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Stereotactic radiosurgery for intracranial chordomas: an international multiinstitutional study

Stylianos Pikis, Georgios Mantziaris, Selcuk Peker, Yavuz Samanci, Ahmed M. Nabeel, Wael A. Reda, Sameh R. Tawadros, Amr M. N. El-Shehaby, Khaled Abdelkarim, Reem M. Emad Eldin, Darrah Sheehan, Kimball Sheehan, Roman Liscak, Tomas Chytka, Manjul Tripathi, Renu Madan, Herwin Speckter, Wenceslao Hernández, Gene H. Barnett, Yusuke S. Hori, Nisha Dabhi, Salman Aldakhil, David Mathieu, Douglas Kondziolka, Kenneth Bernstein, Zhishuo Wei, Ajay Niranjan, Charles R. Kersh, L. Dade Lunsford, and Jason P. Sheehan

OBJECTIVE

The object of this study was to evaluate the safety, efficacy, and long-term outcomes of stereotactic radiosurgery (SRS) in the management of intracranial chordomas.

METHODS

This retrospective multicenter study involved consecutive patients managed with single-session SRS for an intracranial chordoma at 10 participating centers. Radiological and neurological outcomes were assessed after SRS, and predictive factors were evaluated via statistical methodology.

RESULTS

A total of 93 patients (56 males [60.2%], mean age 44.8 years [SD 16.6]) underwent single-session SRS for intracranial chordoma. SRS was utilized as adjuvant treatment in 77 (82.8%) cases, at recurrence in 13 (14.0%) cases, and as primary treatment in 3 (3.2%) cases. The mean tumor volume was 8 cm3 (SD 7.3), and the mean prescription volume was 9.1 cm3 (SD 8.7). The mean margin and maximum radiosurgical doses utilized were 17 Gy (SD 3.6) and 34.2 Gy (SD 6.4), respectively. On multivariate analysis, treatment failure due to tumor progression (p = 0.001) was associated with an increased risk for post-SRS neurological deterioration, and a maximum dose > 29 Gy (p = 0.006) was associated with a decreased risk. A maximum dose > 29 Gy was also associated with improved local tumor control (p = 0.02), whereas the presence of neurological deficits prior to SRS (p = 0.04) and an age > 65 years at SRS (p = 0.03) were associated with worse local tumor control. The 5- and 10-year tumor progression-free survival rates were 54.7% and 34.7%, respectively. An age > 65 years at SRS (p = 0.01) was associated with decreased overall survival. The 5- and 10-year overall survival rates were 83% and 70%, respectively.

CONCLUSIONS

SRS appears to be a safe and relatively effective adjuvant management option for intracranial chordomas. The best outcomes were obtained in younger patients without significant neurological deficits. Further well-designed studies are necessary to define the best timing for the use of SRS in the multidisciplinary management of intracranial chordomas.

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Imaging-defined necrosis after treatment with single-fraction stereotactic radiosurgery and immune checkpoint inhibitors and its potential association with improved outcomes in patients with brain metastases: an international multicenter study of 697 patients

Eric J. Lehrer, Manmeet S. Ahluwalia, Jason Gurewitz, Kenneth Bernstein, Douglas Kondziolka, Ajay Niranjan, Zhishuo Wei, L. Dade Lunsford, Kareem R. Fakhoury, Chad G. Rusthoven, David Mathieu, Claire Trudel, Timothy D. Malouff, Henry Ruiz-Garcia, Phillip Bonney, Lindsay Hwang, Cheng Yu, Gabriel Zada, Samir Patel, Christopher P. Deibert, Piero Picozzi, Andrea Franzini, Luca Attuati, Rahul N. Prasad, Raju R. Raval, Joshua D. Palmer, Cheng-Chia Lee, Huai-Che Yang, Brianna M. Jones, Sheryl Green, Jason P. Sheehan, and Daniel M. Trifiletti

OBJECTIVE

Immune checkpoint inhibitors (ICIs) and stereotactic radiosurgery (SRS) are commonly utilized in the management of brain metastases. Treatment-related imaging changes (TRICs) are a frequently observed clinical manifestation and are commonly classified as imaging-defined radiation necrosis. However, these findings are not well characterized and may predict a response to SRS and ICIs. The objective of this study was to investigate predictors of TRICs and their impact on patient survival.

METHODS

This retrospective multicenter cohort study was conducted through the International Radiosurgery Research Foundation. Member institutions submitted de-identified clinical and dosimetric data for patients with non–small cell lung cancer (NSCLC), melanoma, and renal cell carcinoma (RCC) brain metastases that had been treated with SRS and ICIs. Data were collected from March 2020 to February 2021. Univariable and multivariable Cox and logistic regression analyses were performed. The Kaplan-Meier method was used to evaluate overall survival (OS). The diagnosis-specific graded prognostic assessment was used to guide variable selection. TRICs were determined on the basis of MRI, PET/CT, or MR spectroscopy, and consensus by local clinical providers was required.

RESULTS

The analysis included 697 patients with 4536 brain metastases across 11 international institutions in 4 countries. The median follow-up after SRS was 13.6 months. The median age was 66 years (IQR 58–73 years), 54.1% of patients were male, and 57.3%, 36.3%, and 6.4% of tumors were NSCLC, melanoma, and RCC, respectively. All patients had undergone single-fraction radiosurgery to a median margin dose of 20 Gy (IQR 18–20 Gy). TRICs were observed in 9.8% of patients. The median OS for all patients was 24.5 months. On univariable analysis, Karnofsky Performance Status (KPS; HR 0.98, p < 0.001), TRICs (HR 0.67, p = 0.03), female sex (HR 0.67, p < 0.001), and prior resection (HR 0.60, p = 0.03) were associated with improved OS. On multivariable analysis, KPS (HR 0.98, p < 0.001) and TRICs (HR 0.66, p = 0.03) were associated with improved OS. A brain volume receiving ≥ 12 Gy of radiation (V12Gy) ≥ 10 cm3 (OR 2.78, p < 0.001), prior whole-brain radiation therapy (OR 3.46, p = 0.006), and RCC histology (OR 3.10, p = 0.01) were associated with an increased probability of developing TRICs. The median OS rates in patients with and without TRICs were 29.0 and 23.1 months, respectively (p = 0.03, log-rank test).

CONCLUSIONS

TRICs following ICI and SRS were associated with a median OS benefit of approximately 6 months in this retrospective multicenter study. Further prospective study and additional stratification are needed to validate these findings and further elucidate the role and etiology of this common clinical scenario.

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Stereotactic radiosurgery for treatment of radiation-induced meningiomas: a multiinstitutional study

Adomas Bunevicius, Mohand Suleiman, Samir Patel, Roberto Martínez Álvarez, Nuria E. Martinez Moreno, Roman Liscak, Jaromir Hanuska, Anne-Marie Langlois, David Mathieu, Christine Mau, Catherine Caldwell, Leonard C. Tuanquin, Brad E. Zacharia, James McInerney, Cheng-Chia Lee, Huai-Che Yang, Jennifer L. Peterson, Daniel M. Trifiletti, Akiyoshi Ogino, Hideyuki Kano, Ronald E. Warnick, Anissa Saylany, Love Y. Buch, John Y. K. Lee, Ben A. Strickland, Gabriel Zada, Eric L. Chang, L. Dade Lunsford, and Jason Sheehan

OBJECTIVE

Radiation-induced meningiomas (RIMs) are associated with aggressive clinical behavior. Stereotactic radiosurgery (SRS) is sometimes considered for selected RIMs. The authors investigated the effectiveness and safety of SRS for the management of RIMs.

METHODS

From 12 institutions participating in the International Radiosurgery Research Foundation, the authors pooled patients who had prior cranial irradiation and were subsequently clinically diagnosed with WHO grade I meningiomas that were managed with SRS.

RESULTS

Fifty-two patients underwent 60 SRS procedures for histologically confirmed or radiologically suspected WHO grade I RIMs. The median ages at initial cranial radiation therapy and SRS for RIM were 5.5 years and 39 years, respectively. The most common reasons for cranial radiation therapy were leukemia (21%) and medulloblastoma (17%). There were 39 multiple RIMs (35%), the mean target volume was 8.61 ± 7.80 cm3, and the median prescription dose was 14 Gy. The median imaging follow-up duration was 48 months (range 4–195 months). RIM progressed in 9 patients (17%) at a median duration of 30 months (range 3–45 months) after SRS. Progression-free survival at 5 years post-SRS was 83%. Treatment volume ≥ 5 cm3 predicted progression (HR 8.226, 95% CI 1.028–65.857, p = 0.047). Seven patients (14%) developed new neurological symptoms or experienced SRS-related complications or T2 signal change from 1 to 72 months after SRS.

CONCLUSIONS

SRS is associated with durable local control of RIMs in the majority of patients and has an acceptable safety profile. SRS can be considered for patients and tumors that are deemed suboptimal, poor surgical candidates, and those whose tumor again progresses after removal.

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Hypopituitarism after Gamma Knife radiosurgery for pituitary adenomas: a multicenter, international study

Diogo Cordeiro, Zhiyuan Xu, Gautam U. Mehta, Dale Ding, Mary Lee Vance, Hideyuki Kano, Nathaniel Sisterson, Huai-che Yang, Douglas Kondziolka, L. Dade Lunsford, David Mathieu, Gene H. Barnett, Veronica Chiang, John Lee, Penny Sneed, Yan-Hua Su, Cheng-chia Lee, Michal Krsek, Roman Liscak, Ahmed M. Nabeel, Amr El-Shehaby, Khaled Abdel Karim, Wael A. Reda, Nuria Martinez-Moreno, Roberto Martinez-Alvarez, Kevin Blas, Inga Grills, Kuei C. Lee, Mikulas Kosak, Christopher P. Cifarelli, Gennadiy A. Katsevman, and Jason P. Sheehan

OBJECTIVE

Recurrent or residual adenomas are frequently treated with Gamma Knife radiosurgery (GKRS). The most common complication after GKRS for pituitary adenomas is hypopituitarism. In the current study, the authors detail the timing and types of hypopituitarism in a multicenter, international cohort of pituitary adenoma patients treated with GKRS.

METHODS

Seventeen institutions pooled clinical data obtained from pituitary adenoma patients who were treated with GKRS from 1988 to 2016. Patients who had undergone prior radiotherapy were excluded. A total of 1023 patients met the study inclusion criteria. The treated lesions included 410 nonfunctioning pituitary adenomas (NFPAs), 262 cases of Cushing’s disease (CD), and 251 cases of acromegaly. The median follow-up was 51 months (range 6–246 months). Statistical analysis was performed using a Cox proportional hazards model to evaluate factors associated with the development of new-onset hypopituitarism.

RESULTS

At last follow-up, 248 patients had developed new pituitary hormone deficiency (86 with NFPA, 66 with CD, and 96 with acromegaly). Among these patients, 150 (60.5%) had single and 98 (39.5%) had multiple hormone deficiencies. New hormonal changes included 82 cortisol (21.6%), 135 thyrotropin (35.6%), 92 gonadotropin (24.3%), 59 growth hormone (15.6%), and 11 vasopressin (2.9%) deficiencies. The actuarial 1-year, 3-year, 5-year, 7-year, and 10-year rates of hypopituitarism were 7.8%, 16.2%, 22.4%, 27.5%, and 31.3%, respectively. The median time to hypopituitarism onset was 39 months.

In univariate analyses, an increased rate of new-onset hypopituitarism was significantly associated with a lower isodose line (p = 0.006, HR = 8.695), whole sellar targeting (p = 0.033, HR = 1.452), and treatment of a functional pituitary adenoma as compared with an NFPA (p = 0.008, HR = 1.510). In multivariate analyses, only a lower isodose line was found to be an independent predictor of new-onset hypopituitarism (p = 0.001, HR = 1.38).

CONCLUSIONS

Hypopituitarism remains the most common unintended effect of GKRS for a pituitary adenoma. Treating the target volume at an isodose line of 50% or greater and avoiding whole-sellar radiosurgery, unless necessary, will likely mitigate the risk of post-GKRS hypopituitarism. Follow-up of these patients is required to detect and treat latent endocrinopathies.

Open access

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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Stereotactic radiosurgery for Koos grade IV vestibular schwannoma: a multi-institutional study

Stylianos Pikis, Georgios Mantziaris, Rithika Kormath Anand, Ahmed M. Nabeel, Darrah Sheehan, Kimball Sheehan, Wael A. Reda, Sameh R. Tawadros, Khaled Abdelkarim, Amr M. N. El-Shehaby, Reem Emad Eldin, Selcuk Peker, Yavuz Samanci, Tehila Kaisman-Elbaz, Herwin Speckter, Wenceslao Hernández, Julio Isidor, Manjul Tripathi, Renu Madan, Brad E. Zacharia, Lekhaj C. Daggubati, Nuria Martínez Moreno, Roberto Martínez Álvarez, Anne-Marie Langlois, David Mathieu, Christopher P. Deibert, Vivek R. Sudhakar, Christopher P. Cifarelli, Denisse Arteaga Icaza, Daniel T. Cifarelli, Zhishuo Wei, Ajay Niranjan, Gene H. Barnett, L. Dade Lunsford, Greg N. Bowden, and Jason P. Sheehan

OBJECTIVE

Though stereotactic radiosurgery (SRS) is an established safe treatment for small- and medium-sized vestibular schwannomas (VSs), its role in the management of Koos grade IV VS is still unclear. In this retrospective multicenter study, the authors evaluated tumor control and the patient outcomes of primary, single-session SRS treatment for Koos grade IV VS.

METHODS

This study included patients treated with primary, single-session SRS for Koos grade IV VS at 10 participating centers. Only those patients presenting with non–life-threatening or incapacitating symptoms and at least 12 months of clinical and neuroimaging follow-up were eligible for inclusion. Relevant data were collected, and the Kaplan-Meier method was used to perform time-dependent analysis for post-SRS tumor control, hearing preservation, and facial nerve function preservation. Univariate and multivariate analyses were performed for outcome measures using Cox regression analysis.

RESULTS

Six hundred twenty-seven patients (344 females, median patient age 54 [IQR 22] years) treated with primary SRS were included in this study. The median tumor volume was 8.7 (IQR 5) cm3. Before SRS, serviceable hearing, facial nerve weakness (House-Brackmann grade > I), and trigeminal neuropathy were present in 205 (33%), 48 (7.7%), and 203 (32.4%) patients, respectively. The median prescription dose was 12 (IQR 1) Gy. At a median radiological follow-up of 38 (IQR 54) months, tumor control was achieved in 94.1% of patients. Early tumor expansion occurred in 67 (10.7%) patients and was associated with a loss of tumor control at the last follow-up (p = 0.001). Serviceable hearing preservation rates at the 5- and 10-year follow-ups were 65% and 44.6%, respectively. Gardner-Robertson class > 1 (p = 0.003) and cochlear dose ≥ 4 Gy (p = 0.02) were risk factors for hearing loss. Facial nerve function deterioration occurred in 19 (3.0%) patients at the last follow-up and was associated with margin doses ≥ 13 Gy (p = 0.03) and early tumor expansion (p = 0.04). Post-SRS, 33 patients developed hydrocephalus requiring shunting. Adverse radiation effects occurred in 92 patients and were managed medically or surgically in 34 and 18 cases, respectively.

CONCLUSIONS

SRS is a safe and effective method of obtaining tumor control in patients with Koos grade IV VS presenting with non–life-threatening or debilitating symptoms, especially those with surgical comorbidities that contraindicate resection. To decrease the incidence of post-SRS facial palsy, a prescription dose < 13 Gy is recommended.

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Local control and survival after stereotactic radiosurgery for colorectal cancer brain metastases: an international multicenter analysis

Othman Bin-Alamer, Hussam Abou-Al-Shaar, Raj Singh, Arka N. Mallela, Andrew Legarreta, Greg Bowden, David Mathieu, Haley K. Perlow, Joshua D. Palmer, Shahed Elhamdani, Matthew Shepard, Yun Liang, Ahmed M. Nabeel, Wael A. Reda, Sameh R. Tawadros, Khaled Abdelkarim, Amr M. N. El-Shehaby, Reem Emad Eldin, Ahmed Hesham Elazzazi, Ronald E. Warnick, Yair M. Gozal, Megan Daly, Brendan McShane, Marcel Addis-Jackson, Gokul Karthikeyan, Sian Smith, Piero Picozzi, Andrea Franzini, Tehila Kaisman-Elbaz, Huai-che Yang, Judith Hess, Kelsey Templeton, Xiaoran Zhang, Zhishuo Wei, Stylianos Pikis, Georgios Mantziaris, Gabriela Simonova, Roman Liscak, Selcuk Peker, Yavuz Samanci, Veronica Chiang, Charles R. Kersh, Cheng-Chia Lee, Daniel M. Trifiletti, Ajay Niranjan, Constantinos G. Hadjipanayis, L. Dade Lunsford, and Jason P. Sheehan

OBJECTIVE

The goal of this study was to characterize local tumor control (LC), overall survival (OS), and safety of stereotactic radiosurgery for colorectal brain metastasis (CRBM).

METHODS

Ten international institutions participating in the International Radiosurgery Research Foundation provided data for this retrospective case series. This study included 187 patients with CRBM (281 tumors), with a median age of 62 years and 56.7% being male. Most patients (53.5%) had solitary tumors, although 10.7% had > 5 tumors. The median tumor volume was 2.7 cm3 (IQR 0.22–8.1 cm3), and the median margin dose was 20 Gy (IQR 18–22 Gy).

RESULTS

The 3-year LC and OS rates were 72% and 20%, respectively. Symptomatic adverse radiation effects occurred in 1.6% of patients. In the multivariate analysis, age > 65 years and tumor volume > 4.0 cm3 were significant predictors of tumor progression (hazard ratio [HR] 2.6, 95% CI 1.4–4.9; p = 0.003 and HR 3.4, 95% CI 1.7–6.9; p < 0.001, respectively). Better performance status (Karnofsky Performance Scale score > 80) was associated with a reduced risk of tumor progression (HR 0.38, 95% CI 0.19–0.73; p = 0.004). Patient age > 62 years (HR 1.6, 95% CI 1.1–2.3; p = 0.03) and the presence of active extracranial disease (HR 1.7, 95% CI 1.1–2.4; p = 0.009) were significantly associated with worse OS.

CONCLUSIONS

Stereotactic radiosurgery offers a high LC rate and a low rate of symptomatic adverse radiation effects for the majority of CRBMs. The OS and LC favored younger patients with high functional performance scores and inactive extracranial disease.

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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.

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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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Persistent postconcussive symptoms in children and adolescents with mild traumatic brain injury receiving initial head computed tomography

Lennart Riemann, Daphne C. Voormolen, Katrin Rauen, Klaus Zweckberger, Andreas Unterberg, Alexander Younsi, and the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Investigators and Participants

OBJECTIVE

The aim of this paper was to evaluate the prevalence of postconcussive symptoms and their relation to health-related quality of life (HRQOL) in pediatric and adolescent patients with mild traumatic brain injury (mTBI) who received head CT imaging during initial assessment.

METHODS

Patients aged between 5 and 21 years with mTBI (Glasgow Coma Scale scores 13–15) and available Rivermead Post Concussion Questionnaire (RPQ) at 6 months of follow-up in the multicenter, prospectively collected CENTER-TBI (Collaborative European NeuroTrauma Effectiveness Research in TBI) study were included. The prevalence of postconcussive symptoms was assessed, and the occurrence of postconcussive syndrome (PSC) based on the ICD-10 criteria, was analyzed. HRQOL was compared in patients with and without PCS using the Quality of Life after Brain Injury (QOLIBRI) questionnaire.

RESULTS

A total of 196 adolescent or pediatric mTBI patients requiring head CT imaging were included. High-energy trauma was prevalent in more than half of cases (54%), abnormalities on head CT scans were detected in 41%, and admission to the regular ward or intensive care unit was necessary in 78%. Six months postinjury, 36% of included patients had experienced at least one moderate or severe symptom on the RPQ. PCS was present in 13% of adolescents and children when considering symptoms of at least moderate severity, and those patients had significantly lower QOLIBRI total scores, indicating lower HRQOL, compared with young patients without PCS (57 vs 83 points, p < 0.001).

CONCLUSIONS

Adolescent and pediatric mTBI patients requiring head CT imaging show signs of increased trauma severity. Postconcussive symptoms are present in up to one-third of those patients, and PCS can be diagnosed in 13% 6 months after injury. Moreover, PCS is significantly associated with decreased HRQOL.