In 1958, Edward L. Kaplan and Paul Meier collaborated to publish a seminal paper on how to deal with incomplete observations. Subsequently, the Kaplan-Meier curves and estimates of survival data have become a familiar way of dealing with differing survival times (times-to-event), especially when not all the subjects continue in the study. “Survival” times need not relate to actual survival with death being the event; the “event” may be any event of interest. Kaplan-Meier analyses are also used in non-medical disciplines. The purpose of this paper is to explain how Kaplan-Meier curves are generated and analyzed. Throughout this article we will discuss Kaplan-Meier (K-M) estimates in the context of “survival” before the event of interest. Two small groups of hypothetical data are used as examples in order for the reader to clearly see how the process works. These examples also illustrate the crucially important point that comparative analysis depends upon the whole curve and not upon isolated points.

The consensus panel agreed on statements that address the continuum of care, from initial tube management to complications in children and adults with a tracheostomy. The panel also highlighted areas where consensus could not be reached and where more research is needed. This consensus statement should be used by physicians, nurses, and other stakeholders caring for patients with a tracheostomy.

IMPORTANCE Delays in the delivery of care for head and neck cancer (HNC) are a key driver of poor oncologic outcomes and thus represent an important therapeutic target. OBJECTIVE To synthesize information about the association between delays in the delivery of care for HNC and oncologic outcomes. EVIDENCE REVIEW A systematic review of the English-language literature in PubMed/MEDLINE and Scopus published between January 1, 2007, and February 28, 2018, was performed to identify articles addressing the association between treatment delays and oncologic outcomes for patients with HNC. Articles that were included (1) addressed cancer of the oral cavity, oropharynx, hypopharynx, or larynx; (2) discussed patients treated in 2004 or later; (3) analyzed time of diagnosis to treatment initiation (DTI), time from surgery to the initiation of postoperative radiotherapy, and/or treatment package time (TPT; the time from surgery through the completion of postoperative radiotherapy); (4) included a clear definition of treatment delay; and (5) analyzed the association between the treatment time interval and an oncologic outcome measure. Quality assessment was performed using the Institute of Health Economics Quality Appraisal Checklist for Case Series Studies. FINDINGS A total of 18 studies met inclusion criteria and formed the basis of the systematic review. Nine studies used the National Cancer Database and 6 studies were single-institution retrospective reviews. Of the 13 studies assessing DTI, 9 found an association between longer DTI and poorer overall survival; proposed DTI delay thresholds ranged from more than 20 days to 120 days or more. Four of the 5 studies assessing time from surgery to the initiation of postoperative radiotherapy (and all 4 studies assessing guideline-adherent time to postoperative radiotherapy) found an association between a timely progression from surgery to the initiation of postoperative radiotherapy and improved overall or recurrence-free survival. Of the 5 studies examining TPT, 4 found that prolonged TPT correlated with poorer overall survival; proposed thresholds for prolonged TPT ranged from 77 days or more to more than 100 days. CONCLUSIONS AND RELEVANCE Timely care regarding initiation of treatment, postoperative radiotherapy, and TPT is associated with survival for patients with HNC, although significant heterogeneity exists for defining delayed DTI and TPT. Further research is required to standardize optimal time goals, identify barriers to timely care for each interval, and design interventions to minimize delays.

◥Purpose: Pembrolizumab improved survival in patients with recurrent or metastatic head and neck squamous-cell carcinoma (HNSCC). The aims of this study were to determine if pembrolizumab would be safe, result in pathologic tumor response (pTR), and lower the relapse rate in patients with resectable human papillomavirus (HPV)-unrelated HNSCC.Patients and Methods: Neoadjuvant pembrolizumab (200 mg) was administered and followed 2 to 3 weeks later by surgical tumor ablation. Postoperative (chemo)radiation was planned. Patients with high-risk pathology (positive margins and/or extranodal extension) received adjuvant pembrolizumab. pTR was quantified as the proportion of the resection bed with tumor necrosis, keratinous debris, and giant cells/histiocytes: pTR-0 (<10%), pTR-1 (10%-49%), and pTR-2 (≥50%). Coprimary endpoints were pTR-2 among all patients and 1-year relapse rate in patients with high-risk pathology (historical: 35%). Correlations of baseline PD-L1 and T-cell infiltration with pTR were assessed. Tumor clonal dynamics were evaluated (Clin-icalTrials.gov NCT02296684).Results: Thirty-six patients enrolled. After neoadjuvant pembrolizumab, serious (grades 3-4) adverse events and unexpected surgical delays/complications did not occur. pTR-2 occurred in eight patients (22%), and pTR-1 in eight other patients (22%). One-year relapse rate among 18 patients with high-risk pathology was 16.7% (95% confidence interval, 3.6%-41.4%). pTR ≥10% correlated with baseline tumor PD-L1, immune infiltrate, and IFNg activity. Matched samples showed upregulation of inhibitory checkpoints in patients with pTR-0 and confirmed clonal loss in some patients.Conclusions: Among patients with locally advanced, HPVunrelated HNSCC, pembrolizumab was safe, and any pathologic response was observed in 44% of patients with 0% pathologic complete responses. The 1-year relapse rate in patients with high-risk pathology was lower than historical.

Background Determine the effect of National Comprehensive Cancer Network Guideline- adherent initiation of postoperative radiation therapy (PORT), and different time to PORT intervals, on overall survival (OS) in patients with head and neck squamous cell carcinoma (HNSCC). Methods Reviewing the National Cancer Database (NCDB) from 2006–2014, 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 effect of initiating PORT ≤ 6 weeks of surgery, and different time to PORT intervals, on survival. Results 41,291 patients were included in the study. After adjusting 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 (HR 1.21; 99% CI 1.15–1.28). Relative to starting PORT 5 to ≤ 6 weeks postoperatively, initiating PORT earlier was not associated with improved survival (≤ 4 weeks: aHR 0.93; 99% CI 0.85–1.02, 4 to ≤ 5 weeks: aHR 0.92; 99% CI 0.84–1.01). Increasing duration of delays beyond 7 weeks were associated with progressive small survival decrements (aHR 1.09, 1.10, and 1.12 for 7 to ≤ 8 weeks, 8 to ≤ 10 weeks, and > 10 weeks). Conclusions Non-adherence to NCCN Guidelines for initiating PORT within 6 weeks of surgery is associated with decreased survival. There is no survival benefit to initiating PORT earlier within the recommended 6-week timeframe. Increasing durations of delays beyond 7 weeks are associated with small progressive survival decrements.