Dataset Information

Differential Outcomes Among Immunosuppressed Patients With Merkel Cell Carcinoma: Impact of Immunosuppression Type on Cancer-specific and Overall Survival.

ABSTRACT:

Objectives

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer with higher incidence among whites, elderly, and immunosuppressed patients. Although immunosuppressed MCC patients are at higher risk of recurrence and MCC-related death, it is unknown whether immunosuppression type is associated with differential outcomes.

Materials and methods

We retrospectively evaluated 89 nonmetastatic MCC patients with a diagnosis of chronic immunosuppression. Immunosuppression was categorized as chronic lymphocytic leukemia (31% of cohort), other hematologic malignancies (18%), solid organ transplant (21%), autoimmune disease (21%), and human immunodeficiency virus acquired deficiency syndrome (8%). Progression-free survival (PFS) and MCC-specific survival (MSS) were estimated with the cumulative incidence function. Overall survival (OS) was estimated by the Kaplan-Meier method.

Results

With a median follow-up of 52 months, 53 deaths occurred (42 from MCC, 7 unknown, and 4 non-MCC). Two-year PFS, MSS, and OS were 30%, 55%, and 52%, respectively. Human immunodeficiency virus/acquired deficiency syndrome and solid organ transplant patients were diagnosed with MCC at a younger age (median 55 and 59 y, respectively) and with more advanced stage disease compared with other immunosuppressed subgroups. PFS did not significantly differ among the 5 immunosuppression subgroups (P=0.30), but significant differences were observed in MSS and OS (both P=0.01). Controlling for potential confounders for OS, including age and stage, immunosuppression type was still significantly associated with risk of death (P=0.01).

Conclusions

Among immunosuppressed MCC patients, recurrent MCC is the major cause of mortality. The risk of death from MCC differs among immunosuppression types, suggesting important biological differences in host-tumor immune interactions.

SUBMITTER: Cook M

PROVIDER: S-EPMC8666386 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Publications

Differential Outcomes Among Immunosuppressed Patients With Merkel Cell Carcinoma: Impact of Immunosuppression Type on Cancer-specific and Overall Survival.

Cook Maclean M Baker Kelsey K Redman Mary M Lachance Kristina K Nguyen Macklin H MH Parvathaneni Upendra U Bhatia Shailender S Nghiem Paul P Tseng Yolanda D YD

American journal of clinical oncology 20190101 1

<h4>Objectives</h4>Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer with higher incidence among whites, elderly, and immunosuppressed patients. Although immunosuppressed MCC patients are at higher risk of recurrence and MCC-related death, it is unknown whether immunosuppression type is associated with differential outcomes.<h4>Materials and methods</h4>We retrospectively evaluated 89 nonmetastatic MCC patients with a diagnosis of chronic immunosuppression. Immunosuppr ...[more]

PMID: 30211723

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Project description:BackgroundMerkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine carcinoma of the skin. As the clinical course can be variable, prognostic markers are needed to better stratify patients. Prior literature, composed of small series with limited sample size, has demonstrated that tumor-infiltrating lymphocytes (TILs) are an important prognostic marker in MCC. To validate these findings on a population level, we sought to analyze and report the prognostic value of TILs in a large national data set.Materials and methodsA retrospective observational cohort study was conducted of patients with nonmetastatic MCC from 2010 to 2015 using the National Cancer Database. Individual variables trending toward significance using a univariable analysis were included in a multivariable Cox proportional hazards model to assess their independent effect on overall survival (OS). TILs were subclassified into none, nonbrisk, and brisk and the survival analysis was performed. Propensity score-weighted multivariable analysis (PS MVA) was performed to adjust for additional confounding.ResultsA total of 2,182 patients met inclusion criteria: 611 (28.0%) were identified as having TILs present, and 1,571 (72.0%) had TILs absent in the tumor. On MVA, subdivision of TIL status into nonbrisk (hazard ratio [HR], 0.750; 95% confidence interval [CI], 0.602-0.933) and brisk (HR, 0.499; 95% CI, 0.338-0.735) was associated with incrementally improved OS compared with no TILs. The association of nonbrisk and brisk TILs with improved OS was retained on PS MVA (Nonbrisk: HR, 0.720; 95% CI, 0.550-0.944; Brisk: HR, 0.483; 95% CI, 0.286-0.814).ConclusionThe presence of nonbrisk and brisk TILs is associated with incrementally improved OS in patients with nonmetastatic MCC in a large national data set. This pathologic feature can aid with risk stratification, estimation of prognosis, and, importantly, decision-making with respect to treatment intensification in high-risk patients.Implications for practiceMerkel cell carcinoma (MCC) is an aggressive neuroendocrine cutaneous malignancy with variable clinical course. Prognostic markers are needed to better risk stratify patients. We present the largest retrospective observational cohort study of patients with nonmetastatic MCC using the National Cancer Database. Our analysis demonstrates an association between increasing degrees of tumor-infiltrating lymphocytes and incrementally improved survival. These conclusions improve pathologic risk stratification, and decision-making with respect to treatment intensification. Intensification may include adjuvant radiation therapy to the primary site after wide excision despite small tumor size, to the nodal basin in sentinel lymph node-negative patients, or offering closer follow-up.

Project description:BackgroundMerkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine carcinoma of the skin, with a high recurrence rate and a high mortality rate worldwide. The purpose of this article is to construct a nomogram that incorporates significant clinical parameters and predicts the survival of individuals with MCC.MethodsThe Surveillance, Epidemiology, and End Results (SEER) database was employed to retrospectively analyze all confirmed MCC cases from 2004 to 2015. The data was collected from 3,688 patients, and was randomized as the training or validation group (1:1 ratio). The independent factors which predicted the cancer-specific survival (CSS) and overall survival (OS) for MCC cases were searched for nomogram construction respectively. Independent parameters that affected CSS were determined using the Fine and Gray competing risk regression model. In addition, the time-dependent receiver operating characteristic (ROC) curve was constructed. Then, the area under the curve (AUC) values, calibration curve, and the concordance index (C-index) were used to determine the nomogram performance. At last, decision curve analysis (DCA) was conducted to determine the net clinical benefit.ResultsThe multivariate analysis results revealed that sex, age, race, marriage, American Joint Committee on Cancer (AJCC) stage, chemotherapy and radiotherapy were independent OS prognostic factors. Furthermore, competing risk analysis showed age, sex, AJCC stage, chemotherapy were the independent CSS prognostic factors. For validation, the C-index value of OS nomogram was 0.703 (95% CI: 0.686-0.721), while C-index value of CSS nomogram was 0.737 (95% CI: 0.710-0.764). Both C-index and AUC suggested that nomograms had superior performance to that of the AJCC stage system. In addition, according to the calibration curve, both nomograms were capable of accurate prediction of MCC prognosis. The DCA showed that the net benefits of the nomograms were superior among various threshold probabilities than these of AJCC stage system.ConclusionsThe present work established and verified the novel nomograms to predict the OS and CSS of MCC patients. If further confirmed in future studies, it may become another helpful tool for risk stratification and management of MCC patients.

Project description:ImportanceMerkel cell carcinoma (MCC) is a rare cutaneous malignant neoplasm with increasing incidence and high mortality. Although it is accepted that the optimal treatment for localized tumors is surgical, the data surrounding the optimal surgical approach are mixed, and current National Comprehensive Cancer Network guidelines state that Mohs micrographic surgery (MMS) and wide local excision (WLE) can both be used. The current National Comprehensive Cancer Network guidelines do not advocate a preference for MMS or WLE and suggest that they can be used interchangeably.ObjectiveTo evaluate the association of surgical approach with overall survival after excision of localized T1/T2 MCC.Design, setting, and participantsThis retrospective cohort study used the National Cancer Database to assess adults with T1/T2 MCC who were diagnosed between January 1, 2004, and December 31, 2018, with pathologically confirmed, negative regional lymph nodes and treated with surgery. The National Cancer Database includes all reportable cases from Commission on Cancer-accredited facilities. Data analysis was performed from October 2022 to May 2023.ExposureSurgical approach.Main outcomes and measuresOverall survival.ResultsA total of 2313 patients (mean [SD] age, 71 [10.6] years; 1340 [57.9%] male) were included in the study. Excision with MMS had the best unadjusted survival, with mean (SE) survival rates of 87.4% (3.4%) at 3 years, 84.5% (3.9%) at 5 years, and 81.8% (4.6%) at 10 years vs 86.1% (0.9%) at 3 years, 76.9% (1.2%) at 5 years, and 60.9% (2.0%) at 10 years for patients treated with WLE. Patients treated with narrow-margin excision had similar survival as those treated with WLE, with mean (SE) survival rates of 84.8% (1.4%) at 3 years, 78.3% (1.7%) at 5 years, and 60.8% (3.6%) at 10 years. On multivariable survival analysis, excision with MMS was associated with significantly improved survival compared with WLE (hazard ratio, 0.59; 95% CI, 0.36-0.97; P = .04). High-volume MCC centers were significantly more likely to use MMS over WLE compared with other centers (odds ratio, 1.99; 95% CI, 1.63-2.44; P < .001).Conclusions and relevanceIn this cohort study, the use of MMS (compared with WLE) was associated with significantly improved survival for patients with localized MCC with pathologically confirmed negative lymph nodes treated with surgery. These data suggest that Mohs surgery may provide a more effective treatment for MCC primary tumors than conventional WLE, although the lack of randomization and potential for selection bias in this study highlight the need for future prospective work evaluating this issue.

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:ImportanceCurrent recommendations regarding the size of local excision (LE) margins for Merkel cell carcinoma (MCC) have not been well established.ObjectiveTo assess whether larger clinical LE margins and receipt of adjuvant radiotherapy are associated with improvements in overall survival (OS) among patients with localized MCC.Design, setting, and participantsThis large multicenter retrospective cohort study used records from the National Cancer Database to identify adult patients with localized stage I or stage II MCC who underwent LE between January 1, 2004, and December 31, 2015. Data were analyzed from August 1, 2020, to January 25, 2021.ExposuresLocal excision margin size and adjuvant radiotherapy.Main outcomes and measuresOverall and net survival were assessed using Cox multivariable regression analysis.ResultsA total of 6156 patients with localized MCC (median age at diagnosis, 77 years [range, 27-90 years]; 2500 women [40.6%]). In the multivariable regression analysis, LE clinical margins larger than 1.0 cm were associated with improvements in OS (HR, 0.88; 95% CI, 0.81-0.95; P < .001) compared with margins of 1.0 cm or smaller, regardless of tumor subsite. At 5 years after surgery, LE margins of 1.0 cm or smaller were associated with a net survival of 76.7%, while LE margins larger than 1.0 cm were associated with a net survival of 89.8% (P < .001). Stratification of LE margins into 3 subgroups indicated that LE margins of 1.1 to 2.0 cm (HR, 0.87; 95% CI, 0.76-0.99; P = .047) and larger than 2.0 cm (HR, 0.84; 95% CI, 0.72-0.98; P = .03) were associated with improvements in OS compared with margins of 1.0 cm or smaller. In patients with less aggressive disease (ie, those who were immunocompetent and had tumors ≤1.0 cm, no lymphovascular invasion, and negative pathologic margins), LE margins larger than 1.0 cm were also associated with improvements in OS (HR, 0.87; 95% CI, 0.78-0.97; P = .01). Among patients who received adjuvant radiotherapy, larger LE margins were associated with improvements in OS (HR, 0.87; 95% CI, 0.76-0.98; P = .03). Receipt of adjuvant radiotherapy was also associated with improvements in OS within the 3 LE margin subgroups. Patients who received adjuvant radiotherapy and had LE margins of 1.0 cm or smaller (HR, 0.81; 95% CI, 0.74-0.89; P < .001) experienced OS that was comparable to that in patients who did not receive adjuvant radiotherapy and had LE margins larger than 1.0 cm (HR, 0.80; 95% CI, 0.71-0.89; P = .87).Conclusions and relevanceIn this study, LE clinical margins larger than 1.0 cm were associated with improvements in OS, and these improvements were independent of tumor subsite, receipt of adjuvant radiotherapy, positive pathologic margins, or adverse pathologic features for stage I to stage II MCC. Patients with LE margins of 1.0 cm or smaller who received adjuvant radiotherapy experienced OS that was similar to that of patients with larger LE margins who did not receive radiotherapy. The combination of LE clinical margins larger than 1.0 cm and adjuvant radiotherapy was associated with the highest OS.

Dataset Information

Differential Outcomes Among Immunosuppressed Patients With Merkel Cell Carcinoma: Impact of Immunosuppression Type on Cancer-specific and Overall Survival.

Objectives

Materials and methods

Results

Conclusions

Publications

Differential Outcomes Among Immunosuppressed Patients With Merkel Cell Carcinoma: Impact of Immunosuppression Type on Cancer-specific and Overall Survival.

Similar Datasets

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