Please cite this article in press as: Morais S, et al. Risk and survival of third primary cancers in a population-based cohort of gastric cancer patients. Dig Liver Dis (2018), https://doi.org/10.1016/j.dld.2018.12.003 ARTICLE IN PRESS G Model YDLD-3950; No. of Pages 5 Digestive and Liver Disease xxx (2018) xxx–xxx Contents lists available at ScienceDirect Digestive and Liver Disease journal homepage: www.elsevier.com/locate/dld Oncology Risk and survival of third primary cancers in a population-based cohort of gastric cancer patients Samantha Morais a , Luís Antunes b , Maria José Bento b , Nuno Lunet a,c,* a EPIUnit — Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal b Servic ¸ o de Epidemiologia — Instituto Português de Oncologia do Porto, Porto, Portugal c Departamento de Ciências da Saúde Pública e Forenses e Educac ¸ ão Médica, Faculdade de Medicina da Universidade do Porto, Porto, Portugal a r t i c l e i n f o Article history: Received 21 September 2018 Accepted 3 December 2018 Available online xxx Keywords: Epidemiology Mortality Multiple primary neoplasms Registries Stomach neoplasms a b s t r a c t Background: The growing number of gastric cancers together with improved survival resulted in an increasing population of survivors at risk of multiple primary cancers. Aims: To estimate the 10-year risk and survival of third primary cancers (TPCs) among gastric first primary cancers (FPCs). Methods: Gastric FPCs from the Portuguese North Region Cancer Registry, diagnosed in 2000-2006 (n = 7409), were followed for a TPC (31/12/2012), and for all-cause death (31/12/2017). The cumula- tive incidence of TPCs was estimated. Patients with a TPC were matched (1:1, by sex, age group, years between FPC and second primary cancer [SPC] diagnosis, and SPC location) to FPC + SPC patients without a TPC. Results: Overall, 25 (0.3% of FPCs and 6.8% of SPCs) TPCs were diagnosed. The most common sites were tobacco-related, mainly including digestive organs. Among all FPCs, 10-year cumulative incidence (95% confidence interval [CI]) of a TPC was 0.4% (0.2–0.5%) and among SPCs 7.6% (4.4–10.8%). For TPCs, com- pared to matched patients, age-adjusted hazard ratio (95%CI) for death was 1.68 (0.77–3.67). The 10-year cumulative mortality of TPCs and matched patients was 92.6% and 67.9%, respectively. Conclusions: A clustering of tobacco-related cancers was observed in TPCs, with a 10-year cumulative incidence of 0.4% among FPCs. TPCs had worse survival than patients without a TPC. © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. 1. Introduction Gastric cancer is the fifth most common malignancy in the world and the third leading cause of death from cancer [1]. Though the survival of these patients remains poor [2], an increase has been observed as a result of gradual improvements in diagnosis and treatment [3], leading to a growing number of gastric cancer sur- vivors. These patients are at higher risk of long-term sequelae, including cardiovascular diseases and multiple primary cancers (MPCs) [4]. Although many studies have described the epidemio- logical and clinical characteristics of patients with second primary cancers (SPCs) [4–7], there is a lack of published data addressing the risk and survival of patients with higher order primary can- cers [8]. Despite this, there are studies that show that they are not * Corresponding author at: Departamento de Ciências da Saúde Pública e Forenses e Educac ¸ ão Médica, Faculdade de Medicina da Universidade do Porto, Porto, Portugal. E-mail address: nlunet@med.up.pt (N. Lunet). that uncommon [4,9,10]; in particular, a previous study in Northern Portugal found that 4% of all MPCs were third tumours [5]. However, the risk and survival of TPCs has not been previously investigated among population-based survivors of gastric cancer. Therefore, considering gastric cancer as a model of a cancer with low 5-year survival [2] but which is frequent in Northern Portugal [11] and responsible for a high proportion of SPCs [5], this study aimed to estimate the 10-year risk and survival of third primary cancers (TPCs) among gastric first primary cancer (FPC) patients. 2. Methods A population-based cohort of gastric (International Statistical Classification of Diseases and Related Health Problems 10th Revi- sion [ICD-10] C16 [12]) FPCs (n = 7409) from the North Region Cancer Registry of Portugal (RORENO), diagnosed in 2000-2006 was followed for the diagnosis of MPCs (31/12/2012) and vital status (31/12/2017). MPCs were defined as proposed by the Inter- national Association of Cancer Registries and International Agency for Research on Cancer [13]. These were considered to be SPCs https://doi.org/10.1016/j.dld.2018.12.003 1590-8658/© 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.