Between evidence and new perspectives on the current state of the multimodal approach to gastric cancer: Is there still a role for radiation therapy?

Table 4 The main phase I/II trials in gastric cancer that evaluate the postoperative therapy

Trial	Year/type	N° of patients	Treatment schedule	Median FU	Severe toxicity	Clinical efficacy	Survival	Limits/characteristics
Michel[37]	2014/Phase I	21	FOLFIRIx4→RCT	26.6 mo	During FOLFIRI (23.8) During RT (9.5)	Median PFS: 22.8 mo	Median OS: 32.9 mo	Parallel study with a neoadjuvant schedule (see above). Study closed for futility (42.9% completed the schedule)
Wang[41]	2014/ Phase I	18	5FU + RT→FOLFOX4 (8) FOLFOX4→5FU+RT (7) 5FU + RT (3)	45 mo	Nausea (11.1) Vomiting (5.6) Esophagitis (5.6) Leukopenia (11.1) Neutropenia (5.6)	4-yr LRC: 93.8%	4-yr OS: 68.1%	MTD: 5FU 800 mg/m2 twice daily
Zhai[42]	2014/ Phase II	30	FOLFOX6x2→5FU + RT	21 mo	Nausea (33.3) Vomiting (33.3) Diarrhea (6.7) Hepatic (3.3) Cutaneous (3.3) Neutropenia (40) Sensory (23.3)	3-yr DFS: 65%	3-yr OS: 72.7%
Wang[43]	2014/ Phase II	110	FOLFOXx1→FOLFOXd1, 22 + RT→FOLFOXx5	43 mo	Nausea and vomiting (14.5) Diarrhea (0.9) Anorexia (11.8) Fatigue (6.4) Abdominal pain (2.7) Leuko-/neutropenia (9.1) Hemorrhage (0.9)	3-yr RFS: 67.8%	3-yr OS: 77.6%	Stage ≤ IIIA significant factor predicting more favorable OS
Qiu[48]	2015/ Phase I	21	SOXx1→S-1 + RT	26 mo	Nausea (19) Vomiting (19) Fatigue (4.7) Anorexia (14.2) Leukopenia (4.7)	2-yr DFS: 66.7%	2-yr OS: 90.4%	MTD: S-1 70 mg/m2·d
Shim[49]	2016/ Phase II	46	SPx1→S-1 + RT→SPx2	56.5 mo	Nausea (17.4) Vomiting (8.7) Diarrhea (4.3) Anorexia (15.2) Fatigue (6.5) Neutropenia (28.2) Anemia (6.5) Thrombocytopenia (4.3)	3-yr DFS: 65.2%	3-yr OS:76.1%	Treatment compliance: 73.9% Intestinal-type tumor showed better DFS and OS
Goody[46]	2016/ Phase I/II	55	5FU-CDDP + RT	36.4 mo	Hematological (36.3) Constitutional (9) Dermatologic (3.6) Gastrointestinal (18.1) Infection (5.4) Muscoloskeletal (1.8)	2-yr LRR: 16.8% 2-yr RFS: 74%	2-yr OS: 85%	MTD: CDDP 40 mg/m2 w1,3,5,7 Treatment compliance: 85.5%
Liu[44]	2017/ Phase II	55	mDCFx2→TXL + RT→ mDCFx2	61 mo	Nausea (63) Vomiting (49) Diarrhea (12) Anorexia (34) Fatigue (31) Neutropenia (60) Thrombocytopenia (51) Thrombocytopenia (15) Anemia (13) Febrile neutropenia (10)	3-yr PFS: 75% 5-yr PFS: 59%	3-yr OS: 72% 5-yr OS:61%	Treatment compliance 76%
Liu[45]	2017/ Phase II	36	mDCFx2→wTXL + RT→mDCFx2	35.6 mo	Nausea (63) Vomiting (48) Diarrhea (9) Anorexia (33) Stomatitis (44) Fatigue (27) Neutropenia (53) Thrombocytopenia (62) Thrombocytopenia (16) Anemia (13) Febrile neutropenia (9)	RR: 83% CR: 36% 3-yr PFS: 32%	3-yr OS: 42%	Inoperable patients. RT was delivered with IMRT technique
Wang[50]	2018/ Phase I/II	73	S-1 + RT Various adjuvant CT before or after RT	37.6 mo	Nausea (9.6) Vomiting (5.7) Anorexia (9.6) Esophagitis (3.8) Stomatitis (1.9) Fatigue (1.9) Leukopenia (11.5) Neutropenia (3.8)	3-yr LRFS: 92.2%	3-yr OS: 70%	MTD: S-1 80 mg/m2

CRT: Chemoradiotherapy; RT: Radiotherapy; CR: Complete response; OS: Overall survival; NR: Not reported; MTD: Maximum tolerated dose; PD Progressive disease; DFS: Disease-free survival; PFS: Progression-free survival; LRC: Loco-regional control; RFS: Relapse-free survival; RR: Response rate; LRFS: Local relapse-free survival.