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Stereotactic radiosurgery for brain metastasis from cholangiocarcinoma

Ali Haluk Düzkalir, Yavuz Samanci, Cheng-Chia Lee, Huai-Che Yang, Ajay Niranjan, L. Dade Lunsford, Zhishuo Wei, Priyanka N. Srinivasan, Samantha Dayawansa, Jason P. Sheehan, Samir Patel, David Mathieu, Brad E. Zacharia, Brandon Santhumayor, Douglas Kondziolka, and Selcuk Peker

OBJECTIVE

Accounting for approximately 15% of primary liver cancers and 3% of gastrointestinal malignancies, cholangiocarcinoma (CCA) poses a serious health concern given its high mortality rate. Managing brain metastases (BMs) from CCA is challenging because of their rarity and poor prognosis, with little guidance on treatment from the literature. In this study, the authors aimed to evaluate the safety and efficacy of stereotactic radiosurgery (SRS) in managing BMs from CCA.

METHODS

This multicenter retrospective study included 13 CCA patients with 41 BMs treated with SRS from October 2006 to April 2022 at eight institutions affiliated with the International Radiosurgery Research Foundation. Inclusion criteria were a CCA diagnosis, an age over 18 years, no other malignancies, single-fraction SRS treatment for BMs, and at least one follow-up image. Data on demographics, tumor characteristics, treatment details, and outcomes were collected. The primary endpoints were local control (LC), intracranial progression-free survival (PFS), and overall survival (OS). The secondary endpoint was the development of adverse radiation effects (AREs).

RESULTS

The median radiological follow-up was 5 months (range 1–18 months). At the last follow-up, LC was achieved in 39 (95.1%) of 41 BMs. New distant metastases were observed in 3 patients (23.1%), and the mean intracranial PFS was 9.4 months (95% CI 6.5–12.3 months). Six-month and 1-year OS rates were 38.5% and 11.5%, respectively, and the median OS was 6 months (95% CI 4.9–7.2 months). Concurrent immunotherapy was associated with a high risk of local failure (HR 29.665, 95% CI 1.799–489.206, p = 0.018), and the absence of systemic chemotherapy before SRS was linked to reduced OS (HR 6.658, 95% CI 1.173–37.776, p = 0.032). Regarding AREs, only 1 patient (7.7%) experienced right hemiparesis and was treated with corticosteroid therapy.

CONCLUSIONS

SRS is an effective option for managing BMs in CCA patients, showing promise in LC and a high safety profile.

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Stereotactic radiosurgery in the management of skull base chordomas: a comprehensive systematic review and meta-analysis

Seyed Farzad Maroufi, Mohammad Sadegh Fallahi, Mohammadmahdi Sabahi, Seyede Parmis Maroufi, and Jason P. Sheehan

OBJECTIVE

Chordoma is a primary bone tumor with limited literature on its management because of its rarity. Resection, while considered the first-line treatment, does not always provide adequate tumor control. In this systematic review, the authors aimed to provide comprehensive insights by managing these tumors with stereotactic radiosurgery (SRS).

METHODS

A systematic review was conducted according to PRISMA guidelines using the PubMed, Scopus, Web of Science, Embase, and Cochrane Library databases. Search terms included chordoma and radiosurgery and their equivalent terms. Data on baseline characteristics, SRS details, and outcomes were extracted. The Joanna Briggs Institute checklist was used to assess risk of bias. A meta-analysis was performed on relevant variables.

RESULTS

A total of 33 eligible studies encompassing 714 patients with skull base chordomas were included. Most studies had a low risk of bias. Patients, predominantly male (57.37%) with a mean age of 46.54 years, exhibited a conventional chordoma subtype (74.77%) and primary lesions (77.91%), mainly in the clivus (98.04%). The mean lesion volume was 13.49 cm3, and 96.68% of patients had undergone prior surgical attempts. Gamma Knife radiosurgery (88.76%) was the predominant SRS method. Radiologically, 27.19% of patients experienced tumor regression, while 55.02% showed no signs of disease progression at the latest follow-up. Progression occurred after a mean of 48.02 months. Symptom improvement was noted in 27.98% of patients. Radiosurgery was associated with a relatively low overall adverse event rate (11.94%), mainly cranial nerve deficits (8.72%). Meta-regression revealed that age and primary lesion type influenced symptom improvement, while factors like extent of resection, radiotherapy, and SRS type affected adverse event rates.

CONCLUSIONS

This systematic review provides evidence on the safety and effectiveness of radiosurgery in the management of skull base chordomas. Local tumor control was achieved in the majority of patients treated with SRS. Various baseline characteristics and SRS features have been analyzed to identify modifying factors for each outcome to provide a framework for informed decision-making when managing these patients.

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Long-term radiographic and endocrinological outcomes of stereotactic radiosurgery for recurrent or residual nonfunctioning pituitary adenomas

Ahmed Shaaban, Chloé Dumot, Georgios Mantziaris, Sam Dayawansa, Selcuk Peker, Yavuz Samanci, Ahmed M. Nabeel, Wael A. Reda, Sameh R. Tawadros, Khaled Abdel Karim, Amr M. N. El-Shehaby, Reem M. Emad Eldin, Ahmed Ragab Abdelsalam, Roman Liscak, Jaromir May, Elad Mashiach, Fernando De Nigris Vasconcellos, Kenneth Bernstein, Douglas Kondziolka, Herwin Speckter, Ruben Mota, Anderson Brito, Shray K. Bindal, Ajay Niranjan, L. Dade Lunsford, Carolina Gesteira Benjamin, Timoteo Almeida, Jennifer Z. Mao, David Mathieu, Jean-Nicolas Tourigny, Manjul Tripathi, Joshua David Palmer, Jennifer Matsui, Joseph Crooks, Rodney E. Wegner, Matthew J. Shepard, and Jason P. Sheehan

OBJECTIVE

Stereotactic radiosurgery (SRS) is used for the treatment of residual/recurrent nonfunctional pituitary adenoma (NFPA). The aim of this study was to evaluate the factors related to long-term tumor control and delayed endocrinopathies following SRS.

METHODS

This retrospective, multicenter study included patients with recurrent/residual NFPA treated with single-fraction SRS; they were then divided into two arms. The first arm included patients with at least 5 years of radiographic follow-up and all patients with local tumor progression. The second arm included patients with at least 5 years of endocrinological follow-up and all patients who developed endocrinopathy. Study endpoints were tumor control and new or worsening hypopituitarism after SRS and were analyzed using Cox regression and Kaplan-Meier methodology.

RESULTS

There were 360 patients in the tumor control arm (median age 52.7 [IQR 42.9–61] years, 193 [53.6%] males) and 351 patients in the hypopituitarism arm (median age 52.5 [IQR 43–61] years, 186 [53.0%] males). The median follow-up in the tumor control evaluation group was 7.95 (IQR 5.7–10.5) years. Tumor control rates at 5, 8, 10, and 15 years were 93% (95% CI 90%–95%), 87% (95% CI 83%–91%), 86% (95% CI 82%–90%), and 69% (95% CI 59%–81%), respectively. The median follow-up in the endocrinopathy evaluation group was 8 (IQR 5.9–10.7) years. Pituitary function preservation rates at 5, 8, 10, and 15 years were 83% (95% CI 80%–87%), 81% (95% CI 77%–85%), 78% (95% CI 74%–83%), and 71% (95% CI 63%–79%), respectively. A margin dose > 15 Gy (HR 0.8, 95% CI 0.7–0.9; p < 0.001) and a delay from last resection to SRS > 1 year (HR 0.9, 95% CI 0.7–0.9; p = 0.04) were significant factors related to tumor control in multivariable analysis. A maximum dose to the pituitary stalk ≤ 10 Gy (HR 1.1, 95% CI 1.09–1.2; p < 0.001) was associated with pituitary function preservation. New visual deficits after SRS occurred in 7 (1.94%) patients in the tumor control group and 8 (2.3%) patients in the endocrinopathy group. Other new cranial nerve deficits post-SRS occurred in 4 of 160 patients with data in the tumor control group and 3 of 140 patients with data in the endocrinopathy group.

CONCLUSIONS

SRS affords favorable and durable tumor control for the vast majority of NFPAs. Post-SRS hypopituitarism occurs in a minority of patients, but this risk increases with time and warrants long-term follow-up.

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Dural arteriovenous fistulas are not observed to convert to a higher grade after partial embolization

Erin Walker, Anja Srienc, Daphne Lew, Ridhima Guniganti, Giuseppe Lanzino, Waleed Brinjikji, Minako Hayakawa, Edgar A. Samaniego, Colin P. Derdeyn, Rose Du, Rosalind Lai, Jason P. Sheehan, Robert M. Starke, Adib Abla, Ahmed Abdelsalam, Bradley Gross, Felipe Albuquerque, Michael T. Lawton, Louis J. Kim, Michael Levitt, Sepideh Amin-Hanjani, Ali Alaraj, Ethan Winkler, W. Christopher Fox, Adam Polifka, Samuel Hall, Diederik Bulters, Andrew Durnford, Junichiro Satomi, Yoshiteru Tada, J. Marc C. van Dijk, Adriaan R. E. Potgieser, Ching-Jen Chen, Andrea Becerril-Gaitan, Joshua W. Osbun, and Gregory J. Zipfel

OBJECTIVE

Borden-Shucart type I dural arteriovenous fistulas (dAVFs) lack cortical venous drainage and occasionally necessitate intervention depending on patient symptoms. Conversion is the rare transformation of a low-grade dAVF to a higher grade. Factors associated with increased risk of dAVF conversion to a higher grade are poorly understood. The authors hypothesized that partial treatment of type I dAVFs is an independent risk factor for conversion.

METHODS

The multicenter Consortium for Dural Arteriovenous Fistula Outcomes Research database was used to perform a retrospective analysis of all patients with type I dAVFs.

RESULTS

Three hundred fifty-eight (33.2%) of 1077 patients had type I dAVFs. Of those 358 patients, 206 received endovascular treatment and 131 were not treated. Two (2.2%) of 91 patients receiving partial endovascular treatment for a low-grade dAVF experienced conversion to a higher grade, 2 (1.5%) of 131 who were not treated experienced conversion, and none (0%) of 115 patients who received complete endovascular treatment experienced dAVF conversion. The majority of converted dAVFs localized to the transverse-sigmoid sinus and all received embolization as part of their treatment.

CONCLUSIONS

Partial treatment of type I dAVFs does not appear to be significantly associated with conversion to a higher grade.

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Stereotactic radiosurgery with versus without embolization for intracranial dural arteriovenous fistulas: a systematic review and meta-analysis

Seyed Farzad Maroufi, Mohammad Sadegh Fallahi, Moein Ghasemi, and Jason P. Sheehan

OBJECTIVE

Stereotactic radiosurgery (SRS) has been established as a safe and alternative treatment for dural arteriovenous fistulas (dAVFs). While embolization alone is the most commonly used modality for the treatment of dAVFs, the adjunctive use of embolization with SRS, with the growing use of SRS, has gained increasing interest in the past few years. However, the relative efficacy and safety of SRS combined with embolization versus SRS alone for dAVFs remains uncertain. Hence, this systematic review aimed to evaluate the efficacy of SRS with adjunctive embolization for intracranial dAVFs.

METHODS

A systematic review and meta-analysis was conducted by searching electronic databases, including PubMed, Embase, and the Cochrane Library, up to August 2023. All studies evaluating the utilization of adjunctive embolization and SRS for dAVFs were included. Risk of bias was assessed using the Newcastle-Ottawa Scale. A meta-analysis was conducted on the suitable outcomes.

RESULTS

Eighteen studies involving 715 patients were included. The mean age of the participants in the study was 64.30 years in the adjunctive embolization group and 60.51 years in the SRS-alone group. In the adjunctive embolization group 41.3% of patients were female, compared with 47.1% in the SRS-only group. The dAVF obliteration rates were 64.7% and 65.7% in the adjunctive embolization and SRS-alone groups, respectively. These obliteration rates were comparable between the two groups (p = 0.96), as were the symptom improvement rates (p = 0.35). Adverse events were rare, and were more commonly associated with the adjunctive embolization procedure, although further causal analysis was not possible.

CONCLUSIONS

This study provides evidence that adjunctive embolization plus SRS provides similar obliteration and symptom improvement rates compared with SRS alone, with both having very limited SRS-related adverse events. Considering the added burden and adverse events of additional endovascular treatment, the authors recommend embolization be reserved for more complex dAVFs or when embolization can potentially be curative alone or provide more rapid symptomatic relief or protection during the radiosurgical latency period.

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The relevance of biologically effective dose for pain relief and sensory dysfunction after Gamma Knife radiosurgery for trigeminal neuralgia: an 871-patient multicenter study

Ronald E. Warnick, Ian Paddick, David Mathieu, Elizabeth Adam, Christian Iorio-Morin, William Leduc, Andréanne Hamel, Sarah E. Johnson, Mohamad Bydon, Ajay Niranjan, L. Dade Lunsford, Zhishuo Wei, Kaitlin Waite, Shalini Jose, Selcuk Peker, Mustafa Yavuz Samanci, Ece Tek, Georgios Mantziaris, Stylianos Pikis, Jason P. Sheehan, Manjul Tripathi, Narendra Kumar, Juan Diego Alzate, Kenneth Bernstein, Peter Ahorukomeye, Varun R. Kshettry, Herwin Speckter, Wenceslao Hernandez, Dušan Urgošík, Roman Liščák, Andrew I. Yang, John Y. K. Lee, Samir Patel, Dorian M. Kusyk, Matthew J. Shepard, and Douglas Kondziolka

OBJECTIVE

Recent studies have suggested that biologically effective dose (BED) is an important correlate of pain relief and sensory dysfunction after Gamma Knife radiosurgery (GKRS) for trigeminal neuralgia (TN). The goal of this study was to determine if BED is superior to prescription dose in predicting outcomes in TN patients undergoing GKRS as a first procedure.

METHODS

This was a retrospective study of 871 patients with type 1 TN from 13 GKRS centers. Patient demographics, pain characteristics, treatment parameters, and outcomes were reviewed. BED was compared with prescription dose and other dosimetric factors for their predictive value.

RESULTS

The median age of the patients was 68 years, and 60% were female. Nearly 70% of patients experienced pain in the V2 and/or V3 dermatomes, predominantly on the right side (60%). Most patients had modified BNI Pain Intensity Scale grade IV or V pain (89.2%) and were taking 1 or 2 pain medications (74.1%). The median prescription dose was 80 Gy (range 62.5–95 Gy). The proximal trigeminal nerve was targeted in 77.9% of cases, and the median follow-up was 21 months (range 6–156 months). Initial pain relief (modified BNI Pain Intensity Scale grades I–IIIa) was noted in 81.8% of evaluable patients at a median of 30 days. Of 709 patients who achieved initial pain relief, 42.3% experienced at least one pain recurrence after GKRS at a median of 44 months, with 49.0% of these patients undergoing a second procedure. New-onset facial numbness occurred in 25.3% of patients after a median of 8 months. Age ≥ 63 years was associated with a higher probability of both initial pain relief and maintaining pain relief. A distal target location was associated with a higher probability of initial and long-term pain relief, but also a higher incidence of sensory dysfunction. BED ≥ 2100 Gy2.47 was predictive of pain relief at 30 days and 1 year for the distal target, whereas physical dose ≥ 85 Gy was significant for the proximal target, but the restricted range of BED values in this subgroup could be a confounding factor. A maximum brainstem point dose ≥ 29.5 Gy was associated with a higher probability of bothersome facial numbness.

CONCLUSIONS

BED and physical dose were both predictive of pain relief and could be used as treatment planning goals for distal and proximal targets, respectively, while considering maximum brainstem point dose < 29.5 Gy as a potential constraint for bothersome numbness.

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Repeat stereotactic radiosurgery for persistent cerebral arteriovenous malformations in pediatric patients

Gracie Garcia, Georgios Mantziaris, Stylianos Pikis, Chloe Dumot, L. Dade Lunsford, Ajay Niranjan, Zhishuo Wei, Priyanka Srinivasan, Lilly W. Tang, Roman Liscak, Jaromir May, Cheng-Chia Lee, Huai-Che Yang, Selcuk Peker, Yavuz Samanci, Ahmed M. Nabeel, Wael A. Reda, Sameh R. Tawadros, Khaled Abdel Karim, Amr M. N. El-Shehaby, Reem Emad Eldin, Ahmed Hesham Elazzazi, Nuria Martínez Moreno, Roberto Martínez Álvarez, Varun Padmanaban, Francis J. Jareczek, James McInerney, Kevin M. Cockroft, Juan Diego Alzate, Douglas Kondziolka, Manjul Tripathi, and Jason P. Sheehan

OBJECTIVE

The purpose of this study was to describe the long-term outcomes and associated risks related to repeat stereotactic radiosurgery (SRS) for persistent arteriovenous malformations (AVMs) in pediatric patients.

METHODS

Under the auspices of the International Radiosurgery Research Foundation, this retrospective multicenter study analyzed pediatric patients who underwent repeat, single-session SRS between 1987 and 2022. The primary outcome variable was a favorable outcome, defined as nidus obliteration without hemorrhage or neurological deterioration. Secondary outcomes included rates and probabilities of hemorrhage, radiation-induced changes (RICs), and cyst or tumor formation.

RESULTS

The cohort included 83 pediatric patients. The median patient age was 11 years at initial SRS and 15 years at repeat SRS. Fifty-seven children (68.7%) were managed exclusively using SRS, and 42 (50.6%) experienced hemorrhage prior to SRS. Median AVM diameter and volume were substantially different between the first (25 mm and 4.5 cm3, respectively) and second (16.5 mm and 1.6 cm3, respectively) SRS, while prescription dose and isodose line remained similar. At the 5-year follow-up evaluation from the second SRS, nidus obliteration was achieved in 42 patients (50.6%), with favorable outcome in 37 (44.6%). The median time to nidus obliteration and hemorrhage was 35.5 and 38.5 months, respectively. The yearly cumulative probability of favorable outcome increased from 2.5% (95% CI 0.5%–7.8%) at 1 year to 44% (95% CI 32%–55%) at 5 years. The probability of achieving obliteration followed a similar pattern and reached 51% (95% CI 38%–62%) at 5 years. The 5-year risk of hemorrhage during the latency period after the second SRS reached 8% (95% CI 3.2%–16%). Radiographically, 25 children (30.1%) had RICs, but only 5 (6%) were symptomatic. Delayed cyst formation occurred in 7.2% of patients, with a median onset of 47 months. No radiation-induced neoplasia was observed.

CONCLUSIONS

The study results showed nidus obliteration in most pediatric patients who underwent repeat SRS for persistent AVMs. The risks of symptomatic RICs and latency period hemorrhage were quite low. These findings suggest that repeat radiosurgery should be considered when treating pediatric patients with residual AVM after prior SRS. Further study is needed to define the role of repeat SRS more fully in this population.

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Pediatric cerebral cavernous malformations and stereotactic radiosurgery: an analysis of 50 cases from a multicentric study

Georgios Mantziaris, Chloe Dumot, Stylianos Pikis, Selcuk Peker, Yavuz Samanci, Gokce D. Ardor, Ahmed M. Nabeel, Wael A. Reda, Sameh R. Tawadros, Khaled Abdel Karim, Amr M. N. El-Shehaby, Reem M. Emad Eldin, Ahmed H. Elazzazi, Darrah Sheehan, Kimball Sheehan, Nuria Martínez Moreno, Roberto Martínez Álvarez, Roman Liscak, Jaromir May, Manjul Tripathi, Akshay Rajput, Narendra Kumar, Rupinder Kaur, Juan Diego Alzate, Douglas Kondziolka, Sam Dayawansa, and Jason P. Sheehan

OBJECTIVE

Cerebral cavernous malformations (CCMs) are the second most common vascular anomaly affecting the CNS in children. Although stereotactic radiosurgery (SRS) has been proposed as an alternative to microsurgery in the management of selected cases in adults, there is a paucity of studies focusing on pediatric patients. The aim of this study was to present the outcomes and associated risks of SRS in this subgroup of patients.

METHODS

This retrospective multicenter study included pediatric patients treated with single-session SRS for CCMs. The annual hemorrhage rate (AHR) was calculated before and after SRS in hemorrhagic lesions. The Engel classification was used to describe post-SRS epileptic control. Adverse radiation effects (AREs) and the occurrence of new neurological deficits were recorded.

RESULTS

The study included 50 patients (median age 15.1 [IQR 5.6] years) harboring 62 CCMs. Forty-two (84%) and 22 (44%) patients had a history of hemorrhage or epilepsy prior to SRS, respectively. The AHR from diagnosis to SRS excluding the first hemorrhage was 7.19 per 100 CCM-years, dropping to 3.15 per 100 CCM-years after treatment. The cumulative risk of first hemorrhage after SRS was 7.4% (95% CI 0%–14.3%) at 5 years and 23.6% (95% CI 0%–42.2%) at 10 years. Eight hemorrhagic events involving 6 CCMs in 6 patients were recorded in the post-SRS follow-up period; 4 patients presented with transient symptoms and 4 with permanent symptoms. Of the 22 patients with pre-SRS seizures, 11 were seizure free at the last follow-up (Engel class I), 6 experienced improvement (Engel class II or III), 5 had no improvement (Engel class IVA or IVB), and 1 experienced worsening (Engel class IVC). Radiographic AREs were documented in 14.5% (9/62) of CCMs, with 4 being symptomatic.

CONCLUSIONS

Single-session SRS reduces the CCM hemorrhage rate in the pediatric population and provides adequate seizure control.

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Effect of cerebral arteriovenous malformation location on outcomes of repeat, single-fraction stereotactic radiosurgery: a matched-cohort analysis

Georgios Mantziaris, Stylianos Pikis, Chloe Dumot, Sam Dayawansa, Roman Liscak, Jaromir May, Cheng-Chia Lee, Huai-Che Yang, Nuria Martínez Moreno, Roberto Martinez Álvarez, L. Dade Lunsford, Ajay Niranjan, Zhishuo Wei, Priyanka Srinivasan, Lilly W. Tang, Ahmed M. Nabeel, Wael A. Reda, Sameh R. Tawadros, Khaled Abdel Karim, Amr M. N. El-Shehaby, Reem M. Emad Eldin, Ahmed Hesham Elazzazi, Selcuk Peker, Yavuz Samanci, Varun Padmanaban, Francis J. Jareczek, James McInerney, Kevin M. Cockroft, David Mathieu, Salman Aldakhil, Juan Diego Alzate, Douglas Kondziolka, Manjul Tripathi, Joshua D. Palmer, Rituraj Upadhyay, Michelle Lin, Gabriel Zada, Cheng Yu, Christopher P. Cifarelli, Daniel T. Cifarelli, Ahmed Shaaban, Zhiyuan Xu, and Jason P. Sheehan

OBJECTIVE

Patients with deep-seated arteriovenous malformations (AVMs) have a higher rate of unfavorable outcome and lower rate of nidus obliteration after primary stereotactic radiosurgery (SRS). The aim of this study was to evaluate and quantify the effect of AVM location on repeat SRS outcomes.

METHODS

This retrospective, multicenter study involved 505 AVM patients managed with repeat, single-session SRS. The endpoints were nidus obliteration, hemorrhage in the latency period, radiation-induced changes (RICs), and favorable outcome. Patients were split on the basis of AVM location into the deep (brainstem, basal ganglia, thalamus, deep cerebellum, and corpus callosum) and superficial cohorts. The cohorts were matched 1:1 on the basis of the covariate balancing score for volume, eloquence of location, and prescription dose.

RESULTS

After matching, 149 patients remained in each cohort. The 5-year cumulative probability rates for favorable outcome (probability difference −18%, 95% CI −30.9 to −5.8%, p = 0.004) and AVM obliteration (probability difference –18%, 95% CI –30.1% to −6.4%, p = 0.007) were significantly lower in the deep AVM cohort. No significant differences were observed in the 5-year cumulative probability rates for hemorrhage (probability difference 3%, 95% CI –2.4% to 8.5%, p = 0.28) or RICs (probability difference 1%, 95% CI –10.6% to 11.7%, p = 0.92). The median time to delayed cyst formation was longer with deep-seated AVMs (deep 62 months vs superficial 12 months, p = 0.047).

CONCLUSIONS

AVMs located in deep regions had significantly lower favorable outcomes and obliteration rates compared with superficial lesions after repeat SRS. Although the rates of hemorrhage in the latency period and RICs in the two cohorts were comparable, delayed cyst formation occurred later in patients with deep-seated AVMs.

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Clinical outcomes following stereotactic radiosurgery for cerebral cavernous malformations of the basal ganglia and thalamus

Raj Singh, Chloe Dumot, Georgios Mantziaris, Sam Dayawansa, Zhiyuan Xu, Stylianos Pikis, Selcuk Peker, Yavuz Samanci, Gokce D. Ardor, Ahmed M. Nabeel, Wael A. Reda, Sameh R. Tawadros, Khaled Abdel Karim, Amr M. N. El-Shehaby, Reem M. Emad Eldin, Darrah Sheehan, Kimball Sheehan, Ahmed H. Elazzazi, Nuria Martínez Moreno, Roberto Martínez Álvarez, Roman Liscak, Jaromir May, David Mathieu, Jean-Nicolas Tourigny, Manjul Tripathi, Akshay Rajput, Narendra Kumar, Rupinder Kaur, Piero Picozzi, Andrea Franzini, Herwin Speckter, Wenceslao Hernandez, Anderson Brito, Ronald E. Warnick, Juan Diego Alzate, Douglas Kondziolka, Greg N. Bowden, Samir Patel, and Jason P. Sheehan

OBJECTIVE

There are few reports of outcomes following stereotactic radiosurgery (SRS) for the management of cerebral cavernous malformations (CCMs) of the basal ganglia or thalamus. Therefore, the authors aimed to clarify these outcomes.

METHODS

Centers participating in the International Radiosurgery Research Foundation were queried for CCM cases managed with SRS from October 2001 to February 2021. The primary outcome of interest was hemorrhage-free survival (HFS) with a secondary outcome of symptomatic adverse radiation events (AREs). Assessment of the association of prognostic factors with HFS was conducted via Kaplan-Meier analysis and log-rank test. Chi-square tests were conducted to assess potential factors associated with the incidence of AREs.

RESULTS

Seventy-three patients were identified. The median patient age was 43.5 years (range 4.4–79.5 years). Fifty-nine (80.8%) patients had hemorrhage prior to SRS. The median treatment volume was 0.9 cm3 (range 0.07–10.1 cm3) with a median margin prescription dose (MPD) of 12 Gy (range 10–20 Gy). One-, 3-, 5-, and 10-year HFS were 93.0%, 89.9%, 89.9%, and 83.0%, respectively, with one hemorrhage-related death approximately 1 year after SRS and nearly 60% and 30% of patients having improvement or stability of symptoms, respectively. There was no correlation between lesion size or MPD and HFS. Seven (9.6%) patients experienced AREs (MPDs > 12 Gy in all cases). Lesion size > 1.0 cm3 was correlated with the incidence of an ARE (p = 0.019). Forty-two (93.3%) of 45 patients treated with an MPD ≤ 12 Gy experienced neither hemorrhage nor AREs following SRS versus 17 (60.7%) of 28 patients treated with an MPD > 12 Gy (p = 0.0006).

CONCLUSIONS

SRS is a reasonable treatment strategy and confers clinical stability or improvement and hemorrhage avoidance in patients harboring CCMs of the basal ganglia or thalamus. An MPD of approximately 12 Gy is recommended for the management of CCM.