Treatment sequence, hospital practice patterns, and completion of multimodality therapy for locally advanced gastric cancer.

14 Background: Optimal oncologic care for patients with locally advanced gastric cancer includes multimodality therapy (MMT). While both perioperative chemotherapy and postoperative chemoradiotherapy are recommended, it is unclear whether one approach is more effective for ensuring patients complete MMT. Methods: National cohort study of 5,450 patients with locally advanced gastric cancer (i.e.: ≥cT2 and/or cN+) treated at 983 hospitals within the National Cancer Data Base (2006-15). Patients were categorized as having surgery first or chemotherapy first (patients not undergoing resection after chemotherapy or not receiving adjuvant after surgery were included based on intent-to-treat). MMT was defined as surgical resection with either neoadjuvant chemotherapy or adjuvant chemoradiotherapy. Hospitals were categorized into terciles based on utilization of chemotherapy first: 1.) predominantly chemotherapy first; 2.) mixed pattern; 2.) predominantly surgery first. The association between patient-level treatment, hospital practice pattern, and MMT completion was evaluated using multivariable hierarchical regression and the association with overall risk of death using multivariable Cox shared frailty modeling. Results: Overall, 55.5% of surgery first and 64.8% of chemotherapy first patients completed MMT (p<0.001) and five-year survival for those completing MMT was 45.5% and 46.6%, respectively (log-rank, p=0.91). At the patient-level, chemotherapy first was significantly associated with MMT completion (Odds Ratio [OR] 1.61 [1.39– 1.86]). By comparison, relative to mixed hospitals, care at surgery first hospitals was associated with MMT completion (OR 1.32 [1.08 – 1.59]), which was due to differences in case-mix and the proportion of patients not receiving resection after chemotherapy (surgery first hospitals—4.1%; mixed hospitals—19.0%; chemotherapy first hospitals—29.4%, p<0.001). MMT by either approach was associated with lower risk of death (ref—surgery only; chemotherapy first – Hazard Ratio [HR] 0.77 [0.68 – 0.86]; surgery first – HR 0.77 [0.68 – 0.87]) while hospital practice pattern was not. Conclusions: The type of MMT strategy is less important than ensuring patients complete MMT. After accounting for treatment drop-outs (which are substantial with either strategy), chemotherapy first appears more effective in the general community for ensuring patients complete MMT. National guidelines should be modified to emphasize neoadjuvant over surgery first MMT strategies.