Volume staged stereotactic radiosurgery and endovascular embolization in the treatment of cerebral proliferative angiopathy: lessons learned.

Purpose of the ArticleCerebral proliferative angiopathy (CPA) is a rare and recently characterized vascular malformation that is often mistaken for a large, diffuse arteriovenous malformation (AVM). However, distinguishing the two entities is critical, as while the diseases may appear similar on imaging, they are completely different entities. The most distinguishing features of CPA compared to AVM are the presence of normal functioning brain within the 'nidus' of the abnormality and the proliferative nature of the nidus. While the management of AVM is considered well understood, the management of CPA is unclear. Typical treatment may include conservative management, targeted embolization, and/or surgical revascularization.Materials and MethodsHere, we present a patient who was initially diagnosed with a large, diffuse AVM in the posterior fossa. Initially managed conservatively, the development of progressive, debilitating neurologic symptoms prompted treatment. We pursued staged endovascular intervention and improved her initial outlook. Thereafter, volume-staged stereotactic radiosurgery (VS-SRS) was pursued to attempt to achieve a definitive treatment.Results and ConclusionsUltimately, while the treatment proved successful clinically and radiographically, the post-treatment course was exceptionally challenging. In retrospect, it is clear the working diagnosis was incorrect, and CPA was the true diagnosis. To our knowledge, this is the first known application of this treatment approach for CPA. However, the post-treatment course and final clinical outcome likely reflect the important differences between AVM and CPA. For these reasons, we are cautious to recommend the treatment course as prescribed in this case but hope to highlight important lessons learned in managing this rare condition.

Linac-based stereotactic radiosurgery (SRS) in the treatment of refractory trigeminal neuralgia: Detailed description of SRS procedure and reported clinical outcomes.

PURPOSE/OBJECTIVES: To present our linac-based SRS procedural technique for medically and/or surgically refractory trigeminal neuralgia (TN) treatment and simultaneously report our clinical outcomes. MATERIALS AND METHODS: Twenty-seven refractory TN patients who were treated with a single fraction of 80 Gy to TN. Treatment delivery was performed with a 4 mm cone size using 7-arc arrangement with differential-weighting for Novalis-TX with six MV-SRS (1000 MU/min) beam and minimized dose to the brainstem. Before each treatment, Winston-Lutz quality assurance (QA) with submillimeter accuracy was performed. Clinical treatment response was evaluated using Barrow Neurological Institute (BNI) pain intensity score, rated from I to V. RESULTS: Out of 27 patients, 22 (81%) and 5 (19%) suffered from typical and atypical TN, respectively, and had median follow-up interval of 12.5 months (ranged: 1-53 months). For 80 Gy prescriptions, delivered total average MU was 19440 ± 611. Average beam-on-time was 19.4 ± 0.6 min. Maximum dose and dose to 0.5 cc of brainstem were 13.4 ± 2.1 Gy (ranged: 8.4-15.9 Gy) and 3.6 ± 0.4 Gy (ranged: 3.0-4.9 Gy), respectively. With a median follow-up of 12.5 months (ranged: 1-45 months) in typical TN patients, the proportion of patients achieving overall pain relief was 82%, of which half achieved a complete pain relief with BNI score of I-II and half demonstrated partial pain reduction with BNI score of IIIA-IIIB. Four typical TN patients (18%) had no response to radiosurgery treatment. Of the patients who responded to treatment, actuarial pain recurrence free survival rates were approximately 100%, 75%, and 50% at 12 months, 15 months, and 24 months, respectively. Five atypical TN patients were included, who did not respond to treatment (BNI score: IV-V). However, no radiation-induced cranial-toxicity was observed in all patients treated. CONCLUSION: Linac-based SRS for medically and/or surgically refractory TN is a fast, effective, and safe treatment option for patients with typical TN who had excellent response rates. Patients, who achieve response to treatment, often have durable response rates with moderate actuarial pain recurrence free survival. Longer follow-up interval is anticipated to confirm our clinical observations.

Incidence of Intracranial Melanoma Progression in the Setting of Positive Extracranial Response to Targeted Therapy and Immunotherapy: An Indication for More Frequent Screening in This Population?

Background and objective The incidence of intracranial metastases from melanoma is on the rise. In this study, we aimed to determine the incidence of intracranial disease progression in patients on BRAF/MEK targeted therapy and immunotherapy in the setting of controlled or improving extracranial disease. Methods This was a single-center, retrospective review that involved patients who underwent stereotactic radiosurgery (SRS) for intracranial metastatic melanoma between January 1, 2014, and December 31, 2018. We focused on BRAF/MEK mutation status and dates of treatment with BRAF/MEK targeted therapy, immunotherapy [ipilimumab (Yervoy), nivolumab (Opdivo), or pembrolizumab (Keytruda)], and combination targeted and immunotherapy. Results A total of 51 patients were enrolled: 36 males and 15 females. The average age of the patients was 58.6 years, and 26 among them were BRAF mutation-positive. Seventeen had prior surgery with SRS as adjuvant therapy. The other 34 had SRS as primary treatment. Forty-two patients had extracranial disease present at the time of SRS. There were 34 patients treated with targeted and immune therapy. Overall, 16 patients (47.1%) demonstrated controlled or improving extracranial disease, and 18 (52.9%) demonstrated progressing extracranial disease at the time of SRS. In the subgroup analysis, patients treated with BRAF/MEK targeted therapy demonstrated a 75% rate of extracranial disease control. The extracranial disease was controlled in 43.75% of patients on immunotherapy with intracranial progression, while it was controlled in 30% of patients on both BRAF/MEK targeted therapy and immunotherapy with intracranial progression. Sixteen patients (47.1%) developed intracranial metastasis in our study while having a stable systemic disease with BRAF/MEK targeted therapy, immunotherapy, or a combination of the two. Conclusion Based on our findings, a systemic response to targeted therapy and immunotherapy does not necessarily parallel intracranial protection.