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Radiation-induced lung toxicity in non-small-cell lung cancer: Understanding the interactions of clinical factors and cytokines with the dose-toxicity relationship.

ABSTRACT: BACKGROUND AND PURPOSE:Current methods to estimate risk of radiation-induced lung toxicity (RILT) rely on dosimetric parameters. We aimed to improve prognostication by incorporating clinical and cytokine data, and to investigate how these factors may interact with the effect of mean lung dose (MLD) on RILT. MATERIALS AND METHODS:Data from 125 patients treated from 2004 to 2013 with definitive radiotherapy for stages I-III NSCLC on four prospective clinical trials were analyzed. Plasma levels of 30 cytokines were measured pretreatment, and at 2 and 4weeks midtreatment. Penalized logistic regression models based on combinations of MLD, clinical factors, and cytokine levels were developed. Cross-validated estimates of log-likelihood and area under the receiver operating characteristic curve (AUC) were used to assess accuracy. RESULTS:In prognosticating grade 3 or greater RILT by MLD alone, cross-validated log-likelihood and AUC were -28.2 and 0.637, respectively. Incorporating clinical features and baseline cytokine levels increased log-likelihood to -27.6 and AUC to 0.669. Midtreatment cytokine data did not further increase log-likelihood or AUC. Of the 30 cytokines measured, higher levels of 13 decreased the effect of MLD on RILT, corresponding to a lower odds ratio for RILT per Gy MLD, while higher levels of 4 increased the association. CONCLUSIONS:Although the added prognostic benefit from cytokine data in our model was modest, understanding how clinical and biologic factors interact with the MLD-RILT relationship represents a novel framework for understanding and investigating the multiple factors contributing to radiation-induced toxicity.

SUBMITTER: Hawkins PG

PROVIDER: S-EPMC5645039 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Radiation-induced lung toxicity in non-small-cell lung cancer: Understanding the interactions of clinical factors and cytokines with the dose-toxicity relationship.

Hawkins Peter G PG Boonstra Philip S PS Hobson Stephen T ST Hearn Jason W D JWD Hayman James A JA Ten Haken Randall K RK Matuszak Martha M MM Stanton Paul P Kalemkerian Gregory P GP Ramnath Nithya N Lawrence Theodore S TS Schipper Matthew J MJ Spring Kong Feng-Ming FM Jolly Shruti S

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 20170923 1

<h4>Background and purpose</h4>Current methods to estimate risk of radiation-induced lung toxicity (RILT) rely on dosimetric parameters. We aimed to improve prognostication by incorporating clinical and cytokine data, and to investigate how these factors may interact with the effect of mean lung dose (MLD) on RILT.<h4>Materials and methods</h4>Data from 125 patients treated from 2004 to 2013 with definitive radiotherapy for stages I-III NSCLC on four prospective clinical trials were analyzed. Pl ...[more]

PMID: 28947099

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Project description:PurposeDose to normal lung has commonly been linked with radiation-induced lung toxicity (RILT) risk, but incorporating functional lung metrics in treatment planning may help further optimize dose delivery and reduce RILT incidence. The purpose of this study was to investigate the impact of the dose delivered to functional lung regions by analyzing perfusion (Q), ventilation (V), and combined V/Q single-photon-emission computed tomography (SPECT) dose-function metrics with regard to RILT risk in patients with non-small cell lung cancer (NSCLC) patients who received radiation therapy (RT).Methods and materialsSPECT images acquired from 88 patients with locally advanced NSCLC before undergoing conventionally fractionated RT were retrospectively analyzed. Dose was converted to the nominal dose equivalent per 2 Gy fraction, and SPECT intensities were normalized. Regional lung segments were defined, and the average dose delivered to each lung region was quantified. Three functional categorizations were defined to represent low-, normal-, and high-functioning lungs. The percent of functional lung category receiving ≥20 Gy and mean functional intensity receiving ≥20 Gy (iV20) were calculated. RILT was defined as grade 2+ radiation pneumonitis and/or clinical radiation fibrosis. A logistic regression was used to evaluate the association between dose-function metrics and risk of RILT.ResultsBy analyzing V/Q normalized intensities and functional distributions across the population, a wide range in functional capability (especially in the ipsilateral lung) was observed in patients with NSCLC before RT. Through multivariable regression models, global lung average dose to the lower lung was found to be significantly associated with RILT, and Q and V iV20 were correlated with RILT when using ipsilateral lung metrics. Through a receiver operating characteristic analysis, combined V/Q low-function receiving ≥20 Gy (low-functioning V/Q20) in the ipsilateral lung was found to be the best predictor (area under the curce: 0.79) of RILT risk.ConclusionsIrradiation of the inferior lung appears to be a locational sensitivity for RILT risk. The multivariable correlation between ipsilateral lung iV20 and RILT, as well as the association of low-functioning V/Q20 and RILT, suggest that irradiating low-functioning regions in the lung may lead to higher toxicity rates.

Dataset Information

Radiation-induced lung toxicity in non-small-cell lung cancer: Understanding the interactions of clinical factors and cytokines with the dose-toxicity relationship.

Publications

Radiation-induced lung toxicity in non-small-cell lung cancer: Understanding the interactions of clinical factors and cytokines with the dose-toxicity relationship.

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