Investigating the SPECT Dose-Function Metrics Associated With Radiation-Induced Lung Toxicity Risk in Patients With Non-small Cell Lung Cancer Undergoing Radiation Therapy

Daniel R Owen; Yilun Sun; Philip S Boonstra; Matthew McFarlane; Benjamin L Viglianti; James M Balter; Issam El Naqa; Matthew J Schipper; Caitlin A Schonewolf; Randall K Ten Haken; Feng-Ming S Kong; Shruti Jolly; Martha M Matuszak

doi:10.1016/j.adro.2021.100666

Investigating the SPECT Dose-Function Metrics Associated With Radiation-Induced Lung Toxicity Risk in Patients With Non-small Cell Lung Cancer Undergoing Radiation Therapy

Adv Radiat Oncol. 2021 Feb 7;6(3):100666. doi: 10.1016/j.adro.2021.100666. eCollection 2021 May-Jun.

Authors

Affiliations

¹ Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
² Department of Biostatistics, University of Michigan, Ann Arbor, Michigan.
³ Department of Radiology, University of Michigan, Ann Arbor, Michigan.
⁴ Veterans Administration, Nuclear Medicine Service, Ann Arbor Michigan.
⁵ Hong Kong University Shenzhen Hospital and Queen Mary Hospital, Hong Kong University Li Ka Shing Medical School, Department of Clinical Oncology, Hong Kong.
⁶ Department of Radiation Oncology, Case Western Reserve University, Cleveland, Ohio.

Abstract

Purpose: Dose 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 materials: SPECT 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.

Results: By 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.

Conclusions: Irradiation 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.

Abstract

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