ACCELERATED HYPERFRACTIONATED HEPATIC IRRADIATION IN THE MANAGEMENT OF PATIENTS WITH LIVER METASTASES - RESULTS OF THE RTOG DOSE ESCALATINGPROTOCOL

Purpose: This study was prepared to address two objectives: (a) to det ermine whether progressively higher total doses of hepatic irradiation can prolong survival in a selected population of patients with liver metastases; (b) to refine existing concepts of liver tolerance for fra ctionated external radiation employing a fraction size which might be appropriate in clinical protocols evaluating elective or adjuvant radi ation of the liver. Methods and Materials: One hundred seventy-three a nalyzable patients with computed tomography measurable liver metastase s from primary cancers of the gastrointestinal tract were entered on a dose escalating protocol of twice daily hepatic irradiation employing fractions of 1.5 Gy separated by 4 hr or longer. Sequential groups of patients received 27 Gy, 30 Gy, and 33 Gy to the entire liver and wer e monitored for acute and late toxicities, survival, and cause of deat h. Dose escalation was implemented following survival of 10 patients a t each dose level for a period of 6 months or longer without clinical or biochemical evidence of radiation hepatitis. Results: The use of pr ogressively larger total doses of radiation did not prolong median sur vival or decrease the frequency with which liver metastases were the c ause of death. None of 122 patients entered at the 27 Gy and 30 Gy dos e levels revealed clinical or biochemical evidence of radiation induce d liver injury. Five of 51 patients entered at the 33 Gy level reveale d clinical or biochemical evidence of late liver injury with an actuar ial risk of severe (Grade 3) radiation hepatitis of 10.0% (+/-7.3% S.E .) at 6 months, resulting in closure of the study to patient entry. Co nclusion: The study design could not credibly establish a safe dose fo r hepatic irradiation, however, it did succeed in determining that 33 Gy in fractions of 1.5 Gy is unsafe, carrying a substantial risk of de layed radiation injury. The absence of apparent late liver injury at t he 27 Gy and 30 Gy dose levels suggests that a prior clinical trial of adjuvant hepatic irradiation in patients with resected colon cancer m ay have employed an insufficient radiation dose (21 Gy) to fully test the question.