Background

Low grade glioma (LGG) is a heterogeneous disease. Recently, the 2016 WHO classification of brain tumors has underlined the role of genetic and molecular features. Molecular astrocytomas have been defined as grade II tumors with IDH mutation and without 1p19q codeletion.

Methods

We evaluated 213 consecutive patients with LGG who received surgery or biopsy and had adequate tissue to assess molecular characterization. IDH mutations were assessed by immunohystochemistry (IHC) and next generation sequencing (NGS) in IHC negative cases, MGMT methylation status was assessed by polymerase chain reaction (PCR) and 1p19q deletion was assessed by fluorescence in situ hybridation (FISH).

Results

198 patients (93.0%) showed IDH-mutation. Ninety patients (49.2%) were 1p19q non codeleted (molecular astrocytomas). The median follow up was 98.3 months. Median age was 36 (range: 18-69), 11 patients (12.2%) underwent biopsy, 48 (53.3%) patients subtotal resection and 31 (34.4%) patients total resection. According to RTOG criteria, 68 patients (75.6%) were considered high risk (> 40 years and/or incomplete resection), and 22 patients (24.4%) were considered low risk (< 40 years and/or complete resection). 59 patients (65.5%) did not receive any post-surgical treatment, but only follow-up, 31 patients (34.4%) received post-surgical treatments: 20 (22.2%) received radiotherapy (RT), 7 (7.8%) received chemotherapy (CT), 4 (4.4%) received CT+RT. Median progression-free survival (PFS) was 44.3 months. Significant differences in PFS were observed between treated and untreated patients (64.8 vs 35.7 months p = 0.004) and treated with RT versus follow-up (60.0 vs 35.7 months p = 0.004). Multivariate analysis confirmed the treatment after surgery as an independent prognostic factor (HR 0.456, p = 0.005). Median overall survival (OS) was 164.0 months. At time of analysis no significant differences in OS were available.

Conclusions

Post-surgical treatment after resection of IDH mutant molecular astrocytomas is an independent prognostic factor. A longer follow-up is needed for worthy results in terms of OS.

Legal entity responsible for the study

N/A

Funding

None

Disclosure

All authors have declared no conflicts of interest.

Background

Gal-1 is a β-galactoside binding protein that plays an important role in cancer progression and has been implicated in resistance to chemotherapy and anti-VEGF therapy. Gal-1 mediates glioma aggressiveness and its expression increases with grade and correlates with worse outcome. Our aim was to evaluate the prognostic significance of Gal-1 in a homogenous cohort of GB.

Methods

GLIOCAT is a multicenter study of newly diagnosed 432 GB patients treated with Stupp regimen. Tissue from 272 patients was used to generate a tissue microarray and Gal-1 expression in cytoplasm (C) and nucleus (N) was analyzed by immunohistochemistry. Results were evaluated by three reviewers and quantified by H-Score. Expression levels were correlated with clinical characteristics, known prognostic factors and response to anti-angiogenic treatment. Preliminary results will be presented at 2017 ASCO, abstract e13526. We will report here the final results.

Results

We defined a cut off for Gal-1 H-Score of ≥ 157 (cytoplasm, C) and ≥123 (nucleus, N). High combined Gal-1 expression significantly correlated with worse OS. No correlation was found with PFS.Table:

330PD

Multivariate analysis: KPS, age, MGMT methylation status, extent of resection and Gal-1 expression were independent prognostic factors for survival. High Gal-1 expression correlated with worse OS at recurrence in 61 patients with antiangiogenic treatment (13.8 vs 17.8months, p = 0.084) and in 80 with other therapies (17.7 vs 29.3months, p = 0.001).

Conclusions

Gal-1 expression represents an independent prognostic factor for GB patients treated initially with standard therapy and with other therapies at recurrence.

Legal entity responsible for the study

Gliocat group

Funding

Marató TV3 2012

Disclosure

All authors have declared no conflicts of interest.

Background

There is a relative paucity of data regarding outcomes of pleomorphic xanthoastrocytomas (PXA) particularly with respect to the impact of emerging molecular markers. We present our institutional experience of PXA and correlate their outcomes with various clinical and pathological factors.

Methods

Between 2006 to 2016, 37 patients with histologically verified PXA form the study cohort. All patients underwent maximal safe resection; those who had good resection, low MIB-1 index and young age were observed. Adjuvant radiotherapy was given in patients with atypical features on histology, high MIB-1 index and recurrence after first surgery or with significant residual disease. Patients diagnosed with anaplastic PXA were managed by multi-modality approach comprising maximal safe resection, radiotherapy and systemic therapy. BRAFV600E mutation testing was attempted in all 37 paraffin embedded tissue blocks. Progression free survival (PFS) and overall survival (OS) and potential prognostic factors affecting outcomes were analyzed.

Results

Median age at diagnosis was 20 years (range 4–45). Tumors were predominantly in the temporal lobe and seizures were the most frequent symptom at presentation. Gross total resection (GTR) was achieved in 23 cases (62%), a subtotal resection (STR) in 13 cases (35%) and biopsy in one patient. At a median follow-up of 33 months, 3-year and 5-year OS was 80.2% & 74% respectively. Patients who underwent GTR had a better PFS as compared to those who underwent STR (3-year estimates 85.6% vs. 32.3%; p = 0.001). 10 patients (27%) were classified as having anaplastic PXA. PFS was significantly superior in PXA grade II as compared to the anaplastic PXA group (3-year estimates 80.2% vs. 32%; p = 0.007). Of the 27 patients where BRAF V600E testing was successful, 13 patients showed a mutation (48%). 3-year PFS & OS survival in BRAFV600E mutated patients was 51.9% & 76.9% compared to 73% & 75% in BRAFV600E non-mutated patients, respectively. No patient had an IDH1 mutation.

Conclusions

Anaplastic PXA has worse outcomes as compared to PXA grade II. This data may provide valuable insights and set as a benchmark for imparting targeted therapies.

Legal entity responsible for the study

Nil

Funding

Brain Tumour Foundation of India

Disclosure

All authors have declared no conflicts of interest.

Background

Although immunotherapy is not an established treatment option in high grade glial tumors, trials are ongoing. One of the main predictive factor for response to immune checkpoint inhibitors is PD-L1 expression status and this can change over time with the effect of therapies like chemotherapy and radiotherapy. The aim of this study is to determine whether PD-L1 expression status changes in recurrent gliomas after chemoradiotherapy and the impact of this change on survival.

Methods

PD-L1 expression of 29 patients was evaluated by an expert pathologist with immunohistochemistry. PD-L1 positivity was defined as expression in ≥ 1% of tumor cells. Change in PD-L1 expression status was defined as an absolute 5% difference between two resections.

Results

Of the 29 patients, 15 patients (51.7%) had PD-L1 expression in ≥ 1% of tumor cells and 7 patients (24.1%) had PD-L1 expression in ≥ 10% of tumor cells at diagnosis. Median survival of patients with baseline PD-L1 <%10 was 26 months, and in patients with PD-L1 ≥%10 was 18 mo (P = 0.063). The PD-L1 status did not change in 17 patients (58.6%). 8 patients had PD-L1 negative tumors both at diagnosis and at recurrence, while 9 patients had PD-L1 positive tumors both at diagnosis and at recurrence. In 6 patients (20.7%) a negative-to-positive switch and in 6 patients (20.7%) a positive to negative switch were seen. The change in PD-L1 status over time was not statistically significant. The change of PD-L1 over time did not influenced overall survival of the patients (P = 0.45).

Conclusions

The PD-L1expression status changes in more than 40% of high grade glial tumors at recurrence after receiving chemotherapy and radiotherapy. So immune responsiveness of glial tumors can be modified by treatments. As the patients in this study did not receive immunotherapy after recurrence, the change in PD-L1 expression probably did not affect survival.

Legal entity responsible for the study

Basak Oyan, Seyma Eren, Ozlem Sonmez

Funding

Yeditepe University Hospital

Disclosure

All authors have declared no conflicts of interest.

Background

Primary central nervous system lymphoma (PCNSL) is a rare subtype of agressive non-hodgkin lymphoma (NHL), and is most commonly of B cell phenotype. The standard treatment is not well established but high dose methotraxate is the most commonly used regimen. Intravenous rituximab (iv Rtx) treatment is integrated into the protocols for systemic B cell lymphomas. However there are mixed results with the use of Rtx. The aim of this meta-analysis is to investigate the role of iv Rtx in the treatment of PCNSL.

Methods

PubMed and EBSCOhost databases are searched for rituximab, primary central nervous lymphoma, rituximab, survival. Browsing databases was done in English.

Results

580 patients were included to meta-analysis. Pooled hazard ratio showed that overall survival is correlated with iv Rtx (HR, 0,498; 95% CI, 0,366 - 0,678; p:<0,001). Pooled hazard ratio was calculated by using fixed effect model. The quality determinations of 7 studies were done by using Newcastle-Ottowa Scale. The studies were counted low quality with the score 1-3, average quality with the score 4-6, high quality with the score7-9. Median score of the studies was calculated as 5.

Conclusions

In this meta-analysis, we showed that the addition of iv Rtx as part of a treatment protocol for PCNSL has a positive impact on survival.

Legal entity responsible for the study

Mustafa Yıldırım

Funding

None

Disclosure

All authors have declared no conflicts of interest.

Background

TTFields is a novel cancer treatment modality using a patient-operated home-use device delivering alternating electrical fields interfering with cell division and selectively disrupting mitosis. Clinical trials are ongoing in various solid tumors and phase 3 trials in glioblastoma (GBM) were recently concluded.

Methods

TTFields were tested in two large phase 3 trials in patients with recurrent (EF-11; n = 237) and newly diagnosed GBM (EF-14; n = 695). Both trials aimed at improving overall survival (OS) with TTFields and included quality of life (QOL) using the EORTC QLQ C-30 with brain cancer module (BN-20) as a secondary endpoint.

Results

In recurrent GBM, TTFields monotherapy was compared to best physician’s choice chemotherapy and failed to demonstrate a superior OS. However, improved response rate (14% vs 9.6%) and a comparable OS (HR 0.86 [CI 0.66–1.12]; p = 0.27) suggested clinical activity. The absence of systemic toxicity was favorably noted by many patients. In newly diagnosed GBM, TTFields was added to standard adjuvant TMZ chemotherapy and led to a significant prolongation of OS (HR 0.63 [CI 0.53-0.76]; p = 0.000059), without added systemic toxicity. OS was extended in all patient subgroups tested including MGMT unmethylated tumors and elderly GBM. More TTFields patients reported stable or improved scores on global health status, pain, physical functioning and leg weakness (all p≤.01). Deterioration free survival was significantly longer with TTFields for global health, physical and emotional functioning, pain and leg weakness (all p<.01). Time to deterioration was shorter for itchy skin and longer for pain (both p<.001).

Conclusions

TTFields are an effective treatment for GBM with a novel mechanism of action and unique delivery method. Patients become rapidly independent in handling the device allowing patients to control their treatment at home with stable or improved QOL. The significant survival benefit observed in GBM serves as a proof of principle and establishes this novel modality as a promising anti-cancer therapy in a variety of solid tumors. Due to the lack of overlapping toxicities it can be easily combined with established treatments.

Clinical trial identification

NCT#00379470 and NCT#00916409

Legal entity responsible for the study

Novocure Ltd.

Funding

Novocure Ltd.

Disclosure

R. Stupp: Travel funding from Novocure Ltd. The institutions received research funding for the phase 3 trials mentioned in the abstract from Novocure Ltd. S. Taillibert: The institution received funding for the two phase 3 trials in this abstract from Novocure Ltd. J. Honnorat: Participated in a Novocure sponsored advisory board. The institution received funding for the two phase 3 trials in this abstract from Novocure Ltd. T. Chen: The institution received research funding for the phase 3 trial in newly diagnosed GBM from Novocure Ltd. J. Sroubek: The institution received research funding for the phase 3 trials in this abstract from Novocure Ltd. S.H. Paek, J. Bruna Escuder, J. Easaw, C.Y. Kim: The institution received research funding from Novocure Ltd. for the phase 3 trial in ndGBM. C. David: The institution received research funding from Novocure Ltd. for the ndGBM phase 3 trial. R. Desai: The institution received research funding for the study from Novocure. Y. Kew: The institution received research funding for the phase 3 study from Novocure. A. Olivi: The institution received research funding for the EF14 study from Novocure. A. Hottinger: Honoraria for advisory boards from Novocure. The institution received research funding for both phase 3 trials mentioned in the abstract from Novocure). E.D. Kirson: Employee of Novocure and stock owner. G. Lavy-Shahaf: Employee of Novocure. M.E. Hegi: The institution received research funding from Novocure for performing genetic analyses of the tissue samples in the study. Z. Ram: Paid consultant to Novocure Ltd. All other authors have declared no conflicts of interest.

Background

Although temozolomide (TMZ) was known to induce thrombocytopenia with subsequent cycle delay, dose reduction and early treatment discontinuation in glioblastoma multiforme (GBM), no early predictive test of these side effects has been yet clearly established. In this context, our aim was to identify the best threshold of early platelet variation predicting TMZ-induced thrombocytopenia during the TMZ maintenance phase and to validate it in an independent series of GBM patients.

Methods

It was a retrospective trial including patients suffering from newly diagnosed GBM and treated with TMZ at 75 mg/m2/day concomitant to radiotherapy (RT) followed by TMZ maintenance, according to the Stupp protocol. In a training set, variations of platelet concentrations occurring from the first week to week 6 (ΔW6) were analyzed to identify the most relevant platelet decrease during RT-TMZ associated with at least one clinically relevant TMZ-induced thrombocytopenia (≤100 G/l) in the maintenance phase. An independent validation cohort was used to validate the performance of the ΔW6 threshold.

Results

A total of 147 patients were included: 85 in the training set and 62 in the validation cohort. Twenty seven patients (18%) experienced at least one TMZ-induced thrombocytopenia in the maintenance phase, respectively 14 (16%) and 13 patients (21%) in each cohort; and was the most frequent cause of TMZ schedule changes (49%, 30/61). A platelet decrease at W6 ≥35% (ΔW6≥35%) was identified as the best predictive variation of clinically induced thrombocytopenia with an AUC of 0.83, a sensitivity (Se) of 65% and a specificity (Sp) of 96%. In the validation set, a presence of a ΔW6≥35% of platelet variation was associated with: Se 77% [95% CI 66%-87%], Sp 73% [62%-84%], positive predictive value 42% [29%-54%] and negative predictive value 92% [86%-99%].

Conclusions

Our results showed that a platelet decrease at W6 ≥35% during the RT-TMZ phase may be an early, widely faisable and costless marker of clinically relevant TMZ-induded thrombocyponia during the TMZ maintenance. Prospective studies are needed to evaluate the usefulness of this test for early TMZ schedule adaptation.

Legal entity responsible for the study

Cancer Center Henri Becquerel

Funding

Cancer Center Henri Becquerel and IRIB

Disclosure

All authors have declared no conflicts of interest.

Background

There is no standard treatment in recurrent GB and overall survival (OS) ranges from 3 to 9 months (m). The aim of this study was to identify clinical or biological factors that guide the best therapeutic strategy.

Methods

We identified 397 patients (Pts) from GLIOCAT database (432 patients uniformly treated with Stupp’s regimen) who had recurrent GB: 250 Pts received 1 or more active treatment (TT) and 147 Pts didn’t. We analysed clinical and molecular characteristics, treatments received, OS and progression-free survival (PFS).

Results

The median TT lines after recurrence was 1 (0-5). At 1^st recurrence surgery was performed in 51 (30 alone), RT in 8 and systemic therapy (ST) in 208 Pts (189 without any local TT): Bevazicumab (BV) ± Irinotecan (IR) 90; clinical trial (CT) 42; TMZ 27; Nitrosoureas (NU) 27]. Pts without any TT were older (p < 0.001), had worse KPS (p < 0.001), worse Mini-Mental (MM) (p = 0.003), more biopsies than resection (p < 0.001) and did not complete the 6 cycles of adjuvant TMZ (p < 0.001) analyzed by χ². In the multivariate analysis the only two variables statistically significant for OS were receiving treatment at progression (OS 2.5m vs 10.6m p < 0.0001) and biopsy versus partial or complete resection at diagnosis (p = 0.005). Methylated MGMT tumours had a worse OS from the time of relapse, irrespective of the treatment administered (p = 0.014). Salvage surgery did not present better OS (p = 0.69). 230 Pts had a 2^nd recurrence: 128 received a 2^nd line TT (surgery 8; RT 5 and ST 114: BV ± IR 42; NU 31; TMZ 19; CT 11; other 11). 110 Pts had a 3th recurrence: 42 received a 3^th line. Pts who received TT had better OS than those who did not receive TT in 2^nd (p < 0.0001) and in 3th recurrence (p < 0.0001) evaluated by Log rank test (Kaplan-Meier). BV was the TT that obtained the highest median PFS in the 1^st and 2^nd relapse. There were no significant differences in OS between the different TT regimens (median OS from relapse 7.7 m).

Conclusions

Pts who received TT at recurrence offered a better OS in multivariate analysis. Pts undergoing surgery did not present better OS than those who only received ST. MGMT methylation is not a predictor of better OS in recurrence. Pts treated with BV had longer PFS but not OS.

Legal entity responsible for the study

GLIOCAT

Funding

None

Disclosure

M. Gil-Gil: Membership on a Roche advisory board.

All other authors have declared no conflicts of interest.

Disclosure

M. Gil-Gil: Membership on a Roche advisory board.

All other authors have declared no conflicts of interest.