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: The 2016 WHO classification of CNS tumors included molecular parameters in addition to histology to redefine many tumor entities. Low-grade glioma (LGG) are divided into isocitrate dehydrogenase (IDH) wild type or mutant. Absence of IDH mutation is a rare event in LGG, and IDH wild type are considered a provisional entity. The technique used to assess IDH mutation is essential to determine the real impact of this tumor type. Methods: The observation of a particularly favorable outcome in a group of 42 patients with a diagnosis of IDH wild type LGG (OS = 93.7 months) led us to retest IDH mutation with a more sensitive technique. Next Generation Sequencing (NGS) was used to retest IDH status in tumor samples, the results of NGS assay were compared with previous findings. Results: Initial assessment of IDH mutation in this 42 patients had been performed using PCR in 19 cases and immunohistochemistry in 2 cases. twenty-one (50%) of the 42 initial IDH wild type LGGs were discovered to be IDH mutant when tested with NGS. Four patients had R132H mutation while in the remaining 17 cases a rare IDH mutation was detected. In particular 4 patients showed IDH2 mutation, 5 patients had IDH1 R132C mutation, 5 patient had IDH1 R132G mutation and 3 patients had IDH1 R132S mutation. Median OS of NGS confirmed IDH mutated LGG was 164.0 months vs 32.2 months for NGS IDH wild type LGG reflecting the very distinct clinical course of these two entities. Conclusions: Repeating testing in IDH wild type LGG cases is crucial, as well as the technique used to assess this mutation. NGS is able to assess IDH mutations in 50% of patients previously misdiagnosed. IDH wild type LGG remains a rare entity with dismal prognosis. Legal entity responsible for the study: N/A Funding: None Disclosure: All authors have declared no conflicts of interest.

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 immunohistochemistry (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.

Background: Molecular characterization of low grade gliomas (LGG) is essential for diagnosis and treatment of these diseases. LGG patients (pts) with IDH mutation and 1p19q codeletion (codel) are characterized by a median OS (mOS) longer than 10 years. Thus, the role of treatments and side effects should be carefully evaluated. Methods: We evaluated LGG pts from our data warehouse (n = 679 pts) who received surgery and had sufficient tissue to assess biomarkers characterization. Pts with gliomatosis were excluded. IDH1/2 assessment was performed on formalin-fixed paraffin-embedded samples by qPCR. In wild type cases we performed NGS. 1p/19 codel analysis was performed by FISH. Results: 93 consecutive LGG with IDH mutation and codel were included. The median follow up (FU) was 96.1 months. Mean age was 40 yrs (range: 25-66); 8 pts (8.6%) underwent biopsy, 61 pts (65.6%) partial resection, 24 pts (25.8%) complete resection. 84 pts (90.3%) were considered high risk using RTOG criteria (> 40 years and/or incomplete resection). Fifty pts (53.7%) received only FU, 17 pts (18.3%) received chemotherapy (CT), 18 pts (19.4%) received radiotherapy (RT), 8 pts (8.6%) received RT + CT. Median PFS (mPFS) was 59.6 months (95%CI: 41.8-77.4) and was significantly longer in pts who received postsurgical treatments (79.5 months, 95%CI: 66.4-92.7) than pts who received FU (46.3 months, 95%CI: 36.0-56.5; P = 0.001). mPFS was 50.8 months (95%CI: 17.4-84.3), 103.6 months (95%CI: 11.7-195.6) and 120.2 months (95%CI: 40.5-199.8) in pts treated with CT alone, RT alone and RT + CT, respectively. Multivariate analysis showed that receiving a post-surgical treatment (P < 0.001), and the extent of resection (P = 0.043) were significantly correlated with PFS. Conclusions: Our study evaluated the role of treatments in LGG pts assessed with NGS and FISH. Post-surgical treatments are crucial to extend PFS in pts with IDH mutation and codel. The choice of post-surgical treatments seems to have a role, being CT alone less effective than RT and RT+CT. Longer FU is needed to provide information about OS. Legal entity responsible for the study: N/A Funding: None Disclosure: All authors have declared no conflicts of interest.

The standard treatment in children with average-risk medulloblastoma (MB) is reduced-dose radiotherapy (RT) followed by chemotherapy. However, in adults, there is no agreement on the use of adjuvant chemotherapy. We performed a retrospective analysis of adult MB patients with average-risk disease, defined as no postsurgical residual (or ≤1.5 cm2) and no metastatic disease (M0). Main inclusion criteria were: age >16 years, post-surgical treatment with craniospinal irradiation with or without adjuvant chemotherapy (cisplatin and etoposide ± cyclophosphamide). From 1988 to 2012 were accrued 43 average-risk MB patients treated with surgery and adjuvant RT. Fifteen (34.9 %) patients received also chemotherapy: 7 before RT, 5 after RT, and 3 before and after RT. Reasons to administer chemotherapy were presence of residual disease (even if ≤1.5 cm) and delay in RT. After a median follow up time of 10 years (range: 8–13), median survival was 18 years (95 % CI 9–28) in patients who receive RT alone, and was not reached in patients treated with RT plus chemotherapy. The survival rates at 5, 10 and 15 years were 100 %, 78.6 % (95 % CI 60.0–97.2 %) and 60.2 % (95 % CI 36.9–83.5 %), in patients treated with RT alone, and 100, 100 and 100 %, in patients treated with RT plus chemotherapy (p = 0.079). Our findings suggest a role for adjuvant chemotherapy in the treatment of average-risk MB adult patients. Further improvements might drive to add chemotherapy in average-risk setting with less favourable biological signatures (i.e., non-WNT group).

Molecular characterization of low grade gliomas (LGG) has improved in recent years and is essential for diagnosis and treatment of these diseases. Moreover, clinical factors, such as age and the extent of surgery retain a prognostic role in LGG that were assessed for IDH1/2, 1p/19q codeletion, and MGMT methylation status. we retrospectively evaluated all adult LGG patients (pts) from our data warehouse who received surgery and had sufficient tissue to assess biomarkers characterization. IDH1/2 assessment was performed on formalin-fixed paraffin-embedded samples by PCR, MGMT by methylation specific PCR, 1p/19 codeletion by FISH. 198 consecutive LGG were included. The median age was 38 (range:18–72). Median follow up was 74.0 months, 109 pts (55.1%) were <40 years of age; 26 pts (13.1%) underwent biopsy, 119 pts (60.1%) partial resection, 53 pts (26.8%) complete resection. Twenty-eight pts (14.1%) were considered low risk (<40 years with complete resection). IDH1/2 mutation was found in 79.8% of pts. 1p/19q codeletion was found in 41.4% of pts, MGMT methylation in 57.1% of pts. Median survival in low risk patients was 211.0 months (95%CI: 190.4–231.6) and was 145.3 months (95%CI: 108.5–182.2) in high risk patients (P = 0.006). Median survival for patients with IDH1/2 mutation was 159 months (95%CI: 103.3–214.7) and was 87.9 months in patients IDH1/2 wild type (95%CI: 61.1–114.6, P < 0.001). Multivariate analysis showed that clinical risk (P = 0.006), IDH1/2 mutation (P < 0.001) and 1p/19q codeletion (P = 0.03) were significantly correlated with overall survival. MGMT methylation was not significant. Molecular characteristic of LGG define the prognosis of these tumors. Moreover, clinical risk assessment retains a role even in the era of molecular characterization.

To the authors' knowledge, there is a scarcity of accurate data regarding the feasibility of standard chemotherapy with procarbazine, lomustine, and vincristine (PCV) in a homogeneous series of patients with primary anaplastic oligodendroglioma (AO) and oligoastrocytoma (AOA) that was recurrent after surgery and standard radiotherapy. The aim of the current study was to evaluate the overall response rate, toxicity, and time to progression (TTP) with the use of standard PCV in this setting.

Recurrent central neurocytoma is very rare and to the authors' knowledge data regarding its response to chemotherapy currently are not available.