Radiation dose and fraction in immunotherapy: one-size regimen does not fit all settings, so how does one choose?
Recent evidence indicates that ionizing radiation can enhance immune responses to tumors. Advances in radiation delivery techniques allow hypofractionated delivery of conformal radiotherapy. Hypofractionation or other modifications of standard fractionation may improve radiation’s ability to promote...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2021-04-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/9/4/e002038.full |
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| author | Marka Crittenden Sandra Demaria C Norman Coleman Jonathan Schoenfeld Arta Monjazeb Samir Khleif Seema Gupta Andrew Sikora Zachary Morris Chandan Guha Stephen Shiao Silvia Chiara Formenti Bhadrasain Vikram Mansoor M Ahmed |
| author_facet | Marka Crittenden Sandra Demaria C Norman Coleman Jonathan Schoenfeld Arta Monjazeb Samir Khleif Seema Gupta Andrew Sikora Zachary Morris Chandan Guha Stephen Shiao Silvia Chiara Formenti Bhadrasain Vikram Mansoor M Ahmed |
| author_sort | Marka Crittenden |
| collection | DOAJ |
| description | Recent evidence indicates that ionizing radiation can enhance immune responses to tumors. Advances in radiation delivery techniques allow hypofractionated delivery of conformal radiotherapy. Hypofractionation or other modifications of standard fractionation may improve radiation’s ability to promote immune responses to tumors. Other novel delivery options may also affect immune responses, including T-cell activation and tumor-antigen presentation changes. However, there is limited understanding of the immunological impact of hypofractionated and unique multifractionated radiotherapy regimens, as these observations are relatively recent. Hence, these differences in radiotherapy fractionation result in distinct immune-modulatory effects. Radiation oncologists and immunologists convened a virtual consensus discussion to identify current deficiencies, challenges, pitfalls and critical gaps when combining radiotherapy with immunotherapy and making recommendations to the field and advise National Cancer Institute on new directions and initiatives that will help further development of these two fields.This commentary aims to raise the awareness of this complexity so that the need to study radiation dose, fractionation, type and volume is understood and valued by the immuno-oncology research community. Divergence of approaches and findings between preclinical studies and clinical trials highlights the need for evaluating the design of future clinical studies with particular emphasis on radiation dose and fractionation, immune biomarkers and selecting appropriate end points for combination radiation/immune modulator trials, recognizing that direct effect on the tumor and potential abscopal effect may well be different. Similarly, preclinical studies should be designed as much as possible to model the intended clinical setting. This article describes a conceptual framework for testing different radiation therapy regimens as separate models of how radiation itself functions as an immunomodulatory ‘drug’ to provide alternatives to the widely adopted ‘one-size-fits-all’ strategy of frequently used 8 Gy×3 regimens immunomodulation. |
| format | Article |
| id | doaj-art-c9d0e7b47c2848329b1c154fd9781046 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2021-04-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-c9d0e7b47c2848329b1c154fd97810462025-02-10T12:35:09ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262021-04-019410.1136/jitc-2020-002038Radiation dose and fraction in immunotherapy: one-size regimen does not fit all settings, so how does one choose?Marka Crittenden0Sandra Demaria1C Norman Coleman2Jonathan Schoenfeld3Arta Monjazeb4Samir Khleif5Seema Gupta6Andrew Sikora7Zachary Morris8Chandan Guha9Stephen Shiao10Silvia Chiara Formenti11Bhadrasain Vikram12Mansoor M Ahmed13Department of Radiation Oncology, Providence Portland Medical Center, Portland, Oregon, USA1Weill Cornell Medicine, Department of Radiation Oncology, New York, NY, USARadiation Research Program, National Cancer Institute Division of Cancer Treatment and Diagnosis, Bethesda, Maryland, USADepartment of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USARadiation Oncology, UC Davis, Davis, California, USAThe Loop Immuno-Oncology Laboratory, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia, USAThe Loop Immuno-Oncology Laboratory, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia, USAHead and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA1University of Wisconsin-Madison, Madison, WI, USARadiation Oncology, Pathology and Urology, and Institute of Onco-Physics, Montefiore Hospital and Medical Center, Bronx, New York, USARadiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California, USADepartment of Radiation Oncology, Weill Cornell Medical College, New York, New York, USARadiation Research Program, National Cancer Institute Division of Cancer Treatment and Diagnosis, Bethesda, Maryland, USARadiation Research Program, National Cancer Institute Division of Cancer Treatment and Diagnosis, Bethesda, Maryland, USARecent evidence indicates that ionizing radiation can enhance immune responses to tumors. Advances in radiation delivery techniques allow hypofractionated delivery of conformal radiotherapy. Hypofractionation or other modifications of standard fractionation may improve radiation’s ability to promote immune responses to tumors. Other novel delivery options may also affect immune responses, including T-cell activation and tumor-antigen presentation changes. However, there is limited understanding of the immunological impact of hypofractionated and unique multifractionated radiotherapy regimens, as these observations are relatively recent. Hence, these differences in radiotherapy fractionation result in distinct immune-modulatory effects. Radiation oncologists and immunologists convened a virtual consensus discussion to identify current deficiencies, challenges, pitfalls and critical gaps when combining radiotherapy with immunotherapy and making recommendations to the field and advise National Cancer Institute on new directions and initiatives that will help further development of these two fields.This commentary aims to raise the awareness of this complexity so that the need to study radiation dose, fractionation, type and volume is understood and valued by the immuno-oncology research community. Divergence of approaches and findings between preclinical studies and clinical trials highlights the need for evaluating the design of future clinical studies with particular emphasis on radiation dose and fractionation, immune biomarkers and selecting appropriate end points for combination radiation/immune modulator trials, recognizing that direct effect on the tumor and potential abscopal effect may well be different. Similarly, preclinical studies should be designed as much as possible to model the intended clinical setting. This article describes a conceptual framework for testing different radiation therapy regimens as separate models of how radiation itself functions as an immunomodulatory ‘drug’ to provide alternatives to the widely adopted ‘one-size-fits-all’ strategy of frequently used 8 Gy×3 regimens immunomodulation.https://jitc.bmj.com/content/9/4/e002038.full |
| spellingShingle | Marka Crittenden Sandra Demaria C Norman Coleman Jonathan Schoenfeld Arta Monjazeb Samir Khleif Seema Gupta Andrew Sikora Zachary Morris Chandan Guha Stephen Shiao Silvia Chiara Formenti Bhadrasain Vikram Mansoor M Ahmed Radiation dose and fraction in immunotherapy: one-size regimen does not fit all settings, so how does one choose? Journal for ImmunoTherapy of Cancer |
| title | Radiation dose and fraction in immunotherapy: one-size regimen does not fit all settings, so how does one choose? |
| title_full | Radiation dose and fraction in immunotherapy: one-size regimen does not fit all settings, so how does one choose? |
| title_fullStr | Radiation dose and fraction in immunotherapy: one-size regimen does not fit all settings, so how does one choose? |
| title_full_unstemmed | Radiation dose and fraction in immunotherapy: one-size regimen does not fit all settings, so how does one choose? |
| title_short | Radiation dose and fraction in immunotherapy: one-size regimen does not fit all settings, so how does one choose? |
| title_sort | radiation dose and fraction in immunotherapy one size regimen does not fit all settings so how does one choose |
| url | https://jitc.bmj.com/content/9/4/e002038.full |
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