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Roman O. Kowalchuk, Ajay Niranjan, Judith Hess, Joseph P. Antonios, Michael Y. Zhang, Steve Braunstein, Richard B. Ross, Stylianos Pikis, Christopher P. Deibert, Cheng-chia Lee, Huai-che Yang, Anne-Marie Langlois, David Mathieu, Selcuk Peker, Yavuz Samanci, Chad G. Rusthoven, Veronica Chiang, Zhishuo Wei, L. Dade Lunsford, Daniel M. Trifiletti, and Jason P. Sheehan

OBJECTIVE

Stereotactic radiosurgery (SRS) is an effective treatment for intracranial metastatic disease, but its role in triple-negative breast cancer requires further study. Herein, the authors report overall survival (OS) and local tumor control in a multiinstitutional cohort with triple-negative breast cancer metastases treated with SRS.

METHODS

Patients treated from 2010 to 2019 at 9 institutions were included in this retrospective study if they had biopsy-proven triple-negative breast cancer with intracranial metastatic lesions treated with SRS. Patients were excluded if they had undergone prior SRS, whole-brain radiation therapy, or resection of the metastatic lesions. A retrospective chart review was conducted to determine OS, local control, and treatment efficacy.

RESULTS

Sixty-eight patients with 315 treated lesions were assessed. Patients had a median Karnofsky Performance Status of 80 (IQR 70–90) and age of 57 years (IQR 48–67 years). Most treated patients had 5 or fewer intracranial lesions, with 34% of patients having a single lesion. Treated lesions were small, having a median volume owf 0.11 cm3 (IQR 0.03–0.60 cm3). Patients were treated with a median margin dose of 18 Gy (IQR 18–20 Gy) to the median 71% isodose line (IQR 50%–84%). Overall, patients had a 1-year OS of 43% and 2-year OS of 20%. Most patients (88%) were followed until death, by which time local tumor progression had occurred in only 7% of cases. Furthermore, 76% of the lesions demonstrated regression. Tumor volume was correlated with local tumor progression (p = 0.012). SRS was very well tolerated, and only 3 patients (5%) developed symptomatic radiation necrosis.

CONCLUSIONS

SRS is a safe and efficacious treatment for well-selected patients with triple-negative breast cancer, especially for those with a favorable performance status and small- to moderate-volume metastatic lesions.

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Georgios Mantziaris, Stylianos Pikis, Tomas Chytka, Roman Liščák, Kimball Sheehan, Darrah Sheehan, Selcuk Peker, Yavuz Samanci, Shray K. Bindal, Ajay Niranjan, L. Dade Lunsford, Rupinder Kaur, Renu Madan, Manjul Tripathi, Dhiraj J. Pangal, Ben A. Strickland, Gabriel Zada, Anne-Marie Langlois, David Mathieu, Ronald E. Warnick, Samir Patel, Zayda Minier, Herwin Speckter, Zhiyuan Xu, Rithika Kormath Anand, and Jason P. Sheehan

OBJECTIVE

Radiological progression occurs in 50%–60% of residual nonfunctioning pituitary adenomas (NFPAs). Stereotactic radiosurgery (SRS) is a safe and effective management option for residual NFPAs, but there is no consensus on its optimal timing. This study aims to define the optimal timing of SRS for residual NFPAs.

METHODS

This retrospective, multicenter study involved 375 patients with residual NFPAs managed with SRS. The patients were divided into adjuvant (ADJ; treated for stable residual NFPA within 6 months of resection) and progression (PRG) cohorts (treated for residual NFPA progression). Factors associated with tumor progression and clinical deterioration were analyzed.

RESULTS

Following propensity-score matching, each cohort consisted of 130 patients. At last follow-up, tumor control was achieved in 93.1% of patients in the ADJ cohort and in 96.2% of patients in the PRG cohort (HR 1.6, 95% CI 0.55–4.9, p = 0.37). Hypopituitarism was associated with a maximum point dose of > 8 Gy to the pituitary stalk (HR 4.5, 95% CI 1.6–12.6, p = 0.004). No statistically significant difference was noted in crude new-onset hypopituitarism rates (risk difference [RD] = −0.8%, p > 0.99) or visual deficits (RD = −2.3%, p = 0.21) between the two cohorts at the last follow-up. The median time from resection to new hypopituitarism was longer in the PRG cohort (58.9 vs 29.7 months, p = 0.01).

CONCLUSIONS

SRS at residual NFPA progression does not appear to alter the probability of tumor control or hormonal/visual deficits compared with adjuvant SRS. Deferral of radiosurgical management to the time of radiological progression could significantly prolong the time to radiosurgically induced pituitary dysfunction. A lower maximum point dose (< 8 Gy) to the pituitary stalk portended a more favorable chance of preserving pituitary function after SRS.

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Othman Bin-Alamer, Arka N. Mallela, Paolo Palmisciano, Zachary C. Gersey, Turki Elarjani, Mohamed A. Labib, Georgios A. Zenonos, Amir R. Dehdashti, Jason P. Sheehan, William T. Couldwell, L. Dade Lunsford, and Hussam Abou-Al-Shaar

OBJECTIVE

The objective of this retrospective study was to compare the survival of patients with biopsy-proven skull base chordoma who had undergone stereotactic radiosurgery (SRS) with versus without prior fractionated radiation therapy (RT).

METHODS

Relevant articles from database inception to September 2021 were retrieved from the PubMed, Scopus, Web of Science, and Cochrane databases for a systematic review of treatment protocols. Studies were included if they 1) involved adult patients (age ≥ 18 years) with histologically and radiologically confirmed chordomas located within the clival skull base region and treated with SRS; 2) reported data on clinical features, SRS protocols, and outcomes; and 3) were written in the English language. Studies were excluded if they 1) were literature reviews, case reports, technical notes, abstracts, or autopsy reports; 2) did not clearly differentiate the data of patients with chordomas from the data of patients with different tumors or the data of patients with chordomas in locations other than the skull base; or 3) lacked histological confirmation or treatment and outcome data. Extracted data included the following: study author and publication year, patient age and sex, symptoms, cranial nerve involvement, invaded structures, lesion size, treatment modality, surgical details, histopathological type, RT modality, SRS parameters, complications, postradiosurgery outcomes, complications, and survival outcomes.

RESULTS

After the selection process, 15 articles describing 130 patients met the study eligibility criteria, including 94 patients who had undergone postresection SRS (NoRT group) and 36 who had undergone postresection fractionated RT and subsequent SRS (RT group). The NoRT and RT groups were comparable in age (51.3 vs 47.4 years, respectively), sex (57.1% vs 58.3% male), tumor volume (9.5 vs 11.2 cm3), SRS treatment parameters (maximum dose: 35.4 vs 42.2 Gy, marginal dose: 19.6 vs 20.6 Gy, treatment isodose line: 60.2% vs 65.2%), and SRS adverse effects (10.9% vs 17.6%). For the entire cohort, the 3-, 5-, and 10-year progression-free survival (PFS) rates were 23%, 9%, and 3%, respectively, and the overall survival (OS) rates were 94%, 82%, and 76%, respectively. In the NoRT group, SRS was adjuvant treatment after resection in 38 patients (40.4%), salvage treatment for recurrent tumor treated with resection alone in 10 (10.6%), and not specified in 46 (48.9%). In the RT group, SRS was boost treatment in 9 patients (25.0%), salvage treatment after recurrence in 22 (61.1%), and not specified in 5 (13.9%). There was no difference between the two groups in terms of median PFS (24.0 months [Q1 34.0, Q3 15.0] vs 23.8 months [34.0, 18.0], respectively; p = 0.8) or median OS (293.0 months [not reached, 137.4] vs not reached [not reached, 48.0], respectively; p = 0.36). The adverse radiation effect rates were comparable between the groups (10.9% vs 17.6%, respectively; p = 0.4).

CONCLUSIONS

The role of SRS in the management of skull base chordomas is still evolving. This systematic literature review of biopsy-proven chordoma revealed that tumor control and survival rates for SRS alone after chordoma surgery were not inferior to those encountered after SRS plus fractionated RT.

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Zhishuo Wei, Lena Vodovotz, Diego D. Luy, Hansen Deng, Ajay Niranjan, and L. Dade Lunsford

OBJECTIVE

Young patients with hypothalamic hamartomas (HHs) often present with intractable epilepsy. Currently there are no established management guidelines for HH. The authors retrospectively reviewed their single-institution experience to delineate the role of stereotactic radiosurgery (SRS).

METHODS

Seven patients with HHs (4 females; median age 13.7 years, range 2.5–25 years) with no prior resection underwent SRS between 1987 and 2022. The clinical history, epilepsy profile, radiographic findings, and neurological outcomes were characterized. HH topographical types were classified according to the Régis classification. Outcome measures included Engel seizure classification, HH response, and the need for additional surgical interventions.

RESULTS

All patients had Engel class IV epilepsy. A Leksell Gamma Knife was used to deliver a median margin dose of 18 Gy (range 16–20 Gy) to a median hamartoma volume of 0.37 cm3 (range 0.20–0.89 cm3). Seizure reduction was confirmed in 6 patients, and 2 patients had regression of their hamartoma. Two patients underwent resection and/or laser interstitial thermal therapy after SRS. At follow-up, 1 patient was seizure free, 4 patients achieved Engel class II, 1 patient had Engel class III, and 1 patient had Engel class IV seizure outcomes.

CONCLUSIONS

SRS as the initial management option for HH was associated with a low risk of adverse effects. In this institutional series reviewing small-volume HHs treated with SRS, no adverse radiation effect was detected, and the majority of patients experienced seizure reduction. SRS should be considered as the first-line treatment for seizure control in patients with small-volume HHs.

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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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Luigi Albano, Hansen Deng, Zhishuo Wei, Lena Vodovotz, Ajay Niranjan, and L. Dade Lunsford

OBJECTIVE

Gamma Knife radiosurgery (GKRS) is an effective treatment for vestibular schwannomas (VSs) and has been used in > 100,000 cases worldwide. In the present study the authors sought to define the serial volumetric tumor response of Koos grade I–IV VS after radiosurgery.

METHODS

A total of 201 consecutive VS patients underwent GKRS at a single institution between 2015 and 2019. All patients had a minimum follow-up of 18 months and at least 2 interval postprocedure MRI scans. The contrast-enhanced tumor volumes were contoured manually and compared between pre- and post-GKRS imaging. The percentages of tumor volume change at 18 months (short-term follow-up) and up to 5 years after GKRS (long-term follow-up) were compared with the baseline tumor volume. An increase of 20% was considered a significant increase of tumor volume. Trends of tumor volume over time were assessed with linear models using time as a continuous variable. A test for linear trend was evaluated according to the initial Koos tumor classification.

RESULTS

Koos grade II VS was the most frequently occurring tumor (n = 74, 36.8%), followed by grade III (n = 57, 28.4%), grade I (n = 41, 20.4%), and grade IV (n = 29, 14.4%). The mean tumor volume at the time of GKRS was 2.12 ± 2.82 cm3 (range 0.12–18.77 cm3) and the median margin dose was 12 Gy. Short-term follow-up revealed that tumor volumes transiently increased in 34.2% and 28.4% of patients at 6 and 18 months, respectively, regardless of Koos grade. Linear regression analysis of Koos grade II, III, and IV tumors showed a significant longitudinal volume decrease on long-term follow-up. At last follow-up (median 30 months, range 18–54 months), 19 patients (9.4%) showed a persistent increase of tumor volume. Five patients received additional management after GKRS.

CONCLUSIONS

Although selected VS patients demonstrate an early and measurable transient volumetric increase after GKRS, > 90% have stable or reduced tumor volumes over an observed period of up to 5 years. Volumetric regression is most pronounced in Koos grade II, III, and IV tumors and may not be fully detectable until 3 years after GKRS.

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Othman Bin-Alamer, David Fogg, Zhishuo Wei, James Duehr, Arka N. Mallela, Ajay Niranjan, L. Dade Lunsford, and Hussam Abou-Al-Shaar

OBJECTIVE

Vestibular schwannomas (VSs) are benign tumors of the cerebellopontine angle that are typically managed with stereotactic radiosurgery (SRS). Intratumoral hemorrhage (ITH) of VSs is a rare occurrence that results in worsening vestibular and new cranial nerve deficits. Few reports have described the management and outcomes of this entity after SRS. To further delineate the incidence and impact of this event, the authors performed a retrospective review of their VS SRS patients at a single center.

METHODS

Between 1987 and 2022, 2058 patients with VSs underwent Gamma Knife radiosurgery (GKRS) at the University of Pittsburgh Medical Center. The authors performed a review of the prospectively maintained VS database at their center to identify patients with ITH. The presentation, management, and clinical and imaging outcomes of the patients are reported.

RESULTS

A total of 1902 VS patients had sufficient clinical and imaging follow-up data. Five Koos grade III (n = 1) and IV (n = 4) VS patients developed ITH after GKRS, resulting in a cumulative incidence rate of 0.26%. The age at presentation ranged from 62 to 79 years, and 3 patients were male. The time from VS diagnosis to GKRS ranged from 1 to 13 months, and the time from GKRS to ITH ranged from 2 to 130 months. Three patients had bleeding risk factors. One patient required urgent surgical intervention due to the ITH volume, while the other 4 patients were initially observed. Three patients remained stable and required no delayed intervention; 1 patient required delayed resection because of symptom progression and hemorrhagic expansion. Histopathological analysis revealed multiple fragments of S-100–positive cells, hemorrhage, and hemosiderin-laden macrophages. At last follow-up, 4 patients had clinically improved and 1 patient remained stable.

CONCLUSIONS

ITH after VS radiosurgery is a rare phenomenon with a cumulative incidence rate of 0.26% in this series. Patient-tailored management in the form of observation or resection is based on patient presentation, acuity, and ITH size.

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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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Georgios Mantziaris, Joshua Diamond, Stylianos Pikis, Farid M. El Hefnawi, Ghusn Al Sideiri, François-Louis Coupé, David Mathieu, Cheng-Chia Lee, Jaromir May, Roman Liščák, Selcuk Peker, Yavuz Samanci, Ajay Niranjan, L. Dade Lunsford, and Jason P. Sheehan

OBJECTIVE

The optimal treatment for recurrent and residual gangliogliomas remains unclear. The aim of this study was to evaluate the safety and efficacy of stereotactic radiosurgery (SRS) in the management of patients with recurrent or residual intracranial ganglioglioma.

METHODS

This retrospective multicenter study involved patients managed with SRS for ganglioglioma. The study endpoints included local tumor control and tumor- or SRS-related neurological morbidity following treatment. Factors associated with tumor progression and neurological morbidity were also analyzed.

RESULTS

The cohort included 20 patients (11 males [55%]) with a median age of 24.5 (IQR 14) years who had been managed with SRS for ganglioglioma. Five-year radiological progression-free survival was 85.6%. After SRS, 2 patients (10%) experienced transient neurological deterioration. At a median clinical follow-up of 88.5 (IQR 112.5) months, 1 patient (5%) experienced seizure worsening and 1 (5%) required further resection of the tumor because of radiological progression. No mortality was noted in this series.

CONCLUSIONS

SRS appears to be a safe and effective treatment option for surgically inaccessible, recurrent, and residual gangliogliomas. In this series, the 5-year progression-free survival rate after SRS was 85.6%. Gross-total resection remains the primary treatment of choice for patients with newly diagnosed or recurrent ganglioglioma. SRS may be considered for patients unfit for surgery and those with surgically inaccessible newly diagnosed, residual, and recurrent lesions.

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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.