Seiji Fukuoka

Combination Chemotherapy of Cisplatin, Ifosfamide, and Irinotecan with rhG-CSF Support in Patients with Brain Metastases from Non-Small Cell Lung Cancer

Background: Brain metastases develop frequently in patients with non-small cell lung cancer (NSCLC), and the prognosis for these patients is very poor. We evaluated the role of chemotherapy for patients with brain metastases from NSCLC. Methods: We analyzed 30 patients who were discovered to have brain metastases during the diagnosis of 121 patients enrolled in three consecutive clinical trials on advanced NSCLC assessing combination chemotherapy of cisplatin, ifosfamide and irinotecan with rhG-CSF support. Response in the brain lesions was evaluated by contrast-enhanced MRI scans after at least two courses. Results: Fourteen patients achieved a partial response (PR) but there was no change (NC) in 13 patients and progressive disease (PD) in 1. Among patients with extracranial lesions, 18 had a PR and 11 had NC. The response rate in brain metastases was 50.0%, and that in extracranial primary and metastatic lesions was 62.1%. The median duration of response for intra- and extracranial lesions was 140 and 147 days, respectively. After completing chemotherapy, Gamma Knife radiosurgery was performed on 2 patients in remission and 8 patients at disease progression. The median survival time and 1-year survival rate were 382 days and 56.1%, respectively. Conclusions: Both the response rate and survival data in this retrospective study suggest a high degree of activity of this combination chemotherapy in patients with brain metastases from NSCLC.

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 radiosurgery for hemangiomas of the cavernous sinus: a seven-institute study in Japan

OBJECT Gamma Knife radiosurgery (GKS) is currently used for primary or postoperative management of cavernous sinus (CS) hemangiomas. The authors describe their experience with 30 cases of CS hemangioma successfully managed with GKS. METHODS Thirty patients with CS hemangiomas, including 19 female and 11 male patients with a mean age of 53 years (range 19-78 years) underwent GKS at 7 facilities in Japan. Pathological entity was confirmed using surgical specimens in 17 patients, and neuroimaging diagnosis only in 13. Eight patients were asymptomatic before GKS, while 22 had ocular movement disturbances and/or optic nerve impairments. The mean tumor volume was 11.5 cm(3) (range 1.5-51.4 cm(3)). The mean dose to the tumor periphery was 13.8 Gy (range 10.0-17.0 Gy). RESULTS The mean follow-up period was 53 months (range 12-138 months). Among the 22 patients with symptoms prior to GKS, complete remission was achieved in 2, improvement in 13, and no change in 7. Hemifacial sensory disturbance developed following GKS in 1 patient. The most recent MR images showed remarkable shrinkage in 18, shrinkage in 11, and no change in 1 patient. CONCLUSIONS Gamma Knife radiosurgery proved to be an effective treatment strategy for managing CS hemangiomas. Given the diagnostic accuracy of recently developed neuroimaging techniques and the potentially serious bleeding associated with biopsy sampling or attempted surgical removal, the authors recommend that GKS be the primary treatment in most patients who have a clear neuroimaging diagnosis of this condition.

Apoptosis following Gamma Knife Radiosurgery in a Case of Acoustic Schwannoma

A 25-year-old woman with a large acoustic schwannoma underwent surgical excision 18 months after Gamma Knife radiosurgery because of transient expansion of the tumor causing ataxia. Histopathologial investigation by the TUNEL method revealed the presence of some apoptotic cells. The findings were compared with findings from a control group of 7 operated cases where radiosurgery had not been used. There was no apoptosis found in any of these cases. In addition, another case which resulted in a regrowing tumor following Gamma Knife treatment also showed no apoptosis. These findings suggest apoptosis may be a possible mechanism in reducing tumor size following Gamma Knife radiosurgery.

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.

Transient ischemic attacks caused by unruptured intracranial aneurysm

A case is reported of a 56-year-old man in whom an unruptured aneurysm of the left middle cerebral artery was the source of emboli resulting in transient ischemic attacks (TIAs). The potential relationship between TIAs and an unruptured aneurysm is discussed, and the literature is reviewed.

Completely thrombosed giant aneurysm of the angular artery

An unusual case of a completely thrombosed giant aneurysm arising from the angular artery is reported. A 69-year-old women developed a subarachnoid hemorrhage with a large intracranial hematoma. Computed tomography scans and cerebral angiography could not detect the aneurysm. The rarity of aneurysms in this position is stressed and the difficulty of diagnosis in this case is discussed.

Effect of gamma knife irradiation on relaxation and contraction responses of the common carotid artery in the rat

SummaryThis report concerns a pilot study of the short- and long-term effects of gamma knife radiosurgery on vascular responses. The investigation was carried out on male Sprague-Dawley rats, and the relaxation and contraction responses of the right common carotid artery (CCA) were assessed following irradiation (100 Gy). The non-treated CCA of the same animals served as internal controls. Non-irradiated rats were used to control the effect of normal aging on vascular function. Isometric tension was determined on in vitro preparations of arterial rings. Acetylcholine-mediated, endothelium-dependent relaxation was impaired one month after radiosurgery, as was endothelium-independent relaxation induced by sodium nitroprusside, but the effect on the latter was minimal. The irradiated CCA was also impaired with respect to contraction responses induced by norepinephrine, endothelin-1 or phorbol dibutyrate. This impairment appeared to be biphasic, as it was evident one day after radiosurgery, followed by a partial recovery one week later, and again manifest after one month. At the light microscope level, the carotid arteries appeared to be well preserved throughout the experiment. However, obvious ultrastructural changes were noted in endothelial and smooth muscle cells of specimens obtained three months after radiosurgery. The present data indicate that high dose gamma knife radiosurgery affects the functions of both, the vascular endothelium and the vascular smooth muscles in an apparent time-dependent fashion. Because of its increasing application to patients, there is the need for studying the effects of gamma knife radiosurgery on cerebral arteries, since functional vascular changes may occur in the absence of obvious histological alterations. Our results on CCAs point to the feasibility of such experimental investigations.