Improved guideline compliance and textbook oncologic outcomes among patients undergoing multimodal treatment and minimally invasive surgery for locally advanced gastric cancer.

BACKGROUND: Although receipt of neoadjuvant chemotherapy has been identified to improve unfavorable survival outcomes among patients with locally advanced gastric cancer (LAGC), several randomized controlled trials have not demonstrated a difference in oncological outcomes/overall survival (OS) among patients undergoing minimally invasive surgery (MIS) versus open gastrectomy. This study aimed to investigate National Comprehensive Cancer Network (NCCN) guideline adherence and textbook oncological outcome (TOO) among patients undergoing MIS versus open surgery for LAGC. METHODS: In this cross-sectional study, patients with stage II/III LAGC (cT2-T4N0-3M0) who underwent curative-intent treatment between 2013 and 2019 were evaluated using the National Cancer Database. Multivariable analysis was performed to assess the association between surgical approach, NCCN guideline adherence, TOO, and OS. The study was registered on the International Standard Randomised Controlled Trial Number registry (registration number: ISRCTN53410429) and conducted according to the Strengthening The Reporting Of Cohort Studies in Surgery and Strengthening the Reporting of Observational Studies in Epidemiology guidelines. RESULTS: Among 13,885 patients, median age at diagnosis was 68 years (IQR, 59-76); most patients were male (n = 9887, 71.2%) and identified as White (n = 10,295, 74.1%). Patients who underwent MIS (n = 4692, 33.8%) had improved NCCN guideline adherence and TOO compared with patients who underwent open surgery (51.3% vs 43.5% and 36.7% vs 27.3%, respectively; both P < .001). Adherence to NCCN guidelines and likelihood to achieve TOO increased from 2013 to 2019 (35.6% vs 50.9% and 31.4% vs 46.4%, respectively; both P < .001). Moreover, improved median OS was observed among patients with NCCN guideline adherence and TOO undergoing MIS versus open surgery (57.3 vs 49.8 months [P = .041] and 68.4 vs 60.6 months [P = .025], respectively). CONCLUSIONS: An overall increase in guideline-adherent treatment and achievement of TOO among patients with LAGC undergoing multimodal and curative-intent treatment in the United States was observed. Adoption of minimally invasive gastrectomy may result in improved short- and long-term outcomes.

Disparities in NCCN Guideline-Compliant Care for Patients with Early-Stage Pancreatic Adenocarcinoma at Minority-Serving versus Non-Minority-Serving Hospitals.

BACKGROUND: Racial/ethnic disparities in pancreatic adenocarcinoma (PDAC) outcomes may relate to receipt of National Comprehensive Cancer Network (NCCN) guideline-compliant care. We assessed the association between treatment at minority-serving hospitals (MSH) and receipt of NCCN-compliant care. PATIENTS AND METHODS: Patients who underwent resection of early-stage PDAC between 2006 and 2019 were identified from the National Cancer Database (NCDB). MSH was defined as the top decile of facilities treating minority ethnicities (Black and/or Hispanic). Factors associated with receipt of NCCN-compliant care and its impact on overall survival (OS) were assessed. RESULTS: Among 44,873 patients who underwent resection of PDAC, most were treated at non-MSH (n = 42,571, 94.9%), while a smaller subset were treated at MSH (n = 2302, 5.1%). Patients treated at MSH were more likely to be at a younger median age (MSH 66 years versus non-MSH 67 years), Black or Hispanic (MSH 58.4% versus non-MSH 12.0%), and not insured (MSH 7.8% versus non-MSH 1.6%). While 71.7% (n = 31,182) of patients were compliant with NCCN care, guideline-compliant care was lower at MSH (MSH 62.5% versus non-MSH 72.2%). On multivariable analysis, receiving care at MSH was associated with not receiving guideline-compliant care [odds ratio (OR) 0.63, 95% confidence interval (CI) 0.53-0.74]. At non-MSH, non-white patients had lower odds of receiving guideline-compliant PDCA care (OR 0.85, 95% CI 0.78-0.91). Failure to comply was associated with worse overall survival (OS) [hazard ratio (HR) 1.50, 95% CI 1.46-1.54, all p < 0.001]. CONCLUSIONS: Patients with PDAC treated at MSH and minorities treated at non-MSH were less likely to receive NCCN-compliant care. Failure to comply with guideline-based PDAC treatment was associated with worse OS.

Clinical development of IDH1 inhibitors for cancer therapy.

Isocitrate dehydrogenase 1 (IDH1) has been investigated as a promising therapeutic target in select cancers with a mutated version of the enzyme (mtIDH1). With only one phase III trial published to date and two indications approved for routine clinical use by the FDA, we reviewed the entire clinical trial portfolio to broadly understand mtIDH1 inhibitor activity in patients. We queried PubMed.gov and ClinicalTrials.gov to identify published and ongoing clinical trials related to IDH1 and cancer. Progression-free survival (PFS), overall survival (OS), 2-hydroxyglutarate levels, and adverse events were summarized. To date, ten clinical trials investigating mtIDH1 inhibitors among patients with diverse malignancies (cholangiocarcinoma, acute myeloid leukemia, chondrosarcoma, glioma) have been published. Almost every trial (80%) has investigated ivosidenib. In multiple phase I trials, ivosidenib treatment resulted in promising radiographic and biochemical responses with improved survival outcomes (relative to historic data) among patients with both solid and hematologic mtIDH1 malignancies. Among patients enrolled in a phase III trial with advanced cholangiocarcinoma, ivosidenib resulted in a PFS rate of 32% at 6 months, as compared to 0% with placebo. There was a 5.2 month increase in OS with ivosidenib relative to placebo, after considering crossover. The treatment-specific grade ≥3 adverse event rate of ivosidenib was 2%-26% among all patients, and was just 3.6% among 284 patients who had a solid tumor across four trials. Although <1% of malignancies harbor IDH1 mutations, small molecule mtIDH1 inhibitors, namely ivosidenib, appear to be biologically active and well tolerated in patients with solid and hematologic mtIDH1 malignancies.