Risk factors of metachronous peritoneal carcinomatosis after potentially curative gastric cancer resection in the CRITICS trial.

person Irene A Caspers Antoni van Leeuwenhoek/Netherlands Cancer Institute, Amsterdam, Netherlands info_outline Irene A Caspers, Karolina Sikorska, Astrid E. Slagter, Elma Meershoek – Klein Kranenbarg, Cornelis J.H. Van De Velde, Pehr A. Lind, Marianne Nordsmark, Edwin PM Jansen, Marcel Verheij, Johanna W. van Sandick, Annemieke Cats, Nicole C.T. van Grieken

Authors person Irene A Caspers Antoni van Leeuwenhoek/Netherlands Cancer Institute, Amsterdam, Netherlands info_outline Irene A Caspers, Karolina Sikorska, Astrid E. Slagter, Elma Meershoek – Klein Kranenbarg, Cornelis J.H. Van De Velde, Pehr A. Lind, Marianne Nordsmark, Edwin PM Jansen, Marcel Verheij, Johanna W. van Sandick, Annemieke Cats, Nicole C.T. van Grieken Organizations Antoni van Leeuwenhoek/Netherlands Cancer Institute, Amsterdam, Netherlands, Leiden University Medical Center, Department of Surgery, Leiden, Netherlands, Karolinska Institute/Stockholm Soder Hospital, Stockholm, Sweden, Aarhus University Hospital, Aarhus, Denmark, Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Pathology, Cancer Center Amsterdam, De Boelelaan 1117, Amsterdam, Netherlands Abstract Disclosures Research Funding No funding received None Background: Peritoneal carcinomatosis (PC) is accountable for over 50% of metastatic spread in gastric cancer (GC). Little is known about factors contributing to the risk of metachronous PC as a single site of metastases after preoperative chemotherapy and potentially curative resection. An accurate prediction model of risk factors identifying high risk populations may pave the way for new treatment strategies, such as intraperitoneal chemotherapy. In this analysis, risk factors for the development of isolated metachronous PC after preoperative chemotherapy and surgical resection were investigated. Methods: In the CRITICS trial, 788 patients with resectable GC were randomized for preoperative chemotherapy and gastrectomy followed by either chemotherapy or chemoradiotherapy. Patients who underwent a potentially curative resection without peritoneal metastases at time of surgery were included in this analysis. Univariate and multivariate analyses were performed using a competing risk model. Results: In total, 617 patients met the inclusion criteria. Overall, 97 of 617 (16%) patients developed metachronous PC. The peritoneum was the first site of recurrence in 64 of 617 (10%) patients. Diffuse or mixed type GC, ypT4 stage and ypN3 stage or a lymph node ratio (LNR) with >20% tumor positivity were independent predictors of isolated PC in both univariate and multivariate analyses with hazard ratios (HR) of 2.90, 2.63 and 2.31, respectively (Table). ypT4 and ypN3 stage or a LNR >20% were also independent predictors of distant recurrence or death with HR of 1.46 and 2.34, respectively. Patients in whom all predictors were present had the highest 2 year cumulative incidences of both isolated PC development and other events of 39.6% and 48.8%, respectively. Conclusions: Diffuse or mixed tumor type, ypT4 and ypN3 or a LNR >20% were identified as independent risk factors for metachronous PC as a single site of metastases in a large cohort of patients treated with preoperative chemotherapy followed by surgical resection. The combination of these factors might identify a subgroup that could benefit from preventive treatment strategies. Uni-/multivariate competing risk analysis on isolated metachronous PC. Other events are competing risk. Univariate analysis* Factor HR 95% CI p value Allocated treatment Chemoradiotherapy Chemotherapy # 0.98 0.77–1.25 0.89 ypT-stage ypT0-pT3 ypT4 # 1.83 1.38–2.34 <0.001 ypN-stage and lymph node ratio ypN3 or pos. LNR>20% 3.09 1.89–5.04 <0.001 Lauren classification Intestinal Diffuse or mixed # 3.47 1.95–6.17 <0.001 Multivariate analysis ypT-stage ypT0-pT3 ypT4 # 2.63 1.60–4.31 <0.001 ypN-stage and lymph node ratio ypN3 or pos. LNR>20% 2.31 1.40–3.82 0.001 Lauren classification Intestinal Diffuse or mixed # 2.90 1.48–5.68 0.002 *Data of the additionally included factors age, sex and tumor localization are not shown. #reference.