Hematological toxicity in patients with solid malignant tumors treated with radiation – Temporal analysis, dose response and impact on survival

Terrones-Campos, Cynthia; Ledergerber, Bruno; Vogelius, I.R.; Helleberg, Marie; Specht, Lena; Lundgren, Jens D

doi:10.1016/j.radonc.2021.02.029

Cited by 19 publications

(3 citation statements)

References 36 publications

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“…This is especially important since lymphocytes, including T cells, are known to be particularly radiosensitive ( 30 – 33 ). As a matter of fact, one of the side effects commonly observed in radiotherapy patients is radiation-induced lymphopenia, which is characterized by a significant drop in the quantity of lymphocytes circulating in the blood after irradiation ( 34 ). Numerous studies tend to show that severe lymphopenia during radiotherapy is a poor prognostic factor for overall survival and progression-free survival in several tumor locations ( 35 – 38 ).…”

Section: Introductionmentioning

confidence: 99%

Analytical models for external photon beam radiotherapy out-of-field dose calculation: a scoping review

et al. 2023

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A growing body of scientific evidence indicates that exposure to low dose ionizing radiation (< 2 Gy) is associated with a higher risk of developing radio-induced cancer. Additionally, it has been shown to have significant impacts on both innate and adaptive immune responses. As a result, the evaluation of the low doses inevitably delivered outside the treatment fields (out-of-field dose) in photon radiotherapy is a topic that is regaining interest at a pivotal moment in radiotherapy. In this work, we proposed a scoping review in order to identify evidence of strengths and limitations of available analytical models for out-of-field dose calculation in external photon beam radiotherapy for the purpose of implementation in clinical routine. Papers published between 1988 and 2022 proposing a novel analytical model that estimated at least one component of the out-of-field dose for photon external radiotherapy were included. Models focusing on electrons, protons and Monte-Carlo methods were excluded. The methodological quality and potential limitations of each model were analyzed to assess their generalizability. Twenty-one published papers were selected for analysis, of which 14 proposed multi-compartment models, demonstrating that research efforts are directed towards an increasingly detailed description of the underlying physical phenomena. Our synthesis revealed great inhomogeneities in practices, in particular in the acquisition of experimental data and the standardization of measurements, in the choice of metrics used for the evaluation of model performance and even in the definition of regions considered out-of-the-field, which makes quantitative comparisons impossible. We therefore propose to clarify some key concepts. The analytical methods do not seem to be easily suitable for massive use in clinical routine, due to the inevitable cumbersome nature of their implementation. Currently, there is no consensus on a mathematical formalism that comprehensively describes the out-of-field dose in external photon radiotherapy, partly due to the complex interactions between a large number of influencing factors. Out-of-field dose calculation models based on neural networks could be promising tools to overcome these limitations and thus favor a transfer to the clinic, but the lack of sufficiently large and heterogeneous data sets is the main obstacle.

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Section: Introductionmentioning

confidence: 99%

Analytical models for external photon beam radiotherapy out-of-field dose calculation: a scoping review

et al. 2023

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“…There are also studies wherein both radiotherapy and concurrent CRT significantly decreased the mean absolute number of lymphocytes compared to pretreatment levels, but no differences were detected in the characteristics of the lymphopenia induced by the two treatments in cervical cancer [ 9 , 10 ]. A study evaluated the radiation-induced hematological toxicity in patients with solid malignant tumors, which showed that at the end of radiotherapy, the patients with EC had the second lowest lymphocyte counts among common solid tumors, only better than head and neck cancer [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Severe Radiation-Induced Lymphopenia Affects the Outcomes of Esophageal Cancer: A Comprehensive Systematic Review and Meta-Analysis

Dai

Tian

et al. 2022

Cancers

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The aim of the current study was to evaluate the influence of severe radiation-induced lymphopenia (RIL) on the outcomes of esophageal cancer (EC). A systematic review and meta-analysis was performed through the PRISMA guideline. Seventeen studies were included in the current systematic review, with eight included in the meta-analyses. Meta-analyses found that severe RIL was associated with lower pathologic complete response (pCR) rate (odds ratio (OR) = 0.44, 95% confidence interval (CI) = 0.30–0.66, I2 = 0%), inferior overall survival (OS) (hazard ratio (HR) = 1.50, 95% CI = 1.29–1.75, I2 = 6%), and worse progression-free survival (PFS) (HR = 1.70, 95% CI = 1.39–2.07, I2 = 0%) of EC patients. The lymphocyte nadir was found during 4–6 weeks after the start of radiotherapy. The leading dosimetric factors associated with severe RIL included larger PTV, higher dose to heart and body, and higher effective dose to the immune cells (EDIC). Clinical risk factors for RIL mainly comprised lower baseline ALC, higher tumor length and clinical stage, and distal EC. In conclusion, severe RIL might be associated with a lower pCR rate and worse OS and PFS of EC patients. Minimizing the dosimetric risk factors, especially in patients with clinical risk factors, might benefit their outcomes.

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“…Radiation-induced lymphopenia (RIL) describes the depletion of circulating lymphocytes by external radiation fields. RIL has been reported to correlate strongly with overall survival and tumor recurrence in non-small cell lung cancer (Cho et al 2016, 2019, Kim et al 2021, high-grade glioma (Grossman et al 2015, Mendez et al 2016, Rudra et al 2018, pancreatic cancer (Balmanoukian et al 2012, Lee et al 2020, esophageal cancer (So et al 2020, hepatocellular carcinoma (Byun et al 2019, De et al 2021, Terrones-Campos et al 2021, and pediatric medulloblastoma (Grassberger et al 2021). There is presently no direct calculation method for reporting the absorbed dose to circulating lymphocytes, and so various dose-volume metrics have been explored as an indicator for RIL.…”

Section: Introductionmentioning

confidence: 99%

HEDOS—a computational tool to assess radiation dose to circulating blood cells during external beam radiotherapy based on whole-body blood flow simulations

et al. 2021

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We have developed a time-dependent computational framework, hematological dose (HEDOS), to estimate dose to circulating blood cells from radiation therapy treatment fields for any treatment site. Two independent dynamic models were implemented in HEDOS: one describing the spatiotemporal distribution of blood particles (BPs) in organs and the second describing the time-dependent radiation field delivery. A whole-body blood flow network based on blood volumes and flow rates from ICRP Publication 89 was simulated to produce the spatiotemporal distribution of BPs in organs across the entire body using a discrete-time Markov process. Constant or time-varying transition probabilities were applied and their impact on transition time was investigated. The impact of treatment time and anatomical site were investigated using imaging data and dose distributions from a liver cancer and a brain cancer patient. The simulations revealed different dose levels to the circulating blood for brain irradiation compared to liver irradiation even for similar field sizes due to the different blood flow properties of the two organs. The volume of blood receiving any dose (V >0 Gy) after a single radiation fraction increases from 1.2% for a 1 s delivery time to 20.9% for 120 s delivery time for the brain cancer treatment, and from 10% (1 s) to 48.7% (120 s) for a liver cancer treatment. Other measures of the low-dose bath to the circulating blood such as the dose to small volumes of blood (D 2%) decreases with longer delivery time. Furthermore, we demonstrate that the blood dose-volume histogram is highly sensitive to changes in the treatment time, indicating that dynamic modeling of blood flow and radiation fields is necessary to evaluate dose to circulating blood cells for the assessment of radiation-induced lymphopenia. HEDOS is publicly available and allows for the estimation of patient-specific dose to circulating blood cells based on organ DVHs, thus enabling the study of the impact of different treatment plans, dose rates, and fractionation schemes.

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Hematological toxicity in patients with solid malignant tumors treated with radiation – Temporal analysis, dose response and impact on survival

Cited by 19 publications

References 36 publications

Analytical models for external photon beam radiotherapy out-of-field dose calculation: a scoping review

Analytical models for external photon beam radiotherapy out-of-field dose calculation: a scoping review

Severe Radiation-Induced Lymphopenia Affects the Outcomes of Esophageal Cancer: A Comprehensive Systematic Review and Meta-Analysis

HEDOS—a computational tool to assess radiation dose to circulating blood cells during external beam radiotherapy based on whole-body blood flow simulations

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