Carbon Ion Radiotherapy For Hepatocellular Carcinoma Research Articles

Prognostic analysis of radiation-induced liver damage following carbon-ion radiotherapy for hepatocellular carcinoma

BackgroundRadiation-induced liver damage (RILD) occasionally occurs following carbon-ion radiotherapy (CIRT) for liver tumors, such as hepatocellular carcinoma (HCC), in patients with impaired liver function disease. However, the associated risk factors remain unknown. The present study aimed to determine the risk factors of RILD after CIRT.MethodsWe retrospectively analyzed 108 patients with HCC treated with CIRT at the Osaka Heavy Ion Therapy Center between December 2018 and December 2022. RILD was defined as a worsening of two or more points in the Child–Pugh score within 12 months following CIRT. The median age of the patients was 76 years (range 47–95 years), and the median tumor diameter was 41 mm (range 5–160 mm). Based on the pretreatment liver function, 98 and 10 patients were categorized as Child–Pugh class A and B, respectively. We analyzed patients who received a radiation dose of 60 Gy (relative biological effectiveness [RBE]) in four fractions. The median follow-up period was 9.7 months (range 2.3–41.1 months), and RILD was observed in 11 patients (10.1%).ResultsMultivariate analysis showed that pretreatment Child–Pugh score B (p = 0.003, hazard ratio [HR] = 6.90) and normal liver volume spared from < 30 Gy RBE (VS30 < 739 cm3) (p = 0.009, HR = 5.22) were significant risk factors for RILD. The one-year cumulative incidences of RILD stratified by Child–Pugh class A or B and VS30 < 739 cm3 or ≥ 739 cm3 were 10.3% or 51.8% and 39.6% or 9.2%, respectively.ConclusionIn conclusion, the pretreatment Child–Pugh score and VS30 of the liver are significant risk factors for RILD following CIRT for HCC.

Carbon-ion radiotherapy for hepatocellular carcinoma with major vascular invasion: a retrospective cohort study

BackgroundMacroscopic vascular invasion (MVI) significantly impacts survival in patients with hepatocellular carcinoma (HCC), warranting systemic therapy over locoregional therapy. Despite novel approaches, HCC with MVI has a poor prognosis compared to early-to intermediate-stage HCC. This study aimed to evaluate the safety and efficacy of carbon-ion radiotherapy (C-ion RT) for HCC characterized by MVI.MethodsThis retrospective cohort study evaluated HCC patients with MVI treated using C-ion RT with a dose of 45.0–48.0 Gy/2 fractions or 52.8–60.0 Gy/4 fractions between 1995 and 2020 at our institution in Japan. We analyzed the prognostic factors and rates of local recurrence, survival, and adverse events. The local recurrence rate was determined using the cumulative incidence function, with death as a competing event. Survival rates were determined using the Kaplan–Meier method. The log-rank test for univariate analysis and the Cox proportional hazards model for multivariate analysis were used to compare subgroups.ResultsIn total, 76 patients with a median age of 71 years (range, 45–86 years) were evaluated. Among them, 68 had Child–Pugh grade A while eight had grade B disease. In 17 patients, the vascular tumor thrombus reached the inferior vena cava or main trunk of the portal vein. Over a median follow-up period of 27.9 months (range, 1.5–180.4 months), the 2-year overall survival, progression-free survival, and local recurrence rates were 70.0% (95% confidence interval [CI]: 57.7–79.4%), 32.7% (95% CI: 22.0–43.8%), and 8.9% (95% CI: 1.7–23.5%), respectively. A naïve tumor and a single lesion were significant prognostic factors for overall survival in the univariate analysis. Albumin-bilirubin grade 1 and a single lesion were independent prognostic factors in the multivariate analysis. Overall, four patients (5%) experienced grade 3 late adverse events, with no observed grade 4 or 5 acute or late adverse events.ConclusionsC-ion RT for HCC with MVI showed favorable local control and survival benefits with minimal toxicity.

Indications of IMRT, PRT and CIRT for HCC from comparisons of dosimetry and normal tissue complication possibility.

To identify the indications for hepatocellular carcinoma (HCC) irradiated by intensity-modulated photon radiotherapy (IMRT), proton radiotherapy (PRT) or carbon-ion radiotherapy (CIRT) by comparing of dosimetric parameters and incidences of classic radiation-induced liver disease (RILD). In all, 40HCCs were divided into groupA (tumors located > 1 cm away from gastrointestinal [GI] tract), and groupB (tumors located < 1 cm away from GI tract). The prescribed curative doses were 60 Gy (relative biological effectiveness [RBE]) in 10fractions for groupA, and 67.5 Gy (RBE) in 15fractions for groupB. IMRT, PRT and CIRT plans were separately generated to reach the curative doses and coverage. Dosimetric parameters evaluated were mean dose to normal liver (MDTNL) and the volume of normal liver receiving more than 1 Gy (RBE) (V1). Lyman-Kutcher-Burman model was used to determine the incidences of classic RILD, and Power model of non-linear regression, to estimate the tumor volume that could be irradiated with the curative doses within dose constraint of MDTNL. With comparable target doses, the MDTNL (Gy [RBE]) were 18.8 ± 3.7, 13.5 ± 3.1 and 12.8 ± 2.7 in groupA and 24.9 ± 7.1, 18.2 ± 3.7 and 17.5 ± 3.7 in groupB, respectively, for IMRT, PRT and CIRT. The classic RILD incidences (%) were 22.3 ± 30.0 in IMRT, 2.3 ± 4.9 in PRT and 1.2 ± 2.4 in CIRT. V1 (%) were 89.9 ± 8.8, 43.0 ± 10.2 and 45.9 ± 8.8, respectively, for IMRT, PRT and CIRT. PRT and CIRT could spare the liver more than IMRT. IMRT could deliver the curative doses to HCC up to adiameter of 7.9 cm; PRT, up to 13.2 cm; and CIRT, up to 14.8 cm.

Short-course carbon-ion radiotherapy for hepatocellular carcinoma: A multi-institutional retrospective study.

Carbon-ion radiation therapy has shown encouraging results in hepatocellular carcinoma patients in single-centre studies. We evaluated the effectiveness and safety of short-course carbon-ion radiation therapy for hepatocellular carcinoma in a multicentre study conducted by the Japan Carbon Ion Radiation Oncology Study Group. Consecutive hepatocellular carcinoma patients who were treated with carbon-ion radiation therapy in four or fewer fractions at four Japanese institutions between April 2005 and November 2014 were analysed retrospectively. The primary outcome was overall survival; secondary outcomes were local control rate, treatment-related toxicity and radiation-induced liver disease. A total of 174 patients were included in this study. Prescribed carbon-ion radiation therapy doses were (relative biological effectiveness): 48.0Gy in two fractions (n=46), and 52.8Gy (n=108) and 60.0Gy (n=20) in four fractions. The median follow-up period was 20.3 (range, 2.9-103.5) months. The overall survival and local control rates at 1, 2 and 3years were 95.4%, 82.5% and 73.3%; and 94.6%, 87.7% and 81.0% respectively. Multivariate analysis revealed that Eastern Cooperative Oncology Group performance status 1-2, Child-Pugh class B, maximum tumour diameter ≥3cm, multiple tumours and serum alpha foetoprotein level >50ng/mL were significant prognostic factors of overall survival. No treatment-related death occurred during the follow-up period. Grades 3 or 4 treatment-related toxicities were observed in 10 patients (5.7%); radiation-induced liver disease was observed in three patients (1.7%). Short-course carbon-ion radiation therapy is a safe, effective and potentially curative therapy for hepatocellular carcinoma.

A case of the cirrhotic patient performed living donor liver transplantation after carbon-ion radiotherapy for hepatocellular carcinoma

The patient was a 50-year-old female with an initial diagnosis of a single hepatocellular carcinoma in liver cirrhosis. The tumor was located in the posterior liver segment (S7) and measured 5cm with a rapid growth rate and portal invasion. The pre-treatment Child-Pugh (C-P) was grade A (six points). The total prescribed dose of carbon-ion radiotherapy (C-ion RT) was 60Gy (relative biological effectiveness) given in 4 fractions. Thereafter, tumor shrinkage and rapid decrease of the serum alpha-fetoprotein level were observed. At 1-year follow-up a new lesion was diagnosed in the left lobe and the underlying liver failure had worsened to C-P grade B (eight points). Thus, she was recommended to undergo living-donor liver transplantation (LDLT). The postoperative course was uneventful. At pathological examination, no viable tumor cells in the region treated with C-ion RT were detected. At the time of the last follow-up, the patient was in overall good general condition with no signs of tumor recurrence.

Association between changes in serum α-fetoprotein level and patterns of recurrence in patients undergoing carbon-ion radiotherapy for hepatocellular carcinoma

Objective This study aims to assess the usefulness of monitoring serum α-fetoprotein (AFP) levels for predicting recurrence patterns in patients with hepatocellular carcinoma (HCC) treated with carbon-ion radiotherapy.

Association between Changes of Serum α-fetoprotein (AFP) Level and Patterns of Recurrence in Patients undergoing Carbon-ion Radiotherapy for Hepatocellular Carcinoma

Association between Changes of Serum α-fetoprotein (AFP) Level and Patterns of Recurrence in Patients undergoing Carbon-ion Radiotherapy for Hepatocellular Carcinoma

Two-fraction carbon ion radiotherapy for hepatocellular carcinoma: Preliminary results of a phase I/II clinical trial

4124 Background: We reported that the 4-fraction/1-week carbon ion radiotherapy, that had been conducted from April 2001 to February 2003 within a phase II clinical study, appeared to be safe and to have a promising potential as a new, radical, and minimally invasive therapeutic option for hepatocellular carcinoma (HCC) at the last ASCO annual meeting. The next clinical trial of 2-fraction/2-day carbon ion radiotherapy is going on within a phase I/II study from April 2003. Patients and Methods: Twenty-five patients with histologically proven HCC were treated with 2-fraction/2-day carbon ion radiotherapy of 32.0GyE in 6, 33.6GyE in 7, 35.2GyE in 6, and 37.0GyE in 6 in a step-wise dose-escalation study from April 2003 to August 2004. Common Toxicity Criteria, RTOG/EORTC criteria were used for evaluation of toxicity. Serial changes in Child-Pugh score were investigated after the start of therapy to evaluate its invasiveness to the liver. Anti-tumor effect was evaluated by the tumor response and directly- calculated local control rate. Results: During a median follow-up of 12.1 (3.9–19.5) months, no severe adverse effects and no treatment-related deaths occurred. In the early phase, no change in the Child-Pugh score was observed in 79% (19/24), only a 1-point increase in 17% (4/24), and 2-point increase in 4% (1/24) of the patients. In the late phase, similar observations were made in 75% (12/16), 6% (1/16), and 19% (3/16), respectively. The overall tumor response rate was 96% (24/25) at 6 months after the therapy. Local control rates were 96% (24/25) and 93% (13/14) at 6 and 12 months, respectively. Overall survival rates were 100% at 6 and 12 months, respectively. There were preliminarily no differences between the results in the current study and those in the 4-fraction carbon ion radiotherapy. Conclusion: Two-fraction carbon ion radiotherapy for HCC appears preliminarily to be safe and effective. However, further observation is needed to confirm its clinical usefulness. No significant financial relationships to disclose.