136P - Circadian rhythm positioned chronomodulated-SBRT with Cancer associated fibroblast elimination theranostic treatment to harmonize resistant TFG-Beta stromal microenvironment in conjunction with PDL-1 based immunotherapy in disseminated cancers-Concept randomised study.

Background

Intrinsic links of variation in immune function and phases of circadian rhythm is the basis of chronotherapy. Modulating immune potentiating nature of modern anti-cancer treatment combinations such as PDL1 inhibitors, Stereotactic body radiotherapy (SBRT), stromal targeted theranostic using chronobiology is an unfathomed area of research. SBRT releases tumour neo-antigens, the anti PDL1 therapy aids in effective cytotoxic T cell activity and anti-stromal theranostic modulates the resistant tumour stroma with an anti TGF Beta activity in an immune favouring way. Chrono-phased SBRT -Timing the SBRT at the best immune functioning part of the day could be an effective synergism to the amalgam.

Methods

26 disseminated cancer patients eligible for anti-PDL1 drug were treated with Actinium-225 tagged fibroblast activated protein (FAP) based Alpha theranostic to target the cancer associated fibroblasts (CAFs) forming the tumor stroma and were randomized to receive SBRT at any given part of the day versus a chrono-phased SBRT-7am to 9am after verifying the circadian rhythm.Intactness of the circadian rhythm in these patients were assessed using sleep log. Baseline cytokine profile, WBC, ALC and NL ratio were compared to immediate therapy level and post 3-months. Response to therapy was radiologically assessed using RECIST 1.1 criteria.

Results

Table: 136P

Conclusions

While augmenting immune responses to cancer immune-modulatory therapies is an area of active probing, using the immune sensitive phase of circadian rhythm to obtain therapeutic benefit seams beneficial. Our study suggests that the technique is feasible, and our early results are encouraging with better quality of life with chrono-sbrt.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.