Outcomes of patients with nonmetastatic gastric adenocarcinoma according to perioperative treatment strategy: a real-world, population-based study

Aim: To assess the survival outcomes of patients with nonmetastatic gastric cancer according to the type of perioperative treatment strategy used (surgery-only, adjuvant chemo-radiotherapy, adjuvant chemotherapy, perioperative chemotherapy) in a population-based setting. Materials & methods: Surveillance, Epidemiology and End Results research-plus database was explored, and patients with nonmetastatic gastric cancer who were treated with an oncologic surgery were reviewed. Multivariable Cox regression analysis was used to examine the impact of treatment strategy on overall and cancer-specific survival. Results: A total of 11,526 patients were found to be eligible and they were included in the current analysis. Looking at the percentages of different treatment strategies throughout the study years (2006–2017), the use of the following strategies increased: adjuvant chemotherapy (20.1 vs 10.6%), and perioperative chemotherapy (21.3 vs 0.5%); while the use of the following strategies decreased: surgery only (36.2 vs 58.2%), and adjuvant chemo-radiotherapy (22.4 vs 30.6%). Using multivariable Cox regression analysis, the following factors were associated with worse overall survival: older age (hazard [HR]: 1.021; 95% CI: 1.018–1.023), males (HR: 1.09; 95% CI: 1.04–1.14), Black race (HR: 1.11; 95% CI: 1.04–1.19), cardia subsite (HR: 1.09; 95% CI: 1.02–1.17), grade 3–4 (HR:1.32; 95% CI: 1.25–1.40), diffuse histology (HR: 1.46; 95% CI: 1.35–1.58), clinically node positive (HR:1.43; 95% CI: 1.34–1.53), total gastrectomy (HR: 1.20; 95% CI: 1.13–1.28), and surgery-only approach (HR: 1.65; 95% CI: 1.55–1.75). Conclusion: Among patients with localized gastric cancer, patients who were treated with surgery-only, and to a less extent, patients who were treated with surgery followed by adjuvant chemotherapy have worse survival outcomes; while those treated with perioperative chemotherapy have the best survival outcomes.

Patterns of Perioperative Treatment and Survival of Localized, Resected, Intermediate- or High-Grade Soft Tissue Sarcoma: A 2000–2017 Netherlands Cancer Registry Database Analysis

Background. Standard therapy for localized soft tissue sarcoma (STS) is wide, limb-sparing resection. For intermediate- or high-grade tumors, (neo)adjuvant therapies are frequently added to the treatment plan. In this study, data from a Dutch nationwide database are used to (1) assess whether perioperative management of STS follows ESMO guidelines, (2) characterize prognostic factors for overall survival (OS), and (3) assess the association between perioperative treatment and survival. Methods. All intermediate- or high-grade, localized STS cases, who have undergone surgery and diagnosed between 2000 and 2017, were identified in the Netherlands Cancer Registry (NCR) database. Variables with demographic, treatment, and survival data were obtained. Survival curves were estimated by Kaplan–Meier’s method, and the effect of prognostic factors on OS was assessed in a multivariable Cox regression analysis. Results. A total of 4957 patients were identified. There were slightly more males (54.7%). Median age at diagnosis was 64 years, and 53.6% of the tumors were located in the extremities. Radiotherapy (RT) was administered to 2481 (50.1%) patients, and 252 (5.1%) patients were treated with perioperative systemic chemotherapy. The total use of perioperative RT did not significantly change in the last 20 years, but the timing followed clinical guidelines: preoperative RT increased significantly (2000–2008: 3.7%, 2009–2017: 22.3%; p < 0.001 ), whereas the use of postoperative RT diminished (2000–2008: 45.9%, 2009–2017: 26.1%; p < 0.001 ). The use of perioperative chemotherapy slightly decreased (2000–2008: 5.9%, 2009–2017: 4.4%; p = 0.015). 5-year OS was 59.6% (95% CI: 58.2–61.0). Sex, age, year of diagnosis, tumor location, tumor size, histological grade, depth, histological subtype, surgical margins, and the use of perioperative RT were identified as independent predictors for OS. Conclusion. Preoperative RT is gradually replacing postoperative RT for localized STS in the Netherlands. The use of perioperative chemotherapy is rare and has slightly decreased in recent years. Identified baseline characteristics and treatment factors predicting OS may aid in future treatment decisions.

Preliminary efficacy and safety of perioperative treatment of camrelizumab combined with apatinib in resectable hepatocellular carcinoma (HCC): A prospective phase II study.

4082 Background: Although there is no standard perioperative treatment for resectable HCC characterized with high recurrence rate, the strategy of immunotherapy combined with targeted agents is promising in neoadjuvant/adjuvant therapy in various tumors. Methods: In this perspective, single-arm, exploratory phase II trial (NCT04297202), eligible patients (pts) were systemic treatment-naive resectable HCC in intermediate/advanced stage. Preoperative combined treatment of anti-PD-1 antibody camrelizumab (200 mg q2w for 3 cycles) and VEGFR-2 inhibitor apatinib (250 mg qd for 21 days) was started on day 1 cycle 1. On the 7th day after the 3 cycles, radiological imaging was assessed to confirm whether to conduct the hepatectomy. Four weeks after the surgery, combined treatment (camrelizumab 200 mg q3w, apatinib 250 mg qd, 3 weeks per cycle) was resumed for the postoperative 8 cycles. The primary endpoint was major pathologic response (MPR) defined as 50%-99% tumor necrosis in resected tissue. Gene expression profiles (GEPs) using immune-related RNA with pre-treatment specimens were analyzed. The association between immune signatures and pathological response (responders (R) vs. non-responders (NR)) was assessed. Results: A total of 20 pts were enrolled between Dec 5, 2019 and Jan 27, 2021, with a median follow-up of 5.7 months (range 0.7-9.0). All pts were ECOG PS 0-1 and Child-Pugh class A. There were 85% pts with hepatitis B and 10% with hepatitis C, and 55% in BCLC stage B, 35% in stage C and 10% in stage A. In preoperative phase, with 2 withdraw of informed consent form, partial response was reached in 3/18 (16.7%) and 8/18 (44.4%) pts per RECIST 1.1 and mRECIST, respectively, while disease progression was found in 1/18 (5.6%) pts impossible for hepatectomy, which made the resection rate 17/18 (94.4%). After the surgery, one was found to be combined hepatocellular-cholangiocarcinoma by histopathological examination and failed to proceed the postoperative study. The rates of MPR and pathological complete response (pCR) were 5/17 (29.4%) and 1/17 (5.9%), respectively. The preliminary analysis of GEPs (R:NR = 3:4) revealed higher levels of chemokines ( CXCL10 and CXCL11) in responders and higher MS4A4A (marker gene of macrophages ) in non-responders. The most common TEAEs included hypertension (95%), proteinuria (40%), AST elevation (40%), and platelet count decrease (45%). Grade 3 TEAEs were hypertension (20%), rash (10%), and platelet count decrease (10%). No grade 4/5 TEAEs was observed. The most common surgical complications were ALT and AST increase each with the incidence of 70% (all grades) and 45% (grade ≥ 3). Conclusions: This study preliminarily demonstrated that the perioperative treatment of camrelizumab combined with apatinib improved the MPR and pCR with managable safety in intermediate/advanced resectable HCC. Clinical trial information: NCT04297202.