“Immunotherapy in cancer, fighting fire with fire”
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Arina, A., et al. (2020). "Radiotherapy and Immunotherapy for Cancer: From “Systemic” to “Multisite”." Clinical Cancer Research 26(12): 2777-2782 GS https://doi.org/10.1158/1078-0432.CCR-19-2034
In the era of cancer immunotherapy, there is significant interest in combining conventional cancer therapies, such as radiotherapy, with drugs that stimulate the immune system. The observation that ionizing radiation applied to murine tumors delays the growth of distant tumors (“abscopal effect”) and that this effect is potentiated by immunostimulatory drugs, led to clinical trials in which often only one lesion is irradiated in combination with immunotherapy drugs. The results of these initial clinical trials combining radio therapy and immunotherapy show that a meaningful abscopal effect is still infrequent. Recent preclinical data suggest that preexistent intratumoral T cells can survive radiation and contribute to its therapeutic effect. In this review, we discuss possible mechanisms underlying the preclinical/clinical discrepancies regarding the abscopal effect, and we propose the irradiation of multiple or all tumor sites in combination with systemic immunotherapy as a possible avenue to increase the efficacy of radio-immunotherapy.
Colciago, R. R., et al. (2023). "Overview of the synergistic use of radiotherapy and immunotherapy in cancer treatment: current challenges and scopes of improvement." Expert Review of Anticancer Therapy 23(2): 135-145
https://www.tandfonline.com/doi/full/10.1080/14737140.2023.2173175
Oncological treatments are changing rapidly due to the advent of several targeted anticancer drugs and regimens. The primary new area of research in oncological medicine is the implementation of a combination of novel therapies and standard care. In this scenario, radioimmunotherapy is one of the most promising fields, as proven by the exponential growth of publications in this context during the last decade. This review provides an overview of the synergistic use of radiotherapy and immunotherapy and addresses questions like the importance of this subject, aspects clinicians look for in patients to administer this combined therapy, individuals who would benefit the most from this treatment, how to achieve abscopal effect and when does radio-immunotherapy become standard clinical practice. Answers to these queries generate further issues that need to be addressed and solved. The abscopal and bystander effects are not utopia, rather physiological phenomena that occur in our bodies. Nevertheless, substantial evidence regarding the combination of radioimmunotherapy is lacking. In conclusion, joining forces and finding answers to all these open questions is of paramount importance.
Jagodinsky, J. C., et al. (2020). "The Promise of Combining Radiation Therapy With Immunotherapy." International Journal of Radiation Oncology*Biology*Physics 108(1): 6-16 https://www.sciencedirect.com/science/article/pii/S0360301620310439.
The development of immunotherapy in oncology builds upon many years of scientific investigation into the cellular mechanics underlying interactions between tumor cells and immune cell populations. The past decade has brought an accelerating pace to the clinical investigation of new immunotherapy agents, particularly in the setting of metastatic disease. The integration of immunotherapy into phase 3 clinical trial design has lagged in settings of advanced locoregional disease, where combination with radiation therapy may be critical. Yet, such may be the settings where immunotherapies have their greatest potential to affect patient survival and achieve curative outcomes. In this review, we discuss the interaction of radiation with the immune system and the potential to augment antitumor immunity through combined-modality approaches that integrate radiation and immunotherapies. The dynamics of cellular and tumor response to radiation offer unique opportunities for beneficial interplay with immunotherapy that may go unrecognized with conventional screening and monotherapy clinical testing of novel pharmaceutical agents. Using immune checkpoint blockade as a primary example, we discuss recent preclinical and clinical studies that illustrate the potential synergy of such therapies in combination with radiation, and we highlight the potential clinical value of such interactions. For various immunotherapy agents, their greatest clinical effect may rest in combination with radiation, and efforts to facilitate systematic investigation of this approach are highly warranted.
Verma, S., et al. (2024). "Immunotherapy and Radiation Therapy Sequencing in Breast Cancer: A Systematic Review." International Journal of Radiation Oncology*Biology*Physics 118(5): 1422-1434 https://www.sciencedirect.com/science/article/pii/S0360301624000063
Purpose In the past decade, immune checkpoint inhibitors (ICIs) have emerged as a treatment option for metastatic breast cancer (BC). More recently, ICIs have been approved in the perioperative setting. This has led to clinical scenarios where radiation therapy (RT) is given concurrently with ICIs. On the other hand, moderate and ultrahypofractionated schedules of RT are being widely adopted in the adjuvant setting, in addition to an increased use of metastasis-directed therapy. Furthermore, RT can modulate the tumor microenvironment and induce a systemic response at nonirradiated sites, an “abscopal effect.” The amplification of antitumor immune response is used as the rationale behind the concomitant use of ICIs and RT. To date, there is a lack of literature on the optimal sequence, timing, dose/fractionation schema, and treated RT volumes with ICIs in patients with BC, especially in the era of ultrahypofractionation. Methods and Materials We conducted a systematic review to delineate the reported treatment details, safety, and efficacy of combining ICI and RT in patients with BC. PubMed, Embase, and Cochrane CENTRAL were searched between 2014 and 2023. Data were extracted to assess the details of ICIs/RT delivery, safety, and efficacy. Results Of the 12 eligible studies, 9 involved patients with metastatic BC. Most studies were phase 1/2, had a small sample size (range, 8-28), and were heterogenous in patient population and reported outcomes. The combination was reported to be safe. We identified 1 study in the perioperative setting, which did a posthoc analysis of safety/efficacy of ICIs in the adjuvant setting with receipt and pattern of RT. Conclusions In conclusion, there are limited data on the dose, timing, fractionation, and volumes of RT in both the adjuvant and metastatic setting in BC. Ongoing/future trials should collect and report such data on RT details, whenever RT is used in combination with ICIs.
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