Background: Patients (Pts) with pre-existing liver dysfunction are at high risk for further damage after SBRT. We completed a phase 2 study of individualized SBRT, utilizing pre- and during-treatment indocyanine green (ICG) clearance to adapt treatment and maximize both safety and efficacy. Methods: From 5/10-10/14, pts with hepatocellular carcinoma (HCC) or metastases (mets) were enrolled and underwent SBRT planning up to a target dose of 50-60 Gy or as limited by a 15% normal tissue complication probability for radiation-induced liver disease (RILD). ICG retention at 15 minutes (ICGR15) was measured prior to and 1 month after 3 of 5 planned treatments. Using a Bayesian adaptive model, RT dose was scaled down as necessary for the final 2 treatments to keep ICGR15 < 44% after the full treatment and thus minimize toxicity. Follow up was every 3 months for 2 years. Results: 90 pts received SBRT to 116 tumors and had at least 1 year of potential follow up. Median age was 62 years, range 34-85. 69 had HCC, 4 intrahepatic cholangiocarcinoma, and 17 mets. 62 had cirrhosis, most commonly HCV and alcoholic. Median Child-Pugh (CP) score was 6, range 5-9. 20 pts were CP B/C. Median pre-RT ICGR15 was 22, range 4-75, normal 4-10. Pts had a median of 1.5 (range 0-6) prior liver-directed therapies, most commonly transarterial chemoembolization (70), prior RT (36), and radiofrequency ablation (13). Median tumor size was 3 cm, and 12 had portal vein involvement. 63 received all 5 fractions (48 full dose, 15 with dose reduction due to elevated ICGR15); 27 received only 3 treatments. Median prescription dose was 47 Gy. Treatment was well tolerated with no classical RILD and a lower complication rate than expected without adaptation. 4 pts had grade 3 ascites. 2 pts had GI bleed after SBRT. 14% and 10% of pts experienced at least a 1 or 2 point increase in CP 6 months post SBRT. Local control (95%CI) at 1 and 2 yrs was 99 (96,100)% and 90 (81,100)%. 4 recurrent tumors were 3 HCC and 1 met, measuring 26, 12, 30, 38mm; treated to 30, 50, 33, 30 Gy. Conclusions: Individualized adaptive SBRT, based on ICG clearance is a promising method of allowing pts to receive the maximally aggressive dose based on each pt’s individual tolerance to RT. Funded by P01 CA59827