Neoadjuvant chemoradiotherapy followed by laparoscopic distal gastrectomy in advanced gastric cancer: A case report and review of literature

Table 1 Phase II published studies of neoadjuvant/preoperative radiation/chemoradiation following curative gastrectomy in gastric cancer (with or without esophagogastric junction)

Author	Year of published	N (RT + Surgery /RT)	Eligibility	Preoperative treatment arms	Surgery	Response rate	Survival	Adverse outcomes
Roth et al[21]	2003	18/18	Stomach, LAGC	CF × 2 + RT (3 titers)	D2	6% pCR, 50% ORR	2-yr OS 71%, 3-yr OS 59%	No TRM; no postoperative death; 17% minimal peritoneal carcinomatosis; 44% grade 3-4 AE
Skoropad et al[22]	2003	67/91	Stomach (43% distal), cM0	45 Gy/25 fractions + metronidazole	D1	NA	5-yr OS 46%, 10-yr OS 36%, MST 46 mo	No TRM; 26% metastasis/inoperable; 6% postoperative death; 4% grade 4 AE
Ajani et al[23]	2004	29/33	Stomach/EGJ (24% distal), cT2-3NxM0 or cT1N1M0	45 Gy/25 fractions + 5-Fu	D2	30% pCR, 55% ORR	2-yr OS 54%, MST 34 mo	3% TRM; 3% postoperative death; 12% metastasis/inoperable; no grade 4 AE
Ajani et al[24]	2006	36/43	Stomach/EGJ (23% antrum), cT2-3NxM0 or cT1N1M0	CF × 2 → 45Gy/25 fractions + 5-Fu	D2 recommended	26% pCR.	1-yr OS 72%, MST 23 mo	No TRM; no postoperative death; 17% progression; 5% grade 3 AE; 58% site failure
Wydmanski et al[25]	2007	32/40	Stomach, LAGC (31% middle/distal)	45 Gy/25 fractions + 5-Fu	D2 recommended	18% pCR, 38% ORR	1-yr OS 75%, 2-yr OS 63%, MST not reach	5% TRM; no postoperative death; 12.5% metastasis/inoperable; no grade 4 AE
Rivera et al[26]	2011	8/13	Stomach/EGJ (41% distal), initially unresectable cM0	IC × 2 → 45 Gy/25 fractions + IC	D1 and beyond	No pCR, 8% PR	2-yr OS 27%, MST 10.5 mo (in 17 patients)	15% TRM, 12.5% postoperative death; 23% metastasis/inoperable; 46% grade 3-4 neutropenia
Pera et al[27]	2012	31/41	Stomach/EGJ/Esophagus (29% stomach), locally advanced (M0)	Oxaliplatin/cisplatin/5-FU + 45 Gy/25 fractions	D2 recommended	22% pCR, 44% ORR	2-yr OS 58%, MST 28 mo	2% TRM; 13% postoperative death; 24% progression/inoperable; 14% grade 3-4 neutropenia
Michel et al[28]	2014	31/42	Stomach/EGJ (45% lower), cT > 2 or cN > 1 (M0)	FOLFIRI × 4 → 50 Gy/25 fractions + 5-Fu	D2 recommended	7% pCR	2-yr OS 27%, MST 26 mo	No TRM; 17% postoperative death; 6% metastasis; 41% grade 3-4 AE
Trip et al[29]	2014	24/25	Stomach, cTNM IB-IV (M0)	45 Gy/25 fractions + TC	D1+, D2	16% pCR, 77% ORR	MST 15 mo	No TRM; 4% postoperative death; 4% progression; no grade 4 AE
Liu et al[30]	2018	33/36	Stomach/EGJ, cTNM III (53% lower)	SOX × 1 → 45 Gy/25 fractions + S-1 → SOX×1	D2 recommended	8% pCR, ORR 42%	1-yr OS 92%, 2-yr OS 56%, MST 30 mo	No TRM, no postoperative death; 3% metastasis; no grade 4 AE
Kim et al[31]	2019	31/39	Stomach/EGJ (33% antrum), high-risk	TPS × 2 → 45 Gy/25 fractions + CS	D2	10% pCR, 33% ORR	3-yr OS 76%, MST not reach	No TRM; no postoperative death; 15% metastasis/inoperable; no grade 4 AE during CRT

AE: Adverse events; CF: Cisplatin/5-Fu; CRT: Chemoradiotherapy; CS: Cisplatin/S-1; DCF: Docetaxel/Cisplatin/5–Fu; EGJ: Esophagogastric junction; FOLFIRI: Fluorouracil/Leucovorin/Irinotecan; Gy: Grey; IC: Irinotecan/Cisplatin; LAGC: Locally advanced gastric cancer; MST: Median survival time; NA: Not available; ORR: Objective response rate; OS: Overall survival; pCR, Pathological complete response; PR: Partial response; RT: Radiotherapy; SOX: S-1/Oxaliplatin; TC: Paclitaxel/Carboplatin; TPS: Docetaxel/Cisplatin/S-1; TRM: Treatment-related mortality.

Table 2 Phase III published and ongoing studies of neoadjuvant/preoperative radiation/chemoradiation following curative gastrectomy in gastric cancer (with or without esophagogastric junction)

Ref.	Trial (accrual period)	No pts	Eligibility	Treatment/Design	Surgery	Response rate	Survival	Adverse outcomes
Skoropad et al[32]	(1974-1978)	102	Stomach/EGJ, cM0	20 Gy/5 fractions → S vs S	D1 and beyond	NA	5-yr OS 30% vs 39%, NS; 10-yr OS 32% vs 18%, NS	Complications 57% vs 49%, NS; postoperative death 9.8% vs 11.8%, NS
Leong et al[33]	TOPGEAR (2009-2014)	75	Stomach/EGJ, cTNM IB-IIIC	ECF×2 → 45 Gy/25 fractions + 5-Fu→ S →ECF × 3 vs ECF × 3 → S →ECF × 3	D2, D1+	NA	In progress	No/noncurative surgery, 15% vs 10%, NS; Grade 3-4 AE 52% vs 50%, NS; surgical complications 22% vs 22% NS
https://clinicaltrials.gov/ct2/show/study/NCT01815853	Neo-CRAG (2013-)	620 (estimated)	LAGC, cT3N2/N3M0, cT4aN+M0, cT4bNanyM0	45 Gy/25 fractions → XELOX × 3 → S → XELOX × 3 vs XELOX × 3 → S → XELOX × 3	D2	In progress	In progress	In progress
Liu et al[34]	PREACT (2016-)	682 (estimated)	Stomach/EGJ, LAGC	SOX × 1 → 45 Gy/25 fractions + S-1 → SOX × 1 → S → SOX × 3 vs SOX × 3 → S → SOX × 3	D2 recommended	In progress	In progress	In progress

AE: Adverse events; ECF: Epirubicin/cisplatin/5-Fu; EGJ: Esophagogastric junction; Gy: Grey; LAGC: Locally advanced gastric cancer; NA: Not available; NS: Not significant; OS: Overall survival; S: Surgery; SOX: S-1/Oxaliplatin; XELOX: Capecitabine/Oxaliplatin.