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.
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.