Functional dosimetric metrics for predicting radiation-induced lung injury in non-small cell lung cancer patients treated with chemoradiotherapy

Abstract

BackgroundRadiation-induced lung injury (RILI) is an important dose-limiting toxicity during thoracic radiotherapy. The purpose of this study is to investigate single photon emission computed tomography (SPECT) perfusion-weighted functional dose-volume histogram (FDVH) for predicting RILI in non-small cell lung cancer (NSCLC) patients treated with definitive chemoradiotherapy.MethodsFifty-seven locally advanced NSCLC patients receiving chemoradiotherapy were enrolled prospectively. Patients had treatment scans and dose calculations to provide a standard dose-volume histogram (DVH). Fusion of SPECT and computed tomography scans provided perfusion-weighted FDVH and associated functional dosimetric parameters (relative volumes of functional lung receiving more than a threshold dose of 5 – 60 Gy at increments of 5 Gy [FV5 – FV60]). The predictive abilities of FDVH and DVH were calculated and compared based on the area under receiver operating characteristic (ROC) curve (AUC).ResultsThe accumulative incidence of ≥ 2 grade RILI was 19.3% with a median follow-up of 12 months. Univariate analysis showed that the functional (FV5 – FV60) and standard (V5 – V40) parameters were associated with RILI (all value of p < 0.05). Close correlations between a variety of functional and standard parameters were found. By ROC curve analysis, functional metrics (AUCs were 0.784 – 0.869) provided similarly (p value 0.233 – 1.000) predictive outcome to standard metrics (AUCs were 0.695 – 0.902) in lower – median dose level parameters (FV5 – FV40). However, FDVH seemed to add some predictive value in higher dose level, the best statistical significance for comparing FV60 with V60 was 0.693 vs. 0.511 (p = 0.055).ConclusionsFunctional metrics are identified as reliable predictors for RILI, however, this observation still needs to be further verified using a larger sample size.

Framework for radiation pneumonitis risk stratification based on anatomic and perfused lung dosimetry

“…Hoover et al retrospectively reviewed SPECT/CT-based perfusion/ventilation lung parameters of patients undergoing thoracic radiotherapy, and their data suggested a higher sensitivity and specificity with perfused mean lung dose for radiation pneumonitis correlation (AUC = 0.81), compared to standard dose-volume constraints (AUC ≤ 0.73) [22]. Wang et al echoes similar results, showing high correlation of perfusion metrics with radiation-induced lung injury and spatial differences between anatomic lung V 60Gy and perfused lung V 60Gy [23]. Recent data also showed that patients who had perfused-MLD > 16 Gy, perfused V 20Gy > 30%, and perfused V 30Gy > 23% went on to develop radiation pneumonitis [16].…”

“…In addition to investigations on baseline SPECT/CT imaging prior to radiation therapy [16,22,23], other studies have also correlated changes between pre- and post-treatment functional lung imaging and its relationship to radiation pneumonitis. Farr et al noted a higher risk of symptomatic pneumonitis in those patients who had a reduction in perfusion at 3 months post-radiotherapy compared to patients who did not, with a relative risk estimate of 3.6 [24].…”

Early radiation‐induced changes evaluated by intravoxel incoherent motion in the major salivary glands

“…Similarly, a few studies have recently proposed novel models to quantify or predict normal tissue radiation toxicity using functional information from FDG-PET (8), single photon emission computed tomography perfusion (34,35), and DCE-MRI (36). These studies, that propose new metrics as the metabolic dose, functional dose or bio-dose, show an emerging interest toward an innovative approach to RT that integrates into the treatment strategies the individual differences in tumor biology and radiation sensitivity of normal tissues (19)(20)(21)(22).…”

DART-bid (Dose-differentiated accelerated radiation therapy, 1.8 Gy twice daily)–a novel approach for non-resected NSCLC: final results of a prospective study, correlating radiation dose to tumor volume

“…Usually in dose escalation protocols, for reasons of tolerability, doses are determined by dose constraints for normal tissues, not by features relevant for tumor control as e.g. tumor size [3,6,7,17-19]. As a consequence large tumors are often treated with smaller doses than small tumors and presumably high volume tumors are occasionally excluded from enrolment in protocols.…”