The overview and prospects of BNCT facility at Tsing Hua Open-pool reactor.

The whole picture of the BNCT facility at Tsing Hua Open-pool Reactor will be presented which consists of the following aspects: the construction project, the beam quality, routine operations including the QA program for the beam delivery, determination of boron-10 concentration in blood, T/N ratio, and the clinical affairs including the patient recruit procedure and the patient irradiation procedure. The facility is positioned to serve for conducting clinical trials, emergent (compassionate) treatments, and R&D works.

A comparison of dose distributions in gross tumor volume between boron neutron capture therapy alone and combined boron neutron capture therapy plus intensity modulation radiation therapy for head and neck cancer.

Nine patients with recurrent head and neck (H&N) cancer received boron neutron capture therapy (BNCT) in one fraction at the Tsing-Hua Open pool reactor (THOR) utilizing the THORplan treatment planning system (TPS). The aims of the present study were to evaluate the use of intensity modulated radiation therapy (IMRT) of 45 Gy in 20 fractions to compensate for the dose heterogeneity in gross tumor volume observed with single-fraction BNCT with mean prescription dose 19 Gy (w), and to evaluate planning quality indices of simulated BNCT+IMRT versus single-fraction BNCT alone. All IMRT plans were generated using the Eclipse TPS which employs the analytical anisotropic algorithm. The conformity index for the gross tumor volume (GTV) was better for the BNCT+IMRT plan than for the BNCT-alone plan (p = 0.003). In addition, the BNCT+IMRT plan provided significantly better homogeneity in the GTV (p = 0.03). The cold spots in inhomogeneous dose distribution in the BNCT plan may be a key factor for H&N cancer recurrence. Our results suggest that single-fraction BNCT combined with compensated multi-fraction IMRT improves treatment homogeneity and conformity than single-fraction BNCT alone, especially for tumor volumes >100 cm3, and possibly increases local tumor control.

Fractionated Boron Neutron Capture Therapy in Locally Recurrent Head and Neck Cancer: A Prospective Phase I/II Trial.

PURPOSE: To investigate the efficacy and safety of fractionated boron neutron capture therapy (BNCT) for recurrent head and neck (H&N) cancer after photon radiation therapy. METHODS AND MATERIALS: In this prospective phase 1/2 trial, 2-fraction BNCT with intravenous L-boronophenylalanine (L-BPA, 400 mg/kg) was administered at a 28-day interval. Before each fraction, fluorine-18-labeled-BPA-positron emission tomography was conducted to determine the tumor/normal tissue ratio of an individual tumor. The prescription dose (D80) of 20 Gy-Eq per fraction was selected to cover 80% of the gross tumor volume by using a dose volume histogram, while minimizing the volume of oral mucosa receiving >10 Gy-Eq. Tumor responses and adverse effects were assessed using the Response Evaluation Criteria in Solid Tumors v1.1 and the Common Terminology Criteria for Adverse Events v3.0, respectively. RESULTS: Seventeen patients with a previous cumulative radiation dose of 63-165 Gy were enrolled. All but 2 participants received 2 fractions of BNCT. The median tumor/normal tissue ratio was 3.4 for the first fraction and 2.5 for the second, whereas the median D80 for the first and second fraction was 19.8 and 14.6 Gy-Eq, respectively. After a median follow-up period of 19.7 months (range, 5.2-52 mo), 6 participants exhibited a complete response and 6 exhibited a partial response. Regarding acute toxicity, 5 participants showed grade 3 mucositis and 1 participant showed grade 4 laryngeal edema and carotid hemorrhage. Regarding late toxicity, 2 participants exhibited grade 3 cranial neuropathy. Four of six participants (67%) receiving total D80 > 40 Gy-Eq had a complete response. Two-year overall survival was 47%. Two-year locoregional control was 28%. CONCLUSIONS: Our results suggested that 2-fraction BNCT with adaptive dose prescription was effective and safe in locally recurrent H&N cancer. Modifications to our protocol may yield more satisfactory results in the future.

HDR Brachytherapy Dose Distribution is Influenced by the Metal Material of the Applicator.

Applicators containing metal have been widely used in recent years when applying brachytherapy to patients with cervical cancer. However, the high dose rate (HDR) treatment-planning system (TPS) that is currently used in brachytherapy still assumes that the treatment environment constitutes a homogeneous water medium and does not include a dose correction for the metal material of the applicator. The primary purpose of this study was to evaluate the HDR (192)Ir dose distribution in cervical cancer patients when performing brachytherapy using a metal-containing applicator. Thermoluminescent dosimeter (TLD) measurements and Monte Carlo N-Particle eXtended (MCNPX) code were used to explore the doses to the rectum and bladder when using a Henschke applicator containing metal during brachytherapy. When the applicator was assumed to be present, the absolute dose difference between the TLD measurement and MCNPX simulation values was within approximately 5%. A comparison of the MCNPX simulation and TPS calculation values revealed that the TPS overestimated the International Commission of Radiation Units and Measurement (ICRU) rectum and bladder reference doses by 57.78% and 49.59%, respectively. We therefore suggest that the TPS should be modified to account for the shielding effects of the applicator to ensure the accuracy of the delivered doses.

Pharmacokinetics of BPA in gliomas with ultrasound induced blood-brain barrier disruption as measured by microdialysis.

The blood-brain barrier (BBB) can be transiently disrupted by focused ultrasound (FUS) in the presence of microbubbles for targeted drug delivery. Previous studies have illustrated the pharmacokinetics of drug delivery across the BBB after sonication using indirect visualization techniques. In this study, we investigated the in vivo extracellular kinetics of boronophenylalanine-fructose (BPA-f) in glioma-bearing rats with FUS-induced BBB disruption by microdialysis. After simultaneous intravenous administration of BPA and FUS exposure, the boron concentration in the treated brains was quantified by inductively coupled plasma mass spectroscopy. With FUS, the mean peak concentration of BPA-f in the glioma dialysate was 3.6 times greater than without FUS, and the area under the concentration-time curve was 2.1 times greater. This study demonstrates that intracerebral microdialysis can be used to assess local BBB transport profiles of drugs in a sonicated site. Applying microdialysis to the study of metabolism and pharmacokinetics is useful for obtaining selective information within a specific brain site after FUS-induced BBB disruption.

Fractionated BNCT for locally recurrent head and neck cancer: experience from a phase I/II clinical trial at Tsing Hua Open-Pool Reactor.

To introduce our experience of treating locally and regionally recurrent head and neck cancer patients with BNCT at Tsing Hua Open-Pool Reactor in Taiwan, 12 patients (M/F=10/2, median age 55.5 Y/O) were enrolled and 11 received two fractions of treatment. Fractionated BNCT at 30-day interval with adaptive planning according to changed T/N ratios was feasible, effective and safe for selected recurrent head and neck cancer in this trial.

Skin dose impact from vacuum immobilization device and carbon fiber couch in intensity modulated radiation therapy for prostate cancer.

To investigate the unexpected skin dose increase from intensity-modulated radiation therapy (IMRT) on vacuum cushions and carbon-fiber couches and then to modify the dosimetric plan accordingly. Eleven prostate cancer patients undergoing IMRT were treated in prone position with a vacuum cushion. Two under-couch beams scattered the radiation from the vacuum cushion and carbon-fiber couch. The IMRT plans with both devices contoured were compared with the plans not contouring them. The skin doses were measured using thermoluminescent dosimeters (TLDs) placed on the inguinal regions in a single IMRT fraction. Tissue equivalent thickness was transformed for both devices with the relative densities. The TLD-measured skin doses (59.5 +/- 9.5 cGy and 55.6 +/- 5.9 cGy at left and right inguinal regions, respectively) were significantly higher than the calculated doses (28.7 +/- 4.7 cGy; p = 2.2 x 10(-5) and 26.2 +/- 4.3 cGy; p = 1.5 x 10(-5)) not contouring the vacuum cushion and carbon-fiber couch. The calculated skin doses with both devices contoured (59.1 +/- 8.8 cGy and 55.5 +/- 5.7 cGy) were similar to the TLD-measured doses. In addition, the calculated skin doses using the vacuum cushion and a converted thickness of the simulator couch were no different from the TLD-measured doses. The recalculated doses of rectum and bladder did not change significantly. The dose that covered 95% of target volume was less than the prescribed dose in 4 of 11 patients, and this problem was solved after re-optimization applying the corrected contours. The vacuum cushion and carbon-fiber couch contributed to increased skin doses. The tissue-equivalent-thickness method served as an effective way to correct the dose variations.