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 23 publications

(8 citation statements)

References 36 publications

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“…While it is possible that background radiation (estimated to be 5-8% of the prescription dose) could affect lymphocyte populations outside the radiation field, such doses are unlikely to affect erythrocyte, granulocyte, and megakaryocyte precursors in the bone marrow 73 . Interestingly, similar effects on peripheral blood cells have been observed in humans receiving pelvic RT, where again the timing of changes are more suggestive of effects on peripheral circulating blood cells rather than bone marrow suppression 75 , 76 .…”

Section: Discussionsupporting

confidence: 56%

Ablative radiotherapy improves survival but does not cure autochthonous mouse models of prostate and colorectal cancer

et al. 2023

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Background Genetically engineered mouse models (GEMMs) of cancer are powerful tools to study mechanisms of disease progression and therapy response, yet little is known about how these models respond to multimodality therapy used in patients. Radiation therapy (RT) is frequently used to treat localized cancers with curative intent, delay progression of oligometastases, and palliate symptoms of metastatic disease. Methods Here we report the development, testing, and validation of a platform to immobilize and target tumors in mice with stereotactic ablative RT (SART). Xenograft and autochthonous tumor models were treated with hypofractionated ablative doses of radiotherapy. Results We demonstrate that hypofractionated regimens used in clinical practice can be effectively delivered in mouse models. SART alters tumor stroma and the immune environment, improves survival in GEMMs of primary prostate and colorectal cancer, and synergizes with androgen deprivation in prostate cancer. Complete pathologic responses were achieved in xenograft models, but not in GEMMs. Conclusions While SART is capable of fully ablating xenografts, it is unable to completely eradicate disease in GEMMs, arguing that resistance to potentially curative therapy can be modeled in GEMMs.

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Section: Discussionsupporting

confidence: 56%

Ablative radiotherapy improves survival but does not cure autochthonous mouse models of prostate and colorectal cancer

et al. 2023

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“…For 3 Gy BMS the body V 10Gy decreases by 537 cc in comparison to no BMS. The volume of the body exposed to radiation was also shown to be significantly correlated with HT ( 31 ). Furthermore, our findings indicate that the high-risk patients show a larger potential for benefiting in BMS.…”

Section: Discussionmentioning

confidence: 95%

The impact of bone marrow sparing on organs at risk dose for cervical cancer: a Pareto front analysis

Kuipers

Godart

et al. 2023

Front. Oncol.

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Background and purposeTo quantify the increase in bladder and rectum dose of a bone marrow sparing (BMS) VMAT strategy for primary treatment of locally advanced cervical cancer (LACC).Materials and methodsTwenty patients with stage IB-IVA cervical cancer were selected for this study. The whole Pelvic Bones (PB) was taken as substitute for bone marrow. For every patient, Pareto-optimal plans were generated to explore the trade-off between rectum, bladder, and PB mean dose. The PB mean dose was decreased in steps of 1 Gy. For each step, the increase in rectum and bladder mean dose was quantified. The increase in mean dose of other OAR compared to no BMS was constrained to 1 Gy.ResultsIn total, 931 plans of 19 evaluable patients were analyzed. The average [range] mean dose of PB without BMS was 22.8 [20.7-26.2] Gy. When maximum BMS was applied, the average reduction in mean PB dose was 5.4 [3.0-6.8] Gy resulting in an average mean PB dose of 17.5 [15.8-19.8] Gy. For <1 Gy increase in both the bladder and the rectum mean dose, the PB mean dose could be decreased by >2 Gy, >3 Gy, >4 Gy, and >5 Gy for 19/19, 13/19, 5/19, and 1/19 patients, respectively.ConclusionBased on the comprehensive three-dimensional Pareto front analysis, we conclude that 2-5 Gy BMS can be implemented without a clinically relevant increase in mean dose to other OAR. If BMS is too dominant, it results in a large increase in mean dose to other OAR. Therefore, we recommend implementing moderate BMS for the treatment of LACC patients with VMAT.

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

Cited by 23 publications

References 36 publications

Ablative radiotherapy improves survival but does not cure autochthonous mouse models of prostate and colorectal cancer

Ablative radiotherapy improves survival but does not cure autochthonous mouse models of prostate and colorectal cancer

The impact of bone marrow sparing on organs at risk dose for cervical cancer: a Pareto front analysis

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

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