Perioperative outcomes following reoperation for recurrent insular gliomas

OBJECTIVEGreater extent of resection (EOR) improves overall survival and progression-free survival for patients with low- and high-grade glioma. While resection for newly diagnosed insular gliomas can be performed with minimal morbidity, perioperative morbidity is not clearly defined for patients undergoing a repeat resection for recurrent insular gliomas. In this study the authors report on tumor characteristics, tumor EOR, and functional outcomes in patients undergoing reoperation for recurrent insular glioma.METHODSAdult patients with insular gliomas (WHO grades II–IV) who underwent index resection followed by reoperation were identified through the University of California San Francisco Brain Tumor Center. Treatment history and functional outcomes were collected retrospectively from the electronic medical record. Pre- and postoperative tumor volumes were quantified using software with region-of-interest analysis based on FLAIR and T1-weighted postgadolinium sequences from pre- and postoperative MRI.RESULTSForty-four patients (63.6% male, 36.4% female) undergoing 49 reoperations for recurrent insular tumors were identified with a median follow-up of 741 days. Left- and right-sided tumors comprised 52.3% and 47.7% of the cohort, respectively. WHO grade II, III, and IV gliomas comprised 46.9%, 28.6%, and 24.5% of the cohort, respectively. Ninety-five percent (95.9%) of cases involved language and/or motor mapping. Median EOR of the insular component of grade II, III, and IV tumors were 82.1%, 75.0%, and 94.6%, respectively. EOR during reoperation was not impacted by Berger-Sanai insular zone or tumor side. At the time of reoperation, 44.9% of tumors demonstrated malignant transformation to a higher WHO grade. Ninety-day postoperative assessment confirmed that 91.5% of patients had no new postoperative deficit attributable to surgery. Of those with new deficits, 3 (6.4%) had a visual field cut and 1 (2.1%) had hemiparesis (strength grade 1–2/5). The presence of a new postoperative deficit did not vary with EOR.CONCLUSIONSRecurrent insular gliomas, regardless of insular zone and pathology, may be reoperated on with an overall acceptable degree of resection and safety despite their anatomical and functional complexities. The use of intraoperative mapping utilizing asleep or awake methods may reduce morbidity to acceptable rates despite prior surgery.

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Influence of VEGF-A, VEGFR-1-3, and neuropilin 1-2 on progression-free: and overall survival in WHO grade II and III meningioma patients

Journal of Molecular Histology ◽

10.1007/s10735-020-09940-2 ◽

2021 ◽

Vol 52 (2) ◽

pp. 233-243

Author(s):

Simon Bernatz ◽

Daniel Monden ◽

Florian Gessler ◽

Tijana Radic ◽

Elke Hattingen ◽

...

Keyword(s):

Overall Survival ◽

Tumor Cells ◽

Progression Free Survival ◽

Staining Intensity ◽

Who Grade ◽

Positive Correlation ◽

Protein Levels ◽

Angiogenic Therapy ◽

Neuropilin 1 ◽

Grade Ii

AbstractHigher grade meningiomas tend to recur. We aimed to evaluate protein levels of vascular endothelial growth factor (VEGF)-A with the VEGF-receptors 1-3 and the co-receptors Neuropilin (NRP)-1 and -2 in WHO grade II and III meningiomas to elucidate the rationale for targeted treatments. We investigated 232 specimens of 147 patients suffering from cranial meningioma, including recurrent tumors. Immunohistochemistry for VEGF-A, VEGFR-1-3, and NRP-1/-2 was performed on tissue micro arrays. We applied a semiquantitative score (staining intensity x frequency). VEGF-A, VEGFR-1-3, and NRP-1 were heterogeneously expressed. NRP-2 was mainly absent. We demonstrated a significant increase of VEGF-A levels on tumor cells in WHO grade III meningiomas (p = 0.0098). We found a positive correlation between expression levels of VEGF-A and VEGFR-1 on tumor cells and vessels (p < 0.0001). In addition, there was a positive correlation of VEGF-A and VEGFR-3 expression on tumor vessels (p = 0.0034). VEGFR-2 expression was positively associated with progression-free survival (p = 0.0340). VEGF-A on tumor cells was negatively correlated with overall survival (p = 0.0084). The VEGF-A-driven system of tumor angiogenesis might still present a suitable target for adjuvant therapy in malignant meningioma disease. However, its role in malignant tumor progression may not be as crucial as expected. The value of comprehensive testing of the ligand and all receptors prior to administration of anti-angiogenic therapy needs to be evaluated in clinical trials.

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RTID-05. INDIGO: A GLOBAL, RANDOMIZED, DOUBLE-BLIND, PHASE 3 STUDY OF VORASIDENIB (AG-881) VS PLACEBO IN PATIENTS WITH RESIDUAL/RECURRENT GRADE II GLIOMA WITH AN ISOCITRATE DEHYDROGENASE 1/2 (IDH1/2) MUTATION

Neuro-Oncology ◽

10.1093/neuonc/noaa215.810 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii194-ii194

Author(s):

Ingo Mellinghoff ◽

Martin van den Bent ◽

Jennifer Clarke ◽

Elizabeth Maher ◽

Katherine Peters ◽

...

Keyword(s):

High Risk ◽

Dose Escalation ◽

Objective Response ◽

Data Monitoring Committee ◽

Progression Free Survival ◽

High Risk Population ◽

Low Grade ◽

Who Grade ◽

Free Survival ◽

Grade Ii

Abstract BACKGROUND Low-grade gliomas (LGGs; WHO grade II) are incurable and ultimately progress to high-grade gliomas. The current treatment options are surgery followed by observation (“watch and wait”) for patients with lower risk for disease progression or postoperative chemoradiotherapy (high-risk population). There are no approved targeted therapies. IDH1 and IDH2 mutations (mIDH1/2) occur in approximately 80% and 4% of LGGs, respectively, and promote tumorigenesis via neomorphic production of D-2-hydroxyglutarate. Vorasidenib, an oral, potent, reversible, brain-penetrant pan-inhibitor of mIDH1/2, was evaluated in 76 patients with glioma in two phase 1 studies (dose escalation and perioperative) and was associated with a favorable safety profile at daily doses below 100 mg. Preliminary clinical activity was observed in non-enhancing glioma patients in both studies, with an objective response rate (ORR) of 18.2% and median progression-free survival of 31.4 months in the dose escalation study. METHODS Approximately 366 patients will be randomized 1:1 to vorasidenib (50 mg QD) or matched placebo and stratified by 1p19q status (intact vs co-deleted). Key eligibility criteria: age ≥ 12 years; grade II oligodendroglioma or astrocytoma (per WHO 2016 criteria) not in need of immediate treatment and without high-risk features; centrally confirmed mIDH1/2 status; ≥ 1 surgery for glioma with most recent ≥ 1 year but ≤ 5 years before randomization, and no other anticancer therapy; Karnofsky performance status ≥ 80%; and centrally confirmed measurable, non-enhancing disease evaluable by magnetic resonance imaging. Crossover from placebo to the vorasidenib arm is permitted upon centrally confirmed radiographic progression per RANO-LGG criteria. Primary endpoint: progression-free survival assessed by independent review. Secondary endpoints: safety and tolerability, tumor growth rate assessed by volume, ORR, overall survival, and quality of life. Clinical data will be reviewed regularly by an independent data monitoring committee. The study is currently enrolling patients in the US, with additional countries planned (NCT04164901).

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Stereotactic radiation treatment for recurrent nonbenign meningiomas

Journal of Neurosurgery ◽

10.3171/jns.2007.106.5.846 ◽

2007 ◽

Vol 106 (5) ◽

pp. 846-854 ◽

Cited By ~ 48

Author(s):

Carlos A. Mattozo ◽

Antonio A. F. De Salles ◽

Ivan A. Klement ◽

Alessandra Gorgulho ◽

David McArthur ◽

...

Keyword(s):

Radiation Treatment ◽

Progression Free Survival ◽

Malignant Progression ◽

World Health ◽

Who Grade ◽

Stereotactic Radiation ◽

Grade Ii ◽

Health Organization ◽

Grade Iii

Object The authors analyzed the results of stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) for the treatment of recurrent meningiomas that were described at initial resection as showing aggressive, atypical, or malignant features (nonbenign). Methods Twenty-five patients who underwent SRS and/or SRT for nonbenign meningiomas between December 1992 and August 2004 were included. Thirteen of these patients underwent treatment for multiple primary or recurrent lesions. In all, 52 tumors were treated. All histological sections were reviewed and reclassified according to World Health Organization (WHO) 2000 guidelines as benign (Grade I), atypical (Grade II), or anaplastic (Grade III) meningiomas. The median follow-up period was 42 months. Seventeen (68%) of the cases were reclassified as follows: WHO Grade I (five cases), Grade II (11 cases), and Grade III (one case). Malignant progression occurred in eight cases (32%) during the follow-up period; these cases were considered as a separate group. The 3-year progression-free survival (PFS) rates for the Grades I, II, and III, and malignant progression groups were 100, 83, 0, and 11%, respectively (p < 0.001). In the Grade II group, the 3-year PFS rates for patients treated with SRS and SRT were 100 and 33%, respectively (p = 0.1). After initial treatment, 22 new tumors required treatment using SRS or SRT; 17 (77%) of them occurred inside the original resection cavity. Symptomatic edema developed in one patient (4%). Conclusions Stereotactic radiation treatment provided effective local control of “aggressive” Grade I and Grade II meningiomas, whereas Grade III lesions were associated with poor outcome. The outcome of cases in the malignant progression group was intermediate between that of the Grade II and Grade III groups, with the lesions showing a tendency toward malignancy.

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MNGI-01. A PHASE 0 TRIAL OF RIBOCICLIB IN AGGRESSIVE MENINGIOMA PATIENTS INCORPORATING A TUMOR PHARMACODYNAMIC- AND PHARMACOKINETIC-GUIDED EXPANSION COHORT

Neuro-Oncology ◽

10.1093/neuonc/noz175.583 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi139-vi139

Author(s):

An-Chi Tien ◽

Jing Li ◽

Xun Bao ◽

Alanna DeRogatis ◽

Yoko Fujita ◽

...

Keyword(s):

Cellular Proliferation ◽

Tumor Tissue ◽

Tumor Resection ◽

Progression Free Survival ◽

Who Grade ◽

Drug Concentrations ◽

Grade Ii ◽

Expansion Cohort ◽

Pharmacologically Active

Abstract BACKGROUND New approaches are urgently needed for aggressive meningiomas, which remain largely incurable. Forkhead Box M1 (FOXM1) has been identified as a master transcription factor in aggressive meningiomas and Cyclin D-dependent Kinases (CDK) are positive regulators of cell-cycle entry, promoting tumorigenesis through FOXM1 activation. We evaluated the tumor pharmacokinetics (PK), tumor pharmacodynamics (PD), and preliminary clinical response of ribociclib, a selective CDK4/6-inhibitor, in aggressive meningioma patients. METHODS Eight aggressive WHO Grade II/III meningioma patients with intact RB expression were enrolled and administered oral ribociclib daily for 5 days prior to tumor resection. Plasma, tumor, and cerebrospinal fluid (CSF) samples were collected at 2, 8, or 24 h after the last dose. Total and unbound drug concentrations were determined using a validated LC-MS/MS method. PD effects, including RB and FoxM1 phosphorylation, were compared to matched archival tissue. Patients with PK and PD responses in tumor tissue, defined as unbound ribociclib concentration > 5-fold in vitro IC50 (0.04µM) and >20% decrease in pRB levels, respectively, were enrolled into an expansion cohort for preliminary assessment of progression-free survival. RESULTS The median CSF concentration of ribociclib was 0.25 µM. In tumor tissue, the median unbound ribociclib concentration was 1.36 µM and the median unbound tumor-to-plasma ratio was 5.34. Suppression of G1-to-S phase was inferred in tumors with declining FoxM1 phosphorylation (50%), RB phosphorylation (38%), and cellular proliferation (75%). Four patients demonstrated concurrent PK and PD responses and were graduated to continuous ribociclib therapy. At 14 months, two of these patients (one Grade II and one Grade III) demonstrate partial responses per RANO criteria. CONCLUSION Ribociclib achieves pharmacologically-active concentrations in aggressive meningioma tissue. Target modulation was demonstrated by a decrease in FOXM1-mediated tumor proliferation. Further investigation of ribociclib as a therapeutic strategy for aggressive meningiomas is warranted.

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MNGI-10. ATYPICAL MENINGIOMA: EARLY OUTCOMES WITH OR WITHOUT POSTOPERATIVE RADIATION

Neuro-Oncology ◽

10.1093/neuonc/noz175.592 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi141-vi141

Author(s):

Peter Pan ◽

David Pisapia ◽

Rohan Ramakrishna ◽

Theodore Schwartz ◽

Philip Stieg ◽

...

Keyword(s):

Single Case ◽

Previous Treatment ◽

Progression Free Survival ◽

Atypical Meningioma ◽

Who Grade ◽

Long Term Stability ◽

Grade Ii ◽

Atypical Meningiomas ◽

Lost To Follow Up

Abstract BACKGROUND Adjuvant radiotherapy (RT) in atypical meningioma, especially for gross-totally resected tumors, remains controversial. METHODS We retrospectively identified histologically-confirmed cases of WHO Grade II atypical meningioma at a large academic institution from 2004–2018. Clinicodemographic, surgical, radiation therapy (RT), and histopathologic data were collected, as well as imaging and clinical outcomes, with a median follow-up time of 26 months (IQR 32). Patients were stratified by resection status and whether or not upfront RT was administered. Additionally, subanalyses were performed to compare external beam RT (EBRT) and stereotactic radiosurgery (SRS). Progression was defined by radiology report. RESULTS Of 122 patients, 45 were excluded for lacking adequate records of previous treatment, less than 3 months follow-up, or lacking MR imaging. Of 77 patients analyzed, 57% (44/77) were female; median 59-years-old. 48% (24/50) of gross-total-resections (GTR) received upfront RT – only a single case progressed, at 39 months. Of 26 GTR patients without upfront RT, 8/26 (31%) progressed at median 19.5 months – of these, 2 were lost to follow-up, 5 received salvage RT, and 1 had surgery alone. Adjuvant RT was associated with superior progression free survival (PFS) in GTR (Cox proportional hazard ratio 0.15, likelihood-ratio p=0.025; median PFS not reached). Of 15 subtotal resections (STR) receiving upfront RT, 11 received EBRT and 4 received SRS – 6 progressed (median 37 months), all after EBRT. Upfront SRS demonstrated superior PFS over EBRT following STR (p=0.036). Across the cohort there was one confirmed death, a GTR patient (without RT) who suffered an ischemic stroke at 11 months. CONCLUSION This large single-center retrospective analysis indicates adjuvant RT improves PFS in GTR atypical meningiomas, in concordance with prior studies. It is limited by short median follow-up, possibly related to long-term stability in treated patients. In STR tumors, SRS may contribute to improved PFS compared to EBRT.

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IMT-01 THERAPEUTIC EFFECT AGAINST LOWER GRADE GLIOMA INDUCED BY DENDRITIC CELL BASED IMMUNOTHERAPY

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz039.076 ◽

2019 ◽

Vol 1 (Supplement_2) ◽

pp. ii17-ii17

Author(s):

Yasuharu Akasaki ◽

Jun Takei ◽

Yuko Kamata ◽

Yohei Yamamoto ◽

Ryosuke Mori ◽

...

Keyword(s):

Glioma Cells ◽

Progression Free Survival ◽

Cervical Region ◽

Lower Grade ◽

Mri Findings ◽

Who Grade ◽

Lower Grade Glioma ◽

Major Interest ◽

Grade Ii

Abstract BACKGROUND This trial was designed to evaluate the safety and clinical responses to an immunotherapy with fusions of dendritic and glioma cells in patients with lower grade glioma (LGG; WHO grade II-III glioma). METHOD Autologous cultured glioma cells obtained from surgical specimens were fused with autologous dendritic cells (DC) using polyethylene glycol. The fusion cells (FC) were inoculated intradermally in the cervical region of subjects. Toxicity, progression-free survival (PFS), overall survival (OS), and MRI findings were evaluated. DNA for whole exome and RNA for whole transcriptome extracted from HLA-A*24:02 positive glioma cells were analyzed by next generation sequencer. Variant peptides showing strong binding affinity to HLA-A*24:02 but not the corresponding wild type peptides were selected as candidate of neo-antigens. RESULTS The number of subjects of this trial were 24 (initially diagnosed cases: 20, recurrence cases: 4). WHO grade III cases were 20, and grade II cases were 4. Male were 15, and female were 9. Mean of follow up periods were 53.0 months (the longest follow up period: 1322 months). The number of events on PFS and OS were 8 and 6, respectively. Mean of candidate of neo-antigen peptides in HLA-A*24:02 positive patients (n=8) was 34. Among these candidates, twelve types of common neo-antigen peptide were identified. Neo-antigen peptides specifically expressed in the glioma cells from the effective group were not identified. CONCLUSIONS These results indicate that the efficacy of FC-immunotherapy may not always depend on the number of gene mutations or the expression of the specific neo-antigens. FC-immunotherapy, as a means of producing specific immunity against neo-antigens may safely induce anti-tumor effects in patients with LGG. Analysis of prognostic factor in glioma immunotherapy may be the next area of major interest.

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MNG-03 PD-L1 EXPRESSION, PATIENT PROGNOSIS AND INITIAL WHO GRADE IN GRADE II/III MENINGIOMA

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz039.162 ◽

2019 ◽

Vol 1 (Supplement_2) ◽

pp. ii36-ii36

Author(s):

Dai Kamamoto ◽

Hikaru Sasaki ◽

Ryota Sasao ◽

Takumi Fujiyama ◽

Kazunari Yoshida

Keyword(s):

Radiation Therapy ◽

Progression Free Survival ◽

Who Grade ◽

Free Survival ◽

Specific Data ◽

Tumor Immune Evasion ◽

Significant Difference ◽

Grade Ii ◽

Patient Prognosis ◽

The Relationship

Abstract The optimal treatment for grade II/III meningioma is operation with or without radiation therapy. However, their natural course is sometimes aggressive with high recurrent rate. There is no effective treatment other than operation and radiation therapy, therefore, a new therapeutic strategy for grade II/III meningioma is urgently required.PD-1 and PD-L1 play important roles as immune-checkpoint mediators within tumor microenvironment and the antibodies to these molecules are now approved for the treatment of various kinds of cancers. In Japan, anti-PD-1 antibody and anti-CTLA-4 antibody are approved for unresectable melanoma or advanced / recurrent non-small cell lung cancer and their high effectiveness has been reported. We investigated the expression of PD-L1 (clone:28-8) in 51 cases of grade II/III meningioma by immunohistochemistry and analyzed the relationship between the expression with overall survival, progression free survival and initial WHO grade. For now, we have evaluated 25 cases of PD-L1 immunohistochemistry and PD-L1 showed positivity in 15 cases. There is no correlation observed between PD-L1 expression and patients’ prognosis. Although it does not reach a significant difference, the WHO grade at the time of initial operation tends to be high in those with high PD-L1 staining rate.Similar studies that were previously reported did not use antibodies targeting clone 28-8, which was used as a companion diagnosis for nivolumab administration, but “Correlation between PD-L1 expression and WHO grade”, or “PD-L1 expression is an independent prognostic factor” have been reported. In our investigation, which was using antibodies for companion diagnosis, PD-L1 was positive in more than half of Grade II / III meningiomas and it also related to WHO grade. These results suggest the possibility that tumor immune evasion mechanisms are also working in meningiomas. At the conference, we will report it with the specific data from all cases with a literature review.

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P14.60 FET PET response upon radiochemotherapy followed by Tumor Treating Fields (TTFields) in a patient with progressive high-grade glioma

Neuro-Oncology ◽

10.1093/neuonc/noz126.295 ◽

2019 ◽

Vol 21 (Supplement_3) ◽

pp. iii81-iii81

Author(s):

A F Keßler ◽

J Weiland ◽

T Linsenmann ◽

R Ernestus ◽

C Hagemann ◽

...

Keyword(s):

Tumor Progression ◽

Treatment Response ◽

High Grade Glioma ◽

High Grade ◽

Who Grade ◽

Fet Pet ◽

Tumor Treating Fields ◽

Grade Ii ◽

The Right ◽

Pet Scans

Abstract BACKGROUND The addition of Tumor Treating Fields (TTFields) to the first-line therapy in glioblastoma (GBM) demonstrated significantly improved progression free survival, overall survival and longterm survival rates in the EF-14 phase 3 trial. However, responder analysis of patients with recurrent GBM (rGBM) treated with TTFields monotherapy (in the EF-11 trial) revealed delayed response monitored by MRI analysis. More recent data suggests that O-(2-18F-fluoroethyl)-L-tyrosine (FET) PET may add valuable information for monitoring therapy response of glioblastoma patients treated with TTFields. Here, we report on FET PET response in a patient with progressive anaplastic astrocytoma WHO grade III (AA) treated with TTFields in combination with temozolomide (TMZ) chemotherapy. METHODS We present a 38-year old patient with an initial diagnosis of a diffuse astrocytoma WHO grade II in 2011, and malignisation to an AA on progression. The treatment regimen included initially radio-chemotherapy (RCT) with TMZ. On further progression of the AA in 2017, TTFields were added to another 6 cycles of TMZ. Several FET PET scans for differentiation of tumor progression from treatment-related changes were performed over time. The definitive diagnosis (tumor progression and grading) was confirmed by histopathology after stereotactic biopsy (SB). RESULTS In 2012, the patient was first diagnosed with a low grade astrocytoma WHO grade II of the right frontal, temporal and parietal lobe including infiltration of thalamus and corpus was confirmed by SB, followed by irradiation. On progression in 2015, a FET PET Scan showed FET avidity in all tumor affected regions of the brain. SB confirmed an AA, while FET PET scans showed only a mild response in the temporoparietal region after 6 cycles of TMZ. In 2017, the next progression without further malignisation was confirmed by SB and treated RCT with 41.4 Gy and TMZ chemotherapy, followed by application of TTFields with an average usage rate of 85.7 % over 6 months. Thus, the TTFields adherence was well above the independent prognostic threshold of 75 %. No additional adverse events due to the combined therapy of TTFields and TMZ were observed. Due to a new contrast enhancing lesion in the right frontal lobe (10x7mm), another FET PET scan was performed 1.5 years later. In this scan, obtained after combined TTFields and RCT therapy a strong response regarding FET avidity was observed. CONCLUSION In summary, FET PET is able to add important additional information for evaluation of treatment response in high grade glioma patients, in particular for TTFields treated patients, while adding TTFields to radiochemotherapy might even enhance treatment response of high grade glioma. Further studies might elucidate the role of FET PET imaging for therapy monitoring in high grade glioma patients treated with TTFields.

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Trabectedin for recurrent WHO grade II or III meningioma: A randomized phase II study of the EORTC Brain Tumor Group (EORTC-1320-BTG).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.2007 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 2007-2007 ◽

Cited By ~ 5

Author(s):

Matthias Preusser ◽

Antonio Silvani ◽

Emilie Le Rhun ◽

Riccardo Soffietti ◽

Giuseppe Lombardi ◽

...

Keyword(s):

Adverse Events ◽

Progression Free Survival ◽

Standard Of Care ◽

Somatostatin Analogue ◽

Synthesis Methods ◽

Serious Adverse Events ◽

Who Grade ◽

Sea Squirt ◽

Grade Ii ◽

Grade 3

2007 Background: EORTC-1320-BTG investigated the activity, safety and quality of life of therapy with the tetrahydroisoquinoline alkaloid trabectedin (Yondelis) in patients with recurrent higher-grade meningiomas. Trabectedin was originally derived from the Caribbean sea squirt, Ecteinascidia turbinata, and currently is manufactured by total synthesis. Methods: Adult patients with histological diagnosis of WHO grade II or III meningioma and radiologically documented progression after maximal feasible surgery and radiotherapy were randomly assigned in a 2:1 ratio to receive intravenous trabectedin (1.5 mg/m2every three weeks) or local standard of care (LOC). The primary endpoint was progression-free survival (PFS). Results: Within 22.1 months, we randomized a total of 90 patients (n=29 in LOC arm, n=61 in trabectedin arm) in 35 institutions and nine countries. In the LOC arm, the following treatments were administered: hydroxyurea (n=11), bevacizumab (n=9), none (n=4), chemotherapy (n=3), somatostatin analogue (n=1), combined chemotherapy and somatostatin analogue (n=1). With 71 PFS events, median PFS was 4.17 months in the LOC and 2.43 months in the trabectedin arm (hazard ratio [HR] for progression, 1.42; 80% CI, 1.00-2.03; p=0.204) with a PFS-6 rate of 29.1% (95% CI, 11.9%-48.8%) in the LOC and 21.1% (95% CI, 11.3%-32.9%) in the trabectedin arm. Median OS was 10.61 months in the LOC and 11.37 months in the trabectedin arm (HR for death, 0.98; 95% CI, 0.54-1.76; p=0.94).Grade 3 to 5 adverse events occurred in 44.4% (18.5% related, 4 serious adverse events, 0 lethal events) of the patients in the LOC and 59% (32.8% related, 57 serious adverse events and 2 toxic deaths) of patient in the trabectedin arm. Conclusions: In this first prospective randomized trial performed in recurrent grade II or III meningioma, trabectedin did not improve PFS and OS and was associated with significantly higher toxicity as compared to LOC treatment. The data collected in this study may serve as benchmark for future clinical trials in this setting. Clinical trial information: NCT02234050.

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PL3.2 Trabectedin for recurrent WHO grade II or III meningioma: a randomized phase II study of the EORTC Brain Tumor Group (EORTC-1320-BTG)

Neuro-Oncology ◽

10.1093/neuonc/noz126.005 ◽

2019 ◽

Vol 21 (Supplement_3) ◽

pp. iii2-iii3 ◽

Cited By ~ 1

Author(s):

M Preusser ◽

A Silvani ◽

E Le Rhun ◽

R Soffietti ◽

G Lombardi ◽

...

Keyword(s):

Adverse Events ◽

Progression Free Survival ◽

Standard Of Care ◽

Somatostatin Analogue ◽

Serious Adverse Events ◽

Who Grade ◽

Sea Squirt ◽

Tumor Group ◽

Grade Ii ◽

Grade 3

Abstract BACKGROUND EORTC-1320-BTG investigated the activity, safety and quality of life of therapy with the tetrahydroisoquinoline alkaloid trabectedin (Yondelis®) in patients with recurrent higher-grade meningiomas. Trabectedin was originally derived from the Caribbean sea squirt, Ecteinascidia turbinata, and currently is manufactured by total synthesis. METHODS Adult patients with histological diagnosis of WHO grade II or III meningioma and radiologically documented progression after maximal feasible surgery and radiotherapy were randomly assigned in a 2:1 ratio to receive intravenous trabectedin (1.5 mg/m2every three weeks) or local standard of care (LOC). The primary endpoint was progression-free survival (PFS). RESULTS Within 22.1 months, we randomized a total of 90 patients (n=29 in LOC arm, n=61 in trabectedin arm) in 35 institutions and nine countries. In the LOC arm, the following treatments were administered: hydroxyurea (n=11), bevacizumab (n=9), none (n=4), chemotherapy (n=3), somatostatin analogue (n=1), combined chemotherapy and somatostatin analogue (n=1). With 71 PFS events, median PFS was 4.17 months in the LOC and 2.43 months in the trabectedin arm (hazard ratio [HR] for progression, 1.42; 80% CI, 1.00–2.03; p=0.204) with a PFS-6 rate of 29.1% (95% CI, 11.9%-48.8%) in the LOC and 21.1% (95% CI, 11.3%-32.9%) in the trabectedin arm. Median OS was 10.61 months in the LOC and 11.37 months in the trabectedin arm (HR for death, 0.98; 95% CI, 0.54–1.76; p=0.94).Grade 3 to 5 adverse events occurred in 44.4% (18.5% related, 4 serious adverse events, 0 lethal events) of the patients in the LOC and 59% (32.8% related, 57 serious adverse events and 2 toxic deaths) of patient in the trabectedin arm. CONCLUSIONS In this first prospective randomized trial performed in recurrent grade II or III meningioma, trabectedin did not improve PFS and OS and was associated with significantly higher toxicity as compared to LOC treatment. The data collected in this study may serve as benchmark for future clinical trials in this setting.

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