Christian Iorio-Morin and Mathieu Levesque
Christian Iorio-Morin, Laurence Masson-Côté, Youssef Ezahr, Jocelyn Blanchard, Annie Ebacher, and David Mathieu
Optimal case management after surgical removal of brain metastasis remains controversial. Although postoperative whole-brain radiation therapy (WBRT) has been shown to prevent local recurrence and decrease deaths, this modality can substantially decrease neurocognitive function and quality of life. Stereotactic radiosurgery (SRS) can theoretically achieve the same level of local control with fewer side effects, although studies conclusively demonstrating such outcomes are lacking. To assess the effectiveness and safety profile of tumor bed SRS after resection of brain metastasis, the authors performed a retrospective analysis of 110 patients who had received such treatment at the Centre Hospitalier Universitaire de Sherbrooke. They designed the study to identify risk factors for local recurrence and placed special emphasis on factors that could potentially be addressed.
Patients who had received treatment from 2004 through 2013 were included if they had undergone surgical removal of 1 or more brain metastases and if the tumor bed was treated by SRS regardless of the extent of resection or prior WBRT. All cases were retrospectively analyzed for patient and tumor-specific factors, treatment protocol, adverse outcomes, cavity outcomes, and survival for as long as follow-up was available. Univariate and multivariate Cox regression analyses were performed to identify risk factors for local recurrence and predictors of increased survival times.
Median patient age at first SRS treatment was 58 years (range 37–84 years). The most frequently diagnosed primary tumor was non–small cell lung cancer. The rate of gross-total resection was 81%. The median Karnofsky Performance Scale score was 90%. Tumor bed SRS was performed at a median of 3 weeks after surgery. Median follow-up and survival times were 10 and 11 months, respectively. Actuarial local control of the cavity at 12 months was 73%; median time to recurrence was 6 months. According to multivariate analysis, risk factors for recurrence were a longer surgery-to-SRS delay (HR 1.625, p = 0.003) and a lower maximum radiation dose delivered to the cavity (HR 0.817, p = 0.006). Factors not associated with increased recurrence were subtotal or piecemeal resections, prior WBRT, histology of the primary tumor, and larger cavity volume. No factors predictive of survival were identified. Symptomatic radiation-induced enhancement occurred in 6% of patients and leptomeningeal dissemination in 11%. Pathologically confirmed radiation-induced necrosis occurred in 1 (0.9%) patient.
Adjuvant tumor bed SRS after the resection of brain metastasis is a valuable alternative to adjuvant WBRT. Risk factors for local recurrence are lower maximum radiation dose and a surgery-to-SRS delay longer than 3 weeks. Outcomes were not worse for patients who had undergone prior WBRT and subtotal or piecemeal resections. Pending the results of prospective randomized controlled trials, the authors' study supports the safety and efficacy of adjuvant SRS after resection of brain metastasis. SRS should be performed as early as possible, ideally within 3 weeks of the surgery.
Anne-Marie Langlois, Christian Iorio-Morin, Andrew Faramand, Ajay Niranjan, L. Dade Lunsford, Nasser Mohammed, Jason P. Sheehan, Roman Liščák, Dušan Urgošík, Douglas Kondziolka, Cheng-chia Lee, Huai-che Yang, Ahmet F. Atik, and David Mathieu
Cranial nerve (CN) schwannomas are intracranial tumors that are commonly managed by stereotactic radiosurgery (SRS). There is a large body of literature supporting the use of SRS for vestibular schwannomas. Schwannomas of the oculomotor nerves (CNs III, IV, and VI) are rare skull base tumors, occurring close to the brainstem and often involving the cavernous sinus. Resection can cause significant morbidity, including loss of nerve function. As for other schwannomas, SRS can be used to manage these tumors, but only a handful of cases have been published so far, often among reports of other uncommon schwannoma locations.
The goal of this study was to collect retrospective multicenter data on tumor control, clinical evolution, and morbidity after SRS. This study was performed through the International Radiosurgery Research Foundation. Patients managed with single-session SRS for an oculomotor cranial nerve schwannoma (CN III, IV, or VI) were included. The diagnosis was based on diplopia or ptosis as the main presenting symptom and anatomical location on the trajectory of the presumed cranial nerve of origin, or prior resection confirming diagnosis. Demographic, SRS dose planning, clinical, and imaging data were collected from chart review of the treated patients. Chi-square and Kaplan-Meier analyses were performed.
Seven institutions submitted data for a total of 25 patients. The median follow-up time was 41 months. The median age at the time of treatment was 52 years. There were 11 CN III schwannomas, 11 CN IV schwannomas, and 3 CN VI schwannomas. The median target volume was 0.74 cm3, and the median marginal dose delivered was 12.5 Gy. After SRS, only 2 patients (including the only patient with neurofibromatosis type 2) had continued tumor growth. Crude local control was 92% (23/25), and the 10-year actuarial control was 86%. Diplopia improved in the majority of patients (11/21), and only 3 had worsening following SRS, 2 of whom also had worsened ptosis, both in the context of tumor progression.
SRS for schwannomas of the oculomotor, trochlear, and abducens nerves is effective and provides tumor control rates similar to those for other cranial nerve schwannomas. SRS allows improvement of diplopia in the majority of patients. SRS should therefore be considered as a first-line treatment option for oculomotor nerve schwannomas.
Diogo Cordeiro, Zhiyuan Xu, Chelsea E. Li, Christian Iorio-Morin, David Mathieu, Nathaniel D. Sisterson, Hideyuki Kano, Luca Attuati, Piero Picozzi, Kimball A. Sheehan, Cheng-chia Lee, Roman Liscak, Jana Jezkova, L. Dade Lunsford, and Jason Sheehan
Nelson’s syndrome is a rare and challenging neuroendocrine disorder, and it is associated with elevated adrenocorticotrophic hormone (ACTH) level, skin hyperpigmentation, and pituitary adenoma growth. Management options including resection and medical therapy are traditional approaches. Ionizing radiation in the form of Gamma Knife radiosurgery (GKRS) is also being utilized to treat Nelson’s syndrome. In the current study the authors sought to better define the therapeutic role of stereotactic radiosurgery (SRS) in Nelson’s syndrome.
Study patients with Nelson’s syndrome were treated with single-fraction GKRS (median margin dose of 25 Gy) at 6 different centers as part of an International Radiosurgery Research Foundation (IRRF) investigation. Data including neurological function, endocrine response, and radiological tumor response were collected and sent to the study-coordinating center for review. Fifty-one patients with median endocrine and radiological follow-ups of 91 and 80.5 months from GKRS, respectively, were analyzed for endocrine remission, tumor control, and neurological outcome. Statistical methods were used to identify prognostic factors for these endpoints.
At last follow-up, radiological tumor control was achieved in 92.15% of patients. Endocrine remission off medical management and reduction in pre-SRS ACTH level were achieved in 29.4% and 62.7% of patients, respectively. Improved remission rates were associated with a shorter time interval between resection and GKRS (p = 0.039). Hypopituitarism was seen in 21.6% and new visual deficits were demonstrated in 15.7% of patients.
GKRS affords a high rate of pituitary adenoma control and improvement in ACTH level for the majority of Nelson’s syndrome patients. Hypopituitarism is the most common adverse effect from GKRS in Nelson’s syndrome patients and warrants longitudinal follow-up for detection and endocrine replacement.
Rebecca M. Burke, Ching-Jen Chen, Dale Ding, Thomas J. Buell, Jennifer D. Sokolowski, Cheng-Chia Lee, Hideyuki Kano, Kathryn N. Kearns, Shih-Wei Tzeng, Huai-che Yang, Paul P. Huang, Douglas Kondziolka, Natasha Ironside, David Mathieu, Christian Iorio-Morin, Inga S. Grills, Caleb Feliciano, Gene H. Barnett, Robert M. Starke, L. Dade Lunsford, and Jason P. Sheehan
Stereotactic radiosurgery (SRS) is a treatment option for pediatric brain arteriovenous malformations (AVMs), and early obliteration could encourage SRS utilization for a subset of particularly radiosensitive lesions. The objective of this study was to determine predictors of early obliteration after SRS for pediatric AVMs.
The authors performed a retrospective review of the International Radiosurgery Research Foundation AVM database. Obliterated pediatric AVMs were sorted into early (obliteration ≤ 24 months after SRS) and late (obliteration > 24 months after SRS) responders. Predictors of early obliteration were identified, and the outcomes of each group were compared.
The overall study cohort was composed of 345 pediatric patients with obliterated AVMs. The early and late obliteration cohorts were made up of 95 (28%) and 250 (72%) patients, respectively. Independent predictors of early obliteration were female sex, a single SRS treatment, a higher margin dose, a higher isodose line, a deep AVM location, and a smaller AVM volume. The crude rate of post-SRS hemorrhage was 50% lower in the early (3.2%) than in the late (6.4%) obliteration cohorts, but this difference was not statistically significant (p = 0.248). The other outcomes of the early versus late obliteration cohorts were similar, with respect to symptomatic radiation-induced changes (RICs), cyst formation, and tumor formation.
Approximately one-quarter of pediatric AVMs that become obliterated after SRS will achieve this radiological endpoint within 24 months of initial SRS. The authors identified multiple factors associated with early obliteration, which may aid in prognostication and management. The overall risks of delayed hemorrhage, RICs, cyst formation, and tumor formation were not statistically different in patients with early versus late obliteration.
Ching-Jen Chen, Cheng-Chia Lee, Hideyuki Kano, Kathryn N. Kearns, Dale Ding, Shih-Wei Tzeng, Ahmet Atik, Krishna Joshi, Gene H. Barnett, Paul P. Huang, Douglas Kondziolka, David Mathieu, Christian Iorio-Morin, Inga S. Grills, Thomas J. Quinn, Zaid A. Siddiqui, Kim Marvin, Caleb Feliciano, Andrew Faramand, L. Dade Lunsford, and Jason P. Sheehan
Contrary to the better described obliteration- and hemorrhage-related data after stereotactic radiosurgery (SRS) of brain arteriovenous malformations (AVMs) in pediatric patients, estimates of the rarer complications, including cyst and tumor formation, are limited in the literature. The aim of the present study was to assess the long-term outcomes and risks of SRS for AVMs in pediatric patients (age < 18 years).
The authors retrospectively analyzed the International Radiosurgery Research Foundation pediatric AVM database for the years 1987 to 2018. AVM obliteration, post-SRS hemorrhage, cyst formation, and tumor formation were assessed. Cumulative probabilities, adjusted for the competing risk of death, were calculated.
The study cohort comprised 539 pediatric AVM patients (mean follow-up 85.8 months). AVM obliteration was observed in 64.3% of patients, with cumulative probabilities of 63.6% (95% CI 58.8%–68.0%), 77.1% (95% CI 72.1%–81.3%), and 88.1% (95% CI 82.5%–92.0%) over 5, 10, and 15 years, respectively. Post-SRS hemorrhage was observed in 8.4% of patients, with cumulative probabilities of 4.9% (95% CI 3.1%–7.2%), 9.7% (95% CI 6.4%–13.7%), and 14.5% (95% CI 9.5%–20.5%) over 5, 10, and 15 years, respectively. Cyst formation was observed in 2.1% of patients, with cumulative probabilities of 5.5% (95% CI 2.3%–10.7%) and 6.9% (95% CI 3.1%–12.9%) over 10 and 15 years, respectively. Meningiomas were observed in 2 patients (0.4%) at 10 and 12 years after SRS, with a cumulative probability of 3.1% (95% CI 0.6%–9.7%) over 15 years.
AVM obliteration can be expected after SRS in the majority of the pediatric population, with a relatively low risk of hemorrhage during the latency period. Cyst and benign tumor formation after SRS can be observed in 7% and 3% of patients over 15 years, respectively. Longitudinal surveillance for delayed neoplasia is prudent despite its low incidence.
I. Jonathan Pomeraniec, Hideyuki Kano, Zhiyuan Xu, Brandon Nguyen, Zaid A. Siddiqui, Danilo Silva, Mayur Sharma, Hesham Radwan, Jonathan A. Cohen, Robert F. Dallapiazza, Christian Iorio-Morin, Amparo Wolf, John A. Jane Jr., Inga S. Grills, David Mathieu, Douglas Kondziolka, Cheng-Chia Lee, Chih-Chun Wu, Christopher P. Cifarelli, Tomas Chytka, Gene H. Barnett, L. Dade Lunsford, and Jason P. Sheehan
Gamma Knife radiosurgery (GKRS) is frequently used to treat residual or recurrent nonfunctioning pituitary macroadenomas. There is no consensus as to whether GKRS should be used early after surgery or if radiosurgery should be withheld until there is evidence of imaging-defined progression of tumor. Given the high incidence of adenoma progression after subtotal resection over time, the present study intended to evaluate the effect of timing of radiosurgery on outcome.
This is a multicenter retrospective review of patients with nonfunctioning pituitary macroadenomas who underwent transsphenoidal surgery followed by GKRS from 1987 to 2015 at 9 institutions affiliated with the International Gamma Knife Research Foundation. Patients were matched by adenoma and radiosurgical parameters and stratified based on the interval between last resection and radiosurgery. Operative results, imaging data, and clinical outcomes were compared across groups following early (≤ 6 months after resection) or late (> 6 months after resection) radiosurgery.
After matching, 222 patients met the authors’ study criteria (from an initial collection of 496 patients) and were grouped based on early (n = 111) or late (n = 111) GKRS following transsphenoidal surgery. There was a greater risk of tumor progression after GKRS (p = 0.013) and residual tumor (p = 0.038) in the late radiosurgical group over a median imaging follow-up period of 68.5 months. No significant difference in the occurrence of post-GKRS endocrinopathy was observed (p = 0.68). Thirty percent of patients without endocrinopathy in the early cohort developed new endocrinopathies during the follow-up period versus 27% in the late cohort (p = 0.84). Fourteen percent of the patients in the early group and 25% of the patients in the late group experienced the resolution of endocrine dysfunction after original presentation (p = 0.32).
In this study, early GKRS was associated with a lower risk of radiological progression of subtotally resected nonfunctioning pituitary macroadenomas compared with expectant management followed by late radiosurgery. Delaying radiosurgery may increase patient risk for long-term adenoma progression. The timing of radiosurgery does not appear to significantly affect the rate of delayed endocrinopathy.