scholarly journals Intraventricular Meningiomas: Clinical-Pathological and Genetic Features of a Monocentric Series

2022 ◽  
Vol 29 (1) ◽  
pp. 178-185
Author(s):  
Serena Ammendola ◽  
Michele Simbolo ◽  
Chiara Ciaparrone ◽  
Paola Chiara Rizzo ◽  
Maria Caffo ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Copy Number Variations ◽  
Low Grade ◽  
Check Point ◽  
Mutational Burden ◽  
Genetic Features ◽  
Tumor Mutational Burden ◽  
Life Threatening ◽  
Grade Ii ◽  
Generation Sequencing

Intraventricular meningiomas (IVMs) are rare (0.5–5%) and usually low-grade (90% grade I) brain neoplasms. Their recurrence rate is lower than that of extra-axial meningiomas, but their surgical resection can be burdened with life-threatening complications, which represent the major cause of the reported 4% mortality. The aim of this study is to characterize the molecular portrait of IVMs to identify potential therapeutic targets. For this, we explored mutations and copy number variations (CNV) of 409 cancer-related genes and tumor mutational burden (TMB) of six cases, using next-generation sequencing. Five IVMs were grade I and one was grade II; none recurred, in spite of partial surgical resection in one case. NF2 mutation was the only recurring alteration and was present in three of the six IVMs, in association with SMARCB1 mutation in one case. None of the cases was hypermutated (TMB > 10 mutations/Mb). NF2-mutant progressing or recurring IVMs could potentially be treated with targeted therapies applied to other NF2-mutant tumors, as an alternative to surgery or radiosurgery, while in view of their low TMB they are unlikely candidates to immune check-point inhibition.

Impact of next-generation sequencing (NGS) on diagnostic and therapeutic options in soft-tissue and bone sarcoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11001-11001 ◽  
Author(s):  
Mrinal M. Gounder ◽  
Siraj Mahamed Ali ◽  
Victoria Robinson ◽  
Mark Bailey ◽  
Richard Ferraro ◽  
...  
Keyword(s):  
Clear Cell ◽  
Study Drug ◽  
Bone Sarcoma ◽  
Resistance Mutations ◽  
Glomus Tumors ◽  
Therapeutic Implications ◽  
Mutational Burden ◽  
Tumor Mutational Burden ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

11001 Background: The utility of NGS in management of sarcoma pts remains undefined. Methods: We retrospectively analyzed the NGS profile of patients who were sequenced using a panel of 405 cancer-related genes in DNA and 265 genes rearranged in RNA. Diagnostic and therapeutic implications of mutations (mut) were evaluated through published literature (OncoKb.org, Pubmed). An algorithm was applied to determine germline mut. Following IRB approval, we evaluated the clinical outcomes of pts who underwent NGS at MSKCC. Results: From 2012–2016, 5635 pts worldwide with 56 histologies were tested. Median age of 52 yrs ( < 1-88), 52% females and sarcoma NOS (n = 858) was most frequent. Tumors were sequenced to a mean coverage of 634X; 1165 fusions and > 60,000 mut were found. Mut suspicious for germline defects were seen in 542 pts (9.6%) in known and novel genes ( BRCA, ARID1, FANC). Tumor mutational burden was 2.5/Mb (0–329) and glomus tumors and EHE had the highest and lowest mut, respectively. 16% and 7% of pts had treatment-linked alterations (TLA) known to respond to an FDA approved or study drug, respectively. 42% of pts had TLA eligible for NCI-MATCH, ASCO-TAPUR or other studies. Novel TLA include AKT, ESR1, BRCA, NTRK, PTCH1, SMARCB1 and others. Of the 107 MSKCC pts with clinical data, 60/107 (57%) had at least one TLA, of which 31 (30%) enrolled on a matched trial and 26 pts were ineligible or lacked access to trials. Partial/complete responses were seen with inhibitors to NTRK, IDH1, BRAF, PI3K/mTOR, MDM2, SMARCB1 and others. NGS changed the initial pathology diagnosis and treatments in 5% pts (e.g. LMS to liposarcoma, clear cell to melanoma). Resistance mutations averted futile therapies in 5% pts (e.g. Rb loss and palbociclib in liposarcoma). Conclusions: Our data suggests that NGS has a significant impact in aiding diagnosis and selecting matched therapies in sarcoma. Suspected germline aberrations, while intriguing, needs further validation.

Safety and Efficacy of Surgical Resection of Unruptured Low-grade Arteriovenous Malformations From the Modern Decade

Neurosurgery ◽  
2015 ◽  
Vol 77 (6) ◽  
pp. 948-953 ◽  
Author(s):  
Karam Moon ◽  
Michael R. Levitt ◽  
Rami O. Almefty ◽  
Peter Nakaji ◽  
Felipe C. Albuquerque ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Neurological Deficit ◽  
Arteriovenous Malformations ◽  
Low Grade ◽  
Stroke Rate ◽  
Modified Rankin Scale ◽  
Postoperative Neurological Deficit ◽  
Clinical Impairment ◽  
Grade Ii

BACKGROUND: Recent studies have questioned the utility of surgical resection of unruptured brain arteriovenous malformations (bAVMs). OBJECTIVE: We performed an assessment of outcomes and complications of surgical resection of low-grade bAVMs (Spetzler-Martin grade I or II) at a single high-volume neurosurgical center. METHODS: We reviewed all unruptured low-grade bAVMs treated with surgery (with or without preoperative embolization) between January 2004 and January 2014. Stroke rate, mortality, and clinical and radiographic outcomes were examined. RESULTS: Of 95 patients treated surgically, 85 (25 grade I, 60 grade II) met inclusion criteria, and all achieved radiographic cure postoperatively. Ten patients (11.8%) were lost to follow-up; the mean follow-up of the remaining 85 was 3.3 years. Three patients (3.5%) with grade II bAVMs experienced a stroke; no patients died. Although 20 patients (23.5%) had temporary postoperative neurological deficit, only 3 (3.5%) had new clinical impairment (modified Rankin Scale score ≥2) at last follow-up. Eight of the 13 patients (61.5%) with preexisting clinical impairment had improved modified Rankin Scale scores of 0 or 1; and 17 of 30 patients (56.7%) with preoperative seizures were seizure-free without antiepileptic medication postoperatively. No significant differences existed in stroke rate or clinical outcome between grades I and II patients at follow-up (Fisher exact test, P = .55 and P &gt; .99, respectively). CONCLUSION: Surgical resection of low-grade unruptured bAVMs is safe, with a high rate of improvement in functional status and seizure reduction. Although transient postoperative neurological deficit was observed in some patients, permanent treatment-related neurological morbidity was rare.

scholarly journals ATIM-31. SAFETY OF TUMOR-SPECIFIC PEPTIDE VACCINE TARGETING ISOCITRATE DEHYDROGENASE 1 MUTATION IN RECURRENT RESECTABLE LOW GRADE GLIOMA PATIENTS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi8-vi8
Author(s):  
Katherine Peters ◽  
Kendra Congdon ◽  
Gary Archer ◽  
Sarah Woodring ◽  
Denise Jaggers ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Isocitrate Dehydrogenase ◽  
Phase 1 ◽  
Peptide Vaccine ◽  
Resonance Spectroscopy ◽  
Low Grade ◽  
Isocitrate Dehydrogenase 1 ◽  
Who Grade ◽  
Grade Ii ◽  
Specific Peptide

Abstract BACKGROUND Low grade gliomas (LGGs) represent 10–15% of glial tumors in adults and while LGG patients have a better prognosis over high-grade gliomas, these cancers ultimately recur and transform to more aggressive tumors. Isocitrate dehydrogenase 1 (IDH1) is commonly mutated in LGG, and when mutated, it is the oncogenic driver by leading to the production of oncometabolite 2-hydroxyglutarate (2-HG). We developed a phase 1 study for recurrent resectable IDH1 mutant LGG utilizing a tumor-specific peptide vaccine targeting IDH1 mutant protein that spans the mutated region of IDHR132H (PEPIDH1M vaccine). METHODS We performed a phase 1, single-center, clinical trial in recurrent resectable IDH1 mutant WHO grade II glioma patients. Subjects received three PEPIDH1M vaccine q2wks and then proceeded to surgical resection. If subject’s tumor retained grade II status, then the subject proceeded with 12 cycles of daily TMZ (50 mg/m2 X 28 days) and PEPIDH1M vaccine (12 injections q4wks). If subject’s tumor transformed to grade III, then subject proceeded to radiation therapy (RT) with concurrent TMZ followed by 12 cycles of daily TMZ (50 mg/m2 X 28 days) and PEPIDH1M vaccine (12 injections q4wks). Primary endpoint was safety of PEPIDH1M vaccine in combination with adjuvant TMZ and/or XRT/TMZ and evaluable subjects needed to receive ≥6 PEPIDH1M vaccines. We assessed safety using CTCAE 4.03. RESULTS We enrolled 24 recurrent LGG subjects with mean age of 43.8 yrs (sd=11.4 yrs). Twenty subjects completed ≥6 PEPIDH1M vaccines. Most common related toxicity was grade 1 injection site reaction (N=20) and skin induration (n=17) with no grade 3–4 related toxicities. CONCLUSIONS PEPIDH1M vaccine in combination with surgical resection, daily TMZ and/or RT + TMZ with daily TMZ was safe and well tolerated in recurrent IDH1 mutant LGG. We are currently exploring secondary/correlative endpoints including immunogenicity of PEPIDH1M vaccine and magnetic resonance spectroscopy for 2-HG.

Sign in / Sign up

Export Citation Format

Share Document