Salvage Gamma Knife Radiosurgery Research Articles

Germline BAP1 Mutation in a Family With Multi-Generational Meningioma With Rhabdoid Features: A Case Series and Literature Review.

Meningioma is the most common primary brain tumor, and recurrence risk increases with increasing WHO Grade from I to III. Rhabdoid meningiomas are a subset of WHO Grade III tumors with rhabdoid cells, a high proliferation index, and other malignant features that follow an aggressive clinical course. Some meningiomas with rhabdoid features either only focally or without other malignant features are classified as lower grade yet still recur early. Recently, inactivating mutations in the tumor suppressor gene BAP1 have been associated with poorer prognosis in rhabdoid meningioma and meningioma with rhabdoid features, and germline mutations have been linked to a hereditary tumor predisposition syndrome (TPDS) predisposing patients primarily to melanoma and mesothelioma. We present the first report of a familial BAP1 inactivating mutation identified after multiple generations of a family presented with meningiomas with rhabdoid features instead of with previously described BAP1 loss-associated malignancies. A 24-year-old female presented with a Grade II meningioma with rhabdoid and papillary features treated with subtotal resection, adjuvant external beam radiation therapy, and salvage gamma knife radiosurgery six years later. Around that time, her mother presented with a meningioma with rhabdoid and papillary features managed with resection and adjuvant radiation therapy. Germline testing was positive for a pathogenic BAP1 mutation in both patients. Sequencing of both tumors demonstrated biallelic BAP1 inactivation via the combination of germline BAP1 mutation and either loss of heterozygosity or somatic mutation. No additional mutations implicated in oncogenesis were noted from either patient’s germline or tumor sequencing, suggesting that the inactivation of BAP1 was responsible for pathogenesis. These cases demonstrate the importance of routine BAP1 tumor testing in meningioma with rhabdoid features regardless of grade, germline testing for patients with BAP1 inactivated tumors, and tailored cancer screening in this population.

Frameless Stereotactic Radiosurgery on the Gamma Knife Icon: Early Experience From 100 Patients.

The Gamma Knife (GK) Icon (Elekta AB) uses a cone-beam computed tomography (CBCT) scanner and an infrared camera system to support the delivery of frameless stereotactic radiosurgery (SRS). There are limited data on patients treated with frameless GK radiosurgery (GKRS). To describe the early experience, process, technical details, and short-term outcomes with frameless GKRS at our institution. We reviewed our patient selection and described the workflow in detail, including image acquisition, treatment planning, mask-based immobilization, stereotactic CBCT localization, registration, treatment, and intrafraction monitoring. Because of the short interval of follow-up, we provide crude rates of local control. Data from 100 patients are reported. Median age is 67 yr old. 56 patients were treated definitively, 21 postoperatively, and 23 had salvage GKRS for recurrence after surgery. Forty-two patients had brain metastases, 26 meningiomas, 16 vestibular schwannomas, 9 high-grade gliomas, and 7 other histologies. Median doses to metastases were 20 Gy in 1 fraction (range: 14-21), 24 Gy in 3 fractions (range: 19.5-27), and 25 Gy in 5 fractions (range: 25-30 Gy). Thirteen patients underwent repeat SRS to the same area. Median treatment time was 17.7 min (range: 5.8-61.7). We found an improvement in our workflow and a greater number of patients eligible for GKRS because of the ability to fractionate treatments. We report a large cohort of consecutive patients treated with frameless GKRS. We look forward to studies with longer follow-up to provide valuable data on clinical outcomes and to further our understanding of the radiobiology of hypofractionation in the brain.

Evaluation of radiological recurrence patterns following gamma knife radiosurgery for solitary meningioma previously treated via cranial surgery

The use of gamma knife radiosurgery (GKS) for meningiomas after cranial surgery has been extensively evaluated; however, studies on tumor progression, including recurrence out of the margin dose line, are scarce. Hence, we aimed to evaluate the meningioma recurrence after GKS within and out of the margin dose. We included 37 consecutive patients with World Health Organization (WHO) grade 1 meningiomas who were treated with GKS following cranial surgery. Radiologically indicated recurrences were classified into three patterns by their relationship to the margin dose and tumor. The median follow-up was 58.9 months; 2 (5.4%) patients died. Only 2 (5.4%) patients did not keep active daily lives because of tumor progression. Cumulative local control at 5 years was 85.2%. Local recurrence and recurrence out of the margin dose occurred in 5 (13.5%) and 13 (35.1%) patients, respectively. A larger preoperative maximum diameter was a risk factor for local recurrence (hazard ratio [HR]: 2.118; P = 0.033), adjacent progression (HR: 1.633; P = 0.015), and remote progression (HR: 2.016; P = 0.003). Symptomatic adverse radiation effects occurred in 1 patient. Salvage GKS and cranial surgery were performed in 9 (24.3%) and 8 (21.6%) patients, respectively. Progression to WHO grade 2–3 occurred in 5 (13.5%) patients. A larger preoperative maximum diameter was a risk factor for progression of WHO grade (HR: 2.016, P = 0.033). Progression out of the margin dose was associated with a larger preoperative tumor size.

Salvage gamma knife radiosurgery for active brain metastases from small-cell lung cancer after whole-brain radiation therapy: a retrospective multi-institutional study (JLGK1701).

To evaluate the efficacy of gamma knife radiosurgery (GKS) for brain metastases (BMs) from small-cell lung cancer after whole-brain radiotherapy (WBRT). We retrospectively analyzed the usefulness and safety of GKS in 163 patients from 15 institutions with 1-10 active BMs after WBRT. The usefulness and safety of GKS were evaluated using statistical methods. The median age was 66years, and 79.1% of patients were men. The median number and largest diameter of BM were 2.0 and 1.4cm, respectively. WBRT was administered prophylactically in 46.6% of patients. The median overall survival (OS) was 9.3months, and the neurologic mortality was 20.0%. Crude incidences of local control failure and new lesion appearance were 36.6% and 64.9%, respectively. A BM diameter ≥ 1.0cm was a significant risk factor for local progression (hazard ratio [HR] 2.556, P = 0.039) and neurologic death (HR 4.940, P = 0.031). Leukoencephalopathy at the final follow-up was more prevalent in the therapeutic WBRT group than in the prophylactic group (P = 0.019). The symptom improvement rate was 61.3%, and neurological function was preserved for a median of 7.6months. Therapeutic WBRT was not a significant risk factor for OS, neurological death, local control, or functional deterioration (P = 0.273, 0.490, 0.779, and 0.560, respectively). Symptomatic radiation-related adverse effects occurred in 7.4% of patients. GKS can safely preserve neurological function and prevent neurologic death in patients with 1-10 small, active BMs after prophylactic and therapeutic WBRT.

RADI-07. GAMMA KNIFE RADIOSURGERY FOR SMALL CELL LUNG CANCER: PROGNOSTIC FACTORS INCLUDING ADDITIONAL LESIONS IDENTIFIED ON THE DAY OF RADIOSURGERY

OBJECTIVES: Prophylactic cranial irradiation (PCI) and whole brain radiation (WBRT) are standard of care for intracranial disease in small cell lung cancer (SCLC) patients. We sought to identify predictors of overall survival (OS) in SCLC patients treated with salvage Gamma Knife radiosurgery (GKRS) for brain metastases after prior WBRT or PCI. METHODS: Retrospective analyses were conducted on 26 SCLC patients treated with GKRS at one institution between May 2010 and June 2018. Factors predictive of OS were analyzed using Cox proportional hazards regression and Wilcoxon sum-rank testing. RESULTS: Median follow-up and median OS following GKRS was 6.6 mos (range 0.7–24.2 mos). Median OS was 21.4 mos from initial diagnosis (range 7.3–49.3 mos). Presence of extracranial metastases at the time of GKRS was not significantly associated with median OS after GKRS (5.8 mos for patients with extracranial metastases vs 7.2 mos for patients without, p=0.425). Mean number of lesions was 2.7 (range 1–10) on diagnostic brain MRIs and 4.1 (range 1–12) on GKRS planning MRIs. Eleven patients (42%) had the same number of lesions between diagnostic MRI and GKRS MRI, and 15 patients (58%) had additional lesions on the GKRS MRI. Number of lesions treated and total tumor volume were not associated with median OS. Patients who had additional lesions on GKRS MRI compared to diagnostic MRI had lower median OS from initial diagnosis of SCLC (29.9 mos vs 18.1 mos, p=0.0182) and a trend toward lower median OS from time of GKRS (7.3 mos vs 4.8 mos, p=0.0547) compared to patients who did not have additional lesions. CONCLUSIONS: Finding additional brain metastases on GKRS planning MRIs is associated with decreased OS in SCLC patients treated with salvage GKRS. Presence of extracranial metastases at the time of GKRS and number or total volume of brain metastases were not associated with OS.

Salvage Gamma Knife Radiosurgery following First Treatment: Impact of Relevant Clinical Variables, MRI Features, and Dose

Salvage Gamma Knife Radiosurgery following First Treatment: Impact of Relevant Clinical Variables, MRI Features, and Dose

Gamma Knife radiosurgery for locally recurrent choroidal melanoma following plaque radiotherapy

BackgroundFor the majority of eyes with choroidal melanoma, radiation therapy is the treatment of choice. Local recurrence after radiation therapy can occur, however, and when it does, salvaging the globe with useful vision is atypical.Case presentationWe report a case of late, local failure 7 years following previous brachytherapy successfully managed with Gamma Knife radiosurgery (GKR). With 3 years of follow up after GKR, the visual acuity is 20/20 and there is no evidence of systemic metastases.ConclusionTo our knowledge, this is the first report of successful salvage GKR therapy after brachytherapy failure in an eye with choroidal melanoma. GKR is an option for select cases of local recurrence after radiation plaque brachytherapy.

Evaluation of new lesions and symptoms after gamma knife radiosurgery for brain metastases: a retrospective cohort study.

Symptomatic new lesions that appear after gamma knife radiosurgery (GKRS) for brain metastases have not been thoroughly described. Among 238 patients who underwent a single session of GKRS without whole-brain radiotherapy or surgery for brain metastases between 2009 and 2014, a total of 165 (69.3%) patients underwent follow-up magnetic resonance imaging (MRI). Their electrical health records were reviewed retrospectively. The median age was 68years, and 62.4% patients were men. The median number of brain metastases was 2. The most frequent primary organ site was the lung (71.5%). Then, we evaluated predictors for the symptoms of new lesions. New lesions and leptomeningeal dissemination were observed in 101 (61.2%) and 23 (14.2%) patients, respectively. The median number of new lesions was 2; moreover, 20 of 101 patients (19.8%) with new lesions had tumours with the largest diameters of > 1cm. Among 101 patients with new lesions, 13 were symptomatic (12.9%). Patients with larger new lesions (> 1cm of the largest diameter) experienced symptoms more frequently (odds ratio 7.6, P < 0.01). Symptoms resolved after salvage GKRS in seven of 11 patients who abided by the recommended follow-up MRI schedule. No significant risk factors were found for symptoms of new lesions. The incidence of symptomatic new lesions that appeared after GKRS was low, and more than half of the patients showed improvements in their symptoms after salvage GKRS. However, careful MRI-based assessments and salvage GKRS are critical for the quality of life.

Salvage gamma knife radiosurgery in the management of dysembryoplastic neuroepithelial tumors: Long-term outcome in a single-institution case series

Background:Dysembryoplastic neuroepithelial tumors (DNT/DNET) are rare epileptogenic tumors. Microsurgery remains the best treatment option, although case reports exist on the use of gamma knife radiosurgery (GKRS) in selected cases. We investigated the long-term outcome of GKRS-treated DNTs at our institution in the context of current diagnostic and treatment options.Case Descriptions:We conducted a retrospective review of three consecutive adult patients (≥18 years) treated with salvage GKRS between 2002 and 2010 at Karolinska University Hospital, Stockholm, Sweden. The case series was supplemented by a review of current literature. A 20-year-old male underwent subtotal resection (STR) in 1997 and 2002 of DNT resulting in temporary control of intractable epilepsy despite antiepileptic drug treatment (AED). Long-term seizure control was obtained after GKRS of two separate residual DNT components along the surgical margin (2005 and 2010). A 27-year-old male undergoing gross total resection of the contrast-enhancing portion of a DNT (1999) resulted in temporary control of intractable epilepsy despite AEDs; lasting clinical control of seizures was achieved in 2002 after GKRS of a small, recurrent DNT component. A 28-year-old male underwent STR of DNT (1994 and 2004) resulting in temporary control of intractable epilepsy. Lasting seizure control was gained after GKRS of a residual tumor (2005).Conclusion:GKRS as performed in our series was effective in terms of tumor and seizure control. No adverse radiation effects were recorded. Prospective studies are warranted to establish the role of GKRS in the treatment of DNTs.

Salvage Gamma Knife Radiosurgery after failed management of bilateral trigeminal neuralgia.

Background:The incidence of bilateral trigeminal neuralgia (TN) is 1-6% of total number of TN cases. Gamma Knife Radiosurgery (GKRS) is effective in treating unilateral TN; however, outcomes of bilateral TN treated by GKRS have not been well evaluated. The purpose of this study is to evaluate the long-term GKRS outcomes of bilateral TN at our institution and compare with our published treatment outcomes of unilateral TN.Methods:Between 2000 and 2006, eight patients with bilateral TN were treated with GKRS. Data available on seven patients were collected. Facial pain outcomes were defined using the Barrow Neurological Institute pain intensity scale. Outcomes and toxicities were compared to published outcomes of unilateral TN patients treated with GKRS at our institution.Results:The incidence of bilateral TN in our series is 2.3%. Treatment outcomes were excellent in 5/14, good in 1/14, and poor in 8/14. Median follow-up time was 58 months. Median time-to-failure was 38 months. Pain control rate was 80% at 12 months and 65% at 36 months. Bothersome side effects were seen in 4/14 nerves treated. Compared with our long-term unilateral TN cohort, there was no statistically significant difference in outcome, time-to-failure, or rate of toxicity.Conclusion:Bilateral TN is rare, and effective treatment is crucial to improve the quality of life of those afflicted. Salvage GKRS is a reasonable treatment modality for individuals with bilateral TN.

Clinical outcomes following salvage Gamma Knife radiosurgery for recurrent glioblastoma.

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor with a survival prognosis of 14-16 mo for the highest functioning patients. Despite aggressive, multimodal upfront therapies, the majority of GBMs will recur in approximately six months. Salvage therapy options for recurrent GBM (rGBM) are an area of intense research. This study compares recent survival and quality of life outcomes following Gamma Knife radiosurgery (GKRS) salvage therapy. Following a PubMed search for studies using GKRS as salvage therapy for malignant gliomas, nine articles from 2005 to July 2013 were identified which evaluated rGBM treatment. In this review, we compare Overall survival following diagnosis, Overall survival following salvage treatment, Progression-free survival, Time to recurrence, Local tumor control, and adverse radiation effects. This report discusses results for rGBM patient populations alone, not for mixed populations with other tumor histology grades. All nine studies reported median overall survival rates (from diagnosis, range: 16.7-33.2 mo; from salvage, range: 9-17.9 mo). Three studies identified median progression-free survival (range: 4.6-14.9 mo). Two showed median time to recurrence of GBM. Two discussed local tumor control. Six studies reported adverse radiation effects (range: 0%-46% of patients). The greatest survival advantages were seen in patients who received GKRS salvage along with other treatments, like resection or bevacizumab, suggesting that appropriately tailored multimodal therapy should be considered with each rGBM patient. However, there needs to be a randomized clinical trial to test GKRS for rGBM before the possibility of selection bias can be dismissed.

Efficacy and limitations of salvage gamma knife radiosurgery for brain metastases of small-cell lung cancer after whole-brain radiotherapy

The efficacy and limitations of salvage gamma knife surgery (GKS) have not been thoroughly described. This study evaluated the efficacy of GKS for treating brain metastases associated with small-cell lung cancer (SCLC) after whole-brain radiotherapy (WBRT) as the first-line radiation therapy. Forty-four patients with recurrent or new SCLC-associated brain metastases underwent GKS after receiving WBRT (median age, 62years; median duration between WBRT and first GKS, 8.8months). The median Karnofsky performance status (KPS) score was 100 (range, 40-100), and the median number of brain metastases at the first GKS was five. Ten patients who partially or completely responded to chemotherapy received prophylactic cranial irradiation (PCI) for limited disease. The median prescribed dose and number of lesions treated with the initial GKS were 20.0Gy and 3.5, respectively, and the tumor control rate was 95.8% (median follow-up period, 4.0months). The 6-month new lesion-free survival, functional preservation rates, and overall survival were 50.0%, 94.7%, and 5.8months, respectively. Neurological death occurred in 17.9% of cases. The poor prognostic factors for new lesion-free survival time and functional preservation were >5 brain metastases and carcinomatous meningitis, respectively. Poor prognostic factors for survival time were KPS <70, >10 brain metastases, diameter of the largest tumor >20mm, and carcinomatous meningitis. Median overall survival time from brain metastasis diagnosis was 16.9months. GKS may be an effective option for controlling SCLC-associated brain metastases after WBRT and for preventing neurological death in patients without carcinomatous meningitis.

The Role of Radiosurgery in Patients with Brain Metastasis from Small Cell Lung Carcinoma

The purpose of this retrospective study was to evaluate the outcome of gamma knife radiosurgery (GKRS) and/or whole brain radiation therapy (WBRT) for the treatment of small cell lung carcinoma (SCLC) metastasis to the brain. From 2000 to 2010, 50 patients underwent GKRS for metastatic brain lesions originating from SCLC. Among these patients, 11 received prophylactic cranial irradiation (PCI) before the development of metastatic lesions (PCI group), and GKRS was performed as an initial treatment for newly diagnosed lesions in 12 patients who had not received PCI (primary GKRS group). In addition, GKRS was performed as a salvage treatment for progressive lesions after WBRT in 27 patients (salvage GKRS group). The medical records and imaging data of all patients were retrospectively analyzed. The overall survival of the 50 patients was 20.8 months (range 1-53) after the diagnosis of primary tumor and 12.0 months (range 1-47) after the development of cerebral metastasis. Median survival after GKRS was 4.8 months (range 1-15) in the PCI group, 4.6 months (range 0-18) in the primary GKRS group, and 7.6 months (range 0-33) in the salvage GKRS group. Further treatment for progressive lesions after GKRS was necessary in 15 patients, after a mean interval of 3.8 months. Causes of death were systemic organ failure in 15 patients, deterioration of neurological state in 13 patients, and unknown or combined causes in 16 patients. The local control rate of the lesions treated with GKRS was 76.4% (decreased in 13 patients and stable in 16 patients at the final imaging follow-up (mean 5.60 months). GKRS is an effective local treatment for brain metastasis from SCLC both as an initial treatment for newly diagnosed lesions after PCI and as a salvage treatment for recurrent or progressive lesions. However, the survival benefit is not significant because most patients die of systemic multi-organ failure with a short life expectancy.

Salvage Gamma Knife Stereotactic Radiosurgery for Surgically Refractory Trigeminal Neuralgia

To evaluate the clinical outcome of patients with surgically refractory trigeminal neuralgia (TN) treated with rescue gamma knife radiosurgery (GKRS). Seventy-nine patients with typical TN received salvage GKRS between 1997 and 2002 at the Barrow Neurological Institute (BNI). All patients had recurrent pain following at least one prior surgical intervention. Prior surgical interventions included percutaneous destructive procedures, microvascular decompression (MVD), or GKRS. Thirty-one (39%) had undergone at least two prior procedures. The most common salvage dose was 80 Gy, although 40-50 Gy was typical in patients who had received prior radiosurgery. Pain outcome was assessed using the BNI Pain Intensity Score, and quality of life was assessed using the Brief Pain Inventory. Median follow-up after salvage GKRS was 5.3 years. Actuarial analysis demonstrated that at 5 years, 20% of patients were pain-free and 50% had pain relief. Pain recurred in patients who had an initial response to GKRS at a median of 1.1 years. Twenty-eight (41%) required a subsequent surgical procedure for recurrence. A multivariate Cox proportional hazards model suggested that the strongest predictor of GKRS failure was a history of prior MVD (p=0.029). There were no instances of serious morbidity or mortality. Ten percent of patients developed worsening facial numbness and 8% described their numbness as "very bothersome." GKRS salvage for refractory TN is well tolerated and results in long-term pain relief in approximately half the patients treated. Clinicians may reconsider using GKRS to salvage patients who have failed prior MVD.

Outcome of repeated radiosurgery for recurrent metastatic brain tumors

Objective We investigated the outcome of repeated gamma knife radiosurgery (GKS) for local or remote recurrence after initial radiosurgery. Material and methods We retrospectively reviewed 204 patients who were treated with GKS. Among them 43 patients (21%) underwent GKS more than once. The second GKS was given for recurrence at the previously treated sites in 16 patients, new lesions at remote sites in 13, and both local recurrence and new lesions in 14. Results The median survival from the first GKS was 36 (7–190) weeks in all patients and 68 (16–156) weeks in 43 patients with repeated GKS. The median time from the first GKS to the second was 37 weeks. The median survival from the second radiosurgical intervention was 32 (7–132) weeks. Local control rate at 6 months after salvage GKS was 90.7%. RPA class was the commonly dominant prognostic factor in both initial and salvage GKS. Conclusion Recurrence is common for patients with metastatic brain tumors after initial radiosurgery. Local control and survival time after salvage treatment are comparable with those after initial radiosurgery. GKS as a salvage treatment may provide additional survival benefit in selected patients.