Hideyuki Kano

Gamma Knife stereotactic radiosurgery for idiopathic trigeminal neuralgia

OBJECT Trigeminal neuralgia pain causes severe disability. Stereotactic radiosurgery is the least invasive surgical option for patients with trigeminal neuralgia. Since different medical and surgical options have different rates of pain relief and morbidity, it is important to evaluate longer-term outcomes. METHODS The authors retrospectively reviewed outcomes in 503 medically refractory patients with trigeminal neuralgia who underwent Gamma Knife surgery (GKS). The median patient age was 72 years (range 26-95 years). Prior surgery had failed in 205 patients (43%). The GKS typically was performed using MR imaging guidance, a single 4-mm isocenter, and a maximum dose of 80 Gy. RESULTS Patients were evaluated for up to 16 years after GKS; 107 patients had > 5 years of follow-up. Eighty-nine percent of patients achieved initial pain relief that was adequate or better, with or without medications (Barrow Neurological Institute [BNI] Scores I-IIIb). Significant pain relief (BNI Scores I-IIIa) was achieved in 73% at 1 year, 65% at 2 years, and 41% at 5 years. Including Score IIIb (pain adequately controlled with medication), a BNI score of I-IIIb was found in 80% at 1 year, 71% at 3 years, 46% at 5 years, and 30% at 10 years. A faster initial pain response including adequate and some pain relief was seen in patients with trigeminal neuralgia without additional symptoms, patients without prior surgery, and patients with a pain duration of < or = 3 years. One hundred ninety-three (43%) of 450 patients who achieved initial pain relief reported some recurrent pain 3-144 months after initial relief (median 50 months). Factors associated with earlier pain recurrence that failed to maintain adequate or some pain relief were trigeminal neuralgia with additional symptoms and > or = 3 prior failed surgical procedures. Fifty-three patients (10.5%) developed new or increased subjective facial paresthesias or numbness and 1 developed deafferentation pain; these symptoms resolved in 17 patients. Those who developed sensory loss had better long-term pain control (78% at 5 years). CONCLUSIONS Gamma Knife surgery proved to be safe and effective in the treatment of medically refractory trigeminal neuralgia and is of value for initial or recurrent pain management. Despite the goal of minimizing sensory loss with this procedure, some sensory loss may improve long-term outcomes. Pain relapse is amenable to additional GKS or another procedure.

Outcome predictors of Gamma Knife surgery for melanoma brain metastases. Clinical article.

OBJECT To evaluate the role of stereotactic radiosurgery (SRS) in the management of brain metastases from melanoma, the authors assessed clinical outcomes and prognostic factors for survival and tumor control. METHODS The authors reviewed 333 consecutive patients with melanoma who underwent SRS for 1570 brain metastases from cutaneous and mucosal/acral melanoma. The patient population consisted of 109 female and 224 male patients with a median age of 53 years. Two hundred eleven patients (63%) had multiple metastases. One hundred eighteen patients (35%) underwent whole-brain radiation therapy (WBRT). The target volume ranged from 0.1 cm(3) to 37.2 cm(3). The median marginal dose was 18 Gy. RESULTS Actuarial survival rates were 70% at 3 months, 47% at 6 months, 25% at 12 months, and 10% at 24 months after radiosurgery. Factors associated with longer survival included controlled extracranial disease, better Karnofsky Performance Scale score, fewer brain metastases, no prior WBRT, no prior chemotherapy, administration of immunotherapy, and no intratumoral hemorrhage before radiosurgery. The median survival for patients with a solitary brain metastasis, controlled extracranial disease, and administration of immunotherapy after radiosurgery was 22 months. Sustained local tumor control was achieved in 73% of the patients. Sixty-four (25%) of 259 patients who had follow-up imaging after SRS had evidence of delayed intratumoral hemorrhage. Sixteen patients underwent a craniotomy due to intratumoral hemorrhage. Seventeen patients (6%) had asymptomatic and 21 patients (7%) had symptomatic radiation effects. Patients with ≤ 8 brain metastases, no prior WBRT, and the recursive partitioning analysis Class I had extended survivals (median 54.3 months). CONCLUSIONS Stereotactic radiosurgery is an especially valuable option for patients with controlled systemic disease even if they have multiple metastatic brain tumors.

Stereotactic radiosurgery as primary and salvage treatment for brain metastases from breast cancer. Clinical article.

OBJECT To evaluate the role of stereotactic radiosurgery (SRS) in the management of brain metastases from breast cancer, the authors assessed clinical outcomes and prognostic factors for survival. METHODS The records from 350 consecutive female patients who underwent SRS for 1535 brain metastases from breast cancer were reviewed. The median patient age was 54 years (range 19-84 years), and the median number of tumors per patient was 2 (range 1-18 lesions). One hundred seventeen patients (33%) had a single metastasis to the brain, and 233 patients (67%) had multiple brain metastases. The median tumor volume was 0.7 cm(3) (range 0.01-48.9 cm(3)), and the median total tumor volume for each patient was 4.9 cm(3) (range 0.09-74.1 cm(3)). RESULTS Overall survival after SRS was 69%, 49%, and 26% at 6, 12, and 24 months, respectively, with a median survival of 11.2 months. Factors associated with a longer survival included controlled extracranial disease, a lower recursive partitioning analysis (RPA) class, a higher Karnofsky Performance Scale score, a smaller number of brain metastases, a smaller total tumor volume per patient, the presence of deep cerebral or brainstem metastases, and HER2/neu overexpression. Sustained local tumor control was achieved in 90% of the patients. Factors associated with longer progression-free survival included a better RPA class, fewer brain metastases, a smaller total tumor volume per patient, and a higher tumor margin dose. Symptomatic adverse radiation effects occurred in 6% of patients. Overall, the condition of 82% of patients improved or remained neurologically stable. CONCLUSIONS Stereotactic radiosurgery was safe and effective in patients with brain metastases from breast cancer and should be considered for initial treatment.

T1/T2 matching to differentiate tumor growth from radiation effects after stereotactic radiosurgery.

OBJECTIVEWe define magnetic resonance imaging (MRI) and clinical criteria that differentiate radiation effect (RE) from tumor progression after stereotactic radiosurgery (SRS). METHODSWe correlated postoperative imaging and histopathological data in 68 patients who underwent delayed resection of a brain metastasis after SRS. Surgical resection was required in these patients because of clinical and imaging evidence of lesion progression 0.3 to 27.7 months after SRS. At the time of SRS, the median target volume was 7.1 mL (range, 0.5–26 mL), which increased to 14 mL (range, 1.3–81 mL) at the time of surgery. After initial SRS, routine contrast-enhanced MRI was used to assess tumor response and to detect potential adverse radiation effects. We retrospectively correlated these serial MRIs with the postoperative histopathology to determine if any routine MRI features might differentiate tumor progression from RE. RESULTSThe median time from SRS to surgical resection was 6.9 months (range, 0.3–27.7 months). A shorter interval from SRS to resection was associated with a higher rate of tumor recurrence (P = .014). A correspondence between the contrast-enhanced volume on T1-weighted images and the low signal–defined lesion margin on T2-weighted images (“T1/T2 match”) was associated with tumor progression at histopathology (P < .0001). Lack of a clear and defined lesion margin on T2-weighted images compared to the margin of contrast uptake on T1-weighted images (“T1/T2 mismatch”) was significantly associated with a higher rate of RE in pathological specimens (P < .0001). The sensitivity of the T1/T2 mismatch in identifying RE was 83.3%, and the specificity was 91.1%. CONCLUSIONSWe found that time to progression and T1/T2 mismatch were able to differentiate tumor progression from RE in most patients. When REs are suspected, surgery may not be necessary if patients respond to conservative measures. When tumor progression is suspected, resection or repeat radiosurgery can be effective, depending on the degree of mass effect.

Gamma Knife radiosurgery for the management of nonfunctioning pituitary adenomas: A multicenter study

OBJECT Pituitary adenomas are fairly common intracranial neoplasms, and nonfunctioning ones constitute a large subgroup of these adenomas. Complete resection is often difficult and may pose undue risk to neurological and endocrine function. Stereotactic radiosurgery has come to play an important role in the management of patients with nonfunctioning pituitary adenomas. This study examines the outcomes after radiosurgery in a large, multicenter patient population. METHODS Under the auspices of the North American Gamma Knife Consortium, 9 Gamma Knife surgery (GKS) centers retrospectively combined their outcome data obtained in 512 patients with nonfunctional pituitary adenomas. Prior resection was performed in 479 patients (93.6%) and prior fractionated external-beam radiotherapy was performed in 34 patients (6.6%). The median age at the time of radiosurgery was 53 years. Fifty-eight percent of patients had some degree of hypopituitarism prior to radiosurgery. Patients received a median dose of 16 Gy to the tumor margin. The median follow-up was 36 months (range 1-223 months). RESULTS Overall tumor control was achieved in 93.4% of patients at last follow-up; actuarial tumor control was 98%, 95%, 91%, and 85% at 3, 5, 8, and 10 years postradiosurgery, respectively. Smaller adenoma volume (OR 1.08 [95% CI 1.02-1.13], p = 0.006) and absence of suprasellar extension (OR 2.10 [95% CI 0.96-4.61], p = 0.064) were associated with progression-free tumor survival. New or worsened hypopituitarism after radiosurgery was noted in 21% of patients, with thyroid and cortisol deficiencies reported as the most common postradiosurgery endocrinopathies. History of prior radiation therapy and greater tumor margin doses were predictive of new or worsening endocrinopathy after GKS. New or progressive cranial nerve deficits were noted in 9% of patients; 6.6% had worsening or new onset optic nerve dysfunction. In multivariate analysis, decreasing age, increasing volume, history of prior radiation therapy, and history of prior pituitary axis deficiency were predictive of new or worsening cranial nerve dysfunction. No patient died as a result of tumor progression. Favorable outcomes of tumor control and neurological preservation were reflected in a 4-point radiosurgical pituitary score. CONCLUSIONS Gamma Knife surgery is an effective and well-tolerated management strategy for the vast majority of patients with recurrent or residual nonfunctional pituitary adenomas. Delayed hypopituitarism is the most common complication after radiosurgery. Neurological and cranial nerve function were preserved in more than 90% of patients after radiosurgery. The radiosurgical pituitary score may predict outcomes for future patients who undergo GKS for a nonfunctioning adenoma.

Stereotactic radiosurgery for arteriovenous malformations, Part 6: multistaged volumetric management of large arteriovenous malformations

OBJECT The object of this study was to define the long-term outcomes and risks of arteriovenous malformation (AVM) management using 2 or more stages of stereotactic radiosurgery (SRS) for symptomatic large-volume lesions unsuitable for surgery. METHODS In 1992, the authors prospectively began to stage the treatment of anatomical components to deliver higher single doses to AVMs with a volume of more than 10 cm(3). Forty-seven patients with such AVMs underwent volume-staged SRS. In this series, 18 patients (38%) had a prior hemorrhage and 21 patients (45%) underwent prior embolization. The median interval between the first-stage SRS and the second-stage SRS was 4.9 months (range 2.8-13.8 months). The median target volume was 11.5 cm(3) (range 4.0-26 cm(3)) in the first-stage SRS and 9.5 cm(3) in the second-stage SRS. The median margin dose was 16 Gy (range 13-18 Gy) for both stages. RESULTS In 17 patients, AVM obliteration was confirmed after 2-4 SRS procedures at a median follow-up of 87 months (range 0.4-209 months). Five patients had near-total obliteration (volume reduction > 75% but residual AVM). The actuarial rates of total obliteration after 2-stage SRS were 7%, 20%, 28%, and 36% at 3, 4, 5, and 10 years, respectively. The 5-year total obliteration rate after the initial staged volumetric SRS with a margin dose of 17 Gy or more was 62% (p = 0.001). Sixteen patients underwent additional SRS at a median interval of 61 months (range 33-113 months) after the initial 2-stage SRS. The overall rates of total obliteration after staged and repeat SRS were 18%, 45%, and 56% at 5, 7, and 10 years, respectively. Ten patients sustained hemorrhage after staged SRS, and 5 of these patients died. Three of 16 patients who underwent repeat SRS sustained hemorrhage after the procedure and died. Based on Kaplan-Meier analysis (excluding the second hemorrhage in the patient who had 2 hemorrhages), the cumulative rates of AVM hemorrhage after SRS were 4.3%, 8.6%, 13.5%, and 36.0% at 1, 2, 5, and 10 years, respectively. This corresponded to annual hemorrhage risks of 4.3%, 2.3%, and 5.6% for Years 0-1, 1-5, and 5-10 after SRS. Multiple hemorrhages before SRS correlated with a significantly higher risk of hemorrhage after SRS. Symptomatic adverse radiation effects were detected in 13% of patients, but no patient died as a result of an adverse radiation effect. Delayed cyst formation did not occur in any patient after SRS. CONCLUSIONS Prospective volume-staged SRS for large AVMs unsuitable for surgery has potential benefit but often requires more than 2 procedures to complete the obliteration process. To have a reasonable chance of benefit, the minimum margin dose should be 17 Gy or greater, depending on the AVM location. In the future, prospective volume-staged SRS followed by embolization (to reduce flow, obliterate fistulas, and occlude associated aneurysms) may improve obliteration results and further reduce the risk of hemorrhage after SRS.

Stereotactic radiosurgery for arteriovenous malformations, Part 1: management of Spetzler-Martin Grade I and II arteriovenous malformations.

OBJECT The aim of this paper was to define the outcomes and risks of stereotactic radiosurgery (SRS) for Spetzler-Martin Grade I and II arteriovenous malformations (AVMs). METHODS Between 1987 and 2006, the authors performed Gamma Knife surgery in 996 patients with brain AVMs, including 217 patients with AVMs classified as Spetzler-Martin Grade I or II. The median maximum diameter and target volumes were 1.9 cm (range 0.5-3.8 cm) and 2.3 cm(3) (range 0.1-14.1 cm(3)), respectively. The median margin dose was 22 Gy (range 15-27 Gy). RESULTS Arteriovenous malformation obliteration was confirmed by MR imaging in 148 patients and by angiography in 100 patients with a median follow-up of 64 months (range 6-247 months). The actuarial rates of total obliteration determined by angiography or MR imaging after 1 SRS procedure were 58%, 87%, 90%, and 93% at 3, 4, 5, and 10 years, respectively. The median time to complete MR imaging-determined obliteration was 30 months. Factors associated with higher AVM obliteration rates were smaller AVM target volume, smaller maximum diameter, and greater marginal dose. Thirteen patients (6%) suffered hemorrhages during the latency period, and 6 patients died. Cumulative rates of AVM hemorrhage 1, 2, 3, 5, and 10 years after SRS were 3.7%, 4.2%, 4.2%, 5.0%, and 6.1%, respectively. This corresponded to rates of annual bleeding risk of 3.7%, 0.3%, and 0.2% for Years 0-1, 1-5, and 5-10, respectively, after SRS. The presence of a coexisting aneurysm proximal to the AVM correlated with a significantly higher hemorrhage risk. Temporary symptomatic adverse radiation effects developed in 5 patients (2.3%) after SRS, and 2 patients (1%) developed delayed cysts. CONCLUSIONS Stereotactic radiosurgery is a gradually effective and relatively safe option for patients with smaller volume Spetzler-Martin Grade I or II AVMs who decline initial resection. Hemorrhage after obliteration did not occur in this series. Patients remain at risk for a bleeding event during the latency interval until obliteration occurs. Patients with aneurysms and an AVM warrant more aggressive surgical or endovascular treatment to reduce the risk of a hemorrhage in the latency period after SRS.

Long-term control of petroclival meningiomas through radiosurgery

OBJECT Because of their critical location adjacent to brain, cranial nerve, and vascular structures, petroclival meningiomas remain a clinical challenge. The authors evaluated outcomes in 168 patients with petroclival meningiomas who underwent Gamma Knife surgery (GKS) during a 21-year interval. METHODS Gamma Knife surgery was used as either primary or adjuvant treatment of 168 petroclival meningiomas involving the region between the petrous apex and the upper two-thirds of the clivus. The most common presenting symptoms were trigeminal nerve dysfunction, balance problems, diplopia, and hearing loss. The median tumor volume was 6.1 cm3 (range 0.3-32.5 cm3), and the median radiation dose to the tumor margin was 13 Gy (range 9-18 Gy). RESULTS During a median follow-up of 72 months, neurological status improved in 44 patients (26%), remained stable in 98 (58%), and worsened in 26 (15%). Tumor volume decreased in 78 patients (46%), remained stable in 74 (44%), and increased in 16 (10%), all of whom were subjected to additional management strategies. Overall 5- and 10-year progression-free survival rates were 91 and 86%, respectively. Patients followed up for at least 10 years (31 patients) had tumor and symptom control rates of 97 and 94%, respectively. Eight patients had repeat radiosurgery, 4 underwent delayed resection, and 4 had fractionated radiation therapy. Cerebrospinal fluid diversion was performed in 7 patients (4%). Significant risk factors for tumor progression were a tumor volume > or = 8 cm3 (p = 0.001) and male sex (p = 0.02). CONCLUSIONS In this 21-year experience, GKS for petroclival meningiomas obviated initial or further resection in 98% of patients and was associated with a low risk of adverse radiation effects. The authors believe that radiosurgery should be considered as an initial option for patients with smaller-volume, symptomatic petroclival meningiomas.

Stereotactic radiosurgery for symptomatic solitary cerebral cavernous malformations considered high risk for resection

OBJECT A retrospective study was conducted to reassess the benefit and safety of stereotactic radiosurgery (SRS) in patients with solitary cerebral cavernous malformations (CCMs) that bleed repeatedly and are poor candidates for surgical removal. METHODS Between 1988 and 2005 at the University of Pittsburgh, the authors performed SRS in 103 evaluable patients (57 males and 46 females) with solitary symptomatic CCMs. The mean patient age was 39.3 years. Ninety-eight percent of these patients had experienced 2 or more hemorrhages associated with new neurological deficits. Seventeen patients (16.5%) had undergone attempted resection before radiosurgery. Ninety-three CCMs were located in deep brain structures and 10 were in subcortical lobar areas of functional brain importance. The median malformation volume was 1.31 ml, and the median tumor margin dose was 16 Gy. RESULTS The follow-up ranged from 2 to 20 years. The annual hemorrhage rate--that is, a new neurological deficit associated with imaging evidence of a new hemorrhage--before SRS was 32.5%. After SRS 22 hemorrhages were observed within 2 years (10.8% annual hemorrhage rate) and 4 hemorrhages were observed after 2 years (1.06% annual hemorrhage rate). The risk of hemorrhage from a CCM was significantly reduced after radiosurgery (p < 0.0001). Overall, new neurological deficits due to adverse radiation effects following SRS developed in 14 patients (13.5%), with most occurring early in our experience. Modifications in technique (treatment volume within the T2-weighted MR imaging-defined margin, use of MR imaging, and dose reduction for CCM in critical brainstem locations) further reduced risks after SRS. CONCLUSIONS Data in this study provide further evidence that SRS is a relatively safe procedure that reduces the rebleeding rate for CCMs located in high-surgical-risk areas of the brain.

Long-term outcomes after gamma knife stereotactic radiosurgery for nonfunctional pituitary adenomas.

BACKGROUND Nonfunctional pituitary adenomas (NFPAs) represent approximately 50% of all pituitary tumors. OBJECTIVE To evaluate the long-term outcomes of stereotactic radiosurgery for NFPAs. METHODS We evaluated the management outcomes of Gamma Knife radiosurgery in 125 patients with NFPAs over an interval of 22 years. The median patient age was 54 years (range, 16-88 years). One hundred ten patients (88%) had residual or recurrent tumors after ≥ 1 surgical procedures, and 17 (14%) had undergone prior fractionated radiation therapy. The median target volume was 3.5 cm3 (range, 0.4-28.1 cm3), and the median tumor margin dose was 13.0 Gy (range, 10-25 Gy). RESULTS Tumor volume decreased in 66 patients (53%), remained stable in 46 (37%), and increased in 13 (10.4%) during a median of 62 months (maximum, 19 years) of imaging follow-up. The actuarial tumor control rates at 1, 5, and 10 years were 99%, 94%, and 76%, respectively. Factors associated with a reduced progression-free survival included larger tumor volume (≥ 4.5 cm3) and ≥ 2 prior recurrences. Of 88 patients with residual pituitary function, 21 (24%) suffered new hormonal deficits at a median of 24 months (range, 3-114 months). Prior radiation therapy increased the risk of developing new pituitary hormonal deficits. One patient (0.8%) had a decline in visual function, and 2 (1.6%) developed new cranial neuropathies without tumor progression. CONCLUSION Stereotactic radiosurgery can provide effective management for patients with newly diagnosed NFPAs and for those after prior resection and/or radiation therapy.