A Prospective Trial Evaluating the Safety and Systemic Response From the Concurrent Use of Radiation Therapy with Checkpoint Inhibitor Immunotherapy in Metastatic Non–Small Cell Lung Cancer

Mattes, Malcolm D.; Eubank, Timothy D.; Almubarak, Mohammed; Wen, Sijin; Marano, Gary; Jacobson, Geraldine M.; Patrick, C.

doi:10.1016/j.cllc.2021.01.012

Cited by 21 publications

(13 citation statements)

References 31 publications

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“…Multiple studies have shown a synergistic effect of combining radiotherapy with immunotherapy [17][18][19][20][21][22]. A recent report evaluating immunotherapy efficacy after SRS demonstrated patients with melanoma brain metastases had better outcomes if the immunotherapy was delivered within 7 days of radiation [23].…”

Section: Introductionmentioning

confidence: 99%

Effects of whole-brain radiation therapy on the blood–brain barrier in immunocompetent and immunocompromised mouse models

et al. 2023

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Background Approximately 20% of all cancer patients will develop brain metastases in their lifespan. The standard of care for patients with multiple brain metastases is whole-brain radiation therapy, which disrupts the blood–brain barrier. Previous studies have shown inflammatory mediators play a role in the radiation-mediated increase in permeability. Our goal was to determine if differential permeability post-radiation occurs between immunocompetent and immunocompromised mice. Methods We utilized a commissioned preclinical irradiator to irradiate brains of C57Bl/6J wild-type and athymic nude mice. Acute (3–24 h) effects on blood–brain barrier integrity were evaluated with our in-situ brain perfusion technique and quantitative fluorescent and phosphorescent microscopy. The presence of inflammatory mediators in the brain and serum was determined with a proinflammatory cytokine panel. Results Blood–brain barrier integrity and efflux transporter activity were altered in the immunocompetent mice 12 h following irradiation without similar observations in the immunocompromised mice. We observed increased TNF-α concentrations in the serum of wild-type mice immediately post-radiation and nude mice 12 h post-radiation. The brain concentration of CXCL1 was also increased in both mouse strains at the 12-h time point. Conclusions The immune response plays a role in the magnitude of blood–brain barrier disruption following irradiation in a time- and size-dependent manner.

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Section: Introductionmentioning

confidence: 99%

Effects of whole-brain radiation therapy on the blood–brain barrier in immunocompetent and immunocompromised mouse models

et al. 2023

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“…Three CTCAE grade 3 pneumonitis, 2 CTCAE grade 3 colitis, and 1 CTCAE grade 3 hepatic toxicity all within the radiation field were reported. In the setting of metastatic NSCLC, a phase 1 trial 94 and PEMBRO-RT 95 suggested that combining RT with pembrolizumab was well tolerated. One patient developed a nephritis post-SBRT to a retroperitoneal lesion, which was close to the kidney, after a third course of pembrolizumab, and another patient developed a vertebral body compression fracture post spine SBRT.…”

Section: Resultsmentioning

confidence: 99%

Safety and Tolerability of Metastasis-Directed Radiation Therapy in the Era of Evolving Systemic, Immune, and Targeted Therapies

Guimond¹,

Tsai²,

Hosni³

et al. 2022

Advances in Radiation Oncology

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“…The limited available data in this area suggest that patients receiving concurrent ICI and radiation therapy have favorable outcomes in terms of cancer control and severity of adverse events. [26][27][28][29][30] Radiation exposure is known to induce immunogenic cell death via multiple mechanisms. 31 We hypothesize that radiation therapy to the bone decreased the response of immune cells residing in the bone marrow, thereby decreasing the rate of immunity to self.…”

Section: Discussionmentioning

confidence: 99%

Immune checkpoint inhibitor–related adverse events: Real-world experience from a single veterans’ affairs medical center

Benz

Sherman

Dasanu

et al. 2023

J Oncol Pharm Pract

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Background Immune checkpoint inhibitors (ICIs) are antineoplastic agents associated with a multitude of immune-related adverse events (irAEs). Available data from clinical trials include highly selective patient populations which may limit their applicability to real-world clinical practice. Methods We present a retrospective cohort study of cancer patients treated with ICI therapy at the Zablocki VA Medical Center between 2014 and 2021. Information on demographics, cancer diagnosis, type of therapy, treatment duration, comorbidities, irAE type, and overall survival were collected. Results We identified 187 patients who received at least one dose of ICI. About half the patients experienced at least one irAE, the most common categories being fatigue, pulmonary, and endocrine irAEs. Approximately half of the irAEs were diagnosed within the first three months of starting ICI therapy, and 60.38% of those who experienced irAEs discontinued ICI therapy. Patients who experienced endocrine or intestinal irAEs had a significantly longer overall survival. Conclusion Immune-related complications due to ICI therapy are common and can frequently lead to treatment discontinuation in the real-world setting. Endocrine and intestinal irAEs may correlate with improved survival. The ICI-treated patients who received palliative radiation therapy to the bone had less irAEs, possibly due to immunogenic cell death.

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A Prospective Trial Evaluating the Safety and Systemic Response From the Concurrent Use of Radiation Therapy with Checkpoint Inhibitor Immunotherapy in Metastatic Non–Small Cell Lung Cancer

Cited by 21 publications

References 31 publications

Effects of whole-brain radiation therapy on the blood–brain barrier in immunocompetent and immunocompromised mouse models

Effects of whole-brain radiation therapy on the blood–brain barrier in immunocompetent and immunocompromised mouse models

Safety and Tolerability of Metastasis-Directed Radiation Therapy in the Era of Evolving Systemic, Immune, and Targeted Therapies

Immune checkpoint inhibitor–related adverse events: Real-world experience from a single veterans’ affairs medical center

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