Daichi Takizawa

Proton beam therapy for pediatric ependymoma

The aim of this study was to evaluate the efficacy of proton beam therapy for pediatric patients with ependymoma.

Analysis of repeated proton beam therapy for patients with hepatocellular carcinoma

PURPOSE To evaluate the feasibility and efficacy of repeated proton beam therapy (PBT) and to analyze the dose-volume relationship. PATIENTS AND METHODS A retrospective analysis was performed in 83 patients who received definitive repeated PBT. Proton beams were delivered with expiratory gating. The numbers of treatment courses were 2, 3, and 4 in 68, 12, and 3 patients, respectively. MIM software was used for dose analysis. RESULTS The planned median total dose was 70.5 GyE for all tumors and the median doses for the 1st, 2nd, 3rd and 4th treatments were 71.0, 70.0, 70.0, and 69.3 GyE, respectively. There was no severe acute toxicity, and no radiation-induced liver dysfunction (RILD) was observed. The median overall survival (OS) period from the first PBT was 61months (95% CI: 50-71months), and the 2- and 5-year OS rates were 87.5% (95%CI: 80.2-94.8%) and 49.4% (95%CI: 37.6-61.2%), respectively. The maximal delivered dose to the liver ranged from 66.7 to 248.1 GyE (mean: 124.93 GyE) and the mean liver dose ranged from 5.4 to 66.5 GyE (mean: 24.23 GyE). CONCLUSION Repeated PBT was well tolerated and safe, even though the liver doses in many patients deviated substantially from well-known critical levels for RILD.

Proton beam therapy for metastatic liver tumors

PURPOSE The purpose of this study was to investigate the safety and efficacy of proton beam therapy (PBT) for the treatment of metastatic liver tumors. MATERIAL AND METHODS A total of 140 patients with liver metastasis who received PBT were retrospectively investigated. The main primary tumor sites were the colorectum (60) and the pancreas (19). RESULTS One hundred thirty-three patients (95%) completed treatment. Two patients experienced late adverse effects (rib fracture and cholangitis). The 5-year overall survival (OS) rate was 24%. In the 85 patients with lesions confined to the liver, the 5-year OS rate of was 28%, and in the 55 patients with lesions both inside and outside the liver, it was 16% (P=0.007). Among the patients with lesions confined to the liver, the 5-year OS rate of the 62 patients who received curative treatment was 30%, and that of the 23 patients who received palliative treatment, 23% (P=0.016). Multivariate analysis showed that the treatment strategy (curative and palliative) alone was associated with the OS rate (P=0.02). CONCLUSION PBT is a potentially safe and effective treatment for metastatic liver tumors.

A comparative study of dose distribution of PBT, 3D-CRT and IMRT for pediatric brain tumors

IntroductionIt was reported that proton beam therapy (PBT) reduced the normal brain dose compared with X-ray therapy for pediatric brain tumors. We considered whether there was not the condition that PBT was more disadvantageous than intensity modulated photon radiotherapy (IMRT) and 3D conventional radiotherapy (3D-CRT) for treatment of pediatric brain tumors about the dose reduction for the normal brain when the tumor location or tumor size were different.MethodsThe subjects were 12 patients treated with PBT at our institute, including 6 cases of ependymoma treated by local irradiation and 6 cases of germinoma treated by irradiation of all four cerebral ventricles. IMRT and 3D-CRT treatment plans were made for these 12 cases, with optimization using the same planning conditions as those for PBT. Model cases were also compared using sphere targets with different diameters or locations in the brain, and the normal brain doses with PBT, IMRT and 3D-CRT were compared using the same planning conditions.ResultsPBT significantly reduced the average dose to normal brain tissue compared to 3D-CRT and IMRT in all cases. There was no difference between 3D-CRT and IMRT. The average normal brain doses for PBT, 3D-CRT, and IMRT were 5.1–34.8% (median 14.9%), 11.0–48.5% (23.8%), and 11.5–53.1% (23.5%), respectively, in ependymoma cases; and 42.3–61.2% (48.9%), 54.5–74.0% (62.8%), and 56.3–72.1% (61.2%), respectively, in germinoma cases. In the model cases, PBT significantly reduced the average normal brain dose for larger tumors and for tumors located at the periphery of the brain.ConclusionPBT reduces the average dose to normal brain tissue, compared with 3D-CRT and IMRT. The effect is higher for a tumor that is larger or located laterally.

Follow-up study of liver metastasis from breast cancer treated by proton beam therapy

Liver metastasis from breast cancer (LMBC) is an incurable, fatal disease with a very poor prognosis. Although various local treatments have been applied, their clinical utility has not been established. The purpose of this study was to investigate the safety and effectiveness of proton beam therapy (PBT) for the treatment of patients with LMGC. A total of 8 female patients (aged 38-63 years) with LMBC who received PBT between 2002 and 2012 were retrospectively reviewed. Patients who had tumors confined to the liver were investigated, whereas patients with extrahepatic tumors were excluded. A total of 5 patients had solitary tumors and 3 had multiple tumors. The total irradiation dose was 66-72.6 Gray equivalent [Gy relative biological effectiveness (RBE)] and 2 patients received concurrent chemotherapy or hormone therapy. The overall and progression-free survival (OS and PFS) rates, local control (LC) rate and adverse effects were investigated. All the patients completed treatment without interruption and late adverse effects of grade >3 were not observed. The OS rate was 88/73/58%, the PFS rate was 50/25/0% and the LC rate was 86/86/86% at 1/3/5 years, respectively. Thus, PBT is a safe treatment and the OS and PFS rates are comparable to those with other local treatments. PBT may be considered as an effective local treatment option for the treatment of LMBC patients.

Long-term single-institute experience with trimodal bladder-preserving therapy with proton beam therapy for muscle-invasive bladder cancer

Objective We retrospectively elucidated the oncological outcomes, prognostic factors and toxicities of proton beam therapy in trimodal bladder-preserving therapy for muscle-invasive bladder cancer at our institution. Methods From 1990 to 2015, 70 patients with cT2–3N0M0 muscle-invasive bladder cancer underwent trimodal bladder-preserving therapy consisting of maximal transurethral resection of the bladder tumor, small pelvis photon irradiation, intra-arterial chemotherapy and proton beam therapy. The overall survival rate, progression-free survival rate, time to progression, predictive factors for progression and toxicities were analyzed. Progression was defined as when muscle-invasive recurrence, distant metastasis or upper urinary tract recurrence was observed. Results The patients’ median age was 65 (range 36–85) years. The median follow-up period was 3.4 (range 0.6–19.5) years. The 5-year cumulative overall survival rate, progression-free survival rate and time to progression rate were 82%, 77%, and 82%, respectively. In univariate and multivariate analyses, tumor multiplicity and tumor size (≥5 cm) were significant and independent factors associated with progression (hazard ratio 3.5, 95% confidence interval 1.1–12; hazard ratio 5.0, 95% confidence interval 1.3–17; P < 0.05 for all). As for toxicity, 26 (18%) patients had grade 3–4 acute hematologic toxicities and 2 (3%) patients had grade 3 late genitourinary toxicity. No patient had to discontinue the treatment due to acute toxicity. Conclusions Our bladder-preserving therapy with proton beam therapy was well tolerated and achieved a favorable mortality rate. Tumor multiplicity and tumor size were important risk factors for progression. Our findings indicate that this therapy can be an effective treatment option for selected muscle-invasive bladder cancer patients.

Proton beam therapy for liver metastases from gastric cancer

Abstract Liver metastases from gastric cancer (LMGC) is a non-curable, fatal disease with a 5-year survival rate of <10%. Although various local treatments have been applied, their clinical utility has not been established. The purpose of this study was to investigate the safety and effectiveness of proton beam therapy (PBT) for the treatment of patients with LMGC. A total of nine patients (seven men, two women; aged 56–78 years) with LMGC who received PBT between 2002 and 2012 were retrospectively reviewed. Patients who had tumors confined to the liver were investigated, and patients who had extrahepatic tumors were excluded. Six of the patients had solitary tumors, and three patients had multiple tumors. The total irradiation dose was 64–77 Gy relative biological effectiveness (RBE), and three patients received concurrent chemotherapy. The overall and progression-free survival (OS and PFS) rates, local control (LC) rate, and adverse effects were investigated. All patients completed treatment without interruption, and late adverse effects of higher than Grade 3 were not observed. The OS rates at 1, 3 and 5 years were 100%, 78% and 56%, respectively (median, 5.5 years); the PFS rates were 67%, 40% and 40% (median, 2.6 years); and the LC rates were 89%, 71% and 71%. PBT was demonstrated to be a safe treatment, and the OS and PFS rates were not inferior to those for other types of local treatment. Therefore, PBT should be considered as an effective local treatment option for patients with LMGC.