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.

Medulloblastoma with epithelioid features in the cerebellar vermis.

A 6-year-old girl was admitted with a mass lesion in the cerebellar vermis. She underwent subtotal tumor resection, and on immunohistopathology the tumor consisted of two different parts: typical medulloblastoma (MB) characteristics and atypical teratoid/rhabdoid tumor (AT/RT) features, despite positive integrase interactor 1 expression. The patient was diagnosed with MB with epithelioid features. Chemoradiation therapy was started because of tumor recurrence at the primary site and dissemination to the spinal cord, as determined on magnetic resonance imaging 2 weeks after surgery. The patient died due to tumor progression 13 months after initial diagnosis, although transient partial remission was achieved.

Gamma knife radiosurgery of craniopharyngioma: results of 30 cases treated at Nagoya Radiosurgery Center.

Evaluation of 30 cases of craniopharyngioma treated by Gamma Knife at Nagoya Radiosurgery Center (NRC), Nagoya Kyoritsu Hospital since July, 2004 has been made. The mean volume of the tumor was 2.64 ml, which was treated with the marginal dose of 11.7 Gy. Mean follow-up period was 79.9 months. The effects were evaluated by MRI findings, neuro-endocrine and hypothalamic signs and symptoms, complications and KPS every 3~6 months. As the results, complete remission was obtained in 8, partial remission in 12, no change in 6, progression in 3, in which two died by hypothalamic invasion. Tumor response rate was 68.9% and control rate 87.9%. Actuarial survival was 96% at 5 and 86% at 10 years. However, progression free survival was 76% and 76%, respectively. Using marginal dose of 11.7Gy to a smaller tumor, better control without complications has been obtained. KPS was excellent in 14, good in 9, fair in 2, poor in 1 and unknown in a case. Finally, there were three deaths, where two were died of tumor progression and one by infirmity. The progression of hypothalamic symptoms other than diabetes insipidus were found in two cases. Volume reduction and effective dose setting will be important for the improvement of QOL and survival after combined microsurgery and radiosurgery of craniopharyngioma.

Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study.

BACKGROUND: We aimed to examine whether stereotactic radiosurgery without whole-brain radiotherapy (WBRT) as the initial treatment for patients with five to ten brain metastases is non-inferior to that for patients with two to four brain metastases in terms of overall survival. METHODS: This prospective observational study enrolled patients with one to ten newly diagnosed brain metastases (largest tumour <10 mL in volume and <3 cm in longest diameter; total cumulative volume ≤15 mL) and a Karnofsky performance status score of 70 or higher from 23 facilities in Japan. Standard stereotactic radiosurgery procedures were used in all patients; tumour volumes smaller than 4 mL were irradiated with 22 Gy at the lesion periphery and those that were 4-10 mL with 20 Gy. The primary endpoint was overall survival, for which the non-inferiority margin for the comparison of outcomes in patients with two to four brain metastases with those of patients with five to ten brain metastases was set as the value of the upper 95% CI for a hazard ratio (HR) of 1·30, and all data were analysed by intention to treat. The study was finalised on Dec 31, 2012, for analysis of the primary endpoint; however, monitoring of stereotactic radiosurgery-induced complications and neurocognitive function assessment will continue for the censored subset until the end of 2014. This study is registered with the University Medical Information Network Clinical Trial Registry, number 000001812. FINDINGS: We enrolled 1194 eligible patients between March 1, 2009, and Feb 15, 2012. Median overall survival after stereotactic radiosurgery was 13·9 months [95% CI 12·0-15·6] in the 455 patients with one tumour, 10·8 months [9·4-12·4] in the 531 patients with two to four tumours, and 10·8 months [9·1-12·7] in the 208 patients with five to ten tumours. Overall survival did not differ between the patients with two to four tumours and those with five to ten (HR 0·97, 95% CI 0·81-1·18 [less than non-inferiority margin], p=0·78; pnon-inferiority<0·0001). Stereotactic radiosurgery-induced adverse events occurred in 101 (8%) patients; nine (2%) patients with one tumour had one or more grade 3-4 event compared with 13 (2%) patients with two to four tumours and six (3%) patients with five to ten tumours. The proportion of patients who had one or more treatment-related adverse event of any grade did not differ significantly between the two groups of patients with multiple tumours (50 [9%] patients with two to four tumours vs 18 [9%] with five to ten; p=0·89). Four patients died, mainly of complications relating to stereotactic radiosurgery (two with one tumour and one each in the other two groups). INTERPRETATION: Our results suggest that stereotactic radiosurgery without WBRT in patients with five to ten brain metastases is non-inferior to that in patients with two to four brain metastases. Considering the minimal invasiveness of stereotactic radiosurgery and the fewer side-effects than with WBRT, stereotactic radiosurgery might be a suitable alternative for patients with up to ten brain metastases. FUNDING: Japan Brain Foundation.

Dosimetric comparison of absolute and relative dose distributions between tissue maximum ratio and convolution algorithms for acoustic neurinoma plans in Gamma Knife radiosurgery.

BACKGROUND: The treatment planning for Gamma Knife (GK) stereotactic radiosurgery (SRS) that performs dose calculations based on tissue maximum ratio (TMR) algorithm has disadvantages in predicting dose in tissue heterogeneity. The latest version of the planning software is equipped with a convolution dose algorithm as an optional extra and the new algorithm is able to compensate for head inhomogeneity. However, the effect of this improved calculation method requires detailed validation in clinical cases. In this study, we compared absolute and relative dose distributions of treatment plans for acoustic neurinoma between TMR and the convolution calculation. METHODS: Twenty-nine clinically used plans created by TMR algorithm were recalculated by convolution method. Differences between TMR and convolution were evaluated in terms of absolute dose (beam-on time), dosimetric parameters including target coverage, selectivity, conformity index, gradient index, radical homogeneity index and the dose-volume relationship. RESULTS: The discrepancy in estimated absolute dose to the target ranged from 1 to 7 % between TMR and convolution. In addition, dosimetric parameters of the two methods achieved statistical significance. However, it was difficult to see the change of relative dose distribution by visual assessment on a monitor. CONCLUSIONS: Convolution, heterogeneity correction calculation, and the algorithm are necessary to reduce the dosimetric uncertainty of each case in GK SRS.

Useful base plate to support the head during Leksell skull frame placement in gamma knife perfexion radiosurgery.

We developed an original base plate to support both the patient's head and a Leksell stereotactic skull frame during frame placement in the supine position. The base plate is made of transparent acrylic board with holes at the posterior posts for injection of local anesthetics and maneuver of fixation screws through them. A stable and comfortable position of the patient's head in a supine position is obtained and maintained on this base plate with an air-pressure cuff beneath the patient's head. The patient is able to keep a stable, relaxed and comfortable posture during the procedures of skull frame placement.

Gamma knife radiosurgery of brain metastasis from malignant pleural mesothelioma--report of three cases with autopsy study in a case.

The median survival time of malignant pleural mesothelioma (MPM) has been 9 months. Given the short survival, there have been only few cases in which brain metastases have been diagnosed and treated before death. Three cases of brain metastases treated by gamma knife radiosurgery (GKR) are reported. Case I showed a metastatic lesion in the right frontal lobe which was treated by GKR two years after diagnosis of MPM. The lesion markedly reduced and the symptoms were improved, But the patient died of progression of pleural tumor four months after GKR. A year and three months after the diagnosis, asymptomatic bifrontal lesions were treated with GKR. However, Case 2 died of abdominal mass a month after. Case 3 showed headache one and half year after the diagnosis. Three brain lesions were treated by GKR, which disappeared in 4 months. The patient died of new multiple brain metastases and periventricular dissemination seven months after. The autopsy revealed a MPM occupying the left pleural cavity. No neoplastic lesion was found in gamma knife-treated sites. The cause of death was the mass effect by new metastatic lesions. GKR was found effective also for the treatment of brain metastasis of MPM.

Effect of skull contours on dose calculations in Gamma Knife Perfexion stereotactic radiosurgery.

In treatment planning of Leksell Gamma Knife (LGK) radiosurgery, the skull geometry defined by generally dedicated scalar measurement has a crucial effect on dose calculation. The LGK Perfexion (PFX) unit is equipped with a cone-shaped collimator divided into eight sectors, and its configuration is entirely different from previous model C. Beam delivery on the PFX is made by a combination of eight sectors, but it is also mechanically available from one sector with the remaining seven blocked. Hence the treatment time using one sector is more likely to be affected by discrepancies in the skull shape than that of all sectors. In addition, the latest version (Ver. 10.1.1) of the treatment planning system Leksell GammaPlan (LGP) includes a new function to directly generate head surface contouring from computed tomography (CT) images in conjunction with the Leksell skull frame. This paper evaluates change of treatment time induced by different skull models. A simple simulation using a uniform skull radius of 80 mm and anthropomorphic phantom was implemented in LGP to find the trend between dose and skull measuring error. To evaluate the clinical effect, we performed an interobserver comparison of ruler measurement for 41 patients, and compared instrumental and CT-based contours for 23 patients. In the phantom simulation, treatment time errors were less than 2% when the difference was within 3 mm. In the clinical cases, the variability of treatment time induced by the differences in interobserver measurements was less than 0.91%, on average. Additionally the difference between measured and CT-based contours was good, with a difference of -0.16% ± 0.66% (mean ±1 standard deviation) on average and a maximum of 3.4%. Although the skull model created from CT images reduced the dosimetric uncertainty caused by different measurers, these results showed that even manual skull measurement could reproduce the skull shape close to that of a patient's head within an acceptable range.

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.

Gamma knife stereotactic radiosurgery for atypical and malignant meningiomas.

BACKGROUND: Non-benign meningioma has a known trend to recur repeatedly. The results of Gamma Knife stereotactic radiosurgery (GKS) for recurrent or residual atypical and malignant meningiomas are reported. METHODS: Thirty patients (13 men, 17 women) with World Health Organization (WHO) grade II (24 cases) or grade III (6 cases) intracranial meningiomas underwent GKS. Their age varied from 30 to 86 years (mean 64 years). Before GKS, the tumor was surgically resected in all patients, and 11 of them also underwent conventional external beam radiation therapy, LINAC-based stereotactic radiotherapy (SRT), or intensity-modulated radiation therapy. FINDINGS: Of the 30 patients, 23 were followed after the initial GKS for a median period of 28 months (range 2-135 months). Local tumor control after treatment was 74 % at 1 year, 52 % at 2 years, and 34 % at 3 years. A total of 15 patients underwent repeat GKS (one to nine times) because of local or distant intracranial tumor progression, seven were subjected to surgical re-resection of the neoplasm, and four had additional SRT. At the time of the last follow-up, 21 patients were alive, and 2 had died. One of the latter expired because of brain tumor progression at 91 months after the initial GKS, and the other patient died from lung cancer. CONCLUSIONS: Although atypical and malignant meningiomas have a trend to recur repeatedly, aggressive tumor management with repeat GKS at the time of progression can provide long survival in these patients.

Stereotactic radiotherapy for spinal intradural metastases developing within or adjacent to the previous irradiation field--report of three cases.

Results of stereotactic radiotherapy (SRT) for spinal intradural metastases developing inside or adjacent to the previous external-beam radiation therapy (EBRT) field are shown in 3 cases. One case of spinal intramedullary metastasis and two cases of intradural extramedullary metastases were treated using a Novalis shaped-beam SRT. Case 1 developed an intramedullary metastatic tumor in the C1 spinal medulla inside the previous whole brain EBRT field and another lesion adjacent to the field in the C2 spinal medulla. Case 2 developed intradural extramedullary metastasis around C6-8 inside the previous EBRT field for the primary lung adenocarcinoma. Case 3 developed multiple spinal intradural extramedullary metastatic deposits after surgical resection and following whole brain EBRT for brain metastasis. We delivered 24 to 36 Gy in 5 to 12 fractions. The treated tumors were stable or decreased in size until the patients' death from the primary cancer (10, 22, and 5 months). Neurological symptoms were stable or improved in all 3 patients. Palliative SRT using Novalis is expected to be safe and effective even if the patient develops spinal intradural metastases within or adjacent to the previous irradiation field.

[A case of calcineurin-inhibitor induced pain syndrome associated with tacrolimus therapy for ulcerative colitis].

A 23-year-old woman was admitted with a relapse of ulcerative colitis. Tacrolimus therapy was initiated following inadequate response to corticosteroid therapy. Although the symptoms partially improved, she suddenly developed severe pain localized to the lower limbs on day 16 of tacrolimus therapy. By day 17, she was unable to move. Magnetic resonance imaging revealed born marrow edema in the lower limbs. We suspected calcineurin-inhibitor induced pain syndrome (CIPS) due to tacrolimus therapy. The pain improved within approximately four weeks of tacrolimus cessation. CIPS that is not associated with organ transplantation is a rare occurrence. Here we report a rare case of CIPS that was caused by tacrolimus therapy in a patient with ulcerative colitis.

Regression curves of brain metastases after gamma knife irradiation: Difference by tumor and patient characteristics.

Regression curves and local control rates of brain metastases after gamma knife treatment were evaluated to investigate differences in tumor response to radiation. A total of 203 metastases were serially evaluated using contrast-enhanced MRI (or computed tomography) at 1, 2, 3, 4.5 and 6 months after a 20-Gy dose. Differences were evaluated in regression curves and control rates between tumors ≥10 mm and tumors <10 mm in mean diameter, among three major histological subtypes of lung cancer, among adenocarcinomas of the lung, breast and colorectum, and between tumors in patients with above and below median hemoglobin levels. Smaller tumors shrank faster and yielded better control rates than larger tumors. Metastases from small cell and squamous cell carcinomas of the lung shrank faster than those from lung adenocarcinoma, but 6-month control rates were not different. Breast adenocarcinomas tended to shrink faster than lung adenocarcinomas, but the control rates were not different among adenocarcinomas of the lung, breast and colorectum. Tumors in patients with higher hemoglobin levels tended to shrink faster but the control rates were not different. Small cell and squamous cell carcinomas of the lung regress more rapidly than adenocarcinomas, although local control rates might not differ significantly.

Stereotactic body radiotherapy using a radiobiology-based regimen for stage I nonsmall cell lung cancer: a multicenter study.

BACKGROUND: The most common regimen of stereotactic body radiotherapy (SBRT) for stage I nonsmall cell lung cancer in Japan is 48 grays (Gy) in 4 fractions over 4 days. Radiobiologically, however, higher doses are necessary to control larger tumors, and interfraction intervals should be >24 hours to take advantage of reoxygenation. In this study, the authors tested the following regimen: For tumors that measured <1.5 cm, 1.5 to 3.0 cm, and >3.0 cm in greatest dimension, radiation doses of 44 Gy, 48 Gy, and 52 Gy, respectively, were given in 4 fractions with interfraction intervals of ≥3 days. METHODS: Among 180 patients with histologically proven disease who entered the study, 120 were medically inoperable, and 60 were operable. The median patient age was 77 years (range, 29-92 years). SBRT was performed with 6-megavolt photons using 4 noncoplanar beams and 3 coplanar beams. Isocenter doses of 44 Gy, 48 Gy, and 52 Gy were received by 4 patients, 124 patients, and 52 patients, respectively. RESULTS: The overall survival rate for all 180 patients was 69% at 3 years and 52% at 5 years. The 3-year survival rate was 74% for operable patients and 59% for medically inoperable patients (P = .080). The 3-year local control rate was 86% for tumors ≤3 cm (44/48 Gy) and 73% for tumors >3 cm (52 Gy; P = .050). Grade ≥2 radiation pneumonitis developed in 13% of patients (10% of the 44-Gy/48-Gy group and 21% of the 52-Gy group; P = .056). All other grade 2 toxicities developed in <4% of patients. CONCLUSIONS: The SBRT protocol used in this study yielded reasonable local control and overall survival rates and acceptable toxicity. Dose escalation is being investigated.

Potential use of lactosylated dendrimer (G3)/α-cyclodextrin conjugates as hepatocyte-specific siRNA carriers for the treatment of familial amyloidotic polyneuropathy.

To reveal the potential use of lactosylated-dendrimer (G3) conjugates with α-cyclodextrin (Lac-α-CDE (G3)) as novel hepatocyte-specific siRNA carriers in order to treat transthyretin (TTR)-related familial amyloidotic polyneuropathy (FAP), we evaluated the RNAi effect of siRNA complexes with Lac-α-CDE (G3) both in vitro and in vivo. Herein, we targeted TTR gene expression because TTR-related FAP was often caused by amyloidogenic TTR (ATTR), which mainly expresses in hepatocytes. Lac-α-CDE (G3, average degree of substitution of lactose (DSL) 1.2)/siRNA complex had a potent RNAi effect against TTR gene expression through adequate physicochemical properties, asialoglycoprotein receptor (ASGP-R)-mediated cellular uptake, efficient endosomal escape and the delivery of the siRNA complex to cytoplasm, but not nucleus, with negligible cytotoxicity. Lac-α-CDE (G3, DSL 1.2)/siRNA complex had the potential to induce the in vivo RNAi effect after intravenous administration in the liver of mice. The blood chemistry values in the α-CDE (G3) and Lac-α-CDE (G3, DSL 1.2) systems were almost equivalent to those in the control system (5% mannitol solution). Taken together, these results suggest that Lac-α-CDE (G3, DSL 1.2) has the potential for a novel hepatocyte-selective siRNA carrier in vitro and in vivo, and has a possibility as a therapeutic tool for FAP to the liver transplantation.

Cyclodextrin, a novel therapeutic tool for suppressing amyloidogenic transthyretin misfolding in transthyretin-related amyloidosis.

TTR (transthyretin), a ß-sheet-rich protein, is the precursor protein of familial amyloidotic polyneuropathy and senile systemic amyloidosis. Although it has been widely accepted that protein misfolding of the monomeric form of TTR is a rate-limiting step for amyloid formation, no effective therapy targeting this misfolding step is available. In the present study, we focused on CyDs (cyclodextrins), cyclic oligosaccharides composed of glucose units, and reported the inhibitory effect of CyDs on TTR amyloid formation. Of various branched ß-CyDs, GUG-ß-CyD [6-O-α-(4-O-α-D-glucuronyl)-D-glucosyl-ß-CyD] showed potent inhibition of TTR amyloid formation. Far-UV CD spectra analysis showed that GUG-ß-CyD reduced the conformational change of TTR in the process of amyloid formation. In addition, tryptophan fluorescence and 1H-NMR spectroscopy analyses indicated that GUG-ß-CyD stabilized the TTR conformation via interaction with the hydrophobic amino acids of TTR, especially tryptophan. Moreover, GUG-ß-CyD exerted its inhibitory effect by reducing TTR deposition in transgenic rats possessing a human variant TTR gene in vivo. Collectively, these results indicate that GUG-ß-CyD may inhibit TTR misfolding by stabilizing its conformation, which, in turn, suppresses TTR amyloid formation.

Prognostic factors for tumor recurrence after gamma knife radiosurgery of partially resected and recurrent craniopharyngiomas.

A study was conducted to clarify the prognostic factors related to recurrence of craniopharyngioma and to improve the quality of life of patients by the treatment with intentional partial removal and gamma knife radiosurgery. One hundred cases of craniopharyngioma have been treated at Komaki City Hospital since 1991. In a mean follow-up period of 65.5 months, the tumor control rate was 79.5%. The 5- and 10-year actuarial survival rates were 94.1% and 91%, respectively. However, the recurrence-free survival rates were 73.6% at 5 years and 60.2% at 10 years. Nine factors thought to be related to the recurrence were selected from past references and previous studies, including gender, age, pediatric (< or =17 years) or adult patient, partial removal or recurrence, mean tumor diameter, tumor type (solid or cyst), pathological types (squamous cell or adamantinoma), number of previous treatments, and radiation dose. Statistical analysis was performed to determine which factors had a significant prognostic impact. Multivariate analysis showed that mean tumor diameter and radiation dose were independent predictors of outcome. To maximize the prognostic power of these factors, cut-off levels were determined using ROC analysis. These levels were 19 mm for tumor diameter and 13.2 Gy for marginal dose. Significant prognostic factors related to recurrence of craniopharyngioma are tumor diameter and radiation dose. A tumor diameter of <19 mm and a marginal dose of > or =13.2 Gy are favorable prognostic factors for gamma knife radiosurgery.

[Setup accuracy of stereotactic body radiation therapy (SBRT) using virtual isocenter in image-guided radiation therapy (IGRT)].

We use Novalis Body system for stereotactic body radiation therapy (SBRT) in lung and liver tumors. Novalis system is dedicated to SBRT with image-guided patient setup system ExacTrac. The spinal bone is the main landmark in patient setup during SBRT using ExacTrac kV X-ray system. When the target tumor is located laterally distant from the spinal bone at the midline, it is difficult to ensure the accuracy of the setup, especially if there are rotational gaps (yaw, pitch and roll) in the setup. For this, we resolve the problem by using a virtual isocenter (VIC) different from isocenter (IC) .We evaluated the setup accuracy in a rand phantom by using VIC and checked the setup errors using rand phantom and patient cases by our original method during the setup for IC. The accuracy of setup using VIC was less than 1.0 mm. Our original method was useful for checking patient setup when VIC used.

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.

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.