Axel Sahovaler1,2, Rohin J Krishnan3, David H Yeh1, Qi Zhou4, David Palma5, Kevin Fung1, John Yoo1, Anthony Nichols1, S Danielle MacNeil1. 1. Department of Otolaryngology-Head and Neck Surgery, Western University, London, Ontario, Canada. 2. Head and Neck Surgery Unit, General Surgery Department, Italian Hospital of Buenos Aires, Buenos Aires, Argentina. 3. Epidemiology and Biostatistics Department, Western University, London, Ontario, Canada. 4. Research Methods and Clinical Impact Department, McMaster University, Hamilton, Ontario, Canada. 5. Department of Oncology, Western University, London, Ontario, Canada.
Abstract
IMPORTANCE: There is a need to summarize the available evidence and provide quantitative data of the most important prognostic factors for patients with metastatic cutaneous squamous cell carcinoma of the head and neck region with regional lymph node metastasis (McSCCHN). OBJECTIVE: To undertake a PRISMA-compliant systematic review and meta-analysis of all published studies on the risk factors for overall survival (OS), locoregional control (LRC), locoregional recurrence (LRR), and disease-specific survival (DSS) for patients with McSCCHN. DATA SOURCES: PubMed, CINAHL, and Embase were searched from 1946 to August 2018 for English-language articles. STUDY SELECTION: Inclusion criteria were randomized clinical trials or observational studies reporting on at least 10 patients with McSCCHN; studies analyzing 1 defined risk factor; reporting OS, LRC, LRR, or DSS; and clinical follow-up of 1 year of more. For the final analysis we included risk factors that were analyzed for the same outcome in at least 3 studies. Of the 2923 articles screened, 21 articles met the inclusion criteria. DATA EXTRACTION AND SYNTHESIS: PRISMA guidelines were used for abstracting the data. Two reviewers independently abstracted the data. Risk of bias was estimated with the Newcastle-Ottawa Scale. Meta-analysis was performed using the random-effects model. All analysis took place between January and October 2018. MAIN OUTCOMES AND MEASURES: The primary end point was OS. Secondary end points included LRC, LRR, and DSS. RESULTS: A total of 20 observational studies and 1 randomized clinical trial were identified, representing 3534 patients (some reviewed articles reported no demographic characteristics), and were included in the analysis. Significant risk factors associated with OS were immunosuppression (hazard ratio [HR] of death, 2.66; 95% CI, 2.26-3.13), extracapsular spread (HR, 1.90; 95% CI, 1.12-3.23), adjuvant radiotherapy (HR, 0.45; 95% CI, 0.27-0.78), lymph node ratio (HR, 1.91; 95% CI, 1.09-3.35), and advanced age (HR, 1.03; 95% CI, 1.00-1.07). Immunosuppression (HR, 3.82; 95% CI, 2.47-5.92) and adjuvant radiotherapy (HR, 0.52; 95% CI, 0.33-0.84) were also significant risk factors for DSS. CONCLUSIONS AND RELEVANCE: Immunosuppressed patients and those with extracapsular extension have poor prognosis. Adjuvant radiotherapy is associated with an improvement in OS. These risk factors will assist with better risk stratification and may also help to inform future clinical trials.
IMPORTANCE: There is a need to summarize the available evidence and provide quantitative data of the most important prognostic factors for patients with metastatic cutaneous squamous cell carcinoma of the head and neck region with regional lymph node metastasis (McSCCHN). OBJECTIVE: To undertake a PRISMA-compliant systematic review and meta-analysis of all published studies on the risk factors for overall survival (OS), locoregional control (LRC), locoregional recurrence (LRR), and disease-specific survival (DSS) for patients with McSCCHN. DATA SOURCES: PubMed, CINAHL, and Embase were searched from 1946 to August 2018 for English-language articles. STUDY SELECTION: Inclusion criteria were randomized clinical trials or observational studies reporting on at least 10 patients with McSCCHN; studies analyzing 1 defined risk factor; reporting OS, LRC, LRR, or DSS; and clinical follow-up of 1 year of more. For the final analysis we included risk factors that were analyzed for the same outcome in at least 3 studies. Of the 2923 articles screened, 21 articles met the inclusion criteria. DATA EXTRACTION AND SYNTHESIS: PRISMA guidelines were used for abstracting the data. Two reviewers independently abstracted the data. Risk of bias was estimated with the Newcastle-Ottawa Scale. Meta-analysis was performed using the random-effects model. All analysis took place between January and October 2018. MAIN OUTCOMES AND MEASURES: The primary end point was OS. Secondary end points included LRC, LRR, and DSS. RESULTS: A total of 20 observational studies and 1 randomized clinical trial were identified, representing 3534 patients (some reviewed articles reported no demographic characteristics), and were included in the analysis. Significant risk factors associated with OS were immunosuppression (hazard ratio [HR] of death, 2.66; 95% CI, 2.26-3.13), extracapsular spread (HR, 1.90; 95% CI, 1.12-3.23), adjuvant radiotherapy (HR, 0.45; 95% CI, 0.27-0.78), lymph node ratio (HR, 1.91; 95% CI, 1.09-3.35), and advanced age (HR, 1.03; 95% CI, 1.00-1.07). Immunosuppression (HR, 3.82; 95% CI, 2.47-5.92) and adjuvant radiotherapy (HR, 0.52; 95% CI, 0.33-0.84) were also significant risk factors for DSS. CONCLUSIONS AND RELEVANCE: Immunosuppressed patients and those with extracapsular extension have poor prognosis. Adjuvant radiotherapy is associated with an improvement in OS. These risk factors will assist with better risk stratification and may also help to inform future clinical trials.
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