Vol 27, No 2 (2022)
Review paper
Published online: 2022-02-08
Integrating stereotactic radiotherapy and systemic therapies
Rep Pract Oncol Radiother 2022;27(2):310-317.
Abstract
This paper focuses on stereotactic radiotherapy (SRT) interactions with targeted therapies and immune system modulating agents because SRT inevitably interacts with them in the treatment of oligometastatic patients.
Radiation oncologists need to be aware of the advantages and risks of these interactions which can, on one hand, enhance the effect of therapy or, on the other, potentiate reciprocal toxicities. To date, few prospective studies have evaluated the interactions of SRT with new-generation drugs and data are mainly based on retrospective experiences, which are often related to small sample sizes.
Keywords: stereotactic radiotherapyoligometastasistargeted therapiesimmune system modulating drugsimmunotherapyradiosurgery
References
- Tree AC, Khoo VS, Eeles RA, et al. Stereotactic body radiotherapy for oligometastases. Lancet Oncol. 2013; 14(1): e28–e37.
- Zeng J, Baik C, Bhatia S, et al. Combination of stereotactic ablative body radiation with targeted therapies. Lancet Oncol. 2014; 15(10): e426–e434.
- Arcangeli S, Jereczek-Fossa BA, Alongi F, et al. Combination of novel systemic agents and radiotherapy for solid tumors - part I: An AIRO (Italian association of radiotherapy and clinical oncology) overview focused on treatment efficacy. Crit Rev Oncol Hematol. 2019; 134: 87–103.
- Arcangeli S, Jereczek-Fossa BA, Alongi F, et al. Combination of novel systemic agents and radiotherapy for solid tumors - Part II: An AIRO (Italian association of radiotherapy and clinical oncology) overview focused on treatment toxicity. Crit Rev Oncol Hematol. 2019; 134: 104–119.
- Brown JM, Carlson DJ, Brenner DJ. The tumor radiobiology of SRS and SBRT: are more than the 5 Rs involved? Int J Radiat Oncol Biol Phys. 2014; 88(2): 254–262.
- Guinde J, Carron R, Tomasini P, et al. Bevacizumab Plus Radiosurgery for Nonsquamous Non-Small Cell Lung Cancer Patients with Brain Metastases: Safe Combination? World Neurosurg. 2017; 107: 1047.e1–1047.e4.
- Yomo S, Hayashi M. Salvage stereotactic radiosurgery with adjuvant use of bevacizumab for heavily treated recurrent brain metastases: a preliminary report. J Neurooncol. 2016; 127(1): 119–126.
- Yasuda T, Muragaki Y, Nitta M, et al. Effectiveness of Stereotactic Radiotherapy and Bevacizumab for Recurrent High-Grade Gliomas: A Potential Therapy for Isocitrate Dehydrogenase Wild-Type Recurrent High-Grade Gliomas. World Neurosurg. 2018; 114: e1138–e1146.
- Delishaj D, Ursino S, Pasqualetti F, et al. Bevacizumab for the Treatment of Radiation-Induced Cerebral Necrosis: A Systematic Review of the Literature. J Clin Med Res. 2017; 9(4): 273–280.
- Pollom EL, Deng L, Pai RK, et al. Gastrointestinal Toxicities With Combined Antiangiogenic and Stereotactic Body Radiation Therapy. Int J Radiat Oncol Biol Phys. 2015; 92(3): 568–576.
- Ahluwalia MS, Chao ST, Parsons MW, et al. Phase II trial of sunitinib as adjuvant therapy after stereotactic radiosurgery in patients with 1-3 newly diagnosed brain metastases. J Neurooncol. 2015; 124(3): 485–491.
- Kao J, Chen CT, Tong CCL, et al. Concurrent sunitinib and stereotactic body radiotherapy for patients with oligometastases: final report of a prospective clinical trial. Target Oncol. 2014; 9(2): 145–153.
- Arneson K, Mondschein J, Stavas M, et al. A phase I trial of concurrent sorafenib and stereotactic radiosurgery for patients with brain metastases. J Neurooncol. 2017; 133(2): 435–442.
- Robbins J, Wollner I, Ryu S. Sorafenib induced radiation recall dermatitis after spine radiosurgery. J Radiosurg SBRT. 2011; 1(1): 71–74.
- Sahin B, Mustafayev T, Aydin G, et al. Non-small Cell Lung Cancer with Multiple Brain Metastases Treated with Radiosurgery and Erlotinib: A Case Report. Cureus. 2017; 9(12): e2003.
- Lin CH, Hsu KH, Chang SN, et al. Increased survival with the combination of stereotactic radiosurgery and gefitinib for non-small cell lung cancer brain metastasis patients: a nationwide study in Taiwan. Radiat Oncol. 2015; 10: 127.
- Dasgupta T, Haas-Kogan DA, Yang X, et al. Genotype-dependent cooperation of ionizing radiation with BRAF inhibition in BRAF V600E-mutated carcinomas. Invest New Drugs. 2013; 31(5): 1136–1141.
- Sambade MJ, Peters EC, Thomas NE, et al. Melanoma cells show a heterogeneous range of sensitivity to ionizing radiation and are radiosensitized by inhibition of B-RAF with PLX-4032. Radiother Oncol. 2011; 98(3): 394–399.
- Anker CJ, Grossmann KF, Atkins MB, et al. Avoiding Severe Toxicity From Combined BRAF Inhibitor and Radiation Treatment: Consensus Guidelines from the Eastern Cooperative Oncology Group (ECOG). Int J Radiat Oncol Biol Phys. 2016; 95(2): 632–646.
- Trino E, Mantovani C, Badellino S, et al. Radiosurgery/stereotactic radiotherapy in combination with immunotherapy and targeted agents for melanoma brain metastases. Expert Rev Anticancer Ther. 2017; 17(4): 347–356.
- Mignot F, Ajgal Z, Xu H, et al. Concurrent administration of anti-HER2 therapy and radiotherapy: Systematic review. Radiother Oncol. 2017; 124(2): 190–199.
- Geraud A, Xu HP, Beuzeboc P, et al. Preliminary experience of the concurrent use of radiosurgery and T-DM1 for brain metastases in HER2-positive metastatic breast cancer. J Neurooncol. 2017; 131(1): 69–72.
- Carlson JA, Nooruddin Z, Rusthoven C, et al. Trastuzumab emtansine and stereotactic radiosurgery: an unexpected increase in clinically significant brain edema. Neuro Oncol. 2014; 16(7): 1006–1009.
- Mitsuya K, Watanabe J, Nakasu Y, et al. Expansive hematoma in delayed cerebral radiation necrosis in patients treated with T-DM1: a report of two cases. BMC Cancer. 2016; 16: 391.
- Figura NB, Potluri TK, Mohammadi H, et al. CDK 4/6 inhibitors and stereotactic radiation in the management of hormone receptor positive breast cancer brain metastases. J Neurooncol. 2019; 144(3): 583–589.
- Mole RH. Whole body irradiation; radiobiology or medicine? Br J Radiol. 1953; 26(305): 234–241.
- Durante M, Reppingen N, Held KD. Immunologically augmented cancer treatment using modern radiotherapy. Trends Mol Med. 2013; 19(9): 565–582.
- Formenti SC, Demaria S. Combining radiotherapy and cancer immunotherapy: a paradigm shift. J Natl Cancer Inst. 2013; 105(4): 256–265.
- Demaria S, Bhardwaj N, McBride WH, et al. Combining radiotherapy and immunotherapy: a revived partnership. Int J Radiat Oncol Biol Phys. 2005; 63(3): 655–666.
- Tsai CS, Chen FH, Wang CC, et al. Macrophages from irradiated tumors express higher levels of iNOS, arginase-I and COX-2, and promote tumor growth. Int J Radiat Oncol Biol Phys. 2007; 68(2): 499–507.
- Chiang CS, Fu SY, Wang SC, et al. Irradiation promotes an m2 macrophage phenotype in tumor hypoxia. Front Oncol. 2012; 2: 89.
- Schaue D, Xie MW, Ratikan JA, et al. Regulatory T cells in radiotherapeutic responses. Front Oncol. 2012; 2: 90.
- Dong H, Strome SE, Salomao DR, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002; 8(8): 793–800.
- Yu X, Harden K, Gonzalez LC, et al. The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells. Nat Immunol. 2009; 10(1): 48–57.
- Formenti SC, Demaria S. Radiation therapy to convert the tumor into an in situ vaccine. Int J Radiat Oncol Biol Phys. 2012; 84(4): 879–880.
- Josefsson SE, Beiske K, Blaker YN, et al. TIGIT and PD-1 Mark Intratumoral T Cells with Reduced Effector Function in B-cell Non-Hodgkin Lymphoma. Cancer Immunol Res. 2019; 7(3): 355–362.
- Yovino S, Kleinberg L, Grossman SA, et al. The etiology of treatment-related lymphopenia in patients with malignant gliomas: modeling radiation dose to circulating lymphocytes explains clinical observations and suggests methods of modifying the impact of radiation on immune cells. Cancer Invest. 2013; 31(2): 140–144.
- Schad MD, Dutta SW, Muller DM, et al. Radiation-related Lymphopenia after Pelvic Nodal Irradiation for Prostate Cancer. Adv Radiat Oncol. 2019; 4(2): 323–330.
- Palma DA, Louie AV, Rodrigues GB. New Strategies in Stereotactic Radiotherapy for Oligometastases. Clin Cancer Res. 2015; 21(23): 5198–5204.
- 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.
- Golden EB, Demaria S, Schiff PB, et al. An abscopal response to radiation and ipilimumab in a patient with metastatic non-small cell lung cancer. Cancer Immunol Res. 2013; 1(6): 365–372.
- Postow MA, Callahan MK, Barker CA, et al. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med. 2012; 366(10): 925–931.
- Vanpouille-Box C, Alard A, Aryankalayil MJ, et al. DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity. Nat Commun. 2017; 8: 15618.
- Salama AKS, Postow MA, Salama JK. Irradiation and immunotherapy: From concept to the clinic. Cancer. 2016; 122(11): 1659–1671.
- Knisely JPS, Yu JB, Flanigan J, et al. Radiosurgery for melanoma brain metastases in the ipilimumab era and the possibility of longer survival. J Neurosurg. 2012; 117(2): 227–233.
- Kiess AP, Wolchok JD, Barker CA, et al. Stereotactic radiosurgery for melanoma brain metastases in patients receiving ipilimumab: safety profile and efficacy of combined treatment. Int J Radiat Oncol Biol Phys. 2015; 92(2): 368–375.
- Fang P, Jiang W, Allen P, et al. Radiation necrosis with stereotactic radiosurgery combined with CTLA-4 blockade and PD-1 inhibition for treatment of intracranial disease in metastatic melanoma. J Neurooncol. 2017; 133(3): 595–602.
- Kim PH, Suh CH, Kim HoS, et al. Immune checkpoint inhibitor therapy may increase the incidence of treatment-related necrosis after stereotactic radiosurgery for brain metastases: a systematic review and meta-analysis. Eur Radiol. 2021; 31(6): 4114–4129.
- 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.
- Dovedi SJ, Adlard AL, Lipowska-Bhalla G, et al. Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade. Cancer Res. 2014; 74(19): 5458–5468.
- Luke JJ, Lemons JM, Karrison TG, et al. Safety and Clinical Activity of Pembrolizumab and Multisite Stereotactic Body Radiotherapy in Patients With Advanced Solid Tumors. J Clin Oncol. 2018; 36(16): 1611–1618.
- Britschgi C, Riesterer O, Burger IA, et al. Report of an abscopal effect induced by stereotactic body radiotherapy and nivolumab in a patient with metastatic non-small cell lung cancer. Radiat Oncol. 2018; 13(1): 102.
- Borius PY, Régis J, Carpentier A, et al. Safety of radiosurgery concurrent with systemic therapy (chemotherapy, targeted therapy, and/or immunotherapy) in brain metastases: a systematic review. Cancer Metastasis Rev. 2021; 40(1): 341–354.
- Sha CM, Lehrer EJ, Hwang C, et al. Toxicity in combination immune checkpoint inhibitor and radiation therapy: A systematic review and meta-analysis. Radiother Oncol. 2020; 151: 141–148.
- Mazzola R, Jereczek-Fossa BA, Franceschini D, et al. Oligometastasis and local ablation in the era of systemic targeted and immunotherapy. Radiat Oncol. 2020; 15(1): 92.
- Luo LY, O'Hara MH, Mitchell TC, et al. Combining Radiation with Immunotherapy: The University of Pennsylvania Experience. Semin Radiat Oncol. 2020; 30(2): 173–180.
- Kroeze SGC, Fritz C, Schaule J, et al. Toxicity of concurrent stereotactic radiotherapy and targeted therapy or immunotherapy: A systematic review. Cancer Treat Rev. 2017; 53(3): 25–37.
- Breen WG, Leventakos K, Dong H, et al. Radiation and immunotherapy: emerging mechanisms of synergy. J Thorac Dis. 2020; 12(11): 7011–7023.
- Lubas MJ, Kumar SS. The Combined Use of SBRT and Immunotherapy-a Literature Review. Curr Oncol Rep. 2020; 22(12): 117.
- Olson R, Mathews L, Liu M, et al. Stereotactic ablative radiotherapy for the comprehensive treatment of 1-3 Oligometastatic tumors (SABR-COMET-3): study protocol for a randomized phase III trial. BMC Cancer. 2020; 20(1): 380.
- Palma DA, Olson R, Harrow S, et al. Stereotactic ablative radiotherapy for the comprehensive treatment of 4-10 oligometastatic tumors (SABR-COMET-10): study protocol for a randomized phase III trial. BMC Cancer. 2019; 19(1): 816.
- Gaya A, Hawkins M, Kirby A. on behalf of the CORE Trial Management Group. CORE — Randomised trial of conventional care versus radioablation [stereotactic body radiotherapy (SBRT)] for extracranial metastases. Radiosurgery Society’s SRS/SBRT Scientific Meeting, Florida 2016 : USA.
- Guckenberger M, Lievens Y, Bouma AB, et al. Characterisation and classification of oligometastatic disease: a European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer consensus recommendation. Lancet Oncol. 2020; 21(1): e18–e28.