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Severe lymphopenia during neoadjuvant chemoradiation for esophageal cancer: A propensity matched analysis of the relative risk of proton versus photon-based radiation therapy.

ABSTRACT: BACKGROUND AND PURPOSE:Circulating lymphocytes are exquisitely sensitive to radiation exposure, even to low scattered doses which can vary drastically between radiation modalities. We compared the relative risk of radiation-induced lymphopenia between intensity modulated radiation therapy (IMRT) or proton beam therapy (PBT) in esophageal cancer (EC) patients undergoing neoadjuvant chemoradiation therapy (nCRT). MATERIAL AND METHODS:EC patients treated with IMRT and PBT were propensity matched based on key clinical variables. Treatment-associated lymphopenia was graded using CTCAE v.4.0. Using matched cohorts, univariate and multivariable multiple logistic regression was used to identify factors associated with increased risk of grade 4 lymphopenia as well as characterize their relative contributions. RESULTS:Among the 480 patients treated with nCRT, 136 IMRT patients were propensity score matched with 136 PBT patients. In the matched groups, a greater proportion of the IMRT patients (55/136, 40.4%) developed grade 4 lymphopenia during nCRT compared with the PBT patients (24/136, 17.6%, P?

SUBMITTER: Shiraishi Y

PROVIDER: S-EPMC5999560 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Severe lymphopenia during neoadjuvant chemoradiation for esophageal cancer: A propensity matched analysis of the relative risk of proton versus photon-based radiation therapy.

Shiraishi Yutaka Y Fang Penny P Xu Cai C Song Juhee J Krishnan Sunil S Koay Eugene J EJ Mehran Reza J RJ Hofstetter Wayne L WL Blum-Murphy Mariela M Ajani Jaffer A JA Komaki Ritsuko R Minsky Bruce B Mohan Radhe R Hsu Charles C CC Hobbs Brian P BP Lin Steven H SH

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 20171214 1

<h4>Background and purpose</h4>Circulating lymphocytes are exquisitely sensitive to radiation exposure, even to low scattered doses which can vary drastically between radiation modalities. We compared the relative risk of radiation-induced lymphopenia between intensity modulated radiation therapy (IMRT) or proton beam therapy (PBT) in esophageal cancer (EC) patients undergoing neoadjuvant chemoradiation therapy (nCRT).<h4>Material and methods</h4>EC patients treated with IMRT and PBT were propen ...[more]

PMID: 29248170

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Project description:PurposeTo 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 materialsWe 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.ResultsModel 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.ConclusionsProton 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.

Project description:PurposeIn patients treated with chemoradiation for esophageal cancer (EC), randomized trial data demonstrate that proton beam therapy (PBT) reduces toxicities and postoperative complications (POCs) compared with intensity-modulated radiation therapy (IMRT). However, whether radiation therapy modality affects postoperative health care resource utilization remains unknown.Materials and methodsWe examined 287 patients with EC who received chemoradiation (prescribed 50.4 Gy/GyE) followed by esophagectomy, including a real-world observational cohort of 237 consecutive patients treated from 2007 to 2013 with PBT (n = 81) versus IMRT (n = 156); and an independent, contemporary comparison cohort of 50 patients from a randomized trial treated from 2012 to 2019 with PBT (n = 21) versus IMRT (n = 29). Postoperative complications were abstracted from medical records. Health care charges were obtained from institutional claims and adjusted for inflation (2021 dollars). Charge differences (Δ = $PBT - $IMRT) were compared by treatment using adjusted generalized linear models with the gamma distribution.ResultsBaseline PBT versus IMRT characteristics were not significantly different. In the observational cohort, during the neoadjuvant chemoradiation phase, health care charges were higher for PBT versus IMRT (Δ = +$71,959; 95% confidence interval [CI], $62,274-$82,138; P < .001). There was no difference in surgical charges (Δ = -$2234; 95% CI, -$6003 to $1695; P = .26). However, during postoperative hospitalization following esophagectomy, health care charges were lower for PBT versus IMRT (Δ = -$25,115; 95% CI, -$37,625 to -$9776; P = .003). In the comparison cohort, findings were analogous: Charges were higher for PBT versus IMRT during chemoradiation (Δ = +$61,818; 95% CI, $49,435-$75,069; P < .001), not different for surgery (Δ = -$4784; 95% CI, -$6439 to $3487; P = .25), and lower for PBT postoperatively (Δ = -$27,048; 95% CI, -$41,974 to -$5300; P = .02). Lower postoperative charges for PBT were especially seen among patients with any POCs in the contemporary comparison (Δ = -$176,448; 95% CI, -$209,782 to -$78,813; P = .02).ConclusionHigher up-front chemoradiation resource utilization for PBT in patients with EC was partially offset postoperatively, moderated by reduction in POC risks. Results extend existing clinical evidence of toxicity reduction with PBT.

Dataset Information

Severe lymphopenia during neoadjuvant chemoradiation for esophageal cancer: A propensity matched analysis of the relative risk of proton versus photon-based radiation therapy.

Publications

Severe lymphopenia during neoadjuvant chemoradiation for esophageal cancer: A propensity matched analysis of the relative risk of proton versus photon-based radiation therapy.

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