Cardiovascular Morbidity Following Definitive Chemoradiotherapy for Lung Cancer in an Appalachian Population

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Lung cancer (n=86). Intervention: Cardiac radiation exposure (Heart V20) vs. Lower cardiac radiation exposure. Primary outcome: Occurrence of any cardiovascular adverse event (CVAE) (HR 1.024, 95% CI 1.005-1.044, p=0.015).

Q: What does this research mean for the field?

Cardiovascular adverse events occur in a majority (59%) of Appalachian patients following definitive chemoradiotherapy for lung cancer, with the risk significantly increased by higher cardiac radiation doses (V20 and V30). Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Vivian Salama; Joseph Schmidlen; John Christopher Knoth; Troy Nguyen; Aaron Naveen Joseph; Matthew Trotta; R Siochi; Raymond R. Raylman; Jeffrey Ryckman; Mohammed Almubarak; Christopher M. Bianco; David A. Clump; Mina F. Hanna; Phillip M. Pifer

doi:10.3390/cancers18172830

September 1, 2026CancersOpen Access

Cardiovascular Morbidity Following Definitive Chemoradiotherapy for Lung Cancer in an Appalachian Population

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Key result

Each 1% increase in heart V20 is linked to ~2% more cardiovascular events after chemoradiotherapy.

HR 1.024
95% CI 1.005-1.044
P=0.015
n=86

Figures

Why the study?

Cardiovascular morbidity following definitive chemoradiotherapy for lung cancer is a major concern in Appalachia due to high rates of smoking and pre-existing cardiovascular disease.

Key Points

To characterize the incidence, clinical spectrum, timing, and predictors of cardiovascular adverse events in Appalachian patients undergoing definitive chemoradiotherapy for lung cancer.
Retrospective cohort study of 86 Appalachian patients with lung cancer treated with definitive chemoradiotherapy between 2013 and 2025.
Cardiovascular adverse events (CVAEs) and overall survival were analyzed using Kaplan–Meier methods and multivariable Cox proportional hazards models.
Exploratory machine-learning classifiers evaluated the predictability of CVAE occurrence and patient mortality.
Fifty-one patients (59%) experienced a post-treatment CVAE, most commonly non-ST-elevation myocardial infarction (29%) and pericardial disease (29%), with an estimated cumulative CVAE occurrence of 28.3% at 1 year and 50.0% at 2 years.
Higher heart V20 (HR, 1.024 per 1% increase; 95% CI, 1.005–1.044; p = 0.015) and heart V30 (HR, 1.031 per 1% increase; 95% CI, 1.004–1.058; p = 0.025) were independently associated with increased CVAE hazard after adjusting for age, cardiovascular comorbidity, and M stage.
Median overall survival was 29 months, and pre-existing cardiovascular comorbidity was significantly associated with higher mortality hazard across models (HR range, 2.16–2.45).

Study Design

Type

Cohort (n=86)

Multicenter

No

Structured PICO

P

Population

86 adult patients with lung cancer treated with definitive chemoradiotherapy in an Appalachian population, followed for a median of 30.5 months.

E

Exposure

Definitive-intent chemoradiotherapy (CRT) to the primary lung tumor and mediastinal nodal metastasis using 3DCRT, IMRT, or VMAT (median RT total dose 60 Gy in 30 fractions), with concurrent systemic therapy (most commonly carboplatin/paclitaxel) and immunotherapy.

O

Outcome

Occurrence of any cardiovascular adverse event (CVAE) during or after radiation treatment (composite of NSTEMI, STEMI, arrhythmia, congestive heart failure, pericardial disease, cardiac death, new cardiology referral for concerning cardiac symptoms, valvular dysfunction, new clinical diagnosis of CAD, and other major structural or functional cardiac abnormalities).composite

Main Result

Hazard Ratio: 1.024 (95% CI 1.005–1.044)

p-value: p=0.015

In a high-risk Appalachian lung cancer cohort, definitive chemoradiotherapy was associated with a 59% incidence of cardiovascular adverse events, with higher cardiac radiation doses (V20, V30) independently predicting increased risk.

Limitations

Retrospective single-institution design
Small sample size
Cardiovascular events aggregated into a composite outcome
Lack of standardized severity grading for CVAEs
Potential confounding from concurrent systemic therapies
Exploratory machine learning models lacked external validation
Retrospective design
Single-institution study
Lack of external validation for machine learning models

Implication

High CVAE rates after chemoradiotherapy may warrant cardiac monitoring in lung cancer; leaves open whether heart V20 constraints improve outcomes.

Abstract

Background/Objectives: Cardiovascular morbidity following definitive chemoradiotherapy (CRT) for lung cancer is a major concern in Appalachia due to high rates of smoking and pre-existing cardiovascular disease. This study characterized the cardiovascular burden following CRT in a real-world Appalachian population. Methods: A retrospective study was conducted among Appalachian patients with lung cancer treated with definitive CRT from 2013 to 2025. Cardiovascular adverse event (CVAE) incidence, spectrum, and temporal distribution were characterized. Kaplan–Meier and Cox regression analyses evaluated time to CVAE and overall survival (OS). Exploratory machine-learning (ML) models assessed CVAE and mortality prediction. Results: Fifty-one patients (59%) experienced a CVAE. NSTEMI (15/51, 29%) and pericardial disease (15/51, 29%) were most frequent, followed by arrhythmia (8/51, 16%). Ischemic events occurred predominantly within the first year, whereas pericardial events were concentrated within 2 years. Median CVAE-free survival was 22.6 months, with estimated cumulative CVAE occurrence of 28.3% at 1 year and 50.0% at 2 years. After adjustment for age, cardiovascular comorbidity, and M stage, heart V20 (HR, 1.024 per 1% increase; 95% CI, 1.005–1.044; p = 0.015) and V30 (HR, 1.031; 95% CI, 1.004–1.058; p = 0.025) were associated with increased CVAE hazard. Median OS was 29 months; pre-existing cardiovascular comorbidity was associated with mortality (HR range, 2.16–2.45). Exploratory ML showed limited CVAE prediction but moderate mortality discrimination after feature selection (maximum AUC, 0.71). Conclusions: Cardiovascular morbidity was common and accumulated over time following definitive CRT in this Appalachian cohort. These findings support attention to baseline cardiovascular risk, cardiac radiation exposure, and longitudinal cardiovascular surveillance.

Discussion

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Cite This Study

Salama et al. (2026) conducted a cohort in Lung cancer (n=86). Cardiac radiation exposure (Heart V20) vs. Lower cardiac radiation exposure was evaluated on Occurrence of any cardiovascular adverse event (CVAE) (HR 1.024, 95% CI 1.005-1.044, p=0.015). In an Appalachian lung cancer cohort, 59% of patients experienced a cardiovascular adverse event following definitive chemoradiotherapy, with each 1% increase in heart V20 associated with a higher hazard of events (HR 1.024).

synapsesocial.com/papers/6a99355b636c6408cfa7d922 https://doi.org/10.3390/cancers18172830

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Cardiovascular Morbidity Following Definitive Chemoradiotherapy for Lung Cancer in an Appalachian Population

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Cardiovascular Morbidity Following Definitive Chemoradiotherapy for Lung Cancer in an Appalachian Population

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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