title: Long-term outcomes of proton beam therapy in patients with previously untreated hepatocellular carcinoma.
abstract: Long-term efficacy of proton beam therapy (PBT) remains unclear for patients with previously untreated hepatocellular carcinoma (HCC). We aimed to study the long-term outcomes of PBT according to Barcelona Clinic Liver Cancer (BCLC) staging classifications in patients with previously untreated HCC. The major eligibility criteria of this observational study were an Eastern Cooperative Oncology Group performance status (PS) 0-2, Child-Pugh grade A or B, previously untreated HCC covered within an irradiation field, and no massive ascites. A total of 66.0-77.0 GyE was administered in 10-35 fractions. Local tumor control (LTC), defined as no progression in the irradiated field, progression-free survival (PFS), and overall survival (OS) were assessed according to BCLC staging. From 2002 to 2009 at our institution, 129 patients were eligible. The 5-year LTC, PFS, and OS rates were 94%, 28%, and 69% for patients with 0/A stage disease (n = 9/21), 87%, 23%, and 66% for patients with B stage disease (n = 34), and 75%, 9%, and 25% for patients with C stage disease (n = 65), respectively. The 5-year LTC and OS rates of 15 patients with tumor thrombi in major vessels were 90% and 34%, respectively. Multivariate analyses revealed that PS (0 versus 1-2) was a significant prognostic factor for OS. No grade 3 or higher adverse effects were observed. PBT showed favorable long-term efficacies with mild adverse effects in BCLC stage 0 to C, and can be an alternative treatment for localized HCC especially when accompanied with tumor thrombi. This study was registered with UMIN Clinical Trials Registry (UMIN000025342).
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Fukuda
authors.affiliation: Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Okumura
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Abei
authors.affiliation: Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Fukumitsu
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ishige
authors.affiliation: Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Masashi
authors.identifier: http://orcid.org/0000-0001-7837-1301
authors.initials: M
authors.lastname: Mizumoto
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Hasegawa
authors.affiliation: Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Haruko
authors.initials: H
authors.lastname: Numajiri
authors.affiliation: Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Ohnishi
authors.affiliation: Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ishikawa
authors.affiliation: Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuboi
authors.affiliation: Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sakurai
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Ichinosuke
authors.initials: I
authors.lastname: Hyodo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000532:radiotherapy*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D061766:Proton Therapy / Q000009:adverse effects / Q000379:methods*; D015996:Survival Rate; D016896:Treatment Outcome
keywords: Aged patients; Barcelona Clinic Liver Cancer staging; hepatocellular carcinoma; proton beam therapy; vascular tumor thrombi