Variability in multimodality treatment influences survival in non-metastatic gastric cancer patients.

BACKGROUND: While gastric cancer is a leading cause of cancer-related mortality in Eastern Europe and Asia, it is less common in the USA. Recommendations regarding optimal treatment of non-metastatic gastric cancer (nmGC) with regard to type and extent of surgery, choice and sequence of chemotherapeutic agents, and use of radiation therapy vary across geographic locations. To determine how variability in treatment practices affects patient outcomes, we conducted a retrospective study to evaluate clinical outcomes in nmGC patients treated at four high-volume academic institutions. METHODS: California Cancer Registry data were collected for nmGC patients who underwent gastrectomy with curative intent from 2010 to 2018. We conducted chart reviews of the patients' electronic health records to validate clinical factors and outcomes. We performed multivariable Cox regressions to determine prognostic factors for outcomes. RESULTS: Demographics of study cohort (n=326): mean age 66 years; 64% male; 44% Caucasian, 35% Asian, 16% Latino. Tumor stage: 48% loco-regional (pT4 or pN1+) vs. 52% localized (pT1-3, pN0). Histology: 47% intestinal, 30% diffuse, 8% mixed, 15% unknown. Surgery: 34% open gastrectomy, 48% laparoscopic, 18% unknown; number of recovered lymph nodes varied from 0 to 60 in any tumor stage. Chemotherapy: 20% neoadjuvant alone, 25% adjuvant alone, 16% perioperative, 39% none. Multimodality therapy: 44% surgery only, 31% chemotherapy, 25% chemotherapy and radiation. With a median post-surgical follow-up of 6 years, 24% of patients developed recurrence and 40% had died. Compared to open surgery, laparoscopic surgeries were associated with fewer recovered lymph nodes (mean =18 vs. 25, P=0.0042). Fewer recovered lymph nodes were associated with a significant decrease in 5-year overall survival [hazard ratio (HR) =1.9, 95% confidence interval (CI): 1.3-2.8]. Timing of chemotherapy and addition of radiation therapy to chemotherapy did not confer further improvements in survival; in contrast, greater lymph node recovery plus chemotherapy were associated with a significant increase in survival (HR =0.3, 95% CI: 0.1-0.6). CONCLUSIONS: This study highlights major practice differences in the management of nmGC patients across providers and institutions. Further efforts should be made to standardize the use of chemotherapy and adequate recovery and assessment of lymph nodes in this patient population.

Embedded palliative care for patients with metastatic colorectal cancer: a mixed-methods pilot study.

PURPOSE: Palliative care is recommended for patients with metastatic cancer, but there has been limited research about embedded palliative care for specific patient populations. We describe the impact of a pilot program that provided routine, early, integrated palliative care to patients with metastatic colorectal cancer. METHODS: Mixed methods pre-post intervention cohort study at an academic cancer center. Thirty control then 30 intervention patients with metastatic colorectal cancer were surveyed at baseline and 1, 3, 6, 9, and 12 months thereafter about symptoms, quality-of-life, and likelihood of cure. We compared survey responses, trends over time, rates of advance care planning, and healthcare utilization between groups. Patients, family caregivers, and clinicians were interviewed. RESULTS: Patients in the intervention group were followed for an average of 6.5 months and had an average of 3.5 palliative care visits. At baseline, symptoms were mild (average 1.85/10) and 78.2% of patients reported good/excellent quality-of-life. Half (50.9%) believed they were likely to be cured of cancer. Over time, symptoms and quality-of-life metrics remained similar between groups, however intervention patients were more realistic about their likelihood of cure (p = 0.008). Intervention patients were more likely to have a surrogate documented (83.3% vs. 26.7%, p < 0.0001), an advance directive completed (63.3% vs. 13.3%, p < 0.0001), and non-full code status (43.3% vs. 16.7%, p < 0.03). All patients and family caregivers would recommend the program to others with cancer. CONCLUSIONS: We describe the impact of an embedded palliative care program for patients with metastatic colorectal cancer, which improved prognostic awareness and rates of advance care planning.

A Phase I First-in-Human Study of Nesvacumab (REGN910), a Fully Human Anti-Angiopoietin-2 (Ang2) Monoclonal Antibody, in Patients with Advanced Solid Tumors.

PURPOSE: Nesvacumab (REGN910) is a fully human immunoglobulin G1 (IgG1) monoclonal antibody that specifically binds and inactivates the Tie2 receptor ligand Ang2 with high affinity, but shows no binding to Ang1. The main objectives of this trial were to determine the safety, tolerability, dose-limiting toxicities (DLT), and recommended phase II dose (RP2D) of nesvacumab. EXPERIMENTAL DESIGN: Nesvacumab was administered intravenously every two weeks with dose escalations from 1 to 20 mg/kg in patients with advanced solid tumors. RESULTS: A total of 47 patients were treated with nesvacumab. No patients in the dose escalation phase experienced DLTs, therefore a maximum tolerated dose (MTD) was not reached. The most common nesvacumab-related adverse events were fatigue (23.4%), peripheral edema (21.3%), decreased appetite, and diarrhea (each 10.6%; all grade ≤ 2). Nesvacumab was characterized by linear kinetics and had a terminal half-life of 6.35 to 9.66 days in a dose-independent manner. Best response by RECIST 1.1 in 43 evaluable patients included 1 partial response (adrenocortical carcinoma) of 24 weeks duration. Two patients with hepatocellular carcinoma had stable disease (SD) > 16 weeks, with tumor regression and >50% decrease in α-fetoprotein. Analyses of putative angiogenesis biomarkers in serum and tumor biopsies were uninformative for treatment duration. CONCLUSIONS: Nesvacumab safety profile was acceptable at all dose levels tested. Preliminary antitumor activity was observed in patients with treatment-refractory advanced solid tumors. On the basis of cumulative safety, antitumor activity, pharmacokinetic and pharmacodynamic data, the 20 mg/kg dose was determined to be the RP2D.