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  • By Author: Kondziolka, Douglas x
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Jason P. Sheehan, Inga Grills, Veronica L. Chiang, Huamei Dong, Arthur Berg, Ronald E. Warnick, Douglas Kondziolka and Brian Kavanagh

OBJECTIVE

Stereotactic radiosurgery (SRS) is increasingly used for the treatment of brain metastasis. To date, most studies have focused on survival, radiological response, or surrogate quality endpoints such as Karnofsky Performance Scale status or neurocognitive indices. The current study prospectively evaluated pre-procedural factors impacting quality of life in brain metastasis patients undergoing SRS.

METHODS

Using a national, cloud-based platform, patients undergoing SRS for brain metastasis were accrued to the registry. Quality of life prior to SRS was assessed using the 5-level EQ-5D (EQ5D-L) validated tool; additionally, patient and treatment attributes were collected. Patient quality of life was assessed as part of routine follow-up after SRS. Factors predicting a difference in the aggregate EQ5D-L score or the subscores were evaluated. Pre-SRS covariates impacting changes in EQ5D-L were statistically evaluated. Statistical analyses were conducted using multivariate linear regression models.

RESULTS

EQ5D-L results were available for 116 patients. EQ5D-L improvement (average of 0.387) was noted in patients treated with earlier SRS (p = 0.000175). Worsening overall EQ5D-L (average of 0.052 per lesion) was associated with an increased number of brain metastases at the time of initial presentation (p = 0.0399). Male sex predicted a risk of worsening (average of 0.347) of the pain and discomfort subscore at last follow-up (p = 0.004205). Baseline subscores of pain/discomfort were not correlated with pain/discomfort subscores at follow-up (p = 0.604), whereas baseline subscores of anxiety/depression were strongly positively correlated with the anxiety/depression follow-up subscores (p = 0.0039).

CONCLUSIONS

After SRS, quality of life was likely to improve in patients treated early with SRS and worsen in those with a greater number of brain metastases. Sex differences appear to exist regarding pain and discomfort worsening after SRS. Those with high levels of anxiety and depression at SRS may benefit from medical treatment as this particular quality of life factor generally remains unchanged after SRS.

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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.

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Gautam U. Mehta, Georgios Zenonos, Mohana Rao Patibandla, Chung Jung Lin, Amparo Wolf, Inga Grills, David Mathieu, Brendan McShane, John Y. Lee, Kevin Blas, Douglas Kondziolka, Cheng-Chia Lee, L. Dade Lunsford and Jason P. Sheehan

OBJECTIVE

Meningiomas are the most common benign extramedullary lesions of the foramen magnum; however, their optimal management remains undefined. Given their location, foramen magnum meningiomas (FMMs) can cause significant morbidity, and complete microsurgical removal can be challenging. Anterior and anterolateral FMMs carry greater risks with surgery, but they comprise the majority of these lesions. As an alternative to resection, stereotactic radiosurgery (SRS) has been used to treat FMMs in small case series. To more clearly define the outcomes of SRS and to delineate a rational management paradigm for these lesions, the authors analyzed the safety and efficacy of SRS for FMM in an international multicenter trial.

METHODS

Seven medical centers participating in the International Gamma Knife Research Foundation (IGKRF) provided data for this retrospective cohort study. Patients who were treated with Gamma Knife radiosurgery and whose clinical and radiological follow-up was longer than 6 months were eligible for study inclusion. Data from pre- and post-SRS radiological and clinical evaluations were analyzed. Stereotactic radiosurgery treatment variables were recorded.

RESULTS

Fifty-seven patients (39 females and 18 males, with a median age of 64 years) met the study inclusion criteria. Thirty-two percent had undergone prior microsurgical resection. Patients most frequently presented with cranial neuropathy (39%), headache (35%), numbness (32%), and ataxia (30%). Median pre-SRS tumor volume was 2.9 cm3. Median SRS margin dose was 12.5 Gy (range 10–16 Gy). At the last follow-up after SRS, 49% of tumors were stable, 44% had regressed, and 7% had progressed. Progression-free survival rates at 5 and 10 years were each 92%. A greater margin dose was associated with a significantly increased likelihood of tumor regression, with 53% of tumors treated with > 12 Gy regressing. Fifty-two percent of symptomatic patients noted some clinical improvement. Adverse radiation effects were limited to hearing loss and numbness in 1 patient (2%).

CONCLUSIONS

Stereotactic radiosurgery for FMM frequently results in tumor control or tumor regression, as well as symptom improvement. Margin doses > 12 Gy were associated with increased rates of tumor regression. Stereotactic radiosurgery was generally safe and well tolerated. Given its risk-benefit profile, SRS may be particularly useful in the management of small- to moderate-volume anterior and anterolateral FMMs.

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Or Cohen-Inbar, Cheng-Chia Lee, Seyed H. Mousavi, Hideyuki Kano, David Mathieu, Antonio Meola, Peter Nakaji, Norissa Honea, Matthew Johnson, Mahmoud Abbassy, Alireza M. Mohammadi, Danilo Silva, Huai-Che Yang, Inga Grills, Douglas Kondziolka, Gene H. Barnett, L. Dade Lunsford and Jason Sheehan

OBJECTIVE

Hemangiopericytomas (HPCs) are rare tumors widely recognized for their aggressive clinical behavior, high recurrence rates, and distant and extracranial metastases even after a gross-total resection. The authors report a large multicenter study, through the International Gamma Knife Research Foundation (IGKRF), reviewing management and outcome following stereotactic radiosurgery (SRS) for recurrent or newly discovered HPCs.

METHODS

Eight centers participating in the IGKRF participated in this study. A total of 90 patients harboring 133 tumors were identified. Patients were included if they had a histologically diagnosed HPC managed with SRS during the period 1988–2014 and had a minimum of 6 months' clinical and radiological follow-up. A de-identified database was created. The patients' median age was 48.5 years (range 13–80 years). Prior treatments included embolization (n = 8), chemotherapy (n = 2), and fractionated radiotherapy (n = 34). The median tumor volume at the time of SRS was 4.9 cm3 (range 0.2–42.4 cm3). WHO Grade II (typical) HPCs formed 78.9% of the cohort (n = 71). The median margin and maximum doses delivered were 15 Gy (range 2.8–24 Gy) and 32 Gy (range 8–51 Gy), respectively. The median clinical and radiographic follow-up periods were 59 months (range 6–190 months) and 59 months (range 6–183 months), respectively. Prognostic variables associated with local tumor control and post-SRS survival were evaluated using Cox univariate and multivariate analysis. Actuarial survival after SRS was analyzed using the Kaplan-Meier method.

RESULTS

Imaging studies performed at last follow-up demonstrated local tumor control in 55% of tumors and 62.2% of patients. New remote intracranial tumors were found in 27.8% of patients, and 24.4% of patients developed extracranial metastases. Adverse radiation effects were noted in 6.7% of patients. During the study period, 32.2% of the patients (n = 29) died. The actuarial overall survival was 91.5%, 82.1%, 73.9%, 56.7%, and 53.7% at 2, 4, 6, 8, and 10 years, respectively, after initial SRS. Local progression–free survival (PFS) was 81.7%, 66.3%, 54.5%, 37.2%, and 25.5% at 2, 4, 6, 8, and 10 years, respectively, after initial SRS. In our cohort, 32 patients underwent 48 repeat SRS procedures for 76 lesions. Review of these 76 treated tumors showed that 17 presented as an in-field recurrence and 59 were defined as an out-of-field recurrence. Margin dose greater than 16 Gy (p = 0.037) and tumor grade (p = 0.006) were shown to influence PFS. The development of extracranial metastases was shown to influence overall survival (p = 0.029) in terms of PFS; repeat (multiple) SRS showed additional benefit.

CONCLUSIONS

SRS provides a reasonable rate of local tumor control and a low risk of adverse effects. It also leads to neurological stability or improvement in the majority of patients. Long-term close clinical and imaging follow-up is necessary due to the high probability of local recurrence and distant metastases. Repeat SRS is often effective for treating new or recurrent HPCs.