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2553 Background: The blockade of lymphocyte-activation gene 3 (LAG-3), an inhibitory receptor on tumor-infiltrating lymphocytes, is currently under investigation in many extracranial tumor entities. Methods: 54 patients with diffuse glioma were included: 35 patients with glioblastoma (GBM, median age at diagnosis: 61 years) as well as 14 with WHO grade II and 5 with WHO grade III glioma (lower-grade glioma, LGG, median age at diagnosis: 45 years). Isocitrate dehydrogenase 1/2 mutations (IDH-mt) were present in 17/54 patients and 37/54 patients had IDH wildtype (IDH-wt) tumors. LAG-3 expression on tumor-infiltrating lymphocytes (TILs) was analyzed by immunohistochemistry (monoclonal anti-LAG-3 antibody, clone 17B4, LSBio Inc.). Results: LAG-3+ TILs could be observed in 5/54 (9.3%) samples, while CD3+ TILs were present in 32/54 (59.3%) and CD8+ TILs in 24/54 (44.4%) samples. Only IDH-wt glioma presented with LAG-3+ TILs (p = 0.168). Samples with LAG-3+ TILs presented with a numerical trend towards higher presence of CD3+ (5/27 CD3+ vs. 0/22 CD3−, p = 0.072) and CD8+ TILs (4/24 CD8+ vs. 1/30 CD8−, p = 0.159). 4/7 (57.1%) samples presenting with PD-1+ TILs also presented with LAG-3+ TILs (p = 0.001). Furthermore, glioma samples with LAG3+ TILs presented with higher expression of PD-L1 (median: 1% vs. 0%; p = 0.166). There was no difference in overall survival (OS) according to LAG-3+ TIL infiltration (median OS in LAG-3+: 21.7 months vs. LAG-3−: 41.4 months, p > 0.05). Conclusions: LAG-3+ TILs are rarely observed in IDH-wt and absent in IDH-mt glioma. Gliomas with an active inflammatory microenvironment present more frequently with LAG3+ TILs. The diverse composition of the inflammatory microenvironment and particular inflammatory subgroups should be considered in future clinical trials on immune-modulating therapies in glioma.

2062 Background: The importance of QOL and neurocognitive functions in patients with GBM is meanwhile beyond controversy. We followed newly diagnosed patients with GBM during first and second line therapy by evaluating their QOL and cognitive functions Methods: Consecutive newly diagnosed patients with GBM were included in this study. To assess QOL we used the EORTC QLQ C30 and BN20 questionnaire and the computer based NeuroCog FX for neurocognitive assessments. The first assessment was done at the beginning of radiotherapy and was followed by further 5 evaluations every three months Results: 42 patients underwent radiation therapy with concomitant and adjuvant temozolomide. Non enzyme enhancing antiepileptic drugs (NEIAED) was prescribed for the majority of the patients (71%). Median progression free survival was 9.6 months (2.5-30.9 months). Second line therapies applied were bevacizumab in 11 patients (26%), dose-dense temozolomide in 10 patients (24%) and imatinib in 8 patients. (19%). Neither QOL nor...

2012 Background: Density of tumor-infiltrating lymphocytes (TILs) has a prognostic impact in various extracranial solid tumors. We characterized TILs in patients with brain metastases (BM). Methods...

2011 Background: We aimed to investigate programmed cell death (PD)1 and PD-ligand (L)1 expression and relevance in glioblastoma. Methods: 135 specimens of 117 patients (median age 60); median KPS ...

2053 Background: The sub-cohort of brain metastases (BM) patients (pts) with single BM has relatively favorable survival times, but novel prognostic factors are needed to individualize patient management. Methods: We retrospectively evaluated pre-operative magnetic resonance images in patients, who underwent neurosurgical resection of a single BM. The localization and largest diameter of the BM was recorded. The extent of brain edema (BE) was graded on contrast-enhanced T1, T2 and fluid-attenuated inversion recovery (FLAIR) images as follows: BE 1 cm without affection of the contralateral hemisphere, BE >1cm with affection of the contralateral hemisphere. Further, immunohistochemically assessed expression of hypoxia-induced factor 1 alpha (HIF1a) was analyzed in each BM tissue specimen. Results: 159 pts were studied (81 male, 78 female; age range 24 to 80 years, median 58). The primary tumors were lung carcinoma in 74, breast cancer in 26, kidney cancer in 13, colorectal cancer in 11, melanoma in 9 and other tumor types in 26 cases. At univariate analysis, we found a significant positive correlation of overall survival time (OS) with young age, Karnofsky index >80, non-melanoma histology, and, surprisingly, large BE (p

2014 Background: Historically, median overall survival (OS) times of glioblastoma (GBM) patients ranged from 6–9 months with 3-year survival rates of 2–5 %. In 2005, a randomised phase III trial de...

2029 Background: The prognostic value and clinical utility of Ki67 tumor cell proliferation index in anaplastic oligodendroglial tumors is unclear. Methods: We performed anti-Ki67 immunostaining (M...

8099 Background: An evaluation of clinical characteristics and potential risk factors affecting outcome in patients with MALT lymphoma was performed at our institution. Patients and Methods: As of 1997, a total of 170 consecutive patients with histologically verified MALT lymphoma (99 female/71 male) underwent uniform staging and assessment of clinical characteristics including assessment of genetic changes, presence of autoimmune disease (AD), Helicobacter pylori (HP)-status, monoclonal immunoglobulins (MG) and plasmacytic differentiation (PD). All patients with follow-up at our institution were analysed, and influence of various parameters on dissemination and outcome were evaluated. Sixty-four patients (38%) had gastric MALT-lymphoma (GML) and 106 (62%) extragastric MALT-lymphoma (EGML). Results: 66/170 patients (39%) had multiorgan-involvement upon presentation, while only 3 patients had bone marrow involvement. Patients with EGML (49/106, 46%) were at significantly higher risk for multiorgan-disease than patients with GML (17/64, 27%, p = 0.013). 58 patients had genetic aberrations, with t(11;18) being more common in GML (p = 0.002) and trisomy 3 (p = 0.03) and trisomy 18 (p = 0.02) in EGML. Among GML, translocation t(11;18) was significantly associated with multiorgan-disease, as was trisomy18 in EGML (p = 0.038). After a median follow-up time of 40 months, 139 patients (86%) are alive. 58 patients (39%) have relapsed, with the median to relapse being 60 months. Overall, multifocality and extragastric origin (p < 0.001) were significantly associcated with relapse, while patients with t(11;18) had a significantly longer time to relapse (131 vs 49 months). Survival and relapse were not affected by the form of therapy applied (i.e. local vs systemic). An underlying AD was found in 65 patients (38%), and was significantly associated with EGML (p = 0.007) and multifocality (p = 0.04), but did not influence relapse and survival. HP-positivity was significantly associated with GML (p = 0.001), and patients with EGML did not respond to HP-eradication. Conslusion: Our data suggest dissemination and (late) relapse to be relatively common in MALT-lymphoma. Based on our findings, however, an individualized staging approach and risk-assessment is possible. No significant financial relationships to disclose.

6583 Background: Mantle cell lymphoma (MCL) remains difficult to treat by conventional treatment approaches. Since the microenvironment plays an important role for growth and survival of malignant B-cells, we hypothesized that a treatment strategy targeting both the tumor cell and the microenvironment could be active in MCL. Methods: A phase 2 clinical trial was performed to evaluate the toxicity and efficacy of rituximab plus thalidomide (R+THAL) in patients (pts) with CD20 positive relapsed MCL (previously treated by CHOP or a CHOP-like regimen). R was administered at 375 mg/m2 on days 1, 8, 15, and 22; THAL was given at a daily dose of 200mg starting on day 1 and a dose escalation to 400mg on day 15 (continued until progression or relapse). Results: 16 pts with MCL were treated (8 pts at first relapse including 2 pts after autologous transplantation, 5 pts at ≥ second relapse, 1 pt with primary CHOP-resistant MCL). Median age of pts was 67 (range, 45 to 76) years, and time from initial diagnosis ranged...