Journal Article

Severity of radiation pneumonitis, from clinical, dosimetric and biological features: a pilot study

Martínez, José Ignacio, Aso, Samantha, Palmero, Ramon, López, Rosa, Montes, Ana, Cubero, Noelia, Rodríguez, Laura, Guerrero, Thomas, Navarro-Martin, Arturo, Molina, María, Castillo, Edward, Padrones, Susana, Castillo, Richard, Manresa, Federico

2020

Overview

Background and objective Radiation pneumonitis (RP) could be a lethal complication of lung cancer treatment. No reliable predictors of RP severity have been recognized. This prospective pilot study was performed to identify early predictors of high grade lung toxicity and to evaluate clinical, biological or dosimetric features associated with different grades of toxicity. Method Sixteen patients with non-small cell lung cancer with indication of concurrent chemoradiotherapy using 60 Gy/2 Gy/fraction starting at cycle one of platinum based chemotherapy were included. Bronchoalveolar lavage (BAL), pulmonary function testing (PFT), and 18 F-2-fluoro-2-deoxy-D-glucose positron-emission tomography was performed before radiotherapy (RT), after three weeks of treatment, and two months post-RT. For analysis, patients were grouped by grade (low [G1-G2] vs. high [G3-G5]). The two groups were compared to identify predictors of RP. Protein expression BAL and lung tissue metabolism was evaluated in two patients (RP-G1 vs. RP-G3). Categorical variables such as comorbidities, stages and locations were summarized as percentages. Radiation doses, pulmonary function values and time to RP were summarized by medians with ranges or as means with standard deviation. Longitudinal analysis PFT was performed by a T-test. Results All 16 patients developed RP, as follows: G1 (5 pts; 31.3%); G2 (5 pts; 31.3%); G3 (5 pts; 31.3%); and G5 (1 pts; 6.1%). Patients with high grade RP presented significant decrease ( p  = 0.02) in diffusing lung capacity for carbon monoxide (DLCO) after three weeks of RT. No correlation between dosimetric values and RP grades was observed. BAL analysis of the selected patients showed that CXCL-1, CD154, IL-1ra, IL-23, MIF, PAI-1 and IFN-γ were overexpressed in the lungs of the RP-G3 patient, even before treatment. The pre-RT SUVmax value in the RP-G3 patient was non-significantly higher than in the patient with RP-G1. Conclusions RT induces some degree of RP. Our data suggest that decrease in DLCO% is the most sensitive parameter for the early detection of RP. Moreover, we detect biological differences between the two grades of pneumonitis, highlighting the potential value of some cytokines as a prognostic marker for developing high grade lung toxicity. Further multicenter studies with larger sample size are essential to validate these findings.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Aged / Alveoli / Biomedical and Life Sciences / Biomedicine / Bronchoscopy / Bronchus / Cancer Research / Carbon monoxide / Carcinoma, Non-Small-Cell Lung - physiopathology / Carcinoma, Non-Small-Cell Lung - radiotherapy / Care and treatment / CD40L protein / Chemoradiotherapy / Chemotherapy / Clinical Radiation Oncology / Complications and side effects / Cytokines / Cytokines - analysis / Development and progression / Dosimetry / Emission analysis / Female / Forced Expiratory Volume / Glucose / Humans / Imaging / Interleukin 1 receptor antagonist / Interleukin 1 receptors / Interleukin 23 / Lung cancer / Lung diseases / Lung function / Lung Neoplasms - physiopathology / Lung Neoplasms - radiotherapy / Lungs / Male / Medical imaging / Metabolism / Middle Aged / Non-small cell lung cancer / Non-small cell lung carcinoma / Oncology / Parameter sensitivity / Patients / Pilot Projects / Platinum / Pneumonia / Pneumonitis / Positron emission tomography / Prospective Studies / Protein turnover / Proteins / Pulmonary functions / Radiation / Radiation dosage / Radiation pneumonitis / Radiation Pneumonitis - diagnosis / Radiation Pneumonitis - etiology / Radiation therapy / Radiology / Radiotherapy / Radiotherapy Dosage / Respiratory function / Severity of Illness Index / Small cell lung carcinoma / Software / Toxicity / Wound healing / X-rays / γ-Interferon