Vol 26, No 2 (2021)
Research paper
Published online: 2021-03-04
Chemoradiotherapy or chemotherapy as adjuvant treatment for resected gastric cancer: should we use selection criteria?
Rep Pract Oncol Radiother 2021;26(2):266-280.
Abstract
Background: The management of gastric adenocarcinoma is essentially based on surgery followed by adjuvant treatment. Adjuvant chemotherapy (CT) as well as chemoradiotherapy (CTRT) have proven their effectiveness in survival outcomes compared to surgery alone. However, there is little data comparing the two adjuvant approaches.
This study aimed to compare the prognosis and survival outcomes of patients with gastric adenocarcinoma operated and treated by adjuvant radio-chemotherapy or chemotherapy
Materials and methods: We retrospectively evaluated 80 patients with locally advanced gastric cancer (LGC) who received adjuvant treatment. We compared survival outcomes and patterns of recurrence of 53 patients treated by CTRT and those of 27 patients treated by CT.
Results: After a median follow-up of 38.48 months, CTRT resulted in a significant improvement of the 5-year PFS (60.9% vs. 36%, p = 0.03) and the 5-year OS (55.9% vs. 33%, p = 0.015) compared to adjuvant CT. The 5-year OS was significantly increased by adjuvant CTRT (p = 0.046) in patients with lymph node metastasis, and particularly those with advanced pN stage (p = 0.0078) and high lymph node ratio (LNR) exceeding 25% (p = 0.012). Also, there was a significant improvement of the PFS of patients classified pN2–N3 (p = 0.022) with a high LNR (p = 0.018). CTRT was also associated with improved OS and PFS in patients with lymphovascular and perineural invasion (LVI and PNI) compared to chemotherapy.
Conclusion: There is a particular survival benefit of adding radiotherapy to chemotherapy in patients with selected criteria such as lymph node involvement, high LNR LVI, and PNI.
Keywords: gastric cancerchemoradiotherapychemotherapysurvival
References
- Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2015. CA Cancer J Clin. 2015; 65(1): 5–29.
- McCulloch P, Nita ME, Kazi H, et al. Extended versus limited lymph nodes dissection technique for adenocarcinoma of the stomach. Cochrane Database Syst Rev. 2004(4): CD001964.
- Gunderson L. Gastric cancer — patterns of relapse after surgical resection. Seminars in Radiation Oncology. 2002; 12(2): 150–161.
- Landry J, Tepper J, Wood W, et al. Patterns of failure following curative resection of gastric carcinoma. Int J Radiat Oncol Biol Phys. 1990; 19(6): 1357–1362.
- Macdonald JS, Smalley SR, Benedetti J, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001; 345(10): 725–730.
- Panzini I, Gianni L, Fattori PP, et al. Adjuvant chemotherapy in gastric cancer: a meta-analysis of randomized trials and a comparison with previous meta-analyses. Tumori. 2002; 88(1): 21–27.
- Mari E, Floriani I, Tinazzi A, et al. Efficacy of adjuvant chemotherapy after curative resection for gastric cancer: a meta-analysis of published randomised trials. A study of the GISCAD (Gruppo Italiano per lo Studio dei Carcinomi dell'Apparato Digerente). Ann Oncol. 2000; 11(7): 837–843.
- Janunger KG, Hafström L, Glimelius B. Chemotherapy in gastric cancer: a review and updated meta-analysis. Eur J Surg. 2002; 168(11): 597–608.
- Sakuramoto S, Sasako M, Yamaguchi T, et al. ACTS-GC Group. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007; 357(18): 1810–1820.
- Huang YY, Yang Q, Zhou SW, et al. Postoperative chemoradiotherapy versus postoperative chemotherapy for completely resected gastric cancer with D2 Lymphadenectomy: a meta-analysis. PLoS One. 2013; 8(7): e68939.
- Park SeH, Sohn TS, 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 Clin Oncol. 2015; 33(28): 3130–3136.
- Hamilton SR, Aaltonen LA. Pathology and genetics of tumours of the digestive system. Vol. 48. IARC Press, Lyon 2000.
- Japanese Gastric Cancer Association. Japanese Classification of Gastric Carcinoma — 2nd English Edition. Gastric Cancer. 1998; 1(1): 10–24.
- Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2010 (ver. 3). Gastric Cancer. 2011; 14(2): 113–123.
- Japanese Gastric Cancer Association. Gastric cancer treatment guidelines in Japan (ver. 4). Gastric Cancer. 2014; 20(1): 1–19.
- Smalley SR, Benedetti JK, Haller DG, 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 Clin Oncol. 2012; 30(19): 2327–2333.
- National Institutes of Health. Common terminology criteria for adverse events (CTCAE ) version 4. NIH 2009.
- Bockbrader M, Kim E. Role of intensity-modulated radiation therapy in gastrointestinal cancer. Expert Rev Anticancer Ther. 2009; 9(5): 637–647.
- D'Angelica M, Gonen M, Brennan MF, et al. Patterns of initial recurrence in completely resected gastric adenocarcinoma. Ann Surg. 2004; 240(5): 808–816.
- Lee J, Lim DoH, Kim S, 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(3): 268–273.
- Kim TH, Park SR, Ryu KW, et al. Phase 3 trial of postoperative chemotherapy alone versus chemoradiation therapy in stage III-IV gastric cancer treated with R0 gastrectomy and D2 lymph node dissection. Int J Radiat Oncol Biol Phys. 2012; 84(5): e585–e592.
- Zhu Wg, Xua Df, 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. Radiother Oncol. 2012; 104(3): 361–366.
- Hundahl SA, Macdonald JS, Benedetti J, et al. Southwest Oncology Group and the Gastric Intergroup. Surgical treatment variation in a prospective, randomized trial of chemoradiotherapy in gastric cancer: the effect of undertreatment. Ann Surg Oncol. 2002; 9(3): 278–286.
- Dikken JL, Jansen EPM, Cats A, et al. Impact of the extent of surgery and postoperative chemoradiotherapy on recurrence patterns in gastric cancer. J Clin Oncol. 2010; 28(14): 2430–2436.
- Chang JS, Koom WS, Lee Y, et al. Postoperative adjuvant chemoradiotherapy in D2-dissected gastric cancer: is radiotherapy necessary after D2-dissection? World J Gastroenterol. 2014; 20(36): 12900–12907.
- Kattan MW, Karpeh MS, Mazumdar M, et al. Postoperative nomogram for disease-specific survival after an R0 resection for gastric carcinoma. J Clin Oncol. 2003; 21(19): 3647–3650.
- Chen D, Jiang B, Xing J, et al. Validation of the memorial Sloan-Kettering Cancer Center nomogram to predict disease-specific survival after R0 resection in a Chinese gastric cancer population. PLoS One. 2013; 8(10): e76041.
- Chang JS, Lim JS, Noh SH, et al. Patterns of regional recurrence after curative D2 resection for stage III (N3) gastric cancer: implications for postoperative radiotherapy. Radiother Oncol. 2012; 104(3): 367–373.
- Marchet A, Mocellin S, Ambrosi A, et al. Italian Research Group for Gastric Cancer (IRGGC). The ratio between metastatic and examined lymph nodes (N ratio) is an independent prognostic factor in gastric cancer regardless of the type of lymphadenectomy: results from an Italian multicentric study in 1853 patients. Ann Surg. 2007; 245(4): 543–552.
- Lee SY, Hwang I, Park YS, et al. Metastatic lymph node ratio in advanced gastric carcinoma: a better prognostic factor than number of metastatic lymph nodes? Int J Oncol. 2010; 36(6): 1461–1467.
- Costa WL, Coimbra FJF, Fogaroli RC, et al. Adjuvant chemoradiotherapy after d2-lymphadenectomy for gastric cancer: the role of n-ratio in patient selection. results of a single cancer center. Radiat Oncol. 2012; 7: 169.
- Kim JP, Lee JH, Kim SJ, et al. Clinicopathologic characteristics and prognostic factors in 10 783 patients with gastric cancer. Gastric Cancer. 1998; 1(2): 125–133.
- Kim DH, Kim SuMi, Hyun JK, et al. Changes in postoperative recurrence and prognostic risk factors for patients with gastric cancer who underwent curative gastric resection during different time periods. Ann Surg Oncol. 2013; 20(7): 2317–2327.
- Marrelli D, Stefano ADe, Manzoni Gde, et al. Prediction of Recurrence After Radical Surgery for Gastric Cancer. Ann Surg. 2005; 241(2): 247–255.
- Otsuji E, Kuriu Y, Ichikawa D, et al. Time to death and pattern of death in recurrence following curative resection of gastric carcinoma: analysis based on depth of invasion. World J Surg. 2004; 28(9): 866–869.
- Xue L, Chen XL, Lin PP, et al. Impact of capillary invasion on the prognosis of gastric adenocarcinoma patients: A retrospective cohort study. Oncotarget. 2016; 7(21): 31215–31225.
- Deng J, You Q, Gao Y, et al. Prognostic value of perineural invasion in gastric cancer: a systematic review and meta-analysis. PLoS One. 2014; 9(2): e88907.
- Yu JIl, Lim DoH, Ahn YC, et al. Effects of adjuvant radiotherapy on completely resected gastric cancer: A radiation oncologist's view of the ARTIST randomized phase III trial. Radiother Oncol. 2015; 117(1): 171–177.
- Agolli L, Maurizi Enrici R, Osti MF. Adjuvant radiochemotherapy for gastric cancer: Should we use prognostic factors to select patients? World J Gastroenterol. 2016; 22(3): 1131–1138.
- Dikken JL, van Sandick JW, Swellengrebel HM, et al. Neo-adjuvant chemotherapy followed by surgery and chemotherapy or by surgery and chemoradiotherapy for patients with resectable gastric cancer (CRITICS). BMC Cancer. 2011; 11(6): 329–1013.