While 30 Gy in a single-dose SBRT has been demonstrated to be safe for liver tumors, higher radiation dose is likely required to control larger tumors. Radiation dose escalation beyond 30 Gy to the entire tumor will be significantly limited by potential toxicity to nearby tissues and organs. vGRID therapy, which treats part of the tumor to a high dose while the rest of the tumor to a lower dose, may allow safe dose escalation beyond 30 Gy. As described above, our treatment planning simulation has demonstrated an ability to safely dose escalate using the vGRID technique while keeping radiation doses to surrounding tissues and organs to lower than well-accepted dose limits.~The overall goal of this study is to assess the MTD of SBRT to live tumors using the vGRID radiation technique. We have specifically chosen dose level 1 to be 27 Gy (below the 30 Gy SBRT dose used in the trial by Goodman et al which was demonstrated to be safe). Further, this dose of 27 Gy x 1 will have a point dose biological equivalent dose (BED) of 100 (using alpha/beta ratio of 10), similar to the BED of 100 used in the cooperative group trial RTOG 1112 for HCC. While unlikely, if DLT's are experienced in our lowest dose cohort, we will de-escalate radiation dose to 40 Gy in 5 fractions (BED 72) which was previously shown to be safe in Child's Pugh Class B patients, with a 2 year LC of 90% (Andolino IJROBP 2011).~The dose levels for this phase I trial are: 1) 27 Gy, 2) 32 Gy, 3) 37 Gy, 4) 42 Gy, 5) 47 Gy. Our third highest dose of 37 Gy x1 has a BED of 173.9 (alpha/beta ratio of 10), which is similar to Rusthoven's 60 Gy in 3 fractions for liver metastases (Rusthoven JCO 2009).~Our highest dose cohort is 47 Gy x 1, which has a BED of 267.9 to the tumor, will represent significant dose escalation compared to current treatment (2.7x the biological dose to tumor), and if found to be safe, will be used for the future Phase II trial.~This trial will provide the MTD for radiation therapy for liver tumors and describe the toxicity profile using the vGRID therapy technique. Based on trials using this type of radiation in other cancers demonstrating low toxicity rates even with very high radiation doses and high efficacy, it is likely that vGRID therapy in this trial will be well tolerated and allow dose escalation beyond currently common doses for liver tumors.~The safety of this trial is maximized by treatment planning following strict dose limits to nearby tissues and organs. Even though part of the tumor will receive dose escalated vGRID radiation, treatment plans must meet strict criteria regarding dose limits to nearby tissues and organs that are known to be safe to patients.~Upon completion of vGRID radiation, patients will than begin treatment standard of care treatment option Atezolizumab. The rationale for following vGRID radiation followed Atezolizumab is to potentiate the immune microenvironment and enhance synergy of anti-tumor effect.~Atezolizumab is often given with bevacizumab per the landmark study IMbrave150 in unresectable HCC patients (Finn RS NEJM 2020). However, given the added risk of GI toxicity from bevacizumab with radiation, we have stipulated in this trial to hold bevacizumab with cycle 1 of atezolizumab, which is to begin 12 - 16 days after completion of radiation.
This trial will provide the maximum tolerated dose for radiation therapy for liver tumors and describe the toxicity profile using the vGRID therapy technique. Based on trials using this type of radiation in other cancers demonstrating low toxicity rates even with very high radiation doses and high efficacy, it is likely that vGRID therapy in this trial will be well tolerated and allow dose escalation beyond currently common doses for liver tumors.