Abscopal Effect of Radiotherapy in the Immunotherapy Era: Systematic Review of Reported Cases

Abstract

Mounting evidence suggests that radiation stimulates the immune system and this contributes to the abscopal effect, which is defined as “response at a distance from the irradiated volume.” Though identified more than 50 years ago, the abscopal effect is revisited today. One rationale is that the abscopal effect is often observed with efficient immunotherapy. Here, we give an overview of the clinical data on the abscopal effect, generated by a combination of immunotherapy and radiotherapy (RT). Only papers that included RT in combination with immunotherapy were evaluated according to four main categories including RT parameters, sequencing of therapies, the definition of the abscopal effect, and patient selection. Twenty-four cases in 15 reports were reviewed. The results varied. Patient ages ranged from 24 to 74. RT dose (median total dose 18-58 Gy) varied. Biologically effective dose (BED) 10 was calculated to be a median 49.65 Gy (28-151 Gy). The time to a documented abscopal response ranged from less than a month to 12 months. The large variation concerning fractionation and sequencing of therapies indicates that these conflicting points need to be resolved, to generate for the abscopal effect to be clinically significant.

Radiation therapy for augmenting the efficacy of immunotherapy in advanced non-small cell lung cancer: a case-controlled study

“…Even small doses of radiation therapy to single sites have been shown to trigger a heightened immune response at metastatic sites with immunotherapy, particularly in patients with low tumour PDL1 expression [12]. However, the optimal combinations, sequences and doses to generate an abscopal effect are not well defined [13]. There is also increasing preclinical and clinical evidence to suggest that irradiation of multiple sites may enhance the effects of immunotherapy compared to single-site irradiation [14].…”

Immunotherapy Combined With Chemotherapy and Radiotherapy for a Patient With Cancer of Unknown Primary: A Case Report

“…Further research is warranted to identify optimal approaches for incorporating radiotherapy in combination treatments with respect to dosage, as well as the fractionation and sequencing of therapies. 22 We reported a unique case of CUP with multiple systemic metastases in a 36-year-old male. In patients in whom the primary tumor site cannot be identi ed, apart from conventional chemotherapy and radiotherapy, immunotherapy can also be an effective treatment with fewer side effects and better patient tolerance.…”

Abscopal effect in head and neck cancer: a unicorn summoned once every eon?

“…in order to maximize the probability of inducing abscopal effect. 1 Also, there is an unmet need for reliable predictors in order to identify those patients who would most likely benefit from combined radioimmunotherapy interventions. 12…”

“…However, mounting preclinical and clinical evidence suggest that radiation is capable of inducing tumor-specific immune-mediated responses. 1 Abscopal effect is the reduction of tumor lesions located outside the irradiation field, assuming no other active systemic cytotoxic is administered concurrently. The term was first coined by Mole and etymologically is derived from the Latin prefix "ab" which means "position away from" and the word "scopos" which means "target".…”