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.

Objective To examine the financial impact of quality improvement using Medicare payment data. Background Demonstrating a business case for quality improvement – i.e. 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 two 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 two time periods. The top 20% of hospitals demonstrated a 38% decrease (14.3% vs. 11.6%, p<.001) in complications; in contrast the bottom 20% demonstrated a 25% increase (11.1% vs. 16.5%, p<.001). There was a strong relationship between quality improvement and payments. The top hospitals reduced their payments by $1544 per patient (95% CI, $1334-1755), whereas the bottom of hospitals had no significant change (average $67 increase, 95% CI, -$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.

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.

After price-standardization to account for intended differences in Medicare spending, risk-adjusted Medicare payments for an episode of surgical care were similar at teaching hospitals and nonteaching hospitals for three complex inpatient operations.

Background Appendiceal adenocarcinoma (AA) is an orphan disease with unique clinical attributes but often treated as colorectal cancer (CRC). Understanding key molecular differences between AA and CRC is critical. Methods We performed retrospective analyses of AA patients (N = 266) with tumour and/or blood next-generation sequencing (NGS) (2013–2018) with in-depth clinicopathological annotation. Overall survival (OS) was examined. For comparison, CRC cohorts annotated for sidedness, consensus molecular subtypes (CMS) and mutations (N = 3283) were used. Results Blood-NGS identified less RAS/GNAS mutations compared to tissue-NGS (4.2% vs. 60.9%, P < 0.0001) and showed poor concordance with tissue for well-/moderately differentiated tumours. RAS (56.2%), GNAS (28.1%) and TP53 (26.9%) were most frequent mutations. Well/moderately differentiated tumours harboured more RAS (69.2%/64.0% vs. 40.5%) and GNAS (48.7%/32.0% vs. 10.1%) while moderate/poorly differentiated tumours had more TP53 (26.0%/27.8% vs. 7.7%) mutations. Appendiceal adenocarcinoma (compared to CRC) harboured significantly fewer APC (9.1% vs. 55.4%) and TP53 (26.9% vs. 67.5%) and more GNAS mutations (28.1% vs. 2.0%) (P < 0.0001). Appendiceal adenocarcinoma mutation profile did not resemble either right-sided CRC or any of the four CMS in CRC. High grade, but no mutation, was independently predictive of survival. Conclusion Integrated clinico-molecular profiling of AA identified key molecular drivers distinct from CRC. Appendiceal adenocarcinoma has a predominantly grade-driven biology that trumps mutations.

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 &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

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