Age-stratified associations between radiotherapy and SPMs for FPHNC: a population-based cohort study

Abstract Background Second primary malignancies (SPMs) account for over 30% of total deaths in head and neck cancer (HNC) patients. The increasing use of radiotherapy raises concerns about the elevated risk of radiation-associated SPMs. This study aimed to investigate the age-stratified association...

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Main Authors: Yuan-Yuan Li, Qiong Liu, Si-Qi Ying, Xiu-Quan Wu, Xiao-Hui Zhang, Xiao-Mei Xie, Bing-Dong Sui, Yan Jin, Yang Jiao, Franklin R. Tay
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Military Medical Research
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Online Access:https://doi.org/10.1186/s40779-025-00612-4
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author Yuan-Yuan Li
Qiong Liu
Si-Qi Ying
Xiu-Quan Wu
Xiao-Hui Zhang
Xiao-Mei Xie
Bing-Dong Sui
Yan Jin
Yang Jiao
Franklin R. Tay
author_facet Yuan-Yuan Li
Qiong Liu
Si-Qi Ying
Xiu-Quan Wu
Xiao-Hui Zhang
Xiao-Mei Xie
Bing-Dong Sui
Yan Jin
Yang Jiao
Franklin R. Tay
author_sort Yuan-Yuan Li
collection DOAJ
description Abstract Background Second primary malignancies (SPMs) account for over 30% of total deaths in head and neck cancer (HNC) patients. The increasing use of radiotherapy raises concerns about the elevated risk of radiation-associated SPMs. This study aimed to investigate the age-stratified association between radiotherapy and SPM risk in survivors of non-metastatic primary HNC. Methods Using data from the Surveillance, Epidemiology, and End Results program (2004−2015), incidence rate ratios (IRRs) and standardized incidence ratios (SIRs) were evaluated for solid and hematologic SPMs associated with radiotherapy within different age groups. Follow-up for hematologic and solid SPMs began 2 and 5 years, respectively, after the diagnosis of first primary HNC. The IRRs for SPMs were compared between radiotherapy-exposed and unexposed groups using multivariable modified Poisson regression. The SIRs were computed as the ratio of observed cancers in the cohort to expected cases derived from sex-, age-, and calendar year-matched general population incidence rates. Results The study included 75,209 2-year survivors, with 73.2% being male and a median age of 60 years. Of these, 58,063 had survived 5 years or more. Radiotherapy was associated with an increased risk of solid SPMs [IRR = 1.16, 95% confidence interval (CI) 1.08−1.24; P < 0.001]. The associations varied significantly among young (aged 15−39 years), middle-aged (aged 40 − 64 years), and elderly (aged 65−89 years) patients. Specifically, radiotherapy was associated with an increased risk of solid SPMs in middle-aged patients (IRR = 1.21, 95% CI 1.11−1.32; P < 0.001), and a decreased risk of hematologic SPMs in elderly patients (IRR = 0.77, 95% CI 0.60−0.99; P = 0.045). Compared with the general population, young patients had an elevated risk of radiotherapy-associated second primary non-Hodgkin lymphoma (SIR = 4.01, 95% CI 1.47−8.74). Middle-aged patients showed the highest SIR for SPMs in the bones/joints (SIR = 7.72, 95% CI 4.32−12.73), while elderly patients had the highest SIR for second primary esophageal malignancies (SIR = 3.87, 95% CI 2.91−5.05). Males were more likely to develop solid SPMs compared to females. Conclusions This study reveals an age-stratified association between radiotherapy and the risk of SPMs in HNC patients. These findings highlight the importance of considering patient age when making treatment decisions for HNC and suggest that long-term surveillance is necessary for high-risk groups.
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spelling doaj-art-c94bd7f8d277470589c82a464a0b2d7b2025-08-20T03:08:24ZengBMCMilitary Medical Research2054-93692025-05-0112111310.1186/s40779-025-00612-4Age-stratified associations between radiotherapy and SPMs for FPHNC: a population-based cohort studyYuan-Yuan Li0Qiong Liu1Si-Qi Ying2Xiu-Quan Wu3Xiao-Hui Zhang4Xiao-Mei Xie5Bing-Dong Sui6Yan Jin7Yang Jiao8Franklin R. Tay9State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, the Fourth Military Medical UniversityDepartment of General Dentistry, Xiamen University Affiliated Chenggong Hospital, the 73rd Army Hospital of Chinese PLAState Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, the Fourth Military Medical UniversityDepartment of Neurosurgery, Xijing Hospital, the Fourth Military Medical UniversityState Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, the Fourth Military Medical UniversityDepartment of General Dentistry, Xiamen University Affiliated Chenggong Hospital, the 73rd Army Hospital of Chinese PLAState Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, the Fourth Military Medical UniversityState Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, the Fourth Military Medical UniversityDepartment of Stomatology, the Seventh Medical Center of PLA General HospitalDepartment of Endodontics, the Dental College of Georgia, Augusta UniversityAbstract Background Second primary malignancies (SPMs) account for over 30% of total deaths in head and neck cancer (HNC) patients. The increasing use of radiotherapy raises concerns about the elevated risk of radiation-associated SPMs. This study aimed to investigate the age-stratified association between radiotherapy and SPM risk in survivors of non-metastatic primary HNC. Methods Using data from the Surveillance, Epidemiology, and End Results program (2004−2015), incidence rate ratios (IRRs) and standardized incidence ratios (SIRs) were evaluated for solid and hematologic SPMs associated with radiotherapy within different age groups. Follow-up for hematologic and solid SPMs began 2 and 5 years, respectively, after the diagnosis of first primary HNC. The IRRs for SPMs were compared between radiotherapy-exposed and unexposed groups using multivariable modified Poisson regression. The SIRs were computed as the ratio of observed cancers in the cohort to expected cases derived from sex-, age-, and calendar year-matched general population incidence rates. Results The study included 75,209 2-year survivors, with 73.2% being male and a median age of 60 years. Of these, 58,063 had survived 5 years or more. Radiotherapy was associated with an increased risk of solid SPMs [IRR = 1.16, 95% confidence interval (CI) 1.08−1.24; P < 0.001]. The associations varied significantly among young (aged 15−39 years), middle-aged (aged 40 − 64 years), and elderly (aged 65−89 years) patients. Specifically, radiotherapy was associated with an increased risk of solid SPMs in middle-aged patients (IRR = 1.21, 95% CI 1.11−1.32; P < 0.001), and a decreased risk of hematologic SPMs in elderly patients (IRR = 0.77, 95% CI 0.60−0.99; P = 0.045). Compared with the general population, young patients had an elevated risk of radiotherapy-associated second primary non-Hodgkin lymphoma (SIR = 4.01, 95% CI 1.47−8.74). Middle-aged patients showed the highest SIR for SPMs in the bones/joints (SIR = 7.72, 95% CI 4.32−12.73), while elderly patients had the highest SIR for second primary esophageal malignancies (SIR = 3.87, 95% CI 2.91−5.05). Males were more likely to develop solid SPMs compared to females. Conclusions This study reveals an age-stratified association between radiotherapy and the risk of SPMs in HNC patients. These findings highlight the importance of considering patient age when making treatment decisions for HNC and suggest that long-term surveillance is necessary for high-risk groups.https://doi.org/10.1186/s40779-025-00612-4Population-based cohort studyHead and neck cancer (HNC)Second primary malignancy (SPM)RadiotherapyAge
spellingShingle Yuan-Yuan Li
Qiong Liu
Si-Qi Ying
Xiu-Quan Wu
Xiao-Hui Zhang
Xiao-Mei Xie
Bing-Dong Sui
Yan Jin
Yang Jiao
Franklin R. Tay
Age-stratified associations between radiotherapy and SPMs for FPHNC: a population-based cohort study
Military Medical Research
Population-based cohort study
Head and neck cancer (HNC)
Second primary malignancy (SPM)
Radiotherapy
Age
title Age-stratified associations between radiotherapy and SPMs for FPHNC: a population-based cohort study
title_full Age-stratified associations between radiotherapy and SPMs for FPHNC: a population-based cohort study
title_fullStr Age-stratified associations between radiotherapy and SPMs for FPHNC: a population-based cohort study
title_full_unstemmed Age-stratified associations between radiotherapy and SPMs for FPHNC: a population-based cohort study
title_short Age-stratified associations between radiotherapy and SPMs for FPHNC: a population-based cohort study
title_sort age stratified associations between radiotherapy and spms for fphnc a population based cohort study
topic Population-based cohort study
Head and neck cancer (HNC)
Second primary malignancy (SPM)
Radiotherapy
Age
url https://doi.org/10.1186/s40779-025-00612-4
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