Dosimetric Evaluation of an Abscopal Response in an Oligometastatic Melanoma Patient Receiving Pembrolizumab and Stereotactic Body Radiation (SBRT) at the Same Time
Keywords:
Stereotactic body radiotherapy (SBRT), Dosimetric, Immunotherapy, RadiationAbstract
Recently, preclinical and clinical evidence has shown that a synergy may exist between radiation and immune check-point therapies such as pembrolizumab. Radiation has been shown to activate the immune system, and in combination with immunotherapy may lead to systemic anti-tumor responses. However, the exact dose regimens needed to induce synergistic responses are unclear. Here, we report a dosimetric characterization of a patient treated with stereotactic radiation in combination with immune check-point therapy.
References
Marconi R, Strolin S, Bossi G, Strigari L. A meta-analysis of the abscopal effect in preclinical models: Is the biologically effective dose a relevant physical trigger? PLoS One. 2017; 12(2): e0171559. doi: 10.1371/journal.pone.0171559
Reynders K, Illidge T, Siva S, Chang JY, De Ruysscher D. The abscopal effect of local radiotherapy: Using immunotherapy to make a rare event clinically relevant. Cancer Treat Rev. 2015; 41(6): 503-510. doi: 10.1016/j.ctrv.2015.03.011
Crittenden M, Kohrt H, Levy R, et al. Current clinical trials test-ing combinations of immunotherapy and radiation. Semin Radiat Oncol. 2015; 25(1): 54-64. doi: 10.1016/j.semradonc.2014.07.003
Sharabi A, Kim SS, Kato S, et al. Exceptional response to nivolumab and stereotactic body radiation therapy (SBRT) in neu-roendocrine cervical carcinoma with high tumor mutational bur-den: Management considerations from the center for personalized cancer therapy at UC San Diego Moores Cancer Center. Oncologist. 2017; 22(6): 631-637. doi: 10.1634/theoncologist.2016-0517
Haymaker CL, Kim D, Uemura M, et al. Metastatic melanoma patient had a complete response with clonal expansion after whole brain radiation and PD-1 blockade. Cancer Immunol Res. 2017; 5(2): 100-105. doi: 10.1158/2326-6066.CIR-16-0223
Dewan MZ, Galloway AE, Kawashima N, et al. Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin Cancer Res. 2009; 15(17): 5379-5388. doi: 10.1158/1078-0432.CCR-09-0265
Lugade AA, Moran JP, Gerber SA, Rose RC, Frelinger JG, Lord EM. Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor. J Immunol. 2005; 174(12): 7516-7523. doi: 10.4049/ jimmunol.174.12.7516
Lee Y, Auh SL, Wang Y, et al. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: Changing strategies for cancer treatment. Blood. 2009; 114(3): 589-595. doi: 10.1182/ Sims-Mourtada J, et al blood-2009-02-206870
Klein B, Loven D, Lurie H, et al. The effect of irradiation on ex-pression of HLA class I antigens in human brain tumors in culture. J Neurosurg. 1994; 80(6): 1074-1077. doi: 10.3171/jns.1994.80.6.1074
Santin AD, Hiserodt JC, Fruehauf J, DiSaia PJ, Pecorelli S, Granger GA. Effects of irradiation on the expression of surface antigens in human ovarian cancer. Gynecol Oncol. 1996; 60(3): 468- 474.
Santin AD, Hermonat PL, Hiserodt JC, et al. Effects of irradia-tion on the expression of major histocompatibility complex class I antigen and adhesion costimulation molecules ICAM-1 in human cervical cancer. Int J Radiat Oncol Biol Phys. 1997; 39(3): 737-742. doi: 10.1006/gyno.1996.0075
Ceradini DJ, Kulkarni AR, Callaghan MJ, et al. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 in-duction of SDF-1. Nat Med. 2004; 10(8): 858-864. doi: 10.1038/ nm1075
Kioi M, Vogel H, Schultz G, Hoffman RM, Harsh GR, Brown JM. Inhibition of vasculogenesis, but not angiogenesis, prevents the recurrence of glioblastoma after irradiation in mice. J Clin In-vest. 2010; 120(3): 694-705. doi: 10.1172/JCI40283
Westendorf AM, Skibbe K, Adamczyk A, et al. Hypoxia en-hances immunosuppression by inhibiting CD4+ effector T cell function and promoting treg activity. Cell Physiol Biochem. 2017; 41(4): 1271-1284. doi: 10.1159/000464429
Prakash H, Klug F, Nadella V, Mazumdar V, Schmitz-Winnen-thal H, Umansky L. Low doses of gamma irradiation potentially modifies immunosuppressive tumor microenvironment by retun-ing tumor-associated macrophages: Lesson from insulinoma. Carci-nogenesis. 2016; 37(3): 301-313. doi: 10.1093/carcin/bgw007
Klug F, Prakash H, Huber PE, et al. Low-dose irradiation pro-grams macrophage differentiation to an iNOS(+)/M1 phenotype that orchestrates effective T cell immunotherapy. Cancer Cell. 2013; 24(5): 589-602. doi: 10.1016/j.ccr.2013.09.014
Dovedi SJ, Cheadle EJ, Popple A, et al. Fractionated radiation therapy stimulates anti-tumor immunity mediated by both resi-dent and infiltrating polyclonal T-cell populations when combined with PD1 blockade. Clin Cancer Res. 2017; 23(18): 5514-5526. doi: 10.1158/1078-0432.CCR-16-1673
Schaue D, Ratikan JA, Iwamoto KS, McBride WH. Maximiz-ing tumor immunity with fractionated radiation. Int J Radiat Oncol Biol Phys. 2012; 83(4): 1306-1310. doi: 10.1016/j.ijrobp.2011.09.049
Qu Y, Jin S, Zhang A, et al. Gamma-ray resistance of regulato-ry CD4+CD25+Foxp3+ T cells in mice. Radiat Res. 2010; 173(2): 148-157. doi: 10.1667/RR0978.1
Schaue D, Ratikan JA, Iwamoto KS, McBride WH. Maximizing tumor immunity with fractionated radiation. Int J Radiat Oncol Biol Phys. 83(4): 1306-1310. doi: 10.1016/j.ijrobp.2011.09.049
Greenberg RA. Complex responses to DNA damage. Paper presented at: Epigenetics in Cancer; April 25, 2017; Philadelphia, PA, USA: The Wistar Institute. Submit your article to this journal | https://openventio.org/submit-manuscript/ 4 Sims-Mourtada J, et al
Dovedi SJ, Cheadle EJ, Popple A, et al. Fractionated radiation therapy stimulates anti-tumor immunity mediated by both resi-dent and infiltrating polyclonal T-cell populations when combined with PD1 blockade. Clin Cancer Res. 2017; 23(18): 5514-5526. doi: 10.1158/1078-0432.CCR-16-1673
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
All content published in Cancer Studies and Molecular Medicine (CSMM) is licensed under the Creative Commons Attribution 4.0 International License (CC BY 4.0). This license allows anyone to copy, distribute, transmit, and adapt the work — including for commercial purposes — provided appropriate credit is given to the original author(s) and source.
