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The Effect of Radiotherapy Dose and Volume on Relapse in Merkel Cell Cancer of the Skin
Proceedings of the 51st Annual ASTRO Meeting therapy for AMFS has consisted of excision or amputation, with very limited use of radiation therapy or chemotherapy. In this report, we review the outcome of 17 patients with AMFS treated at our institution. Materials/Methods: A retrospective review of all cases of AMFS in the past 5 years identified in the Sarcoma Database in the Department of Radiation Oncology at our institution was conducted. Patients’ treatment records and follow-up visits were reviewed. Results: Seventeen patients were identified. All of the patients underwent surgical resection: 15 excisions, 2 amputations. Positive margins after excisions were noted in 5 patients and were widely positive in 1 patient. Of the 17 patients, 15 patients received some form of radiation. Average total dose was 56.4 Gy. 8 patients received pre-operative RT alone, 6 patients received pre-operative RT and postoperative RT, and 1 patient received pre-operative RT and intraoperative RT. Average follow-up was 32.8 months. One patient presented with recurrent disease and was treated with excision, and pre and post operative RT. He is currently 23 months free of disease. No local recurrence was noted in the remaining patients. Of the 14 patients undergoing pre-op XRT, complete pathologic necrosis or no tumor was seen in one of the patients. No metastatic disease was noted in any of the patients. There was no significant radiation toxicity observed in any of the patients. Conclusions: Our data is consistent with local control of distal extremity sarcomas with excision and radiation therapy, suggesting that RT is an appropriate option in the limb sparing control of patients with AMFS, even those with positive margins. Author Disclosure: A. Tejwani, None; W. Kobayashi, None; Y. Chen, None; G.P. Nielsen, None; A.L. Rosenberg, None; S.S. Yoon, None; D. Springfield, None; D.I. Rosenthal, None; F.J. Hornicek, None; T.F. DeLaney, None.
2763
Recurrence Patterns and Survival in Patients with Intermediate and High-grade Myxofibrosarcoma
K. E. Haglund1, C. P. Raut2,3, A. F. Nascimento2, Q. Wang3, S. George2,3, E. H. Baldini2,3 1 Harvard Radiation Oncology Program, Boston, MA, 2Brigham & Women’s Hospital, Boston, MA, 3Dana-Farber Cancer Institute, Boston, MA
Purpose/Objective(s): MFS is a rare sarcoma with a predilection for multiple local recurrences (LR). In the absence of any large published series, optimal treatment has not been defined. We reviewed our experience to determine the impact of surgery and radiation therapy (RT) on pattern of recurrence, limb salvage, and overall survival (OS). Materials/Methods: Between 1995 and 2005, 36 patients with localized intermediate or high-grade MFS received treatment at Dana-Farber/Brigham and Women’s Hospital Cancer Center (DFBWHCC). Data on clinicopathological features, treatments, and pt outcomes were reviewed. LR and OS rates were estimated using the Kaplan-Meier method. Comparisons of the difference in distributions were assessed by the log–rank test. Results: Median age was 72.5 years (range, 42–96). Tumors were of high (n = 34) or intermediate (n = 2) grade. Median size was 7.5 cm (range, 0.7–22). Twelve patients (33%) had Stage II and 24 (67%) had Stage III disease. Disease sites were extremities (n = 32) and trunk (n = 4). All patients underwent surgery as part of initial treatment: 20 (56%) had re-resection at DFBWHCC after open biopsy or marginal resections elsewhere. One pt (3%) had amputation, the remainder had radical (n = 27, 75%) or wide (n = 8, 22%) excision. Final margins were microscopically positive in 9 patients (25%). RT was given to 28 patients (78%) either pre-operatively (n = 5; median, 50 Gy), postoperatively (n = 19; median, 62.5 Gy), or both (n = 4; median total, 64 Gy). Among the 8 patients who did not receive RT, 5 had negative surgical margins (mean, 1.5 cm; range, 0.5–3.5 cm), 2 had no residual tumor on re-excision, and 1 developed rapid LR before planned postoperative RT. One pt with a 22-cm MFS received preoperative chemotherapy (CT). No patients received adjuvant CT. After a median follow-up of 3.5 years (range, 0.4–12.4), 11 patients (30%) developed LR. Among those, median time to first LR was 21 mos (range, 6–48). The 4- year actuarial LR rate was 40%. Limb salvage was ultimately achieved for only 4 of 11 (36%) due to multiple LRs. The median number of LRs was 1 (range, 1–4). There were no significant predictors for LR on univariate analysis. Crude LR rates for patients treated with and without RT were 36% and 12%, respectively (p = NS); the rates for patients with positive and negative margins were 44% and 26%, (p = NS), respectively. Distant recurrence (DR) occurred in 6 patients (17%), most commonly in lung (n = 5). Among those 6 patients, median time to first DR was 21 mos (range, 4.8–97). Four of 6 DRs (67%) developed without any LR. Median OS was 96 mos and 4- year actuarial OS was 65%. Seven patients (20%) had tumor-related deaths, 6 of whom had DR. Conclusions: Despite aggressive surgery and RT, intermediate and high-grade MFS has a high rate of LR which adversely impacts limb preservation. More aggressive local treatment strategies are necessary. Author Disclosure: K.E. Haglund, None; C.P. Raut, None; A.F. Nascimento, None; Q. Wang, None; S. George, None; E.H. Baldini, None.
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The Effect of Radiotherapy Dose and Volume on Relapse in Merkel Cell Cancer of the Skin
M. C. Foote1,2, J. Harvey1, S. Porceddu1, G. Dickie3, S. Hewitt4, S. Colquist5, D. Zarate5, M. Poulsen1 1 Princess Alexandra Hospital, Brisbane, Australia, 2University of Queensland, Brisbane, Australia, 3Royal Brisbane and Womens Hospital, Brisbane, Australia, 4The Townsville Hospital, Townsville, Australia, 5Queensland Cancer Control Analysis Team, Brisbane, Australia Purpose/Objective(s): To assess the effect of radiotherapy (RT) dose and volume on relapse patterns in patients with Stage I–III Merkel cell carcinoma (MCC). Materials/Methods: Retrospective analysis of 112 patients diagnosed with MCC between January 2000 and December 2005 and given radiotherapy with curative intent. The effect of dose on relapse rate was analysed with adjustments for stage and surgical margins. Results: Of the 112 evaluable patients 88% had RT to the site of primary disease for gross (11%) or subclinical (78%) disease. Eighty-nine percent of patients had RT to the regional lymph nodes; gross disease accounting for 19% and subclinical disease
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(adjuvant or elective) in 71%. The 2 year and 5 year overall survival (OS) was 72% and 53%, respectively, and the 2 year locoregional control (LRC) rate was 75%. The in-field relapse rate was 3% for primary disease and relapse was significantly lower for patients receiving $ 50 Gy (HR = 0.22, CI: 0.06–0.86). Surgical margins did not affect the local relapse rate. The in-field relapse rate was 11% for RT to the nodes with dose being significant for nodal gross disease (HR = 0.24, CI: 0.07–0.87) and subclinical disease (HR = 0.44, CI: 0.14–1.42). Patients not receiving elective nodal RT had a much higher rate of nodal relapse compared to those who did (HR = 6.03, CI: 1.34–27.10). Conclusions: This study indicates a dose response for subclinical and gross MCC. Doses of 50 Gy for subclinical disease and 55– 60 Gy for gross disease are recommended. The draining nodal basin should be treated in all patients. Author Disclosure: M.C. Foote, None; J. Harvey, None; S. Porceddu, None; G. Dickie, None; S. Hewitt, None; S. Colquist, None; D. Zarate, None; M. Poulsen, None.
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Spatially Fractionated Grid Radiation (SFGRT): A Novel Approach in the Management of Recurrent and Unresectable Soft Tissue Sarcoma
M. Mohiuddin, T. Miller, P. Ronjon, U. Malik Geisinger Cancer Institute, Wilkes-Barre, PA Purpose/Objective(s): While radiation therapy is occasionally utilized for palliative treatment of large recurrence, and/or unresectable soft tissue sarcomas, their response to treatment has generally been poor. A novel approach of spatially fractionated grid radiation (SFGRT) allows safe delivery of high dose radiation which can be combined with conventionally fractionated external beam radiation to produce dramatic shrinkage of these tumors. This report evaluates the toxicity and effectiveness of this approach in treatment of advanced and bulky sarcomas. Materials/Methods: Thirty-three (33) patients with recurrent and/or unresectable soft tissue sarcomas were treated with high dose megavoltage radiation using an SFGRT technique. Seven patients received grid radiation to multiple sites for a total of 44 sites irradiated. Tumor size ranged from 6 to 32 cm with a median of 13 cm. Single dose of SFGRT 12 to 20 Gy, (median 15 Gy) to D-max was delivered using 6 MV photons. Four patients received SFGRT alone, and 40 patients received further external beam radiation. 22 to 70 Gy, median 50 Gy, 20 treatments were delivered to the abdomen and pelvis, 3 to the head and neck region, 7 to the thorax and 15 to the extremities. Results: Twelve patients achieved a clinical/pathological complete response (26%), and 22 patients (50%) achieved a partial response, 7 patients had stable disease, and 3 patients experienced tumor progression. The response rate for SFGRT followed by definitive external radiation .50 Gy was 95% (45% CR, 50% PR) as compared to 59%, (10% CR, 50% PR) in patients receiving \50 Gy external radiation. Survival of patients ranged from 2 months to 44 months with a median of 9 months. Nine patients were alive greater than one year. Two patients experienced Grade 3 skin reaction, but there was no late subcutaneous mucosal or other toxicity. Conclusions: The combined use of SFGRT and external beam radiation is an effective way for treating large recurrent and unresectable soft tissue sarcomas. Dramatic shrinkage of tumor is observed and long term control can be achieved. This approach can be especially useful in the management of retroperitoneal and intrathoracic sarcomas where resection is not feasible. Author Disclosure: M. Mohiuddin, None; T. Miller, None; P. Ronjon, None; U. Malik, None.
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Adjuvant Radiation after Limb-sparing Surgery Improves Overall Survival for Large (.5cm) High-grade Soft Tissue Sarcomas of the Extremities
D. Schreiber, J. Rineer, D. Vongtama, A. Wortham, R. Sroufe, M. Olsheski, P. Han, D. Schwartz, K. Choi, M. Z. Rotman SUNY Downstate Medical Center, Brooklyn, NY Purpose/Objective(s): Two randomized trials and several retrospective reports have shown an improvement in local control for high-grade soft tissue sarcomas (STS) of the extremities with the addition of adjuvant radiation to surgery. However, a survival benefit has not been noted. In addition, some have recently questioned whether select patients with small (#5cm) tumors should be observed and not receive adjuvant radiation at all. We analyzed the Surveillance, Epidemiology, and End Results database to evaluate the impact of adjuvant radiation (postopRT) on survival. Materials/Methods: We selected patients, ages 20–79, diagnosed between 1998–2005 with high-grade STS of the upper or lower extremities who were definitively treated with limb sparing radical surgery with or without postopRT. Rhabdomyosarcoma and Ewings sarcoma were excluded. Patients were stratified based on size of the lesion (#5cm or .5cm). Kaplan-Meier and Cox regression analysis were used to compare overall survival (OS) between the two arms. Results: A total of 862 patients were identified, of which 625 received postopRT and 237 received surgery alone. The most common histologies were malignant fibrous histiocytoma (49.1%), liposarcoma (17.8%), and leiomyosarcoma (12.3%). For the whole cohort, there was a significant improvement in 5 year OS from 59.5% to 68.1% with the addition of postopRT (p = 0.015). When stratified by tumor size, there was no significant benefit to the addition of postopRT for tumors #5cm, with a 5 year OS of 76.5% for surgery alone versus 84.7% for postoperative radiation (p = 0.198). However, for tumors .5cm, there was a significant improvement in 5 year OS for postopRT, from 42.9% to 60.3% (p\0.001). On multivariate analysis, the most significant predictors for improved survival were tumor size #5cm (HR 0.38, 95% CI 0.27–0.54, p\0.001) and postopRT (HR 0.62, 95% CI 0.46–0.85, p=0.002). Conclusions: In this large retrospective review, the addition of postopRT improves overall survival for high-grade extremity STS compared with surgery alone. When stratified by tumor size, there is only a survival benefit for tumors .5cm. There does not appear to be a survival benefit to postopRT for tumors #5cm. Author Disclosure: D. Schreiber, None; J. Rineer, None; D. Vongtama, None; A. Wortham, None; R. Sroufe, None; M. Olsheski, None; P. Han, None; D. Schwartz, None; K. Choi, None; M.Z. Rotman, None.
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Recurrence Patterns and Survival in Patients with Intermediate and High-grade Myxofibrosarcoma
K. E. Haglund1, C. P. Raut2,3, A. F. Nascimento2, Q. Wang3, S. George2,3, E. H. Baldini2,3 1 Harvard Radiation Oncology Program, Boston, MA, 2Brigham & Women’s Hospital, Boston, MA, 3Dana-Farber Cancer Institute, Boston, MA
Purpose/Objective(s): MFS is a rare sarcoma with a predilection for multiple local recurrences (LR). In the absence of any large published series, optimal treatment has not been defined. We reviewed our experience to determine the impact of surgery and radiation therapy (RT) on pattern of recurrence, limb salvage, and overall survival (OS). Materials/Methods: Between 1995 and 2005, 36 patients with localized intermediate or high-grade MFS received treatment at Dana-Farber/Brigham and Women’s Hospital Cancer Center (DFBWHCC). Data on clinicopathological features, treatments, and pt outcomes were reviewed. LR and OS rates were estimated using the Kaplan-Meier method. Comparisons of the difference in distributions were assessed by the log–rank test. Results: Median age was 72.5 years (range, 42–96). Tumors were of high (n = 34) or intermediate (n = 2) grade. Median size was 7.5 cm (range, 0.7–22). Twelve patients (33%) had Stage II and 24 (67%) had Stage III disease. Disease sites were extremities (n = 32) and trunk (n = 4). All patients underwent surgery as part of initial treatment: 20 (56%) had re-resection at DFBWHCC after open biopsy or marginal resections elsewhere. One pt (3%) had amputation, the remainder had radical (n = 27, 75%) or wide (n = 8, 22%) excision. Final margins were microscopically positive in 9 patients (25%). RT was given to 28 patients (78%) either pre-operatively (n = 5; median, 50 Gy), postoperatively (n = 19; median, 62.5 Gy), or both (n = 4; median total, 64 Gy). Among the 8 patients who did not receive RT, 5 had negative surgical margins (mean, 1.5 cm; range, 0.5–3.5 cm), 2 had no residual tumor on re-excision, and 1 developed rapid LR before planned postoperative RT. One pt with a 22-cm MFS received preoperative chemotherapy (CT). No patients received adjuvant CT. After a median follow-up of 3.5 years (range, 0.4–12.4), 11 patients (30%) developed LR. Among those, median time to first LR was 21 mos (range, 6–48). The 4- year actuarial LR rate was 40%. Limb salvage was ultimately achieved for only 4 of 11 (36%) due to multiple LRs. The median number of LRs was 1 (range, 1–4). There were no significant predictors for LR on univariate analysis. Crude LR rates for patients treated with and without RT were 36% and 12%, respectively (p = NS); the rates for patients with positive and negative margins were 44% and 26%, (p = NS), respectively. Distant recurrence (DR) occurred in 6 patients (17%), most commonly in lung (n = 5). Among those 6 patients, median time to first DR was 21 mos (range, 4.8–97). Four of 6 DRs (67%) developed without any LR. Median OS was 96 mos and 4- year actuarial OS was 65%. Seven patients (20%) had tumor-related deaths, 6 of whom had DR. Conclusions: Despite aggressive surgery and RT, intermediate and high-grade MFS has a high rate of LR which adversely impacts limb preservation. More aggressive local treatment strategies are necessary. Author Disclosure: K.E. Haglund, None; C.P. Raut, None; A.F. Nascimento, None; Q. Wang, None; S. George, None; E.H. Baldini, None.
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The Effect of Radiotherapy Dose and Volume on Relapse in Merkel Cell Cancer of the Skin
M. C. Foote1,2, J. Harvey1, S. Porceddu1, G. Dickie3, S. Hewitt4, S. Colquist5, D. Zarate5, M. Poulsen1 1 Princess Alexandra Hospital, Brisbane, Australia, 2University of Queensland, Brisbane, Australia, 3Royal Brisbane and Womens Hospital, Brisbane, Australia, 4The Townsville Hospital, Townsville, Australia, 5Queensland Cancer Control Analysis Team, Brisbane, Australia Purpose/Objective(s): To assess the effect of radiotherapy (RT) dose and volume on relapse patterns in patients with Stage I–III Merkel cell carcinoma (MCC). Materials/Methods: Retrospective analysis of 112 patients diagnosed with MCC between January 2000 and December 2005 and given radiotherapy with curative intent. The effect of dose on relapse rate was analysed with adjustments for stage and surgical margins. Results: Of the 112 evaluable patients 88% had RT to the site of primary disease for gross (11%) or subclinical (78%) disease. Eighty-nine percent of patients had RT to the regional lymph nodes; gross disease accounting for 19% and subclinical disease
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(adjuvant or elective) in 71%. The 2 year and 5 year overall survival (OS) was 72% and 53%, respectively, and the 2 year locoregional control (LRC) rate was 75%. The in-field relapse rate was 3% for primary disease and relapse was significantly lower for patients receiving $ 50 Gy (HR = 0.22, CI: 0.06–0.86). Surgical margins did not affect the local relapse rate. The in-field relapse rate was 11% for RT to the nodes with dose being significant for nodal gross disease (HR = 0.24, CI: 0.07–0.87) and subclinical disease (HR = 0.44, CI: 0.14–1.42). Patients not receiving elective nodal RT had a much higher rate of nodal relapse compared to those who did (HR = 6.03, CI: 1.34–27.10). Conclusions: This study indicates a dose response for subclinical and gross MCC. Doses of 50 Gy for subclinical disease and 55– 60 Gy for gross disease are recommended. The draining nodal basin should be treated in all patients. Author Disclosure: M.C. Foote, None; J. Harvey, None; S. Porceddu, None; G. Dickie, None; S. Hewitt, None; S. Colquist, None; D. Zarate, None; M. Poulsen, None.
2765
Spatially Fractionated Grid Radiation (SFGRT): A Novel Approach in the Management of Recurrent and Unresectable Soft Tissue Sarcoma
M. Mohiuddin, T. Miller, P. Ronjon, U. Malik Geisinger Cancer Institute, Wilkes-Barre, PA Purpose/Objective(s): While radiation therapy is occasionally utilized for palliative treatment of large recurrence, and/or unresectable soft tissue sarcomas, their response to treatment has generally been poor. A novel approach of spatially fractionated grid radiation (SFGRT) allows safe delivery of high dose radiation which can be combined with conventionally fractionated external beam radiation to produce dramatic shrinkage of these tumors. This report evaluates the toxicity and effectiveness of this approach in treatment of advanced and bulky sarcomas. Materials/Methods: Thirty-three (33) patients with recurrent and/or unresectable soft tissue sarcomas were treated with high dose megavoltage radiation using an SFGRT technique. Seven patients received grid radiation to multiple sites for a total of 44 sites irradiated. Tumor size ranged from 6 to 32 cm with a median of 13 cm. Single dose of SFGRT 12 to 20 Gy, (median 15 Gy) to D-max was delivered using 6 MV photons. Four patients received SFGRT alone, and 40 patients received further external beam radiation. 22 to 70 Gy, median 50 Gy, 20 treatments were delivered to the abdomen and pelvis, 3 to the head and neck region, 7 to the thorax and 15 to the extremities. Results: Twelve patients achieved a clinical/pathological complete response (26%), and 22 patients (50%) achieved a partial response, 7 patients had stable disease, and 3 patients experienced tumor progression. The response rate for SFGRT followed by definitive external radiation .50 Gy was 95% (45% CR, 50% PR) as compared to 59%, (10% CR, 50% PR) in patients receiving \50 Gy external radiation. Survival of patients ranged from 2 months to 44 months with a median of 9 months. Nine patients were alive greater than one year. Two patients experienced Grade 3 skin reaction, but there was no late subcutaneous mucosal or other toxicity. Conclusions: The combined use of SFGRT and external beam radiation is an effective way for treating large recurrent and unresectable soft tissue sarcomas. Dramatic shrinkage of tumor is observed and long term control can be achieved. This approach can be especially useful in the management of retroperitoneal and intrathoracic sarcomas where resection is not feasible. Author Disclosure: M. Mohiuddin, None; T. Miller, None; P. Ronjon, None; U. Malik, None.
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Adjuvant Radiation after Limb-sparing Surgery Improves Overall Survival for Large (.5cm) High-grade Soft Tissue Sarcomas of the Extremities
D. Schreiber, J. Rineer, D. Vongtama, A. Wortham, R. Sroufe, M. Olsheski, P. Han, D. Schwartz, K. Choi, M. Z. Rotman SUNY Downstate Medical Center, Brooklyn, NY Purpose/Objective(s): Two randomized trials and several retrospective reports have shown an improvement in local control for high-grade soft tissue sarcomas (STS) of the extremities with the addition of adjuvant radiation to surgery. However, a survival benefit has not been noted. In addition, some have recently questioned whether select patients with small (#5cm) tumors should be observed and not receive adjuvant radiation at all. We analyzed the Surveillance, Epidemiology, and End Results database to evaluate the impact of adjuvant radiation (postopRT) on survival. Materials/Methods: We selected patients, ages 20–79, diagnosed between 1998–2005 with high-grade STS of the upper or lower extremities who were definitively treated with limb sparing radical surgery with or without postopRT. Rhabdomyosarcoma and Ewings sarcoma were excluded. Patients were stratified based on size of the lesion (#5cm or .5cm). Kaplan-Meier and Cox regression analysis were used to compare overall survival (OS) between the two arms. Results: A total of 862 patients were identified, of which 625 received postopRT and 237 received surgery alone. The most common histologies were malignant fibrous histiocytoma (49.1%), liposarcoma (17.8%), and leiomyosarcoma (12.3%). For the whole cohort, there was a significant improvement in 5 year OS from 59.5% to 68.1% with the addition of postopRT (p = 0.015). When stratified by tumor size, there was no significant benefit to the addition of postopRT for tumors #5cm, with a 5 year OS of 76.5% for surgery alone versus 84.7% for postoperative radiation (p = 0.198). However, for tumors .5cm, there was a significant improvement in 5 year OS for postopRT, from 42.9% to 60.3% (p\0.001). On multivariate analysis, the most significant predictors for improved survival were tumor size #5cm (HR 0.38, 95% CI 0.27–0.54, p\0.001) and postopRT (HR 0.62, 95% CI 0.46–0.85, p=0.002). Conclusions: In this large retrospective review, the addition of postopRT improves overall survival for high-grade extremity STS compared with surgery alone. When stratified by tumor size, there is only a survival benefit for tumors .5cm. There does not appear to be a survival benefit to postopRT for tumors #5cm. Author Disclosure: D. Schreiber, None; J. Rineer, None; D. Vongtama, None; A. Wortham, None; R. Sroufe, None; M. Olsheski, None; P. Han, None; D. Schwartz, None; K. Choi, None; M.Z. Rotman, None.