Phase I feasibility and dose escalation multicenter trial of stereotactic body radiation therapy for liver metastases

Abstract

4157 Background: Stereotactic body radiation therapy (SBRT) involves the application of high dose, stereotactically localized, and tightly focused irradiation to tumors in the lung, liver, and other extracranial sites.It is an attractively non-invasive method of eradicating discrete foci of metastatic disease, a clinically appropriate consideration for patients with good performance status and limited systemic disease burden. SBRT is currently being evaluated in a multi-center IRB approved phase I/II clinical trial coordinated by the University of Colorado. Methods: Eligible patients had image-based evidence of 1–3 liver metastases from any solid tumor excluding germ cell histology, and stable or absent extra-hepatic disease.The protocol required that at least 700 cc of uninvolved normal liver receive less than a total cumulative dose of 15 Gy.Dose escalation started at 36 Gy in 3 fractions (12 Gy per fraction) over 3 to 10 days and was escalated by 6 Gy per cohort using the standard phase I design, up to the maximum tolerated dose (MTD) or a designated limit of 60 Gy in 3 fractions.Gross tumor volume (GTV) was delineated on the contrast enhanced planning CT scan.GTV was expanded by 5 mm radially and 10 mm craniocaudally to define the planning target volume(PTV).Breathing control or gating was used in all cases.Dose limiting toxicity (DLT) was defined as grade 3 liver, gastric, small bowel or spinal cord toxicity and any grade 4 toxicity ascribed to radiotherapy. Results: Since November, 2002, 9 subjects were enrolled. Patient accrual is ongoing. All patients completed protocol treatment as planned. 7 of 9 subjects remain alive at the time of interim analysis. The two deaths were not attributable to protocol treatment.No DLTs have been observed. Conclusions: An MTD has not yet been reached, and observations thus far indicate that it is safe to administer 48 Gy in three 16 Gy fractions to 1–3 liver metastases, as long as at least 700 cc of uninvolved normal liver receives less than 15 Gy.Additional observations from the next planned dose escalation cohort(s) will be presented at the time of the meeting. Supported (in part) by a grant from the ACS. No significant financial relationships to disclose.