1 dog; no late effects were noted. PMID:27152041

  1. Targeting accuracy of an image guided gating system for stereotactic body radiotherapy

    NASA Astrophysics Data System (ADS)

    Tenn, Stephen E.; Solberg, Timothy D.; Medin, Paul M.

    2005-12-01

    Recently, a commercial system capable of x-ray image guided patient positioning and respiratory gated delivery has become available. Here we describe the operational principles of this system and investigate its geometric targeting accuracy under controlled conditions. The system tracks breathing via infrared (IR) detection of reflective markers located on the patient's abdomen. Localization kilovoltage (kV) x-rays are triggered from within the gated delivery window portion of the breathing trace and after positioning, the tumour will cross the linac isocentre during gated delivery. We tested geometric accuracy of this system by localizing and delivering gated fields to a moving phantom. Effects of phantom speed, gating window location, timing errors and phantom rotations on positioning and gating accuracy were investigated. The system delivered gated fields to both a moving and static phantom with equal accuracy. The position of the gating window affects accuracy only to the extent that an asymmetric breathing motion could affect dose distribution within its boundaries. Positioning errors were found to be less then 0.5 ± 0.2 mm for phantom rotations up to 5°. We found and corrected a synchronization error caused by a faulty x-ray duration setting and detected a 60 ± 20 ms time delay in our linear accelerator.

  2. Strategies of dose escalation in the treatment of locally advanced non-small cell lung cancer: image guidance and beyond.

    PubMed

    Chi, Alexander; Nguyen, Nam Phong; Welsh, James S; Tse, William; Monga, Manish; Oduntan, Olusola; Almubarak, Mohammed; Rogers, John; Remick, Scot C; Gius, David

    2014-01-01

    Radiation dose in the setting of chemo-radiation for locally advanced non-small cell lung cancer (NSCLC) has been historically limited by the risk of normal tissue toxicity and this has been hypothesized to correlate with the poor results in regard to local tumor recurrences. Dose escalation, as a means to improve local control, with concurrent chemotherapy has been shown to be feasible with three-dimensional conformal radiotherapy in early phase studies with good clinical outcome. However, the potential superiority of moderate dose escalation to 74 Gy has not been shown in phase III randomized studies. In this review, the limitations in target volume definition in previous studies; and the factors that may be critical to safe dose escalation in the treatment of locally advanced NSCLC, such as respiratory motion management, image guidance, intensity modulation, FDG-positron emission tomography incorporation in the treatment planning process, and adaptive radiotherapy, are discussed. These factors, along with novel treatment approaches that have emerged in recent years, are proposed to warrant further investigation in future trials in a more comprehensive and integrated fashion. PMID:24999451

  3. Pelvic Nodal Radiotherapy in Patients With Unfavorable Intermediate and High-Risk Prostate Cancer: Evidence, Rationale, and Future Directions

    SciTech Connect

    Morikawa, Lisa K.; Roach, Mack

    2011-05-01

    Over the past 15 years, there have been three major advances in the use of external beam radiotherapy in the management of men with clinically localized prostate made. They include: (1) image guided (IG) three-dimensional conformal/intensity modulated radiotherapy; (2) radiation dose escalation; and (3) androgen deprivation therapy. To date only the last of these three advances have been shown to improve overall survival. The presence of occult pelvic nodal involvement could explain the failure of increased conformality and dose escalation to prolong survival, because the men who appear to be at the greatest risk of death from clinically localized prostate cancer are those who are likely to have lymph node metastases. This review discusses the evidence for prophylactic pelvic nodal radiotherapy, including the key trials and controversies surrounding this issue.

  4. Comparison of Spine, Carina, and Tumor as Registration Landmarks for Volumetric Image-Guided Lung Radiotherapy

    SciTech Connect

    Higgins, Jane Bezjak, Andrea; Franks, Kevin; Le, Lisa W.; Cho, B.C.; Payne, David; Bissonnette, Jean-Pierre

    2009-04-01

    Purpose: To assess the feasibility, reproducibility, and accuracy of volumetric lung image guidance using different thoracic landmarks for image registration. Methods and Materials: In 30 lung patients, four independent observers conducted automated and manual image registrations on Day 1 cone-beam computed tomography data sets using the spine, carina, and tumor (720 image registrations). The image registration was timed, and the couch displacements were recorded. The intraclass correlation was used to assess reproducibility, and the Bland-Altman analysis was used to compare the automatic and manual matching methods. Tumor coverage (accuracy) was assessed through grading the tumor position after image matching against the internal target volume and planning target volume. Results: The image-guided process took an average of 1 min for all techniques, with the exception of manual tumor matching, which took 4 min. Reproducibility was greatest for automatic carina matching (intraclass correlation, 0.90-0.93) and lowest for manual tumor matching (intraclass correlation, 0.07-0.43) in the left-right, superoinferior, and anteroposterior directions, respectively. The Bland-Altman analysis showed no significant difference between the automatic and manual registration methods. The tumor was within the internal target volume 62% and 60% of the time and was outside the internal target volume, but within the planning target volume, 38% and 40% of the time after automatic spine and automatic carina matching, respectively. Conclusion: For advanced lung cancer, the spine or carina can be used equally for cone-beam computed tomography image registration without compromising target coverage. The carina was more reproducible than the spine, but additional analysis is required to confirm its validation as a tumor surrogate. Soft-tissue registration is unsuitable at present, given the limitations in contrast resolution and the high interobserver variability.

  5. Prostate Radiotherapy in the Era of Advanced Imaging and Precision Medicine

    PubMed Central

    Dulaney, Caleb R.; Osula, Daniel O.; Yang, Eddy S.; Rais-Bahrami, Soroush

    2016-01-01

    Tremendous technological advancements in prostate radiotherapy have decreased treatment toxicity and improved clinical outcomes for men with prostate cancer. While these advances have allowed for significant treatment volume reduction and whole-organ dose escalation, further improvement in prostate radiotherapy has been limited by classic techniques for diagnosis and risk stratification. Developments in prostate imaging, image-guided targeted biopsy, next-generation gene expression profiling, and targeted molecular therapies now provide information to stratify patients and select treatments based on tumor biology. Image-guided targeted biopsy improves detection of clinically significant cases of prostate cancer and provides important information about the biological behavior of intraprostatic lesions which can further guide treatment decisions. We review the evolution of prostate magnetic resonance imaging (MRI) and MRI-ultrasound fusion-guided prostate biopsy. Recent advancements in radiation therapy including dose escalation, moderate and extreme hypofractionation, partial prostate radiation therapy, and finally dose escalation by simultaneous integrated boost are discussed. We also review next-generation sequencing and discuss developments in targeted molecular therapies. Last, we review ongoing clinical trials and future treatment paradigms that integrate targeted biopsy, molecular profiling and therapy, and prostate radiotherapy. PMID:27022486

  6. Prostate Radiotherapy in the Era of Advanced Imaging and Precision Medicine.

    PubMed

    Dulaney, Caleb R; Osula, Daniel O; Yang, Eddy S; Rais-Bahrami, Soroush

    2016-01-01

    Tremendous technological advancements in prostate radiotherapy have decreased treatment toxicity and improved clinical outcomes for men with prostate cancer. While these advances have allowed for significant treatment volume reduction and whole-organ dose escalation, further improvement in prostate radiotherapy has been limited by classic techniques for diagnosis and risk stratification. Developments in prostate imaging, image-guided targeted biopsy, next-generation gene expression profiling, and targeted molecular therapies now provide information to stratify patients and select treatments based on tumor biology. Image-guided targeted biopsy improves detection of clinically significant cases of prostate cancer and provides important information about the biological behavior of intraprostatic lesions which can further guide treatment decisions. We review the evolution of prostate magnetic resonance imaging (MRI) and MRI-ultrasound fusion-guided prostate biopsy. Recent advancements in radiation therapy including dose escalation, moderate and extreme hypofractionation, partial prostate radiation therapy, and finally dose escalation by simultaneous integrated boost are discussed. We also review next-generation sequencing and discuss developments in targeted molecular therapies. Last, we review ongoing clinical trials and future treatment paradigms that integrate targeted biopsy, molecular profiling and therapy, and prostate radiotherapy. PMID:27022486

  7. Image-guided adaptive radiotherapy for prostate and head-and-neck cancers

    NASA Astrophysics Data System (ADS)

    O'Daniel, Jennifer C.

    In the current practice of radiation therapy, daily patient alignments have been based on external skin marks or on bone. However, internal organ variation (both motion and volumetric changes) between treatment fractions can displace the treatment target, causing target underdosage and normal tissue overdosage. In order to deliver the radiation treatment as planned, more accurate knowledge of the daily internal anatomy was needed. Additionally, treatments needed to adapt to these variations by either shifting the patient to account for the daily target position or by altering the treatment plan. In this dissertation, the question of whether inter-fractional variations in internal patient anatomy combined with external set-up uncertainties produced measurable differences between planned and delivered doses for prostate and head-and-neck cancer patients was investigated. Image-guided adaptive treatment strategies to improve tumor coverage and/or reduce normal tissue dose were examined. Treatment deliveries utilizing various alignment procedures for ten prostate cancer patients and eleven head-and-neck cancer patients, each of whom received multiple CT scans over the course of treatment, were simulated. The largest prostate dose losses between planning and delivery were correlated with anterior/posterior and superior/inferior prostate displacement. Daily bone alignment sufficiently maintained target coverage for 70% of patients, ultrasound for 90%, and CT for 100%. A no-action-level correction protocol, which corrected the daily bone alignment for the systematic internal displacement of the prostate based on a pre-determined number of CT image sets, successfully improved the prostate and seminal vesicle dosimetric coverage. Three CT image sets were sufficient to accurately correct the bone alignment scheme for the prostate internal systematic shifts. For head-and-neck cancer patient treatment, setup uncertainties and internal organ variations did not greatly affect

  8. Geometric-model-based segmentation of the prostate and surrounding structures for image-guided radiotherapy

    NASA Astrophysics Data System (ADS)

    Tang, Xiaoli; Jeong, Yongwon; Radke, Richard J.; Chen, George T. Y.

    2004-01-01

    We present a computer vision tool to improve the clinical outcome of patients undergoing radiation therapy for prostate cancer by improving irradiation technique. While intensity modulated radiotherapy (IMRT) allows one to irradiate a specific region in the body with high accuracy, it is still difficult to know exactly where to aim the radiation beam on every day of the 30~40 treatments that are necessary. This paper presents a geometric model-based technique to accurately segment the prostate and other surrounding structures in a daily serial CT image, compensating for daily motion and shape variation. We first acquire a collection of serial CT scans of patients undergoing external beam radiotherapy, and manual segmentation of the prostate and other nearby structures by radiation oncologists. Then we train shape and local appearance models for the structures of interest. When new images are available, an iterative algorithm is applied to locate the prostate and surrounding structures automatically. Our experimental results show that excellent matches can be given to the prostate and surrounding structure. Convergence is declared after 10 iterations. For 256 x 256 images, the mean distance between the hand-segmented contour and the automatically estimated contour is about 1.5 pixels (2.44 mm), with variance about 0.6 pixel (1.24 mm).

  9. Medical applications of fast 3D cameras in real-time image-guided radiotherapy (IGRT) of cancer

    NASA Astrophysics Data System (ADS)

    Li, Shidong; Li, Tuotuo; Geng, Jason

    2013-03-01

    Dynamic volumetric medical imaging (4DMI) has reduced motion artifacts, increased early diagnosis of small mobile tumors, and improved target definition for treatment planning. High speed cameras for video, X-ray, or other forms of sequential imaging allow a live tracking of external or internal movement useful for real-time image-guided radiation therapy (IGRT). However, none of 4DMI can track real-time organ motion and no camera has correlated with 4DMI to show volumetric changes. With a brief review of various IGRT techniques, we propose a fast 3D camera for live-video stereovision, an automatic surface-motion identifier to classify body or respiratory motion, a mechanical model for synchronizing the external surface movement with the internal target displacement by combination use of the real-time stereovision and pre-treatment 4DMI, and dynamic multi-leaf collimation for adaptive aiming the moving target. Our preliminary results demonstrate that the technique is feasible and efficient in IGRT of mobile targets. A clinical trial has been initiated for validation of its spatial and temporal accuracies and dosimetric impact for intensity-modulated RT (IMRT), volumetric-modulated arc therapy (VMAT), and stereotactic body radiotherapy (SBRT) of any mobile tumors. The technique can be extended for surface-guided stereotactic needle insertion in biopsy of small lung nodules.

  10. MR-CT registration using a Ni-Ti prostate stent in image-guided radiotherapy of prostate cancer

    SciTech Connect

    Korsager, Anne Sofie; Ostergaard, Lasse Riis; Carl, Jesper

    2013-06-15

    Purpose: In image-guided radiotherapy of prostate cancer defining the clinical target volume often relies on magnetic resonance (MR). The task of transferring the clinical target volume from MR to standard planning computed tomography (CT) is not trivial due to prostate mobility. In this paper, an automatic local registration approach is proposed based on a newly developed removable Ni-Ti prostate stent.Methods: The registration uses the voxel similarity measure mutual information in a two-step approach where the pelvic bones are used to establish an initial registration for the local registration.Results: In a phantom study, the accuracy was measured to 0.97 mm and visual inspection showed accurate registration of all 30 data sets. The consistency of the registration was examined where translation and rotation displacements yield a rotation error of 0.41 Degree-Sign {+-} 0.45 Degree-Sign and a translation error of 1.67 {+-} 2.24 mm.Conclusions: This study demonstrated the feasibility for an automatic local MR-CT registration using the prostate stent.

  11. Magnitude of speed of sound aberration corrections for ultrasound image guided radiotherapy for prostate and other anatomical sites

    SciTech Connect

    Fontanarosa, Davide; Meer, Skadi van der; Bloemen-van Gurp, Esther; Stroian, Gabriela; Verhaegen, Frank

    2012-08-15

    Purpose: The purpose of this work is to assess the magnitude of speed of sound (SOS) aberrations in three-dimensional ultrasound (US) imaging systems in image guided radiotherapy. The discrepancy between the fixed SOS value of 1540 m/s assumed by US systems in human soft tissues and its actual nonhomogeneous distribution in patients produces small but systematic errors of up to a few millimeters in the positions of scanned structures. Methods: A correction, provided by a previously published density-based algorithm, was applied to a set of five prostate, five liver, and five breast cancer patients. The shifts of the centroids of target structures and the change in shape were evaluated. Results: After the correction the prostate cases showed shifts up to 3.6 mm toward the US probe, which may explain largely the reported positioning discrepancies in the literature on US systems versus other imaging modalities. Liver cases showed the largest changes in volume of the organ, up to almost 9%, and shifts of the centroids up to more than 6 mm either away or toward the US probe. Breast images showed systematic small shifts of the centroids toward the US probe with a maximum magnitude of 1.3 mm. Conclusions: The applied correction in prostate and liver cancer patients shows positioning errors of several mm due to SOS aberration; the errors are smaller in breast cancer cases, but possibly becoming more important when breast tissue thickness increases.

  12. Image-guided radiotherapy of the prostate using daily CBCT: the feasibility and likely benefit of implementing a margin reduction

    PubMed Central

    Benson, R J; Fairfoul, J; Cook, J; Huddart, R; Poynter, A

    2014-01-01

    Objective: To investigate whether planning target volume (PTV) margins may be safely reduced in radiotherapy of localized prostate cancer incorporating daily online tube potential-cone beam CT (CBCT) image guidance and the anticipated benefit in predicted rectal toxicity. Methods: The prostate-only clinical target volume (CTV2) and rectum were delineated on 1 pre-treatment CBCT each week in 18 randomly selected patients. By transposing these contours onto the original plan, dose–volume histograms (DVHs) for CTV2 and the rectum were each calculated and combined, for each patient, to produce a single mean DVH representative of the dose delivered over the treatment course. Plans were reoptimized using reduced CTV2 to PTV2 margins and the consequent radiobiological impact modelled by the tumour control probability (TCP) and normal tissue complication probability (NTCP) of the rectum. Results: All CBCT images were deemed of sufficient quality to identify the CTV and rectum. No loss of TCP was observed when plans using the standard 5-mm CTV2 to PTV2 margin of the centre were reoptimized with a 4- or 3-mm margin. Margin reduction was associated with a significant decrease in rectal NTCP (5–4 mm; p < 0.05 and 5–3 mm; p < 0.01). Conclusion: Using daily online image guidance with CBCT, a reduction in CTV2 to PTV2 margins to 3 mm is achievable without compromising tumour control. The consequent sparing of surrounding normal tissues is associated with reduced anticipated rectal toxicity. Advances in knowledge: Margin reduction is feasible and potentially beneficial. Centres with image-guided radiotherapy capability should consider assessing whether margin reduction is possible within their institutes. PMID:25354015

  13. Improvement in toxicity in high risk prostate cancer patients treated with image-guided intensity-modulated radiotherapy compared to 3D conformal radiotherapy without daily image guidance

    PubMed Central

    2014-01-01

    Background Image-guided radiotherapy (IGRT) facilitates the delivery of a very precise radiation dose. In this study we compare the toxicity and biochemical progression-free survival between patients treated with daily image-guided intensity-modulated radiotherapy (IG-IMRT) and 3D conformal radiotherapy (3DCRT) without daily image guidance for high risk prostate cancer (PCa). Methods A total of 503 high risk PCa patients treated with radiotherapy (RT) and endocrine treatment between 2000 and 2010 were retrospectively reviewed. 115 patients were treated with 3DCRT, and 388 patients were treated with IG-IMRT. 3DCRT patients were treated to 76 Gy and without daily image guidance and with 1–2 cm PTV margins. IG-IMRT patients were treated to 78 Gy based on daily image guidance of fiducial markers, and the PTV margins were 5–7 mm. Furthermore, the dose-volume constraints to both the rectum and bladder were changed with the introduction of IG-IMRT. Results The 2-year actuarial likelihood of developing grade > = 2 GI toxicity following RT was 57.3% in 3DCRT patients and 5.8% in IG-IMRT patients (p < 0.001). For GU toxicity the numbers were 41.8% and 29.7%, respectively (p = 0.011). On multivariate analysis, 3DCRT was associated with a significantly increased risk of developing grade > = 2 GI toxicity compared to IG-IMRT (p < 0.001, HR = 11.59 [CI: 6.67-20.14]). 3DCRT was also associated with an increased risk of developing GU toxicity compared to IG-IMRT. The 3-year actuarial biochemical progression-free survival probability was 86.0% for 3DCRT and 90.3% for IG-IMRT (p = 0.386). On multivariate analysis there was no difference in biochemical progression-free survival between 3DCRT and IG-IMRT. Conclusion The difference in toxicity can be attributed to the combination of the IMRT technique with reduced dose to organs-at-risk, daily image guidance and margin reduction. PMID:24495815

  14. Daily targeting of liver tumors: Screening patients with a mock treatment and using a combination of internal and external fiducials for image-guided respiratory-gated radiotherapy

    SciTech Connect

    Krishnan, Sunil; Briere, Tina Marie; Dong Lei; Murthy, Ravi; Ng, Chaan; Balter, Peter; Mohan, Radhe; Gillin, Michael T.; Beddar, A. Sam

    2007-12-15

    The feasibility and accuracy of using a mock treatment to screen suitable patients for respiratory-gated image-guided radiotherapy was investigated. Radio-opaque fiducials implanted adjacent to the liver tumor were used for online positioning to minimize the systematic error in patient positioning. The consistency in the degree of correlation between the external and internal fiducials was analyzed during a mock treatment. This technique could screen patients for gated therapy, reduce setup inaccuracy, and possibly individualize treatment margins.

  15. Robotic Image-Guided Stereotactic Radiotherapy, for Isolated Recurrent Primary, Lymph Node or Metastatic Prostate Cancer

    SciTech Connect

    Jereczek-Fossa, Barbara Alicja; Beltramo, Giancarlo; Fariselli, Laura; Fodor, Cristiana; Santoro, Luigi; Vavassori, Andrea; Zerini, Dario; Gherardi, Federica; Ascione, Carmen; Bossi-Zanetti, Isa; Mauro, Roberta; Bregantin, Achille; Bianchi, Livia Corinna; De Cobelli, Ottavio; Orecchia, Roberto

    2012-02-01

    Purpose: To evaluate the outcome of robotic CyberKnife (Accuray, Sunnyvale, CA)-based stereotactic radiotherapy (CBK-SRT) for isolated recurrent primary, lymph node, or metastatic prostate cancer. Methods and Materials: Between May 2007 and December 2009, 34 consecutive patients/38 lesions were treated (15 patients reirradiated for local recurrence [P], 4 patients reirradiated for anastomosis recurrence [A], 16 patients treated for single lymph node recurrence [LN], and 3 patients treated for single metastasis [M]). In all but 4 patients, [{sup 11}C]choline positron emission tomography/computed tomography was performed. CBK-SRT consisted of reirradiation and first radiotherapy in 27 and 11 lesions, respectively. The median CBK-SRT dose was 30 Gy in 4.5 fractions (P, 30 Gy in 5 fractions; A, 30 Gy in 5 fractions; LN, 33 Gy in 3 fractions; and M, 36 Gy in 3 fractions). In 18 patients (21 lesions) androgen deprivation was added to CBK-SRT (median duration, 16.6 months). Results: The median follow-up was 16.9 months. Acute toxicity included urinary events (3 Grade 1, 2 Grade 2, and 2 Grade 3 events) and rectal events (1 Grade 1 event). Late toxicity included urinary events (3 Grade 1, 2 Grade 2, and 2 Grade 3 events) and rectal events (1 Grade 1 event and 1 Grade 2 event). Biochemical response was observed in 32 of 38 evaluable lesions. Prostate-specific antigen stabilization was seen for 4 lesions, and in 2 cases prostate-specific antigen progression was reported. The 30-month progression-free survival rate was 42.6%. Disease progression was observed for 14 lesions (5, 2, 5, and 2 in Groups P, A, LN, and M respectively). In only 3 cases, in-field progression was seen. At the time of analysis (May 2010), 19 patients are alive with no evidence of disease and 15 are alive with disease. Conclusions: CyberKnife-based stereotactic radiotherapy is a feasible approach for isolated recurrent primary, lymph node, or metastatic prostate cancer, offering excellent in-field tumor

  16. Phase II Trial of Hypofractionated Image-Guided Intensity-Modulated Radiotherapy for Localized Prostate Adenocarcinoma

    SciTech Connect

    Martin, Jarad M.; Rosewall, Tara; Bayley, Andrew; Bristow, Robert; Chung, Peter; Crook, Juanita; Gospodarowicz, Mary; McLean, Michael; Menard, Cynthia; Milosevic, Michael; Warde, Padraig; Catton, Charles

    2007-11-15

    Purpose: To assess in a prospective trial the feasibility and late toxicity of hypofractionated radiotherapy (RT) for prostate cancer. Methods and Materials: Eligible patients had clinical stage T1c-2cNXM0 disease. They received 60 Gy in 20 fractions over 4 weeks with intensity-modulated radiotherapy including daily on-line image guidance with intraprostatic fiducial markers. Results: Between June 2001 and March 2004, 92 patients were treated with hypofractionated RT. The cohort had a median prostate-specific antigen value of 7.06 ng/mL. The majority had Gleason grade 5-6 (38%) or 7 (59%) disease, and 82 patients had T1c-T2a clinical staging. Overall, 29 patients had low-risk, 56 intermediate-risk, and 7 high-risk disease. Severe acute toxicity (Grade 3-4) was rare, occurring in only 1 patient. Median follow-up was 38 months. According to the Phoenix definition for biochemical failure, the rate of biochemical control at 14 months was 97%. According to the previous American Society for Therapeutic Radiology and Oncology definition, biochemical control at 3 years was 76%. The incidence of late toxicity was low, with no severe (Grade {>=}3) toxicity at the most recent assessment. Conclusions: Hypofractionated RT using 60 Gy in 20 fractions over 4 weeks with image guidance is feasible and is associated with low rates of late bladder and rectal toxicity. At early follow-up, biochemical outcome is comparable to that reported for conventionally fractionated controls. The findings are being tested in an ongoing, multicenter, Phase III trial.

  17. Performance characteristics of mobile MOSFET dosimeter for kilovoltage X-rays used in image guided radiotherapy

    PubMed Central

    Kumar, A. Sathish; Singh, I. Rabi Raja; Sharma, S. D.; Ravindran, B. Paul

    2015-01-01

    The main objective of this study was to investigate the characteristics of metal oxide semiconductor field effect transistor (MOSFET) dosimeter for kilovoltage (kV) X-ray beams in order to perform the in vivo dosimetry during image guidance in radiotherapy. The performance characteristics of high sensitivity MOSFET dosimeters were investigated for 80, 90, 100, 110, 120, and 125 kV X-ray beams used for imaging in radiotherapy. This study was performed using Clinac 2100 C/D medical electron linear accelerator with on-board imaging and kV cone beam computed tomography system. The characteristics studied in this work include energy dependence, angular dependence, and linearity. The X-ray beam outputs were measured as per American Association of Physicists in Medicine (AAPM) TG 61 recommendations using PTW parallel plate (PP) ionization chamber, which was calibrated in terms of air kerma (Nk) by the National Standard Laboratory. The MOSFET dosimeters were calibrated against the PP ionization chamber for all the kV X-ray beams and the calibration coefficient was found to be 0.11 cGy/mV with a standard deviation of about ±1%. The response of MOSFET was found to be energy independent for the kV X-ray energies used in this study. The response of the MOSFET dosimeter was also found independent of angle of incidence for the gantry angles in the range of 0° to 360° in-air as well as at 3 cm depth in tissue equivalent phantom. PMID:26500397

  18. Performance characteristics of mobile MOSFET dosimeter for kilovoltage X-rays used in image guided radiotherapy.

    PubMed

    Kumar, A Sathish; Singh, I Rabi Raja; Sharma, S D; Ravindran, B Paul

    2015-01-01

    The main objective of this study was to investigate the characteristics of metal oxide semiconductor field effect transistor (MOSFET) dosimeter for kilovoltage (kV) X-ray beams in order to perform the in vivo dosimetry during image guidance in radiotherapy. The performance characteristics of high sensitivity MOSFET dosimeters were investigated for 80, 90, 100, 110, 120, and 125 kV X-ray beams used for imaging in radiotherapy. This study was performed using Clinac 2100 C/D medical electron linear accelerator with on-board imaging and kV cone beam computed tomography system. The characteristics studied in this work include energy dependence, angular dependence, and linearity. The X-ray beam outputs were measured as per American Association of Physicists in Medicine (AAPM) TG 61 recommendations using PTW parallel plate (PP) ionization chamber, which was calibrated in terms of air kerma (Nk) by the National Standard Laboratory. The MOSFET dosimeters were calibrated against the PP ionization chamber for all the kV X-ray beams and the calibration coefficient was found to be 0.11 cGy/mV with a standard deviation of about ±1%. The response of MOSFET was found to be energy independent for the kV X-ray energies used in this study. The response of the MOSFET dosimeter was also found independent of angle of incidence for the gantry angles in the range of 0° to 360° in-air as well as at 3 cm depth in tissue equivalent phantom. PMID:26500397

  19. Tumor Control Outcomes After Hypofractionated and Single-Dose Stereotactic Image-Guided Intensity-Modulated Radiotherapy for Extracranial Metastases From Renal Cell Carcinoma

    SciTech Connect

    Zelefsky, Michael J.; Greco, Carlo; Motzer, Robert; Magsanoc, Juan Martin; Pei Xin; Lovelock, Michael; Mechalakos, Jim; Zatcky, Joan; Fuks, Zvi; Yamada, Yoshiya

    2012-04-01

    Purpose: To report tumor local progression-free outcomes after treatment with single-dose, image-guided, intensity-modulated radiotherapy and hypofractionated regimens for extracranial metastases from renal cell primary tumors. Patients and Methods: Between 2004 and 2010, 105 lesions from renal cell carcinoma were treated with either single-dose, image-guided, intensity-modulated radiotherapy to a prescription dose of 18-24 Gy (median, 24) or hypofractionation (three or five fractions) with a prescription dose of 20-30 Gy. The median follow-up was 12 months (range, 1-48). Results: The overall 3-year actuarial local progression-free survival for all lesions was 44%. The 3-year local progression-free survival for those who received a high single-dose (24 Gy; n = 45), a low single-dose (<24 Gy; n = 14), or hypofractionation regimens (n = 46) was 88%, 21%, and 17%, respectively (high single dose vs. low single dose, p = .001; high single dose vs. hypofractionation, p < .001). Multivariate analysis revealed the following variables were significant predictors of improved local progression-free survival: 24 Gy dose compared with a lower dose (p = .009) and a single dose vs. hypofractionation (p = .008). Conclusion: High single-dose, image-guided, intensity-modulated radiotherapy is a noninvasive procedure resulting in high probability of local tumor control for metastatic renal cell cancer generally considered radioresistant according to the classic radiobiologic ranking.

  20. Prospective Study of Cone-Beam Computed Tomography Image-Guided Radiotherapy for Prone Accelerated Partial Breast Irradiation

    SciTech Connect

    Jozsef, Gabor; DeWyngaert, J. Keith; Becker, Stewart J.; Lymberis, Stella; Formenti, Silvia C.

    2011-10-01

    Purpose: To report setup variations during prone accelerated partial breast irradiation (APBI). Methods: New York University (NYU) 07-582 is an institutional review board-approved protocol of cone-beam computed tomography (CBCT) to deliver image-guided ABPI in the prone position. Eligible are postmenopausal women with pT1 breast cancer excised with negative margins and no nodal involvement. A total dose of 30 Gy in five daily fractions of 6 Gy are delivered to the planning target volume (the tumor cavity with 1.5-cm margin) by image-guided radiotherapy. Patients are set up prone, on a dedicated mattress, used for both simulation and treatment. After positioning with skin marks and lasers, CBCTs are performed and the images are registered to the planning CT. The resulting shifts (setup corrections) are recorded in the three principal directions and applied. Portal images are taken for verification. If they differ from the planning digital reconstructed radiographs, the patient is reset, and a new CBCT is taken. Results: 70 consecutive patients have undergone a total of 343 CBCTs: 7 patients had four of five planned CBCTs performed. Seven CBCTs (2%) required to be repeated because of misalignment in the comparison between portal and digital reconstructed radiograph image after the first CBCT. The mean shifts and standard deviations in the anterior-posterior (AP), superior-inferior (SI), and medial-lateral (ML) directions were -0.19 (0.54), -0.02 (0.33), and -0.02 (0.43) cm, respectively. The average root mean squares of the daily shifts were 0.50 (0.28), 0.29 (0.17), and 0.38 (0.20). A conservative margin formula resulted in a recommended margin of 1.26, 0.73, 0.96 cm in the AP, SI, and ML directions. Conclusion: CBCTs confirmed that the NYU prone APBI setup and treatment technique are reproducible, with interfraction variation comparable to those reported for supine setup. The currently applied margin (1.5 cm) adequately compensates for the setup variation detected.

  1. Optimization and quality assurance of an image-guided radiation therapy system for intensity-modulated radiation therapy radiotherapy

    SciTech Connect

    Tsai, Jen-San; Micaily, Bizhan; Miyamoto, Curtis

    2012-10-01

    To develop a quality assurance (QA) of XVI cone beam system (XVIcbs) for its optimal imaging-guided radiotherapy (IGRT) implementation, and to construe prostate tumor margin required for intensity-modulated radiation therapy (IMRT) if IGRT is unavailable. XVIcbs spatial accuracy was explored with a humanoid phantom; isodose conformity to lesion target with a rice phantom housing a soap as target; image resolution with a diagnostic phantom; and exposure validation with a Radcal ion chamber. To optimize XVIcbs, rotation flexmap on coincidency between gantry rotational axis and that of XVI cone beam scan was investigated. Theoretic correlation to image quality of XVIcbs rotational axis stability was elaborately studied. Comprehensive QA of IGRT using XVIcbs has initially been explored and then implemented on our general IMRT treatments, and on special IMRT radiotherapies such as head and neck (H and N), stereotactic radiation therapy (SRT), stereotactic radiosurgery (SRS), and stereotactic body radiotherapy (SBRT). Fifteen examples of prostate setup accounted for 350 IGRT cone beam system were analyzed. IGRT accuracy results were in agreement {+-} 1 mm. Flexmap 0.25 mm met the manufacturer's specification. Films confirmed isodose coincidence with target (soap) via XVIcbs, otherwise not. Superficial doses were measured from 7.2-2.5 cGy for anatomic diameters 15-33 cm, respectively. Image quality was susceptible to rotational stability or patient movement. IGRT using XVIcbs on general IMRT treatments such as prostate, SRT, SRS, and SBRT for setup accuracy were verified; and subsequently coordinate shifts corrections were recorded. The 350 prostate IGRT coordinate shifts modeled to Gaussian distributions show central peaks deviated off the isocenter by 0.6 {+-} 3.0 mm, 0.5 {+-} 4.5 mm in the X(RL)- and Z(SI)-coordinates, respectively; and 2.0 {+-} 3.0 mm in the Y(AP)-coordinate as a result of belly and bladder capacity variations. Sixty-eight percent of confidence was

  2. SU-E-J-205: Monte Carlo Modeling of Ultrasound Probes for Real-Time Ultrasound Image-Guided Radiotherapy

    SciTech Connect

    Hristov, D; Schlosser, J; Bazalova, M; Chen, J

    2014-06-01

    Purpose: To quantify the effect of ultrasound (US) probe beam attenuation for radiation therapy delivered under real-time US image guidance by means of Monte Carlo (MC) simulations. Methods: MC models of two Philips US probes, an X6-1 matrix-array transducer and a C5-2 curved-array transducer, were built based on their CT images in the EGSnrc BEAMnrc and DOSXYZnrc codes. Due to the metal parts, the probes were scanned in a Tomotherapy machine with a 3.5 MV beam. Mass densities in the probes were assigned based on an electron density calibration phantom consisting of cylinders with mass densities between 0.2–8.0 g/cm{sup 3}. Beam attenuation due to the probes was measured in a solid water phantom for a 6 MV and 15 MV 15x15 cm{sup 2} beam delivered on a Varian Trilogy linear accelerator. The dose was measured with the PTW-729 ionization chamber array at two depths and compared to MC simulations. The extreme case beam attenuation expected in robotic US image guided radiotherapy for probes in upright position was quantified by means of MC simulations. Results: The 3.5 MV CT number to mass density calibration curve was found to be linear with R{sup 2} > 0.99. The maximum mass densities were 4.6 and 4.2 g/cm{sup 3} in the C5-2 and X6-1 probe, respectively. Gamma analysis of the simulated and measured doses revealed that over 98% of measurement points passed the 3%/3mm criteria for both probes and measurement depths. The extreme attenuation for probes in upright position was found to be 25% and 31% for the C5-2 and X6-1 probe, respectively, for both 6 and 15 MV beams at 10 cm depth. Conclusion: MC models of two US probes used for real-time image guidance during radiotherapy have been built. As a Result, radiotherapy treatment planning with the imaging probes in place can now be performed. J Schlosser is an employee of SoniTrack Systems, Inc. D Hristov has financial interest in SoniTrack Systems, Inc.

  3. [Small animal image-guided radiotherapy: A new era for preclinical studies].

    PubMed

    Delpon, G; Frelin-Labalme, A-M; Heinrich, S; Beaudouin, V; Noblet, C; Begue, M; Le Deroff, C; Pouzoulet, F; Chiavassa, S

    2016-02-01

    Preclinical external beam radiotherapy irradiations used to be delivered with a static broad beam. To promote the transfer from animal to man, the preclinical treatment techniques dedicated to the animal have been optimized to be similar to those delivered to patients in clinical practice. In this context, preclinical irradiators have been developed. Due to the small sizes of the animals, and the irradiation beams, the scaling to the small animal dimensions involves specific problems. Reducing the size and energy of the irradiation beams require very high technical performance, especially for the mechanical stability of the irradiator and the spatial resolution of the imaging system. In addition, the determination of the reference absorbed dose rate must be conducted with a specific methodology and suitable detectors. To date, three systems are used for preclinical studies in France. The aim of this article is to present these new irradiators dedicated to small animals from a physicist point of view, including the commissioning and the quality control. PMID:26856635

  4. Localization Accuracy of the Clinical Target Volume During Image-Guided Radiotherapy of Lung Cancer

    SciTech Connect

    Hugo, Geoffrey D.; Weiss, Elisabeth; Badawi, Ahmed; Orton, Matthew

    2011-10-01

    Purpose: To evaluate the position and shape of the originally defined clinical target volume (CTV) over the treatment course, and to assess the impact of gross tumor volume (GTV)-based online computed tomography (CT) guidance on CTV localization accuracy. Methods and Materials: Weekly breath-hold CT scans were acquired in 17 patients undergoing radiotherapy. Deformable registration was used to propagate the GTV and CTV from the first weekly CT image to all other weekly CT images. The on-treatment CT scans were registered rigidly to the planning CT scan based on the GTV location to simulate online guidance, and residual error in the CTV centroids and borders was calculated. Results: The mean GTV after 5 weeks relative to volume at the beginning of treatment was 77% {+-} 20%, whereas for the prescribed CTV, it was 92% {+-} 10%. The mean absolute residual error magnitude in the CTV centroid position after a GTV-based localization was 2.9 {+-} 3.0 mm, and it varied from 0.3 to 20.0 mm over all patients. Residual error of the CTV centroid was associated with GTV regression and anisotropy of regression during treatment (p = 0.02 and p = 0.03, respectively; Spearman rank correlation). A residual error in CTV border position greater than 2 mm was present in 77% of patients and 50% of fractions. Among these fractions, residual error of the CTV borders was 3.5 {+-} 1.6 mm (left-right), 3.1 {+-} 0.9 mm (anterior-posterior), and 6.4 {+-} 7.5 mm (superior-inferior). Conclusions: Online guidance based on the visible GTV produces substantial error in CTV localization, particularly for highly regressing tumors. The results of this study will be useful in designing margins for CTV localization or for developing new online CTV localization strategies.

  5. Image-Guided Radiotherapy for Left-Sided Breast Cancer Patients: Geometrical Uncertainty of the Heart

    SciTech Connect

    Topolnjak, Rajko; Borst, Gerben R.; Nijkamp, Jasper

    2012-03-15

    Purpose: To quantify the geometrical uncertainties for the heart during radiotherapy treatment of left-sided breast cancer patients and to determine and validate planning organ at risk volume (PRV) margins. Methods and Materials: Twenty-two patients treated in supine position in 28 fractions with regularly acquired cone-beam computed tomography (CBCT) scans for offline setup correction were included. Retrospectively, the CBCT scans were reconstructed into 10-phase respiration correlated four-dimensional scans. The heart was registered in each breathing phase to the planning CT scan to establish the respiratory heart motion during the CBCT scan ({sigma}{sub resp}). The average of the respiratory motion was calculated as the heart displacement error for a fraction. Subsequently, the systematic ({Sigma}), random ({sigma}), and total random ({sigma}{sub tot}={radical}({sigma}{sup 2}+{sigma}{sub resp}{sup 2})) errors of the heart position were calculated. Based on the errors a PRV margin for the heart was calculated to ensure that the maximum heart dose (D{sub max}) is not underestimated in at least 90% of the cases (M{sub heart} = 1.3{Sigma}-0.5{sigma}{sub tot}). All analysis were performed in left-right (LR), craniocaudal (CC), and anteroposterior (AP) directions with respect to both online and offline bony anatomy setup corrections. The PRV margin was validated by accumulating the dose to the heart based on the heart registrations and comparing the planned PRV D{sub max} to the accumulated heart D{sub max}. Results: For online setup correction, the cardiac geometrical uncertainties and PRV margins were N-Ary-Summation = 2.2/3.2/2.1 mm, {sigma} = 2.1/2.9/1.4 mm, and M{sub heart} = 1.6/2.3/1.3 mm for LR/CC/AP, respectively. For offline setup correction these were N-Ary-Summation = 2.4/3.7/2.2 mm, {sigma} = 2.9/4.1/2.7 mm, and M{sub heart} = 1.6/2.1/1.4 mm. Cardiac motion induced by breathing was {sigma}{sub resp} = 1.4/2.9/1.4 mm for LR/CC/AP. The PRV D{sub max

  6. Image-Guided Radiotherapy Using a Modified Industrial Micro-CT for Preclinical Applications

    PubMed Central

    Felix, Manuela C.; Fleckenstein, Jens; Kirschner, Stefanie; Hartmann, Linda; Wenz, Frederik; Brockmann, Marc A.

    2015-01-01

    Purpose/Objective Although radiotherapy is a key component of cancer treatment, its implementation into pre-clinical in vivo models with relatively small target volumes is frequently omitted either due to technical complexity or expected side effects hampering long-term observational studies. We here demonstrate how an affordable industrial micro-CT can be converted into a small animal IGRT device at very low costs. We also demonstrate the proof of principle for the case of partial brain irradiation of mice carrying orthotopic glioblastoma implants. Methods/Materials A commercially available micro-CT originally designed for non-destructive material analysis was used. It consists of a CNC manipulator, a transmission X-ray tube (10–160 kV) and a flat-panel detector, which was used together with custom-made steel collimators (1–5 mm aperture size). For radiation field characterization, an ionization chamber, water-equivalent slab phantoms and radiochromic films were used. A treatment planning tool was implemented using a C++ application. For proof of principle, NOD/SCID/γc−/− mice were orthotopically implanted with U87MG high-grade glioma cells and irradiated using the novel setup. Results The overall symmetry of the radiation field at 150 kV was 1.04±0.02%. The flatness was 4.99±0.63% and the penumbra widths were between 0.14 mm and 0.51 mm. The full width at half maximum (FWHM) ranged from 1.97 to 9.99 mm depending on the collimator aperture size. The dose depth curve along the central axis followed a typical shape of keV photons. Dose rates measured were 10.7 mGy/s in 1 mm and 7.6 mGy/s in 5 mm depth (5 mm collimator aperture size). Treatment of mice with a single dose of 10 Gy was tolerated well and resulted in central tumor necrosis consistent with therapeutic efficacy. Conclusion A conventional industrial micro-CT can be easily modified to allow effective small animal IGRT even of critical target volumes such as the brain. PMID:25993010

  7. Predictors of Local Control After Single-Dose Stereotactic Image-Guided Intensity-Modulated Radiotherapy for Extracranial Metastases

    SciTech Connect

    Greco, Carlo; Zelefsky, Michael J.; Lovelock, Michael; Fuks, Zvi; Hunt, Margie; Rosenzweig, Kenneth; Zatcky, Joan; Kim, Balem; Yamada, Yoshiya

    2011-03-15

    Purpose: To report tumor local control after treatment with single-dose image-guided intensity-modulated radiotherapy (SD-IGRT) to extracranial metastatic sites. Methods and Materials: A total of 126 metastases in 103 patients were treated with SD-IGRT to prescription doses of 18-24 Gy (median, 24 Gy) between 2004 and 2007. Results: The overall actuarial local relapse-free survival (LRFS) rate was 64% at a median follow-up of 18 months (range, 2-45 months). The median time to failure was 9.6 months (range, 1-23 months). On univariate analysis, LRFS was significantly correlated with prescription dose (p = 0.029). Stratification by dose into high (23 to 24 Gy), intermediate (21 to 22 Gy), and low (18 to 20 Gy) dose levels revealed highly significant differences in LRFS between high (82%) and low doses (25%) (p < 0.0001). Overall, histology had no significant effect on LRFS (p = 0.16). Renal cell histology displayed a profound dose-response effect, with 80% LRFS at the high dose level (23 to 24 Gy) vs. 37% with low doses ({<=}22 Gy) (p = 0.04). However, for patients who received the high dose level, histology was not a statistically significant predictor of LRFS (p = 0.90). Target organ (bone vs. lymph node vs. soft tissues) (p = 0.5) and planning target volume size (p = 0.55) were not found to be associated with long-term LRFS probability. Multivariate Cox regression analysis confirmed prescription dose to be a significant predictor of LRFS (p = 0.003). Conclusion: High-dose SD-IGRT is a noninvasive procedure resulting in high probability of local tumor control. Single-dose IGRT may be effectively used to locally control metastatic deposits regardless of histology and target organ, provided sufficiently high doses (> 22 Gy) of radiation are delivered.

  8. Dose-Response Relationship for Image-Guided Stereotactic Body Radiotherapy of Pulmonary Tumors: Relevance of 4D Dose Calculation

    SciTech Connect

    Guckenberger, Matthias Wulf, Joern; Mueller, Gerd; Krieger, Thomas; Baier, Kurt; Gabor, Manuela; Richter, Anne; Wilbert, Juergen; Flentje, Michael

    2009-05-01

    Purpose: To evaluate outcome after image-guided stereotactic body radiotherapy (SBRT) for early-stage non-small-cell lung cancer (NSCLC) and pulmonary metastases. Methods and Materials: A total of 124 patients with 159 pulmonary lesions (metastases n = 118; NSCLC, n = 41; Stage IA, n = 13; Stage IB, n = 19; T3N0, n = 9) were treated with SBRT. Patients were treated with hypofractionated schemata (one to eight fractions of 6-26 Gy); biologic effective doses (BED) to the clinical target volume (CTV) were calculated based on four-dimensional (4D) dose calculation. The position of the pulmonary target was verified using volume imaging before all treatments. Results: With mean/median follow-up of 18/14 months, actuarial local control was 83% at 36 months with no difference between NSCLC and metastases. The dose to the CTV based on 4D dose calculation was closely correlated with local control: local control rates were 89% and 62% at 36 months for >100 Gy and <100 Gy BED (p = 0.0001), respectively. Actuarial freedom from regional and systemic progression was 34% at 36 months for primary NSCLC group; crude rate of regional failure was 15%. Three-year overall survival was 37% for primary NSCLC and 16% for metastases; no dose-response relationship for survival was observed. Exacerbation of comorbidities was the most frequent cause of death for primary NSCLC. Conclusions: Doses of >100 Gy BED to the CTV based on 4D dose calculation resulted in excellent local control rates. This cutoff dose is not specific to the treatment technique and protocol of our study and may serve as a general recommendation.

  9. Image-Guided Radiotherapy for Liver Cancer Using Respiratory-Correlated Computed Tomography and Cone-Beam Computed Tomography

    SciTech Connect

    Guckenberger, Matthias Sweeney, Reinhart A.; Wilbert, Juergen; Krieger, Thomas; Richter, Anne; Baier, Kurt; Mueller, Gerd; Sauer, Otto; Flentje, Michael

    2008-05-01

    Purpose: To evaluate a novel four-dimensional (4D) image-guided radiotherapy (IGRT) technique in stereotactic body RT for liver tumors. Methods and Materials: For 11 patients with 13 intrahepatic tumors, a respiratory-correlated 4D computed tomography (CT) scan was acquired at treatment planning. The target was defined using CT series reconstructed at end-inhalation and end-exhalation. The liver was delineated on these two CT series and served as a reference for image guidance. A cone-beam CT scan was acquired after patient positioning; the blurred diaphragm dome was interpreted as a probability density function showing the motion range of the liver. Manual contour matching of the liver structures from the planning 4D CT scan with the cone-beam CT scan was performed. Inter- and intrafractional uncertainties of target position and motion range were evaluated, and interobserver variability of the 4D-IGRT technique was tested. Results: The workflow of 4D-IGRT was successfully practiced in all patients. The absolute error in the liver position and error in relation to the bony anatomy was 8 {+-} 4 mm and 5 {+-} 2 mm (three-dimensional vector), respectively. Margins of 4-6 mm were calculated for compensation of the intrafractional drifts of the liver. The motion range of the diaphragm dome was reproducible within 5 mm for 11 of 13 lesions, and the interobserver variability of the 4D-IGRT technique was small (standard deviation, 1.5 mm). In 4 patients, the position of the intrahepatic lesion was directly verified using a mobile in-room CT scanner after application of intravenous contrast. Conclusion: The results of our study have shown that 4D image guidance using liver contour matching between respiratory-correlated CT and cone-beam CT scans increased the accuracy compared with stereotactic positioning and compared with IGRT without consideration of breathing motion.

  10. On the use of an analytic source model for dose calculations in precision image-guided small animal radiotherapy

    NASA Astrophysics Data System (ADS)

    Granton, Patrick V.; Verhaegen, Frank

    2013-05-01

    Precision image-guided small animal radiotherapy is rapidly advancing through the use of dedicated micro-irradiation devices. However, precise modeling of these devices in model-based dose-calculation algorithms such as Monte Carlo (MC) simulations continue to present challenges due to a combination of very small beams, low mechanical tolerances on beam collimation, positioning and long calculation times. The specific intent of this investigation is to introduce and demonstrate the viability of a fast analytical source model (AM) for use in either investigating improvements in collimator design or for use in faster dose calculations. MC models using BEAMnrc were developed for circular and square fields sizes from 1 to 25 mm in diameter (or side) that incorporated the intensity distribution of the focal spot modeled after an experimental pinhole image. These MC models were used to generate phase space files (PSFMC) at the exit of the collimators. An AM was developed that included the intensity distribution of the focal spot, a pre-calculated x-ray spectrum, and the collimator-specific entrance and exit apertures. The AM was used to generate photon fluence intensity distributions (ΦAM) and PSFAM containing photons radiating at angles according to the focal spot intensity distribution. MC dose calculations using DOSXYZnrc in a water and mouse phantom differing only by source used (PSFMC versus PSFAM) were found to agree within 7% and 4% for the smallest 1 and 2 mm collimator, respectively, and within 1% for all other field sizes based on depth dose profiles. PSF generation times were approximately 1200 times faster for the smallest beam and 19 times faster for the largest beam. The influence of the focal spot intensity distribution on output and on beam shape was quantified and found to play a significant role in calculated dose distributions. Beam profile differences due to collimator alignment were found in both small and large collimators sensitive to shifts of 1

  11. Dosimetric impact of setup errors in head and neck cancer patients treated by image-guided radiotherapy

    PubMed Central

    Kaur, Inderjit; Rawat, Sheh; Ahlawat, Parveen; Kakria, Anjali; Gupta, Gourav; Saxena, Upasna; Mishra, Manindra Bhushan

    2016-01-01

    To assess and analyze the impact of setup uncertainties on target volume coverage and doses to organs at risk (OAR) in head and neck cancer (HNC) patients treated by image-guided radiotherapy (IGRT). Translational setup errors in 25 HNC patients were observed by kilovoltage cone beam computed tomography (kV CBCT). Two plans were generated. Plan one – the original plan which was the initially optimized and approved plan of the patient. All patients were treated according to their respective approved plans at a defined isocenter. Plan two – the plan sum which was the sum of all plans recalculated at a different isocenter according to setup errors in x, y, and z-direction. Plan sum was created to evaluate doses that would have been received by planning target volume (PTV) and OARs if setup errors were not corrected. These 2 plans were analyzed and compared in terms of target volume coverage and doses to OARs. A total 503 kV CBCT images were acquired for evaluation of setup errors in 25 HNC patients. The systematic (mean) and random errors (standard deviation) combined for 25 patients in x, y, and z directions were 0.15 cm, 0.21 cm, and 0.19 cm and 0.09 cm, 0.12 cm, and 0.09 cm, respectively. The study showed that there was a significant difference in PTV coverage between 2 plans. The doses to various OARs showed a nonsignificant increase in the plan sum. The correction of translational setup errors is essential for IGRT treatment in terms of delivery of planned optimal doses to target volume. PMID:27217627

  12. Learning statistical correlation for fast prostate registration in image-guided radiotherapy

    SciTech Connect

    Shi Yonghong; Liao Shu; Shen Dinggang

    2011-11-15

    Purpose: In adaptive radiation therapy of prostate cancer, fast and accurate registration between the planning image and treatment images of the patient is of essential importance. With the authors' recently developed deformable surface model, prostate boundaries in each treatment image can be rapidly segmented and their correspondences (or relative deformations) to the prostate boundaries in the planning image are also established automatically. However, the dense correspondences on the nonboundary regions, which are important especially for transforming the treatment plan designed in the planning image space to each treatment image space, are remained unresolved. This paper presents a novel approach to learn the statistical correlation between deformations of prostate boundary and nonboundary regions, for rapidly estimating deformations of the nonboundary regions when given the deformations of the prostate boundary at a new treatment image. Methods: The main contributions of the proposed method lie in the following aspects. First, the statistical deformation correlation will be learned from both current patient and other training patients, and further updated adaptively during the radiotherapy. Specifically, in the initial treatment stage when the number of treatment images collected from the current patient is small, the statistical deformation correlation is mainly learned from other training patients. As more treatment images are collected from the current patient, the patient-specific information will play a more important role in learning patient-specific statistical deformation correlation to effectively reflect prostate deformation of the current patient during the treatment. Eventually, only the patient-specific statistical deformation correlation is used to estimate dense correspondences when a sufficient number of treatment images have been acquired from the current patient. Second, the statistical deformation correlation will be learned by using a

  13. SU-E-J-144: MRI Visualization of a Metallic Fiducial Marker Used for Image Guided Prostate Radiotherapy

    SciTech Connect

    Yee, S; Krauss, D; Yan, D

    2014-06-01

    Purpose: Unlike on the daily CBCT used for the image-guided radiation therapy, the visualization of an implantable metallic fiducial marker on the planning MRI images has been a challenge due to the inherent insensitivity of metal in MRI, and very thin (∼ 1 mm or less) diameter. Here, an MRI technique to visualize a marker used for prostate cancer radiotherapy is reported. Methods: During the MRI acquisitions, a multi-shot turbo spin echo (TSE) technique (TR=3500 ms, TE=8.6 ms, ETL=17, recon voxel=0.42x0.42x3.5 mm3) was acquired in Philips 3T Ingenia together with a T2-weighted multi-shot TSE (TR=5381 ms, TE=110 ms, ETL=17, recon voxel=0.47×0.47×3 mm3) and a balanced turbo field echo (bTFE, flip angle 60, TR=2.76 ms, TE=1.3 ms, 0.85×0.85×3 mm3, NSA=4). In acquiring the MRI to visualize the fiducial marker, a particular emphasis was made to improve the spatial resolution and visibility in the generally dark, inhomogeneous prostate area by adjusting the slice profile ordering and TE values of TSE acquisition (in general, the lower value of TE in TSE acquisition generates a brighter signal but at the cost of high spatial resolution since the k-space, responsible for high spatial resolution, is filled with noisier data). Results: While clearly visible in CT, the marker was not visible in either T2-weighted TSE or bTFE, although the image qualities of both images were superior. In the new TSE acquisition (∼ a proton-density weighted image) adjusted by changing the profile ordering and the TE value, the marker was visible as a negative (but clear) contrast in the magnitude MRI, and as a positive contrast in the imaginary image of the phase-sensitive MRI. Conclusion: A metallic fiducial marker used for image guidance before prostate cancer radiotherapy can be made visible in MRI, which may facilitate more use of MRI in planning and guiding such radiation therapy.

  14. SU-D-9A-07: Imaging Dose and Cancer Risk in Image-Guided Radiotherapy of Cancers

    SciTech Connect

    Zhou, L; Bai, S; Zhang, Y; Ming, X; Zhang, Y; Deng, J

    2014-06-01

    Purpose: To systematically evaluate the imaging doses and cancer risks associated with various imaging procedures involving ionizing radiation during image-guided radiotherapy of an increasingly large number of cancer patients. Methods: 141 patients (52 brain cases, 47 thoracic cases, 42 abdominal cases, aged 3 to 91 years old) treated between October 2009 and March 2010 were included in this IRB-approved retrospective study. During the whole radiotherapy course, each patient underwent at least one type of imaging procedures, i.e., kV portal, MV portal and kVCBCT, besides CT simulations. Based on Monte Carlo modeling and particle transport in human anatomy of various dimensions, the correlations between the radiation doses to the various organs-at-risk (OARs) at the head, the thoracic and the abdominal regions and one's weight, circumference, scan mAs and kVp have been obtained and used to estimate the radiation dose from a specific imaging procedure. The radiation-induced excess relative risk (ERR) was then estimated with BEIR VII formulism based on one's gender, age and radiation dose. 1+ ERR was reported in this study as relative cancer risk. Results: For the whole cohort of 141 patients, the mean imaging doses from various imaging procedures were 8.3 cGy to the brain, 10.5 cGy to the lungs and 19.2 cGy to the red bone marrow, respectively. Accordingly, the cancer risks were 1.140, 1.369 and 2.671, respectively. In comparison, MV portal deposited largest doses to the lungs while kVCBCT delivered the highest doses to the red bone marrow. Conclusion: The compiled imaging doses to a patient during his/her treatment course were patient-specific and site-dependent, varying from 1.2 to 263.5 cGy on average, which were clinically significant and should be included in the treatment planning and overall decision-making. Our results indicated the necessity of personalized imaging to maximize its clinical benefits while reducing the associated cancer risks. Sichuan

  15. Dose escalation with stereotactic body radiation therapy boost for locally advanced non small cell lung cancer

    PubMed Central

    2013-01-01

    Introduction Low survival outcomes have been reported for the treatment of locally advanced non small cell lung cancer (LA-NSCLC) with the standard of care treatment of concurrent chemoradiation (cCRT). We present our experience of dose escalation using stereotactic body radiosurgery (SBRT) following conventional cCRT for patients with LA-NSCLC. Methods Sixteen patients with a median age of 67.5 treated with fractionated SBRT from 2010 to 2012 were retrospectively analyzed. Nine (56%) of the patients had stage IIIB, 6 (38%) has stage IIIA, and 1 (6%) had recurrent disease. Majority of the patients (63%) presented with N2 disease. All patients had a PET CT for treatment planning. Patients received conventional cCRT to a median dose of 50.40 Gy (range 45–60) followed by an SBRT boost with an average dose of 25 Gy (range 20–30) given over 5 fractions. Results With a median follow-up of 14 months (range, 1–14 months), 1-year overall survival (OS), progression free survival (PFS), local control (LC), regional control (RC), and distant control (DC) rates were, 78%, 42%, 76%, 79%, and 71%, respectively. Median times to disease progression and regional failure were 10 months and 18 months, respectively. On univariate analysis, advanced age and nodal status were worse prognostic factors of PFS (p < 0.05). Four patients developed radiation pneumonitis and one developed hemoptysis. Treatment was interrupted in one patient who required hospitalization due to arrhythmias and pneumonia. Conclusion Risk adaptive dose escalation with SBRT following external beam radiotherapy is possible and generally tolerated treatment option for patients with LA-NSCLC. PMID:23842112

  16. Dose-Escalated Robotic SBRT for Stage I-II Prostate Cancer.

    PubMed

    Meier, Robert

    2015-01-01

    Stereotactic body radiotherapy (SBRT) is the precise external delivery of very high-dose radiotherapy to targets in the body, with treatment completed in one to five fractions. SBRT should be an ideal approach for organ-confined prostate cancer because (I) dose-escalation should yield improved rates of cancer control; (II) the unique radiobiology of prostate cancer favors hypofractionation; and (III) the conformal nature of SBRT minimizes high-dose radiation delivery to immediately adjacent organs, potentially reducing complications. This approach is also more convenient for patients, and is cheaper than intensity-modulated radiotherapy (IMRT). Several external beam platforms are capable of delivering SBRT for early-stage prostate cancer, although most of the mature reported series have employed a robotic non-coplanar platform (i.e., CyberKnife). Several large studies report 5-year biochemical relapse rates which compare favorably to IMRT. Rates of late GU toxicity are similar to those seen with IMRT, and rates of late rectal toxicity may be less than with IMRT and low-dose rate brachytherapy. Patient-reported quality of life (QOL) outcomes appear similar to IMRT in the urinary domain. Bowel QOL may be less adversely affected by SBRT than with other radiation modalities. After 5 years of follow-up, SBRT delivered on a robotic platform is yielding outcomes at least as favorable as IMRT, and may be considered appropriate therapy for stage I-II prostate cancer. PMID:25905037

  17. Dose-Escalated Robotic SBRT for Stage I–II Prostate Cancer

    PubMed Central

    Meier, Robert

    2015-01-01

    Stereotactic body radiotherapy (SBRT) is the precise external delivery of very high-dose radiotherapy to targets in the body, with treatment completed in one to five fractions. SBRT should be an ideal approach for organ-confined prostate cancer because (I) dose-escalation should yield improved rates of cancer control; (II) the unique radiobiology of prostate cancer favors hypofractionation; and (III) the conformal nature of SBRT minimizes high-dose radiation delivery to immediately adjacent organs, potentially reducing complications. This approach is also more convenient for patients, and is cheaper than intensity-modulated radiotherapy (IMRT). Several external beam platforms are capable of delivering SBRT for early-stage prostate cancer, although most of the mature reported series have employed a robotic non-coplanar platform (i.e., CyberKnife). Several large studies report 5-year biochemical relapse rates which compare favorably to IMRT. Rates of late GU toxicity are similar to those seen with IMRT, and rates of late rectal toxicity may be less than with IMRT and low-dose rate brachytherapy. Patient-reported quality of life (QOL) outcomes appear similar to IMRT in the urinary domain. Bowel QOL may be less adversely affected by SBRT than with other radiation modalities. After 5 years of follow-up, SBRT delivered on a robotic platform is yielding outcomes at least as favorable as IMRT, and may be considered appropriate therapy for stage I–II prostate cancer. PMID:25905037

  18. Increasing Use of Dose-Escalated External Beam Radiation Therapy for Men With Nonmetastatic Prostate Cancer

    SciTech Connect

    Swisher-McClure, Samuel; Mitra, Nandita; Woo, Kaitlin; Smaldone, Marc; Uzzo, Robert; Bekelman, Justin E.

    2014-05-01

    Purpose: To examine recent practice patterns, using a large national cancer registry, to understand the extent to which dose-escalated external beam radiation therapy (EBRT) has been incorporated into routine clinical practice for men with prostate cancer. Methods and Materials: We conducted a retrospective observational cohort study using the National Cancer Data Base, a nationwide oncology outcomes database in the United States. We identified 98,755 men diagnosed with nonmetastatic prostate cancer between 2006 and 2011 who received definitive EBRT and classified patients into National Comprehensive Cancer Network (NCCN) risk groups. We defined dose-escalated EBRT as total prescribed dose of ≥75.6 Gy. Using multivariable logistic regression, we examined the association of patient, clinical, and demographic characteristics with the use of dose-escalated EBRT. Results: Overall, 81.6% of men received dose-escalated EBRT during the study period. The use of dose-escalated EBRT did not vary substantially by NCCN risk group. Use of dose-escalated EBRT increased from 70.7% of patients receiving treatment in 2006 to 89.8% of patients receiving treatment in 2011. On multivariable analysis, year of diagnosis and use of intensity modulated radiation therapy were significantly associated with receipt of dose-escalated EBRT. Conclusions: Our study results indicate that dose-escalated EBRT has been widely adopted by radiation oncologists treating prostate cancer in the United States. The proportion of patients receiving dose-escalated EBRT increased nearly 20% between 2006 and 2011. We observed high utilization rates of dose-escalated EBRT within all disease risk groups. Adoption of intensity modulated radiation therapy was strongly associated with use of dose-escalated treatment.

  19. Personalized Assessment of kV Cone Beam Computed Tomography Doses in Image-guided Radiotherapy of Pediatric Cancer Patients

    SciTech Connect

    Zhang Yibao; Yan Yulong; Nath, Ravinder; Bao Shanglian; Deng Jun

    2012-08-01

    Purpose: To develop a quantitative method for the estimation of kV cone beam computed tomography (kVCBCT) doses in pediatric patients undergoing image-guided radiotherapy. Methods and Materials: Forty-two children were retrospectively analyzed in subgroups of different scanned regions: one group in the head-and-neck and the other group in the pelvis. Critical structures in planning CT images were delineated on an Eclipse treatment planning system before being converted into CT phantoms for Monte Carlo simulations. A benchmarked EGS4 Monte Carlo code was used to calculate three-dimensional dose distributions of kVCBCT scans with full-fan high-quality head or half-fan pelvis protocols predefined by the manufacturer. Based on planning CT images and structures exported in DICOM RT format, occipital-frontal circumferences (OFC) were calculated for head-and-neck patients using DICOMan software. Similarly, hip circumferences (HIP) were acquired for the pelvic group. Correlations between mean organ doses and age, weight, OFC, and HIP values were analyzed with SigmaPlot software suite, where regression performances were analyzed with relative dose differences (RDD) and coefficients of determination (R{sup 2}). Results: kVCBCT-contributed mean doses to all critical structures decreased monotonically with studied parameters, with a steeper decrease in the pelvis than in the head. Empirical functions have been developed for a dose estimation of the major organs at risk in the head and pelvis, respectively. If evaluated with physical parameters other than age, a mean RDD of up to 7.9% was observed for all the structures in our population of 42 patients. Conclusions: kVCBCT doses are highly correlated with patient size. According to this study, weight can be used as a primary index for dose assessment in both head and pelvis scans, while OFC and HIP may serve as secondary indices for dose estimation in corresponding regions. With the proposed empirical functions, it is possible

  20. SU-E-J-10: Imaging Dose and Cancer Risk in Image-Guided Radiotherapy of Cancers

    SciTech Connect

    Zhou, L; Bai, S; Zhang, Y; Deng, J

    2015-06-15

    Purpose: To systematically evaluate imaging doses and cancer risks to organs-at-risk as a Result of cumulative doses from various radiological imaging procedures in image-guided radiotherapy (IGRT) in a large cohort of cancer patients. Methods: With IRB approval, imaging procedures (computed tomography, kilo-voltage portal imaging, megavoltage portal imaging and kilo-voltage cone-beam computed tomography) of 4832 cancer patients treated during 4.5 years were collected with their gender, age and circumference. Correlations between patient’s circumference and Monte Carlo simulated-organ dose were applied to estimate organ doses while the cancer risks were reported as 1+ERR using BEIR VII models. Results: 80 cGy or more doses were deposited to brain, lungs and RBM in 273 patients (maximum 136, 278 and 267 cGy, respectively), due largely to repetitive imaging procedures and non-personalized imaging settings. Regardless of gender, relative cancer risk estimates for brain, lungs, and RBM were 3.4 (n = 55), 2.6 (n = 49), 1.8 (n = 25) for age group of 0–19; 1.2 (n = 87), 1.4 (n = 98), 1.3 (n = 51) for age group of 20–39; 1.0 (n = 457), 1.1 (n = 880), 1.8 (n=360) for age group of 40–59; 1.0 (n = 646), 1.1 (n = 1400), 2.3 (n = 716) for age group of 60–79 and 1.0 (n = 108),1.1 (n = 305),1.6 (n = 147) for age group of 80–99. Conclusion: The cumulative imaging doses and associated cancer risks from multi-imaging procedures were patient-specific and site-dependent, with up to 2.7 Gy imaging dose deposited to critical structures in some pediatric patients. The associated cancer risks in brain and lungs for children of age 0 to 19 were 2–3 times larger than those for adults. This study indicated a pressing need for personalized imaging protocol to maximize its clinical benefits while reducing associated cancer risks. Sichuan University Scholarship.

  1. Patient-Specific Three-Dimensional Concomitant Dose From Cone Beam Computed Tomography Exposure in Image-Guided Radiotherapy

    SciTech Connect

    Spezi, Emiliano; Downes, Patrick; Jarvis, Richard; Radu, Emil; Staffurth, John

    2012-05-01

    Purpose: The purpose of the present study was to quantify the concomitant dose received by patients undergoing cone beam computed tomography (CBCT) scanning in different clinical scenarios as a part of image-guided radiotherapy (IGRT) procedures. Methods and Materials: We calculated the three-dimensional concomitant dose received as a result of CBCT scans in 6 patients representing different clinical scenarios: two pelvis, two head and neck, and two chest. We assessed the effect that a daily on-line IGRT strategy would have on the patient dose distribution, assuming 40 CBCT scans throughout the treatment course. The additional dose to the planning target volume margin region was also estimated. Results: In the pelvis, a single CBCT scan delivered a mean dose to the femoral heads of 2-6 cGy and the rectum of 1-2 cGy. An additional dose to the planning target volume was within 1-3 cGy. In the chest, the mean dose to the planning target volume varied from 2.5 to 5 cGy. The lung and spinal cord planning organ at risk volume received {<=}4 cGy and {<=}5 cGy, respectively. In the head and neck, a single CBCT scan delivered a mean dose of 0.3 cGy, with bony structures receiving 0.5-0.8 cGy. The femoral heads received an additional dose of 1.5-2.5 Gy. A reduction of 20-30% in the mean dose to the organs at risk was achieved using bowtie filtration. In the head and neck, the dose to the eyes and brainstem was eliminated by decreasing the craniocaudal field size. Conclusions: The additional dose from on-line IGRT procedures can be clinically relevant. The organ dose can be significantly reduced with the use of appropriate patient-specific settings. The concomitant dose from CBCT should be accounted for and the acquisition settings optimized for optimal IGRT strategies on a patient basis.

  2. Clinical Evaluation of Positioning Verification Using Digital Tomosynthesis and Bony Anatomy and Soft Tissues for Prostate Image-Guided Radiotherapy

    SciTech Connect

    Yoo, Sua Wu, Q. Jackie; Godfrey, Devon; Yan Hui; Ren Lei; Das, Shiva; Lee, William R.; Yin Fangfang

    2009-01-01

    Purpose: To evaluate on-board digital tomosynthesis (DTS) for patient positioning vs. two-dimensional (2D) radiography and three-dimensional cone beam (CBCT). Methods and Materials: A total of 92 image sessions from 9 prostate cancer patients were analyzed. An on-board image set was registered to a corresponding reference image set. Four pairs of image sets were used: digitally reconstructed radiographs vs. on-board orthogonal paired radiographs for the 2D method, coronal-reference DTS vs. on-board coronal DTS for the coronal-DTS method, sagittal-reference DTS vs. on-board sagittal DTS for the sagittal-DTS method, and planning CT vs. CBCT for the CBCT method. The registration results were compared. Results: The systematic errors in all methods were <1 mm/1{sup o}. When registering the bony anatomy, the mean vector difference was 0.21 {+-} 0.11 cm between 2D and CBCT, 0.11 {+-} 0.08 cm between CBCT and coronal DTS, and 0.14 {+-} 0.07 cm between CBCT and sagittal DTS. The correlation between CBCT to DTS was stronger (coefficient = 0.92-0.95) than the correlation between 2D and CBCT or DTS (coefficient = 0.81-0.83). When registering the soft tissue, the mean vector difference was 0.18 {+-} 0.11 cm between CBCT and coronal DTS and 0.29 {+-} 0.17 cm between CBCT and sagittal DTS. The correlation coefficient of CBCT to sagittal DTS and to coronal DTS was 0.84 and 0.92, respectively. Conclusion: DTS could provide equivalent results to CBCT when the bony anatomy is used as landmarks for prostate image-guided radiotherapy. For soft tissue-based positioning verification, coronal DTS produced equivalent results to CBCT, but sagittal DTS alone was insufficient. DTS could allow for comparable soft tissue-based target localization with faster scanning time and a lower imaging dose compared with CBCT.

  3. Whole brain radiotherapy plus simultaneous in-field boost with image guided intensity-modulated radiotherapy for brain metastases of non-small cell lung cancer

    PubMed Central

    2014-01-01

    Background Whole brain radiotherapy (WBRT) plus sequential focal radiation boost is a commonly used therapeutic strategy for patients with brain metastases. However, recent reports on WBRT plus simultaneous in-field boost (SIB) also showed promising outcomes. The objective of present study is to retrospectively evaluate the efficacy and toxicities of WBRT plus SIB with image guided intensity-modulated radiotherapy (IG-IMRT) for inoperable brain metastases of NSCLC. Methods Twenty-nine NSCLC patients with 87 inoperable brain metastases were included in this retrospective study. All patients received WBRT at a dose of 40 Gy/20 f, and SIB boost with IG-IMRT at a dose of 20 Gy/5 f concurrent with WBRT in the fourth week. Prior to each fraction of IG-IMRT boost, on-line positioning verification and correction were used to ensure that the set-up errors were within 2 mm by cone beam computed tomography in all patients. Results The one-year intracranial control rate, local brain failure rate, and distant brain failure rate were 62.9%, 13.8%, and 19.2%, respectively. The two-year intracranial control rate, local brain failure rate, and distant brain failure rate were 42.5%, 30.9%, and 36.4%, respectively. Both median intracranial progression-free survival and median survival were 10 months. Six-month, one-year, and two-year survival rates were 65.5%, 41.4%, and 13.8%, corresponding to 62.1%, 41.4%, and 10.3% of intracranial progression-free survival rates. Patients with Score Index for Radiosurgery in Brain Metastases (SIR) >5, number of intracranial lesions <3, and history of EGFR-TKI treatment had better survival. Three lesions (3.45%) demonstrated radiation necrosis after radiotherapy. Grades 2 and 3 cognitive impairment with grade 2 radiation leukoencephalopathy were observed in 4 (13.8%) and 4 (13.8%) patients. No dosimetric parameters were found to be associated with these late toxicities. Patients received EGFR-TKI treatment had higher incidence of grades 2–3

  4. MRI-guided prostate adaptive radiotherapy - A systematic review.

    PubMed

    McPartlin, A J; Li, X A; Kershaw, L E; Heide, U; Kerkmeijer, L; Lawton, C; Mahmood, U; Pos, F; van As, N; van Herk, M; Vesprini, D; van der Voort van Zyp, J; Tree, A; Choudhury, A

    2016-06-01

    Dose escalated radiotherapy improves outcomes for men with prostate cancer. A plateau for benefit from dose escalation using EBRT may not have been reached for some patients with higher risk disease. The use of increasingly conformal techniques, such as step and shoot IMRT or more recently VMAT, has allowed treatment intensification to be achieved whilst minimising associated increases in toxicity to surrounding normal structures. To support further safe dose escalation, the uncertainties in the treatment target position will need be minimised using optimal planning and image-guided radiotherapy (IGRT). In particular the increasing usage of profoundly hypo-fractionated stereotactic therapy is predicated on the ability to confidently direct treatment precisely to the intended target for the duration of each treatment. This article reviews published studies on the influences of varies types of motion on daily prostate position and how these may be mitigated to improve IGRT in future. In particular the role that MRI has played in the generation of data is discussed and the potential role of the MR-Linac in next-generation IGRT is discussed. PMID:27162159

  5. Dose Escalation for Metastatic Spinal Cord Compression in Patients With Relatively Radioresistant Tumors

    SciTech Connect

    Rades, Dirk; Freundt, Katja; Meyners, Thekla; Bajrovic, Amira; Basic, Hiba; Karstens, Johann H.; Adamietz, Irenaeus A.; Wildfang, Ingeborg; Rudat, Volker; Schild, Steven E.; Dunst, Juergen

    2011-08-01

    Purpose: Radiotherapy alone is the most common treatment for metastatic spinal cord compression (MSCC) from relatively radioresistant tumors such as renal cell carcinoma, colorectal cancer, and malignant melanoma. However, the results of the 'standard' regimen 30 Gy/10 fractions need to be improved with respect to functional outcome. This study investigated whether a dose escalation beyond 30 Gy can improve treatment outcomes. Methods and Materials: A total of 91 patients receiving 30 Gy/10 fractions were retrospectively compared to 115 patients receiving higher doses (37.5 Gy/15 fractions, 40 Gy/20 fractions) for motor function and local control of MSCC. Ten further potential prognostic factors were evaluated: age, gender, tumor type, performance status, number of involved vertebrae, visceral or other bone metastases, interval from tumor diagnosis to radiotherapy, pretreatment ambulatory status, and time developing motor deficits before radiotherapy. Results: Motor function improved in 18% of patients after 30 Gy and in 22% after higher doses (p = 0.81). On multivariate analysis, functional outcome was associated with visceral metastases (p = 0.030), interval from tumor diagnosis to radiotherapy (p = 0.010), and time developing motor deficits (p < 0.001). The 1-year local control rates were 76% after 30 Gy and 80% after higher doses, respectively (p = 0.64). On multivariate analysis, local control was significantly associated with visceral metastases (p = 0.029) and number of involved vertebrae (p = 0.043). Conclusions: Given the limitations of a retrospective study, escalation of the radiation dose beyond 30 Gy/10 fractions did not significantly improve motor function and local control of MSCC in patients with relatively radioresistant tumors.

  6. A Phase I Dose Escalation Study of Hypofractionated IMRT Field-in-Field Boost for Newly Diagnosed Glioblastoma Multiforme

    SciTech Connect

    Monjazeb, Arta M.; Ayala, Deandra; Jensen, Courtney; Case, L. Douglas; Bourland, J. Daniel; Ellis, Thomas L.; McMullen, Kevin P.; Chan, Michael D.; Tatter, Stephen B.; Lesser, Glen J.; Shaw, Edward G.

    2012-02-01

    Objectives: To describe the results of a Phase I dose escalation trial for newly diagnosed glioblastoma multiforme (GBM) using a hypofractionated concurrent intensity-modulated radiotherapy (IMRT) boost. Methods: Twenty-one patients were enrolled between April 1999 and August 2003. Radiotherapy consisted of daily fractions of 1.8 Gy with a concurrent boost of 0.7 Gy (total 2.5 Gy daily) to a total dose of 70, 75, or 80 Gy. Concurrent chemotherapy was not permitted. Seven patients were enrolled at each dose and dose limiting toxicities were defined as irreversible Grade 3 or any Grade 4-5 acute neurotoxicity attributable to radiotherapy. Results: All patients experienced Grade 1 or 2 acute toxicities. Acutely, 8 patients experienced Grade 3 and 1 patient experienced Grade 3 and 4 toxicities. Of these, only two reversible cases of otitis media were attributable to radiotherapy. No dose-limiting toxicities were encountered. Only 2 patients experienced Grade 3 delayed toxicity and there was no delayed Grade 4 toxicity. Eleven patients requiring repeat resection or biopsy were found to have viable tumor and radiation changes with no cases of radionecrosis alone. Median overall and progression-free survival for this cohort were 13.6 and 6.5 months, respectively. One- and 2-year survival rates were 57% and 19%. At recurrence, 15 patients received chemotherapy, 9 underwent resection, and 5 received radiotherapy. Conclusions: Using a hypofractionated concurrent IMRT boost, we were able to safely treat patients to 80 Gy without any dose-limiting toxicity. Given that local failure still remains the predominant pattern for GBM patients, a trial of dose escalation with IMRT and temozolomide is warranted.

  7. Decision Regret in Men Undergoing Dose-Escalated Radiation Therapy for Prostate Cancer

    SciTech Connect

    Steer, Anna N.; Aherne, Noel J.; Gorzynska, Karen; Hoffman, Matthew; Last, Andrew; Hill, Jacques; Shakespeare, Thomas P.

    2013-07-15

    Purpose: Decision regret (DR) is a negative emotion associated with medical treatment decisions, and it is an important patient-centered outcome after therapy for localized prostate cancer. DR has been found to occur in up to 53% of patients treated for localized prostate cancer, and it may vary depending on treatment modality. DR after modern dose-escalated radiation therapy (DE-RT) has not been investigated previously, to our knowledge. Our primary aim was to evaluate DR in a cohort of patients treated with DE-RT. Methods and Materials: We surveyed 257 consecutive patients with localized prostate cancer who had previously received DE-RT, by means of a validated questionnaire. Results: There were 220 responses (85.6% response rate). Image-guided intensity modulated radiation therapy was given in 85.0% of patients and 3-dimensional conformal radiation therapy in 15.0%. Doses received included 73.8 Gy (34.5% patients), 74 Gy (53.6%), and 76 Gy (10.9%). Neoadjuvant androgen deprivation (AD) was given in 51.8% of patients and both neoadjuvant and adjuvant AD in 34.5%. The median follow-up time was 23 months (range, 12-67 months). In all, 3.8% of patients expressed DR for their choice of treatment. When asked whether they would choose DE-RT or AD again, only 0.5% probably or definitely would not choose DE-RT again, compared with 8.4% for AD (P<.01). Conclusion: Few patients treated with modern DE-RT express DR, with regret appearing to be lower than in previously published reports of patients treated with radical prostatectomy or older radiation therapy techniques. Patients experienced more regret with the AD component of treatment than with the radiation therapy component, with implications for informed consent. Further research should investigate regret associated with individual components of modern therapy, including AD, radiation therapy and surgery.

  8. Can we avoid dose escalation for intermediate-risk prostate cancer in the setting of short-course neoadjuvant androgen deprivation?

    PubMed Central

    Shakespeare, Thomas P; Wilcox, Shea W; Aherne, Noel J

    2016-01-01

    Background Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve the outcomes in patients with intermediate-risk prostate cancer. Despite this, there are only few reports evaluating DE-EBRT for patients with intermediate-risk prostate cancer receiving neoadjuvant ADT, and virtually no studies investigating dose escalation >74 Gy in this setting. We aimed to determine whether DE-EBRT >74 Gy improved the outcomes for patients with intermediate-risk prostate cancer who received neoadjuvant ADT. Findings In our institution, patients with intermediate-risk prostate cancer were treated with neoadjuvant ADT and DE-EBRT, with doses sequentially increasing from 74 Gy to 76 Gy and then to 78 Gy between 2006 and 2012. We identified 435 patients treated with DE-EBRT and ADT, with a median follow-up of 70 months. For the 74 Gy, 76 Gy, and 78 Gy groups, five-year biochemical disease-free survival rates were 95.0%, 97.8%, and 95.3%, respectively; metastasis-free survival rates were 99.1%, 100.0%, and 98.6%, respectively; and prostate cancer-specific survival rate was 100% for all three dose levels. There was no significant benefit for dose escalation either on univariate or multivariate analysis for any outcome. Conclusion There was no benefit for DE-EBRT >74 Gy in our cohort of intermediate-risk prostate cancer patients treated with neoadjuvant ADT. Given the higher risks of toxicity associated with dose escalation, it may be feasible to omit dose escalation in this group of patients. Randomized studies evaluating dose de-escalation should be considered. PMID:27073327

  9. Evaluations of an adaptive planning technique incorporating dose feedback in image-guided radiotherapy of prostate cancer

    SciTech Connect

    Liu Han; Wu Qiuwen

    2011-12-15

    treatment course, then 11 patients fail. If the same criteria is assessed at the end of each week (every five fractions), then 14 patients fail, with three patients failing the 1st or 2nd week but passing at the end. The average dose deficit from these 14 patients was 4.4%. They improved to 2% after the weekly compensation. Out of these 14 patients who needed dose compensation, ten passed the dose criterion after weekly dose compensation, three patients failed marginally, and one patient still failed the criterion significantly (10% deficit), representing 3.6% of the patient population. A more aggressive compensation frequency (every three fractions) could successfully reduce the dose deficit to the acceptable level for this patient. The average number of required dose compensation re-planning per patient was 0.82 (0.79) per patient for schedule A (B) delivery strategy. The doses to OARs were not significantly different from the online IG only plans without dose compensation. Conclusions: We have demonstrated the effectiveness of offline dose compensation technique in image-guided radiotherapy for prostate cancer. It can effectively account for residual uncertainties which cannot be corrected through online IG. Dose compensation allows further margin reduction and critical organs sparing.

  10. Dosimetric evaluation of the OneDose MOSFET for measuring kilovoltage imaging dose from image-guided radiotherapy procedures

    SciTech Connect

    Ding, George X.; Coffey, Charles W.

    2010-09-15

    Purpose: The purpose of this study is to investigate the feasibility of using a single-use dosimeter, OneDose MOSFET designed for in vivo patient dosimetry, for measuring the radiation dose from kilovoltage (kV) x rays resulting from image-guided procedures. Methods: The OneDose MOSFET dosimeters were precalibrated by the manufacturer using Co-60 beams. Their energy response and characteristics for kV x rays were investigated by using an ionization chamber, in which the air-kerma calibration factors were obtained from an Accredited Dosimetry Calibration Laboratory (ADCL). The dosimetric properties have been tested for typical kV beams used in image-guided radiation therapy (IGRT). Results: The direct dose reading from the OneDose system needs to be multiplied by a correction factor ranging from 0.30 to 0.35 for kilovoltage x rays ranging from 50 to 125 kVp, respectively. In addition to energy response, the OneDose dosimeter has up to a 20% reduced sensitivity for beams (70-125 kVp) incident from the back of the OneDose detector. Conclusions: The uncertainty in measuring dose resulting from a kilovoltage beam used in IGRT is approximately 20%; this uncertainty is mainly due to the sensitivity dependence of the incident beam direction relative to the OneDose detector. The ease of use may allow the dosimeter to be suitable for estimating the dose resulting from image-guided procedures.

  11. Dose Escalation for Prostate Cancer Using the Three-Dimensional Conformal Dynamic Arc Technique: Analysis of 542 Consecutive Patients

    SciTech Connect

    Jereczek-Fossa, Barbara A. Vavassori, Andrea; Fodor, Cristiana; Santoro, Luigi; Zerini, Dario; Cattani, Federica; Garibaldi, Cristina; Cambria, Raffaella; Fodor, Andrei; Boboc, Genoveva Ionela; Vitolo, Viviana; Ivaldi, Giovanni Battista; Musi, Gennaro; De Cobelli, Ottavio; Orecchia, Roberto

    2008-07-01

    Purpose: To present the results of dose escalation using three-dimensional conformal dynamic arc radiotherapy (3D-ART) for prostate cancer. Methods and Materials: Five hundred and forty two T1-T3N0M0 prostate cancer patients were treated with 3D-ART. Dose escalation (from 76 Gy/38 fractions to 80 Gy/40 fractions) was introduced in September 2003; 32% of patients received 80 Gy. In 366 patients, androgen deprivation was added to 3D-ART. Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria and Houston definition (nadir + 2) were used for toxicity and biochemical failure evaluation, respectively. Median follow-up was 25 months. Results: Acute toxicity included rectal (G1-2 28.9%; G3 0.5%) and urinary events (G1-2 57.9%; G3-4 2.4%). Late toxicity included rectal (G1-2 15.8%; G3-4 3.1%) and urinary events (G1-2 26.9%; G3-4 1.6%). Two-year failure-free survival and overall survival rates were 94.1% and 97.9%, respectively. Poor prognostic group (GS, iPSA, T), transurethral prostate resection, and dose >76 Gy showed significant association to high risk of progression in multivariate analysis (p = 0.014, p = 0.045, and p 0.04, respectively). The negative effect of dose >76 Gy was not observed (p 0.10), when the analysis was limited to 353 patients treated after September 2003 (when dose escalation was introduced). Higher dose was not associated with higher late toxicity. Conclusions: Three-dimensional-ART is a feasible modality allowing for dose escalation (no increase in toxicity has been observed with higher doses). However, the dose increase from 76 to 80 Gy was not associated with better tumor outcome. Further investigation is warranted for better understanding of the dose effect for prostate cancer.

  12. [F-18]-fluorodeoxyglucose positron emission tomography for targeting radiation dose escalation for patients with glioblastoma multiforme: Clinical outcomes and patterns of failure

    SciTech Connect

    Douglas, James G. . E-mail: drjay@u.washington.edu; Stelzer, Keith J.; Mankoff, David A.; Tralins, Kevin S.; Krohn, Kenneth A.; Muzi, Mark; Silbergeld, Daniel L.; Rostomily, Robert C.; Scharnhorst, Jeffrey B.S.; Spence, Alexander M.

    2006-03-01

    Purpose: [F-18]-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging for brain tumors has been shown to identify areas of active disease. Radiation dose escalation in the treatment of glioblastoma multiforme may lead to improved disease control. Based on these premises, we initiated a prospective study of FDG-PET for the treatment planning of radiation dose escalation for the treatment of glioblastoma multiforme. Methods and Materials: Forty patients were enrolled. Patients were treated with standard conformal fractionated radiotherapy with volumes defined by MRI imaging. When patients reached a dose of 45-50.4 Gy, they underwent FDG-PET imaging for boost target delineation, for an additional 20 Gy (2 Gy per fraction) to a total dose of 79.4 Gy (n = 30). Results: The estimated 1-year and 2-year overall survival (OS) for the entire group was 70% and 17%, respectively, with a median overall survival of 70 weeks. The estimated 1-year and 2-year progression-free survival (PFS) was 18% and 3%, respectively, with a median of 24 weeks. No significant improvements in OS or PFS were observed for the study group in comparison to institutional historical controls. Conclusions: Radiation dose escalation to 79.4 Gy based on FDG-PET imaging demonstrated no improvement in OS or PFS. This study establishes the feasibility of integrating PET metabolic imaging into radiotherapy treatment planning.

  13. Dosimetric Impact and Theoretical Clinical Benefits of Fiducial Markers for Dose Escalated Prostate Cancer Radiation Treatment

    SciTech Connect

    Gauthier, Isabelle Carrier, Jean-Francois; Beliveau-Nadeau, Dominic; Fortin, Bernard; Taussky, Daniel

    2009-07-15

    Purpose: To assess the impact of fiducial markers and daily kilovoltage imaging (FM-kV) on dose-volume histogram (DVH) parameters and normal tissue complication probabilities (NTCPs) for the rectum and bladder during prostate cancer radiotherapy. Methods and Materials: Two different setup scenarios were compared for 20 patients treated with three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer to a total dose of 76 Gy: a traditional setup with planning target volume (PTV) margins associated with skin mark alignment vs. another setup using FM-kV. Various DVH parameters were compared, including Radiation Therapy Oncology Group (RTOG) dose-volume constraints for the rectum and bladder. Analysis of NTCPs was also performed according to the Lyman model. Results: With the traditional setup, 85% of patients had rectal V70{sub Gy} >25% compared with 45% with FM-kV. Moreover, 30% of patients with traditional setup vs. 5% with FM-kV did not fulfill at least 3 RTOG constraint parameters for the rectum. Mean rectal and bladder dose were 4.7 Gy and 6.7 Gy less, respectively, with FM-kV. The NTCP for the rectum was 11.5% with the traditional setup and 9% with FM-kV. This indicates that with FM-kV, the prescription dose could be increased by 2.1 Gy while keeping the same level of late rectal toxicity as with the traditional setup. Conclusions: Use of FM-kV is an efficient way of lowering the proportion of patients not fulfilling RTOG rectal and bladder dose-volume constraints. The results of the NTCP analysis suggest that the PTV margin reduction allowed by FM-kV should decrease the rate of late rectal toxicities or may allow moderate dose escalation.

  14. Re-irradiation of unresectable recurrent head and neck cancer: using Helical Tomotherapy as image-guided intensity-modulated radiotherapy

    PubMed Central

    Jeong, Songmi; Yoo, Eun Jung; Kim, Ji Yoon; Han, Chi Wha; Kim, Ki Jun

    2013-01-01

    Purpose Re-irradiation (re-RT) is considered a treatment option for inoperable locoregionally recurrent head and neck cancer (HNC) after prior radiotherapy. We evaluated the efficacy and safety of re-RT using Helical Tomotherapy as image-guided intensity-modulated radiotherapy in recurrent HNC. Materials and Methods Patients diagnosed with recurrent HNC and received re-RT were retrospectively reviewed. Primary endpoint was overall survival (OS) and secondary endpoints were locoregional control and toxicities. Results The median follow-up period of total 9 patients was 18.7 months (range, 4.1 to 76 months) and that of 3 alive patients was 49 months (range, 47 to 76 months). Median dose of first radiotherapy and re-RT was 64.8 and 47.5 Gy10. Median cumulative dose of the two courses of radiotherapy was 116.3 Gy10 (range, 91.8 to 128.9 Gy10) while the median interval between the two courses of radiation was 25 months (range, 4 to 137 months). The response rate after re-RT of the evaluated 8 patients was 75% (complete response, 4; partial response, 2). Median locoregional relapse-free survival after re-RT was 11.9 months (range, 3.4 to 75.1 months) and 5 patients eventually presented with treatment failure (in-field failure, 2; in- and out-field failure, 2; out-field failure, 1). Median OS of the 8 patients was 20.3 months (range, 4.1 to 75.1 months). One- and two-year OS rates were 62.5% and 50%, respectively. Grade 3 leucopenia developed in one patient as acute toxicity, and grade 2 osteonecrosis and trismus as chronic toxicity in another patient. Conclusion Re-RT using Helical Tomotherapy for previously irradiated patients with unresectable locoregionally recurrent HNC may be a feasible treatment option with long-term survival and acceptable toxicities. PMID:24501708

  15. Tissue feature-based intra-fractional motion tracking for stereoscopic x-ray image guided radiotherapy

    NASA Astrophysics Data System (ADS)

    Xie, Yaoqin; Xing, Lei; Gu, Jia; Liu, Wu

    2013-06-01

    Real-time knowledge of tumor position during radiation therapy is essential to overcome the adverse effect of intra-fractional organ motion. The goal of this work is to develop a tumor tracking strategy by effectively utilizing the inherent image features of stereoscopic x-ray images acquired during dose delivery. In stereoscopic x-ray image guided radiation delivery, two orthogonal x-ray images are acquired either simultaneously or sequentially. The essence of markerless tumor tracking is the reliable identification of inherent points with distinct tissue features on each projection image and their association between two images. The identification of the feature points on a planar x-ray image is realized by searching for points with high intensity gradient. The feature points are associated by using the scale invariance features transform descriptor. The performance of the proposed technique is evaluated by using images of a motion phantom and four archived clinical cases acquired using either a CyberKnife equipped with a stereoscopic x-ray imaging system, or a LINAC equipped with an onboard kV imager and an electronic portal imaging device. In the phantom study, the results obtained using the proposed method agree with the measurements to within 2 mm in all three directions. In the clinical study, the mean error is 0.48 ± 0.46 mm for four patient data with 144 sequential images. In this work, a tissue feature-based tracking method for stereoscopic x-ray image guided radiation therapy is developed. The technique avoids the invasive procedure of fiducial implantation and may greatly facilitate the clinical workflow.

  16. Image-Guided Radiotherapy (IGRT) for Prostate Cancer Comparing kV Imaging of Fiducial Markers With Cone Beam Computed Tomography (CBCT)

    SciTech Connect

    Barney, Brandon M.; Lee, R. Jeffrey; Handrahan, Diana; Welsh, Keith T.; Cook, J. Taylor; Sause, William T.

    2011-05-01

    Purpose: To present our single-institution experience with image-guided radiotherapy comparing fiducial markers and cone-beam computed tomography (CBCT) for daily localization of prostate cancer. Methods and Materials: From April 2007 to October 2008, 36 patients with prostate cancer received intensity-modulated radiotherapy with daily localization by use of implanted fiducials. Orthogonal kilovoltage (kV) portal imaging preceded all 1244 treatments. Cone-beam computed tomography images were also obtained before 286 treatments (23%). Shifts in the anterior-posterior (AP), superior-inferior (SI), and left-right (LR) dimensions were made from kV fiducial imaging. Cone-beam computed tomography shifts based on soft tissues were recorded. Shifts were compared by use of Bland-Altman limits of agreement. Mean and standard deviation of absolute differences were also compared. A difference of 5 mm or less was acceptable. Subsets including start date, body mass index, and prostate size were analyzed. Results: Of 286 treatments, 81 (28%) resulted in a greater than 5.0-mm difference in one or more dimensions. Mean differences in the AP, SI, and LR dimensions were 3.4 {+-} 2.6 mm, 3.1 {+-} 2.7 mm, and 1.3 {+-} 1.6 mm, respectively. Most deviations occurred in the posterior (fiducials, 78%; CBCT, 59%), superior (79%, 61%), and left (57%, 63%) directions. Bland-Altman 95% confidence intervals were -4.0 to 9.3 mm for AP, -9.0 to 5.3 mm for SI, and -4.1 to 3.9 mm for LR. The percentages of shift agreements within {+-}5 mm were 72.4% for AP, 72.7% for SI, and 97.2% for LR. Correlation between imaging techniques was not altered by time, body mass index, or prostate size. Conclusions: Cone-beam computed tomography and kV fiducial imaging are similar; however, more than one-fourth of CBCT and kV shifts differed enough to affect target coverage. This was even more pronounced with smaller margins (3 mm). Fiducial imaging requires less daily physician input, is less time-consuming, and is

  17. Performance of a Novel Repositioning Head Frame for Gamma Knife Perfexion and Image-Guided Linac-Based Intracranial Stereotactic Radiotherapy

    SciTech Connect

    Ruschin, Mark; Nayebi, Nazanin; Carlsson, Per; Brown, Kevin

    2010-09-01

    Purpose: To evaluate the geometric positioning and immobilization performance of a vacuum bite-block repositioning head frame (RHF) system for Perfexion (PFX-SRT) and linac-based intracranial image-guided stereotactic radiotherapy (SRT). Methods and Materials: Patients with intracranial tumors received linac-based image-guided SRT using the RHF for setup and immobilization. Three hundred thirty-three fractions of radiation were delivered in 12 patients. The accuracy of the RHF was estimated for linac-based SRT with online cone-beam CT (CBCT) and for PFX-SRT with a repositioning check tool (RCT) and offline CBCT. The RCT's ability to act as a surrogate for anatomic position was estimated through comparison to CBCT image matching. Immobilization performance was evaluated daily with pre- and postdose delivery CBCT scans and RCT measurements. Results: The correlation coefficient between RCT- and CBCT-reported displacements was 0.59, 0.75, 0.79 (Right, Superior, and Anterior, respectively). For image-guided linac-based SRT, the mean three-dimensional (3D) setup error was 0.8 mm with interpatient ({Sigma}) and interfraction ({sigma}) variations of 0.1 and 0.4 mm, respectively. For PFX-SRT, the initial, uncorrected mean 3D positioning displacement in stereotactic coordinates was 2.0 mm, with {Sigma} = 1.1 mm and {sigma} = 0.8 mm. Considering only RCT setups <1mm (PFX action level) the mean 3D positioning displacement reduced to 1.3 mm, with {Sigma} = 0.9 mm and {sigma} = 0.4 mm. The largest contributing systematic uncertainty was in the superior-inferior direction (mean displacement = -0.5 mm; {Sigma} = 0.9 mm). The largest mean rotation was 0.6{sup o} in pitch. The mean 3D intrafraction motion was 0.4 {+-} 0.3 mm. Conclusion: The RHF provides excellent immobilization for intracranial SRT and PFX-SRT. Some small systematic uncertainties in stereotactic positioning exist and must be considered when generating PFX-SRT treatment plans. The RCT provides reasonable surrogacy

  18. Estimate of the shielding effect on secondary cancer risk due to cone-beam CT in image-guided radiotherapy

    NASA Astrophysics Data System (ADS)

    Sung, Jiwon; Baek, Tae Seong; Yoon, Myonggeun; Kim, Dong Wook; Kim, Dong Hyun

    2014-09-01

    This study evaluated the effect of a simple shielding method using a thin lead sheet on the imaging dose caused by cone-beam computed tomography (CBCT) in image-guided radiation therapy (IGRT). Reduction of secondary doses from CBCT was measured using a radio-photoluminescence glass dosimeter (RPLGD) placed inside an anthropomorphic phantom. The entire body, except for the region scanned by using CBCT, was shielded by wrapping it with a 2-mm lead sheet. Changes in secondary cancer risk due to shielding were calculated using BEIR VII models. Doses to out-of-field organs for head-and-neck, chest, and pelvis scans were decreased 15 ~ 100%, 23 ~ 90%, and 23 ~ 98%, respectively, and the average reductions in lifetime secondary cancer risk due to the 2-mm lead shielding were 1.6, 11.5, and 12.7 persons per 100,000, respectively. These findings suggest that a simple, thin-lead-sheet-based shielding method can effectively decrease secondary doses to out-of-field regions for CBCT, which reduces the lifetime cancer risk on average by 9 per 100,000 patients.

  19. 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.

  20. A Study on Target Positioning Error and Its Impact on Dose Variation in Image-Guided Stereotactic Body Radiotherapy for the Spine

    SciTech Connect

    Kim, Siyong Jin, Hosang; Yang, Huey; Amdur, Robert J.

    2009-04-01

    Purpose: To investigate the amount of target positioning error and evaluate its dosimetric impact during image-guided stereotactic body radiotherapy for single-fraction spine treatment. Methods and Materials: A prescription dose of 15 Gy and five to nine coplanar intensity-modulated beams were used. The patient was immobilized with a custom-fit vacuum mold, and the target was localized with a volumetric cone-beam CT image. A robotic couch with six degrees of freedom was used for target adjustment. For evaluation a cone-beam CT image was obtained at the end of treatment. Both target positioning error and its dosimetric impact were investigated for the first 9 cases. Results: For cases studied, translational errors were 0.9 {+-} 0.5 mm (lateral), 1.2 {+-} 0.9 mm (longitudinal), 0.7 {+-} 0.6 mm (vertical), and 1.8 {+-} 1.0 mm (vector), and rotational errors were 1.6 deg. {+-} 1.3 deg. (pitch), 0.8 deg. {+-} 0.9 deg. (roll), and 0.8 deg. {+-} 0.4{sup o} (yaw). For the clinical target volume, D{sub 95} (dose to 95% of target volume), D{sub 90}, D{sub max}, and D{sub mean} were evaluated. Only 1 case showed significant dose variations, reaching up to 18% in D{sub 95}. The spinal cord dose was evaluated by observing D{sub 0.1} (dose to 0.1 cm{sup 3}), D{sub 0.5}, D{sub 1.0}, and D{sub max}. Although 1 case showed a dose change reaching up to 30% in D{sub max}, cord dose was within the planning tolerance limit in all but 2 cases (3% higher in one and 0.4% higher in the other). Conclusion: The implemented image-guided stereotactic body radiotherapy provides precise target localization. However, despite reasonably precise spatial precision, dosimetric perturbation can be significant because of both extremely steep dose gradients and close distances between the target and the spinal cord.

  1. [Use of gold radionuclide markers implanted into the prostate for image-guided radiotherapy in prostate cancer: side effects caused by the marker implantation].

    PubMed

    Kliton, Jorgo; Ágoston, Péter; Szabó, Zoltán; Major, Tibor; Polgár, Csaba

    2014-09-01

    The purpose of the study was to introduce the use of the gold radiopaque markers implanted into the prostate for image-guided radiotherapy of prostate cancer patients and to present the side effects caused by the marker implantation. Between November 2011 and November 2013, three radiopaque, gold-plated markers (Best Medical International, Springfield, VA, USA, 1.0 mm x 3.0 mm) were implanted transperineally into the prostate of 60 patients under transrectal ultrasound guidance. Local anaesthesia was performed in all patients. A week after the procedure the patients filled in a questionnaire regarding the pain, dysuria, urinary frequency, nycturia, rectal bleeding, haematuria, haematospermia or fever symptoms caused by the implantation. The pain caused by the intervention was scored on a 1-10 scale, where 1 was a very weak and 10 was an unbearable pain. Ten days after the implantation a treatment planning CT was performed and subsequently patients started intensity-modulated radiation therapy (IMRT) within one week. During the treatments markers were used for daily verification and correction of patient's setup. No patients experienced fever or infection. Based on the questionnaires nobody experienced dysuria or rectal bleeding after implantation. Among the 60 patients studied, five (8 %) had haematospermia, nine (15 %) haematuria, which lasted in average of 3.4 and 1.8 days, respectively. The average pain score on 1-10 scale was 4.2 (range: 0-9). After the marker implantation 18 patients (30%) reported less, 10 patients (17%) more, and 27 patients (45%) equal amount of pain compared to biopsy. Five patients, who had a biopsy performed under general anaesthesia, did not answer this question. None of the patients needed analgesics after implantation. The gold marker implantation implemented for image-guided radiotherapy was well tolerated under a local anaesthesia. The complications were limited, rate and frequency of perioperative pain was comparable to the pain

  2. Do We Need Daily Image-Guided Radiotherapy by Megavoltage Computed Tomography in Head and Neck Helical Tomotherapy? The Actual Delivered Dose to the Spinal Cord

    SciTech Connect

    Duma, Marciana Nona; Kampfer, Severin; Schuster, Tibor; Aswathanarayana, Nandana; Fromm, Laura-Sophie; Molls, Michael; Andratschke, Nicolaus; Geinitz, Hans

    2012-09-01

    Purpose: To quantify the actual delivered dose to the cervical spinal cord with different image-guided radiotherapy (IGRT) approaches during head and neck (HN) cancer helical tomotherapy. Methods and Materials: Twenty HN patients (HNpts) treated with bilateral nodal irradiation were analyzed. Daily megavoltage computed tomography MVCT) scans were performed for setup purposes. The maximum dose on the planning CT scan (plan-Dmax) and the magnitude and localization of the actual delivered Dmax (a-Dmax) were analyzed for four scenarios: daily image-guided radiotherapy (dIGRT), twice weekly IGRT (2 Multiplication-Sign WkIGRT), once weekly IGRT (1 Multiplication-Sign WkIGRT), and no IGRT at all (non-IGRT). The spinal cord was recontoured on 236 MVCTs for each scenario (total, 944 fractions), and the delivered dose was recalculated for each fraction (fx) separately. Results: Fifty-one percent of the analyzed fx for dIGRT, 56% of the analyzed fx for the 2 Multiplication-Sign WkIGRT, 62% of the analyzed fx for the 1 Multiplication-Sign WkIGRT, and 63% of the analyzed fx for the non-IGRT scenarios received a higher a-Dmax than the plan-Dmax. The median increase of dose in these fx was 3.3% more for dIGRT, 5.8% more for 2 Multiplication-Sign WkIGRT, 10.0% more for 1 Multiplication-Sign WkIGRT, and 9.5% more for non-IGRT than the plan-Dmax. The median spinal cord volumes receiving a higher dose than the plan-Dmax were 0.02 cm{sup 3} for dIGRT, 0.11 cm{sup 3} for 2 Multiplication-Sign WkIGRT, 0.31 cm{sup 3} for 1 Multiplication-Sign WkIGRT, and 0.22 cm{sup 3} for non-IGRT. Differences between the dIGRT and all other scenarios were statistically significant (p < 0.05). Conclusions: Compared to the Dmax of the initial plan, daily IGRT had the smallest increase in dose. Furthermore, daily IGRT had the lowest proportion of fractions and the smallest volumes affected by a dose that was higher than the planned dose. For patients treated with doses close to the tolerance dose of the

  3. Polymeric micelles as a diagnostic tool for image-guided drug delivery and radiotherapy of HER2 overexpressing breast cancer

    NASA Astrophysics Data System (ADS)

    Hoang, Nu Bryan

    Block copolymer micelles have emerged as a viable formulation strategy with several drugs relying on this technology in clinical evaluation. To date, information on the tumor penetration and intratumoral distribution of block copolymer micelles (BCM) has been quite limited. Thus, there is impetus to develop a radiolabeled formulation that can be used to gain invaluable insight into the intratumoral distribution of the BCMs. This information could then be used to direct formulation strategies as a means to optimize treatment outcomes. This thesis describes the synthesis and characterization of a targeted block copolymer micelle system based on poly(ethylene glycol)-block -poly(epsilon-caprolactone) labeled with the radionuclide Indium-111 (111In). The incorporation of the imageable component, 111In permits pursuit of image-guided drug delivery for real-time monitoring of tumor localization and intratumoral distribution. Intracellular trafficking of drugs and therapies such as Auger electron emitting radionuclides to perinuclear and nuclear regions of cells is critical to realizing their full therapeutic potential. HER2 specific antibodies (trastuzumab fab fragments) and nuclear localization signal peptides were conjugated to the surface of the BCMs to direct uptake in HER2 expressing cells and subsequent localization in the cell nucleus. Cell uptake was HER2 density dependent, confirming receptor-mediated internalization of the BCMs. Importantly, conjugation of NLS resulted in a significant increase in nuclear uptake of the radionuclide 111In. Successful nuclear targeting was shown to improve the antiproliferative effect of the Auger electrons. In addition, a significant radiation enhancement effect was observed by concurrent delivery of low-dose MTX and 111In in all breast cancer cell lines evaluated. Imaging enabled the accurate quantification of the specific tumor uptake of the micelles and visualization of their degree of tumor penetration in relation to

  4. Assessment of contrast enhanced respiration managed cone-beam CT for image guided radiotherapy of intrahepatic tumors

    SciTech Connect

    Jensen, Nikolaj K. G.; Stewart, Errol; Lock, Michael; Fisher, Barbara; Kozak, Roman; Chen, Jeff; Lee, Ting-Yim; Wong, Eugene

    2014-05-15

    Purpose: Contrast enhancement and respiration management are widely used during image acquisition for radiotherapy treatment planning of liver tumors along with respiration management at the treatment unit. However, neither respiration management nor intravenous contrast is commonly used during cone-beam CT (CBCT) image acquisition for alignment prior to radiotherapy. In this study, the authors investigate the potential gains of injecting an iodinated contrast agent in combination with respiration management during CBCT acquisition for liver tumor radiotherapy. Methods: Five rabbits with implanted liver tumors were subjected to CBCT with and without motion management and contrast injection. The acquired CBCT images were registered to the planning CT to determine alignment accuracy and dosimetric impact. The authors developed a simulation tool for simulating contrast-enhanced CBCT images from dynamic contrast enhanced CT imaging (DCE-CT) to determine optimal contrast injection protocols. The tool was validated against contrast-enhanced CBCT of the rabbit subjects and was used for five human patients diagnosed with hepatocellular carcinoma. Results: In the rabbit experiment, when neither motion management nor contrast was used, tumor centroid misalignment between planning image and CBCT was 9.2 mm. This was reduced to 2.8 mm when both techniques were employed. Tumors were not visualized in clinical CBCT images of human subjects. Simulated contrast-enhanced CBCT was found to improve tumor contrast in all subjects. Different patients were found to require different contrast injections to maximize tumor contrast. Conclusions: Based on the authors’ animal study, respiration managed contrast enhanced CBCT improves IGRT significantly. Contrast enhanced CBCT benefits from patient specific tracer kinetics determined from DCE-CT.

  5. Setup Variations in Radiotherapy of Anal Cancer: Advantages of Target Volume Reduction Using Image-Guided Radiation Treatment

    SciTech Connect

    Chen Yijen; Suh, Steve; Nelson, Rebecca A.; Liu An; Pezner, Richard D.; Wong, Jeffrey Y.C.

    2012-09-01

    Purpose: To define setup variations in the radiation treatment (RT) of anal cancer and to report the advantages of image-guided RT (IGRT) in terms of reduction of target volume and treatment-related side effects. Methods and Materials: Twelve consecutive patients with anal cancer treated by combined chemoradiation by use of helical tomotherapy from March 2007 to November 2008 were selected. With patients immobilized and positioned in place, megavoltage computed tomography (MVCT) scans were performed before each treatment and were automatically registered to planning CT scans. Patients were shifted per the registration data and treated. A total of 365 MVCT scans were analyzed. The primary site received a median dose of 55 Gy. To evaluate the potential dosimetric advantage(s) of IGRT, cases were replanned according to Radiation Therapy Oncology Group 0529, with and without adding recommended setup variations from the current study. Results: Significant setup variations were observed throughout the course of RT. The standard deviations for systematic setup correction in the anterior-posterior (AP), lateral, and superior-inferior (SI) directions and roll rotation were 1.1, 3.6, and 3.2 mm, and 0.3 Degree-Sign , respectively. The average random setup variations were 3.8, 5.5, and 2.9 mm, and 0.5 Degree-Sign , respectively. Without daily IGRT, margins of 4.9, 11.1, and 8.5 mm in the AP, lateral, and SI directions would have been needed to ensure that the planning target volume (PTV) received {>=}95% of the prescribed dose. Conversely, daily IGRT required no extra margins on PTV and resulted in a significant reduction of V15 and V45 of intestine and V10 of pelvic bone marrow. Favorable toxicities were observed, except for acute hematologic toxicity. Conclusions: Daily MVCT scans before each treatment can effectively detect setup variations and thereby reduce PTV margins in the treatment of anal cancer. The use of concurrent chemotherapy and IGRT provided favorable

  6. Improved Clinical Outcomes With High-Dose Image Guided Radiotherapy Compared With Non-IGRT for the Treatment of Clinically Localized Prostate Cancer

    SciTech Connect

    Zelefsky, Michael J.; Kollmeier, Marisa; Cox, Brett; Fidaleo, Anthony; Sperling, Dahlia; Pei, Xin; Carver, Brett; Coleman, Jonathan; Lovelock, Michael; Hunt, Margie

    2012-09-01

    Purpose: To compare toxicity profiles and biochemical tumor control outcomes between patients treated with high-dose image-guided radiotherapy (IGRT) and high-dose intensity-modulated radiotherapy (IMRT) for clinically localized prostate cancer. Materials and Methods: Between 2008 and 2009, 186 patients with prostate cancer were treated with IGRT to a dose of 86.4 Gy with daily correction of the target position based on kilovoltage imaging of implanted prostatic fiducial markers. This group of patients was retrospectively compared with a similar cohort of 190 patients who were treated between 2006 and 2007 with IMRT to the same prescription dose without, however, implanted fiducial markers in place (non-IGRT). The median follow-up time was 2.8 years (range, 2-6 years). Results: A significant reduction in late urinary toxicity was observed for IGRT patients compared with the non-IGRT patients. The 3-year likelihood of grade 2 and higher urinary toxicity for the IGRT and non-IGRT cohorts were 10.4% and 20.0%, respectively (p = 0.02). Multivariate analysis identifying predictors for grade 2 or higher late urinary toxicity demonstrated that, in addition to the baseline Internatinoal Prostate Symptom Score, IGRT was associated with significantly less late urinary toxicity compared with non-IGRT. The incidence of grade 2 and higher rectal toxicity was low for both treatment groups (1.0% and 1.6%, respectively; p = 0.81). No differences in prostate-specific antigen relapse-free survival outcomes were observed for low- and intermediate-risk patients when treated with IGRT and non-IGRT. For high-risk patients, a significant improvement was observed at 3 years for patients treated with IGRT compared with non-IGRT. Conclusions: IGRT is associated with an improvement in biochemical tumor control among high-risk patients and a lower rate of late urinary toxicity compared with high-dose IMRT. These data suggest that, for definitive radiotherapy, the placement of fiducial markers

  7. X-ray volumetric imaging in image-guided radiotherapy: The new standard in on-treatment imaging

    SciTech Connect

    McBain, Catherine A.; Henry, Ann M. . E-mail: catherine.mcbain@christie-tr.nwest.nhs.uk; Sykes, Jonathan; Amer, Ali; Marchant, Tom; Moore, Christopher M.; Davies, Julie; Stratford, Julia; McCarthy, Claire; Porritt, Bridget; Williams, Peter; Khoo, Vincent S.; Price, Pat

    2006-02-01

    Purpose: X-ray volumetric imaging (XVI) for the first time allows for the on-treatment acquisition of three-dimensional (3D) kV cone beam computed tomography (CT) images. Clinical imaging using the Synergy System (Elekta, Crawley, UK) commenced in July 2003. This study evaluated image quality and dose delivered and assessed clinical utility for treatment verification at a range of anatomic sites. Methods and Materials: Single XVIs were acquired from 30 patients undergoing radiotherapy for tumors at 10 different anatomic sites. Patients were imaged in their setup position. Radiation doses received were measured using TLDs on the skin surface. The utility of XVI in verifying target volume coverage was qualitatively assessed by experienced clinicians. Results: X-ray volumetric imaging acquisition was completed in the treatment position at all anatomic sites. At sites where a full gantry rotation was not possible, XVIs were reconstructed from projection images acquired from partial rotations. Soft-tissue definition of organ boundaries allowed direct assessment of 3D target volume coverage at all sites. Individual image quality depended on both imaging parameters and patient characteristics. Radiation dose ranged from 0.003 Gy in the head to 0.03 Gy in the pelvis. Conclusions: On-treatment XVI provided 3D verification images with soft-tissue definition at all anatomic sites at acceptably low radiation doses. This technology sets a new standard in treatment verification and will facilitate novel adaptive radiotherapy techniques.

  8. SU-E-T-306: Study of the Reduction Technique for the Secondary Cancer Risk Due to Cone Beam CT in Image Guided Radiotherapy

    SciTech Connect

    Sung, J; Kim, D; Kim, D; Chung, W; Baek, T; Lee, H; Yoon, M

    2014-06-01

    Purpose: This study evaluated the effectiveness of a thin lead sheet based simple shielding method for imaging doses from cone beam computed tomography (CBCT) in image-guided radiotherapy (IGRT). Methods: The entire body, except for the region scanned by CBCT, was shielded by wrapping in a 2 mm lead sheet. Reduction of secondary doses from CBCT was measured using a radio-photoluminescence glass dosimeter (RPLGD) placed inside an anthropomorphic phantom and changes in secondary cancer risk due to the shielding effect were estimated using BEIR VII model. Results: Doses to out-of-field organs for head-and-neck, chest, and pelvis scans were decreased 15∼100 %, 23∼90 %, and 23∼98 %, respectively, and the average reductions in lifetime secondary cancer risk due to the 2 mm lead shielding were 1.61, 10.4, and 12.8 persons per 100,000, respectively. Conclusion: This study suggests that a simple thin lead sheet based shielding method results in a non-negligible reduction of secondary doses to out-of-field regions for CBCT.

  9. The clinical feasibility and performance of an orthogonal X-ray imaging system for image-guided radiotherapy in nasopharyngeal cancer patients: Comparison with cone-beam CT.

    PubMed

    Zhao, Li-Rong; Zhou, Yi-Bing; Li, Guang-Hui; Li, Qi-Ming; Yang, Ding-Qiang; Li, Han-Xu; Wan, Jiu-Qing; Sun, Jian-Guo

    2016-01-01

    The demand for greater accuracy of intensity-modulated radiotherapy (IMRT) has driven the development of more advanced verification systems for image-guided radiotherapy (IGRT). The purpose of this study is to investigate setup discrepancies measured between an orthogonal X-ray guidance system (XGS-10) and cone-beam computed tomography (CBCT) of Varian in the IMRT of patients with nasopharyngeal cancer (NPC). The setup errors measured by XGS-10 and CBCT at the treatment unit with respect to the planning CTs were recorded for 30 patients with NPC. The differences in residual setup errors between XGS-10 system and CBCT were computed and quantitatively analyzed. The time of image acquisition and image registration was recorded. The radiation doses delivered by CBCT and XGS-10 were measured using PTW0.6CC ionization chambers and a water phantom. The differences between setup errors measured by the XGS-10 system and CBCT were generally <1.5 mm for translations, indicating a reasonably good agreement between the two systems for patients with NPC in the translation directions of A-P (P = 0.856), L-R (P = 0.856) and S-I (P = 0.765). Moreover, compared with CBCT, XGS-10 took much shorter image acquisition and registration time (P <0.001) and delivered only a small fraction of extra radiation dose to the patients (P <0.001). These results indicate that XGS-10 offers high localization accuracy similar to CBCT and additional benefits including prompt imaging process, low imaging radiation exposure, real time monitoring, which therefore represents a potential attractive alternative to CBCT for clinical use. PMID:26703446

  10. Esophageal Cancer Dose Escalation Using a Simultaneous Integrated Boost Technique

    SciTech Connect

    Welsh, James; Palmer, Matthew B.; Ajani, Jaffer A.; Liao Zhongxing; Swisher, Steven G.; Hofstetter, Wayne L.; Allen, Pamela K.; Settle, Steven H.; Gomez, Daniel; Likhacheva, Anna; Cox, James D.; Komaki, Ritsuko

    2012-01-01

    Purpose: We previously showed that 75% of radiation therapy (RT) failures in patients with unresectable esophageal cancer are in the gross tumor volume (GTV). We performed a planning study to evaluate if a simultaneous integrated boost (SIB) technique could selectively deliver a boost dose of radiation to the GTV in patients with esophageal cancer. Methods and Materials: Treatment plans were generated using four different approaches (two-dimensional conformal radiotherapy [2D-CRT] to 50.4 Gy, 2D-CRT to 64.8 Gy, intensity-modulated RT [IMRT] to 50.4 Gy, and SIB-IMRT to 64.8 Gy) and optimized for 10 patients with distal esophageal cancer. All plans were constructed to deliver the target dose in 28 fractions using heterogeneity corrections. Isodose distributions were evaluated for target coverage and normal tissue exposure. Results: The 50.4 Gy IMRT plan was associated with significant reductions in mean cardiac, pulmonary, and hepatic doses relative to the 50.4 Gy 2D-CRT plan. The 64.8 Gy SIB-IMRT plan produced a 28% increase in GTV dose and comparable normal tissue doses as the 50.4 Gy IMRT plan; compared with the 50.4 Gy 2D-CRT plan, the 64.8 Gy SIB-IMRT produced significant dose reductions to all critical structures (heart, lung, liver, and spinal cord). Conclusions: The use of SIB-IMRT allowed us to selectively increase the dose to the GTV, the area at highest risk of failure, while simultaneously reducing the dose to the normal heart, lung, and liver. Clinical implications warrant systematic evaluation.

  11. Image-guided robotic stereotactic body radiotherapy for benign spinal tumors: theUniversity of California San Francisco preliminary experience.

    PubMed

    Sahgal, A; Chou, D; Ames, C; Ma, L; Lamborn, K; Huang, K; Chuang, C; Aiken, A; Petti, P; Weinstein, P; Larson, D

    2007-12-01

    We evaluate our preliminary experience using the Cyberknife Radiosurgery System in treating benign spinal tumors. A retrospective review of 16 consecutively treated patients, comprising 19 benign spinal tumors, was performed. Histologic types included neurofibroma [11], chordoma [4], hemangioma [2], and meningioma [2]. Three patients had Neurofibromatosis Type 1 (NF1). Only one tumor, recurrent chordoma, had been previously irradiated, and as such not considered in the local failure analysis. Local failure, for the remaining 18 tumors, was based clinically on symptom progression and/or tumor enlargement based on imaging. Indications for spine stereotactic body radiotherapy (SBRT) consisted of either adjuvant to subtotal resection (5/19), primary treatment alone (12/19), boost following external beam radiotherapy (1/19), and salvage following previous radiation (1/19). Median tumor follow-up is 25 months (2-37), and one patient (with NF1) died at 12 months from a stroke. The median total dose, number of fractions, and prescription isodose was 21 Gy (10-30 Gy), 3 fx (1-5 fx), 80% (42-87%). The median tumor volume was 7.6 cc (0.2-274.1 cc). The median V100 (volume V receiving 100% of the prescribed dose) and maximum tumor dose was 95% (77-100%) and 26.7 Gy (15.4-59.7 Gy), respectively. Three tumors progressed at 2, 4, and 36 months post-SR (n=18). Two tumors were neurofibromas (both in NF1 patients), and the third was an intramedullary hemangioblastoma. Based on imaging, two tumors had MRI documented progression, three had regressed, and 13 were unchanged (n=18). With short follow-up, local control following Cyberknife spine SBRT for benign spinal tumors appear acceptable. PMID:17994789

  12. [Postoperative radiotherapy of prostate cancer].

    PubMed

    Guérif, S; Latorzeff, I; Lagrange, J-L; Hennequin, C; Supiot, S; Garcia, A; François, P; Soulié, M; Richaud, P; Salomon, L

    2014-10-01

    Between 10 and 40% of patients who have undergone a radical prostatectomy may have a biologic recurrence. Local or distant failure represents the possible patterns of relapse. Patients at high-risk for local relapse have extraprostatic disease, positive surgical margins or seminal vesicles infiltration or high Gleason score at pathology. Three phase-III randomized clinical trials have shown that, for these patients, adjuvant irradiation reduces the risk of tumoral progression without higher toxicity. Salvage radiotherapy for late relapse allows a disease control in 60-70% of the cases. Several research in order to improve the therapeutic ratio of the radiotherapy after prostatectomy are evaluate in the French Groupe d'Étude des Tumeurs Urogénitales (Gétug) and of the French association of urology (Afu). The Gétug-Afu 17 trial will provide answers to the question of the optimal moment for postoperative radiotherapy for pT3-4 R1 pN0 Nx patients, with the objective of comparing an immediate treatment to a differed early treatment initiated at biological recurrence. The Gétug-Afu 22 questions the place of a short hormonetherapy combined with image-guided, intensity-modulated radiotherapy (IMRT) in adjuvant situation for a detectable prostate specific antigen (PSA). The implementation of a multicenter quality control within the Gétug-Afu in order to harmonize a modern postoperative radiotherapy will allow the development of a dose escalation IMRT after surgery. PMID:25195116

  13. SU-E-J-12: An Image-Guided Soft Robotic Patient Positioning System for Maskless Head-And-Neck Cancer Radiotherapy: A Proof-Of-Concept Study

    SciTech Connect

    Ogunmolu, O; Gans, N; Jiang, S; Gu, X

    2015-06-15

    Purpose: We propose a surface-image-guided soft robotic patient positioning system for maskless head-and-neck radiotherapy. The ultimate goal of this project is to utilize a soft robot to realize non-rigid patient positioning and real-time motion compensation. In this proof-of-concept study, we design a position-based visual servoing control system for an air-bladder-based soft robot and investigate its performance in controlling the flexion/extension cranial motion on a mannequin head phantom. Methods: The current system consists of Microsoft Kinect depth camera, an inflatable air bladder (IAB), pressured air source, pneumatic valve actuators, custom-built current regulators, and a National Instruments myRIO microcontroller. The performance of the designed system was evaluated on a mannequin head, with a ball joint fixed below its neck to simulate torso-induced head motion along flexion/extension direction. The IAB is placed beneath the mannequin head. The Kinect camera captures images of the mannequin head, extracts the face, and measures the position of the head relative to the camera. This distance is sent to the myRIO, which runs control algorithms and sends actuation commands to the valves, inflating and deflating the IAB to induce head motion. Results: For a step input, i.e. regulation of the head to a constant displacement, the maximum error was a 6% overshoot, which the system then reduces to 0% steady-state error. In this initial investigation, the settling time to reach the regulated position was approximately 8 seconds, with 2 seconds of delay between the command start of motion due to capacitance of the pneumatics, for a total of 10 seconds to regulate the error. Conclusion: The surface image-guided soft robotic patient positioning system can achieve accurate mannequin head flexion/extension motion. Given this promising initial Result, the extension of the current one-dimensional soft robot control to multiple IABs for non-rigid positioning control

  14. Outcome of Elderly Patients with Meningioma after Image-Guided Stereotactic Radiotherapy: A Study of 100 Cases

    PubMed Central

    Budach, Volker; Graaf, Lukas; Gollrad, Johannes; Badakhshi, Harun

    2015-01-01

    Introduction. Incidence of meningioma increases with age. Surgery has been the mainstay treatment. Elderly patients, however, are at risk of severe morbidity. Therefore, we conducted this study to analyze long-term outcomes of linac-based fractionated stereotactic radiotherapy (FSRT) for older adults (aged ≥65 years) with meningioma and determine prognostic factors. Materials and Methods. Between October 1998 and March 2009, 100 patients (≥65, median age, 71 years) were treated with FSRT for meningioma. Two patients were lost to follow-up. Eight patients each had grade I and grade II meningiomas, and five patients had grade III meningiomas. The histology was unknown in 77 cases (grade 0). Results. The median follow-up was 37 months, and 3-year, 5-year, and 10-year progression-free survival (PFS) rates were 93.7%, 91.1%, and 82%. Patients with grade 0/I meningioma showed 3- and 5-year PFS rates of 98.4% and 95.6%. Patients with grade II or III meningiomas showed 3-year PFS rates of 36%. 93.8% of patients showed local tumor control. Multivariate analysis did not indicate any significant prognostic factors. Conclusion. FSRT may play an important role as a noninvasive and safe method in the clinical management of older patients with meningioma. PMID:26101778

  15. Clinical Feasibility of Using an EPID in cine Mode for Image-Guided Verification of Stereotactic Body Radiotherapy

    SciTech Connect

    Berbeco, Ross I.

    2007-09-01

    Purpose: To introduce a novel method for monitoring tumor location during stereotactic body radiotherapy (SBRT) while the treatment beam is on by using a conventional electronic portal imaging device (EPID). Methods and Materials: In our clinic, selected patients were treated under a phase I institutional review board-approved SBRT protocol for limited hepatic metastases from solid tumors. Before treatment planning multiple gold fiducial markers were implanted on the periphery of the tumor. During treatment the EPID was used in cine mode to collect the exit radiation and produce a sequence of images for each field. An in-house program was developed for calculating the location of the fiducials and their relative distance to the planned locations. Results: Three case studies illustrate the utility of the technique. Patient A exhibited a systematic shift of 4 mm during one of the treatment beams. Patient B showed an inferior drift of the target of approximately 1 cm from the time of setup to the end of the fraction. Patient C had a poor setup on the first day of treatment that was quantified and accounted for on subsequent treatment days. Conclusions: Target localization throughout each treatment beam can be quickly assessed with the presented technique. Treatment monitoring with an EPID in cine mode is shown to be a clinically feasible and useful tool.

  16. A Phase I clinical and pharmacology study using amifostine as a radioprotector in dose-escalated whole liver radiation therapy

    PubMed Central

    Feng, Mary; Smith, David E.; Normolle, Daniel P.; Knol, James A.; Pan, Charlie C.; Ben-Josef, Edgar; Lu, Zheng; Feng, Meihua R.; Chen, Jun; Ensminger, William; Lawrence, Theodore S.

    2011-01-01

    PURPOSE Diffuse intrahepatic tumors are difficult to control. Whole liver radiotherapy has been limited by toxicity, most notably radiation-induced liver disease (RILD). Amifostine is a prodrug free-radical scavenger that selectively protects normal tissues and, in a preclinical model of intrahepatic cancer, systemic amifostine reduced normal liver radiation damage without compromising tumor effect.(1) We hypothesized that amifostine would permit escalation of whole liver radiation dose to potentially control microscopic disease. We also aimed to characterize the pharmacokinetics of amifostine and its active metabolite WR-1065 to optimize timing of radiotherapy. METHODS AND MATERIALS We conducted a radiation dose escalation trial for patients with diffuse, intrahepatic cancer treated with whole liver radiation and intravenous amifostine. Radiation dose was assigned using the Time-to-Event Continual Reassessment Method. A companion pharmacokinetic study was performed. RESULTS 23 patients were treated, with a maximum dose of 40 Gy. Using a logistical regression model, compared to our previously treated patients, amifostine increased liver tolerance by 3.3 ± 1.1 Gy (p=0.007) (approximately 10%) with similar response rates. Peak concentrations of WR-1065 were 25 μM with an elimination half life of 1.5 hours; these levels are consistent with radioprotective effects of amifostine in patients. CONCLUSION These findings demonstrate for the first time that amifostine is a normal liver radioprotector. They further suggest that it may be useful to combine amifostine with fractionated or stereotactic body radiation therapy for patients with focal intrahepatic cancer. PMID:22440042

  17. Definition and visualisation of regions of interest in post-prostatectomy image-guided intensity modulated radiotherapy

    SciTech Connect

    Bell, Linda J Cox, Jennifer; Eade, Thomas; Rinks, Marianne; Kneebone, Andrew

    2014-09-15

    Standard post-prostatectomy radiotherapy (PPRT) image verification uses bony anatomy alignment. However, the prostate bed (PB) moves independently of bony anatomy. Cone beam computed tomography (CBCT) can be used to soft tissue match, so radiation therapists (RTs) must understand pelvic anatomy and PPRT clinical target volumes (CTV). The aims of this study are to define regions of interest (ROI) to be used in soft tissue matching image guidance and determine their visibility on planning CT (PCT) and CBCT. Published CTV guidelines were used to select ROIs. The PCT scans (n = 23) and CBCT scans (n = 105) of 23 post-prostatectomy patients were reviewed. Details on ROI identification were recorded. Eighteen patients had surgical clips. All ROIs were identified on PCTs at least 90% of the time apart from mesorectal fascia (MF) (87%) due to superior image quality. When surgical clips are present, the seminal vesicle bed (SVB) was only seen in 2.3% of CBCTs and MF was unidentifiable. Most other structures were well identified on CBCT. The anterior rectal wall (ARW) was identified in 81.4% of images and penile bulb (PB) in 68.6%. In the absence of surgical clips, the MF and SVB were always identified; the ARW was identified in 89.5% of CBCTs and PB in 73.7%. Surgical clips should be used as ROIs when present to define SVB and MF. In the absence of clips, SVB, MF and ARW can be used. RTs must have a strong knowledge of soft tissue anatomy and PPRT CTV to ensure coverage and enable soft tissue matching.

  18. Intrafraction Variation of Mean Tumor Position During Image-Guided Hypofractionated Stereotactic Body Radiotherapy for Lung Cancer

    SciTech Connect

    Shah, Chirag; Grills, Inga S.; Kestin, Larry L.; McGrath, Samuel; Ye Hong; Martin, Shannon K.; Yan Di

    2012-04-01

    Purpose: Prolonged delivery times during daily cone-beam computed tomography (CBCT)-guided lung stereotactic body radiotherapy (SBRT) introduce concerns regarding intrafraction variation (IFV) of the mean target position (MTP). The purpose of this study was to evaluate the magnitude of the IFV-MTP and to assess target margins required to compensate for IFV and postonline CBCT correction residuals. Patient, treatment, and tumor characteristics were analyzed with respect to their impact on IFV-MTP. Methods and Materials: A total of 126 patients with 140 tumors underwent 659 fractions of lung SBRT. Dose prescribed was 48 or 60 Gy in 12 Gy fractions. Translational target position correction of the MTP was performed via onboard CBCT. IFV-MTP was measured as the difference in MTP between the postcorrection CBCT and the posttreatment CBCT excluding residual error. Results: IFV-MTP was 0.2 {+-} 1.8 mm, 0.1 {+-} 1.9 mm, and 0.01 {+-} 1.5 mm in the craniocaudal, anteroposterior, and mediolateral dimensions and the IFV-MTP vector was 2.3 {+-} 2.1 mm. Treatment time and excursion were found to be significant predictors of IFV-MTP. An IFV-MTP vector greater than 2 and 5 mm was seen in 40.8% and 7.2% of fractions, respectively. IFV-MTP greater than 2 mm was seen in heavier patients with larger excursions and longer treatment times. Significant differences in IFV-MTP were seen between immobilization devices. The stereotactic frame immobilization device was found to be significantly less likely to have an IFV-MTP vector greater than 2 mm compared with the alpha cradle, BodyFIX, and hybrid immobilization devices. Conclusions: Treatment time and respiratory excursion are significantly associated with IFV-MTP. Significant differences in IFV-MTP were found between immobilization devices. Target margins for IFV-MTP plus post-correction residuals are dependent on immobilization device with 5-mm uniform margins being acceptable for the frame immobilization device.

  19. Does Image-Guided Radiotherapy Improve Toxicity Profile in Whole Pelvic-Treated High-Risk Prostate Cancer? Comparison Between IG-IMRT and IMRT

    SciTech Connect

    Chung, Hans T. Xia Ping; Chan, Linda W.; Park-Somers, Eileen; Roach, Mack

    2009-01-01

    Purpose: To evaluate the impact of adding image-guided (IG) technique to intensity-modulated radiotherapy (IMRT) on dosimetric avoidance of organs at risk (OAR) and acute toxicities. Methods and Materials: A total of 25 consecutively treated patients (10 from National University Hospital and 15 from University of California San Francisco) with high-risk prostate cancer formed the study cohort. All received definitive IMRT with prophylactic nodal RT. Similar IMRT contouring and planning techniques were used at both centers. At University of California, San Francisco, intraprostatic fiducial markers were used for daily pretreatment on-line corrections (IG-IMRT). In contrast, at the National University Hospital, no fiducial markers were used (IMRT). At University of California, San Francisco, the planning target volume margins to the prostate were 2-3 mm. At the National University Hospital, they were 1 cm circumferentially, except for 0.5 cm posteriorly. The acute rectal and bladder toxicities and dosimetric endpoints to the planning target volume and organs at risk were compared. Results: The planning target volume dose coverage was not significantly different between IMRT and IG-IMRT for the prostate, seminal vesicles, and lymph nodes. The volume of rectum and bladder receiving {>=}40, {>=}60, and {>=}70 Gy were all significantly less using IG-IMRT (p <0.001). IG-IMRT yielded lower acute Radiation Therapy Oncology Group Grade 2 rectal (80% vs. 13%, p = 0.004) and bladder (60% vs. 13%, p = 0.014) toxicities. Conclusions: IG-IMRT, using daily target localization with fiducial markers, permits the use of smaller margins and correspondingly lower doses to the organs at risk, such as the rectum and bladder. These tangible gains appear to translate into lower clinically significant toxicities.

  20. SU-E-J-151: Dosimetric Evaluation of DIR Mapped Contours for Image Guided Adaptive Radiotherapy with 4D Cone-Beam CT

    SciTech Connect

    Balik, S; Weiss, E; Williamson, J; Hugo, G; Jan, N; Zhang, L; Roman, N; Christensen, G

    2014-06-01

    Purpose: To estimate dosimetric errors resulting from using contours deformably mapped from planning CT to 4D cone beam CT (CBCT) images for image-guided adaptive radiotherapy of locally advanced non-small cell lung cancer (NSCLC). Methods: Ten locally advanced non-small cell lung cancer (NSCLC) patients underwent one planning 4D fan-beam CT (4DFBCT) and weekly 4DCBCT scans. Multiple physicians delineated the gross tumor volume (GTV) and normal structures in planning CT images and only GTV in CBCT images. Manual contours were mapped from planning CT to CBCTs using small deformation, inverse consistent linear elastic (SICLE) algorithm for two scans in each patient. Two physicians reviewed and rated the DIR-mapped (auto) and manual GTV contours as clinically acceptable (CA), clinically acceptable after minor modification (CAMM) and unacceptable (CU). Mapped normal structures were visually inspected and corrected if necessary, and used to override tissue density for dose calculation. CTV (6mm expansion of GTV) and PTV (5mm expansion of CTV) were created. VMAT plans were generated using the DIR-mapped contours to deliver 66 Gy in 33 fractions with 95% and 100% coverage (V66) to PTV and CTV, respectively. Plan evaluation for V66 was based on manual PTV and CTV contours. Results: Mean PTV V66 was 84% (range 75% – 95%) and mean CTV V66 was 97% (range 93% – 100%) for CAMM scored plans (12 plans); and was 90% (range 80% – 95%) and 99% (range 95% – 100%) for CA scored plans (7 plans). The difference in V66 between CAMM and CA was significant for PTV (p = 0.03) and approached significance for CTV (p = 0.07). Conclusion: The quality of DIR-mapped contours directly impacted the plan quality for 4DCBCT-based adaptation. Larger safety margins may be needed when planning with auto contours for IGART with 4DCBCT images. Reseach was supported by NIH P01CA116602.

  1. Electronic portal imaging vs kilovoltage imaging in fiducial marker image-guided radiotherapy for prostate cancer: an analysis of set-up uncertainties

    PubMed Central

    Gill, S; Thomas, J; Fox, C; Kron, T; Thompson, A; Chander, S; Williams, S; Tai, K H; Duchesne, G; Foroudi, F

    2012-01-01

    Objectives The purpose of this study was to compare interfraction prostate displacement data between electronic portal imaging (EPI) and kilovoltage imaging (KVI) treatment units and discuss the impact of any difference on margin calculations for prostate cancer image-guided radiotherapy (IGRT). Methods Prostate interfraction displacement data was collected prospectively for the first 4 fractions in 333 patients treated with IGRT with daily pre-treatment EPI or KVI orthogonal imaging. Displacement was recorded in the anteroposterior (AP), left–right (LR) and superoinferior (SI) directions. The proportion of displacement <3 mm and the difference in median absolute displacements were calculated in all directions. Results 1088 image pairs were analysed in total, 448 by EPI and 640 by KVI. There were 23% (95% confidence interval [CI] 18–28%) more displacements under 3 mm for EPI than for KVI in the AP direction, 14% (95% CI 10–19%) more in the LR direction and 10% (95% CI 5–15%) more in the SI direction. The differences in absolute median displacement (KVI>EPI) were AP 1 mm, LR 1 mm and SI 0.5 mm. Wilcoxon rank-sum test showed that distributions were significantly different for all three dimensions (p<0.0001 for AP and LR and p=0.02 for SI). Conclusion EPI has a statistically significant smaller set-up error distribution than KVI. We would expect that, because fiducial marker imaging is less clear for EPI, the clinical target volume to planning target volume margin would be greater when using IGRT; however, relying wholly on displacement data gives the opposite result. We postulate that this is owing to observer bias, which is not accounted for in margin calculation formulas. PMID:21976627

  2. Interfractional Prostate Shifts: Review of 1870 Computed Tomography (CT) Scans Obtained During Image-Guided Radiotherapy Using CT-on-Rails for the Treatment of Prostate Cancer

    SciTech Connect

    Wong, James R. Gao Zhanrong; Uematsu, Minoru; Merrick, Scott; Machernis, Nolan P.; Chen, Timothy; Cheng, C.W.

    2008-12-01

    Purpose: To review 1870 CT scans of interfractional prostate shift obtained during image-guided radiotherapy. Methods and Materials: A total of 1870 pretreatment CT scans were acquired with CT-on-rails, and the corresponding shift data for 329 patients with prostate cancer were analyzed. Results: Of the 1870 scans reviewed, 44% required no setup adjustments in the anterior-posterior (AP) direction, 14% had shifts of 3-5 mm, 29% had shifts of 6-10 mm, and 13% had shifts of >10 mm. In the superior-inferior direction, 81% had no adjustments, 2% had shifts of 3-5 mm, 15% had shifts of 6-10 mm, and 2% had shifts of >10 mm. In the left-right direction, 65% had no adjustment, 13% had shifts of 3-5 mm, 17% had shifts of 6-10 mm, and 5% had shifts of >10 mm. Further analysis of the first 66 consecutive patients divided into three groups according to body mass index indicates that the shift in the AP direction for the overweight subgroup was statistically larger than those for the control and obese subgroups (p < 0.05). The interfractional shift in the lateral direction for the obese group (1 SD, 5.5 mm) was significantly larger than those for the overweight and control groups (4.1 and 2.9 mm, respectively) (p < 0.001). Conclusions: These data demonstrate that there is a significantly greater shift in the AP direction than in the lateral and superior-inferior directions for the entire patient group. Overweight and obese patient groups show a significant difference from the control group in terms of prostate shift.

  3. Residual Seminal Vesicle Displacement in Marker-Based Image-Guided Radiotherapy for Prostate Cancer and the Impact on Margin Design

    SciTech Connect

    Smitsmans, Monique H.P.; Bois, Josien de; Sonke, Jan-Jakob; Catton, Charles N.; Jaffray, David A.; Lebesque, Joos V.; Herk, Marcel van

    2011-06-01

    Purpose: The objectives of this study were to quantify residual interfraction displacement of seminal vesicles (SV) and investigate the efficacy of rotation correction on SV displacement in marker-based prostate image-guided radiotherapy (IGRT). We also determined the effect of marker registration on the measured SV displacement and its impact on margin design. Methods and Materials: SV displacement was determined relative to marker registration by using 296 cone beam computed tomography scans of 13 prostate cancer patients with implanted markers. SV were individually registered in the transverse plane, based on gray-value information. The target registration error (TRE) for the SV due to marker registration inaccuracies was estimated. Correlations between prostate gland rotations and SV displacement and between individual SV displacements were determined. Results: The SV registration success rate was 99%. Displacement amounts of both SVs were comparable. Systematic and random residual SV displacements were 1.6 mm and 2.0 mm in the left-right direction, respectively, and 2.8 mm and 3.1 mm in the anteroposterior (AP) direction, respectively. Rotation correction did not reduce residual SV displacement. Prostate gland rotation around the left-right axis correlated with SV AP displacement (R{sup 2} = 42%); a correlation existed between both SVs for AP displacement (R{sup 2} = 62%); considerable correlation existed between random errors of SV displacement and TRE (R{sup 2} = 34%). Conclusions: Considerable residual SV displacement exists in marker-based IGRT. Rotation correction barely reduced SV displacement, rather, a larger SV displacement was shown relative to the prostate gland that was not captured by the marker position. Marker registration error partly explains SV displacement when correcting for rotations. Correcting for rotations, therefore, is not advisable when SV are part of the target volume. Margin design for SVs should take these uncertainties into

  4. SU-E-J-47: Development of a High-Precision, Image-Guided Radiotherapy, Multi- Purpose Radiation Isocenter Quality-Assurance Calibration and Checking System

    SciTech Connect

    Liu, C; Yan, G; Helmig, R; Lebron, S; Kahler, D

    2014-06-01

    Purpose: To develop a system that can define the radiation isocenter and correlate this information with couch coordinates, laser alignment, optical distance indicator (ODI) settings, optical tracking system (OTS) calibrations, and mechanical isocenter walkout. Methods: Our team developed a multi-adapter, multi-purpose quality assurance (QA) and calibration device that uses an electronic portal imaging device (EPID) and in-house image-processing software to define the radiation isocenter, thereby allowing linear accelerator (Linac) components to be verified and calibrated. Motivated by the concept that each Linac component related to patient setup for image-guided radiotherapy based on cone-beam CT should be calibrated with respect to the radiation isocenter, we designed multiple concentric adapters of various materials and shapes to meet the needs of MV and KV radiation isocenter definition, laser alignment, and OTS calibration. The phantom's ability to accurately define the radiation isocenter was validated on 4 Elekta Linacs using a commercial ball bearing (BB) phantom as a reference. Radiation isocenter walkout and the accuracy of couch coordinates, ODI, and OTS were then quantified with the device. Results: The device was able to define the radiation isocenter within 0.3 mm. Radiation isocenter walkout was within ±1 mm at 4 cardinal angles. By switching adapters, we identified that the accuracy of the couch position digital readout, ODI, OTS, and mechanical isocenter walkout was within sub-mm. Conclusion: This multi-adapter, multi-purpose isocenter phantom can be used to accurately define the radiation isocenter and represents a potential paradigm shift in Linac QA. Moreover, multiple concentric adapters allowed for sub-mm accuracy for the other relevant components. This intuitive and user-friendly design is currently patent pending.

  5. Dosimetric characterization of a multileaf collimator for a new four-dimensional image-guided radiotherapy system with a gimbaled x-ray head, MHI-TM2000

    SciTech Connect

    Nakamura, Mitsuhiro; Sawada, Akira; Ishihara, Yoshitomo; Takayama, Kenji; Mizowaki, Takashi; Kaneko, Shuji; Yamashita, Mikiko; Tanabe, Hiroaki; Kokubo, Masaki; Hiraoka, Masahiro

    2010-09-15

    Purpose: To present the dosimetric characterization of a multileaf collimator (MLC) for a new four-dimensional image-guided radiotherapy system with a gimbaled x-ray head, MHI-TM2000. Methods: MHI-TM2000 has an x-ray head composed of an ultrasmall linear accelerator guide and a system-specific MLC. The x-ray head can rotate along the two orthogonal gimbals (pan and tilt rotations) up to {+-}2.5 deg., which swings the beam up to {+-}41.9 mm in each direction from the isocenter on the isocenter plane perpendicular to the beam. The MLC design is a single-focus type, has 30 pairs of 5 mm thick leaves at the isocenter, and produces a maximum field size of 150x150 mm{sup 2}. Leaf height and length are 110 and 260 mm, respectively. Each leaf end is circular, with a radius of curvature of 370 mm. The distance that each leaf passes over the isocenter is 77.5 mm. Radiation leakage between adjacent leaves is minimized by an interlocking tongue-and-groove (T and G) arrangement with the height of the groove part 55 mm. The dosimetric characterizations including field characteristics, leaf position accuracy, leakage, and T and G effect were evaluated using a well-commissioned 6 MV photon beam, EDR2 films (Kodak, Rochester, NY), and water-equivalent phantoms. Furthermore, the field characteristics and leaf position accuracy were evaluated under conditions of pan or tilt rotation. Results: The differences between nominal and measured field sizes were within {+-}0.5 mm. Although the penumbra widths were greater with wider field size, the maximum width was <5.5 mm even for the fully opened field. Compared to the results of field characteristics without pan or tilt rotation, the variation in field size, penumbra width, flatness, and symmetry was within {+-}1 mm/1% at the maximum pan or tilt rotational angle. The leaf position accuracy was 0.0{+-}0.1 mm, ranging from -0.3 to 0.2 mm at four gantry angles of 0 deg., 90 deg., 180 deg., and 270 deg. with and without pan or tilt rotation

  6. SU-E-J-14: A Novel Approach to Evaluate the Dosimetric Effect of Rectal Variation During Image Guided Prostate Radiotherapy

    SciTech Connect

    Murray, J; McQuaid, D; Dunlop, A; Nill, S; Gulliford, S; Buettner, F; Hall, E; Dearnaley, D

    2014-06-01

    Purpose: Deformable registration establishes the spatial correspondence back to the reference image in order to accumulate dose. However, in prostate radiotherapy the changing shape and volume of the rectum present a challenge to accurate deformable registration and consequently calculation of delivered dose. We explored an alternative approach to calculating accumulated dose to the rectum, independent of deformable registration. Methods: This study was performed on three patients who received online image-guided radiotherapy (IGRT) with daily CBCT (XVI-system,Elekta) and target localization using intraprostatic fiducials. On each CBCT, the rectum was manually contoured and bulk density assignments were made allowing dose to be calculated for each fraction. Dose-surface maps (DSM) were generated (MATLAB,Mathworks,Natick,MA) by considering the rectum as a cylinder and sampling the dose at 21-equispaced points on each CT slice. The cylinder was “cut” at the posterior-most position on each CT and unfolded to generate a DSM. These were normalised in the longitudinal direction by interpolation creating maps of 21×21 pixels. A DSM was produced for each CBCT and the dose was accumulated. Results: The mean accumulated delivered rectal surface dose was on average 7.5(+/−3.5)% lower than the planned dose. The dose difference maps consistently show that the greatest variation in dose between planned and delivered dose is away from where the rectal surface is adjacent to the prostate. Conclusion: Estimation of dose accumulation using DSM provides an alternative method for determining actual delivered dose to the rectum. The dose difference is greatest in areas away from the region where the rectal surface abuts the prostate, the region where set-up is verified. The change in size and shape of the rectum was shown to resultin a change in the accumulated dose compared to the planned dose and this will have an impact on determining the relationships between dose delivered

  7. Accuracy and efficiency of an infrared based positioning and tracking system for patient set-up and monitoring in image guided radiotherapy

    NASA Astrophysics Data System (ADS)

    Jia, Jing; Xu, Gongming; Pei, Xi; Cao, Ruifen; Hu, Liqin; Wu, Yican

    2015-03-01

    monitoring during image guided radiotherapy treatments.

  8. Potential for dose-escalation and reduction of risk in pancreatic cancer using IMRT optimization with lexicographic ordering and gEUD-based cost functions.

    PubMed

    Spalding, Aaron C; Jee, Kyung-Wook; Vineberg, Karen; Jablonowski, Marla; Fraass, Benedick A; Pan, Charlie C; Lawrence, Theodore S; Haken, Randall K Ten; Ben-Josef, Edgar

    2007-02-01

    Radiotherapy for pancreatic cancer is limited by the tolerance of local organs at risk (OARs) and frequent overlap of the planning target volume (PTV) and OAR volumes. Using lexicographic ordering (LO), a hierarchical optimization technique, with generalized equivalent uniform dose (gEUD) cost functions, we studied the potential of intensity modulated radiation therapy (IMRT) to increase the dose to pancreatic tumors and to areas of vascular involvement that preclude surgical resection [surgical boost volume (SBV)]. We compared 15 forward planned three-dimensional conformal (3DCRT) and IMRT treatment plans for locally advanced unresectable pancreatic cancer. We created IMRT plans optimized using LO with gEUD-based cost functions that account for the contribution of each part of the resulting inhomogeneous dose distribution. LO-IMRT plans allowed substantial PTV dose escalation compared with 3DCRT; median increase from 52 Gy to 66 Gy (a=-5,p<0.005) and median increase from 50 Gy to 59 Gy (a=-15,p<0.005). LO-IMRT also allowed increases to 85 Gy in the SBV, regardless of a value, along with significant dose reductions in OARs. We conclude that LO-IMRT with gEUD cost functions could allow dose escalation in pancreas tumors with concomitant reduction in doses to organs at risk as compared with traditional 3DCRT. PMID:17388169

  9. Potential for dose-escalation and reduction of risk in pancreatic cancer using IMRT optimization with lexicographic ordering and gEUD-based cost functions

    SciTech Connect

    Spalding, Aaron C.; Jee, Kyung-Wook; Vineberg, Karen; Jablonowski, Marla; Fraass, Benedick A.; Pan, Charlie C.; Lawrence, Theodore S.; Ten Haken, Randall K.; Ben-Josef, Edgar

    2007-02-15

    Radiotherapy for pancreatic cancer is limited by the tolerance of local organs at risk (OARs) and frequent overlap of the planning target volume (PTV) and OAR volumes. Using lexicographic ordering (LO), a hierarchical optimization technique, with generalized equivalent uniform dose (gEUD) cost functions, we studied the potential of intensity modulated radiation therapy (IMRT) to increase the dose to pancreatic tumors and to areas of vascular involvement that preclude surgical resection [surgical boost volume (SBV)]. We compared 15 forward planned three-dimensional conformal (3DCRT) and IMRT treatment plans for locally advanced unresectable pancreatic cancer. We created IMRT plans optimized using LO with gEUD-based cost functions that account for the contribution of each part of the resulting inhomogeneous dose distribution. LO-IMRT plans allowed substantial PTV dose escalation compared with 3DCRT; median increase from 52 Gy to 66 Gy (a=-5,p<0.005) and median increase from 50 Gy to 59 Gy (a=-15,p<0.005). LO-IMRT also allowed increases to 85 Gy in the SBV, regardless of a value, along with significant dose reductions in OARs. We conclude that LO-IMRT with gEUD cost functions could allow dose escalation in pancreas tumors with concomitant reduction in doses to organs at risk as compared with traditional 3DCRT.

  10. Image-guided positioning and tracking.

    PubMed

    Ruan, Dan; Kupelian, Patrick; Low, Daniel A

    2011-01-01

    Radiation therapy aims at maximizing tumor control while minimizing normal tissue complication. The introduction of stereotactic treatment explores the volume effect and achieves dose escalation to tumor target with small margins. The use of ablative irradiation dose and sharp dose gradients requires accurate tumor definition and alignment between patient and treatment geometry. Patient geometry variation during treatment may significantly compromise the conformality of delivered dose and must be managed properly. Setup error and interfraction/intrafraction motion are incorporated in the target definition process by expanding the clinical target volume to planning target volume, whereas the alignment between patient and treatment geometry is obtained with an adaptive control process, by taking immediate actions in response to closely monitored patient geometry. This article focuses on the monitoring and adaptive response aspect of the problem. The term "image" in "image guidance" will be used in a most general sense, to be inclusive of some important point-based monitoring systems that can be considered as degenerate cases of imaging. Image-guided motion adaptive control, as a comprehensive system, involves a hierarchy of decisions, each of which balances simplicity versus flexibility and accuracy versus robustness. Patient specifics and machine specifics at the treatment facility also need to be incorporated into the decision-making process. Identifying operation bottlenecks from a system perspective and making informed compromises are crucial in the proper selection of image-guidance modality, the motion management mechanism, and the respective operation modes. Not intended as an exhaustive exposition, this article focuses on discussing the major issues and development principles for image-guided motion management systems. We hope these information and methodologies will facilitate conscientious practitioners to adopt image-guided motion management systems

  11. Functional Image-Guided Radiotherapy Planning in Respiratory-Gated Intensity-Modulated Radiotherapy for Lung Cancer Patients With Chronic Obstructive Pulmonary Disease

    SciTech Connect

    Kimura, Tomoki; Nishibuchi, Ikuno; Murakami, Yuji; Kenjo, Masahiro; Kaneyasu, Yuko; Nagata, Yasushi

    2012-03-15

    Purpose: To investigate the incorporation of functional lung image-derived low attenuation area (LAA) based on four-dimensional computed tomography (4D-CT) into respiratory-gated intensity-modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) in treatment planning for lung cancer patients with chronic obstructive pulmonary disease (COPD). Methods and Materials: Eight lung cancer patients with COPD were the subjects of this study. LAA was generated from 4D-CT data sets according to CT values of less than than -860 Hounsfield units (HU) as a threshold. The functional lung image was defined as the area where LAA was excluded from the image of the total lung. Two respiratory-gated radiotherapy plans (70 Gy/35 fractions) were designed and compared in each patient as follows: Plan A was an anatomical IMRT or VMAT plan based on the total lung; Plan F was a functional IMRT or VMAT plan based on the functional lung. Dosimetric parameters (percentage of total lung volume irradiated with {>=}20 Gy [V20], and mean dose of total lung [MLD]) of the two plans were compared. Results: V20 was lower in Plan F than in Plan A (mean 1.5%, p = 0.025 in IMRT, mean 1.6%, p = 0.044 in VMAT) achieved by a reduction in MLD (mean 0.23 Gy, p = 0.083 in IMRT, mean 0.5 Gy, p = 0.042 in VMAT). No differences were noted in target volume coverage and organ-at-risk doses. Conclusions: Functional IGRT planning based on LAA in respiratory-guided IMRT or VMAT appears to be effective in preserving a functional lung in lung cancer patients with COPD.

  12. Development of an ultrasmall C-band linear accelerator guide for a four-dimensional image-guided radiotherapy system with a gimbaled x-ray head

    SciTech Connect

    Kamino, Yuichiro; Miura, Sadao; Kokubo, Masaki; Yamashita, Ichiro; Hirai, Etsuro; Hiraoka, Masahiro; Ishikawa, Junzo

    2007-05-15

    We are developing a four-dimensional image-guided radiotherapy system with a gimbaled x-ray head. It is capable of pursuing irradiation and delivering irradiation precisely with the help of an agile moving x-ray head on the gimbals. Requirements for the accelerator guide were established, system design was developed, and detailed design was conducted. An accelerator guide was manufactured and basic beam performance and leakage radiation from the accelerator guide were evaluated at a low pulse repetition rate. The accelerator guide including the electron gun is 38 cm long and weighs about 10 kg. The length of the accelerating structure is 24.4 cm. The accelerating structure is a standing wave type and is composed of the axial-coupled injector section and the side-coupled acceleration cavity section. The injector section is composed of one prebuncher cavity, one buncher cavity, one side-coupled half cavity, and two axial coupling cavities. The acceleration cavity section is composed of eight side-coupled nose reentrant cavities and eight coupling cavities. The electron gun is a diode-type gun with a cerium hexaboride (CeB{sub 6}) direct heating cathode. The accelerator guide can be operated without any magnetic focusing device. Output beam current was 75 mA with a transmission efficiency of 58%, and the average energy was 5.24 MeV. Beam energy was distributed from 4.95 to 5.6 MeV. The beam profile, measured 88 mm from the beam output hole on the axis of the accelerator guide, was 0.7 mmx0.9 mm full width at half maximum (FWHM) width. The beam loading line was 5.925 (MeV)-I{sub b} (mA)x0.00808 (MeV/mA), where I{sub b} is output beam current. The maximum radiation leakage of the accelerator guide at 100 cm from the axis of the accelerator guide was calculated as 0.33 cGy/min at the rated x-ray output of 500 cGy/min from the measured value. This leakage requires no radiation shielding for the accelerator guide itself per IEC 60601-2-1.

  13. Development of an ultrasmall C-band linear accelerator guide for a four-dimensional image-guided radiotherapy system with a gimbaled x-ray head.

    PubMed

    Kamino, Yuichiro; Miura, Sadao; Kokubo, Masaki; Yamashita, Ichiro; Hirai, Etsuro; Hiraoka, Masahiro; Ishikawa, Junzo

    2007-05-01

    We are developing a four-dimensional image-guided radiotherapy system with a gimbaled x-ray head. It is capable of pursuing irradiation and delivering irradiation precisely with the help of an agile moving x-ray head on the gimbals. Requirements for the accelerator guide were established, system design was developed, and detailed design was conducted. An accelerator guide was manufactured and basic beam performance and leakage radiation from the accelerator guide were evaluated at a low pulse repetition rate. The accelerator guide including the electron gun is 38 cm long and weighs about 10 kg. The length of the accelerating structure is 24.4 cm. The accelerating structure is a standing wave type and is composed of the axial-coupled injector section and the side-coupled acceleration cavity section. The injector section is composed of one prebuncher cavity, one buncher cavity, one side-coupled half cavity, and two axial coupling cavities. The acceleration cavity section is composed of eight side-coupled nose reentrant cavities and eight coupling cavities. The electron gun is a diode-type gun with a cerium hexaboride (CeB6) direct heating cathode. The accelerator guide can be operated without any magnetic focusing device. Output beam current was 75 mA with a transmission efficiency of 58%, and the average energy was 5.24 MeV. Beam energy was distributed from 4.95 to 5.6 MeV. The beam profile, measured 88 mm from the beam output hole on the axis of the accelerator guide, was 0.7 mm X 0.9 mm full width at half maximum (FWHM) width. The beam loading line was 5.925 (MeV)-Ib (mA) X 0.00808 (MeV/mA), where Ib is output beam current. The maximum radiation leakage of the accelerator guide at 100 cm from the axis of the accelerator guide was calculated as 0.33 cGy/min at the rated x-ray output of 500 cGy/min from the measured value. This leakage requires no radiation shielding for the accelerator guide itself per IEC 60601-2-1. PMID:17555261

  14. Adaptive Image-Guided Radiotherapy (IGRT) Eliminates the Risk of Biochemical Failure Caused by the Bias of Rectal Distension in Prostate Cancer Treatment Planning: Clinical Evidence

    SciTech Connect

    Park, Sean S.; Yan Di; McGrath, Samuel; Dilworth, Joshua T.; Liang Jian; Ye Hong; Krauss, Daniel J.; Martinez, Alvaro A.; Kestin, Larry L.

    2012-07-01

    Purpose: Rectal distension has been shown to decrease the probability of biochemical control. Adaptive image-guided radiotherapy (IGRT) corrects for target position and volume variations, reducing the risk of biochemical failure while yielding acceptable rates of gastrointestinal (GI)/genitourinary (GU) toxicities. Methods and Materials: Between 1998 and 2006, 962 patients were treated with computed tomography (CT)-based offline adaptive IGRT. Patients were stratified into low (n = 400) vs. intermediate/high (n = 562) National Comprehensive Cancer Network (NCCN) risk groups. Target motion was assessed with daily CT during the first week. Electronic portal imaging device (EPID) was used to measure daily setup error. Patient-specific confidence-limited planning target volumes (cl-PTV) were then constructed, reducing the standard PTV and compensating for geometric variation of the target and setup errors. Rectal volume (RV), cross-sectional area (CSA), and rectal volume from the seminal vesicles to the inferior prostate (SVP) were assessed on the planning CT. The impact of these volumetric parameters on 5-year biochemical control (BC) and chronic Grades {>=}2 and 3 GU and GI toxicity were examined. Results: Median follow-up was 5.5 years. Median minimum dose covering cl-PTV was 75.6 Gy. Median values for RV, CSA, and SVP were 82.8 cm{sup 3}, 5.6 cm{sup 2}, and 53.3 cm{sup 3}, respectively. The 5-year BC was 89% for the entire group: 96% for low risk and 83% for intermediate/high risk (p < 0.001). No statistically significant differences in BC were seen with stratification by RV, CSA, and SVP in quartiles. Maximum chronic Grades {>=}2 and 3 GI toxicities were 21.2% and 2.9%, respectively. Respective values for GU toxicities were 15.5% and 4.3%. No differences in GI or GU toxicities were noted when patients were stratified by RV. Conclusions: Incorporation of adaptive IGRT reduces the risk of geometric miss and results in excellent biochemical control that is

  15. A Phase I Clinical and Pharmacology Study Using Amifostine as a Radioprotector in Dose-escalated Whole Liver Radiation Therapy

    SciTech Connect

    Feng, Mary; Smith, David E.; Normolle, Daniel P.; Knol, James A.; Pan, Charlie C.; Ben-Josef, Edgar; Lu Zheng; Feng, Meihua R.; Chen Jun; Ensminger, William; Lawrence, Theodore S.

    2012-08-01

    Purpose: Diffuse intrahepatic tumors are difficult to control. Whole-liver radiotherapy has been limited by toxicity, most notably radiation-induced liver disease. Amifostine is a prodrug free-radical scavenger that selectively protects normal tissues and, in a preclinical model of intrahepatic cancer, systemic amifostine reduced normal liver radiation damage without compromising tumor effect. We hypothesized that amifostine would permit escalation of whole-liver radiation dose to potentially control microscopic disease. We also aimed to characterize the pharmacokinetics of amifostine and its active metabolite WR-1065 to optimize timing of radiotherapy. Methods and Materials: We conducted a radiation dose-escalation trial for patients with diffuse, intrahepatic cancer treated with whole-liver radiation and intravenous amifostine. Radiation dose was assigned using the time-to-event continual reassessment method. A companion pharmacokinetic study was performed. Results: Twenty-three patients were treated, with a maximum dose of 40 Gy. Using a logistical regression model, compared with our previously treated patients, amifostine increased liver tolerance by 3.3 {+-} 1.1 Gy (p = 0.007) (approximately 10%) with similar response rates. Peak concentrations of WR-1065 were 25 {mu}M with an elimination half-life of 1.5 h; these levels are consistent with radioprotective effects of amifostine in patients. Conclusion: These findings demonstrate for the first time that amifostine is a normal liver radioprotector. They further suggest that it may be useful to combine amifostine with fractionated or stereotactic body radiation therapy for patients with focal intrahepatic cancer.

  16. Radiobiological Determination of Dose Escalation and Normal Tissue Toxicity in Definitive Chemoradiation Therapy for Esophageal Cancer

    SciTech Connect

    Warren, Samantha; Partridge, Mike; Carrington, Rhys; Hurt, Chris; Crosby, Thomas; Hawkins, Maria A.

    2014-10-01

    Purpose: This study investigated the trade-off in tumor coverage and organ-at-risk sparing when applying dose escalation for concurrent chemoradiation therapy (CRT) of mid-esophageal cancer, using radiobiological modeling to estimate local control and normal tissue toxicity. Methods and Materials: Twenty-one patients with mid-esophageal cancer were selected from the SCOPE1 database (International Standard Randomised Controlled Trials number 47718479), with a mean planning target volume (PTV) of 327 cm{sup 3}. A boost volume, PTV2 (GTV + 0.5 cm margin), was created. Radiobiological modeling of tumor control probability (TCP) estimated the dose required for a clinically significant (+20%) increase in local control as 62.5 Gy/25 fractions. A RapidArc (RA) plan with a simultaneously integrated boost (SIB) to PTV2 (RA{sub 62.5}) was compared to a standard dose plan of 50 Gy/25 fractions (RA{sub 50}). Dose-volume metrics and estimates of normal tissue complication probability (NTCP) for heart and lungs were compared. Results: Clinically acceptable dose escalation was feasible for 16 of 21 patients, with significant gains (>18%) in tumor control from 38.2% (RA{sub 50}) to 56.3% (RA{sub 62.5}), and only a small increase in predicted toxicity: median heart NTCP 4.4% (RA{sub 50}) versus 5.6% (RA{sub 62.5}) P<.001 and median lung NTCP 6.5% (RA{sub 50}) versus 7.5% (RA{sub 62.5}) P<.001. Conclusions: Dose escalation to the GTV to improve local control is possible when overlap between PTV and organ-at-risk (<8% heart volume and <2.5% lung volume overlap for this study) generates only negligible increase in lung or heart toxicity. These predictions from radiobiological modeling should be tested in future clinical trials.

  17. Image-guided brachytherapy (IGBT) combined with whole pelvic intensity-modulated radiotherapy (WP-IMRT) for locally advanced cervical cancer: a prospective study from Chiang Mai University Hospital, Thailand

    PubMed Central

    Wanwilairat, Somsak; Chakrabandhu, Somvilai; Klunklin, Pitchayaponne; Onchan, Wimrak; Tippanya, Damrongsak; Nopnop, Wannapa; Galalae, Razvan; Chitapanarux, Imjai

    2013-01-01

    Purpose A report of preliminary results and toxicity profiles using image-guided brachytherapy (IGBT) combined with whole pelvic intensity-modulated radiation therapy (WP-IMRT) for locally advanced cervical cancer. Material and methods Fifteen patients with locally advanced cervical cancer were enrolled into the study. WP-IMRT was used to treat the Clinical Target Volume (CTV) with a dose of 45 Gy in 25 fractions. Concurrent cisplatin (40 mg/m2) was prescribed during radiotherapy (RT) on weekly basis. IGBT using computed tomography was performed at the dose of 7 Gy × 4 fractions to the High-Risk Clinical Target Volume (HR-CTV). Results The mean cumulative doses – in terms of equivalent dose of 2 Gy (EQD2) – of IGBT plus WP-IMRT to HR-CTV, bladder, rectum, and sigmoid colon were 88.3, 85.0, 68.2 and 73.6 Gy, respectively. In comparison with standard (point A prescription) dose-volume histograms, volume-based image-guided brachytherapy improved the cumulative doses for bladder of 67%, rectum of 47% and sigmoid of 46%. At the median follow-up time of 14 months, the local control, metastasis-free survival and overall survival rates were 93%, 100% and 93%, respectively. No grade 3-4 acute and late toxicities were observed. Conclusion The combination of image-guided brachytherapy and intensity-modulated radiotherapy improved the dose distribution to tumor volumes and avoided overdose in OARs which could be converted in excellent local control and toxicity profiles. PMID:23634150

  18. Estimated limits of IMRT dose escalation using varied planning target volume margins

    NASA Astrophysics Data System (ADS)

    Goulet, Christopher C.; Herman, Michael G.; Hillman, David W.; Davis, Brian J.

    2008-07-01

    To estimate the limits of dose escalation for prostate cancer as a function of planning target volume (PTV) margins, the maximum achievable dose (MAD) was determined through iterative plan optimizations from data sets of 18 patients until the dose constraints for rectum, bladder and PTV could no longer be met. PTV margins of 10, 5 and 3 mm yielded a mean MAD of 83.0 Gy (range, 73.8-108.0 Gy), 113.1 Gy (range, 90.0-151.2 Gy) and 135.9 Gy (range, 102.6-189.0 Gy), respectively. All comparisons of MAD among margin groups were statistically significant (P < 0.001). Comparison of prostate volumes of 30-50 mL (n = 8) with volumes of 51-70 mL (n = 7) and 71-105 mL (n = 3) showed an inverse relationship with MAD. Decreases in PTV margin significantly decreased the PTV overlap of the rectum (P < 0.001 for all margin comparisons). With decreases in the PTV margin and maintenance of identical dose constraints, doses well above those currently prescribed for treatment of localized prostate cancer appear feasible. However, the dose escalation suggested by these findings is a theoretical estimate, and additional dose constraints will likely be necessary to limit toxicity to normal tissue.

  19. SU-E-T-622: Identification and Improvement of Patients Eligible for Dose Escalation with Matched Plans

    SciTech Connect

    Bush, K; Holcombe, C; Kapp, D; Buyyounouski, M; Hancock, S; Xing, L; Atwood, T; King, M

    2014-06-15

    Purpose: Radiation-therapy dose-escalation beyond 80Gy may improve tumor control rates for patients with localized prostate cancer. Since toxicity remains a concern, treatment planners must achieve dose-escalation while still adhering to dose-constraints for surrounding structures. Patientmatching is a machine-learning technique that identifies prior patients that dosimetrically match DVH parameters of target volumes and critical structures prior to actual treatment planning. We evaluated the feasibility of patient-matching in (1)identifying candidates for safe dose-escalation; and (2)improving DVH parameters for critical structures in actual dose-escalated plans. Methods: We analyzed DVH parameters from 319 historical treatment plans to determine which plans could achieve dose-escalation (8640cGy) without exceeding Zelefsky dose-constraints (rectal and bladder V47Gy<53%, and V75.6Gy<30%, max-point dose to rectum of 8550cGy, max dose to PTV< 9504cGy). We then estimated the percentage of cases that could achieve safe dose-escalation using software that enables patient matching (QuickMatch, Siris Medical, Mountain View, CA). We then replanned a case that had violated DVH constraints with DVH parameters from patient matching, in order to determine whether this previously unacceptable plan could be made eligible with this automated technique. Results: Patient-matching improved the percentage of patients eligible for dose-escalation from 40% to 63% (p=4.7e-4, t-test). Using a commercial optimizer augmented with patient-matching, we demonstrated a case where patient-matching improved the toxicity-profile such that dose-escalation would have been possible; this plan was rapidly achieved using patientmatching software. In this patient, all lower-dose constraints were met with both the denovo and patient-matching plan. In the patient-matching plan, maximum dose to the rectum was 8385cGy, while the denovo plan failed to meet the maximum rectal constraint at 8571c

  20. A Phase I Dose-Escalation Study (ISIDE-BT-1) of Accelerated IMRT With Temozolomide in Patients With Glioblastoma

    SciTech Connect

    Morganti, Alessio G.; Balducci, Mario; Salvati, Maurizio; Esposito, Vincenzo; Romanelli, Pantaleo; Ferro, Marica; Calista, Franco; Digesu, Cinzia; Macchia, Gabriella; Ianiri, Massimo; Deodato, Francesco; Cilla, Savino; Piermattei, Angelo M.P.; Valentini, Vincenzo; Cellini, Numa; Cantore, Gian Paolo

    2010-05-01

    Purpose: To determine the maximum tolerated dose (MTD) of fractionated intensity-modulated radiotherapy (IMRT) with temozolomide (TMZ) in patients with glioblastoma. Methods and Materials: A Phase I clinical trial was performed. Eligible patients had surgically resected or biopsy-proven glioblastoma. Patients started TMZ (75 mg/day) during IMRT and continued for 1 year (150-200 mg/day, Days 1-5 every 28 days) or until disease progression. Clinical target volume 1 (CTV1) was the tumor bed +- enhancing lesion with a 10-mm margin; CTV2 was the area of perifocal edema with a 20-mm margin. Planning target volume 1 (PTV1) and PTV2 were defined as the corresponding CTV plus a 5-mm margin. IMRT was delivered in 25 fractions over 5 weeks. Only the dose for PTV1 was escalated (planned dose escalation: 60 Gy, 62.5 Gy, 65 Gy) while maintaining the dose for PTV2 (45 Gy, 1.8 Gy/fraction). Dose limiting toxicities (DLT) were defined as any treatment-related nonhematological adverse effects rated as Grade >=3 or any hematological toxicity rated as >=4 by Radiation Therapy Oncology Group (RTOG) criteria. Results: Nineteen consecutive glioblastoma were treated with step-and-shoot IMRT, planned with the inverse approach (dose to the PTV1: 7 patients, 60 Gy; 6 patients, 62.5 Gy; 6 patients, 65 Gy). Five coplanar beams were used to cover at least 95% of the target volume with the 95% isodose line. Median follow-up time was 23 months (range, 8-40 months). No patient experienced DLT. Grade 1-2 treatment-related neurologic and skin toxicity were common (11 and 19 patients, respectively). No Grade >2 late neurologic toxicities were noted. Conclusion: Accelerated IMRT to a dose of 65 Gy in 25 fractions is well tolerated with TMZ at a daily dose of 75 mg.

  1. SU-E-T-500: Dose Escalation Strategy for Lung Cancer Patients Using a Biologically- Guided Target Definition

    SciTech Connect

    Shusharina, N; Khan, F; Choi, N; Sharp, G

    2014-06-01

    Purpose: Dose escalation strategy for lung cancer patients can lead to late symptoms such as pneumonitis and cardiac injury. We propose a strategy to increase radiation dose for improving local tumor control while simultaneously striving to minimize the injury of organs at risk (OAR). Our strategy is based on defining a small, biologically-guided target volume for receiving additional radiation dose. Methods: 106 patients with lung cancer treated with radiotherapy were selected for patients diagnosed with stage II and III disease. Previous research has shown that 50% of the maximum SUV threshold in FDG-PET imaging is appropriate for delineation of the most aggressive part of a tumor. After PET- and CT-derived targets were contoured, an IMRT treatment plan was designed to deliver 60 Gy to the GTV as delineated on a 4D CT (Plan 1). A second plan was designed with additional dose of 18 Gy to the PET-derived volume (Plan 2). A composite plan was generated by the addition of Plan 1 and Plan 2. Results: Plan 1 was compared to the composite plan and increases in OAR dose were assessed. For seven patients on average, lung V5 was increased by 1.4% and V20 by 4.2% for ipsilateral lung and by 13.5% and 7% for contralateral lung. For total lung, V5 and V20 were increased by 4.5% and 4.8% respectively. Mean lung dose was increased by 9.7% for the total lung. The maximum dose to the spinal cord increased by 16% on average. For the heart, V20 increased by 4.2% and V40 by 5.2%. Conclusion: It seems feasible that an additional 18 Gy of radiation dose can be delivered to FDG PET-derived subvolume of the CT-based GTV of the primary tumor without significant increase in total dose to the critical organs such as lungs, spinal cord and heart.

  2. Clinical applications of image guided-intensity modulated radiation therapy (IG-IMRT) for conformal avoidance of normal tissue

    NASA Astrophysics Data System (ADS)

    Gutierrez, Alonso Navar

    2007-12-01

    Recent improvements in imaging technology and radiation delivery have led to the development of advanced treatment techniques in radiotherapy which have opened the door for novel therapeutic approaches to improve the efficacy of radiation cancer treatments. Among these advances is image-guided, intensity modulated radiation therapy (IG-IMRT), in which imaging is incorporated to aid in inter-/intra-fractional target localization and to ensure accurate delivery of precise and highly conformal dose distributions. In principle, clinical implementation of IG-IMRT should improve normal tissue sparing and permit effective biological dose escalation thus widening the radiation therapeutic window and lead to increases in survival through improved local control of primary neoplastic diseases. Details of the development of three clinical applications made possible solely with IG-IMRT radiation delivery techniques are presented: (1) Laparoscopically implanted tissue expander radiotherapy (LITE-RT) has been developed to enhance conformal avoidance of normal tissue during the treatment of intra-abdominopelvic cancers. LITE-RT functions by geometrically displacing surrounding normal tissue and isolating the target volume through the interfractional inflation of a custom-shaped tissue expander throughout the course of treatment. (2) The unique delivery geometry of helical tomotherapy, a novel form of IG-IMRT, enables the delivery of composite treatment plan m which whole brain radiotherapy (WBRT) with hippocampal avoidance, hypothesized to reduce the risk of memory function decline and improve the patient's quality of life, and simultaneously integrated boost to multiple brain metastases to improve intracranial tumor control is achieved. (3) Escalation of biological dose to targets through integrated, selective subvolume boosts have been shown to efficiently increase tumor dose without significantly increasing normal tissue dose. Helical tomotherapy was used to investigate the

  3. CYP2D6 genotype- and endoxifen-guided tamoxifen dose escalation increases endoxifen serum concentrations without increasing side effects.

    PubMed

    Dezentjé, V O; Opdam, F L; Gelderblom, H; Hartigh den, J; Van der Straaten, T; Vree, R; Maartense, E; Smorenburg, C H; Putter, H; Dieudonné, A S; Neven, P; Van de Velde, C J H; Nortier, J W R; Guchelaar, H-J

    2015-10-01

    Breast cancer patients with absent or reduced CYP2D6 activity and consequently low endoxifen levels may benefit less from tamoxifen treatment. CYP2D6 poor and intermediate metabolizers may need a personalized increased tamoxifen dose to achieve effective endoxifen serum concentrations, without increasing toxicity. From a prospective study population of early breast cancer patients using tamoxifen (CYPTAM: NTR1509), 12 CYP2D6 poor and 12 intermediate metabolizers were selected and included in a one-step tamoxifen dose escalation study during 2 months. The escalated dose was calculated by multiplying the individual's endoxifen level at baseline relative to the average endoxifen concentration observed in CYP2D6 extensive metabolizers by 20 mg (120 mg maximum). Endoxifen levels and tamoxifen toxicity were determined at baseline and after 2 months, just before patients returned to the standard dose of 20 mg. Tamoxifen dose escalation in CYP2D6 poor and intermediate metabolizers significantly increased endoxifen concentrations (p < 0.001; p = 0.002, respectively) without increasing side effects. In intermediate metabolizers, dose escalation increased endoxifen to levels comparable with those observed in extensive metabolizers. In poor metabolizers, the mean endoxifen level increased from 24 to 81 % of the mean concentration in extensive metabolizers. In all patients, the endoxifen threshold of 5.97 ng/ml (=16.0 nM) reported by Madlensky et al. was reached following dose escalation. CYP2D6 genotype- and endoxifen-guided tamoxifen dose escalation increased endoxifen concentrations without increasing short-term side effects. Whether such tamoxifen dose escalation is effective and safe in view of long-term toxic effects is uncertain and needs to be explored. PMID:26369533

  4. Phase I Dose-Escalation Study of Nimustine in Tumor-Bearing Dogs

    PubMed Central

    TAKAHASHI, Masashi; GOTO-KOSHINO, Yuko; FUKUSHIMA, Kenjiro; KANEMOTO, Hideyuki; NAKASHIMA, Ko; FUJINO, Yasuhito; OHNO, Koichi; ENDO, Yasuyuki; TSUJIMOTO, Hajime

    2014-01-01

    ABSTRACT Nimustine (ACNU) is an alkylating agent of the nitrosourea and can be an antineoplastic agent in dogs. But, there has been no report on its dose-limiting toxicity (DLT) in dogs. This study was a phase I dose-escalation clinical trial to determine the maximum tolerated dose (MTD) and DLT of ACNU in tumor-bearing dogs. The starting dosage was 25 mg/m2, and subsequent dosages were administered in increments of 5 mg/m2 in cohort of 3 dogs. Eight dogs were included, the MTD was determined to be 25 mg/m2, DLT was neutropenia, and the optimal interval was considered to be 21 days. The data herein provide a basis for the subsequent phase II trial of ACNU in dogs. PMID:24521794

  5. Mesalamine Dose Escalation Reduces Fecal Calprotectin In Patients With Quiescent Ulcerative Colitis

    PubMed Central

    Osterman, Mark T.; Aberra, Faten N; Cross, Raymond; Liakos, Steven; McCabe, Robert; Shafran, Ira; Wolf, Douglas; Hardi, Robert; Nessel, Lisa; Brensinger, Colleen; Gilroy, Erin; Lewis, James D.

    2014-01-01

    Background & Aims Among patients with quiescent ulcerative colitis (UC), lower fecal concentrations of calprotectin are associated with lower rates of relapse. We performed an open-label, randomized, controlled trial to investigate whether increasing doses mesalamine reduce concentrations of fecal calprotectin (FC) in patients with quiescent UC. Methods We screened 119 patients with UC in remission, based on Simple Clinical Colitis Activity Index scores, FC >50 mcg/g, and intake of no more than 3g/day of mesalamine. Participants taking mesalamine formulations other than multimatrix mesalamine were switched to multimatrix mesalamine (2.4 g/day) for 6 weeks; 52 participants were then randomly assigned (1:1) to a group that continued its current dose of mesalamine (controls, n=26) or a group that increased its dose by 2.4 g/day for 6 weeks (n=26). The primary outcome was continued remission with FC<50 mcg/g. Secondary outcomes were continued remission with FC<100 mcg/g or <200 mcg/g (among patients with pre-randomization values above these levels). Results The primary outcome was achieved by 3.8% of controls and 26.9% of the dose escalation group (P=.0496). More patients in the dose escalation group reduced FC to below 100 mcg/g (P=.04) and 200 mcg/g (P=.005). Among the patients who were still in remission after the randomization phase, clinical relapse occurred sooner in patients with FC >200 mcg/g compared to those with FC <200 mcg/g (P=.01). Conclusion Among patients with quiescent UC and increased levels of FC, increasing the dose of mesalamine by 2.4 g/day reduced fecal concentrations of calprotectin to those associated with lower rates of relapse. Clinicaltrials.gov: NCT00652145 PMID:24793028

  6. Radiation Therapy Dose Escalation for Glioblastoma Multiforme in the Era of Temozolomide

    SciTech Connect

    Badiyan, Shahed N.; Markovina, Stephanie; Simpson, Joseph R.; Robinson, Clifford G.; DeWees, Todd; Tran, David D.; Linette, Gerry; Jalalizadeh, Rohan; Dacey, Ralph; Rich, Keith M.; Chicoine, Michael R.; Dowling, Joshua L.; Leuthardt, Eric C.; Zipfel, Gregory J.; Kim, Albert H.; Huang, Jiayi

    2014-11-15

    Purpose: To review clinical outcomes of moderate dose escalation using high-dose radiation therapy (HDRT) in the setting of concurrent temozolomide (TMZ) in patients with newly diagnosed glioblastoma multiforme (GBM), compared with standard-dose radiation therapy (SDRT). Methods and Materials: Adult patients aged <70 years with biopsy-proven GBM were treated with SDRT (60 Gy at 2 Gy per fraction) or with HDRT (>60 Gy) and TMZ from 2000 to 2012. Biological equivalent dose at 2-Gy fractions was calculated for the HDRT assuming an α/β ratio of 5.6 for GBM. Results: Eighty-one patients received SDRT, and 128 patients received HDRT with a median (range) biological equivalent dose at 2-Gy fractions of 64 Gy (61-76 Gy). Overall median follow-up time was 1.10 years, and for living patients it was 2.97 years. Actuarial 5-year overall survival (OS) and progression-free survival (PFS) rates for patients that received HDRT versus SDRT were 12.4% versus 13.2% (P=.71), and 5.6% versus 4.1% (P=.54), respectively. Age (P=.001) and gross total/near-total resection (GTR/NTR) (P=.001) were significantly associated with PFS on multivariate analysis. Younger age (P<.0001), GTR/NTR (P<.0001), and Karnofsky performance status ≥80 (P=.001) were associated with improved OS. On subset analyses, HDRT failed to improve PFS or OS for those aged <50 years or those who had GTR/NTR. Conclusion: Moderate radiation therapy dose escalation above 60 Gy with concurrent TMZ does not seem to improve clinical outcomes for patients with GBM.

  7. Long-Term Failure Patterns and Survival in a Randomized Dose-Escalation Trial for Prostate Cancer. Who Dies of Disease?

    SciTech Connect

    Kuban, Deborah A.; Levy, Lawrence B.; Cheung, M. Rex; Lee, Andrew K.; Choi, Seungtaek; Frank, Steven; Pollack, Alan

    2011-04-01

    Purpose: To report long-term failure patterns and survival in a randomized radiotherapy dose escalation trial for prostate cancer. Materials and Methods: A total of 301 patients with Stage T1b-T3 prostate cancer treated to 70 Gy versus 78 Gy now have a median follow-up of 9 years. Failure patterns and survival were compared between dose levels. The cumulative incidence of death from prostate cancer versus other causes was examined and regression analysis was used to establish predictive factors. Results: Patients with pretreatment prostate-specific antigen (PSA) >10 ng/mL or high-risk disease had higher biochemical and clinical failures rates when treated to 70 Gy. These patients also had a significantly higher risk of dying of prostate cancer. Patients <70 years old at treatment died of prostate cancer nearly three times more frequently than of other causes when they were radiated to 70 Gy, whereas those treated to 78 Gy died of other causes more frequently. Patients age 70 or older treated to 70 Gy died of prostate cancer as often as other causes, and those receiving 78 Gy never died of prostate cancer within 10 years of follow-up. In regression analysis, factors predicting for death from prostate cancer were pretreatment PSA >10.5 ng/mL, Gleason score 9 and 10, recurrence within 2.6 years of radiation, and doubling time of <3.6 months at the time of recurrence. Conclusions: Moderate dose escalation (78 Gy) decreases biochemical and clinical failure as well as prostate cancer death in patients with pretreatment PSA >10 ng/mL or high-risk disease.

  8. Phase Ib, Dose Escalation Study of Oral LDE225 in Combination With BKM120 in Patients With Advanced Solid Tumors

    ClinicalTrials.gov

    2016-02-18

    Dose Escalation; Safety; Preliminary Efficacy; Advanced Solid Tumors; Metastatic Breast Cancer; Advanced Pancreatic Adenocarcinoma; Metastatic Colorectal Cancer; Recurrent Glioblastoma Multiforme; Gastric Cancer; Gastroesophageal Junction Cancer; Triple Negative Metastatic Breast Cancer; Hormone Receptor Positive (ER+/PR+, and Her2-) Metastatic Breast Cancer

  9. SU-E-J-219: Quantitative Evaluation of Motion Effects On Accuracy of Image-Guided Radiotherapy with Fiducial Markers Using CT Imaging

    SciTech Connect

    Ali, I; Oyewale, S; Ahmad, S; Algan, O; Alsbou, N

    2014-06-01

    Purpose: To investigate quantitatively patient motion effects on the localization accuracy of image-guided radiation with fiducial markers using axial CT (ACT), helical CT (HCT) and cone-beam CT (CBCT) using modeling and experimental phantom studies. Methods: Markers with different lengths (2.5 mm, 5 mm, 10 mm, and 20 mm) were inserted in a mobile thorax phantom which was imaged using ACT, HCT and CBCT. The phantom moved with sinusoidal motion with amplitudes ranging 0–20 mm and a frequency of 15 cycles-per-minute. Three parameters that include: apparent marker lengths, center position and distance between the centers of the markers were measured in the different CT images of the mobile phantom. A motion mathematical model was derived to predict the variations in the previous three parameters and their dependence on the motion in the different imaging modalities. Results: In CBCT, the measured marker lengths increased linearly with increase in motion amplitude. For example, the apparent length of the 10 mm marker was about 20 mm when phantom moved with amplitude of 5 mm. Although the markers have elongated, the center position and the distance between markers remained at the same position for different motion amplitudes in CBCT. These parameters were not affected by motion frequency and phase in CBCT. In HCT and ACT, the measured marker length, center and distance between markers varied irregularly with motion parameters. The apparent lengths of the markers varied with inverse of the phantom velocity which depends on motion frequency and phase. Similarly the center position and distance between markers varied inversely with phantom speed. Conclusion: Motion may lead to variations in maker length, center position and distance between markers using CT imaging. These effects should be considered in patient setup using image-guided radiation therapy based on fiducial markers matching using 2D-radiographs or volumetric CT imaging.

  10. Biological equivalent dose studies for dose escalation in the stereotactic synchrotron radiation therapy clinical trials

    SciTech Connect

    Prezado, Y.; Fois, G.; Edouard, M.; Nemoz, C.; Renier, M.; Requardt, H.; Esteve, F.; Adam, JF.; Elleaume, H.; Bravin, A.

    2009-03-15

    Synchrotron radiation is an innovative tool for the treatment of brain tumors. In the stereotactic synchrotron radiation therapy (SSRT) technique a radiation dose enhancement specific to the tumor is obtained. The tumor is loaded with a high atomic number (Z) element and it is irradiated in stereotactic conditions from several entrance angles. The aim of this work was to assess dosimetric properties of the SSRT for preparing clinical trials at the European Synchrotron Radiation Facility (ESRF). To estimate the possible risks, the doses received by the tumor and healthy tissues in the future clinical conditions have been calculated by using Monte Carlo simulations (PENELOPE code). The dose enhancement factors have been determined for different iodine concentrations in the tumor, several tumor positions, tumor sizes, and different beam sizes. A scheme for the dose escalation in the various phases of the clinical trials has been proposed. The biological equivalent doses and the normalized total doses received by the skull have been calculated in order to assure that the tolerance values are not reached.

  11. Phase I study of idarubicin dose escalation for remission induction therapy in acute myeloid leukemia.

    PubMed

    Lee, Mark Hong; Kim, Sung-Yong

    2016-10-01

    The maximum tolerated dose (MTD) of idarubicin should be reevaluated in the treatment of acute myeloid leukemia (AML) in the era of granulocyte colony-stimulating factor and better supportive care. We conducted a phase I study to investigate the safety of escalating doses of idarubicin in combination with cytarabine 100 mg/m(2)/day for seven days for previously untreated AML. The starting dose of idarubicin was 12 mg/m(2)/day for three days with dose escalations by 3 mg/m(2)/day up to 18 mg/m(2)/day. The study design was adopted from traditional 3 + 3 design for phase I cancer clinical trials. The grade 4 hematologic toxicities were observed at all dose levels; however, these toxicities did not meet the criteria of the hematologic dose-limiting toxicities as defined in this study. There were no instances of grade 4 non-hematologic toxicities at any dose levels. The MTD of idarubicin was not reached in this trial. PMID:26750985

  12. Only modest long-term opioid dose escalation occurs over time in chronic nonmalignant pain management.

    PubMed

    Chapman, C Richard; Bradshaw, David H

    2013-12-01

    Clinical experience and the literature increasingly support differentiating chronic pain associated with malignant disease from chronic pain associated with nonmalignant conditions when defining optimal pharmacotherapy. The use of opioids for chronic nonmalignant pain has grown steadily despite the lack of a strong evidence base that can guide practice. A fundamental question is whether patients develop tolerance and need repeated dose escalations to sustain pain control. We examined opioid prescribing data from United Kingdom Clinical Practice Research Datalink longitudinal database of general practice records and tracked dose changes but not pain reports in a sample of 4035 patients who received oral or transdermal-extended release opioids for chronic nonmalignant pain. The median number of days on opioid pharmacotherapy for all patients was 311. Thirty percent of patients never changed doses during the course of treatment. In patients who never changed medications, the mean morphine equivalent 24-hour dose increased from beginning to end of opioid pharmacotherapy only by 1.4 fold, t = 25.73, Cohen's d = .427 and was independent of both age and gender. Comparison across extended release morphine, oxycodone, and fentanyl revealed that it was significantly greatest for patients using fentanyl and least for those using morphine. PMID:24143927

  13. Influence of 11C-choline PET/CT on radiotherapy planning in prostate cancer

    PubMed Central

    López, Escarlata; Lazo, Antonio; Gutiérrez, Antonio; Arregui, Gregorio; Núñez, Isabel; Sacchetti, Antonio

    2014-01-01

    Aim To evaluate the influence of 11C-choline PET/CT on radiotherapy planning in prostate cancer patients. Background Precise information on the extension of prostate cancer is crucial for the choice of an appropriate therapeutic strategy. 11C-choline positron emission tomography (11C-choline PET/CT) has two roles in radiation oncology (RT): (1) patient selection for treatment and (2) target volume selection and delineation. In conjunction with high-accuracy techniques, it might offer an opportunity of dose escalation and better tumour control while sparing healthy tissues. Materials and methods We carried out a retrospective study in order to analyse RT planning modification based on 11C-choline PET/CT in 16 prostate cancer patients. Patients were treated with hypofractionated step-and-shoot Intensity Modulated Radiotherapy (IMRT), or Volumetric Modulated Arc Therapy (VMAT), and a daily cone-beam CT for Image Guided Radiation Therapy (IGRT). All patients underwent a 11C-choline-PET/CT scan prior to radiotherapy. Results In 37.5% of cases, a re-delineation and new dose prescription occurred. Data show good preliminary clinical results in terms of biochemical control and toxicity. No gastrointestinal (GI)/genitourinary (GU) grade III toxicities were observed after a median follow-up of 9.5 months. Conclusions In our experience, concerning the treatment of prostate cancer (PCa), 11C-choline PET/CT may be helpful in radiotherapy planning, either for dose escalation or exclusion of selected sites. PMID:25859399

  14. High Dose-Per-Fraction Irradiation of Limited Lung Volumes Using an Image-Guided, Highly Focused Irradiator: Simulating Stereotactic Body Radiotherapy Regimens in a Small-Animal Model

    SciTech Connect

    Cho, Jaeho; Kodym, Reinhard; Seliounine, Serguei

    2010-07-01

    Purpose: To investigate the underlying biology associated with stereotactic body radiotherapy (SBRT), both in vivo models and image-guided, highly focal irradiation systems are necessary. Here, we describe such an irradiation system and use it to examine normal tissue toxicity in a small-animal model at lung volumes similar to those associated with human therapy. Methods and Materials: High-dose radiation was delivered to a small volume of the left lung of C3H/HeJCr mice using a small-animal stereotactic irradiator. The irradiator has a collimation mechanism to produce focal radiation beams, an imaging subsystem consisting of a fluorescent screen coupled to a charge-coupled device camera, and a manual positioning stage. Histopathologic examination and micro-CT were used to evaluate the radiation response. Results: Focal obliteration of the alveoli by fibrous connective tissue, hyperplasia of the bronchiolar epithelium, and presence of a small number of inflammatory cells are the main reactions to low-volume/high-dose irradiation of the mouse lung. The tissue response suggested a radiation dose threshold for early phase fibrosis lying between 40 and 100 Gy. The irradiation system satisfied our requirements of high-dose-rate, small beam diameter, and precise localization and verification. Conclusions: We have established an experimental model and image-guided animal irradiation system for the study of high dose per fraction irradiations such as those used with SBRT at volumes analogous to those used in human beings. It will also allow the targeting of specific anatomical structures of the thorax or ultimately, orthotopic tumors of the lung.

  15. Squamous-cell carcinoma of the anus: progress in radiotherapy treatment.

    PubMed

    Glynne-Jones, Rob; Tan, David; Hughes, Robert; Hoskin, Peter

    2016-07-01

    Chemoradiotherapy is the standard-of-care treatment of squamous-cell carcinoma of the anus (SCCA), and this has not changed in decades. Radiation doses of 50-60 Gy, as used in many phase III trials, result in substantial late morbidities and fail to control larger and node-positive tumours. Technological advances in radiation therapy are improving patient outcomes and quality of life, and should be applied to patients with SCCA. Modern techniques such as intensity-modulated radiotherapy (IMRT), rotational IMRT, image-guided radiotherapy using cone-beam CT, and stereotactic techniques have enabled smaller margins and highly conformal plans, resulting in decreased radiation doses to the organs at risk and ensuring a shorter overall treatment time. In this Perspectives article, the use of novel approaches to target delineation, optimized radiotherapy techniques, adaptive radiotherapy, dose-escalation with external-beam radiotherapy (EBRT) or brachytherapy, and the potential for modified fractionation are discussed in the context of SCCA. PMID:26813935

  16. Dose Escalation and Dosimetry of First in Human Alpha Radioimmunotherapy with 212Pb-TCMC-trastuzumab

    PubMed Central

    Meredith, Ruby; Torgue, Julien; Shen, Sui; Fisher, Darrell R.; Banaga, Eileen; Bunch, Patty; Morgan, Desiree; Fan, Jinda; Straughn, J. Michael

    2015-01-01

    Our purpose was to study the safety, distribution, pharmacokinetics, immunogenicity and tumor response of intraperitoneal (IP) 212Pb-TCMC-trastuzumab (TCMC is S-2-(4-isothiocyantobenzl)-1, 4, 7, 10-tetraaza-1, 4, 7, 10=tetra (2-carbamoylmethl) cyclododecane) in patients with HER-2 expressing malignancy. Methods In a standard 3+3 Phase 1 design for dose escalation, 212Pb-TCMC-trastuzumab was delivered IP less than 4 hours after giving 4mg/kg IV trastuzumab to patients with peritoneal carcinomatosis who had failed standard therapies. Results Five dosage levels (7.4, 9.6, 12.6, 16.3, 21.1 MBq/m2) showed minimal toxicity at >1 year for the first group and >4 months for others. The lack of substantial toxicity was consistent with the dosimetry assessments (mean equivalent dose to marrow = 0.18 mSv/MBq). Radiation dosimetry assessment was performed using pharmacokinetics data obtained in the initial cohort (n=3). Limited redistribution of radioactivity out of the peritoneal cavity to circulating blood, which cleared via urinary excretion and no specific uptake in major organs was observed in 24 hours. Maximum serum concentration of the radiolabeled antibody was 22.9% at 24h (decay corrected to injection time) and 500 Bq/mL (decay corrected to collection time). Non-decay corrected cumulative urinary excretion was ≤6% in 24h (2.3 half lives). Dose rate measurements performed at 1m from the patient registered less than 5μSv/hr (using portable detectors) in the latest cohort, significantly less than what is normally observed using nuclear medicine imaging agents. Anti-drug antibody assays performed on serum from the first 4 cohorts were all negative. Conclusions Five dose levels of IP 212Pb-TCMC-trastuzumab treatment of patients with peritoneal carcinomatosis showed little agent related toxicity, consistent with the dosimetry calculations. PMID:25157044

  17. Dose Escalated Liver Stereotactic Body Radiation Therapy at the Mean Respiratory Position

    SciTech Connect

    Velec, Michael; Moseley, Joanne L.; Dawson, Laura A.; Brock, Kristy K.

    2014-08-01

    Purpose: The dosimetric impact of dose probability based planning target volume (PTV) margins for liver cancer patients receiving stereotactic body radiation therapy (SBRT) was compared with standard PTV based on the internal target volume (ITV). Plan robustness was evaluated by accumulating the treatment dose to ensure delivery of the intended plan. Methods and Materials: Twenty patients planned on exhale CT for 27 to 50 Gy in 6 fractions using an ITV-based PTV and treated free-breathing were retrospectively evaluated. Isotoxic, dose escalated plans were created on midposition computed tomography (CT), representing the mean breathing position, using a dose probability PTV. The delivered doses were accumulated using biomechanical deformable registration of the daily cone beam CT based on liver targeting at the exhale or mean breathing position, for the exhale and midposition CT plans, respectively. Results: The dose probability PTVs were on average 38% smaller than the ITV-based PTV, enabling an average ± standard deviation increase in the planned dose to 95% of the PTV of 4.0 ± 2.8 Gy (9 ± 5%) on the midposition CT (P<.01). For both plans, the delivered minimum gross tumor volume (GTV) doses were greater than the planned nominal prescribed dose in all 20 patients and greater than the planned dose to 95% of the PTV in 18 (90%) patients. Nine patients (45%) had 1 or more GTVs with a delivered minimum dose more than 5 Gy higher with the midposition CT plan using dose probability PTV, compared with the delivered dose with the exhale CT plan using ITV-based PTV. Conclusions: For isotoxic liver SBRT planned and delivered at the mean respiratory, reduced dose probability PTV enables a mean escalation of 4 Gy (9%) in 6 fractions over ITV-based PTV. This may potentially improve local control without increasing the risk of tumor underdosing.

  18. Efficacy of dose escalation on TCP, recurrence and second cancer risks: a mathematical study

    PubMed Central

    Dhawan, A; Kohandel, M; Sivaloganathan, S

    2014-01-01

    Objective: We investigated the effects of conventional and hypofractionation protocols by modelling tumour control probability (TCP) and tumour recurrence time, and examined their impact on second cancer risks. The main objectives of this study include the following: (a) incorporate tumour recurrence time and second cancer risks into the TCP framework and analyse the effects of variable doses and (b) investigate an efficient protocol to reduce the risk of a secondary malignancy while maximizing disease-free survival and tumour control. Methods: A generalized mathematical formalism was developed that incorporated recurrence and second cancer risk models into the TCP dynamics. Results: Our results suggest that TCP and relapse time are almost identical for conventional and hypofractionated regimens; however, second cancer risks resulting from hypofractionation were reduced by 22% when compared with the second cancer risk associated with a conventional protocol. The hypofractionated regimen appears to be sensitive to dose escalation and the corresponding impact on tumour recurrence time and reduction in second cancer risks. The reduction in second cancer risks is approximately 20% when the dose is increased from 60 to 72 Gy in a hypofractionated protocol. Conclusion: Our results suggest that hypofractionation may be a more efficient regimen in the context of TCP, relapse time and second cancer risks. Overall, our study demonstrates the importance of including a second cancer risk model in designing an efficient radiation regimen. Advances in knowledge: The impact of various fractionation protocols on TCP and relapse in conjunction with second cancer risks is an important clinical question that is as yet unexplored PMID:25210783

  19. Antigen dose escalation study of a VEGF-based therapeutic cancer vaccine in non human primates.

    PubMed

    Morera, Yanelys; Bequet-Romero, Mónica; Ayala, Marta; Pérez, Pedro Puente; Castro, Jorge; Sánchez, Javier; Alba, José Suárez; Ancízar, Julio; Cosme, Karelia; Gavilondo, Jorge V

    2012-01-01

    CIGB-247 is a cancer therapeutic, based on recombinant modified human vascular endothelial growth factor (VEGF) as antigen, in combination with the oil free adjuvant VSSP (very small sized proteoliposomes of Neisseria meningitidis outer membrane). Our previous experimental studies in mice with CIGB-247 have shown that the vaccine has both anti-tumoral and anti-metastatic activity, and produces both antibodies that block VEGF-VEGF receptor interaction, and a specific T-cell cytotoxic response against tumor cells. CIGB-247, with an antigen dose of 100 μg, has been characterized by an excellent safety profile in mice, rats, rabbits, and non human primates. In this article we extend the immunogenicity and safety studies of CIGB-247 in non human primates, scaling the antigen dose from 100 μg to 200 and 400 μg/vaccination. Our results indicate that such dose escalation did not affect animal behavior, clinical status, and blood parameters and biochemistry. Also, vaccination did not interfere with skin deep skin wound healing. Anti-VEGF IgG antibodies and specific T-cell mediated responses were documented at all three studied doses. Antigen dose apparently did not determine differences in maximum antibody titer during the 8 weekly immunization induction phase, or the subsequent increase in antibodies seen for monthly boosters delivered afterwards. Higher antigen doses had a positive influence in antibody titer maintenance, after cessation of immunizations. Boosters were important to achieve maximum antibody VEGF blocking activity, and specific T-cell responses in all individuals. Purified IgG from CIGB-247 immunized monkey sera was able to impair proliferation and formation of capillary-like structures in Matrigel, for HMEC cells in culture. Altogether, these results support the further clinical development of the CIGB-247 therapeutic cancer vaccine, and inform on the potential mechanisms involved in its effect. PMID:22075086

  20. Phase I 3D Conformal Radiation Dose Escalation Study in Newly Diagnosed Glioblastoma: RTOG 9803

    PubMed Central

    Tsien, Christina; Moughan, Jennifer; Michalski, Jeff M; Gilbert, Mark R.; Purdy, James; Simpson, Joseph; Kresel, John J.; Curran, Walter J.; Diaz, A.; Mehta, Minesh P.

    2010-01-01

    Purpose Phase I trial to evaluate the feasibility and toxicity of dose escalated 3DCRT concurrent with chemotherapy in patients with primary supratentorial GBM. Materials/Methods 209 patients were enrolled. All received 46 Gy in 2 Gy fractions to PTV1, defined as GTV plus 1.8 cm. Subsequent boost was given to PTV2, defined as GTV plus 0.3 cm. Patients were stratified into two groups (gp): (Gp 1: PTV2 < 75 cc, and Gp 2: PTV2≥75 cc). Four RT dose levels were evaluated: 66, 72 ,78 and 84 Gy. BCNU 80 mg/m2 was given during RT, then q 8 weeks for 6 cycles. Pre-treatment characteristics were well balanced. Results Acute and late grade (Gr) 3/4 RT-related toxicities were no more frequent at higher RT dose or with larger tumors. There were no DLTs (acute ≥ Gr 3 irreversible CNS toxicities) observed on any dose level in either group. Based on the absence of DLTs, dose was escalated to 84 Gy in both groups. Late RT necrosis was noted at 66 (1 pt), 72 (2), 78 (2) and 84 Gy (3) in Group 1. In Group 2, late RT necrosis was noted at 78 (1 pt) and 84 Gy (2). Median time to RT necrosis was 8.8 months (range: 5.1–12.5). Median survival in Group 1: 11.8–19.3 months. Median survival in Group 2: 8.2–13.9 months. Conclusions Our study shows the feasibility of delivering higher than standard (60 Gy) RT dose with concurrent chemotherapy for primary GBM with an acceptable risk of late CNS toxicity. PMID:18723297

  1. Dose-Escalation Study for Cardiac Radiosurgery in a Porcine Model

    SciTech Connect

    Blanck, Oliver; Bode, Frank; Gebhard, Maximilian; Hunold, Peter; Brandt, Sebastian; Bruder, Ralf; Grossherr, Martin; Vonthein, Reinhard; Rades, Dirk; Dunst, Juergen

    2014-07-01

    Purpose: To perform a proof-of-principle dose-escalation study to radiosurgically induce scarring in cardiac muscle tissue to block veno-atrial electrical connections at the pulmonary vein antrum, similar to catheter ablation. Methods and Materials: Nine mini-pigs underwent pretreatment magnetic resonance imaging (MRI) evaluation of heart function and electrophysiology assessment by catheter measurements in the right superior pulmonary vein (RSPV). Immediately after examination, radiosurgery with randomized single-fraction doses of 0 and 17.5-35 Gy in 2.5-Gy steps were delivered to the RSPV antrum (target volume 5-8 cm{sup 3}). MRI and electrophysiology were repeated 6 months after therapy, followed by histopathologic examination. Results: Transmural scarring of cardiac muscle tissue was noted with doses ≥32.5 Gy. However, complete circumferential scarring of the RSPV was not achieved. Logistic regressions showed that extent and intensity of fibrosis significantly increased with dose. The 50% effective dose for intense fibrosis was 31.3 Gy (odds ratio 2.47/Gy, P<.01). Heart function was not affected, as verified by MRI and electrocardiogram evaluation. Adjacent critical structures were not damaged, as verified by pathology, demonstrating the short-term safety of small-volume cardiac radiosurgery with doses up to 35 Gy. Conclusions: Radiosurgery with doses >32.5 Gy in the healthy pig heart can induce circumscribed scars at the RSPV antrum noninvasively, mimicking the effect of catheter ablation. In our study we established a significant dose-response relationship for cardiac radiosurgery. The long-term effects and toxicity of such high radiation doses need further investigation in the pursuit of cardiac radiosurgery for noninvasive treatment of atrial fibrillation.

  2. Tolerance to Dose Escalation in Minibeam Radiation Therapy Applied to Normal Rat Brain: Long-Term Clinical, Radiological and Histopathological Analysis.

    PubMed

    Prezado, Yolanda; Deman, Pierre; Varlet, Pascale; Jouvion, Gregory; Gil, Silvia; Le Clec'H, Céline; Bernard, Hélène; Le Duc, Géraldine; Sarun, Sukhena

    2015-09-01

    The major limitation to reaching a curative radiation dose in radioresistant tumors such as malignant gliomas is the high sensitivity to radiation and subsequent damage of the surrounding normal tissues. Novel dose delivery methods such as minibeam radiation therapy (MBRT) may help to overcome this limitation. MBRT utilizes a combination of spatial fractionation of the dose and submillimetric (600 μm) field sizes with an array ("comb") of parallel thin beams ("teeth"). The dose profiles in MBRT consist of peaks and valleys. In contrast, the seamless irradiations of the several squared centimeter field sizes employed in standard radiotherapy result in homogeneous dose distributions (and consequently, flat dose profiles). The innovative dose delivery methods employed in MBRT, unlike standard radiation therapy, have demonstrated remarkable normal tissue sparing. In this pilot work, we investigated the tolerance of the rat brain after whole-brain MBRT irradiation. A dose escalation was used to study the tissue response as a function of dose, so that a threshold could be established: doses as high as 100 Gy in one fraction were still well tolerated by the rat brain. This finding suggests that MBRT may be used to deliver higher and potentially curative radiation doses in clinical practice. PMID:26284420

  3. SU-E-J-44: A Novel Approach to Quantify Patient Setup and Target Motion for Real-Time Image-Guided Radiotherapy (IGRT)

    SciTech Connect

    Li, S; Charpentier, P; Sayler, E; Micaily, B; Miyamoto, C; Geng, J

    2015-06-15

    Purpose Isocenter shifts and rotations to correct patient setup errors and organ motion cannot remedy some shape changes of large targets. We are investigating new methods in quantification of target deformation for realtime IGRT of breast and chest wall cancer. Methods Ninety-five patients of breast or chest wall cancer were accrued in an IRB-approved clinical trial of IGRT using 3D surface images acquired at daily setup and beam-on time via an in-room camera. Shifts and rotations relating to the planned reference surface were determined using iterative-closest-point alignment. Local surface displacements and target deformation are measured via a ray-surface intersection and principal component analysis (PCA) of external surface, respectively. Isocenter shift, upper-abdominal displacement, and vectors of the surface projected onto the two principal components, PC1 and PC2, were evaluated for sensitivity and accuracy in detection of target deformation. Setup errors for some deformed targets were estimated by superlatively registering target volume, inner surface, or external surface in weekly CBCT or these outlines on weekly EPI. Results Setup difference according to the inner-surface, external surface, or target volume could be 1.5 cm. Video surface-guided setup agreed with EPI results to within < 0.5 cm while CBCT results were sometimes (∼20%) different from that of EPI (>0.5 cm) due to target deformation for some large breasts and some chest walls undergoing deep-breath-hold irradiation. Square root of PC1 and PC2 is very sensitive to external surface deformation and irregular breathing. Conclusion PCA of external surfaces is quick and simple way to detect target deformation in IGRT of breast and chest wall cancer. Setup corrections based on the target volume, inner surface, and external surface could be significant different. Thus, checking of target shape changes is essential for accurate image-guided patient setup and motion tracking of large deformable

  4. SU-E-J-55: End-To-End Effectiveness Analysis of 3D Surface Image Guided Voluntary Breath-Holding Radiotherapy for Left Breast

    SciTech Connect

    Lin, M; Feigenberg, S

    2015-06-15

    Purpose To evaluate the effectiveness of using 3D-surface-image to guide breath-holding (BH) left-side breast treatment. Methods Two 3D surface image guided BH procedures were implemented and evaluated: normal-BH, taking BH at a comfortable level, and deep-inspiration-breath-holding (DIBH). A total of 20 patients (10 Normal-BH and 10 DIBH) were recruited. Patients received a BH evaluation using a commercialized 3D-surface- tracking-system (VisionRT, London, UK) to quantify the reproducibility of BH positions prior to CT scan. Tangential 3D/IMRT plans were conducted. Patients were initially setup under free-breathing (FB) condition using the FB surface obtained from the untaged CT to ensure a correct patient position. Patients were then guided to reach the planned BH position using the BH surface obtained from the BH CT. Action-levels were set at each phase of treatment process based on the information provided by the 3D-surface-tracking-system for proper interventions (eliminate/re-setup/ re-coaching). We reviewed the frequency of interventions to evaluate its effectiveness. The FB-CBCT and port-film were utilized to evaluate the accuracy of 3D-surface-guided setups. Results 25% of BH candidates with BH positioning uncertainty > 2mm are eliminated prior to CT scan. For >90% of fractions, based on the setup deltas from3D-surface-trackingsystem, adjustments of patient setup are needed after the initial-setup using laser. 3D-surface-guided-setup accuracy is comparable as CBCT. For the BH guidance, frequency of interventions (a re-coaching/re-setup) is 40%(Normal-BH)/91%(DIBH) of treatments for the first 5-fractions and then drops to 16%(Normal-BH)/46%(DIBH). The necessity of re-setup is highly patient-specific for Normal-BH but highly random among patients for DIBH. Overall, a −0.8±2.4 mm accuracy of the anterior pericardial shadow position was achieved. Conclusion 3D-surface-image technology provides effective intervention to the treatment process and ensures

  5. Imaging Guided Breast Interventions.

    PubMed

    Masroor, Imrana; Afzal, Shaista; Sufian, Saira Naz

    2016-06-01

    Breast imaging is a developing field, with new and upcoming innovations, decreasing the morbidity and mortality related to breast pathologies with main emphasis on breast cancer. Breast imaging has an essential role in the detection and management of breast disease. It includes a multimodality approach, i.e. mammography, ultrasound, magnetic resonance imaging, nuclear medicine techniques and interventional procedures, done for the diagnosis and definitive management of breast abnormalities. The range of methods to perform biopsy of a suspicious breast lesion found on imaging has also increased markedly from the 1990s with hi-technological progress in surgical as well as percutaneous breast biopsy methods. The image guided percutaneous breast biopsy procedures cause minimal breast scarring, save time, and relieve the patient of the anxiety of going to the operation theatre. The aim of this review was to describe and discuss the different image guided breast biopsy techniques presently employed along with the indications, contraindication, merits and demerits of each method. PMID:27353993

  6. SU-C-18A-04: 3D Markerless Registration of Lung Based On Coherent Point Drift: Application in Image Guided Radiotherapy

    SciTech Connect

    Nasehi Tehrani, J; Wang, J; Guo, X; Yang, Y

    2014-06-01

    Purpose: This study evaluated a new probabilistic non-rigid registration method called coherent point drift for real time 3D markerless registration of the lung motion during radiotherapy. Method: 4DCT image datasets Dir-lab (www.dir-lab.com) have been used for creating 3D boundary element model of the lungs. For the first step, the 3D surface of the lungs in respiration phases T0 and T50 were segmented and divided into a finite number of linear triangular elements. Each triangle is a two dimensional object which has three vertices (each vertex has three degree of freedom). One of the main features of the lungs motion is velocity coherence so the vertices that creating the mesh of the lungs should also have features and degree of freedom of lung structure. This means that the vertices close to each other tend to move coherently. In the next step, we implemented a probabilistic non-rigid registration method called coherent point drift to calculate nonlinear displacement of vertices between different expiratory phases. Results: The method has been applied to images of 10-patients in Dir-lab dataset. The normal distribution of vertices to the origin for each expiratory stage were calculated. The results shows that the maximum error of registration between different expiratory phases is less than 0.4 mm (0.38 SI, 0.33 mm AP, 0.29 mm RL direction). This method is a reliable method for calculating the vector of displacement, and the degrees of freedom (DOFs) of lung structure in radiotherapy. Conclusions: We evaluated a new 3D registration method for distribution set of vertices inside lungs mesh. In this technique, lungs motion considering velocity coherence are inserted as a penalty in regularization function. The results indicate that high registration accuracy is achievable with CPD. This method is helpful for calculating of displacement vector and analyzing possible physiological and anatomical changes during treatment.

  7. Minimal Inter-Fractional Fiducial Migration during Image-Guided Lung Stereotactic Body Radiotherapy Using SuperLock Nitinol Coil Fiducial Markers

    PubMed Central

    Rong, Yi; Bazan, Jose G.; Sekhon, Ashley; Haglund, Karl; Xu-Welliver, Meng; Williams, Terence

    2015-01-01

    Objectives Stereotactic body radiotherapy (SBRT) is being increasingly used for the treatment of patients with lung cancer or lung metastasis who are medically unfit to undergo resection. In order to improve accuracy and confidence in targeting tumors, many centers rely on fiducial implantation. We evaluated the migration of a novel fiducial marker specifically designed for lung tissue implanted via electromagnetic navigation bronchoscopy (ENB). Methods We retrospectively quantified the individual and group migrations of SuperLock nitinol coil fiducials for 15 patients receiving lung stereotactic body radiotherapy (SBRT), in order to evaluate the reliability of using these fiducials as a target surrogate for cases where tumors cannot be clearly delineated on cone beam CTs (CBCTs). For each fraction, we compared the individual and group migrations of the fiducials between the planning CT and the acquired CBCT. The group migration was defined as the distance between the centroids of the fiducial group and GTV. Results A total of 16 lung targets were included in our study for these 15 patients (one patient with two targets). Of 55 fiducials placed, we observed a 100% retention rate. The mean individual migration was 1.87 mm (range, 0.63–5.25 mm) with a standard deviation of 1.26 mm. The mean group migration was 1.94 mm (range, 0.03–6.19 mm) with a standard deviation of 1.45 mm. Overall, there was minimal change in the relative locations of the markers with respect to each other, as well as to the target. Conclusions We found that the SuperLock nitinol coil fiducial marker positions are stable throughout the radiation treatment, and can be used as a reliable surrogate to target, and to avoid geometric misses during gated treatments. PMID:26158847

  8. Image-Guided Radiotherapy for Prostate Cancer: A Prospective Trial of Concomitant Boost Using Indium-111-Capromab Pendetide (ProstaScint) Imaging

    SciTech Connect

    Wong, William W.; Schild, Steven E.; Vora, Sujay A.; Ezzell, Gary A.; Nguyen, Ba D.; Ram, Panol C.; Roarke, Michael C.

    2011-11-15

    Purpose: To evaluate, in a prospective study, the use of {sup 111}In-capromab pendetide (ProstaScint) scan to guide the delivery of a concomitant boost to intraprostatic region showing increased uptake while treating the entire gland with intensity-modulated radiotherapy for localized prostate cancer. Methods and Materials: From September 2002 to November 2005, 71 patients were enrolled. Planning pelvic CT and {sup 111}In-capromab pendetide scan images were coregistered. The entire prostate gland received 75.6 Gy/42 fractions, whereas areas of increased uptake in {sup 111}In-capromab pendetide scan received 82 Gy. For patients with T3/T4 disease, or Gleason score {>=}8, or prostate-specific antigen level >20 ng/mL, 12 months of adjuvant androgen deprivation therapy was given. In January 2005 the protocol was modified to give 6 months of androgen deprivation therapy to patients with a prostate-specific antigen level of 10-20 ng/mL or Gleason 7 disease. Results: Thirty-one patients had low-risk, 30 had intermediate-risk, and 10 had high-risk disease. With a median follow-up of 66 months, the 5-year biochemical control rates were 94% for the entire cohort and 97%, 93%, and 90% for low-, intermediate-, and high-risk groups, respectively. Maximum acute and late urinary toxicities were Grade 2 for 38 patients (54%) and 28 patients (39%) and Grade 3 for 1 and 3 patients (4%), respectively. One patient had Grade 4 hematuria. Maximum acute and late gastrointestinal toxicities were Grade 2 for 32 patients (45%) and 15 patients (21%), respectively. Most of the side effects improved with longer follow-up. Conclusion: Concomitant boost to areas showing increased uptake in {sup 111}In-capromab pendetide scan to 82 Gy using intensity-modulated radiotherapy while the entire prostate received 75.6 Gy was feasible and tolerable, with 94% biochemical control rate at 5 years.

  9. SU-E-CAMPUS-J-04: Image Guided Radiation Therapy (IGRT): Review of Technical Standards and Credentialing in Radiotherapy Clinical Trials

    SciTech Connect

    Giaddui, T; Chen, W; Yu, J; Gong, Y; Galvin, J; Xiao, Y; Cui, Y; Yin, F; Craig, T; Dawson, L; Al-Hallaq, H; Chmura, S

    2014-06-15

    Purpose: To review IGRT credentialing experience and unexpected technical issues encountered in connection with advanced radiotherapy technologies as implemented in RTOG clinical trials. To update IGRT credentialing procedures with the aim of improving the quality of the process, and to increase the proportion of IGRT credentialing compliance. To develop a living disease site-specific IGRT encyclopedia. Methods: Numerous technical issues were encountered during the IGRT credentialing process. The criteria used for credentialing review were based on: image quality; anatomy included in fused data sets and shift results. Credentialing requirements have been updated according to the AAPM task group reports for IGRT to ensure that all required technical items are included in the quality review process. Implementation instructions have been updated and expanded for recent protocols. Results: Technical issues observed during the credentialing review process include, but are not limited to: poor quality images; inadequate image acquisition region; poor data quality; shifts larger than acceptable; no soft tissue surrogate. The updated IGRT credentialing process will address these issues and will also include the technical items required from AAPM: TG 104; TG 142 and TG 179 reports. An instruction manual has been developed describing a remote credentialing method for reviewers. Submission requirements are updated, including images/documents as well as facility questionnaire. The review report now includes summary of the review process and the parameters that reviewers check. We have reached consensus on the minimum IGRT technical requirement for a number of disease sites. RTOG 1311(NRG-BR002A Phase 1 Study of Stereotactic Body Radiotherapy (SBRT) for the Treatment of Multiple Metastases) is an example, here; the protocol specified the minimum requirement for each anatomical sites (with/without fiducials). Conclusion: Technical issues are identified and reported. IGRT

  10. Development of image quality assurance measures of the ExacTrac localization system using commercially available image evaluation software and hardware for image-guided radiotherapy.

    PubMed

    Stanley, Dennis N; Papanikolaou, Nikos; Gutiérrez, Alonso N

    2014-01-01

    Quality assurance (QA) of the image quality for image-guided localization systems is crucial to ensure accurate visualization and localization of target volumes. In this study, a methodology was developed to assess and evaluate the constancy of the high-contrast spatial resolution, dose, energy, contrast, and geometrical accuracy of the BrainLAB ExacTrac system. An in-house fixation device was constructed to hold the QCkV-1 phantom firmly and reproducibly against the face of the flat panel detectors. Two image sets per detector were acquired using ExacTrac preset console settings over a period of three months. The image sets were analyzed in PIPSpro and the following metrics were recorded: high-contrast spatial resolution (f30, f40, f50 (lp/mm)), noise, and contrast-to-noise ratio. Geometrical image accu- racy was evaluated by assessing the length between to predetermined points of the QCkV-1 phantom. Dose and kVp were recorded using the Unfors RaySafe Xi R/F Detector. The kVp and dose were evaluated for the following: Cranial Standard (CS) (80 kV,80 mA,80 ms), Thorax Standard (TS) (120 kV,160 mA,160 ms), Abdomen Standard (AS) (120 kV,160 mA,130 ms), and Pelvis Standard (PS) (120 kV,160 mA,160 ms). With regard to high-contrast spatial resolution, the mean values of the f30 (lp/mm), f40 (lp/mm) and f50 (lp/mm) for the left detector were 1.39 ± 0.04, 1.24 ± 0.05, and 1.09 ± 0.04, respectively, while for the right detector they were 1.38 ± 0.04, 1.22 ± 0.05, and 1.09 ± 0.05, respectively. Mean CNRs for the left and right detectors were 148 ± 3 and 143 ± 4, respectively. For geometrical accuracy, both detectors had a measured image length of the QCkV-1 of 57.9 ± 0.5 mm. The left detector showed dose measurements of 20.4 ± 0.2 μGy (CS), 191.8 ± 0.7 μGy (TS), 154.2 ± 0.7 μGy (AS), and 192.2 ± 0.6 μGy (PS), while the right detector showed 20.3 ± 0.3 μGy (CS), 189.7 ± 0.8 μGy (TS), 151.0 ± 0.7 μGy (AS), and 189.7 ± 0.8 μGy (PS), respectively. For X

  11. Tungsten Sulfide Quantum Dots as Multifunctional Nanotheranostics for In Vivo Dual-Modal Image-Guided Photothermal/Radiotherapy Synergistic Therapy.

    PubMed

    Yong, Yuan; Cheng, Xiaju; Bao, Tao; Zu, Mian; Yan, Liang; Yin, Wenyan; Ge, Cuicui; Wang, Dongliang; Gu, Zhanjun; Zhao, Yuliang

    2015-12-22

    Designing a multifunctional nanomedicine for integration of precise diagnosis and effective treatment of tumors is desirable but remains a great challenge. Here, we report a multifunctional nanomedicine based on WS2 quantum dots (QDs), which was prepared by a facile and "green" method through physical grinding and ultrasonication. The as-obtained WS2 QDs with small size (3 nm) possess not only significant X-ray computed tomography (CT)/photoaccoustic (PA) imaging signal enhancement but also remarkable photothermal therapy (PTT)/radiotherapy (RT) synergistic effect for tumor treatment. With CT/PA imaging and the synergistic effect between PTT and RT, the tumor could be accurately positioned and thoroughly eradicated in vivo after intravenous injection of WS2 QDs. Moreover, hematoxylin and eosin staining, blood hematology, and biochemistry analysis revealed no noticeable toxicity of WS2 QDs in vitro and in vivo, which confirmed that WS2 QDs possess good biocompatibility. This multifunctional nanoparticle could play an important role in facilitating simultaneously multimodal imaging and synergistic therapy between PTT and RT to achieve better therapeutic efficacy. PMID:26495962

  12. Is a Clinical Target Volume (CTV) Necessary in the Treatment of Lung Cancer in the Modern Era Combining 4-D Imaging and Image-guided Radiotherapy (IGRT)?

    PubMed Central

    Kilburn, Jeremy M; Lucas, John T; Soike, Michael H; Ayala-Peacock, Diandra N; Blackstock, Arthur W; Hinson, William H; Munley, Michael T; Petty, William J

    2016-01-01

    Objective: We hypothesized that omission of clinical target volumes (CTV) in lung cancer radiotherapy would not compromise control by determining retrospectively if the addition of a CTV would encompass the site of failure. Methods: Stage II-III patients were treated from 2009-2012 with daily cone-beam imaging and a 5 mm planning target volume (PTV) without a CTV. PTVs were expanded 1 cm and termed CTVretro. Recurrences were scored as 1) within the PTV, 2) within CTVretro, or 3) outside the PTV. Locoregional control (LRC), distant control (DC), progression-free survival (PFS), and overall survival (OS) were estimated. Result: Among 110 patients, Stage IIIA 57%, IIIB 32%, IIA 4%, and IIB 7%. Eighty-six percent of Stage III patients received chemotherapy. Median dose was 70 Gy (45-74 Gy) and fraction size ranged from 1.5-2.7 Gy. Median follow-up was 12 months, median OS was 22 months (95% CI 19-30 months), and LRC at two years was 69%. Fourteen local and eight regional events were scored with two CTVretro failures equating to a two-year CTV failure-free survival of 98%. Conclusion: Omission of a 1 cm CTV expansion appears feasible based on only two events among 110 patients and should be considered in radiation planning. PMID:26929893

  13. FIRE: an open-software suite for real-time 2D/3D image registration for image guided radiotherapy research

    NASA Astrophysics Data System (ADS)

    Furtado, H.; Gendrin, C.; Spoerk, J.; Steiner, E.; Underwood, T.; Kuenzler, T.; Georg, D.; Birkfellner, W.

    2016-03-01

    Radiotherapy treatments have changed at a tremendously rapid pace. Dose delivered to the tumor has escalated while organs at risk (OARs) are better spared. The impact of moving tumors during dose delivery has become higher due to very steep dose gradients. Intra-fractional tumor motion has to be managed adequately to reduce errors in dose delivery. For tumors with large motion such as tumors in the lung, tracking is an approach that can reduce position uncertainty. Tumor tracking approaches range from purely image intensity based techniques to motion estimation based on surrogate tracking. Research efforts are often based on custom designed software platforms which take too much time and effort to develop. To address this challenge we have developed an open software platform especially focusing on tumor motion management. FLIRT is a freely available open-source software platform. The core method for tumor tracking is purely intensity based 2D/3D registration. The platform is written in C++ using the Qt framework for the user interface. The performance critical methods are implemented on the graphics processor using the CUDA extension. One registration can be as fast as 90ms (11Hz). This is suitable to track tumors moving due to respiration (~0.3Hz) or heartbeat (~1Hz). Apart from focusing on high performance, the platform is designed to be flexible and easy to use. Current use cases range from tracking feasibility studies, patient positioning and method validation. Such a framework has the potential of enabling the research community to rapidly perform patient studies or try new methods.

  14. A Method to Estimate Mean Position, Motion Magnitude, Motion Correlation, and Trajectory of a Tumor From Cone-Beam CT Projections for Image-Guided Radiotherapy

    SciTech Connect

    Poulsen, Per Rugaard Cho, Byungchul; Keall, Paul J.

    2008-12-01

    Purpose: To develop a probability-based method for estimating the mean position, motion magnitude, and trajectory of a tumor using cone-beam CT (CBCT) projections. Method and Materials: CBCT acquisition was simulated for more than 80 hours of patient-measured trajectories for thoracic/abdominal tumors and prostate. The trajectories were divided into 60-second segments for which CBCT was simulated by projecting the tumor position onto a rotating imager. Tumor (surrogate) visibility on all projections was assumed. The mean and standard deviation of the tumor position and motion correlation along the three axes were determined with maximum likelihood estimation based on the projection data, assuming a Gaussian spatial distribution. The unknown position component along the imager axis was approximated by its expectation value, determined by the Gaussian distribution. Transformation of the resulting three-dimensional position to patient coordinates provided the estimated trajectory. Two trajectories were experimentally investigated by CBCT acquisition of a phantom. Results: The root-mean-square error of the estimated mean position was 0.05 mm. The root-mean-square error of the trajectories was <1 mm in 99.1% of the thorax/abdomen cases and in 99.7% of the prostate cases. The experimental trajectory estimation agreed with the actual phantom trajectory within 0.44 mm in any direction. Clinical applicability was demonstrated by estimating the tumor trajectory for a pancreas cancer case. Conclusions: A method for estimation of mean position, motion magnitude, and trajectory of a tumor from CBCT projections has been developed. The accuracy was typically much better than 1 mm. The method is applicable to motion-inclusive, respiratory-gated, and tumor-tracking radiotherapy.

  15. Comparison of Localization Performance with Implanted Fiducial Markers and Cone-Beam Computed Tomography for On-line Image-Guided Radiotherapy of the Prostate

    PubMed Central

    Moseley, Douglas J; White, Elizabeth A; Wiltshire, Kirsty L; Rosewall, Tara; Sharpe, Michael B; Siewerdsen, Jeffrey H; Bissonnette, Jean-Pierre; Gospodarowicz, Mary; Warde, Padraig; Catton, Charles N; Jaffray, David A

    2007-01-01

    Purpose To assess the accuracy of kV cone-beam CT (CBCT) based setup corrections as compared to orthogonal MV portal image-based corrections for patients undergoing external-beam radiotherapy of the prostate. Method and Materials Daily cone-beam CT volumetric images were acquired after setup for patients with three intra-prostatic fiducial markers. The estimated couch shifts were compared retrospectively to patient adjustments based on two orthogonal MV portal images (the current clinical standard of care in our institution). The CBCT soft-tissue based shifts were also estimated by digitally removing the gold markers in each projection to suppress the artifacts in the reconstructed volumes. A total of 256 volumetric images for 15 patients were analyzed. Results The Pearson coefficient of correlation for the patient position shifts using fiducial markers in MV vs kV was (R2 = 0.95, 0.84, 0.81) in the L/R, A/P and S/I directions respectively. The correlation using soft-tissue matching was ((R2 = 0.90, 0.49, 0.51) in the L/R, A/P and S/I directions. A Bland-Altman analysis showed no significant trends in the data. The percentage of shifts within a +/−3mm tolerance (the clinical action level) was (99.7, 95.5, 91.3) for fiducial marker matching and (99.5, 70.3, 78.4) for soft-tissue matching. Conclusions Cone-beam CT is an accurate and precise tool for image-guidance. It provides an equivalent means of patient setup correction for prostate patients with implanted gold fiducial markers. Use of the additional information provided by the visualization of soft-tissue structures is an active area of research. PMID:17293243

  16. Evaluation of overall setup accuracy and adequate setup margins in pelvic image-guided radiotherapy: Comparison of the male and female patients

    SciTech Connect

    Laaksomaa, Marko; Kapanen, Mika; Tulijoki, Tapio; Peltola, Seppo; Hyödynmaa, Simo; Kellokumpu-Lehtinen, Pirkko-Liisa

    2014-04-01

    We evaluated adequate setup margins for the radiotherapy (RT) of pelvic tumors based on overall position errors of bony landmarks. We also estimated the difference in setup accuracy between the male and female patients. Finally, we compared the patient rotation for 2 immobilization devices. The study cohort included consecutive 64 male and 64 female patients. Altogether, 1794 orthogonal setup images were analyzed. Observer-related deviation in image matching and the effect of patient rotation were explicitly determined. Overall systematic and random errors were calculated in 3 orthogonal directions. Anisotropic setup margins were evaluated based on residual errors after weekly image guidance. The van Herk formula was used to calculate the margins. Overall, 100 patients were immobilized with a house-made device. The patient rotation was compared against 28 patients immobilized with CIVCO's Kneefix and Feetfix. We found that the usually applied isotropic setup margin of 8 mm covered all the uncertainties related to patient setup for most RT treatments of the pelvis. However, margins of even 10.3 mm were needed for the female patients with very large pelvic target volumes centered either in the symphysis or in the sacrum containing both of these structures. This was because the effect of rotation (p ≤ 0.02) and the observer variation in image matching (p ≤ 0.04) were significantly larger for the female patients than for the male patients. Even with daily image guidance, the required margins remained larger for the women. Patient rotations were largest about the lateral axes. The difference between the required margins was only 1 mm for the 2 immobilization devices. The largest component of overall systematic position error came from patient rotation. This emphasizes the need for rotation correction. Overall, larger position errors and setup margins were observed for the female patients with pelvic cancer than for the male patients.

  17. Image-guided intensity-modulated radiotherapy for refractory bilateral breast cancer in a patient with extensive cutaneous metastasis in the chest and abdominal walls

    PubMed Central

    Lu, Yueh-Feng; Lin, Yu-Chin; Chen, Kuo-Hsin; Shueng, Pei-Wei; Yeh, Hsin-Pei; Hsieh, Chen-Hsi

    2016-01-01

    Treatment for bilateral breast cancer with chest wall and abdominal skin invasion normally involves conventional radiotherapy (RT); however, conventional RT provides inadequate target volume coverage and excessive treatment of large volumes of normal tissue. Helical tomotherapy (HT) has the ability to deliver continuous craniocaudal irradiation that suppresses junction problems and provides good conformity of dose distribution. A 47-year-old female with stage IV bilateral breast cancer with chest wall and pectoralis major muscle invasion, lymphadenopathy, bilateral pleural effusion, and multiple bone metastases received chemotherapy and target therapy beginning in January 2014; 4 months after the initiation of chemotherapy, computed tomography revealed progression of chest and abdominal wall invasion. A total dose of 70.2 Gy was delivered to both breasts, the chest wall, the abdominal wall, and the bilateral supraclavicular nodal areas in 39 fractions via HT. The total planning target volume was 4,533.29 cm3. The percent of lung volume receiving at least 20 Gy (V20) was 28%, 22%, and 25% for the right lung, left lung, and whole lung, respectively. The mean dose to the heart was 8.6 Gy. Follow-up computed tomography revealed complete response after the RT course. Grade 1 dysphagia, weight loss, grade 2 neutropenia, and grade 3 dermatitis were noted during the RT course. Pain score decreased from 6 to 1. No cardiac, pulmonary, liver, or intestinal toxicity developed during treatment or follow-up. Concurrent HT with or without systemic treatment could be a safe salvage therapy for chemorefractory locally advanced breast cancer patients with extensive cutaneous metastasis. PMID:27284253

  18. Real-time intensity based 2D/3D registration using kV-MV image pairs for tumor motion tracking in image guided radiotherapy

    NASA Astrophysics Data System (ADS)

    Furtado, H.; Steiner, E.; Stock, M.; Georg, D.; Birkfellner, W.

    2014-03-01

    Intra-fractional respiratorymotion during radiotherapy is one of themain sources of uncertainty in dose application creating the need to extend themargins of the planning target volume (PTV). Real-time tumormotion tracking by 2D/3D registration using on-board kilo-voltage (kV) imaging can lead to a reduction of the PTV. One limitation of this technique when using one projection image, is the inability to resolve motion along the imaging beam axis. We present a retrospective patient study to investigate the impact of paired portal mega-voltage (MV) and kV images, on registration accuracy. We used data from eighteen patients suffering from non small cell lung cancer undergoing regular treatment at our center. For each patient we acquired a planning CT and sequences of kV and MV images during treatment. Our evaluation consisted of comparing the accuracy of motion tracking in 6 degrees-of-freedom(DOF) using the anterior-posterior (AP) kV sequence or the sequence of kV-MV image pairs. We use graphics processing unit rendering for real-time performance. Motion along cranial-caudal direction could accurately be extracted when using only the kV sequence but in AP direction we obtained large errors. When using kV-MV pairs, the average error was reduced from 3.3 mm to 1.8 mm and the motion along AP was successfully extracted. The mean registration time was of 190+/-35ms. Our evaluation shows that using kVMV image pairs leads to improved motion extraction in 6 DOF. Therefore, this approach is suitable for accurate, real-time tumor motion tracking with a conventional LINAC.

  19. Is Androgen Deprivation Therapy Necessary in All Intermediate-Risk Prostate Cancer Patients Treated in the Dose Escalation Era?

    SciTech Connect

    Castle, Katherine O.; Hoffman, Karen E.; Levy, Lawrence B.; Lee, Andrew K.; Choi, Seungtaek; Nguyen, Quynh N.; Frank, Steven J.; Pugh, Thomas J.; McGuire, Sean E.; Kuban, Deborah A.

    2013-03-01

    Purpose: The benefit of adding androgen deprivation therapy (ADT) to dose-escalated radiation therapy (RT) for men with intermediate-risk prostate cancer is unclear; therefore, we assessed the impact of adding ADT to dose-escalated RT on freedom from failure (FFF). Methods: Three groups of men treated with intensity modulated RT or 3-dimensional conformal RT (75.6-78 Gy) from 1993-2008 for prostate cancer were categorized as (1) 326 intermediate-risk patients treated with RT alone, (2) 218 intermediate-risk patients treated with RT and ≤6 months of ADT, and (3) 274 low-risk patients treated with definitive RT. Median follow-up was 58 months. Recursive partitioning analysis based on FFF using Gleason score (GS), T stage, and pretreatment PSA concentration was applied to the intermediate-risk patients treated with RT alone. The Kaplan-Meier method was used to estimate 5-year FFF. Results: Based on recursive partitioning analysis, intermediate-risk patients treated with RT alone were divided into 3 prognostic groups: (1) 188 favorable patients: GS 6, ≤T2b or GS 3+4, ≤T1c; (2) 71 marginal patients: GS 3+4, T2a-b; and (3) 68 unfavorable patients: GS 4+3 or T2c disease. Hazard ratios (HR) for recurrence in each group were 1.0, 2.1, and 4.6, respectively. When intermediate-risk patients treated with RT alone were compared to intermediate-risk patients treated with RT and ADT, the greatest benefit from ADT was seen for the unfavorable intermediate-risk patients (FFF, 74% vs 94%, respectively; P=.005). Favorable intermediate-risk patients had no significant benefit from the addition of ADT to RT (FFF, 94% vs 95%, respectively; P=.85), and FFF for favorable intermediate-risk patients treated with RT alone approached that of low-risk patients treated with RT alone (98%). Conclusions: Patients with favorable intermediate-risk prostate cancer did not benefit from the addition of ADT to dose-escalated RT, and their FFF was nearly as good as patients with low-risk disease

  20. Incidence of Secondary Cancer Development After High-Dose Intensity-Modulated Radiotherapy and Image-Guided Brachytherapy for the Treatment of Localized Prostate Cancer

    SciTech Connect

    Zelefsky, Michael J.; Housman, Douglas M.; Pei Xin; Alicikus, Zumre; Magsanoc, Juan Martin; Dauer, Lawrence T.; St Germain, Jean; Yamada, Yoshiya; Kollmeier, Marisa; Cox, Brett; Zhang Zhigang

    2012-07-01

    Purpose: To report the incidence and excess risk of second malignancy (SM) development compared with the general population after external beam radiotherapy (EBRT) and brachytherapy to treat prostate cancer. Methods and Materials: Between 1998 and 2001, 1,310 patients with localized prostate cancer were treated with EBRT (n = 897) or brachytherapy (n = 413). We compared the incidence of SMs in our patients with that of the general population extracted from the National Cancer Institute's Surveillance, Epidemiology, and End Results data set combined with the 2000 census data. Results: The 10-year likelihood of SM development was 25% after EBRT and 15% after brachytherapy (p = .02). The corresponding 10-year likelihood for in-field SM development in these groups was 4.9% and 1.6% (p = .24). Multivariate analysis showed that EBRT vs. brachytherapy and older age were the only significant predictors for the development of all SMs (p = .037 and p = .030), with a trend for older patients to develop a SM. The increased incidence of SM for EBRT patients was explained by the greater incidence of skin cancer outside the radiation field compared with that after brachytherapy (10.6% and 3.3%, respectively, p = .004). For the EBRT group, the 5- and 10-year mortality rate was 1.96% and 5.1% from out-of field cancer, respectively; for in-field SM, the corresponding mortality rates were 0.1% and 0.7%. Among the brachytherapy group, the 5- and 10-year mortality rate related to out-of field SM was 0.8% and 2.7%, respectively. Our observed SM rates after prostate RT were not significantly different from the cancer incidence rates in the general population. Conclusions: Using modern sophisticated treatment techniques, we report low rates of in-field bladder and rectal SM risks after prostate cancer RT. Furthermore, the likelihood of mortality secondary to a SM was unusual. The greater rate of SM observed with EBRT vs. brachytherapy was related to a small, but significantly increased

  1. A Phase II prospective nonrandomized trial of magnetic resonance imaging-guided hematopoietic bone marrow-sparing radiotherapy for gastric cancer patients with concurrent chemotherapy

    PubMed Central

    Wang, Jianyang; Tian, Yuan; Tang, Yuan; Wang, Xin; Li, Ning; Ren, Hua; Fang, Hui; Feng, Yanru; Wang, Shulian; Song, Yongwen; Liu, Yueping; Wang, Weihu; Li, Yexiong; Jin, Jing

    2016-01-01

    Purpose This study aimed to spare hematopoietical bone marrow (BM) identified by magnetic resonance (MR) radiation in order to alleviate acute hematologic toxicity (HT) for gastric cancer patients treated with postoperative chemoradiotherapy (CRT). Methods A prospective, open-label, single-arm Phase II study (Clinicaltrials.gov; NCT 01863420) was conducted in 25 patients with gastric cancer who were eligible for postoperative concurrent CRT. The MR images of vertebral body T8-L4 were fused with images of simulating computed tomography. Hematopoietical BM was contoured according to the MR and spared in radiotherapy plan. The CRT regimen consisted of daily capecitabine (1600 mg/m2/d) and 45 Gy of radiation at 1.8 Gy per day. Primary endpoints were grade ≥3 HT that occurred within 2 months of initiation of CRT. The relationship between HT and dose–volume of BM was estimated by multivariable linear regression model. Results Twenty four patients (96%) had T3–4 disease and 22 (88%) had disease with node positive. The median age was 53 years (range, 28–73 years). Before concurrent CRT, adjuvant chemotherapy was administered with a mean cycle of 4.3±0.5. Only five patients (20%) developed grade 3–4 HT during treatment, among whom two (8.0%) patients experienced grade 3–4 leucopenia, two (8.0%) experienced neutropenia, and two (8.0%) experienced thrombocytopenia, respectively. None of the patients showed grade 3–4 anemia. Multivariable linear regression revealed increased BM-V5 (P=0.03) and BM-V20 (P=0.002) were found to be significantly associated with decreased white blood cells nadirs in multivariable regression; increased BM-V20 (P<0.001) with decreased absolute neutrophil count nadirs, increased BM-V30 (P=0.002) and volume of BM (P=0.001) with decreased platelet count nadirs. Conclusion Irradiation of active BM identified by MR is associated with HTs. Techniques to limit low-dose radiation, especially V20, to BM could reduce HT in gastric cancer patients

  2. High Retention and Safety of Percutaneously Implanted Endovascular Embolization Coils as Fiducial Markers for Image-Guided Stereotactic Ablative Radiotherapy of Pulmonary Tumors

    SciTech Connect

    Hong, Julian C.; Yu Yao; Rao, Aarti K.; Dieterich, Sonja; Maxim, Peter G.; Le, Quynh-Thu; Diehn, Maximilian; Sze, Daniel Y.; Kothary, Nishita; Loo, Billy W.

    2011-09-01

    Purpose: To compare the retention rates of two types of implanted fiducial markers for stereotactic ablative radiotherapy (SABR) of pulmonary tumors, smooth cylindrical gold 'seed' markers ('seeds') and platinum endovascular embolization coils ('coils'), and to compare the complication rates associated with the respective implantation procedures. Methods and Materials: We retrospectively analyzed the retention of percutaneously implanted markers in 54 consecutive patients between January 2004 and June 2009. A total of 270 markers (129 seeds, 141 coils) were implanted in or around 60 pulmonary tumors over 59 procedures. Markers were implanted using a percutaneous approach under computed tomography (CT) guidance. Postimplantation and follow-up imaging studies were analyzed to score marker retention relative to the number of markers implanted. Markers remaining near the tumor were scored as retained. Markers in a distant location (e.g., pleural space) were scored as lost. CT imaging artifacts near markers were quantified on radiation therapy planning scans. Results: Immediately after implantation, 140 of 141 coils (99.3%) were retained, compared to 110 of 129 seeds (85.3%); the difference was highly significant (p < 0.0001). Of the total number of lost markers, 45% were reported lost during implantation, but 55% were lost immediately afterwards. No additional markers were lost on longer-term follow-up. Implanted lesions were peripherally located for both seeds (mean distance, 0.33 cm from pleural surface) and coils (0.34 cm) (p = 0.96). Incidences of all pneumothorax (including asymptomatic) and pneumothorax requiring chest tube placement were lower in implantation of coils (23% and 3%, respectively) vs. seeds (54% and 29%, respectively; p = 0.02 and 0.01). The degree of CT artifact was similar between marker types. Conclusions: Retention of CT-guided percutaneously implanted coils is significantly better than that of seed markers. Furthermore, implanting coils is at

  3. Current role of spacers for prostate cancer radiotherapy

    PubMed Central

    Pinkawa, Michael

    2015-01-01

    Radiotherapy is an established curative treatment method for prostate cancer. Optimal tumor control rates can only be achieved with high local doses, associated with a considerable risk of rectal toxicity. Apart from already widely adapted technical advances, as intensity-modulated radiation therapy, the application of spacers placed between the prostate and rectum has been increasingly used in the last years. Biodegradable spacers, including hydrogel, hyaluronic acid, collagen or an implantable balloon, can be injected or inserted in a short procedure under transrectal ultrasound guidance via a transperineal approach. A distance of about 1.0-1.5 cm is usually achieved between the rectum and prostate, excluding the rectal wall from the high isodoses. Several studies have shown well tolerated injection procedures and treatments. Apart from considerable reduction of rectal irradiation, a prospective randomized trial demonstrated a reduction of rectal toxicity after hydrogel injection in men undergoing prostate image-guided intensity-modulated radiation therapy. The results are encouraging for continuing evaluation in dose escalation, hypofractionation, stereotactic radiotherapy or re-irradiation trials in the future. PMID:26677428

  4. Optimizing Collimator Margins for Isotoxically Dose-Escalated Conformal Radiation Therapy of Non-Small Cell Lung Cancer

    SciTech Connect

    Warren, Samantha; Panettieri, Vanessa; Panakis, Niki; Bates, Nicholas; Lester, Jason F.; Jain, Pooja; Landau, David B.; Nahum, Alan E.; Mayles, W. Philip M.; Fenwick, John D.

    2014-04-01

    Purpose: Isotoxic dose escalation schedules such as IDEAL-CRT [isotoxic dose escalation and acceleration in lung cancer chemoradiation therapy] (ISRCTN12155469) individualize doses prescribed to lung tumors, generating a fixed modeled risk of radiation pneumonitis. Because the beam penumbra is broadened in lung, the choice of collimator margin is an important element of the optimization of isotoxic conformal radiation therapy for lung cancer. Methods and Materials: Twelve patients with stage I-III non-small cell lung cancer (NSCLC) were replanned retrospectively using a range of collimator margins. For each plan, the prescribed dose was calculated according to the IDEAL-CRT isotoxic prescription method, and the absolute dose (D{sub 99}) delivered to 99% of the planning target volume (PTV) was determined. Results: Reducing the multileaf collimator margin from the widely used 7 mm to a value of 2 mm produced gains of 2.1 to 15.6 Gy in absolute PTV D{sub 99}, with a mean gain ± 1 standard error of the mean of 6.2 ± 1.1 Gy (2-sided P<.001). Conclusions: For NSCLC patients treated with conformal radiation therapy and an isotoxic dose prescription, absolute doses in the PTV may be increased by using smaller collimator margins, reductions in relative coverage being offset by increases in prescribed dose.

  5. Dose Escalation of Total Marrow Irradiation With Concurrent Chemotherapy in Patients With Advanced Acute Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

    SciTech Connect

    Wong, Jeffrey Y.C.; Forman, Stephen; Somlo, George; Liu An; Schultheiss, Timothy; Radany, Eric; Palmer, Joycelynne; Stein, Anthony

    2013-01-01

    Purpose: We have demonstrated that toxicities are acceptable with total marrow irradiation (TMI) at 16 Gy without chemotherapy or TMI at 12 Gy and the reduced intensity regimen of fludarabine/melphalan in patients undergoing hematopoietic cell transplantation (HCT). This article reports results of a study of TMI combined with higher intensity chemotherapy regimens in 2 phase I trials in patients with advanced acute myelogenous leukemia or acute lymphoblastic leukemia (AML/ALL) who would do poorly on standard intent-to-cure HCT regimens. Methods and Materials: Trial 1 consisted of TMI on Days -10 to -6, etoposide (VP16) on Day -5 (60 mg/kg), and cyclophosphamide (CY) on Day -3 (100 mg/kg). TMI dose was 12 (n=3 patients), 13.5 (n=3 patients), and 15 (n=6 patients) Gy at 1.5 Gy twice daily. Trial 2 consisted of busulfan (BU) on Days -12 to -8 (800 {mu}M min), TMI on Days -8 to -4, and VP16 on Day -3 (30 mg/kg). TMI dose was 12 (n=18) and 13.5 (n=2) Gy at 1.5 Gy twice daily. Results: Trial 1 had 12 patients with a median age of 33 years. Six patients had induction failures (IF), and 6 had first relapses (1RL), 9 with leukemia blast involvement of bone marrow ranging from 10%-98%, 5 with circulating blasts (24%-85%), and 2 with chloromas. No dose-limiting toxicities were observed. Eleven patients achieved complete remission at Day 30. With a median follow-up of 14.75 months, 5 patients remained in complete remission from 13.5-37.7 months. Trial 2 had 20 patients with a median age of 41 years. Thirteen patients had IF, and 5 had 1RL, 2 in second relapse, 19 with marrow blasts (3%-100%) and 13 with peripheral blasts (6%-63%). Grade 4 dose-limiting toxicities were seen at 13.5 Gy (stomatitis and hepatotoxicity). Stomatitis was the most frequent toxicity in both trials. Conclusions: TMI dose escalation to 15 Gy is possible when combined with CY/VP16 and is associated with acceptable toxicities and encouraging outcomes. TMI dose escalation is not possible with BU/VP16 due to

  6. Phase 1 Study of Dose Escalation in Hypofractionated Proton Beam Therapy for Non-Small Cell Lung Cancer

    SciTech Connect

    Gomez, Daniel R.; Gillin, Michael; Liao, Zhongxing; Wei, Caimiao; Lin, Steven H.; Swanick, Cameron; Alvarado, Tina; Komaki, Ritsuko; Cox, James D.; Chang, Joe Y.

    2013-07-15

    Background: Many patients with locally advanced non-small cell lung cancer (NSCLC) cannot undergo concurrent chemotherapy because of comorbidities or poor performance status. Hypofractionated radiation regimens, if tolerable, may provide an option to these patients for effective local control. Methods and Materials: Twenty-five patients were enrolled in a phase 1 dose-escalation trial of proton beam therapy (PBT) from September 2010 through July 2012. Eligible patients had histologically documented lung cancer, thymic tumors, carcinoid tumors, or metastatic thyroid tumors. Concurrent chemotherapy was not allowed, but concurrent treatment with biologic agents was. The dose-escalation schema comprised 15 fractions of 3 Gy(relative biological effectiveness [RBE])/fraction, 3.5 Gy(RBE)/fraction, or 4 Gy(RBE)/fraction. Dose constraints were derived from biologically equivalent doses of standard fractionated treatment. Results: The median follow-up time for patients alive at the time of analysis was 13 months (range, 8-28 months). Fifteen patients received treatment to hilar or mediastinal lymph nodes. Two patients experienced dose-limiting toxicity possibly related to treatment; 1 received 3.5-Gy(RBE) fractions and experienced an in-field tracheoesophageal fistula 9 months after PBT and 1 month after bevacizumab. The other patient received 4-Gy(RBE) fractions and was hospitalized for bacterial pneumonia/radiation pneumonitis 4 months after PBT. Conclusion: Hypofractionated PBT to the thorax delivered over 3 weeks was well tolerated even with significant doses to the lungs and mediastinal structures. Phase 2/3 trials are needed to compare the efficacy of this technique with standard treatment for locally advanced NSCLC.

  7. Sunitinib dose-escalation overcomes transient resistance in clear cell renal cell carcinoma and is associated with epigenetic modifications

    PubMed Central

    Adelaiye, Remi; Ciamporcero, Eric; Miles, Kiersten Marie; Sotomayor, Paula; Bard, Jonathan; Tsompana, Maria; Conroy, Dylan; Shen, Li; Ramakrishnan, Swathi; Ku, Sheng-Yu; Orillion, Ashley; Prey, Joshua; Fetterly, Gerald; Buck, Michael; Chintala, Sreenivasulu; Bjarnason, Georg A.; Pili, Roberto

    2014-01-01

    Sunitinib is considered a first-line therapeutic option for patients with advanced clear cell renal cell carcinoma (ccRCC). Despite sunitinib clinical efficacy, eventually patients develop drug resistance and disease progression. Herein, we tested the hypothesis whether initial sunitinib resistance may be transient and could be overcome by dose increase. In selected patients initially treated with 50 mg sunitinib and presenting with minimal toxicities, sunitinib dose was escalated to 62.5 mg and/or 75 mg at the time of tumor progression. Mice bearing two different patient-derived ccRCC xenografts (PDXs) were treated 5 days/week with a dose-escalation schema (40-60-80 mg/kg sunitinib). Tumor tissues were collected prior to dose increments for immunohistochemistry analyses and drug levels. Selected intra-patient sunitinib dose escalation was safe and several patients had added progression free survival. In parallel, our preclinical results showed that PDXs, although initially responsive to sunitinib at 40 mg/kg, eventually developed resistance. When the dose was incrementally increased, again we observed tumor response to sunitinib. A resistant phenotype was associated with transient increase of tumor vasculature despite intratumor sunitinib accumulation at higher dose. In addition, we observed associated changes in the expression of the methyltransferase EZH2 and histone marks at the time of resistance. Furthermore, specific EZH2 inhibition resulted in increased in vitro anti-tumor effect of sunitinib. Overall, our results suggest that initial sunitinib-induced resistance may be overcome, in part, by increasing the dose, and highlight the potential role of epigenetic changes associated with sunitinib resistance that can represent new targets for therapeutic intervention. PMID:25519701

  8. Perineural Invasion Predicts Increased Recurrence, Metastasis, and Death From Prostate Cancer Following Treatment With Dose-Escalated Radiation Therapy

    SciTech Connect

    Feng, Felix Y.; Qian Yushen; Stenmark, Matthew H.; Halverson, Schuyler; Blas, Kevin; Vance, Sean; Sandler, Howard M.; Hamstra, Daniel A.

    2011-11-15

    Purpose: To assess the prognostic value of perineural invasion (PNI) for patients treated with dose-escalated external-beam radiation therapy for prostate cancer. Methods and Materials: Outcomes were analyzed for 651 men treated for prostate cancer with EBRT to a minimum dose {>=}75 Gy. We assessed the impact of PNI as well as pretreatment and treatment-related factors on freedom from biochemical failure (FFBF), freedom from metastasis (FFM), cause-specific survival (CSS), and overall survival. Results: PNI was present in 34% of specimens at biopsy and was significantly associated with higher Gleason score (GS), T stage, and prostate-specific antigen level. On univariate and multivariate analysis, the presence of PNI was associated with worse FFBF (hazard ratio = 1.7, p <0.006), FFM (hazard ratio = 1.8, p <0.03), and CSS (HR = 1.4, p <0.05) compared with absence of PNI; there was no difference in overall survival. Seven-year rates of FFBF, FFM, and CCS were 64% vs. 80%, 84% vs. 92%, and 91% vs. 95% for those patients with and without PNI, respectively. On recursive partitioning analysis, PNI predicted for worse FFM and CSS in patients with GS 8-10, with FFM of 67% vs. 89% (p <0.02), and CSS of 69% vs. 91%, (p <0.04) at 7 years for those with and without PNI, respectively. Conclusions: The presence of PNI in the prostate biopsy predicts worse clinical outcome for patients treated with dose-escalated external-beam radiation therapy. Particularly in patients with GS 8-10 disease, the presence of PNI suggests an increased risk of metastasis and prostate cancer death.

  9. No signs of dose escalations of potent opioids prescribed after tibial shaft fractures: a study of Swedish National Registries

    PubMed Central

    2014-01-01

    Background The pattern of opioid use after skeletal trauma is a neglected topic in pain medicine. The purpose of this study was to analyse the long-term prescriptions of potent opioids among patients with tibial shaft fractures. Methods Data were extracted from the Swedish National Hospital Discharge Register, the National Pharmacy Register, and the Total Population Register, and analysed accordingly. The study period was 2005–2008. Results We identified 2,571 patients with isolated tibial shaft fractures. Of these, 639 (25%) collected a prescription for opioids after the fracture. The median follow-up time was 17 (interquartile range [IQR] 7–27) months. Most patients with opioid prescriptions after fracture were male (61%) and the median age was 45 (16–97) years. The leading mechanism of injury was fall on the same level (41%). At 6 and 12 months after fracture, 21% (95% CI 17–24) and 14% (11–17) were still being treated with opioids. Multiple Cox regression-analysis (adjusted for age, sex, type of treatment, and mechanism of injury) revealed that older patients (age >50 years) were more likely to end opioid prescriptions (Hazard ratio 1.5 [95% CI 1.3-1.9]). During follow-up, the frequency of patients on moderate and high doses declined. Comparison of the daily morphine equivalent dose among individuals who both had prescriptions during the first 3 months and the 6th month indicated that the majority of these patients (11/14) did not have dose escalations. Conclusions We did not see any signs in registry-data of major dose escalations over time in patients on potent opioids after tibial shaft fractures. PMID:24418163

  10. Parameters Favorable to Intraprostatic Radiation Dose Escalation in Men With Localized Prostate Cancer

    SciTech Connect

    Housri, Nadine; Ning, Holly; Ondos, John; Choyke, Peter; Camphausen, Kevin; Citrin, Deborah; Arora, Barbara; Shankavaram, Uma; Kaushal, Aradhana

    2011-06-01

    Purpose: To identify , within the framework of a current Phase I trial, whether factors related to intraprostatic cancer lesions (IPLs) or individual patients predict the feasibility of high-dose intraprostatic irradiation. Methods and Materials: Endorectal coil MRI scans of the prostate from 42 men were evaluated for dominant IPLs. The IPLs, prostate, and critical normal tissues were contoured. Intensity-modulated radiotherapy plans were generated with the goal of delivering 75.6 Gy in 1.8-Gy fractions to the prostate, with IPLs receiving a simultaneous integrated boost of 3.6 Gy per fraction to a total dose of 151.2 Gy, 200% of the prescribed dose and the highest dose cohort in our trial. Rectal and bladder dose constraints were consistent with those outlined in current Radiation Therapy Oncology Group protocols. Results: Dominant IPLs were identified in 24 patients (57.1%). Simultaneous integrated boosts (SIB) to 200% of the prescribed dose were achieved in 12 of the 24 patients without violating dose constraints. Both the distance between the IPL and rectum and the hip-to-hip patient width on planning CT scans were associated with the feasibility to plan an SIB (p = 0.002 and p = 0.0137, respectively). Conclusions: On the basis of this small cohort, the distance between an intraprostatic lesion and the rectum most strongly predicted the ability to plan high-dose radiation to a dominant intraprostatic lesion. High-dose SIB planning seems possible for select intraprostatic lesions.

  11. Association of dose escalation of octreotide long-acting release on clinical symptoms and tumor markers and response among patients with neuroendocrine tumors.

    PubMed

    Al-Efraij, Khalid; Aljama, Mohammed A; Kennecke, Hagen Fritz

    2015-06-01

    Patients with nonresectable metastatic neuroendocrine tumors (NETs) experience symptoms of hormone hypersecretion including diarrhea, flushing, and bronchoconstriction, which can interfere with quality of life [Anthony and Vinik (2011) Pancreas, 40:987]. Treatment with a long-acting release formulation of octreotide, a somatostatin analog, can help to alleviate these symptoms. Although high doses of octreotide are often required for adequate symptom control, the relationship between octreotide dose escalation and symptom control in the NET context is not well quantified in the literature. A retrospective chart review was conducted of nonresectable metastatic NET patients who received a dose greater than 30 mg intramuscular octreotide long-acting formulation (O-LAR) at any time between January 2005 and December 2011 at the British Columbia Cancer Agency (BCCA). The association between dose escalation of O-LAR, chromogranin A (CGA), 24-h urine 5-hydoxyindoacetate (5-HIAA), symptom control, and radiological progression was explored. Dose escalation of O-LAR was associated with improved symptom control in NET patients who were refractory to the standard dose levels. Reduction of serum CGA & 5-HIAA levels by at least 10% was observed in 31% and 23% respectively. Retrospective review of imaging did not document any reductions in tumor volume. Higher doses of O-LAR are associated with improved symptom control in NET patients. The variability in tumor marker levels in response to O-LAR dose escalation may indicate that tumor marker levels may not be an accurate assessment of therapeutic efficacy. PMID:25727756

  12. Exploring the Feasibility of Dose Escalation Positron Emission Tomography-Positive Disease with Intensity-Modulated Radiation Therapy and the Effects on Normal Tissue Structures for Thoracic Malignancies

    SciTech Connect

    Turner, Lehendrick M.; Howard, Joshua A.; Dehghanpour, Pouya; Barrett, Renee D.; Rebueno, Neal; Palmer, Matthew; Vedam, Sastry; Klopp, Ann; Komaki, Ritsuko; Welsh, James W.

    2011-01-01

    The pattern of failure is one of the major causes of mortality among thoracic patients. Studies have shown a correlation between local control and dose. Intensity-modulated radiation therapy (IMRT) has resulted in conformal dose distributions while limiting dose to normal tissue. However, thoracic malignancies treated with IMRT to highly conformal doses up to 70 Gy still have been found to fail. Thus, the need for dose escalation through simultaneous integrated boost (SIB) may prove effective in minimizing reoccurrences. For our study, 28 thoracic IMRT plans were reoptimized via dose escalation to the gross tumor volume (GTV) and planning target volume (PTV) of 79.2 Gy and 68.4 Gy, respectively. Reoccurrences in surrounding regions of microscopic disease are rare therefore, dose-escalating regional nodes (outside GTV) were not included. Hence, the need to edit GTV margins was acceptable for our retrospective study. A median dose escalation of approximately 15 Gy (64.8-79.2 Gy) via IMRT using SIB was deemed achievable with minimal percent differences received by critical structures compared with the original treatment plan. The target's mean doses were significantly increased based on p-value analysis, while the normal tissue structures were not significantly changed.

  13. Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

    SciTech Connect

    Vainshtein, Jeffrey M.; Schipper, Matthew; Zalupski, Mark M.; Lawrence, Theodore S.; Abrams, Ross; Francis, Isaac R.; Khan, Gazala; Leslie, William; Ben-Josef, Edgar

    2013-05-01

    Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factors on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression

  14. Is the “3+3” dose escalation phase 1 clinical trial design suitable for therapeutic cancer vaccine development? A recommendation for alternative design

    PubMed Central

    Rahma, Osama E.; Gammoh, Emily; Simon, Richard M.; Khleif, Samir N.

    2014-01-01

    Purpose Phase 1 clinical trials are generally conducted to identify the maximum tolerated dose (MTD) or the biologically active dose (BAD) using a traditional dose escalation design. This design may not be applied to cancer vaccines, given their unique mechanism of action. The FDA recently published “Guidance for Industry: Clinical Considerations for Therapeutic Cancer Vaccines.” However, many questions about the design of cancer vaccine studies remain unanswered. Experimental Design We analyzed the toxicity profile in 239 phase 1 therapeutic cancer vaccine trials. We addressed the ability of dose escalation to determine the MTD or the BAD in trials that used a dose escalation design. Results The rate of grade 3/4 vaccine-related systemic toxicities was 1.25 adverse event per 100 patients and 2 per 1000 vaccines. Only 2 out of the 127 dose escalation trials reported vaccine-related dose limiting toxicities, both of which used bacterial vector vaccines. Out of the 116 trials analyzed for the dose-immune response relationship, we found a statistically significant dose-immune response correlation only when the immune response was measured by antibodies (p<0.001) or delayed type hypersensitivity (p<0.05). However, the increase in cellular immune response did not appear further sustainable with the continued increase in dose. Conclusions Our analysis suggests that the risks of serious toxicities with therapeutic cancer vaccines are extremely low and that toxicities do not correlate with dose levels. Accordingly, the conventional dose escalation design is not suitable for cancer vaccines with few exceptions. Here we propose an alternative design for therapeutic cancer vaccine development. PMID:25037736

  15. Phase I Three-Dimensional Conformal Radiation Dose Escalation Study in Newly Diagnosed Glioblastoma: Radiation Therapy Oncology Group Trial 98-03

    SciTech Connect

    Tsien, Christina Moughan, Jennifer; Michalski, Jeff M.; Gilbert, Mark R.; Purdy, James; Simpson, Joseph; Kresel, John J.; Curran, Walter J.; Diaz, Aidnag; Mehta, Minesh P.

    2009-03-01

    Purpose: To evaluate in a Phase I trial the feasibility and toxicity of dose-escalated three-dimensional conformal radiotherapy (3D-CRT) concurrent with chemotherapy in patients with primary supratentorial glioblastoma (GBM). Methods and Materials: A total of 209 patients were enrolled. All received 46 Gy in 2-Gy fractions to the first planning target volume (PTV{sub 1}), defined as the gross tumor volume (GTV) plus 1.8 cm. A subsequent boost was given to PTV{sub 2}, defined as GTV plus 0.3 cm. Patients were stratified into two groups (Group 1: PTV{sub 2} <75 cm{sup 3}; Group 2: PTV{sub 2} {>=}75 cm{sup 3}). Four RT dose levels were evaluated: 66, 72, 78, and 84 Gy. Carmustine 80 mg/m{sup 2} was given during RT, then every 8 weeks for 6 cycles. Pretreatment characteristics were well balanced. Results: Acute and late Grade 3/4 RT-related toxicities were no more frequent at higher RT dose or with larger tumors. There were no dose-limiting toxicities (acute Grade {>=}3 irreversible central nervous system toxicities) observed on any dose level in either group. On the basis of the absence of dose-limiting toxicities, dose was escalated to 84 Gy in both groups. Late RT necrosis was noted at 66 Gy (1 patient), 72 Gy (2 patients), 78 Gy (2 patients), and 84 Gy (3 patients) in Group 1. In Group 2, late RT necrosis was noted at 78 Gy (1 patient) and 84 Gy (2 patients). Median time to RT necrosis was 8.8 months (range, 5.1-12.5 months). Median survival in Group 1 was 11.6-19.3 months. Median survival in Group 2 was 8.2-13.9 months. Conclusions: Our study shows the feasibility of delivering higher than standard (60 Gy) RT dose with concurrent chemotherapy for primary GBM, with an acceptable risk of late central nervous system toxicity.

  16. A Dosimetric Comparison between Conventional Fractionated and Hypofractionated Image-guided Radiation Therapies for Localized Prostate Cancer

    PubMed Central

    Li, Ming; Li, Gao-Feng; Hou, Xiu-Yu; Gao, Hong; Xu, Yong-Gang; Zhao, Ting

    2016-01-01

    Background: Image-guided radiation therapy (IGRT) is the preferred method for curative treatment of localized prostate cancer, which could improve disease outcome and reduce normal tissue toxicity reaction. IGRT using cone-beam computed tomography (CBCT) in combination with volumetric-modulated arc therapy (VMAT) potentially allows smaller treatment margins and dose escalation to the prostate. The aim of this study was to compare the difference of dosimetric diffusion in conventional IGRT using 7-field, step-and-shoot intensity-modulated radiation therapy (IMRT) and hypofractionated IGRT using VMAT for patients with localized prostate cancer. Methods: We studied 24 patients who received 78 Gy in 39 daily fractions or 70 Gy in 28 daily fractions to their prostate with/without the seminal vesicles using IMRT (n = 12) or VMAT (n = 12) for prostate cancer between November 2013 and October 2015. Image guidance was performed using kilovoltage CBCT scans equipped on the linear accelerator. Offline planning was performed using the daily treatment images registered with simulation computed tomography (CT) images. A total of 212 IMRT plans in conventional cohort and 292 VMAT plans in hypofractionated cohort were enrolled in the study. Dose distributions were recalculated on CBCT images registered with the planning CT scanner. Results: Compared with 7-field, step-and-shoot IMRT, VMAT plans resulted in improved planning target volume (PTV) D95% (7663.17 ± 69.57 cGy vs. 7789.17 ± 131.76 cGy, P < 0.001). VMAT reduced the rectal D25 (P < 0.001), D35 (P < 0.001), and D50 (P < 0.001), bladder V50 (P < 0.001), D25 (P = 0.002), D35 (P = 0.028), and D50 (P = 0.029). However, VMAT did not statistically significantly reduce the rectal V50, compared with 7-field, step-and-shoot IMRT (25.02 ± 5.54% vs. 27.43 ± 8.79%, P = 0.087). Conclusions: To deliver the hypofractionated radiotherapy in prostate cancer, VMAT significantly increased PTV D95% dose and decreased the dose of radiation

  17. 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

  18. A study to investigate dose escalation of doxorubicin in ABVD chemotherapy for Hodgkin lymphoma incorporating biomarkers of response and toxicity

    PubMed Central

    Gibb, A; Greystoke, A; Ranson, M; Linton, K; Neeson, S; Hampson, G; Illidge, T; Smith, E; Dive, C; Pettitt, A; Lister, A; Johnson, P; Radford, J

    2013-01-01

    Background: Myelotoxicity during initial cycles of chemotherapy for Hodgkin lymphoma is associated with better outcome, supporting the concept of individualised dosing based on pharmacodynamic end points to optimise results. This study was performed to identify the maximum tolerated dose (MTD) of doxorubicin within cycles 1–3 ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). Circulating biomarkers of response (nucleosomal DNA, nDNA) and epithelial toxicity (Cytokeratin 18, CK18) were also measured. Methods: Dose escalation of doxorubicin in cycles 1–3 ABVD supported by pegfilgrastim was performed on a six-patient cohort basis (35, 45 and 55 mg m–2) with doxorubicin reduced to 25 mg m–2 or omitted in cycles 4–6 to maintain cumulative exposure of 103–130% standard ABVD. BVD was given at standard doses throughout. Six additional subjects were recruited at the MTD. Results: Twenty-four subjects were recruited. Dose-limiting toxicities (DLTs) of grade 3 neuropathy, pneumonitis, palmar-plantar erythema and neutropenic infection were observed at 55 mg m–2, so 45 mg m–2 was declared the MTD. In patients who subsequently experienced DLT at any time, large increases in CK18 were seen on day 3 of cycle 1 ABVD. Conclusion: Escalated ABVD incorporating doxorubicin at 45 mg m–2 in cycles 1–3 can be delivered safely with pegfilgrastim support. Circulating cell death biomarkers may assist in the development of future individualised dosing strategies. PMID:24136151

  19. The Missing Pieces in Reporting of Randomized Controlled Trials of External Beam Radiation Therapy Dose Escalation for Prostate Cancer.

    PubMed

    Zaorsky, Nicholas G; Egleston, Brian L; Horwitz, Eric M; Dicker, Adam P; Nguyen, Paul L; Showalter, Timothy N; Den, Robert B

    2016-08-01

    Randomized controlled trials (RCTs) are the most rigorous way of determining whether a cause-effect relation exists between treatment and outcome and for assessing the cost-effectiveness of a treatment. For many patients, cancer is a chronic illness; RCTs evaluating treatments for indolent cancers must evolve to facilitate medical decision-making, as "concrete" patient outcomes (eg, survival) will likely be excellent independent of the intervention, and detecting a difference between trial arms may be impossible. In this commentary, we articulate 9 recommendations that we hope future clinical trialists and funding agencies (including those under the National Cancer Institute) will take into consideration when planning RCTs to help guide subsequent interpretation of results and clinical decision making, based on RCTs of external beam radiation therapy dose escalation for the most common indolent cancer in men, that is, prostate cancer. We recommend routinely reporting: (1) race; (2) medical comorbidities; (3) psychiatric comorbidities; (4) insurance status; (5) education; (6) marital status; (7) income; (8) sexual orientation; and (9) facility-related characteristics (eg, number of centers involved, type of facilities, yearly hospital volumes). We discuss how these factors independently affect patient outcomes and toxicities; future clinicians and governing organizations should consider this information to plan RCTs accordingly (to maximize patient accrual and total n), select appropriate endpoints (eg, toxicity, quality of life, sexual function), actively monitor RCTs, and report results so as to identify the optimal treatment among subpopulations. PMID:27322694

  20. Phase I Dose-Escalation Study of Docetaxel, Cisplatin, and 5-Fluorouracil Combination Chemotherapy in Patients With Advanced Esophageal Carcinoma

    PubMed Central

    Satomura, Hitoshi; Nakajima, Masanobu; Sasaki, Kinro; Yamaguchi, Satoru; Domeki, Yasushi; Takahashi, Masakazu; Muroi, Hiroto; Kubo, Tsukasa; Kikuchi, Maiko; Otomo, Haruka; Ihara, Keisuke; Kato, Hiroyuki

    2015-01-01

    A dose-escalation study of docetaxel (DOC), cisplatin (CDDP), and 5-fluorouracil (5-FU; DCF combination regimen) was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD) and dose-limiting toxicities (DLT) in advanced esophageal carcinoma. Eighteen patients with esophageal carcinoma were enrolled and received DCF combination therapy at different dose levels. DLTs included febrile neutropenia and oral mucositis. DLT occurred in 2 out of 6 patients at level 2 and 3. The study proceeded to level 4, according to the protocol. The level 4 dose was defined as the MTD and the level 3 dose was defined as the RD. The RD for DCF combination chemotherapy for advanced esophageal carcinoma in the present study was 70 mg/m2 DOC plus 70 mg/m2 CDDP on day 1 plus 700 mg/m2 5-FU on days 1–5 at 4-week intervals. This regimen was tolerable and highly active. A phase II study has been started. PMID:26414837

  1. A phase I dose-escalation study of a biosimilar trastuzumab in Chinese metastasis breast cancer patients.

    PubMed

    Zhou, Xinna; Yu, Jing; Wang, Wenmiao; Song, Guohong; Wang, Xiaoli; Ren, Jun; Di, Lijun; Wang, Xinghe

    2015-01-01

    Trastuzumab has been widely used among the breast cancer patients with human epidermal growth factor receptor 2 (HER2) overexpression. The genetically engineered trastuzumab traded as Cipterbin® was developed in China since 2003. We have disclosed the phase I clinical trial data of safety, pharmacokinetic profile (PK) in patients with metastasis breast cancer. Subjects identified as HER2 strong positive received single intravenously doses of 100, 250 or 500 mg Cipterbin® in dose-escalation manner. The safety evaluations were recorded and plasma concentration profiles for the drug were analyzed. 27 Chinese metastatic breast cancer patients were enrolled in this study. Patients in each group of different dosage were well-tolerated. The most frequently drug-related adverse events were fever (59.3 %), transaminase increased (22.2 %), chills (18.5 %) and arrhythmia (18.5 %). Only one patient with severe adverse event was observed in 250 mg group revealing brachycardia. PK profile analysis showed that sera steady concentration could be reached in dose-proportional manner, except volume of distribution (Vd) and clearance (CL), which reached peak values at 250 mg administration cohort. This genetically engineered HER2-target antibody had demonstrated the accepted safety with well-tolerated. PMID:26702392

  2. Acute Toxicity in High-Risk Prostate Cancer Patients Treated With Androgen Suppression and Hypofractionated Intensity-Modulated Radiotherapy

    SciTech Connect

    Pervez, Nadeem; Small, Cormac; MacKenzie, Marc; Yee, Don; Parliament, Matthew; Ghosh, Sunita; Mihai, Alina; Amanie, John; Murtha, Albert; Field, Colin; Murray, David; Fallone, Gino; Pearcey, Robert

    2010-01-15

    Purpose: To report acute toxicity resulting from radiotherapy (RT) dose escalation and hypofractionation using intensity-modulated RT (IMRT) treatment combined with androgen suppression in high-risk prostate cancer patients. Methods and Materials: Sixty patients with a histological diagnosis of high-risk prostatic adenocarcinoma (having either a clinical Stage of >=T3a or an initial prostate-specific antigen [PSA] level of >=20 ng/ml or a Gleason score of 8 to 10 or a combination of a PSA concentration of >15 ng/ml and a Gleason score of 7) were enrolled. RT prescription was 68 Gy in 25 fractions (2.72 Gy/fraction) over 5 weeks to the prostate and proximal seminal vesicles. The pelvic lymph nodes and distal seminal vesicles concurrently received 45 Gy in 25 fractions. The patients were treated with helical TomoTherapy-based IMRT and underwent daily megavoltage CT image-guided verification prior to each treatment. Acute toxicity scores were recorded weekly during RT and at 3 months post-RT, using Radiation Therapy Oncology Group acute toxicity scales. Results: All patients completed RT and follow up for 3 months. The maximum acute toxicity scores were as follows: 21 (35%) patients had Grade 2 gastrointestinal (GI) toxicity; 4 (6.67%) patients had Grade 3 genitourinary (GU) toxicity; and 30 (33.33%) patients had Grade 2 GU toxicity. These toxicity scores were reduced after RT; there were only 8 (13.6%) patients with Grade 1 GI toxicity, 11 (18.97%) with Grade 1 GU toxicity, and 5 (8.62%) with Grade 2 GU toxicity at 3 months follow up. Only the V60 to the rectum correlated with the GI toxicity. Conclusion: Dose escalation using a hypofractionated schedule to the prostate with concurrent pelvic lymph node RT and long-term androgen suppression therapy is well tolerated acutely. Longer follow up for outcome and late toxicity is required.

  3. Whole Brain Irradiation With Hippocampal Sparing and Dose Escalation on Multiple Brain Metastases: A Planning Study on Treatment Concepts

    SciTech Connect

    Prokic, Vesna; Wiedenmann, Nicole; Fels, Franziska; Schmucker, Marianne; Nieder, Carsten; Grosu, Anca-Ligia

    2013-01-01

    Purpose: To develop a new treatment planning strategy in patients with multiple brain metastases. The goal was to perform whole brain irradiation (WBI) with hippocampal sparing and dose escalation on multiple brain metastases. Two treatment concepts were investigated: simultaneously integrated boost (SIB) and WBI followed by stereotactic fractionated radiation therapy sequential concept (SC). Methods and Materials: Treatment plans for both concepts were calculated for 10 patients with 2-8 brain metastases using volumetric modulated arc therapy. In the SIB concept, the prescribed dose was 30 Gy in 12 fractions to the whole brain and 51 Gy in 12 fractions to individual brain metastases. In the SC concept, the prescription was 30 Gy in 12 fractions to the whole brain followed by 18 Gy in 2 fractions to brain metastases. All plans were optimized for dose coverage of whole brain and lesions, simultaneously minimizing dose to the hippocampus. The treatment plans were evaluated on target coverage, homogeneity, and minimal dose to the hippocampus and organs at risk. Results: The SIB concept enabled more successful sparing of the hippocampus; the mean dose to the hippocampus was 7.55 {+-} 0.62 Gy and 6.29 {+-} 0.62 Gy, respectively, when 5-mm and 10-mm avoidance regions around the hippocampus were used, normalized to 2-Gy fractions. In the SC concept, the mean dose to hippocampus was 9.8 {+-} 1.75 Gy. The mean dose to the whole brain (excluding metastases) was 33.2 {+-} 0.7 Gy and 32.7 {+-} 0.96 Gy, respectively, in the SIB concept, for 5-mm and 10-mm hippocampus avoidance regions, and 37.23 {+-} 1.42 Gy in SC. Conclusions: Both concepts, SIB and SC, were able to achieve adequate whole brain coverage and radiosurgery-equivalent dose distributions to individual brain metastases. The SIB technique achieved better sparing of the hippocampus, especially when a10-mm hippocampal avoidance region was used.

  4. Sex Differences in Dose Escalation and Overdose Death during Chronic Opioid Therapy: A Population-Based Cohort Study

    PubMed Central

    Kaplovitch, Eric; Gomes, Tara; Camacho, Ximena; Dhalla, Irfan A.; Mamdani, Muhammad M.; Juurlink, David N.

    2015-01-01

    Background The use of opioids for noncancer pain is widespread, and more than 16,000 die of opioid-related causes in the United States annually. The patients at greatest risk of death are those receiving high doses of opioids. Whether sex influences the risk of dose escalation or opioid-related mortality is unknown. Methods and Findings We conducted a cohort study using healthcare records of 32,499 individuals aged 15 to 64 who commenced chronic opioid therapy for noncancer pain between April 1, 1997 and December 31, 2010 in Ontario, Canada. Patients were followed from their first opioid prescription until discontinuation of therapy, death from any cause or the end of the study period. Among patients receiving chronic opioid therapy, 589 (1.8%) escalated to high dose therapy and n = 59 (0.2%) died of opioid-related causes while on treatment. After multivariable adjustment, men were more likely than women to escalate to high-dose opioid therapy (adjusted hazard ratio 1.44; 95% confidence interval 1.21 to 1.70) and twice as likely to die of opioid-related causes (adjusted hazard ratio 2.04; 95% confidence interval 1.18 to 3.53). These associations were maintained in a secondary analysis of 285,520 individuals receiving any opioid regardless of the duration of therapy. Conclusions Men are at higher risk than women for escalation to high-dose opioid therapy and death from opioid-related causes. Both outcomes were more common than anticipated. PMID:26291716

  5. Phase I dose-escalation and pharmacokinetic study of oral gefitinib and irinotecan in children with refractory solid tumors

    PubMed Central

    Brennan, R. C.; Furman, W.; Mao, S.; Wu, J.; Turner, D. C.; Stewart, C. F.; Santana, V.; McGregor, L. M.

    2015-01-01

    Purpose This phase I study endeavored to estimate the maximum tolerated dose (MTD) and describe the dose-limiting toxicities (DLTs) of oral irinotecan with gefitinib in children with refractory solid tumors. Methods Oral irinotecan was administered on days 1-5 and 8-12 with oral gefitinib (fixed dose, 150mg/m2/day) on days 1-12 of a 21-day course. The Escalation with Overdose Control (EWOC) method guided irinotecan dose escalation (7 dose levels, range 5mg/m2/day to 40mg/m2/day). Results Sixteen of 19 patients were evaluable, with serial pharmacokinetic studies in 10 patients. Diagnoses included osteosarcoma (N=5), neuroblastoma (N=3), sarcoma (N=3), and others (N=5). Patients received a median of two courses (range 1-20), with at least two patients treated on dose levels 2-7. Three patients had five DLTs; the most common being metabolic (hypokalemia, N=2 and hypophosphatemia, N=1) at dose levels two (10mg/m2) and four (20mg/m2). One patient experienced grade 3 diarrhea (40mg/m2). Irinotecan bioavailability was 2.5-fold higher when co-administered with gefitinib while the conversion rate of irinotecan to SN-38 lactone was unaffected. The study closed due to poor accrual before evaluation of the next recommended irinotecan dose level (35mg/m2). Of eleven patients receiving at least two courses of therapy, three had stable disease (SD) lasting two to four courses and one patient maintained a complete response through 18 courses. Conclusions The combination of oral gefitinib and irinotecan has acceptable toxicity and anti-tumor activity in pediatric patients with refractory solid tumors. Pharmacokinetic analysis confirms that co-administration of gefitinib increases irinotecan bioavailability leading to an increased SN-38 lactone systemic exposure. PMID:25257509

  6. Activity of the MEK Inhibitor Trametinib (GSK1120212) in Advanced Melanoma in a Phase I, Dose-escalation Trial

    PubMed Central

    Falchook, Gerald S; Lewis, Karl D; Infante, Jeffrey R; Gordon, Michael S; Vogelzang, Nicholas J; DeMarini, Douglas J; Sun, Peng; Moy, Christopher; Szabo, Stephen A.; Roadcap, Lori T; Peddareddigari, Vijay G R; Lebowitz, Peter F; Le, Ngocdiep T; Burris, Howard A; Messersmith, Wells A; O'Dwyer, Peter J; Kim, Kevin B.; Flaherty, Keith; Bendell, Johanna C.; Gonzalez, Rene; Kurzrock, Razelle; Fecher, Leslie A

    2014-01-01

    Summary Purpose The mitogen-activated extracellular signal-related kinase kinase (MEK) is a member of the RAS/RAF/MEK/ERK signalling cascade, which is commonly activated in melanoma. Direct inhibition of MEK inhibits ERK signalling. Methods We conducted a multicentre, first-in-human, three-part study (dose escalation, cohort expansion, and pharmacodynamic evaluation) to evaluate the oral small-molecule MEK inhibitor trametininb (GSK1120212) in advanced cancer. Intermittent and continuous dosing regimens were evaluated. Safety and efficacy data in patients with melanoma are presented here, with exploratory analyses of available tumour tissues performed on an Illumina genotyping platform. This completed study is registered with ClinicalTrials.gov, number NCT00687622. Findings Ninety-seven melanoma patients, including 81 with cutaneous or unknown primary melanoma (36 BRAF-mutant, 39 BRAF wild-type, six BRAF status unknown) and 16 uveal melanoma patients were enrolled. The most common treatment-related adverse events were rash/dermatitis acneiform (80 out of 97; 82%) and diarrhoea (n=44; 45%), most of which were grade 2 or lower. No cutaneous squamous cell carcinomas were observed. Among the 36 BRAF-mutant patients, 30 were BRAF-inhibitor naïve. Among these 30 patients, 2 complete responses (CRs) and 10 partial responses (PRs) were observed (unconfirmed response rate=40%) including 2 confirmed CRs and 8 confirmed PRs (confirmed response rate=33%); the median progression-free survival was 5·7 months (95% CI, 4·0–7·4). Among the 6 BRAF-mutant patients who received prior BRAF inhibitor therapy, 1 unconfirmed PR was observed. Among 39 patients with BRAF wild-type melanoma, 4 PRs (all confirmed) were observed (confirmed response rate=10%). Conclusions To our knowledge, this is the first demonstration of substantial clinical activity by a MEK inhibitor in melanoma. These data suggest that MEK is a valid therapeutic target. PMID:22805292

  7. Incorporating breath holding and image guidance in the adjuvant gastric cancer radiotherapy: a dosimetric study

    PubMed Central

    2012-01-01

    Background The respiratory related target motion and setup error will lead to a large margin in the gastric radiotherapy. The purpose of this study is to investigate the dosimetric benefit and the possibility of incorporating the breath-hold (BH) technique with online image-guided radiotherapy in the adjuvant gastric cancer radiotherapy. Methods Setup errors and target motions of 22 post-operative gastric cancer patients with surgical clips were analyzed. Clips movement was recorded using the digital fluoroscopics and the probability distribution functions (pdf) of the target motions were created for both the free breathing (FB) and BH treatment. For dosimetric comparisons, two intensity-modulated radiotherapy (IMRT) treatment plans, i.e. the free breathing treatment plan (IMRTFB) and the image-guided BH treatment plan (IMRTIGBH) using the same beam parameters were performed among 6 randomly selected patients. Different margins for FB and BH plans were derived. The plan dose map was convoluted with various pdfs of the setup errors and the target motions. Target coverage and dose to organs at risk were compared and the dose-escalation probability was assessed. Results The mean setup errors were 1.2 mm in the superior-inferior (SI), 0.0 mm in the left-right (LR), and 1.4 mm in the anterior-posterior (AP) directions. The mean target motion for the free breathing (vs. BH) was 11.1 mm (vs. 2.2 mm), 1.9 mm (vs. 1.1 mm), and 5.5 mm (vs. 1.7 mm) in the SI, LR, and AP direction, respectively. The target coverage was comparable for all the original plans. IMRTIGBH showed lower dose to the liver compared with IMRTFB (p = 0.01) but no significant difference in the kidneys. Convolved IMRTIGBH showed better sparing in kidneys (p < 0.01) and similar in liver (p = 0.08). Conclusions Combining BH technique with online image guided IMRT can minimize the organ motion and improve the setup accuracy. The dosimetric comparison showed the dose could be

  8. Preclinical pharmacokinetic evaluation of resveratrol trimethyl ether in sprague-dawley rats: the impacts of aqueous solubility, dose escalation, food and repeated dosing on oral bioavailability.

    PubMed

    Lin, Hai-Shu; Ho, Paul C

    2011-10-01

    Resveratrol trimethyl ether (trans-3,5,4'-trimethoxystilbene, RTE) is a naturally occurring and pharmacologically active resveratrol derivative. To evaluate its suitability as a drug candidate, a pharmacokinetic study was carried out in Sprague-Dawley rats with the emphasis to identify the impact of aqueous solubility, dose escalation, food, and repeated dosing on its oral bioavailability. Upon single intravenous administration (5 mg/kg), RTE displayed moderate clearance (35.5 ± 5.3 mL/min/kg) and a fairly long terminal elimination half-life (511 ± 136 min); dose escalation (5-20 mg/kg) did not cause nonlinear pharmacokinetics. When given orally in suspension (60 mg/kg), RTE was poorly absorbed with negligible bioavailability (< 1.5%), fasting further decreased its bioavailability (<1%). However, when administered in a solution formulated with randomly methylated-β-cyclodextrin (15 mg/kg), RTE was rapidly absorbed with good bioavailability (46.5 ± 4.8%). Dose escalation resulted in increased bioavailability (64.6 ± 8.0%) at the dose of 60 mg/kg. Repeated RTE dosing (7 daily oral doses) did not alter the clearance, terminal elimination half-life and bioavailability. In summary, the aqueous solubility of RTE was a barrier to oral absorption; repeated RTE administrations did not alter its pharmacokinetic profiles; as RTE possessed appropriate pharmacokinetic profiles, further investigation on RTE as a drug candidate is warranted. PMID:21520090

  9. Overview of image-guided radiation therapy

    SciTech Connect

    Xing Lei . E-mail: lei@reyes.stanford.edu; Thorndyke, Brian; Schreibmann, Eduard; Yang Yong; Li, T.-F.; Kim, Gwe-Ya; Luxton, Gary; Koong, Albert

    2006-07-01

    Radiation therapy has gone through a series of revolutions in the last few decades and it is now possible to produce highly conformal radiation dose distribution by using techniques such as intensity-modulated radiation therapy (IMRT). The improved dose conformity and steep dose gradients have necessitated enhanced patient localization and beam targeting techniques for radiotherapy treatments. Components affecting the reproducibility of target position during and between subsequent fractions of radiation therapy include the displacement of internal organs between fractions and internal organ motion within a fraction. Image-guided radiation therapy (IGRT) uses advanced imaging technology to better define the tumor target and is the key to reducing and ultimately eliminating the uncertainties. The purpose of this article is to summarize recent advancements in IGRT and discussed various practical issues related to the implementation of the new imaging techniques available to radiation oncology community. We introduce various new IGRT concepts and approaches, and hope to provide the reader with a comprehensive understanding of the emerging clinical IGRT technologies. Some important research topics will also be addressed.

  10. Intensity Modulated Radiation Therapy for Retroperitoneal Sarcoma: A Case for Dose Escalation and Organ at Risk Toxicity Reduction

    PubMed Central

    Koshy, Mary; Lawson, Joshua D.; Staley, Charles A.; Esiashvili, Natia; Howell, Rebecca; Ghavidel, Shahram; Davis, Lawrence W.

    2003-01-01

    of dose to critical normal structures such as small bowel, liver, and kidney. Escalation of dose has a positive impact on local control for retroperitoneal sarcoma; IMRT may be an effective method to achieve this goal. We are evaluating preoperative dose escalation to 59.4 Gy. PMID:18521378

  11. Image-guided tissue engineering

    PubMed Central

    Ballyns, Jeffrey J; Bonassar, Lawrence J

    2009-01-01

    Replication of anatomic shape is a significant challenge in developing implants for regenerative medicine. This has lead to significant interest in using medical imaging techniques such as magnetic resonance imaging and computed tomography to design tissue engineered constructs. Implementation of medical imaging and computer aided design in combination with technologies for rapid prototyping of living implants enables the generation of highly reproducible constructs with spatial resolution up to 25 μm. In this paper, we review the medical imaging modalities available and a paradigm for choosing a particular imaging technique. We also present fabrication techniques and methodologies for producing cellular engineered constructs. Finally, we comment on future challenges involved with image guided tissue engineering and efforts to generate engineered constructs ready for implantation. PMID:19583811

  12. Intensity modulated radiation therapy with simultaneous integrated boost based dose escalation on neoadjuvant chemoradiation therapy for locally advanced distal esophageal adenocarcinoma

    PubMed Central

    Zeng, Ming; Aguila, Fernando N; Patel, Taral; Knapp, Mark; Zhu, Xue-Qiang; Chen, Xi-Lin; Price, Phillip D

    2016-01-01

    AIM: To evaluate impact of radiation therapy dose escalation through intensity modulated radiation therapy with simultaneous integrated boost (IMRT-SIB). METHODS: We retrospectively reviewed the patients who underwent four-dimensional-based IMRT-SIB-based neoadjuvant chemoradiation protocol. During the concurrent chemoradiation therapy, radiation therapy was through IMRT-SIB delivered in 28 consecutive daily fractions with total radiation doses of 56 Gy to tumor and 5040 Gy dose-painted to clinical tumor volume, with a regimen at the discretion of the treating medical oncologist. This was followed by surgical tumor resection. We analyzed pathological completion response (pCR) rates its relationship with overall survival and event-free survival. RESULTS: Seventeen patients underwent dose escalation with the IMRT-SIB protocol between 2007 and 2014 and their records were available for analysis. Among the IMRT-SIB-treated patients, the toxicity appeared mild, the most common side effects were grade 1-3 esophagitis (46%) and pneumonitis (11.7%). There were no cardiac events. The Ro resection rate was 94% (n = 16), the pCR rate was 47% (n = 8), and the postoperative morbidity was zero. There was one mediastinal failure found, one patient had local failure at the anastomosis site, and the majority of failures were distant in the lung or bone. The 3-year disease-free survival and overall survival rates were 41% (n = 7) and 53% (n = 9), respectively. CONCLUSION: The dose escalation through IMRT-SIB in the chemoradiation regimen seems responsible for down-staging the distal esophageal with well-tolerated complications. PMID:27190587

  13. Modelling PK/QT relationships from Phase I dose-escalation trials for drug combinations and developing quantitative risk assessments of clinically relevant QT prolongations.

    PubMed

    Sinclair, Karen; Kinable, Els; Grosch, Kai; Wang, Jixian

    2016-05-01

    In current industry practice, it is difficult to assess QT effects at potential therapeutic doses based on Phase I dose-escalation trials in oncology due to data scarcity, particularly in combinations trials. In this paper, we propose to use dose-concentration and concentration-QT models jointly to model the exposures and effects of multiple drugs in combination. The fitted models then can be used to make early predictions for QT prolongation to aid choosing recommended dose combinations for further investigation. The models consider potential correlation between concentrations of test drugs and potential drug-drug interactions at PK and QT levels. In addition, this approach allows for the assessment of the probability of QT prolongation exceeding given thresholds of clinical significance. The performance of this approach was examined via simulation under practical scenarios for dose-escalation trials for a combination of two drugs. The simulation results show that invaluable information of QT effects at therapeutic dose combinations can be gained by the proposed approaches. Early detection of dose combinations with substantial QT prolongation is evaluated effectively through the CIs of the predicted peak QT prolongation at each dose combination. Furthermore, the probability of QT prolongation exceeding a certain threshold is also computed to support early detection of safety signals while accounting for uncertainty associated with data from Phase I studies. While the prediction of QT effects is sensitive to the dose escalation process, the sensitivity and limited sample size should be considered when providing support to the decision-making process for further developing certain dose combinations. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26991506

  14. PSA Response to Neoadjuvant Androgen Deprivation Therapy Is a Strong Independent Predictor of Survival in High-Risk Prostate Cancer in the Dose-Escalated Radiation Therapy Era

    SciTech Connect

    McGuire, Sean E.; Lee, Andrew K.; Cerne, Jasmina Z.; Munsell, Mark F.; Levy, Lawrence B.; Kudchadker, Rajat J.; Choi, Seungtaek L.; Nguyen, Quynh N.; Hoffman, Karen E.; Pugh, Thomas J.; Frank, Steven J.; Corn, Paul G.; Logothetis, Christopher J.; Kuban, Deborah A.

    2013-01-01

    Purpose: The aim of the study was to evaluate the prognostic value of prostate-specific antigen (PSA) response to neoadjuvant androgen deprivation therapy (ADT) prior to dose-escalated radiation therapy (RT) and long-term ADT in high-risk prostate cancer. Methods and Materials: We reviewed the charts of all patients diagnosed with high-risk prostate cancer and treated with a combination of long-term ADT (median, 24 months) and dose-escalated (median, 75.6 Gy) RT between 1990 and 2007. The associations among patient, tumor, and treatment characteristics with biochemical response to neoadjuvant ADT and their effects on failure-free survival (FFS), time to distant metastasis (TDM), prostate cancer-specific mortality (PCSM) and overall survival (OS) were examined. Results: A total of 196 patients met criteria for inclusion. Median follow-up time for patients alive at last contact was 7.0 years (range, 0.5-18.1 years). Multivariate analysis identified the pre-RT PSA concentration (<0.5 vs {>=}0.5 ng/mL) as a significant independent predictor of FFS (P=.021), TDM (P=.009), PCSM (P=.039), and OS (P=.037). On multivariate analysis, pretreatment PSA (iPSA) and African-American race were significantly associated with failure to achieve a pre-RT PSA of <0.5 ng/mL. Conclusions: For high-risk prostate cancer patients treated with long-term ADT and dose-escalated RT, a pre-RT PSA level {>=}0.5 ng/mL after neoadjuvant ADT predicts for worse survival measures. Both elevated iPSA and African-American race are associated with increased risk of having a pre-RT PSA level {>=}0.5 ng/mL. These patients should be considered for clinical trials that test newer, more potent androgen-depleting therapies such as abiraterone and MDV3100 in combination with radiation.

  15. Personalized estimation of dose to red bone marrow and the associated leukaemia risk attributable to pelvic kilo-voltage cone beam computed tomography scans in image-guided radiotherapy

    NASA Astrophysics Data System (ADS)

    Zhang, Yibao; Yan, Yulong; Nath, Ravinder; Bao, Shanglian; Deng, Jun

    2012-07-01

    The aim of this study is to investigate the imaging dose to red bone marrow (RBM) and the associated leukaemia risks attributable to pelvic kilo-voltage cone beam computed tomography (kVCBCT) scans in image-guided radiation therapy (IGRT). The RBM doses of 42 patients (age 2.7-86.4 years) were calculated using Monte Carlo simulations. The trabecular spongiosa was segmented to substitute RBM rather than the whole bone. Quantitative correlations between anthropometric variables such as age, physical bone density (PBD) and RBM dose were established. Personalized leukaemia risk was evaluated using an improved Boice model which included the age-associated RBM involvement. An incremental leukaemia risk of 29%-82% (mean = 45%) was found to be associated with 40 pelvic kVCBCT scans in the subject group used in a typical external beam radiation therapy course. Higher risks were observed in children. Due to the enhanced photoelectric effect in high atomic number materials, PBD was observed to strongly affect the RBM dose. Considerable overestimations (9%-42%, mean = 28%) were observed if the whole bone doses were used as surrogates of RBM doses. The personalized estimation of RBM dose and associated leukaemia risk caused by pelvic kVCBCT scans is clinically feasible with the proposed empirical models. Higher radiogenic cancer risks are associated with repeated kVCBCT scans in IGRT of cancer patients, especially children.

  16. Image-guided endobronchial ultrasound

    NASA Astrophysics Data System (ADS)

    Higgins, William E.; Zang, Xiaonan; Cheirsilp, Ronnarit; Byrnes, Patrick; Kuhlengel, Trevor; Bascom, Rebecca; Toth, Jennifer

    2016-03-01

    Endobronchial ultrasound (EBUS) is now recommended as a standard procedure for in vivo verification of extraluminal diagnostic sites during cancer-staging bronchoscopy. Yet, physicians vary considerably in their skills at using EBUS effectively. Regarding existing bronchoscopy guidance systems, studies have shown their effectiveness in the lung-cancer management process. With such a system, a patient's X-ray computed tomography (CT) scan is used to plan a procedure to regions of interest (ROIs). This plan is then used during follow-on guided bronchoscopy. Recent clinical guidelines for lung cancer, however, also dictate using positron emission tomography (PET) imaging for identifying suspicious ROIs and aiding in the cancer-staging process. While researchers have attempted to use guided bronchoscopy systems in tandem with PET imaging and EBUS, no true EBUS-centric guidance system exists. We now propose a full multimodal image-based methodology for guiding EBUS. The complete methodology involves two components: 1) a procedure planning protocol that gives bronchoscope movements appropriate for live EBUS positioning; and 2) a guidance strategy and associated system graphical user interface (GUI) designed for image-guided EBUS. We present results demonstrating the operation of the system.

  17. FOLFIRI and regorafenib combination therapy with dose escalation of irinotecan as fourth-line treatment for patients with metastatic colon cancer according to UGT1A1 genotyping.

    PubMed

    Lu, Chien-Yu; Yeh, Yung-Sung; Huang, Ching-Wen; Ma, Cheng-Jen; Yu, Fang-Jung; Wang, Jaw-Yuan

    2014-01-01

    Here we report a case of metastatic colon cancer treated with 5-fluorouracil, leucovorin, and escalated doses of irinotecan (FOLFIRI) combined with regorafenib in the fourth-line setting after uridine diphosphate glucuronosyltransferase (UGT)1A1 genotyping analysis. A 66-year-old male was initially diagnosed with Union Internationale Contre le Cancer stage III descending colon cancer and underwent curative surgery. He received postoperative adjuvant chemotherapy; however, liver metastasis developed and a partial hepatectomy was performed thereafter. Unfortunately, pulmonary metastases and recurrent liver tumors were found despite a series of systemic treatments with multiple combinations of cytotoxic and biologic agents. Recently, a novel multikinase inhibitor, regorafenib, was approved for the treatment of metastatic colorectal cancer refractory to other therapeutic modalities. As further treatment, we combined regorafenib with FOLFIRI, which included dose escalations of irinotecan, after UGT1A1 genotyping analysis. The therapeutic results were promising, with the improvement in liver and pulmonary metastases being classified as stable disease and partial response, respectively. Moreover, the progression-free survival was over 6 months. FOLFIRI, with dose escalation of irinotecan according to UGT1A1 genotyping plus regorafenib appears to be a promising salvage therapy for patients with refractory metastatic colorectal cancer. PMID:25473295

  18. [Current situation and future prospects of radiotherapy for malignant gliomas].

    PubMed

    Terahara, Atsuro

    2013-10-01

    Prognosis of malignant gliomas remains poor, although adjuvant radiotherapy increases survival time. To improve treatment outcomes, high-precision radiotherapy techniques such as three-dimensional conformal radiotherapy, stereotactic irradiation, intensity modulated radiotherapy, and charged particle radiotherapy have been developed for dose distribution optimization and dose escalation. Improvements in clinical outcomes with these new treatment strategies have been reported; however, the efficacy of these treatment strategies has not yet been verified in randomized trials. Further development of radiation delivery techniques, including boron neutron capture therapy, and ways of achieving more adequate target volume delineation using modern multimodality imaging technology are currently being intensively investigated to further improve patient outcomes. PMID:24105051

  19. From clinical imaging and computational models to personalised medicine and image guided interventions.

    PubMed

    Hawkes, David J

    2016-10-01

    This short paper describes the development of the UCL Centre for Medical Image Computing (CMIC) from 2006 to 2016, together with reference to historical developments of the Computational Imaging sciences Group (CISG) at Guy's Hospital. Key early work in automated image registration led to developments in image guided surgery and improved cancer diagnosis and therapy. The work is illustrated with examples from neurosurgery, laparoscopic liver and gastric surgery, diagnosis and treatment of prostate cancer and breast cancer, and image guided radiotherapy for lung cancer. PMID:27407003

  20. Computational challenges for image-guided radiation therapy: framework and current research.

    PubMed

    Xing, Lei; Siebers, Jeffrey; Keall, Paul

    2007-10-01

    It is arguable that the imaging and delivery hardware necessary for delivering real-time adaptive image-guided radiotherapy is available on high-end linear accelerators. Robust and computationally efficient software is the limiting factor in achieving highly accurate and precise radiotherapy to the constantly changing anatomy of a cancer patient. The limitations are not caused by the availability of algorithms but rather issues of reliability, integration, and calculation time. However, each of the software components is an active area of research and development at academic and commercial centers. This article describes the software solutions in 4 broad areas: deformable image registration, adaptive replanning, real-time image guidance, and dose calculation and accumulation. Given the pace of technological advancement, the integration of these software solutions to develop real-time adaptive image-guided radiotherapy and the associated challenges they bring will be implemented to varying degrees by all major manufacturers over the coming years. PMID:17903702

  1. Early Outcomes From Three Prospective Trials of Image-Guided Proton Therapy for Prostate Cancer

    SciTech Connect

    Mendenhall, Nancy P.; Li Zuofeng; Hoppe, Bradford S.; Marcus, Robert B.; Mendenhall, William M.; Nichols, R. Charles; Morris, Christopher G.; Williams, Christopher R.; Costa, Joseph; Henderson, Randal

    2012-01-01

    Purpose: To report early outcomes with image-guided proton therapy for prostate cancer. Methods and Materials: We accrued 211 prostate cancer patients on prospective Institutional Review Board-approved trials of 78 cobalt gray equivalent (CGE) in 39 fractions for low-risk disease, dose escalation from 78 to 82 CGE for intermediate-risk disease, and 78 CGE with concomitant docetaxel followed by androgen deprivation for high-risk disease. Minimum follow-up was 2 years. Results: One intermediate-risk patient and 2 high-risk patients had disease progression. Pretreatment genitourinary (GU) symptom management was required in 38% of patients. A cumulative 88 (42%) patients required posttreatment GU symptom management. Four transient Grade 3 GU toxicities occurred, all among patients requiring pretreatment GU symptom management. Multivariate analysis showed correlation between posttreatment GU 2+ symptoms and pretreatment GU symptom management (p < 0.0001) and age (p = 0.0048). Only 1 Grade 3+ gastrointestinal (GI) symptom occurred. The prevalence of Grade 2+ GI symptoms was 0 (0%), 10 (5%), 12 (6%), and 8 (4%) at 6, 12, 18, and 24 months, with a cumulative incidence of 20 (10%) patients at 2 years after proton therapy. Univariate and multivariate analyses showed significant correlation between Grade 2+ rectal bleeding and proctitis and the percentage of rectal wall (rectum) receiving doses ranging from 40 CGE (10 CGE) to 80 CGE. Conclusions: Early outcomes with image-guided proton therapy suggest high efficacy and minimal toxicity with only 1.9% Grade 3 GU symptoms and <0.5% Grade 3 GI toxicities.

  2. Continued Benefit to Androgen Deprivation Therapy for Prostate Cancer Patients Treated With Dose-Escalated Radiation Therapy Across Multiple Definitions of High-Risk Disease

    SciTech Connect

    Stenmark, Matthew H.; Blas, Kevin; Halverson, Schuyler; Sandler, Howard M.; Feng, Felix Y.; Hamstra, Daniel A.

    2011-11-15

    Purpose: To analyze prognostic factors in patients with high-risk prostate cancer treated with dose-escalated external-beam radiation therapy (EBRT) and androgen deprivation (ADT). Methods and Materials: Between 1998 and 2008 at University of Michigan Medical Center, 718 men were consecutively treated with EBRT to at least 75 Gy. Seven definitions of high-risk prostate cancer, applying to 11-33% of patients, were evaluated. Biochemical failure (BF), salvage ADT use, metastatic progression, and prostate cancer-specific mortality (PCSM) were estimated by the Kaplan-Meier method and Cox proportional hazards regression. Results: Each high-risk definition was associated with increased BF (hazard ratio [HR] 2.8-3.9, p < 0.0001), salvage ADT use (HR 3.9-6.3, p < 0.0001), metastasis (HR 3.7-6.6, p < 0.0001), and PCSM (HR 3.7-16.2, p < 0.0001). Furthermore, an increasing number of high-risk features predicted worse outcome. Adjuvant ADT yielded significant reductions in both metastases (HR 0.19-0.38, p < 0.001) and PCSM (HR 0.38-0.50, p < 0.05) for all high-risk definitions (with the exception of clinical Stage T3-4 disease) but improved BF only for those with elevated Gleason scores (p < 0.03, HR 0.25-0.48). When treated with ADT and dose-escalated EBRT, patients with Gleason scores 8 to 10, without other high-risk features, had 8-year freedom from BF of 74%, freedom from distant metastases of 93%, and cause-specific survival of 92%, with salvage ADT used in 16% of patients. Conclusion: Adjuvant ADT results in a significant improvement in clinical progression and PCSM across multiple definitions of high-risk disease even with dose-escalated EBRT. There is a subset of patients, characterized by multiple high-risk features or the presence of Gleason Pattern 5, who remain at significant risk for metastasis and PCSM despite current treatment.

  3. A dosimetric evaluation of dose escalation for the radical treatment of locally advanced vulvar cancer by intensity-modulated radiation therapy

    SciTech Connect

    Bloemers, Monique C.W.M.; Portelance, Lorraine; Ruo, Russell; Parker, William; Souhami, Luis

    2012-10-01

    The purpose of this planning study was to determine whether intensity-modulated radiation therapy (IMRT) reduces the radiation dose to organs at risk (OAR) when compared with 3D conventional radiation therapy (3D-CRT) in patients with vulvar cancer treated by irradiation. This study also investigated the use of sequential IMRT boost (seq-IMRT) and simultaneous integrated boost (SIB-IMRT) for dose escalation in the treatment of locally advanced vulvar cancer. Five vulvar cancer patients treated in the postoperative setting and 5 patients treated with definitive intent (def-group) were evaluated. For the postoperative group, 3D-CRT and IMRT plans to a total dose (TD) of 45 Gy were generated. For the def-group, 4 plans were generated: a 3D-CRT and an IMRT plan to a TD of 56.4 Gy, a SIB-IMRT plan to a TD of 56 Gy, and a SIB-IMRT with dose escalation (SIB-IMRT-esc): TD of 67.2 Gy. Mean dose and dose-volume histograms were compared using Student's t-test. IMRT significantly (all p < 0.05) reduced the D{sub mean}, V30, and V40 for all OAR in the adjuvant setting. The V45 was also significantly reduced for all OAR except the bladder. For patients treated in the def-group, all IMRT techniques significantly reduced the D{sub mean}, V40, and V45 for all OAR. The mean femur doses with SIB-IMRT and SIB-IMRT-esc were 47% and 49% lower compared with 3D-CRT. SIB-IMRT-esc reduced the doses to the OAR compared with seq-3D-CRT but increased the D{sub max.} for the small bowel, rectum, and bladder. IMRT reduces the dose to the OAR compared with 3D-CRT in patients with vulvar cancer receiving irradiation to a volume covering the vulvar region and nodal areas without compromising the dosimetric coverage of the target volume. IMRT for vulvar cancer is feasible and an attractive option for dose escalation studies.

  4. Impact of conventional fractionated RT to pelvic lymph nodes and dose-escalated hypofractionated RT to prostate gland using IMRT treatment delivery in high-risk prostate cancer

    NASA Astrophysics Data System (ADS)

    Pervez, Nadeem

    Prostate cancer is the most common cancer among Canadian men. The standard treatment in high-risk category is radical radiation, with androgen suppression treatment (AST). Significant disease progression is reported despite this approach. Radiation dose escalation has been shown to improve disease-free survival; however, it results in higher toxicities. Hypofractionated radiation schedules (larger dose each fraction in shorter overall treatment time) are expected to deliver higher biological doses. A hypofractionated scheme was used in this study to escalate radiation doses with AST. Treatment was well tolerated acutely. Early results of self-administered quality of life reported by patients shows a decrease in QOL which is comparable to other treatment schedules. Significant positional variation of the prostate was observed during treatment. Therefore, we suggest daily target verification to avoid a target miss. Initial late effects are reasonable and early treatment outcomes are promising. Longer follow-up is required for full outcomes assessments.

  5. A phase I dose-escalation study of MSC1992371A, an oral inhibitor of aurora and other kinases, in advanced hematologic malignancies.

    PubMed

    Graux, Carlos; Sonet, Anne; Maertens, Johan; Duyster, Justus; Greiner, Jochen; Chalandon, Yves; Martinelli, Giovanni; Hess, Dagmar; Heim, Dominik; Giles, Francis J; Kelly, Kevin R; Gianella-Borradori, Athos; Longerey, Blandine; Asatiani, Ekaterine; Rejeb, Narmyn; Ottmann, Oliver G

    2013-09-01

    A phase I dose-escalation study of MSC1992371A, an oral aurora kinase inhibitor, was carried out in patients with hematologic malignancies. Patients received escalating doses either on days 1-3 and 8-10 (n=36) or on days 1-6 (n=39) of a 21-day cycle. The maximum tolerated doses were 37 and 28 mg/m(2)/day, respectively. Dose-limiting toxicities included severe neutropenia with infection and sepsis, mucositis/stomatitis, and diarrhea. Complete responses occurred in 3 patients. Four disease-specific expansion cohorts then received the dose and schedule dictated by the escalation phase but the study was prematurely discontinued due to hematologic and gastrointestinal toxicity at clinically effective doses. PMID:23746966

  6. A Phase 1, Multi-Center, Open-Label, Dose-Escalation Study of 131I-CLR1404 in Subjects with Relapsed or Refractory Advanced Solid Malignancies.

    PubMed

    Lubner, Sam Joseph; Mullvain, Jacqueline; Perlman, Scott; Pishvaian, Michael; Mortimer, Joanne; Oliver, Katherine; Heideman, Jennifer; Hall, Lance; Weichert, Jamey; Liu, Glenn

    2015-01-01

    This study explores the imaging and therapeutic properties of a novel radiopharmaceutical, (131)I-CLR1404. Phase 1a data demonstrated safety and tumor localization by SPECT-CT. This 1b study assessed safety, imaging characteristics, and possible antineoplastic properties and provided further proof-of-concept of phospholipid ether analogues' retention within tumors. A total of 10 patients received (131)I-CLR1404 in an adaptive dose-escalation design. Imaging characteristics were consistent with prior studies, showing tumor uptake in primary tumors and metastases. At doses of 31.25 mCi/m(2) and greater, DLTs were thrombocytopenia and neutropenia. Disease-specific studies are underway to identify cancers most likely to benefit from (131)I-CLR1404 monotherapy. PMID:26536061

  7. Does Hormone Therapy Reduce Disease Recurrence in Prostate Cancer Patients Receiving Dose-Escalated Radiation Therapy? An Analysis of Radiation Therapy Oncology Group 94-06

    SciTech Connect

    Valicenti, Richard K.; Bae, Kwounghwa; Michalski, Jeff; Sandler, Howard; Shipley, William; Lin, Alex; Cox, James

    2011-04-01

    Purpose: The purpose of this study was to evaluate the effect on freedom from biochemical failure (bNED) or disease-free survival (DFS) by adding hormone therapy (HT) to dose-escalated radiation therapy (HDRT). Methods and Materials: We used 883 analyzable prostate cancer patients who enrolled on Radiation Therapy Oncology Group (RTOG) 94-06, a Phase I/II dose escalation trial, and whose mean planning target volume dose exceeded 73.8 Gy (mean, 78.5 Gy; maximum, 84.3 Gy). We defined biochemical failure according to the Phoenix definition. Results: A total of 259 men started HT 2 to 3 months before HDRT, but not longer than 6 months, and 66 men with high-risk prostate cancer received HT for a longer duration. At 5 years, the biochemical failure rates after HDRT alone were 12%, 18%, and 29% for low-, intermediate-, and high-risk patients, respectively (p < 0.0001). Cox proportional hazards regression analysis adjusted for covariates revealed that pretreatment PSA level was a significant factor, whereas risk group, Gleason score, T-stage, and age were not. When the patients were stratified by risk groups, the Cox proportion hazards regression model (after adjusting for pretreatment PSA, biopsy Gleason score, and T stage) did not reveal a significant effect on bNED or DFS by adding HT to HDRT Conclusion: The addition of HT did not significantly improve bNED survival or DFS in all prostate cancer patients receiving HDRT, but did approach significance in high-risk patient subgroup. The result of this study is hypothesis generating and requires testing in a prospective randomized trial.

  8. A Phase 1 Dose-Escalation Study of ASP2409, a Selective T-Cell Costimulation Inhibitor, in Stable Rheumatoid Arthritis Patients on Methotrexate Therapy.

    PubMed

    Zhang, Wenhui; Kernstock, Robert M; Karrer, Erik E; Cohen, Stanley B; Chindalore, Vishala L; Kivitz, Alan J; Blahunka, Paul C; Delgado-Herrera, Leticia; Zeiher, Bernhardt G; Samberg, Nancy L; Garg, Jay P

    2016-07-01

    ASP2409 represents a new class of CTLA4-Ig molecules with higher binding avidity and selectivity to CD86. This first-in-human study was to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of ASP2409 in stable rheumatoid arthritis patients on methotrexate therapy with a randomized, double-blind, placebo-controlled dose-escalation study design. Patients were enrolled and randomized in each of 8 dose-escalation cohorts ranging from 0.001 to 3.0 mg/kg to receive either ASP2409 or placebo in a sequential manner. Escalation to higher dose levels occurred in the absence of dose-limiting toxicity. A total of 57 patients completed the study. ASP2409 showed nonlinear PK over the dose range of 0.01 to 3.0 mg/kg following a single intravenous administration, indicating target-mediated drug disposition. Area under the concentration-time curve (AUC) and maximum concentration (Cmax ) increased at a greater than dose-proportional rate. The half-life of ASP2409 increased dose dependently and ranged from 1.57 to 6.68 days. ASP2409 showed a dose-dependent increase in the extent and duration of CD86 receptor occupancy. There were no clinically relevant safety issues up to a single dose of 3.0 mg/kg. No maximum tolerated dose was reached. The incidence and duration of antidrug antibodies did not correlate with adverse events. ClinicalTrials.gov identifier: NCT02171143. PMID:27310327

  9. A 3-year survey quantifying the risk of dose escalation of benzodiazepines and congeners to identify risk factors to aid doctors to more rationale prescribing

    PubMed Central

    Tvete, Ingunn Fride; Bjørner, Trine; Aursnes, Ivar Andreas; Skomedal, Tor

    2013-01-01

    Objectives This study investigated and quantified risk factors of dose escalation, as an indication of drug misuse and dependency of benzodiazepines and congeners, among presumably drug naïve patients in the Norwegian drug prescription database, observed over 3 years. Design Observational study. Setting Prescription database study. Participants We defined an excessive user as one redeeming more than two defined daily doses per day in 3 months. Primary and secondary outcome measures We examined the risk of excessive use over time and the effect of risk factors through multistate logistic regression and scenarios. Results Most of the 81 945 patients had zopiclone or zolpidem as the initial drug (63.8%), followed by diazepam (25.3%), oxazepam (6.1%), nitrazepam/flunitrazepam (2.9%), hydroxyzine/buspirone (1.6%) and alprazolam (0.3%). At any time 23% redeemed prescriptions, about 34% did not redeem any prescriptions beyond any 3-month period and 0.9% ended up as excessive users. Patients previously using drugs, such as opioids, antialcohol or smoke cessation treatment, had a higher risk to become excessive users compared to patients who had not. Patients whose first prescription was for oxazepam or nitrazepam/flunitrazepam had a higher risk of becoming an excessive user compared to those who started with diazepam. A specialist in general practice as the first-time prescriber was associated with a lower risk compared to doctors without specialty. Conclusions Most benzodiazepine use occurred according to guidelines. Still, some experienced dose escalation over time, and risk factors were previous use of other psychotropic drugs, long time use, choice of first-time drug and prescriber's specialty. This could incite doctors to have a cessation plan when issuing first-time prescriptions. PMID:24097305

  10. Stereotactic Body Radiation Therapy for Prostate Cancer: Review of Experience of a Multicenter Phase I/II Dose-Escalation Study

    PubMed Central

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

    2014-01-01

    Introduction: Stereotactic body radiation therapy (SBRT) is an area of active investigation for treatment of prostate cancer. In our phase I dose-escalation study, maximum-tolerated dose (MTD) was not reached, and subsequently phase II study has been completed. The purpose of this article is to review our experiences of dose-escalated SBRT for localized prostate cancer. Methods and materials: Patients enrolled to phase I/II study from 2006 to 2011 were reviewed. Prescription dose groups were 45, 47.5, and 50 Gray (Gy) in five fractions over 2.5 weeks. Toxicity and quality of life questionnaire data were collected and analyzed. Descriptive statistics were obtained in the form of means, medians, and ranges for the continuous variables, and frequencies and percentages for the categoric variables. Results: Ninety-one patients were enrolled from five institutions. Median follow-up for prostate specific antigen (PSA) evaluation was 42 months. PSA control remains at 99%. While the MTD was not reached in the phase I study, excess high grade rectal toxicity (10.6%) was noted in the phase II study. The 13 patients treated to 50 Gy in the phase I study that did not have high grade rectal toxicity, in retrospect met these parameters and have not had further events on longer follow-up. Conclusion: Prostate specific antigen control rate, even for patients with intermediate risk, is thus far excellent at these dose levels. This study provides a platform for exploration of SBRT based clinical trials aimed at optimizing outcome for intermediate and high risk patients. High grade toxicities specifically related to the rectum were observed in a small but meaningful minority at the highest dose level. Dose constraints based on physiologic parameters have been defined to mitigate this risk, and strategies to minimize rectal exposure to such doses are being explored. PMID:25505731

  11. Short-term Androgen-Deprivation Therapy Improves Prostate Cancer-Specific Mortality in Intermediate-Risk Prostate Cancer Patients Undergoing Dose-Escalated External Beam Radiation Therapy

    SciTech Connect

    Zumsteg, Zachary S.; Spratt, Daniel E.; Pei, Xin; Yamada, Yoshiya; Kalikstein, Abraham; Kuk, Deborah; Zhang, Zhigang; Zelefsky, Michael J.

    2013-03-15

    Purpose: We investigated the benefit of short-term androgen-deprivation therapy (ADT) in patients with intermediate-risk prostate cancer (PC) receiving dose-escalated external beam radiation therapy. Methods and Materials: The present retrospective study comprised 710 intermediate-risk PC patients receiving external beam radiation therapy with doses of ≥81 Gy at a single institution from 1992 to 2005, including 357 patients receiving neoadjuvant and concurrent ADT. Prostate-specific antigen recurrence-free survival (PSA-RFS) and distant metastasis (DM) were compared using the Kaplan-Meier method and Cox proportional hazards models. PC-specific mortality (PCSM) was assessed using competing-risks analysis. Results: The median follow-up was 7.9 years. Despite being more likely to have higher PSA levels, Gleason score 4 + 3 = 7, multiple National Comprehensive Cancer Network intermediate-risk factors, and older age (P≤.001 for all comparisons), patients receiving ADT had improved PSA-RFS (hazard ratio [HR], 0.598; 95% confidence interval [CI], 0.435-0.841; P=.003), DM (HR, 0.424; 95% CI, 0.219-0.819; P=.011), and PCSM (HR, 0.380; 95% CI, 0.157-0.921; P=.032) on univariate analysis. Using multivariate analysis, ADT was an even stronger predictor of improved PSA-RFS (adjusted HR [AHR], 0.516; 95% CI, 0.360-0.739; P<.001), DM (AHR, 0.347; 95% CI, 0.176-0.685; P=.002), and PCSM (AHR, 0.297; 95% CI, 0.128-0.685; P=.004). Gleason score 4 + 3 = 7 and ≥50% positive biopsy cores were other independent predictors of PCSM. Conclusions: Short-term ADT improves PSA-RFS, DM, and PCSM in patients with intermediate-risk PC undergoing dose-escalated external beam radiation therapy.

  12. Isotoxic Dose Escalation in the Treatment of Lung Cancer by Means of Heterogeneous Dose Distributions in the Presence of Respiratory Motion

    SciTech Connect

    Baker, Mariwan; Nielsen, Morten; Hansen, Olfred; Jahn, Jonas Westberg; Korreman, Stine; Brink, Carsten

    2011-11-01

    Purpose: To test, in the presence of intrafractional respiration movement, a margin recipe valid for a homogeneous and conformal dose distribution and to test whether the use of smaller margins combined with heterogeneous dose distributions allows an isotoxic dose escalation when respiratory motion is considered. Methods and Materials: Twenty-three Stage II-III non-small-cell lung cancer patients underwent four-dimensional computed tomography scanning. The gross tumor volume and clinical target volume (CTV) were outlined in the mid-ventilation phase. The CTV-to-planning target volume (PTV) margin was calculated by use of a standard margin recipe and the patient-specific respiration pattern. Standard three-dimensional treatment plans were generated and recalculated on the remaining respiration phases. The planning was repeated for a CTV-to-PTV margin decreased by 2.5 and 5 mm relative to the initial margin in all directions. Time-averaged dose-volume histograms (four-dimensional dose-volume histograms) were calculated to evaluate the CTV-to-PTV margin. Finally, the dose was escalated in the plans with decreased PTV such that the mean lung dose (predictor of radiation-induced pneumonitis) was equal to mean lung dose in the plan by use of the initially calculated margin. Results: A reduction of the standard margin by 2.5 mm compared with the recipe resulted in too low of a minimum dose for some patients. A combination of dose escalation and use of heterogeneous dose distribution was able to increase the minimum dose to the target by approximately 10% and 20% for a CTV-to-PTV margin reduction of 2.5 mm and 5.0 mm, respectively. Conclusion: The margin recipe is valid for intrafractional respiration-induced tumor motions. It is possible to increase the dose to the target without increased mean lung dose with an inhomogeneous dose distribution.

  13. Image-guided total marrow and total lymphatic irradiation using helical tomotherapy

    SciTech Connect

    Schultheiss, Timothy E. . E-mail: Schultheiss@coh.org; Wong, Jeffrey; Liu, An; Olivera, Gustavo; Somlo, George

    2007-03-15

    Purpose: To develop a treatment technique to spare normal tissue and allow dose escalation in total body irradiation (TBI). We have developed intensity-modulated radiotherapy techniques for the total marrow irradiation (TMI), total lymphatic irradiation, or total bone marrow plus lymphatic irradiation using helical tomotherapy. Methods and Materials: For TBI, we typically use 12 Gy in 10 fractions delivered at an extended source-to-surface distance (SSD). Using helical tomotherapy, it is possible to deliver equally effective doses to the bone marrow and lymphatics while sparing normal organs to a significant degree. In the TMI patients, whole body skeletal bone, including the ribs and sternum, comprise the treatment target. In the total lymphatic irradiation, the target is expanded to include the spleen and major lymph node areas. Sanctuary sites for disease (brain and testes) are included when clinically indicated. Spared organs include the lungs, esophagus, parotid glands, eyes, oral cavity, liver, kidneys, stomach, small and large intestine, bladder, and ovaries. Results: With TBI, all normal organs received the TBI dose; with TMI, total lymphatic irradiation, and total bone marrow plus lymphatic irradiation, the visceral organs are spared. For the first 6 patients treated with TMI, the median dose to organs at risk averaged 51% lower than would be achieved with TBI. By putting greater weight on the avoidance of specific organs, greater sparing was possible. Conclusion: Sparing of normal tissues and dose escalation is possible using helical tomotherapy. Late effects such as radiation pneumonitis, veno-occlusive disease, cataracts, neurocognitive effects, and the development of second tumors should be diminished in severity and frequency according to the dose reduction realized for the organs at risk.

  14. Image-Guided Adrenal and Renal Biopsy

    PubMed Central

    Sharma, Karun V.; Venkatesan, Aradhana M.; Swerdlow, Daniel; DaSilva, Daniel; Beck, Avi; Jain, Nidhi; Wood, Bradford J.

    2010-01-01

    Image-guided biopsy is a safe and well-established technique that is familiar to most interventional radiologists (IRs). Improvements in image-guidance, biopsy tools and biopsy techniques now routinely allow for safe biopsy of renal and adrenal lesions which traditionally were considered difficult to reach or technically challenging. Image-guided biopsy is used to establish the definitive tissue diagnosis in adrenal mass lesions that can not be fully characterized with imaging or laboratory tests alone. It is also used to establish definitive diagnosis in some cases of renal parenchymal disease and has an expanding role in diagnosis and characterization of renal masses prior to treatment. Although basic principles and techniques for image-guided needle biopsy are similar regardless of organ, this paper will highlight some technical considerations, indications and complications which are unique to the adrenal gland and kidney because of their anatomic location and physiologic features. PMID:20540919

  15. Improving Performance During Image-Guided Procedures

    PubMed Central

    Duncan, James R.; Tabriz, David

    2015-01-01

    Objective Image-guided procedures have become a mainstay of modern health care. This article reviews how human operators process imaging data and use it to plan procedures and make intraprocedural decisions. Methods A series of models from human factors research, communication theory, and organizational learning were applied to the human-machine interface that occupies the center stage during image-guided procedures. Results Together, these models suggest several opportunities for improving performance as follows: 1. Performance will depend not only on the operator’s skill but also on the knowledge embedded in the imaging technology, available tools, and existing protocols. 2. Voluntary movements consist of planning and execution phases. Performance subscores should be developed that assess quality and efficiency during each phase. For procedures involving ionizing radiation (fluoroscopy and computed tomography), radiation metrics can be used to assess performance. 3. At a basic level, these procedures consist of advancing a tool to a specific location within a patient and using the tool. Paradigms from mapping and navigation should be applied to image-guided procedures. 4. Recording the content of the imaging system allows one to reconstruct the stimulus/response cycles that occur during image-guided procedures. Conclusions When compared with traditional “open” procedures, the technology used during image-guided procedures places an imaging system and long thin tools between the operator and the patient. Taking a step back and reexamining how information flows through an imaging system and how actions are conveyed through human-machine interfaces suggest that much can be learned from studying system failures. In the same way that flight data recorders revolutionized accident investigations in aviation, much could be learned from recording video data during image-guided procedures. PMID:24921628

  16. Daily Image Guidance With Cone-Beam Computed Tomography for Head-and-Neck Cancer Intensity-Modulated Radiotherapy: A Prospective Study

    SciTech Connect

    Den, Robert B.; Doemer, Anthony; Kubicek, Greg; Bednarz, Greg; Galvin, James M.; Keane, William M.; Xiao Ying; Machtay, Mitchell

    2010-04-15

    Purpose: To report on a prospective clinical trial of the use of daily kilovoltage cone-beam computed tomography (CBCT) to evaluate the interfraction and residual error motion of patients undergoing intensity-modulated radiotherapy for head-and-neck cancer. Methods and Materials: Patients were treated with intensity-modulated radiotherapy with an Elekta linear accelerator using a mounted CBCT scanner. CBCT was performed before every treatment, and translational (but not rotational) corrections were performed. At least once per week, a CBCT scan was obtained after intensity-modulated radiotherapy. Variations were measured in the medial-lateral, superoinferior, and anteroposterior dimensions, as well as in the rotation around these axes. Results: A total of 28 consecutive patients (1,013 CBCT scans) were studied. The average interfraction shift was 1.4 +- 1.4, 1.7 +- 1.9, and 1.8 +- 2.1 mm in the medial-lateral, superoinferior, and anteroposterior dimensions, respectively. The corresponding average residual error shifts were 0.7 +- 0.8, 0.9 +- 0.9, and 0.9 +- 0.9 mm. These data indicate that in the absence of daily CBCT image-guided radiotherapy, a clinical target volume to planning target volume margin of 3.9, 4.1, and 4.9 mm is needed in the medial-lateral, superoinferior, and anteroposterior dimensions, respectively. With daily CBCT, corresponding margins of 1.6, 2.5, and 1.9 mm should be acceptable. Subgroup analyses showed that larynx cancers and/or intratreatment weight loss indicate a need for slightly larger clinical target volume to planning target volume margins. Conclusion: The results of our study have shown that image-guided radiotherapy using CBCT for head-and-neck cancer is effective. These data suggest it allows a reduction in the clinical target volume to planning target volume margins by about 50%, which could facilitate future studies of dose escalation and/or improved toxicity reduction. Caution is particularly warranted for cases in which the

  17. Image-Guided Percutaneous Ablation of Bone and Soft Tissue Tumors

    PubMed Central

    Kurup, A. Nicholas; Callstrom, Matthew R.

    2010-01-01

    Image-guided percutaneous ablation of bone and soft tissue tumors is an effective minimally invasive alternative to conventional therapies, such as surgery and external beam radiotherapy. Proven applications include treatment of benign primary bone tumors, particularly osteoid osteoma, as well as palliation of painful bone metastases. Use of percutaneous ablation in combination with cementoplasty can provide stabilization of metastases at risk for fracture. Local control of oligometastatic disease and treatment of desmoid tumors are emerging applications. PMID:22550367

  18. Innovation in image-guided spine intervention.

    PubMed

    Murphy, Kieran J

    2011-04-01

    Image-guided spine intervention continues to evolve and is still an intellectually active field. But it is important not to confuse market and commercial success with intellectual, medical, or long-term success. What drives this evolution and innovation, and where is the activity currently? The history of vertebroplasty is a good case in point. PMID:21500137

  19. Hepatocellular carcinoma: modern image-guided therapies.

    PubMed

    Puppala, Sapna; Patel, Rafiuddin; Yap, Ki Sing; Patel, Jai; Wah, Tze; Snoddon, Andrew

    2016-03-01

    The most common primary malignancy of the liver and the third leading cause of cancer mortality worldwide is hepatocellular carcinoma (HCC), which presents a major global health problem due to its increasing incidence. Most cases of HCC are secondary to either infection (hepatitis B or C) or cirrhosis (alcohol being the most common cause). Clinical presentation is variable and the tumour can be an incidental finding. Treatment options for HCC and prognosis are dependent on many factors but most importantly tumour size and staging. The last two decades have revolutionised the treatment of HCC using image-guided techniques. The concepts of imaging and image-guided techniques are still young and not well described in standard textbooks and hence an up to date review article is essential. The clinical subspecialities may lack familiarity with image-guided techniques but are responsible for management of these patients before and after the treatment by interventional radiologists. This article reviews current image-guided techniques, evidence and outcomes and provides educational highlights and question and answers. The article provides an overview in a simple understandable manner to enable readers from various levels of practice and training to benefit from and apply in their practice. PMID:26787919

  20. 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

  1. [Prostate cancer external beam radiotherapy].

    PubMed

    de Crevoisier, R; Pommier, P; Latorzeff, I; Chapet, O; Chauvet, B; Hennequin, C

    2016-09-01

    The prostate external beam radiotherapy techniques are described, when irradiating the prostate or after prostatectomy, with and without pelvic lymph nodes. The following parts are presented: indications of radiotherapy, total dose and fractionation, planning CT image acquisition, volume of interest delineation (target volumes and organs at risk) and margins, Intensity modulated radiotherapy planning and corresponding dose-volume constraints, and finally Image guided radiotherapy. PMID:27516051

  2. Image-guided high-dose-rate brachytherapy in inoperable endometrial cancer

    PubMed Central

    Petsuksiri, J; Chansilpa, Y; Hoskin, P J

    2014-01-01

    Inoperable endometrial cancer may be treated with curative aim using radical radiotherapy alone. The radiation techniques are external beam radiotherapy (EBRT) alone, EBRT plus brachytherapy and brachytherapy alone. Recently, high-dose-rate brachytherapy has been used instead of low-dose-rate brachytherapy. Image-guided brachytherapy enables sufficient coverage of tumour and reduction of dose to the organs at risk, thus increasing the therapeutic ratio of treatment. Local control rates with three-dimensional brachytherapy appear better than with conventional techniques (about 90–100% and 70–90%, respectively). PMID:24807067

  3. DVC1-0101 to Treat Peripheral Arterial Disease: A Phase I/IIa Open-label Dose-escalation Clinical Trial

    PubMed Central

    Yonemitsu, Yoshikazu; Matsumoto, Takuya; Itoh, Hiroyuki; Okazaki, Jin; Uchiyama, Makiko; Yoshida, Kumi; Onimaru, Mitsuho; Onohara, Toshihiro; Inoguchi, Hiroyuki; Kyuragi, Ryoichi; Shimokawa, Mototsugu; Ban, Hiroshi; Tanaka, Michiko; Inoue, Makoto; Shu, Tsugumine; Hasegawa, Mamoru; Nakanishi, Yoichi; Maehara, Yoshihiko

    2013-01-01

    We here report the results of a Phase I/IIa open-label four dose-escalation clinical study assessing the safety, tolerability, and possible therapeutic efficacy of a single intramuscular administration of DVC1-0101, a new gene transfer vector based on a nontransmissible recombinant Sendai virus (rSeV) expressing the human fibroblast growth factor-2 (FGF-2) gene (rSeV/dF-hFGF2), in patients with peripheral arterial disease (PAD). Gene transfer was done in 12 limbs of 12 patients with rest pain, and three of them had ischemic ulcer(s). No cardiovascular or other serious adverse events (SAEs) caused by gene transfer were detected in the patients over a 6-month follow-up. No infectious viral particles, as assessed by hemagglutination activity, were detected in any patient during the study. No representative elevation of proinflammatory cytokines or plasma FGF-2 was seen. Significant and continuous improvements in Rutherford category, absolute claudication distance (ACD), and rest pain were observed (P < 0.05 to 0.01). To the best of our knowledge, this is the first clinical trial of the use of a gene transfer vector based on rSeV. The single intramuscular administration of DVC1-0101 to PAD patients was safe and well tolerated, and resulted in significant improvements of limb function. Larger pivotal studies are warranted as a next step. PMID:23319060

  4. 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.

  5. Cost savings of anti-TNF therapy using a test-based strategy versus an empirical dose escalation in Crohn's disease patients who lose response to infliximab

    PubMed Central

    Roblin, Xavier; Attar, Alain; Lamure, Michel; Savarieau, Bernard; Brunel, Pierre; Duru, Gérard; Peyrin-Biroulet, Laurent

    2015-01-01

    Background The use of pharmacokinetics is associated with cost savings in anti-tumor necrosis factor (anti-TNF) therapy, but the long-term cost savings in a large cohort of Crohn's disease (CD) patients are unknown. Aim The goal of this study was to compare the cost of anti-TNF therapy in two cohorts of CD patients losing response to infliximab, one using a test-based strategy and one an empirical dose escalation. Methods We used a selected mathematical model to describe the trajectories of CD patients based on a discrete event system. This design allowed us to track over a given period a double cohort of patients who moved randomly and asynchronously from one state to another, while keeping all the information on their entire trajectory. Both cohorts were modeled using state diagram parameters where transition probabilities from one state to another are derived from literature data. Costs were estimated based on the French health care system. Results Cost savings among the 10,000 CD patients using a test-based strategy were €131,300,293 at 5 years. At 5 years the mean cost saving was €13,130 per patient. The direct cost of the test had no impact on the results until the cost per test reached €2,000. Conclusions A test-based strategy leads to major cost savings related to anti-TNF therapy in CD. PMID:27123185

  6. The impact of dose escalation and resistance modulation in older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome: the results of the LRF AML14 trial.

    PubMed

    Burnett, Alan K; Milligan, Donald; Goldstone, Anthony; Prentice, Archibald; McMullin, Mary-Frances; Dennis, Michael; Sellwood, Elizabeth; Pallis, Monica; Russell, Nigel; Hills, Robert K; Wheatley, Keith

    2009-05-01

    The acute myeloid leukaemia (AML)14 trial addressed four therapeutic questions in patients predominantly aged over 60 years with AML and High Risk Myelodysplastic Syndrome: (i) Daunorubicin 50 mg/m(2) vs. 35 mg/m(2); (ii) Cytarabine 200 mg/m(2) vs. 400 mg/m(2) in two courses of DA induction; (iii) for part of the trial, patients allocated Daunorubicin 35 mg/m(2) were also randomized to receive, or not, the multidrug resistance modulator PSC-833 in a 1:1:1 randomization; and (iv) a total of three versus four courses of treatment. A total of 1273 patients were recruited. The response rate was 62% (complete remission 54%, complete remission without platelet/neutrophil recovery 8%); 5-year survival was 12%. No benefits were observed in either dose escalation randomization, or from a fourth course of treatment. There was a trend for inferior response in the PSC-833 arm due to deaths in induction. Multivariable analysis identified cytogenetics, presenting white blood count, age and secondary disease as the main predictors of outcome. Although patients with high Pgp expression and function had worse response and survival, this was not an independent prognostic factor, and was not modified by PSC-833. In conclusion, these four interventions have not improved outcomes in older patients. New agents need to be explored and novel trial designs are required to maximise prospects of achieving timely progress. PMID:19291085

  7. Safety, tolerability and pharmacokinetics of 2-pyridylacetic acid, a major metabolite of betahistine, in a phase 1 dose escalation study in subjects with ADHD.

    PubMed

    Moorthy, Ganesh; Sallee, Floyd; Gabbita, Prasad; Zemlan, Frank; Sallans, Larry; Desai, Pankaj B

    2015-10-01

    Betahistine, a potent histamine H3 receptor antagonist, is being developed for the treatment of attention deficit hyperactivity disorder (ADHD) that manifests with symptoms such as hyperactivity, impulsivity and inattention. This study describes the pharmacokinetics of betahistine in ADHD subjects at doses higher than 50 mg. These assessments were made during a randomized, placebo-controlled, single blind, dose escalation study to determine the safety, tolerability and pharmacokinetics of once daily doses of 50 mg, 100 mg and 200 mg of betahistine in subjects with ADHD. Plasma levels of 2-pyridylacetic acid (2-PAA), a major metabolite of betahistine were quantified using a validated LC-MS/MS method and used for pharmacokinetic analysis and dose proportionality of betahistine. A linear relationship was observed in Cmax and AUC0-4 of 2-PAA with the betahistine dose (R2 0.9989 and 0.9978, respectively) and dose proportionality coefficients (β) for the power model were 0.8684 (Cmax) and 1.007 (AUC0-4). A population pharmacokinetic model with first-order absorption of betahistine and metabolism to 2-PAA, followed by a first-order elimination of 2-PAA provides estimates of clearance that underscored the linear increase in systemic exposure with dose. There were no serious adverse events reported in the study, betahistine was safe and well tolerated at all the dose levels tested. PMID:25904220

  8. Recombinant T-Cell Receptor Ligand (RTL) for Treatment of Multiple Sclerosis: A Double-Blind, Placebo-Controlled, Phase 1, Dose-Escalation Study

    PubMed Central

    Yadav, Vijayshree; Bourdette, Dennis N.; Bowen, James D.; Lynch, Sharon G.; Mattson, David; Preiningerova, Jana; Bever, Christopher T.; Simon, Jack; Goldstein, Andrew; Burrows, Gregory G.; Offner, Halina; Ferro, Al J.; Vandenbark, Arthur A.

    2012-01-01

    Background. Recombinant T-cell receptor ligand 1000 (RTL1000) is a single-chain protein construct containing the outer two domains of HLA-DR2 linked to myelin-oligodendrocyte-glycoprotein- (MOG-) 35–55 peptide. Analogues of RTL1000 induce T-cell tolerance, reverse clinical and histological disease, and promote repair in experimental autoimmune encephalomyelitis (EAE) in DR2 transgenic, C57BL/6, and SJL/J mice. Objective. Determining the maximum tolerated dose, safety, and tolerability of RTL1000 in multiple sclerosis (MS) subjects. Methods. This was a multicenter, Phase I dose-escalation study in HLA-DR2+ MS subjects. Consecutive cohorts received RTL1000 doses of 2, 6, 20, 60, 200, and 100 mg, respectively. Subjects within each cohort randomly received a single intravenous infusion of RTL1000 or placebo at a 4 : 2 ratio. Safety monitoring included clinical, laboratory, and brain magnetic resonance imaging (MRI) evaluations. Results. Thirty-four subjects completed the protocol. All subjects tolerated the 2–60 mg doses of RTL1000. Doses ≥100 mg caused hypotension and diarrhea in 3 of 4 subjects, leading to discontinuation of further enrollment. Conclusions. The maximum tolerated dose of RTL1000 in MS subjects is 60 mg, comparable to effective RTL doses in EAE. RTL1000 is a novel approach for MS treatment that may induce immunoregulation without immunosuppression and promote neural repair. PMID:22548151

  9. Endovascular image-guided interventions (EIGIs)

    PubMed Central

    Rudin, Stephen; Bednarek, Daniel R.; Hoffmann, Kenneth R.

    2009-01-01

    Minimally invasive interventions are rapidly replacing invasive surgical procedures for the most prevalent human disease conditions. X-ray image-guided interventions carried out using the insertion and navigation of catheters through the vasculature are increasing in number and sophistication. In this article, we offer our vision for the future of this dynamic field of endovascular image-guided interventions in the form of predictions about (1) improvements in high-resolution detectors for more accurate guidance, (2) the implementation of high-resolution region of interest computed tomography for evaluation and planning, (3) the implementation of dose tracking systems to control patient radiation risk, (4) the development of increasingly sophisticated interventional devices, (5) the use of quantitative treatment planning with patient-specific computer fluid dynamic simulations, and (6) the new expanding role of the medical physicist. We discuss how we envision our predictions will come to fruition and result in the universal goal of improved patient care. PMID:18293585

  10. Image-guided ablation for hepatocellular carcinoma.

    PubMed

    Lencioni, Riccardo; Crocetti, Laura

    2013-01-01

    Image-guided ablation is accepted as the best therapeutic choice for patients with early-stage hepatocellular carcinoma (HCC) when surgical options-including resection and transplantation-are precluded. The term image-guided tumor ablation is defined as the direct application of chemical substances or sources of energy to a focal tumor in an attempt to achieve eradication or substantial tumor destruction. Over the past 25 years, several methods for local tumor destruction have been developed and clinically tested. Radiofrequency ablation (RFA) has shown superior anticancer effect and greater survival benefit with respect to the seminal percutaneous technique, ethanol injection, in meta-analyses of randomized controlled trials, and is currently established as the standard ablative modality. Nevertheless, novel thermal and nonthermal techniques for tumor ablation-including microwave ablation and irreversible electroporation-seem to have potential to improve the efficacy of RFA and are currently undergoing clinical investigation. PMID:22941021

  11. Characterization and Management of Interfractional Anatomic Changes for Pancreatic Cancer Radiotherapy

    SciTech Connect

    Liu Feng; Erickson, Beth; Peng Cheng; Li, X. Allen

    2012-07-01

    Purpose: To quantitatively characterize interfractional anatomic variations in pancreatic cancer radiotherapy (RT) and to study dosimetric advantages for using an online adaptive replanning scheme to account for these variations. Methods and Materials: Targets and organs at risk (OAR) were delineated by autosegmentation based on daily computed tomography (CT) images acquired using a respiration-gated in-room CT during daily image-guided RT (IGRT) for 10 pancreatic cancer patients. Various parameters, including the maximum overlap ratio (MOR) between the volumes based on planning and daily CTs for a structure, while the overlapping volumes were maximized, were used to quantify the interfractional organ deformation with the intrafractional variations largely excluded. An online adaptive RT (ART) was applied to these daily CTs. To evaluate the dosimetric benefits of ART, the dose distributions from the online ART were compared to those from the repositioning in the current standard IGRT practice. Results: The interfractional anatomic variations, particularly the organ deformation, are significant during pancreas irradiation. For the patients studied, the average MORs of all daily CTs were 80.2%, 61.7%, and 72.2% for pancreatic head, duodenum, and stomach, respectively. The online ART leads to improved dosimetric plan with better target coverage and/or OAR sparing than IGRT repositioning. For the patients studied, the mean V{sub 50.4Gy} (volume covered by 50.4 Gy) for the duodenum was reduced from 43.4% for IGRT to 15.6% for the online ART scheme. Conclusions: The online adaptive RT scheme can effectively account for the significant interfractional anatomic variations observed in pancreas irradiation. The dosimetric advantages with the online ART may enable safe dose escalation in radiation therapy for pancreatic cancer.

  12. A multicenter, randomized trial of flat dosing versus intrapatient dose escalation of single-agent carboplatin as first-line chemotherapy for advanced ovarian cancer: an SGCTG (SCOTROC 4) and ANZGOG study on behalf of GCIG

    PubMed Central

    Banerjee, S.; Rustin, G.; Paul, J.; Williams, C.; Pledge, S.; Gabra, H.; Skailes, G.; Lamont, A.; Hindley, A.; Goss, G.; Gilby, E.; Hogg, M.; Harper, P.; Kipps, E.; Lewsley, L-A; Hall, M.; Vasey, P.; Kaye, S. B.

    2015-01-01

    Background The aim of the study is to demonstrate that intrapatient dose escalation of carboplatin would improve the outcome in ovarian cancer compared with flat dosing. Patients and methods Patients with untreated stage IC-IV ovarian cancer received six cycles of carboplatin area under the curve 6 (AUC 6) 3 weekly either with no dose modification except for toxicity (Arm A) or with dose escalations in cycles 2–6 based on nadir neutrophil and platelet counts (Arm B). The primary end-point was progression-free survival (PFS). Results Nine hundred and sixty-four patients were recruited from 71 centers. Dose escalation was achieved in 77% of patients who had ≥1 cycle. The median AUCs (cycle 2–6) received were 6.0 (Arm A) and 7.2 (Arm B) (P < 0.001). Grade 3/4 non-hematological toxicity was higher in Arm B (31% versus 22% P = 0.001). The median PFS was 12.1 months in Arm A and B [hazard ratio (HR) 0.99; 95% confidence interval (CI) 0.85–1.15; P = 0.93]. The median overall survival (OS) was 34.1 and 30.7 months in Arms A and B, respectively (HR 0.98; 95% CI 0.81–1.18, P = 0.82). In multivariate analysis, baseline neutrophil (P < 0.001), baseline platelet counts (P < 0.001) and the difference between white blood cell (WBC) and neutrophil count (P = 0.009) had a significant adverse prognostic value. Conclusions Intrapatient dose escalation of carboplatin based on nadir blood counts is feasible and safe. However, it provided no improvement in PFS or OS compared with flat dosing. Baseline neutrophils over-ride nadir counts in prognostic significance. These data may have wider implications particularly in respect of the management of chemotherapy-induced neutropenia. PMID:23041585

  13. Retrospective Evaluation Reveals That Long-term Androgen Deprivation Therapy Improves Cause-Specific and Overall Survival in the Setting of Dose-Escalated Radiation for High-Risk Prostate Cancer

    SciTech Connect

    Feng, Felix Y.; Blas, Kevin; Olson, Karin; Stenmark, Matthew; Sandler, Howard; Hamstra, Daniel A.

    2013-05-01

    Purpose: To evaluate the role of androgen deprivation therapy (ADT) and duration for high-risk prostate cancer patients treated with dose-escalated radiation therapy (RT). Methods and Materials: A retrospective analysis of high-risk prostate cancer patients treated with dose-escalated RT (minimum 75 Gy) with or without ADT was performed. The relationship between ADT use and duration with biochemical failure (BF), metastatic failure (MF), prostate cancer-specific mortality (PCSM), non-prostate cancer death (NPCD), and overall survival (OS) was assessed as a function of pretreatment characteristics, comorbid medical illness, and treatment using Fine and Gray's cumulative incidence methodology. Results: The median follow-up time was 64 months. In men with National Comprehensive Cancer Network defined high-risk prostate cancer treated with dose-escalated RT, on univariate analysis, both metastasis (P<.0001; hazard ratio 0.34; 95% confidence interval 0.18-0.67; cumulative incidence at 60 months 13% vs 35%) and PCSM (P=.015; hazard ratio 0.41; 95% confidence interval 0.2-1.0; cumulative incidence at 60 months 6% vs 11%) were improved with the use of ADT. On multivariate analysis for all high-risk patients, Gleason score was the strongest negative prognostic factor, and long-term ADT (LTAD) improved MF (P=.002), PCSM (P=.034), and OS (P=.001). In men with prostate cancer and Gleason scores 8 to 10, on multivariate analysis after adjustment for other risk features, there was a duration-dependent improvement in BF, metastasis, PCSM, and OS, all favoring LTAD in comparison with STAD or RT alone. Conclusion: For men with high-risk prostate cancer treated with dose-escalated EBRT, this retrospective study suggests that the combination of LTAD and RT provided a significant improvement in clinical outcome, which was especially true for those with Gleason scores of 8 to 10.

  14. A non-randomized dose-escalation Phase I trial of a protein-based immunotherapeutic for the treatment of breast cancer patients with HER2-overexpressing tumors.

    PubMed

    Limentani, Steven A; Campone, Mario; Dorval, Thierry; Curigliano, Giuseppe; de Boer, Richard; Vogel, Charles; White, Shane; Bachelot, Thomas; Canon, Jean-Luc; Disis, Mary; Awada, Ahmad; Berlière, Martine; Amant, Frédéric; Levine, Ellis; Burny, Wivine; Callegaro, Andrea; de Sousa Alves, Pedro Miguel; Louahed, Jamila; Brichard, Vincent; Lehmann, Frédéric F

    2016-04-01

    This Phase I dose-escalation study (NCT00058526) assessed the safety and immunogenicity of an anti-cancer immunotherapeutic (recombinant HER2 protein (dHER2) combined with the immunostimulant AS15) in patients with early-stage HER2-overexpressing breast cancer (BC). Sixty-one trastuzumab-naive patients with stage II-III HER2-positive BC received the dHER2 immunotherapeutic after surgical resection and adjuvant therapy. They were allocated into four cohorts receiving different doses of dHER2 (20, 100, 500 µg) combined with a fixed AS15 dose. Safety and immunogenicity (dHER2-specific antibody responses) were assessed. After completing the immunization schedule (three or six doses over 14 weeks) and a six-month follow-up, the patients were followed for 5 years for late toxicity, long-term immunogenicity, and clinical status. The immunizations were well tolerated, and increasing doses of dHER2 had no impact on the frequency or severity of adverse events. Few late toxicities were reported, and after 5 years 45/54 patients (83.3 %) were still alive, while 28/45 (62 %) with known disease status were disease free. Regarding the immunogenicity of the compound, a positive association was found between the dHER2 dose, the immunization schedule, and the prevalence of dHER2-specific humoral responses. Among the patients receiving the most intense immunization schedule with the highest dHER2 dose, 6/8 maintained their dHER2-specific antibody response 5 years after immunization. The dHER2 immunotherapeutic had an acceptable safety profile in early HER2-positive BC patients. dHER2-specific antibody responses were induced, with the rate of responders increasing with the dHER2 dose and the number and frequency of immunizations. PMID:26993131

  15. Phase 1, placebo-controlled, dose escalation trial of chicory root extract in patients with osteoarthritis of the hip or knee

    PubMed Central

    2010-01-01

    Background Extracts of chicory root have anti-inflammatory properties in vitro and in animal models of arthritis. The primary objective of this investigator-initiated, Phase 1, placebo-controlled, double blind, dose-escalating trial was to determine the safety and tolerability of a proprietary bioactive extract of chicory root in patients with osteoarthritis (OA). Secondary objectives were to assess effects on the signs and symptoms of this disorder. Methods Individuals greater than 50 years of age with OA of the hip or knee were eligible for trial entry. A total of 40 patients were enrolled in 3 cohorts and were treated with escalating chicory doses of 600 mg/day, 1200 mg/day and 1800 mg/day for 1 month. The ratio of active treatment to placebo was 5:3 in cohorts 1 and 2 (8 patients) each and 16:8 in cohort 3 (24 patients). Safety evaluations included measurement of vital signs and routine lab tests at baseline and the end of the treatment period. Efficacy evaluations at baseline and final visits included self-assessment questionnaires and measurement of the 25-foot walking time. Results In the highest dose cohort, 18 patients who completed treatment per protocol were analyzed for efficacy. In this group, 13 patients showed at least 20% improvement in the defined response domains of pain, stiffness and global assessment: 9 of 10 (90%) patients randomized to active treatment with chicory and 4 of 8 (50%) patients randomized to placebo (P = 0.06). In general, the treatment was well-tolerated. Only one patient who was treated with the highest dose of chicory had to discontinue treatment due to an adverse event. Conclusions The results of this pilot study suggest that a proprietary bioactive extract of chicory root has a potential role in the management of OA and merits further investigation. Clinicaltrials.gov identifier: NCT 01010919. PMID:20618964

  16. Phase IB randomized, double-blinded, placebo-controlled, dose escalation study of polyphenon E in women with hormone receptor-negative breast cancer.

    PubMed

    Crew, Katherine D; Brown, Powel; Greenlee, Heather; Bevers, Therese B; Arun, Banu; Hudis, Clifford; McArthur, Heather L; Chang, Jenny; Rimawi, Mothaffar; Vornik, Lana; Cornelison, Terri L; Wang, Antai; Hibshoosh, Hanina; Ahmed, Aqeel; Terry, Mary Beth; Santella, Regina M; Lippman, Scott M; Hershman, Dawn L

    2012-09-01

    Epidemiologic data support an inverse association between green tea intake and breast cancer risk, and numerous experimental studies have shown the antitumor effects of its main component, epigallocatechin gallate (EGCG). We conducted a phase IB dose escalation trial in women with a history of stage I to III hormone receptor-negative breast cancer of an oral green tea extract, polyphenon E (Poly E) 400, 600, 800 twice daily or matching placebo for 6 months. The primary endpoint was to determine the maximum tolerated dose (MTD), defined as the dose that causes 25% dose-limiting toxicity (DLT, grade ≥II). Assignment to dose level was based upon an adaptive design, the continual reassessment method. A mammogram and random core biopsy of the contralateral breast were obtained at baseline and 6 months and serial blood/urine collections every 2 months for biomarker analyses. Forty women were randomized: 10 to placebo, 30 to Poly E (16 at 400 mg, 11 at 600 mg, 3 at 800 mg). There was one DLT at 400 mg (grade III rectal bleeding), three DLTs at 600 mg (grade II weight gain, grade III indigestion and insomnia), and one DLT at 800 mg (grade III liver function abnormality). The DLT rate at 600 mg was 27% (3 of 11). Pharmacologic levels of total urinary tea polyphenols were achieved with all three dose levels of Poly E. Using a novel phase I trial design, we determined the MTD for Poly E to be 600 mg twice daily. This study highlights the importance of assessing toxicity for any chemopreventive agent being developed for chronic use in healthy individuals. PMID:22827973

  17. Phase IB Randomized, Double-Blinded, Placebo-Controlled, Dose Escalation Study of Polyphenon E in Women with Hormone Receptor-Negative Breast Cancer

    PubMed Central

    Crew, Katherine D.; Brown, Powel; Greenlee, Heather; Bevers, Therese B.; Arun, Banu; Hudis, Clifford; McArthur, Heather L.; Chang, Jenny; Rimawi, Mothaffar; Vornik, Lana; Cornelison, Terri L.; Wang, Antai; Hibshoosh, Hanina; Ahmed, Aqeel; Terry, Mary Beth; Santella, Regina M.; Lippman, Scott M.; Hershman, Dawn L.

    2013-01-01

    Epidemiologic data support an inverse association between green tea intake and breast cancer risk and numerous experimental studies have demonstrated the anti-tumor effects of its main component, epigallocatechin gallate (EGCG). We conducted a phase IB dose escalation trial in women with a history of stage I-III hormone receptor-negative breast cancer of an oral green tea extract, Polyphenon E (Poly E) 400mg, 600mg, 800mg bid or matching placebo for 6 months. The primary endpoint was to determine the maximum tolerated dose (MTD), defined as the dose that causes 25% dose limiting toxicity (DLT, grade≥2). Assignment to dose level was based upon an adaptive design, the continual reassessment method. A mammogram and random core biopsy of the contralateral breast were obtained at baseline and 6 months and serial blood/urine collections every 2 months for biomarker analyses. Forty women were randomized: 10 to placebo, 30 to Poly E (16 at 400mg, 11 at 600mg, 3 at 800mg). There was 1 DLT at 400mg (grade 3 rectal bleeding), 3 DLTs at 600mg (grade 2 weight gain, grade 3 indigestion and insomnia), and 1 DLT at 800mg (grade 3 liver function abnormality). The DLT rate at 600mg was 27% (3/11). Pharmacologic levels of total urinary tea polyphenols were achieved with all three dose levels of Poly E. Using a novel phase I trial design, we determined the MTD for Poly E to be 600mg bid. This study highlights the importance of assessing toxicity for any chemopreventive agent being developed for chronic use in healthy individuals. PMID:22827973

  18. Phase I Dose-Escalation Study of MEDI-573, a Bispecific, Antiligand Monoclonal Antibody against IGFI and IGFII, in Patients with Advanced Solid Tumors

    PubMed Central

    Haluska, Paul; Menefee, Michael; Plimack, Elizabeth R.; Rosenberg, Jonathan; Northfelt, Donald; LaVallee, Theresa; Shi, Li; Yu, Xiang-Qing; Burke, Patricia; Huang, Jaiqi; Viner, Jaye; McDevitt, Jennifer; LoRusso, Patricia

    2015-01-01

    Purpose This phase I, multicenter, open-label, single-arm, dose-escalation, and dose-expansion study evaluated the safety, tolerability, and antitumor activity of MEDI-573 in adults with advanced solid tumors refractory to standard therapy or for which no standard therapy exists. Experimental Design Patients received MEDI-573 in 1 of 5 cohorts (0.5, 1.5, 5, 10, or 15 mg/kg) dosed weekly or 1 of 2 cohorts (30 or 45 mg/kg) dosed every 3 weeks. Primary end points included the MEDI-573 safety profile, maximum tolerated dose (MTD), and optimal biologic dose (OBD). Secondary end points included MEDI-573 pharmacokinetics (PK), pharmacodynamics, immunogenicity, and antitumor activity. Results In total, 43 patients (20 with urothelial cancer) received MEDI-573. No dose-limiting toxicities were identified, and only 1 patient experienced hyperglycemia related to treatment. Elevations in levels of insulin and/or growth hormone were not observed. Adverse events observed in >10% of patients included fatigue, anorexia, nausea, diarrhea, and anemia. PK evaluation demonstrated that levels of MEDI-573 increased with dose at all dose levels tested. At doses >5 mg/kg, circulating levels of insulin-like growth factor (IGF)-I and IGFII were fully suppressed. Of 39 patients evaluable for response, none experienced partial or complete response and 13 had stable disease as best response. Conclusions The MTD of MEDI-573 was not reached. The OBD was 5 mg/kg weekly or 30 or 45 mg/kg every 3 weeks. MEDI-573 showed preliminary antitumor activity in a heavily pretreated population and had a favorable tolerability profile, with no notable perturbations in metabolic homeostasis. PMID:25024259

  19. Combination of Trabectedin and Gemcitabine for Advanced Soft Tissue Sarcomas: Results of a Phase I Dose Escalating Trial of the German Interdisciplinary Sarcoma Group (GISG)

    PubMed Central

    Kasper, Bernd; Reichardt, Peter; Pink, Daniel; Sommer, Michaela; Mathew, Monika; Rauch, Geraldine; Hohenberger, Peter

    2015-01-01

    Background: Evaluation of the potential efficacy and safety of combination therapies for advanced soft tissue sarcomas (STS) has increased substantially after approval of trabectedin and pazopanib. Trabectedin’s introduction in Europe in 2007 depended mainly on its activity in so-called L-sarcomas (liposarcoma and leiomyosarcoma); combination of trabectedin with other chemotherapies used in STS seems of particular interest. Methods: We initiated within the German Interdisciplinary Sarcoma Group (GISG) a phase I dose escalating trial evaluating the combination of trabectedin and gemcitabine in patients with advanced and/or metastatic L-sarcomas (GISG-02; ClinicalTrials.gov NCT01426633). Patients were treated with increasing doses of trabectedin and gemcitabine. The primary endpoint was to determine the maximum tolerated dose. Results: Five patients were included in the study. Two patients were treated on dose level 1 comprising trabectedin 0.9 mg/m2 on day 1 and gemcitabine 700 mg/m2 on days 1 + 8, every 3 weeks. Due to dose-limiting toxicity (DLT) in both patients (elevated transaminases and thrombocytopenia), an additional three patients were treated on dose level −1 with trabectedin 0.7 mg/m2 plus gemcitabine 700 mg/m2. Of these three patients, two demonstrated another DLT; therefore, the trial was stopped and none of the dose levels could be recommended for phase II testing. Conclusion: The GISG-02 phase I study was stopped with the conclusion that the combination of gemcitabine and trabectedin is generally not recommended for the treatment of patients with advanced and/or metastatic leiomyosarcoma or liposarcoma. Also, this phase I study strongly supports the necessity for careful evaluation of combination therapies. PMID:25591040

  20. A multicenter phase I/II dose escalation study of single-dose cidofovir gel for treatment of recurrent genital herpes.

    PubMed

    Sacks, S L; Shafran, S D; Diaz-Mitoma, F; Trottier, S; Sibbald, R G; Hughes, A; Safrin, S; Rudy, J; McGuire, B; Jaffe, H S

    1998-11-01

    A randomized, double-blind, clinic-initiated, sequential dose-escalation pilot study was performed to compare the safety and efficacy of single applications of 1, 3, and 5% cidofovir gel with placebo in the treatment of early, lesional, recurrent genital herpes at five Canadian outpatient sites. Ninety-six patients began treatment within 12 h of lesion appearance and were evaluated twice daily until healing of the lesion occurred. Cidofovir gel at all strengths significantly decreased the median time to negative virus culture in a dose-dependent fashion (3.0 days in the placebo group versus 2.2, 1.3, and 1.1 days in the 1, 3, and 5% cidofovir gel treatment groups, respectively; P = 0.02, 0.0001, and 0.0003, respectively). A trend toward a reduction in the median time to complete healing in association with treatment was present, but the differences were not statistically significant (5.0 days in the placebo group versus 4.3, 4.1, and 4.6 days in the 1, 3, and 5% cidofovir gel treatment groups, respectively). Application site reactions occurred in 3, 5, 19, and 22% of the patients in these four groups, respectively. Treatment-associated lesion recrudescence with delayed healing, which is suggestive of local toxicity, was observed in three patients treated with 5% cidofovir gel and one patient treated with 3% cidofovir gel. In summary, single-dose application of cidofovir gel confers a significant antiviral effect on lesions of recurrent genital herpes. Additional studies are warranted to further identify the optimal efficacious dose of cidofovir in association with the maximum gel strength that can be tolerated. PMID:9797239

  1. Assessment of Planning Target Volume Margins for Intensity-Modulated Radiotherapy of the Prostate Gland: Role of Daily Inter- and Intrafraction Motion

    SciTech Connect

    Tanyi, James A.; He, Tongming; Summers, Paige A.; Mburu, Ruth G.; Kato, Catherine M.; Rhodes, Stephen M.; Hung, Arthur Y.; Fuss, Martin

    2010-12-01

    Purpose: To determine planning target volume margins for prostate intensity-modulated radiotherapy based on inter- and intrafraction motion using four daily localization techniques: three-point skin mark alignment, volumetric imaging with bony landmark registration, volumetric imaging with implanted fiducial marker registration, and implanted electromagnetic transponders (beacons) detection. Methods and Materials: Fourteen patients who underwent definitive intensity-modulated radiotherapy for prostate cancer formed the basis of this study. Each patient was implanted with three electromagnetic transponders and underwent a course of 39 treatment fractions. Daily localization was based on three-point skin mark alignment followed by transponder detection and patient repositioning. Transponder positioning was verified by volumetric imaging with cone-beam computed tomography of the pelvis. Relative motion between the prostate gland and bony anatomy was quantified by offline analyses of daily cone-beam computed tomography. Intratreatment organ motion was monitored continuously by the Calypso (registered) System for quantification of intrafraction setup error. Results: As expected, setup error (that is, inter- plus intrafraction motion, unless otherwise stated) was largest with skin mark alignment, requiring margins of 7.5 mm, 11.4 mm, and 16.3 mm, in the lateral (LR), longitudinal (SI), and vertical (AP) directions, respectively. Margin requirements accounting for intrafraction motion were smallest for transponder detection localization techniques, requiring margins of 1.4 mm (LR), 2.6 mm (SI), and 2.3 mm (AP). Bony anatomy alignment required 2.1 mm (LR), 9.4 mm (SI), and 10.5 mm (AP), whereas image-guided marker alignment required 2.8 mm (LR), 3.7 mm (SI), and 3.2 mm (AP). No marker migration was observed in the cohort. Conclusion: Clinically feasible, rapid, and reliable tools such as the electromagnetic transponder detection system for pretreatment target localization

  2. Radiotherapy of Cervical Cancer.

    PubMed

    Vordermark, Dirk

    2016-01-01

    Curative-intent radical radiotherapy of cervical cancer consists of external-beam radiotherapy, brachytherapy, and concomitant chemotherapy with cisplatin. For each element, new developments aim to improve tumor control rates or treatment tolerance. Intensity-modulated radiotherapy (IMRT) has been shown to reduce gastrointestinal toxicity and can be used to selectively increase the radiotherapy dose. Individualized, image-guided brachytherapy enables better adaptation of high-dose volumes to the tumor extension. Intensification of concomitant or sequential systemic therapy is under evaluation. PMID:27614991

  3. Radiotherapy.

    PubMed

    Adamietz, Irenaus A

    2010-01-01

    The intrathoracic growth of the tumor causes several severe symptoms as cough, dyspnea, chest pain, hemoptysis, hoarseness, anorexia/nausea, and dysphagia. In patients with manifest or threatening symptoms radiotherapy (RT) as an effective measure should be implemented into the management concept. Palliative RT radiotherapy prefers short hypofractionated schemas (e.g. 10 x 3 Gy, 4 x 5 Gy, 2 x 8 Gy, 1 x 10 Gy). Careful radiation planning supports the precision of palliative RT and reduces significantly the complication rate. A good response and prolonged palliation effects (6-12 months) can be achieved in many cases. However, the minimum biologically equivalent dose should not be less than 35 Gy. RT produces a good outcome in all types of metastases of lung carcinoma. In emergencies like VCSS or spinal cord compression RT should be initiated immediately. The selection of the optimal therapy for locally advanced lung carcinoma with malignant airway obstruction is difficult. Both brachytherapy and percutaneous irradiation are effective, however published results including local a sum of response, functionality and life quality demonstrates more benefit by percutaneous RT. Due to different physical properties of these two methods the combination of brachytherapy and external beam irradiation may be advantageous. PMID:19955803

  4. Stereofluoroscopic image-guided robotic biopsy system

    NASA Astrophysics Data System (ADS)

    Shi, Minyan; Liu, Hong; Tao, Gang; Fajardo, Laurie L.

    1999-07-01

    This paper presents the key techniques of a stereo- fluoroscopic image-guided robotic biopsy system: 3D position reconstruction, 3D path planning, path registration and robot trajectory control with safety considerations. This system automatically adjusts the needle inserting path according to a real-time 3D position error feedback. This system is particularly applicable to the soft tissue and organ biopsy, with advantages of increased accuracy, short completion time and minimum invasiveness to the patient. Simulation shows the safety and accuracy of this robotic biopsy system.

  5. Using Generalized Equivalent Uniform Dose Atlases to Combine and Analyze Prospective Dosimetric and Radiation Pneumonitis Data From 2 Non-Small Cell Lung Cancer Dose Escalation Protocols

    SciTech Connect

    Liu Fan; Yorke, Ellen D.; Belderbos, Jose S.A.; Borst, Gerben R.; Rosenzweig, Kenneth E.; Lebesque, Joos V.; Jackson, Andrew

    2013-01-01

    Purpose: To demonstrate the use of generalized equivalent uniform dose (gEUD) atlas for data pooling in radiation pneumonitis (RP) modeling, to determine the dependence of RP on gEUD, to study the consistency between data sets, and to verify the increased statistical power of the combination. Methods and Materials: Patients enrolled in prospective phase I/II dose escalation studies of radiation therapy of non-small cell lung cancer at Memorial Sloan-Kettering Cancer Center (MSKCC) (78 pts) and the Netherlands Cancer Institute (NKI) (86 pts) were included; 10 (13%) and 14 (17%) experienced RP requiring steroids (RPS) within 6 months after treatment. gEUD was calculated from dose-volume histograms. Atlases for each data set were created using 1-Gy steps from exact gEUDs and RPS data. The Lyman-Kutcher-Burman model was fit to the atlas and exact gEUD data. Heterogeneity and inconsistency statistics for the fitted parameters were computed. gEUD maps of the probability of RPS rate {>=}20% were plotted. Results: The 2 data sets were homogeneous and consistent. The best fit values of the volume effect parameter a were small, with upper 95% confidence limit around 1.0 in the joint data. The likelihood profiles around the best fit a values were flat in all cases, making determination of the best fit a weak. All confidence intervals (CIs) were narrower in the joint than in the individual data sets. The minimum P value for correlations of gEUD with RPS in the joint data was .002, compared with P=.01 and .05 for MSKCC and NKI data sets, respectively. gEUD maps showed that at small a, RPS risk increases with gEUD. Conclusions: The atlas can be used to combine gEUD and RPS information from different institutions and model gEUD dependence of RPS. RPS has a large volume effect with the mean dose model barely included in the 95% CI. Data pooling increased statistical power.

  6. Quality of Life (QOL) Analysis of a Randomized Radiation Dose Escalation Non-Small Cell Lung Cancer (NSCLC) Study: Radiation Therapy Oncology Group (RTOG) Trial 0617

    PubMed Central

    Movsas, Benjamin; Hu, Chen; Sloan, Jeffrey; Bradley, Jeffrey; Komaki, Ritsuko; Masters, Gregory; Kavadi, Vivek; Narayan, Samir; Michalski, Jeff; Johnson, Douglas W.; Koprowski, Christopher; Curran, Walter J.; Garces, Yolanda I.; Gaur, Rakesh; Wynn, Raymond B.; Schallenkamp, John; Gelblum, Daphna Y.; MacRae, Robert M; Paulus, Rebecca; Choy, Hak

    2015-01-01

    Importance A recent randomized radiation dose escalation trial in unresectable stage III NSCLC showed a lower survival in the high-dose arm (74Gy vs. 60Gy) with concurrent chemotherapy. Quality of life (QOL), an important secondary endpoint, is presented here. Objective The primary QOL hypothesis predicted a clinically meaningful decline (CMD) in QOL via the Functional Assessment of Cancer Therapy-Lung Cancer Subscale (FACT-LCS) in the high-dose RT-arm at 3 months. Design RTOG 0617 was a randomized phase III study (conducted from Nov 2007 to Nov 2011) in stage III NSCLC using a 2×2 factorial design and stratified by histology, PET staging, performance status and radiation technique (3D-conformal RT [3DCRT] vs. intensity-modulated radiation [IMRT]). Setting 185 institutions in the USA and Canada. Participants Of 424 eligible stage III NSCLC patients randomized, 360 (85%) consented to QOL, of whom 313 (88%) completed baseline QOL assessments. Intervention for Clinical Trials 74Gy vs. 60Gy with concurrent and consolidation carboplatin/paclitaxel +/− cetuximab. Main Outcomes and Measures QOL was collected prospectively via FACT-Trial Outcome Index (FACT-TOI), equaling Physical-Well-Being (PWB) + Functional-Well-Being (FWB) + Lung Cancer Subscale (LCS). Data are presented at baseline & 3 and 12 months via minimal clinically meaningful changes of >=2 points for PWB, FWB or LCS or >=5 points for TOI. Results Patient demographics and baseline QOL scores were comparable between the 74Gy and 60Gy arms. Two-hundred-nineteen (72%) of living patients who completed QOL at baseline did so at 3 months and 137 (57%) of living patients did so at 12 months. Significantly more patients on 74Gy arm had clinically meaningful decline in FACT-LCS at 3 months than on the 60Gy arm (45% vs. 30%, p=0.02). At 12 months, fewer patients who received IMRT (vs 3DCRT) had clinically meaningful decline in FACT-LCS (21% vs 46%, p=0.003). Baseline FACT-TOI was associated with overall survival in

  7. Sifalimumab, a Human Anti–Interferon-α Monoclonal Antibody, in Systemic Lupus Erythematosus: A Phase I Randomized, Controlled, Dose-Escalation Study

    PubMed Central

    Petri, Michelle; Wallace, Daniel J; Spindler, Alberto; Chindalore, Vishala; Kalunian, Kenneth; Mysler, Eduardo; Neuwelt, C Michael; Robbie, Gabriel; White, Wendy I; Higgs, Brandon W; Yao, Yihong; Wang, Liangwei; Ethgen, Dominique; Greth, Warren

    2013-01-01

    Objective To evaluate the safety and tolerability of multiple intravenous (IV) doses of sifalimumab in adults with moderate-to-severe systemic lupus erythematosus (SLE). Methods In this multicenter, double-blind, placebo-controlled, sequential dose-escalation study, patients were randomized 3:1 to receive IV sifalimumab (0.3, 1.0, 3.0, or 10.0 mg/kg) or placebo every 2 weeks to week 26, then followed up for 24 weeks. Safety assessment included recording of treatment-emergent adverse events (AEs) and serious AEs. Pharmacokinetics, immunogenicity, and pharmacodynamics were evaluated, and disease activity was assessed. Results Of 161 patients, 121 received sifalimumab (26 received 0.3 mg/kg; 25, 1.0 mg/kg; 27, 3.0 mg/kg; and 43, 10 mg/kg) and 40 received placebo. Patients were predominantly female (95.7%). At baseline, patients had moderate-to-severe disease activity (mean SLE Disease Activity Index score 11.0), and most (75.2%) had a high type I interferon (IFN) gene signature. In the sifalimumab group versus the placebo group, the incidence of ≥1 treatment-emergent AE was 92.6% versus 95.0%, ≥1 serious AE was 22.3% versus 27.5%, and ≥1 infection was 67.8% versus 62.5%; discontinuations due to AEs occurred in 9.1% versus 7.5%, and death occurred in 3.3% (n = 4) versus 2.5% (n = 1). Serum sifalimumab concentrations increased in a linear and dose-proportional manner. Inhibition of the type I IFN gene signature was sustained during treatment in patients with a high baseline signature. No statistically significant differences in clinical activity (SLEDAI and British Isles Lupus Assessment Group score) between sifalimumab and placebo were observed. However, when adjusted for excess burst steroids, SLEDAI change from baseline showed a positive trend over time. A trend toward normal complement C3 or C4 level at week 26 was seen in the sifalimumab groups compared with baseline. Conclusion The observed safety/tolerability and clinical activity profile of sifalimumab

  8. Safety and Reactogenicity of an MSP-1 Malaria Vaccine Candidate: A Randomized Phase Ib Dose-Escalation Trial in Kenyan Children

    PubMed Central

    Withers, Mark R; McKinney, Denise; Ogutu, Bernhards R; Waitumbi, John N; Milman, Jessica B; Apollo, Odika J; Allen, Otieno G; Tucker, Kathryn; Soisson, Lorraine A; Diggs, Carter; Leach, Amanda; Wittes, Janet; Dubovsky, Filip; Stewart, V. Ann; Remich, Shon A; Cohen, Joe; Ballou, W. Ripley; Holland, Carolyn A; Lyon, Jeffrey A; Angov, Evelina; Stoute, José A; Martin, Samuel K; Heppner, D. Gray

    2006-01-01

    Objective: Our aim was to evaluate the safety, reactogenicity, and immunogenicity of an investigational malaria vaccine. Design: This was an age-stratified phase Ib, double-blind, randomized, controlled, dose-escalation trial. Children were recruited into one of three cohorts (dosage groups) and randomized in 2:1 fashion to receive either the test product or a comparator. Setting: The study was conducted in a rural population in Kombewa Division, western Kenya. Participants: Subjects were 135 children, aged 12–47 mo. Interventions: Subjects received 10, 25, or 50 μg of falciparum malaria protein 1 (FMP1) formulated in 100, 250, and 500 μL, respectively, of AS02A, or they received a comparator (Imovax® rabies vaccine). Outcome Measures: We performed safety and reactogenicity parameters and assessment of adverse events during solicited (7 d) and unsolicited (30 d) periods after each vaccination. Serious adverse events were monitored for 6 mo after the last vaccination. Results: Both vaccines were safe and well tolerated. FMP1/AS02A recipients experienced significantly more pain and injection-site swelling with a dose-effect relationship. Systemic reactogenicity was low at all dose levels. Hemoglobin levels remained stable and similar across arms. Baseline geometric mean titers were comparable in all groups. Anti-FMP1 antibody titers increased in a dose-dependent manner in subjects receiving FMP1/AS02A; no increase in anti-FMP1 titers occurred in subjects who received the comparator. By study end, subjects who received either 25 or 50 μg of FMP1 had similar antibody levels, which remained significantly higher than that of those who received the comparator or 10 μg of FMP1. A longitudinal mixed effects model showed a statistically significant effect of dosage level on immune response (F3,1047 = 10.78, or F3, 995 = 11.22, p < 0.001); however, the comparison of 25 μg and 50 μg recipients indicated no significant difference (F1,1047 = 0.05; p = 0.82). Conclusions

  9. A phase I/II trial of stereotactic body radiation therapy (SBRT) for lung metastases: Initial report of dose escalation and early toxicity

    SciTech Connect

    Schefter, Tracey E. . E-mail: Tracey.Schefter@uchsc.edu; Kavanagh, Brian D.; Raben, David; Kane, Madeleine; Chen Changhu; Stuhr, Kelly; Kelly, Karen; Mitchell, John D.; Bunn, Paul A.; Gaspar, Laurie E.

    2006-11-15

    Purpose: To determine the maximum tolerated dose (MTD) of stereotactic body radiation therapy (SBRT) for lung metastases. Methods and Materials: A Phase I clinical trial was conducted. Eligible patients had one to three pulmonary metastases from a solid tumor, cumulative tumor diameter <7 cm, and adequate pulmonary function (forced expiratory volume in 1 s {>=}1.0 L). The planning target volume (PTV) was typically constructed from the gross tumor volume (GTV) by adding a 5-mm radial and 10-mm craniocaudal margin. The first cohort received 48 Gy to the PTV in three fractions (F). SBRT dose was escalated in subsequent cohorts up to a preselected maximum of 60 Gy/3 F. The percent of normal lung receiving more than 15 Gy (V{sub 15}) was restricted to less than 35%. Respiratory control and a dynamic conformal arc SBRT technique were used. Dose-limiting toxicity (DLT) included acute Grade 3 lung or esophageal toxicity or any acute Grade 4 toxicity within 3 months. After the Phase I dose escalation, the trial continued as a Phase II study, and patients in this cohort are included to increase the number of patients evaluable for early toxicity assessment. Results: Twenty-five eligible patients have been enrolled to date. In the Phase I component of the trial, there were 12 patients (7 male, 5 female): median age, 55 years (range, 31-83 years); the most common primary site was colorectal (4 patients). Seven patients had two lung lesions, and 1 patient had three lesions. The median aggregate volume of all GTVs was 18.7 mL (range, 2-40 mL). No patient experienced a DLT, and dose was escalated to 60 Gy/3 F without reaching the MTD; including the additional Phase II cohort patients, 16 patients have been treated to a dose of 60 Gy/3F without experiencing a DLT in the first 3 months. The equivalent uniform dose to the GTV in the highest dose group ranged from 66 to 77 Gy in 3 F. Conclusions: In patients with limited pulmonary metastases, radiobiologically potent doses of SBRT

  10. Gleason Pattern 5 Is the Greatest Risk Factor for Clinical Failure and Death From Prostate Cancer After Dose-Escalated Radiation Therapy and Hormonal Ablation

    SciTech Connect

    Sabolch, Aaron; Feng, Felix Y.; Daignault-Newton, Stephanie; Halverson, Schuyler; Blas, Kevin; Phelps, Laura; Olson, Karin B.; Sandler, Howard M.; Hamstra, Daniel A.

    2011-11-15

    Purpose: The division of Gleason score (GS) into three categories (2-6, 7, 8-10) may not fully use its prognostic power, as revealed by recent reports demonstrating the presence of Gleason Pattern 5 (GP5) as a strong predictor for biochemical recurrence. Therefore, we analyzed the clinical outcomes in patients treated with dose-escalated radiation therapy (RT) based on the presence or absence of GP5. Methods and Materials: Outcomes were analyzed for 718 men treated for localized prostate cancer with external-beam RT to a minimum planning target volume dose of at least 75 Gy. We assessed the impact of GP5 and that of pretreatment- and treatment-related factors on freedom from biochemical failure, freedom from metastasis (FFM), cause-specific survival (CSS), and overall survival (OS). Results: At biopsy, 89% of patients had no GP5, and 11% (76/718) had GP5. There were no differences in age, comorbid illness, T stage, prostate-specific antigen, or the use or duration of androgen deprivation therapy between GS8 without GP5 and GS8-10 with GP5. The presence of GP5 predicted lower FFM (p < 0.002; hazard ratio [HR] 3.4 [1.7-7.1]); CSS (p < 0.0001; HR 12.9 [5.4-31]); and OS (p < 0.0001; HR 3.6 [2.0-6.5]) in comparison with GS8 (without GP5). The 8-year FFM, CSS, and OS were 89%, 98%, and 57%, respectively, for those with Gleason 8 prostate cancer without GP5 in comparison with 61%, 55%, and 31%, respectively, for those with GP5. In addition, both FFM and CSS were strongly influenced by androgen deprivation therapy given concurrently with RT. On multivariate analysis, GP5 was the strongest prognostic factor for all clinical endpoints, including OS. Conclusion: The presence of GP5 predicts for worse clinical behavior, which therefore needs to be accounted for by risk stratification schemes. Further intensification of local and/or systemic therapy may be appropriate for such patients.

  11. Safety and Pharmacokinetics of Isavuconazole as Antifungal Prophylaxis in Acute Myeloid Leukemia Patients with Neutropenia: Results of a Phase 2, Dose Escalation Study

    PubMed Central

    Cornely, Oliver A.; Böhme, Angelika; Schmitt-Hoffmann, Anne

    2015-01-01

    Isavuconazole is a novel broad-spectrum triazole antifungal agent. This open-label dose escalation study assessed the safety and pharmacokinetics of intravenous isavuconazole prophylaxis in patients with acute myeloid leukemia who had undergone chemotherapy and had preexisting/expected neutropenia. Twenty-four patients were enrolled, and 20 patients completed the study. The patients in the low-dose cohort (n = 11) received isavuconazole loading doses on day 1 (400/200/200 mg, 6 h apart) and day 2 (200/200 mg, 12 h apart), followed by once-daily maintenance dosing (200 mg) on days 3 to 28. The loading and maintenance doses were doubled in the high-dose cohort (n = 12). The mean ± standard deviation plasma isavuconazole areas under the concentration-time curves for the dosing period on day 7 were 60.1 ± 22.3 μg · h/ml and 113.1 ± 19.6 μg · h/ml for the patients in the low-dose and high-dose cohorts, respectively. The adverse events in five patients in the low-dose cohort and in eight patients in the high-dose cohort were considered to be drug related. Most were mild to moderate in severity, and the most common adverse events were headache and rash (n = 3 each). One patient in the high-dose cohort experienced a serious adverse event (unrelated to isavuconazole treatment), and two patients each in the low-dose and high-dose cohorts discontinued the study due to adverse events. Of the 20 patients who completed the study, 18 were classified as a treatment success. In summary, the results of this analysis support the safety and tolerability of isavuconazole administered at 200 mg and 400 mg once-daily as prophylaxis in immunosuppressed patients at high risk of fungal infections. (This study is registered at ClinicalTrials.gov under registration number NCT00413439.) PMID:25624327

  12. Method comparison of ultrasound and kilovoltage x-ray fiducial marker imaging for prostate radiotherapy targeting.

    PubMed

    Fuller, Clifton David; Thomas, Charles R; Schwartz, Scott; Golden, Nanalei; Ting, Joe; Wong, Adrian; Erdogmus, Deniz; Scarbrough, Todd J

    2006-10-01

    Several measurement techniques have been developed to address the capability for target volume reduction via target localization in image-guided radiotherapy; among these have been ultrasound (US) and fiducial marker (FM) software-assisted localization. In order to assess interchangeability between methods, US and FM localization were compared using established techniques for determination of agreement between measurement methods when a 'gold-standard' comparator does not exist, after performing both techniques daily on a sequential series of patients. At least 3 days prior to CT simulation, four gold seeds were placed within the prostate. FM software-assisted localization utilized the ExacTrac X-Ray 6D (BrainLab AG, Germany) kVp x-ray image acquisition system to determine prostate position; US prostate targeting was performed on each patient using the SonArray (Varian, Palo Alto, CA). Patients were aligned daily using laser alignment of skin marks. Directional shifts were then calculated by each respective system in the X, Y and Z dimensions before each daily treatment fraction, previous to any treatment or couch adjustment, as well as a composite vector of displacement. Directional shift agreement in each axis was compared using Altman-Bland limits of agreement, Lin's concordance coefficient with Partik's grading schema, and Deming orthogonal bias-weighted correlation methodology. 1,019 software-assisted shifts were suggested by US and FM in 39 patients. The 95% limits of agreement in X, Y and Z axes were +/-9.4 mm, +/-11.3 mm and +/-13.4, respectively. Three-dimensionally, measurements agreed within 13.4 mm in 95% of all paired measures. In all axes, concordance was graded as 'poor' or 'unacceptable'. Deming regression detected proportional bias in both directional axes and three-dimensional vectors. Our data suggest substantial differences between US and FM image-guided measures and subsequent suggested directional shifts. Analysis reveals that the vast

  13. Image-Guided Spinal Ablation: A Review.

    PubMed

    Tsoumakidou, Georgia; Koch, Guillaume; Caudrelier, Jean; Garnon, Julien; Cazzato, Roberto Luigi; Edalat, Faramarz; Gangi, Afshin

    2016-09-01

    The image-guided thermal ablation procedures can be used to treat a variety of benign and malignant spinal tumours. Small size osteoid osteoma can be treated with laser or radiofrequency. Larger tumours (osteoblastoma, aneurysmal bone cyst and metastasis) can be addressed with radiofrequency or cryoablation. Results on the literature of spinal microwave ablation are scarce, and thus it should be used with caution. A distinct advantage of cryoablation is the ability to monitor the ice-ball by intermittent CT or MRI. The different thermal insulation, temperature and electrophysiological monitoring techniques should be applied. Cautious pre-procedural planning and intermittent intra-procedural monitoring of the ablation zone can help reduce neural complications. Tumour histology, patient clinical-functional status and life-expectancy should define the most efficient and least disabling treatment option. PMID:27329231

  14. A multicenter phase 1/2a dose-escalation study of the antioxidant moiety of vitamin E 2,2,5,7,8-pentamethyl-6-chromanol (APC-100) in men with advanced prostate cancer.

    PubMed

    Kyriakopoulos, Christos E; Heath, Elisabeth I; Eickhoff, Jens C; Kolesar, Jill; Yayehyirad, Mulusew; Moll, Thomas; Wilding, George; Liu, Glenn

    2016-04-01

    Background A phase 1/2a dose escalation study of APC-100 (2,2,5,7,8-Pentamethyl-6-chromanol) was conducted to determine maximum tolerated dose (MTD), recommended phase 2 dose, toxicities and efficacy in men with castrate-resistant prostate cancer (CRPC). Methods This open label phase 1/2a study utilizes a time-to-event reassessment method (TITE-CRM) design. Patients in cohorts of 3 were treated with escalating doses of APC-100 (900 mg-2400 mg) orally once daily continuously. Cycles were 28 days. Results Twenty patients with CRPC were enrolled in the dose escalation cohort. One possible DLT (elevated ALT) was seen at dose level 1. No other DLTs were seen and no dose reductions were required. Most frequent AEs included nausea (grade 1 in 6 patients) and elevated transaminases (grade 1-3 in 5 patients). After enrolment of 20 patients the MTD was not reached, however the maximal feasible dose was exceeded due to the number of capsules ingested. Five of the 20 patients had stable disease as their best response. The median progression free survival (PFS) for the cohort was 2.8 months (range 1-8). Conclusions APC-100 is a novel agent with dual mechanism of action functioning both as potent antioxidant as well as antiandrogen. No detectable APC-100 was found in the plasma at dose level 5 (2100 mg) and it was felt that maximal feasibility was nearly reached. APC-100 is being reformulated as a tablet to allow further dose escalation. Once a recommended phase 2 dose is established, future studies in prostate cancer chemoprevention should be conducted. PMID:26924129

  15. A phase I dose-escalation trial of high-dose melphalan with palifermin for cytoprotection followed by autologous stem cell transplantation for patients with multiple myeloma with normal renal function.

    PubMed

    Abidi, Muneer H; Agarwal, Rishi; Tageja, Nishant; Ayash, Lois; Deol, Abhinav; Al-Kadhimi, Zaid; Abrams, Judith; Cronin, Simon; Ventimiglia, Marie; Lum, Lawrence; Ratanatharathorn, Voravit; Zonder, Jeffrey; Uberti, Joseph

    2013-01-01

    Melphalan 200 mg/m(2) is the standard conditioning regimen for patients with multiple myeloma (MM) with normal renal function (NRF) undergoing autologous stem cell transplant (ASCT). In an effort to escalate the dose of melphalan and to improve the efficacy, we designed a dose-escalation study of melphalan in conjunction with palifermin in patients with NRF, with the hope that a higher dose of melphalan can be administered with an acceptable degree of oral mucositis (OM). We enrolled 19 patients (18 evaluable) with NRF. Dose-escalation of melphalan administered on day -2 began at 200 mg/m(2) with palifermin administered at a fixed dose of 60 mcg/kg/day. Palifermin was given as an i.v. bolus on day -5, -4, and -3, and then on day +1, +2, and +3. Subsequent dose escalations of melphalan were done at 20 mg/m(2) increments up to a maximum dose of 280 mg/m(2). Of 18 evaluable patients, there were no treatment-related deaths by day 100. The median age was 48.5 years (range, 33-65 years). The most common adverse events related to palifermin included rash (18 events, no ≥ grade 3 events), elevation of amylase (10 events, 4 were grade 3 but asymptomatic), and lipase (5 events, 2 were grade 3 but asymptomatic), edema (11 events, no ≥ grade 3). The overall incidence of OM grade 3 was 44% (8/18) with a median duration of severe mucositis of 5 days (range, 3-6 days). Eleven patients (61%) required opioid analgesics. None of the patients received total parenteral nutrition (TPN)/nasogastric feeding. Two of 6 patients who were given melphalan 280 mg/m(2) did not develop OM. Cardiac dose-limiting toxicity (DLT) in the form of atrial fibrillation did occur in 1 of 6 patients treated with melphalan 280 mg/m(2). Palifermin has permitted safe dose escalation of melphalan up to 280 mg/m(2), thus reaching the cumulative dosage of melphalan administered in tandem ASCT. This higher dose of melphalan has the potential to improve the efficacy and, hopefully, outcomes of patients with MM

  16. Is Intermediate Radiation Dose Escalation With Concurrent Chemotherapy for Stage III Non–Small-Cell Lung Cancer Beneficial? A Multi-Institutional Propensity Score Matched Analysis

    SciTech Connect

    Rodrigues, George; Oberije, Cary; Senan, Suresh; Tsujino, Kayoko; Wiersma, Terry; Moreno-Jimenez, Marta; Kim, Tae Hyun; Marks, Lawrence B.; Rengan, Ramesh; De Petris, Luigi; Ramella, Sara; DeRuyck, Kim; De Dios, Núria Rodriguez; Warner, Andrew; Bradley, Jeffrey D.; Palma, David A.

    2015-01-01

    Purpose: The clinical benefits and risks of dose escalation (DE) for stage III non–small-cell lung cancer (NSCLC) remain uncertain despite the results from Radiation Therapy Oncology Group (RTOG) protocol 0617. There is significant heterogeneity of practice, with many clinicians prescribing intermediate dose levels between the 0617 study arms of 60 and 74 Gy. This study investigated whether this strategy is associated with any survival benefits/risks by analyzing a large multi-institutional database. Methods and Materials: An individual patient database of stage III NSCLC patients treated with radical intent concurrent chemoradiation therapy was created (13 institutions, n=1274 patients). Patients were divided into 2 groups based on tumor Biological Effective Dose at 10 Gy (BED 10): those receiving standard dose (SD; n=552), consisting of 72Gy ≤ BED 10 ≤ 76.8 Gy (eg 60-64 Gy/30-32 fractions [fr]), and those receiving intermediate dose (ID; n=497), consisting of 76.8Gy < BED 10 < 100.8 Gy (eg >64 Gy/32 fr and <74 Gy/37 fr), with lower-dose patients (n=225) excluded from consideration. Patients were then matched using propensity scores, leading to 2 matched groups of 196 patients. Outcomes were compared using various statistics including interquartile range (IQR), Kaplan-Meier curves, and adjusted Cox regression analysis. Results: Matched groups were found to be balanced except for N stage (more N3 disease in SD), median treatment year (SD in 2003; ID in 2007), platinum and taxane chemotherapy (SD in 28%; ID in 39%), and median follow-up (SD were 89 months; ID were 40 months). Median dose fractionation was 60 Gy/30 fr in SD (BED 10 IQR: 72.0-75.5 Gy) and 66 Gy/33 fr (BED 10 IQR: 78.6-79.2 Gy) in ID. Survival curves for SD and ID matched cohorts were statistically similar (P=.27); however, a nonstatistically significant trend toward better survival for ID was observed after 15 months (median survival SD: 19.3 months; ID: 21.0

  17. IMRT for Image-Guided Single Vocal Cord Irradiation

    SciTech Connect

    Osman, Sarah O.S.; Astreinidou, Eleftheria; Boer, Hans C.J. de; Keskin-Cambay, Fatma; Breedveld, Sebastiaan; Voet, Peter; Al-Mamgani, Abrahim; Heijmen, Ben J.M.; Levendag, Peter C.

    2012-02-01

    Purpose: We have been developing an image-guided single vocal cord irradiation technique to treat patients with stage T1a glottic carcinoma. In the present study, we compared the dose coverage to the affected vocal cord and the dose delivered to the organs at risk using conventional, intensity-modulated radiotherapy (IMRT) coplanar, and IMRT non-coplanar techniques. Methods and Materials: For 10 patients, conventional treatment plans using two laterally opposed wedged 6-MV photon beams were calculated in XiO (Elekta-CMS treatment planning system). An in-house IMRT/beam angle optimization algorithm was used to obtain the coplanar and non-coplanar optimized beam angles. Using these angles, the IMRT plans were generated in Monaco (IMRT treatment planning system, Elekta-CMS) with the implemented Monte Carlo dose calculation algorithm. The organs at risk included the contralateral vocal cord, arytenoids, swallowing muscles, carotid arteries, and spinal cord. The prescription dose was 66 Gy in 33 fractions. Results: For the conventional plans and coplanar and non-coplanar IMRT plans, the population-averaged mean dose {+-} standard deviation to the planning target volume was 67 {+-} 1 Gy. The contralateral vocal cord dose was reduced from 66 {+-} 1 Gy in the conventional plans to 39 {+-} 8 Gy and 36 {+-} 6 Gy in the coplanar and non-coplanar IMRT plans, respectively. IMRT consistently reduced the doses to the other organs at risk. Conclusions: Single vocal cord irradiation with IMRT resulted in good target coverage and provided significant sparing of the critical structures. This has the potential to improve the quality-of-life outcomes after RT and maintain the same local control rates.

  18. Interactive image-guided hepatic surgery

    NASA Astrophysics Data System (ADS)

    Stefansic, James D.; Herline, Alan J.; Bass, W. Andrew; Chapman, William C.; Galloway, Robert L., Jr.

    1999-05-01

    While laparoscopes are used for numerous minimally invasive procedures, minimally invasive liver resection and ablation occur infrequently. the paucity of cases is due to limited field of view and difficulty in determination of tumor location and margins under video guidance. By merging minimally invasive surgery with interactive, image-guided surgery, we hope to make laparoscopic liver procedures feasible. In previous work, we described methods for tracking an endoscope accurately in patient space and registration between endoscopic image space and physical space using the direct linear transformation (DLT). We have now developed a PC-based software system to display up to four 512 Χ 512 images indicating current surgical position using an active optical tracking system. We have used this system in several open liver cases and believe that a surface-based registration technique can be used to register physical space to tomographic space after liver mobilization. For preliminary phantom liver studies, our registration error is approximately 2.0mm. The surface-based registration technique will allow better localization of non-visible liver tumors, more accurate probe placement for ablation procedures, and more accurate margin determination for open surgical liver cases. The surface-based registration technique will allow better localization of non-visible liver tumors, more accurate probe placement for ablation procedures, and more accurate margin determination for open surgical liver cases. The surface-based/DLT registration methods, in combination with the video display and tracked endoscope, will hopefully make laparoscopic liver cryoablation and resection procedures feasible.

  19. Motion compensated SLAM for image guided surgery.

    PubMed

    Mountney, Peter; Yang, Guang-Zhong

    2010-01-01

    The effectiveness and clinical benefits of image guided surgery are well established for procedures where there is manageable tissue motion. In minimally invasive cardiac, gastrointestinal, or abdominal surgery, large scale tissue deformation prohibits accurate registration and fusion of pre- and intraoperative data. Vision based techniques such as structure from motion and simultaneous localization and mapping are capable of recovering 3D structure and laparoscope motion. Current research in the area generally assumes the environment is static, which is difficult to satisfy in most surgical procedures. In this paper, a novel framework for simultaneous online estimation of laparoscopic camera motion and tissue deformation in a dynamic environment is proposed. The method only relies on images captured by the laparoscope to sequentially and incrementally generate a dynamic 3D map of tissue motion that can be co-registered with pre-operative data. The theoretical contribution of this paper is validated with both simulated and ex vivo data. The practical application of the technique is further demonstrated on in vivo procedures. PMID:20879352

  20. An EW technology research of jamming IR imaging guided missiles

    NASA Astrophysics Data System (ADS)

    Wu, Xiu-qin; Rong, Hua; Liang, Jing-ping; Chen, Qi; Chen, Min-rong

    2009-07-01

    The IR-Imaging-Guided Weapons have been playing an important role in the modern warfare by means of select attacking the vital parts of targets with the features of highly secret attacking, high precision, and excellent anti-jamming capability ,therefore, they are viewed to be one of the promising precisely guided weapons ,receiving great concern through out the world. This paper discusses the characteristics of IR-Imaging guidance systems at the highlight of making a study of correlated technologies of jamming IR-Imaging-Guided Weapons on the basis of elaborating the operational principles of IR-Imaging-guided Weapons.

  1. Use of an image-guided robotic radiosurgery system for the treatment of canine nonlymphomatous nasal tumors.

    PubMed

    Glasser, Seth A; Charney, Sarah; Dervisis, Nikolaos G; Witten, Matthew R; Ettinger, Susan; Berg, Jason; Joseph, Richard

    2014-01-01

    An image-guided robotic stereotactic radiosurgery (SRS) system can be used to deliver curative-intent radiation in either single fraction or hypofractionated doses. Medical records for 19 dogs with nonlymphomatous nasal tumors treated with hypofractionated image-guided robotic stereotactic body radiotherapy (SBRT), either with or without adjunctive treatment, were retrospectively analyzed for survival and prognostic factors. Median survival time (MST) was evaluated using Kaplan-Meier survival curves. Age, breed, tumor type, stage, tumor size, prescribed radiation dose, and heterogeneity index were analyzed for prognostic significance. Dogs were treated with three consecutive-day, 8-12 gray (Gy) fractions of image-guided robotic SBRT. Overall MST was 399 days. No significant prognostic factors were identified. Acute side effects were rare and mild. Late side effects included one dog with an oronasal fistula and six dogs with seizures. In three of six dogs, seizures were a presenting complaint prior to SBRT. The cause of seizures in the remaining three dogs could not be definitively determined due to lack of follow-up computed tomography (CT) imaging. The seizures could have been related to either progression of disease or late radiation effect. Results indicate that image-guided robotic SBRT, either with or without adjunctive therapy, for canine nonlymphomatous nasal tumors provides comparable survival times (STs) to daily fractionated megavoltage radiation with fewer required fractions and fewer acute side effects. PMID:24446402

  2. Treatment Planning Study to Determine Potential Benefit of Intensity-Modulated Radiotherapy Versus Conformal Radiotherapy for Unresectable Hepatic Malignancies

    SciTech Connect

    Eccles, Cynthia L.; Bissonnette, Jean-Pierre; Craig, Tim; Taremi, Mojgan; Wu Xia; Dawson, Laura A.

    2008-10-01

    Purpose: To compare intensity-modulated radiotherapy (IMRT) with conformal RT (CRT) for hypofractionated isotoxicity liver RT and explore dose escalation using IMRT for the same/improved nominal risk of liver toxicity in a treatment planning study. Methods and Materials: A total of 26 CRT plans were evaluated. Prescription doses (24-54 Gy within six fractions) were individualized on the basis of the effective liver volume irradiated maintaining {<=}5% risk of radiation-induced liver disease. The dose constraints included bowel (0.5 cm{sup 3}) and stomach (0.5 cm{sup 3}) to {<=}30 Gy, spinal cord to {<=}25 Gy, and planning target volume (PTV) to {<=}140% of the prescribed dose. Two groups were evaluated: (1) PTV overlapping or directly adjacent to serial functioning normal tissues (n = 14), and (2) the liver as the dose-limiting normal tissue (n = 12). IMRT plans using direct machine parameter optimization maintained the CRT plan beam arrangements, an estimated radiation-induced liver disease risk of 5%, and underwent dose escalation, if all normal tissue constraints were maintained. Results: IMRT improved PTV coverage in 19 of 26 plans (73%). Dose escalation was feasible in 9 cases by an average of 3.8 Gy (range, 0.6-13.2) in six fractions. Three of seven plans without improved PTV coverage had small gross tumor volumes ({<=}105 cm{sup 3}) already receiving 54 Gy, the maximal prescription dose allowed. In the remaining cases, the PTV range was 9.6-689 cm{sup 3}; two had overlapped organs at risk; and one had four targets. IMRT did not improve these plans owing to poor target coverage (n = 2) and nonliver (n = 2) dose limits. Conclusion: Direct machine parameter optimization IMRT improved PTV coverage while maintaining normal tissue tolerances in most CRT liver plans. Dose escalation was possible in a minority of patients.

  3. Functional and molecular image guidance in radiotherapy treatment planning optimization.

    PubMed

    Das, Shiva K; Ten Haken, Randall K

    2011-04-01

    Functional and molecular imaging techniques are increasingly being developed and used to quantitatively map the spatial distribution of parameters, such as metabolism, proliferation, hypoxia, perfusion, and ventilation, onto anatomically imaged normal organs and tumor. In radiotherapy optimization, these imaging modalities offer the promise of increased dose sparing to high-functioning subregions of normal organs or dose escalation to selected subregions of the tumor as well as the potential to adapt radiotherapy to functional changes that occur during the course of treatment. The practical use of functional/molecular imaging in radiotherapy optimization must take into cautious consideration several factors whose influences are still not clearly quantified or well understood including patient positioning differences between the planning computed tomography and functional/molecular imaging sessions, image reconstruction parameters and techniques, image registration, target/normal organ functional segmentation, the relationship governing the dose escalation/sparing warranted by the functional/molecular image intensity map, and radiotherapy-induced changes in the image intensity map over the course of treatment. The clinical benefit of functional/molecular image guidance in the form of improved local control or decreased normal organ toxicity has yet to be shown and awaits prospective clinical trials addressing this issue. PMID:21356479

  4. Evaluation of Image-Guided Positioning for Frameless Intracranial Radiosurgery

    SciTech Connect

    Lamba, Michael Breneman, John C.; Warnick, Ronald E.

    2009-07-01

    Purpose: The standard for target alignment and immobilization in intracranial radiosurgery is frame-based alignment and rigid immobilization using a stereotactic head ring. Recent improvements in image-guidance systems have introduced the possibility of image-guided radiosurgery with nonrigid immobilization. We present data on the alignment accuracy and patient stability of a frameless image-guided system. Methods and Materials: Isocenter alignment errors were measured for in vitro studies in an anthropomorphic phantom for both frame-based stereotactic and frameless image-guided alignment. Subsequently, in vivo studies assessed differences between frame-based and image-guided alignment in patients who underwent frame-based intracranial radiosurgery. Finally, intratreatment target stability was determined by image-guided alignment performed before and after image-guided mask immobilized radiosurgery. Results: In vitro hidden target localization errors were comparable for the framed (0.7 {+-} 0.5 mm) and image-guided (0.6 {+-} 0.2 mm) techniques. The in vivo differences in alignment were 0.9 {+-} 0.5 mm (anteroposterior), -0.2 {+-} 0.4 mm (superoinferior), and 0.3 {+-} 0.5 mm (lateral). For in vivo stability tests, the mean distance differed between the pre- and post-treatment positions with mask-immobilized radiosurgery by 0.5 {+-} 0.3 mm. Conclusion: Frame-based and image-guided alignment accuracy in vitro was comparable for the system tested. In vivo tests showed a consistent trend in the difference of alignment in the anteroposterior direction, possibly due to torque to the ring and mounting system with frame-based localization. The mask system as used appeared adequate for patient immobilization.

  5. Stereotactic body radiotherapy for prostate cancer.

    PubMed

    Henderson, D R; Tree, A C; van As, N J

    2015-05-01

    The use of stereotactic body radiotherapy (SBRT) for localised prostate cancer is now supported by a substantial body of non-randomised data, with medium-term outcomes consistent with current standard radiotherapy. The ability to deliver profoundly hypofractionated treatment, combined with the relatively low α/β ratio of prostate cancer, may result in a more favourable therapeutic ratio, presenting an opportunity for isotoxic dose escalation. Furthermore, as treatment can be given in five attendances, SBRT has the potential both to reduce costs and improve patient quality of life. However, in a treatment landscape with many competing options of broadly similar efficacy, randomised trials are essential to define the relative benefits of this approach. SBRT also has an emerging application in oligometastatic prostate cancer, with promising early outcomes for delaying disease progression and deferring the need for androgen deprivation therapy. PMID:25707911

  6. Clinical Implication of UGT1A1 Promoter Polymorphism for Irinotecan Dose Escalation in Metastatic Colorectal Cancer Patients Treated with Bevacizumab Combined with FOLFIRI in the First-line Setting12

    PubMed Central

    Lu, Chien-Yu; Huang, Ching-Wen; Wu, I-Chen; Tsai, Hsiang-Lin; Ma, Cheng-Jen; Yeh, Yung-Sung; Chang, Se-Fen; Huang, Meng-Lin; Wang, Jaw-Yuan

    2015-01-01

    PURPOSE: This study aimed to identify the efficacy and toxicity of the FOLFIRI regimen (fluorouracil, leucovorin, and irinotecan) with irinotecan dose escalation plus bevacizumab as first-line chemotherapy for metastatic colorectal cancer (mCRC) via UGT1A1 genotyping. METHODS: We administered bevacizumab plus FOLFIRI with irinotecan dose escalation to treat 70 mCRC patients. The UGT1A1 *1/*1 and *1/*28 genotypes started with a 180-mg/m2 dose of irinotecan, and UGT1A1 *28/*28 genotype started with a dose of 120 mg/m2. The dose of irinotecan was escalated at increasing intervals of 20 to 30 mg/m2 until grade 3/4 adverse events (AEs) occurred. The clinical response rate, toxicity, and survival were analyzed. RESULTS: The clinical response and disease control rates of mCRC patients treated with FOLFIRI plus bevacizumab were significantly better in patients with UGT1A1 *1/*1 and *1/*28 genotypes than in patients with UGT1A1 *28/*28 (P = .006 and P < .001, respectively). Grade 3/4 AEs were significantly more common in mCRC patients with the UGT1A1 *28/*28 genotype (P < .001). Progression-free survival was significantly higher in UGT1A1 *1/*1 and *1/*28 patients (P = .002). mCRC patients who underwent metastasectomy achieved better overall survival than those who did not undergo metastasectomy (P = .015). CONCLUSIONS: Our study showed that mCRC patients with UGT1A1 *1/*1 and *1/*28 genotypes could receive escalated doses of irinotecan to obtain a more favorable clinical outcome without significant AEs. PMID:26692528

  7. A phase I clinical trial of dose escalation of lobaplatin in combination with fixed-dose docetaxel for the treatment of human solid tumours that had progressed following chemotherapy.

    PubMed

    Peng, Yu; Liu, Yue-E; Ren, Xiao-Can; Chen, Xue-Ji; Su, Hui-Ling; Zong, Jie; Feng, Zeng-Li; Wang, Dong-Ying; Lin, Qiang; Gao, Xian-Shu

    2015-01-01

    In this study, the maximum tolerated dose (MTD) of lobaplatin (LBP) when it was combined with docetaxel (TXT) for the treatment of solid tumours that had progressed following chemotherapy was determined, and toxicities to this regimen were evaluated. A modified Fibonacci method was used for the dose escalation of LBP. The patients received TXT (at a fixed dose of 60 mg/m(2)) on day one (d1) and LBP (at an initial tested dose of 30 mg/m(2)) on day two (d2) of a treatment cycle that was repeated every 21 days. Each dose group consisted of at least three cases. In the absence of dose-limiting toxicity (DLT), we proceeded to the next dose group, with a dose increment of 5 mg/m(2) between groups, until DLT occurred. The dose immediately below the dose that produced DLT was regarded as the MTD. The 17 patients examined in this study completed a total of 58 cycles of chemotherapy, and a total of three dose-escalation groups (30 mg/m(2) LBP, 35 mg/m(2) LBP, and 40 mg/m(2) LBP) were established. The main adverse event that was observed was myelosuppression. DLT occurred in four patients, including three patients in the 40 mg/m(2) LBP group and one patient in the 35 mg/m(2) LBP group. In total, three out of the four patients in the 40 mg/m(2) LBP group exhibited DLT. We determined that the treatment administered to the 35 mg/m(2) LBP group represented the MTD. Thus, our phase I trial revealed that the MTD for the tested LBP combination regimen was 35 mg/m(2) LBP and 60 mg/m(2) TXT. This regimen resulted in mild adverse reactions and favourable patient tolerance. Therefore, we recommend the use of these dosages in phase II clinical trials. PMID:25435935

  8. BOOK REVIEW: Image-Guided IMRT

    NASA Astrophysics Data System (ADS)

    Mayles, P.

    2006-12-01

    This book provides comprehensive coverage of the subject of intensity modulated radiotherapy and the associated imaging. Most of the names associated with advanced radiotherapy can be found among the 80 authors and the book is therefore an authoritative reference text. The early chapters deal with the basic principles and include an interesting comparison between views of quality assurance for IMRT from Europe and North America. It is refreshing to see that the advice given has moved on from the concept of individual patient based quality control to more generic testing of the delivery system. However, the point is made that the whole process including the data transfer needs to be quality assured and the need for thorough commissioning of the process is emphasised. The `tricks' needed to achieve a dose based IMRT plan are well covered by the group at Ghent and there is an interesting summary of biological aspects of treatment planning for IMRT by Andrzej Niemierko. The middle section of the book deals with advanced imaging aspects of both treatment planning and delivery. The contributions of PET and MR imaging are well covered and there is a rather rambling section on molecular imaging. Image guidance in radiotherapy treatment is addressed including the concept of adaptive radiotherapy. The treatment aspects could perhaps have merited some more coverage, but there is a very thorough discussion of 4D techniques. The final section of the book considers each site of the body in turn. This will be found useful by those wishing to embark on IMRT in a new area, although some of the sections are more comprehensive than others. The book contains a wealth of interesting and thought provoking articles giving details as well as broad principles, and would be a useful addition to every departmental library. The editors have done a good job of ensuring that the different chapters are complementary, and of encouraging a systematic approach to the descriptions of IMRT in

  9. [Which rules apply to hypofractionated radiotherapy?].

    PubMed

    Supiot, S; Clément-Colmou, K; Paris, F; Corre, I; Chiavassa, S; Delpon, G

    2015-10-01

    Hypofractionated radiotherapy is now more widely prescribed due to improved targeting techniques (intensity modulated radiotherapy, image-guided radiotherapy and stereotactic radiotherapy). Low dose hypofractionated radiotherapy is routinely administered mostly for palliative purposes. High or very high dose hypofractionated irradiation must be delivered according to very strict procedures since every minor deviation can lead to major changes in dose delivery to the tumor volume and organs at risk. Thus, each stage of the processing must be carefully monitored starting from the limitations and the choice of the hypofractionation technique, tumour contouring and dose constraints prescription, planning and finally dose calculation and patient positioning verification. PMID:26321647

  10. Towards magnetic resonance imaging guided radiation therapy (MRIgRT)

    NASA Astrophysics Data System (ADS)

    Stanescu, Teodor Marius

    The goal of this work is to address key aspects of the magnetic resonance imaging guided radiation therapy (MRIgRT) process of cancer sites. MRIgRT is implemented by using a system comprised of a magnetic resonance imaging (MRI) scanner coupled with a radiation source, in our case a radiotherapy accelerator (Linac). The potential benefits of MRIgRT are the real-time tracking of the tumor and neighbouring healthy anatomy during treatment irradiation leading to on-line treatment plan optimization. Ultimately, this results in an increased accuracy and efficiency of the overall treatment process. A large research effort is conducted at Cross Cancer Institute to develop a hybrid MRI-Linac system consisting of a bi-planar 0.2 T permanent magnet coupled with a 6 MV Linac. The present work is part of this project and aims to address the following key components: (a) magnetic shielding and dosimetric effects of the MRI-Linac system, (b) measure and correction of scanner-related MR image distortions, and (c) MRI-based treatment planning procedure for intracranial lesions. The first two components are essential for the optimal construction and operation of the MRI-Linac system while the third one represents a direct application of the system. The linac passive shielding was achieved by (a) adding two 10 cm thick steel (1020) plates placed at a distance of 10 cm from the structure on opposite sides of the magnet; and (b) a box lined with a 1 mm MuMetal(TM) wall surrounding the Linac. For our proposed MRI-Linac configuration (i.e. 0.2 T field and rotating bi-planar geometry) the maximum dose difference from zero magnetic field case was found to be within 6% and 12% in a water and water-lung-water phantom, respectively. We developed an image system distortion correction method for MRI that relies on adaptive thresholding and an iterative algorithm to determine the 3D distortion field. Applying this technique the residual image distortions were reduced to within the voxel

  11. Image-guided urological interventions: What the urologists must know

    PubMed Central

    Das, Chandan J.; Baliyan, Vinit; Sharma, Sanjay

    2015-01-01

    Advances in imaging technology, especially in the last two decades, have led to a paradigm shift in the field of image-guided interventions in urology. While the traditional biopsy and drainage techniques are firmly established, image-based stone management and endovascular management of hematuria have evolved further. Ablative techniques for renal and prostate cancer and prostate artery embolization for benign prostatic hypertrophy have evolved into viable alternative treatments. Many urologic diseases that were earlier treated surgically are now effectively managed using minimally invasive image-guided techniques, often on a day care basis using only local anesthesia or conscious sedation. This article presents an overview of the technique and status of various image-guided urological procedures, including recent emerging techniques. PMID:26166963

  12. Structure-constrained image-guided inversion of geophysical data

    NASA Astrophysics Data System (ADS)

    Zhou, Jieyi

    The regularization term in the objective function of an inverse problem is equivalent to the "model covariance" in Tarantola's wording. It is not entirely reasonable to consider the model covariance to be isotropic and homogenous, as done in classical Tikhonov regularization, because the correlation relationships among model cells are likely to change with different directions and locations. The structure-constrained image-guided inversion method, presented in this thesis, aims to solve this problem, and can be used to integrate different types of geophysical data and geological information. The method is first theoretically developed and successfully tested with electrical resistivity data. Then it is applied to hydraulic tomography, and promising hydraulic conductivity models are obtained as well. With a correct guiding image, the image-guided inversion results not only follow the correct structure patterns, but also are closer to the true model in terms of parameter values, when compared with the conventional inversion results. To further account for the uncertainty in the guiding image, a Bayesian inversion scheme is added to the image-guided inversion algorithm. Each geophysical model parameter and geological (structure) model parameter is described by a probability density. Using the data misfit of image-guided inversion of the geophysical data as criterion, a stochastic (image-guided) inversion algorithm allows one to optimize both the geophysical model and the geological model at the same time. The last problem discussed in this thesis is, image-guided inversion and interpolation can help reduce non-uniqueness and improve resolution when utilizing spectral induced polarization data and petrophysical relationships to estimate permeability.

  13. Minimally Invasive Spinal Surgery with Intraoperative Image-Guided Navigation

    PubMed Central

    Kim, Terrence T.; Johnson, J. Patrick; Pashman, Robert; Drazin, Doniel

    2016-01-01

    We present our perioperative minimally invasive spine surgery technique using intraoperative computed tomography image-guided navigation for the treatment of various lumbar spine pathologies. We present an illustrative case of a patient undergoing minimally invasive percutaneous posterior spinal fusion assisted by the O-arm system with navigation. We discuss the literature and the advantages of the technique over fluoroscopic imaging methods: lower occupational radiation exposure for operative room personnel, reduced need for postoperative imaging, and decreased revision rates. Most importantly, we demonstrate that use of intraoperative cone beam CT image-guided navigation has been reported to increase accuracy. PMID:27213152

  14. Minimally Invasive Spinal Surgery with Intraoperative Image-Guided Navigation.

    PubMed

    Kim, Terrence T; Johnson, J Patrick; Pashman, Robert; Drazin, Doniel

    2016-01-01

    We present our perioperative minimally invasive spine surgery technique using intraoperative computed tomography image-guided navigation for the treatment of various lumbar spine pathologies. We present an illustrative case of a patient undergoing minimally invasive percutaneous posterior spinal fusion assisted by the O-arm system with navigation. We discuss the literature and the advantages of the technique over fluoroscopic imaging methods: lower occupational radiation exposure for operative room personnel, reduced need for postoperative imaging, and decreased revision rates. Most importantly, we demonstrate that use of intraoperative cone beam CT image-guided navigation has been reported to increase accuracy. PMID:27213152

  15. Image-Guided Tumor Ablation: Emerging Technologies and Future Directions

    PubMed Central

    McWilliams, Justin P.; Lee, Edward W.; Yamamoto, Shota; Loh, Christopher T.; Kee, Stephen T.

    2010-01-01

    As the trend continues toward the decreased invasiveness of medical procedures, image-guided percutaneous ablation has begun to supplant surgery for the local control of small tumors in the liver, kidney, and lung. New ablation technologies, and refinements of existing technologies, will enable treatment of larger and more complex tumors in these and other organs. At the same time, improvements in intraprocedural imaging promise to improve treatment accuracy and reduce complications. In this review, the latest advancements in clinical and experimental ablation technologies will be summarized, and new applications of image-guided tumor ablation will be discussed. PMID:22550370

  16. Image-guided in vivo dosimetry for quality assurance of IMRT treatment for prostate cancer

    SciTech Connect

    Wertz, Hansjoerg . E-mail: hansjoerg.wertz@radonk.ma.uni-heidelberg.de; Boda-Heggemann, Judit; Walter, Cornelia; Dobler, Barbara; Mai, Sabine; Wenz, Frederik; Lohr, Frank

    2007-01-01

    Purpose: In external beam radiotherapy (EBRT) and especially in intensity-modulated radiotherapy (IMRT), the accuracy of the dose distribution in the patient is of utmost importance. It was investigated whether image guided in vivo dosimetry in the rectum is a reliable method for online dose verification. Methods and Materials: Twenty-one dose measurements were performed with an ionization chamber in the rectum of 7 patients undergoing IMRT for prostate cancer. The position of the probe was determined with cone beam computed tomography (CBCT). The point of measurement was determined relative to the isocenter and relative to an anatomic reference point. The dose deviations relative to the corresponding doses in the treatment plan were calculated. With an offline CT soft-tissue match, patient positioning after ultrasound was verified. Results: The mean magnitude {+-} standard deviation (SD) of patient positioning errors was 3.0 {+-} 2.5 mm, 5.1 {+-} 4.9 mm, and 4.3 {+-} 2.4 mm in the left-right, anteroposterior and craniocaudal direction. The dose deviations in points at corresponding positions relative to the isocenter were -1.4 {+-} 4.9% (mean {+-} SD). The mean dose deviation at corresponding anatomic positions was 6.5 {+-} 21.6%. In the rare event of insufficient patient positioning, dose deviations could be >30% because of the close proximity of the probe and the posterior dose gradient. Conclusions: Image-guided dosimetry in the rectum during IMRT of the prostate is a feasible and reliable direct method for dose verification when probe position is effectively controlled.

  17. Image-guided therapy: evolution and breakthrough.

    PubMed

    Haigron, Pascal; Dillenseger, Jean-Louis; Luo, Limin; Coatrieux, Jean-Louis

    2010-01-01

    Beyond the advances made in computer-assisted interventions and robotic systems, the demand for more efficient and safer therapies remains challenging. Thus, if it is possible to improve the instrument tracking, steering, and target localization, to miniaturize the sensors and actuators, and to conduct preoperatively planned minimally invasive therapies, we still need new resources to achieve permanent destruction of abnormal tissues or suppression of pathological processes. Most of the physics-based (or energy-based) therapeutic principles at our disposal have been established a long time ago, but their actions on basic cellular and molecular mechanisms are not yet fully understood. They all have a wide spectrum of clinical targets in terms of organs and pathologies, modes of application (external, interstitial, intraluminal, etc.) with advantages and side-effect drawbacks, proven indications, and contraindications. Some of them may still face controversies regarding their outcomes. This short article, mainly focused on tumor destruction, briefly reviews in its first part some of these techniques and sketches the next generation under investigation. The former include radio frequency (RF), high-intensity focused ultrasound (HiFU), microwaves, and cryotherapy, of which all are temperature based. Laser-based approaches [e.g., photodynamic therapy (PDT) at large] are also discussed. Radiotherapy and its variants (hadrontherapy, brachytherapy, Gamma Knife, and CyberKnife) remain, of course, as the reference technique in cancer treatment. The next breakthroughs are examined in the second part of the article. They are based on the close association between imaging agents, drugs, and some stimulation techniques. The ongoing research efforts in that direction show that, if they are still far from clinical applications, strong expectations are made. From the point of view of interventional planning and image guidance, all of them share a lot of concerns. PMID:20176527

  18. Prognostic advantage of irinotecan dose escalation according to uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) genotyping in patients with metastatic colorectal cancer treated with bevacizumab combined with 5-fluorouracil/leucovorin with irinotecan in a first-line setting.

    PubMed

    Lu, Chien-Yu; Huang, Ching-Wen; Hu, Huang-Ming; Tsai, Hsiang-Lin; Huang, Chun-Ming; Yu, Fang-Jung; Huang, Ming-Yii; Chang, Se-Fen; Huang, Meng-Lin; Wang, Jaw-Yuan

    2014-08-01

    This study compared the clinical responses of patients with metastatic colorectal cancer (mCRC) with 5-fluorouracil/leucovorin with irinotecan (FOLFIRI) plus bevacizumab therapy either with or without uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) genotyping and irinotecan dose escalation. Of 107 total patients with mCRC, 79 were classified as the study group and 28 as the control group. The study group received irinotecan dose escalation based on UGT1A1 genotyping whereas the control group did not. Clinicopathologic features, response rates, and survival were compared for the 2 groups. The clinical response rate of patients with mCRC treated with FOLFIRI plus bevacizumab under UGT1A1 genotyping and irinotecan dose escalation was significantly better than that of those without these prospective tests and dose escalation (P = 0.028). Both progression-free survival (PFS) and overall survival were significantly greater in clinical responders than nonresponders (both, P < 0.001), and PFS was significantly greater among the study group patients than among the control group patients, with a median PFS of 12.2 months vs 9.4 months (P = 0.025). Grade 3/4 adverse events were not significantly different between the 2 groups (P = 0.189). Patients with mCRC undergoing UGT1A1 genotyping may receive escalated doses of irinotecan to obtain a better clinical response/outcome with comparable toxicities. PMID:24462762

  19. Two phase I dose-escalation/pharmacokinetics studies of low temperature liposomal doxorubicin (LTLD) and mild local hyperthermia in heavily pretreated patients with local regionally recurrent breast cancer

    PubMed Central

    Zagar, Timothy M.; Vujaskovic, Zeljko; Formenti, Silvia; Rugo, Hope; O’Connor, Brigid; Myerson, Robert; Stauffer, Paul; Hsu, I-Chow; Diederich, Chris; Straube, William; Boss, Mary-Keara; Boico, Alina; Craciunescu, Oana; Maccarini, Paolo; Needham, David; Borys, Nicholas; Blackwell, Kimberly L.

    2014-01-01

    Purpose Unresectable chest wall recurrences of breast cancer (CWR) in heavily pretreated patients are especially difficult to treat. We hypothesised that thermally enhanced drug delivery using low temperature liposomal doxorubicin (LTLD), given with mild local hyperthermia (MLHT), will be safe and effective in this population. Patients and methods This paper combines the results of two similarly designed phase I trials. Eligible CWR patients had progressed on the chest wall after prior hormone therapy, chemotherapy, and radiotherapy. Patients were to get six cycles of LTLD every 21–35 days, followed immediately by chest wall MLHT for 1 hour at 40–42 °C. In the first trial 18 subjects received LTLD at 20, 30, or 40 mg/m2; in the second trial, 11 subjects received LTLD at 40 or 50 mg/m2. Results The median age of all 29 patients enrolled was 57 years. Thirteen patients (45%) had distant metastases on enrolment. Patients had received a median dose of 256 mg/m2 of prior anthracyclines and a median dose of 61 Gy of prior radiation. The median number of study treatments that subjects completed was four. The maximum tolerated dose was 50 mg/m2, with seven subjects (24%) developing reversible grade 3–4 neutropenia and four (14%) reversible grade 3–4 leucopenia. The rate of overall local response was 48% (14/29, 95% CI: 30–66%), with. five patients (17%) achieving complete local responses and nine patients (31%) having partial local responses. Conclusion LTLD at 50 mg/m2 and MLHT is safe. This combined therapy produces objective responses in heavily pretreated CWR patients. Future work should test thermally enhanced LTLD delivery in a less advanced patient population. PMID:25144817

  20. Recent advancements in toxicity prediction following prostate cancer radiotherapy.

    PubMed

    Ospina, J D; Fargeas, A; Dréan, G; Simon, A; Acosta, O; de Crevoisier, R

    2015-01-01

    In external beam radiotherapy for prostate cancer limiting toxicities for dose escalation are bladder and rectum toxicities. Normal tissue complication probability models aim at quantifying the risk of developping adverse events following radiotherapy. These models, originally proposed in the context of uniform irradiation, have evolved to implementations based on the state-of-the-art classification methods which are trained using empirical data. Recently, the use of image processing techniques combined with population analysis methods has led to a new generation of models to understand the risk of normal tissue complications following radiotherapy. This paper overviews those methods in the case of prostate cancer radiation therapy and propose some lines of future research. PMID:26737471

  1. Image-guided surgery using multimodality strategy and molecular probes.

    PubMed

    Xi, Lei; Jiang, Hubei

    2016-01-01

    The ultimate goal of cancer surgery is to maximize the excision of tumorous tissue with minimal damage to the collateral normal tissues, reduce the postoperative recurrence, and improve the survival rate of patients. In order to locate tumor lesions, highlight tumor margins, visualize residual disease in the surgical wound, and map potential lymph node metastasis, various imaging techniques and molecular probes have been investigated to assist surgeons to perform more complete tumor resection. Combining imaging techniques with molecular probes is particularly promising as a new approach for image-guided surgery. Considering inherent limitations of different imaging techniques and insufficient sensitivity of nonspecific molecular probes, image-guided surgery with multimodality strategy and specific molecular probes appears to be an optimal choice. In this article, we briefly describe typical imaging techniques and molecular probes followed by a focused review on the current progress of multimodal image-guided surgery with specific molecular navigation. We also discuss optimal strategy that covers all stages of image-guided surgery including preoperative scanning of tumors, intraoperative inspection of surgical bed and postoperative care of patients. PMID:26053199

  2. Polymer fiber-image-guide-based embedded optical circuit board.

    PubMed

    Ai, J; Li, Y

    1999-01-10

    We propose a poly(methyl methacrylate) fiber-image-guide-based embedded optical circuit board for future optoelectronic array-interconnection applications. An experimental prototypical board that embeds perfect-shuffle and banyan interconnect patterns of 16 x 16 parallel links, each of which offers a fiber pixel density of >1000 pixels/mm(2), are demonstrated experimentally. PMID:18305618

  3. Proton Radiotherapy for Liver Tumors: Dosimetric Advantages Over Photon Plans

    SciTech Connect

    Wang Xiaochun Krishnan, Sunil; Zhang Xiaodong; Dong Lei; Briere, Tina; Crane, Christopher H.; Martel, Mary; Gillin, Michael; Mohan, Radhe; Beddar, Sam

    2008-01-01

    The purpose of the study is to dosimetrically investigate the advantages of proton radiotherapy over photon radiotherapy for liver tumors. The proton plan and the photon plan were designed using commercial treatment planning systems. The treatment target dose conformity and heterogeneity and dose-volume analyses of normal structures were compared between proton and photon radiotherapy for 9 patients with liver tumors. Proton radiotherapy delivered a more conformal target dose with slightly less homogeneity when compared with photon radiotherapy. Protons significantly reduced the fractional volume of liver receiving dose greater or equal to 30 Gy (V{sub 30}) and the mean liver dose. The stomach and duodenal V{sub 45} were significantly lower with the use of proton radiotherapy. The V{sub 40} and V{sub 50} of the heart and the maximum spinal cord dose were also significantly lower with the use of proton radiotherapy. Protons were better able to spare one kidney completely and deliver less dose to one (generally the left) kidney than photons. The mean dose to the total body and most critical structures was significantly decreased using protons when compared to corresponding photon plans. In conclusion, our study suggests the dosimetric benefits of proton radiotherapy over photon radiotherapy. These dosimetric advantages of proton plans may permit further dose escalation with lower risk of complications.

  4. COSMIC: A Regimen of Intensity Modulated Radiation Therapy Plus Dose-Escalated, Raster-Scanned Carbon Ion Boost for Malignant Salivary Gland Tumors: Results of the Prospective Phase 2 Trial

    SciTech Connect

    Jensen, Alexandra D.; Nikoghosyan, Anna V.; Lossner, Karen; Haberer, Thomas; Jäkel, Oliver; Münter, Marc W.; Debus, Jürgen

    2015-09-01

    Purpose: To investigate the effect of intensity modulated radiation therapy (IMRT) and dose-escalated carbon ion (C12) therapy in adenoid cystic carcinoma (ACC) and other malignant salivary gland tumors (MSGTs) of the head and neck. Patients and Methods: COSMIC (combined treatment of malignant salivary gland tumors with intensity modulated radiation therapy and carbon ions) is a prospective phase 2 trial of 24 Gy(RBE) C12 followed by 50 Gy IMRT in patients with pathologically confirmed MSGT. The primary endpoint is mucositis Common Terminology Criteria grade 3; the secondary endpoints are locoregional control (LC), progression-free survival (PFS), overall survival (OS), and toxicity. Toxicity was scored according to the Common Terminology Criteria for Adverse Events version 3; treatment response was scored according to Response Evaluation Criteria in Solid Tumors 1.1. Results: Between July 2010 and August 2011, 54 patients were accrued, and 53 were available for evaluation. The median follow-up time was 42 months; patients with microscopically incomplete resections (R1, n=20), gross residual disease (R2, n=17), and inoperable disease (n=16) were included. Eighty-nine percent of patients had ACC, and 57% had T4 tumors. The most common primary sites were paranasal sinus (34%), submandibular gland, and palate. At the completion of radiation therapy, 26% of patients experienced grade 3 mucositis, and 20 patients reported adverse events of the ear (38%). The most common observed late effects were grade 1 xerostomia (49%), hearing impairment (25%, 2% ipsilateral hearing loss), and adverse events of the eye (20%), but no visual impairment or loss of vision. Grade 1 central nervous system necrosis occurred in 6%, and 1 grade 4 ICA hemorrhage without neurologic sequelae. The best response was 54% (complete response/partial remission). At 3 years, the LC, PFS, and OS were 81.9%, 57.9%, and 78.4%, respectively. No difference was found regarding resection status. The

  5. Individualized Dose Prescription for Hypofractionation in Advanced Non-Small-Cell Lung Cancer Radiotherapy: An in silico Trial

    SciTech Connect

    Hoffmann, Aswin L.; Troost, Esther G.C.; Huizenga, Henk; Kaanders, Johannes H.A.M.; Bussink, Johan

    2012-08-01

    Purpose: Local tumor control and outcome remain poor in patients with advanced non-small-cell lung cancer (NSCLC) treated by external beam radiotherapy. We investigated the therapeutic gain of individualized dose prescription with dose escalation based on normal tissue dose constraints for various hypofractionation schemes delivered with intensity-modulated radiation therapy. Methods and Materials: For 38 Stage III NSCLC patients, the dose level of an existing curative treatment plan with standard fractionation (66 Gy) was rescaled based on dose constraints for the lung, spinal cord, esophagus, brachial plexus, and heart. The effect on tumor total dose (TTD) and biologic tumor effective dose in 2-Gy fractions (TED) corrected for overall treatment time (OTT) was compared for isotoxic and maximally tolerable schemes given in 15, 20, and 33 fractions. Rescaling was accomplished by altering the dose per fraction and/or the number of fractions while keeping the relative dose distribution of the original treatment plan. Results: For 30 of the 38 patients, dose escalation by individualized hypofractionation yielded therapeutic gain. For the maximally tolerable dose scheme in 33 fractions (MTD{sub 33}), individualized dose escalation resulted in a 2.5-21% gain in TTD. In the isotoxic schemes, the number of fractions could be reduced with a marginal increase in TED. For the maximally tolerable dose schemes, the TED could be escalated up to 36.6%, and for all patients beyond the level of the isotoxic and the MTD{sub 33} schemes (range, 3.3-36.6%). Reduction of the OTT contributed to the therapeutic gain of the shortened schemes. For the maximally tolerable schemes, the maximum esophageal dose was the dominant dose-limiting constraint in most patients. Conclusions: This modeling study showed that individualized dose prescription for hypofractionation in NSCLC radiotherapy, based on scaling of existing treatment plans up to normal tissue dose constraints, enables dose

  6. Increasing Tumor Volume is Predictive of Poor Overall and Progression-Free Survival: Secondary Analysis of the Radiation Therapy Oncology Group 93-11 Phase I-II Radiation Dose-Escalation Study in Patients with Inoperable Non-Small-Cell Lung Cancer

    SciTech Connect

    Werner-Wasik, Maria Swann, R. Suzanne; Bradley, Jeffrey; Graham, Mary; Emami, Bahman; Purdy, James; Sause, William

    2008-02-01

    Purpose: Patients with non-small-cell lung cancer (NSCLC) in the Radiation Therapy Oncology Group (RTOG) 93-11 trial received radiation doses of 70.9, 77.4, 83.8, or 90.3 Gy. The locoregional control and survival rates were similar among the various dose levels. We investigated the effect of the gross tumor volume (GTV) on the outcome. Methods and Materials: The GTV was defined as the sum of the volumes of the primary tumor and involved lymph nodes. The tumor response, median survival time (MST), and progression-free survival (PFS) were analyzed separately for smaller ({<=}45 cm{sup 3}) vs. larger (>45 cm{sup 3}) tumors. Results: The distribution of the GTV was as follows: {<=}45 cm{sup 3} in 79 (49%) and >45 cm{sup 3} in 82 (51%) of 161 patients. The median GTV was 47.3 cm{sup 3}. N0 status and female gender were associated with better tumor responses. Patients with smaller ({<=}45 cm{sup 3}) tumors achieved a longer MST and better PFS than did patients with larger (>45 cm{sup 3}) tumors (29.7 vs. 13.3 months, p < 0.0001; and 15.8 vs. 8.3 months, p < 0.0001, respectively). Increasing the radiation dose had no effect on the MST or PFS. On multivariate analysis, only a smaller GTV was a significant prognostic factor for improved MST and PFS (hazard ratio [HR], 2.12, p = 0.0002; and HR, 2.0, p = 0.0002, respectively). The GTV as a continuous variable was also significantly associated with the MST and PFS (HR, 1.59, p < 0.0001; and HR, 1.39, p < 0.0001, respectively). Conclusions: Radiation dose escalation up to 90.3 Gy did not result in improved MST or PFS. The tumor responses were greater in node-negative patients and women. An increasing GTV was strongly associated with decreased MST and PFS. Future radiotherapy trials patients might need to use stratification by tumor volume.

  7. Image-guided navigation: a cost effective practical introduction using the Image-Guided Surgery Toolkit (IGSTK).

    PubMed

    Güler, Özgür; Yaniv, Ziv

    2012-01-01

    Teaching the key technical aspects of image-guided interventions using a hands-on approach is a challenging task. This is primarily due to the high cost and lack of accessibility to imaging and tracking systems. We provide a software and data infrastructure which addresses both challenges. Our infrastructure allows students, patients, and clinicians to develop an understanding of the key technologies by using them, and possibly by developing additional components and integrating them into a simple navigation system which we provide. Our approach requires minimal hardware, LEGO blocks to construct a phantom for which we provide CT scans, and a webcam which when combined with our software provides the functionality of a tracking system. A premise of this approach is that tracking accuracy is sufficient for our purpose. We evaluate the accuracy provided by a consumer grade webcam and show that it is sufficient for educational use. We provide an open source implementation of all the components required for a basic image-guided navigation as part of the Image-Guided Surgery Toolkit (IGSTK). It has long been known that in education there is no substitute for hands-on experience, to quote Sophocles, "One must learn by doing the thing; for though you think you know it, you have no certainty, until you try.". Our work provides this missing capability in the context of image-guided navigation. Enabling a wide audience to learn and experience the use of a navigation system. PMID:23367310

  8. The role of intensity modulated radiotherapy in gynecological radiotherapy: Present and future

    PubMed Central

    Fernandez-Ots, Ana; Crook, Juanita

    2013-01-01

    Aim This manuscript reviews the English language literature on the use of intensity modulated radiation therapy (IMRT) for gynecologic malignancies, focusing on the treatment cervical cancer. Background Radiation therapy plays a key role in both definitive and adjuvant treatment of these patients, although efforts continue to minimize acute and chronic toxicity. IMRT is an attractive option because of the potential to dose escalate to the target while sparing organs at risk. Methods and Materials The English language literature was reviewed for relevant studies. Results Multiple heterogeneous studies have showed dosimetric and clinical benefits with reduction in acute and late gastrointestinal, genitourinary and hematologic toxicity, especially in the post hysterectomy scenario and for dose escalation to para-aortic nodes. Consensus is evolving regarding necessary margins and target delineation in the context of organ movement and tumor shrinkage during the course of radiotherapy. Protocols with daily soft-tissue visualization are being investigated. Conclusions Consistency in approach and reporting are vital in order to acquire the data to justify the considerable increased expense of IMRT. PMID:24416580

  9. High-dose radiation improved local tumor control and overall survival in patients with inoperable/unresectable non-small-cell lung cancer: Long-term results of a radiation dose escalation study

    SciTech Connect

    Kong, F.-M. . E-mail: Fengkong@med.umich.edu; Haken, Randall K. ten; Schipper, Matthew J.; Sullivan, Molly A.; Chen, Ming; Lopez, Carlos; Kalemkerian, Gregory P.; Hayman, James A.

    2005-10-01

    Purpose: To determine whether high-dose radiation leads to improved outcomes in patients with non-small-cell lung cancer (NSCLC). Methods and Materials: This analysis included 106 patients with newly diagnosed or recurrent Stages I-III NSCLC, treated with 63-103 Gy in 2.1-Gy fractions, using three-dimensional conformal radiation therapy (3D-CRT) per a dose escalation trial. Targets included the primary tumor and any lymph nodes {>=}1 cm, without intentionally including negative nodal regions. Nineteen percent of patients (20/106) received neoadjuvant chemotherapy. Patient, tumor, and treatment factors were evaluated for association with outcomes. Estimated median follow-up was 8.5 years. Results: Median survival was 19 months, and 5-year overall survival (OS) was 13%. Multivariate analysis revealed weight loss (p = 0.011) and radiation dose (p = 0.0006) were significant predictors for OS. The 5-year OS was 4%, 22%, and 28% for patients receiving 63-69, 74-84, and 92-103 Gy, respectively. Although presence of nodal disease was negatively associated with locoregional control under univariate analysis, radiation dose was the only significant predictor when multiple variables were included (p = 0.015). The 5-year control rate was 12%, 35%, and 49% for 63-69, 74-84, and 92-103 Gy, respectively. Conclusions: Higher dose radiation is associated with improved outcomes in patients with NSCLC treated in the range of 63-103 Gy.

  10. A Phase I Clinical Study of a Live Attenuated Bordetella pertussis Vaccine - BPZE1; A Single Centre, Double-Blind, Placebo-Controlled, Dose-Escalating Study of BPZE1 Given Intranasally to Healthy Adult Male Volunteers

    PubMed Central

    Thorstensson, Rigmor; Trollfors, Birger; Al-Tawil, Nabil; Jahnmatz, Maja; Bergström, Jakob; Ljungman, Margaretha; Törner, Anna; Wehlin, Lena; Van Broekhoven, Annie; Bosman, Fons; Debrie, Anne-Sophie; Mielcarek, Nathalie; Locht, Camille

    2014-01-01

    Background Acellular pertussis vaccines do not control pertussis. A new approach to offer protection to infants is necessary. BPZE1, a genetically modified Bordetella pertussis strain, was developed as a live attenuated nasal pertussis vaccine by genetically eliminating or detoxifying 3 toxins. Methods We performed a double-blind, placebo-controlled, dose-escalating study of BPZE1 given intranasally for the first time to human volunteers, the first trial of a live attenuated bacterial vaccine specifically designed for the respiratory tract. 12 subjects per dose group received 103, 105 or 107 colony-forming units as droplets with half of the dose in each nostril. 12 controls received the diluent. Local and systemic safety and immune responses were assessed during 6 months, and nasopharyngeal colonization with BPZE1 was determined with repeated cultures during the first 4 weeks after vaccination. Results Colonization was seen in one subject in the low dose, one in the medium dose and five in the high dose group. Significant increases in immune responses against pertussis antigens were seen in all colonized subjects. There was one serious adverse event not related to the vaccine. Other adverse events were trivial and occurred with similar frequency in the placebo and vaccine groups. Conclusions BPZE1 is safe in healthy adults and able to transiently colonize the nasopharynx. It induces immune responses in all colonized individuals. BPZE1 can thus undergo further clinical development, including dose optimization and trials in younger age groups. Trial Registration ClinicalTrials.gov NCT01188512 PMID:24421886

  11. Design, implementation and investigation of an image guide-based optical flip-flop array

    NASA Technical Reports Server (NTRS)

    Griffith, P. C.

    1987-01-01

    Presented is the design for an image guide-based optical flip-flop array created using a Hughes liquid crystal light valve and a flexible image guide in a feedback loop. This design is used to investigate the application of image guides as a communication mechanism in numerical optical computers. It is shown that image guides can be used successfully in this manner but mismatch match between the input and output fiber arrays is extremely limiting.

  12. Use of image guided radiation therapy techniques and imaging dose measurement at Indian hospitals: A survey

    PubMed Central

    Deshpande, Sudesh; Dhote, D. S.; Kumar, Rajesh; Naidu, Suresh; Sutar, A.; Kannan, V.

    2015-01-01

    A national survey was conducted to obtain information about the use of image-guided radiotherapy (IGRT) techniques and IGRT dose measurement methods being followed at Indian radiotherapy centers. A questionnaire containing parameters relevant to use of IGRT was prepared to collect the information pertaining to (i) availability and type of IGRT delivery system, (ii) frequency of image acquisition protocol and utilization of these images for different purpose, and (iii) imaging dose measurement. The questionnaire was circulated to 75 hospitals in the country having IGRT facility, and responses of 51 centers were received. Survey results showed that among surveyed hospitals, 86% centers have IGRT facility, 78% centers have kilo voltage three-dimensional volumetric imaging. 75% of hospitals in our study do not perform computed tomography dose index measurements and 89% of centers do not perform patient dose measurements. Moreover, only 29% physicists believe IGRT dose is additional radiation burden to patient. This study has brought into focus the need to design a national protocol for IGRT dose measurement and development of indigenous tools to perform IGRT dose measurements. PMID:26865758

  13. Use of image guided radiation therapy techniques and imaging dose measurement at Indian hospitals: A survey.

    PubMed

    Deshpande, Sudesh; Dhote, D S; Kumar, Rajesh; Naidu, Suresh; Sutar, A; Kannan, V

    2015-01-01

    A national survey was conducted to obtain information about the use of image-guided radiotherapy (IGRT) techniques and IGRT dose measurement methods being followed at Indian radiotherapy centers. A questionnaire containing parameters relevant to use of IGRT was prepared to collect the information pertaining to (i) availability and type of IGRT delivery system, (ii) frequency of image acquisition protocol and utilization of these images for different purpose, and (iii) imaging dose measurement. The questionnaire was circulated to 75 hospitals in the country having IGRT facility, and responses of 51 centers were received. Survey results showed that among surveyed hospitals, 86% centers have IGRT facility, 78% centers have kilo voltage three-dimensional volumetric imaging. 75% of hospitals in our study do not perform computed tomography dose index measurements and 89% of centers do not perform patient dose measurements. Moreover, only 29% physicists believe IGRT dose is additional radiation burden to patient. This study has brought into focus the need to design a national protocol for IGRT dose measurement and development of indigenous tools to perform IGRT dose measurements. PMID:26865758

  14. Recent advances in image-guided targeted prostate biopsy.

    PubMed

    Brown, Anna M; Elbuluk, Osama; Mertan, Francesca; Sankineni, Sandeep; Margolis, Daniel J; Wood, Bradford J; Pinto, Peter A; Choyke, Peter L; Turkbey, Baris

    2015-08-01

    Prostate cancer is a common malignancy in the United States that results in over 30,000 deaths per year. The current state of prostate cancer diagnosis, based on PSA screening and sextant biopsy, has been criticized for both overdiagnosis of low-grade tumors and underdiagnosis of clinically significant prostate cancers (Gleason score ≥7). Recently, image guidance has been added to perform targeted biopsies of lesions detected on multi-parametric magnetic resonance imaging (mpMRI) scans. These methods have improved the ability to detect clinically significant cancer, while reducing the diagnosis of low-grade tumors. Several approaches have been explored to improve the accuracy of image-guided targeted prostate biopsy, including in-bore MRI-guided, cognitive fusion, and MRI/transrectal ultrasound fusion-guided biopsy. This review will examine recent advances in these image-guided targeted prostate biopsy techniques. PMID:25596716

  15. Solid Lipid Nanoparticles for Image-Guided Therapy of Atherosclerosis.

    PubMed

    Oumzil, Khalid; Ramin, Michael A; Lorenzato, Cyril; Hémadou, Audrey; Laroche, Jeanny; Jacobin-Valat, Marie Josée; Mornet, Stephane; Roy, Claude-Eric; Kauss, Tina; Gaudin, Karen; Clofent-Sanchez, Gisèle; Barthélémy, Philippe

    2016-03-16

    Although the application of nanotechnologies to atherosclerosis remains a young field, novel strategies are needed to address this public health issue. In this context, the magnetic resonance imaging (MRI) approach has been gradually investigated in order to enable image-guided treatments. In this contribution, we report a new approach based on nucleoside-lipids allowing the synthesis of solid lipid nanoparticles (SLN) loaded with iron oxide particles and therapeutic agents. The insertion of nucleoside-lipids allows the formation of stable SLNs loaded with prostacycline (PGI2) able to inhibit platelet aggregation. The new SLNs feature better relaxivity properties in comparison to the clinically used contrast agent Feridex, indicating that SLNs are suitable for image-guided therapy. PMID:26751997

  16. Image-guided drainage of cystic vestibular schwannomata.

    PubMed

    Barrett, Chris; Prasad, K S Manjunath; Hill, John; Johnson, Ian; Heaton, Judith M; Crossman, John E; Mendelow, Alexander D

    2010-01-01

    The management of vestibular schwannomata is controversial. Surveillance remains an acceptable option for elderly patients or those with small lesions. Stereoradiosurgery is also an option, while surgery is often preferred in younger patients with larger lesions. In elderly patients with lesions causing brainstem compression, craniotomy is a major undertaking. We report two cases of cystic cerebellopontine angle tumours in patients with co-morbidity, who were managed successfully with image-guided insertion of a cystoperitoneal shunt. PMID:19693430

  17. Image-Guided Abdominal Surgery and Therapy Delivery

    PubMed Central

    Galloway, Robert L.; Herrell, S. Duke; Miga, Michael I.

    2013-01-01

    Image-Guided Surgery has become the standard of care in intracranial neurosurgery providing more exact resections while minimizing damage to healthy tissue. Moving that process to abdominal organs presents additional challenges in the form of image segmentation, image to physical space registration, organ motion and deformation. In this paper, we present methodologies and results for addressing these challenges in two specific organs: the liver and the kidney. PMID:25077012

  18. Novel Image-Guided Management of a Uterine Arteriovenous Malformation

    SciTech Connect

    Przybojewski, Stefan J. Sadler, David J.

    2011-02-15

    The investigators present a novel image-guided embolization, not previously described, of a uterine arteriovenous malformation (AVM) resistant to endovascular management. The uterus was exposed surgically, and Histoacryl (Braun, Fulda, Germany) was injected directly into the nidus using ultrasound guidance and fluoroscopy. The patient had a successful full-term pregnancy after this procedure. This technique may be a useful alternative management strategy in patients with uterine AVM who fail traditional endovascular embolization and who still desire fertility.

  19. Magnetic resonance imaging for prostate cancer radiotherapy.

    PubMed

    Dinh, Cuong V; Steenbergen, Peter; Ghobadi, Ghazaleh; Heijmink, Stijn W T J P; Pos, Floris J; Haustermans, Karin; van der Heide, Uulke A

    2016-03-01

    For radiotherapy of prostate cancer, MRI is used increasingly for delineation of the prostate gland. For focal treatment of low-risk prostate cancer or focal dose escalation for intermediate and high-risk cancer, delineation of the tumor is also required. While multi-parametric MRI is well established for detection of tumors and for staging of the disease, delineation of the tumor inside the prostate is not common practice. Guidelines, such as the PI-RADS classification, exist for tumor detection and staging, but no such guidelines are available for tumor delineation. Indeed, interobserver studies show substantial variation in tumor contours. Computer-aided tumor detection and delineation may help improve the robustness of the interpretation of multi-parametric MRI data. Comparing the performance of an earlier developed model for tumor segmentation with expert delineations, we found a significant correlation between tumor probability in a voxel and the number of experts identifying this voxel as tumor. This suggests that the model agrees with 'the wisdom of the crowd', and thus could serve as a reference for individual physicians in their decision making. With multi-parametric MRI it becomes feasible to revisit the GTV-CTV concept in radiotherapy of prostate cancer. While detection of index lesions is quite reliable, contouring variability and the low sensitivity to small lesions suggest that the remainder of the prostate should be treated as CTV. Clinical trials that investigate the options for dose differentiation, for example with dose escalation to the visible tumor or dose reduction to the CTV, are therefore warranted. PMID:26858164

  20. A phase I dose-escalation clinical trial of a peptide-based human papillomavirus therapeutic vaccine with Candida skin test reagent as a novel vaccine adjuvant for treating women with biopsy-proven cervical intraepithelial neoplasia 2/3

    PubMed Central

    Greenfield, William W; Stratton, Shawna L; Myrick, Rebecca S; Vaughn, Rita; Donnalley, Lisa M; Coleman, Hannah N; Mercado, Maria; Moerman-Herzog, Andrea M; Spencer, Horace J; Andrews-Collins, Nancy R; Hitt, Wilbur C; Low, Gordon M; Manning, Nirvana A; McKelvey, Samantha S; Smith, Dora; Smith, Michael V; Phillips, Amy M; Quick, C Matthew; Jeffus, Susanne K; Hutchins, Laura F; Nakagawa, Mayumi

    2015-01-01

    PURPOSE: Non-surgical treatments for cervical intraepithelial neoplasia 2/3 (CIN2/3) are needed as surgical treatments have been shown to double preterm delivery rate. The goal of this study was to demonstrate safety of a human papillomavirus (HPV) therapeutic vaccine called PepCan, which consists of four current good-manufacturing production-grade peptides covering the HPV type 16 E6 protein and Candida skin test reagent as a novel adjuvant. PATIENTS AND METHODS: The study was a single-arm, single-institution, dose-escalation phase I clinical trial, and the patients (n = 24) were women with biopsy-proven CIN2/3. Four injections were administered intradermally every 3 weeks in limbs. Loop electrical excision procedure (LEEP) was performed 12 weeks after the last injection for treatment and histological analysis. Six subjects each were enrolled (50, 100, 250, and 500 μg per peptide). RESULTS: The most common adverse events (AEs) were injection site reactions, and none of the patients experienced dose-limiting toxicities. The best histological response was seen at the 50 μg dose level with a regression rate of 83% (n = 6), and the overall rate was 52% (n = 23). Vaccine-induced immune responses to E6 were detected in 65% of recipients (significantly in 43%). Systemic T-helper type 1 (Th1) cells were significantly increased after four vaccinations (P = 0.02). CONCLUSION: This study demonstrated that PepCan is safe. A significantly increased systemic level of Th1 cells suggests that Candida, which induces interleukin-12 (IL-12) in vitro, may have a Th1 promoting effect. A phase II clinical trial to assess the full effect of this vaccine is warranted. PMID:26451301

  1. A randomized, double blind, dose escalation, first time in human study to assess the safety, tolerability, pharmacokinetics, and antiviral activity of single doses of GSK2485852 in chronically infected hepatitis C subjects.

    PubMed

    Wilfret, David A; Walker, Jill; Voitenleitner, Christian; Baptiste-Brown, Sharon; Lovern, Mark; Kim, Joseph; Adkison, Kimberly; Shotwell, Brad; Mathis, Amanda; Moss, Lee; Lee, Daniel; Yu, Lou; Gan, Jianjun; Spaltenstein, Andrew

    2014-11-01

    This first-time-in-human, randomized, double-blind, placebo-controlled, dose-escalation study assessed the safety, tolerability, pharmacokinetics, and antiviral activity of GSK2485852, a hepatitis C virus (HCV) NS5B inhibitor, in 27 chronically infected HCV genotype-1 subjects. Subjects received GSK2485852 70, 420, and 70 mg with a moderate fat/caloric meal. Safety, pharmacokinetics, antiviral activity, HCV genotype/phenotype, and interleukin 28B genotype were evaluated. A statistically significant reduction in HCV ribonucleic acid (RNA) was observed after a single dose of 420 mg GSK2485852 (-1.33 log10  IU/mL) compared with placebo (-0.09 log10  IU/mL) at 24 hours post-dose. Subjects receiving 70 mg GSK2485852 were exposed to concentrations above the protein-adjusted 90% effective concentration for a short time; none experienced a significant decline in HCV RNA (-0.47 log10  copies/mL). GSK2485852 was readily absorbed; however, the observed geometric mean maximum plasma concentration (Cmax ) and area under the curve (AUC) values were significantly lower than expected due to a higher-than-predicted-oral clearance. Co-administration with food reduced the AUC and Cmax of GSK2485852 by 40% and 70%, respectively. Two metabolites were detected in human blood with one having approximately 50% higher concentrations than those of the parent. GSK2485852 was well-tolerated and exhibited antiviral activity after a single 420 mg dose in HCV subjects. PMID:27129119

  2. A phase I dose-escalation study to a predefined dose of a transforming growth factor-β1 monoclonal antibody (TβM1) in patients with metastatic cancer

    PubMed Central

    COHN, ALLEN; LAHN, MICHAEL M.; WILLIAMS, KRISTEN E.; CLEVERLY, ANN L.; PITOU, CELINE; KADAM, SUNIL K.; FARMEN, MARK W.; DESAIAH, DURISALA; RAJU, ROBERT; CONKLING, PAUL; RICHARDS, DONALD

    2014-01-01

    Transforming growth factor β (TGF-β) plays an important role in cancer. Monoclonal antibodies (mAb) designed to specifically block the TGF-β ligands, are expected to inhibit tumor progression in patients with metastatic cancer. TβM1 is a humanized mAb optimized for neutralizing activity against TGF-β1. The objective of this clinical trial was to assess the safety and tolerability of TβM1 in patients with metastatic cancer. In this phase I, uncontrolled, non-randomized, dose-escalation study, 18 eligible adult patients who had measurable disease per RECIST and a performance status of ≤2 on the ECOG scale were administered TβM1 intravenously over 10 min at doses of 20, 60, 120 and 240 mg on day 1 of each 28-day cycle. Safety was assessed by adverse events (as defined by CTCAE version 3.0) and possible relationship to study drug, dose-limiting toxicities and laboratory changes. Systemic drug exposure and pharmacodynamic (PD) parameters were assessed. TβM1 was safe when administered once monthly. The pharmacokinetic (PK) profile was consistent with a mAb with a mean elimination half-life approximately 9 days. Although anticipated changes in PD markers such as serum VEGF, bFGF and mRNA expression of SMAD7 were observed in whole-blood, suggesting activity of TβM1 on the targeted pathway, these changes were not consistent to represent a PD effect. Additionally, despite the presence of an activated TGF-β1 expression signature in patients’ whole blood, the short dosing duration did not translate into significant antitumor effect in the small number of patients investigated in this study PMID:25270361

  3. Dose Escalation Versus Standard in Laryngopharyngeal Cancers

    ClinicalTrials.gov

    2016-05-02

    Malignant Neoplasm of Oropharynx Stage III; Malignant Neoplasm of Larynx Stage III; Malignant Neoplasm of Hypopharynx Stage III; Malignant Neoplasm of Oropharynx Stage IVa; Malignant Neoplasm of Oropharynx Stage IVb; Malignant Neoplasm of Larynx Stage IV; Malignant Neoplasm of Hypopharynx Stage IVa; Malignant Neoplasm of Hypopharynx Stage IVb

  4. Method comparison of ultrasound and kilovoltage x-ray fiducial marker imaging for prostate radiotherapy targeting

    NASA Astrophysics Data System (ADS)

    Fuller, Clifton David; Thomas, Charles R., Jr.; Schwartz, Scott; Golden, Nanalei; Ting, Joe; Wong, Adrian; Erdogmus, Deniz; Scarbrough, Todd J.

    2006-10-01

    Several measurement techniques have been developed to address the capability for target volume reduction via target localization in image-guided radiotherapy; among these have been ultrasound (US) and fiducial marker (FM) software-assisted localization. In order to assess interchangeability between methods, US and FM localization were compared using established techniques for determination of agreement between measurement methods when a 'gold-standard' comparator does not exist, after performing both techniques daily on a sequential series of patients. At least 3 days prior to CT simulation, four gold seeds were placed within the prostate. FM software-assisted localization utilized the ExacTrac X-Ray 6D (BrainLab AG, Germany) kVp x-ray image acquisition system to determine prostate position; US prostate targeting was performed on each patient using the SonArray (Varian, Palo Alto, CA). Patients were aligned daily using laser alignment of skin marks. Directional shifts were then calculated by each respective system in the X, Y and Z dimensions before each daily treatment fraction, previous to any treatment or couch adjustment, as well as a composite vector of displacement. Directional shift agreement in each axis was compared using Altman-Bland limits of agreement, Lin's concordance coefficient with Partik's grading schema, and Deming orthogonal bias-weighted correlation methodology. 1019 software-assisted shifts were suggested by US and FM in 39 patients. The 95% limits of agreement in X, Y and Z axes were ±9.4 mm, ±11.3 mm and ±13.4, respectively. Three-dimensionally, measurements agreed within 13.4 mm in 95% of all paired measures. In all axes, concordance was graded as 'poor' or 'unacceptable'. Deming regression detected proportional bias in both directional axes and three-dimensional vectors. Our data suggest substantial differences between US and FM image-guided measures and subsequent suggested directional shifts. Analysis reveals that the vast majority of

  5. Image-guided transorbital procedures with endoscopic video augmentation

    PubMed Central

    DeLisi, Michael P.; Mawn, Louise A.; Galloway, Robert L.

    2014-01-01

    Purpose: Surgical interventions to the orbital space behind the eyeball are limited to highly invasive procedures due to the confined nature of the region along with the presence of several intricate soft tissue structures. A minimally invasive approach to orbital surgery would enable several therapeutic options, particularly new treatment protocols for optic neuropathies such as glaucoma. The authors have developed an image-guided system for the purpose of navigating a thin flexible endoscope to a specified target region behind the eyeball. Navigation within the orbit is particularly challenging despite its small volume, as the presence of fat tissue occludes the endoscopic visual field while the surgeon must constantly be aware of optic nerve position. This research investigates the impact of endoscopic video augmentation to targeted image-guided navigation in a series of anthropomorphic phantom experiments. Methods: A group of 16 surgeons performed a target identification task within the orbits of four skull phantoms. The task consisted of identifying the correct target, indicated by the augmented video and the preoperative imaging frames, out of four possibilities. For each skull, one orbital intervention was performed with video augmentation, while the other was done with the standard image guidance technique, in random order. Results: The authors measured a target identification accuracy of 95.3% and 85.9% for the augmented and standard cases, respectively, with statistically significant improvement in procedure time (Z = −2.044, p = 0.041) and intraoperator mean procedure time (Z = 2.456, p = 0.014) when augmentation was used. Conclusions: Improvements in both target identification accuracy and interventional procedure time suggest that endoscopic video augmentation provides valuable additional orientation and trajectory information in an image-guided procedure. Utilization of video augmentation in transorbital interventions could further minimize

  6. Image-guided inversion of electrical resistivity data

    NASA Astrophysics Data System (ADS)

    Zhou, J.; Revil, A.; Karaoulis, M.; Hale, D.; Doetsch, J.; Cuttler, S.

    2014-04-01

    Electrical resistivity tomography (ERT) is based on solving a Poisson equation for the electrical potential and is characterized by a good sensitivity only in the vicinity of the electrodes used to gather the data. To provide more information to ERT, we propose an image-guided or structure-constrained inversion of the apparent resistivity data. This approach uses structural information obtained directly from a guiding image. This guiding image can be drawn from a high resolution geophysical method based on the propagation equation (e.g. migrated seismic or ground penetrating radar images) or possibly from a geological cross-section of the subsurface based on some prior geological expertise. The locations and orientations of the structural features can be extracted by image processing methods to determine the structure tensor and the semblances of the guiding image at a set of pixel. Then, we introduce these structural constraints into the inversion of the apparent resistivity data by weighting the four-direction smoothing matrix to smooth along, but not across, structural features. This approach allows preserving both discontinuities and coherences in the inversion of the resistivity data. The image-guided inversion is also combined with an image-guided interpolation approach used to focus a smooth resistivity image. This yields structurally-appealing resistivity tomograms, while the whole process remains computationally efficient. Such a procedure generates a more realistic resistivity distribution (closer to the true ones), which can be, in turn, used quantitatively using appropriate petrophysical transforms, to obtain parameters of interest such as porosity and saturation. We check the validity of this approach using two synthetic case studies as well as two real datasets. For the field data, the image used to guide the inversion of the electrical resistivity data is a GPR section in the first case and a combination of seismic and structural information in the

  7. Compact instrument for fluorescence image-guided surgery

    NASA Astrophysics Data System (ADS)

    Wang, Xinghua; Bhaumik, Srabani; Li, Qing; Staudinger, V. Paul; Yazdanfar, Siavash

    2010-03-01

    Fluorescence image-guided surgery (FIGS) is an emerging technique in oncology, neurology, and cardiology. To adapt intraoperative imaging for various surgical applications, increasingly flexible and compact FIGS instruments are necessary. We present a compact, portable FIGS system and demonstrate its use in cardiovascular mapping in a preclinical model of myocardial ischemia. Our system uses fiber optic delivery of laser diode excitation, custom optics with high collection efficiency, and compact consumer-grade cameras as a low-cost and compact alternative to open surgical FIGS systems. Dramatic size and weight reduction increases flexibility and access, and allows for handheld use or unobtrusive positioning over the surgical field.

  8. Image-guided breast biopsy: state-of-the-art.

    PubMed

    O'Flynn, E A M; Wilson, A R M; Michell, M J

    2010-04-01

    Percutaneous image-guided breast biopsy is widely practised to evaluate predominantly non-palpable breast lesions. There has been steady development in percutaneous biopsy techniques. Fine-needle aspiration cytology was the original method of sampling, followed in the early 1990s by large core needle biopsy. The accuracy of both has been improved by ultrasound and stereotactic guidance. Larger bore vacuum-assisted biopsy devices became available in the late 1990s and are now commonplace in most breast units. We review the different types of breast biopsy devices currently available together with various localization techniques used, focusing on their advantages, limitations and current controversial clinical management issues. PMID:20338392

  9. Image-Guided Thromboembolectomy of Acute Arterial Occlusion in Children.

    PubMed

    Kim, Song-Yi; Han, Ahram; Choi, Chanjoong; Min, Sang-Il; Kim, Hyo-Cheol; Ha, Jongwon; Min, Seung-Kee

    2016-07-01

    Acute arterial thromboembolism (ATE) is rare in childhood, but this medical emergency requires immediate treatment. Described herein are separate instances of lower extremity ATE in 2 children, both of whom were successfully managed through image-guided thromboembolectomy (IGT). One patient, a 34-month-old female child with nephrotic syndrome, developed bilateral iliac and popliteal thromboembolic arterial occlusions after high-dose steroid therapy. Another 9-year-old girl suffered an embolism of left popliteal artery due to infectious endocarditis. Both patients underwent IGT using over-the-wire Fogarty catheters. During follow-up, presenting symptoms resolved without significant complications. PMID:27177711

  10. [Image-guided stereotaxic biopsy of central nervous system lesions].

    PubMed

    Nasser, J A; Confort, C I; Ferraz, A; Esperança, J C; Duarte, F

    1998-06-01

    In a series of 44 image guided stereotactic biopsy from August 1995 until March 1997, findings were as follows (frequency order). Tumors, glioblastoma was the most frequent. Primary lymphoma and other conditions associated to AIDS. Metastasis, three cases, Vasculites, two cases, Arachnoid cyst, Creutzfeldt-Jakob, cortical degeneration, inespecific calcification (one case each). The age varied from 1 to 83 years. Forty one lesions were supratentorial, two infratentorial, and one was outside the brain (dura and skull) and we used stereotaxy to localize it. There was no mortality and morbidity was 2.3%. The literature is reviewed. We conclude that this procedure is safe and highly diagnostic. PMID:9698729

  11. Robotic Image-Guided Needle Interventions of the Prostate

    PubMed Central

    Mozer, Pierre C; Partin, Alan W; Stoianovici, Dan

    2009-01-01

    Prostate biopsy and needle-directed prostate therapies are currently performed free-handed or with needle external templates under ultrasound guidance. Direct image-guided intervention robots are modern instruments that have the potential to substantially enhance these procedures. These may increase the accuracy and repeatability with which needles are placed in the gland. The authors’ group has developed a robot for precise prostate targeting that operates remotely alongside the patient in the magnetic resonance imaging scanner, as guided according to the image. PMID:19390670

  12. Benefit of three-dimensional image-guided stereotactic localization in the hypofractionated treatment of lung cancer

    SciTech Connect

    Wang Lu . E-mail: lu.wang@fccc.edu; Feigenberg, Steve; Chen Lili; Pasklev, Kamen M.S.; Ma, Charlie C.-M.

    2006-11-01

    Purpose: The aim of this study was to investigate the benefit of image-guided stereotactic localization in the hypofractionated treatment for medically inoperable non-small-cell lung cancer. Methods and Materials: A stereotactic body localizer (SBL) system was used for patient immobilization, reliable image registration among multiphase computed tomography (CT) scanning, and image-guided stereotactic localization. Three sets of CT scans were taken (free breathing, and breath holding at the end-tidal inspiration and expiration, respectively) to contrast target motion. Target delineation was performed on all 3 sets of images and the combination of the targets forms an internal target volume (ITV). In this retrospective study of treatment dose verification, we performed image fusion between the simulation CT scan and each pretreatment CT scan to obtain the same target and critical structure information. The same treatment plans were reloaded onto each pretreatment CT scan with their respective stereotactic coordinate system. The changes in dose distributions were assessed by dose-volume histograms of the planning target volume (PTV) and the critical structures before and after isocenter corrections which were prompted by image-guided stereotactic localization. We compared D{sub 95}, D{sub 99}, and V{sub 95} for the PTV and internal target volume, and V{sub 2} and V{sub 3} for the ipsilateral lung. Results: Our retrospective study for 10 patients with 40 dose reconstructions showed that the average D{sub 95}, D{sub 99}, and V{sub 95} of the PTVs are 92.1%, 88.1%, and 95.8% of the planned values before isocenter corrections. With the corrections, all of these values are improved to 100% of the planned values. Conclusions: Three-dimensional image guidance is crucial for stereotactic radiotherapy of lung tumors.

  13. Image Guided Endoscopic Evacuation of Spontaneous Intracerebral Hemorrhage

    PubMed Central

    Miller, Chad M; Vespa, Paul; Saver, Jeffrey L; Kidwell, Chelsea S; Carmichael, Stanley T.; Alger, Jeffry; Frazee, John; Starkman, Sid; Liebeskind, David; Nenov, Valeriy; Elashoff, Robert; Martin, Neil

    2014-01-01

    Background Spontaneous intracerebral hemorrhage (ICH) is a devastating disease with high morbidity and mortality. ICH lacks an effective medical or surgical treatment despite the acknowledged pathophysiological benefits of achieved hemostasis and clot removal. Image guided stereotactic endoscopic hematoma evacuation is a promising minimally invasive approach designed to limit operative injury and maximize hematoma removal. Methods A single center randomized controlled trial was designed to assess the safety and efficacy of stereotactic hematoma evacuation compared to best medical management. Patients were randomized within 24 hours of hemorrhage in a 3:2 fashion to best medical management plus endoscopic hematoma evacuation or best medical management alone. Data was collected to assess efficacy and safety of hematoma evacuation and to identify procedural components requiring technical improvement. Results 10 patients have been enrolled and randomized to treatment. Six patients underwent endoscopic evacuation with a hematoma volume reduction of 80% +/−13 at 24 hours post procedure. The medical arm demonstrated a hematoma enlargement of 78% +/−142 during this same period. Rehemorrhage rates and deterioration rates were similar in the two groups. Mortality was 20% in the endoscopic group and 50% in the medical treatment cohort. The endoscopic technique was shown to be effective in identification and evacuation of hematomas while reduction in the number of endoscopic passes and maintenance of hemostasis require further study. Conclusion Image guided stereotactic endoscopic hematoma removal is a promising minimally invasive technique that is effective in immediate hematoma evacuation. This technique deserves further investigation to determine its role in ICH management. PMID:18424298

  14. Miniature image guided three-axis scanning and positioning system

    NASA Astrophysics Data System (ADS)

    Avirovik, Dragan; Dave, Digant; Priya, Shashank

    2012-04-01

    We have developed a high precision three axes scanning and positioning system for integration with Multifunctional Image Guided Surgical (MIGS) Platform. The stage integrates three main components: an optical coherence tomography (OCT) probe, laser scalpel and suction cup. The requirements for this stage were to provide scanning area of 400mm2, resolution of less than 10 microns and scanning velocity in the range of 10 - 40 mm/s. The stage was modeled using computer aided design software NX Unigraphics. In addition to the parameters mentioned above, additional boundary conditions for the stage were set as low volume and modularity. Optimized stage model was fabricated by using rapid prototyping technique that integrates low cost stepper motors, threaded rod drive train and a stepper motor controller. The EZ4axis stepper motor controller was able to provide 1/8th microstep resolution control over the motors, which met the criterion desired for the MIGS platform. Integration of computer controlled three-axis stage with MIGS platform provides the opportunity for conducting intricate surgical procedures using remote control or joystick. The device is image guided using the OCT probe and it is able to pin point any location requiring a laser scalpel incision. Due to the scanning capabilities, a high quality threedimensional image of the tissue topography is obtained which allows the surgeon to make a confident decision of where to apply the laser scalpel and make an incision.

  15. Image-guided plasma therapy of cutaneous wound

    NASA Astrophysics Data System (ADS)

    Zhang, Zhiwu; Ren, Wenqi; Yu, Zelin; Zhang, Shiwu; Yue, Ting; Xu, Ronald

    2014-02-01

    The wound healing process involves the reparative phases of inflammation, proliferation, and remodeling. Interrupting any of these phases may result in chronically unhealed wounds, amputation, or even patient death. Despite the clinical significance in chronic wound management, no effective methods have been developed for quantitative image-guided treatment. We integrated a multimodal imaging system with a cold atmospheric plasma probe for image-guided treatment of chronic wound. Multimodal imaging system offers a non-invasive, painless, simultaneous and quantitative assessment of cutaneous wound healing. Cold atmospheric plasma accelerates the wound healing process through many mechanisms including decontamination, coagulation and stimulation of the wound healing. The therapeutic effect of cold atmospheric plasma is studied in vivo under the guidance of a multimodal imaging system. Cutaneous wounds are created on the dorsal skin of the nude mice. During the healing process, the sample wound is treated by cold atmospheric plasma at different controlled dosage, while the control wound is healed naturally. The multimodal imaging system integrating a multispectral imaging module and a laser speckle imaging module is used to collect the information of cutaneous tissue oxygenation (i.e. oxygen saturation, StO2) and blood perfusion simultaneously to assess and guide the plasma therapy. Our preliminary tests show that cold atmospheric plasma in combination with multimodal imaging guidance has the potential to facilitate the healing of chronic wounds.

  16. Technology and human errors in image-guided surgeries

    NASA Astrophysics Data System (ADS)

    Jiang, Zhaowei; Miao, Song; Zamorano, Lucia J.; Li, Qinghang; Gong, JianXing; Diaz, Fernando

    1998-06-01

    Using image guidance for stereotactic surgery has been widely adopted in neurosurgery, orthopedic surgery and other surgery operations. Careful, precise and robust implementation of image-guidance can offer surgeon accurate intra-operative information that traditional techniques can not reach. Weak design, careless utilization, and dilemma in quality assurance protocol may result in severe scenarios. It is because that introducing image guidance into the operating room involves high precise technologies, delicate instruments and sophisticated processes. These can offer precision as well as space for human errors. A method based on the 'failure modes and effects analysis' is introduced to systematically study human errors in the image-guided surgery field. The paper presented the fundamental steps and architectures of the method. For better understanding of the method, a simple example is also provided. Analyzing human errors with the 'failure mode and effects analysis' benefits the development life cycle of the image-guided surgery system. It also helps for designing the clinical quality assurance process and the training courses for surgeons.

  17. Web hospital information system for image-guided procedures

    NASA Astrophysics Data System (ADS)

    Liu, Haiying; Tsai, Weu-Tek; Canessa, Gino; Canessa, John C.

    2002-05-01

    A complete Web based hospital information system, which can allow medical doctors to access and modify patient information and records anywhere in the world via the Internet, was developed. More specifically, this Web information system can be linked seamlessly to our fully computerized MR image-guided neurosurgery suite. This information system, which utilizes the unprecedented Internet infrastructure and adopts the most updated software technologies, addresses the urgent need for handling today's hospital information flow and management. With this new information system in our surgery suite, images and records that have been transferred directly from a diagnostic system such as MR, CT, etc. to the DICOM archive are accessible via a secured Internet connection. When data is accessed via the Web, it can be retrieved in several formats, including raw DICOM and binary, which are extremely useful for various research and development purposes, as well as new applications that require access to the original image data. The Internet-based Web Hospital Information System (WHIS) can easily match the existing standards for this type of information system in a hospital and can accommodate any anticipated requirements for image-guided minimally invasive surgery in the future. A practical and potentially low cost Web Hospital information system, which is functionality- driven, will be presented in this paper. It provides an extremely intuitive interactive environment, as well as a very user-friendly interface for use by both medical doctors and patients.

  18. Image-Guided Robotic Stereotactic Body Radiation Therapy for Liver Metastases: Is There a Dose Response Relationship?

    SciTech Connect

    Vautravers-Dewas, Claire; Dewas, Sylvain; Bonodeau, Francois; Adenis, Antoine; Lacornerie, Thomas; Penel, Nicolas; Lartigau, Eric; Mirabel, Xavier

    2011-11-01

    Purpose: To evaluate the outcome, tolerance, and toxicity of stereotactic body radiotherapy, using image-guided robotic radiation delivery, for the treatment of patients with unresectable liver metastases. Methods and Material: Patients were treated with real-time respiratory tracking between July 2007 and April 2009. Their records were retrospectively reviewed. Metastases from colorectal carcinoma and other primaries were not necessarily confined to liver. Toxicity was evaluated using National Cancer Institute Common Criteria for Adverse Events version 3.0. Results: Forty-two patients with 62 metastases were treated with two dose levels of 40 Gy in four Dose per Fraction (23) and 45 Gy in three Dose per Fraction (13). Median follow-up was 14.3 months (range, 3-23 months). Actuarial local control for 1 and 2 years was 90% and 86%, respectively. At last follow-up, 41 (66%) complete responses and eight (13%) partial responses were observed. Five lesions were stable. Nine lesions (13%) were locally progressed. Overall survival was 94% at 1 year and 48% at 2 years. The most common toxicity was Grade 1 or 2 nausea. One patient experienced Grade 3 epidermitis. The dose level did not significantly contribute to the outcome, toxicity, or survival. Conclusion: Image-guided robotic stereotactic body radiation therapy is feasible, safe, and effective, with encouraging local control. It provides a strong alternative for patients who cannot undergo surgery.

  19. Current Brachytherapy Quality Assurance Guidance: Does It Meet the Challenges of Emerging Image-Guided Technologies?

    SciTech Connect

    Williamson, Jeffrey F.

    2008-05-01

    In the past decade, brachytherapy has shifted from the traditional surgical paradigm to more modern three-dimensional image-based planning and delivery approaches. The role of intraoperative and multimodality image-based planning is growing. Published American Association of Physicists in Medicine, American College of Radiology, European Society for Therapeutic Radiology and Oncology, and International Atomic Energy Agency quality assurance (QA) guidelines largely emphasize the QA of planning and delivery devices rather than processes. These protocols have been designed to verify compliance with major performance specifications and are not risk based. With some exceptions, complete and clinically practical guidance exists for sources, QA instrumentation, non-image-based planning systems, applicators, remote afterloading systems, dosimetry, and calibration. Updated guidance is needed for intraoperative imaging systems and image-based planning systems. For non-image-based brachytherapy, the American Association of Physicists in Medicine Task Group reports 56 and 59 provide reasonable guidance on procedure-specific process flow and QA. However, improved guidance is needed even for established procedures such as ultrasound-guided prostate implants. Adaptive replanning in brachytherapy faces unsolved problems similar to that of image-guided adaptive external beam radiotherapy.

  20. Technical Note: Rapid prototyping of 3D grid arrays for image guided therapy quality assurance

    SciTech Connect

    Kittle, David; Holshouser, Barbara; Slater, James M.; Guenther, Bob D.; Pitsianis, Nikos P.; Pearlstein, Robert D.

    2008-12-15

    Three dimensional grid phantoms offer a number of advantages for measuring imaging related spatial inaccuracies for image guided surgery and radiotherapy. The authors examined the use of rapid prototyping technology for directly fabricating 3D grid phantoms from CAD drawings. We tested three different fabrication process materials, photopolymer jet with acrylic resin (PJ/AR), selective laser sintering with polyamide (SLS/P), and fused deposition modeling with acrylonitrile butadiene styrene (FDM/ABS). The test objects consisted of rectangular arrays of control points formed by the intersections of posts and struts (2 mm rectangular cross section) and spaced 8 mm apart in the x, y, and z directions. The PJ/AR phantom expanded after immersion in water which resulted in permanent warping of the structure. The surface of the FDM/ABS grid exhibited a regular pattern of depressions and ridges from the extrusion process. SLS/P showed the best combination of build accuracy, surface finish, and stability. Based on these findings, a grid phantom for assessing machine-dependent and frame-induced MR spatial distortions was fabricated to be used for quality assurance in stereotactic neurosurgical and radiotherapy procedures. The spatial uniformity of the SLS/P grid control point array was determined by CT imaging (0.6x0.6x0.625 mm{sup 3} resolution) and found suitable for the application, with over 97.5% of the control points located within 0.3 mm of the position specified in CAD drawing and none of the points off by more than 0.4 mm. Rapid prototyping is a flexible and cost effective alternative for development of customized grid phantoms for medical physics quality assurance.

  1. First-In-Human, Double-Blind, Placebo-Controlled, Randomized, Dose-Escalation Study of BG00010, a Glial Cell Line-Derived Neurotrophic Factor Family Member, in Subjects with Unilateral Sciatica

    PubMed Central

    Rolan, Paul E.; O’Neill, Gilmore; Versage, Eve; Rana, Jitesh; Tang, Yongqiang; Galluppi, Gerald; Aycardi, Ernesto

    2015-01-01

    Objective To evaluate the safety, tolerability, and pharmacokinetics of single doses of BG00010 (neublastin, artemin, enovin) in subjects with unilateral sciatica. Methods This was a single-center, blinded, placebo-controlled, randomized Phase 1 sequential-cohort, dose-escalation study (ClinicalTrials.gov identifier NCT00961766; funded by Biogen Idec). Adults with unilateral sciatica were enrolled at The Royal Adelaide Hospital, Australia. Four subjects were assigned to each of eleven cohorts (intravenous BG00010 0.3, 1, 3, 10, 25, 50, 100, 200, 400, or 800 μg/kg, or subcutaneous BG00010 50 μg/kg) and were randomized 3:1 to receive a single dose of BG00010 or placebo. The primary safety and tolerability assessments were: adverse events; clinical laboratory parameters and vital signs; pain as measured by a Likert rating scale; intra-epidermal nerve fiber density; and longitudinal assessment of quantitative sensory test parameters. Blood, serum, and plasma samples were collected for pharmacokinetic and pharmacodynamic assessments. Subjects were blinded to treatment assignment throughout the study. The investigator was blinded to treatment assignment until the Data Safety Review Committee review of unblinded data, which occurred after day 28. Results Beyond the planned enrollment of 44 subjects, four additional subjects were enrolled into to the intravenous BG00010 200 μg/kg cohort after one original subject experienced mild generalized pruritus. Therefore, a total of 48 subjects were enrolled between August 2009 and December 2011; all were included in the safety analyses. BG00010 was generally well tolerated: in primary analyses, the most common treatment-emergent adverse events were changes in temperature perception, pruritus, rash, or headache; no trends were observed in clinical laboratory parameters, vital signs, intra-epidermal nerve fiber density, or quantitative sensory testing. BG00010 was not associated with any clear, dose-dependent trends in Likert pain

  2. Phase I study of simultaneous dose escalation and schedule acceleration of cyclophosphamide-doxorubicin-etoposide using granulocyte colony-stimulating factor with or without antimicrobial prophylaxis in patients with small-cell lung cancer.

    PubMed Central

    Ardizzoni, A.; Pennucci, M. C.; Danova, M.; Viscoli, C.; Mariani, G. L.; Giorgi, G.; Venturini, M.; Mereu, C.; Scolaro, T.; Rosso, R.

    1996-01-01

    A phase I study was designed to assess whether dose intensity of an 'accelerated' cyclophosphamide-doxorubicin-etoposide (CDE) regimen plus granulocyte colony-stimulating factor (G-CSF) could be increased further, in an outpatient setting, by escalating the dose of each single drug of the regimen. Patients with previously untreated small-cell lung cancer (SCLC) received escalating doses of cyclophosphamide (C) 1100-1300 mg m-2 intravenously (i.v.) on day 1, doxorubicin (D) 50-60 mg m-2 i.v. on day 1, etoposide (E) 110-130 mg m-2 i.v. on days 1, 2, 3 and every 14 days for at least three courses. Along with chemotherapy, G-CSF (filgastrim) 5 micrograms kg-1 from day 5 to day 11 was administered subcutaneously (s.c.) to all patients. Twenty-five patients were enrolled into the study. All patients at the first dose level (C 1100, D 50, E 110 x 3) completed three or more cycles at the dose and schedule planned by the protocol and no 'dose-limiting toxicity' (DLT) was seen. At the second dose level (C 1200, D 55, E 120 x 3) three out of five patients had a DLT consisting of 'granulocytopenic fever' (GCPF). Another six patients were treated at this dose level with the addition of ciprofloxacin 500 mg twice a day and only two patients had a DLT [one episode of documented oral candidiasis and one of 'fever of unknown origin' (FUO) with generalised mucositis]. Accrual of patients proceeded to the third dose level (C 1300, D 60, E 130 x 3) with the prophylactic use of ciprofloxacin. Four out of six patients experienced a DLT consisting of GCPF or documented non-bacterial infection. Accrual of patients at the third dose level was then resumed adding to ciprofloxacin anti-fungal prophylaxis (fluconazole 100 mg daily) and anti-viral prophylaxis (acyclovir 800 mg twice a day) from day 5 to 11. Out of five patients treated three experienced a DLT consisting of severe leucopenia and fever or infection. With a simultaneous dose escalation and schedule acceleration it is indeed

  3. [Design of an FPGA-based image guided surgery hardware platform].

    PubMed

    Zou, Fa-Dong; Qin, Bin-Jie

    2008-07-01

    An FPGA-Based Image Guided Surgery Hardware Platform has been designed and implemented in this paper. The hardware platform can provide hardware acceleration for image guided surgery. It is completed with a video decoder interface, a DDR memory controller, a 12C bus controller, an interrupt controller and so on. It is able to perform real time video endoscopy image capturing in the surgery and to preserve the hardware interface for image guided surgery algorithm module. PMID:18973036

  4. Improved survival with the addition of radiotherapy to androgen deprivation: questions answered and a review of current controversies in radiotherapy for non-metastatic prostate cancer.

    PubMed

    Amini, Arya; Kavanagh, Brian D; Rusthoven, Chad G

    2016-01-01

    The contemporary standard of care for locally advanced high-risk prostate cancer includes a combination of dose-escalated radiotherapy (RT) plus androgen-deprivation therapy (ADT). However, 20 years ago, at the inception of the National Cancer Institute of Canada (NCIC) led study (NCIC Clinical Trials Group PR.3/Medical Research Council PR07/Intergroup T94-0110), the survival impact of prostate RT for high-risk disease was uncertain. Recently, Mason, Warde and colleagues presented the final results of this NCIC/MRC study (PMID: 25691677) randomizing 1,205 high-risk prostate cancer patients to ADT + RT vs. ADT alone. These updated results confirm substantial improvements with the addition of RT to ADT for the endpoints of overall survival (OS), disease-free survival (DFS), and biochemical recurrence. Close examination of subtleties of this trial's design highlight some of the most salient controversies in the field of prostate RT, including the risk-stratified roles of ADT, optimal ADT duration, and RT field design in the dose-escalated and intensity-modulated radiotherapy (IMRT) era. PMID:26855950

  5. Anal Cancer: An Examination of Radiotherapy Strategies

    SciTech Connect

    Glynne-Jones, Rob; Lim, Faye

    2011-04-01

    The Radiation Therapy Oncology Group 9811, ACCORD-03, and ACT II Phase III trials in anal cancer showed no benefit for cisplatin-based induction and maintenance chemotherapy, or radiation dose-escalation >59 Gy. This review examines the efficacy and toxicity of chemoradiation (CRT) in anal cancer, and discusses potential alternative radiotherapy strategies. The evidence for the review was compiled from randomized and nonrandomized trials of radiation therapy and CRT. A total of 103 retrospective/observational studies, 4 Phase I/II studies, 16 Phase II prospective studies, 2 randomized Phase II studies, and 6 Phase III trials of radiotherapy or chemoradiation were identified. There are no meta-analyses based on individual patient data. A 'one-size-fits-all' approach for all stages of anal cancer is inappropriate. Early T1 tumors are probably currently overtreated, whereas T3/T4 lesions might merit escalation of treatment. Intensity-modulated radiotherapy or the integration of biological therapy may play a role in future.

  6. Current advances in radiotherapy of head and neck malignancies.

    PubMed

    Roopashri, G; Baig, Muqeet

    2013-12-01

    Necessity is the mother of all inventions. This is also true in case of cancer therapy. With increasing incidence of head and neck malignancies, remarkable developments have been made towards cancer development and treatment which continues to be a major challenge. Approximately fifty percent of all cancer patients receive radiotherapy which contributes towards forty percent of curative treatment for cancer. New developments in radiation oncology have helped to improve outlook for patients and find more effective treatment. With the advent of new technologies, radiotherapy seems to be promising in patients with head and neck malignancies these advancements include Altered fractionation, Three-dimensional conformal radiotherapy, Intensity-modulated radiotherapy, Image Guided Radiotherapy, Stereotactic radiation, Charged-particle radiotherapy, and Intraoperative radiotherapy. How to cite this article: Roopashri G, Baig M. Current advances in radiotherapy of head and neck malignancies. J Int Oral Health 2013; 5(6):119-23 . PMID:24453456

  7. Photoacoustic image-guided needle biopsy of sentinel lymph nodes

    NASA Astrophysics Data System (ADS)

    Kim, Chulhong; Erpelding, Todd N.; Akers, Walter J.; Maslov, Konstantin; Song, Liang; Jankovic, Ladislav; Margenthaler, Julie A.; Achilefu, Samuel; Wang, Lihong V.

    2011-03-01

    We have implemented a hand-held photoacoustic and ultrasound probe for image-guided needle biopsy using a modified clinical ultrasound array system. Pulsed laser light was delivered via bifurcated optical fiber bundles integrated with the hand-held ultrasound probe. We photoacoustically guided needle insertion into rat sentinel lymph nodes (SLNs) following accumulation of indocyanine green (ICG). Strong photoacoustic image contrast of the needle was achieved. After intradermal injection of ICG in the left forepaw, deeply positioned SLNs (beneath 2-cm thick chicken breast) were easily indentified in vivo and in real time. Further, we confirmed ICG uptake in axillary lymph nodes with in vivo and ex vivo fluorescence imaging. These results demonstrate the clinical potential of this hand-held photoacoustic system for facile identification and needle biopsy of SLNs for cancer staging and metastasis detection in humans.

  8. Optical imaging-guided cancer therapy with fluorescent nanoparticles

    PubMed Central

    Jiang, Shan; Gnanasammandhan, Muthu Kumara; Zhang, Yong

    2010-01-01

    The diagnosis and treatment of cancer have been greatly improved with the recent developments in nanotechnology. One of the promising nanoscale tools for cancer diagnosis is fluorescent nanoparticles (NPs), such as organic dye-doped NPs, quantum dots and upconversion NPs that enable highly sensitive optical imaging of cancer at cellular and animal level. Furthermore, the emerging development of novel multi-functional NPs, which can be conjugated with several functional molecules simultaneously including targeting moieties, therapeutic agents and imaging probes, provides new potentials for clinical therapies and diagnostics and undoubtedly will play a critical role in cancer therapy. In this article, we review the types and characteristics of fluorescent NPs, in vitro and in vivo imaging of cancer using fluorescent NPs and multi-functional NPs for imaging-guided cancer therapy. PMID:19759055

  9. Image-guided focal therapy for prostate cancer.

    PubMed

    Sankineni, Sandeep; Wood, Bradford J; Rais-Bahrami, Soroush; Walton Diaz, Annerleim; Hoang, Anthony N; Pinto, Peter A; Choyke, Peter L; Türkbey, Barış

    2014-11-01

    The adoption of routine prostate specific antigen screening has led to the discovery of many small and low-grade prostate cancers which have a low probability of causing mortality. These cancers, however, are often treated with radical therapies resulting in long-term side effects. There has been increasing interest in minimally invasive focal therapies to treat these tumors. While imaging modalities have improved rapidly over the past decade, similar advances in image-guided therapy are now starting to emerge--potentially achieving equivalent oncologic efficacy while avoiding the side effects of conventional radical surgery. The purpose of this article is to review the existing literature regarding the basis of various focal therapy techniques such as cryotherapy, microwave, laser, and high intensity focused ultrasound, and to discuss the results of recent clinical trials that demonstrate early outcomes in patients with prostate cancer. PMID:25205025

  10. The evolution of image-guided lumbosacral spine surgery

    PubMed Central

    Faulkner, Austin R.; Pasciak, Alexander S.; Bradley, Yong C.

    2015-01-01

    Techniques and approaches of spinal fusion have considerably evolved since their first description in the early 1900s. The incorporation of pedicle screw constructs into lumbosacral spine surgery is among the most significant advances in the field, offering immediate stability and decreased rates of pseudarthrosis compared to previously described methods. However, early studies describing pedicle screw fixation and numerous studies thereafter have demonstrated clinically significant sequelae of inaccurate surgical fusion hardware placement. A number of image guidance systems have been developed to reduce morbidity from hardware malposition in increasingly complex spine surgeries. Advanced image guidance systems such as intraoperative stereotaxis improve the accuracy of pedicle screw placement using a variety of surgical approaches, however their clinical indications and clinical impact remain debated. Beginning with intraoperative fluoroscopy, this article describes the evolution of image guided lumbosacral spinal fusion, emphasizing two-dimensional (2D) and three-dimensional (3D) navigational methods. PMID:25992368

  11. Toward Intraoperative Image-Guided Transoral Robotic Surgery.

    PubMed

    Liu, Wen P; Reaugamornrat, Sureerat; Deguet, Anton; Sorger, Jonathan M; Siewerdsen, Jeffrey H; Richmon, Jeremy; Taylor, Russell H

    2013-09-01

    This paper presents the development and evaluation of video augmentation on the stereoscopic da Vinci S system with intraoperative image guidance for base of tongue tumor resection in transoral robotic surgery (TORS). Proposed workflow for image-guided TORS begins by identifying and segmenting critical oropharyngeal structures (e.g., the tumor and adjacent arteries and nerves) from preoperative computed tomography (CT) and/or magnetic resonance (MR) imaging. These preoperative planned data can be deformably registered to the intraoperative endoscopic view using mobile C-arm cone-beam computed tomography (CBCT) [1, 2]. Augmentation of TORS endoscopic video defining surgical targets and critical structures has the potential to improve navigation, spatial orientation, and confidence in tumor resection. Experiments in an