Immunomodulatory Effects of Stereotactic Body Radiation Therapy: Preclinical Insights and Clinical Opportunities

Marciscano, Ariel E.; Haimovitz‐Friedman, Adriana; Lee, Percy; Tran, Phuoc T.; Tomé, Wolfgang A.; Guha, Chandan; Kong, Feng-Ming Spring; Sahgal, Arjun; Naqa, Issam El; Rimner, Andreas; Marks, Lawrence B.; Formenti, Silvia C.; DeWeese, Theodore L.

doi:10.1016/j.ijrobp.2019.02.046

Cited by 63 publications

(65 citation statements)

References 144 publications

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“…Cancer cells learn to evade the immune system by exploiting immune checkpoint pathways that prevent T lymphocytes from recognizing tumour‐specific antigens . There has been a recent change in clinical practice to incorporate immune checkpoint inhibitors into the management of a wide variety of advanced tumours, including melanoma, nonsmall cell lung cancer, lymphoma, head and neck tumours, gastrointestinal tumours, and genitourinary tumours . Their use can also be extended to soft tissue sarcoma and osteosarcoma .…”

Section: Immunotherapy Approaches For Canine Sarcomasmentioning

confidence: 99%

“…Single, large ablative doses of radiation may particularly hamper effective antitumour immune responses; thus, focus has been on fractionated radiation regimens and SBRT protocols . SBRT is theoretically less systemically immunosuppressive than conventional radiation, in which patients have circulating lymphocytes that may be irradiated over 5 to 6 weeks .…”

Section: Immunotherapy Approaches For Canine Sarcomasmentioning

confidence: 99%

“…124,125 There has been a recent change in clinical practice to incorporate immune checkpoint inhibitors into the management of a wide variety of advanced tumours, including melanoma, nonsmall cell lung cancer, lymphoma, head and neck tumours, gastrointestinal tumours, and genitourinary tumours. 60,126,127 Their use can also be extended to soft tissue sarcoma and osteosarcoma. 5,128 Since tumour infiltrating lymphocytes may represent a biomarker for the immune responsiveness of a tumour, there has been tremendous interest in further defining the role and potential of these pathway with an anti-PD-1 or PD-L1 antibody can restore multiple effector functions of antigen-specific T cells, overcoming immune escape mechanisms by cancer cells.…”

Section: Checkpoint Inhibitorsmentioning

confidence: 99%

“…126,156 Single, large ablative doses of radiation may particularly hamper effective antitumour immune responses; thus, focus has been on fractionated radiation regimens and SBRT protocols. 60,157,158 SBRT is theoretically less systemically immunosuppressive than conventional radiation, in which patients have circulating lymphocytes that may be irradiated over 5 to 6 weeks. 60,126 Early studies have demonstrated that immunotherapy and radiation can safely be administered together and may induce responses, [159][160][161][162] but questions remain regarding the optimal timing of systemic treatment with radiation, radiation dose, and tumour volume irradiated.…”

Section: Rt and Immunotherapy For Sarcomasmentioning

confidence: 99%

“…For measurable tumours, stereotactic body RT (SBRT), a means in which large doses of radiation can be precisely administered to a tightly defined tumour target, may offer theoretical advantages over conventional RT protocols that involve low daily doses of radiation for 5 to 6 weeks. [59][60][61] This is particularly attractive for patients that need to be treated at a specialty hospital that is a long distance from home and shortens the time from diagnosis to surgery. Clinically, preoperative SBRT remains investigational with only a small study in human subjects that demonstrated its feasibility and lack of postsurgical complications.…”

mentioning

confidence: 99%

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Emerging therapeutic approaches for canine sarcomas: Pushing the boundaries beyond the conventional

Borgatti

Dickerson

Lawrence

2019

Vet Comparative Oncology

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Sarcomas represent a group of genomically chaotic, highly heterogenous tumours of mesenchymal origin with variable mutational load. Conventional therapy with surgery and radiation therapy is effective for managing small, low‐grade sarcomas and remains the standard therapeutic approach. For advanced, high‐grade, recurrent, or metastatic sarcomas, systemic chemotherapy provides minimal benefit, therefore, there is a drive to develop novel approaches. The discovery of “Coley's toxins” in the 19th century, and their use to stimulate the immune system supported the application of unconventional therapies for the treatment of sarcomas. While promising, this initial work was abandoned and treatment paradigm and disease course of sarcomas was largely unchanged for several decades. Exciting new therapies are currently changing treatment algorithms for advanced carcinomas and melanomas, and similar approaches are being applied to advance the field of sarcoma research. Recent discoveries in subtype‐specific cancer biology and the identification of distinct molecular targets have led to the development of promising targeted strategies with remarkable potential to change the landscape of sarcoma therapy in dogs. The purpose of this review article is to describe the current standard of care and limitations as well as emerging approaches for sarcoma therapy that span many of the most active paradigms in oncologic research, including immunotherapies, checkpoint inhibitors, and drugs capable of cellular metabolic reprogramming.

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Section: Immunotherapy Approaches For Canine Sarcomasmentioning

confidence: 99%

Section: Immunotherapy Approaches For Canine Sarcomasmentioning

confidence: 99%

Section: Checkpoint Inhibitorsmentioning

confidence: 99%

Section: Rt and Immunotherapy For Sarcomasmentioning

confidence: 99%

mentioning

confidence: 99%

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Emerging therapeutic approaches for canine sarcomas: Pushing the boundaries beyond the conventional

Borgatti

Dickerson

Lawrence

2019

Vet Comparative Oncology

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Evaluation of Definitive Stereotactic Body Radiotherapy and Outcomes in Adults With Extracranial Oligometastasis

et al. 2020

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Stereotactic Ablative Radiotherapy for the Management of Spinal Metastases

et al. 2020

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IMPORTANCERising cancer incidence combined with improvements in systemic and local therapies extending life expectancy are translating into more patients with spinal metastases. This makes the multidisciplinary management of spinal metastases and development of new therapies increasingly important. Spinal metastases may cause significant pain and reduced quality of life and lead to permanent neurological disability if compression of the spinal cord and/or nerve root occurs. Until recently, treatments for spinal metastases were not optimal and provided temporary local control and pain relief. Spinal stereotactic ablative radiotherapy (SABR) is an effective approach associated with an improved therapeutic ratio, with evolving clinical application.OBJECTIVE To review the literature of spinal SABR for spinal metastases, discuss a multidisciplinary approach to appropriate patient selection and technical considerations, and summarize current efforts to combine spinal SABR with systemic therapies. EVIDENCE REVIEWThe MEDLINE database was searched to identify articles reporting on spinal SABR to September 30, 2018. Articles including clinical trials, prospective and retrospective studies, systematic reviews, and consensus recommendations were selected for relevance to multidisciplinary management of spinal metastases.RESULTS Fifty-nine unique publications with 5655 patients who underwent SABR for spinal metastases were included. Four comprehensive frameworks for patient selection were discussed. Spinal SABR was associated with 1-year local control rates of approximately 80% to 90% in the de novo setting, greater than 80% in the postoperative setting, and greater than 65% in the reirradiation setting. The most commonly discussed adverse effect was development of a vertebral compression fracture with variable rates, most commonly reported as approximately 10% to 15%. High-level data on the combination of SABR with modern therapies are still lacking. At present, 19 clinical trials are ongoing, mainly focusing on combined modality therapies, radiotherapy prescription dose, and oligometastic disease.CONCLUSIONS AND RELEVANCE These findings suggest that spinal SABR may be an effective treatment option for well-selected patients with spinal metastases, achieving high rates of local tumor control with moderate rates of adverse effects. Optimal management should include review by a multidisciplinary care team.

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Immunomodulatory Effects of Stereotactic Body Radiation Therapy: Preclinical Insights and Clinical Opportunities

Cited by 63 publications

References 144 publications

Emerging therapeutic approaches for canine sarcomas: Pushing the boundaries beyond the conventional

Emerging therapeutic approaches for canine sarcomas: Pushing the boundaries beyond the conventional

Evaluation of Definitive Stereotactic Body Radiotherapy and Outcomes in Adults With Extracranial Oligometastasis

Stereotactic Ablative Radiotherapy for the Management of Spinal Metastases

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