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Short-Course Radiation Therapy for Merkel Cell Carcinoma: Relative Effectiveness in a “Radiosensitive” Tumor
S160
International Journal of Radiation Oncology Biology Physics
Purpose/Objective(s): Patients (pts) who are chronically immunosuppressed (IS) have higher rates of cutaneous squamous cell carcinoma of the head and neck (cSCC-HN), one of the most aggressive forms of skin cancer. This multi-institutional study analyzes the effect of immune status on disease outcomes in pts with primary or recurrent stage I-IV cSCC-HN treated with surgery and postoperative radiation therapy (RT). Materials/Methods: Pts who received surgical resection and postoperative RT between 1995-2015 at Cleveland Clinic, Washington University St. Louis, and University of California San Francisco were identified in each institution’s respective IRB approved registry. Pts were categorized as IS if they were diagnosed with chronic hematologic malignancy, HIV/AIDS, or were treated with immunosuppressive therapy for organ transplantation 6 months prior to diagnosis. Overall survival (OS), locoregional recurrence free survival (LRRFS), and progression free survival (PFS) were calculated using the Kaplan Meier method. Univariate (UVA) and multivariate (MVA) analysis was performed using Cox proportional hazards regression to identify patient, tumor, and treatment related variables associated with locoregional recurrence (LRR). Results: In this study of 205 pts, 138 (67.3%) were immunocompetent (IC) and 67 (32.7%) were IS. Poor differentiation (PD) (55.2% vs. 36.2%; P Z 0.009) was more frequent in IS pts. Perineural invasion (PNI) (53.7% vs. 46.4%; P Z 0.323) and nodal extracapsular extension (77.3% vs. 64.2%; P Z 0.664) were numerically, but not statistically different between groups. LRRFS (47.3% vs. 86.1%; P < 0.0001) and PFS (38.7% vs. 71.6%; P Z 0.002) were significantly lower in IS pts compared to IC at 2 years. OS in IS pts at 2 years was not statistically different (60.9% vs. 78.1%; P Z 0.135). UVA on all pts demonstrated that IS status (HR Z 3.82; P < 0.0001), recurrent disease (HR Z 1.90; P Z 0.025), PD (HR Z 2.30; P Z 0.002), and PNI (HR Z 1.78; P Z 0.03) were significantly associated with higher rates of LRR. On MVA, IS status (HR Z 3.79; P < 0.0001), recurrent disease (HR Z 2.67; P Z 0.001), PD (HR Z 2.08; P Z 0.006), and PNI (HR Z 2.05; P Z 0.009) remained significantly associated with higher rates of LRR. Conclusion: This multi-institutional analysis demonstrates that IS pts with cSCC-HN more frequently present with high-risk pathologic features and have dramatically lower LRRFS and PFS at 2 years compared to IC pts. IS status, recurrent disease, PD, and PNI were significantly associated with higher LRR. Intensification strategies for IS pts merit investigation. Author Disclosure: B. Manyam: None. A.A. Garsa: None. R. Chin: None. C.A. Reddy: None. B. Gastman: None. A.T. Vidimos: None. W.L. Thorstad: None. S.S. Yom: Research Grant; Genentech. B. Nussenbaum: None. S. Wang: None. S. Koyfman: None.
Materials/Methods: Medical records of patients with Merkel cell carcinoma treated with short courses of radiotherapy (3 fractions or less) were reviewed retrospectively. Demographic, disease and treatment related parameters were compiled. Response was characterized by RECIST. Summary statistics were generated and comparisons between groups were carried out using Fisher’s exact tests. Results: Twenty patients with 67 irradiated tumors were identified; 52 tumors were treated with either 8 Gy/1 fraction (n Z 31) or 24 Gy/3 fractions (n Z 21). Median follow-up was 488 days. Mean patient age was 72 years (range Z 51-96), median tumor size was 30 mm (range Z 11300). Three of 31 tumors (10%) exhibited a complete response after 8 Gy/1 fraction, while 10/21 tumors (48%) treated with 24 Gy/3 fractions completely responded. Recurrence occurred in 41% of tumors treated with 8 Gy/1 fraction, while this event occurred in 4.8% of those treated with 24 Gy/3 fractions (P Z 0.04). There was no significant difference in rate of recurrence based on host immune status, genomic mutational load, or pretreatment tumor size. Conclusion: Merkel cell carcinoma is a relatively radiosensitive tumor, but complete and durable response after low dose radiotherapy (8 Gy/1 fraction) was uncommon in our experience. Higher dose regimens appeared to produce greater rates of durable tumor control. Additional studies from other centers in larger groups of patients with longer follow-up are necessary to corroborate these observations. Author Disclosure: N. Cimbak: None. C.A. Barker: Research Grant; Elekta, University of California San Francisco. Honoraria; American College of Mohs Surgery. Consultant; Patient Resource. Travel Expenses; American Academy of Dermatology, American College of Mohs Surgery. Organized Subcommittee; American Society of Radiation Oncology.
361 Short-Course Radiation Therapy for Merkel Cell Carcinoma: Relative Effectiveness in a “Radiosensitive” Tumor N. Cimbak and C.A. Barker, Jr; Memorial Sloan Kettering Cancer Center, New York, NY Purpose/Objective(s): Merkel cell carcinoma is a rare, but relatively radiosensitive cutaneous malignancy that often occurs in elderly and infirmed patients. In this population, a long course of conventionally fractionated radiotherapy for primary or metastatic tumor control is often not feasible. Recently, investigators reported remarkably high rates of tumor response and control with a single low dose of radiotherapy (8 Gy/1 fraction, Iyer et al, Cancer Medicine 2015). We sought to confirm the observation of these investigators, and determine the relative efficacy of a higher dose regimen (24 Gy/3 fractions). We hypothesized that rates of response would be higher among tumors irradiated with higher doses, and irradiated tumor recurrence would be less frequent.
362 Long-Term Decision Regret After Postprostatectomy Image Guided Intensity Modulated Radiation Therapy T.P. Shakespeare,1,2 S. Chin,3 M. Hoffman,1 and N. Aherne1; 1North Coast Cancer Institute, Coffs Harbour, Australia, 2University of New South Wales Rural Clinical School, Coffs Harbour, Australia, 3Westmead Hospital, Westmead, Australia Purpose/Objective(s): Decision regret (DR) is a negative emotion experienced when a patient believes that their outcome may have been better if they had decided differently about their management approach. Although some studies investigate DR after treatment for localized prostate cancer, none have reported DR in patients undergoing surgery with post-prostatectomy radiotherapy. Our primary aim was to evaluate DR in this group of patients overall, and for specific components of therapy. Materials/Methods: We surveyed 83 consecutive patients, with a minimum 5 years follow-up, treated with post-prostatectomy imageguided intensity-modulated radiotherapy (PP-IG-IMRT). All patients were treated on the www.EviQ.org.au radiotherapy protocols using fiducial markers, MRI-CT fusion and inverse-planned IMRT, to a dose of 64-66 Gy. We used a validated 2-item questionnaire. Men were classed as regretful if they either indicated that it was true that they would have been better off had they chosen another treatment, or they wished they could change their mind about a treatment at least some of the time. Results: We received 71 responses (85.5%). The median patient age was 72 years (range 56-85), median time since surgery was 92 months, and median follow-up post-IMRT was 78 months. Adjuvant IG-IMRT was used in 28% of patients, salvage in 72%, and ADT in 48%. A total of 70% of patients remained disease-free, 16% had PSA-failure, and 14% had locoregional/distant failures. In all 16.9% of patients were regretful. There was four-fold more regret for the radical prostatectomy component of treatment compared to PP-IG-IMRT (16.9%
International Journal of Radiation Oncology Biology Physics
Purpose/Objective(s): Patients (pts) who are chronically immunosuppressed (IS) have higher rates of cutaneous squamous cell carcinoma of the head and neck (cSCC-HN), one of the most aggressive forms of skin cancer. This multi-institutional study analyzes the effect of immune status on disease outcomes in pts with primary or recurrent stage I-IV cSCC-HN treated with surgery and postoperative radiation therapy (RT). Materials/Methods: Pts who received surgical resection and postoperative RT between 1995-2015 at Cleveland Clinic, Washington University St. Louis, and University of California San Francisco were identified in each institution’s respective IRB approved registry. Pts were categorized as IS if they were diagnosed with chronic hematologic malignancy, HIV/AIDS, or were treated with immunosuppressive therapy for organ transplantation 6 months prior to diagnosis. Overall survival (OS), locoregional recurrence free survival (LRRFS), and progression free survival (PFS) were calculated using the Kaplan Meier method. Univariate (UVA) and multivariate (MVA) analysis was performed using Cox proportional hazards regression to identify patient, tumor, and treatment related variables associated with locoregional recurrence (LRR). Results: In this study of 205 pts, 138 (67.3%) were immunocompetent (IC) and 67 (32.7%) were IS. Poor differentiation (PD) (55.2% vs. 36.2%; P Z 0.009) was more frequent in IS pts. Perineural invasion (PNI) (53.7% vs. 46.4%; P Z 0.323) and nodal extracapsular extension (77.3% vs. 64.2%; P Z 0.664) were numerically, but not statistically different between groups. LRRFS (47.3% vs. 86.1%; P < 0.0001) and PFS (38.7% vs. 71.6%; P Z 0.002) were significantly lower in IS pts compared to IC at 2 years. OS in IS pts at 2 years was not statistically different (60.9% vs. 78.1%; P Z 0.135). UVA on all pts demonstrated that IS status (HR Z 3.82; P < 0.0001), recurrent disease (HR Z 1.90; P Z 0.025), PD (HR Z 2.30; P Z 0.002), and PNI (HR Z 1.78; P Z 0.03) were significantly associated with higher rates of LRR. On MVA, IS status (HR Z 3.79; P < 0.0001), recurrent disease (HR Z 2.67; P Z 0.001), PD (HR Z 2.08; P Z 0.006), and PNI (HR Z 2.05; P Z 0.009) remained significantly associated with higher rates of LRR. Conclusion: This multi-institutional analysis demonstrates that IS pts with cSCC-HN more frequently present with high-risk pathologic features and have dramatically lower LRRFS and PFS at 2 years compared to IC pts. IS status, recurrent disease, PD, and PNI were significantly associated with higher LRR. Intensification strategies for IS pts merit investigation. Author Disclosure: B. Manyam: None. A.A. Garsa: None. R. Chin: None. C.A. Reddy: None. B. Gastman: None. A.T. Vidimos: None. W.L. Thorstad: None. S.S. Yom: Research Grant; Genentech. B. Nussenbaum: None. S. Wang: None. S. Koyfman: None.
Materials/Methods: Medical records of patients with Merkel cell carcinoma treated with short courses of radiotherapy (3 fractions or less) were reviewed retrospectively. Demographic, disease and treatment related parameters were compiled. Response was characterized by RECIST. Summary statistics were generated and comparisons between groups were carried out using Fisher’s exact tests. Results: Twenty patients with 67 irradiated tumors were identified; 52 tumors were treated with either 8 Gy/1 fraction (n Z 31) or 24 Gy/3 fractions (n Z 21). Median follow-up was 488 days. Mean patient age was 72 years (range Z 51-96), median tumor size was 30 mm (range Z 11300). Three of 31 tumors (10%) exhibited a complete response after 8 Gy/1 fraction, while 10/21 tumors (48%) treated with 24 Gy/3 fractions completely responded. Recurrence occurred in 41% of tumors treated with 8 Gy/1 fraction, while this event occurred in 4.8% of those treated with 24 Gy/3 fractions (P Z 0.04). There was no significant difference in rate of recurrence based on host immune status, genomic mutational load, or pretreatment tumor size. Conclusion: Merkel cell carcinoma is a relatively radiosensitive tumor, but complete and durable response after low dose radiotherapy (8 Gy/1 fraction) was uncommon in our experience. Higher dose regimens appeared to produce greater rates of durable tumor control. Additional studies from other centers in larger groups of patients with longer follow-up are necessary to corroborate these observations. Author Disclosure: N. Cimbak: None. C.A. Barker: Research Grant; Elekta, University of California San Francisco. Honoraria; American College of Mohs Surgery. Consultant; Patient Resource. Travel Expenses; American Academy of Dermatology, American College of Mohs Surgery. Organized Subcommittee; American Society of Radiation Oncology.
361 Short-Course Radiation Therapy for Merkel Cell Carcinoma: Relative Effectiveness in a “Radiosensitive” Tumor N. Cimbak and C.A. Barker, Jr; Memorial Sloan Kettering Cancer Center, New York, NY Purpose/Objective(s): Merkel cell carcinoma is a rare, but relatively radiosensitive cutaneous malignancy that often occurs in elderly and infirmed patients. In this population, a long course of conventionally fractionated radiotherapy for primary or metastatic tumor control is often not feasible. Recently, investigators reported remarkably high rates of tumor response and control with a single low dose of radiotherapy (8 Gy/1 fraction, Iyer et al, Cancer Medicine 2015). We sought to confirm the observation of these investigators, and determine the relative efficacy of a higher dose regimen (24 Gy/3 fractions). We hypothesized that rates of response would be higher among tumors irradiated with higher doses, and irradiated tumor recurrence would be less frequent.
362 Long-Term Decision Regret After Postprostatectomy Image Guided Intensity Modulated Radiation Therapy T.P. Shakespeare,1,2 S. Chin,3 M. Hoffman,1 and N. Aherne1; 1North Coast Cancer Institute, Coffs Harbour, Australia, 2University of New South Wales Rural Clinical School, Coffs Harbour, Australia, 3Westmead Hospital, Westmead, Australia Purpose/Objective(s): Decision regret (DR) is a negative emotion experienced when a patient believes that their outcome may have been better if they had decided differently about their management approach. Although some studies investigate DR after treatment for localized prostate cancer, none have reported DR in patients undergoing surgery with post-prostatectomy radiotherapy. Our primary aim was to evaluate DR in this group of patients overall, and for specific components of therapy. Materials/Methods: We surveyed 83 consecutive patients, with a minimum 5 years follow-up, treated with post-prostatectomy imageguided intensity-modulated radiotherapy (PP-IG-IMRT). All patients were treated on the www.EviQ.org.au radiotherapy protocols using fiducial markers, MRI-CT fusion and inverse-planned IMRT, to a dose of 64-66 Gy. We used a validated 2-item questionnaire. Men were classed as regretful if they either indicated that it was true that they would have been better off had they chosen another treatment, or they wished they could change their mind about a treatment at least some of the time. Results: We received 71 responses (85.5%). The median patient age was 72 years (range 56-85), median time since surgery was 92 months, and median follow-up post-IMRT was 78 months. Adjuvant IG-IMRT was used in 28% of patients, salvage in 72%, and ADT in 48%. A total of 70% of patients remained disease-free, 16% had PSA-failure, and 14% had locoregional/distant failures. In all 16.9% of patients were regretful. There was four-fold more regret for the radical prostatectomy component of treatment compared to PP-IG-IMRT (16.9%