Adjuvant Chemoradiotherapy for Gastric Tumors with D2 Dissection: A Controversial Problem
Objectives: What would be the optimal adjuvant therapy in operated gastric and gastro-esophageal junction (GEJ) adenocarcinoma patients who underwent D2 lymph node dissection remains to be a controversial issue in oncology. The objective of this study is to determine disease-free survival (DFS) and overall survival (OS) data in patients with gastric and GEJ adenocarcinoma with D2 dissected who receive adjuvant chemotherapy (CT) and adjuvant chemoradiotherapy (CRT), to examine the adverse effect profiles developed during treatment, to determine whether adding CRT to the treatment impacts the completion of adjuvant chemotherapy.
Methods: Fifty-seven patients older than 18 years of age with D2 dissection, pathologically stage I-IIIC who received adjuvant CT and CRT treatment were included. Patients who were metastatic at the time of diagnosis, received neoadjuvant chemotherapy or CRT, did not have adequate follow-up and whose data could not be reached were excluded from the study.
Results: In the study, while 3-year DFS was 60%, 3-year OS was 62.5%. 3-year OS was 53.3% for those with a performance score of 0-1 after CRT, while 3-year OS was 16% for those with a score of 2-3 (p=0.003). The 3-year DFS was 45% for those with 0-1 eastern cooperative oncology group (ECOG) performance score after CRT, while 3-year DFS was 16% for those with 2-3 (p=0.006). The estimated median OS and DFS were significantly shorter in 15 patients who could not complete adjuvant chemotherapy after CRT (75 months vs. 22 months for OS; p=0.00), (87 vs. 17 months for DFS; p<0.001). The most common adverse effect was fatigue (91%), and the most common hematological adverse effect was anemia (89.5%).
Conclusion: Adding CRT to adjuvant chemotherapy in operated gastric and GEJ cancer patients who underwent D2 lymph node dissection might decrease the overall adjuvant treatment completion rate and the overall performance score of the patients and cause the risk of decreasing the success of adjuvant therapy by impacting the profile of adverse effects.
1.Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69–90.
2. Songun I, Putter H, Kranenbarg EM, Sasako M, van de Velde CJ. Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial. Lancet Oncol 2010;11:439–49.
3. Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, et al; FLOT4-AIO Investigators. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet 2019;393:1948–57.
4. Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 2001;345:725–30.
5. Dai Q, Jiang L, Lin RJ, Wei KK, Gan LL, Deng CH, et al. Adjuvant chemoradiotherapy versus chemotherapy for gastric cancer: a meta-analysis of randomized controlled trials. J Surg Oncol 2015;111:277–84.
6. Lee J, Lim DH, Kim S, Park SH, Park JO, Park YS, et al. Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST trial. J Clin Oncol 2012;30:268–73.
7. National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology. Available at: https://www. nccn.org/professionals/physician_gls. Accessed Oct 14, 2020.
8. Smyth EC, Verheij M, Allum W, Cunningham D, Cervantes A, Arnold D; ESMO Guidelines Committee. Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2016;27:v38–v49.
9. Park SH, Sohn TS, Lee J, Lim DH, Hong ME, Kim KM, 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 Clin Oncol 2015;33:3130–6.
10. Park SH, Lim DH, Sohn TS, Lee J, Zang DY, Kim ST, et al; ARTIST 2 investigators. 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. Ann Oncol 2021;32:368–74.
11. Dikken JL, Jansen EP, Cats A, Bakker B, Hartgrink HH, Kranenbarg EM, et al. Impact of the extent of surgery and postoperative chemoradiotherapy on recurrence patterns in gastric cancer. J Clin Oncol 2010;28:2430–6.
12. Yu C, Yu R, Zhu W, Song Y, Li T. Intensity-modulated radiotherapy combined with chemotherapy for the treatment of gastric cancer patients after standard D1/D2 surgery. J Cancer Res Clin Oncol 2012;138:255–9.
13. Fuchs CS, Niedzwiecki D, Mamon HJ, Tepper JE, Ye X, Swanson RS, et al. Adjuvant chemoradiotherapy with epirubicin, cisplatin, and fluorouracil compared with adjuvant chemoradiotherapy with fluorouracil and leucovorin after curative resection of gastric cancer: results from CALGB 80101 (Alliance). J Clin Oncol 2017;35:3671–7.
14. Jang RW, Caraiscos VB, Swami N, Banerjee S, Mak E, Kaya E, et al. Simple prognostic model for patients with advanced cancer based on performance status. J Oncol Pract 2014;10:e335– 41.