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Does Regional Radiation Therapy Impact Outcome for High-Risk, Node-Positive Cutaneous Melanoma?
Oral Scientific Sessions S157
Volume 96 Number 2S Supplement 2016 Purpose/Objective(s): Hepcidin is a hormone that was identified and characterized in the year 2000 with a key role in regulating iron metabolism. The increased serum hepcidin level was associated with lymph node metastasis and tumor clinical stage of non-small cell lung cancer (NSCLC). Our preliminary data (not published yet) found that expression of Hepcidin was highly correlated and predictive of overall survival (OS). Hamp is known as coding gene of Hepcidin. BMP/Smad4 is an important regulating pathway for the expression of hepcidin. In this study, we investigated if SNPs in the BMP/Smad4/Hamp pathway are associated with outcome in patients receiving definitive RT for NSCLC. Materials/Methods: A total of 623 patients who received 60 Gy for NSCLC identified from a single-institution database were included. Potentially functional and tagging SNPs of genes BMP2 (rs170986, rs1979855, rs1980499, rs235768, and rs3178250), BMP4 (rs17563, rs4898820, and rs762642), Smad4 (rs12456284), and Hamp (rs1882694, rs10402233, rs10421768, rs12971321) were genotyped by TaqMan realtime polymerase chain reaction. Kaplan-Meier cumulative probability and Cox proportional hazards were used to evaluate the potential effect of these SNPs on OS, LRPFS (local regional progression-free survival), progression-free survival (PFS), and DM (distant metastasis). All clinical characteristics were evaluated and included in the multivariate model if P < 0.1. Results: The median age of patients in this study was 66 years (range, 3588 years), and most (488 [73.2%]) had stage III NSCLC. The median gross tumor volume (GTV) was 91.6cm3 (range, 1.5-1271.5 cm3), the median radiation dose was 69.5 Gy (range, 60-87.5 Gy), and the median mean lung dose (MLD) was 17.965 Gy (range, 0.153-32.741 Gy). Radiation modalities were proton beam therapy (n Z 135, 21.7%), intensity-modulated RT (n Z 300, 48.2%), and 3-dimensional conformal RT (n Z 170, 27.3%). In addition, 226 patients (36.3%) received induction chemotherapy and 551 patients (88.4%) received concurrent chemotherapy. OS, LRPFS, PFS, and DM were observed in this study. Hamp rs1882694 AC/CC genotypes were found to be significantly associated with poor OS in multivariate analysis (HR Z 1.301; 95% CI Z 1.040 to 1.627; P Z 0.021). This significant allele was also obviously associated with poor LRPFS (HR Z 1.648; 95% CI Z 1.188 to 2.286; P Z 0.003); poor PFS (HR Z 1.435; 95% CI Z 1.127 to 1.827; P Z 0.003) and increased risk of DM (HR Z 1.348; 95% CI Z 1.025 to 1.773; P Z 0.033) in multivariate analysis. BMP2 rs1979855 AG/GG genotypes were significantly associated with poor LRPFS (HR Z 1.433; 95% CI Z 1.042 to 1.970; P Z 0.027) and poor PFS (HR Z 1.433; 95% CI Z 1.128 to 1.820; P Z 0.003) in multivariate analysis. Conclusion: SNPs in BMP/Smad4/Hamp pathway were also significantly associated with outcome after definitive radiotherapy for NSCLC. A validation study involving patients from an ongoing prospective trial is underway. Author Disclosure: J. Yang: None. T. Xu: None. X. Yuan: None. D.R. Gomez: None. Y. Song: None. R.U. Komaki: None. Z. Liao: None.
clarify the role of RRT among a cohort of node positive melanoma patients. Materials/Methods: A single-institution IRB-approved study was performed including 699 patients with node positive cutaneous melanoma without distant metastatic disease treated from July 1998e2015. Exclusion criteria included patients with satellite or in-transit metastasis only (AJCC N2c stage), unknown recurrence, unclear treatment records, or <12 months follow-up. After exclusion, 570 patients remained for analysis. Patients were treated with excision and either SLND + completion lymph node dissection or therapeutic lymph node dissection. Post-operative RRT was delivered to the involved nodal basin in 98 (17.2%) cases to a median dose of 54 Gy (range Z 30-60 Gy) in 27 fractions (range Z 5-30). The primary outcome was regional control (RC) at any time point. Kaplan-Meier (KM) analysis, the log-rank test, and Cox Hazards multivariate (MV) models were used to compare outcomes. Results: Median follow-up was 70 months (range Z 12-178). RRT was more frequently delivered to patients who were: older (median 66 vs. 58 yrs; P < 0.01); male (78.6% vs. 64.4%; P < 0.01); had head and neck primary tumors (39.8% vs. 14.4%; P < 0.01); AJCC T4 primary tumors (40.8% vs. 30.7%; P < 0.01); more lymph nodes involved (median 3 vs. 1; P < 0.01); larger lymph nodes (median 2.5 vs. 2.0 cm; P Z 0.06); AJCC N3 nodal disease (64.3% vs. 23.3%; P < 0.01); and extracapsular extension (ECE) present (35.7% vs. 14.4%; P < 0.01). Post-operative RRT was associated with a reduced risk of regional recurrence among all patients on univariate (UV) (6-yr KM RC estimate: 91.2% vs. 73.3%, resp.; P < 0.01) and MV analysis (Hazard Ratio [HR] Z 0.24 [95% CI Z 0.11-0.51]; P < 0.01). Other variables associated with regional recurrence included: patient age (HR Z 1.02 [95% CI Z 1.01-1.03]; P < 0.01); AJCC tumor T3/T4 stage (HR Z 1.92 [95% CI Z 1.05-3.53]; P Z 0.03); AJCC nodal N1b/N2b/N3 stage (HR Z 1.74 [95% CI Z 1.05-2.87]; P Z 0.03); LN size >2 cm (HR Z 1.89 [95% CI Z 1.073.33]; P Z 0.03); and ECE present (HR Z 1.87 [95% CI Z 1.11-3.16]; P Z 0.02). Among higher-risk subgroups, RRT was associated with a reduced risk of regional recurrence among patients with ECE (n Z 157; 6-yr KM RC: 93.6% vs. 58.6%, resp.; P < 0.01) and an AJCC N1b/N2b/ N3 nodal stage (n Z 306; 6-yr KM RC: 89.3% vs. 61.0%, resp.; P < 0.01). Conclusion: RRT was associated with a reduced risk of regional recurrence among patients with ECE and more advanced nodal disease. In the era of increasingly effective systemic therapies, the value of improved regional control potentially takes on greater significance. Author Disclosure: A. Parekh: None. T. Strom: None. A.O. Naghavi: None. J.J. Caudell: None. J.S. Zager: Advisory Board; IGEA. Scientific Advisory Board; Delcath Systems, Inc. J.L. Messina: Independent Contractor; Glaxo Smith Kline, Direct Corporation. J.F. Torres-Roca: Patent/License Fees/Copyright; Cybergenix, Inc. V.K. Sondak: Advisory Board; Amgen, BMS, Merck, Navidea, Novartis, Provectus. A. Trotti: None. L.B. Harrison: None.
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Does Regional Radiation Therapy Impact Outcome for High-Risk, Node-Positive Cutaneous Melanoma? A. Parekh,1 T. Strom,2 A.O. Naghavi,2 J.J. Caudell,2 J.S. Zager,2 J.L. Messina,2 J.F. Torres-Roca,2 V.K. Sondak,2 A. Trotti,3 and L.B. Harrison2; 1University of Chicago, Chicago, IL, 2H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 3Moffitt Cancer Center and Research Institute, Tampa, FL
The Influence of Postoperative Lymph Node Radiation Therapy on Overall Survival of Patients With Stage III Melanoma: A National Cancer Data Base Analysis H. Danish,1 K. Patel,1 J. Switchenko,2 T.W. Gillespie,3 J. Jhaveri,1 M. Chowdhary,4 M. Abugideiri,5 K.A. Delman,3 D.H. Lawson,6 and M.K. Khan1; 1Department of Radiation Oncology, Winship Cancer Institute at Emory University, Atlanta, GA, 2Department of Biostatistics and Bioinformatics, Winship Cancer Institute, Emory University, Atlanta, GA, 3Department of Surgery, Winship Cancer Institute of Emory University, Atlanta, GA, 4Emory University School of Medicine, Atlanta, GA, 5Winship Cancer Institute at Emory University, Atlanta, GA, 6 Department of Hematology and Medical Oncology, Winship Cancer Institute at Emory University, Atlanta, GA
Purpose/Objective(s): Regional radiotherapy (RRT) has been shown to reduce the risk of regional recurrence with node positive cutaneous melanoma. However, risk factors for regional recurrence, especially in the era of sentinel node dissection (SLND), are less clear. Our goals were to clarify risk factors associated with regional recurrence and to
Volume 96 Number 2S Supplement 2016 Purpose/Objective(s): Hepcidin is a hormone that was identified and characterized in the year 2000 with a key role in regulating iron metabolism. The increased serum hepcidin level was associated with lymph node metastasis and tumor clinical stage of non-small cell lung cancer (NSCLC). Our preliminary data (not published yet) found that expression of Hepcidin was highly correlated and predictive of overall survival (OS). Hamp is known as coding gene of Hepcidin. BMP/Smad4 is an important regulating pathway for the expression of hepcidin. In this study, we investigated if SNPs in the BMP/Smad4/Hamp pathway are associated with outcome in patients receiving definitive RT for NSCLC. Materials/Methods: A total of 623 patients who received 60 Gy for NSCLC identified from a single-institution database were included. Potentially functional and tagging SNPs of genes BMP2 (rs170986, rs1979855, rs1980499, rs235768, and rs3178250), BMP4 (rs17563, rs4898820, and rs762642), Smad4 (rs12456284), and Hamp (rs1882694, rs10402233, rs10421768, rs12971321) were genotyped by TaqMan realtime polymerase chain reaction. Kaplan-Meier cumulative probability and Cox proportional hazards were used to evaluate the potential effect of these SNPs on OS, LRPFS (local regional progression-free survival), progression-free survival (PFS), and DM (distant metastasis). All clinical characteristics were evaluated and included in the multivariate model if P < 0.1. Results: The median age of patients in this study was 66 years (range, 3588 years), and most (488 [73.2%]) had stage III NSCLC. The median gross tumor volume (GTV) was 91.6cm3 (range, 1.5-1271.5 cm3), the median radiation dose was 69.5 Gy (range, 60-87.5 Gy), and the median mean lung dose (MLD) was 17.965 Gy (range, 0.153-32.741 Gy). Radiation modalities were proton beam therapy (n Z 135, 21.7%), intensity-modulated RT (n Z 300, 48.2%), and 3-dimensional conformal RT (n Z 170, 27.3%). In addition, 226 patients (36.3%) received induction chemotherapy and 551 patients (88.4%) received concurrent chemotherapy. OS, LRPFS, PFS, and DM were observed in this study. Hamp rs1882694 AC/CC genotypes were found to be significantly associated with poor OS in multivariate analysis (HR Z 1.301; 95% CI Z 1.040 to 1.627; P Z 0.021). This significant allele was also obviously associated with poor LRPFS (HR Z 1.648; 95% CI Z 1.188 to 2.286; P Z 0.003); poor PFS (HR Z 1.435; 95% CI Z 1.127 to 1.827; P Z 0.003) and increased risk of DM (HR Z 1.348; 95% CI Z 1.025 to 1.773; P Z 0.033) in multivariate analysis. BMP2 rs1979855 AG/GG genotypes were significantly associated with poor LRPFS (HR Z 1.433; 95% CI Z 1.042 to 1.970; P Z 0.027) and poor PFS (HR Z 1.433; 95% CI Z 1.128 to 1.820; P Z 0.003) in multivariate analysis. Conclusion: SNPs in BMP/Smad4/Hamp pathway were also significantly associated with outcome after definitive radiotherapy for NSCLC. A validation study involving patients from an ongoing prospective trial is underway. Author Disclosure: J. Yang: None. T. Xu: None. X. Yuan: None. D.R. Gomez: None. Y. Song: None. R.U. Komaki: None. Z. Liao: None.
clarify the role of RRT among a cohort of node positive melanoma patients. Materials/Methods: A single-institution IRB-approved study was performed including 699 patients with node positive cutaneous melanoma without distant metastatic disease treated from July 1998e2015. Exclusion criteria included patients with satellite or in-transit metastasis only (AJCC N2c stage), unknown recurrence, unclear treatment records, or <12 months follow-up. After exclusion, 570 patients remained for analysis. Patients were treated with excision and either SLND + completion lymph node dissection or therapeutic lymph node dissection. Post-operative RRT was delivered to the involved nodal basin in 98 (17.2%) cases to a median dose of 54 Gy (range Z 30-60 Gy) in 27 fractions (range Z 5-30). The primary outcome was regional control (RC) at any time point. Kaplan-Meier (KM) analysis, the log-rank test, and Cox Hazards multivariate (MV) models were used to compare outcomes. Results: Median follow-up was 70 months (range Z 12-178). RRT was more frequently delivered to patients who were: older (median 66 vs. 58 yrs; P < 0.01); male (78.6% vs. 64.4%; P < 0.01); had head and neck primary tumors (39.8% vs. 14.4%; P < 0.01); AJCC T4 primary tumors (40.8% vs. 30.7%; P < 0.01); more lymph nodes involved (median 3 vs. 1; P < 0.01); larger lymph nodes (median 2.5 vs. 2.0 cm; P Z 0.06); AJCC N3 nodal disease (64.3% vs. 23.3%; P < 0.01); and extracapsular extension (ECE) present (35.7% vs. 14.4%; P < 0.01). Post-operative RRT was associated with a reduced risk of regional recurrence among all patients on univariate (UV) (6-yr KM RC estimate: 91.2% vs. 73.3%, resp.; P < 0.01) and MV analysis (Hazard Ratio [HR] Z 0.24 [95% CI Z 0.11-0.51]; P < 0.01). Other variables associated with regional recurrence included: patient age (HR Z 1.02 [95% CI Z 1.01-1.03]; P < 0.01); AJCC tumor T3/T4 stage (HR Z 1.92 [95% CI Z 1.05-3.53]; P Z 0.03); AJCC nodal N1b/N2b/N3 stage (HR Z 1.74 [95% CI Z 1.05-2.87]; P Z 0.03); LN size >2 cm (HR Z 1.89 [95% CI Z 1.073.33]; P Z 0.03); and ECE present (HR Z 1.87 [95% CI Z 1.11-3.16]; P Z 0.02). Among higher-risk subgroups, RRT was associated with a reduced risk of regional recurrence among patients with ECE (n Z 157; 6-yr KM RC: 93.6% vs. 58.6%, resp.; P < 0.01) and an AJCC N1b/N2b/ N3 nodal stage (n Z 306; 6-yr KM RC: 89.3% vs. 61.0%, resp.; P < 0.01). Conclusion: RRT was associated with a reduced risk of regional recurrence among patients with ECE and more advanced nodal disease. In the era of increasingly effective systemic therapies, the value of improved regional control potentially takes on greater significance. Author Disclosure: A. Parekh: None. T. Strom: None. A.O. Naghavi: None. J.J. Caudell: None. J.S. Zager: Advisory Board; IGEA. Scientific Advisory Board; Delcath Systems, Inc. J.L. Messina: Independent Contractor; Glaxo Smith Kline, Direct Corporation. J.F. Torres-Roca: Patent/License Fees/Copyright; Cybergenix, Inc. V.K. Sondak: Advisory Board; Amgen, BMS, Merck, Navidea, Novartis, Provectus. A. Trotti: None. L.B. Harrison: None.
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Does Regional Radiation Therapy Impact Outcome for High-Risk, Node-Positive Cutaneous Melanoma? A. Parekh,1 T. Strom,2 A.O. Naghavi,2 J.J. Caudell,2 J.S. Zager,2 J.L. Messina,2 J.F. Torres-Roca,2 V.K. Sondak,2 A. Trotti,3 and L.B. Harrison2; 1University of Chicago, Chicago, IL, 2H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 3Moffitt Cancer Center and Research Institute, Tampa, FL
The Influence of Postoperative Lymph Node Radiation Therapy on Overall Survival of Patients With Stage III Melanoma: A National Cancer Data Base Analysis H. Danish,1 K. Patel,1 J. Switchenko,2 T.W. Gillespie,3 J. Jhaveri,1 M. Chowdhary,4 M. Abugideiri,5 K.A. Delman,3 D.H. Lawson,6 and M.K. Khan1; 1Department of Radiation Oncology, Winship Cancer Institute at Emory University, Atlanta, GA, 2Department of Biostatistics and Bioinformatics, Winship Cancer Institute, Emory University, Atlanta, GA, 3Department of Surgery, Winship Cancer Institute of Emory University, Atlanta, GA, 4Emory University School of Medicine, Atlanta, GA, 5Winship Cancer Institute at Emory University, Atlanta, GA, 6 Department of Hematology and Medical Oncology, Winship Cancer Institute at Emory University, Atlanta, GA
Purpose/Objective(s): Regional radiotherapy (RRT) has been shown to reduce the risk of regional recurrence with node positive cutaneous melanoma. However, risk factors for regional recurrence, especially in the era of sentinel node dissection (SLND), are less clear. Our goals were to clarify risk factors associated with regional recurrence and to