Teruhito Aihara

Current status of boron neutron capture therapy of high grade gliomas and recurrent head and neck cancer

Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Clinical interest in BNCT has focused primarily on the treatment of high grade gliomas, recurrent cancers of the head and neck region and either primary or metastatic melanoma. Neutron sources for BNCT currently have been limited to specially modified nuclear reactors, which are or until the recent Japanese natural disaster, were available in Japan, the United States, Finland and several other European countries, Argentina and Taiwan. Accelerators producing epithermal neutron beams also could be used for BNCT and these are being developed in several countries. It is anticipated that the first Japanese accelerator will be available for therapeutic use in 2013. The major hurdle for the design and synthesis of boron delivery agents has been the requirement for selective tumor targeting to achieve boron concentrations in the range of 20 μg/g. This would be sufficient to deliver therapeutic doses of radiation with minimal normal tissue toxicity. Two boron drugs have been used clinically, a dihydroxyboryl derivative of phenylalanine, referred to as boronophenylalanine or “BPA”, and sodium borocaptate or “BSH” (Na2B12H11SH). In this report we will provide an overview of other boron delivery agents that currently are under evaluation, neutron sources in use or under development for BNCT, clinical dosimetry, treatment planning, and finally a summary of previous and on-going clinical studies for high grade gliomas and recurrent tumors of the head and neck region. Promising results have been obtained with both groups of patients but these outcomes must be more rigorously evaluated in larger, possibly randomized clinical trials. Finally, we will summarize the critical issues that must be addressed if BNCT is to become a more widely established clinical modality for the treatment of those malignancies for which there currently are no good treatment options.

First clinical case of boron neutron capture therapy for head and neck malignancies using 18F-BPA PET

We investigated the application of boron neutron capture therapy (BNCT) to suitable cancers other than glioblastoma and melanoma. Head and neck malignancies were consequently selected as adaptable cancers. We reported the clinical results of our first case treated and discussed several advantages to the application of BNCT to head and neck tumors.

Boron neutron capture therapy outcomes for advanced or recurrent head and neck cancer

We retrospectively review outcomes of applying boron neutron capture therapy (BNCT) to unresectable advanced or recurrent head and neck cancers. Patients who were treated with BNCT for either local recurrent or newly diagnosed unresectable head or neck cancers between December 2001 and September 2007 were included. Clinicopathological characteristics and clinical outcomes were retrieved from hospital records. Either a combination of borocaptate sodium and boronophenylalanine (BPA) or BPA alone were used as boron compounds. In all the treatment cases, the dose constraint was set to deliver a dose <10–12 Gy-eq to the skin or oral mucosa. There was a patient cohort of 62, with a median follow-up of 18.7 months (range, 0.7–40.8). A total of 87 BNCT procedures were performed. The overall response rate was 58% within 6 months after BNCT. The median survival time was 10.1 months from the time of BNCT. The 1- and 2-year overall survival (OS) rates were 43.1% and 24.2%, respectively. The major acute Grade 3 or 4 toxicities were hyperamylasemia (38.6%), fatigue (6.5%), mucositis/stomatitis (9.7%) and pain (9.7%), all of which were manageable. Three patients died of treatment-related toxicity. Three patients experienced carotid artery hemorrhage, two of whom had coexistent infection of the carotid artery. This study confirmed the feasibility of our dose-estimation method and that controlled trials are warranted.

Superselective angiographic embolization for intractable epistaxis

Conclusions. Routine embolization of the ipsilateral facial artery (FA) is effective because of the high success rate. The use of different embolic materials for the internal maxillary artery (IMA) and the FA was considered safe because of the absence of major complications. Objective. To evaluate outcomes of routine embolization of the FA as well as the IMA ipsilateral to the bleeding site for intractable epistaxis, and outcomes using different embolic materials for the FA and the IMA. Patients and methods. Twenty-two patients with intractable epistaxis who underwent superselective embolization were retrospectively analyzed with a mean follow-up of 7 months. The FA and the IMA ipsilateral to the bleeding site were embolized. Two embolic materials, gelatin sponge and microcoils, were used for the IMA and the FA, respectively. Results. The short-term success rate within the first 7 days was 77.3% (17/22). The long-term success rate was 95.5% (21/22). There were no major complications in 22 cases. Minor complications occurred in 13 cases (59%). These minor complications usually did not last more than a week and most resolved within a day.

BNCT for advanced or recurrent head and neck cancer.

The therapeutic effect of surgery and/or combination of conventional chemoradiotherapy is limited in the patients with recurrent squamous cell carcinoma (SCC) and locally advanced non-squamous cell carcinoma without malignant melanoma (non-SCC) of the head and neck. Currently, clinical trials of BNCT for head and neck cancers are being conducted in some institutes to verify its the effectiveness. BNCT was performed in 10 patients with recurrent SCC, 7 patients with recurrent non-SCC and 3 patients with newly diagnosed non-SCC in our university between October 2003 and September 2007. Eleven patients showed complete remission and 7 patients showed partial remission of irradiated site. The effective rate [(CR+PR)/total cases] was 90%. No severe acute or chronic normal-tissue reactions were observed in any patients. BNCT is effective and safe in the patients with recurrent SCC and locally advanced non-SCC.

Dose distribution resulting from changes in aeration of nasal cavity or paranasal sinus cancer in the proton therapy.

BACKGROUND AND PURPOSE Aeration in the nasal cavity and paranasal sinus (NCPS) was investigated during the course of proton therapy (PT), and the influence of aeration on the dose distribution was determined. MATERIAL AND METHODS Twenty patients with NCPS cancer (10 nasal cavity, 10 paranasal sinus) were analyzed. All the patients received a total proton beam irradiation dose of 38-78.4 Gray equivalents (GyE). Two to five CT examinations were performed during the course of treatment. The aeration ratio inside the cavity/sinus was calculated for each CT observation. Moreover, a simulation study supposing that the first treatment plan had been continued until the end of treatment was performed using the subsequent CT findings. RESULTS The aeration ratio was increased in 18 patients. The largest increase was from 15% to 82%. Three patients had a simulated maximum cumulative dose in the brainstem of beyond 60 GyE, while 10 patients had a simulated maximum cumulative dose in the optic chiasm of beyond 50 GyE. The shortest simulated time period to reach the dose limitation was 21 days. CONCLUSIONS Aeration in the NCPS is altered during the course of PT treatment and can greatly alter the dose distribution in the brainstem and optic chiasm.

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.

Registration error of the liver CT using deformable image registration of MIM Maestro and Velocity AI

BackgroundUnderstanding the irradiated area and dose correctly is important for the reirradiation of organs that deform after irradiation, such as the liver. We investigated the spatial registration error using the deformable image registration (DIR) software products MIM Maestro (MIM) and Velocity AI (Velocity).MethodsImage registration of pretreatment computed tomography (CT) and posttreatment CT was performed in 24 patients with liver tumors. All the patients received proton beam therapy, and the follow-up period was 4–14 (median: 10) months. We performed DIR of the pretreatment CT and compared it with that of the posttreatment CT by calculating the dislocation of metallic markers (implanted close to the tumors).ResultsThe fiducial registration error was comparable in both products: 0.4–32.9 (9.3 ± 9.9) mm for MIM and 0.5–38.6 (11.0 ± 10.0) mm for Velocity, and correlated with the tumor diameter for MIM (r = 0.69, P = 0.002) and for Velocity (r = 0.68, P = 0.0003). Regarding the enhancement effect, the fiducial registration error was 1.0–24.9 (7.4 ± 7.7) mm for MIM and 0.3–29.6 (8.9 ± 7.2) mm for Velocity, which is shorter than that of plain CT (P = 0.04, for both).ConclusionsThe DIR performance of both MIM and Velocity is comparable with regard to the liver. The fiducial registration error of DIR depends on the tumor diameter. Furthermore, contrast-enhanced CT improves the accuracy of both MIM and Velocity.Institutional review board approvalH28-102; July 14, 2016 approved.

Sudden Deafness and Right-to-Left Shunts

Purpose: One of the etiologies for idiopathic sudden deafness is considered to be ischemia of the inner ear. Cryptogenic stroke is caused by a right-to-left shunt (RLS). The present study investigated whether RLS is associated with the occurrence of sudden deafness. Methods: Contrast saline transcranial Doppler ultrasonography was performed to detect RLS. Subjects comprised 23 consecutive sudden deafness patients and 46 age- and gender-matched controls. Clinical characteristics, including vascular risk factors, were compared between sudden deafness and control groups. Results: RLS was more frequent in the sudden deafness group than in controls (48 vs. 17%, p = 0.011). No significant differences in other clinical characteristics were seen between groups. Conclusion: RLS may be a potential cause of sudden deafness.

Laryngeal tuberculosis following laryngeal carcinoma

Laryngeal tuberculosis is a rare entity and the disease related to laryngeal cancer is extremely rare. We describe a case of laryngeal tuberculosis in a 74-year-old man with a history of radiotherapy for laryngeal carcinoma four months earlier. Laryngoscopy demonstrated a white mass on the right vocal fold at the site carcinoma had previously occupied. Recurrence of the cancer was suspected, but the biopsy result showed histological features of tuberculosis. We discuss the derangement of the hosts mucosal barrier by the malignancy as a contributing factor in secondary tuberculous infection. Tubercular bacilli may be reactivated due to the immunosuppression associated with the therapy.