Association Between Adjuvant Radiotherapy in Adults with Gastric Cancer and Risk of Second Primary Malignancy: a Retrospective Cohort Study Using the Surveillance, Epidemiology and End Results Database

Overview

Journal BMJ Open

Specialty General Medicine

Date 2025 Feb 12

PMID 39938963

Authors

Zheng Li

Zefeng Li

Chongyuan Sun

Xiaojie Zhang

He Fei

Cheng Xing

Dongbing Zhao

Affiliations

Soon will be listed here.

Abstract

Objectives: This study aims to assess the association between adjuvant radiotherapy and the development of second primary malignancies (SPMs) and identify its determinants in patients who have undergone surgical treatment for gastric cancer.

Design: Retrospective cohort study using the Surveillance, Epidemiology and End Results (SEER) database.

Setting: Cohorts (18 registries, 2000-2018, from SEER) were screened for any malignancy that developed after sufficient latency from diagnosis of surgically treated non-metastatic gastric cancer.

Participants: 24 777 surgically treated gastric cancer cases were included in the cohort. Among them, 6128 patients underwent adjuvant radiotherapy.

Outcome Measures: The cumulative incidence of SPMs was estimated using Fine and Gray's competing risk model and the radiotherapy-correlated risks were calculated using Poisson regression analysis.

Results: Among patients with sufficient latency, there was no significant association between radiotherapy and the risk of developing second primary solid malignancies (relative risk=1.05, 95% CI 0.83 to 1.33) or haematological malignancies (relative risk=1.17, 95% CI 0.62 to 2.11). Interestingly, radiotherapy was associated with a reduced cumulative incidence of second lung and bronchus cancer compared with no radiotherapy, with a 15-year incidence of 1.4%-3.17% (p<0.05). Radiotherapy was not associated with a significant increase in standardised incidence ratios of SPMs.

Conclusions: Adjuvant radiotherapy was not associated with an increased risk of developing SPMs in surgically treated patients with gastric cancer. Clinical trials are warranted to further verify the findings.

References

Berrington de Gonzalez A, Wong J, Kleinerman R, Kim C, Morton L, Bekelman J . Risk of second cancers according to radiation therapy technique and modality in prostate cancer survivors. Int J Radiat Oncol Biol Phys. 2015; 91(2):295-302. PMC: 4484296. DOI: 10.1016/j.ijrobp.2014.10.040. View

. Japanese gastric cancer treatment guidelines 2014 (ver. 4). Gastric Cancer. 2016; 20(1):1-19. PMC: 5215069. DOI: 10.1007/s10120-016-0622-4. View

Yang J, Li Y, Liu Q, Li L, Feng A, Wang T . Brief introduction of medical database and data mining technology in big data era. J Evid Based Med. 2020; 13(1):57-69. PMC: 7065247. DOI: 10.1111/jebm.12373. View

Grandt C, Brackmann L, Poplawski A, Schwarz H, Hummel-Bartenschlager W, Hankeln T . Radiation-response in primary fibroblasts of long-term survivors of childhood cancer with and without second primary neoplasms: the KiKme study. Mol Med. 2022; 28(1):105. PMC: 9450413. DOI: 10.1186/s10020-022-00520-6. View

Dijkstra E, Hospers G, Meershoek-Klein Kranenbarg E, Fleer J, Roodvoets A, Bahadoer R . Quality of life and late toxicity after short-course radiotherapy followed by chemotherapy or chemoradiotherapy for locally advanced rectal cancer - The RAPIDO trial. Radiother Oncol. 2022; 171:69-76. DOI: 10.1016/j.radonc.2022.04.013. View

Hong S, Bi M, Yu H, Yan Z, Wang H . Radiation therapy enhanced therapeutic efficacy of anti-PD1 against gastric cancer. J Radiat Res. 2020; 61(6):851-859. PMC: 7674687. DOI: 10.1093/jrr/rraa077. View

Mohamad O, Tabuchi T, Nitta Y, Nomoto A, Sato A, Kasuya G . Risk of subsequent primary cancers after carbon ion radiotherapy, photon radiotherapy, or surgery for localised prostate cancer: a propensity score-weighted, retrospective, cohort study. Lancet Oncol. 2019; 20(5):674-685. DOI: 10.1016/S1470-2045(18)30931-8. View

Kamran S, Berrington de Gonzalez A, Ng A, Haas-Kogan D, Viswanathan A . Therapeutic radiation and the potential risk of second malignancies. Cancer. 2016; 122(12):1809-21. DOI: 10.1002/cncr.29841. View

Wu W, Li Y, Feng A, Li L, Huang T, Xu A . Data mining in clinical big data: the frequently used databases, steps, and methodological models. Mil Med Res. 2021; 8(1):44. PMC: 8356424. DOI: 10.1186/s40779-021-00338-z. View

10.

Jin J, Tang Y, Hu C, Jiang L, Jiang J, Li N . Multicenter, Randomized, Phase III Trial of Short-Term Radiotherapy Plus Chemotherapy Versus Long-Term Chemoradiotherapy in Locally Advanced Rectal Cancer (STELLAR). J Clin Oncol. 2022; 40(15):1681-1692. PMC: 9113208. DOI: 10.1200/JCO.21.01667. View

11.

Martling A, Smedby K, Birgisson H, Olsson H, Granath F, Ekbom A . Risk of second primary cancer in patients treated with radiotherapy for rectal cancer. Br J Surg. 2016; 104(3):278-287. DOI: 10.1002/bjs.10327. View

12.

Ng A, Bernardo M, Weller E, Backstrand K, Silver B, Marcus K . Second malignancy after Hodgkin disease treated with radiation therapy with or without chemotherapy: long-term risks and risk factors. Blood. 2002; 100(6):1989-96. DOI: 10.1182/blood-2002-02-0634. View

13.

Wu Y, Li Y, Han C, Chong Y, Kang K, Liu Z . Risk of second primary malignancies associated with radiotherapy in prostate cancer patients: competing risk analysis. Future Oncol. 2022; 18(4):445-455. DOI: 10.2217/fon-2021-0332. View

14.

Smyth E, Schoder H, Strong V, Capanu M, Kelsen D, Coit D . A prospective evaluation of the utility of 2-deoxy-2-[(18) F]fluoro-D-glucose positron emission tomography and computed tomography in staging locally advanced gastric cancer. Cancer. 2012; 118(22):5481-8. DOI: 10.1002/cncr.27550. View

15.

Chargari C, Goodman K, Diallo I, Guy J, Rancoule C, Cosset J . Risk of second cancers in the era of modern radiation therapy: does the risk/benefit analysis overcome theoretical models?. Cancer Metastasis Rev. 2016; 35(2):277-88. DOI: 10.1007/s10555-016-9616-2. View

16.

Stiekema J, Trip A, Jansen E, Aarts M, Boot H, Cats A . Does adjuvant chemoradiotherapy improve the prognosis of gastric cancer after an r1 resection? Results from a dutch cohort study. Ann Surg Oncol. 2014; 22(2):581-8. DOI: 10.1245/s10434-014-4032-8. View

17.

Fuchs C, Tomasek J, Yong C, Dumitru F, Passalacqua R, Goswami C . Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2013; 383(9911):31-39. DOI: 10.1016/S0140-6736(13)61719-5. View

18.

Shitara K, Doi T, Dvorkin M, Mansoor W, Arkenau H, Prokharau A . Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2018; 19(11):1437-1448. DOI: 10.1016/S1470-2045(18)30739-3. View

19.

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

20.

Pasqual E, Schonfeld S, Morton L, Villoing D, Lee C, Berrington de Gonzalez A . Association Between Radioactive Iodine Treatment for Pediatric and Young Adulthood Differentiated Thyroid Cancer and Risk of Second Primary Malignancies. J Clin Oncol. 2022; 40(13):1439-1449. PMC: 9061144. DOI: 10.1200/JCO.21.01841. View