title: Regional Radiation Therapy Impacts Outcome for Node-Positive Cutaneous Melanoma.
abstract: Background:Regional radiation therapy (RT) 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 lymph node biopsy (SLNB), are less clear. Our goals were to identify risk factors associated with regional recurrence and to determine whether a radiosensitivity index (RSI) gene expression signature (GES) could identify patients who experience a survival benefit with regional RT.Methods:A single-institution, Institutional Review Board-approved study was performed including 410 patients treated with either SLNB with or without completion lymph node dissection (LND; n=270) or therapeutic LND (n=91). Postoperative regional RT was delivered to the involved nodal basin in 83 cases (20.2%), to a median dose of 54 Gy (range, 30-60 Gy) in 27 fractions (range, 5-30). Primary outcomes were regional control and overall survival by RSI GES status.Results:Median follow-up was 69 months (range, 13-180). Postoperative regional RT was associated with a reduced risk of regional recurrence among all patients on univariate (5-year estimate: 95.0% vs 83.3%;P=.036) and multivariate analysis (hazard ratio[HR], 0.15; 95% CI, 0.05-0.43;P<.001). Among higher-risk subgroups, regional RT was associated with a lower risk of regional recurrence among patients with clinically detected lymph nodes (n=175; 5-year regional control: 94.1% vs 69.5%;P=.003) and extracapsular extension (ECE) present (n=138; 5-year regional control: 96.7% vs 62.2%;P<.001). Among a subset of radiated patients with gene expression data available, a low RSI GES (radiosensitive) tumor status was associated with improved survival compared with a high RSI GES (5-year: 75% vs 0%; HR, 10.68; 95% CI, 1.24-92.14).Conclusions:Regional RT was associated with a reduced risk of regional recurrence among patients with ECE and clinically detected nodal disease. Gene expression data show promise for better predicting radiocurable patients in the future. In the era of increasingly effective systemic therapies, the value of improved regional control potentially takes on greater significance.
authors.affiliation: Department of Radiation Oncology, Moffitt Cancer Center and Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas
authors.forename: Tobin
authors.initials: T
authors.lastname: Strom
authors.affiliation: Department of Radiation Oncology, Moffitt Cancer Center and Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas|Department of Oncologic Sciences, University of South Florida Morsani College of Medicine
authors.forename: Javier F
authors.initials: JF
authors.lastname: Torres-Roca
authors.affiliation: Department of Radiation Oncology, Moffitt Cancer Center and Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas
authors.forename: Akash
authors.initials: A
authors.lastname: Parekh
authors.affiliation: Department of Radiation Oncology, Moffitt Cancer Center and Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas
authors.forename: Arash O
authors.initials: AO
authors.lastname: Naghavi
authors.affiliation: Department of Radiation Oncology, Moffitt Cancer Center and Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas|Department of Oncologic Sciences, University of South Florida Morsani College of Medicine
authors.forename: Jimmy J
authors.initials: JJ
authors.lastname: Caudell
authors.affiliation: Department of Radiation Oncology, Moffitt Cancer Center and Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Oliver
authors.affiliation: Department of Oncologic Sciences, University of South Florida Morsani College of Medicine|Department of Cutaneous Oncology, Moffitt Cancer Center|Department of Pathology & Cell Biology and Dermatology, University of South Florida Morsani College of Medicine
authors.forename: Jane L
authors.initials: JL
authors.lastname: Messina
authors.affiliation: Department of Oncologic Sciences, University of South Florida Morsani College of Medicine|Department of Cutaneous Oncology, Moffitt Cancer Center
authors.forename: Nikhil I
authors.initials: NI
authors.lastname: Khushalani
authors.affiliation: Department of Oncologic Sciences, University of South Florida Morsani College of Medicine|Department of Cutaneous Oncology, Moffitt Cancer Center
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Zager
authors.affiliation: Department of Oncologic Sciences, University of South Florida Morsani College of Medicine|Department of Cutaneous Oncology, Moffitt Cancer Center
authors.forename: Amod
authors.initials: A
authors.lastname: Sarnaik
authors.affiliation: Center for Translational Research, Moffitt Cancer Center
authors.forename: James J
authors.initials: JJ
authors.lastname: Mulé
authors.affiliation: Department of Radiation Oncology, Moffitt Cancer Center and Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas|Department of Oncologic Sciences, University of South Florida Morsani College of Medicine
authors.forename: Andy M
authors.initials: AM
authors.lastname: Trotti
authors.affiliation: Department of Biomedical Informatics, Moffitt Cancer Center, Tampa, Florida
authors.forename: Steven A
authors.initials: SA
authors.lastname: Eschrich
authors.affiliation: Department of Oncologic Sciences, University of South Florida Morsani College of Medicine|Department of Cutaneous Oncology, Moffitt Cancer Center|Department of Pathology & Cell Biology and Dermatology, University of South Florida Morsani College of Medicine
authors.forename: Vernon K
authors.initials: VK
authors.lastname: Sondak
authors.affiliation: Department of Radiation Oncology, Moffitt Cancer Center and Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas|Department of Oncologic Sciences, University of South Florida Morsani College of Medicine
authors.forename: Louis B
authors.initials: LB
authors.lastname: Harrison
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D015331:Cohort Studies; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000532:radiotherapy*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D018714:Radiotherapy, Adjuvant / Q000379:methods; D019233:Retreatment; D012878:Skin Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000532:radiotherapy*; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult; D000096142:Cutaneous Malignant Melanoma
chemical_list: D014408:Biomarkers, Tumor