The influence of postoperative lymph node radiation therapy on overall survival of patients with stage III melanoma, a National Cancer Database analysis

Abstract Background In patients with stage III melanoma, the use of adjuvant radiation therapy (RT) after lymph node dissection (LND) may be currently considered in selected high-risk patients to improve local-regional control. Melanomas harbor BRAF mutations (BRAF+) in 40–50% of cases, the majority of which are on the V600E residue. This study sought to compare the clinical outcomes after RT between patients with BRAF + and BRAF- melanoma. Methods This was a retrospective review of 105 Stage III melanoma patients treated at our institution with LND followed by adjuvant RT from 2006–2019. BRAF mutational status was determined on the primary skin or nodal tissue samples from all patients. We compared characteristics of the BRAF + and BRAF- groups using Fisher’s exact test and Wilcoxon rank sum test and performed univariate and multivariate analysis using Kaplan-Meier estimates, log-rank tests, and Cox proportional hazards modeling with the clinical outcomes of local-regional control (LRC), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS). Results Fifty-three (50%) patients harbored a BRAF mutation (92%, pV600E). BRAF + patients were younger and had primary tumors more commonly found in the trunk vs head and neck compared to BRAF- patients (p < 0.05). The 5 year local-regional control in the BRAF + patients was 60% compared to 81% in the BRAF- patients (HR 4.5, 95% CI 1.3–15.5, p = 0.02). There were no significant differences in 5-year DMFS, DFS, and OS rates between the two BRAF patient groups. The presence of 4 or more positive LNs remained a significant prognostic factor for LRC, DFS, and OS in multivariate analysis. Conclusions Stage III melanoma patients with BRAF mutation treated with adjuvant RT had > 4 times increased risk of loco-regional recurrence. These results could be useful for adjuvant RT consideration in lymph node positive melanoma patients and supports other data that BRAF mutation confers radiation resistance.

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Mitotic rate in node-positive stage III melanoma: it might be as important a prognostic factor as node number

Japanese Journal of Clinical Oncology ◽

10.1093/jjco/hyab031 ◽

2021 ◽

Author(s):

Faruk Tas ◽

Kayhan Erturk

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Lymph Node ◽

Survival Rate ◽

Prognostic Indicator ◽

Mitotic Rate ◽

Stage Iii ◽

Node Number ◽

Node Positive ◽

Stage Iii Melanoma

Abstract Background Stage III melanoma is a heterogenous disease, and the number of tumor-involved lymph nodes is the most significantly unfavorable prognostic indicator for relapse and outcome. The aim of this study is to investigate the possible effects of the various clinicopathological factors on the course of node-positive stage III disease. Methods A total of 389 node-positive stage III cutaneous melanomas were included in the study and analyzed retrospectively. All underwent pathological nodal staging by sentinel lymph node biopsy or elective lymph node dissection. Results The group was male-dominant (59%) and the median age was 50 years. The largest group of patients was N1 (n = 221, 56.8%) followed by N2 (n = 105, 27.0%) and N3 (n = 63, 16.2%). N1 melanomas were less frequently associated with relapses than melanomas with multiple lymph node metastases (P = 0.05). The 5-year relapse-free survival rate was 37.9%. The melanomas with multiple lymph nodes metastases (P = 0.01), higher mitotic rate (P = 0.005) and ulceration (P = 0.02) had worse RFS. In the multivariate analysis only the significances of the N2–N3 stage (P = 0.016) and higher mitosis (P = 0.012) persisted. The severe lymph node metastasis (N2–N3) was associated with a higher mortality rate in comparison with the single nodal involvement (P = 0.05). The 5-year overall survival rate was 52.1%. Presence of relapse (P = 0.0001), higher mitotic rate (P = 0.03) and N2–N3 stage (P = 0.04) were inversely correlated with the overall survival. When relapse was included in the multivariate analysis, it was the only significant prognostic factor on survival (P = 0.0001), whereas mitosis became the only significant factor on survival with the exclusion of relapse from the multivariate analysis (P = 0.031). Conclusion In node-positive stage III melanoma, tumor mitotic rate might be just as significant a prognostic indicator as the metastatic lymph node number.

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Outcome and Prognostic Factors in Stage III Favorable-Histology Wilms Tumor: A Report From the Children’s Oncology Group Study AREN0532

Journal of Clinical Oncology ◽

10.1200/jco.2017.73.7999 ◽

2018 ◽

Vol 36 (3) ◽

pp. 254-261 ◽

Cited By ~ 24

Author(s):

Conrad V. Fernandez ◽

Elizabeth A. Mullen ◽

Yueh-Yun Chi ◽

Peter F. Ehrlich ◽

Elizabeth J. Perlman ◽

...

Keyword(s):

Overall Survival ◽

Radiation Therapy ◽

Lymph Node ◽

Residual Disease ◽

Wilms Tumor ◽

Stage Iii ◽

Lymph Node Status ◽

Oncology Group ◽

Favorable Histology ◽

Node Status

Background The National Wilms Tumor Study (NWTS) approach to treating stage III favorable-histology Wilms tumor (FHWT) is Regimen DD4A (vincristine, dactinomycin, and doxorubicin) and radiation therapy. Further risk stratification is required to improve outcomes and reduce late effects. We evaluated clinical and biologic variables for patients with stage III FHWT without combined loss of heterozygosity (LOH) at chromosomes 1p and 16q treated in the Children’s Oncology Group protocol AREN0532. Methods From October 2006 to August 2013, 588 prospectively treated, centrally reviewed patients with stage III FHWT were treated with Regimen DD4A and radiation therapy. Tumor LOH at 1p and 16q was determined by microsatellite analysis. Ineligible patients (n = 5) and those with combined LOH 1p/16q (n = 40) were excluded. Results A total of 535 patients with stage III disease were studied. Median follow-up was 5.2 years (range, 0.2 to 9.5). Four-year event-free survival (EFS) and overall survival estimates were 88% (95% CI, 85% to 91%) and 97% (95% CI, 95% to 99%), respectively. A total of 58 of 66 relapses occurred in the first 2 years, predominantly pulmonary (n = 36). Eighteen patients died, 14 secondary to disease. A better EFS was associated with negative lymph node status ( P < .01) and absence of LOH 1p or 16q ( P < .01), but not with gross residual disease or peritoneal implants. In contrast, the 4-year EFS was only 74% in patients with combined positive lymph node status and LOH 1p or 16q. A total of 123 patients (23%) had delayed nephrectomy. Submitted delayed nephrectomy histology showed anaplasia (n = 8; excluded from survival analysis); low risk/completely necrotic (n = 7; zero relapses), intermediate risk (n = 63; six relapses), and high-risk/blastemal type (n=7; five relapses). Conclusion Most patients with stage III FHWT had good EFS/overall survival with DD4A and radiation therapy. Combined lymph node and LOH status was highly predictive of EFS and should be considered as a potential prognostic marker for future trials.

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Extended lymph node dissection is associated with improved overall survival in patients with very high-risk prostate cancer: A national cancer database analysis

European Urology Supplements ◽

10.1016/s1569-9056(19)31589-1 ◽

2019 ◽

Vol 18 (1) ◽

pp. e2198

Author(s):

A. Sood ◽

J. Keeley ◽

S. Arora ◽

D. Dalela ◽

W. Jeong ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Lymph Node ◽

National Cancer Database ◽

Node Dissection ◽

Database Analysis ◽

Extended Lymph Node Dissection ◽

High Risk Prostate Cancer ◽

Risk Prostate Cancer ◽

Very High

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Phase II Multicenter Study of Neoadjuvant Biochemotherapy for Patients With Stage III Malignant Melanoma

Journal of Clinical Oncology ◽

10.1200/jco.2005.04.5344 ◽

2006 ◽

Vol 24 (19) ◽

pp. 3157-3163 ◽

Cited By ~ 42

Author(s):

Karl D. Lewis ◽

William A. Robinson ◽

Martin McCarter ◽

Nathan Pearlman ◽

Steven J. O'Day ◽

...

Keyword(s):

Overall Survival ◽

Lymph Node ◽

Sentinel Lymph Node ◽

Response Rate ◽

Statistical Significance ◽

Interleukin 2 ◽

Stage Iii ◽

Relapse Free Survival ◽

Free Survival ◽

Stage Iii Melanoma

Purpose To determine the relapse-free survival, overall survival, and response rate of patients with stage III melanoma treated with neoadjuvant biochemotherapy in a multicenter setting. Patients and Methods Patients with pathologically proven stage III melanoma, either via clinical detection or sentinel lymph node positivity, were eligible for enrollment. Patients received two cycles of preoperative biochemotherapy followed by complete regional lymphadenectomy and two postoperative courses of biochemotherapy. The biochemotherapy regimen consisted of the following: cisplatin 20 mg/m2 on days 1 to 4, dacarbazine 800 mg/m2 on day 1 only, vinblastine 1.6 mg/m2 on days 1 to 4, interleukin-2 total dose of 36 MU/m2 during 4 days, and interferon alfa 5 MU/m2 on days 1 to 5. Growth factor support was administered with each cycle. Results Ninety-two patients were eligible for the study. At a median follow-up of 40.4 months, relapse-free survival and overall survival are 64% and 78%, respectively. There was a lower relapse rate and improved survival for patients with a positive sentinel lymph node compared with patients with clinically detected lymph nodes, although this difference did not reach statistical significance. Of the 50 patients with measurable disease, the overall response rate was 26%. Toxicity of the biochemotherapy was high but generally manageable. Conclusion The current study has expanded the preliminary evidence on neoadjuvant biochemotherapy for stage III melanoma.

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BRAF mutation correlates with worse local–regional control following radiation therapy in patients with stage III melanoma

Radiation Oncology ◽

10.1186/s13014-021-01903-5 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Adam R. Wolfe ◽

Priyanka Chablani ◽

Michael R. Siedow ◽

Eric D. Miller ◽

Steve Walston ◽

...

Keyword(s):

Multivariate Analysis ◽

Radiation Therapy ◽

Lymph Node ◽

Regional Lymph Node ◽

Stage Iii ◽

Free Survival ◽

Regional Control ◽

Melanoma Patients ◽

Stage Iii Melanoma ◽

Local Regional Control

Abstract Background In patients with stage III melanoma, the use of adjuvant radiation therapy (RT) after lymph node dissection (LND) may be currently considered in selected high-risk patients to improve tumor control. Melanomas harbor BRAF mutations (BRAF+) in 40–50% of cases, the majority of which are on the V600E residue. This study sought to compare the clinical outcomes after RT between patients with BRAF+ and BRAF− melanoma. Methods This was a retrospective review of 105 Stage III melanoma patients treated at our institution with LND followed by adjuvant RT from 2006 to 2019. BRAF mutational status was determined on the primary skin or nodal tissue samples from all patients. We compared characteristics of the BRAF+ and BRAF− groups using Fisher’s exact test and Wilcoxon rank sum test and performed univariate and multivariate analysis using Kaplan–Meier estimates, log-rank tests, and Cox proportional hazards modeling with the clinical outcomes of local–regional lymph node control, distant metastasis-free survival (DMFS), recurrence-free survival (RFS), and overall survival (OS). Results Fifty-three (50%) patients harbored a BRAF mutation (92%, pV600E). BRAF+ patients were younger and had primary tumors more commonly found in the trunk vs head and neck compared to BRAF- patients (p < 0.05). The 5 year local–regional control in the BRAF + patients was 60% compared to 81% in the BRAF- patients (HR 4.5, 95% CI 1.3–15.5, p = 0.02). There were no significant differences in 5-year DMFS, RFS, and OS rates between the two BRAF patient groups. The presence of 4 or more positive LNs remained a significant prognostic factor for local–regional lymph node control, RFS, and OS in multivariate analysis. Conclusions Stage III melanoma patients with BRAF mutation treated with adjuvant RT had > 4 times increased risk of local recurrence or regional lymph node recurrence. These results could be useful for adjuvant RT consideration in lymph node positive melanoma patients and supports other data that BRAF mutation confers radiation resistance.

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