Stereotactic Radiosurgery for Trigeminal Neuralgia Caused by Vertebrobasilar Compression: A Report of Four Cases.

BACKGROUND: Microvascular decompression (MVD) of the trigeminal nerve is an effective procedure for treating patients with trigeminal neuralgia (TGN). However, vertebrobasilar decompression involves technical difficulties and demonstrates a higher risk of minor trigeminal hypesthesia/hypalgesia, transient diplopia, and hearing loss. Stereotactic radiosurgery (SRS) has been an effective alternative treatment for TGN. Few studies reported the treatment results of SRS for TGN caused by vertebrobasilar compression. This report presents the treatment results of SRS using gamma knife (GK) in four TGN cases. MATERIALS AND METHODS: GK-SRS was performed for TGN due to vertebrobasilar compression in four patients, including two males and two females, aged 67-90 years. The maximum dose of 80 Gy was delivered at the retrogasserian portion (RGP) of the ipsilateral trigeminal nerve root. RESULTS: All four cases with TGN achieved relief in four to 10 months after GK-SRS. However, TGN recurred 41 months after GK-SRS in one of the four cases. A second GK-SRS at the root entry zone (REZ) at a maximum dose of 70 Gy relieved pain again 10 days later. TGN in another case among the four partially recurred in three years but did not deteriorate until the patient died from old age 62 months after GK-SRS. The other three cases, including the one with repeat GK-SRS, were alive with complete TGN remission at the end of follow-up of 20-52 months. GK-SRS-related adverse effects were not observed in any case. CONCLUSIONS: GK-SRS was a safe and effective treatment in all four TGN cases due to vertebral artery (VA)-basilar artery (BA) compression, although a second treatment session was added again for pain recurrence in one of the four cases.

Cerebellar Hemangioblastoma Associated With a Vascular Malformation: A Case Report Treated With Surgery and Radiosurgery.

Hemangioblastoma is well known as an essentially benign cystic and/or solid tumor classified WHO grade I, mainly originated in the posterior fossa. One of the characteristics of this tumor is very rich vasculature in and around the tumor. We have encountered a case of hemangioblastoma in association with a vascular anomaly near the tumor, though they were located separately by the tentorium. A vascular anomaly with arteriovenous (AV) shunting flow in the left occipital lobe was verified at angiography, which received a blood supply from left occipital artery and drained to occipital cortical veins. Successful removal of the cerebellar tumor and pathological diagnosis of hemangioblastoma was made. The second angiography in our hospital demonstrated the same vascular anomaly above the tentorium with feeding artery of posterior cerebral artery, a small nidus, and cortical draining veins, which were less obviously stained. Only the arteriovenous malformation (AVM) nidus in sigmoid vein was targeted for radiosurgery and 20 Gy at the margin was delivered. Since AV shunting was less remarkable on the second angiography than that on the first angiography may be because of a decreased vascular supply to the supratentorial AVM after surgical resection of the infratentorial hemangioblastoma and might indicate an indirect connection between the two lesions.

Stereotactic Radiotherapy for Localized External Auditory Canal Carcinomas: Report of Four Cases.

External auditory canal carcinoma (EACC) is sometimes diagnosed at an early stage because it arises superficially in the ear canal and may cause ear obstruction symptoms early. In addition, in the early stage of EACCs, involvement of lymph nodes or distant metastases are reported less frequently. And so, stereotactic radiotherapy (SRT) concentrating high-dose radiation on the primary tumor may be an effective option. The aim of this study is to evaluate the preliminary results of upfront SRT for early-stage localized EACCs. Four cases (four females, 84 to 98 years old) with EACC of N0M0 (=no lymph node involvement and no distant metastasis) were treated. All four tumors (0.30 - 11.1 ml in volume) were diagnosed as squamous cell carcinoma histologically. A total dose of 24 - 33 Gy in 3 - 5 fractions (D95 [dose delivered to 95% of the target volume]=100% dose) was delivered by SRT using CyberKnife. All four cases were alive at the end of the follow-up period of 19 to 106 months. In three cases (tumor volume, 0.3 - 3.5 ml) the treated tumors had regressed or disappeared by the end of the follow-up period of 106, 28, and 19 months respectively. In the remaining one case, the treated tumor (11.1 ml) regrew and cervical lymph node metastasis occurred, and both were treated with SRT again 6 months and 20 months after the initial SRT respectively. The tumors were still stable at 39 months after the initial SRT. In conclusion, in three cases the small tumors had regressed or disappeared without lymph node involvement or distant metastasis. In the remaining case, additional SRT was performed for recurrent tumors, after which the patient's condition remained stable. SRT may be an effective option for early-stage EACCs.

Neuroendocrine Carcinoma of Uterine Cervix: Stereotactic Radiotherapy for Brain Metastasis and Stereotactic Body Radiotherapy for Renal and Pancreatic Metastases.

A case of cervical neuroendocrine carcinoma (NEC) of the uterine cervix (NECUC) was presented. After total hysterectomy with bilateral salpingo-oophorectomy and adjuvant chemotherapy, a left renal tumor and a pancreatic lesion developed and were both diagnosed on pathological examination as metastases from NEC. In addition, a brainstem metastasis causing neurologic signs developed. The brain lesion was treated by stereotactic radiotherapy (SRT) and the renal and pancreatic lesions by stereotactic body radiotherapy (SBRT). Despite control of the renal and pancreatic lesions, multiple small lung metastases developed later. Recurrence and newly developed brain metastases were treated by repeat stereotactic radiosurgery (SRS)/SRT successfully. Chemotherapy was continued and controlled the lung metastases until three and a half years after the initial operation of the uterus.

Dosimetric Comparison of Hypofractionated Multi-Beam Intensity-Modulated Radiation Therapy and Volumetric Modulated Arc Therapy With Flattened Beam and Flattening-Filter-Free Beam for Skull Base Meningioma Adjacent to Optic Pathways.

Background Since the optic pathways are the most vulnerable to radiation, the treatment of skull base tumors involving them is challenging. In this study simulation plans by multi-beam (MB) intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT), both with the flattened beam (FB) and flattening-filter-free beam (FFF), were compared in terms of covering of the target and sparing of the optic pathways. Materials and methods Treatment planning was simulated by MB-IMRT with FB and FFF and by 2-rotational VMAT with FB and FFF in three cases of skull base meningioma [volume of the planned target volume (PTV; PTV margin=2 mm except for overlapping area with optic pathways or brainstem): 8.6 ml, 34.6 ml, and 55.3 ml respectively], which were treated previously by multi-fractionated MB-IMRT [45 Gy/18 fx. (fraction) with 7-, 6-, and 5-beam] using a conventional Novalis (BrainLAB, Tokyo, Japan) planned by iPlan (BrainLAB, Tokyo, Japan). In all three cases, the optic pathways were adjacent to the lesion. The reference CT with contouring data set of target volumes [gross tumor volume (GTV) and PTV] and OARs (organs at risk) was transferred from iPlan to Eclipse (Varian Medical Systems, Tokyo, Japan). In this study, hypofractionated radiation therapy by 30 Gy/5 fx. was designed; 95% dose (28.5 Gy/5 fx.) was prescribed to D95 (dose to 95% volume of PTV). Conformity index (CI), homogeneity index (HI, D5/D95), D[0.1 ml] (dose to 0.1 ml) for optic pathways, and D[1 ml] for brainstem and eyes, and V[20 Gy] (volume delivered with 20 Gy or more/5 fx.) of the whole brain were evaluated. Results The indices did not differ between FB and FFF, in either MB-IMRT or VMAT. Between MB-IMRT and VMAT, the indices were similar. The mean dose of PTV and HI was a little larger with MB-IMRT than with VMAT. D[0.1 ml] of the optic pathways and D[1 ml] of the ipsilateral eye were smaller with VMAT in all three cases. D[1 ml] of the brainstem was smaller with VMAT in two cases, though it was similar in one case. Conclusion Based on our findings, VMAT with FFF might be the optimal method to treat cases of skull base meningioma involving optic pathways. However, further studies involving more cases are required to arrive at a conclusive verdict.

Stereotactic Radiosurgery and Stereotactic Radiotherapy for Malignant Skull Base Tumors.

The role of stereotactic radiosurgery/stereotactic radiotherapy (SRS/SRT) for malignant skull base tumors was summarized and discussed. The treatment of skull base tumors remains challenging. Their total resection is often difficult. SRS/SRT is one useful treatment option for residual or recurrent tumors after surgical resection in cases of primary skull base tumors. If skull base metastasis and skull base invasion are relatively localized, they can be candidates for SRS/SRT. Low rates of cervical lymph node involvement in early-stage (N0M0, no lymph node involvement or distant metastasis) nasal and paranasal carcinomas (NpNCa) and external auditory canal carcinomas (EACCa) have been reported in the literature. Such cases might be good candidates for SRS/SRT as the initial therapy. We previously reported the results of SRS/SRT for various malignant extra-axial skull base tumors. In addition, treatment results of early-stage head and neck carcinomas were summarized. Those of our data and those of other reported series were reviewed here to clarify the usefulness of SRS/SRT for malignant extra-axial skull base tumors.

Radiosurgery for Patients with More Than Ten Brain Metastases.

Purpose In this article, we report on Gamma Knife radiosurgery performed on patients with more than 10 brain metastases. Although the standard treatment for multiple brain metastases is currently believed to be whole-brain irradiation, many patients are averse to it due to the potential for serious complications such as cognitive impairment. Cases and Methods Here, 70 cases of Gamma Knife radiosurgery for metastatic foci originating from various primary cancer are reviewed. Several different treatment protocols were selected: (1) single session, (2) two or three consecutive sessions, (3) fractionated irradiation for large tumor and stereotactic radiosurgery (SRS) for small ones, and (4) salvage treatment for recurrent tumors after whole-brain irradiation. Results Despite the long beam-on-time (BOT) necessary for Gamma Knife radiosurgery and unavoidable spillage irradiation to the entire brain, all the treatments were completed without any major difficulties. Conclusion SRS or radiotherapy might be a treatment choice for patients with more than 10 brain metastases. However, the very long treatment time and big spillage irradiation to the entire brain warrants that large metastatic foci should be removed before or after radiosurgery.

One-Day Two-Fraction Radiosurgery for Brain Metastases Using Gamma Knife.

OBJECTIVE: We aimed to evaluate the feasibility of a one-day two-fraction Gamma Knife radiosurgery (GKRS) for brain metastases. CASES AND METHODS: Ten cases with ten brain metastases (four cases of lung adenocarcinoma, one small cell lung carcinoma (SCLC), two renal cell carcinoma, one breast cancer, one esophageal carcinoma, and one bile duct carcinoma) were treated by one-day two-fraction (with an interval of more than six hours) GKRS under rigid skull frame fixation. Of the ten brain metastases, five lesions were in the frontal lobe, one in temporal, one in occipital, and three in the cerebellar hemisphere. The mean planning target volume (PTV) of the ten brain tumors was 7.8 ml (median, 8.0; range, 3.8 - 11.8). The ten targets of the mean prescription isodose volume (PIV) of 10.1 ml (median, 10.1; range, 4.4 - 15.9) were treated with a mean margin dose of 20.4 Gy (median, 20.5; range, 16.4 - 22) in two fractions. In five cases, other small brain metastases (one to seven tumors) were also treated simultaneously in a single fraction GKRS. The indication of two-fraction radiosurgery was large lesion size in eight, retreatment in three, the proximity of the motor area in three, and pre-existing perifocal edema symptom of dysarthria in two, nausea and vomiting in one, and dementia in one. RESULTS: Eight cases were alive at the end of the follow-up period of one to nine months (median, 6). One patient with SCLC died four and a half months after GKRS, from aggressive regrowth of the treated frontal lesion after transient marked shrinkage. Another patient died four months after GKRS due to the progression of other brain tumors treated by single fraction GKRS at the same time. In nine of 10 cases, the size of the treated tumors was controlled until the end of the follow-up period or the patient's death. In two cases, an additional GKRS was performed for newly developed brain metastases at distant locations at six months and five months after one-day two-fraction GKRS, respectively, and controlled at the end of the follow-up period. CONCLUSIONS: A relatively high dose may be safely delivered to large lesions, to those close to the important structures, or those with perifocal edema by one-day two-fraction radiosurgery. Local control was good except for a relapsed SCLC metastasis case. Evaluation in more cases with a longer follow-up period is necessary to determine definite indications and optimal prescription doses.

Stereotactic Radiotherapy with Fractionation for the Lesions in and Around the Brainstem and Optic Nerve.

Purpose Among the components of the central nervous system, the optic nerve and the brainstem are considered to be the eloquent structures that are sensitive to stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT). SRS or SRT with fractionation in areas adjacent to these tissues is both promising and challenging. Materials and methods To clarify the precise dose distribution achievable with fractionation in and around the optic nerve and brainstem, theoretical simulations were performed, based on the biological effective dose (BED). Results These simulations clearly showed that the doses to the optic nerve and brainstem can be adjusted using fractionation, meaning that the prescribed doses to the surrounding brain tissue can be reduced. Conversely doses to the lesions themselves can be increased by fractionation, while maintaining a stable dose to normal optic nerve and brainstem tissue.

Primary Central Nervous System Lymphoma with Peripheral Nerve Involvement: Case Report.

A 50-year-old man presented with dizziness and hearing disturbance in the right ear. Magnetic resonance imaging (MRI) revealed a well-enhanced mass lesion in the right cerebellopontine (CP) angle that appeared to originate in the cerebellum. A surgical specimen obtained at the subtotal resection with craniotomy revealed a diffuse large B-cell lymphoma (DLBCL). During the three courses of chemotherapy with high-dose methotrexate (MTX) with leucovorin rescue, he developed a right abducens palsy, left oculomotor palsy, left facial palsy, right trigeminal sensory disturbance, and paraparesis. Although the brain MRI showed that the CP angle tumor had disappeared completely following chemotherapy, enhanced lesions along the cauda equina were detected on a lumbar spine MRI. FDG-PET (18 F-fluorodeoxyglucose positron emission tomography) revealed multiple high-uptake abnormalities in the cranial nerves and spinal nerves. Tumor cells were found in the cerebrospinal fluid specimen from a lumbar puncture. Craniospinal irradiation was performed, including all the abnormal FDG high-uptake areas, and was effective in relieving the patient's symptoms. On FDG-PET, the high-uptake abnormalities in the peripheral nerves disappeared. However, five weeks after the irradiation, he developed right trigeminal sensory disturbance, hoarseness, dysphagia, and right arm pain. FDG-PET disclosed multiple high-uptake abnormalities in more peripheral portions of the cranial nerves and spinal nerves. Chemotherapy with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine (Oncovin®), and prednisolone (R-CHOP) was then resorted to which mitigated his symptoms. On follow-up FDG-PET, the high-uptake abnormalities in the peripheral nerves disappeared again.

Japanese Structure Survey of Radiation Oncology in 2011.

We evaluated the evolving structure of radiation oncology in Japan in terms of equipment, personnel, patient load and geographic distribution to identify and overcome any existing limitations. From March 2012 to August 2015, the Japanese Society for Radiation Oncology conducted a questionnaire based on the Japanese national structure survey of radiation oncology in 2011. Data were analyzed based on the institutional stratification by the annual number of new patients treated with radiotherapy per institution. The estimated annual numbers of new and total (new plus repeat) patients treated with radiation were 211 000 and 250 000, respectively. Additionally, the estimated cancer incidence was 851 537 cases with approximately 24.8% of all newly diagnosed patients being treated with radiation. The types and numbers of treatment devices actually used included linear accelerator (LINAC; n = 836), telecobalt (n = 3), Gamma Knife (n = 46), 60Co remote afterloading system (RALS; n = 24), and 192Ir RALS (n = 125). The LINAC system used dual-energy functions in 619 units, 3D conformal radiotherapy functions in 719 and intensity-modulated radiotherapy (IMRT) functions in 412. There were 756 JRS or JASTRO-certified radiation oncologists, 1018.5 full-time equivalent (FTE) radiation oncologists, 2026.7 FTE radiotherapy technologists, 149.1 FTE medical physicists, 141.5 FTE radiotherapy quality managers and 716.3 FTE nurses. The frequency of IMRT use significantly increased during this time. To conclude, although there was a shortage of personnel in 2011, the Japanese structure of radiation oncology has clearly improved in terms of equipment and utility.

A comprehensive understanding of lowly-hydrolyzed polyvinyl alcohol-based ternary solid dispersions with the use of a combined mixture-process design.

We recently reported lowly hydrolyzed polyvinyl alcohol (L-PVA, 70-74% hydrolyzed, about 580 polymerized, JR-05) as a promising matrix for hot-melt extrusion (HME) due to its unique micelle formation ability compared to the most commonly used PVA (87-89% hydrolyzed, about 580 polymerized). In the present study, we focused on the effect of composition [indomethacin (IND), L-PVA, sorbitol] and process parameters (temperature and screw speed) on each response, i.e. processing torque, and physicochemical properties such as residual crystallinity, residual ratio, and area under the dissolution curve (AUDC) in supersaturated solution using a HME by applying the design of experiment (DoE) approach. To overcome the poor processability of L-PVA, given its semicrystalline nature, we applied sorbitol as a plasticizer and systematically and simultaneously evaluated its influence on the outputs based on the mixture design combined with process factors. Few studies have focused on comprehensive evaluation of the composition and HME process conditions because obtaining a design space requires numerous experiments. We found that incorporating sorbitol into the L-PVA greatly improved the processing torque. However, sorbitol negatively influenced the degree of residual crystallinity and the AUDC of IND. Lastly, we established a laboratory-scale design space that could achieve high supersaturation and ensure adequate miscibility between each component, using an acceptable processing torque for HME, by applying the minimum amount of sorbitol. These fundamental results suggest that sorbitol maximizes the potency of L-PVA as a carrier in HME.

Predictive factors of prognosis after radiation and steroid pulse therapy in thyroid eye disease.

To identify predictive factors of prognosis after radiotherapy with concurrent steroid pulse therapy for thyroid eye disease, retrospective analyses were performed among 77 patients. Clinical activity score and magnetic resonance imaging were used to evaluate degrees of orbital inflammation. As a pre-treatment work-up, the thyroid-stimulating antibody (TSAb) level was measured. During a median follow-up of 25.0 months, the 2-year cumulative relapse-free rate (CRFR) was 80.9%. In the univariate analysis, a worse 2-year CRFR was significantly associated with the presence of optic neuropathy (P = 0.001), a higher TSAb rate (P = 0.001), and lower standard deviation (SD) of signal intensity at the extraocular muscle in T2-weighted images (P = 0.006). In the multivariate analysis, TSAb rate and SD affected the CRFR independently. When TSAb activity of 2800% was set as a cut-off at 2 years after treatment, the predictive sensitivity and specificity of relapse were 81.2% and 90.6%, respectively. With regard to SD, the respective sensitivity and specificity values were 81.2% and 82.7% when 100 was set as a cut-off. In conclusion, high TSAb and low SD were significant risk factors for cumulative relapse in orbital radiotherapy. Cut-off values of 2800% for TSAb and 100 for SD may be suitable.

Radiosurgery for Epidermoid Tumors: Dramatic Pain Relief from Trigeminal Neuralgia.

Purpose  The purpose of this study is to discuss the long-term effects of radiosurgery for epidermoid tumors, including the symptoms of trigeminal neuralgia and/or facial spasm, which we have originally reported before. Background Intracranial epidermoids are slow-growing tumors that can become symptomatic once they develop into large tumors. The mainstay of the treatment is surgery. However, eradicating the whole tumor is often difficult and some tumors may recur. In addition to their mass effects on the brain, these tumors are often associated with hyperactive nerve dysfunction syndromes such as trigeminal neuralgia, glossopharyngeal neuralgia, and/or facial spasm. Cases and methods  We report 13 cases of epidermoid tumors, 12 of which were located in the cerebellopontine angle (CPA), which were treated using 14 radiosurgery procedures. The inclusion criteria for radiosurgery were the presence of well-localized small tumors and/or severe associated neuralgia or facial spasms. The mean target volume ranged from 0.17 to 9.5 cm3 with a mean of 2.85 cm3. The lesions were treated with a mean maximum and a marginal dose of 28.2 Gy and 14.2 Gy, respectively. Results Among the 14 gamma knife procedures that were performed in 13 patients, dose planning to ensure total and partial coverage for relief from hyperactive cranial nerve dysfunction (HCND) was performed. Six cases were totally and another eight were partially covered at the dose planning. The irradiated tumors showed a minor decrease or no remarkable changes during a mean follow-up period of 86.1 months. Tumor progression requiring a second surgery was seen in two cases. The trigeminal neuralgias either improved or disappeared soon after the procedure, enabling the discontinuation of the medication. Conclusion  Radiosurgery led to a dramatic improvement in HCND. In fact, the immediate cure of neuralgia after the radiosurgery was observed in several cases, even after partial coverage with radiosurgery. The interface between the tumor and the nerve was the main target. The definite mechanisms for this favorable outcome have not been verified yet, but the functional modulation by the radiosurgery could be one. Electrophysiological alteration at the interface between the tumor and nerve has been considered. When the tumors were totally covered with radiosurgery, persistent tumor control was expected. Sufficient tumor control is possible if the tumor can be covered entirely with radiosurgery. Functional modulation of trigeminal neuralgia and facial spasms can also be attained even by partial dose planning for the nerve-tumor interface.

Japanese structure survey of radiation oncology in 2010.

We evaluated the evolving structure of radiation oncology in Japan in terms of equipment, personnel, patient load, and geographic distribution to identify and overcome any existing limitations. From March 2011 to June 2013, the Japanese Society for Radiation Oncology conducted a questionnaire based on the Japanese national structure survey of radiation oncology in 2010. Data were analyzed based on the institutional stratification by the annual number of new patients treated with radiotherapy per institution. The estimated annual numbers of new and total (new plus repeat) patients treated with radiation were 211 000 and 251 000, respectively. Additionally, the estimated cancer incidence was 805 236 cases, with ~26.2% of all newly diagnosed patients being treated with radiation. The types and numbers of treatment devices actually used included linear accelerator (LINAC; n = 829), telecobalt (n = 9), Gamma Knife (n = 46), 60Co remote afterloading system (RALS; n = 28), and 192Ir RALS (n = 131). The LINAC system used dual-energy functions in 586 units, three-dimensional conformal radiotherapy functions in 663, and intensity-modulated radiotherapy (IMRT) functions in 337. There were 564 JASTRO-certified radiation oncologists, 959.2 full-time equivalent (FTE) radiation oncologists, 1841.3 FTE radiotherapy technologists, 131.3 FTE medical physicists, 121.5 FTE radiotherapy quality managers, and 649.6 FTE nurses. The frequency of IMRT use significantly increased during this year. To conclude, although there was a shortage of personnel in 2010, the Japanese structure of radiation oncology has clearly improved in terms of equipment and utility.

Theoretical and practical evaluation of lowly hydrolyzed polyvinyl alcohol as a potential carrier for hot-melt extrusion.

Polyvinyl alcohol (PVA) is considered to be an unsuitable carrier for hot-melt extrusion (HME) due to its low processability. In this study, we focused on a lowly hydrolyzed PVA (JR-05, 70.0-74.0% hydrolyzed, L-PVA) to evaluate the potential use of L-PVA as a carrier for HME using the Hoftyzer and Krevelen method and thermodynamic models. These evaluations for drug-polymer systems based on the Flory-Huggins theory predicted the physicochemical properties of the solubility and miscibility between indomethacin (IND) and PVAs. Prior to initiating formulation studies, construction of IND and PVA phase diagrams provided guidance for design process conditions in HME. On the basis of the results of the validation studies, a conventional grade of PVA (JP-05, 87.0-89.0% hydrolyzed) is unlikely to be suitable as a carrier of HME due to its low plasticity, resulting in rapid recrystallization in the evaluation of in vitro dissolution and stability caused by poor miscibility. On the other hand, JR-05 demonstrated high processability, leading to the preparation of miscible extrudate with a high stability and an excellent in vitro dissolution profile due to its unique micelle-forming capability. These findings suggest that L-PVA brings about new carrier options among non-ionic polymers for HME.

Stereotactic Radiotherapy for Intramedullary Spinal Arteriovenous Malformations.

Introduction Preliminary results of stereotactic radiotherapy (SRT) for spinal arteriovenous malformation (AVM) in five cases are presented.  Methods Two cases were male and three were female. Their median age was 32 years (range: 23 to 54 years). The spinal intramedullary AVMs were located in the cervical spine in three and in the thoracic spine in two. SRT with 20 Gy in four fractions was delivered to the nidus in every case. Results At the end of the median follow-up period of 5.5 years (range: 3 to 8.5 years), the neurological symptoms and signs were improved or unchanged as compared with before treatment, although a temporary adverse effect developed between a half year and one year after SRT in one case. The nidi were obliterated five and a half years after SRT in one case and three years after SRT in one. In the other three cases, the nidi were unchanged. Conclusion SRT with 20 Gy in four fractions was thought to be a safe treatment, though this study dealt with only a small number of patients with a short-term follow-up period.

Identification of molecular-interaction sites between lowly hydrolyzed polyvinyl alcohols and indomethacin by NMR spectroscopy.

To evaluate the potency of hydrolyzed polyvinyl alcohols (PVAs) as matrices for solid dispersion (SD) formulations, we examined their inhibitory effects on precipitation of a poorly water-soluble drug, indomethacin (IND). Additionally, to clarify their mechanism, we investigated the intermolecular interaction of IND with PVAs in the supersaturated aqueous solution of IND. In the present study, we used five kinds of PVAs, i.e. JR-05 (70.0-74.0% hydrolyzed), JL-05E (80.0-84.0% hydrolyzed), JP-05 (87.0-89.0% hydrolyzed), JT-05 (93.5-94.5% hydrolyzed) and JF-05 (98.0-99.0% hydrolyzed). Of various PVAs, the lowly hydrolyzed PVAs such as JR-05 and JL-05E dramatically inhibited the precipitate formation of IND. Interestingly, the lowly hydrolyzed PVAs possessed micelle-forming ability, and inhibited the nucleation and crystal growth of IND. Moreover, strong hydrophobic interactions between vinyl acetate unit of lowly hydrolyzed PVA and hydrophobic moiety of IND were suggested based on the results of nuclear magnetic resonance (1H NMR) and nuclear overhauser effect spectroscopy (NOESY) in deuterium oxide. To the best of our knowledge, this is the first report describing the inhibitory effects of the hydrolyzed degree of PVAs on the precipitation of a drug, and demonstrating the intermolecular interaction between PVAs and a drug using NOESY in water.

CyberKnife Stereotactic Radiosurgery and Hypofractionated Stereotactic Radiotherapy As First-line Treatments for Imaging-diagnosed Intracranial Meningiomas.

Definitive radiotherapy is an important alternative treatment for meningioma patients who are inoperable or refuse surgery. We evaluated the efficacy and toxicity of CyberKnife-based stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (hSRT) as first-line treatments for intracranial meningiomas that were diagnosed using magnetic resonance imaging (MRI) and/or computed tomography (CT). Between February 2005 and September 2015, 41 patients with intracranial meningiomas were treated with CyberKnife-based SRS or hSRT. Eleven of those tumors were located in the skull base. The median tumor volume was 10.4 ml (range, 1.4-56.9 ml). The median prescribed radiation dose was 17 Gy (range, 13-20 Gy to the 61-88% isodose line) for SRS (n = 9) and 25 Gy (range, 14-38 Gy to the 44-83% isodose line) for hSRT (n = 32). The hSRT doses were delivered in 2 to 10 daily fractions. The median follow-up period was 49 months (range, 7-138). The 5-year progression-free survival rate (PFS) for all 41 patients was 86%. The 3-year PFS was 69% for the 14 patients with tumor volumes of ≥13.5 ml (30 mm in diameter) and 100% for the 27 patients with tumor volumes of <13.5 ml (P = 0.031). Grade >2 toxicities were observed in 5 patients (all of them had tumor volumes of ≥13.5 ml). SRS and hSRT are safe and effective against relatively small (<13.5 ml) meningiomas.

Dosimetric Study of Automatic Brain Metastases Planning in Comparison with Conventional Multi-Isocenter Dynamic Conformal Arc Therapy and Gamma Knife Radiosurgery for Multiple Brain Metastases.

OBJECTIVE: The efficacy of stereotactic radiosurgery (SRS) using Gamma Knife (GK) (Elekta, Tokyo) is well known. Recently, Automatic Brain Metastases Planning (ABMP) Element (BrainLAB, Tokyo) for a LINAC-based radiation system was commercially released. It covers multiple off-isocenter targets simultaneously inside a multi-leaf collimator field and enables SRS / stereotactic radiotherapy (SRT) with a single group of LINAC-based dynamic conformal multi-arcs (DCA) for multiple brain metastases. In this study, dose planning of ABMP (ABMP-single isocenter DCA (ABMP-SIDCA)) for SRS of small multiple brain metastases was evaluated in comparison with those of conventional multi-isocenter DCA (MIDCA-SRS) (iPlan, BrainLAB, Tokyo) and GK-SRS (GKRS). METHODS: Simulation planning was performed with ABMP-SIDCA and GKRS in the two cases of multiple small brain metastases (nine tumors in both), which had been originally treated with iPlan-MIDCA. First, a dosimetric comparison was done between ABMP-SIDCA and iPlan-MIDCA in the same setting of planning target volume (PTV) margin and D95 (dose covering 95% of PTV volume). Second, dosimetry of GKRS with a margin dose of 20 Gy was compared with that of ABMP-SIDCA in the setting of PTV margin of 0, 1 mm, and 2 mm, and D95=100% dose (20 Gy). RESULTS: First, the maximum dose of PTV and minimum dose of gross tumor volume (GTV) were significantly greater in ABMP-SIDCA than in iPlan-MIDCA. Conformity index (CI, 1/Paddick's CI) and gradient index (GI, V (half of prescription dose) / V (prescription dose)) in ABMP-SIDCA were comparable with those of iPlan-MIDCA. Second, PIV (prescription isodose volume) of GKRS was consistent with that of 1 mm margin - ABMP-SIDCA plan in Case 1 and that of no-margin ABMP-SIDCA plan in Case 2. Considering the dose gradient, the mean of V (half of prescription dose) of ABMP-SIDCA was not broad, comparable to GKRS, in either Case 1 or 2. CONCLUSIONS: The conformity and dose gradient with ABMP-SIDCA were as good as those of conventional MIDCA for each lesion. If the conditions of the LINAC system permit a minimal PTV margin (1 mm or less), ABMP-SIDCA might provide excellent dose fall-off comparable with that of GKRS thereby enabling a short treatment time.