Phase I Radiation Dose-Escalation Study to Investigate the Dose-Limiting Toxicity of Concurrent Intra-Arterial Chemotherapy for Unresectable Hepatocellular Carcinoma

Abstract

Concurrent intra-arterial chemotherapy and radiotherapy (iA-CCRT) can increase the response rate in hepatocellular carcinoma (HCC), but may cause a higher toxicity. We conducted this Phase I study to investigate the dose-limiting toxicity of iA-CCRT for HCC. In total, 52.5 Gy in 25 fractions was prescribed as planning target volume (PTV) 1 at dose level 1. The dose escalation was 0.2 Gy per fraction and up to 2.5 Gy, with 62.5 Gy at level 3. Concurrent intra-arterial 5-fluorouracil was administered during the first and fifth weeks of radiotherapy (RT). Toxicities were graded using the Common Toxicity Criteria for Adverse Events, version 4.0. Results: Seventeen patients with HCC were analyzed: four at dose level 1, 6 at level 2, and 7 at level 3. The mean irradiated dose administered to the uninvolved liver at each dose level was 21.3, 21.6, and 18.2 Gy, respectively. There was no grade ≥3 gastrointestinal toxicity; two patients experienced grade 3 hyperbilirubinemia. All patients had Child-Pugh class A disease, but 3 patients developed class B disease after iA-CCRT. During a median follow-up of 13 months, the median progression-free survival (PFS) and overall survival (OS) were 10 and 22 months, respectively. Patients treated at dose level 3 showed improved PFS and OS. Conclusions: Radiation dose escalation of iA-CCRT did not cause any significant toxicities in patients with advanced HCC. Further large-scale studies with long-term follow-up are needed to determine the efficacy and feasibility of higher doses of iA-CCRT.

External Beam Radiation Therapy for Primary Liver Cancers: An ASTRO Clinical Practice Guideline

“…50 It should be noted that there are multiple studies using standard fractionated EBRT with concurrent hepatic arterial infusion or systemic chemotherapy in the Asian literature for HCC with favorable clinical outcomes. [103][104][105][106] Given the concerns for increased toxicity, concurrent combination of EBRT and targeted therapy should be used in the context of a clinical trial.…”

Fluorescent Imaging-Guided Chemo- and Photodynamic Therapy of Hepatocellular Carcinoma with HCPT@NMOFs-RGD Nanocomposites

“… 1 , 2 Although early HCC can be managed by ablation, 3 the results of surgery are poor in patients with advanced disease due to the presence of extrahepatic infiltration and metastases. 4 Chemotherapy is one of the standard strategies for patients with advanced HCC. 5 Among chemotherapeutic drugs, 10-hydroxycamptothecin (HCPT), a topoisomerase I inhibitor, inhibits cell proliferation and has a broad spectrum of antitumor activity against breast, colon, lung, and ovarian cancers in clinical practice.…”

Gut microbiome dysbiosis in patients with hepatitis B virus-related hepatocellular carcinoma after extended hepatectomy liver failure

“…The main causes of HCC in the Chinese population are viral hepatitis or cirrhosis, especially the hepatitis B virus (4,5). Currently, numerous therapeutic approaches have been applied for treating HCC, such as surgical resection, liver transplantation, ablation treatments (3,6), transcatheter arterial chemoembolization (TACE) (7), radiotherapy (8), and targeted therapy (9). In advanced cases, tyrosine-protein kinase inhibitors (i.e., sorafenib) are considered conventional first-line therapy (10), whereas immune-checkpoint inhibitors are regarded as new treatment options with a limited therapeutic response (11).…”