Yves Paul Vincent Mbous, Rowida Mohamed, Usha Sambamoorthi, Murtuza Bharmal, Khalid M Kamal, Traci LeMasters, Joanna Kolodney, George A Kelley
{"title":"早期默克尔细胞癌治疗的有效性和安全性：随机和非随机研究的系统回顾和荟萃分析。","authors":"Yves Paul Vincent Mbous, Rowida Mohamed, Usha Sambamoorthi, Murtuza Bharmal, Khalid M Kamal, Traci LeMasters, Joanna Kolodney, George A Kelley","doi":"10.1002/cam4.70553","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>The lack of consensus on the benefits and harms of standard therapies, including surgery (SRx), radiotherapy (RTx), chemotherapy (CTx), and their combinations among early-stage MCC, prompted this study.</p><p><strong>Methods: </strong>A systematic review and meta-analysis of randomized and non-randomized studies published between January 01, 1972, and January 31, 2023, and having overall survival (OS), local recurrence (LR), regional recurrence (RR), disease-specific survival (DSS), and/or disease-free survival (DFS) as outcomes was conducted using the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed (NCBI), Scopus (ELSEVIER), and Web of Science (CLAVIRATE) databases. Hazard ratios (HRs) and their variances were pooled using the inverse variance heterogeneity model.</p><p><strong>Results: </strong>Forty-nine studies representing 46,215 participants were included in the meta-analysis. A statistically significant improvement in OS was observed for groups administered adjuvant RTx (SRx + RTx) compared to SRx only (HR = 0.78, 95% CI, 0.62-0.99), albeit with statistically significant heterogeneity (Q = 532.30, p < 0.001) and a large amount of inconsistency (I<sup>2</sup> = 94%, 95% CI, 93.0-95.5). Both LR (HR = 1.52, 95% CI, 0.37-6.19) and RR (HR = 0.41, 95% CI, 0.09-1.78) were not statistically significant. In addition, DSS (HR = 0.58, 95% CI, 0.24-1.40) was not statistically significant but DFS was (HR = 0.35, 95% CI, 0.13-0.93). Subgroup analyses revealed that adjuvant radiotherapy was more effective in local than regional MCC. The E-value suggested that the RTx dose was a confounder of the observed effectiveness of adjuvant RTx; and also, the use of CTx following adjuvant RTx, did not impact the strength of evidence for OS.</p><p><strong>Conclusions: </strong>Although adjuvant RTx improves survival and recurrence outcomes among early-stage MCC, the safety and effectiveness of standard therapies in MCC remains poorly studied and, thus, affects the synthesis of evidence across important patient and clinical characteristics. Future research on the comparative effectiveness of different therapies is needed.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 1","pages":"e70553"},"PeriodicalIF":2.9000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696246/pdf/","citationCount":"0","resultStr":"{\"title\":\"Effectiveness and Safety of Treatments for Early-Stage Merkel Cell Carcinoma: A Systematic Review and Meta-Analysis of Randomized and Non-Randomized Studies.\",\"authors\":\"Yves Paul Vincent Mbous, Rowida Mohamed, Usha Sambamoorthi, Murtuza Bharmal, Khalid M Kamal, Traci LeMasters, Joanna Kolodney, George A Kelley\",\"doi\":\"10.1002/cam4.70553\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>The lack of consensus on the benefits and harms of standard therapies, including surgery (SRx), radiotherapy (RTx), chemotherapy (CTx), and their combinations among early-stage MCC, prompted this study.</p><p><strong>Methods: </strong>A systematic review and meta-analysis of randomized and non-randomized studies published between January 01, 1972, and January 31, 2023, and having overall survival (OS), local recurrence (LR), regional recurrence (RR), disease-specific survival (DSS), and/or disease-free survival (DFS) as outcomes was conducted using the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed (NCBI), Scopus (ELSEVIER), and Web of Science (CLAVIRATE) databases. Hazard ratios (HRs) and their variances were pooled using the inverse variance heterogeneity model.</p><p><strong>Results: </strong>Forty-nine studies representing 46,215 participants were included in the meta-analysis. A statistically significant improvement in OS was observed for groups administered adjuvant RTx (SRx + RTx) compared to SRx only (HR = 0.78, 95% CI, 0.62-0.99), albeit with statistically significant heterogeneity (Q = 532.30, p < 0.001) and a large amount of inconsistency (I<sup>2</sup> = 94%, 95% CI, 93.0-95.5). Both LR (HR = 1.52, 95% CI, 0.37-6.19) and RR (HR = 0.41, 95% CI, 0.09-1.78) were not statistically significant. In addition, DSS (HR = 0.58, 95% CI, 0.24-1.40) was not statistically significant but DFS was (HR = 0.35, 95% CI, 0.13-0.93). Subgroup analyses revealed that adjuvant radiotherapy was more effective in local than regional MCC. The E-value suggested that the RTx dose was a confounder of the observed effectiveness of adjuvant RTx; and also, the use of CTx following adjuvant RTx, did not impact the strength of evidence for OS.</p><p><strong>Conclusions: </strong>Although adjuvant RTx improves survival and recurrence outcomes among early-stage MCC, the safety and effectiveness of standard therapies in MCC remains poorly studied and, thus, affects the synthesis of evidence across important patient and clinical characteristics. 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Effectiveness and Safety of Treatments for Early-Stage Merkel Cell Carcinoma: A Systematic Review and Meta-Analysis of Randomized and Non-Randomized Studies.
Objective: The lack of consensus on the benefits and harms of standard therapies, including surgery (SRx), radiotherapy (RTx), chemotherapy (CTx), and their combinations among early-stage MCC, prompted this study.
Methods: A systematic review and meta-analysis of randomized and non-randomized studies published between January 01, 1972, and January 31, 2023, and having overall survival (OS), local recurrence (LR), regional recurrence (RR), disease-specific survival (DSS), and/or disease-free survival (DFS) as outcomes was conducted using the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed (NCBI), Scopus (ELSEVIER), and Web of Science (CLAVIRATE) databases. Hazard ratios (HRs) and their variances were pooled using the inverse variance heterogeneity model.
Results: Forty-nine studies representing 46,215 participants were included in the meta-analysis. A statistically significant improvement in OS was observed for groups administered adjuvant RTx (SRx + RTx) compared to SRx only (HR = 0.78, 95% CI, 0.62-0.99), albeit with statistically significant heterogeneity (Q = 532.30, p < 0.001) and a large amount of inconsistency (I2 = 94%, 95% CI, 93.0-95.5). Both LR (HR = 1.52, 95% CI, 0.37-6.19) and RR (HR = 0.41, 95% CI, 0.09-1.78) were not statistically significant. In addition, DSS (HR = 0.58, 95% CI, 0.24-1.40) was not statistically significant but DFS was (HR = 0.35, 95% CI, 0.13-0.93). Subgroup analyses revealed that adjuvant radiotherapy was more effective in local than regional MCC. The E-value suggested that the RTx dose was a confounder of the observed effectiveness of adjuvant RTx; and also, the use of CTx following adjuvant RTx, did not impact the strength of evidence for OS.
Conclusions: Although adjuvant RTx improves survival and recurrence outcomes among early-stage MCC, the safety and effectiveness of standard therapies in MCC remains poorly studied and, thus, affects the synthesis of evidence across important patient and clinical characteristics. Future research on the comparative effectiveness of different therapies is needed.
期刊介绍：
Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas:
Clinical Cancer Research
Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations
Cancer Biology:
Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery.
Cancer Prevention:
Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach.
Bioinformatics:
Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers.
Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.
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