Predictors of response and survival after concurrent chemotherapy and radiation for locally advanced squamous cell carcinomas of the head and neck.

BACKGROUND: The objective of this study was to determine prognostic factors for response and survival on three consecutive institutional trials utilizing concurrent chemotherapy and radiation for locally advanced squamous cell carcinomas of the head and neck (SCCHN). METHODS: Since 1985, patients with locally advanced SCCHN at the University of Maryland have been managed with concurrent chemotherapy and radiation therapy (RT). Three consecutive pilot studies have been performed evaluating the utility of weekly chemotherapy with standard fractionated RT. Chemotherapy consisted of carboplatin either alone (28 patients) or in combination with bleomycin (23 patients) or paclitaxel (60 patients). In all three studies, RT was given to 70.2 gray (Gy) at 1.8 Gy/fraction/day to the primary site. All patients had locally advanced SCCHN and were believed to be poor surgical candidates. Sixty-seven percent of patients had T4 disease, and 21% had T3 disease. Seventy-five percent of patients had N2-N3 disease. One hundred eleven patients were examinable for toxicity, response, and survival analysis. Factors including age, race, gender, primary site location, histologic grade, T classification, N classification, and treatment regimen were evaluated to identify predictors of these endpoints. RESULTS: The median follow-up for patients treated on study 1 (carboplatin and RT) and study 2 (carboplatin and bleomycin [C + B]/RT) was 98 months, and it was 30 months for study 3 (carboplatin and paclitaxel [C + P]/RT). The complete response rates were 54%, 52%, and 70% respectively (P = 0.01). Multivariate analysis identified length of treatment break (\u3c 1 week vs. \u3e 1 week) as the only predictor of complete response to therapy. The local control for the entire group was 50%. The local control for C + P/RT was 63%, versus 32% and 36% for C/RT and C + B/RT respectively (P = 0.004). The 2-, 3-, and 5-year disease free and overall survivals for the entire population were 41%, 41%, and 35% and 42%, 36%, and 33%, respectively. The 3-year overall survival rates by treatment regimen were 18% (C/RT), 35% (C + B/RT), and 47% (C + P/RT; P = 0.01). On univariate analysis, age younger than 50 years (P = 0.01), treatment with C + P/RT (P = 0.005), and treatment break of 5 days or fewer (P \u3c 0.05) were also predictive of improved overall survival. On multivariate analysis, only complete response (P \u3c 0.0001) and treatment with C + P/RT (P = 0.02) remained statistically significant. CONCLUSIONS: Chemoradiation provides patients with locally advanced SCCHN the opportunity for long term survival. Among the three chemoradiation regimens studied, C + P/RT was associated with the best complete response and survival rates. Complete response to therapy was the single most important predictor of overall survival. These three consecutive concurrent chemotherapy and radiation trials achieved a 5-year survival of greater than 30% for the entire population. These results support the use of this nonoperative approach for this group of patients with a historically poor prognosis

Safety of open ventral hernia repair in high-risk patients with metabolic syndrome: a multi-institutional analysis of 39,118 cases

© 2018 American Society for Bariatric Surgery Background: Metabolic syndrome (MetS) entails the simultaneous presence of a constellation of dangerous risk factors including obesity, diabetes, hypertension, and dyslipidemia. The prevalence of MetS in Western society continues to rise and implies an elevated risk for surgical complications and/or poor surgical outcomes within the affected population. Objective: To assess the risks and outcomes of multi-morbid patients with MetS undergoing open ventral hernia repair. Setting: Multi-institutional case-control study in the United States. Methods: The American College of Surgeons National Surgical Quality Improvement Program database was sampled for patients undergoing initial open ventral hernia repair from 2012 through 2014 and then stratified into 2 cohorts based on the presence or absence of MetS. Statistical analyses were performed to evaluate preoperative co-morbidities, intraoperative details, and postoperative morbidity and mortality to identify risk factors for adverse outcomes. Results: Mean age (61.0 versus 56.0 yr, P\u3c.001), body mass index (39.2 versus 31.1, P\u3c.001), and prevalence of co-morbidities of multiple organ systems were significantly higher (P\u3c.001) in the MetS cohort compared to control. Patients with MetS received higher American Society of Anesthesiologists classifications (81.0% versus 43.1% class 3 or higher, P\u3c.001), were more likely to require operation as emergency cases (11.4% versus 7.2%, P\u3c.001), required longer operative times (103 versus 87 min, P\u3c.001), had longer hospitalizations (3.5 versus 2.4 d, P\u3c.001), and had more contaminated wounds (15.9% versus 12.0% class 2 or higher, P\u3c.001). Overall, they had more medical (7.5% versus 4.2%, P\u3c.001), and surgical complications (9.7% versus 5.4%, P\u3c.001), experienced more readmissions (8.3% versus 5.7%, P\u3c.001) and reoperations (3.4% versus 2.5%, P\u3c.001), and were at higher risk for eventual death (.8% versus.5%, P=.008). Conclusions: The presence of MetS is related to a multitude of unfavorable outcomes and increased mortality after open ventral hernia repair compared with a non-MetS control group. MetS is a useful marker for high operative risk in a population that is generally prone to obesity and its associated diseases

The use of carboplatin and paclitaxel with daily radiotherapy in patients with locally advanced squamous cell carcinomas of the head and neck.

PURPOSE: Unresectable squamous cell carcinomas of the head and neck (SCCHN) continue to pose a significant therapeutic challenge. This report defines the toxicities, efficacy, and prognostic factors associated with the combination of carboplatin (CBDCA), paclitaxel, and once-daily radiation for patients with locally advanced disease. Additionally, the pharmacokinetics of paclitaxel were investigated. METHODS AND MATERIALS: From 1993-1998, 62 patients with Stage III-IV SCCHN were treated with 70.2 Gy of RT at 1.8 Gy/fraction/day to the primary site. Weekly chemotherapy was given during RT consisting of paclitaxel (45 mg/m(2)/wk) and CBDCA (100 mg/m(2)/wk). All patients presented with locally advanced disease; 77% had T4 disease and 21% had T3 disease. Fifty-eight percent had N2b-N3 disease. RESULTS: Sixty patients were evaluable for response and survival with a median follow-up of 30 months (range 7-70). Ninety-eight percent of patients completed prescribed therapy. One patient died after refusing medical management for pseudomembranous colitis and is scored as a Grade 5 toxicity. Two patients suffered Grade 4 leukopenia. Median number of break days was two. A clinical complete response (CR) at the primary site was obtained in 82%, with a total (primary site and neck) CR rate of 75%. The median survival for the entire cohort is 33 months. Response to therapy and status of the neck at presentation were the only prognostic factors found to influence survival. The median survival for patients who attained a CR is 49 months versus 9 months in those who did not attain a CR (p \u3c 0.0001). The 2- and 3-year overall survival for complete responders are 79% and 61%. Plasma paclitaxel concentrations in the range shown to be radiosensitizing were achieved. CONCLUSIONS: Weekly carboplatin and paclitaxel given concurrently with definitive once-daily external beam radiation therapy is well tolerated with over 90% of patients completing prescribed therapy. An ultimate CR rate of greater than 70% was obtained, which translated directly into improved survival. With 48% 3-year overall survival for the entire group, this regimen is an excellent option for this group of patients with a historically poor prognosis