✓ The authors describe two patients in whom tumor swelling and brain swelling (and possible tumor swelling), respectively, developed after undergoing gamma knife surgery. One had a skull defect with a palpable parasagittal tumor. One had neurofibromatosis Type 2 with multiple tumors, one of which was parasagittal.
Report of two cases
Amr El Shehaby, Jeremy C. Ganz, Wael A. Reda and Ayman Hafez
Jeremy C. Ganz, Wael A. Reda, Khalid Abdelkarim and Ayman Hafez
Object. The authors studied the relationship between dose planning parameters and complications in the treatment of cerebral arteriovenous malformations (AVMs).
Methods. There were 41 continuous unselected patients. The mean follow-up period was 19 months; the mean age was 28 years; the male/female ratio was 2.2:1.0; the median prescription dose was 25 Gy (range 14–25 Gy); the median prescription isodose was 50%. The median lesion volume was 4.4 cm3. The median lesion coverage was 93%; and the mean conformity index was 1.22.
The authors found no relationship between lesion volume or integral dose and the development of the clinical effects based on the adverse radiation effects (AREs); however, there was a significant relationship between both target volume and integral dose with the development of AREs as well as the severity of the AREs.
Conclusions. The integral dose could be used as a guideline for the prescription dose. Arguments are made for maximizing the prescription dose for the long-term safety of the patient.
Report of two cases
Wael Abdel Halim Reda, Alla Abdel Hay and Jeremy C. Ganz
✓ Cyst-associated tumors are classified as cysts with neoplastic mural nodules and intratumoral cysts. The solid component of many of these tumors may be appropriate for gamma knife radiosurgery (GKS). At present there is no systematic protocol for GKS treatment of patients harboring tumors with a cystic component. The purpose of this paper is to suggest such a program.
Two cases are presented. One patient had a hemangioblastoma with a cyst and a mural nodule. The second patient had a craniopharyngioma with one large and two small intratumoral cysts. The course in both cases has been satisfactory in the short term. Although the 1-year follow-up period, however, does not provide a basis for determining the correct overall management of such tumors, the treatment strategy does illustrate a program for the management of tumors with associated cysts.
Cysts with tumor nodules in their walls should first be treated with GKS followed by aspiration of the cyst contents, unless special circumstances make this unsuitable. This strategy enables treatment planning to take advantage of the natural barrier a cyst may place between a tumor and important surrounding structures.
Intratumoral cysts may be aspirated and then treated with GKS, with every attempt made to cover the entire target volume including any residual cyst with the prescription dose. This form of treatment requires very careful follow up.
It is probable that in some cases reaccumulation of cyst fluid may require the insertion of an Ommaya reservoir for repeated aspiration or the installation of cytotoxic agents such as bleomycin. This form of treatment is much less traumatic than surgery and does not hinder the performance of subsequent surgery, should this become necessary.
Report of two cases
Amr El Shehaby, Jeremy C. Ganz, Wael A. Reda and Ayman Hafez
✓ In two patients in whom gamma knife surgery was performed for meningiomas clinically significant volume increases were observed in the first 3 months after treatment. Clinical examination and various imaging studies form the basis of the report in these patients. In each case, the volume increase was temporary.
Amr M. N. El-Shehaby, Wael A. Reda, Sameh R. Tawadros and Khaled M. Abdel Karim
The primary concern when performing Gamma Knife surgery for pituitary adenoma is preservation of vision and pituitary function while achieving tumor growth control. Higher prescribed radiation doses are typically correlated with higher incidences of postradiosurgical hormone deficiencies. The goal of the present study was to retrospectively analyze the feasibility of using a lower prescribed radiation dose in the treatment of nonfunctioning pituitary adenomas and the effect of this dose on vision, pituitary function, and tumor growth control.
The study was conducted in 38 patients with nonfunctioning pituitary adenomas, who were treated between January 2002 and July 2008. Twenty-one patients were available for follow-up (13 men and 8 women). The mean follow-up period was 44 months (range 24–90 months). Nineteen patients had previously undergone surgery. Pituitary dysfunction developed after surgery in 3 patients. One patient had an abnormal pituitary hormone profile before radiosurgery due to an attack of pituitary apoplexy. Visual field defects were present in 12 patients. The prescribed radiation dose was 12 Gy in all patients. The tumor volume ranged from 0.5 to 11.8 cm3 (mean 4.8 cm3). The maximum dose to the visual pathway was kept below 10 Gy. The mean maximum dose delivered to the visual pathway was 7.9 Gy.
The patients were followed up for a period of 24 to 90 months (mean 44 months). The size of the tumor decreased in 11 patients (52%) and remained stable in 9 patients (43%). In 1 patient there was tumor growth outside the previous radiation field (on the contralateral side). Among the 12 patients with visual field defects, 9 (75%) experienced an improvement and the remaining patients' vision remained stable. In only 4 patients was the visual improvement associated with tumor shrinkage. The hormone profile remained normal in all patients except for the 4 patients who had pituitary dysfunction before radiosurgery.
The 12-Gy prescribed dose used in this study seems to be sufficient for producing tumor control while sparing the patient from radiation-induced pituitary dysfunction. In addition, visual improvement was reported in a number of cases. A larger series and longer follow-up are required to confirm these results.
Amr M. N. El-Shehaby, Wael A. Reda, Khaled M. Abdel Karim, Reem M. Emad Eldin and Ahmed M. Nabeel
Because of their critical and central location, it is deemed necessary to fractionate when considering irradiating optic pathway/hypothalamic gliomas. Stereotactic fractionated radiotherapy is considered safer when dealing with gliomas in this location. In this study, the safety and efficacy of single-session stereotactic radiosurgery for optic pathway/hypothalamic gliomas were reviewed.
Between December 2004 and June 2014, 22 patients with optic pathway/hypothalamic gliomas were treated by single-session Gamma Knife radiosurgery. Twenty patients were available for follow-up for a minimum of 1 year after treatment. The patients were 5 to 43 years (median 16 years) of age. The tumor volume was 0.15 to 18.2 cm3 (median 3.1 cm3). The prescription dose ranged from 8 to 14 Gy (median 11.5 Gy).
The mean follow-up period was 43 months. Five tumors involved the optic nerve only, and 15 tumors involved the chiasm/hypothalamus. Two patients died during the follow-up period. The tumors shrank in 12 cases, remained stable in 6 cases, and progressed in 2 cases, thereby making the tumor control rate 90%. Vision remained stable in 12 cases, improved in 6 cases, and worsened in 2 cases in which there was tumor progression. Progression-free survival was 83% at 3 years.
The initial results indicate that single-session Gamma Knife radiosurgery is a safe and effective treatment option for optic pathway/hypothalamic gliomas.
Amr M. N. El-Shehaby, Wael A. Reda, Khaled M. Abdel Karim, Ahmed M. Nabeel, Reem M. Emad Eldin and Sameh R. Tawadros
The objective of this study was to assess hearing function after Gamma Knife treatment of cerebellopontine angle (CPA) meningiomas and assess factors affecting hearing outcome. Additionally, the authors opted to compare these results with those after Gamma Knife treatment of vestibular schwannomas (VSs), because most of the information on hearing outcome after stereotactic radiosurgery (SRS) comes from reports on VS treatment. Hearing preservation, to the best of the authors’ knowledge, has never been separately addressed in studies involving Gamma Knife radiosurgery (GKRS) for CPA meningiomas.
This study included all patients who underwent a single session of GKRS between 2002 and 2014. The patients were divided into two groups. Group A included 66 patients with CPA meningiomas with serviceable hearing and tumor extension into the region centered on the internal auditory meatus. Group B included 144 patients with VSs with serviceable hearing. All patients had serviceable hearing before treatment (Gardner-Robertson [GR] Grades I and II). The median prescription dose was 12 Gy (range 10–12 Gy) in both groups. The median follow-up of groups A and B was 42 months (range 6–149 months) and 49 months (range 6–149 months), respectively.
At the last follow-up, the tumor control rate was 97% and 94% in groups A and B, respectively. Hearing preservation was defined as maintained serviceable hearing according to GR hearing score. The hearing preservation rate was 98% and 66% and the 7-year actuarial serviceable hearing preservation rate was 75% and 56%, respectively, between both groups. In group A, the median maximum cochlear dose in the patients with stable and worsened hearing grade was 6.3 Gy and 5.5 Gy, respectively. In group B, factors affecting hearing preservation were cochlear dose ≤ 7 Gy, follow-up duration, and tumor control. The only determinant of hearing preservation between both groups was tumor type.
GKRS for CPA meningiomas provides excellent hearing preservation in addition to high tumor control rate. Hearing outcome is better with CPA meningiomas than with VSs. Further long-term prospective studies on determinants of hearing outcome after GKRS for CPA meningiomas should be conducted.
Amitabh Gupta, Zhiyuan Xu, Hideyuki Kano, Nathaniel Sisterson, Yan-Hua Su, Michal Krsek, Ahmed M. Nabeel, Amr El-Shehaby, Khaled A. Karim, Nuria Martínez-Moreno, David Mathieu, Brendan J. McShane, Roberto Martínez-Álvarez, Wael A. Reda, Roman Liscak, Cheng-Chia Lee, L. Dade Lunsford and Jason P. Sheehan
Gamma Knife radiosurgery (GKS) is typically used after failed resection in patients with Cushing’s disease (CD) and acromegaly. Little is known about the upfront role of GKS for patients with CD and acromegaly. In this study, the authors examine the outcome of upfront GKS for patients with these functioning adenomas.
An international group of 7 Gamma Knife centers sent pooled data from 46 patients (21 with CD and 25 with acromegaly) undergoing upfront GKS to the coordinating center of the study for analysis. Diagnosis was established on the basis of clinical, endocrine, and radiological studies. All patients were treated on a common radiosurgical platform and longitudinally followed for tumor control, endocrine remission, and hypopituitarism. Patients received a tumor median margin dose of 25 Gy (range 12–40.0 Gy) at a median isodose of 50%.
The median endocrine follow-up was 69.5 months (range 9–246 months). Endocrine remission was achieved in 51% of the entire cohort, with 28% remission in acromegaly and 81% remission for those with CD at the 5-year interval. Patients with CD achieved remission earlier as compared to those with acromegaly (p = 0.0005). In patients post-GKS, the pituitary adenoma remained stable (39%) or reduced (61%) in size. Hypopituitarism occurred in 9 patients (19.6%), and 1 (2.2%) developed third cranial nerve (CN III) palsy. Eight patients needed further intervention, including repeat GKS in 6 and transsphenoidal surgery in 2.
Upfront GKS resulted in good tumor control as well as a low rate of adverse radiation effects in the whole group. Patients with CD achieved a faster and far better remission rate after upfront GKS in comparison to patients with acromegaly. GKS can be considered as an upfront treatment in carefully selected patients with CD who are unwilling or unable to undergo resection, but it has a more limited role in acromegaly.
Adomas Bunevicius, Hideyuki Kano, Cheng-Chia Lee, Michal Krsek, Ahmed M. Nabeel, Amr El-Shehaby, Khaled Abdel Karim, Nuria Martinez-Moreno, David Mathieu, John Y. K. Lee, Inga Grills, Douglas Kondziolka, Roberto Martinez-Alvarez, Wael A. Reda, Roman Liscak, Yan-Hua Su, L. Dade Lunsford, Mary Lee Vance and Jason P. Sheehan
The optimal time to perform stereotactic radiosurgery after incomplete resection of adrenocorticotropic hormone (ACTH)–producing pituitary adenoma in patients with Cushing’s disease (CD) remains unclear. In patients with persistent CD after resection of ACTH-producing pituitary adenoma, the authors evaluated the association of the interval between resection and Gamma Knife radiosurgery (GKRS) with outcomes.
Pooled data from 10 institutions participating in the International Radiosurgery Research Foundation were used in this study.
Data from 255 patients with a mean follow-up of 65.59 ± 49.01 months (mean ± SD) were analyzed. Seventy-seven patients (30%) underwent GKRS within 3 months; 46 (18%) from 4 to 6 months; 34 (13%) from 7 to 12 months; and 98 (38%) at > 12 months after the resection. Actuarial endocrine remission rates were higher in patients who underwent GKRS ≤ 3 months than when treatment was > 3 months after the resection (78% and 65%, respectively; p = 0.017). Endocrine remission rates were lower in patients who underwent GKRS at > 12 months versus ≤ 12 months after the resection (57% vs 76%, respectively; p = 0.006). In multivariate Cox regression analyses adjusted for clinical and treatment characteristics, early GKRS was associated with increased probability of endocrine remission (hazard ratio [HR] 1.518, 95% CI 1.039–2.218; p = 0.031), whereas late GKRS (HR 0.641, 95% CI 0.448–0.919; p = 0.015) was associated with reduced probability of endocrine remission. The incidence of some degree of new pituitary deficiency (p = 0.922), new visual deficits (p = 0.740), and other cranial nerve deficits (p = 0.610) was not significantly related to time from resection to GKRS.
Early GKRS is associated with an improved endocrine remission rate, whereas later GKRS is associated with a lower rate of endocrine remission after pituitary adenoma resection. Early GKRS should be considered for patients with CD after incomplete pituitary adenoma resection.
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
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.
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.
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).
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.