Combining spatially fractionated radiation therapy (SFRT) and immunotherapy opens new rays of hope for enhancing therapeutic ratio

Lu, Qiuxia; Yan, Weisi; Zhu, Alan; Tubin, Slavisa; Mourad, Waleed F.; Yang, Jun

doi:10.1016/j.ctro.2023.100691

Cited by 4 publications

(1 citation statement)

References 127 publications

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“…Those technics use grids or tiny collimated beams to create a heterogenous pattern of hot spots and cold spots within the tumor target, with the aim of being able to safely deliver higher radiation doses per fraction. The impact on the incidence of lymphopenia remains to be explored but spatially fractionated radiotherapy is presumed to combine favorably with immune-checkpoint inhibitors ( 92 ), suggesting enhanced immune fitness compared with homogenous beam distribution. One hypothesis—mainly built on nonclinical experiments—is that the heterogeneous peak and valley dose deposition may induce higher levels of tumor immunologic cell death that can propagate to underirradiated tumor cells in the vicinity through by-stander effects while relatively sparing the regionally circulating immune effector cells ( 93, 94 ).…”

Section: The Optimal Radiotherapy Settingsmentioning

confidence: 99%

Translational Frontiers and Clinical Opportunities of Immunologically Fitted Radiotherapy

Morel,

Robert,

Paragios

et al. 2024

Clinical Cancer Research

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Ionising radiations can have a wide range of impacts on tumour-immune interactions, which are being studied with the greatest interest and at an accelerating pace by the medical community. Despite its undeniable immunostimulatory potential, it clearly appears that radiotherapy as it is prescribed and delivered nowadays often alters the host’s immunity towards a suboptimal state. This may impair the full recovery of a sustained and efficient anti-tumour immunosurveillance post-treatment. An emerging concept is arising from this awareness and consists in re-considering the way of designing radiation treatment plannings, notably by taking into account the individualised risks of deleterious radio-induced immune alteration that can be deciphered from the planned beam trajectory through lymphocyte-rich organs. In this review, we critically appraise key aspects to consider while planning immunologically-fitted radiotherapy, including the challenges linked to the identification of new dose constraints to immune-rich structures. We also discuss how pharmacological immunomodulation could be advantageously used in combination with radiotherapy to compensate for the radio-induced loss, for example with (i) agonists of interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15 or IL-21, similarly to G-CSF being used for the prophylaxis of severe chemo-induced neutropenia, or with (ii) myeloid-derived suppressive cells (MDSC) blockers.

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Section: The Optimal Radiotherapy Settingsmentioning

confidence: 99%

Translational Frontiers and Clinical Opportunities of Immunologically Fitted Radiotherapy

Morel,

Robert,

Paragios

et al. 2024

Clinical Cancer Research

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Mechanistic in silico explorations of the immunogenic and synergistic effects of radiotherapy and immunotherapy: a critical review

Ng,

MacKinnon,

Cook

et al. 2024

Phys Eng Sci Med

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Immunotherapy is a rapidly evolving field, with many models attempting to describe its impact on the immune system, especially when paired with radiotherapy. Tumor response to this combination involves a complex spatiotemporal dynamic which makes either clinical or pre-clinical in vivo investigation across the resulting extensive solution space extremely difficult. In this review, several in silico models of the interaction between radiotherapy, immunotherapy, and the patient’s immune system are examined. The study included only mathematical models published in English that investigated the effects of radiotherapy on the immune system, or the effect of immuno-radiotherapy with immune checkpoint inhibitors. The findings indicate that treatment efficacy was predicted to improve when both radiotherapy and immunotherapy were administered, compared to radiotherapy or immunotherapy alone. However, the models do not agree on the optimal schedule and fractionation of radiotherapy and immunotherapy. This corresponds to relevant clinical trials, which report an improved treatment efficacy with combination therapy, however, the optimal scheduling varies between clinical trials. This discrepancy between the models can be attributed to the variation in model approach and the specific cancer types modeled, making the determination of the optimum general treatment schedule and model challenging. Further research needs to be conducted with similar data sets to evaluate the best model and treatment schedule for a specific cancer type and stage.

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A Comparative Study on Radiosensitivity of Canine Osteosarcoma Cell Lines Subjected to Spatially Fractionated Radiotherapy

Khan,

Scholl,

Henry

et al. 2024

Radiation Research

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Canine appendicular osteosarcoma (OSCA) is a highly aggressive cancer, constituting 85% of all bone tumors in dogs, predominantly affecting larger breeds and exhibiting a high metastatic rate. This disease also shares many genomic similarities with human osteosarcomas, making it an ideal comparative model for treatment discovery. In this study, we characterized the radiobiological properties of several OSCA cell lines when subjected to spatially fractionated radiation therapy (SFRT) and chemotherapy. Specifically, we focused on lower (peak) doses from SFRT ranging from 1 to 10 Gy. These canine OSCA cell lines serve as useful models for osteosarcoma research that can be utilized to find translational treatments for both canine and human patients. This study reaffirms established clinical wisdom regarding the notoriously radioresistant profile of osteosarcomas but additionally offers compelling evidence supporting SFRT as a promising treatment option that could be used in conjunction with other cytotoxic agents.

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Combining spatially fractionated radiation therapy (SFRT) and immunotherapy opens new rays of hope for enhancing therapeutic ratio

Cited by 4 publications

References 127 publications

Translational Frontiers and Clinical Opportunities of Immunologically Fitted Radiotherapy

Translational Frontiers and Clinical Opportunities of Immunologically Fitted Radiotherapy

Mechanistic in silico explorations of the immunogenic and synergistic effects of radiotherapy and immunotherapy: a critical review

A Comparative Study on Radiosensitivity of Canine Osteosarcoma Cell Lines Subjected to Spatially Fractionated Radiotherapy

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