The current data and challenge of radiotherapy in the case management of gastric cancer

doi:10.19401/j.cnki.1007-3639.2022.07.001

Abstract

Abstract:

Gastric cancer is one of the common malignant tumors of digestive tract. Radiotherapy is one of the important comprehensive treatment modalities for patients with gastric cancer. In recent years, there have been breakthroughs in perioperative treatment for locally advanced gastric cancer by radiotherapy and other treatments. The positive impact of such therapies on survival in patients with gastric cancer has become clearer over time. In recent years, new achievements have been made in the fields of neoadjuvant radiotherapy, adjuvant radiotherapy, advanced tumor radiotherapy and combined immunoradiotherapy for gastric cancer. This article analyzed the relevant research progress at home and abroad, and systematically expounded the current status and progress of radiotherapy in the treatment of gastric cancer.

Key words: Gastric cancer, Radiotherapy, Neoadjuvant therapy, Adjuvant therapy

CLC Number:

R735.2

CAI Gang, WANG Shubei, CHEN Jiayi. The current data and challenge of radiotherapy in the case management of gastric cancer[J]. China Oncology, 2022, 32(7): 581-587.

Figures/Tables 2

Tab. 1

Tab. 2

References 42

[1]	ZHENG R, ZHANG S, ZENG H, et al. Cancer incidence and mortality in China, 2016[J]. J Natl Cancer Cent, 2022, 2(1): 1-9.
[2]	LANDRY J, TEPPER J E, WOOD W C, et al. Patterns of failure following curative resection of gastric carcinoma[J]. Int J Radiat Oncol Biol Phys, 1990, 19(6): 1357-1362. doi: 10.1016/0360-3016(90)90344-J
[3]	VAN HAGEN P, HULSHOF M C, VAN LANSCHOT J J, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer[J]. N Engl J Med, 2012, 366(22): 2074-2084. doi: 10.1056/NEJMoa1112088
[4]	STAHL M, WALZ M K, RIERA-KNORRENSCHILD J, et al. Preoperative chemotherapy versus chemoradiotherapy in locally advanced adenocarcinomas of the oesophagogastric junction (POET): long-term results of a controlled randomised trial[J]. Eur J Cancer, 2017, 81: 183-190. doi: 10.1016/j.ejca.2017.04.027
[5]	LEONG T, SMITHERS B M, HAUSTERMANS K, et al. TOPGEAR: a randomized, phase Ⅲ trial of perioperative ECF chemotherapy with or without preoperative chemoradiation for resectable gastric cancer: interim results from an international, intergroup trial of the AGITG, TROG, EORTC and CCTG[J]. Ann Surg Oncol, 2017, 24(8): 2252-2258. doi: 10.1245/s10434-017-5830-6
[6]	AJANI J A, WINTER K, OKAWARA G S, et al. Phase Ⅱ trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response[J]. J Clin Oncol, 2006, 24(24): 3953-3958. doi: 10.1200/JCO.2006.06.4840
[7]	AJANI J A, MANSFIELD P F, JANJAN N, et al. Multi-institutional trial of preoperative chemoradiotherapy in patients with potentially resectable gastric carcinoma[J]. J Clin Oncol, 2004, 22(14): 2774-2780. doi: 10.1200/JCO.2004.01.015
[8]	AJANI J A, MANSFIELD P F, CRANE C H, et al. Paclitaxel-based chemoradiotherapy in localized gastric carcinoma: degree of pathologic response and not clinical parameters dictated patient outcome[J]. J Clin Oncol, 2005, 23(6): 1237-1244. doi: 10.1200/JCO.2005.01.305
[9]	WANG F H, ZHANG X T, LI Y F, et al. The Chinese Society of Clinical Oncology (CSCO): clinical guidelines for the diagnosis and treatment of gastric cancer, 2021[J]. Cancer Commun (Lond), 2021, 41(8): 747-795.
[10]	MACDONALD J S, SMALLEY S R, BENEDETTI J, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction[J]. N Engl J Med, 2001, 345(10): 725-730. doi: 10.1056/NEJMoa010187
[11]	SMALLEY S R, BENEDETTI J K, HALLER D G, et al. Updated analysis of SWOG-directed intergroup study 0116: a phase Ⅲ trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection[J]. J Clin Oncol, 2012, 30(19): 2327-2333. doi: 10.1200/JCO.2011.36.7136
[12]	DIKKEN J L, JANSEN E P M, CATS A, et al. Impact of the extent of surgery and postoperative chemoradiotherapy on recurrence patterns in gastric cancer[J]. J Clin Oncol, 2010, 28(14): 2430-2436. doi: 10.1200/JCO.2009.26.9654
[13]	STIEKEMA J, TRIP A K, JANSEN E P M, et al. The prognostic significance of an R1 resection in gastric cancer patients treated with adjuvant chemoradiotherapy[J]. Ann Surg Oncol, 2014, 21(4): 1107-1114. doi: 10.1245/s10434-013-3397-4
[14]	PARK S H, SOHN T S, LEE J, et al. Phase Ⅲ trial to compare adjuvant chemotherapy with capecitabine and cisplatin versus concurrent chemoradiotherapy in gastric cancer: final report of the adjuvant chemoradiotherapy in stomach tumors trial, including survival and subset analyses[J]. J Clin Oncol, 2015, 33(28): 3130-3136. doi: 10.1200/JCO.2014.58.3930
[15]	ZHU W G, XUA D F, PU J, et al. A randomized, controlled, multicenter study comparing intensity-modulated radiotherapy plus concurrent chemotherapy with chemotherapy alone in gastric cancer patients with D2 resection[J]. Radiother Oncol, 2012, 104(3): 361-366. doi: 10.1016/j.radonc.2012.08.024
[16]	PARK S H, LIM D H, SOHN T S, et al. A randomized phase Ⅲ trial comparing adjuvant single-agent S1, S-1 with oxaliplatin, and postoperative chemoradiation with S-1 and oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial[J]. Ann Oncol, 2021, 32(3): 368-374. doi: 10.1016/j.annonc.2020.11.017
[17]	CATS A, JANSEN E P M, VAN GRIEKEN N C T, et al. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial[J]. Lancet Oncol, 2018, 19(5): 616-628. doi: 10.1016/S1470-2045(18)30132-3
[18]	DE STEUR W O, VAN AMELSFOORT R M, HARTGRINK H H, et al. Adjuvant chemotherapy is superior to chemoradiation after D2 surgery for gastric cancer in the per-protocol analysis of the randomized CRITICS trial[J]. Ann Oncol, 2021, 32(3): 360-367. doi: 10.1016/j.annonc.2020.11.004
[19]	YU C, YU R, ZHU W, et al. Intensity-modulated radiotherapy combined with chemotherapy for the treatment of gastric cancer patients after standard D1/D2 surgery[J]. J Cancer Res Clin Oncol, 2012, 138(2): 255-259. doi: 10.1007/s00432-011-1085-y
[20]	DAI Q, JIANG L, LIN R J, et al. Adjuvant chemoradiotherapy versus chemotherapy for gastric cancer: a meta-analysis of randomized controlled trials[J]. J Surg Oncol, 2015, 111(3): 277-284. doi: 10.1002/jso.23795
[21]	PENG J, WEI Y H, ZHOU F X, et al. D2-resected stage Ⅲc gastric cancer patients benefit from adjuvant chemoradiotherapy[J]. Cancer Med, 2016, 5(10): 2773-2780. doi: 10.1002/cam4.873
[22]	FAN M, LI G C, SHEN L J, et al. Identification of patients with lymph node metastasis from gastric cancer who may benefit from adjuvant chemoradiotherapy after D2 dissection: do N3 patients benefit from additional radiation?[J]. Br J Radiol, 2016, 89(1059): 20150758.
[23]	ZHOU M L, YANG W, WANG Y Q, et al. Adjuvant chemoradiotherapy versus adjuvant chemotherapy for patients with N3 gastric cancer after D2/R0 resection: a retrospective study based on propensity score analyses[J]. Cancer Manag Res, 2019, 11: 4855-4870. doi: 10.2147/CMAR.S195130
[24]	SMYTH E C, VERHEIJ M, ALLUM W, et al. Gastric cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up[J]. Ann Oncol, 2016, 27: v38-v49. doi: 10.1093/annonc/mdw350
[25]	AJANI J A, D’AMICO T A, BENTREM D J, et al. Gastric cancer, version 2.2022, NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw, 2022, 20(2): 167-192. doi: 10.6004/jnccn.2022.0008
[26]	WANG S B, QI W X, CHEN J Y, et al. Competing risk nomogram predicting initial loco-regional recurrence in gastric cancer patients after D2 gastrectomy[J]. Radiat Oncol, 2019, 14(1): 128. doi: 10.1186/s13014-019-1332-y
[27]	LI F X, ZHANG R P, LIANG H, et al. The pattern and risk factors of recurrence of proximal gastric cancer after curative resection[J]. J Surg Oncol, 2013, 107(2): 130-135. doi: 10.1002/jso.23252
[28]	KARPEH M S, LEON L, KLIMSTRA D, et al. Lymph node staging in gastric cancer: is location more important than Number? An analysis of 1 038 patients[J]. Ann Surg, 2000, 232(3): 362-371. doi: 10.1097/00000658-200009000-00008
[29]	NAM H, LIM D H, KIM S, et al. A new suggestion for the radiation target volume after a subtotal gastrectomy in patients with stomach cancer[J]. Int J Radiat Oncol Biol Phys, 2008, 71(2): 448-455. doi: 10.1016/j.ijrobp.2007.09.055
[30]	ZHU H T, ZHAO Y L, WU Y F, et al. Features of metastasis in different lymph node groups and their significance in lymph node dissection in total gastrectomy for gastric cancer[J]. Chin J Oncol, 2008, 30(11): 863-865.
[31]	YU J I, LIM D H, AHN Y C, et al. Effects of adjuvant radiotherapy on completely resected gastric cancer: a radiation oncologist’s view of the artist randomized phase Ⅲ trial[J]. Radiother Oncol, 2015, 117(1): 171-177. doi: 10.1016/j.radonc.2015.08.009
[32]	CHANG J S, LIM J S, NOH S H, et al. Patterns of regional recurrence after curative D2 resection for stage Ⅲ (N3) gastric cancer: implications for postoperative radiotherapy[J]. Radiother Oncol, 2012, 104(3): 367-373. doi: 10.1016/j.radonc.2012.08.017
[33]	YOON H I, CHANG J S, LIM J S, et al. Defining the target volume for post-operative radiotherapy after D2 dissection in gastric cancer by CT-based vessel-guided delineation[J]. Radiother Oncol, 2013, 108(1): 72-77. doi: 10.1016/j.radonc.2013.05.025
[34]	CHANG J S, KIM K H, YOON H I, et al. Locoregional relapse after gastrectomy with D2 lymphadenectomy for gastric cancer[J]. Br J Surg, 2017, 104(7): 877-884. doi: 10.1002/bjs.10502
[35]	李桂超, 章真, 马学军, 等. 胃癌根治术后局部或区域性复发部位规律及复发后放疗疗效在确定术后放疗靶区中的意义[J]. 肿瘤, 2012, 32(10): 794-799.
	LI G C, ZHANG Z, MA X J, et al. The value of patterns of loco-regional recurrence of gastric cancer after curative resection and efficacy of radiation therapy for cancer recurrence in target definition in postoperative radiotherapy[J]. Tumor, 2012, 32(10): 794-799.
[36]	WANG S B, QI W X, CHEN J Y, et al. Identification of patients with locally advanced gastric cancer who may benefit from adjuvant chemoradiotherapy after D2 dissection: a propensity score matching analysis[J]. Front Oncol, 2021, 11: 648978.
[37]	中国医师协会放射肿瘤治疗医师分会, 中华医学会放射肿瘤治疗学分会, 中国抗癌协会肿瘤放疗专业委员会. 中国胃癌放疗指南(2020版)[J]. 中华放射肿瘤学杂志, 2021, 30(10): 989-1001.
	Society of Radiation Oncologists, Chinese Medical Doctor Association; Society of Radiation Oncology, Chinese Medical Association; Professional Committee on Oncology Radiotherapy, Chinese Anti-Cancer Association. Radiotherapy guidelines for gastric cancer in China (2020ed)[J]. Chin J Radiat Oncol, 2021, 30(10): 989-1001.
[38]	SAIKAWA Y, KUBOTA T, KUMAGAI K, et al. Phase Ⅱ study of chemoradiotherapy with S-1 and low-dose cisplatin for inoperable advanced gastric cancer[J]. Int J Radiat Oncol Biol Phys, 2008, 71(1): 173-179. doi: 10.1016/j.ijrobp.2007.09.010
[39]	AJANI J A, KOMAKI R, PUTNAM J B, et al. A three-step strategy of induction chemotherapy then chemoradiation followed by surgery in patients with potentially resectable carcinoma of the esophagus or gastroesophageal junction[J]. Cancer, 2001, 92(2): 279-286. doi: 10.1002/1097-0142(20010715)92:2<279::AID-CNCR1320>3.0.CO;2-2
[40]	XU C P, XIE J, LIANG N, et al. Concurrent involved-field radiotherapy and XELOX in gastric cancer patients with postoperative oligometastatic recurrence[J]. J Cancer Res Ther, 2014, 10 Suppl: 267-271.
[41]	YUAN S T, WANG F L, LIU N, et al. Concurrent involved-field radiotherapy and xelox versus xelox chemotherapy alone in gastric cancer patients with postoperative locoregional recurrence[J]. Am J Clin Oncol, 2015, 38(2): 130-134. doi: 10.1097/COC.0b013e31828f5cb6
[42]	WEI J, LU X F, LIU Q, et al. Efficacy and safety of sintilimab in combination with concurrent chemoradiotherapy for locally advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma (SHARED): study protocol of a prospective, multi-center, single-arm phase 2 trial[J]. Cancer Manag Res, 2022, 14: 2007-2015. doi: 10.2147/CMAR.S355687

Study	Publication year	Country/region	Study design	Tumor site	Group	R0 resection rate	pCR rate	OS
CROSS^[3]	2012	Netherlands	Phase Ⅲ randomized control	Esophagus/esophagogastric junction	Surgery (n=188); Carboplatin+taxol+radiotherapy+surgery (n=178)	69%; 92%	-; 29%	24.0 months (median OS); 49.4 months (median OS)
POET^[4]	2009	Germany	Phase Ⅲ randomized control	Esophagus/gastric cardia	Cisplatin+FU/LV (n=59); Cisplatin+FU/LV+radiotherapy (concurrent chemotherapy: cisplatin+etoposide) (n=60)	70%; 72%	2%; 16%	24.4% (5-year OS rate); 39.5% (5-year OS rate)
NEO-AEGIS	2021 (preliminary result)	International	Phase Ⅲ randomized control	Esophagus/esophagogastric junction	ECF/ECX/EOF/EOX, FLOT (n=184); Carboplatin+taxol+radiotherapy (n=178)	82%; 95%	5%; 16%	56% (3-year OS rate); 57% (3-year OS rate)
TOPGEAR^[5]	2017 (midterm result)	Europe, Canada	Phase Ⅲ randomized control	Esophagogastric junction/gastric	ECF/ECX+surgery+ECF/ECX (n=60); ECF/ECX+radiotherapy+surgery+ECF/ECX (n=60)
PREACT	Ongoing	China	Phase Ⅲ randomized control	Esophagogastric junction/gastric	SOX+chemoradiotherapy+SOX+surgery+SOX; SOX+surgery+SOX
CRITICS Ⅱ	Ongoing	Netherlands	Phase Ⅲ randomized control	Gastric	DOC+surgery; DOC+chemoradiotherapy+surgery; Chemoradiotherapy+surgery
ESOPEC	Ongoing	Germany	Phase Ⅲ randomized control	Gastric	FLOT+surgery+FOLT; Chemoradiotherapy+surgery
5010	Ongoing	China	Phase Ⅲ randomized control	Gastric	Radiotherapy+XELOX+surgery+XELOX; XELOX+surgery+XELOX

Study	Publication year	Country/region	Study design	Group	Surgical method	DFS	OS
INT-0116^[10]	2012	North America	Phase Ⅱ randomized control	Surgery (n=277); Surgery+radiotherapy+FU/LV (n=282)	D1 or D2	19 months (median DFS); 27 months (median DFS)	27 months (median OS); 35 months (median OS)
ARTIST^[13]	2012	Korea	Phase Ⅲ randomized control	Surgery+XP (n=228); Surgery+XP+radiotherapy (n=230)	D2	74.2% (3-year DFS rate); 78.2% (3-year DFS rate)	73% (5-year OS rate); 75% (5-year OS rate)
ARTIST Ⅱ^[15]	2021	Korea	Phase Ⅲ randomized control	Surgery+S-1 (n=182); Surgery+SOX (n=181); Surgery+SOX+radiotherapy (n=183)	D2	64.8% (3-year DFS rate); 74.3% (3-year DFS rate); 72.8% (3-year DFS rate)
CRITICS^[17]	2018	Netherlands	Phase Ⅲ randomized control	Chemotherapy+surgery+chemotherapy (n=393); Chemotherapy+surgery+chemoradiotherapy (n=395)	D1 or above		ITT: no difference; PP: 57.9% and 45.5% (5-year OS rate)