Proton and Carbon Ion Radiation Therapy Decreased Severe Lymphopenia by Reducing Thoracic Vertebra and Aortic Doses in Non-Small Cell Lung Cancer Versus Intensity Modulated Radiation Therapy

Abstract

Lymphopenia is a common adverse effect of radiotherapy (RT). Little is known about the difference in lymphopenia between intensity-modulated (photon) radiation therapy (IMRT) and proton and carbon ion radiotherapy (PCIRT). This study aimed to investigate lymphopenia differences between IMRT and PCIRT in non-small cell lung cancer (NSCLC). Clinical and dosimetric parameters were collected from 343 patients who received definitive IMRT or PCIRT for NSCLC. Severe lymphopenia (SRL) was defined as an absolute lymphocyte count (ALC) ≤0.5*103 cells/μL. Overall survival (OS) was analyzed using the Kaplan-Meier method. Propensity score matching was performed between the IMRT and PCIRT groups. LASSO analysis was used to select appropriate dosimetric parameters. Univariate and multivariate logistic regression analyses were conducted to identify the predictors of SRL. Compared to the IMRT group, the PCIRT group was less likely to develop SRL (p <0.001). Compared with non-SRL group, SRL group showed significant association with poorer OS, with median survival time of 29.2 vs. 15.0 months (p = 0.046). IMRT was an independent risk factor of SRL (p = 0.004). A lower ALC before RT (p = 0.030) and larger planning target volume (PTV) (p = 0.002) were also significant independent risk factors for SRL. Moreover, the majority of dosimetric parameters of organ at risks in PCIRT were lower than those in IMRT (p <0.001). Thoracic vertebra V5 (p =0.002) and aorta V5 (p =0.026) were identified as independent risk predictors of SRL after adding dosimetric parameters to the regression model. Compared with IMRT, PCIRT could reduce the SRL incidence, possibly by limiting thoracic vertebra and aortic doses, and SRL was associated with poor outcomes in NSCLC patients.