279 Durvalumab after chemoradiotherapy for PD-L1 expressing inoperable stage III NSCLC impacts local-regional control and overall survival

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A304-A304
Author(s):  
Lukas Kaesmann ◽  
Julian Taugner ◽  
Chukwuka Eze ◽  
Claus Belka ◽  
Farkhad Manapov
Keyword(s):  
Overall Survival ◽  
Real World ◽  
Stage Iii ◽  
Historical Cohort ◽  
Free Survival ◽  
Regional Control ◽  
Stage Iii Nsclc ◽  
Local Regional Control ◽  
Nsclc Patients

BackgroundChemoradiotherapy (CRT) followed by maintenance treatment with the PD-L1 inhibitor durvalumab is a new standard of care for inoperable stage III NSCLC. The present study aims to evaluate the oncological outcome of patients treated with CRT alone to those treated with CRT and durvalumab (CRT-IO) in the real-world setting.MethodsRetro- and prospectively collected data of 133 consecutive inoperable stage III NSCLC patients treated between 2011–2019 were evaluated. Local-regional-recurrence-free-survival (LRPFS - defined as progression in the mediastinum, hilum and/or supraclavicular region at both sides and the involved lung), progression-free survival (PFS) and overall survival (OS) were evaluated from last day of thoracic radiotherapy (TRT).ResultsMedian age at diagnosis was 68.5 years; 44 (33%) were female; 58 (44%) were diagnosed with adenocarcinoma. All patients were irradiated to a total dose of at least 60 Gy (EQD2). Median PTV was 709.8 cc (range: 181–1958 cc). 113 (85%) patients were treated with CRT and 20 (15%) PD-L1 expressing patients with CRT-IO. 83% of patients received two cycles of concomitant platinum-based chemotherapy. Median time to initiation of durvalumab after CRT was 0.8 months (range: 0.4–2.1). Median follow-up for entire cohort was 33.3 months (range: 4.8–111.8) and median overall survival (OS) was 24.7 (95% CI: 18.9–30.4) months. In the CRT-IO cohort after a median follow-up of 15.5 (range: 5.1–20.2) months, no deaths were reported at the time of evaluation (August 2020). Improved LRPFS (p=0.013), PFS (p=0.033) and OS (p=0.002) were correlated with CRT-IO compared to the historical cohort of conventional CRT patients.After propensity-score matching (PSM) analysis with age, gender, histology, tumor volume and treatment mode and exact matching for T-and N-stage, 18 CRT-IO patients were matched 1:2 to 36 CRT patients. 12-month LRPFS, PFS and OS rates in the CRT-IO vs CRT cohort were 80% vs 38.8% (p=0.001), 50% vs 22% (p=0.013) and 100% vs 75% (p=0.002), respectively. Also regarding intracranial failure, 6-month brain metastases rates were 0% vs. 6% in the CRT-IO vs CRT cohort (p=0.290).ConclusionsThis real-world analysis demonstrates that durvalumab after CRT has led to significant improvement of local-regional control, PFS and OS in PD-L1 expressing inoperable stage III NSCLC patients compared to a historical cohort.AcknowledgementsThe study was partly presented at 2020 Annual Meeting of the American Society of Clinical Oncology (ASCO).Trial RegistrationN/AEthics ApprovalThe study was approved by Ludwig-Maximilians-University (LMU), Munich, Germany: Institution’s Ethics Board, approval number 17-230.ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

scholarly journals Durvalumab after Chemoradiotherapy for PD-L1 Expressing Inoperable Stage III NSCLC Leads to Significant Improvement of Local-Regional Control and Overall Survival in the Real-World Setting

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1613
Author(s):  
Julian Taugner ◽  
Lukas Käsmann ◽  
Chukwuka Eze ◽  
Amanda Tufman ◽  
Niels Reinmuth ◽  
...  
Keyword(s):  
Overall Survival ◽  
Real World ◽  
Progression Free Survival ◽  
Stage Iii ◽  
Historical Cohort ◽  
Free Survival ◽  
Stage Iii Nsclc ◽  
Local Regional Control ◽  
Nsclc Patients

Concurrent chemoradiotherapy (CRT) followed by maintenance treatment with the PD-L1 inhibitor durvalumab is a new standard of care for inoperable stage III NSCLC. The present study compares the oncological outcome of patients treated with CRT to those treated with CRT and durvalumab (CRT-IO) in the real-world setting. The analysis was performed based on the retro- and prospectively collected data of 144 consecutive inoperable stage III NSCLC patients treated between 2011–2020. Local-regional-progression-free-survival (LRPFS—defined as progression in the mediastinum, hilum and/or supraclavicular region at both sites and the involved lung), progression-free survival (PFS), and overall survival (OS) were evaluated from the last day of thoracic radiotherapy (TRT). Median follow-up for the entire cohort was 33.1 months (range: 6.3–111.8) and median overall survival was 27.2 (95% CI: 19.5–34.9) months. In the CRT-IO cohort after a median follow-up of 20.9 (range: 6.3–27.4) months, median PFS was not reached, LRPFS (p = 0.002), PFS (p = 0.018), and OS (p = 0.005) were significantly improved vs. the historical cohort of conventional CRT patients. After propensity-score matching (PSM) analysis with age, gender, histology, tumor volume, and treatment mode, and exact matching for T-and N-stage, 22 CRT-IO patients were matched 1:2 to 44 CRT patients. Twelve-month LRPFS, PFS, and OS rates in the CRT-IO vs. CRT cohort were 78.9 vs. 45.5% (p = 0.002), 60.0 vs. 31.8% (p = 0.007), and 100 vs. 70.5% (p = 0.003), respectively. This real-world analysis demonstrated that durvalumab after CRT led to significant improvement of local-regional control, PFS, and OS in PD-L1 expressing inoperable stage III NSCLC patients compared to a historical cohort.

Association of planning target volume with disease progression in inoperable stage III non-small cell lung cancer patients treated with chemoradiotherapy and concurrent and/or sequential immune checkpoint inhibition.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20557-e20557
Author(s):  
Julian Taugner ◽  
Monika Karin ◽  
Lukas Käsmann ◽  
Chukwuka Eze ◽  
Julian Guggenberger ◽  
...  
Keyword(s):  
Planning Target Volume ◽  
Progression Free Survival ◽  
Target Volume ◽  
Continuous Variable ◽  
Stage Iii ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Free Survival ◽  
Stage Iii Nsclc ◽  
Nsclc Patients

e20557 Background: The present study evaluates outcome after chemoradiotherapy (CRT) with concurrent and/or sequential Programmed Cell Death 1 (PD-1) or Ligand 1 (PD-L1) immune checkpoint inhibition (CPI) for inoperable stage III NSCLC patients depending on planning target volume (PTV). Methods: Prospective data of thirty-nine consecutive patients with inoperable stage III NSCLC who completed CRT with sequential durvalumab (72%, 28 patients) or concurrent and sequential nivolumab (28%, 11 patients) were analyzed. Different cut offs for PTV as well as PTV as a continuous variable were evaluated for association with progression-free survival (PFS) and extracranial metastasis-free survival (eMFS). Results: All patients were treated with conventionally fractionated TRT to a total dose of at least 60 Gy (range: 60-63.6Gy), 97% (27 patients) received two cycles of concurrent platinum-based chemotherapy. Median follow-up for the entire cohort was 23.2 (range: 6.0-42.6) months; median overall survival (OS) and eMFS were not reached. Median Progression-free survival (PFS) was 22.8 (95% CI: 10.3-35.2) months. Age (65 years), gender and UICC stage had no significant impact on PFS. There was no significant difference between durvalumab and nivolumab patients. Patients with PTV ≥ 900ccm had a significantly shorter PFS (11.77 vs 26.3 months, p = 0.049) and eMFS (11.7 months vs not reached, p = 0.019). Furthermore, patients with PTV ≥ 900ccm and stage IIIC disease (TNM 8th Ed.) achieved a dismal median PFS of only 3.6 months (vs. 26.3 months p < 0.001). PTV as a continuous variable showed a trend for association with PFS (p = 0.064) and was a significant negative prognosticator for eMFS (p = 0.030; HR: 4.065; 95%CI: 1.148-14.397). Conclusions: PTV has a significant impact on the PFS and eMFS after CRT combined with concurrent and/or sequential CPI in inoperable stage III NSCLC. Patients with PTV ≥ 900ccm had a significantly shorter PFS and eMFS.

Differential role of residual metabolic tumor volume in patients with inoperable stage III NSCLC after chemoradiotherapy ± immune checkpoint inhibition.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20558-e20558
Author(s):  
Marcus Unterrainer ◽  
Julian Taugner ◽  
Lukas Käsmann ◽  
Chukwuka Eze ◽  
Wolfgang G. Kunz ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Fdg Pet ◽  
Tumor Volume ◽  
Metabolic Tumor Volume ◽  
Stage Iii ◽  
Free Survival ◽  
Pet Ct ◽  
Stage Iii Nsclc ◽  
Fdg Pet Ct ◽  
Nsclc Patients

e20558 Background: PET-derived metabolic-tumor-volume (MTV) has shown to be an independent prognosticator in non-small cell lung cancer (NSCLC) patients treated with chemoradiotherapy (CRT). We analysed the prognostic value of residual MTV after completion of thoracic irradiation (TRT) in inoperable stage III NSCLC patients treated with CRT with and without immune check-point inhibition (ICI). Methods: Fifty-six inoperable stage III NSCLC patients (16 female, median age: 65 years) underwent 18F-FDG PET/CT at the same institution before and after completion of CRT. MTV was delineated on 18F-FDG PET/CT using a standard threshold (hepatic SUVmean + 2 x standard-deviation). Patients were divided in volumetric subgroups using median split dichotomization (residual MTV ≤4.0 ml & > 4.0 ml). Residual MTV, clinical features and ICI maintenance (RCT-IO; 21/56 (37.5%) patients) were correlated with clinical outcome (progression-free survival (PFS), local PFS (LPFS), metastasis-free survival (MFS), and overall survival (OS). Results: Median follow-up was 52.0 months. 52 (93%) patients were treated with CRT, 12 (21%) patients with CRT followed by durvalumab, and 9 (16%) patients treated with CRT plus nivolumab (concurrent and sequential). In the entire cohort, smaller residual MTV was associated with longer PFS (median 29.3 vs. 10.5 months, p = 0.015); PFS in patients treated with CRT and ICI was also significantly longer compared to the CRT-only subgroup (median 29.3 vs. 11.2 months, p = 0.010). However, residual MTV was predictive for longer PFS in CRT-only (median 33.5 vs. 8.6 months, p = 0.001), but not in the CRT-ICI patients (p = 0.909). Analogously, patients with smaller MTV had a longer LPFS (median 49.9 vs. 16.3 months, p = 0.002); CRT-ICI patients showed a significantly longer LPFS compared to CRT-only patients (median not reached vs. 16.9 months, p = 0.016). Residual MTV remained a significant prognosticator for LPFS in the CRT-only (median 49.9 vs. 10.1 months, p = 0.01), but not in CRT-ICI patients (p = 0.291). Again, smaller residual MTV remained a significant prognosticator for OS in the CRT-only subgroup (median 63.0 vs. 16.3 months, p = 0.004), but not in CRT-ICI patients (p = 0.720). Even in patients with larger residual MTV, the application of ICI significantly improved OS compared to CRT-only subgroup (median not reached vs. 22.9 months, p = 0.004). Conclusions: Smaller residual MTV is associated with superior clinical outcome in inoperable stage III NSCLC, especially in patients undergoing CRT-only. In contrast, in patients undergoing concurrent or sequential consolidation clinical outcome was independent of residual MTV. Hence, even patients with extensive residual MTV might significantly profit from ICI consolidation.

High-dose 3D chemoradiotherapy trials in stage III non-small cell lung cancer (NSCLC) at the University of North Carolina: Long-term follow up and late complications

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7145-7145 ◽  
Author(s):  
C. B. Lee ◽  
M. A. Socinski ◽  
L. Lin ◽  
D. T. Moore ◽  
D. E. Morris ◽  
...  
Keyword(s):  
Overall Survival ◽  
Late Complications ◽  
Concurrent Chemotherapy ◽  
Stage Iii ◽  
Second Primary ◽  
High Dose ◽  
Combined Modality Treatment ◽  
Combined Modality ◽  
Stage Iii Nsclc

7145 Background: Combined modality treatment is the standard of care for patients (pts.) with unresectable stage III NSCLC. Dose escalation of radiotherapy and the use of concurrent chemotherapy are two strategies attempting to improve survival and locoregional control. The intensification of therapy increases the risk of both early and late treatment related toxicities. Methods: From 5/1996 to 8/2004, 112 stage III NSCLC pts. were entered into 4 Phase I/II trials to assess the safety and feasibility of high-dose (74–90 Gy) thoracic conformal radiotherapy (TCRT) in QD or BID fractions. All pts. were treated with platinum-based induction chemotherapy; 3 of the trials also used concurrent chemotherapy. Results: The median follow up of survivors (29/112) on these trials was 4.9 years. The overall response rate after combined modality therapy was 47% (53/112) (CR 4%, 5/112; PR 43%, 48/112). 27% (30/112) had stable disease. The median survival (with 95% CI) was 24 months (18–31 months). 1-, 3-, and 5-year overall survival was 69% (60–77%), 36% (27–45%), and 24% (16–33%) respectively. Late complications of therapy (defined as >90 days post radiotherapy reported to date) are displayed in the table. Two pts. developed a second primary (1 lung, 1 liver carcinoid). In total, 22% (25/112) had late complications. These patients appear to have a significantly better overall survival (p = .007). 12% (13/112) had a brain-only recurrence, although this did not seem to significantly impact overall survival (p = .82). Conclusions: 1) High-dose TCRT is feasible and results in promising survival outcomes. 2) Late complications occur in a minority of patients suggesting the potential benefit of more aggressive TCRT is not outweighed by its risk. 3) Interestingly, brain-only recurrences did not significantly impact survival in these trials. [Table: see text] [Table: see text]

An open-labeled, multicentric clinical study of cetuximab combined with intensity-modulated radiotherapy (IMRT) plus concurrent chemotherapy in locoregionally advanced (LA) nasopharyngeal carcinoma (NPC): A 2-year follow-up report.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5535-5535 ◽  
Author(s):  
Chun-yan Chen ◽  
Chong Zhao ◽  
Li Gao ◽  
Jin-yi Lang ◽  
Jian-ji Pan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Disease Free Survival ◽  
Concurrent Chemotherapy ◽  
Stage Iii ◽  
Chinese Patients ◽  
Recurrence Free Survival ◽  
Spontaneous Bleeding ◽  
Cervical Lymph Nodes ◽  
Free Survival

5535 Background: To evaluate the safety and efficacy outcomes of concurrent cetuximab plus IMRT and cisplatin in Chinese patients with LA NPC. Methods: Patients with primary stage III-IVb (UICC/AJCC 2002 staging system) and non-keratinizing NPC were enrolled in this prospective, multicentric, phase II study. Cisplatin (80mg/m2,q3week) and cetuximab (400mg/m2 one w before radiation, and then 250mg/m2/w) were given concurrently. The prescription dose of IMRT to GTVnx (primary tumor in nasopharynx) was 66 Gy - 75.9 Gy, GTVnd (positive cervical lymph nodes) was 60 Gy - 70Gy, The response rate was evaluated according to RECIST 1.0 criteria, and adverse events (AEs) were graded according to NCI CTCAE V3.0 criteria. Results: From July 2008 to April 2009, 100 patients were enrolled (74 male), with median age of 43 years. The proportion of stage III, IVa and IVb patients were 71%, 22% and 7% respectively. 99% of enrolled patients completed the planned treatment. AEs were within the expected range and manageable. No toxic death occurred during the treatment. Acneiform skin eruptions, mucositis, in-field dermatitis, xerostomia and neucopenia were the most common seen AEs, with 64% grade 2/3 acneiform eruptions, 26% grade 2/3 in-field dermatitis, 90% ≥ grade 2 mucositis (2 cases of grade 4 mucositis with spontaneous bleeding), 40% ≥ grade 2 xerostomia and 8% grade 2/3 neucopenia. With a median follow-up time of 23.5 months, the 2 year overall survival (OS), disease-free survival (DFS), local recurrence-free survival, regional (cervical lymph node) recurrence free survival and distant metastasis-free survival rates for the ITT population were 91%, 89%, 90%, 90% and 89%, respectively Multivariate analysis showed that N stage was the only prognostic factor for OS (p=0.0392, HR=2.946) and DFS (p=0.0062, HR=4.246) in these patients. Conclusions: Cetuximab combined with IMRT plus concurrent cisplatin in patients with LA NPC shows satisfactory 2-year locoregional control rate and 2-year overall survival. The combination seems to be well tolerated with a manageable side-effect profile.

Concurrent and sequential chemoradiation therapy are associated with improved survival among unresected stage III non-small cell lung cancer patients in the United States.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 7043-7043
Author(s):  
Zhiyuan Zheng ◽  
Ramesh Rengan ◽  
Jingxuan Zhao ◽  
Helmneh M. Sineshaw ◽  
Stephen G. Chun ◽  
...  
Keyword(s):  
Median Survival ◽  
Stage Iii ◽  
Treatment Modalities ◽  
Small Cell Lung ◽  
Comorbidity Score ◽  
Stage Iii Nsclc ◽  
Similar Survival ◽  
Nsclc Patients ◽  
Single Modality

7043 Background: Concurrent chemoradiation therapy (cCRT) has been shown to improve survival outcomes among inoperable stage III non-small cell lung cancer (NSCLC) patients compared to sequential CRT (sCRT) and single-modality therapy in clinical trials. However, many “real world” patients do not receive CRT, and less is known about the survival benefits of concurrent CRT vs other treatment modalities in pragmatic, non-clinical trial settings. Methods: We used the National Cancer Database (2004-2011) to identify unresected stage III NSCLC patients (ages 18-79 years) with Charlson comorbidity score ≤1 and 5-year follow up through the end of 2016. cCRT was defined as the initiations of chemotherapy (CT) and radiation therapy (RT) that were ≤14 days (n = 30,290) apart, whereas sCRT was defined as > 14 days apart (total n = 10,596). The remaining three treatment groups included CT only (n = 11,216), RT only (n = 7,772), and neither CT/RT during first course treatment (n = 10,694). Cox proportional hazard model was used to examine the 5-year survival by treatment modalities, controlling for patient demographics, comorbidity score, health insurance, facility type, area-level social deprivation index (SDI, a composite measure for area-level socio-economic status), driving time to the treatment facility, diagnosis year, and region. Adjusted hazard ratios (HR), and medium survivals were generated by treatment modalities. Results: Among 70,568 unresected stage III NSCLC patients, 61,487 (87.1%) patients died within the 5-year follow-up period. In adjusted analyses, cCRT and sCRT had similar survival (median survivals: 15.3 months), whereas other treatment modalities were associated with worse survival compared to cCRT: CT only (median survival: 10.8 months; HR [95%CI]: 1.46 [1.43-1.50]), RT only (median survival: 6.7 months; HR [95%CI]: 1.93[1.88-1.99]), and no treatment (median survival: 3.2 months; HR [95%CI]: 2.64 [2.58-2.71]), all p < 0.001. Higher comorbidity score (Charlson score 1 vs 0, HR [95%CI]: 1.18 [1.16-1.21]), non-private insurance (Medicaid: 1.16 [1.12-1.20]; Medicare: 1.10 [1.08-1.13]; uninsured: 1.21 [1.16-1.26]) were all associated with worse survival (all p < 0.001). Conclusions: Concurrent CRT and sequential CRT have similar survival outcomes among unresected stage III NSCLC patients with minimum comorbidities, however, single modality and no therapy are associated with much poorer survival among “real world” patients, and should be avoided unless clinically appropriate.

220 Real-world outcomes of patients with resected stage IIIA melanoma treated with adjuvant nivolumab

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A239-A239
Author(s):  
Wolfram Samlowski ◽  
Robert Nicholas ◽  
Tayla Poretta ◽  
Andriy Moshyk ◽  
Jonathan Rajkumar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Real World ◽  
Treatment Patterns ◽  
Stage Iii ◽  
List Type ◽  
Stage Iiia ◽  
American Joint Committee ◽  
The Us ◽  
Resected Stage

BackgroundNivolumab is approved in the US and EU for the adjuvant treatment of resected stage III-IV melanoma based on results from the CheckMate-238 clinical trial.1,2 However, the trial did not enroll any patients with Stage IIIA disease per the American Joint Committee on Cancer (AJCC) 7th edition criteria and included a limited number of patients with stage IIIA disease per the AJCC 8th edition.3,4,5Recognizing the need for real-world data to assess outcomes of patients with resected stage IIIA melanoma treated with adjuvant nivolumab, a non-interventional study was conducted to investigate treatment patterns and outcomes among patients receiving adjuvant nivolumab within the US community practice setting.MethodsA retrospective analysis of the US Oncology Network’s iKnowMed medical data was conducted to examine patients with resected stage IIIA melanoma treated with adjuvant nivolumab between 01-Jan-2018 and 31-Dec-2019 with a follow-up period through 31-Mar-2020. Patients were followed for up to 27 months after their sentinel lymph node biopsy. Baseline demographic/clinical characteristics and treatment patterns were examined descriptively. Duration of treatment (DOT) and overall survival were analyzed using the Kaplan-Meier method.ResultsA total of 58 patients with stage IIIA melanoma treated with adjuvant nivolumab were identified. Median age was 57.8 years (range 21.5–93.5), 62.1% were male, and 75.9% were Caucasian. Among patients with a documented Eastern Cooperative Oncology Group (ECOG) performance status (51.7%), all had an ECOG score of 0 or 1. Median follow-up time was 12.6 months (range 0.3–25.1). Median DOT was 10.6 months (range 6.8–12.0). Overall survival rates at 12 and 24 months were 97.7% (95% CI 84.6–99.7) and 92.2% (95% CI 69.6–98.2), respectively.ConclusionsThis real-world analysis of patients with stage IIIA melanoma treated with adjuvant nivolumab showed that a large proportion of patients were alive at the end of the study period, suggesting these patients have a favorable prognosis. Further investigation and follow-up is warranted to assess clinically relevant outcomes among patients with resected stage IIIA melanoma.Ethics ApprovalThe study was approved by US Oncology Inc’s Institutional Review Board, approval number 20-020E-2020-0224-01.ReferencesWeber J, Mandala M, Del Vecchio M, et al. Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma. NEJM 2017;377:1824–35.Weber J, Mandala M, Del Vecchio M, et al. Adjuvant therapy with nivolumab (NIVO) versus ipilimumab (IPI) after complete resection of stage III/IV melanoma: A randomized, double-blind, phase 3 trial (CheckMate 238). Ann Oncol 2017;28(5):632–33.Balch CM, Gershenwald JE, Soong SJ, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 2009;27(36):6199–6206.Gershenwald JE, Scolyer RA, Hess KR, et al. Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin 2017;67(6):472–492.National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Cutaneous Melanoma Version 3.2020 - May 18, 2020. 2020.

scholarly journals BRAF Mutation Correlates with Worse Local-regional Control Following Radiation Therapy in Patients with Stage III Melanoma

2021 ◽  
Author(s):  
Adam R Wolfe ◽  
Priyanka Chablani ◽  
Michael Siedow ◽  
Eric D Miller ◽  
Steve Walston ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Radiation Therapy ◽  
Lymph Node ◽  
Braf Mutation ◽  
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 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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