Short-term outcome of neo-adjuvant chemotherapy for advanced gastric cancer Chan De-Chuan, Chen Teng-Wei, Chen Cheng-Jueng, Yu Jyh-Cherng Division of General surgery Tri-Service General Hospital

Perioperative chemotherapy for locally advanced Gastric Cancer: MAGIC and French trials Surgery alone Stage ≥II Chemoth Surgery Chemoth MAGIC trial: ECF x 3 => Surgery => ECF x 3 (Total 503 pts) French trial: FuP x 2 => Surgery => FuP x 4 (Total 224 pts) increasing the R0 resection rate improving the overall survival R Benefits: New England Journal of Medicine, vol. 355, no. 1, pp. 11–20,2006 Journal of Clinical Oncology, vol. 29, no. 13,pp. 1715–1721, 2011.

MAGIC trial

FNCLCC 94012 - FFCD 9703 Trial Kaplan-Meier curve showing overall survival from date of random assignment.

Stage IV gastric cancer is not always a palliative situation (conversion surgery) Chemotherapy: 60 pt AIO regimen plus irinotecan (b) Conversion surgery: 16 pt Median survival: 24.5m Median survival: 10.1m World J Surg (2014) 38:419–425

The new the classification of stage IV GC 3-year overall survival rate of 50.1% Yoshida, Gastric Cancer (2016) 19:329–338 European Journal of Surgical Oncology (2015)41: 1354–1360

Materials and Methods From 2014.05 to 2016.12 24 stage IV gastric cancer(liver metastasis, PC or distant LN metastasis) or 5 gastric caner with bulky regional LN (≧ 4cm) ECOG PS 0-1 1st line chemotherapy regimen: XELOX ± Paclitaxel Primary end point: response rate Surgical indication: response to C/T, palliative resection for complication

Result: Patient and tumor characteristics Stage IV(n = 24) Bulky LN (n = 5) CRS (n = 13) No CRS (n = 11) Surgery (n = 4) No surgery (n = 1) Patient characteristics Male Female Median age 8 4 58 (28-79) 6 5 57(24-68) 66 (63-70) 1 79 Cancer location Esophagogastric junction Stomach 3 10 Site of metastasis Liver Peritoneum Peritoneum + other Distant lymph node Bulky regional lymph node 9 2 Histology well moderatel moderate-poor poor 11

Result: XELOX-based chemotherapy and response Stage IV(n = 24) Bulky LN (n = 5) CRS (n = 13) No CRS (n = 11) Surgery (n = 4) No surgery (n = 1) n(%) Preoperative chemotherapy Duration (median, month) Median cycles 5.4(2.6-11) 8 (3-16) 7.2(1.9-33.5) 8 (1-33) 6.4(5.9-7.4) 8 5.4 12 Incomplete C/T(< 6 cycles) 3 4 7(24.1) Response Complete Partial Stable Disease progression 1 7 2 6 5(17.2) 13(44.8) 1(3.4) 10(34.5) HIPEC 11

complete response(8); resection; disease free 24.3m 61 y/0 male; cT4aN1M1; liver metastasis (1) complete response(8); resection; disease free 24.3m Before After

61 y/0 male; cT4aN1M1; Liver metastasis (1) Complete response Before After

68 Y/O male; cT4aN1M1; liver metastasis (multiple) complete response (10); on resection; disease free 30.6m After Before

68 Y/O male; cT4aN1M1; liver metastasis (multiple) Complete response Before After

58 Y/O Female; cT4aN1M1; PC(P3) complete response(33), disease free 33 58 Y/O Female; cT4aN1M1; PC(P3) complete response(33), disease free 33.9m Before After

53 Y/O female; cT4aN2M1; PC(P3) partial response(12), LTG+ HIPEC; brain meta; alive 18.4m stomach colon Before After

49 y/o male; cT4aN2M1; distant LN metastasis (Virchow node) partial response(12); LTG; die 18.3m

Result: Surgical procedures and outcome Stage IV(n = 24) Bulky LN (n = 5) surgery (n = 13) No surgery (n = 11) Surgery (n = 4) (n = 1) Surgical procedure Gastrectomy only Additional resection of metastasis CRS + HIPEC 2 9 4 (1HIPEC) Curability classification CC0 CC1 CC2 7 4 Mortality 1 Morbidity Bile leakage Ileus Intraabdominal abscess 3(23.1)

Result: Follow-up Stage IV(n = 24) Bulky LN (n = 5) CRS (n = 13) No CRS (n = 11) Surgery (n = 4) No surgery (n = 1) Median FU(months) 12.2 (3.5-22.5) (1.9-33.9) 16.3 (12.4-35) 11 Median survival from diagnosis 9.5 12.6 1-year OS 1-year PFS 7(53.8) 6(46.2) 6(54.5) 3(27.3) CRS No CRS CRS No CRS

Discussion: compliance Preoperative C/T was performed more than 6 cycles in 75.9 % in our series (regimen: XELOX ±Paclitaxel ) Post-gastrectomy C/T was completed in 64% in INT116 trial Preoperative C/T was completed in 87 % in FNCLCC and FFCD Multicenter Phase III Trial; Post-op C/T in 23% (regimen: CF) Preoperative C/T was completed in 42 % in MAGIC Phase III Trial; Post-op C/T in 34% (regimen: ECF)

Disscussion: response In our series 17.2% of patients with preoperative C/T showed complete response 41.7% of patients with stage IV gastric cancer with preoperative C/T showed tumor progression but 0% of patients with bulky regional LNs In resectable gastric cancer , various trials in the preoperative C/T showed pCR from 10% to 20% 15% of patients with locally advanced cancer undergoing preoperative chemotherapy show risks of tumor progression Journal of the National Cancer Institute, vol. 85, no. 22, pp. 1839–1844, 1993. Annals of Surgical Oncology, vol. 14, no. 7, pp. 2010–2017, 2007

Disscussion: conversion surgery Long-term survival seem to be achieved in stage IV gastric cancer patients with CR to C/T Surgical resection ?

Natural history of PC with palliative treatment - Sadeghi,et al. EVOCAPE 1 (Cancer 2000) : n=125/370 (prospective) Palliative systemic chemotherapy Mean and Median survival : 6.5 and 3.1 months 58% of synchronous carcinomatosis Metastatic gastric cancer with conventional chemotherapy and targeted therapy (2013) Median survival: 8 – 18 months 5-year survival: 0% Gastric cancer 2010, 13:101-108 Lancet oncology 2013,14:490-499

3-year survival rate: 50%. 3-year survival rate: 0%. In terms of survival benefits, clinically curative surgery resulted in better clinical outcomes

Conclusion Advantages of preoperative C/T Downstage the primary tumor and metastatic lesion Increase patient compliance to chemotherapy Conversion surgery for stage IV gastric might be one of the main roles of the surgical oncologist in the near future.