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Low grade gliomas affect predominantly young adults, and have a relatively favorable prognosis compared to grade III and grade IV gliomas. The challenge for an optimal management of these patients is to find the balance between an optimal survival and the preservation of neurological function including cognition. Because all medical treatments may induce side effects, in young and nearly asymptomatic patients the choices can be difficult. This review summarizes the current strategies: a watch-and-wait policy, surgery, chemotherapy, and radiotherapy.

2050 Background: Recurrent low-grade and anaplastic gliomas eventually transform to a higher grade that is characterized by neo-angiogenesis. Sunitinib inhibits multiple tyrosine kinase receptors (including VEGFR, PDGFR and c-Kit) but has no meaningful activity as a mono-therapy for recurrent glioblastoma when given at a daily dose of 37,5 mg (Neyns et al. J Neurooncol. 2011). We investigated sunitinib in combination with lomustine (CCNU) for the treatment of patients (pts) with temozolomide (TMZ) refractory recurrent low-grade or anaplastic glioma. Methods: Pts received a daily dose of 25 mg sunitinib for 28 consecutive days followed by a 14 days treatment-free interval. CCNU was administered as a single dose (80 mg/m²) on day 14 of a 6w cycle. T1 ± Gd and T2/FLAIR weighted MRI images were obtained q6 wks. 18FET-PET was performed at baseline and reassessed in responding pts. Results: 13 pts were enrolled (mean age 40 [range 33-49]; M/F 8/5; KPS 80-90/70-60: 8/5 pts). All pts had PD following surgery, RT and TMZ. In 7 pts, treatment was initiated at 2nd recurrence, in 4 pts at 3rd recurrence and in 2 pts at the 4th recurrence. Most frequent AEs where fatigue (gr 2: n= 3; gr 3: n= 1), thrombopenia (gr 2: n= 1 gr 3: n= 3 gr4: n= 1), neutropenia (gr 2: n= 2; gr3: n= 2; gr4: n= 2) and lymphopenia (gr 2: n=1; gr 3: n=2; gr 4: n=1). In 5/13 pts CCNU had to be discontinued because of AEs. Treatment with sunitinib was continued in these cases without reoccurrence of AEs. BOR according to RANO criteria: 1 CR, 1 PR (not-confirmed) and 2 SD (DCR: 4/13= 31%). In the patient with CR, FET-PET indicated a complete metabolic response. After a mean FU of 7 mths (range 2 -19), 5 pts are alive. The 6-month PFS is 23% (3/13 pts); median PFS is 1,8 mths (95%CI 1.0 - 2,7). A durable disease control was obtained in 3 pts (TTP respectively 14.8, 11.8+ and 19.2+ mths). Conclusions: in this heavily pretreated population with recurrent low-grade and anaplastic glioma the combination of sunitinib and CCNU is associated with acceptable toxicity and offers a durable progression-free survival in a subgroup of pts. Molecular predictive factors identifying the sensitive population would be needed to justify further clinical investigation of this combination.

Background A signal transduction pathway (STP) is a network of intercellular information flow initiated when extracellular signaling molecules bind to cell-surface receptors. Many aberrant STPs have been associated with various cancers. To develop optimal treatments for cancer patients, it is important to discover which STPs are implicated in a cancer or cancer-subtype. The Cancer Genome Atlas (TCGA) makes available gene expression level data on cases and controls in ten different types of cancer including breast cancer, colon adenocarcinoma, glioblastoma, kidney renal papillary cell carcinoma, low grade glioma, lung adenocarcinoma, lung squamous cell carcinoma, ovarian carcinoma, rectum adenocarcinoma, and uterine corpus endometriod carcinoma. Signaling Pathway Impact Analysis (SPIA) is a software package that analyzes gene expression data to identify whether a pathway is relevant in a given condition. Methods We present the results of a study that uses SPIA to investigate all 157 signaling pathways in the KEGG PATHWAY database. We analyzed each of the ten cancer types mentioned above separately, and we perform a pan-cancer analysis by grouping the data for all the cancer types. Results In each analysis several pathways were found to be markedly more significant than all the other pathways. We call them notable. Research has already established a connection between many of these pathways and the corresponding cancer type. However, some of our discovered pathways appear to be new findings. Altogether there were 37 notable findings in the separate analyses, 26 of them occurred in 7 pathways. These 7 pathways included the 4 notable pathways discovered in the pan-cancer analysis. So, our results suggest that these 7 pathways account for much of the mechanisms of cancer. Furthermore, by looking at the overlap among pathways, we identified possible regions on the pathways where the aberrant activity is occurring. Conclusions We obtained 37 notable findings concerning 18 pathways. Some of them appear to be new discoveries. Furthermore, we identified regions on pathways where the aberrant activity might be occurring. We conclude that our results will prove to be valuable to cancer researchers because they provide many opportunities for laboratory and clinical follow-up studies. Electronic supplementary material The online version of this article (doi:10.1186/s12885-015-1484-6) contains supplementary material, which is available to authorized users.