A framework for modeling radiation induced lymphopenia in radiotherapy

Jin, Jian-Yue; Mereniuk, Todd R.; Yalamanchali, Anirudh; Wang, Weili; Machtay, Mitchell; Kong, Feng-Ming; Ellsworth, Susannah G.

doi:10.1016/j.radonc.2019.11.014

Cited by 35 publications

(28 citation statements)

References 26 publications

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“…Saito et al reported that whole-body low-dose irradiation volume was associated with grade 3 or higher RIL in patients undergoing palliative RT (23). The significance of dosimetric correlations suggests that circulating lymphocytes may be considered an organ at risk (OAR) during RT planning (20,24). More detailed modeling of radiation to lymphocytes as an immunosuppression model is ongoing in our group.…”

Section: Discussionmentioning

confidence: 89%

Risk factors for radiation induced lymphopenia in patients with breast cancer receiving adjuvant radiotherapy

Chen

Zhang

et al. 2021

Ann Transl Med

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Background: This study aimed to investigate radiation-induced lymphopenia and its potential risk factors in patients with breast cancer receiving adjuvant radiotherapy.Methods: Breast cancer patients received adjuvant radiotherapy (RT) at our hospital with peripheral lymphocyte counts (PLC) at pre-and immediately after RT (post-RT) were eligible. The primary endpoints were any grade of lymphopenia post-RT and nadir-PLC/pre-PLC <0.8. Patient characteristics, tumor factors, and treatment factors were collected for risk assessment. Data are presented as mean and 95% confidence interval (CI) unless otherwise specified. Matched analysis was used to compare the statistical significance between different RT techniques.Results: A total of 735 consecutive patients met the study criteria. The mean PLC was 1.58×10 9 /L before and 0.99×10 9 /L post-RT (P<0.001). At the end of RT, 60.5% of patients had lymphopenia. Univariate and multivariable logistic analyses showed that RT technique involving RapidArc, mean lung dose, and chemotherapy were significant risk factors (P<0.05) for lymphopenia. RT technique was the only significant risk factor (P<0.05) for nadir-PLC/pre-PLC <0.8. Patients treated with RapidArc had a significantly greater reduction of PLC along with greater V5 of the lungs, even after matching mean lung dose and radiated volume.Conclusions: Lymphopenia is common in patients with breast cancer after adjuvant RT. RT technique is the only significant factor for lymphopenia and nadir-PLC/pre-PLC <0.8, suggesting the significance of RT technique choice to minimize lymphopenia and improve treatment outcomes.

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Section: Discussionmentioning

confidence: 89%

Risk factors for radiation induced lymphopenia in patients with breast cancer receiving adjuvant radiotherapy

Chen

Zhang

et al. 2021

Ann Transl Med

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“…This is not the case in which organs (eg, spleen in the upper abdomen) may have a concentration of lymphocytes, and may have a greater influence on lymphocyte depletion than the body as a whole. Several studies have investigated blood flow models to estimate the dose to the circulating blood during treatment for some cancer sites, such as the lung and brain [ 31 , 32 ]. These models could be used to determine more precise dose to circulating lymphocytes as an input to piecewise linear model to better understand radiation-induced lymphopenia in future studies.…”

Section: Discussionmentioning

confidence: 99%

Radiation-Induced Lymphopenia Risks of Photon Versus Proton Therapy for Esophageal Cancer Patients

Ebrahimi

Lim

Liu

et al. 2021

International Journal of Particle Therapy

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Purpose To assess possible differences in radiation-induced lymphocyte depletion for esophageal cancer patients being treated with the following 3 treatment modalities: intensity-modulated radiation therapy (IMRT), passive scattering proton therapy (PSPT), and intensity-modulated proton therapy (IMPT). Methods and Materials We used 2 prediction models to estimate lymphocyte depletion based on dose distributions. Model I used a piecewise linear relationship between lymphocyte survival and voxel-by-voxel dose. Model II assumes that lymphocytes deplete exponentially as a function of total delivered dose. The models can be fitted using the weekly absolute lymphocyte counts measurements collected throughout treatment. We randomly selected 45 esophageal cancer patients treated with IMRT, PSPT, or IMPT at our institution (15 per modality) to demonstrate the fitness of the 2 models. A different group of 10 esophageal cancer patients who had received PSPT were included in this study of in silico simulations of multiple modalities. One IMRT and one IMPT plan were created, using our standards of practice for each modality, as competing plans to the existing PSPT plan for each patient. We fitted the models by PSPT plans used in treatment and predicted absolute lymphocyte counts for IMRT and IMPT plans. Results Model validation on each modality group of patients showed good agreement between measured and predicted absolute lymphocyte counts nadirs with mean squared errors from 0.003 to 0.023 among the modalities and models. In the simulation study of IMRT and IMPT on the 10 PSPT patients, the average predicted absolute lymphocyte count (ALC) nadirs were 0.27, 0.35, and 0.37 K/μL after IMRT, PSPT, and IMPT treatments using Model I, respectively, and 0.14, 0.22, and 0.33 K/μL using Model II. Conclusions Proton plans carried a lower predicted risk of lymphopenia after the treatment course than did photon plans. Moreover, IMPT plans outperformed PSPT in terms of predicted lymphocyte preservation.

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“…Chen et al reviewed multiple phase I/II clinical trials and reported that RIL reduced the systemic disease control in patients treated with radioimmunotherapy, suggesting that RIL inhibited the immune responses in these patients [ 63 ]. RIL also predicted for a decreased OS in this study [ 63 ], suggesting that the compartment of circulating lymphocytes should be considered an organ at risk [ 64 , 65 ]. To estimate the dose to circulating blood cells from RT, investigators have developed a publicly available time-dependent computational framework, HEDOS (HEmatological DOSe), that evaluates the effect of different treatment plans, dose rates, and fractionation schemes on circulating blood cells [ 66 ].…”

Section: Rt Effects On Circulating Lymphocytes In Hnsccmentioning

confidence: 74%

A Rational Approach to Unilateral Neck RT for Head and Neck Cancers in the Era of Immunotherapy

Chin

Schiff

Brenneman

et al. 2021

Cancers

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Radiotherapy plays an important role in the definitive and adjuvant treatment of head and neck squamous cell carcinoma (HNSCC). However, standard courses of radiation therapy may contribute to the depletion of circulating lymphocytes and potentially attenuate optimal tumor antigen presentation that may be detrimental to the efficacy of novel immunotherapeutic agents. This review explores the advantages of restricting radiation to the primary tumor/tumor bed and ipsilateral elective neck as it pertains to the evolving field of immunotherapy.

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A framework for modeling radiation induced lymphopenia in radiotherapy

Cited by 35 publications

References 26 publications

Risk factors for radiation induced lymphopenia in patients with breast cancer receiving adjuvant radiotherapy

Risk factors for radiation induced lymphopenia in patients with breast cancer receiving adjuvant radiotherapy

Radiation-Induced Lymphopenia Risks of Photon Versus Proton Therapy for Esophageal Cancer Patients

A Rational Approach to Unilateral Neck RT for Head and Neck Cancers in the Era of Immunotherapy

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