Preclinical studies suggest that treatment with neoadjuvant immune checkpoint blockade is associated with enhanced survival and antigen-specific T cell responses over adjuvant treatment 1 ; however, optimal regimens have not been defined. Herein, we report results from a randomized phase II study of neoadjuvant nivolumab versus combined ipilimumab with nivolumab in 23 patients with high-risk resectable melanoma (NCT02519322). RECIST overall response rates (ORR), pathologic complete response rates (pCR), treatment-related adverse events (trAEs), and immune correlates of response were assessed. Treatment with combined ipilimumab and nivolumab yielded high response rates (RECIST ORR 73%, pCR 45%) but substantial toxicity (73% grade 3 trAEs), whereas treatment with nivolumab monotherapy yielded modest responses (ORR 25%, pCR 25%) and low toxicity (8% grade 3 trAEs). Immune correlates of response were identified, demonstrating higher lymphoid infiltrates in responders to both therapies and a more clonal and diverse T cell infiltrate in responders to nivolumab monotherapy. These results are the first to describe the feasibility of neoadjuvant immune checkpoint blockade in melanoma and emphasize the need for additional studies to optimize treatment regimens and to validate putative biomarkers.

Objective To create a method for assessing physician performance and care outcomes that are adjusted for procedure acuity and patient comorbidity. Design Between 2004 and 2008 surgical procedures performed by 10 surgeons were stratified into high-acuity procedures (HAPs) and low-acuity procedures (LAPs). Risk adjustment was made for comorbid conditions examined singly or in groups of 2 or more. Setting A tertiary care medical center. Patients A total of 2618 surgical patients. Main Outcome Measures Performance measures included length of stay; return to operating room within 7 days of surgery; and the occurrence of mortality, hospital readmission, transfusion, and wound infection within 30 days of surgery. Results The transfusion rate was 2.7% and 40.6% for LAPs and HAPs, respectively. Wound infection rates were 1.4% for LAPs vs 14.1% for HAPs, while 30-day mortality rate was 0.3% and 1.6% for LAPs and HAPs, respectively. The mean (SD) hospital stay for LAPs was 2.1 (3.6) vs 10.5 (7.0) days for HAPs. Negative performance factors were significantly higher for patients who underwent HAPs and had comorbid conditions. Differences among surgeons significantly affect the incidence of negative performance indicators. Factors affecting performance measures were procedure acuity, the surgeon, and comorbidity, in order of decreasing significance. Surgeons were ranked low, middle, and high based on negative performance indicators. Conclusions Performance measures following oncologic procedures were significantly affected by comorbid conditions and by procedure acuity. Although the latter most strongly affects quality and performance indicators, both should weigh heavily in physician comparisons. The incidence of negative performance indicators was also influenced by the individual surgeon. These data may serve as a tool to evaluate and improve physician performance and outcomes and to develop risk-adjusted benchmarks. Ultimately, reimbursement may be tied to quantifiable measures of physician and institutional performance.

Background The purpose of this study was to describe the 30-day incidence of complications after total laryngectomy (TL) in a high-volume institution and their impact on hospital length of stay (LOS) and readmission rates. Methods A retrospective, cohort study of all patients who underwent TL at MD Anderson Cancer Center from January 1, 2010 through June 30, 2013 was conducted. Patient demographics, treatment history, LOS, and 30-day post-TL complications and readmissions were extracted from the medical record. Univariate associations were analyzed and stepwise backward selection methods were used to fit multivariate models. Results 245 patients were included. Complications occurred in 83 patients (33.9%) including 3 (1.2%) deaths. Wound complications occurred in 53 patients (21.6%), of which 34 were pharyngocutaneous fistula (PCF) (13.9% overall). 34 patients (13.9%) were readmitted within 30 days. Multivariate analysis revealed the following: wound complications were associated with former (OR 5.1, p=0.03) and current (OR 5.8, p=0.02) smokers; PCF was associated with prior wide-field radiation (OR 3.1, p=0.01) but not prior narrow-field (larynx only) radiation (OR 1.4, p=0.61); LOS was associated with type of flap (p=0.002) and post-operative hematoma (p=0.05); and readmissions were associated with pre-operative hypoalbuminemia (p=0.003) and post-operative wound complications (p<0.001). Conclusions Complications occurred in nearly one third of TL patients, particularly among patients with poor wound healing risk factors such as prior smoking and radiation. Expectedly, LOS was longer among reconstructed patients. Readmission was associated with hypoalbuminemia and post-operative wound complications. These data inform quality improvement efforts and counseling of high-risk patients undergoing TL.

for the MD Anderson Head and Neck Cancer Symptom Working Group IMPORTANCE A major goal of primary transoral robotic surgery (TORS) for oropharyngeal cancer is to optimize swallowing outcomes by personalized treatment based on pathologic staging. However, swallowing outcomes after TORS are uncertain, as are the outcomes compared with nonsurgical options. OBJECTIVES To estimate rates of acute dysphagia and recovery after TORS and to compare swallowing outcomes by primary treatment modality (TORS or radiotherapy). DESIGN, SETTING, AND PARTICIPANTSThis case series study was a secondary analysis of prospective registry data from 257 patients enrolled from March 1, 2015, to February 28, 2018, at a single academic institution who, according to the AJCC Staging Manual, 7th edition TNM classification, had low-to intermediate-risk human papillomavirus-related oropharyngeal squamous cell carcinoma possibly resectable by TORS. EXPOSURE Patients were stratified by primary treatment (75 underwent TORS and 182 received radiotherapy). MAIN OUTCOMES AND MEASURESModified barium swallow (MBS) studies graded per Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) and the MD Anderson Symptom Inventory-Head and Neck Module (MDASI-HN) questionnaires were administered at standard intervals. Prevalence and severity of dysphagia were estimated per DIGEST before and after TORS and 3 to 6 months after treatment. Moderate-severe dysphagia (DIGEST grade Ն2) was assessed using logistic regression and compared by primary treatment group. The MDASI swallowing symptom severity item scores during and after radiotherapy were compared using generalized estimating equations by treatment status at the start of radiotherapy, after induction, and after TORS. RESULTS A total of 257 patients (mean [SD] age, 59.54 [9.07] years; 222 [86.4%] male) were included in the study. Dysphagia severity (per DIGEST) was significantly worse after TORS (r = −0.63; 95% CI, −0.78 to −0.44): 17 patients (22.7%; 95% CI, 13.8%-33.8%) had moderate-severe (DIGEST grade Ն2) acute post-TORS dysphagia significantly associated with primary tumor volume (odds ratio, 1.43; 95% CI, 1.11-1.84). DIGEST improved by 3 to 6 months but remained worse than that at baseline; at 3 to 6 months, the number of patients with DIGEST grade 2 or higher dysphagia was 5 (6.7%; 95% CI, 2.2%-14.9%) after primary TORS and 29 (15.9%; 95% CI, 10.9%-22.1%) after radiotherapy. At the start of radiotherapy, MDASI swallowing symptom severity item scores were significantly worse in the post-TORS group compared with postinduction (mean [SD] change, 2.6 [1.1]) and treatment-naive (mean [SD] change, 1.7 [0.3]) patients. This result inverted at radiotherapy end, and all groups converged at 3 to 6 months.CONCLUSIONS AND RELEVANCE Subacute swallowing outcomes were similar regardless of primary treatment modality among patients with low-to intermediate-risk oropharyngeal squamous cell carcinoma.

Any effect of the width of surgical margins on outcome was not detectable in the small number of patients analyzed. The use of postoperative radiation therapy was associated with a significant improvement in locoregional control. There was no detectable influence of the type of initial therapy on the rates of distant metastases or on survival. Future therapeutic innovations should be directed toward controlling the development of distant metastases in patients with Merkel cell carcinoma.