Time Of Gamma Knife Radiosurgery Research Articles

A Deep Neural Network-Based Model Predicting Peritumoral Edema After Radiosurgery for Meningioma

Gamma Knife radiosurgery (GKS) is a promising treatment option for meningioma. However, the incidence of peritumoral edema (PTE) following GKS has been reported to be 7%-38%. This study aimed to develop a predictive model for post-GKS PTE using a deep neural network (DNN) algorithm. Patients treated with GKS for meningioma between November 2012 and February 2020 at a single tertiary center were reviewed. The primary outcome was newly developed or aggravated PTE after GKS. Clinical data, including radiosurgical parameters, were collected, and imaging data obtained at the time of GKS were incorporated into the model using a 50-layered residual neural network, ResNet50. Consequently, the model efficiency was evaluated considering the accuracy and area under the receiver operating curve (AUC) values. A total of 202 patients were included in this study. The median tumor volume was 2.3 mL, and the median prescription dose was 13 Gy. PTE was observed before GKS in 22 patients. Post-GKS PTE was evident in 28 patients (13.9%), which further evolved to radiation necrosis in 5 patients. The accuracy and AUC values of the hybrid data model based on both clinical and imaging data were 0.725 and 0.701, respectively. The performance of the hybrid data model was superior to that of the other models based on clinical or image data only. The DNN-based model using both clinical and imaging data exhibited fair results in predicting post-GKS PTE in meningioma treatment. Predictive models using imaging data may be helpful in prognostic research.

Efficacy of Gamma Knife Radiosurgery in Refractory Obsessive-Compulsive Disorder: An Indian Experience

Background Obsessive-compulsive disorder (OCD) is a chronic debilitating psychiatric condition with adverse impact on patient's sociooccupational health. Refractoriness to pharmacotherapy and psychotherapy is not uncommon. Gamma Knife radiosurgery (GKRS) is the comprehensively used and reviewed treatment modality in refractory OCD worldwide. In India, the past two decades of increasing GKRS availability has failed to create the necessary local awareness of its usefulness in refractory OCD. Limited native literature deepens the problem. Objective To analyze our experience with GKRS in refractory OCD, and report the safety and efficacy/long-term outcome in patients using the Yale–Brown Obsessive-Compulsive Scale (Y-BOCS). Materials and Methods A retrospective review of patients receiving GKRS for refractory OCD between 2000 and 2020 was carried out. Case files of the eligible ( n = 9) patients were reviewed for clinical, radiotherapeutic, and outcome data. Additionally, patients were contacted via telephone to enquire about their experiences, and to obtain retroactive consent for GKRS in June 2021. Information obtained was collated, computed, and analyzed. Results Male-to-female sex ratio was 8:1. Mean age at the time of GKRS and mean duration of OCD prior to GKRS was 30.1 ± 9.4 and 10.2 ± 5.8 years, respectively. Mean baseline Y-BOCS score was 29.6 ± 4.7. Our first patient received cingulotomy, while the rest underwent anterior capsulotomy. Median margin dose (50% isodose) was 70 Gy. Also, 23.8 ± 7.7 was the mean Y-BOCS score at the last follow-up (median = 30 months). Overall, 44.4% patients showed full/partial response (≥25% reduction in Y-BOCS score) at the last follow-up. In anterior capsulotomy (eight patients), patients with moderate/severe OCD showed better response (4/5 responders) than those with extreme OCD (0/3 responders). Single case of cingulotomy resulted in no response (<25% reduction in Y-BOCS score). No adverse radiation effects were noted. Also, 55.6% patients gave retroactive consent telephonically. Conclusion GKRS is a safe and effective noninvasive treatment modality for refractory OCD. Ventral anterior capsule is the preferred target. Maximum radiation doses of 120 to 160 Gy are well tolerated. Extremely severe OCD cases fared poorer. Proper awareness about the availability and efficacy of GKRS in refractory OCD is required in India.

Significance of Dosimetric Parameters in Patients Undergoing Gamma Knife Radiosurgery for Vestibular Schwannoma.

Vestibular schwannoma (VS) is a benign, encapsulated, and slow-growing tumor of the myelin-forming cells of the 8th cranial nerve. Gamma Knife radiosurgery (GKRS) has become a widely accepted primary treatment modality for small- to medium-sized VSs. In the case of VS, highly conformal, precisely focused radiation is delivered to the acoustic tumor in a single session under the direct supervision of a radiosurgery teamAim:This study aims to determine the significance of Conformity Index and Gradient Index (GI) in patients undergoing GKRS for VS, retrospectively, and re-assess the plans.Materials and Methods:A dosimetric study of 112 patients of VS (both operated and nonoperated) treated on Gamma Knife Perfexion unit at our hospital, over a 3-year period, was carried out retrospectively. The patients’ mean age at the time of GKRS was 48 years and the mean dose to the tumor margin was 13 Gy. The conformality of the treatment plan was determined by Conformity Index. GI determines fall off dose outside the target.Results:The dosimetric parameters such as Conformity Index and GI were calculated using the dose-volume histograms and the volume analysis tools available in the Leksell Gamma Plan using TMR 10 algorithm. The mean Paddick Conformity Index was found to be around 0.80 ± 0.085 and the mean GI was 2.67 ± 0.22.Conclusions:The dosimetric parameters can be used to evaluate the dose coverage and conformity and dose fall off outside the target.

Gamma Knife radiosurgery as salvage therapy for gangliogliomas after initial microsurgical resection

IntroductionGangliogliomas (GG) are considered WHO grade I rare tumors. While they commonly manifest as temporal lobe epilepsy, they can be located anywhere in the brain. Primary treatment is complete microsurgical resection. Remnant or recurrent GG can benefit from radiation therapy. Here, we present a series of GG who received Gamma Knife radiosurgery (GKR) after initial microsurgery. MethodsBetween October 2009 and February 2020, four patients benefitted from such approach. The median age at surgery was 16 years (mean 17, 11–25) and at the time of GKR was 22.5 years (mean 23, 19–28). Initial clinical symptom was epilepsy in 3 cases and incidental in one. Biopsy was firstly performed in one case. One patient had stereotactic electroencephalography. The respective anatomical locations were right parieto-occipital, sylvian, left paraventricular and left inferior parietal. ResultsGamma Knife radiosurgery was performed after a median time of 3.5 years after initial gross total microsurgical resection (GTR). The median follow-up after GKR was 54 months (mean 58.5, 6–120). The median marginal dose was 18 Gy (mean 17.5, 16–18). The median target volume was 0.5 mL (mean 0.904, 0.228–2.3). The median prescription isodose volume was 0.6 mL (mean 0.9, 0.3–2.4). At last follow-up, GG majorly decreased in 3 patients, remained stable in one. ConclusionGamma Knife radiosurgery is safe and effective for remnant GG after GTR. Primary treatment remains microsurgical resection, especially in cases with symptomatic mass effect or with epilepsy. Single fraction GKR can be a valuable option for remnant or recurrent tumors after initial resection.

Gamma Knife radiosurgery as the initial treatment for elderly patients with nonfunctioning pituitary adenomas.

The aim of this study was to investigate the efficacy and safety of initial Gamma Knife radiosurgery (GKRS) for elderly patients with nonfunctioning pituitary adenomas (NFPAs). We retrospectively reviewed 45 elderly patients underwent GKRS as the initial treatment for NFPAs at our institution between December 2007 and December 2017. Patients' radiographic and clinical data were collected. The median age of patients at the time of GKRS was 71years (range 65-82years). The median tumor volume was 2.6 cm3 (range 0.3-21.8 cm3). The median marginal dose was 13Gy (range 6-23Gy). The median maximum dose to the optic apparatus was 6.5Gy (range 2.3-10.3Gy). Thirty-five patients (77.8%) achieved tumor regression, 6 patients (13.3%) had tumor stable and 4 patients (8.9%) occurred tumor progression during a median radiological follow-up time of 51.4months (range 11.1-158.7months). The crude tumor control rate was 91.1%. The actuarial tumor control rates were 100%, 95.0%, 87.6%, and 87.6%, at 1, 3, 5, and 10years after initial GKRS, respectively. New-onset hypopituitarism occurred in 6 patients. Two patients with pre-GKRS visual dysfunction developed further deterioration of visual function. No other radiation-induced complications were noted. Initial GKRS can provide a high tumor control rate as well as low risk of postradiosurgical complications for elderly patients with NFPAs. Attention should be paid to avoid radiation-related adverse effects including hypopituitarism, optic neuropathy and cranial neuropathy in elderly patients.

Outcome and prognostic factors for older patients undergoing radiosurgery for brain metastases

PurposeOlder patients with brain metastases (BM) are often excluded from clinical trials. The aim of our study was to investigate the outcomes following Gamma Knife radiosurgery (GKRS) in young old (65–74 years) and very old (≥75 years) patients with BM. MethodsBetween October 2012 and October 2018, we treated 89 patients aged ≥65 years with GKRS. Patients were divided in two group: young old (YO) and very old (VO) patients. At baseline G8, Graded Prognostic Assessment (DS-GPA) and Basic Score for Brain Metastases (BSBM) were assessed for all patients. Survival analysis was estimated using the Kaplan-Meier (KM) method. Cox regression model was used to investigate the influence of significant factors on KM. ResultsMedian age at the time of GKRS was 72.2 years (range 65–87). A mean of 2.52 lesions were treated per patient (range 1–14). Median overall survival (OS) for YO and VO patients was 14.2 and 15.7 months, respectively. At univariate analysis, there were no significant differences in OS between the two age groups. A high BSBM (p ≤ .0001) and a high DS-GPA score (p = .0069) were associated with longer survival. A low DS-GPA score was the most powerful independent factor for predicting short survival (HR 1.76, 95% CI 1.25–2.46, p = .001) at multivariate analysis. ConclusionGKRS is a safe approach to treat BM in elderly patients. DS-GPA score represents an important prognostic factor for survival in elderly patients undergoing GKRS.

Outcomes of stereotactic radiosurgery for pilocytic astrocytoma: an international multiinstitutional study.

The current standard initial therapy for pilocytic astrocytoma is maximal safe resection. Radiation therapy is considered for residual, recurrent, or unresectable pilocytic astrocytomas. However, the optimal radiation strategy has not yet been established. Here, the authors describe the outcomes of stereotactic radiosurgery (SRS) for pilocytic astrocytoma in a large multiinstitutional cohort. An institutional review board-approved multiinstitutional database of patients treated with Gamma Knife radiosurgery (GKRS) between 1990 and 2016 was queried. Data were gathered from 9 participating International Radiosurgery Research Foundation (IRRF) centers. Patients with a histological diagnosis of pilocytic astrocytoma treated using a single session of GKRS and with at least 6 months of follow-up were included in the analysis. A total of 141 patients were analyzed in the study. The median patient age was 14 years (range 2-84 years) at the time of GKRS. The median follow-up was 67.3 months. Thirty-nine percent of patients underwent SRS as the initial therapy, whereas 61% underwent SRS as salvage treatment. The median tumor volume was 3.45 cm3. The tumor location was the brainstem in 30% of cases, with a nonbrainstem location in the remainder. Five- and 10-year overall survival rates at the last follow-up were 95.7% and 92.5%, respectively. Five- and 10-year progression-free survival (PFS) rates were 74.0% and 69.7%, respectively. On univariate analysis, an age < 18 years, tumor volumes < 4.5 cm3, and no prior radiotherapy or chemotherapy were identified as positive prognostic factors for improved PFS. On multivariate analysis, only prior radiotherapy was significant for worse PFS. This represents the largest study of single-session GKRS for pilocytic astrocytoma to date. Favorable long-term PFS and overall survival were observed with GKRS. Further prospective studies should be performed to evaluate appropriate radiosurgery dosing, timing, and sequencing of treatment along with their impact on toxicity and the quality of life of patients with pilocytic astrocytoma.

RTHP-13. EFFICACY OF FRACTIONATED GAMMA KNIFE RADIOSURGERY FOR ORBITAL CAVERNOUS HEMANGIOMA: 10-YEAR EXPERIENCE AT A SINGLE INSTITUTION

Abstract This study aimed to evaluate the efficacy and safety of fractionated gamma knife radiosurgery (GKS) for the treatment of orbital cavernous hemangioma (OCH). METHODS From January 2007 to June 2018, 34 patients who underwent fractionated GKS (median 20 Gy in 4 fractions) for OCH at a single tertiary institution were reviewed. Ophthalmic evaluations including exophthalmometry, best corrected visual acuity with the Snellen chart and Humphrey visual field were investigated. Changes in lesion volume were also analyzed. RESULTS The median age was 43 years (range, 10–67 years) and 18 patients were male (53%). The median clinical follow-up time was 42 months (range, 12–132 months). The most common presenting symptom was proptosis followed by visual impairment. Proptosis improved in all 27 patients. The mean value of proptosis was reduced from 2.9 mm to 1.1 mm (P &lt; 0.001). Of 15 patients who showed decreased visual acuity preoperatively, 12 patients (80%) had improved in vision. Preoperative visual field defects were evident in 17 patients and resolved in 15 patients (88%) after treatment. The median tumor volume at the time of GKS was 2.2 cm3 (range, 0.2–8.5 cm3). Tumor shrinkage was observed in all patients and the mean volume reduction rate was 64%. No patient experienced GKS-related ocular morbidity, though two transient GKS-related adverse events (6%) were observed. CONCLUSION Fractionated GKS is an effective and safe option for the treatment of OCH, with significant reduction in tumor volume and improvement of ophthalmic outcomes.

RTHP-11. THE EFFECT OF PRESCRIPTION ISODOSE LINE ON LOCAL CONTROL AND RADIOGRAPHIC RESPONSE IN GAMMA KNIFE RADIOSURGERY OF VESTIBULAR SCHWANNOMA

Abstract Traditionally, the 50% isodose line (IDL) is used for prescription dose when vestibular schwannomas (VS) are treated with Gamma Knife radiosurgery (GKRS). To compare the effect of IDL on treatment outcomes, propensity score-matched analysis according to age at time of GKRS and tumor volume (TV) between cohorts treated at 40%IDL and 50%IDL was performed. Patients with no history of neurofibromatosis, GKRS prescribed marginal dose of 12–14 Gy and TV ≤ 10 cc were identified. Patients were excluded if follow-up time was &lt; 2 years. Eventually, 30 and 28 patients were included in 40%IDL and 50%IDL cohorts, respectively. Mean age and TV were not significantly different between 40%IDL and 50%IDL groups; 54.5 versus 54.0 years (p=0.891) and 2148.61 versus 2031.10 mm3 (p=0.844), respectively. Median prescription dose was 12 Gy in both groups. At median follow-up times of 111 and 72 months, the 2, 5 and 10-year local control were 100%, 96.4% and 96.4% for 40%IDL and 96.4%, 86.7%, and 86.7% for 50%IDL (p=0.243), respectively. Among 40 patients with accessible follow-up MRIs (40%IDL-n=19, 50%IDL-n=21), volume reduction at last follow-up MRIs and rate of reduction per year for 40%IDL and 50%IDL were 48.1% versus 38.3% (p=0.05) and 5.5% versus 6% (p=0.749), respectively. Of 21 patients with serviceable hearing prior to GKRS and available audiograms after GKRS (40%IDL-n=8, 50%IDL-n=13), the 2, 5 and 10-year hearing preservation rate were 100%, 83.3% and 62.5% for 40%IDL versus 76.2%, 57.1% and 11.4% for 50%IDL (p=0.017). Facial paresthesia, facial palsy and ataxia/gait disturbance requiring steroid and/or shunt were lower in 40%IDL compared to the 50%IDL; 6.7% versus 17.9% (p=0.208) and 3.3% versus 7.1% (p=0.532). To summarize, VS treated at 40%IDL have slightly better local control, although not statistically significant, compared to tumors treated at 50%IDL. However, hearing preservation and safety seem to be more favorable toward 40%IDL group.

Gamma Knife Radiosurgery for Choroidal Hemangioma: A Single-Institute Series

Choroidal hemangioma (CH) is a benign vascular tumor that induces subretinal fluid collection or exudative retinal detachment and consequent visual symptoms. Current standard treatments for CH include cryotherapy, diathermy, photocoagulation, photodynamic therapy, transpupillary thermotherapy, and radiation therapy. Stereotactic radiosurgery has recently been applied to the treatment of CH because of its characteristic stiff dose-fall-off and accuracy. We have adopted gamma knife radiosurgery (GKRS) to treat CH and have retrospectively assessed tumor volume reductions and improvements to visual acuity achieved thereby. Fourteen patients with CHs were treated with GKRS from November 2006 to December 2017. Eight patients had circumscribed CH, and 6 exhibited diffuse CHs and were diagnosed with Sturge-Weber syndrome. The mean age of patients was 27.1 years (range: 8-68 years) and the mean duration of clinical or radiological follow-up was 40.2 months (range: 5-105 months). The mean volume of the tumors at the time of GKRS was 533.5 mm3 (range: 124-1150 mm3), and the mean prescribed marginal dose was 11.6 Gy (range: 10-16 Gy) with 50% isodose lines. The tumor volume decreased by the last follow-up in all patients. The visual acuity improved in 9 patients (64%) and decreased in 1 (7%). Six patients (43%) required trans-pars plana vitrectomy before or after GKRS. There were no symptomatic complications from radiation injury during the follow-up periods. GKRS could be an acceptable alternative treatment for symptomatic CH when standard therapy is not feasible.

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.

Gamma Knife Radiosurgery for Patients with Multiple Intracranial Meningiomas

The aim of this study was to evaluate the safety and efficacy of Gamma Knife radiosurgery (GKRS) in patients with multiple intracranial meningiomas (MIMs). The authors performed a retrospective analysis of 42 consecutive patients (7 men and 35 women) with MIMs who underwent GKRS. The median age of the patients at the time of GKRS was 57.5 years (range, 27-77 years). A total of 115 tumors among 42 patients were identified through imaging or postoperative histopathologic examination, of which 90 were treated with GKRS. Follow-up imaging studies were available for 75 tumors in 36 patients (83.3%), with a mean follow-up period of 45.0 months (range, 6.6-90.4 months); 41 patients (97.6%) received clinical follow-up for 16.7 to 106.7 months (average, 57.1 months). Local tumor control was achieved in 68 tumors (90.7%) at the last follow-up. On univariate analysis, surgical resection before GKRS more than once (P= 0.048) and high World Health Organization (WHO) classification (grades II and III) (P= 0.001) were associated with tumor progression. Patients with worsening clinical manifestation showed correlation with peritumor edema (P< 0.001) and had >2 lesions treated by GKRS (P<0.001) on univariate analysis. GKRS is a safe and effective treatment for MIMs. Variables including surgical resection before GKRS more than once, high grade WHO classification, peritumor edema, and >2 tumors treated by GKRS are predictors of unfavorable outcome after GKRS.

Efficacy and Safety of Gamma Knife Radiosurgery for Meningiomas in Patients with Neurofibromatosis Type 2: A Long-Term Follow-Up Single-Center Study

To explore the efficacy and safety of Gamma Knife radiosurgery (GKRS) for meningiomas in patients with neurofibromatosis type 2 (NF2). A series of 35 consecutive patients with 99 meningiomas in our department were retrospectively included from January 2000 to December 2015. Clinical records, magnetic resonance images, and follow-up data were reviewed. A total of 35 patients (25 women and 10 men) with 99 NF2-associated meningiomas were identified. All patients initially received GKRS. The patients' median age at the time of GKRS was 40 years (range, 16-61 years). The median prescription dose at the tumor margin was 13 Gy (range, 12-15 Gy). The median follow-up time was 96 months (range, 25-224 months). Twenty-nine patients received GKRS only once, and 6 patients received it multiple times. Six patients (17.1%) had radiation-related complications 7.5 ± 2.4 months after GKRS. Local control rates at 1, 3, and 5 years were 100%, 97.1%, and 90.6%, respectively. Distant control rates at 1, 3, and 5 years were 88.5%, 55.9%, and 45.5%, respectively. Five patients died of concomitant neurologic symptoms. No malignant transformation was observed during the follow-up periods in all 35 patients. GKRS represents an effective and safe management strategy with minimal invasion for patients with NF2-associated meningiomas. Our data showed a high local control rate of NF2-associated meningiomas by GKRS; however, the distant control rate is low, especially in young patients. For these patients, retreatment with GKRS may still be the advisable method.

Efficacy of gamma knife radiosurgery in brain metastases of primary gynecological tumors.

Gynecological brain metastases (BM) are rare and usually develop as part of widespread disseminated disease. Despite treatment, the majority of these patients do not survive > 1year due to advanced extracranial disease. The use of Gamma Knife Radiosurgery (GKRS) for gynecological BM is not well known. The goal of this study is to evaluate the efficacy of GKRS for gynecological BM. We performed a retrospective study of patients with gynecological BM who underwent GKRS between 2002 and 2015. A total of 41 patients were included. Outcome measures were local tumor control (LC), development of new BM and/or leptomeningeal disease, overall intracranial progression free survival (PFS) and survival. LC was 100%, 92%, 80%, 75% and 67% at 3, 6, 9, 12 and 15 months, respectively. PFS was 90%, 61%, 41%, 23% and 13% at 3, 6, 9, 12 and 15 months, respectively. During follow-up (FU), 18 (44%) patients had intracranial progression. Distant BM occurred in 29% of the patients. Local recurrence and distant recurrence occurred after a mean FU time of 15.5 (2.6-71.9) and 11.4 (2-40) months, respectively. Thirty-one (76%) patients died due to extracranial tumor progression and only 2 (5%) patients died due to progressive intracranial disease. The overall mean survival from time of GKRS was 19months (1-109). The 6-month, 1-year, and 2-year survival rate from the time of GKRS were 71%, 46%, and 22%, respectively. GKRS is a good treatment option for controlling gynecological BM. As most patients die due to extracranial tumor progression, their survival might improve with better systemic treatment options in addition to GKRS.

Orbital apex venous cavernous malformation with optic neuropathy: treatment with multisession gamma knife radiosurgery

PurposeTo evaluate the efficacy and safety of multisession gamma knife radiosurgery (GKRS) for orbital apex venous cavernous malformation causing optic neuropathy.MethodsRetrospective cohort study in a single tertiary institution from January...

Breast cancer patients with brain metastasis undergoing GKRS.

Breast cancer (BC) is the second most common cause of brain metastasis in the United States. Compared to whole brain radiation therapy (WBRT), treatment with gamma-knife radiosurgery (GKRS) offers a better chance at neurocognitive preservation. The goal of our retrospective study is to report the overall survival (OS) in patients receiving GKRS and to identify factors that improve survival outcomes. The records of 80 patients with primary BC treated with GKRS at the Yale Comprehensive Cancer Center between 2000 and 2013 were reviewed. OS was calculated from the date of first GKRS treatment. Other factors studied were age, Karnofsky performance status (KPS), tumor subtype, having WBRT and/or surgical resection pre- or post-GKRS, and number of brain metastases treated with GKRS. Median age was 56.2years. OS from first GKRS was 13.1months (95% CI 7.6-21.9). On univariate analysis, improved survival was associated with HER-2 subtype (p = 0.026), KPS score > 80 (p = 0.009), and good control of systemic disease at time of GKRS (p = 0.020). Multivariable analysis detected a significantly longer survival with HER-2 positivity (HR 0.22, 95% CI 0.06-0.76, p = 0.017) and a strong trend in patients with craniotomy prior to GKRS (HR 0.13, 95% CI 0.01-1.11, p = 0.06). GKRS is a promising therapy for treating brain metastasis fromBC, particularly in those with HER-2 positivity and high-performance scores even in those patients with > 5 brain metastases. Furthermore, GKRS may also be a useful adjunct to surgical resection in such patients. High rates of neurological death remain from BCbrain metastases; however, and need further investigation.

Multidisciplinary management of clival chordomas; long-term clinical outcome in a single-institution consecutive series

ObjectiveChordomas of the skull base have high recurrence rates even after radical resection and adjuvant radiotherapy. We evaluate the long-term clinical outcome using multidisciplinary management in the treatment of clival chordomas.MethodsBetween 1984 and 2015, 22 patients diagnosed with an intracranial chordoma were treated at the Karolinska University Hospital, Stockholm, Sweden. Sixteen of 22 were treated with Gamma Knife radiosurgery (GKRS) for tumour residual or progression during the disease course. Seven of 22 received adjuvant fractionated radiotherapy and 5 of these also received proton beam radiotherapy.ResultsFifteen of 22 (68%) patients were alive at follow-up after a median of 80 months (range 22–370 months) from the time of diagnosis. Six were considered disease free after >10-year follow-up. The median tumour volume at the time of GKRS was 4.7 cm3, range 0.8–24.3 cm3. Median prescription dose was 16 Gy, range 12–20 Gy to the 40–50% isodose curve. Five patients received a second treatment with GKRS while one received three treatments. After GKRS patients were followed with serial imaging for a median of 34 months (range 6–180 months). Four of 16 patients treated with GKRS were in need of a salvage microsurgical procedure compared to 5/7 treated with conventional or proton therapy.ConclusionAfter surgery, 7/22 patients received conventional and/or photon therapy, while 15/22 were treated with GKRS for tumour residual or followed with serial imaging with GKRS as needed upon tumour progression. With this multidisciplinary management, 5- and 10-year survivals of 82% and 50% were achieved, respectively.

Safety and results of anti-PD1 combined with radiosurgery for the treatment of melanoma brain metastases.

9552 Background: Anti-PD1 are now pivotal in the treatment of metastatic melanoma (MM). Some concerns have emerged regarding the risk/benefit ratio of their combination with stereotactic radiosurgery. Methods: Retrospective assessment of the interaction between Gamma-Knife radiosurgery (GKRS) and anti-PD1 in terms of toxicity and OS in mm patients (pts) with BM. Patients were included if they were under anti-PD1 (PRE) at time of GKRS, or if they had started anti-PD1 concomitantly with GKRS (CO), or had received anti-PD1 within 3 months after GKRS (POST). Results: Among 47 pts who received GKRS and anti-PD1 during their disease course, 35 fulfilled PRE or CO or POST criteria (anti PD1 1st line therapy in 10 pts and 2d or more in 25 pts). One pt died before radiological evaluation. GKRS targeted a single BM in 10 pts and multiple BMs in 24 (max 19 BMs). Out of the 128 BMs treated, 6 cases of increase of preexisting edema (4.7%) and 8 hemorrhages (6.25%) occurred in 12 pts, but only 5 events (5%) were regarded as Adverse Radiation effects (ARE), being symptomatic in 3 pts (8% of pts). One BM had to be resected because of the occurrence of a symptomatic hemorrhage with hemiparesis 9 month after treatment. Median follow- up from GKRS was 13.7 mths. Median overall survival (OS) from GKRS and 1st BM were 14.8 and 26.5 mths respectively, with 6 and 12 mths 0S rates from GKRS of 65.7% and 57%, respectively. Local failure was observed in 5 pt. Median time to new BM was 12.6 mths. There was no significant difference in outcomes in pts, depending on PRE, CO and POST conditions. Conclusions: In this series, the largest to date of pts with BMs treated by GKRS and anti-PD1,ARE were within the expected range and survival rates appear promising. Given the natural propensity of MM-BMs for bleeding and edema our data do not support an increased risk with the combination of GKRS and anti-PD1. Regarding the timing between anti-PD1 administration and GKRS our data do not support a higher efficacy or higher toxicity among the 3 following potential mechanisms: immuno- sensitization to radiation (PRE), immuno-radio direct synergy (CO) or radiosensitization to immunotherapy (POST).

Gamma knife radiosurgery for brainstem cavernous malformations

ObjectiveThe goal of this retrospective study was to evaluate the efficacy and safety of gamma knife radiosurgery (GKS) for the treatment of brainstem cavernous malformations (CMs). MethodsBetween January of 2009 and December of 2014, 43 patients (20 males and 23 females) with brainstem CMs were treated at the West China Hospital, Sichuan University, Gamma Knife Center. The mean age of these patients was 41.7 years. All of the patients experienced 1 or more episodes of symptomatic bleeding (range 1–4) before undergoing GKS. The mean volume of the malformations at the time of GKS was 442.1mm3, and the mean prescribed marginal radiation dose was 11.9Gy. The mean follow-up period after radiosurgery was 36 months (range 12–120 months). ResultsBefore GKS, 50 hemorrhages (1.2 per patient) were observed (25.0% annual hemorrhage rate). Three hemorrhages following GKS were observed within the first 2 years (3.92% annual hemorrhage rate), and 1 hemorrhage was observed in the period after the first 2 years (1.85% annual hemorrhage rate). In this study of 43 patients, new neurological deficits developed in only 1 patient (2.32%; permanent paresthesia on the left side of the face and the right lower limb of the patient). There were no deaths in this study. ConclusionGKS is a favorable alternative treatment for brainstem CMs. Using a low marginal dose treatment might reduce the rate of hemorrhage and radiation-induced complications.

PC3 - 142 Gamma Knife Radiosurgery in Patients with Persistent Acromegaly or Cushing’s Disease: Long-Term Risk of Hypopituitarism

For patient with a recurrent or residual acromegaly or Cushing’s disease (CD) after resection, Gamma knife radiosurgery (GKRS) is often used. Hypopituitarism is the most common adverse effect after GKRS treatment. The paucity of studies with long-term follow up has hampered understanding of the latent risks of hypopituitarism in patients with a Acromegaly or CD. We report the long-term risks of hypopituitarism for patients treated with GKRS for Acromegaly or CD. Methods: From a prospectively created, IRB approved database, we identified all patients with a Acromegaly or CD treated with GKRS at the University of Virginia from 1989 to 2008. Only patients with a minimum endocrine follow up of 60 months were included. The median follow-up is 159.5 months (60.1-278). Thorough radiological and endocrine assessments were performed immediately before GKRS and at regular follow-up intervals. New onset of hypopituitarism was defined as pituitary hormone deficits after GKRS requiring corresponding hormone replacement. Results: 60 patients with either Acromegaly or CD were included. Median tumor volume at time of GKRS was 1.3 cm3 (0.3-13.4), median margin dose was 25 Gy (6-30). GKRS induced new pituitary deficiency occurred in 58.3% (n=35) of patients. Growth Hormone deficiency was most common (28.3%, n=17). The actuarial overall rates of hypopituitarism at 3, 5, and 10 years were 10%, 21.7%, and 53.3%, respectively. The median time to hypopituitarism was 61 months after GKRS (range, 12-160). Cavernous sinus invasion of the tumor was found to correlate with the occurrence of a new or progressive hypopituitarism after GKRS (p=0.018). Conclusions: Delayed hypopituitarism increases as a function of time after radiosurgery. Hormone axes appear to vary in terms of radiosensitivity. Patients with adenoma in the cavernous sinus are more prone to develop loss of pituitary function after GKRS.