Yoshiyasu Iwai

Methionine positron emission tomography for differentiation of recurrent brain tumor and radiation necrosis after stereotactic radiosurgery--in malignant glioma.

ObjectFollowing stereotactic radiosurgery (SRS), we examined how to differentiate radiation necrosis from recurrent malignant glioma using positron emission tomography (PET) with11C-methionine (Met).MethodsMet-PET scans were obtained from 11 adult cases of recurrent malignant glioma or radiation injury, suspected on the basis of magnetic resonance images (MRI). Patients had previously been treated with SRS after primary treatment. PET images were obtained as a static scan of 10 minutes performed 20 minutes after injection of Met. We defined two visual grades (e.g., positive or negative Met accumulation). On Met-PET scans, the portion of the tumor with the highest accumulation was selected as the region of interest (ROI), tumor-versus-normal ratio (TN) was defined as the ratio of average radioisotope counts per pixel in the tumor (T), divided by average counts per pixel in normal gray matter (N). The standardized uptake value (SUV) was calculated over the same tumor ROI. Met-PET scan accuracy was evaluated by correlating findings with subsequent histological analysis (8 cases) or, in cases without surgery or biopsy, by the subsequent clinical course and MR findings (3 cases).ResultsHistological examinations in 8 cases showed viable glioma cells with necrosis in 6 cases, and necrosis without viable tumor cells in 2 cases. Three other cases were considered to have radiation necrosis because they exhibited stable neurological symptoms with no sign of massive enlargement of the lesion on follow-up MR after 5 months. Mean TN was 1.31 in the radiation necrosis group (5 cases) and 1.87 in the tumor recurrence group (6 cases). Mean SUV was 1.81 in the necrosis group and 2.44 in the recurrence group. There were no statistically significant differences between the recurrence and necrosis groups in TN or SUV. Furthermore, we made a 2 x 2 factorial cross table (accumulation or no accumulation, recurrence or necrosis). From this result, the Met-PET sensitivity, specificity, and accuracy in detecting tumor recurrence were determined to be 100%, 60%, and 82% respectively. In a false positive-case, glial fibrillary acidic protein (GFAP) immunostaining showed a positive finding.ConclusionThere were no significant differences between recurrent malignant glioma and radiation necrosis following SRS in Met-PET. However, this study shows Met-PET has a sensitivity and accuracy for differentiating between recurrent glioma and necrosis, and presents important information for developing treatment strategies against post radiation reactions.

Radiosurgery for acoustic neuromas: results of low-dose treatment.

OBJECTIVEThe results of radiosurgical treatment of acoustic neuromas have improved by reducing the tumor marginal doses. We report relatively long-term follow-up results (>5 yr) for patients who underwent low-dose radiosurgery. METHODSWe treated and followed 51 consecutive patients with unilateral acoustic neuromas who were treated from January 1994 to December 1996 by gamma knife radiosurgery at low doses (≤12 Gy to the tumor margin). The average age of the patients was 55 years (range, 32–76 yr). The treatment volume was 0.7 to 24.9 cm3 (median, 3.6 cm3). The marginal radiation dose was 8 to 12 Gy (median, 12 Gy), and the follow-up period ranged from 18 to 96 months (median, 60 mo). RESULTSClinical tumor growth control (without tumor resection) was achieved in 96% of patients, and the 5-year tumor growth control rate was 92%. Hearing was preserved in 59% of those with preradiosurgical hearing preservation (Gardner-Robertson Classes 1–4), and improvements (>20 dB of improvement) were noted in 9% of the patients with any hearing. Hearing was preserved at a useful level (Gardner-Robertson Classes 1 and 2) in 56% of patients. Although preexisting trigeminal neuropathy worsened in 4% of the patients, our patients did not experience new facial palsies or trigeminal neuropathies after radiosurgery. Facial spasm occurred in 6% of the patients, and intratumoral bleeding occurred in 4% of patients. CONCLUSIONLow-dose radiosurgery (≤12 Gy at the tumor margin) can achieve a high tumor growth control rate and maintain low postradiosurgical morbidity (including hearing preservation) for acoustic neuromas.

Gamma knife radiosurgery for the treatment of cavernous sinus meningiomas.

OBJECTIVEWe report on the efficacy of gamma knife radiosurgery for cavernous sinus meningiomas. METHODSBetween January 1994 and December 1999, we used gamma knife radiosurgery for the treatment of 43 patients with cavernous sinus meningiomas. Forty-two patients were followed up for a mean of 49.4 months (range, 18–84 mo). The patients’ average age was 55 years (range, 18–81 yr). Twenty-two patients (52%) underwent operations before radiosurgery, and 20 patients (48%) underwent radiosurgery after the diagnosis was made by magnetic resonance imaging. The tumor volumes ranged from 1.2 to 101.5 cm3 (mean, 14.7 cm3). The tumors either compressed or were attached to the optic apparatus in 17 patients (40.5%). The marginal radiation dose was 8 to 15 Gy (mean, 11 Gy), and the optic apparatus was irradiated with 2 to 12 Gy (mean, 6.2 Gy). Three patients with a mean tumor diameter greater than 4 cm were treated by two-stage radiosurgery. RESULTSThirty-eight patients (90.5%) demonstrated tumor growth control during the follow-up period after radiosurgery. Tumor regression was observed in 25 patients (59.5%), and growth was unchanged in 13 patients (31%). Regrowth or recurrence occurred in four patients (9.5%). The actual tumor growth control rate at 5 years was 92%. Only one patient (2.4%) experienced regrowth within the treatment field; in other patients, regrowth occurred at sites peripheral to or outside the treatment field. Twelve patients (28.6%) had improved clinically by the time of the follow-up examination. None of the patients experienced optic neuropathy caused by radiation injury or any new neurological deficits after radiosurgery. CONCLUSIONGamma knife radiosurgery may be a useful option for the treatment of cavernous sinus meningiomas not only as an adjuvant to surgery but also as an alternative to surgical removal. We have shown it to be safe and effective even in tumors that adhere to or are in close proximity to the optic apparatus.

Surgery combined with radiosurgery of large acoustic neuromas

UNLABELLED The treatment of acoustic neuromas has been improved by advancements in microsurgical techniques and in radiosurgery. To further elucidate the degree of clinical improvement, we evaluated the treatment results of a combination of surgery and radiosurgery for large acoustic neuromas. METHODS From January 1994 through December 2000, we treated 14 patients with large acoustic neuromas using a combination of surgery and radiosurgery. Of these, 8 were male and 6 were female patients, with an average age of 47 years (range, 18-64). The average maximum diameter of the tumor was 42 mm (range, 30-58 mm). All patients underwent operations using the retrosigmoid approach, and one patient was retreated using the transpetrosal transtentorial approach. The tumors were removed subtotally in thirteen patients and partially in one who had a very large hypervascular acoustic neuroma. There were no mortality and no surgical complications, such as hemorrhage or CSF leakage. Postoperative facial palsy was avoided in 10 patients (71%). Radiosurgery was performed 1 to 6 months (mean, 2.9 months) after surgery. At the time of radiosurgery, the treatment size (mean diameter) became 19.2 mm (range, 9.8-36.1 mm). The average tumor marginal dose was 12.1Gy (range, from 10-14 Gy). The mean follow-up period was 32 months after radiosurgery. RESULTS The tumor size decreased in 6 patients, unchanged in 5 patients, and increased in 3 patients. Only 1 patient (7%) with extra large tumor needed surgical resection 1 year after radiosurgery. Excellent facial nerve function (House & Brackmann Grade I or II) was preserved in 12 patients (85.7%) in the final follow-up. CONCLUSIONS In the case of large acoustic neuromas, subtotal removal and subsequent radiosurgery is one option for maintaining cranial nerve function and long-term tumor growth control.

Gamma Knife radiosurgery for skull base meningioma: long-term results of low-dose treatment: Clinical article

OBJECT In this study, the authors evaluate the long-term results after Gamma Knife radiosurgery of cranial base meningiomas. This study is a follow-up to their previously published report on the early results. METHODS Between January 1994 and December 2001, the authors treated benign cranial base meningiomas in 108 patients using low-dose Gamma Knife radiosurgery. The tumor volumes ranged from 1.7 to 55.3 cm3 (median 8.1 cm3), and the radiosurgery doses ranged from 8 to 12 Gy (median 12 Gy) to the tumor margin. RESULTS The mean duration of follow-up was 86.1 months (range 20-144 months). Tumor volume decreased in 50 patients (46%), remained stable in 51 patients (47%), and increased (local failure) in 7 patients (6%). Eleven patients experienced tumor recurrence outside the treatment field. Among these patients, marginal failure was seen in 5 and distant recurrence was seen in 6. Seven patients were thought to have malignant transformation based on histological or radiological characteristics of the lesion. The actuarial progression-free survival rate, including malignant transformation and outside recurrence, was 93% at 5 years and 83% at 10 years. Neurological status improved in 16 patients (15%). Permanent radiation injury occurred in 7 patients (6%). CONCLUSIONS Gamma Knife radiosurgery is a safe and effective treatment for cranial base meningiomas as demonstrated with a long-term follow-up period of > 7 years. Surgeons must be aware of the possibility of treatment failure, defined as local failure, marginal failure, and malignant transformation; however, this may be the natural course of meningiomas and not related to radiosurgery.

Boost radiosurgery for treatment of brain metastases after surgical resections

BACKGROUND We evaluated results of resection surgery followed by boost radiosurgery for the treatment of brain metastases. METHODS We treated 21 patients (13 male, 8 female) with surgical resection (subtotal or total) followed by boost radiosurgery. The mean patient age was 61 years (range, 41-80 years); supratentorial lesions were treated in 12 patients, and posterior fossa lesions were treated in 9 patients. The most common primary cancers were lung (24%) and colon (24%). Fifty-three percent of patients had brain metastases only, whereas 47% had extracranial metastases. The radiosurgery dose plan was designed to radiate the operative cavity; the mean treatment volume (50% isodose) was 10.7 mL (range, 3.4-23.3 mL), and the mean marginal dose was 17 Gy (range, 13-20 Gy). RESULTS Local control was achieved in 16 (76%) patients. However, new intracranial lesions developed in 10 patients, and meningeal carcinomatosis occurred in 5 patients. Local tumor recurrence occurred more often for patients treated with lower radiotherapy doses (<18 vs > or =18 Gy, P = .03), and meningeal carcinomatosis occurred more often in patients with posterior fossa lesions (P = 0.05). Gamma knife radiosurgery was performed in 13 patients, and whole-brain radiation was performed in 2 patients. No patients experienced symptomatic radiation injury, and the median survival time was 20 months. CONCLUSIONS Although boost radiosurgery is less invasive and reduces morbidity, the radiosurgical dose must be higher than 18 Gy for the treatment to be most effective. Treatment of lesions of the posterior fossa must be considered carefully because of the higher frequency of meningeal carcinomatosis. Also, we recommend that the surgeons who operate on the metastatic tumors must try to decrease the resected cavity volume and to prevent cerebrospinal fluid dissemination at the operation for posterior fossa lesions.

Radiosurgery for nonfunctioning pituitary adenomas.

OBJECTIVE:We evaluated the effectiveness of gamma knife radiosurgery in the treatment of nonfunctioning pituitary adenomas. METHODS:Between January 1994 and December 1999, we treated 34 patients with nonfunctioning pituitary adenomas. Thirty-one of these patients were followed for more than 30 months. Their mean age was 52.9 years. All patients underwent resection before radiosurgery. In four patients, treatment was performed with staged radiosurgery. The treatment volume was 0.7 to 36.2 cm3 (median, 2.5 cm3). The treatment dose ranged from 8 to 20 Gy (median, 14.0 Gy) to the tumor margin. In 15 patients (48.4%), the tumor either compressed or was attached to the optic apparatus. The maximum dose to the optic apparatus was from 2 to 11 Gy (median, 8 Gy). RESULTS:Patients were followed for 30 to 108 months (median, 59.8 mo). The tumor size decreased in 18 patients (58.1%), remained unchanged in 9 patients (29.0%), and increased in four patients (12.9%). The 5-year actual tumor growth control rate was 93%. Among patients with tumor growth, two cases were secondary to cyst formation. Two patients (6.5%) required adrenal and thyroid hormonal replacement during the follow-up period after radiosurgery because of radiation-induced endocrinopathy. None of the patients sustained new cranial nerve deficits, which included optic neuropathy. CONCLUSION:In this series, radiosurgery had a high tumor growth control rate during the long-term follow-up period. Furthermore, we observed a low morbidity rate, with endocrinopathies and optic neuropathies. This low rate included even patients in whom the tumor compressed or was attached to the optic apparatus. We emphasize the necessity of long-term follow-up to evaluate late complications.

Gamma knife surgery for skull base meningiomas: The effectiveness of low-dose treatment

BACKGROUND The surgical removal of skull base meningiomas has a high morbidity rate, even by modern microsurgical standards. We evaluated the results of gamma knife surgery for skull base meningiomas using a relatively low radiation dose for the tumor margins. METHODS We reviewed 24 cases of skull base meningiomas during a 30-month period. The locations of the tumors were the petroclival region in 11 cases, the cavernous sinus region in 9 cases, and the cerebellopontine angle region in 4 cases. Eight patients (33%) had been operated on previously and fourteen patients (67%) had been treated by neuroimaging. The marginal doses for the tumors were 8 Gy to 15 Gy (median, 10.6 Gy). A large petroclival tumor 58 mm in diameter was treated with a staged treatment protocol with a 6-month interval between treatments. RESULTS Tumor regression was observed in 46% of the patients imaged during the follow-up period (median, 17.1 months). No patients revealed tumor growth in the follow-up period (100% tumor control rate). Eleven patients (46%) had improved clinically by the time of the follow-up examinations. Preexisting cranial nerve deficit in one patient worsened because of radiation injury. CONCLUSION Although a longer follow-up period is required, the relatively low minimum tumor radiation dose treatment for skull base meningiomas using a gamma knife seems to be an effective treatment with low morbidity.

Gamma Knife radiosurgery for skull base meningioma: long-term results of low-dose treatment

OBJECT In this study, the authors evaluate the long-term results after Gamma Knife radiosurgery of cranial base meningiomas. This study is a follow-up to their previously published report on the early results. METHODS Between January 1994 and December 2001, the authors treated benign cranial base meningiomas in 108 patients using low-dose Gamma Knife radiosurgery. The tumor volumes ranged from 1.7 to 55.3 cm3 (median 8.1 cm3), and the radiosurgery doses ranged from 8 to 12 Gy (median 12 Gy) to the tumor margin. RESULTS The mean duration of follow-up was 86.1 months (range 20-144 months). Tumor volume decreased in 50 patients (46%), remained stable in 51 patients (47%), and increased (local failure) in 7 patients (6%). Eleven patients experienced tumor recurrence outside the treatment field. Among these patients, marginal failure was seen in 5 and distant recurrence was seen in 6. Seven patients were thought to have malignant transformation based on histological or radiological characteristics of the lesion. The actuarial progression-free survival rate, including malignant transformation and outside recurrence, was 93% at 5 years and 83% at 10 years. Neurological status improved in 16 patients (15%). Permanent radiation injury occurred in 7 patients (6%). CONCLUSIONS Gamma Knife radiosurgery is a safe and effective treatment for cranial base meningiomas as demonstrated with a long-term follow-up period of > 7 years. Surgeons must be aware of the possibility of treatment failure, defined as local failure, marginal failure, and malignant transformation; however, this may be the natural course of meningiomas and not related to radiosurgery.

Two-staged gamma knife radiosurgery for the treatment of large petroclival and cavernous sinus meningiomas

BACKGROUND In this study, we report on the effectiveness and usefulness of two-staged gamma knife radiosurgery (GKS) for large petroclival and cavernous sinus meningiomas that have a high rate of surgical morbidity. METHODS We have treated 7 patients suffering from large petroclival and cavernous sinus meningiomas using two-staged radiosurgery since March 1995. The tumors were located in the petroclival region in 4 patients, the cavernous sinus region in 2 patients, and in the petrocavernous region in the remaining patient. Three of the patients had been surgically treated and 4 patients (57%) were only followed with MR imaging. The volume of the tumors ranged between 34.5 to 101 cm(3) (mean 53.5 cm(3)). The treatment volume was between 6.8 to 29.6 cm(3) (mean 18.6 cm(3)). The treatment interval between the first GKS and second GKS was 6 months. The marginal doses for the tumors were 8 to 12 Gy (mean, 9 Gy). RESULTS Six patients demonstrated tumor growth control during the follow-up period after the first radiosurgery (mean 39 months). Tumor regression was observed in 3 patients (43%). Three patients (43%) had improved clinically by the time of the follow-up examinations. No patient suffered from symptomatic radiation injury. CONCLUSION Although we have treated only 7 patients using two-staged GKS, we believe this treatment may be a very useful option for large petroclival and cavernous sinus meningiomas in selected patients.