Use of Multi-Site Radiation Therapy for Systemic Disease Control

Patel, Roshal R.; Verma, Vivek; Barsoumian, Hampartsoum B.; Ning, Matthew S.; Chun, Stephen G.; Tang, Chad; Chang, Joe Y.; Lee, Percy P.; Gandhi, Saumil; Balter, Peter A; Dunn, Joe Dan; Chen, Fan; Puebla-Osorio, Nahum; Cortez, María Angélica; Welsh, James W.

doi:10.1016/j.ijrobp.2020.08.025

Cited by 35 publications

(30 citation statements)

References 117 publications

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“…In another study, we conducted proteomic analysis to evaluate the upregulation of TME-specific cytokines and stimulatory factors following LDRT. We found upregulation of Granzyme B, MIP1α, and CD137 (4-1BB) in tumor-infiltrating CD4 + T cells, indicating activation and effector functions ( 11 ). LDRT further augmented the efficacy of CPIs such as anti-CTLA-4 and anti-PD1 in murine lung adenocarcinoma models, as evidenced by reduced tumor growth and significantly prolonged survival.…”

Section: Low-dose Radiotherapy (Ldrt)mentioning

confidence: 87%

“…We recently reported a representative case to illustrate these observations ( 11 ). The patient in the study presented with stage-IV melanoma with multiple metastases in liver, lung, bone and brain, which had progressed 3 months after T cell therapy and 1 month after resuming ipilimumab + nivolumab ( Figure 2A ).…”

Section: Low-dose Radiotherapy (Ldrt) For Liver Metastasesmentioning

confidence: 91%

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Novel Use of Low-Dose Radiotherapy to Modulate the Tumor Microenvironment of Liver Metastases

Barsoumian

Bertolet

et al. 2021

Front. Immunol.

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Despite multiple therapeutic approaches, the presence of liver metastases carries a guarded prognosis, urgently necessitating further clinical and scientific research to develop curative interventions. The liver is an immunoprivileged organ that suppresses the effectiveness of immunotherapies in patients with hepatic metastases. Cancer immunotherapies have been successfully bolstered by low-dose radiotherapy (LDRT), which is capable of reprogramming the tumor microenvironment (TME) from an immunosuppressive to an immunostimulatory one. Likewise, LDRT may be able to revoke the immune privilege enjoyed by the liver, permitting successful immunotherapies there. Here, we first review challenges that face the treatment of liver metastases. We next outline emerging preclinical and clinical evidence supporting enhanced systemic tumor control of LDRT in the context of cancer immunotherapy. Finally, we will discuss the rationale of combining liver-directed LDRT with immunostimulatory strategies to overcome immune resistance and achieve better clinical response. This notion is supported by a recent case study in which a patient who had progressed following T cell therapy experienced a complete response after LDRT to the liver.

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Section: Low-dose Radiotherapy (Ldrt)mentioning

confidence: 87%

Section: Low-dose Radiotherapy (Ldrt) For Liver Metastasesmentioning

confidence: 91%

Novel Use of Low-Dose Radiotherapy to Modulate the Tumor Microenvironment of Liver Metastases

Barsoumian

Bertolet

et al. 2021

Front. Immunol.

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“…1,[5][6][7][8] Practice delivery costs increase with the number of treated sites because of proportional resource utilization for separate dosimetric plans, set-up immobilization, image guidance, and treatment delivery. [16][17][18] Each additional SBRT course tends to increase provider delivery costs by 40%-50%, relative to an intensity-modulated RT course to the primary site alone (accounting for all equipment and personnel via time-driven activitybased costing), 17 and component Current Procedural Terminology or HCPCS coding reflects the added work of treating multiple sites.…”

Section: Bundled Payments Undervalue the Cost Of Lct Deliverymentioning

confidence: 99%

“…2,4,6,12,15 These studies have also established radiotherapy (RT) as eponymous with LCT, 1,3,5,[8][9][10] emphasizing the utility of stereotactic ablative (stereotactic body radiotherapy [SBRT]) and radiosurgical (stereotactic radiosurgery) techniques for consolidating multiple lesions within a short timeframe. 1,3,4,9,16 Thus, despite their high delivery costs, 17,18 stereotactic treatments have been rapidly adopted for oligometastatic indications, among which utilization increased 4fold from 2011 to 2017. 12 Author affiliations and support information (if applicable) appear at the end of this article.…”

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confidence: 99%

Oligometastatic Disease in Context of the Radiation Oncology Alternative Payment Model: Implications for Local Consolidative Therapy

Ning

Boyce-Fappiano

Thaker

2021

JCO Oncology Practice

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“…Research has been very controversial with variations in dose or fraction for radiation delivery in the metastatic setting, where the role of treatment parameters such as duration (more or <7 days), fraction size (1.8-3 to 8-30 Gy) and scheduling (single or multiple fractions) are largely unknown. While a short course (1-5 fractions) of high dose radiation can be safely administered and is able to elicit an immunogenic response that can benefit from the addition of ICB, the predominance of the immunosuppressive effects of radiation may limit the effectiveness of ablative doses of radiation, especially if single fractions are used (47,48). Nonetheless, the immune context of the tumor type or even the metastatic organ may require a different dose and/or fractionation to elicit an immunogenic response.…”

Section: Addressing the Evasive Objective Of Durable Responses Of Radmentioning

confidence: 99%

Therapy-Induced Modulation of the Tumor Microenvironment: New Opportunities for Cancer Therapies

et al. 2020

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Advances in immunotherapy have achieved remarkable clinical outcomes in tumors with low curability, but their effects are limited, and increasing evidence has implicated tumoral and non-tumoral components of the tumor microenvironment as critical mediators of cancer progression. At the same time, the clinical successes achieved with minimally invasive and optically-guided surgery and image-guided and ablative radiation strategies have been successfully implemented in clinical care. More effective, localized and safer treatments have fueled strong research interest in radioimmunotherapy, which has shown the potential immunomodulatory effects of ionizing radiation. However, increasingly more observations suggest that immunosuppressive changes, metabolic remodeling, and angiogenic responses in the local tumor microenvironment play a central role in tumor recurrence. In this review, we address challenges to identify responders vs. non-responders to the immune checkpoint blockade, discuss recent developments in combinations of immunotherapy and radiotherapy for clinical evaluation, and consider the clinical impact of immunosuppressive changes in the tumor microenvironment in the context of surgery and radiation. Since the therapy-induced modulation of the tumor microenvironment presents a multiplicity of forms, we propose that overcoming microenvironment related resistance can become clinically relevant and represents a novel strategy to optimize treatment immunogenicity and improve patient outcome.

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Use of Multi-Site Radiation Therapy for Systemic Disease Control

Cited by 35 publications

References 117 publications

Novel Use of Low-Dose Radiotherapy to Modulate the Tumor Microenvironment of Liver Metastases

Novel Use of Low-Dose Radiotherapy to Modulate the Tumor Microenvironment of Liver Metastases

Oligometastatic Disease in Context of the Radiation Oncology Alternative Payment Model: Implications for Local Consolidative Therapy

Therapy-Induced Modulation of the Tumor Microenvironment: New Opportunities for Cancer Therapies

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