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BACKGROUND: Emerging randomized data, mostly from phase II trials, have suggested that patients with oligometastatic cancers may benefit from ablative treatments such as stereotactic ablative radiotherapy (SABR). However, phase III data testing this paradigm are lacking, and many studies have examined SABR in the setting of metachronous oligometastatic disease. The goal of the SABR-SYNC trial is to assess the effect of SABR in patients with oligometastatic cancers and a synchronous primary tumor. METHODS: One hundred and eighty patients will be randomized in a 1:2 ratio between standard of care (SOC) palliative-intent treatments vs. SOC + ablative therapy (SABR preferred) to all sites of known disease. Randomization will be stratified based on histology and number of metastases at enrollment. SABR may be delivered in 1-, 3- and 5-fraction regimens, with recommended doses of 20 Gy, 30 Gy, and 35 Gy, respectively. Non-SABR local modalities (e.g. surgery, thermal ablation, conventional radiation) may be used for treatment of the primary or metastases at the discretion of the treating physicians, if those modalities are clinically preferred. The primary endpoint is overall survival, and secondary endpoints include progression-free survival, time to development of new metastatic lesions, time to initiation of next systemic therapy, quality of life, and toxicity. Translational endpoints include assessment of circulating tumor DNA and immunological predictors of outcomes. DISCUSSION: SABR-SYNC will provide phase III data to assess the impact of SABR on overall survival in a population of patients with synchronous oligometastases. The translational component will attempt to identify novel prognostic and predictive biomarkers to aid in clinical decision making. TRIAL REGISTRATION: Clinicaltrials.gov NCT05717166 (registration date: Feb. 8, 2023).

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PURPOSE: Recent innovations in radiological imaging have enabled the detection of micro-remnant niduses of arteriovenous malformations (AVMs) after gamma knife radiosurgery (GKS), which have not been previously perceptible. Herein, we focus on the difficulty of evaluating micro-remnant AVMs after GKS that are hardly perceptible on conventional examinations and propose integrating follow-up three-dimensional rotational angiography (3D-RA) in the previous gamma plan as a solution. METHODS: We retrospectively searched NTT Medical Center Tokyo hospital database for patients with AVMs who underwent both two-dimensional digital subtraction angiography (2D-DSA) and 3D-RA as follow-up for GKS from February 2021 to January 2024. Patients with suspected nidus occlusion on the latest non-contrast-enhanced magnetic resonance angiography (NC-MRA) were included, and contrast-enhanced magnetic resonance angiography (CE-MRA), 2D-DSA, and 3D-RA were evaluated. RESULTS: Twelve patients with 13 AVM sites were defined as having complete nidus occlusion on upfront NC-MRA. On 2D-DSA, seven AVM sites showed the presence of slight remaining AVMs based on the detection of remnant drainage veins, however the nidus was not detected in three cases. Nevertheless, 3D-RA detected micro-remnant niduses in all seven AVM sites, and four patients underwent re-GKS. Nine patients with ten AVM sites also underwent CE-MRA, and six AVM sites were diagnosed with radiation-induced parenchymal injury. CONCLUSION: Importing the 3D-RA image into the treatment planning has the potential to be more helpful than NC-MRA or CE-MRA to detect micro-remnant AVMs and evaluate the true remnant volume, and may contribute to a more detailed treatment planning, thereby improving the results of GKS retreatment.

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BACKGROUND AND OBJECTIVES: Studies comparing neurological and radiographic outcomes of repeat to initial stereotactic radiosurgery (SRS) intracranial arteriovenous malformations are scarce. Our aim was to perform a retrospective matched comparison of patients initially treated with SRS with those undergoing a second radiosurgical procedure. METHODS: We collected data from arteriovenous malformations managed in 21 centers that underwent initial and repeated radiosurgery from 1987 to 2022. Based on arteriovenous malformations volume, margin dose, deep venous drainage, deep, and critical location, we matched 1:1 patients who underwent an initial SRS for treatment-naive arteriovenous malformations and a group with repeated SRS treatment. RESULTS: After the selection process, our sample consisted of 328 patients in each group. Obliteration in the initial SRs group was 35.8% at 3 and 56.7% at 5 years post-SRS, while the repeat SRS group showed obliteration rates of 33.9% at 3 years and 58.6% at 5 years, without statistically significant differences (P = .75 and P = .88, respectively). There were no statistically significant differences between the 2 groups for obliteration rates (hazard ratio = 0.93; 95% CI, 0.77-1.13; P = .5), overall radiation-induced changes (RIC) (OR = 1.1; 95% CI, 0.75-1.6; P = .6), symptomatic RIC (OR = 0.78; 95% CI, 0.4-1.5; P = .4), and post-SRS hemorrhage (OR = 0.68; 95% CI; P = .3). CONCLUSION: In matched cohort analysis, a second SRS provides comparable outcomes in obliteration and RIC compared with the initial SRS. Dose reduction on repeat SRS may not be warranted.

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BACKGROUND: The aim of this study is comparison the effectiveness of stereotactic, hypofractionated and conventional radiotherapy assessed by the tumor volume changes of paraganglioma located in the head and neck region concerning fractional and total doses. METHODS: We analyzed 76 patients after radiotherapy due to paraganglioma who were assigned to 3 groups considering fractional (≤2 Gy, 3-5.5 Gy, ≥6 Gy) and total (≤20 Gy, 21-40 Gy, >40 Gy) doses. The volumes of irradiated tumors were measured and compared based on diagnostic images performed before and after the treatment. RESULTS: The mean tumor volume after the treatment with the lowest fractional dose (≤2 Gy) was decreased by 14.4 cm3. In patients treated with higher fractional doses (>2 Gy), the mean tumor volumes decreased by less than 1 cm3 for hypofractionated and stereotactic radiotherapy. 15.9 cm3 reduction of the mean tumor volume after the treatment with the highest RT total dose (>40 Gy) was stated. In patients treated with total doses ≤20 Gy and 21-40 Gy, the mean tumor volume was stable and reduced by 1.15 cm3, respectively. The analysis demonstrates a statistically significant (p < 0.05) treatment advantage in patients after the lowest fractional and highest total doses. CONCLUSION: The reduction of the tumor's volume was reported after conventional and unconventional radiotherapy. The most significant depletion of the paraganglioma volume was noted after a factional dose ≤2 Gy and a total dose >40 Gy.

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Surgical removal remains the primary treatment for most brain tumours. However, radiosurgery presents an effective, less invasive alternative or additional treatment for certain types. Our goal was to explore radiosurgery's roles in treating various brain tumours, focussing on its application in low- and middle-income countries (LMICs). We reviewed all relevant systematic reviews, metaanalyses, and guidelines to determine the most effective radiosurgical approaches. Additionally, we consulted a panel of experts with over ten years of experience in LMICs, such as Pakistan. For brain tumours, stereotactic radiosurgery should generally follow a confirmed histopathological diagnosis. Exceptions include tumours identified through Magnetic Resonance Imaging (MRI), like Vestibular Schwannoma (VS), pre-diagnosed Neurofibromatosis type 2 (NF2), multiple typical meningiomas, and metastases with a known histology from another site. While radiosurgery is gaining traction as a primary and adjunct treatment in some LMICs, the lack of regional guidelines, trained personnel, and collaboration among specialists hinders its wider adoption. Addressing these gaps is crucial for expanding radiosurgical care in these regions.

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BACKGROUND: Multimodal therapy for brain arteriovenous malformations (bAVM) with embolization followed by stereotactic radiosurgery (E + SRS) has shown varying outcomes. Its benefits over other treatment modalities have been questioned. The goal of this systematic review was to determine the factors associated with cure and complication rates of this treatment strategy. METHODS: A literature search in Medline and Global Index Medicus, from inception to October 2023, was performed. Studies reporting relevant outcome data from bAVM patients treated with E + SRS were included. Data on several patient, lesion and procedure-related factors were collected. Embolization intent was classified as Targeted (of high-risk features), Devascularizing (feeder embolization/flow reduction) and Occluding (intent-to-cure, nidus embolization). The primary outcome was obliteration rate. Secondary outcomes were post-SRS bleeding (PSB), post-embolization neurological complications (PENC) and post-SRS neurological complications (PSNC). Subgroup analyses included embolic agent, embolization intent and radiosurgery type. Proportional meta-analyses and meta-regressions were performed. RESULTS: Forty-one studies were included in the review. The pooled obliteration rate was 56.45% (95% CI 50.94 to 61.88). Meta-regression analyses showed higher obliteration rates with Copolymers and lower obliteration rates with Devascularizing embolization. The pooled PSB, PENC and PSNC rates were 5.50%, 13.75% and 5.02%, respectively. Meta-regression analyses showed higher rates of PSB, PENC and PSNC with Devascularizing embolization, Liquid & Solid embolic agents and Targeted & Devascularizing intent, respectively. CONCLUSION: Embolic agent and embolization intent were procedural factors associated with treatment outcomes of E + SRS in the management of bAVM patients. The efficacy and safety profiles favor copolymers as embolic agents and disfavor Devascularizing as embolization intent. STUDY REGISTRATION: The protocol of the systematic review was registered in PROSPERO as CRD42023474171.

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Background: Cerebral radiation necrosis (RN), a severe complication of stereotactic radiotherapy (SRT), has been shown to significantly decrease patient survival time and quality of life. The purpose of this study was to analyze whether bevacizumab can prevent or reduce the occurrence of SRT-induced cerebral RN in non-small cell lung cancer (NSCLC) patients with brain metastases. Materials and methods: We retrospectively reviewed the clinical records of NSCLC patients with brain metastases from March 2013 to June 2023 who were treated with SRT. Patients were divided into two groups: those in the bevacizumab group received SRT with four cycles of bevacizumab, and patients in the control group received SRT only. Inverse probability of treatment weighting (IPTW) was performed based on a multinomial propensity score model to balance the baseline characteristics. The chi-square test was used. A Cox model was used to evaluate overall survival (OS). Results: A total of 80 patients were enrolled, namely, 28 patients in the bevacizumab group and 52 patients in the control group. The possibility of developing cerebral RN and/or symptomatic edema (RN/SE) was significantly decreased in patients treated with bevacizumab compared to those who did not receive bevacizumab before IPTW (p=0.036) and after IPTW (p=0.015) according to chi-square analysis. The IPTW-adjusted median OS was 47.7 months (95% CI 27.4-80.8) for patients in the bevacizumab group and 44.1 months (95% CI 36.7-68.0) (p=0.364) for patients in the control group. Conclusion: The application of bevacizumab concurrent with SRT may prevent or reduce the occurrence of cerebral RN in NSCLC patients with brain metastases.

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PURPOSE: To demonstrate the possibility of using a lower imaging rate while maintaining acceptable accuracy by applying motion prediction to minimize the imaging dose in real-time image-guided radiation therapy. METHODS: Time-series of three-dimensional internal marker positions obtained from 98 patients in liver stereotactic body radiation therapy were used to train and test the long-short-term memory (LSTM) network. For real-time imaging, the root mean squared error (RMSE) of the prediction on three-dimensional marker position made by LSTM, the residual motion of the target under respiratory-gated irradiation, and irradiation efficiency were evaluated. In the evaluation of the residual motion, the system-specific latency was assumed to be 100 ms. RESULTS: Except for outliers in the superior-inferior (SI) direction, the median/maximum values of the RMSE for imaging rates of 7.5, 5.0, and 2.5 frames per second (fps) were 0.8/1.3, 0.9/1.6, and 1.2/2.4 mm, respectively. The median/maximum residual motion in the SI direction at an imaging rate of 15.0 fps without prediction of the marker position, which is a typical clinical setting, was 2.3/3.6 mm. For rates of 7.5, 5.0, and 2.5 fps with prediction, the corresponding values were 2.0/2.6, 2.2/3.3, and 2.4/3.9 mm, respectively. There was no significant difference between the irradiation efficiency with and that without prediction of the marker position. The geometrical accuracy at lower frame rates with prediction applied was superior or comparable to that at 15 fps without prediction. In comparison with the current clinical setting for real-time image-guided radiation therapy, which uses an imaging rate of 15.0 fps without prediction, it may be possible to reduce the imaging dose by half or more. CONCLUSIONS: Motion prediction can effectively lower the frame rate and minimize the imaging dose in real-time image-guided radiation therapy.

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PURPOSE: Intraprostatic recurrence (IRR) of prostate cancer after radiation therapy is increasingly identified. Our objective was to review the literature to determine the optimal workup for identifying IRR, the management options, and practical considerations for the delivery of re-irradiation as salvage local therapy. METHODS: We performed a systematic review of available publications and ongoing studies on the topics of IRR, with a focus on salvage re-irradiation. RESULTS: Work up of biochemically recurrent prostate cancer includes PSMA PET/CT and multiparametric MRI, followed by biopsy to confirm IRR. Management options include continued surveillance, palliative hormonal therapy, and salvage local therapy. Salvage local therapy can be delivered using re-irradiation with low dose rate brachytherapy, high dose rate (HDR) brachytherapy, and stereotactic body radiotherapy (SBRT), as well as non-radiation modalities, such as cryotherapy, high-intensity focused ultrasound, irreversible electroporation and radical prostatectomy. Data demonstrate that HDR brachytherapy and SBRT have similar efficacy compared to the other salvage local therapy modalities, while having more favorable side effect profiles. Recommendations for radiation therapy planning and delivery using HDR and SBRT based on the available literature are discussed. CONCLUSION: Salvage re-irradiation is safe and effective and should be considered in patients with IRR.

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Vein of Galen malformations (VOGMs), also known as Vein of Galen Aneurysmal Malformations (VGAMs), are rare and complex cerebrovascular anomalies that pose significant diagnostic and therapeutic challenges. These malformations result from abnormal arteriovenous shunts during embryonic development, leading to a range of severe clinical manifestations, including high-output cardiac failure and hydrocephalus. Advances in prenatal imaging, particularly fetal MRI, have improved early detection, allowing for timely intervention. Endovascular techniques, especially transarterial embolization, have become the primary treatment modality, often preferred over surgical approaches due to their effectiveness and lower risk. However, challenges remain, particularly in managing these malformations in neonates and infants, where the risk of complications is high. Gamma Knife radiosurgery offers a non-invasive alternative for select cases, though its effects are gradual and may carry delayed risks. Despite advancements, the management of VOGMs continues to require a multidisciplinary approach, with ongoing research focused on improving outcomes through a better understanding of the genetic and molecular underpinnings of the disease. Future directions include the integration of genetic studies into clinical practice and the refinement of treatment strategies to optimize outcomes for this complex condition.

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BACKGROUND: The management of vestibular schwannomas (VS) encompasses a choice between conservative "wait-and-scan" (WAS) approach, stereotactic radiosurgery (SRS) or open microsurgical resection. Currently, there is no consensus on the optimal management approach for small to medium sized VS. This study aims to compared outcomes related to hearing in patients with small and medium sized VS who underwent initial treatment with WAS versus SRS. METHODS: A systematic review of the available literature was conducted using PubMed/MEDLINE, Embase, and Cochrane up December 08, 2023. Meta-analysis was performed using a random-effect model to calculate mean difference (MD) and relative risk (RR). A leave-one-out analysis was conducted. The risk of bias was assessed via the Risk of Bias in Non-randomized Studies-Interventions (ROBINS-I) and Cochrane Risk of Bias assessment tool (RoB-2). Ultimately, the certainty of evidence was evaluated using the GRADE assessment. The primary outcomes were serviceable hearing, and pure-tone average (PTA). The secondary outcome was the Penn Acoustic Neuroma Quality of Life Scale (PANQOL) total score. RESULTS: Nine studies were eligible for inclusion, comprising a total of 1,275 patients. Among these, 674 (52.86%) underwent WAS, while 601 patients (47.14%) received SRS. Follow-up duration ranged from two to eight years. The meta-analysis indicated that WAS had a better outcome for serviceable hearing (0.47; 95% CI: 0.32 - 0.68; p < 0.001), as well as for postoperative functional measures including PTA score (MD 13.48; 95% CI 3.83 - 23.13; p < 0.01), and PANQOL total score (MD 3.83; 95% CI 0.42 - 7.25; p = 0.03). The overall certainty of evidence ranged from "very low" to "moderate". CONCLUSIONS: Treating small to medium sized VS with WAS increases the likelihood of preserving serviceable hearing and optimized PANQOL overall postoperative score compared to SRS. Nevertheless, the limited availability of literature and the methodological weakness observed in existing studies outline the need for higher-quality studies.

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This study aims to analyze and evaluate the comparative clinical outcomes associated with microvascular decompression (MVD) and gamma knife radiosurgery (GKRS), focusing on pain relief, pain recurrence, and complications encountered in the treatment of trigeminal neuralgia (TN). Among 155 surgical procedures performed for TN (90 GKRS, and 65 MVD) between March 1997 and December 2020, the exclusion criteria encompassed prior surgical interventions, the presence of other pathological conditions such as tumors, vascular diseases, and multiple sclerosis, as well as patients who were lost to follow-up. Ultimately, 101 patients received their initial treatment for primary TN (47 GKRS, and 54 MVD) and were followed up for more than 1 year. The MVD procedures utilized the suboccipital retrosigmoid sinus approach, whereas GKRS was conducted with MR imaging guidance, employing a single 4mm isocenter, with median GKRS doses of 80 Gy. We retrospectively analyzed patient characteristics, including sites of divisions, distributions of pain, and clinical outcomes. The assessment of outcomes was performed utilizing the Barrow Neurological Institute Pain Intensity Score and the Visual Analog Scale (VAS), with evaluations taking place preoperatively and after 1, 3, 6 and 12 months. Postoperative VAS scores for patients undergoing either MVD or GKRS demonstrated a significant improvement when compared with their preoperative counterparts. The reduction in postoperative VAS scores within the MVD group was significantly more substantial than that observed in patients who underwent GKRS at the initial postoperative evaluations (P = .037). The maintenance of pain relief after MVD proved significantly superior to that following GKRS (P < .01). Both MVD and GKRS present as safe and efficacious therapeutic options for individuals diagnosed with primary TN, though MVD displayed superior initial outcomes in terms of pain relief and its maintenance. However, for older patients or those with medical contraindications to invasive procedures, GKRS emerges as a viable and less invasive alternative for initial treatment in cases of primary TN.

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BACKGROUND AND PURPOSE: Radiation-induced pneumonitis (RP), diagnosed 6-12 weeks after treatment, is a complication of lung tumor radiotherapy. So far, clinical and dosimetric parameters have not been reliable in predicting RP. We propose using non-contrast enhanced magnetic resonance imaging (MRI) based functional parameters acquired over the treatment course for patient stratification for improved follow-up. MATERIALS AND METHODS: 23 lung tumor patients received MR-guided hypofractionated stereotactic body radiation therapy at a 0.35T MR-Linac. Ventilation- and perfusion-maps were generated from 2D-cine MRI-scans acquired after the first and last treatment fraction (Fx) using non-uniform Fourier decomposition. The relative differences in ventilation and perfusion between last and first Fx in three regions (planning target volume (PTV), lung volume receiving more than 20Gy (V20) excluding PTV, whole tumor-bearing lung excluding PTV) and three dosimetric parameters (mean lung dose, V20, mean dose to the gross tumor volume) were investigated. Univariate receiver operating characteristic curve - area under the curve (ROC-AUC) analysis was performed (endpoint RP grade≥1) using 5000 bootstrapping samples. Differences between RP and non-RP patients were tested for statistical significance with the non-parametric Mann-Whitney U test (α=0.05). RESULTS: 14/23 patients developed RP of grade≥1 within 3 months. The dosimetric parameters showed no significant differences between RP and non-RP patients. In contrast, the functional parameters, especially the relative ventilation difference in the PTV, achieved a p-value<0.05 and an AUC value of 0.84. CONCLUSION: MRI-based functional parameters extracted from 2D-cine MRI-scans were found to be predictive of RP development in lung tumor patients.

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OBJECTIVES: Skull base tumors, can cause oculomotor dysfunction, presenting a management challenge given their proximity to cranial nerves. This study investigated the oculomotor outcomes in patients with skull base tumors presenting cranial nerve palsy due to tumor compression and aimed to identify associated factors. METHODS: This retrospective observational cohort study enrolled patients diagnosed with primary skull base tumors who exhibited cranial nerve palsy due to tumor compression, confirmed by magnetic resonance imaging treated at Asan Medical Center between January 2011 and December 2022. Patients were assessed for oculomotor function pre- and post-treatment, and categorized into recovery and non-recovery groups based on outcomes. Factors associated with oculomotor outcomes were also analyzed. RESULTS: Fifty-six patients were enrolled, with the majority (n = 37, 66.1%) demonstrating recovery in oculomotor function post-treatment. The duration from symptom onset to treatment initiation was short in the recovery group, suggesting that early treatment may contribute to improved oculomotor outcomes. The type of tumor was significantly associated with oculomotor outcomes, with patients with pituitary adenoma exhibiting better outcomes. In the recovery group, 19/37 (51.4%) patients underwent surgical resection alone. In contrast, in the non-recovery group, 17/19 (89.5%) patients received primary or adjuvant radiosurgery or radiation therapy. CONCLUSION: Approximately 70% of patients with skull base tumors experienced recovery in oculomotor function post-treatment. The duration before treatment and the type of tumor were significantly associated with the oculomotor outcome. These findings aid neuro-ophthalmologists in predicting oculomotor outcomes for patients with skull base tumors, guiding management strategies for oculomotor dysfunction.

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