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      Radiation recall pneumonitis in the setting of immunotherapy and radiation: a focused review


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          Radiation recall pneumonitis (RRP) is an entity described as pneumonitis localized to a previously irradiated field after exposure to a systemic agent. It has previously been described in the literature in the context of chemotherapeutic agents as well as certain biologics. With immunotherapy taking a more prominent role in the treatment of several different malignancies and its own baseline risk of pneumonitis, it is important to explore the likelihood of RRP, specifically in those patients who have been previously treated with radiation therapy. The current literature regarding RRP with checkpoint inhibitors is reviewed in this article. Alongside this review, we report a case of RRP after pembrolizumab initiation in a patient in our practice.

          Lay abstract

          When patients undergo radiation to the chest there is a risk of inflammation to the lung tissue called pneumonitis. This inflammation can also be a result of certain medications, including checkpoint inhibitors, which are used to treat cancers. There is a specific phenomenon, radiation recall pneumonitis, where patients who receive radiation to the chest followed by checkpoint inhibitors experience pneumonitis only in the lung fields that were exposed to previous radiation. This paper reviews the existing body of literature and describes a case of radiation recall pneumonitis seen in our practice.

          Most cited references23

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          Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial.

          Preclinical studies have found radiotherapy enhances antitumour immune responses. We aimed to assess disease control and pulmonary toxicity in patients who previously received radiotherapy for non-small-cell lung cancer (NSCLC) before receiving pembrolizumab.
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            Combining radiation and immunotherapy: a new systemic therapy for solid tumors?

            With the recent success of checkpoint inhibitors and other immunomodulating agents, there has been renewed interest in the combination of such agents with radiation. The biologic premise behind such a strategy is that the tumor-antigen release achieved by localized radiation will promote specific tumor targeting by the adaptive immune system, which can be augmented further by systemic immune-stimulating agents. In this manner, clinicians hope to induce a phenomenon known as the abscopal effect, whereby localized radiation results in immune-mediated tumor regression in disease sites well outside of the radiation field. Herein, we present a comprehensive overview of the early clinical and preclinical evidence behind this approach.
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              Radiation recall: a well recognized but neglected phenomenon.

              Radiation recall is an inflammatory skin reaction at a previously irradiated field subsequent to the administration of a variety of pharmacologic agents. Although skin has been the major site of radiation recall toxicity, instances involving other organ have been reported. Data for this review were identified by searches of Medline and Cancerlit. The search terms "radiation", "recall", and "toxicity" were used. References identified from within retrieved articles were also used. There was no limitation on year of publication and no abstract forms were included. Only articles published in English were taken into consideration. Idiosyncratic drug hypersensitivity phenomenon is a recent hypothesis which correlates best with the available facts at this moment. The phenomenon may occur days to years after radiotherapy has been completed. The majority of the drugs commonly used in cancer therapy have been involved in the radiation recall phenomenon. A mixed non-specific inflammatory infiltrate seems to be the common histopathologic criteria in previous published reports. Universally, corticosteroids or the use of non-steroidal anti-inflammatory agents, in conjunction with withdrawal of the offending agent, produce prompt improvement. We propose to collect all future radiation recall phenomenon in a Rare Cancer Network database in order to augment our understanding of this rare reaction.

                Author and article information

                Future Science:Open Access
                Future Sci. OA
                Future Science OA
                Future Science Ltd (London, UK )
                10 April 2019
                : 0
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                [1] 1Division of Hematology & Medical Oncology, Donald & Barbara Zucker School of Medicine at Hofstra/Northwell, Lake Success, NY, 11042 USA
                [2] 2Department of Radiation Oncology, Donald & Barbara Zucker School of Medicine at Hofstra/Northwell, Lake Success, NY, 11042 USA
                [3] 3Department of Pathology, Donald & Barbara Zucker School of Medicine at Hofstra/Northwell, Lake Success, NY, 11042 USA
                Author notes
                *Author for correspondence: nseetharamu@ 123456northwell.edu
                © 2019 Future Science Ltd

                This work is licensed under a Creative Commons Attribution 4.0 License

                : 09 November 2018
                : 01 February 2019
                : 10 April 2019
                Self URI (journal page): https://www.future-science.com/loi/fso
                Special Report

                checkpoint inhibitors,immunotherapy,pneumonitis,radiation recall pneumonitis,thoracic radiation


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