Background: Currently bisphosphonates are often administered to patients with osteolytic bone metastases from several neoplasms. Based on favorable experience in other cancers with bone metastases and the lack of effective treatment, we started to use zoledronic acid (ZA), a recently developed synthetic bisphosphonate drug, in the treatment of this disease. In the present study, we retrospectively evaluated the efficacy of ZA for bone metastases from differentiated thyroid carcinoma. Methods: The study consisted of 50 patients with bone metastases from differentiated thyroid carcinoma treated at the Cancer Institute Hospital of Tokyo between 1976 and 2008. Among them, 28 patients who did not undergo bisphosphonate therapy were defined as group A and 22 patients who received ZA therapy were defined as group B. The primary efficacy endpoint for ZA treatment was the reduction in the percentage of patients who developed skeletal-related events (SREs), including bone fracture, spinal cord compression, and hypercalcemia. A secondary endpoint was the interval between a presentation of bone metastases and appearance of SREs. Results: SREs occurred in significantly lower frequency in group B (3 of 22 patients, 14%) than group A (14 of 28 patients, 50%) ( p = 0.007). The use of ZA significantly retarded the onset of the first SRE ( p = 0.04). Two group-B patients developed bisphosphonate-related osteonecrosis of the jaw. Conclusion: Treatment with ZA was effective in reducing SREs or delaying their appearance in patients with bone metastases from differentiated thyroid carcinoma.

The otocyst, an anlage of the inner ear, presents an attractive target to study treatment strategies for genetic hearing loss and inner ear development. We have previously reported that electroporation-mediated transuterine gene transfer of Connexin30, utilizing a monophasic pulse into Connexin30^−/− mouse otocysts at embryonic day 11.5, is able to prevent putative hearing deterioration. However, it is not clear whether supplementary gene transfer can rescue significant morphological changes, caused by genetic deficits. In addition, with the transuterine gene transfer technique utilized in our previous report, the survival rate of embryos and their mothers after treatment was low, which became a serious obstacle for effective in vivo experiments. Here, we set out to elucidate the feasibility of supplementation therapy in Slc26a4 deficient mice, utilizing biphasic pulses, optimized by modifying pulse conditions. Modification of the biphasic pulse conditions during electroporation increased the survival rate. In addition, supplementation of the target gene cDNA into the otocysts of homozygous Slc24a4 knockout mice significantly prevented enlargement of the endolymphatic space in the inner ear areas; moreover, it rescued hearing and vestibular function of mice in vivo.

Background: To review a single institutional experience of the Radiation Therapy Oncology Group (RTOG) 8502 “QUAD shot” regimen using volumetric modulated arc radiotherapy (VMAT) for incurable head and neck cancer (HNC). Methods: Thirty-four consecutive patients with HNC were treated with at least one cycle of the RTOG 8502 regimen. Treatment plans included the use of VMAT with 6 MV photons generated by a linear accelerator. Two daily fractions of 3.7 Gy were delivered with an interval of at least 6 h for 2 consecutive days, totaling 14.8 Gy over 4 fractions. This was repeated every 3–4 weeks for a total of three cycles. No concurrent systemic therapy was performed. Results: The number of completed cycles was 1 in 6 (18%) patients, 2 in 5 (15%), and 3 in 23 (68%). Tumor response was achieved in 29 (85%) patients and symptom relief in 20 (77%) of 26 patients. Overall response (tumor response or symptom relief) was achieved in 32 (94%) patients. All patients who received 2 or more treatment cycles achieved overall response. Median overall survival (OS) was 5.7 months. Multivariate analysis revealed that completion of all three treatment cycles was significantly associated with better OS (P = 0.002). Grade 2 toxicity was observed in four (12%) patients, but no acute Grade ≥ 3 or late toxicity was observed. Conclusions: The RTOG 8502 “QUAD shot” regimen using VMAT is effective for incurable HNC with highly reduced toxicity. Treatment with multiple cycles is recommended for better treatment response and/or survival.