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Abnormal pulmonary function tests predict the development of radiation-induced pneumonitis in advanced non-small cell lung Cancer.

ABSTRACT: BACKGROUND:Radiation pneumonitis (RP) is a frequent complication of concurrent chemoradiotherapy (CCRT) and is associated with severe symptoms that decrease quality of life and might result in pulmonary fibrosis or death. The aim of this study is to identify whether pulmonary function test (PFT) abnormalities may predict RP in non-small cell lung cancer (NSCLC) patients. METHODS:A prospective multi-institutional study was conducted with locally advanced and oligometastatic NSCLC patients. All participants were evaluated at baseline, end of CCRT, week 6, 12, 24, and 48 post-CCRT. They completed forced spirometry with a bronchodilator, body plethysmography, impulse oscillometry, carbon monoxide diffusing capacity (DLCO), molar mass of CO2, six-minute walk test and exhaled fraction of nitric oxide (FeNO). Radiation pneumonitis was assessed with RTOG and CTCAE. The protocol was registered in www.clinicaltrials.gov (NCT01580579), registered April 19, 2012. RESULTS:Fifty-two patients were enrolled; 37 completed one-year follow-up. RP???Grade 2 was present in 11/37 (29%) for RTOG and 15/37 (40%) for CTCAE. Factors associated with RP were age over 60 years and hypofractionated dose. PFT abnormalities at baseline that correlated with the development of RP included lower forced expiratory volume in one second after bronchodilator (p?=?0.02), DLCO (p?=?0.02) and FeNO (p?=?0.04). All PFT results decreased after CCRT and did not return to basal values at follow-up. CONCLUSIONS:FEV1, DLCO and FeNO prior to CCRT predict the development of RP in NSCLC. This study suggests that all patients under CCRT should be assessed by PFT to identify high-risk patients for close follow-up and early treatment.

SUBMITTER: Torre-Bouscoulet L

PROVIDER: S-EPMC5937833 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Abnormal pulmonary function tests predict the development of radiation-induced pneumonitis in advanced non-small cell lung Cancer.

Torre-Bouscoulet L L Muñoz-Montaño W R WR Martínez-Briseño D D Lozano-Ruiz F J FJ Fernández-Plata R R Beck-Magaña J A JA García-Sancho C C Guzmán-Barragán A A Vergara E E Blake-Cerda M M Gochicoa-Rangel L L Maldonado F F Arroyo-Hernández M M Arrieta O O

Respiratory research 20180424 1

<h4>Background</h4>Radiation pneumonitis (RP) is a frequent complication of concurrent chemoradiotherapy (CCRT) and is associated with severe symptoms that decrease quality of life and might result in pulmonary fibrosis or death. The aim of this study is to identify whether pulmonary function test (PFT) abnormalities may predict RP in non-small cell lung cancer (NSCLC) patients.<h4>Methods</h4>A prospective multi-institutional study was conducted with locally advanced and oligometastatic NSCLC p ...[more]

PMID: 29690880

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Project description:BackgroundRadiation pneumonitis and immune-related pneumonitis have been studied independently, but little information has emerged on the interactions between radiation therapy (RT) and immune checkpoint inhibition (ICI). We examine whether RT and ICI are synergistic in causing pneumonitis.MethodsA retrospective cohort was assembled using the Surveillance, Epidemiology, and End Results-Medicare database, including Medicare beneficiaries diagnosed with American Joint Committee on Cancer 7th ed. (AJCC) stages IIIB-IV NSCLC between 2013-2017. Exposures to RT and ICI were determined by evaluating for treatment within 12 months of diagnosis (RT group and ICI group) and for a second exposure (e.g., ICI after RT) within 3 months after the first exposure (RT + ICI group). Untreated controls were matched to treated patients who were diagnosed in the same three-month window. A validated algorithm for identifying cases of pneumonitis in claims data was used to evaluate for the outcome within 6 months after treatment. The primary outcome was the relative excess risk due to interaction (RERI), a quantitative measure of additive interaction between two treatments.ResultsThere were 18,780 patients included in the analysis with 9,345 (49.8%), 7,533 (40.2%), 1,332 (7.1%), and 550 (2.9%) in the control, RT, ICI, and RT + ICI groups, respectively. Relative to controls, the hazards ratios of pneumonitis were 11.5 (95% CI: 7.9 to 17.0), 6.2 (95% CI: 3.8 to 10.3), and 10.7 (95% CI: 6.0 to 19.2) in the RT, ICI, and RT-ICI groups, respectively. The RERIs were -6.1 (95% CI: -13.1 to -0.6, P=0.97) and -4.0 (95% CI: -10.7 to 1.5, P=0.91) in the unadjusted and adjusted analyses, respectively, consistent with no evidence of additive interaction (RERI ≤0) between RT and ICI.ConclusionsIn this study of Medicare beneficiaries with advanced NSCLC, RT and ICI were, at most, additive rather than synergistic in causing pneumonitis. Pneumonitis risk in patients treated with RT and ICI is not more than could be expected from each therapy alone.

Project description:BackgroundPatients undergoing chemoradiation and immune checkpoint inhibitor (ICI) therapy for locally advanced non-small cell lung cancer (NSCLC) experience pulmonary toxicity at higher rates than historical reports. Identifying biomarkers beyond conventional clinical factors and radiation dosimetry is especially relevant in the modern cancer immunotherapy era. We investigated the role of novel functional lung radiomics, relative to functional lung dosimetry and clinical characteristics, for pneumonitis risk stratification in locally advanced NSCLC.MethodsPatients with locally advanced NSCLC were prospectively enrolled on the FLARE-RT trial (NCT02773238). All received concurrent chemoradiation using functional lung avoidance planning, while approximately half received consolidation durvalumab ICI. Within tumour-subtracted lung regions, 110 radiomics features (size, shape, intensity, texture) were extracted on pre-treatment [99mTc]MAA SPECT/CT perfusion images using fixed-bin-width discretization. The performance of functional lung radiomics for pneumonitis (CTCAE v4 grade 2 or higher) risk stratification was benchmarked against previously reported lung dosimetric parameters and clinical risk factors. Multivariate least absolute shrinkage and selection operator Cox models of time-varying pneumonitis risk were constructed, and prediction performance was evaluated using optimism-adjusted concordance index (c-index) with 95% confidence interval reporting throughout.ResultsThirty-nine patients were included in the study and pneumonitis occurred in 16/39 (41%) patients. Among clinical characteristics and anatomic/functional lung dosimetry variables, only the presence of baseline chronic obstructive pulmonary disease (COPD) was significantly associated with the development of pneumonitis (HR 4.59 [1.69-12.49]) and served as the primary prediction benchmark model (c-index 0.69 [0.59-0.80]). Discrimination of time-varying pneumonitis risk was numerically higher when combining COPD with perfused lung radiomics size (c-index 0.77 [0.65-0.88]) or shape feature classes (c-index 0.79 [0.66-0.91]) but did not reach statistical significance compared to benchmark models (p > 0.26). COPD was associated with perfused lung radiomics size features, including patients with larger lung volumes (AUC 0.75 [0.59-0.91]). Perfused lung radiomic texture features were correlated with lung volume (adj R2 = 0.84-1.00), representing surrogates rather than independent predictors of pneumonitis risk.ConclusionsIn patients undergoing chemoradiation with functional lung avoidance therapy and optional consolidative immune checkpoint inhibitor therapy for locally advanced NSCLC, the strongest predictor of pneumonitis was the presence of baseline chronic obstructive pulmonary disease. Results from this novel functional lung radiomics exploratory study can inform future validation studies to refine pneumonitis risk models following combinations of radiation and immunotherapy. Our results support functional lung radiomics as surrogates of COPD for non-invasive monitoring during and after treatment. Further study of clinical, dosimetric, and radiomic feature combinations for radiation and immune-mediated pneumonitis risk stratification in a larger patient population is warranted.

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Abnormal pulmonary function tests predict the development of radiation-induced pneumonitis in advanced non-small cell lung Cancer.

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Abnormal pulmonary function tests predict the development of radiation-induced pneumonitis in advanced non-small cell lung Cancer.

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