RTOG 0438: A phase I trial of highly conformal radiation therapy for patients with liver metastases.

Abstract

257 Background: This multi-institutional phase I trial was conducted to determine the maximally tolerated dose (MTD) of hypofractionated, highly conformal radiation therapy (RT) in patients (pts) with liver metastases. Methods: Eligibility criteria included non-surgical pts with ≤ 5 liver metastases; total measurement for all lesions ≤ 8 cm. There were four dose levels (DLs) escalating from 35 Gy to 50 Gy in 5 Gy increments given in 10 fractions with defined normal tissue dose limits. Accrual began at 40 Gy. The clinical target volume (CTV) included all metastases identified on contrast CT/MRI with a 5 mm margin. The planning target margin ranged from 4 to 30 mm around the CTV. For quality assurance the Image-Guided Therapy Center (ITC) remote review tool was used to evaluate treatment planning images and dosimetry information. Dose limiting toxicities (DLTs) were defined as treatment-related grade (Gr) ≥ 4 hepatic, gastrointestinal (GI), thrombocytopenia, or radiation induced liver disease (RILD) within 90 days (dys) of the start of RT. Results: 26 pts were enrolled between 11/05 and 12/10, and 23 were evaluable; 8, 7, and 8 on the 40, 45, and 50 Gy DLs respectively. Two pts assigned to the 50 Gy DL received 35 Gy because of normal tissue constraints, therefore an additional 2 pts were accrued and treated at the 50 Gy DL. The study was temporarily closed for toxicity evaluation after 6 pts on each DL were followed for a minimum of 90 dys from start of treatment. There were no DLTs observed on any of the DLs. Four pts developed treatment-related Gr 3 toxicities; 2 each on the 45 and 50 Gy DLs. On the 45 Gy DL, 1 pt had two Gr 3 GI toxicities: enteritis (37 dys from RT start) and diarrhea (22 dys) while another pt had Gr 3 lymphopenia (23 dys). On the 50 Gy DL, 1 pt had Gr 3 hyperglycemia (74 dys) and another pt had three Gr 3 toxicities: lymphopenia (13 dys), colonic hemorrhage (325 dys), and GI obstruction (325 dys). Conclusions: When normal tissue constraints could be met, treatment of liver metastases with 50 Gy in 5 Gy/fx is feasible and safe in a multi-institutional setting. Further studies looking at higher doses and alternate fractionation regimens are warranted. Supported by RTOG U10 CA21661, CCOP U10 CA37422 and ATC U24 CA 81647 NCI grants.