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

Yaqi Li; Xingwen Fan; Qi Yu; Haoyang Zhai; Miao Mo; Jiayao Sun; Jing Mi; Renquan Lu; Jingfang Mao; Jian Chen; Ningyi Ma; Wenxuan Yang; Ji Zhu; Guoliang Jiang; Kailiang Wu

doi:10.1016/j.ijrobp.2022.12.030

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

Int J Radiat Oncol Biol Phys. 2023 Jul 1;116(3):579-589. doi: 10.1016/j.ijrobp.2022.12.030. Epub 2022 Dec 28.

Authors

Yaqi Li¹, Xingwen Fan², Qi Yu³, Haoyang Zhai⁴, Miao Mo⁵, Jiayao Sun⁶, Jing Mi⁴, Renquan Lu³, Jingfang Mao⁷, Jian Chen⁸, Ningyi Ma⁸, Wenxuan Yang⁶, Ji Zhu⁷, Guoliang Jiang⁷, Kailiang Wu⁹

Affiliations

¹ Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai, China; Shanghai Key Laboratory of Radiation Oncology, Shanghai, China; Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, Shanghai, China; Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Clinical Research Center for Radiation Oncology, Shanghai, China.
² Shanghai Key Laboratory of Radiation Oncology, Shanghai, China; Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Clinical Research Center for Radiation Oncology, Shanghai, China.
³ Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China.
⁴ Department of Medical Physics, Fudan University Cancer Hospital, Shanghai, China.
⁵ Department of Cancer Prevention, Fudan University Shanghai Cancer Center, Shanghai, China.
⁶ Shanghai Key Laboratory of Radiation Oncology, Shanghai, China; Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, Shanghai, China; Department of Medical Physics, Shanghai Proton and Heavy Ion Center, Shanghai, China.
⁷ Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai, China; Shanghai Key Laboratory of Radiation Oncology, Shanghai, China; Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, Shanghai, China.
⁸ Shanghai Key Laboratory of Radiation Oncology, Shanghai, China; Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, Shanghai, China; Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Shanghai, China.
⁹ Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai, China; Shanghai Key Laboratory of Radiation Oncology, Shanghai, China; Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, Shanghai, China; Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Clinical Research Center for Radiation Oncology, Shanghai, China. Electronic address: Kailiang.wu@sphic.org.cn.

PMID: 36586495
DOI: 10.1016/j.ijrobp.2022.12.030

Abstract

Purpose: Lymphopenia is a common adverse effect of radiation therapy (RT). Little is known about the difference in lymphopenia between intensity modulated (photon) radiation therapy (IMRT) and proton and carbon ion radiation therapy (PCIRT). This study aimed to investigate lymphopenia differences between IMRT and PCIRT in non-small cell lung cancer (NSCLC).

Methods and materials: 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. Least absolute shrinkage and selection operator analysis was used to select appropriate dosimetric parameters. Univariate and multivariate logistic regression analyses were conducted to identify the predictors of SRL.

Results: Compared with the IMRT group, the PCIRT group was less likely to develop SRL (P < .001). Compared with the non-SRL group, the SRL group showed significant association with poorer OS, with a median survival time of 29.2 versus 15.0 months (P = .046). IMRT was an independent risk factor of SRL (P = .004). A lower ALC before RT (P = .030) and larger planning target volume (PTV) (P = .002) were also significant independent risk factors for SRL. Moreover, the majority of dosimetric parameters of organs at risk in PCIRT were lower than those in IMRT (P < .001). Thoracic vertebra V5 (P = .002) and aorta V5 (P = .026) were identified as independent risk predictors of SRL after adding dosimetric parameters to the regression model.

Conclusions: Compared with IMRT, PCIRT could reduce SRL incidence, possibly by limiting thoracic vertebra and aortic doses, and SRL was associated with poor outcomes in patients with NSCLC.

MeSH terms

Carcinoma, Non-Small-Cell Lung*
Heavy Ion Radiotherapy* / adverse effects
Humans
Lung Neoplasms*
Lymphopenia* / etiology
Proton Therapy* / adverse effects
Protons
Radiotherapy Dosage
Radiotherapy, Intensity-Modulated* / adverse effects
Radiotherapy, Intensity-Modulated* / methods
Spine

Substances

Protons