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Adjuvant Radiation Therapy and Chemotherapy in Merkel Cell Carcinoma: Survival Analyses of 6908 Cases From the National Cancer Data Base.

ABSTRACT: BACKGROUND:Merkel cell carcinoma (MCC) has a high risk of recurrence after initial surgical therapy. Adjuvant radiation therapy (RT) and chemotherapy may be used to reduce the risk of locoregional and systemic recurrence, respectively, but there are conflicting data regarding their impact on survival. We performed a retrospective analysis of MCC cases from the National Cancer Data Base (NCDB) to assess whether adjuvant therapy was associated with differences in survival. METHODS:Six thousand nine hundred and eight MCC patients with staging, treatment, and survival data were included. Multivariable analyses were conducted for overall survival (OS) with various treatment modalities while adjusting for prognostic variables including age, sex, comorbidities (Charlson/Deyo score), margin status, primary tumor site and size, and lymph node status. All statistical tests were two-sided. RESULTS:For localized MCC (stage I: n = 3369, stage II: n = 1474 ), surgery plus adjuvant RT was associated with statistically significantly better OS than with surgery alone in multivariable analyses (stage I: hazard ratio [HR] = 0.71, 95% confidence interval [CI] = 0.64 to 0.80, P < .001; stage II: HR?=?0.77, 95% CI?=?0.66 to 0.89, P < .001). In patients with regional nodal metastases (stage III: n = 2065 ), neither adjuvant RT nor chemotherapy was associated with statistically significantly improved or worsened OS. CONCLUSIONS:In this study of the largest MCC cohort reported to date, adjuvant RT was associated with improved OS in stages I-II MCC. Neither adjuvant RT nor chemotherapy was associated with improved OS in stage III MCC. These results, with the limitations of retrospective analyses, are consistent with earlier studies suggesting benefit with adjuvant RT but do not support the routine use of adjuvant chemotherapy in MCC.

SUBMITTER: Bhatia S

PROVIDER: S-EPMC6059142 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Adjuvant Radiation Therapy and Chemotherapy in Merkel Cell Carcinoma: Survival Analyses of 6908 Cases From the National Cancer Data Base.

Bhatia Shailender S Storer Barry E BE Iyer Jayasri G JG Moshiri Ata A Parvathaneni Upendra U Byrd David D Sober Arthur J AJ Sondak Vernon K VK Gershenwald Jeffrey E JE Nghiem Paul P

Journal of the National Cancer Institute 20160531 9

<h4>Background</h4>Merkel cell carcinoma (MCC) has a high risk of recurrence after initial surgical therapy. Adjuvant radiation therapy (RT) and chemotherapy may be used to reduce the risk of locoregional and systemic recurrence, respectively, but there are conflicting data regarding their impact on survival. We performed a retrospective analysis of MCC cases from the National Cancer Data Base (NCDB) to assess whether adjuvant therapy was associated with differences in survival.<h4>Methods</h4>S ...[more]

PMID: 27245173

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Project description:Purpose/objective(s) Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous neoplasm traditionally managed with surgical resection followed by radiotherapy (RT). With the recent approval of checkpoint inhibitors, chemotherapy is less commonly utilized. We analyzed the impact of RT and chemotherapy on overall survival (OS) in patients with MCC using Surveillance, Epidemiology, and End Results (SEER), a population-level database. Materials and methods We performed retrospective analyses on SEER 18 Custom Data registries for MCC (ICD-0-3 8247). Data from 1980 to 2016 was queried for analysis, and an initial list of 9,792 patients was populated (ICD: C00, C07.9, C44, C80.9). Selection for cases with chemotherapy and RT status, single primary tumor, primary tumor location and surgery treatment type yielded 5,002 cases for analysis. Baseline characteristics were compared with Chi-square or Mann-Whitney U test. Univariate and multivariable analysis using Kaplan-Meier and Cox proportional hazards regression modeling were performed. Propensity-score matched analysis with inverse probability of treatment weighting (IPTW) was used to account for indication bias. Results Median follow-up time was 178 months (68 to 217 months). Independent prognostic factors positively correlated with increased OS, for both unadjusted Multivariate analysis and IPTW adjusted MVA were age, male sex, year of diagnosis, stage, RT status, and chemotherapy status. On adjusted MVA, use of chemotherapy was associated with worse OS (hazard ratio: 1.22 [95% CI 1.1-1.35], p<0.001), whereas RT was associated with improved OS (HR:0.9 [95% CI, 0.83-0.97], p=0.008). Conclusions The current study demonstrates that RT is associated with improved survival for patients with MCC. Chemotherapy was associated with worse OS. This supports the recent clinical shift towards immune checkpoints inhibitors as standard of care in the metastatic setting, and promising trials in the adjuvant and advanced settings.

Project description:BackgroundClinically localized Merkel cell carcinoma (MCC) is commonly treated with surgical excision and radiotherapy. The relationship between time to adjuvant radiotherapy and overall survival (OS) remains understudied.MethodsThis retrospective study used data from the National Cancer Database (2006-2019). Patients with clinically localized MCC who received surgical excision and adjuvant radiotherapy were included. Multivariate regressions were used to account for various patient and tumor factors. The primary outcome was 5-year OS, and the secondary outcome was time from diagnosis to adjuvant radiation (TTR).ResultsOf the 1965 patients included, most were male (n = 1242, 63.2%) and white (n = 1915, 97.5%), and the median age was 74 years (interquartile range [IQR]: 66-81). The median TTR was 83 days (IQR: 65-106). A total of 83.6% of patients received radiotherapy to the primary site, 21.3% to the draining nodal basin, 17.1% to both, and 12.2% whose target location of radiotherapy was not recorded in the data. TTR of ≥79 days (the 45th percentile) was associated with worse OS on both univariate and multivariate analyses (log-rank p = 0.0014; hazard ratio [HR]: 1.258, 95% confidence interval [CI]: 1.055-1.500, p = 0.010). This persisted on sub-analyses of patients <80 years old (n = 1407; HR: 1.380, 95% CI: 1.080-1.764, p = 0.010) and of patients with Charlson comorbidity index (CCI) of 0 (n = 1411; HR: 1.284, 95% CI: 1.034-1.595, p = 0.024). Factors associated with delayed TTR included greater age (p = 0.039), male sex (p = 0.04), CCI > 1 (p = 0.036), academic facility (p < 0.001), rural county (p = 0.034), AJCC T2 stage (p = 0.010), negative margins (p = 0.017), 2+ pathologically positive regional nodes (p = 0.011), and margin size >2 cm (p = 0.015).ConclusionsDelayed radiotherapy (≥79 days) was associated with worse OS of MCC patients. Further study in controlled cohorts is needed to ascertain this relationship.

Project description:ObjectiveThere are no randomized data to support the use of postoperative radiation for salivary gland malignancies. This study uses the National Cancer Database (NCDB) to describe the epidemiology of salivary gland cancer patients and to investigate whether treatment with adjuvant radiation improves overall survival.Methods and materialsA total of 8243 patients diagnosed with a major salivary gland cancer were identified from the NCDB. All patients received primary surgical resection of their malignancy. Patients were risk-stratified by adverse features, and overall survival rates were determined. Patients were considered high risk if they had extracapsular extension and/or positive margin after resection. Patients were considered intermediate risk if they did not meet the criteria for high risk but had pT3-T4 disease, pN+ disease, lymphovascular space invasion, adenoid cystic histology, or grade 2-3 disease. Patients who did not meet criteria for high or intermediate risk were considered low risk. Overall patient demographics, disease characteristics, treatment factors, and outcomes were summarized with descriptive statistics and analyzed with STATA.ResultsMedian follow-up in this cohort was 42.4 months, with the median age of 58 years. Patients in the high-risk group had greater survival (hazard ratio [HR], 0.76; P = .002; 95% confidence interval [CI], 0.64-0.91) if they received adjuvant radiation therapy. In contrast, patients in the intermediate- (HR, 1.01; P = .904; 95% CI, 0.85-1.20) and low-risk groups (HR, 0.85; P = .427; 95% CI, 0.57-1.26) did not experience a survival benefit with adjuvant radiation therapy.ConclusionsThis large analysis compared survival outcomes between observation and adjuvant radiation alone in risk-stratified patients after resection of major salivary glands using a national database. The use of adjuvant radiation for high-risk major salivary gland cancers appears to offer a survival benefit. Although an overall survival benefit was not seen in low- and intermediate-risk salivary gland cancers, this study could not address impact on local control because of the limitations of the NCDB.

Dataset Information

Adjuvant Radiation Therapy and Chemotherapy in Merkel Cell Carcinoma: Survival Analyses of 6908 Cases From the National Cancer Data Base.

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Adjuvant Radiation Therapy and Chemotherapy in Merkel Cell Carcinoma: Survival Analyses of 6908 Cases From the National Cancer Data Base.

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