Long-Term Outcome of Unilateral Acoustic Neuromas With or Without Hearing Loss: Over 10 Years and Beyond After Gamma Knife Radiosurgery.

BACKGROUND: Since the long-term outcomes of 162 patients who underwent gamma knife radiosurgery (GKS) as an initial or adjuvant treatment for acoustic neuromas (ANs) with unilateral hearing loss were first reported in 1998, there has been no report of a comprehensive analysis of what has changed in GKS practice. METHODS: We performed a retrospective study of the long-term outcomes of 106 patients with unilateral sporadic ANs who underwent GKS as an initial treatment. The mean patient age was 50 years, and the mean initial tumor volume was 3.68 cm3 (range, 0.10-23.30 cm3). The median marginal tumor dose was 12.5 Gy (range, 8.0-15.0 Gy) and the median follow-up duration was 153 months (range, 120-216 months). RESULTS: The tumor volume increased in 11 patients (10.4%), remained stationary in 27 (25.5%), and decreased in 68 patients (64.2%). The actuarial 3, 5, 10, and 15-year tumor control rates were 95.3 ± 2.1%, 94.3 ± 2.2%, 87.7 ± 3.2%, and 86.6 ± 3.3%, respectively. The 10-year actuarial tumor control rate was significantly lower in the patients with tumor volumes of ≥ 8 cm3 (P = 0.010). The rate of maintaining the same Gardner-Robertson scale grade was 28.6%, and that of serviceable hearing was 46.4%. The rates of newly developed facial and trigeminal neuropathy were 2.8% and 4.7%, respectively. The patients who received marginal doses of less than 12 Gy revealed higher tumor control failure rates (P = 0.129) and newly occurred facial or trigeminal neuropathy rates (P = 0.040 and 0.313, respectively). CONCLUSION: GKS as an initial treatment for ANs could be helpful in terms of tumor control, the preservation of serviceable hearing, and the prevention of cranial neuropathy. It is recommended to perform GKS as soon as possible not only for tumor control in unilateral ANs with hearing loss but also for hearing preservation in those without hearing loss.

Preliminary Study on Natural Killer Cell Activity for Interferon-Gamma Production after Gamma Knife Radiosurgery for Brain Tumors.

OBJECTIVE: High-dose radiation is well known to induce and modulate the immune system. This study was performed to evaluate the correlation between clinical outcomes and changes in natural killer cell activity (NKA) after Gamma Knife Radiosurgery (GKS) in patients with brain cancer. METHODS: We performed an open-label, prospective, cross-sectional study of 38 patients who were treated with GKS for brain tumors, including metastatic and benign brain tumors. All of the patients underwent GKS, and blood samples were collected before and after GKS. NKA was measured using an enzyme-linked immunosorbent assay kit, to measure interferon-gamma (IFNγ) secreted by ex vivo-stimulated NK cells from whole blood. We explored the correlations between NK cell-produced IFNγ (NKA-IFNγ) levels and clinical parameters of patients who were treated with GKS for brain tumors. RESULTS: NKA-IFNγ levels were decreased in metastatic brain tumor patients compared to those with benign brain tumors (p<0.0001). All the patients who used steroid treatment to reduce brain swelling after GKS had an NKA-IFNγ level of zero except one patient. High NKA-IFNγ levels were not associated with a rapid decrease in brain metastasis and did not increase after GKS. CONCLUSION: The activity of NK cells in metastatic brain tumors decreased more than that in benign brain tumors after GKS.

Treatment Planning Factors Associated with Long-Term Outcomes of Gamma Knife Surgery in Patients with Trigeminal Neuralgia.

OBJECTIVE: Gamma Knife surgery (GKS) is an established treatment option for trigeminal neuralgia (TN). However, the long-term efficacy of GKS for patients with TN has not been well studied. The aim of the study is to evaluate the sequential course of pain control after GKS and analyze the factors associated with the long-term analgesic effect, focusing on radiation dosimetry and neurovascular conflict (NVC) factors. METHODS: We analyzed 83 patients undergoing GKS for TN in our institution between 2005 and 2013 with a follow-up duration >7 years. Tolerable pain with increased medication, persistent-intractable pain, and recurrence were classified as poor outcomes, and any other outcome was classified as a favorable outcome. The dosimetry factors and locational relationship between NVC and the target were analyzed in terms of their correlation with a favorable outcome. RESULTS: Adequate pain relief was achieved in 93% of patients a month and a half after GKS, but the pain recurred in 41.5% of patients on average 36 months after treatment. A larger V40Gy (P = 0.002) and higher homogeneity index (P = 0.027) were significantly associated with the long-term favorable outcomes. About 40% of patients had multiple NVC sites, and insufficient inclusion of the NVC in the target was significantly correlated with long-term poor outcomes (P = 0.002). CONCLUSIONS: Targeting the center of the trigeminal nerve in the area of NVC with GKS is associated with favorable long-term pain control.

Frameless Fractionated Gamma Knife Radiosurgery with ICON™ for Large Metastatic Brain Tumors.

BACKGROUND: Recently, a new generation of gamma knife radiosurgery (GKRS) equipped with a frameless immobilization system has encouraged the use of fractionated GKRS as an increasingly favorable treatment option. We investigated the preliminary outcome of efficacy and toxicity associated with frameless fractionated gamma knife radiosurgery (FF GKRS) for the treatment of large metastatic brain tumors. METHODS: Fifteen patients with 17 lesions were treated using FF GKRS and included in this study, because of the large tumor size of more than 10 cm3. FF GKRS was performed based on a thermoplastic mask system for 3 to 5 consecutive days. RESULTS: The mean duration of clinical follow-up was 12 months (range, 4-24), and the local control rate was 100%. Tumor volume decreased in 13 lesions (76.5%), and remained stable in 4 lesions (23.5%). One patient was classified as new lesion development because of the occurrence of leptomeningeal seeding regardless of the tumor volume change. Compared with the initial volume at the time of FF GKRS, tumor volume change at the last follow-up was 62.32% ± 29.80%. Cumulative survival rate at 12 months was 93.3% ± 6.4%. One patient died during the follow-up period because of the progression of the primary disease. No patient showed radiation necrosis on the follow-up images. CONCLUSION: Daily FF GKRS by gamma knife ICON™ revealed satisfactory tumor control rate and low morbidity, despite the short follow-up period. Further prospective studies and a longer follow-up of a large cohort of patients diagnosed with brain metastases are required to elucidate the effect of FF GKRS in brain metastases.

Fractionated Gamma Knife Radiosurgery as Initial Treatment for Large Skull Base Meningioma.

We present our experience on the hypofractionated Gamma Knife radiosurgery (FGKS) for large skull base meningioma as an initial treatment. We retrospectively reviewed 23 patients with large skull base meningioma ≥10 cm3 who underwent FGKS as the initial treatment option. The mean volume of tumors prior to radiosurgery was 21.2±15.63 cm3 (range, 10.09~71.42). The median total margin dose and marginal dose per fraction were 18 Gy (range, 15~20) and 6 Gy (range, 5~6), respectively. Patients underwent three or four fractionations in consecutive days with the same Leksell® frame. The mean follow-up duration was 38 months (range, 17~78). There was no mortality. At the last follow-up, the tumor volume was stationary in 15 patients (65.2%) and had decreased in 8 patients (34.8%). Six patients who had cranial neuropathy at the time of FGKS showed improvement at the last clinical follow-up. Following FGKS, 4 patients (17%) had new cranial neuropathy. The trigeminal neuropathy was the most common and all were transient. The mean Karnofsky Performance Status score at pre-FGKS and the last clinical follow-up was 97.0±10.4 points (median, 100) and 98.6±6.9 (median, 100) points, respectively. FGKS has showed satisfactory tumor control with functional preservation for large skull base meningiomas. Further prospective studies of large cohorts with long term follow-up are required to clarify the efficacy in the tumor control and functional outcome as well as radiation toxicity.

Long-term outcome of gamma knife radiosurgery for treatment of typical trigeminal neuralgia.

PURPOSE: To analyze the long-term outcomes of patients with typical trigeminal neuralgia treated with gamma knife radiosurgery (GKRS). PATIENTS AND METHODS: A total of 62 consecutive patients with typical trigeminal neuralgia were treated with GKRS between 1998 and 2004. Of the 62 patients, 2 were lost to follow-up; the remaining 60 patients were followed for >12 months. The mean prescribed maximal dose was 79.7 Gy (range, 75-80), using a 4-mm shot. RESULTS: Of the 60 patients, 48 were followed for >4 years. An additional 3 patients, followed for <4 years, experienced recurrent pain after a favorable initial response and were incorporated into the long-term response analysis. Of these 51 patients (mean age, 61 +/- 11 years; 37 women [72.5%]; and mean follow-up duration, 58 +/- 14 months), 46 (90.2%) responded to GKRS, as demonstrated by an improvement in their Barrow Neurological Institute pain intensity score. Of the 46 patients, 24 (52.2%) had pain recurrence. The actuarial recurrence-free survival rate was 84.8%, 76.1%, 69.6%, 63.0%, and 45.8% at 1, 2, 3, 4, and 5 years after radiosurgery, respectively. Patient age >70 years correlated with a favorable outcome in terms of pain recurrence after radiosurgery (hazard ratio, 0.125; 95% confidence interval, 0.016-0.975; p = .047) on multivariate analysis. CONCLUSION: GKRS seems to be an effective treatment modality for patients with typical trigeminal neuralgia considering the initial response rate; however, fewer than one-half of patients might continue to benefit from GKRS after long-term follow-up. Elderly patients might be good candidates for radiosurgery considering the long-term durability of efficacy.

Gamma Knife surgery and trigeminal schwannoma: is it possible to preserve cranial nerve function?

OBJECT: The current study was undertaken to evaluate the tumor control rate and functional outcome after Gamma Knife surgery (GKS) in patients with a trigeminal schwannoma. The conditions associated with the development of cranial neuropathies after radiosurgery were scrutinized. METHODS: The authors reviewed the clinical records and radiological data in 22 consecutive patients who received GKS for a trigeminal schwannoma. The median tumor volume was 4.1 ml (0.2-12.0 ml), and the mean tumor margin dose was 13.3 +/- 1.3 Gy at an isodose line of 49.9 +/- 0.6% (mean +/- standard deviation). The median clinical follow-up period was 46 months (range 24-89 months), and the median length of imaging follow-up was 37 months (range 24-79 months). RESULTS: Tumor growth control was achieved in 21 (95%) of the 22 patients. Facial pain responded best to radiosurgery, with two thirds of patients showing improvement. However, only one third of patients with facial hypesthesia improved. Six patients (27%) experienced new or worsening cranial neuropathies after GKS. Ten patients (46%) showed tumor expansion after radiosurgery, and nine of these also showed central enhancement loss. Loss of central enhancement, tumor expansion, and a tumor in a cavernous sinus were found to be significantly related to the emergence of cranial neuropathies. CONCLUSIONS: The use of GKS to treat trigeminal schwannoma resulted in a high rate of tumor control and functional improvement. Cranial neuropathies are bothersome complications of radiosurgery, and tumor expansion in a cavernous sinus after radiosurgery appears to be the proximate cause of the complication. Loss of central enhancement could be used as a warning sign of cranial neuropathies, and for this vigilant patient monitoring is required.

Gamma knife radiosurgery for central neurocytoma: primary and secondary treatment.

BACKGROUND: Little is known about long-term results of gamma knife (GK) stereotactic radiosurgery (SRS) as a primary or a secondary postoperative therapy for central neurocytomas (CNs). The authors retrospectively reviewed long-term outcomes of 13 patients with CN treated with GK SRS. METHODS: Thirteen patients were treated with GK SRS as a primary (6 patients) or a secondary postoperative therapy (7 patients). Follow-up clinical status and brain magnetic resonance imaging (MRI) were thoroughly analyzed. The functional status of patients was assessed with the Karnofsky Performance Scale during follow-up. RESULTS: The median follow-up period for clinical status and imaging studies was 61 months (range, 6 months to 96 months). Tumors decreased in 5 patients who received GK SRS as a primary treatment. However, the tumor recurred in 2 patients treated with a secondary GK SRS after surgery from the residual tumor bed that was not covered by the GK SRS. Parenchymal changes and secondary malignancies were not found in follow-up MRIs of all 13 patients. The Karnofsky Performance Scale score of all patients, except for 1 patient who suffered from an unrelated anteriorly communicating arterial aneurysmal rupture, did not change after GK SRS. CONCLUSIONS: GK SRS may be useful as a primary or a secondary postoperative therapy for the treatment of CN. However, more attention should be paid to residual or recurrent CN during treatment, and regular long-term follow-up MRI should be mandatory to validate the procedure.

Hearing preservation after gamma knife stereotactic radiosurgery of vestibular schwannoma.

BACKGROUND: To evaluate the hearing preservation rate and to determine its prognostic factors after gamma knife (GK) stereotactic radiosurgery (SRS) in patients with vestibular schwannoma, the authors used a prospective study design to analyze these patients. METHODS: Between December 1997 and January 2002, 25 patients with vestibular schwannoma with serviceable hearing were enrolled in the current study. The median tumor volume was 3.0 cc (0.16-9.1 cc). The prescription dose was 12.0 +/- 0.7 gray at an isodose line of 49.8 +/- 1.1%. The tumor control rate and complications were evaluated by focusing on hearing preservation and its prognostic factors. RESULTS: Based on radiologic study, the tumor control rate was 92% during the median follow-up period of 45 months. The trigeminal and facial nerve preservation rates were 95% and 100%, respectively. Thirteen (52%) of the 25 patients preserved serviceable hearing and 9 (36%) patients retained their pre-GK G-R grade levels after GK SRS. However, 16 patients showed hearing deterioration > 20 dB within 3-6 months and this trend continued for 24 months after the treatment. The maximum radiotherapy dose delivered to the cochlear nucleus was the single, significant prognostic factor of hearing deterioration. CONCLUSIONS: The authors concluded that a more sophisticated strategy to prevent hearing deterioration during the first 6 months post-GK SRS is necessary to improve long-term hearing preservation.

Gamma knife surgery of superficially located meningioma.

OBJECT: The authors analyzed tumor control rates and complications in patients with superficially located meningiomas after gamma knife surgery (GKS). METHODS: Between 1998 and 2003, GKS was performed in 23 patients with 26 lesions in whom follow-up imaging for 1 year or more was available. The male/female ratio was 1:22. The mean age was 59 years. The median tumor volume was 4.7 cm3, and the mean margin dose was 16 Gy at the 50% isodose line. Peritumoral edema was revealed on magnetic resonance (MR) imaging in four patients before GKS. Magnetic resonance imaging and clinical examinations were performed every 6 months after GKS. The mean follow-up duration was 32 months. The tumor shrank in eight cases, was stable in 17, and enlarged in one; thus 25 (95%) of 26 tumors were controlled. A peritumoral high signal on T2-weighted MR images was found in eight lesions and preexisting edema was aggravated in three lesions after GKS. Ten of these 11 patients complained of severe headache, and three patients experienced neurological deficits at the same time after a mean latency of 3 months; however, high signal was not demonstrated on imaging before 6 months on average. Steroid agents, when required, gave relief to all patients. The complication rate was 43% (10 of 23 cases). High signal disappeared in nine patients and decreased in the remaining two. High signal was associated with a high integral dose and a large tumor volume. Tumor shrinkage at the last follow-up examination was more prominent in the patients with symptomatic high signal (p = 0.03). CONCLUSIONS: There was a good tumor control rate with a high complication rate. Longer follow up of more patients is needed. Adjusting the dose-volume relationship should be considered to reduce complications.