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Intensity Modulated (IMRT) and Intraoperative Electron (IOERT) Radiation Therapy for Retroperitoneal and Intrapelvic Sarcoma
S138
International Journal of Radiation Oncology Biology Physics
Author Disclosure: A. Bhatnagar: E. Research Grant; Principal Investigator for Industry Sponsored Prospective Trial for Electronic Brachytherapy for Primary Treatment of Non-Melanoma Skin Cancer.
Materials/Methods: Between January 2004 and December 2011, clinical records of 82 consecutive pts with retroperitoneal and intrapelvic sarcomas treated with IMRT at our institution were reviewed. Eighty-one pts (56 primary, 25 recurrent) received curative intent treatment. 76 (92%) pts received preoperative radiation therapy. Seventy-one patients (87%) underwent resection, and IOERT was delivered in 55 (67%) pts. Gross total resection or maximal debulking (with microscopic margins) was achieved in 69 (97%) cases. Thirty patients (37%) received adriamycin, ifosfamide or cisplatin-based chemotherapies; 14 (17%) pts had prior chemotherapy, external beam and/or IOERT. Kaplan-Meier survival analysis and Logrank test were applied. Results: The median follow-up was 19.2 months. Median age was 58.6 years (range, 24.7-90.4 years); 39 (48%) were male. Most common histologies were liposarcoma (32 pts, 39%) and leiomyosarcoma (19 pts, 23%). In 35 (43%) pts, the tumor was greater than 10 cm. Pts were treated with a median dose of 5625 cGy (range, 3,060-6,250 cGy), in 25 fractions (range 17-31 fractions). After completion of IMRT, the median time to surgery and IOERT was 30 days (quartiles, 27-42 days). The median IOERT dose was 1000 cGy (range, 800-2,000 cGy). IOERT was delivered through circular (diameter range, 5-9 cm) or elliptical (short axis, 6-9 cm; long axis, 11-20 cm) applicators. There were 10 local (within IMRT field) and 6 central (within IOERT field) relapses in 13 pts. Local control (LC) rate for all pts was 90 and 70% at 1 and 3 years, respectively. Progression-free survival (PFS) was 73 and 45% at 1 and 3 years. Overall survival (OS) was 86, 67, and 59% at 1, 3, and 4 years (median not reached yet). Compared with recurrent cases, pts with primary tumors were associated with better LC at 3 years (89 vs. 38%, p < 0.00001), with a trend toward better PFS (48 vs. 19%, p Z 0.07), but no difference in OS (67 vs. 69%, p Z 0.90). There was no difference in LC, PFS or OS between pts requiring IOERT boost and pts treated with IMRT alone (all p > 0.40). Three (3.7%) pts had grade 5 toxicity including 2 perioperative and 1 chemoradiation-related deaths (acute renal failure and bacteremia); none of these 3 received IOERT. Three (3.7%) pts experienced grade 4 toxicity due to fistula formation, peripheral neuropathy, and pancytopenia. Thirteen patients (16%) had grade 3 toxicity including bowel obstruction (3), abscess formation (3), peripheral neuropathy (2), and hydronephrosis (2). Conclusions: A strategy of preoperative IMRT and selective IOERT resulted in excellent disease control and survival. Patients treated at primary presentation had higher rates of LC and PFS, compared to patients with recurrence. Significant dose escalation was achieved without excessive rates of radiation-related toxicity. Author Disclosure: T.T. Sio: None. I.A. Petersen: None. K.A. Klein: None. M.G. Haddock: None.
341 Prognosis of Radiation Associated Bone and Soft-tissue Sarcomas Y. Chen,1 G. Calkins,1 F. Hornicek,1 D. Harmon,1 C. Giraud,1 G. Nielsen,1 P. Meltzer,2 H. Suit,1 J. Michaelson,1 and T. DeLaney1; 1Massachusetts General Hospital, Boston, MA, 2National Cancer Institute, National Institutes of Health, Bethesda, MD Purpose/Objective(s): To determine the prognosis of radiation associated soft tissue and bone sarcomas arising within the radiation treatment field of a prior malignancy. Materials/Methods: A total of 9,069 soft tissue and bone sarcoma patients were seen at our institution from 1938 to 2011. We identified 64 radiation associated soft tissue or bone sarcomas (RAS) arising in the radiation treatment fields of prior malignancies. RAS was defined as having a history of radiation treatment at least 1 year prior to the diagnosis of the sarcoma, development within the prior radiation field, and confirmed histology differing from the prior malignancy. Only patients who received radiation at our institution with radiation fields available for review were included; patients treated elsewhere for the prior malignancy, had simultaneous sarcoma and another malignancy, or had no follow-up were excluded. Clinicopathologic characteristics, treatment of the RAS, and survival outcomes were analyzed and compared to sporadic soft tissue and bone sarcomas. Multivariate analysis was performed using Cox proportional hazards. Results: The median follow-up for this cohort of 64 RAS was 21 months (range 1 to 234 months). The median age at the time of prior radiation therapy was 61 years (range 1 to 85 years). The median interval between prior radiation therapy and the development of RAS was 10 years (range 1 to 37 years). The histological subtypes of RAS included MFH (12), fibrosarcoma or fibromyxosarcoma (11), angiosarcoma (9), osteosarcoma (9), leiomyosarcoma (5), adipocytic sarcoma (4, including liposarcoma and myxoid liposarcoma), and others (14). For cases where grading was available, 26 had grade 3/4, 15 had grade 1, and 2 had grade 1. The prior treatment sites included breast (17), head and neck (12), genitourinary (9), CNS (6), lymph nodes (5), thyroid (4), gynecological (4), connective tissue (3), GI (2) retina (1), and others (6). The histology of prior malignancies included 42 carcinomas, 14 hematological malignancies (4 HL, 9 NHL, 1 leukemia), 5 glial/neural, 1 retinoblastoma, 1 Wilms tumor and 1 neuroblastoma. 43 patients received only radiation for the prior malignancy while 21 received both chemotherapy and radiation. Twenty-four RAS were reirradiated, 13 treated with chemotherapy, and 44 surgically resected. Five-year overall survival was 41% +/- 13% for RAS compared with 65% +/- 1% for non-RAS. Multivariate analysis shows that RAS had worse overall survival (HR Z 2.67, p < 0.01) and disease-specific survival (HR Z 3.32, p < 0.01) independent of size, grade, margin, and histology. Conclusions: Radiation associated bone and soft tissue sarcomas arising within the radiation treatment field of a prior malignancy appear to have worse prognosis than spontaneous sarcomas and warrant further characterization to identify potential targets to improve outcomes. Author Disclosure: Y. Chen: None. G. Calkins: None. F. Hornicek: None. D. Harmon: None. C. Giraud: None. G. Nielsen: None. P. Meltzer: None. H. Suit: None. J. Michaelson: None. T. DeLaney: None.
342 Intensity Modulated (IMRT) and Intraoperative Electron (IOERT) Radiation Therapy for Retroperitoneal and Intrapelvic Sarcoma T.T. Sio, I.A. Petersen, K.A. Klein, and M.G. Haddock; Mayo Clinic, Rochester, MN Purpose/Objective(s): To report outcome of patients (pts) with retroperitoneal and intrapelvic soft tissue sarcomas treated with IMRT and IOERT.
343 Retroperitoneal Sarcoma (RPS): Evaluation of Locoregional Recurrences (LRR) After Preoperative Radiation Therapy (RT) and Potential Benefit of Dose Escalation Using Dose Painting S.M. McBride,1 C.P. Raut,2 M. Lapidus,2 P.M. Devlin,2 K.J. Marcus,2 M. Bertagnolli,2 S. George,2 and E.H. Baldini2; 1Harvard Radiation Oncology Program, Boston, MA, 2Brigham and Women’s Hospital, Boston, MA Purpose/Objective(s): After pre-operative RT for RPS, locations of LRRs relative to RT fields are not well documented. This issue bears directly on the potential benefit of dose escalation using dose painting to deliver a boost to high risk margins. Materials/Methods: We reviewed 33 consecutive patients (pts) treated with pre-operative RT and resection between 2002 and 2011. Imaging of all LRRs was reviewed and compared to RT dosimetry plans; local recurrence (LR) was defined as a failure within or marginal to the RT field and regional recurrence (RR) as a failure elsewhere in the retroperitoneum. Our group determined tumor margins that would have been appropriate for a dose painting boost; these margins typically
International Journal of Radiation Oncology Biology Physics
Author Disclosure: A. Bhatnagar: E. Research Grant; Principal Investigator for Industry Sponsored Prospective Trial for Electronic Brachytherapy for Primary Treatment of Non-Melanoma Skin Cancer.
Materials/Methods: Between January 2004 and December 2011, clinical records of 82 consecutive pts with retroperitoneal and intrapelvic sarcomas treated with IMRT at our institution were reviewed. Eighty-one pts (56 primary, 25 recurrent) received curative intent treatment. 76 (92%) pts received preoperative radiation therapy. Seventy-one patients (87%) underwent resection, and IOERT was delivered in 55 (67%) pts. Gross total resection or maximal debulking (with microscopic margins) was achieved in 69 (97%) cases. Thirty patients (37%) received adriamycin, ifosfamide or cisplatin-based chemotherapies; 14 (17%) pts had prior chemotherapy, external beam and/or IOERT. Kaplan-Meier survival analysis and Logrank test were applied. Results: The median follow-up was 19.2 months. Median age was 58.6 years (range, 24.7-90.4 years); 39 (48%) were male. Most common histologies were liposarcoma (32 pts, 39%) and leiomyosarcoma (19 pts, 23%). In 35 (43%) pts, the tumor was greater than 10 cm. Pts were treated with a median dose of 5625 cGy (range, 3,060-6,250 cGy), in 25 fractions (range 17-31 fractions). After completion of IMRT, the median time to surgery and IOERT was 30 days (quartiles, 27-42 days). The median IOERT dose was 1000 cGy (range, 800-2,000 cGy). IOERT was delivered through circular (diameter range, 5-9 cm) or elliptical (short axis, 6-9 cm; long axis, 11-20 cm) applicators. There were 10 local (within IMRT field) and 6 central (within IOERT field) relapses in 13 pts. Local control (LC) rate for all pts was 90 and 70% at 1 and 3 years, respectively. Progression-free survival (PFS) was 73 and 45% at 1 and 3 years. Overall survival (OS) was 86, 67, and 59% at 1, 3, and 4 years (median not reached yet). Compared with recurrent cases, pts with primary tumors were associated with better LC at 3 years (89 vs. 38%, p < 0.00001), with a trend toward better PFS (48 vs. 19%, p Z 0.07), but no difference in OS (67 vs. 69%, p Z 0.90). There was no difference in LC, PFS or OS between pts requiring IOERT boost and pts treated with IMRT alone (all p > 0.40). Three (3.7%) pts had grade 5 toxicity including 2 perioperative and 1 chemoradiation-related deaths (acute renal failure and bacteremia); none of these 3 received IOERT. Three (3.7%) pts experienced grade 4 toxicity due to fistula formation, peripheral neuropathy, and pancytopenia. Thirteen patients (16%) had grade 3 toxicity including bowel obstruction (3), abscess formation (3), peripheral neuropathy (2), and hydronephrosis (2). Conclusions: A strategy of preoperative IMRT and selective IOERT resulted in excellent disease control and survival. Patients treated at primary presentation had higher rates of LC and PFS, compared to patients with recurrence. Significant dose escalation was achieved without excessive rates of radiation-related toxicity. Author Disclosure: T.T. Sio: None. I.A. Petersen: None. K.A. Klein: None. M.G. Haddock: None.
341 Prognosis of Radiation Associated Bone and Soft-tissue Sarcomas Y. Chen,1 G. Calkins,1 F. Hornicek,1 D. Harmon,1 C. Giraud,1 G. Nielsen,1 P. Meltzer,2 H. Suit,1 J. Michaelson,1 and T. DeLaney1; 1Massachusetts General Hospital, Boston, MA, 2National Cancer Institute, National Institutes of Health, Bethesda, MD Purpose/Objective(s): To determine the prognosis of radiation associated soft tissue and bone sarcomas arising within the radiation treatment field of a prior malignancy. Materials/Methods: A total of 9,069 soft tissue and bone sarcoma patients were seen at our institution from 1938 to 2011. We identified 64 radiation associated soft tissue or bone sarcomas (RAS) arising in the radiation treatment fields of prior malignancies. RAS was defined as having a history of radiation treatment at least 1 year prior to the diagnosis of the sarcoma, development within the prior radiation field, and confirmed histology differing from the prior malignancy. Only patients who received radiation at our institution with radiation fields available for review were included; patients treated elsewhere for the prior malignancy, had simultaneous sarcoma and another malignancy, or had no follow-up were excluded. Clinicopathologic characteristics, treatment of the RAS, and survival outcomes were analyzed and compared to sporadic soft tissue and bone sarcomas. Multivariate analysis was performed using Cox proportional hazards. Results: The median follow-up for this cohort of 64 RAS was 21 months (range 1 to 234 months). The median age at the time of prior radiation therapy was 61 years (range 1 to 85 years). The median interval between prior radiation therapy and the development of RAS was 10 years (range 1 to 37 years). The histological subtypes of RAS included MFH (12), fibrosarcoma or fibromyxosarcoma (11), angiosarcoma (9), osteosarcoma (9), leiomyosarcoma (5), adipocytic sarcoma (4, including liposarcoma and myxoid liposarcoma), and others (14). For cases where grading was available, 26 had grade 3/4, 15 had grade 1, and 2 had grade 1. The prior treatment sites included breast (17), head and neck (12), genitourinary (9), CNS (6), lymph nodes (5), thyroid (4), gynecological (4), connective tissue (3), GI (2) retina (1), and others (6). The histology of prior malignancies included 42 carcinomas, 14 hematological malignancies (4 HL, 9 NHL, 1 leukemia), 5 glial/neural, 1 retinoblastoma, 1 Wilms tumor and 1 neuroblastoma. 43 patients received only radiation for the prior malignancy while 21 received both chemotherapy and radiation. Twenty-four RAS were reirradiated, 13 treated with chemotherapy, and 44 surgically resected. Five-year overall survival was 41% +/- 13% for RAS compared with 65% +/- 1% for non-RAS. Multivariate analysis shows that RAS had worse overall survival (HR Z 2.67, p < 0.01) and disease-specific survival (HR Z 3.32, p < 0.01) independent of size, grade, margin, and histology. Conclusions: Radiation associated bone and soft tissue sarcomas arising within the radiation treatment field of a prior malignancy appear to have worse prognosis than spontaneous sarcomas and warrant further characterization to identify potential targets to improve outcomes. Author Disclosure: Y. Chen: None. G. Calkins: None. F. Hornicek: None. D. Harmon: None. C. Giraud: None. G. Nielsen: None. P. Meltzer: None. H. Suit: None. J. Michaelson: None. T. DeLaney: None.
342 Intensity Modulated (IMRT) and Intraoperative Electron (IOERT) Radiation Therapy for Retroperitoneal and Intrapelvic Sarcoma T.T. Sio, I.A. Petersen, K.A. Klein, and M.G. Haddock; Mayo Clinic, Rochester, MN Purpose/Objective(s): To report outcome of patients (pts) with retroperitoneal and intrapelvic soft tissue sarcomas treated with IMRT and IOERT.
343 Retroperitoneal Sarcoma (RPS): Evaluation of Locoregional Recurrences (LRR) After Preoperative Radiation Therapy (RT) and Potential Benefit of Dose Escalation Using Dose Painting S.M. McBride,1 C.P. Raut,2 M. Lapidus,2 P.M. Devlin,2 K.J. Marcus,2 M. Bertagnolli,2 S. George,2 and E.H. Baldini2; 1Harvard Radiation Oncology Program, Boston, MA, 2Brigham and Women’s Hospital, Boston, MA Purpose/Objective(s): After pre-operative RT for RPS, locations of LRRs relative to RT fields are not well documented. This issue bears directly on the potential benefit of dose escalation using dose painting to deliver a boost to high risk margins. Materials/Methods: We reviewed 33 consecutive patients (pts) treated with pre-operative RT and resection between 2002 and 2011. Imaging of all LRRs was reviewed and compared to RT dosimetry plans; local recurrence (LR) was defined as a failure within or marginal to the RT field and regional recurrence (RR) as a failure elsewhere in the retroperitoneum. Our group determined tumor margins that would have been appropriate for a dose painting boost; these margins typically