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Early Experiences From a Clinical Trial of Daily Adaptive Plan Selection in Radiation Therapy for Urinary Bladder Cancer
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International Journal of Radiation Oncology Biology Physics
despite evidence from randomized trials supporting its use during the study period. Though receipt of such therapy was higher in younger patients and in those at highest risk for recurrence, overall rates of utilization are low. Until data from ongoing randomized trials comparing the outcomes of adjuvant radiation therapy to early salvage therapy become available, our study suggests additional effort is needed to ensure patients receive appropriate care as supported by national practice guidelines and level I evidence. Author Disclosure: H. Sineshaw: None. P.J. Gray: None. J.A. Efstathiou: None. A. Jemal: None.
Corporation. S. Leadership; NRG Genitourinary Cancer Committee. W. Shipley: K. Advisory Board; Bladder Cancer Advisory Network, Woods Hole Oceanographic Institute, NCI Bladder Cancer Task Force.
288 The Initial Report of RTOG 0524: Phase I/II Trial of a Combination of Paclitaxel and Trastuzumab With Daily Irradiation or Paclitaxel Alone with Daily Irradiation Following Transurethral Surgery for Non-Cystectomy Candidates With Muscle-Invasive Bladder Cancer H.T. Pham,1 C. Hu,2 M.D. Michaelson,3 D.M. Dahl,3 C. Wu,3 R.M. Whittington,4 G.P. Swanson,5 J. Vuky,1,6 R.J. Lee,7 L. Souhami,8 B.K. Chang,9 A. George,2 H.M. Sandler,10 and W. Shipley3; 1Virginia Mason Medical Center, Seattle, WA, 2Radiation Therapy Oncology GroupStatistical Group, Philadelphia, PA, 3Massachusetts General Hospital, Boston, MA, 4Philadelphia VA Medical Center, Philadelphia, PA, 5 University of Texas Health Science Center, San Antonio, TX, 6Oregon Health & Science University, Portland, OR, 7Intermountain Medical Institute, Salt Lake City, UT, 8McGill University Health Centre, Montreal, QC, Canada, 9Radiation Oncology Associates, Fort Wayne, IN, 10CedarsSinai Medical Center, Los Angeles, CA Purpose/Objective(s): Most patients (pts) with muscle invasive bladder urothelial carcinoma (UC) undergo definitive local treatment with radical cystectomy. Up to 50% of pts with UC may overexpress HER2/neu, and overexpression may be associated with reduced responsiveness to chemoradiation and reduced survival. Many pts with UC have comorbidities that preclude surgery, creating a traditionally underserved population with worse outcomes. RTOG 0524 evaluated the safety and initial efficacy of trimodality, organ-preserving therapy in pts not suitable for cystectomy. Materials/Methods: Pts with invasive bladder UC (stages T2-T4a, N0-1, M0) underwent cystoscopic tumor resection. Tumors were analyzed by HER2/neu immunohistochemistry (IHC) and assigned to chemotherapy group I (IHC 2+ or 3+; paclitaxel and trastuzumab) or II (IHC negative or 1+; paclitaxel alone). Concurrent weekly paclitaxel (50 mg/m2), weekly trastuzumab (group I only) and daily radiation (64.8 Gy total in 36 fractions) were given for seven consecutive weeks. Results: Twenty-one eligible patients were entered in group I and 47 in group 2, with median ages of 80 and 73, respectively. The primary endpoint was acute protocol-defined toxicity related to treatment. Acute toxicity was observed in 7/21 pts (33%) in group I and 14/47 pts (30%) in group II. Most common Grade 3 adverse events in groups I and II were marrow suppression (43% and 17%), diarrhea (33% and 30%) and hyponatremia (14% and 4%). Three deaths on study were attributed to colonic perforation, pneumonia and sudden death. Radiation completion rates were 72% and 85% in the two groups, and full dose chemotherapy completion rates were 52% and 51%. Evaluation by cystoscopy and/or tumor biopsy at 12 weeks noted complete response in 8/13 pts (62%) in group I, in 19/33 pts (58%) in group II, and was not performed in the remaining pts. Conclusions: Trimodality bladder-preserving therapy is an appropriate treatment in non-cystectomy candidates with invasive UC. The response rate for HER2/neu-targeted therapy is encouraging but may increase certain adverse events in this challenging population. Acknowledgment: This project was supported by RTOG grant U10 CA21661, and CCOP grant U10 CA37422 from the National Cancer Institute (NCI) and Genentech Inc. Author Disclosure: H.T. Pham: None. C. Hu: None. M.D. Michaelson: None. D.M. Dahl: None. C. Wu: None. R.M. Whittington: None. G.P. Swanson: None. J. Vuky: None. R.J. Lee: None. L. Souhami: None. B.K. Chang: None. A. George: None. H.M. Sandler: G. Consultant; Sanofi-Aventis, Medivation, Bayer, Eviti, Advanced Medical Isotope
289 Long-Term Outcomes Among Patients Who Achieve Complete or Near-Complete Responses After the Induction Phase of Bladder Preserving Combined Modality Therapy for Muscle-Invasive Bladder Cancer: A Pooled Analysis of RTOG 9906 and 0233 T. Mitin,1 A. George,2 A.L. Zietman,3 D.S. Kaufman,3 R. Uzzo,4 R. Dreicer,5 N. Heney,3 H.J. Wallace,6 L. Souhami,7 M.C. Dobelbower,8 H.M. Sandler,9 and W. Shipley3; 1Oregan Health and Science University, Portland, OR, 2Radiation Therapy Oncology Group, Philadelphia, PA, 3 Massachusetts General Hospital, Boston, MA, 4Fox Chase Cancer Center, Philadelphia, PA, 5Cleveland Clinic, Cleveland, OH, 6University of Vermont, Burlington, VT, 7Centre Universitaire de Sante´ McGill, Montreal, QC, Canada, 8University of Alabama at Birmingham, Birmingham, AL, 9 Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA Purpose/Objective(s): Bladder preserving combined-modality therapy for muscle-invasive bladder cancer (MIBC) includes transurethral resection and concurrent chemo-RT given in two phases. After the induction phase with chemo-RT to 40 Gy the tumor response is assessed by cystoscopic biopsies and urine cytology. Early salvage cystectomy is promptly offered in case of persistent disease, otherwise patients proceed to consolidation chemo-RT to 64 Gy. The two most recent RTOG protocols 9906 and 0233 allowed patients with near-complete response (Ta or Tis) after the induction phase to proceed to consolidation. In order to determine whether patients with near-complete response had worse outcomes than patients with complete response, we performed a retrospective secondary analysis of pooled data from these two trials. Materials/Methods: We performed a pooled analysis of 119 eligible patients with MIBC enrolled on RTOG trials 9906 and 0233, who were classified as having a complete (T0) or near-complete (Ta or Tis) response after induction chemo-RT and completed consolidation with a total RT dose of at least 60 Gy. We estimated bladder recurrence, salvage cystectomy rates and disease-specific survival by the cumulative incidence method and bladder-intact and overall survivals by the Kaplan-Meier method. Results: Among 119 eligible patients, 101 (85%) achieved T0 and 18 (15%) achieved Ta or Tis after induction chemo-RT as judged at the time of cystoscopic evaluation and biopsy (with a median interval to biopsy of 28 days in both groups, p Z 0.25) and proceeded to consolidation. After a median follow-up of 5.9 years, 36/101 (36%) T0 patients vs. 5/18 (28%) Ta or Tis patients experienced bladder recurrence (p Z 0.52). Fourteen patients among complete responders eventually required late salvage cystectomy for tumor recurrence, in comparison to one patient among nearcomplete responders (p Z 0.47). Disease-specific, bladder-intact and overall survivals were not significantly different between T0 and Ta/Tis cases. Conclusions: There is no apparent difference in the bladder recurrence and salvage cystectomy rates between complete and near-complete responders as judged at the time of cystoscopic evaluation after induction phase of bladder preserving CMT. It is appropriate to recommend that patients with Ta or Tis after induction chemo-RT continue with bladder-sparing therapy. Author Disclosure: A. George: None. A.L. Zietman: None. D.S. Kaufman: None. R. Uzzo: None. R. Dreicer: None. N. Heney: None. H.J. Wallace: None. L. Souhami: None. M.C. Dobelbower: None. H.M. Sandler: None. W. Shipley: None.
290 Early Experiences From a Clinical Trial of Daily Adaptive Plan Selection in Radiation Therapy for Urinary Bladder Cancer L.P. Muren,1 A. Vestergaard,1 H. Lindberg,2 K.L. Jakobsen,2 J.B.B. Petersen,1 U.V. Elstrøm,1 and M. Høyer1; 1Aarhus University Hospital, Aarhus, Denmark, 2Herlev University Hospital, Herlev, Denmark
Volume 90 Number 1S Supplement 2014 Purpose/Objective(s): Large changes in bladder shape and size during a course of radiation therapy (RT) make adaptive RT (ART) appealing in the treatment of this tumor site. We are conducting a two-center clinical phase II trial of daily plan selection based ART for bladder cancer with the primary aim of reducing gastro-intestinal morbidity due to sparing of the bowel and the rectum. We here report early dose/volume outcomes from the first twenty patients treated in this trial. Materials/Methods: All patients received 60 Gy in 30 fractions to the bladder; in thirteen of the patients the pelvic lymph nodes were simultaneously treated to 48 Gy. Daily patient set-up was by use of cone-beam CT (CBCT) guidance and treatment was delivered by volumetric modulated arc therapy (VMAT). The first five fractions were delivered using large, population-based margins; the bladder contours from the CBCTs acquired prior to the first four fractions were used to create a library of three plans, corresponding to a small, medium and large size bladder. All patients were from fraction no. 6 treated using daily online plan selection, where the smallest plan covering the bladder was selected prior to each treatment delivery. Volume ratios of PTV for ART vs. non-ART averaged over the treatment course were calculated. DVHs for bowel cavity and rectum were derived by summation of the selected plans and these were compared to standard non-adaptive RT plans using population-based margins. Results: The frequencies of which the small, medium, and large size plans were used over the (total of 600) fractions were similar; plans were used at a median of 9, 9.5 and 10 fractions, respectively. The median volume ratio of PTV-ART vs. non-ART across the treatment course was 0.70 (range: 0.46-0.89). The median rectal volume receiving 50 Gy or more was 5% (range: 0-41%), compared to 17% (range: 0-62%) if the patients had been treated with standard, non-adaptive RT. For the bowel cavity, the median volume receiving more than 45 Gy was 392 cm3 (range: 84-625 cm3), compared to 487 cm3 (range: 126-710 cm3) if not treated with adaptation. Conclusions: Daily adaptive plan selection in RT of bladder cancer results in a considerable normal tissue sparing, which is expected to reduce the risk of gastro-intestinal morbidity. Author Disclosure: L.P. Muren: None. E. Research Grant; Research grant from Varian Medical Systems to our dept., but not to the project described in the abstract. A. Vestergaard: None. H. Lindberg: None. K.L. Jakobsen: None. J.B.B. Petersen: None. U.V. Elstrøm: None. M. Høyer: None.
291 Modern Practice Patterns and Survival for Testicular Seminoma: Results from the National Cancer Data Base P.J. Gray,1 C. Lin,2 A. Jemal,2 and J.A. Efstathiou1; 1Massachusetts General Hospital, Boston, MA, 2American Cancer Society, Atlanta, GA Purpose/Objective(s): The management of testicular seminoma (TS) after orchiectomy is evolving, especially in patients with early-stage disease. We sought to investigate modern trends in the management of TS and to assess the effects of different adjuvant management strategies on survival. Materials/Methods: Data from the National Cancer Data Base on 41,745 patients with TS treated between 1998 and 2010 were analyzed. Logistic regression models were constructed to assess factors associated with adjuvant management paradigms. Cox proportional hazards models were used to analyze five-year survival in those diagnosed between 1998 and 2005. Results: Between 1998 and 2010, for patients with stage IA/B TS, rates of surveillance increased from 23.7% to 46.7% and receipt of adjuvant chemotherapy increased from 1.5% to 16.8%, while receipt of adjuvant radiation therapy decreased from 70.8% to 35.4%. For patients with stage IIA/B TS, receipt of adjuvant radiation therapy declined from 55.9% to 42.2% while receipt of chemotherapy rose from 20.4% to 40.6%. For those patients with stage IA/B TS, black or Hispanic race (OR Z 1.32 and 1.38 respectively vs. white, p both < 0.001) and lack of medical insurance (OR Z 1.29 vs. private insurance, p < 0.001) or insurance through Medicaid (OR Z 1.14 vs. private insurance, p Z
Oral Scientific Sessions S133 0.043) were associated with an increased odds of receiving surveillance while treatment at a high-volume center was associated with decreased odds (OR Z 0.63 vs. low-volume, p < 0.001). For stage IA/B and IIA/B patients who received adjuvant treatment, receipt of care at an NCIdesignated cancer center predicted for decreased receipt of radiation therapy vs. chemotherapy. Unadjusted five-year overall survival rates for patients with stage IA/B disease were 96.3% for surveillance, 98.0% for adjuvant radiation therapy and 94.4% for adjuvant chemotherapy. In a multivariate Cox regression model, receipt of adjuvant radiation therapy was associated with decreased hazard for death at five years (HR Z 0.65, p < 0.001) while receipt of adjuvant chemotherapy was associated with an increased hazard for death (HR Z 1.64, p Z 0.041) compared to receipt of surveillance after orchiectomy. Conclusions: Surveillance after orchiectomy for patients with stage I TS has increased in recent years. Receipt of adjuvant chemotherapy has also increased significantly in stage I and early stage II TS while receipt of radiation therapy has declined. In this large national dataset, patients with stage IA/B disease who receive radiation therapy appear to have improved five-year survival compared to those who receive surveillance or adjuvant chemotherapy. Additional study and longer follow-up (including assessment of late effects of treatment) are needed to validate these findings and confirm the appropriateness of these changing trends in management. Author Disclosure: P.J. Gray: None. C. Lin: None. A. Jemal: None. J.A. Efstathiou: None.
292 Long-Term Toxicity and Cosmetic Results of Partial Versus Whole Breast Irradiation: 10-Year Results of a Phase III APBI Trial C. Polgar, T. Major, Z. Sulyok, Z. Takacsi-Nagy, and J. Fodor; National Institute of Oncology, Budapest, Hungary Purpose/Objective(s): The 10-year survival results of a phase III study comparing breast-conserving treatment with partial (PBI) or whole breast irradiation (WBI) have been published recently. In this analysis long-term toxicity and cosmetic results are reported. Materials/Methods: Between 1998 and 2004, 258 selected, low-risk breast cancer patients were randomized after breast-conserving surgery to receive 50 Gy WBI (n Z 130) or PBI (n Z 128). The latter consisted of either 7 x 5.2 Gy high-dose-rate multicatheter brachytherapy (PBI-HDR; n Z 88) or 50 Gy electron beam irradiation (PBI-ELE; n Z 40). Late radiation side effects were scored by the RTOG/EORTC radiation morbidity scoring scheme. Cosmetic results were evaluated using the Harvard criteria. Follow-up mammograms were reviewed searching for visible signs of fat necrosis. Results: After a median follow-up of 10.2 years, skin side effects (any grade; G) occurred in 12.9%, 40.0%, and 20.5% in PBI-HDR, PBI-ELE, and WBI groups, respectively (pHDR vs WBI Z NS, pHDR vs ELE Z 0.0009, pELE vs WBI Z NS). The respective rate of G3 telangiectasia was 0%, 7.5%, and 2.6% (pHDR vs WBI Z NS, pHDR vs ELE Z 0.0311, pELE vs WBI Z NS). The rate of fibrosis (any G) was 49.4%, 22.5%, and 42.7% after PBI-HDR, PBI-ELE, and WBI, respectively (pHDR vs WBI Z NS, pHDR vs ELE Z 0.0034, pELE vs WBI Z 0.0166). The respective rate of G3 fibrosis was only 2.4%, 0%, and 0.9%; p Z NS). Fat necrosis was detected on follow-up mammograms in 58.1%, 30.0%, and 52.1%, respectively (pHDR vs WBI Z NS, pHDR vs ELE Z 0.0019, pELE vs WBI Z 0.0119). Only one patient (1.2%) in the PBI-HDR group developed fat necrosis requiring surgical intervention. The overall rate of G3 late toxicities was 2.4%, 7.5%, and 3.4% after PBI-HDR, PBI-ELE, and WBI, respectively (p Z NS). The rate of excellent-good cosmetic result was 81.2% in the PBI-HDR, 75.0% in the PBI-ELE, and 62.1% in the control group (pHDR vs WBI Z 0.0003, pHDR vs ELE Z NS, pELE vs WBI Z 0.0972). Conclusions: Significantly better cosmetic outcome can be achieved with carefully designed PBI-HDR multicatheter implants compared with the outcome after PBI-ELE or WBI. Both WBI and PBI (either with HDR or ELE) are well tolerated and severe late side effects are minimal. Slightly more parenchymal side effects occur after PBI-HDR. On the
International Journal of Radiation Oncology Biology Physics
despite evidence from randomized trials supporting its use during the study period. Though receipt of such therapy was higher in younger patients and in those at highest risk for recurrence, overall rates of utilization are low. Until data from ongoing randomized trials comparing the outcomes of adjuvant radiation therapy to early salvage therapy become available, our study suggests additional effort is needed to ensure patients receive appropriate care as supported by national practice guidelines and level I evidence. Author Disclosure: H. Sineshaw: None. P.J. Gray: None. J.A. Efstathiou: None. A. Jemal: None.
Corporation. S. Leadership; NRG Genitourinary Cancer Committee. W. Shipley: K. Advisory Board; Bladder Cancer Advisory Network, Woods Hole Oceanographic Institute, NCI Bladder Cancer Task Force.
288 The Initial Report of RTOG 0524: Phase I/II Trial of a Combination of Paclitaxel and Trastuzumab With Daily Irradiation or Paclitaxel Alone with Daily Irradiation Following Transurethral Surgery for Non-Cystectomy Candidates With Muscle-Invasive Bladder Cancer H.T. Pham,1 C. Hu,2 M.D. Michaelson,3 D.M. Dahl,3 C. Wu,3 R.M. Whittington,4 G.P. Swanson,5 J. Vuky,1,6 R.J. Lee,7 L. Souhami,8 B.K. Chang,9 A. George,2 H.M. Sandler,10 and W. Shipley3; 1Virginia Mason Medical Center, Seattle, WA, 2Radiation Therapy Oncology GroupStatistical Group, Philadelphia, PA, 3Massachusetts General Hospital, Boston, MA, 4Philadelphia VA Medical Center, Philadelphia, PA, 5 University of Texas Health Science Center, San Antonio, TX, 6Oregon Health & Science University, Portland, OR, 7Intermountain Medical Institute, Salt Lake City, UT, 8McGill University Health Centre, Montreal, QC, Canada, 9Radiation Oncology Associates, Fort Wayne, IN, 10CedarsSinai Medical Center, Los Angeles, CA Purpose/Objective(s): Most patients (pts) with muscle invasive bladder urothelial carcinoma (UC) undergo definitive local treatment with radical cystectomy. Up to 50% of pts with UC may overexpress HER2/neu, and overexpression may be associated with reduced responsiveness to chemoradiation and reduced survival. Many pts with UC have comorbidities that preclude surgery, creating a traditionally underserved population with worse outcomes. RTOG 0524 evaluated the safety and initial efficacy of trimodality, organ-preserving therapy in pts not suitable for cystectomy. Materials/Methods: Pts with invasive bladder UC (stages T2-T4a, N0-1, M0) underwent cystoscopic tumor resection. Tumors were analyzed by HER2/neu immunohistochemistry (IHC) and assigned to chemotherapy group I (IHC 2+ or 3+; paclitaxel and trastuzumab) or II (IHC negative or 1+; paclitaxel alone). Concurrent weekly paclitaxel (50 mg/m2), weekly trastuzumab (group I only) and daily radiation (64.8 Gy total in 36 fractions) were given for seven consecutive weeks. Results: Twenty-one eligible patients were entered in group I and 47 in group 2, with median ages of 80 and 73, respectively. The primary endpoint was acute protocol-defined toxicity related to treatment. Acute toxicity was observed in 7/21 pts (33%) in group I and 14/47 pts (30%) in group II. Most common Grade 3 adverse events in groups I and II were marrow suppression (43% and 17%), diarrhea (33% and 30%) and hyponatremia (14% and 4%). Three deaths on study were attributed to colonic perforation, pneumonia and sudden death. Radiation completion rates were 72% and 85% in the two groups, and full dose chemotherapy completion rates were 52% and 51%. Evaluation by cystoscopy and/or tumor biopsy at 12 weeks noted complete response in 8/13 pts (62%) in group I, in 19/33 pts (58%) in group II, and was not performed in the remaining pts. Conclusions: Trimodality bladder-preserving therapy is an appropriate treatment in non-cystectomy candidates with invasive UC. The response rate for HER2/neu-targeted therapy is encouraging but may increase certain adverse events in this challenging population. Acknowledgment: This project was supported by RTOG grant U10 CA21661, and CCOP grant U10 CA37422 from the National Cancer Institute (NCI) and Genentech Inc. Author Disclosure: H.T. Pham: None. C. Hu: None. M.D. Michaelson: None. D.M. Dahl: None. C. Wu: None. R.M. Whittington: None. G.P. Swanson: None. J. Vuky: None. R.J. Lee: None. L. Souhami: None. B.K. Chang: None. A. George: None. H.M. Sandler: G. Consultant; Sanofi-Aventis, Medivation, Bayer, Eviti, Advanced Medical Isotope
289 Long-Term Outcomes Among Patients Who Achieve Complete or Near-Complete Responses After the Induction Phase of Bladder Preserving Combined Modality Therapy for Muscle-Invasive Bladder Cancer: A Pooled Analysis of RTOG 9906 and 0233 T. Mitin,1 A. George,2 A.L. Zietman,3 D.S. Kaufman,3 R. Uzzo,4 R. Dreicer,5 N. Heney,3 H.J. Wallace,6 L. Souhami,7 M.C. Dobelbower,8 H.M. Sandler,9 and W. Shipley3; 1Oregan Health and Science University, Portland, OR, 2Radiation Therapy Oncology Group, Philadelphia, PA, 3 Massachusetts General Hospital, Boston, MA, 4Fox Chase Cancer Center, Philadelphia, PA, 5Cleveland Clinic, Cleveland, OH, 6University of Vermont, Burlington, VT, 7Centre Universitaire de Sante´ McGill, Montreal, QC, Canada, 8University of Alabama at Birmingham, Birmingham, AL, 9 Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA Purpose/Objective(s): Bladder preserving combined-modality therapy for muscle-invasive bladder cancer (MIBC) includes transurethral resection and concurrent chemo-RT given in two phases. After the induction phase with chemo-RT to 40 Gy the tumor response is assessed by cystoscopic biopsies and urine cytology. Early salvage cystectomy is promptly offered in case of persistent disease, otherwise patients proceed to consolidation chemo-RT to 64 Gy. The two most recent RTOG protocols 9906 and 0233 allowed patients with near-complete response (Ta or Tis) after the induction phase to proceed to consolidation. In order to determine whether patients with near-complete response had worse outcomes than patients with complete response, we performed a retrospective secondary analysis of pooled data from these two trials. Materials/Methods: We performed a pooled analysis of 119 eligible patients with MIBC enrolled on RTOG trials 9906 and 0233, who were classified as having a complete (T0) or near-complete (Ta or Tis) response after induction chemo-RT and completed consolidation with a total RT dose of at least 60 Gy. We estimated bladder recurrence, salvage cystectomy rates and disease-specific survival by the cumulative incidence method and bladder-intact and overall survivals by the Kaplan-Meier method. Results: Among 119 eligible patients, 101 (85%) achieved T0 and 18 (15%) achieved Ta or Tis after induction chemo-RT as judged at the time of cystoscopic evaluation and biopsy (with a median interval to biopsy of 28 days in both groups, p Z 0.25) and proceeded to consolidation. After a median follow-up of 5.9 years, 36/101 (36%) T0 patients vs. 5/18 (28%) Ta or Tis patients experienced bladder recurrence (p Z 0.52). Fourteen patients among complete responders eventually required late salvage cystectomy for tumor recurrence, in comparison to one patient among nearcomplete responders (p Z 0.47). Disease-specific, bladder-intact and overall survivals were not significantly different between T0 and Ta/Tis cases. Conclusions: There is no apparent difference in the bladder recurrence and salvage cystectomy rates between complete and near-complete responders as judged at the time of cystoscopic evaluation after induction phase of bladder preserving CMT. It is appropriate to recommend that patients with Ta or Tis after induction chemo-RT continue with bladder-sparing therapy. Author Disclosure: A. George: None. A.L. Zietman: None. D.S. Kaufman: None. R. Uzzo: None. R. Dreicer: None. N. Heney: None. H.J. Wallace: None. L. Souhami: None. M.C. Dobelbower: None. H.M. Sandler: None. W. Shipley: None.
290 Early Experiences From a Clinical Trial of Daily Adaptive Plan Selection in Radiation Therapy for Urinary Bladder Cancer L.P. Muren,1 A. Vestergaard,1 H. Lindberg,2 K.L. Jakobsen,2 J.B.B. Petersen,1 U.V. Elstrøm,1 and M. Høyer1; 1Aarhus University Hospital, Aarhus, Denmark, 2Herlev University Hospital, Herlev, Denmark
Volume 90 Number 1S Supplement 2014 Purpose/Objective(s): Large changes in bladder shape and size during a course of radiation therapy (RT) make adaptive RT (ART) appealing in the treatment of this tumor site. We are conducting a two-center clinical phase II trial of daily plan selection based ART for bladder cancer with the primary aim of reducing gastro-intestinal morbidity due to sparing of the bowel and the rectum. We here report early dose/volume outcomes from the first twenty patients treated in this trial. Materials/Methods: All patients received 60 Gy in 30 fractions to the bladder; in thirteen of the patients the pelvic lymph nodes were simultaneously treated to 48 Gy. Daily patient set-up was by use of cone-beam CT (CBCT) guidance and treatment was delivered by volumetric modulated arc therapy (VMAT). The first five fractions were delivered using large, population-based margins; the bladder contours from the CBCTs acquired prior to the first four fractions were used to create a library of three plans, corresponding to a small, medium and large size bladder. All patients were from fraction no. 6 treated using daily online plan selection, where the smallest plan covering the bladder was selected prior to each treatment delivery. Volume ratios of PTV for ART vs. non-ART averaged over the treatment course were calculated. DVHs for bowel cavity and rectum were derived by summation of the selected plans and these were compared to standard non-adaptive RT plans using population-based margins. Results: The frequencies of which the small, medium, and large size plans were used over the (total of 600) fractions were similar; plans were used at a median of 9, 9.5 and 10 fractions, respectively. The median volume ratio of PTV-ART vs. non-ART across the treatment course was 0.70 (range: 0.46-0.89). The median rectal volume receiving 50 Gy or more was 5% (range: 0-41%), compared to 17% (range: 0-62%) if the patients had been treated with standard, non-adaptive RT. For the bowel cavity, the median volume receiving more than 45 Gy was 392 cm3 (range: 84-625 cm3), compared to 487 cm3 (range: 126-710 cm3) if not treated with adaptation. Conclusions: Daily adaptive plan selection in RT of bladder cancer results in a considerable normal tissue sparing, which is expected to reduce the risk of gastro-intestinal morbidity. Author Disclosure: L.P. Muren: None. E. Research Grant; Research grant from Varian Medical Systems to our dept., but not to the project described in the abstract. A. Vestergaard: None. H. Lindberg: None. K.L. Jakobsen: None. J.B.B. Petersen: None. U.V. Elstrøm: None. M. Høyer: None.
291 Modern Practice Patterns and Survival for Testicular Seminoma: Results from the National Cancer Data Base P.J. Gray,1 C. Lin,2 A. Jemal,2 and J.A. Efstathiou1; 1Massachusetts General Hospital, Boston, MA, 2American Cancer Society, Atlanta, GA Purpose/Objective(s): The management of testicular seminoma (TS) after orchiectomy is evolving, especially in patients with early-stage disease. We sought to investigate modern trends in the management of TS and to assess the effects of different adjuvant management strategies on survival. Materials/Methods: Data from the National Cancer Data Base on 41,745 patients with TS treated between 1998 and 2010 were analyzed. Logistic regression models were constructed to assess factors associated with adjuvant management paradigms. Cox proportional hazards models were used to analyze five-year survival in those diagnosed between 1998 and 2005. Results: Between 1998 and 2010, for patients with stage IA/B TS, rates of surveillance increased from 23.7% to 46.7% and receipt of adjuvant chemotherapy increased from 1.5% to 16.8%, while receipt of adjuvant radiation therapy decreased from 70.8% to 35.4%. For patients with stage IIA/B TS, receipt of adjuvant radiation therapy declined from 55.9% to 42.2% while receipt of chemotherapy rose from 20.4% to 40.6%. For those patients with stage IA/B TS, black or Hispanic race (OR Z 1.32 and 1.38 respectively vs. white, p both < 0.001) and lack of medical insurance (OR Z 1.29 vs. private insurance, p < 0.001) or insurance through Medicaid (OR Z 1.14 vs. private insurance, p Z
Oral Scientific Sessions S133 0.043) were associated with an increased odds of receiving surveillance while treatment at a high-volume center was associated with decreased odds (OR Z 0.63 vs. low-volume, p < 0.001). For stage IA/B and IIA/B patients who received adjuvant treatment, receipt of care at an NCIdesignated cancer center predicted for decreased receipt of radiation therapy vs. chemotherapy. Unadjusted five-year overall survival rates for patients with stage IA/B disease were 96.3% for surveillance, 98.0% for adjuvant radiation therapy and 94.4% for adjuvant chemotherapy. In a multivariate Cox regression model, receipt of adjuvant radiation therapy was associated with decreased hazard for death at five years (HR Z 0.65, p < 0.001) while receipt of adjuvant chemotherapy was associated with an increased hazard for death (HR Z 1.64, p Z 0.041) compared to receipt of surveillance after orchiectomy. Conclusions: Surveillance after orchiectomy for patients with stage I TS has increased in recent years. Receipt of adjuvant chemotherapy has also increased significantly in stage I and early stage II TS while receipt of radiation therapy has declined. In this large national dataset, patients with stage IA/B disease who receive radiation therapy appear to have improved five-year survival compared to those who receive surveillance or adjuvant chemotherapy. Additional study and longer follow-up (including assessment of late effects of treatment) are needed to validate these findings and confirm the appropriateness of these changing trends in management. Author Disclosure: P.J. Gray: None. C. Lin: None. A. Jemal: None. J.A. Efstathiou: None.
292 Long-Term Toxicity and Cosmetic Results of Partial Versus Whole Breast Irradiation: 10-Year Results of a Phase III APBI Trial C. Polgar, T. Major, Z. Sulyok, Z. Takacsi-Nagy, and J. Fodor; National Institute of Oncology, Budapest, Hungary Purpose/Objective(s): The 10-year survival results of a phase III study comparing breast-conserving treatment with partial (PBI) or whole breast irradiation (WBI) have been published recently. In this analysis long-term toxicity and cosmetic results are reported. Materials/Methods: Between 1998 and 2004, 258 selected, low-risk breast cancer patients were randomized after breast-conserving surgery to receive 50 Gy WBI (n Z 130) or PBI (n Z 128). The latter consisted of either 7 x 5.2 Gy high-dose-rate multicatheter brachytherapy (PBI-HDR; n Z 88) or 50 Gy electron beam irradiation (PBI-ELE; n Z 40). Late radiation side effects were scored by the RTOG/EORTC radiation morbidity scoring scheme. Cosmetic results were evaluated using the Harvard criteria. Follow-up mammograms were reviewed searching for visible signs of fat necrosis. Results: After a median follow-up of 10.2 years, skin side effects (any grade; G) occurred in 12.9%, 40.0%, and 20.5% in PBI-HDR, PBI-ELE, and WBI groups, respectively (pHDR vs WBI Z NS, pHDR vs ELE Z 0.0009, pELE vs WBI Z NS). The respective rate of G3 telangiectasia was 0%, 7.5%, and 2.6% (pHDR vs WBI Z NS, pHDR vs ELE Z 0.0311, pELE vs WBI Z NS). The rate of fibrosis (any G) was 49.4%, 22.5%, and 42.7% after PBI-HDR, PBI-ELE, and WBI, respectively (pHDR vs WBI Z NS, pHDR vs ELE Z 0.0034, pELE vs WBI Z 0.0166). The respective rate of G3 fibrosis was only 2.4%, 0%, and 0.9%; p Z NS). Fat necrosis was detected on follow-up mammograms in 58.1%, 30.0%, and 52.1%, respectively (pHDR vs WBI Z NS, pHDR vs ELE Z 0.0019, pELE vs WBI Z 0.0119). Only one patient (1.2%) in the PBI-HDR group developed fat necrosis requiring surgical intervention. The overall rate of G3 late toxicities was 2.4%, 7.5%, and 3.4% after PBI-HDR, PBI-ELE, and WBI, respectively (p Z NS). The rate of excellent-good cosmetic result was 81.2% in the PBI-HDR, 75.0% in the PBI-ELE, and 62.1% in the control group (pHDR vs WBI Z 0.0003, pHDR vs ELE Z NS, pELE vs WBI Z 0.0972). Conclusions: Significantly better cosmetic outcome can be achieved with carefully designed PBI-HDR multicatheter implants compared with the outcome after PBI-ELE or WBI. Both WBI and PBI (either with HDR or ELE) are well tolerated and severe late side effects are minimal. Slightly more parenchymal side effects occur after PBI-HDR. On the