Purpose To compare the effectiveness of octreotide/everolimus vs . sunitinib for the systemic treatment of recurrent aggressive meningiomas. Methods 31 patients with recurrent or refractory WHO II or WHO III meningiomas were examined in two reference centers in Colombia. Patients who had systemic treatment (sunitinib, everolimus/octreotide) and a complete follow-up were included. Overall survival (OS), progression-free survival (PFS) and toxicities were evaluated. Additionally, tissue samples were examined for PDGFRβ and VEGFR2, their expression was correlated with outcomes. Results Twenty-two patients (72%) were female with a median age of 55 years (SD±15.3). The most prevalent histology was anaplastic meningioma in 20 patients (65%) with 48% of patients suffering from three previous relapses before the start of systemic treatment. A total of 14 patients received combination therapy with octreotide/everolimus, 11 received sunitinib and the remaining 6 received other second-line agents. Median OS was 37.3 months (95%CI 28.5–42.1) and the PFS during the treatment with everolimus/octreotide (EO) and sunitinib (Su) was 12.1 months (95%CI 9.2–21.1) and 9.1 months (95%CI 6.8–16.8); p = 0.43), respectively. The OS of the group treated with the EO→Su→Bev sequence (1 st /2 nd /3 rd line) was 6.5 months longer than the Su→EO→Bev sequence (36.0 vs. 29.5 months) (p = 0.0001). When analyzing molecular markers, the positive PDGFRβ and negative VEGFR2 expression were associated with longer survival both in OS and PFS. Conclusion Sunitinib and octreotide/everolimus have similar efficacy and safety in the systemic management of refractory meningioma. VEGFR2 and PDGFRβ expression are associated with better outcomes.
Background: Ampli cation of EGFR and its active mutant EGFRvIII are common in glioblastoma (GB). While EGFR and EGFRvIII play critical roles in pathogenesis, targeted therapy with EGFR-tyrosine kinase inhibitors (TKIs) or antibodies has shown limited e cacy. To improve the likelihood of effectiveness, we targeted adult patients with recurrent GB enriched for simultaneous EGFR ampli cation and EGFRvIII mutation, with osimertinib/bevacizumab at doses described for non-small cell lung cancer (NSCLC).Methods: We retrospectively explored whether previously described EGFRvIII mutation in association with EGFR gene ampli cation could predict response to osimertinib/bevacizumab combination in a subset of 15 patients treated at recurrence. The resistance pattern in a subgroup of subjects is described using a commercial NGS panel in liquid biopsy.Results: There were ten males (66.7%), and the median patient's age was 56 years (range 38-70 years). After their initial diagnosis, 12 patients underwent partial (26.7%) or total resection (53.3%). Subsequently, all cases received IMRT and concurrent and adjuvant temozolomide (TMZ; the median number of cycles 9, range 6-12). The median follow-up after recurrence was 17.1 months (95% CI 12.3-22.6). All patients received osimertinib/bevacizumab as a second-line intervention with a median progression-free survival (PFS) of 5.1 months (95% CI 2.8-7.3) and overall survival (OS) of 9.0 months (95% CI 3.9-14.0). The PFS6 was 46.7%, and the overall response rate (ORR) was 13.3%. After exposure to the osimertinib/bevacizumab combination, the main secondary alterations were MET ampli cation, STAT3, IGF1R, PTEN, and PDGFR.Conclusions: While the osimertinib/bevacizumab combination was marginally effective in most GB patients with simultaneous EGFR ampli cation plus EGFRvIII mutation, a subgroup experienced a long-lasting meaningful bene t. The ndings of this brief cohort justify the continuation of the research in a clinical trial. The pattern of resistance after exposure to osimertinib/bevacizumab includes known mechanisms in the regulation of EGFR, ndings that contribute to the understanding and targeting in a stepwise rational this pathway.
Atypical (WHO grade II) and malignant meningiomas (WHO Grade III) are a rare subset of primary intracranial tumors. Due to the high recurrence rate after surgical resection and radiotherapy, there has been a recent interest in exploring other systemic treatment options for these refractory tumors. Recent advances in molecular sequencing of tumors have elucidated new pathways and drug targets currently being studied. This article provides a thorough overview of novel investigational therapeutics, including targeted therapy, immunotherapy, and new technological modalities for atypical and malignant meningiomas. There is encouraging preclinical evidence regarding the efficacy of the emerging treatments discussed in this chapter. Several clinical trials are currently recruiting patients to translate targeted molecular therapy for recurrent and high-grade meningiomas.
A 16-year-old young man presented to the emergency room with new-onset generalised tonic-clonic seizures. Examination showed a Glasgow score of 13 and predominantly crural left hemiparesis. Imaging demonstrated a right frontoparietal haemorrhage of non-vascular origin with perilesional oedema. Surgical drainage was carried out, but rebleeding occurred within 24 hours following surgery, and again 1 week after discharge. On reinterrogation and examination, infection was suspected and empirical management with doxycycline was begun. Improvement was evident 72 hours after antibiotic initiation, and PCR confirmed the diagnosis; thus, doxycycline was continued for 6 months. After 2 years, seizures recurred and treatment was reinstated with good clinical response. However, seizures reappeared whenever treatment discontinuation was attempted. Lacking alternatives, doxycycline was maintained up to the third year following the initial episode. Subsequently, the patient showed complete resolution without neurological sequelae up to his last follow-up visit, 12 months following treatment cessation.
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