Main Session
Sep 30
QP 36 - From Brachy to Beams to Biologics: Innovations in Esophageal and Liver Cancer

1215 - Long-Term Outcomes of Image-Guided Proton Therapy for Treatment-Naïve Solitary Hepatocellular Carcinoma Amenable to Surgical Resection or Radiofrequency Ablation: A Pooled Analysis of a Phase II Trial and Prospective Cohort

08:20am - 08:25am ET
Room 162

Presenter(s)

Hiromitsu Iwata, MD, PhD Headshot
Hiromitsu Iwata, MD, PhD - Nagoya Proton Therapy Center, Nagoya City University West Medical Center, Nagoya, Aichi

H. Iwata1, Y. Hattori2, K. Nakajima2, S. Sudo Sr2, M. Nishio2, Y. Imai2, K. Hayashi3, T. Toshito4, M. Oguri5, J. Shoji6, A. Hiwatashi5, and H. Ogino2; 1Department of Radiation Oncology, Nagoya Proton Therapy Center, Nagoya City University West Medical Center, Nagoya, Aichi, Japan, 2Department of Radiation Oncology, Nagoya Proton Therapy Center, Nagoya City University West Medical Center, Nagoya, Japan, 3Department of Proton Therapy Technology, Nagoya Proton Therapy Center, Nagoya City University West Medical Center, Nagoya, Japan, 4Department of Proton Therapy Physics, Nagoya Proton Therapy Center, Nagoya City University West Medical Center, Nagoya, Japan, 5Department of Radiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, 6Department of Diagnostic Radiology, Nagoya City University West Medical Center, Nagoya, Japan

Purpose/Objective(s):

Treatment-naïve solitary hepatocellular carcinoma (HCC) amenable to surgical resection or radiofrequency ablation (RFA) is classified as Barcelona Clinic Liver Cancer (BCLC) stage 0/A; however, evidence regarding the long-term outcomes of radiotherapy in this setting remains limited. This study aimed to evaluate the long-term efficacy and safety of image-guided proton therapy (IGPT) for these patients.

Materials/Methods:

This single-institution cohort study retrospectively pooled two prospectively enrolled patient populations: (1) a prospective phase II clinical trial conducted between February 2013 and February 2016 (n = 45) and (2) a prospective observational registry using identical eligibility criteria conducted between March 2016 and March 2022 (n = 65), for a total of 110 patients. Eligibility criteria included treatment-naïve solitary HCC (T1N0M0 according to UICC TNM 7th ed.) amenable to curative therapies but declined surgical resection or RFA. Additional criteria were Child–Pugh class A5–B7, tumor diameter =12 cm, age 20–80 years, and ECOG performance status 0–1. Overall survival (OS), local control (LC), and progression-free survival (PFS) were estimated using the Kaplan–Meier method. Prognostic factors for OS were analyzed using Cox proportional hazards models. Treatment-related toxicity was assessed according to CTCAE version 4.0. Quality of life (QOL) was evaluated using the EORTC QLQ-C30 (ver. 3.0) and QLQ-HCC18 questionnaires and analyzed longitudinally using linear mixed-effects models. All patients underwent fiducial marker implantation and received respiratory-gated IGPT.

Results:

Child–Pugh class was A5, A6, and B7 in 86, 19, and 5 patients, and BCLC stage was 0, A, and C in 38, 68, and 4 patients, respectively. Peripheral tumors were treated with 66 GyRBE in 10 fractions in 88 patients, whereas centrally located tumors received 72.6 GyRBE in 22 fractions in 22 patients. The median maximum tumor diameter was 26 mm (range, 6–111 mm). The median follow-up among surviving patients was 80 months (range, 38–147.5 months). The 5-year OS, LC, and PFS rates were 79.3% (95% CI, 71.5–87.1%), 87.9% (95% CI, 81.4–94.4%), and 40.5% (95% CI, 31.1–49.9%), respectively. On multivariate analysis, Child–Pugh class and elevated PIVKA-II levels were identified as independent unfavorable prognostic factors for OS. Only one patient experienced grade =3 radiation-induced liver disease, and a decline of =2 points in Child–Pugh score within 1 year after treatment was observed in two patients. Major QOL domains, including physical, social, and emotional functioning, were overall well preserved.

Conclusion:

IGPT for treatment-naïve solitary HCC amenable to standard curative therapies demonstrated excellent long-term local control and favorable overall survival with minimal toxicity while preserving quality of life. IGPT may represent a safe and effective local treatment option comparable to surgical resection or RFA in this patient population.