Search

Purpose: Because most previous data on proton therapy for hepatocellular carcinoma (HCC) were retrospectively collected from inoperable or previously treated cases, our aim was to evaluate the outcome of image-guided proton therapy (IGPT) for operable or radiofrequency ablation-treatable primary HCC., Methods and Materials: This phase 2 study prospectively investigated the efficacy and safety of IGPT and quality of life (QoL) after IGPT for operable/ablatable HCC. The primary endpoint was overall survival, and the secondary endpoints were local control, incidence of grade ≥3 adverse events, and changes in QoL. Toxicities were evaluated with Common Terminology Criteria for Adverse Events, version 4.0. QoL scores were assessed with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, version 3.0, and Quality of Life Questionnaire-Hepatocellular Carcinoma/Primary Liver Cancer Module. IGPT was performed using respiratory-gated techniques., Results: Forty-five patients (median age: 68 years; range, 36-80 years) were enrolled between June 2013 and February 2016; 38 were considered operable and 14 were indicated for radiofrequency ablation. The major underlying liver diseases were hepatitis B (n = 16), hepatitis C (n = 13), alcoholic hepatitis (n = 3), and nonalcoholic fatty liver disease (n = 13). The Child-Pugh score was A5 in 32 patients, A6 in 9 patients, and B7 in 4 patients. Thirty-seven patients with a peripherally located tumor were given 66 Gy relative biological effectiveness in 10 fractions, and 8 patients with a centrally located tumor received 72.6 Gy relative biological effectiveness in 22 fractions. The median follow-up period of surviving patients was 60 months (range, 42-75 months). Two- and 5-year overall survival rates were 84% (95% confidence interval [CI], 74%-95%) and 70% (95% CI, 56%-84%), respectively, and local control rates were 95% (95% CI, 89%-100%) and 92% (95% CI, 84%-100%), respectively. Grade 3 radiation-induced liver disease was observed in 1 patient. No significant changes were noted in QoL scores 1 year after treatment, except for body image., Conclusions: Although the primary endpoint did not meet statistical significance as planned in the study design, IGPT is a safe and effective treatment for solitary primary HCC and may become a treatment option., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study is to analyze the technical and clinical success rates and safety of transarterial fiducial marker placement for image-guided proton therapy for malignant liver tumors., Methods and Materials: Fifty-five patients underwent this procedure as an interventional treatment. Five patients had 2 tumors, and 4 tumors required 2 markers each, so the total number of procedures was 64. The 60 tumors consisted of 46 hepatocellular carcinomas and 14 liver metastases. Five-mm-long straight microcoils of 0.018 inches in diameter were used as fiducial markers and placed in appropriate positions for each tumor. We assessed the technical and clinical success rates of transarterial fiducial marker placement, as well as the complications associated with it. Technical success was defined as the successful delivery and placement of the fiducial coil, and clinical success was defined as the completion of proton therapy., Results: All 64 fiducial coils were successfully installed, so the technical success rate was 100 % (64/64). Fifty-four patients underwent proton therapy without coil migration. In one patient, proton therapy was not performed because of obstructive jaundice due to bile duct invasion by hepatocellular carcinoma. Thus, the clinical success rate was 98 % (54/55). Slight bleeding was observed in one case, but it was stopped immediately and then observed. None of the patients developed hepatic infarctions due to fiducial marker migration., Conclusion: Transarterial fiducial marker placement appears to be a useful and safe procedure for proton therapy for malignant liver tumors.

A 70‐year‐old man undergoing treatment for immunoglobulin G4‐related disease developed a liver mass on computed tomography during routine imaging examination. The tumor was located in the hepatic S1/4 region, was 38 mm in size, and showed arterial enhancement on dynamic contrast‐enhanced computed tomography. We performed a liver biopsy and diagnosed moderately differentiated hepatocellular carcinoma. The patient underwent proton beam therapy. The tumor remained unchanged but enlarged after 4 years. The patient was diagnosed with hepatocellular carcinoma recurrence and received hepatic arterial chemoembolization. However, 1 year later, the patient developed jaundice, and the liver tumor grew in size. Unfortunately, the patient passed away. Autopsy revealed that the tumor consisted of spindle‐shaped cells exhibiting nuclear atypia and a fission pattern and tested positive for α‐smooth muscle actin and vimentin. No hepatocellular carcinoma components were observed, and the patient was pathologically diagnosed with hepatic leiomyosarcoma. Next‐generation sequencing revealed somatic mutations in CACNA2D4, CTNNB1, DOCK5, IPO8, MTMR1, PABPC5, SEMA6D, and ZFP36L1. Based on the genetic mutation, sarcomatoid hepatocarcinoma was the most likely pathogenesis in this case. This mutation is indicative of the transition from sarcomatoid hepatocarcinoma to hepatic leiomyosarcoma. [ABSTRACT FROM AUTHOR]

Transient increases in α-fetoprotein (AFP) and protein induced by vitamin K antagonist II (PIVKA-II), so-called flares, are frequently observed after treatment of hepatocellular carcinoma (HCC). In the present study, changes in AFP and PIVKA-II levels after proton therapy (PT), and the relationship between the flare phenomenon and clinical response were investigated. In 82 patients with stage I/II HCC (59 with no recurrence and 23 with out-of-field recurrence within 1 year), serum AFP and PIVKA-II levels were measured at 1, 3, 6, 9 and 12 months post-PT. AFP and PIVKA-II flares were defined as a >20% increase from the preceding serum level above 20 ng/ml (AFP) or 40 mAU/ml (PIVKA-II), followed by a >20% drop. Among the 59 patients with no recurrence, 3 (5.1%) had an AFP flare, while 23 (39%) had a PIVKA-II flare. The median time to AFP and PIVKA-II flare peaks was 1 and 6 months, respectively. In 4 patients, PIVKA-II flares were observed twice during follow-up. In 1 patient, AFP and PIVKA-II flares were observed simultaneously at 1 month post-PT. The PIVKA-II level pre-PT was significantly higher in the PIVKA-II flare-positive group compared with that in the flare-negative group (P=0.015, odds ratio 4.3, 95% confidence interval, 1.3–14.0). In the 23 patients with out-of-field recurrence, the median increase rate of PIVKA-II (203%) was higher than that in the PIVKA-II-flare-positive group (111%, P=0.035) and the time to recurrence (median, 9 months) was longer than the time to peak AFP level (1 month) in the AFP-flare-positive group (P=0.033). There was no significant association between flares and clinical response. Increases in AFP and PIVKA-II levels following PT should be assessed with caution to avoid misinterpretation of therapeutic outcome. [ABSTRACT FROM AUTHOR]

Simple Summary: The number of very elderly patients with hepatocellular carcinoma (HCC) aged 80 years and older has been steadily increasing with extensions in life expectancy due to improvements in medication and healthcare, and many recent studies focused on this specific population. Since these patients often have a higher incidence of associated co-morbidities, and improving or maintaining their quality of life is important, minimally invasive treatment is warranted. We retrospectively investigated the efficacy and safety of image-guided proton therapy (IGPT) for elderly HCC patients. IGPT was safe and considered effective for HCC in elderly patients. Since there was no worsening of quality of life during and after treatment, IGPT may cure HCC with a high probability without changing the daily living of elderly patients. This study retrospectively investigated the efficacy and safety of image-guided proton therapy (IGPT) for elderly (≥80 years old) hepatocellular carcinoma (HCC) patients. Proton therapy was performed using respiratory-gated and image-guided techniques. Seventy-one elderly HCC patients were treated using IGPT. The Child–Pugh score was A5 in 49 patients, A6 in 15, and B7-9 in 7. Forty-seven patients with a peripherally located tumor were administered 66 gray relative biological effectiveness (GyRBE) in 10 fractions, whereas 24 with a centrally located tumor received 72.6 GyRBE in 22 fractions. The median follow-up period of surviving patients was 33 months (range: 9–68). Two-year overall survival (OS) and local control (LC) rates estimated by the Kaplan–Meier method were 76% (95% confidence interval: 66–87%) and 88% (80–97%), respectively. According to the Common Terminology Criteria for Adverse Events version 4.0, no grade 2 or higher radiation-induced liver disease was observed, and only 1 patient developed grade 3 dermatitis. The quality of life score (European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 version 3.0, QLQ-HCC18, and SF-36) did not change after 1 year, except for the three-mental component summary (SF-36, improvement). IGPT is a safe and effective treatment for HCC in elderly patients. [ABSTRACT FROM AUTHOR]