Pulsed vs. Single Shot Immune-Amplified 1 Gy Miniscule Radiotherapy Synchronic with Immune-Check Point Inhibitors and SBRT in Disseminated Malignancies-Immuno-Rad (i-RT) Concept to Reprogram Microenvironment for Inducing in-Situ Vaccination

• Published in: International journal of radiation oncology, biology, physics Vol. 120; no. 2; p. e384
• Main Authors: Lohith, G., Sekar, K., Naseer, M., CT, S., Shivalingappa, S.S., Patil, S., Tippeswamy, R., Ram, A., Suresh, S., Kallur, K., Jayappa, S.B., Ramaswamy, V., BS, A.K.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.10.2024
• ISSN: 0360-3016
• DOI: 10.1016/j.ijrobp.2024.07.852

The role of SBRT (Stereotactic body Radiotherapy) in Neo-Antigen release and Tumor Immune stimulation synchronous with immune checkpoint inhibitors [ICI] is evident. Responses in lesions away from primary and adjacent to target volume in SBRT owing to scatter dose radiation is observed as abscopal and Radscopal effect and hence the evolution of low dose radiation being a potential immune amplifier for in-situ vaccination effect. The benefits from low dose radiation in immune microenvironment modulation and T cell regulation is understood from murine studies and few phase 1 human studies. The role of continuous immune amplification using low dose radiation with every cycle of ICI is not studied. Our study is the first human comparison quest evaluating the effectiveness SBRT and pulsed low dose radiation with every cycle of ICI versus SBRT and single shot low dose radiotherapy only during the first cycle of ICI in disseminated cancers. 10 Patients with disseminated malignancies originating from breast (2), liver (2), esophagus (1) and Renal (3), lung (2) eligible for ICI were randomized to receive SBRT to the primary plus single shot Low dose radiation of 1Gy ,<24 hours post ICI to all metastatic lesions [to a minimum of 1 site > 3cms] to a dose of 24Gy/3 fractions versus SBRT to the primary followed by low dose radiation to all lesions continued with every 15 day cycle of ICI for a minimum of 3 cycles. The response rate at every site was assessed at the end of 3 cycles using i-RECIST criteria on PETCT. Excluding lesions that received SBRT, there was a total of 27 lesions in single shot low dose group-A and 31 lesions in Pulsed low dose group-B. The number of lesions that responded were 1, stable in 12 and 14 progressed in single shot 1Gy radiation and 14 responded,16 stable and 1 progressed in pulsed 1Gy radiation group. Statistically, Fisher's exact test of independence showed a significant association between the groups and outcomes, χ2 = 20.5, p = <0.001, Cramer's V = 0.595. Group that received single shot 1gy were more likely to progress (44.4%) compared to pulsed 1gy group (3.23%) and pulsed 1gy group were more likely to have responded (45.16%) compared to single shot 1gy (3.7%). 1gy single shot (51.85%) and pulsed 1gy (51.61%) were equally likely to have stable disease. Pulsed low dose radiotherapy concurrent with every cycle of ICI has shown significant responses due to radscopal effect with optimum modulation of Immune microenvironment and in amplifying the effect of ICI therapies compared to a single shot 1 Gy therapy with SBRT being common for both arms as a neoantigen releasing in-situ vaccine.