Designation Products: Boron Neutron Capture Therapy for Head and Neck Carcinoma.

The Japanese Ministry of Health, Labour and Welfare approved a drug called borofalan (10 B), a treatment system, and a dose calculation program for boron neutron capture therapy (BNCT) in March 2020. The application pertaining to the products submitted to the Pharmaceuticals and Medical Devices Agency was supported by a Japanese, open-label, uncontrolled trial (Study 002) in patients with unresectable, locally recurrent head and neck squamous cell carcinoma after chemoradiotherapy or radiotherapy, or in those with unresectable locally advanced or locally recurrent (LA/LR) head and neck nonsquamous cell carcinoma. The drug was administered as a single intravenous dose using infusion rates of 200 mg/kg per hour for the first 2 hours after the start of administration and 100 mg/kg per hour during irradiation. Neutron irradiation was performed using the devices at a single dose of 12 Gy-equivalent for oral, pharyngeal, or laryngeal mucosa for up to 60 minutes from 2 hours after the start of drug administration. The primary endpoint was the overall response rate (ORR). The results of Study 002 showed that the ORR based on an assessment of the Independent Central Review Committee per RECIST version 1.1 was 71.4% (90% confidence interval [CI], 51.3%-86.8%). The lower limit of the 90% CI exceeded the prespecified threshold for ORR. When BNCT is applied to patients with unresectable LA/LR head and neck cancer, precautions should be taken, and patients should be monitored for possible onset of dysphagia, brain abscess, skin disorder, crystal urine, cataract, and/or carotid hemorrhage. IMPLICATIONS FOR PRACTICE: Borofalan (10 B), a treatment system and a dose calculation program for boron neutron capture therapy (BNCT), demonstrated significant efficacy in an open-label, uncontrolled trial in which overall response rate was the primary endpoint for patients with unresectable locally advanced or locally recurrent head and neck cancer. Although no information about survival benefits was obtained, BNCT will become an effective treatment option that is expected to manage local lesions that are intractable with any standard therapy. In addition, BNCT is expected to maintain quality of life of the intended patient population, on account of its high tumor selectivity and low invasiveness.

Macular Dysfunction in Oguchi Disease with the Frequent Mutation 1147delA in the SAG Gene.

AIM/BACKGROUND: A 1-bp deletion (1147delA) in the SAG (also known as arrestin or S-antigen) gene is the most frequently seen mutation in Japanese patients suffering from Oguchi disease, a recessively inherited stationary night blindness. We investigated macular function in a patient with Oguchi disease with the 1147delA mutation. METHODS: A 43-year-old Japanese male patient was diagnosed with Oguchi disease. The patient underwent complete ophthalmic examinations, including spectral-domain optical coherence tomography and Humphrey visual field testing. Full-field electroretinograms (ff-ERG) and multifocal ERG (mf-ERG) were recorded. Mutational analysis of the SAG gene was performed. RESULTS: Corrected visual acuity was good in both eyes. Funduscopy showed retinal pigment epithelium atrophy along the vascular arcade bilaterally. The inner segment-outer segment (ISOS) boundary lines were preserved in the foveal and parafoveal areas, whereas ISOS boundary defects and thinning of the outer nuclear layer (ONL) were seen outside the preserved ISOS boundary. Humphrey testing showed significant paracentral field defects in both eyes. In addition to an absence of rod responses, cone and 30-Hz flicker responses were markedly reduced in ff-ERG. The central (ring 1) and paracentral (ring 2) responses with normal latencies were relatively preserved, but the outer waveforms (rings 3-5) were attenuated and prolonged in mf-ERG. The deletion mutation (1147delA) was identified homozygously. CONCLUSIONS: The reduced/delayed mf-ERG responses and visual field defects in paracentral macula areas are most likely to be correlated with ISOS boundary defects and thinning of the ONL. Macular dysfunction can occur in Oguchi disease with the 1147delA mutation in the SAG gene.

Color vision in an elderly patient with protanopic genotype and successfully treated unilateral age-related macular degeneration.

We investigated differences in color discrimination between the fellow eye and the affected eye successfully treated for unilateral age-related macular degeneration (AMD) in a 69-year-old male patient with protanopia. His best-corrected visual acuity (BCVA) was 1.2 in the right eye (RE) and 0.2 in the left eye (LE). Fundus and angiographic findings showed classic choroidal neovascularization (CNV) secondary to AMD in the LE. BCVA of the LE improved to 0.4, and CNV resolved by 15 months after initiating combined anti-vascular endothelial growth factor and photodynamic therapies. After CNV closure, the Farnsworth dichotomous was performed, showing confusion patterns of the protan axis in either eye. The Farnsworth-Munsell 100-hue test showed a total error score of 520 in the LE, much higher than the score of 348 in the RE. Complete genotypes of the long-wavelength-sensitive (L-) cone and middle-wavelength-sensitive (M-) cone opsin genes were determined by polymerase chain reaction, revealing that the patient had a single 5' L-M 3' hybrid gene (encoding an M-cone opsin), with this genotype responsible for protanopia (the L-cone opsin gene was non-functional), instead of the L-cone and M-cone opsin gene arrays. Poorer color vision discrimination in the LE than the RE remained present despite closure of CNV. The presence and type of congenital color vision defect can be confirmed using molecular genetic testing even if complications of acquired retinal diseases such as AMD are identified.