TY - JOUR
T1 - Lymphocyte-Sparing Radiotherapy
T2 - The Rationale for Protecting Lymphocyte-rich Organs When Combining Radiotherapy With Immunotherapy
AU - Lambin, Philippe
AU - Lieverse, Relinde I. Y.
AU - Eckert, Franziska
AU - Marcus, Damienne
AU - Oberije, Cary
AU - van der Wiel, Alexander M. A.
AU - Guha, Chandan
AU - Dubois, Ludwig J.
AU - Deasy, Joseph O.
N1 - Funding Information:
FE was partly funded by the Else-Kroener-Fresenius Research Foundation under Grant 2015_Kolleg.14. FE has a research collaboration with Merck KgAa. FE has research and educational grants from Elekta, Philips, Siemens, Sennewald. JD is funded by the NIH and the Breast Cancer Research Foundation. Partially supported by NIH Core Grant P30 CA 008748. PL acknowledges financial support from ERC advanced grant (ERC-ADG-2015, no. 694812 - Hypoximmuno) and the European Program H2020-2017 (ImmunoSABR – no. 733008). Conflict of interest: Dr. Philippe Lambin reports, within and outside the submitted work, grants/sponsored research agreements from Varian medical, Oncoradiomics, ptTheragnostic, Health Innovation Ventures and DualTpharma. He received an advisor/presenter fee and/or reimbursement of travel costs/external grant writing fee and/or in kind manpower contribution from Oncoradiomics, BHV, Merck and Convert pharmaceuticals. Dr. Lambin has shares in the company Oncoradiomics SA and Convert pharmaceuticals SA and is co-inventor of two issued patents with royalties on radiomics (PCT/NL2014/050248, PCT/NL2014/050728) licensed to Oncoradiomics and one issue patent on mtDNA (PCT/EP2014/059089) licensed to ptTheragnostic/DNAmito, three non-patentable invention (softwares) licensed to ptTheragnostic/DNAmito, Oncoradiomics and Health Innovation Ventures.
Publisher Copyright:
© 2019
PY - 2020/4
Y1 - 2020/4
N2 - There is now strong clinical and preclinical evidence that lymphocytes, for example, CD8(+) T cells, are key effectors of immunotherapy and that irradiation of large blood vessels, the heart, and lymphoid organs (including nodes, spleen, bones containing bone marrow, and thymus in children) causes transient or persistent lymphopenia. Furthermore, there is extensive clinical evidence, across multiple cancer sites and treatment modalities, that lymphopenia correlates strongly with decreased overall survival. At the moment, we lack quantitative evidence to establish the relationship between dose-volume and dose-rate to critical normal structures and lymphopenia. Therefore, we propose that data should be systematically recorded to characterise a possible quantitative relationship. This might enable us to improve the efficacy of radiotherapy and develop strategies to predict and prevent treatment-related lymphopenia. In anticipation of more quantitative data, we recommend the application of the principle of As Low As Reasonably Achievable to lymphocyte-rich regions for radiotherapy treatment planning to reduce the radiation doses to these structures, thus moving toward "Lymphocyte-Sparing Radiotherapy." (C) 2019 Published by Elsevier Inc.
AB - There is now strong clinical and preclinical evidence that lymphocytes, for example, CD8(+) T cells, are key effectors of immunotherapy and that irradiation of large blood vessels, the heart, and lymphoid organs (including nodes, spleen, bones containing bone marrow, and thymus in children) causes transient or persistent lymphopenia. Furthermore, there is extensive clinical evidence, across multiple cancer sites and treatment modalities, that lymphopenia correlates strongly with decreased overall survival. At the moment, we lack quantitative evidence to establish the relationship between dose-volume and dose-rate to critical normal structures and lymphopenia. Therefore, we propose that data should be systematically recorded to characterise a possible quantitative relationship. This might enable us to improve the efficacy of radiotherapy and develop strategies to predict and prevent treatment-related lymphopenia. In anticipation of more quantitative data, we recommend the application of the principle of As Low As Reasonably Achievable to lymphocyte-rich regions for radiotherapy treatment planning to reduce the radiation doses to these structures, thus moving toward "Lymphocyte-Sparing Radiotherapy." (C) 2019 Published by Elsevier Inc.
KW - RADIATION-INDUCED LYMPHOPENIA
KW - LUNG-CANCER PATIENTS
KW - T-CELL RESPONSES
KW - DOSE-RATE
KW - BREAST-CANCER
KW - FRACTIONATED-IRRADIATION
KW - VOLUME
KW - SUBSETS
KW - HEART
KW - INTERLEUKIN-7
U2 - 10.1016/j.semradonc.2019.12.003
DO - 10.1016/j.semradonc.2019.12.003
M3 - Article
C2 - 32381298
SN - 1053-4296
VL - 30
SP - 187
EP - 193
JO - Seminars in Radiation Oncology
JF - Seminars in Radiation Oncology
IS - 2
ER -