Masami Takanashi

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.

Gamma Knife Radiosurgery for Growth Hormone-Secreting Pituitary Adenomas Invading the Cavernous Sinus

The authors assessed whether gamma knife radiosurgery is effective for patients with acromegaly where the pituitary tumors invaded the cavernous sinus. Radiosurgery was performed on 9 patients (average of 20 Gy to the tumor margin), 8 of whom had already undergone transsphenoidal surgery and/or craniotomy with occasional medication of octreotide to reduce tumor size as well as hormonal levels. All tumors have been well controlled so far with follow-up periods ranging from 12 to 69 months (mean: 42). No complications occurred. Forty percent of the patients showed hormonal normalization at 2 years, with the median being 31 months. Similarly, 50% of the patients demonstrated normalization of GH and IGF-I at 36 months. We conclude that gamma knife radiosurgery is a safe and effective tool to treat these tumors invading the cavernous sinus.

Gamma Knife Radiosurgery for Vestibular Schwannomas

The purpose of this study was to analyze tumor control and possible complications of gamma knife radiosurgery (GKRS) in patients with vestibular schwannomas using low marginal doses and conformal multiple shots to fit irregular tumor shapes. The authors evaluated 152 patients with more than 5 years of follow-up. Marginal doses were 9-15 Gy (median 12 Gy), with corresponding treatment volumes ranging from 0.1 to 18.7 cm3 (median 2.0 cm3). The number of isocenters varied from 2 to 24 shots (median 9 shots). The actuarial tumor control rates were 94% at 5 years and 92.4% at 8 years. Larger tumors (p < 0.0001) and those in younger patients (p = 0.018) tended to recur significantly more often. Useful hearing, facial and trigeminal functions were preserved at 71, 100 and 97.4%, respectively. Seventeen percent of all patients developed transient dizziness, with dizziness persisting in 2% of the total. Fifty-six other patients not included in the long-term evaluation consecutively underwent caloric testing and static stabilometry as well as neurological examinations to evaluate vestibular function in detail, both before and after GKRS. The results revealed 90% of the patients to have already developed vestibular dysfunction prior to the treatment despite reported symptoms of dizziness. GKRS did not significantly affect vestibular function. Hydrocephalus was recognized in 5.3% of all patients, and tended to occur in cases with larger tumors (p = 0.0024). GKRS provides a safe and effective therapy for small to medium-sized tumors. However, indications for larger tumors must be carefully considered, as they are more difficult to control and liable to produce ataxia due to transient expansion.

Gamma knife surgery for Cushing's disease

BACKGROUND The efficacy of gamma knife surgery on Cushings disease is not well known to date. In most reported cases of Cushings disease treated with gamma knife, the area to be irradiated was determined with computed tomography or pneumoencephalography. We report two cases of recurrent pituitary-dependent Cushings disease treated with gamma knife using stereotactic magnetic resonance imaging (MRI). MATERIALS AND METHODS Recurrent microadenomas were visualized as hypointense areas using gadolinium-enhanced MRI after two transsphenoidal surgeries in both cases. The doses of irradiation given were 35 Gy and 20 Gy to the margin of the tumors, and less than 8 Gy and 21 Gy to the optic apparatus and cranial nerves in the cavernous sinus, respectively. RESULTS Both patients had clinical remission with normal serum cortisol and adrenocorticotrophic hormone levels, during 2-year follow-up after radiosurgery, without endocrinologic deficiency or neurologic deterioration. CONCLUSIONS Gamma knife surgery can be an alternative therapy for Cushings disease when pituitary adenomas are apart from the optic apparatus and can be visualized clearly by MRI, even if tumors are recurrent after microsurgery.

Gamma Knife Radiosurgery for Skull-Base Meningiomas

OBJECTIVE The primary purpose of this study was to evaluate the efficacy of gamma knife radiosurgery (GKRS) when used as a treatment modality for cavernous sinus or posterior fossa skull-base meningiomas (SBMs), with particular attention given to whether or not intentional partial resection followed by GKRS constitutes an appropriate combination treatment method for larger SBMs. PATIENTS AND METHODS Of the 101 SBM patients in this series, 38 were classified as having cavernous sinus meningiomas (CSMs), and 63 presented with posterior fossa meningiomas (PFMs). The patients with no history of prior surgery (19 CSMs, 57 PFMs) were treated according to a set protocol. Small to medium-sized SBMs were treated by GKRS only. To minimize the risk of functional deficits, larger tumors were treated with the combination of intentional partial resection followed by GKRS. Residual or recurrent tumors in patients who had undergone extirpations prior to GKRS (19 CSMs, 6 PFMs) are not eligible for this treatment method (due to the surgeries not being performed as part of a combination strategy designed to preserve neurological function as the first priority). RESULTS The mean follow-up period was 51.9 months (range, 6-144 months). The overall tumor control rates were 95.5% in CSMs and 98.4% in PFMs. Nearly all tumors treated with GKRS alone were well controlled and the patients had no deficits. Furthermore, none of the patients who had undergone prior surgeries experienced new neurological deficits after GKRS. While new neurological deficits appeared far less often in those receiving the combination of partial resection with subsequent GKRS, extirpations tended to be associated with not only a higher incidence of new deficits but also a significant increase in the worsening of already-existing deficits. CONCLUSION Our results indicate that GKRS is a safe and effective primary treatment for SBMs with small to moderate tumor volumes. We also found that larger SBMs compressing the optic pathway or brain stem can be effectively treated, minimizing any possible functional damage, by a combination of partial resection with subsequent GKRS.