TY  - JOUR
A1  - Müller, Sophie
A1  - Köhler, Franziska
A1  - Hendricks, Anne
A1  - Kastner, Carolin
A1  - Börner, Kevin
A1  - Diers, Johannes
A1  - Lock, Johan F.
A1  - Petritsch, Bernhard
A1  - Germer, Christoph-Thomas
A1  - Wiegering, Armin
T1  - Brain metastases from colorectal cancer: a systematic review of the literature and meta-analysis to establish a guideline for daily treatment
JF  - Cancers
N2  - Colorectal cancer (CRC) is the third most common malignancy worldwide. Most patients with metastatic CRC develop liver or lung metastases, while a minority suffer from brain metastases. There is little information available regarding the presentation, treatment, and overall survival of brain metastases (BM) from CRC. This systematic review and meta-analysis includes data collected from three major databases (PubMed, Cochrane, and Embase) based on the key words “brain”, “metastas*”, “tumor”, “colorectal”, “cancer”, and “malignancy”. In total, 1318 articles were identified in the search and 86 studies matched the inclusion criteria. The incidence of BM varied between 0.1% and 11.5%. Most patients developed metastases at other sites prior to developing BM. Lung metastases and KRAS mutations were described as risk factors for additional BM. Patients with BM suffered from various symptoms, but up to 96.8% of BM patients were asymptomatic at the time of BM diagnosis. Median survival time ranged from 2 to 9.6 months, and overall survival (OS) increased up to 41.1 months in patients on a multimodal therapy regimen. Several factors including age, blood levels of carcinoembryonic antigen (CEA), multiple metastases sites, number of brain lesions, and presence of the KRAS mutation were predictors of OS. For BM diagnosis, MRI was considered to be state of the art. Treatment consisted of a combination of surgery, radiation, or systemic treatment.
KW  - brain metastases
KW  - cerebral metastases
KW  - BM
KW  - colorectal cancer
KW  - CRC
KW  - systematic review
KW  - meta-analysis
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228883
SN  - 2072-6694
VL  - 13
IS  - 4
ER  - 
TY  - JOUR
A1  - Harter, Patrick N.
A1  - Bernatz, Simon
A1  - Scholz, Alexander
A1  - Zeiner, Pia S.
A1  - Zinke, Jenny
A1  - Kiyose, Makoto
A1  - Blasel, Stella
A1  - Beschorner, Rudi
A1  - Senft, Christian
A1  - Bender, Benjamin
A1  - Ronellenfitsch, Michael W.
A1  - Wikman, Harriet
A1  - Glatzel, Markus
A1  - Meinhardt, Matthias
A1  - Juratli, Tareq A.
A1  - Steinbach, Joachim P.
A1  - Plate, Karl H.
A1  - Wischhusen, Jörg
A1  - Weide, Benjamin
A1  - Mittelbronn, Michel
T1  - Distribution and prognostic relevance of tumor-infiltrating lymphocytes (TILs) and PD-1/PD-L1 immune checkpoints in human brain metastases
JF  - Oncotarget
N2  - The activation of immune cells by targeting checkpoint inhibitors showed promising results with increased patient survival in distinct primary cancers. Since only limited data exist for human brain metastases, we aimed at characterizing tumor infiltrating lymphocytes (TILs) and expression of immune checkpoints in the respective tumors. Two brain metastases cohorts, a mixed entity cohort (n = 252) and a breast carcinoma validation cohort (n = 96) were analyzed for CD3+, CD8+, FOXP3+, PD-1+ lymphocytes and PD-L1+ tumor cells by immunohistochemistry. Analyses for association with clinico-epidemiological and neuroradiological parameters such as patient survival or tumor size were performed. TILs infiltrated brain metastases in three different patterns (stromal, peritumoral, diffuse). While carcinomas often show a strong stromal infiltration, TILs in melanomas often diffusely infiltrate the tumors. Highest levels of CD3+ and CD8+ lymphocytes were seen in renal cell carcinomas (RCC) and strongest PD-1 levels on RCCs and melanomas. High amounts of TILs, high ratios of PD-1+/CD8+ cells and high levels of PD-L1 were negatively correlated with brain metastases size, indicating that in smaller brain metastases CD8+ immune response might get blocked. PD-L1 expression strongly correlated with TILs and FOXP3 expression. No significant association of patient survival with TILs was observed, while high levels of PD-L1 showed a strong trend towards better survival in melanoma brain metastases (Log-Rank p = 0.0537). In summary, melanomas and RCCs seem to be the most immunogenic entities. Differences in immunotherapeutic response between tumor entities regarding brain metastases might be attributable to this finding and need further investigation in larger patient cohorts.
KW  - B7-H1
KW  - PD-L1
KW  - immunoresistance
KW  - immunosurveillance
KW  - safety
KW  - survival
KW  - expression
KW  - melanoma
KW  - breast cancer
KW  - PC-1 blockade
KW  - cell lung cancer
KW  - tumor-infiltrating lymphocytes
KW  - brain metastases
KW  - PD-1
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-137107
VL  - 6
IS  - 38
SP  - 40836
EP  - 40849
ER  -