Clinical Impact of Hypofractionated Carbon Ion Radiotherapy on Locally Advanced Hepatocellular Carcinoma

Abstract Background: Hepatocellular carcinoma (HCC) involving a major branch of the portal or hepatic vein is in a locally advanced stage and remains difficult to cure. This study aimed to evaluate the clinical effects of carbon ion radiotherapy (C-ion RT) in locally advanced HCC (LAHCC). Methods: The data of 11 consecutive patients with LAHCC who received C-ion RT were analyzed. The C-ion RT doses of 52.8 Gy (relative biological effectiveness [RBE]) and 60.0 Gy (RBE) were delivered in 4 fractions for standard cases, and the 60.0 Gy dose was delivered in 12 fractions for close-to-gastrointestinal-tract cases. Survival and local control probabilities were calculated using the Kaplan-Meier method. Results: The median follow-up duration after C-ion RT was 36.4 months. The median age at the time of registration for C-ion RT was 76 years. The median tumor size was 53 mm. The numbers of treatment-naive and recurrent HCC patients were 1 and 10, respectively. Direct invasion of the major branch of the portal vein, hepatic vein, or both portal and hepatic veins was observed in three, five, and three patients, respectively. The 3-year overall survival, local control, and progression-free survival rates were 64%, 78%, and 18%, respectively. No patient developed radiation-induced liver diseases or grade 3 or higher toxicities in the acute and late phases. Conclusions: C-ion RT showed favorable clinical outcomes with a high rate of local control and minimal toxicities in LAHCC. Our findings suggest that C-ion RT is a promising multidisciplinary treatment option in LAHCC.

Download Full-text

Clinical Impact of Hypofractionated Carbon Ion Radiotherapy on Locally Advanced Hepatocellular Carcinoma

10.21203/rs.3.rs-33027/v1 ◽

2020 ◽

Author(s):

Shintaro Shiba ◽

Kei Shibuya ◽

Masahiko Okamoto ◽

Shohei Okazaki ◽

Shuichiro Komatsu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatic Vein ◽

Local Control ◽

Multidisciplinary Treatment ◽

Locally Advanced ◽

Carbon Ion Radiotherapy ◽

Advanced Hepatocellular Carcinoma ◽

Clinical Effects ◽

Carbon Ion ◽

Major Branch

Abstract Background Hepatocellular carcinoma (HCC) involving a major branch of the portal or hepatic vein is in a locally advanced stage and remains difficult to cure. This study aimed to evaluate the clinical effects of carbon ion radiotherapy (C-ion RT) in locally advanced HCC (LAHCC). Methods Consecutive 11 patients with LAHCC who received C-ion RT were analyzed. The C-ion RT doses of 52.8 Gy (relative biological effectiveness [RBE]) and 60.0 Gy (RBE) were delivered in four fractions for standard cases and the 60.0 Gy dose was delivered in 12 fractions for close-to-gastrointestinal-tract cases. Survival and local control probabilities were calculated using the Kaplan-Meier method. Results The median follow-up duration after C-ion RT was 36.4 months. The median age at the time of registration of C-ion RT was 76 years. The median tumor size was 53 mm. The number of treatment-naïve and recurrent HCC patients was 1 and 10, respectively. Direct invasion of the major branch of the portal vein, hepatic vein, or both the portal and hepatic veins was observed in three, five, and three patients, respectively. The 3-year overall survival, local control, and progression-free survival rates were 64%, 78%, and 18%, respectively. No patient developed radiation-induced liver diseases or grade 3 or higher toxicities of acute and late phases. Conclusions C-ion RT showed favorable clinical outcomes with a high rate of local control and minimal toxicities in LAHCC. Our findings suggest that C-ion RT is a promising multidisciplinary treatment option in LAHCC.

Download Full-text

Clinical impact of Hypofractionated carbon ion radiotherapy on locally advanced hepatocellular carcinoma

Radiation Oncology ◽

10.1186/s13014-020-01634-z ◽

2020 ◽

Vol 15 (1) ◽

Author(s):

Shintaro Shiba ◽

Kei Shibuya ◽

Masahiko Okamoto ◽

Shohei Okazaki ◽

Shuichiro Komatsu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Locally Advanced ◽

Clinical Impact ◽

Carbon Ion Radiotherapy ◽

Advanced Hepatocellular Carcinoma ◽

Carbon Ion

Download Full-text

Comparison of dose distributions when using carbon ion radiotherapy versus intensity-modulated radiotherapy for hepatocellular carcinoma with macroscopic vascular invasion: A retrospective analysis

10.21203/rs.2.14182/v1 ◽

2019 ◽

Author(s):

Shintaro Shiba ◽

Kei Shibuya ◽

Motohiro Kawashima ◽

Naoko Okano ◽

Takuya Kaminuma ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

High Risk ◽

Locally Advanced ◽

Liver Volume ◽

Intensity Modulated Radiotherapy ◽

Carbon Ion Radiotherapy ◽

Advanced Hepatocellular Carcinoma ◽

Dose Distributions ◽

Carbon Ion ◽

Intensity Modulated

Abstract Background. Studies comparing the dose distributions of carbon ion radiotherapy (C-ion RT) and intensity-modulated radiotherapy (IMRT) in patients with locally advanced hepatocellular carcinoma (LAHCC) are lacking. This study aimed to investigate the dose distributions of these modalities and identify any advantages to using C-ion RT. Methods. Patients with LAHCC who had undergone C-ion RT between June 2010 and November 2018 were retrospectively analyzed. From among 210 patients with hepatocellular carcinoma who received C-ion RT, 10 consecutive patients with LAHCC were included. The dose-volume histogram parameters of clinical plans using C-ion RT at 60 Gy (relative biological effectiveness [RBE]) and simulated plans using IMRT at 60 Gy and 50 Gy were compared. We evaluated the three plans in terms of the following parameters: the percentage of the minimum dose that covered 95% of the target volume (D95); mean liver dose (MLD); and percentage of the normal liver volume that received at least 5 Gy (V5), 10 Gy (V10), 20 Gy (V20), 30 Gy (V30), 40 Gy, and 50 Gy. Patients at high risk of developing radiation-induced liver disease (RILD) were those with MLD and V30 of >23 Gy and >28%, respectively. Results. The V5, V10, V20, and MLD were significantly lower in patients who received 60 Gy (RBE) of C-ion RT than in those who received 60 Gy of IMRT, although the D95 values were not significantly different. The V5, V10, and V20 were also significantly lower in patients who received 60 Gy (RBE) of C-ion RT than in those who received 50 Gy of IMRT; moreover the D95 was significantly superior in the former group. The numbers of high-risk patients who developed RILD when administered 60 Gy (RBE) of C-ion RT, 60 Gy of IMRT, and 50 Gy of IMRT were 1, 7, and 6, respectively. Conclusions. C-ion RT exhibits a better dose distribution to the liver than does IMRT when treating patients with LAHCC. C-ion RT made it possible to treat patients with LAHCC who otherwise could not be treated using IMRT because of the high risk of RILD.

Download Full-text

Effectiveness of Carbon Ion Radiation in Locally Advanced Pancreatic Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.708884 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jakob Liermann ◽

Patrick Naumann ◽

Fabian Weykamp ◽

Philipp Hoegen ◽

Juergen Debus ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Local Control ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Progression Free Survival ◽

Locally Advanced Pancreatic Cancer ◽

Carbon Ion Radiotherapy ◽

Free Survival ◽

Carbon Ion

PurposeEffective treatment strategies for unresectable locally advanced pancreatic cancer (LAPC) patients are eagerly warranted. Recently, convincing oncological outcomes were demonstrated by carbon ion radiotherapy. Nevertheless, there is a lack of evidence for this modern radiation technique due to the limited number of carbon ion facilities worldwide. Here, we analyze feasibility and efficacy of carbon ion radiotherapy in the management of LAPC at Heidelberg Ion Beam Therapy Center (HIT).MethodsBetween 2015 and 2020, 21 LAPC patients were irradiated with carbon ions with a total dose of 48 Gy (RBE) in single doses of 4 Gy (RBE). Three patients (14%) were treated with concomitant chemotherapy with gemcitabine 300 mg/m2 body surface weekly. Toxicity rates were extracted from the charts. Overall survival, progression free survival, local control, and locoregional control were evaluated using Kaplan–Meier estimates.ResultsOne patient developed ascites CTCAE grade III during radiotherapy, which was related to a later histologically confirmed metachronous peritoneal carcinomatosis. No further higher-graded toxicity could be observed. The most common symptoms were nausea and abdominal pain. After a median estimated follow-up time of 19.1 months, the median progression free survival was 3.7 months, and the median overall survival was 11.9 months. The estimated 1-year local control and locoregional control rates were 89 and 84%, respectively.ConclusionCarbon ion radiotherapy of LAPC patients is safely feasible. Local tumor control rates were high. Nevertheless, compared to historical data, an overall survival improvement could not be observed. This could be explained by the poor prognosis of the selected underlying patients that mostly did not respond to prior chemotherapy as well as the early and frequent emergence of distant metastases that demonstrate the necessity of additional chemotherapy in further studies.

Download Full-text

Carbon-ion radiotherapy for locally advanced cervical cancer with bladder invasion

Journal of Radiation Research ◽

10.1093/jrr/rrw070 ◽

2016 ◽

Vol 57 (6) ◽

pp. 684-690 ◽

Cited By ~ 9

Author(s):

Shintaro Shiba ◽

Masaru Wakatsuki ◽

Shingo Kato ◽

Tatsuya Ohno ◽

Noriyuki Okonogi ◽

...

Keyword(s):

Cervical Cancer ◽

Survival Rate ◽

Local Control ◽

Locally Advanced ◽

Carbon Ion Radiotherapy ◽

Therapeutic Effects ◽

Advanced Cervical Cancer ◽

Carbon Ion ◽

Locally Advanced Cervical Cancer ◽

Bladder Invasion

Abstract The purpose of this study was to evaluate the efficacy and toxicities of carbon-ion radiotherapy (C-ion RT) for locally advanced cervical cancer with bladder invasion by a subset analysis of pooled data from eight prospective clinical trials at the National Institute of Radiological Sciences. Between June 1995 and January 2014, 29 patients with locally advanced cervical cancer with bladder invasion were identified. The median age was 56 years old (range 31–79 years old). The median tumor size at diagnosis on magnetic resonance imaging was 6.7 cm (range 3.5–11.0 cm). Histologically, 20 patients had squamous cell carcinoma and 9 had adenocarcinoma. C-ion RT was performed as a dose-escalation study in the initial trials. All patients received prophylactic whole-pelvic or extended-field irradiation and local boost. The total dose to the cervical tumor was 52.8–74.4 Gy (relative biological effectiveness) in 20 or 24 fractions. Weekly cisplatin (40 mg/m2/week, five cycles) was concurrently given to four patients. The median follow-up of all patients was 28.6 months (range 8.8–238.6 months). Grade 2 or higher late complications in the bladder were observed in eight patients, with seven developing vesicovaginal fistula. Six patients had Grade 2 or higher complications in the rectosigmoid colon. The 3-year overall survival rate was 47%, the 3-year local control rate was 66%, and the 3-year disease-free survival rate was 28%. In this study, C-ion RT showed favorable local control with reasonable toxicities, but the results were still unsatisfactory. We have the expectation of improvement of therapeutic effects by using C-ion RT with concurrent chemotherapy.

Download Full-text

Controlling Major Portal Vein Invasion Progression during Lenvatinib Treatment by Carbon-Ion Radiotherapy in Patients with Advanced Hepatocellular Carcinoma

Case Reports in Oncology ◽

10.1159/000517440 ◽

2021 ◽

pp. 1103-1110

Author(s):

Ryoi Yoshida ◽

Keisuke Koroki ◽

Hirokazu Makishima ◽

Sadahisa Ogasawara ◽

Takamasa Ishino ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Portal Vein ◽

Systemic Therapy ◽

Standard Treatment ◽

Carbon Ion Radiotherapy ◽

Advanced Hepatocellular Carcinoma ◽

Portal Vein Invasion ◽

Main Trunk ◽

Advanced Hcc ◽

Carbon Ion

Macrovascular invasion (MVI), including portal vein tumor thrombosis (PVTT), is strongly associated with poor prognosis in patients with hepatocellular carcinoma (HCC). While recommended standard treatment for patients with advanced HCC is systemic therapy, various treatment approaches, including resection, transarterial chemoembolization, and radiation, have been empirically suggested to improve prognosis by eliminating or controlling MVI. Herein, we report our experience of a case with advanced HCC where MVI was controlled by carbon-ion radiotherapy (CIRT) while on systemic therapy, resulting in a prolonged survival. A female patient with HCC in her early 60s had multiple intrahepatic lesions (maximum 60 mm in diameter) with PVTT. The PVTT of this patient had reached the main trunk of the portal vein despite the use of lenvatinib. The other intrahepatic lesions of the patient, except PVTT, had been controlled by lenvatinib. Therefore, hoping to control PVTT, we attempted CIRT. The patient resumed lenvatinib therapy after the irradiation. During lenvatinib re-treatment, no evident progression of PVTT was observed in the patient.

Download Full-text

En bloc transdiaphragmatic lung resection for locally advanced hepatocellular carcinoma: a case report

Journal of Surgical Case Reports ◽

10.1093/jscr/rjaa084 ◽

2020 ◽

Vol 2020 (6) ◽

Author(s):

Kit-fai Lee ◽

Randolph H L Wong ◽

Howard H W Leung ◽

Eugene Y J Lo ◽

Charing C N Chong ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Locally Advanced ◽

Left Lung ◽

Lower Lobe ◽

Uneventful Recovery ◽

Advanced Hepatocellular Carcinoma ◽

Right Hepatectomy ◽

En Bloc ◽

Liver Recurrence ◽

Lung Base

Abstract A 56-year-old man presented with an 11-cm hepatocellular carcinoma (HCC) at segment 7 of liver. To induce left liver hypertrophy, a sequential transarterial chemoembolization (TACE) and portal vein embolization before right hepatectomy were adopted. However, the tumor further increased in size despite TACE and invaded through the diaphragm to the right lung base. Anterior approach right hepatectomy with en bloc wedge resection of the involved right lower lobe of lung by endovascular staplers via transdiaphragmatic approach was performed. The diaphragmatic defect was closed with Goretex mesh. Patient made an uneventful recovery. Pathology confirmed a 12.5 cm poorly differentiated HCC invading through diaphragm to lung. During follow-up, patient developed a 6 cm recurrence at left lung base 17 months after surgery for which he received sorafenib therapy. However, the lung mass further increased in size with new liver recurrence at segment 3 despite treatment. He succumbed 2 years and 3 months after surgery.

Download Full-text

Radiomics and Dosiomics for Predicting Local Control after Carbon-Ion Radiotherapy in Skull-Base Chordoma

Cancers ◽

10.3390/cancers13020339 ◽

2021 ◽

Vol 13 (2) ◽

pp. 339

Author(s):

Giulia Buizza ◽

Chiara Paganelli ◽

Emma D’Ippolito ◽

Giulia Fontana ◽

Silvia Molinelli ◽

...

Keyword(s):

Prognostic Factors ◽

Skull Base ◽

Local Control ◽

Tumour Progression ◽

Risk Groups ◽

Carbon Ion Radiotherapy ◽

Survival Models ◽

Carbon Ion ◽

Combined Models ◽

Skull Base Chordoma

Skull-base chordoma (SBC) can be treated with carbon ion radiotherapy (CIRT) to improve local control (LC). The study aimed to explore the role of multi-parametric radiomic, dosiomic and clinical features as prognostic factors for LC in SBC patients undergoing CIRT. Before CIRT, 57 patients underwent MR and CT imaging, from which tumour contours and dose maps were obtained. MRI and CT-based radiomic, and dosiomic features were selected and fed to two survival models, singularly or by combining them with clinical factors. Adverse LC was given by in-field recurrence or tumour progression. The dataset was split in development and test sets and the models’ performance evaluated using the concordance index (C-index). Patients were then assigned a low- or high-risk score. Survival curves were estimated, and risk groups compared through log-rank tests (after Bonferroni correction α = 0.0083). The best performing models were built on features describing tumour shape and dosiomic heterogeneity (median/interquartile range validation C-index: 0.80/024 and 0.79/0.26), followed by combined (0.73/0.30 and 0.75/0.27) and CT-based models (0.77/0.24 and 0.64/0.28). Dosiomic and combined models could consistently stratify patients in two significantly different groups. Dosiomic and multi-parametric radiomic features showed to be promising prognostic factors for LC in SBC treated with CIRT.

Download Full-text

Carbon ion radiotherapy for prostate cancer with bladder invasion

BMC Urology ◽

10.1186/s12894-021-00871-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yuhei Miyasaka ◽

Hidemasa Kawamura ◽

Hiro Sato ◽

Nobuteru Kubo ◽

Tatsuji Mizukami ◽

...

Keyword(s):

Prostate Cancer ◽

Locally Advanced ◽

Therapeutic Benefit ◽

Carbon Ion Radiotherapy ◽

Safety And Efficacy ◽

Carbon Ion ◽

Grade 3 ◽

Bladder Invasion

Abstract Background The optimal management of clinical T4 (cT4) prostate cancer (PC) is still uncertain. At our institution, carbon ion radiotherapy (CIRT) for nonmetastatic PC, including tumors invading the bladder, has been performed since 2010. Since carbon ion beams provide a sharp dose distribution with minimal penumbra and have biological advantages over photon radiotherapy, CIRT may provide a therapeutic benefit for PC with bladder invasion. Hence, we evaluated CIRT for PC with bladder invasion in terms of the safety and efficacy. Methods Between March 2010 and December 2016, a total of 1337 patients with nonmetastatic PC received CIRT at a total dose of 57.6 Gy (RBE) in 16 fractions over 4 weeks. Among them, seven patients who had locally advanced PC with bladder invasion were identified. Long-term androgen-deprivation therapy (ADT) was also administered to these patients. Adverse events were graded according to the Common Terminology Criteria for Adverse Event version 5.0. Results At the completion of our study, all the patients with cT4 PC were alive with a median follow-up period of 78 months. Grade 2 acute urinary disorders were observed in only one patient. Regarding late toxicities, only one patient developed grade 2 hematuria and urinary urgency. There was no grade 3 or worse toxicity, and gastrointestinal toxicity was not observed. Six (85.7%) patients had no recurrence or metastasis. One patient had biochemical and local failures 42 and 45 months after CIRT, respectively. However, the recurrent disease has been well controlled by salvage ADT. Conclusions Seven patients with locally advanced PC invading the bladder treated with CIRT were evaluated. Our findings seem to suggest positive safety and efficacy profiles for CIRT.

Download Full-text

Carbon Ion Radiotherapy for Oligo-Recurrence in the Lung

Pulmonary Medicine ◽

10.1155/2013/219746 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 5

Author(s):

Naoyoshi Yamamoto ◽

Mio Nakajima ◽

Hirohiko Tsujii ◽

Tadashi Kamada

Keyword(s):

Colorectal Cancer ◽

Lung Cancer ◽

Overall Survival ◽

Survival Rate ◽

Local Control ◽

Local Control Rate ◽

Carbon Ion Radiotherapy ◽

Overall Survival Rate ◽

Carbon Ion ◽

Metastatic Lung

The clinical results after carbon ion radiotherapy for the metastatic lung tumors believed to be in the state of oligo-recurrence were evaluated. One hundred and sixteen lesions in 91 patients with lung cancer metastasis were treated with carbon ion radiotherapy at our institute from April 1997 to February 2011. Regarding the prescribed dose, total dose ranged between 40 gray equivalents (GyE) and 80 GyE, and fraction size ranged from 1 to 16 fractions. After a median followup period of 2.3 years (range, 0.3–13.1 years), the statistical overall survival rate and local control rate were 71.2% and 91.9% at 2 years after treatment, respectively. Treatment-related side effects were not a clinical problem. When classified by the primary organ, there were 49 cases of lung cancer, 20 cases of colorectal cancer, and 22 cases of others. The overall survival rate and local control rate for lung metastasis cases from lung cancer at 2 years after treatment were 81.5% and 92.4%, respectively, and 65.0% and 92.0% regarding lung metastasis from colorectal cancer. Carbon ion beam therapy for the metastatic lung tumors is a safe therapy, and the therapeutic effect is comparable to the outcome obtained from reported surgical resections.

Download Full-text