Association Of Neuro-Oncology Research Articles

Patient and carer involvement in the formulation of research questions: findings from the Italian guideline on palliative care in adults with glioma.

In 2017, the European Association for Neuro-Oncology (EANO) published the guideline for palliative care (PC) in adults with glioma. The Italian Society of Neurology (SIN), the Italian Association for Neuro-Oncology (AINO), and the Italian Society for Palliative Care (SICP) joined forces to update and adapt this guideline to the Italian context and aimed to involve patients and carers in the formulation of the clinical questions. During semi-structured interviews with glioma patients and focus group meetings (FGMs) with family carers of deceased patients, participants rated the importance of a set of pre-specified intervention topics, shared their experience, and suggested additional topics. Interviews and FGMs were audio-recorded, transcribed, coded, and analyzed (framework and content analysis). We held 20 interviews and five FGMs (28 carers). Both parties considered the pre-specified topics as important, chiefly information/communication, psychological support, symptoms management, and rehabilitation. Patients aired the impact of focal neurological and cognitive deficits. Carers reported difficulties in dealing with patient's behavior and personality changes and appreciated the preservation of patient's functioning via rehabilitation. Both affirmed the importance of a dedicated healthcare path and patient's involvement in the decision-making process. Carers expressed the need to be educated and supported in their caregiving role. Interviews and FGMs were well informative and emotionally challenging. Both parties confirmed the importance of the pre-specified topics, and carers suggested one additional topic: education/support to caregivers. Our findings strengthen the importance of a comprehensive care approach and of addressing the needs of both patients and their family carers.

Health professional involvement in the formulation of research questions: findings from the Italian guideline on palliative care in adults with glioma.

In 2017, the European Association of Neuro-Oncology (EANO)published the guideline for palliative care in adults with glioma. The Italian Society of Neurology (SIN), the Italian Society for Palliative Care (SICP), and the Italian Association for Neuro-Oncology (AINO) joined forces to update the guideline, and adapt it to the Italian context. We involved patients, caregivers, and (herein presented) healthcare professionals (HPs) in the formulation of the guideline clinical questions. Online survey of Italian HPs experienced in the care of patients with glioma. Participants rated the importance of 14 pre-specified intervention topics on a 0/10 scale and gave their free comments. Of 244 participants, 149 (61%) were palliative medicine (PM) HPs and 95 Neuro HPs. Their mean age was 48.9years, 63% were women, and 48% had over 12years of experience in the care of glioma patients. Physicians were 68%, followed by nurses (28%), psychologists (7%), therapists (3%), and social workers (2%). Most HPs rated the pre-specified topics as important (score ≥ 7) or critical (score ≥ 9), with some differences between PM and Neuro HP groups. There were 58 free comments: 46 (78%) on nine pre-specified topics, and 13 on four new topics, three of which were guideline-pertinent ("caregiver's support and education"; "family physician's training in neuro-oncology"; and "PM HPs' training in neuro-oncology"). Participation in the survey was high and information-rich, between-group rating differences reflecting HP background. Participants endorsed the 14 intervention topics devised by the guideline panel and identified three additional topics.

P11.59.B Real-life application of the 2021 WHO Classification molecular criteria in Italy: a national survey from the Italian Association of Neuro-Oncology (AINO) Gruppo Giovani

Abstract Background Diffuse gliomas display heterogeneous biology, natural history, response to treatments, and outcome. According to the 2021 WHO Classification, an integration of histological and molecular factors is needed for the diagnosis of diffuse gliomas. The Italian Association of Neuro-Oncology (AINO), with the participation of the Italian Society of Neurosurgery (SINch), promoted a survey to explore how the 2021 WHO molecular diagnostic criteria are integrated into clinical practice in a national framework. Material and Methods A web-based survey containing 38-item multiple-choice questions was sent to members of the AINO and SINch in February 2022 via the respective email listings of these organizations. Results We collected 152 answers. Most attendants were < 45-year-old (117, 77.0%). Participants from North, Centre and South of Italy were 85 (55.9%), 38 (25.0%), and 29 (19.1%). Academic and non-academic hospitals were 35 (46.1%) and 82 (53.9%). The presence of an institutional Brain Tumour Board was reported in 108 cases (71.7%). One hundred forty attendees (92.1%) reported that IDH mutation was assessed in all glioma patients regardless of age. The 1p19q-codeletion was assessed routinely in all IDH-mutant gliomas in 88 (57.9%) or when TP53 mutation and/or ATRX expression was found (45, 29.6%). The MGMTp methylation was assessed, regardless of grading, at diagnosis in 110 (72.4%), and at second surgery in 82 (53.9%). Eighty (52.6%) performed a quantitative analysis of MGMTp status. The CDKN2A/B homozygous deletion in IDH-mutant lower-grade astrocytomas was routinely investigated in 53 (34.9%). Assessment of EGFR amplification, pTERT status or +7/-10 chromosome alterations to stratify IDH-wildtype lower-grade astrocytomas was reported in 76 (50.0%), 43 (28.3%), and 16 (10.5%) cases. Rarer alterations were less commonly investigated (H3K27M: 34, 22.4%; H3G34: 11, 7.2%; BRAF: 18, 11.8%; NTRK: 16, 10.5%), being usually evaluated in selected cases (e.g., younger patients). Academic vs non-academic hospitals treated more patients per year (> 300 in 22/70, 31.4% vs 3/82, 3.7%, p<0.001), had more available molecular technologies (53/70, 75.5% vs 37/82, 45.1, p<0.001), had a higher availability of molecular markers, such as CDKN2A/B deletion (34/70, 48.6% vs 19/82, 23.2%, p=0.001), MGMTp at second surgery (48/69, 69.6% vs 34/72, 47.2%, p=0.008), EGFR/pTERT/+7-10 (46/70, 65.7% vs 32/77, 41.6%, p=0.003), BRAF (14/70, 20.0% vs 4/82, 4.9%, p=0.002), NTRK (14/70, 20.0% vs 2/81, 2.5%, p<0.001). Conclusion The availability of new molecular markers is increasing among Italian Neuro-Oncology Centres. However, there is still a gap with the proposed criteria of the 2021 WHO Classification and the real-life application. A critical issue remains how to select patients who might benefit from the identification of some extremely rare mutations in light of targeted therapies.

Efficacy and safety study of fotemustine and bevacizumab in patients with recurrent glioblastoma.

e14041 Background: Glioblastoma (GBM) is highly vascularized tumor with elevated expression of vascular endothelial growth factor (VEGF). Bevacizumab (Bz) is a humanized monoclonal antibody against VEGF, which alone or associated with chemotherapy has obtained optimal results. However, the most suitable combination with bevacizumab is yet unknown. The objective of our study is to evaluate the efficacy and safety of Bz and fotemustine (Ft) in patients (pts) with recurrent GBM of the Huelva area and to compare our results with those published in the phase II study of the Italian Association of Neuro-oncology (AINO). Methods: Observational and descriptive study of the combination of Ft-Bz in GBM at first relapse after standard radiotherapy and TMZ concomitant in the hospital area of Huelva during the years 2010-2021. We used the same therapeutic scheme of the phase II study of AINO and the IBM SPSS Statistics 22 program to analyze the variables. Results: 42 pts were treated, 16 women and 25 men. Median age 52 years. ECOG 0-1 in 85.4%. 65.9% and 92.7% received antiepileptics and corticosteroids, respectively. In 90.2%, methylation status of the promoter of O6-methylguanine-DNA methyltransferase (MGMT) was not evaluated. Previously, 56.1% of the pts underwent total/subtotal resection, 29.3% partial and 14.6% were not resected, followed by concomitant radiotherapy and temozolamide in 100% of cases. 35.7% relapsed in less than 3 months after adjuvant treatment. 61% presented unifocal relapse and 39% multifocal. 46.3% of the pts had stable disease, 24.4% partial response and 2.4% complete response. 22% presented grade 3-4 toxicity. The most frequent toxicities are listed in the table. The median progression-free survival (PFS) was 6 months (95% CI 4.18-7.82) and the median overall survival (OS) was 7 months (95% CI 4.22-9.77). Conclusions: The results obtained in our study were similar to those of other previously published studies of Bz in combination with Ft. Although PFS was slightly higher than the phase II study AINO, OS was lower, probably due to the inclusion of a high rate of rapid progressors pts. Treatment tolerance was similar to that in the phase II study AINO. An increase in hematologic adverse events stands out in our pts. Therefore, this scheme can be a valid alternative in the management of recurrent GBM.[Table: see text]

Whole brain radiotherapy combined with intrathecal liposomal cytarabine for leptomeningeal metastasis\u2014a\xa0safety analysis and validation of the EANO-ESMO classification

BackgroundAlthough there is no proven standard therapy for leptomeningeal metastases (LM), treatment often includes intrathecal chemotherapy combined with whole brain radiation therapy (WBRT). Little is known about the toxicity of such combination therapies. We performed a retrospective safety analysis for the combination of intrathecal liposomal cytarabine with WBRT in patients with LM and validated the EANO-ESMO (European Association of Neuro-oncology—European Society for Medical Oncology) classification in this unique cohort.MethodsTreatment toxicities in patients diagnosed with LM between 2004 and 2014 were retrospectively analyzed according to RTOG (Radiation Therapy Oncology Group) toxicity criteria and NCI CTCAE V5.0 (National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0). Diagnostic criteria and treatment response as assessed by EANO-ESMO classification were correlated with survival by Kaplan–Meier analysis and Breslow test.ResultsIn all, 40 patients with LM who were treated with combined WBRT and intrathecal cytarabine, were identified. Ten patients (25%) experienced adverse events ≥grade 3 according to RTOG toxicity criteria; in 22 patients (55%) NCI CTCAE ≥grade 3 were detected. Median overall survival was 124 days. Median time to neurological progression was 52 days. Patients with positive cerebrospinal fluid (CSF) cytology (n = 26) showed worse prognosis compared to patients with negative CSF cytology (n = 14; mOS (median overall survival) 84 days versus 198 days, p = 0.006, respectively). The EANO-ESMO response assessment was significantly associated with survival: “stable” (n = 7) mOS 233 days, “response” (n = 10) mOS 206 days, “progression” (n = 17) mOS 45 days, “suspicion of progression” (n = 6) mOS 133 days; overall, p < 0.001.ConclusionsIn this retrospective analysis, combined treatment of WBRT and intrathecal liposomal cytarabine shows an acceptable safety profile and may indicate a trend towards improved efficacy. The EANO-ESMO classification for diagnosis and treatment response predicts survival.

Development of ‘Core Outcome Sets’ for meningioma in clinical studies: The COSMIC project

Abstract Aims To date, meningioma clinical trial activity has been limited, but a number of high-quality studies are underway, with more in development. There is heterogeneity in the outcomes reported in meningioma clinical trials. The COSMIC Project will develop two ‘Core Outcome Sets’ (COS) through comprehensive, transparent, consensus methodology; to ensure outcomes relevant to key stakeholders are reported within and across future meningioma clinical studies. The first will be for use in clinical effectiveness trials (COSMIC: Intervention), the second will be for use in clinical studies of incidental meningioma (COSMIC: Observation). Method Three systematic literature reviews will be performed to generate a long-list of outcomes potentially relevant to meningioma patients, healthcare professionals, researchers, and other stakeholder groups. The first systematic review will present the outcomes reported in published and ongoing meningioma clinical effectiveness trials. The second systematic review will present patient-reported outcomes (PRO) from the measurement tools utilised in meningioma PRO studies. The third systematic review will present the outcomes reported in published and ongoing clinical studies of untreated meningioma. Outcomes will be deduplicated, unique outcomes categorised according to the taxonomy presented by COMET, and the lists combined. The long-list of outcomes will be prioritised through two, 2-round, modified eDelphi surveys including meningioma patients, healthcare professionals, researchers, and other stakeholder groups. Undecided outcomes from both eDelphi surveys will be ratified at two, one-day consensus meeting, with representation from all key stakeholder groups. Results We have formed a study advisory group with international representation from key organisations. The project already has confirmed support from the International Consortium on Meningioma (ICOM), the European Association of Neuro-Oncology (EANO), the Response Assessment in Neuro-Oncology Patient-Reported Outcome group (RANO-PRO), the Society for Neuro-Oncology (SNO), British Neuro-Oncology Society (BNOS), Society of British Neurological Surgeons (SBNS), The Brain Tumour Charity (TBTC), and Brainstrust. Conclusion Standardising minimum outcome reporting in meningioma clinical effectiveness trials and meningioma clinical studies, through the development of these two COS will ensure outcomes reported are relevant to key stakeholder groups, including patients, whilst reducing research waste for a disease with increasing clinical trial activity. We seek to raise awareness of this project and invite participation from a wide range of stakeholders to ensure that the final COS reflects the opinion of the neuro-oncology community. Registration will take place via the study website www.thecosmicproject.org between June-August 2021.

Depatuxizumab Mafodotin (Depatux-M) Plus Temozolomide in Recurrent Glioblastoma Patients: Real-World Experience from a Multicenter Study of Italian Association of Neuro-Oncology (AINO).

Simple SummaryDepatux-M is an antibody-drug conjugate against activated EGFR. The efficacy and tolerability of the Depatux-M and temozolomide combination in recurrent glioblastoma patients were recently analyzed in the INTELLANCE-2/EORTC 1410 phase 2 trial. Despite the trial was negative, it showed interesting results for patients received this combination therapy versus standard treatment. For the first time worldwide, we investigated this treatment in a real-life population. Interestingly, we reported encouraging clinical benefits close to that reported in the previous randomized INTELLANCE 2 trial. Ocular toxicity was manageable. Likely, a subgroup of patients could benefit of this treatment and so, significant molecular predictors of treatment efficacy such as EGFR SNVs should be better investigated in a larger prospective study.Background: Depatuxizumab Mafodotin (Depatux-M; ABT-414) is an antibody-drug conjugate consisting of a specific antibody against activated EGFR and a cytotoxic agent with antimicrotubule activity. The INTELLANCE 2/EORTC 1410 phase 2 trial produced interesting results for the combination regimen of Depatux-M and temozolomide in EGFR-amplified glioblastoma patients at first recurrence. For the first time worldwide, our work investigated the clinical outcome and safety of this combination in a real-life population. Materials and Methods: Patients were enrolled from seven AINO (Italian Association of Neuro-Oncology) Institutions. The major inclusion criteria were: histologically confirmed diagnosis of glioblastoma, EGFR-amplified, one or more prior systemic therapies and ECOG PS ≤ 2. According to the original schedule, patients received Depatux-M 1.25 mg/kg every 2 weeks combined with temozolomide. The primary endpoints of the study were overall survival and safety. Results: A total of 36 patients were enrolled. The median age was 57 years, ECOG PS was 0–1 in 28 patients (88%), MGMT methylated status was found in 22 (64%), 15 patients (42%) received the combined treatment as second-line therapy. The median OS was 8.04 months (95% CI, 5.3–10.7), the 12 month-OS was 37%. On univariate and multivariate analyses, the MGMT methylation status was the only factor resulting significantly associated with survival. Grade 3 ocular toxicity occurred in 11% of patients; no grade 4 ocular toxicity was reported. No death was considered to be drug-related. Conclusions: The study reported the first “real world” experience of Depatux-M plus temozolomide in recurrent glioblastoma patients. Encouraging clinical benefits were demonstrated, even though most patients were treated beyond second-line therapy. Overall, the results are close to those reported in the previous phase 2 trial. Toxicity was moderate and manageable.

369MO Final results of depatuxizumab mafodotin plus temozolomide in recurrent glioblastoma patients: Real-world experience from a multicenter study of Italian Association of Neuro-Oncology (AINO)

Precision medicine is a promising tool in oncology. DepatuxM is a new antibody-drug conjugate, consisting of a specific antibody against activated EGFR and a cytotoxic agent with antimicrotubule activity. The Intellance2/EORTC 1410 phase-II trial, showed interesting results for DepatuxM + TMZ combination in EGFRamplified glioblastoma patients at first recurrence after RT and TMZ. In our study, we investigated clinical outcome and safety of this combination used in recurrent GBM PTS as “compassionate use”.

Medulloblastoma of the adult: results from a multicenter retrospective study by AINO (Italian Association of Neuro-Oncology) and SIN (Italian Society of Neurology).

Medulloblastoma (MB) is the most common primary malignant intracranial tumor in childhood, but it is very rare in adults, and for this reason, the optimal treatment has not yet been defined. We designed a multicentric study in order to define relevant outcome measures for future prospective studies. The project involved 10 Italian centers. The database shared among the centers contains epidemiological, diagnostic (radiological and histological/molecular), therapeutic, recurrence information, and survival data. A total of 152 patients (102 males and 50 females, median age 32) were included in the study. Twenty-three of 152 patients had a diagnosis of classic medulloblastoma, 52/152 had desmoplastic/extensive nodularity, 2/152 had large-cell anaplastic medulloblastoma, and the remaining had diagnoses not otherwise specified. Almost all patients underwent craniospinal irradiation after surgery; in 85.5% of patients, adjuvant chemotherapy, mainly platinum- and etoposide-based chemotherapy, was performed immediately after RT. Upon recurrence, most patients were retreated with various chemotherapy regimens, including intrathecal chemotherapy in patients with leptomeningeal dissemination. The overall survival (OS) rate at 5years was 73.3% (95% CI, 65.0-80.0%). The median OS for the whole group of patients was 112months. The data collected were mainly consistent with the literature. A limitation of this study was the large number of patients lost to follow-up and the lack of molecular data for most patients diagnosed until 2010. An important challenge for the future will be MB biologic characterization in adults, with the identification of specific genetic patterns. It will be important to have more national and international collaborations to provide evidence-based management strategies that attempt to obtain a standard of care.

Italian consensus and recommendations on diagnosis and treatment of low-grade gliomas. An intersociety (SINch/AINO/SIN) document.

In 2018, the SINch (Italian Society of Neurosurgery) Neuro-Oncology Section, AINO (Italian Association of Neuro-Oncology) and SIN (Italian Association of Neurology) Neuro-Oncology Section formed a collaborative Task Force to look at the diagnosis and treatment of low-grade gliomas (LGGs). The Task Force included neurologists, neurosurgeons, neuro-oncologists, pathologists, radiologists, radiation oncologists, medical oncologists, a neuropsychologist and a methodologist. For operational purposes, the Task Force was divided into five Working Groups: diagnosis, surgical treatment, adjuvant treatments, supportive therapies, and follow-up. The resulting guidance document is based on the available evidence and provides recommendations on diagnosis and treatment of LGG patients, considering all aspects of patient care along their disease trajectory.

Gender issues from the perspective of health-care professionals in Neuro-oncology: an EANO and EORTC Brain Tumor Group survey.

Women represent an increasing proportion of the overall workforce in medicine but are underrepresented in leadership roles. To explore gender inequalities and challenges in career opportunities, a web-based survey was conducted among the membership of the European Association of Neuro-Oncology and the Brain Tumor Group of the European Organisation for Research and Treatment of Cancer. A total of 228 colleagues responded to the survey: 129 women (median age 45 years; range, 25-66 years) and 99 men (median age 48 years; range, 24-81 years); 153 participants (67%) were married and 157 participants (69%) had at least 1 child. Women less often declared being married (60% vs 77%, P = .007) or having a child (63% vs 77%, P = .024). Men more frequently had a full-time position (88% vs 75%, P = .036). Women and men both perceived an underrepresentation of women in leadership positions. Half of participants agreed that the most important challenges for women are leading a team and obtaining a faculty position. Fewer women than men would accept such a position (42% vs 56%). The main reasons were limited time for career and an inappropriate work and life balance. Women specifically cited negative discrimination, limited opportunities, and lack of self-confidence. Discrimination of women at work was perceived by 64% of women vs 47% of men (P = .003). Women are perceived as experiencing more difficulties in acquiring a leadership position. Personal preferences may account for an underrepresentation of women in leadership positions, but perceived gender inequalities extend beyond disparities of access to leadership.

Correction to: Efficacy of initial temozolomide for high‑risk low grade gliomas in a phase II AINO (Italian Association for Neuro‑Oncology) study: a post‑hoc analysis within molecular subgroups of WHO 2016.

The third and fourth authors' affiliation was incorrectly specified in the original publication. It is correctly shown here.

P04.09 Patterns of care and impact on survival of first salvage therapy in high-risk grade II gliomas following initial temozolomide

Abstract BACKGROUND Initial chemotherapy with temozolomide (TMZ) may provide benefit in high-risk low-grade gliomas. To date, no standard treatment is validated at first progression. The aim of this retrospective study was to investigate the optimal salvage therapy after the first progression and the factors that influence the PFS and overall survival (OS). MATERIAL AND METHODS we evaluated 71 patients with an histological diagnosis of grade II glioma according to WHO 2016 classification, who were included in a phase II AINO (Italian Association for Neuro-Oncology) trial, and progressed following initial chemotherapy with TMZ. Molecular data were available in all patients: 32 (45.1%) patients were oligodendrogliomas IDH 1/2 mutated and 1p19q codeleted, 11 (15.5%) were diffuse astrocytomas IDH mutant, and 28 (39.4%) were diffuse astrocytomas IDH wild-type. Thirty-five (49.3%) patients were MGMT methylated. Median follow up was 144 months (range 23–180). RESULTS thirty-one patients (43.7%) underwent second surgery, 24 patients (33.8%) second-line chemotherapy (rechallenge with TMZ or nitrosoureas), and 16 patients (22.5%) radiotherapy with a median PFS of 58 months (IC 95% 49–116). The association between prognostic factors and type of salvage therapy revealed a prevalence of younger age (≤ 45 years), non-enhancing tumor and location in eloquent area among patients treated with second surgery or chemotherapy, while aolder age (&gt; 45 years) and contrast-enhancing tumors prevailed among patients receiving radiotherapy. Overall, median PFS was 60 months after second surgery (IC95% 43–116) and chemotherapy (IC95% 51–69), and 38 months after radiotherapy (IC95% 15–64) (p 0.09). No significant benefit in length of PFS was achieved in oligodendrogliomas undergoing second surgery (60 months) as compared with oligodendrogliomas treated with radiation or chemotherapy (58 months, p 0.11). PFS of diffuse astrocytomas IDH wild-type following second surgery (53 months) did not differ from that of patients treated with adjuvant treatments (65 months, p 0.28). Overall, median OS from the first salvage therapy was 117 months (IC95% 93 - 123+): 120 months (IC95% 108–140+) after second surgery, 94 months (IC95% 75–117+) after chemotherapy, and 62 months (IC95% 27–112) after radiotherapy (p 0.04). Median OS (123 months, IC95% 106–154) was prolonged in oligodendrogliomas receiving second surgery as compared to those receiving radiotherapy or chemotherapy (93 months, IC 95% 61–112, p 0.07), while median OS in diffuse astrocytomas IDH wild-type did not differ between those who received second surgery or radiotherapy or chemotherapy. CONCLUSION: W hen feasible, reoperation as first salvage treatment following initial TMZ in grade II gliomas seems to offer a probability of a longer OS as compared with second-line chemotherapy or radiotherapy, and this could hold true especially for oligodendrogliomas.

OS3.1 IDH-wild type grade II gliomas: a retrospective series of AINO (Italian Association of Neuro-Oncology)

OS3.1 IDH-wild type grade II gliomas: a retrospective series of AINO (Italian Association of Neuro-Oncology)

P01.054 Patterns of first tumor progression and impact on survival of salvage therapies in low-grade gliomas following initial chemotherapy with temozolomide

Initial chemotherapy with temozolomide (TMZ) has been suggested to provide some benefit in terms of response and progression-free survival (PFS) in high-risk low-grade gliomas. To date, no standard treatment has been validated at progression. The aim of the study was to investigate which is the optimal salvage therapy after the first progression and the factors that may influence the PFS and the overall survival (OS). We evaluated 49 patients with an histological diagnosis of grade II oligodendroglioma and oligoastrocytoma according to WHO 2007 included in a phase II AINO (Italian Association for Neuro-Oncology) trial, who progressed following initial chemotherapy alone with dose-dense TMZ. Fifteen patients (30.6%) had seizures at the time of progression. Molecular data were available in 48 patients: 29 patients were IDH 1/2 mutated, 23 1p/19q codeleted, and 36 MGMT methylated. Median follow up was 140 months. All patients had local tumor progression and patterns on MRI were as follows: a FLAIR lesion in 25 patients (51.0%), a mild patchy enhancing lesion in 14 patients (28.6%), and a nodular enhancing lesion in the other 10 patients (20.4%). Twenty-four patients (49%) underwent a second-line chemotherapy (TMZ rechallenge or PCV schedule), 12 patients (24.5%) a salvage radiotherapy, 11 patients (22.4%) a second surgery (10 gross-total resection and 1 subtotal resection), while 2 patients (4.1%) received palliative care. The response rate (RANO criteria) following salvage radiotherapy or chemotherapy was as follows: PR in 6/38 patients (15.8%), MR in 9/38 (23.7%), SD in 10/38 (26.3%), and PD in 13/38 (34.2%). Overall, median PFS after first salvage therapy was 18 months (IC95% 11–27). Median PFS was 11 months (IC95% 8–74) after radiotherapy, 14 months after chemotherapy and 31 months after surgery (IC95% 18–51, p 0.013). Median OS from the first salvage therapy was 63 months (IC95% 4 - non reached). Median OS was 44 months (IC95% 4 - not reached) after radiotherapy, 38 months (IC95% 22–80) after chemotherapy, and 87 months after surgery (IC95% 11-not reached, p 0.09). Seizure freedom was achieved in 6/15 (40%) patients following first salvage therapy (3 patients after surgery, 2 patients after chemotherapy, and 1 patient after radiotherapy). Reoperation aiming at total or near/total resection seems to offer a probability of a longer PFS and OS compared with the other treatment options. Seizure response may be achieved in a substantial proportion of patients receiving at tumor progression the different antineoplastic options.

IDH-wild type low grade gliomas: An AINO (Italian Association of Neuro-Oncology) retrospective study.

2050Background: Information regarding clinical characteristics and response to treatments of IDH-wild type grade II gliomas are still lacking. This national retrospective study aimed to investigate...

Neoplastic meningitis in solid tumors: from diagnosis to personalized treatments.

Neoplastic meningitis (NM) is a devastating complication of solid tumors with poor outcome. Some randomized clinical trials have been conducted with heterogeneous inclusion criteria, diagnostic parameters, response evaluation and primary endpoints. Recently, the Leptomeningeal Assessment in Neuro-Oncology (LANO) Group and the European Society for Medical Oncology/European Association for Neuro-Oncology have proposed some recommendations in order to provide diagnostic criteria and response evaluation scores for NM. The aim of these guidelines is to integrate the neurological examination with magnetic resonance imaging and cerebrospinal fluid findings as well as to provide a framework for use in clinical trials. However, this composite assessment needs further validation. Since intrathecal therapy represents a treatment with limited efficacy in NM, many studies have been conducted on systemic therapies, including target therapies, with some encouraging results in terms of disease control. In this review, we have analyzed the clinical aspects and the most recent diagnostic tools and therapeutic options in NM.

A phase II trial of temozolomide (TMZ) 1 week on/1 week off as initial treatment for high risk low grade oligodendroglial tumors: An AINO (Italian Association for Neuro-Oncology) study.

2026 Background: The efficacy of dose-dense temozolomide (TMZ, 1 week on/1 week off ) in grade II gliomas is not well known and could depend on the molecular subtype. Methods: Between 2006 and 2010 a single arm phase II study on 60 patients with grade II oligodendroglial tumors was performed. Inclusion criteria were as follows: 1) age ≥ 18 years; 2) KPS ≥ 70; 3) biopsy-proven grade II oligodendroglioma or oligoastrocytoma ; 4) a measurable residual tumor after surgery. The primary endpoint was tumor response on MRI according to RANO criteria, while the secondary endpoints were progression-free survival (PFS), overall survival (OS), and seizure control. Most patients (65%) had seizures. Molecular factors (IDH 1-2 mutations, 1p19q codeletion, MGMT methylation) were available in 49/60 patients (81.7%). The median number of cycles was 11 (2-18). Median follow up was 64 months (7-112). Results: Response rate was PR in 21/60 (35%) patients, minor PR (mPR) in 14/60 (23%), SD in 21/60 (35%) and PD in 4/60 (7%). Most patients achieved the best tumor response within 6 months after the start of TMZ. Among patients with mPR and PR, 15/49 (30.6%) were IDH1-2 mutated with a PFS of 71.4% at 36 months and 28.6% at 60 months with a median value of 46 months while 11/49 (22.4%) were IDH 1-2 wild-type with a PFS of 45.8% at 36 months and 25% at 60 months with a median value of 34 months. OS was 90.5% at 36 months and 66.7% at 60 months with a median value of 76 months in the IDH1-2 mutated/1p19q codeleted subgroup, while OS was 66.7% at 36 months and 50% at 60 months with a median value of 60 months in the IDH1-2 wild-type subgroup. Responses were higher in MGMT methylated patients. Seizure improvement was achieved in 29/34 patients (85%): 17/33 (52%) patients at 12 months and 18/29 (62.1%) at 24 months were seizure-free. Time to maximal seizure response was earlier than that observed on MRI (3 vs 6 months). Conclusions: Dose-dense TMZ has shown a significant activity in terms of tumor and seizure control, especially in IDH1-2 mutated/1p19q codeleted patients. Seizure reduction could represent an early indicator of response to chemotherapy and maybe predict the duration of response. Clinical trial information: 2007-000386-38.

OS11.1 Temozolomide (TMZ) 1 week on/1 week off as initial treatment for high risk low grade oligodendroglial tumors: a phase II AINO (Italian Association for Neuro-Oncology) study

OS11.1 Temozolomide (TMZ) 1 week on/1 week off as initial treatment for high risk low grade oligodendroglial tumors: a phase II AINO (Italian Association for Neuro-Oncology) study

P08.33 GLIOSTRY (Glioblastoma Registry) of the AINO (Italian Association of Neuro-Oncology): final analysis of factors influencing survival in glioblastoma patients receiving the nitrosourea fotemustine at first progression following chemoradiation.

P08.33 GLIOSTRY (Glioblastoma Registry) of the AINO (Italian Association of Neuro-Oncology): final analysis of factors influencing survival in glioblastoma patients receiving the nitrosourea fotemustine at first progression following chemoradiation.