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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:PurposeAdjuvant durvalumab has become a standard treatment after chemoradiation therapy for patients with locally advanced non-small cell lung cancer (LA-NSCLC). Accordingly, predicting radiation pneumonitis (RP) requiring steroidal treatment (steroid-RP) is of utmost importance because steroidal administration is reported to weaken the effectiveness of immunotherapy. However, grade 2 RP was used as an index of RP in previous studies, but it is an ambiguous definition because it includes not only steroid-RP but also a mild cough requiring only a cough medicine. Therefore, in this study, steroid-RP was used for evaluating RP, and the purpose of this study was to investigate predictive factors of steroid-RP, including original simple interstitial lung abnormality scores (ILASs).Methods and materialsA total of 145 patients with LA-NSCLC who received definitive radiation therapy (DRT) in our institution from January 2014 to May 2017 were identified. Original ILASs, performance status, age, respiratory function, Brinkman index, concurrent administration of chemotherapy, and dose-volume histogram metrics of the lung were analyzed to evaluate their association with steroid-RP. Additionally, 3 diagnostic radiologists evaluated the patients' pre-DRT chest computed tomography images and determined the simple ILASs. ILASs were rated as follows: 0: none; 1: abnormality without honeycombing (ground-glass attenuation, fine reticular opacity, and microcysts); and 2: honeycombing.ResultsThe median follow-up period was 729 days. Thirty-one patients (21.4%) experienced steroid-RP. In the univariate analysis, lung V5/V10/VS5, Brinkman index, and ILASs were significant predictive factors of steroid-RP. Additionally, multivariate analysis including Brinkman index ≥840, lung V5 ≥37%, and an ILAS ≥1 revealed that only an ILAS (P = .001) was an independent predictive factor of steroid-RP.ConclusionsThe original simple ILAS was an easy-to-use tool and a significant predictive factor of steroid-RP in DRT in patients with LA-NSCLC.

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

Publications

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

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