Charged-particle therapy for hepatocellular carcinoma

Abstract

Historically, the use of external-beam radiotherapy for hepatocellular carcinoma (HCC) has been limited by toxicity to the uninvolved liver and surrounding structures. Advances in photon radiotherapy have improved dose conformality to the tumor and facilitated dose escalation, a key contributor to improved HCC radiation treatment outcomes. However, despite these advances in photon radiotherapy, significant volumes of liver still receive low doses of radiation that can preclude dose escalation, particularly in patients with limited functional liver reserves. By capitalizing on the lack of exit dose along the beam path beyond the tumor and higher biological effectiveness, charged-particle therapy offers the promise of maximizing tumor control via dose escalation without excessive liver toxicity. In this review, we discuss the distinctive biophysical attributes of both proton and carbon ion radiotherapy, particularly as they pertain to treatment of HCC. We also review the available literature regarding clinical outcomes and the toxicity of using charged particles for the treatment of HCC.

Figure 1

Proton (Bragg peak and modulated Bragg peak) and 18 MV photon depth dose curves.

Figure 2

Comparison between intensity modulated radiation therapy (photons) and proton radiotherapy (protons) for an unresectable hepatocellular carcinoma in a patient with multiple medical co-morbidities. A. Representative computed tomography (CT) axial, coronal and sagittal slices. Isodose lines are for a delivered proton dose of 66Gy in 20 fractions. B. Dose volume histogram comparison of the photon and proton plans for this patient. Note relative sparing of more liver in the low-dose region (below 30Gy). Mean liver dose was 30Gy for photons and 28Gy for protons.

Figure 3

Radiographic assessment of treatment response. Worsening renal function due to underlying coronary artery disease and peripheral vascular disease prompted switching to non-contrast CT (4 months) and magnetic resonance imaging (beyond 4 months). Note durable local control with progressive reduction in tumor volume and vascularity with evolution of central tumor necrosis.