Christopher P. Scally

Importance: Neurofibromatosis type 1 (NF1) is a complex genetic disorder that is associated with not only neurofibromas, but also an increased susceptibility to other neoplasms. Objective: To evaluate the prevalence of neoplasia and outcomes among patients with NF1. Design, Setting, and Participants: This cohort study was conducted among patients with NF1 at a single academic cancer center from 1985 to 2020 with median (range) follow-up of 2.9 years (36 days to 30.5 years). Of 2427 patients evaluated for NF1, 1607 patients who met the National Institutes of Health consensus criteria for NF1 were included. This group was compared with estimates from Surveillance, Epidemiology, and End Results (SEER) Cancer Statistics Review 1975 to 2015 and SEER participants database unless otherwise specified. Data were analyzed from August 2018 to March 2020. Main Outcomes and Measures: Disease-specific survival (DSS) was measured from diagnosis date to date of neoplasm-specific death or censorship and calculated using the Kaplan-Meier method. Survival curves were compared using the log-rank test. Deaths from disease were considered a DSS end point; other deaths were considered censored observations. Secondary outcome measures were comparisons of (1) overall survival of patients with NF1 with neurofibroma neoplasms vs those without nonneurofibroma neoplasms, (2) neoplasm prevalence in the NF1 group vs general population estimates, and (3) age at diagnosis in the NF1 group vs general population estimates for the most common neoplasms in the NF1 group. Results: Among 1607 patients with NF1, the median (range) age at initial visit was 19 years (1 month to 83 years) and 840 (52.3%) were female patients. Among 666 patients who developed other neoplasms in addition to neurofibromas (41.4%), 295 patients (18.4%) developed glioma and 243 patients (15.1%) developed malignant peripheral nerve sheath tumor (MPNST), the most common neoplasms. Patients with NF1, compared with the general population, developed several neoplasms at a younger mean (SD) age (low-grade glioma: 12.98 [11.09] years vs 37.76 [24.53] years; P < .0001; high-grade glioma [HGG]: 27.31 [15.59] years vs 58.42 [19.09] years; P < .0001; MPNST: 33.88 [14.80] years vs 47.06 [20.76] years; P < .0001; breast cancer: 46.61 [9.94] years vs 61.71 [13.85] years; P < .0001). Patients with NF1 developed neoplasms more frequently compared with the general population (odds ratio, 9.5; 95% CI, 8.5-10.5; P < .0001). Among patients with NF1, significantly lower 5-year DSS rates were found among those with undifferentiated pleomorphic sarcoma (1 of 5 patients [20.0%]), HGG (8 of 34 patients [23.1%]), MPNST (72 of 228 patients [31.6%]), ovarian carcinoma (4 of 7 patients [57.1%]), and melanoma (8 of 12 patients [66.7%]) compared with those who had neoplasms classified as other (110 of 119 patients [92.4%]) (all P < .001) . Conclusions and Relevance: This cohort study found that among patients with NF1, those who developed undifferentiated pleomorphic sarcoma, HGG, MPNST, ovarian carcinoma, or melanoma had significantly lower DSS rates compared with those who developed other neoplasms. This study also found that patients with NF1 developed some neoplasms more frequently and at a younger age compared with individuals without NF1. HGGs and MPNST were noteworthy causes of death among patients NF1. This information may be useful for NF1 patient counseling and follow-up.

OBJECTIVE: The purpose of this study was to identify behaviors that faculty and residents exhibit during intraoperative interactions, which support or inhibit progressive entrustment leading to operative autonomy. BACKGROUND: In the operating room, a critical balance is sought between direct faculty supervision and appropriate increase in resident autonomy with indirect faculty supervision. Little is known regarding perspectives of faculty and residents about how attendings increasingly step back and safely delegate autonomy to trainees. Understanding the context in which these decisions are made is critical to achieving a safe strategy for imparting progressive responsibility. METHODS: A qualitative study was undertaken from January 2014 to February 2015. Semistructured interviews were conducted with 37 faculty and 59 residents from 14 and 41 institutions, respectively. Participants were selected using stratified random sampling from general surgery residency programs across the United States to represent a range of university, university-affiliated, and community programs, and geographic regions. Audio recordings of interviews were transcribed, iteratively analyzed, and emergent themes identified. RESULTS: Six themes were identified as influencing progressive entrustment in the operating room: optimizing faculty intraoperative feedback; policies and regulations affecting role of resident in the operating room; flexible faculty teaching strategies; context-specific variables; leadership opportunities for resident in the case; and safe struggle for resident when appropriate. CONCLUSIONS: Perspectives of faculty and residents while overlapping were different in emphasis. Better understanding faculty-resident interactions, individual behaviors, contextual influences, and national regulations that influence intraoperative education have the potential to significantly affect progressive entrustment in training paradigms.

OBJECTIVE: To examine the financial impact of quality improvement using Medicare payment data. BACKGROUND: Demonstrating a business case for quality improvement--that is, that fewer complications translates into lower costs--is essential to justify investment in quality improvement. Prior research is limited to cross-sectional studies showing that patients with complications have higher costs. We designed a study to better evaluate the relationship between payments and complications by using quality improvement itself as a measured outcome. METHODS: We used national Medicare data for patients undergoing general (n = 1,485,667) and vascular (n = 531,951) procedures. We calculated hospitals' rates of serious complications in 2 time periods: 2003-2004 and 2009-2010. We sorted hospitals into quintiles by the change in complication rates across these time periods. Costs were assessed using price-standardized Medicare payments, and regression analyses used to determine the average change in payments over time. RESULTS: There was significant change in serious complication rates across the 2 time periods. The top 20% of hospitals demonstrated a 38% decrease (14.3% vs 11.6%, P < 0.001) in complications; in contrast the bottom 20% demonstrated a 25% increase (11.1% vs 16.5%, P < 0.001). There was a strong relationship between quality improvement and payments. The top hospitals reduced their payments by $1544 per patient (95% confidence interval: $1334-1755), whereas the bottom of hospitals had no significant change (average $67 increase, 95% confidence interval: -$123 to $258). CONCLUSIONS: Hospitals that reduced their complications over time had significant reductions in Medicare payments. This demonstrates that payers are clearly incentivized to invest in quality improvement.

Abstract Malignant peritoneal mesothelioma (MPeM) is a rare but aggressive malignancy with limited treatment options. VEGF inhibition enhances efficacy of immune-checkpoint inhibitors by reworking the immunosuppressive tumor milieu. Efficacy and safety of combined PD-L1 (atezolizumab) and VEGF (bevacizumab) blockade (AtezoBev) was assessed in 20 patients with advanced and unresectable MPeM with progression or intolerance to prior platinum–pemetrexed chemotherapy. The primary endpoint of confirmed objective response rate per RECISTv1.1 by independent radiology review was 40% [8/20; 95% confidence interval (CI), 19.1–64.0] with median response duration of 12.8 months. Six (75%) responses lasted for &amp;gt;10 months. Progression-free and overall survival at one year were 61% (95% CI, 35–80) and 85% (95% CI, 60–95), respectively. Responses occurred notwithstanding low tumor mutation burden and PD-L1 expression status. Baseline epithelial–mesenchymal transition gene expression correlated with therapeutic resistance/response (r = 0.80; P = 0.0010). AtezoBev showed promising and durable efficacy in patients with advanced MPeM with an acceptable safety profile, and these results address a grave unmet need for this orphan disease. Significance: Efficacy of atezolizumab and bevacizumab vis-à-vis response rates and survival in advanced peritoneal mesothelioma previously treated with chemotherapy surpassed outcomes expected with conventional therapies. Biomarker analyses uncovered epithelial–mesenchymal transition phenotype as an important resistance mechanism and showcase the value and feasibility of performing translationally driven clinical trials in rare tumors. See related commentary by Aldea et al., p. 2674. This article is highlighted in the In This Issue feature, p. 2659