Background: Follow-up after treatment for hepatocellular carcinoma (HCC) can be mostly performed using dynamic CT or MRI, but there is no common evaluation method after radiation therapy. The purpose of this study is to examine factors involved in tumor reduction and local recurrence in patients with HCC treated with proton beam therapy (PBT) and to evaluate HCC shrinkage after PBT. Methods: Cases with only one irradiated lesion or those with two lesions irradiated simultaneously were included in this study. Pre- and post-treatment lesions were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) by measuring the largest diameter. Results: The 6-, 12-, and 24-month CR + PR rates after PBT were 33.1%, 57.5%, and 76.9%, respectively, and the reduction rates were 25.1% in the first 6 months, 23.3% at 6–12 months, and 14.5% at 13–24 months. Cases that reached CR/PR at 6 and 12 months had improved OS compared to non-CR/non-PR cases. Conclusions: It is possible that a lesion that reached SD may subsequently transition to PR; it is reasonable to monitor progress with periodic imaging evaluations even after 1 year of treatment.

Hepatocellular carcinoma (HCC) with bile duct invasion (BDI) (BDIHCC) has a poor prognosis. Moreover, due to the paucity of reports, there is no consensus regarding optimal management of this clinical condition yet. The aim of this study was to clarify the efficacy and safety of proton beam therapy (PBT) for BDIHCC. Between 2009 and 2018, 15 patients with BDIHCC underwent PBT at our institution. The overall survival (OS), local control (LC), and progression-free survival (PFS) curves were constructed using the Kaplan-Meier method. Toxicities were assessed using the Common Terminology Criteria of Adverse Events version 4.0. The median follow-up time was 23.4 months (range, 7.9–54.3). The median age was 71 years (range, 58–90 years). Many patients were Child A (n = 8, 53.3%) and most had solitary tumors (n = 11, 73.3%). Additionally, most patients had central type BDI (n = 11, 73%). The median tumor size was 4.0 cm (range, 1.5–8.0 cm). The 1-, 2-, and 3-year OS rates were 80.0%, 58.7% and 40.2%, respectively, and the corresponding LC and PFS rates were 93.3%, 93.3%, and 74.7% and 72.7%, 9.7%, and 0.0%, respectively. Acute grade 1/2 dermatitis (n = 7, 46.7%), and grades 2 (n = 1, 6.7%) and 3 (n = 1, 6.7%) cholangitis were observed. Late toxicities such as grade 3 gastric hemorrhage and pleural effusion were observed. No toxicities of grade 4 or higher were observed. PBT was feasible with tolerable toxicities for the treatment of BDIHCC.

Objective: To investigate differences in uptake regions between methyl-¹¹C-L-methionine positron emission tomography (¹¹C-MET PET) and gadolinium (Gd)-enhanced magnetic resonance imaging (MRI), and their impact on dose distribution, including changing of the threshold for tumor boundaries. Methods: Twenty consecutive patients with grade 3 or 4 glioma who had recurrence after postoperative radiotherapy (RT) between April 2016 and October 2017 were examined. The study was performed using simulation with the assumption that all patients received RT. The clinical target volume (CTV) was contoured using the Gd-enhanced region (CTV(Gd)), the tumor/normal tissue (T/N) ratios of ¹¹C-MET PET of 1.3 and 2.0 (CTV (T/N 1.3), CTV (T/N 2.0)), and the PET-edge method (CTV(P-E)) for stereotactic RT planning. Differences among CTVs were evaluated. The brain dose at each CTV and the dose at each CTV defined by ¹¹C-MET PET using MRI as the reference were evaluated. Results: The Jaccard index (JI) for concordance of CTV (Gd) with CTVs using ¹¹C-MET PET was highest for CTV (T/N 2.0), with a value of 0.7. In a comparison of pixel values of MRI and PET, the correlation coefficient for cases with higher JI was significantly greater than that for lower JI cases (0.37 vs. 0.20, P = 0.007). D50% of the brain in RT planning using each CTV differed significantly (P = 0.03) and that using CTV (T/N 1.3) were higher than with use of CTV (Gd). V90% and V95% for each CTV differed in a simulation study for actual treatment using CTV (Gd) (P = 1.0 × 10^–7 and 3.0 × 10^–9, respectively) and those using CTV (T/N 1.3) and CTV (P-E) were lower than with CTV (Gd). Conclusions: The region of ¹¹C-MET accumulation is not necessarily consistent with and larger than the Gd-enhanced region. A change of the tumor boundary using ¹¹C-MET PET can cause significant changes in doses to the brain and the CTV.

Introduction: Intermediate-stage hepatocellular carcinoma (HCC) derives limited benefit from transarterial chemoembolization (TACE), which has led to introduction of the concept of “TACE-unsuitable HCC.” Drug therapy may be more beneficial, but intrahepatic lesion control tends to be a problem. Particle therapy including proton beam therapy (PBT) provides high local control (LC) with minimal toxicity, even in advanced cases. On this study, we retrospectively assessed the efficacy and safety of PBT in patients with TACE-unsuitable previously untreated HCC. Methods: Between 2010 and 2018, 202 patients underwent definitive PBT for previously untreated HCC. TACE-unsuitable HCC was defined as one or more of the following; cases exceeding up-to-seven criteria, of ALBI grade 2–3, non-simple nodular type or presence of macroscopic vascular invasion (MVI). Overall survival (OS), LC, progression-free rate (PFR), and time to progression (TTP) were analyzed by the Kaplan-Meier method. Risk factor analysis was performed using a Cox regression model. Adverse events were evaluated based on CTCAE v. 5.0. Results: TACE-unsuitable criteria were present in 165 cases. The median follow-up time was 3.35 years. The 3-year OS was 62.9%, 3-year PFR was 42.4%, and 3-year LC was 89.3%. In multivariate analysis, there were significant associations of ECOG PS, ALBI, and tumor size with OS; and of sex and tumor size with TTP; but no factors related to LC. Two cases had acute adverse events of dermatitis grade 3; and 7 cases had chronic adverse events, including 4 cases of gastrointestinal bleeding grade 3, and one each of hemobilia, pleural effusion, and erosive dermatitis. Conclusion: PBT for TACE-unsuitable previously untreated HCC, which can be a noninferior treatment option if the number of tumors is limited, but suppression of out-of-field recurrence is needed for further prolongation of survival.

Objective To investigate differences in uptake regions between methyl-¹¹C-L-methionine positron emission tomography (¹¹C-MET PET) and gadolinium (Gd)-enhanced MRI, and to examine the effects on dose distribution of changing the threshold value for definition of tumor boundaries.Methods Twenty consecutive patients with grade 3 or 4 glioma who had recurrence after postoperative RT between April 2016 and October 2017 were examined in the study. This study is simulation study assuming all patients received RT. Clinical target volume (CTV) was contoured using the Gd-enhanced region (CTV-Gd), T2-high region (CTV-T2), tumor/normal tissue (T/N) ratios of ¹¹C-MET PET of 1.3 and 2.0 (CTV (T/N 1.3), CTV (T/N 2.0)), and the PET-edge method (CTV(P-E)) for stereotactic radiotherapy planning for recurrent malignant glioma after radiotherapy. Differences among CTVs were evaluated and the dose distribution for the normal brain was simulated for each CTV.Results The Jaccard index (JI) for concordance of CTV (Gd) with CTVs using ¹¹C-MET PET was highest for CTV (T/N 2.0), with a value of 0.7. In a comparison of pixel values of MRI and PET, the correlation coefficient for cases with higher JI was significantly greater than that for lower JI cases (0.37 vs. 0.20, P = 0.007). D50% and D33% of the brain in radiotherapy planning using each CTV differed significantly (P = 0.03, P = 0.02) and those using CTV (T/N 1.3) were higher than with use of CTV (Gd). V90% and V95% for each CTV differed in a simulation study for actual treatment using CTV (Gd) (P = 1.0×10^− 7, P = 3.0×10^− 9) and those using CTV (T/N 1.3) and CTV (P-E) were lower than with CTV (Gd). Comparing with CTV (T2), the JI showed no significant difference with any CTV using PET. D50% and D33% of the brain were significantly higher than any CTV using PET.Conclusions The region of ¹¹C-MET accumulation is not necessarily similar to the Gd-enhanced or T2 high region. A change of the tumor boundary using ¹¹C-MET PET can cause significant changes in doses to the brain and the CTV.

Advances in chemotherapy and radiotherapy have expanded indications for stereotactic radiosurgery/radiotherapy (SRS/SRT) for multiple brain metastases. We introduced the Elements Multiple Brain Mets System (mSRS/SRT system), using the dynamic conformal arc method with a single isocenter, for treatment of multiple brain metastases with SRS/SRT (mSRS/SRT). This study analyzed outcomes of mSRS/SRT. From December 2018 to March 2023, 29 patients (130 lesions) were treated using the mSRS/SRT system. The prescribed dose for the planning target volume, determined by D95%, was 21 or 18 Gy in a single fraction for a tumor diameter ≤2 cm and 27 Gy in 3 fractions or 35 Gy in 5 fractions for a tumor diameter >2 cm. Median follow-up time was 7.2 months. The 12-month overall survival rate was 48.5%, and systemic therapy after mSRS/SRT was associated with better overall survival. The 12-month lesion-based local recurrence rate was 14.4%, and larger tumor diameter was associated with poorer local control, whereas systemic therapy after mSRS/SRT was associated with better local control. The 12-month intracranial control rate was 43.6%, and non-lung primary tumors, a greater number of lesions, and systemic therapy before mSRS/SRT were associated with poorer intracranial control. Acute adverse events included 4 cases of Grade 1 headache, one of Grade 1 nausea, and one of Grade 2 alopecia. Brain necrosis was observed in 9 patients (13 lesions), and all cases were asymptomatic. These results suggest that the mSRS/SRT system may become a treatment option for multiple brain metastases, although further evaluation is needed.