Russell A H, Clyde C, Wasserman T H, Turner S S, Rotman M
Radiological Associates of Sacramento Medical Group, Radiation Oncology Center, CA 95819.
Int J Radiat Oncol Biol Phys. 1993 Sep 1;27(1):117-23. doi: 10.1016/0360-3016(93)90428-x.
This study was prepared to address two objectives: (a) to determine 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 fractionated external radiation employing a fraction size which might be appropriate in clinical protocols evaluating elective or adjuvant radiation of the liver.
One hundred seventy-three analyzable patients with computed tomography measurable liver metastases 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 were monitored for acute and late toxicities, survival, and cause of death. Dose escalation was implemented following survival of 10 patients at each dose level for a period of 6 months or longer without clinical or biochemical evidence of radiation hepatitis.
The use of progressively larger total doses of radiation did not prolong median survival or decrease the frequency with which liver metastases were the cause of death. None of 122 patients entered at the 27 Gy and 30 Gy dose levels revealed clinical or biochemical evidence of radiation induced liver injury. Five of 51 patients entered at the 33 Gy level revealed clinical or biochemical evidence of late liver injury with an actuarial 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.
The study design could not credibly establish a safe dose for hepatic irradiation, however, it did succeed in determining that 33 Gy in fractions of 1.5 Gy is unsafe, carrying a substantial risk of delayed radiation injury. The absence of apparent late liver injury at the 27 Gy and 30 Gy dose levels suggests that a prior clinical trial of adjuvant hepatic irradiation in patients with resected colon cancer may have employed an insufficient radiation dose (21 Gy) to fully test the question.
本研究旨在实现两个目标：（a）确定逐步增加肝脏照射的总剂量是否能延长特定肝转移患者群体的生存期；（b）采用可能适用于评估肝脏选择性或辅助性放疗的临床方案中的分次剂量，完善现有的肝脏对分次外照射耐受性的概念。
173例经计算机断层扫描可测量的胃肠道原发性癌症肝转移患者进入一项剂量递增方案，该方案为每日两次肝脏照射，每次分次剂量为1.5 Gy，间隔4小时或更长时间。连续几组患者接受全肝27 Gy、30 Gy和33 Gy照射，并监测急性和晚期毒性、生存期及死亡原因。在每个剂量水平有10例患者存活6个月或更长时间且无放射性肝炎的临床或生化证据后，实施剂量递增。
使用逐步增大的总辐射剂量并未延长中位生存期，也未降低肝转移作为死亡原因的频率。在27 Gy和30 Gy剂量水平入组的122例患者中，均未出现放射性肝损伤的临床或生化证据。在33 Gy剂量水平入组的51例患者中有5例出现晚期肝损伤的临床或生化证据，6个月时严重（3级）放射性肝炎的精算风险为10.0%（±7.3%标准误），导致该研究停止患者入组。
该研究设计无法可靠地确定肝脏照射的安全剂量，然而，它成功确定了1.5 Gy分次的33 Gy剂量不安全，存在显著的延迟性辐射损伤风险。27 Gy和30 Gy剂量水平未出现明显的晚期肝损伤表明，先前一项针对切除结肠癌患者的辅助性肝脏照射临床试验可能使用了不足的辐射剂量（21 Gy）来充分验证该问题。
