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

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.

Keywords: GASTROENTEROLOGY; Prognosis; RADIOTHERAPY.

Figure 1. Ratio of radiotherapy (RT) to non-radiotherapy (NRT) patients from 2004 to 2015. Lines with specific colours and shapes represent the use of RT in tumours of different sizes (all sizes, ≤5 cm, >5 cm).

Figure 2. RR and 95% CI for the main second primary malignancies adjusted for gender and age. Analysis of prostate cancer was only for men. RR, relative risk; RT radiotherapy.

Figure 3. Comparison of cumulative incidences of second primary solid cancer, lung cancer, breast cancer, gastrointestinal cancer (except stomach), oesophageal cancer, colorectal cancer, hepatobiliary cancer, pancreatic cancer, prostate cancer, bladder cancer, non-Hodgkin’s lymphoma, haematological cancer and leukaemia between subgroups stratified by radiotherapy use. The Fine and Gray test determined the p values. NRT, non-radiotherapy; RT, radiotherapy.

Figure 4. RR and 95% CI for the main second solid primary cancer among subgroups stratified by different characteristics. The units used for age and follow-up are years and months, respectively. RR, relative risk; RT, radiotherapy.

Figure 5. RR and 95% CI for the main second haematological primary cancer among subgroups stratified by different characteristics. The units used for age and follow-up are years and months, respectively. RR, relative risk; RT, radiotherapy.