Delays Starting Postoperative Radiotherapy Among Head and Neck Cancer Patients: A Systematic Review and Meta-analysis.

OBJECTIVE: Initiating postoperative radiotherapy (PORT) within 6 weeks (42 days) of surgery is the first and only Commission on Cancer (CoC) approved quality metric for head and neck squamous cell carcinoma (HNSCC). No study has systematically reviewed nor synthesized the literature to establish national benchmarks for delays in starting PORT. DATA SOURCES: Following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we performed a systematic review of PubMed, Scopus, and CINAHL. REVIEW METHODS: Studies that described time-to-PORT or PORT delays in patients with HNSCC treated in the United States after 2003 were included. Meta-analysis of proportions and continuous measures was performed on nonoverlapping datasets to examine the pooled frequency of PORT delays and time-to-PORT. RESULTS: Thirty-six studies were included in the systematic review and 14 in the meta-analysis. Most studies utilized single-institution (n = 17; 47.2%) or cancer registry (n = 16; 44.4%) data. Twenty-five studies (69.4%) defined PORT delay as >6 weeks after surgery (the definition utilized by the CoC and National Comprehensive Cancer Network Guidelines), whereas 4 (11.1%) defined PORT delay as a time interval other than >6 weeks, and 7 (19.4%) characterized time-to-PORT without defining delay. Meta-analysis revealed that 48.6% (95% confidence interval [CI], 41.4-55.9) of patients started PORT > 6 weeks after surgery. Median and mean time-to-PORT were 45.8 (95% CI, 42.4-51.4 days) and 47.4 days (95% CI, 43.4-51.4 days), respectively. CONCLUSION: Delays in initiating guideline-adherent PORT occur in approximately half of patients with HNSCC. These meta-analytic data can be used to set national benchmarks and assess progress in reducing delays.

Effect of time to initiation of postoperative radiation therapy on survival in surgically managed head and neck cancer.

BACKGROUND: The objective of this study was to determine the effects of National Comprehensive Cancer Network (NCCN) guideline-adherent initiation of postoperative radiation therapy (PORT) and different time-to-PORT intervals on the overall survival (OS) of patients with head and neck squamous cell carcinoma (HNSCC). METHODS: The National Cancer Data Base was reviewed for the period of 2006-2014, and patients with HNSCC undergoing surgery and PORT were identified. Kaplan-Meier survival estimates, Cox regression analysis, and propensity score matching were used to determine the effects of initiating PORT within 6 weeks of surgery and different time-to-PORT intervals on survival. RESULTS: This study included 41,291 patients. After adjustments for covariates, starting PORT >6 weeks postoperatively was associated with decreased OS (adjusted hazard ratio [aHR], 1.13; 99% confidence interval [CI], 1.08-1.19). This finding remained in the propensity score-matched subset (hazard ratio, 1.21; 99% CI, 1.15-1.28). In comparison with starting PORT 5 to 6 weeks postoperatively, initiating PORT earlier was not associated with improved survival (aHR for ≤ 4 weeks, 0.93; 99% CI, 0.85-1.02; aHR for 4-5 weeks, 0.92; 99% CI, 0.84-1.01). Increasing durations of delay beyond 7 weeks were associated with small, progressive survival decrements (aHR, 1.09, 1.10, and 1.12 for 7-8, 8-10, and >10 weeks, respectively). CONCLUSIONS: Nonadherence to NCCN guidelines for initiating PORT within 6 weeks of surgery was associated with decreased survival. There was no survival benefit to initiating PORT earlier within the recommended 6-week timeframe. Increasing durations of delay beyond 7 weeks were associated with small, progressive survival decrements. Cancer 2017;123:4841-50. © 2017 American Cancer Society.

nab-Paclitaxel, cisplatin, and 5-fluorouracil followed by concurrent cisplatin and radiation for head and neck squamous cell carcinoma.

OBJECTIVES: We previously reported the efficacy of nab-paclitaxel added to cisplatin, 5-FU, and cetuximab (APF-C) followed by concurrent high dose bolus cisplatin and radiation therapy (CRT) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). In this phase II trial, we determined the efficacy of APF (without cetuximab) followed by CRT in similar patients. MATERIALS AND METHODS: Eligible patients had stage III-IV oropharynx (OP), larynx, or hypopharynx SCC and adequate organ function and performance status. T1 tumors were excluded. Patients were treated with three cycles of APF followed by CRT. Efficacy endpoints included two-year disease-specific survival (DSS), progression-free survival (PFS), overall survival (OS), and relapse rate. RESULTS: Thirty patients were enrolled. Most patients were smokers (77%) with bulky T3/4 (73%) and N2/3 (83%) tumors. Analyses were stratified for human papilloma virus (HPV) status: HPV-related OPSCC (n=17; 57%) and HPV-unrelated HNSCC (n=13; 43%). With a minimum follow-up of 21months, relapse occurred in 1 (3%) patient. Two-year DSS was 94% in HPV-related OPSCC and 100% in HPV-unrelated HNSCC. Two-year PFS was 94% in HPV-related OPSCC and 100% in HPV-unrelated HNSCC. Two-year OS was 94% in HPV-related OPSCC and 92% in HPV-unrelated HNSCC. Causes of death were relapse (1), treatment-related mortality (1), and co-morbidity (1). Two patients with HPV-unrelated HNSCC treated with APF declined CRT and remained free of relapse at 36 and 28months of follow-up. CONCLUSION: This phase II trial demonstrated favorable two-year DSS, PFS, and OS and a low relapse rate in HPV-unrelated HNSCC and HPV-related OPSCC treated with APF followed by CRT.

Evaluation of Quality Metrics for Surgically Treated Laryngeal Squamous Cell Carcinoma.

Importance: Quality metrics for patients with laryngeal squamous cell carcinoma (SCC) exist, but whether compliance with these metrics correlates with improved survival is unknown. Objective: To examine whether compliance with proposed quality metrics is associated with improved survival in patients with laryngeal SCC treated with surgery with or without adjuvant therapy. Design, Setting, and Participants: This retrospective cohort study included patients from a tertiary care academic medical center who had previously untreated laryngeal SCC and underwent surgery with or without adjuvant therapy from January 1, 2003, through December 31, 2012. Data analysis was performed from August 4, 2015, through December 13, 2015. Interventions: Surgery with or without adjuvant therapy. Main Outcomes and Measures: Compliance with quality metrics from the American Head and Neck Society (AHNS), National Comprehensive Cancer Network (NCCN) guidelines, and institutional metrics with face validity covering pretreatment evaluation, treatment, and posttreatment surveillance was evaluated. The association between compliance with the group of metrics and overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) was explored using Cox proportional hazards analysis. The association between compliance with individual metrics and survival was similarly determined. Results: A total of 243 patients (184 men and 59 women) were included in the study (median age, 62 years; age range, 23-87 years). No association was found between increasing levels of compliance with the AHNS or NCCN metrics and survival. The only AHNS or NCCN metric for which greater compliance correlated with improved survival on multivariable Cox proportional hazards analysis controlling for pT stage, pN stage, extracapsular spread, margin status, and comorbidity was pretreatment multidisciplinary evaluation for patients with stage cT3-4 or cN1-3 disease (OS adjusted hazard ratio [aHR], 0.47; 95% CI, 0.24-0.94; DFS aHR, 0.45; 95% CI, 0.23-0.85). For the institutional metrics, multidisciplinary evaluation for all patients (OS aHR, 0.51; 95% CI, 0.29-0.88; DFS aHR, 0.50, 95% CI, 0.32-0.80) and elective neck dissection yield of 18 lymph nodes or more (DFS aHR, 0.36; 95% CI, 0.14-0.99) were associated with improved survival on multivariable Cox proportional hazards analysis. Conclusions and Relevance: In this cohort of patients with surgically treated laryngeal SCC, multidisciplinary evaluation and elective neck dissection yield of 18 lymph nodes or more are associated with improved survival. Development of better quality metrics is necessary because increased compliance with metrics described by the AHNS and NCCN is not associated with improved survival. Previously described metrics for surgically treated oral cavity cancer are not prognostic for surgically treated laryngeal SCC. Future multi-institutional collaboration will be required to validate these findings, develop better quality metrics, and evaluate whether quality metrics for head and neck cancer are site specific.

Leech therapy for patients with surgically unsalvageable venous obstruction after revascularized free tissue transfer.

OBJECTIVE: To assess the efficacy and associated complications of a leech therapy protocol used for patients with a head and neck free tissue transfer in whom flap viability is threatened because of surgically unsalvageable venous obstruction. DESIGN: Medical record review of a prospective protocol. SETTING: Tertiary care academic medical center. PATIENTS: Of the 450 free tissue transfers to the head and neck region performed by our microvascular program from January 1, 1995, to October 31, 2000, 8 patients (1.8%) developed venous obstruction not considered salvageable by conventional surgical or thrombolytic therapy. INTERVENTIONS: All 8 patients were placed on a protocol using leeches (Hirudo medicinalis), intensive care unit monitoring, antithrombotic pharmacotherapy, frequent hematologic evaluation, blood transfusions as needed, and antibiotic prophylaxis for Aeromonas hydrophila. MAIN OUTCOME MEASURES: Flap salvage rate, number of leeches used per patient, time needed for inosculation, duration of intensive care unit admission, transfusion requirement per patient, and complications during leech therapy. RESULTS: All 8 flaps survived with the application of this protocol. An average of 215 leeches were used per patient, and the average time needed for inosculation was 6.6 days. The average duration in the intensive care unit was 9.6 days. The morbidity of our protocol was substantial, with intensive care unit psychosis, prerenal azotemia, and large transfusion requirements being the most frequent complications. An average of 13 U of packed red blood cells per patient was necessary. CONCLUSIONS: Aggressive application of the presented leech therapy protocol can salvage free tissue transfers with venous obstruction that are otherwise unsalvageable. The associated morbidity can be marked. Thus, judicious application of this protocol for flap preservation is essential.