Background: Papillary tumors of the pineal region (PTPR) are rare neuroepithelial tumors that are known to be at high risk of local recurrence even after gross total resection. They have been recognized as a distinct entity in recent WHO classifications and can be either grade 2 or 3. The optimal management of PTPR, including the potential role of stereotactic radiosurgery (SRS), remains a matter of debate. Only a few single center retrospective outcome studies have been reported in the literature. This study was designed to provide multi-institutional data to strengthen the evidence related to the use of SRS for PTPR.

Methods: Centers participating in the International Radiosurgery Research Foundation were asked to review their database and provide data for patients who had SRS for a histology confirmed PTPR (grade 2 or 3). Clinical and imaging follow-up of at least 6 months was required to be included in the study.

Results: We identified 12 patients (8 male and 4 female) who underwent SRS for PTPR. Six patients had primary SRS after biopsy, 4 had adjuvant SRS after partial resection and 2 had SRS for recurrent tumor. One patient had prior fractionated radiotherapy. The median margin dose used was 16 Gy (range 10-18 Gy) and median treatment volume was 2.67 cc (range 0.54-13 cc). Initial local control was achieved in all patients after SRS, with a mean progression-free survival of 140 months. Four patients had local tumor recurrence, managed by repeat SRS in 3 patients and surgical resection in the other. Those 4 patients remained free of recurrence at the last follow-up. One patient had ventricular and leptomeningeal dissemination which led to death. The global mean survival duration was 184 months, with a 5-year and 10-year survival rate of 80%, and an estimated survival rate of 65% after 237 months. Adverse radiation effects were observed in 5 out of 12 cases, 4 of which were symptomatic, but eventually resolved in all patients.

Conclusion: Stereotactic radiosurgery for the treatment of PTPR is safe and affords local tumor control in most cases. Local recurrence may be treated safely with repeat SRS.

Introduction

Glioblastoma Multiforme (GBM) is an extremely aggressive and lethal primary malignant neoplasm of the brain. Maximal safe resection followed by chemoradiotherapy  and adjuvant Temozolomide has been the standard of care. Even after multimodality treatment, the Median Overall survival is 14.6 months and almost 85 - 90 percent have local recurrence within 2 years.In recurrent GBM, systemic therapy, re-excision and radiotherapy have been tried with no significant proven benefit of one modality over the other.  Despite treatment, Overall survival for such patients is less than a year.

Re irradiation with Stereotactic Body Radiation Therapy (SBRT) is a safe and non-invasive treatment option in recurrent gliomas with comparable outcomes.

Here, we present the survival analysis of 54 patients with recurrent GBM who underwent reirradiation with SBRT technique using Cyberknife.

Materials and methods

54 patients with recurrent Glioblastoma multiforme treated from July 2009 to July 2023 were included in the study. All patients underwent Stereotactic Body Radiotherapy using Cyberknife to a dose of 25 Gy to 35 Gy in 3 to 5 fractions (BED range - 45.82 Gy -59.5 Gy) to the Gross Tumor Volume (GTV) as delineated on DOPA Positron Emission Tomography (PET CT) and Magnetic Resonance Imaging (MRI), along with concurrent Temozolomide. Systemic therapy was started post SBRT in most of the patients. The patients were followed up with clinical assessment and imaging (DOPA PET CT and MRI) at least once in 3 months.

Results

54 patients (M:F = 35:19) with a median age of 40.5 (range - 18 to 84 years) were analysed.  Over 90% patients received adjuvant chemotherapy post SBRT. All the patients tolerated the treatment with negligible side effects. The median Overall survival is 15 months after SBRT with a range of 3 to 105 months. The 1 year, 2 year, 3 year and 5 year survival is 60.4 %, 36.8 %, 24.5 %, 15.3 % respectively.

Conclusion

Re- irradiation with SBRT in recurrent GBM is feasible modality lesser treatment related morbidities, thereby improving the patient compliance. We observed an improved Overall survival compared to existing literature/ historical data.

However, a larger sample size is required to validate the same.

Incidental meningiomas are becoming a common finding. They represent a clinically challenging cohort due to the lack of a detailed consensus on their management. The risk of tumor progression and that of intervention must be considered. Long-term prospective data on incidental meningiomas are sparse. We aimed to evaluate the long-term effect of Gamma Knife Radiosurgery (GKRS), surgical resection and continued observation for growing incidental meningiomas in this study.

A prospective database of 62 patients (70 tumors) commenced under active surveillance was established in 2009. Radiological and clinical data was obtained until sept 2023. The results of long-term observation (group 1) and intervention with GKRS (group 2) or surgery (group 3) at progression was analyzed.

Due to growth, 41 (58.6%) tumors were treated. The mean growth rate was higher prior to GKRS (2.1 cm 3 /y) and surgery (0.4 cm 3 /y) than during long-term active surveillance (0.009 cm 3 /y) (p < 0.001). The meningiomas became in mean 31.3% and 99.1% smaller after GKRS and resection, respectively. In comparison, tumors in the long-term surveillance arm increased in mean 27.2% (p < 0.001). According to the RANO response criteria, the complete, partial, and minimal response versus stable disease rates were higher following intervention, the overall progressive disease rates were similar (Group 1; 20.7%, group 2: 11.4% and group 3: 16.7%) (p = 0.232). Treatment versus no-treatment did not affect overall survival (Group 1; 10.3 y, group 2: 11.8 y and group 3: 13.5 y (p = 0.264), which was comparable to the general population. No symptom development was registered in group 1. In group 2, 2.9% experienced transient (grade 2) adverse events, and in group 3 50% suffered permanent (grade 4) adverse events according to the Common Terminology Criteria for Adverse Events (CTCEAv5) . 

Intervention effectively reduces tumor volume; however, the clinical significance remains uncertain and side effects are not negligible. Active surveillance is safe, saves > 40% of patients from unnecessary interventions and does not seem to compromise future treatments. The optimal timing and risk of intervention should be further explored in

prospective randomized trials.

Glioblastoma (GBM) is the most common primary brain tumor, with survival rates still among the lowest, especially for patients who have not undergone complete resection surgery.

In this preliminary analysis, we aim to evaluate the safety and effectiveness of a multifraction radiosurgery (SRS), a radiotherapy regimen that is different from the standard, in patients with a primary diagnosis of glioblastoma and post-surgical residual tumor. 

From January 2021 to July 2023, 12 adult patients were enrolled. The main inclusion criteria were subtotal resection with a tumor volume ≤60 cc (approximately 5 cm maximum diameter) and a maximum PTV of 150 cm³. 

Target was defined on volumetric MRI as follows: GTV consisted of the tumor resection cavity and residual enhancing tumor; CTV was defined by adding a 3-5 mm margin to the GTV; PTV was the same as the CTV. Patients received multifraction radiosurgery treatment with 30 Gy (6 Gy/fx) over 5 consecutive days, followed by adjuvant temozolomide. Treatment was delivered by CyberKnife (Accuray) technology.

Follow-up consisted of physical examination, MRI, and EORTC-C30 and HADS questionnaire after 45-60 days and then every 2 months. FET-PET and advanced MRI sequences were integrated at progression (PD) in selected cases.

The median follow-up was 10 months (range 4-33). PD occurred in 10 patients (7 marginal, 2 outfield, and 1 both). Median PFS was 5.5 months (range 1-17). At 6 months, the PFS rate was 50%. At time of analysis, 4 patients were alive at 35, 25, 11, and 6 months, 2 without signs of progression. The OS rate at 12 months was 66.7%. 

Events possibly or definitely related to radiation treatment were reported in 7 patients (58.3%): 5 (41.7%) were acute (within 4 months) (2 grade 1, 2 grade 2, 1 grade 3 according to CTCAEv5), and 2 were late (16.7%, both grade 2).  Of these, 4 had regression of the symptoms, and 3 had stabilization. Radiation necrosis was registered in 3 patients (25%): 1 asymptomatic and 2 regressed with bevacizumab.

Current literature does not clearly define the role of SRS in GBM. Our study proposes an SRS protocol in a particularly disadvantaged GBM subpopulation: those patients with post-surgical residual disease and IDH-wild type status. Preliminary results appear promising in terms of PFS and OS with an acceptable level of toxicity risk. Exploring integration with advanced imaging techniques will be analyzed.

Purpose/Objectives: The aim of this study is to describe the potential clinical and dosimetric benefits of the implementation of ZAP-X gyroscopic frameless radiosurgery (GRS) in combination with modulated electro-hyperthermia (mEHT) as a radiosensitizer for the reirradiation of recurrent high grade gliomas by analyzing the first reported series of 8 patients treated in our institutions.

Material/Methods: Clinical and treatment information of 8 patients with 14 lesions that received GRS and mEHT between April 2023 and November 2023 were prospectively included in a database and analyzed.

Results: Eight patients (5 females and 3 males) with a median age of 48 years (30-62) and a median of 2 lesions (1-3) underwent GRS and mEHT during the study period. All patients had received  Stupp protocol and 3 patients had a previous second course of radiation. The median time from previous radiation was 11 months (6 – 21). The median (2.8cm³), minimum (0.2cm³), and maximum PTV volume (51cm³) were registered. 57% (n = 8) of the lesions were treated in 1 fraction, 29% (n = 4) in 5 fractions and 14% (n = 2) in 3 fractions. Median dose in 1 fraction was 15 Gy (15 - 18 Gy). Lesions treated in 5 fractions received 25 Gy or 30 Gy and in 3 fractions received 24 Gy. Median conformity index was 1.18, median homogeneity index was 1.84 and median gradient index 2.84. Median coverage of the prescribed dose was 95%. Median number of placed isocentres was 7. mEHT was applied using an EHY-2000 device, administered every 48 hours during the radiotherapy treatment. Each mEHT treatment had a 60 minute length with power between 60 and 100W, covering the whole brain, and was administered less than 2 hours apart from GRS. 2-3 mEHT aditional treatments were administered after GRS. Median clinical follow-up was 5 months (2-9). 1 patient died of multicentric spread 5 months after treatment, 2 patients received a second GRS for new lesions and one patient experienced a subependymal spread. Local control of the treated lesions was excellent, with no local relapses reported during follow-up. Actuarial overall survival at 6 months was 67%.  Acute and subacute treatment tolerance was acceptable and all patients needed ambulatory steroid medication adjustment. 

Conclusion: High grade glioma reirradiation with GRS in combination with mEHT showed a favourable impact in local control and overall survival with low toxicity. Longer follow-up and larger series is needed to validate these results.

BACKGROUND

Efficacy of SRS is limited due to the radioresistant and invasive nature of glioblastoma. In preclinical experiments, Tumor Treating Fields (TTFields) have been shown to downregulate important genes for DNA damage response and induce replication stress. Therefore, they have been proposed to increase sensitivity to radiation treatment. The integrated use with 18F- fluoroethyltyrosine (FET) -PET decreases the geographical misses.  We hypothesized that combined SRS based on FET-PET and TTFields will be complementary and improving outcomes with minimal toxicity.

 MATERIAL AND METHODS

The TaRrGeT trial is a prospective, pilot, single arm study using historical controls, designed to test effectiveness and safety of TTFields in combination with SRS based on FET-PET for the treatment of recurrent glioblastoma. In this trial, TTFields therapy was initiated before radiosurgery and continued until death or significant decrease of patient’s performance status.

The primary endpoint consisted of the one-year survival rate.

RESULTS

A total of 40 patients with recurrent glioblastoma have been enrolled between March 2021 and July 2023. Thirty percent of patients have been diagnosed in second or third recurrence at the time of enrollment. MGMT unmethylated and IDH wildtype status was found in 52.5% and 87% of patients, respectively.

The study met its primary endpoint with a statistically significant improvement in one-year survival rate compared to EF-11. The one-year overall survival rate from recurrence was 69.5% (vs 20%). Twenty-three patients have been enrolled more than 2 years prior to the analysis, of which 40% are still alive. A case-control comparison with matched patients from the EF-11 trial will be shown during the meeting.

Median survival from recurrence was 14 months. Nineteen patients are still alive at time of analysis with median follow up of 24 months, all but one in intact clinical status at last visit. Median OS from primary diagnosis reached 40 months.

The distribution of adverse events of  ≥ grade 3 (common toxicity criteria, CTC) was comparable to that of established recurrent glioblastoma trials. Notably, radiation necrosis was found in 20% of patients, but grade >1 only in 1 case (G2).

CONCLUSION

The pilot TaRrGeT trial met its primary endpoint indicating that SRS based on FET-PET combined with TTFields is feasible, well tolerated and effective.

Symptomatic radiation necrosis rate was low. The OS, 1- and 2- year survival rates were far above expectations. Patients with long follow up after experimental scheme are able to at least, maintain pre-treatment performance status.

BACKGROUND : Stereotactic radiosurgery (SRS) of larger arteriovenous malformations (AVM) is associated with an elevated incidence of adverse radiation effects (ARE). To date, volume–response and dose–response models have been used to predict such effects.

OBJECTIVES :To understand radiological outcomes and their hemodynamic effects on the regional brain.

 METHODS: A retrospective analysis was conducted at our institution using a prospective registry of patients managed between 2014 and 2020. We included patients with AVM with a nidus larger than 5 cc who received either single-session or volume-staged Gamma Knife radiosurgery. AVM volume changes, volumes of parenchymal response, and obliteration were analyzed and correlated with transit times and diameters of feeding arteries and draining veins.

 RESULTS: Sixteen patients underwent single-session SRS, and 9 patients underwent volume-staged SRS. The average AVM volume was 12.6 cc (5.5-23). The AVM locations were predominantly lobar (80%) and 17 (68%) were in critical locations. The mean margin dose was 17.2 Gy (15-21), and the median V12Gy was 25.5 cc. Fourteen (56%) AVMs had a transit time shorter than 1 second. The median vein-artery ratio (sum diameter of the veins/sum diameter of feeding arteries) was 1.63 (range, 0.60-4.19). Asymptomatic parenchymal effects were detected in 13 (52%) patients and were symptomatic in 4 (16%) patients. The median time to ARE was 12 months (95% CI 7.6-16.4). On univariate analysis, significant predictors of ARE were lower vein-artery ratio (P = .024), longer transit time (P = .05), higher mean dose (P = .028), and higher D95 (P = .036).

 CONCLUSION: Transittimes and vessel diameters  are valuable predictors of the subsequent parenchymal response after SRS. A more quantitative understanding of blood flow is critical for predicting the effects on the regional brain after AVM radiosurgery.

Introduction: The role of stereotactic radiosurgery (SRS) in the management of intracranial dural arteriovenous fistula (dAVF) is unclear due to their rarity and variability in treatment paradigms. 

Methods: Single institution database search from 1990 to 2022. Two hundred twenty-two patients underwent SRS alone (n=56, 25%) or SRS and embolization (n=166, 75%) depending on severity of symptoms or presence of cortical venous drainage (CVD). Imaging used for targeting initially was angiography alone, then angiography plus magnetic resonance imaging (MRI), and most recently MRI alone. Follow-up after SRS was available for 209 patients (median follow-up, 31 months).

Results: Most patients were female (142/222, 64%); the median patient age was 60 years. Common presenting symptoms were tinnitus (55%), visual change/chemosis (21%), headache (10%), and intracerebral hemorrhage (5%). The most frequent dAVF location was transverse/sigmoid (44%), followed by cavernous sinus (24%), jugular bulb (9%), and torcula (5%). CVD was noted in 28% of cases, with 5% having venous ectasia. Borden grades were I (72%), II (20%), and III (8%). Cognard grades were I (44%), IIa (28%), IIb (4%), IIa+b (15%), III (4%), and IV (5%). The median SRS volume was 5.9 cm³; the median margin/maximum doses were 18/36 Gy. Obliteration was noted in 75% of patients (110/147) with follow-up vascular imaging. Symptoms resolved in 77% of patients (160/209) with clinical follow-up. Fourteen patients (6.3%) had complications related to angiography for SRS planning (n=2, 0.9%), embolization (n=3, 1.4%), post-SRS hemorrhage (n=1, 0.5%), delayed sinus thrombosis (n=1, 0.5%), radiation-induced tumors (n=2, 0.9%), and chronic encapsulated expanding hematoma (n=3, 1.4%).

Conclusion: SRS alone or in conjunction with embolization provided obliteration and symptom relief for the majority of dAVF patients with a low rate of procedure related morbidity. Patients are at risk for late radiation-related complications which may require treatment many years after the SRS procedure.

Background and Objective: Since the publication of the ARUBA trial, many studies have assessed the outcome of different treatment options in ARUBA eligible bAVM patients. Studies on the conservative management of exclusively unruptured ARUBA eligible bAVMs are rather scarce.

Methods: A retrospective observational cohort of 107 patients (out of a total of 897 bAVM patients referred to our institution) with at diagnosis unruptured and conservatively managed bAVMs is presented. In a first step, long-term outcome data of our conservative cohort are compared to the ARUBA study’s medical management arm and in a second step, to our follow-up cohort of 472 radiosurgically treated bAVM patients.

Results: In the conservative observation period, 17% of patients suffered from at least one hemorrhage, resulting in an overall calculated annual hemorrhage risk of 2.7%. Cumulative 1, 5 and 10 year overall hemorrhage rates are 3.0%, 11.3% and 15.3%, respectively. Univariate followed by multivariate Cox regression analyses reveal a temporal and deep seated localization and the presence of seizures as independent risk factors for AVM hemorrhage among the conservative cohort. Of note, the radiosurgical treatment of bAVM leads to a significant improvement in the long-term mortality and hemorrhage risk compared to the conservative treatment.

Conclusion: Our data support the conclusion that even in the post-ARUBA era, tailored active treatment options should be offered to ubAVM patients. For patient counseling, individual risk factors should be weighed against the center’s treatment specific risks.

Objective.

Spinal arteriovenous malformations constitute a group of complex vascular lesions, accounting for 3-4% of all intradural lesions of the spinal cord. Microsurgery and endovascular embolization are the mainstays of treatment for these varied lesions, however, success rates and risks depend on the unique anatomy of each lesion. Stereotactic radiosurgery of intracranial AVMs has proven to be an effective treatment method. There are also many reports of the use of radiosurgery in the treatment of primary spinal tumors and metastatic lesions. However, irradiation of spinal malformations is rarely reported due to technical difficulties in implementing this treatment. In the future, stereotactic radiosurgery may become a promising treatment option for spinal AVMs. 

Material and Method

From 2021 to 2023, at the Burdenko Neurosurgical Institute (National Scientific and Practical Center for Neurosurgery named after academician   N.N. Burdenko) 31 patients with vascular pathologies of the spinal cord received radiosurgery (58% women and 42% men). The average age of patients is 39.2 years (median 7-77 years). 3 patients had a dural fistula and 28 patients had arteriovenous malformations. 15 malformations were at the cervical level, 12 malformations at the thoracic level, and 4 at the lumbar spinal cord level.

Treatment was carried out on TrueBeam STX (6 patients), CyberKnife VSI (10 patients) and CyberKnife M6 (15 patients). For 1 fraction treated in 19 patients (61.3%), Dmean was 15.67-24 Gy; 2 fractions in 7 patients (22.5%)  Dmean was 18.95-22 Gy; 3 fractions - in 4 patients (12.9%) – Dmean was 21.04-27 Gy and 5 fractions in 1 patient (3.3%) Dmean was 30 Gy. Average target volume was 4.37 cm3 (median 0.1-100 cm3). 

Results.

Up to date we have information concerning follow up of 12 patients (38%). The median follow-up was 12.25 months (6-25 months). Complete obliteration was revealed In 2 patients according MRI (16.7%) after 13 and 14 months of follow-up, positive dynamics according to control MRI was noted in 5 patients (41.6%), absence changes  - in 5 patients (41.6%). No increase of neurological deficit was recorded.

Conclusion.

Stereotactic radiosurgery   is safe and effective and may be method of choice and can be considered for patients   with spinal AVM  when surgery or endovascular therapy is not indicated or had no results. Continued follow-up observation is required to assess treatment results.

INTRODUCTION:

Cerebral arteriovenous malformations (AVM), whilst uncommon, more typically present in patients aged 30-40 years with haemorrhage the most common presenting occurrence. Whilst the annual haemorrhage is only 3%, for younger patients the life-time haemorrhage rate can be greater than 60%. Surgery has definite benefits, however, many factors can define a non-resectable situation. Historically, a stereotactic radiosurgery (SRS) procedure as a day only outpatient event, has involved application of a neurosurgical head-ring with a cerebral angiogram performed on the day, with planning and treatment occurring on the same day. This is a review of the process over a 20 year time-frame.

METHODS:

In this Ethics approved retrospective review (2022/ETH01472), conducted on all adult patients who presented for AVM treatment with SRS in our Centre from January 2000-December 2019. All included patients has minimum follow up of 1-3 years via clinical assessment and 6-12 monthly MRI imaging. When nil flow was evident on the flow sequence, cerebral angiogram was performed. Obliteration rates, time to obliteration (TTO), complications, and predictors associated with obliteration were investigated.

RESULTS:

There were 136 included AVMs, 49% (n=67) were male, with mean age 41 years (SD 14.3). Haemorrhage leading to presentation occurred in 32% (n=44), 41% (n=56) had headaches, while 13% (n=17) were asymptomatic. Diameter less than 3cm was evident in 68% (n=92), with 88% (n=119) in eloquent brain. AVM volume was <2cm³ in 26% (n=35), 2-4cm³ in 8% (n=11) and > 4cm³ in 66% (n=90). Radiosurgery dose ≥ 18Gy was given in 81%, and < 18Gy in 50% of patients. Overall obliteration rate was 76% (103/136), with rates of 85% (78/92) in maximum diameter <3cm, 58% (23/40) in 3-6cm, and 50% (2/4) in > 6cm. Obliteration rates were higher with a dose ≥18Gy (81%, 92/114), and this was found to be a predictor of obliteration rate on multivariate analysis, with patients being 4.7 times more likely to achieve this (OR 4.7, 95%CI 1.69-13.25, p=0.003). Mean TTO was 48 months, with no significant predictors found. No complication occurred in 73%, 18% developed a temporary event, permanent in 9%, and necrosis occurred in 8%.

CONCLUSION:

Vascular obliteration rates were high in small (<3cm) AVMs, and where ≥ 18Gy was delivered, rates were comparable to those in published Gamma-knife series. Newer methods enable dispensing with the head-ring.

OBJECTIVE The integration of modern neuroimaging into treatment planning has increased the therapeutic potential and safety of stereotactic radiosurgery. The authors report their method of integrating stereotactic diffusion tensor imaging (DTI) tractography into treatment planning for CyberKnife radiosurgery (CKRS). The aim of this study was to evaluate whether the use of diffusion-tensor tractography (DTT) of the corticospinal tract could reduce motor complications after radiosurgery. METHODS Between 2013 and 2020, 56 patients with arteriovenous malformation (AVM) in the deep frontal lobe, deep parietal lobe, basal ganglia, and thalamus who had undergone CKRS. DTI were obtained on the day before the localization of head. Data from stereotactic 3D imaging studies were co-registered with the data from DTI tractography. The combined images were transferred to a Cyberknife treatment-planning workstation. During the procedure of creation of treatment planning, the corticospinal tract was clearly visualized on the Multiplan. Results: 56 patients with AVM volume less than 10 cm3 underwent CKRS in Huashan Hosptial. The follow-up time ranged from 36 to 120 months, with median time of 78 months. The prescription dose was 21Gy-22 Gy in 2 fractions or 21Gy – 22.5 Gy in 3 fractions according to AVM volume. A maximum dose to the corticospinal tract of equal to or less than 21 Gy in 3 fractions or 18 Gy in 2 fractions did not cause new neurological deficits. Total obliteration rates were 72% at more than 3 years after one stage or two stage CKRS. One patient had small intracranial hemorrhage 3 years post obliteration. Mild complications were observed in 6 patients because of brain edema, which was required medication.

CONCLUSIONS Integration of stereotactic tractography into CKRS represents a promising tool for preventing radiosurgery complications by reduction in radiation doses to functional organs at risk, including critical cortical areas and subcortical white matter tracts. DTI improved the obliteration of AVM and reduced the motor deficits

Background and objectives: Lung adenocarcinoma with epidermal growth factor receptor mutation (EGFR-mutant) is the most common etiology of brain metastasis in Taiwan, and which is usually treated with tyrosine kinase inhibitors (TKIs) and gamma knife stereotactic radiosurgery (GKRS). As the emerging of second or third generation TKIs which are dominating on penetrating brain blood barrier, there are debates about whether GKRS should be postponed as a salvage management or upfront with TKIs as an initial treatment of newly diagnosed brain metastases. Therefore, this study purposed to find out the prognostic factors of these patients and compare the clinical outcome of upfront GKRS with TKIs to solely 2^nd or 3^rd generation TKIs in treating patients with EGFR-mutant lung adenocarcinoma brain metastasis.

Methods: We retrospectively collected patients with EGFR-mutant lung adenocarcinoma who received 2nd or 3rd generation TKIs with or without upfront GKRS as initial treatment for their newly diagnosed brain metastasis in two medical centers from Jan 2014 to Dec 2021. Probability of Treatment Weighting (IPTW) was used to match whole potential confounders between these two groups. Furthermore, we use SPSS 23.0 for statistics analysis.

Results: There were 143 patients enrolled in this study, including 98 pts had upfront GKRS with 2^nd or 3^rd generation TKIs and 45 pts with solely 2^nd or 3^rd generation TKIs as their initially treatment on newly diagnosed brain metastasis. After multivariate regression analysis, age, Karnofsky performance scale (KPS), extracranial metastasis status, control of primary tumor and number of brain metastases are statistics significant prognostic factors. After IPTW, there is no statistic significant difference in upfront GKRS with TKIs group and solely TKIs group on all confounders. The upfront GKRS with 2^nd or 3^rdgeneration TKIs group demonstrated significantly prolonged median progression-free survival (40.9 months vs. solely 2^nd or 3^rd generation TKIs group 12.6 months, P<0.001) and median overall survival (59.5 months vs. solely 2^nd or 3^rd generation TKIs group 30.8 months, P<0.001).

 Conclusion: Age, KPS, extracranial metastasis status, primary tumor control and number of brain metastasis are prognostic factors in patients with EGFR-mutant lung adenocarcinoma brain metastasis. Upfront GKRS with new generation TKIs not only provide better local control but also improve prognosis.

OBJECTIVE
Stereotactic radiosurgery (SRS) is the mainstay for treating brain metastases (BMs) from lung cancer (LC). In recent years, immune checkpoint inhibitors (ICIs) have been applied to metastatic LC and have contributed to improved outcomes. The authors investigated whether SRS with concurrent ICIs for LC BMs prolongs overall survival (OS) and improves intracranial disease control, and whether there are any safety concerns.

METHODS
Patients who underwent SRS for LC BMs in our institution between January 2015 and December 2021 were included. Concurrent use of ICIs was defined as no more than 3 months between SRS and ICI administration. The two treatment groups, which had a similar likelihood of receiving concurrent ICIs, were generated by a propensity score matching (PSM) (match ratio 1:1) based on 11 potential prognostic covariates. Patient survival and intracranial disease control were compared between the groups with and without concurrent ICIs (ICI+SRS vs. SRS) by time-dependent analyses taking into account competing events.

RESULTS
In total, 585 LC BM patients (494 NCSCL and 91 SCLC) were eligible. Of those, 93 patients (16%) received concurrent ICIs. Two groups with 89 patients each (ICI+SRS group and SRS group) were generated by PSM. The 1-year survival rates of the ICI+SRS and SRS groups after the initial SRS were 65% and 50%, the median survival times 16.9 and 12.0 months, respectively (HR: 0.62, 95% CI: 0.44–0.87, p = 0.006). The 2-year cumulative neurological mortality rates were 12% and 16%, respectively (HR: 0.55, 95% CI: 0.28–1.10, p = 0.091). The 1-year intracranial progression-free survival rates were 35% and 26% (HR: 0.73, 95% CI: 0.53–0.99, p = 0.047).The 2-year local failure rates were 12% and 18% (HR: 0.72, 95% CI: 0.32–1.61, p = 0.43) and the 2-year distant recurrence rates were 51% and 60% (HR: 0.82 95% CI: 0.55–1.23, p = 0.34). Severe adverse radiation events (CTCAE grade 4) occurred in one patient in each group and CTCAE grade 3 toxicities were observed in 3 patients in the ICI+SRS group and 5 in the SRS group (OR: 1.53, 95% CI: 0.35–7.7, p = 0.75).

CONCLUSIONS
The present study found that SRS with concurrent ICIs for LC BM patients was associated with longer survival and durable intracranial disease control with no apparent increase in treatment-related adverse events.

Introduction Single fraction Gamma Knife radiosurgery (GKRS) is a well-accepted treatment modality for small to medium sized brain metastases (BM). For large BM (LBM; >10-15 cm³), single fraction GKRS is associated with suboptimal LC rates and an increased risk of treatment-related toxicity. For LBM, 2-staged or 3-staged fractionated adaptive GKRS (3-GKRS) has been used to enhance LC while limiting adverse radiation effects. We present our experience with 3-GKRS in LBM >15 cm³. 

Methods Data of patients with LBM >15 cm³ treated with 3-GKRS between January 2018 and March 2023 at the Gamma Knife Center Tilburg were retrospectively collected. The regimen consisted of 3 fractions of 10 Gy prescribed to the isodoseline covering 100% of the target with 2 weeks interval between the subsequent fractions. For each fraction, a new MRI was performed for target delineation and treatment planning. All patients had follow-up appointments with MRI as long as clinical meaningful. In case of new intracranial disease new treatment was offered if appropriate. Descriptive analyses were used to give an overview of the patient and tumor characteristics. Kaplan-Meier curves were used to analyze overall survival.

Results 70 patients (male 51%; median age 68 years (range 40-85 years); 56% non-small cell lung cancer, 17% breast cancer) were treated with 3-GKRS. The median tumor volume of the LBM was 29 cm³ (range 15.2 cm³ - 87.4cm³). The median overall survival was 11 months (95% CI, 9 to 13 months). Six patients (14%) died due to a neurological cause (1 due to the LBM). At the 3^rd fraction, reduction in volume of the LBM was observed in 85.7% of the patients (>65% reduction in 8 patients). LC rates of the LBM were 98.2%, 93.3% and 91.9% at 6 weeks and at 3 and 6 months respectively. Neurological improvement or stabilization was observed in 57.4%, 60.4% and 66.7% of the patients and dexamethason dose could be reduced to ≤1.5mg/day in 63.9%, 71.4% and 75.7% at 6 weeks and at 3 and 6 months, respectively. Transient symptomatic adverse effects were observed in 20.7% of the patients between 5 and 46 months after GKRS.  

Discussion 3-GKRS is well tolerated and a valuable treatment option in patients with LBM. Larger series are needed in order to evaluate for which patients this regimen is an alternative to resection.

Aims: Stereotactic radiosurgery (SRS) is an established non-invasive therapy for multiple brain metastases (BMs). Mono-isocentric techniques allow the delivery of multiple stereotactic courses, in case of intracranial failure. Nevertheless, limited data on the effectiveness and toxicity have been reported, as well as details on patterns of failure. Aim of this study is to evaluate effectiveness and safety of multiple HyperArc courses and patterns of progression in patients affected by BMs with intracranial progression.

Methods: between June 2017 and January 2022, 56 patients were treated for 702 BMs with 197 (range 2-8) HyperArc courses in case of exclusive intracranial progression. Primary tumor was lung in 26 (46.5%), breast in 18 (32%), melanoma in 8 (14%), and other in 4 (7.5%). BM site was: supratentorial in 529 (75%), infratentorial in 160 (23%), brainstem in 13 (2%). The primary end-point was the overall survival (OS), secondary end-points were intracranial progression-free survival (iPFS), toxicity, local control (LC), neurological death (ND), and WBRT-free survival. Site of progression was evaluated against isodoses levels (0, 1, 2, 3, 5, 7, 8, 10, 13, 15, 20, and 24 Gy.).

Results: median SRS dose was 25 Gy (range 24-27 Gy). The 1-year OS was 70%, and the median was 20.8 months (17-36). At the univariate analysis (UVA) BED>51.3Gy and non-melanoma histology significantly correlated with OS. The median time to iPFS was 4.9 months, and the 1-year iPFS was 15%. Globally, 538 new BMs occurred after the first HA cycle in patients with extracranial disease controlled. 95% of them occurred within the isodoses range 0-7 Gy as follows: 27.5% (0 Gy), 19.5% (1 Gy), 16.7% (2 Gy), 16% (3 Gy), 12.5% (5 Gy), 2.8% (7 Gy) (p=0.00). Clinical toxicity was represented by headache 4 (7.1%), and radionecrosis 2 (0.28% of treated metastases). One- and 2-year LC was 90% and 79%, respectively. At the UVA BED>70 Gy and non-melanoma histology were significant predictors of higher LC. The 2-year WBRT-free survival was 70%. After a median follow-up of 20 months, 12 patients deceased by ND (median time 17.4 months).

Conclusion: Intracranical relapses can be safely and effectively treated with repeated HyperArc, with the aim to postpone or avoid WBRT. Diffuse dose by volumetric RT might reduce microscopic disease also at relatively low levels, potentially acting as a virtual CTV. Neurological death is not the most common cause of death in this population, which highlights the impact of extracranial disease on overall survival