帶電粒子在治療肝細胞癌之發展與應用

Advances and Applications of Charged Particle Therapy in Hepatocellular Carcinoma

對於肝細胞癌（肝癌）病人，手術切除和局部治療（包括經皮乙醇注射，射頻熱消融和經動脈化學栓塞）是有效局部控制疾病進展和增加存活率的主要治療方法。由於帶電粒子治療（charged particle therapy, CPT），包括質子放射治療（proton beam radiotherapy）和碳離子放射治療（carbon ion radiotherapy，又稱重粒子治療），可將放射線劑量提高至對肝腫瘤進行有效的放射劑量，並使正常肝實質和鄰近胃腸道避免於放射線傷害之臨床治療優勢，令CPT已成為局部治療肝細胞癌的替代治療策略。本文簡要回顧肝癌病人接受各種CPT的放射劑量（從常規傳統療程到低分次短療程）之療效、安全性和臨床預後。我們發現，CPT的局部控制率更好（約略80％到96％），病程無進展之2年存活率約略40％和3年整體存活率（約略50％到75％）。此外，CPT很少導致晚期第三級胃腸道副作用和輻射所誘發肝毒性。若肝癌位於肝門區域（肝中心腫瘤），建議使用傳統分次CPT，以避免膽道和腸胃道的長期放射線副作用，而位於肝周圍區域（不是肝中心）的較大肝腫瘤，低分次短療程且每次高劑量CPT，可以提供更好的局部控制率。

Surgical resection and local treatments, including percutaneous ethanol injection, radiofrequency thermal ablation, and transarterial chemoembolization are the main modality treatments for loco-regionally controlling disease progression and increasing survival of patients with hepatocellular carcinoma (HCC). Because charged particle therapy (CPT), including proton beam radiotherapy and carbon ion radiotherapy, allows effective radiation doses to hepatic tumors but simultaneously spares the normal liver parenchyma and adjacent gastrointestinal tract from radiation, CPT has become an alternative strategy for locally treating HCC. We briefly reviewed various radiation dosages (from conventional courses to hypofractionated short-courses), the efficacy, the safety, and the clinical outcomes of HCC patients who received CPT. We found that CPT provides a better local control rate, ranging from 80% to 96%, a 2-year progression-free survival around 40%, and a 3-year overall survival ranging from 50% to 75%. Furthermore, CPT results in rare grade 3 toxicities of the late gastrointestinal tract adverse effects and radiation-induced liver disease. For central tumors of HCC, conventional CPT is preferred because it rarely causes late toxicities of the biliary and gastrointestinal tracts, whereas hypofractionated short-course CPT might provide better local control for larger-sized tumors that are located at peripheral areas of liver.