The past decade has thrown much light over understanding of tumor micro-environment and its effects on cancer immune evasion. Fibroblasts are resting mesenchymal cells that can be activated to facilitate tissue repair during wound healing. However, cancer associated fibroblasts (CAF) are functionally intense. CAFs can produce growth factors and cytokines such as transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF) to promote angiogenesis and recruit immuno-suppressive cells into the tumor stroma leading to immune evasion .Our study targets this resistant tumor stroma using actinium tagged Fibroblast activation protein(FAP) imaging followed by a phased SBRT to one or more sites, Thus by modulating the CAF associated tumor immune-tolerance an improved neo-antigen presentation during SBRT could be expected which may lead to better response rates. The study was started after institutional ethical clearance. A total of 5 patients with disseminated metastatic disease who have had first line therapies and failed subsequently on multiple lines of chemotherapy/targeted therapy were recruited post informed consent. A diagnostic actinium tagged FAP imaging was done and on confirmation of the FAPs tumor site uptake, therapeutic doses of Actinium tagged with FAPs to a dose of 300 micro grams Intravenous. Post 5 days of intra-stromal therapy, SBRT was given in 3 to 5 fractions to the core of all visible metastatic lesions. Patients were assessed for response after 6 weeks with a PET-CT and the side effect profile was assessed with liver function tests, kidney function tests at one-week post completion of SBRT (Stereotactic body Radiotherapy) and also at 6 weeks prior to response assessment PET-CT scan. In all the five patients, there were no observed toxicity with respect to the liver and kidney at 1 week and at 6 weeks post therapy. See Table.Abstract 192; TablePR-Partial response, CR-Complete response, SD-Stable DiseasePrimaryRadiationSiteDoseResponse (RT Site)Response (Distant Site)Patient 1BreastSBRT-3 FractionsBone24GyPRPRPatient 2OvarySBRT-3 FractionsLiver36GyCRPRPatient 3ProstateSBRT-5 FractionsBone35GyPRPRPatient 4ProstateSBRT-3 FractionsProstate24GyPRSDPatient 5LungSBRT-5 FractionsLung30GyPRPR Open table in a new tab Evolution of robust treatment strategies targeting tumor microenvironment is a field of exciting research. Effectively tackling the tumor immune evasion mechanisms based on individual tumor microenvironment profiling such as FAP imaging would ultimately aid in improved response to therapy. The early results of our study are encouraging.