2012年10月28-31日，第54届美国放射肿瘤学会（ASTRO）年会在美国波士顿举行。来自世界各地的放射肿瘤学领域的医生及相关人士共计11000多人参会。本届年会的主题是“通过创新改善患者治疗（Advancing Patient Care through Innovation）”。 对本届年会进行了专题报道（http://zt.cmt.com.cn/zt/astro2012/index.html），敬请关注！

　　会上，加拿大学者报告了一项研究：Phase I Study of Sorafenib andSBRTfor Advanced Hepatocellular Carcinoma，其摘要如下：

Purpose/Objective(s)
To determine the maximally tolerated dose of sorafenib, a tyrosine kinase inhibitor with antiangiogenic properties, delivered pre-, during, and post-SBRT in hepatocellular carcinoma (HCC).

Materials/Methods
Eligible patients had advanced HCC not suitable for standard local or regional therapies, with Child-Pugh A liver function. SBRT was delivered in 2 strata: (1) low effective liver volume irradiated (Veff) (<30%, dose range: 39-54 Gy in 6 fractions (fr) over 2 weeks) and (2) High Veff (30%-60%, dose range: 39-54 Gy in 6 fr). Maximal permitted dose to luminal tissue was 31-34 Gy. Study sorafenib was delivered 1 week prior to, during and 4 weeks post SBRT, at which point escalation to full dose sorafenib was permitted. The study sorafenib dose was planned to be escalated in each strata from 400 mg (200 mg po bid) to 600 mg (400 mg po q am and 200 mg po q pm) to 800 mg (400 mg po bid) in a phase I trial design. Dose limiting toxicity (DLT) was defined as grade 4 or 5 related toxicity. Evaluable patients had to receive at least 3 weeks of study dose sorafenib and SBRT and be followed for at least 3 months (mos) without liver PD.

Results
Twenty-four patients consented to this study. Eight were screened ineligible, leaving 16 eligible HCC patients who initiated study therapy (4 Low Veff, median dose 51 Gy; 12 High Veff, median dose 33 Gy). Seventy-five percent of patients were BCLC stage C. The majority had main branch portal vein tumor thrombosis. In the low Veff strata, none of 3 evaluable patients treated with SBRT combined with sorafenib 400 mg developed DLT. A fourth patient was not evaluable due to discontinuation of sorafenib after 11 days due to grade 3 thrombocytopenia. The sorafenib dose level was not escalated in this strata due to poor accrual. In the high Veff strata, 2 of 3 evaluable patients treated with sorafenib 400 mg po daily developed DLT (1 grade 3 large bowel bleed 3.5 mo post-SBRT and 1 grade 3 bowel obstruction 3 mos post-SBRT). Two other patients were taken off study prior to SBRT due to liver enzyme increase and tumor rupture after 7 and 3 days of sorafenib respectively. Thus, sorafenib was de-escalated to 200 mg po daily. One of 6 evaluable patients at this dose level developed DLT (tumor rupture, after 5 weeks of sorafenib and SBRT, with death at 8 weeks). Another patient developed grade 3 liver enzymes after 7 days of sorafenib, and was taken off study. Median survival of the 12 evaluable patients in both strata, including those with DLT, was 8.4 mos (range, 2-12.3 mos). Follow-up is ongoing.

Conclusions
Low liver Veff (<30%) HCC SBRT delivered concurrently with sorafenib 400 mg po daily appears tolerable. However, in high liver Veff (30-60%) HCC SBRT, 400 mg was not tolerable due to luminal GI toxicity, and sorafenib 200 mg po daily was the maximally tolerated dose. Strategies to reduce toxicity from SBRT and sorafenib are needed. Sequential SBRT followed by sorafenib, rather than a concurrent approach, is recommended.