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Definitive Radiation Therapy for Merkel Cell Carcinoma
I. J. Radiation Oncology d Biology d Physics
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Volume 78, Number 3, Supplement, 2010
Heath Status, Physical Functioning, Emotional Functioning, Social Functioning, and Body Image. Nausea, appetite, and insomnia were statistically better for the symptom scales/scores. For APBI, this group returned to their baseline mean score values in 14 out of 18 scales/scores within three months. Within this group, 4 out of 18 scales/scores were statistically significant. These categories included a significant improvement in both Emotional Functioning and Financial Difficulties. From the symptom scores, there was a statistically significant improvement concerning breast symptoms. Conclusions: Both groups returned to their baseline mean score values at three months. However, the IMRT group surpassed their mean score values with higher percentages that were statistically significant. IMRT patients’ had resolution in 14 out of the 18 scale scores and statistically significant improvement in 10 out of 18 scores within three months post treatment. They maintained these scores at 24 months post treatment. Treatment modality has a significant influence on the mean score values, impacting patients’ functioning, symptomatology and overall QOL. Author Disclosure: C.J. Flynn, None; C. Mitchell, None; A. Limbacher, None; F. Vicini, None; A. Martinez, None.
2908
Radiation Induced Malignancy after Prophylactic Radiation Therapy in Prevention of Heterotopic Ossification
W. F. Mourad1, S. Packianathan1, M. C. Baird1, R. A. Shourbaji2, M. A. Khan3, I. Akhtar4, S. Cheng5, J. Caudell1, R. Jennelle1, S. Vijayakumar1 1
University of Mississippi Medical Center, Department of Radiation Oncology, Jackson, MS, 2Jackson State University, Department of Epidemiology and Biostatistics, Jackson, MS, 3University of Mississippi Medical Center, Department of Radiology, Jackson, MS, 4University of Mississippi Medical Center, Department of Pathology, Jackson, MS, 5Cleveland Clinic, Taussig Cancer Institute, Department of Radiation Oncology, Cleveland, OH Purpose/Objective(s): To evaluate the incidence of radiation therapy induced malignancy (RIM) in the prophylaxis of heterotopic ossification (HO). RIM is rare, late sequelae of RT which usually takes place many years after high doses of definitive RT following the treatment of aggressive cancers. However, to the best of our knowledge, RIM has never been reported previously in the context HO prophylaxis as there is not enough data on the incidence of RIM in patients treated for benign conditions at lower doses. HO is the ectopic formation of mature bone in soft tissues which is a common complication following fractures and some elective orthopedic surgeries. RT and/or Indomethacin are often used prophylactically to decrease the risk of HO after surgical intervention for trauma or elective procedures. RT is usually given post-operatively within 72 hours of surgery or preoperatively within 1 to 24 hours prior to surgery. Materials/Methods: This is a single-institution, retrospective study investigating the effect of prophylactic RT on RIM after open reduction internal fixation (ORIF), joint replacement and arthroplasty of all traumatic fractures (TFs). After reviewing Our Medical Center’s database from January 1990 to January 2010 for all upper and lower extremities surgical repair surgeries and RT, we excluded individuals who were treated after 2005, patients with bony metastasis from an underlying malignancy, and patients with concurrent cancer who were treated for HO prophylaxis after hip arthroplasty. Results: Between January 1990 and January 2005, a total of 1,642 patients with various TFs who were treated for HO prophylaxis meet the research criteria. The average age was 37 years (range, 17 - 85 years) and the median follow-up duration was 12.2 years (range, 5 - 15 years). All the patients received single fraction of 700 cGy to the soft tissues without bone shielding. Out of the 1,642 patients, who experienced TFs and received RT, only one case of RIM was identified, which consists of a high grade undifferentiated sarcoma (incidence rate of 0.06%) involving a previously irradiated proximal femur 15 years prior to RIM diagnosis. Conclusions: Our data show that radiation induced malignancy may occur even after low prophylactic radiation doses. The administration of radiation therapy as an effective prophylactic measure against heterotopic ossification in younger patients should only be undertaken after a complete discussion of the risks and benefits of the therapy. Author Disclosure: W.F. Mourad, None; S. Packianathan, None; M.C. Baird, None; R.A. Shourbaji, None; M.A. Khan, None; I. Akhtar, None; S. Cheng, None; J. Caudell, None; R. Jennelle, None; S. Vijayakumar, None.
2909
Definitive Radiation Therapy for Merkel Cell Carcinoma 1
C. Loiselle , L. Fang1, S. Koba1,2, U. Parvathaneni1, P. Nghiem1 1
University of Washington Medical Center, Seattle, WA, 2Saga University, Saga, Japan
Purpose/Objective(s): The current accepted treatment for Merkel cell carcinoma (MCC) is surgical resection followed by adjuvant radiotherapy, as is recommended in the National Comprehensive Cancer Network guidelines. However, few small series and case reports have demonstrated excellent results with radiotherapy alone, consistent with the known radiosensitivity of MCC. This retrospective study was performed to analyze local control (LC) and overall survival (OS) for patients with MCC treated with definitive radiotherapy alone, without surgical resection. Materials/Methods: Between 1983 and 2009, 375 patients with MCC were seen in consultation at Dana Farber Cancer Institute or University of Washington and enrolled in a prospective database. Patients that received definitive radiation therapy without surgical resection as primary therapy were included in this retrospective review. Those with distant metastatic disease on presentation were excluded. Results: Eighteen patients met the inclusion criteria and were included in this analysis. Median follow-up was 20.5 months. Median age was 74 years and median tumor size was 25 mm. Median radiation dose was 60 Gy (range, 45 to 70 Gy). Local control was 94%; for one patient an in-field complete clinical response was not achieved by 4 months after radiation therapy. This patient underwent salvage surgical resection and remains without evidence of disease at the time of last follow-up. Twoyear OS was 74%.
Proceedings of the 52nd Annual ASTRO Meeting Conclusions: Patients treated with definitive radiotherapy for MCC have excellent local control and overall survival rates, comparable to historical outcomes of patients treated with surgery and adjuvant radiation therapy. Given the potential to spare patients the morbidity of an additional treatment modality, radiation monotherapy can be carefully considered in select patients. Author Disclosure: C. Loiselle, None; L. Fang, None; S. Koba, None; U. Parvathaneni, None; P. Nghiem, None.
2910
Radiation Retinopathy and Neuropathy following Plaque Therapy of Small Choroidal Melanoma
D. Wilkinson, V. Torres, M. Kolar, P. Fleming, A. Singh Cleveland Clinic Foundation, Cleveland, OH Purpose/Objective(s): Despite yielding excellent local tumor control, the long term visual outcome following plaque radiotherapy is poor. The purpose of this study is to examine the incidence of radiation retinopathy (RR) and radiation optic neuropathy (RON) following I-125 and Ru-106 plaque therapy for the treatment of small choroidal melanomas as a function of radiation dose to the macula and optic disc. Materials/Methods: A retrospective outcomes and dose analysis was performed for patients treated with either I-125 or Ru-106 plaque therapy between January/2006 and July/2008. The inclusion criteria were tumor measuring up to 4 mm in thickness and minimum follow-up of 18 months. The radiation retinopathy was classified in four groups (Finger Classification), based on the ophthalmoscopic/angiographic signs. Plaques were either COMS (Collaborative Ocular Melanoma Study) with silastic carrier for I-125 or Bebig Ru-106 (Eckert & Ziegler Bebig GmbH, Berlin, Germany). The prescription was 85 Gy to the tumor apex delivered in 72 to 96 hr. Dose estimates to the macula (for RR) and to the optic disc (for RON) were made using the software Plaquesimulator (Bebig) which was also used for treatment planning. Results: A total of 52 eyes/52 patients were analyzed (34 female, 18 male), with 38 (73%) treated using I-125 and 14 (27%) using Ru-106. Local tumor control was achieved in 100% of the patients treated with I-125 plaques and 85.7% with Ru-106. In the I-125 treated group, 12/38 (31.6%) developed signs of RR and RON over a mean follow-up of 28.4 months (range, 22 -36 mo). The RR was classified as group 1: 9%, group 2: 30% and groups 3 and 4: 55.5%. In the Ru-106 treated group, 3/14 (21.4%) presented RR over a mean follow-up of 17.6 months (range, 12-24 mo): Group 1: 33% and Group 3: 66%. The mean dose delivered to the macula in the I-125 treated patients was 60.86 Gy for the subgroup that did not develop RR and 54.8 Gy in the RR subgroup. In the Ru-106 treated group, the macular doses were 23.8 Gy and 80.76 Gy respectively. Patients who developed signs of RR and/or RON had mean macular doses of 29.4 Gy (Group 1), 56.3 Gy (Group 2), and 76.1 Gy (Groups 3 and 4). The mean dose to the optic disc in RON patients was 39.2 Gy; it was 23.1 Gy for patients with no complications. Conclusions: A dose of 85 Gy to the apex of these small melanomas, rather than to the 5mm COMS point, provided adequate local control. The incidence of RR for patients treated with I-125 was slightly higher than with Ru-106, with a longer time interval between the treatment and onset of RR. There was no apparent dependence of the development of RR in I-125 treated patients on the macula point dose. However, there are hints of a dose response for the Ru-106 treated patients, for the development of RON, and for the severity of complications in the RR group of I-125 treated patients. Author Disclosure: D. Wilkinson, None; V. Torres, None; M. Kolar, None; P. Fleming, None; A. Singh, None.
2911
Sphincter-sparing Local Excision and Hypofractionated Radiation Therapy for Anal-rectal Melanoma: A 20 Year Experience
P. Kelly, A. Guadagnolo, J. N. Cormier, M. I. Ross, G. K. Zagars M.D. Anderson Cancer Center, Houston, TX Purpose/Objective(s): Anal-rectal melanoma is a rare disease with a poor prognosis. As outcome is dictated by distant failure, the use of radical, non-sphincter sparing surgery has been questioned. However, concerns remain about the effectiveness of sphincter sparing approaches in controlling the disease locally. Here we report our institution’s 20 year experience with sphincter sparing local excision and hypofractionated radiation therapy in the treatment of anal-rectal melanoma. Materials/Methods: We retrospectively reviewed the records of 55 patients with localized anal-rectal melanoma treated at MD Anderson Cancer Center between 1989 and 2008. All patients received definitive local excision with or without nodal biopsy or dissection. Hypofractionated radiation was delivered preoperatively in 2 patients (25 Gy, 5 daily fractions) and post-operatively in 53 patients (30-36 Gy, 5-6 twice weekly fractions). Extended fields (EF) that targeted the primary site and draining pelvic/inguinal lymphatics were used in 38 patients and limited fields (LF) targeting only the primary site in 17 patients. Univariate and multivariate analyses were performed to assess prognostic influence of clinical, pathologic, and treatment related factors. The endpoints analyzed were local control (LC), nodal control (NC), sphincter preservation (SP), disease free survival (DFS), overall survival (OS), and treatment related toxicity. Actuarial curves were calculated using the Kaplan-Meier method and the log-rank statistic was used to assess for significance of difference between curves. Results: With a median follow-up time of 42 months, the actuarial 5-year rates of LC, NC and SP were 82%, 81% and 98%, respectively. However, due to the high rate of distant metastasis (73% at 5 years), the actuarial 5-year DFS rate was only 27%, and OS at 5 years was 30%. Nodal involvement at presentation was the only factor predictive of inferior DFS or OS. No factor was prognostic for LC. Of note, there was no significant difference in the 5 year rates of LC (EF 81% vs. LF 86%; p = 0.84) or NC (EF 78% vs. LF 88%; p = 0.80) based on field size. Treatment related toxicity occurred in 25 patients (45%), with only 1 severe complication. The most common side effects were radiation proctitis (n = 18) and scrotal edema (n = 9). Whereas the rates of radiation proctitis were not significantly different between the patients treated with EF and LF (34% vs. 28%; p = 0.73), scrotal edema was only seen in the EF group.
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S610
Volume 78, Number 3, Supplement, 2010
Heath Status, Physical Functioning, Emotional Functioning, Social Functioning, and Body Image. Nausea, appetite, and insomnia were statistically better for the symptom scales/scores. For APBI, this group returned to their baseline mean score values in 14 out of 18 scales/scores within three months. Within this group, 4 out of 18 scales/scores were statistically significant. These categories included a significant improvement in both Emotional Functioning and Financial Difficulties. From the symptom scores, there was a statistically significant improvement concerning breast symptoms. Conclusions: Both groups returned to their baseline mean score values at three months. However, the IMRT group surpassed their mean score values with higher percentages that were statistically significant. IMRT patients’ had resolution in 14 out of the 18 scale scores and statistically significant improvement in 10 out of 18 scores within three months post treatment. They maintained these scores at 24 months post treatment. Treatment modality has a significant influence on the mean score values, impacting patients’ functioning, symptomatology and overall QOL. Author Disclosure: C.J. Flynn, None; C. Mitchell, None; A. Limbacher, None; F. Vicini, None; A. Martinez, None.
2908
Radiation Induced Malignancy after Prophylactic Radiation Therapy in Prevention of Heterotopic Ossification
W. F. Mourad1, S. Packianathan1, M. C. Baird1, R. A. Shourbaji2, M. A. Khan3, I. Akhtar4, S. Cheng5, J. Caudell1, R. Jennelle1, S. Vijayakumar1 1
University of Mississippi Medical Center, Department of Radiation Oncology, Jackson, MS, 2Jackson State University, Department of Epidemiology and Biostatistics, Jackson, MS, 3University of Mississippi Medical Center, Department of Radiology, Jackson, MS, 4University of Mississippi Medical Center, Department of Pathology, Jackson, MS, 5Cleveland Clinic, Taussig Cancer Institute, Department of Radiation Oncology, Cleveland, OH Purpose/Objective(s): To evaluate the incidence of radiation therapy induced malignancy (RIM) in the prophylaxis of heterotopic ossification (HO). RIM is rare, late sequelae of RT which usually takes place many years after high doses of definitive RT following the treatment of aggressive cancers. However, to the best of our knowledge, RIM has never been reported previously in the context HO prophylaxis as there is not enough data on the incidence of RIM in patients treated for benign conditions at lower doses. HO is the ectopic formation of mature bone in soft tissues which is a common complication following fractures and some elective orthopedic surgeries. RT and/or Indomethacin are often used prophylactically to decrease the risk of HO after surgical intervention for trauma or elective procedures. RT is usually given post-operatively within 72 hours of surgery or preoperatively within 1 to 24 hours prior to surgery. Materials/Methods: This is a single-institution, retrospective study investigating the effect of prophylactic RT on RIM after open reduction internal fixation (ORIF), joint replacement and arthroplasty of all traumatic fractures (TFs). After reviewing Our Medical Center’s database from January 1990 to January 2010 for all upper and lower extremities surgical repair surgeries and RT, we excluded individuals who were treated after 2005, patients with bony metastasis from an underlying malignancy, and patients with concurrent cancer who were treated for HO prophylaxis after hip arthroplasty. Results: Between January 1990 and January 2005, a total of 1,642 patients with various TFs who were treated for HO prophylaxis meet the research criteria. The average age was 37 years (range, 17 - 85 years) and the median follow-up duration was 12.2 years (range, 5 - 15 years). All the patients received single fraction of 700 cGy to the soft tissues without bone shielding. Out of the 1,642 patients, who experienced TFs and received RT, only one case of RIM was identified, which consists of a high grade undifferentiated sarcoma (incidence rate of 0.06%) involving a previously irradiated proximal femur 15 years prior to RIM diagnosis. Conclusions: Our data show that radiation induced malignancy may occur even after low prophylactic radiation doses. The administration of radiation therapy as an effective prophylactic measure against heterotopic ossification in younger patients should only be undertaken after a complete discussion of the risks and benefits of the therapy. Author Disclosure: W.F. Mourad, None; S. Packianathan, None; M.C. Baird, None; R.A. Shourbaji, None; M.A. Khan, None; I. Akhtar, None; S. Cheng, None; J. Caudell, None; R. Jennelle, None; S. Vijayakumar, None.
2909
Definitive Radiation Therapy for Merkel Cell Carcinoma 1
C. Loiselle , L. Fang1, S. Koba1,2, U. Parvathaneni1, P. Nghiem1 1
University of Washington Medical Center, Seattle, WA, 2Saga University, Saga, Japan
Purpose/Objective(s): The current accepted treatment for Merkel cell carcinoma (MCC) is surgical resection followed by adjuvant radiotherapy, as is recommended in the National Comprehensive Cancer Network guidelines. However, few small series and case reports have demonstrated excellent results with radiotherapy alone, consistent with the known radiosensitivity of MCC. This retrospective study was performed to analyze local control (LC) and overall survival (OS) for patients with MCC treated with definitive radiotherapy alone, without surgical resection. Materials/Methods: Between 1983 and 2009, 375 patients with MCC were seen in consultation at Dana Farber Cancer Institute or University of Washington and enrolled in a prospective database. Patients that received definitive radiation therapy without surgical resection as primary therapy were included in this retrospective review. Those with distant metastatic disease on presentation were excluded. Results: Eighteen patients met the inclusion criteria and were included in this analysis. Median follow-up was 20.5 months. Median age was 74 years and median tumor size was 25 mm. Median radiation dose was 60 Gy (range, 45 to 70 Gy). Local control was 94%; for one patient an in-field complete clinical response was not achieved by 4 months after radiation therapy. This patient underwent salvage surgical resection and remains without evidence of disease at the time of last follow-up. Twoyear OS was 74%.
Proceedings of the 52nd Annual ASTRO Meeting Conclusions: Patients treated with definitive radiotherapy for MCC have excellent local control and overall survival rates, comparable to historical outcomes of patients treated with surgery and adjuvant radiation therapy. Given the potential to spare patients the morbidity of an additional treatment modality, radiation monotherapy can be carefully considered in select patients. Author Disclosure: C. Loiselle, None; L. Fang, None; S. Koba, None; U. Parvathaneni, None; P. Nghiem, None.
2910
Radiation Retinopathy and Neuropathy following Plaque Therapy of Small Choroidal Melanoma
D. Wilkinson, V. Torres, M. Kolar, P. Fleming, A. Singh Cleveland Clinic Foundation, Cleveland, OH Purpose/Objective(s): Despite yielding excellent local tumor control, the long term visual outcome following plaque radiotherapy is poor. The purpose of this study is to examine the incidence of radiation retinopathy (RR) and radiation optic neuropathy (RON) following I-125 and Ru-106 plaque therapy for the treatment of small choroidal melanomas as a function of radiation dose to the macula and optic disc. Materials/Methods: A retrospective outcomes and dose analysis was performed for patients treated with either I-125 or Ru-106 plaque therapy between January/2006 and July/2008. The inclusion criteria were tumor measuring up to 4 mm in thickness and minimum follow-up of 18 months. The radiation retinopathy was classified in four groups (Finger Classification), based on the ophthalmoscopic/angiographic signs. Plaques were either COMS (Collaborative Ocular Melanoma Study) with silastic carrier for I-125 or Bebig Ru-106 (Eckert & Ziegler Bebig GmbH, Berlin, Germany). The prescription was 85 Gy to the tumor apex delivered in 72 to 96 hr. Dose estimates to the macula (for RR) and to the optic disc (for RON) were made using the software Plaquesimulator (Bebig) which was also used for treatment planning. Results: A total of 52 eyes/52 patients were analyzed (34 female, 18 male), with 38 (73%) treated using I-125 and 14 (27%) using Ru-106. Local tumor control was achieved in 100% of the patients treated with I-125 plaques and 85.7% with Ru-106. In the I-125 treated group, 12/38 (31.6%) developed signs of RR and RON over a mean follow-up of 28.4 months (range, 22 -36 mo). The RR was classified as group 1: 9%, group 2: 30% and groups 3 and 4: 55.5%. In the Ru-106 treated group, 3/14 (21.4%) presented RR over a mean follow-up of 17.6 months (range, 12-24 mo): Group 1: 33% and Group 3: 66%. The mean dose delivered to the macula in the I-125 treated patients was 60.86 Gy for the subgroup that did not develop RR and 54.8 Gy in the RR subgroup. In the Ru-106 treated group, the macular doses were 23.8 Gy and 80.76 Gy respectively. Patients who developed signs of RR and/or RON had mean macular doses of 29.4 Gy (Group 1), 56.3 Gy (Group 2), and 76.1 Gy (Groups 3 and 4). The mean dose to the optic disc in RON patients was 39.2 Gy; it was 23.1 Gy for patients with no complications. Conclusions: A dose of 85 Gy to the apex of these small melanomas, rather than to the 5mm COMS point, provided adequate local control. The incidence of RR for patients treated with I-125 was slightly higher than with Ru-106, with a longer time interval between the treatment and onset of RR. There was no apparent dependence of the development of RR in I-125 treated patients on the macula point dose. However, there are hints of a dose response for the Ru-106 treated patients, for the development of RON, and for the severity of complications in the RR group of I-125 treated patients. Author Disclosure: D. Wilkinson, None; V. Torres, None; M. Kolar, None; P. Fleming, None; A. Singh, None.
2911
Sphincter-sparing Local Excision and Hypofractionated Radiation Therapy for Anal-rectal Melanoma: A 20 Year Experience
P. Kelly, A. Guadagnolo, J. N. Cormier, M. I. Ross, G. K. Zagars M.D. Anderson Cancer Center, Houston, TX Purpose/Objective(s): Anal-rectal melanoma is a rare disease with a poor prognosis. As outcome is dictated by distant failure, the use of radical, non-sphincter sparing surgery has been questioned. However, concerns remain about the effectiveness of sphincter sparing approaches in controlling the disease locally. Here we report our institution’s 20 year experience with sphincter sparing local excision and hypofractionated radiation therapy in the treatment of anal-rectal melanoma. Materials/Methods: We retrospectively reviewed the records of 55 patients with localized anal-rectal melanoma treated at MD Anderson Cancer Center between 1989 and 2008. All patients received definitive local excision with or without nodal biopsy or dissection. Hypofractionated radiation was delivered preoperatively in 2 patients (25 Gy, 5 daily fractions) and post-operatively in 53 patients (30-36 Gy, 5-6 twice weekly fractions). Extended fields (EF) that targeted the primary site and draining pelvic/inguinal lymphatics were used in 38 patients and limited fields (LF) targeting only the primary site in 17 patients. Univariate and multivariate analyses were performed to assess prognostic influence of clinical, pathologic, and treatment related factors. The endpoints analyzed were local control (LC), nodal control (NC), sphincter preservation (SP), disease free survival (DFS), overall survival (OS), and treatment related toxicity. Actuarial curves were calculated using the Kaplan-Meier method and the log-rank statistic was used to assess for significance of difference between curves. Results: With a median follow-up time of 42 months, the actuarial 5-year rates of LC, NC and SP were 82%, 81% and 98%, respectively. However, due to the high rate of distant metastasis (73% at 5 years), the actuarial 5-year DFS rate was only 27%, and OS at 5 years was 30%. Nodal involvement at presentation was the only factor predictive of inferior DFS or OS. No factor was prognostic for LC. Of note, there was no significant difference in the 5 year rates of LC (EF 81% vs. LF 86%; p = 0.84) or NC (EF 78% vs. LF 88%; p = 0.80) based on field size. Treatment related toxicity occurred in 25 patients (45%), with only 1 severe complication. The most common side effects were radiation proctitis (n = 18) and scrotal edema (n = 9). Whereas the rates of radiation proctitis were not significantly different between the patients treated with EF and LF (34% vs. 28%; p = 0.73), scrotal edema was only seen in the EF group.
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