scholarly journals DNA Methylation in INA, NHLH2, and THBS4 Is Associated with Metastatic Disease in Renal Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 39
Author(s):  
Olga Katzendorn ◽  
Inga Peters ◽  
Natalia Dubrowinskaja ◽  
Joana M. Moog ◽  
Christel Reese ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Metastatic Disease ◽  
Primary Tumor ◽  
Renal Cell ◽  
Progression Free Survival ◽  
Classification Model ◽  
Primary Tumors ◽  
Independent Information ◽  
Tumor Tissues ◽  
Bivariate Logistic Regression

The detection of DNA methylation in primary tumor tissues could be relevant for early stratification of aggressive renal cell carcinomas (RCCs) as a basis for future personalized adjuvant therapy. Methylated TCGA KIRC based candidate CpG loci in INA, NHLH2, and THBS4 that are possibly associated with RCC metastasis were evaluated by pyrosequencing in 154 paired normal adjacent and primary tumor tissues, as well as in 202 metastatic tissues. Statistical analysis was carried out by bivariate logistic regression for group comparisons, log rank survival analysis, and unsupervised and supervised analysis for the classification of tumors. Increased methylation of INA, NHLH2, and THBS4 loci were significantly associated with distant metastasis in primary tumors (p < 0.05), tissue-specific hypermethylation in metastatic (p = 7.88 × 10−8, 5.57 × 10−10, 2.06 × 10−7) and tumor tissues (p = 3.72 × 10−24, 3.17 × 10−13, 1.58 × 10−19), and shortened progression free survival in patients (p = 0.03). Combined use of CpG site-specific methylation permits the discrimination of tissues with metastatic disease and reveals a significant contribution of CpG sites in all genes to the statistical classification model. Thus, metastasis in RCC is significantly associated with methylation alterations in INA, NHLH2, and THBS4 loci, providing independent information for the potential early detection of aggressive renal cancers as a rationale for stratifying patients to adjuvant therapies.

scholarly journals Circulating Tumor Cell Methylation Profiles Reveal the Classification and Evolution of Non-small Cell Lung Cancer

2021 ◽  
Author(s):  
Jia-Hao Jiang ◽  
Chang-Yue Chen ◽  
Jian Gao ◽  
Jing Li ◽  
Yuan Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Genome Sequencing ◽  
Primary Tumor ◽  
Small Cell ◽  
Whole Genome ◽  
Small Cell Lung ◽  
Primary Tumors ◽  
Tumor Tissues ◽  
Nsclc Patients

Abstract Backgrounds: The ability of circulating tumor cells (CTCs) to identify lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) holds great promise for improving pathological diagnosis and selecting treatment in non-small cell lung cancer (NSCLC). In addition, previous studies have shown that DNA methylation exhibits cell and tissue specificity. Thus, we aimed to explore the methylation status of CTCs in LUAD and LUSC and identify the potential biomarkers. Methods: we first analyzed Infinium 450K methylation profiles obtained from The Cancer Genome Atlas and Gene Expression Omnibus and further identified the results by performing whole-genome sequencing of CTCs in tumor and matched normal lung tissues and white blood cells from 6 NSCLC patients. Results: the bioinformatic analysis revealed that an NSCLC-specific DNA methylation marker panel which could accurately distinguish between LUAD and LUSC with high diagnostic accuracy. The whole-genome sequencing of CTCs in NSCLC patients also showed 100% accuracy for distinguishing between LUAD and LUSC based on CTC methylation profiles. To investigate the function of CTCs, we further analyzed similar and different methylation profiles between CTCs and their primary tumors and found very high similarities between CTCs and their primary tumor tissues, indicating that these cells inherit information from primary tumors. CTCs also showed some characteristics that were different from those of the primary tumor tissues, suggesting that CTCs evolve some unique characteristics after migrating from the primary tumor; these characteristics may be one of the reasons for the ability of tumor cells to evade immune surveillance.Conclusion: thus, our study provides insight into the potential use of CTCs in pathological classification of NSCLC patients as well as CTC primary tumor inheritance and CTC evolution influence metastasis and immune escape.

scholarly journals Evaluating DNA Methylation, Gene Expression, Somatic Mutation, and Their Combinations in Inferring Tumor Tissue-of-Origin

2021 ◽  
Vol 9 ◽  
Author(s):  
Haiyan Liu ◽  
Chun Qiu ◽  
Bo Wang ◽  
Pingping Bing ◽  
Geng Tian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Gene Expression Profile ◽  
Somatic Mutation ◽  
Expression Profile ◽  
Primary Tumor ◽  
Tumor Tissue ◽  
Classification Model ◽  
Primary Tumors ◽  
Tissue Of Origin

Carcinoma of unknown primary (CUP) is a type of metastatic cancer, the primary tumor site of which cannot be identified. CUP occupies approximately 5% of cancer incidences in the United States with usually unfavorable prognosis, making it a big threat to public health. Traditional methods to identify the tissue-of-origin (TOO) of CUP like immunohistochemistry can only deal with around 20% CUP patients. In recent years, more and more studies suggest that it is promising to solve the problem by integrating machine learning techniques with big biomedical data involving multiple types of biomarkers including epigenetic, genetic, and gene expression profiles, such as DNA methylation. Different biomarkers play different roles in cancer research; for example, genomic mutations in a patient’s tumor could lead to specific anticancer drugs for treatment; DNA methylation and copy number variation could reveal tumor tissue of origin and molecular classification. However, there is no systematic comparison on which biomarker is better at identifying the cancer type and site of origin. In addition, it might also be possible to further improve the inference accuracy by integrating multiple types of biomarkers. In this study, we used primary tumor data rather than metastatic tumor data. Although the use of primary tumors may lead to some biases in our classification model, their tumor-of-origins are known. In addition, previous studies have suggested that the CUP prediction model built from primary tumors could efficiently predict TOO of metastatic cancers (Lal et al., 2013; Brachtel et al., 2016). We systematically compared the performances of three types of biomarkers including DNA methylation, gene expression profile, and somatic mutation as well as their combinations in inferring the TOO of CUP patients. First, we downloaded the gene expression profile, somatic mutation and DNA methylation data of 7,224 tumor samples across 21 common cancer types from the cancer genome atlas (TCGA) and generated seven different feature matrices through various combinations. Second, we performed feature selection by the Pearson correlation method. The selected features for each matrix were used to build up an XGBoost multi-label classification model to infer cancer TOO, an algorithm proven to be effective in a few previous studies. The performance of each biomarker and combination was compared by the 10-fold cross-validation process. Our results showed that the TOO tracing accuracy using gene expression profile was the highest, followed by DNA methylation, while somatic mutation performed the worst. Meanwhile, we found that simply combining multiple biomarkers does not have much effect in improving prediction accuracy.

scholarly journals Circulating tumor cell methylation profiles reveal the classification and evolution of non-small cell lung cancer

2021 ◽  
Author(s):  
Jia-Hao Jiang ◽  
Chang-Yue Chen ◽  
Jian Gao ◽  
Jing Li ◽  
Yuan Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Genome Sequencing ◽  
Primary Tumor ◽  
Small Cell ◽  
Whole Genome ◽  
Small Cell Lung ◽  
Primary Tumors ◽  
Tumor Tissues ◽  
Nsclc Patients

Abstract BackgroundsThe ability of circulating tumor cells (CTCs) to identify lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) holds great promise for improving pathological diagnosis and selecting treatment in non-small cell lung cancer (NSCLC). In addition, previous studies have shown that DNA methylation exhibits cell and tissue specificity. Thus, we aimed to explore the methylation status of CTCs in LUAD and LUSC and identify the potential biomarkers.Methodswe first analyzed Infinium 450K methylation profiles obtained from The Cancer Genome Atlas and Gene Expression Omnibus and further identified the results by performing whole-genome sequencing of CTCs in tumor and matched normal lung tissues and white blood cells from 6 NSCLC patients.Resultsthe bioinformatic analysis revealed that an NSCLC-specific DNA methylation marker panel which could accurately distinguish between LUAD and LUSC with high diagnostic accuracy. The whole-genome sequencing of CTCs in NSCLC patients also showed 100% accuracy for distinguishing between LUAD and LUSC based on CTC methylation profiles. To investigate the function of CTCs, we further analyzed similar and different methylation profiles between CTCs and their primary tumors and found very high similarities between CTCs and their primary tumor tissues, indicating that these cells inherit information from primary tumors. CTCs also showed some characteristics that were different from those of the primary tumor tissues, suggesting that CTCs evolve some unique characteristics after migrating from the primary tumor; these characteristics may be one of the reasons for the ability of tumor cells to evade immune surveillance.Conclusionthus, our study provides insight into the potential use of CTCs in pathological classification of NSCLC patients as well as CTC primary tumor inheritance and CTC evolution influence metastasis and immune escape.

Telomerase Expression Predicts Unfavorable Outcome in Osteosarcoma

2004 ◽  
Vol 22 (18) ◽  
pp. 3790-3797 ◽  
Author(s):  
Robert P. Sanders ◽  
Rachid Drissi ◽  
Catherine A. Billups ◽  
Najat C. Daw ◽  
Marcus B. Valentine ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Primary Tumor ◽  
Progression Free Survival ◽  
Outcome Analysis ◽  
Negative Group ◽  
Primary Tumors ◽  
Free Survival ◽  
Positive Group ◽  
Alternative Lengthening ◽  
Group 3

Purpose Osteosarcoma is distinct from most cancers in that the majority of osteosarcomas lack telomerase expression and use the alternative lengthening of telomeres (ALT) mechanism to maintain telomeres. Laboratory studies suggest that compared with ALT, telomerase expression is associated with increased tumor aggressiveness. We evaluated the clinical significance of telomerase expression in human osteosarcoma. Patients and Methods Fifty-six osteosarcomas from 51 patients treated at St Jude Children's Research Hospital between 1982 and 2003 were evaluated for telomerase enzyme activity, mRNA expression of the catalytic component of telomerase (TERT), and presence of the ALT pathway. Results Outcome analysis was based on TERT mRNA expression in the primary tumor samples from 44 patients. Fourteen primary tumors expressed TERT mRNA (32%; eight TERT only, six TERT and ALT) and 30 did not express TERT mRNA (68%; 29 ALT, one no ALT). Progression-free survival (PFS) was inferior in the TERT-positive group compared with the TERT-negative group (3-year estimates, 21.4% ± 9.5% v 63.7% ± 11.1%; P = .014). Likewise, overall survival was inferior in the TERT-positive group compared with the TERT-negative group (3-year estimates, 42.9% ± 12.2% v 70.0% ± 9.9%; P = .031). Among 31 patients with nonmetastatic disease at diagnosis, PFS was lower in the TERT-positive group compared with the TERT-negative group (3-year estimates, 33.3% ± 13.6% v 72.0% ± 11.5%; P = .092). Conclusion Telomerase expression in primary tumor samples is associated with decreased PFS and OS in patients with osteosarcoma. Additional studies are warranted to better define the clinical utility of this molecular marker.

FGFR2 expression to predict survival outcome in patients with metastatic papillary renal cell carcinoma.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 506-506 ◽  
Author(s):  
Ilya Tsimafeyeu ◽  
Alexandra Naumova ◽  
Evgenia Stepanova ◽  
Alfia Khasanova ◽  
Ilya Varlamov ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Tumor Cells ◽  
Renal Cell ◽  
Objective Response ◽  
Progression Free Survival ◽  
Papillary Renal Cell Carcinoma ◽  
Survival Outcome ◽  
Primary Tumors ◽  
Metastatic Sites

506 Background: In our previous study we showed that fibroblast growth factor receptor 2 (FGFR2) mutations are rare across papillary types of renal cell carcinoma (pRCC). The aim of the present study is to test FGFR2 expression for association with survival outcome in the largest patient cohort to date. Methods: Formalin-fixed, paraffin-embedded specimens of removed primary tumors from 214 untreated metastatic pRCC patients were evaluated by immunohistochemistry with FGFR2 antibody (Santa Cruz Biotechnology). Expression was quantified by consensus of two independent observers using a four-value intensity score (0, 1+, 2+, and 3+) and the percentage (0-100%) of the extent of reactivity. Expression was scored according to the percentage of positive cells present among all tumor cells in the section. The cytoplasmic and nuclear expression score was obtained by multiplying the intensity and reactivity extension values (range, 0-300). FGFR2 expression was tested for associations with progression-free survival (PFS), overall survival (OS) and best objective response. Results: Expression of FGFR2 was observed in 23% (49/214) of primary pRCC, mostly in cytoplasm of tumor cells. 2 of 214 (1%) patients had nuclear FGFR2 expression. Intensity was 3+ in all cases. Expression of FGFR2 was significant lower in the normal tissue of kidney (1%, P=0.001). FGFR2 expression was strongly associated with a number of metastatic sites (2 and more metastatic sites vs. 0-1), type 2 of pRCC, lower nucleolar grade (P<0.001). FGFR2-positive patients had significantly shorter OS and PFS in first-line therapy (P<0.05; Table). On multivariate analysis, FGFR2 expression, MSKCC risk group, and type of pRCC were found to be independent predictors of survival. Conclusions: In this study, we described immunohistochemical expression of FGFR2 in a large series of pRCC specimens. FGFR2 expression was found to be prognostic factor for survival in patients with metastatic pRCC. Clinical trial information: rosoncoweb2011. [Table: see text]

Von Hippel-Lindau gene mutation status is associated with a dichotomous response in primary and metastatic tumors in patients receiving bevacizumab and erlotinib for metastatic renal cell carcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15522-15522
Author(s):  
D. Tsavachidou ◽  
N. M. Tannir ◽  
C. G. Wood ◽  
P. Corn ◽  
K. Do ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Gene Mutation ◽  
Metastatic Disease ◽  
Primary Tumor ◽  
Renal Cell ◽  
Response To Therapy ◽  
Gene Inactivation ◽  
Vhl Gene ◽  
Von Hippel Lindau

15522 Background: A single arm phase II study is underway evaluating the safety and clinical benefit of presurgical bevacizumab and erlotinib in the management of patients with untreated conventional renal cell carcinoma (RCC). It is not known how the presence or absence of von Hippel Lindau (VHL) mutations affect the response to therapy in the primary or metastatic site, and whether VHL mutational status is predictive for either. Methods: Patients enrolled had conventional RCC, measurable metastatic disease, a primary tumor in place, no prior systemic therapy, a PS of 0 or 1 and no brain metastases. A total of 35 patients were enrolled as of January 8, 2007. Patients were treated with bevacizumab for 4 cycles and erlotinib for 8 weeks, and underwent cytoreductive nephrectomy at week 10 (4 weeks after the last dose of bevacizumab). A VHL gene mutation and methylation analysis was completed on nephrectomy specimens from the first 18 evaluable patients. Patients were grouped according to the presence or absence of functional VHL gene inactivation (mutation and/or methylation). Two-sample T-test and Fisher’s exact test were performed. Results: Ten patients (55%) demonstrated either VHL mutation or methylation ( table 1 ). Patients with no VHL gene inactivation demonstrated more robust primary tumor shrinkage, but did not demonstrate partial responses (PRs). Table 1 . Conclusions: These findings, although preliminary, suggest a dichotomous response in the primary and metastatic disease sites according to VHL functional status. Ongoing evaluation of new treatment strategies using antivascular/targeted agents in RCC may benefit from molecular stratification. [Table: see text] No significant financial relationships to disclose.

Charting DNA methylation of long non-coding RNA in clear-cell renal cell carcinoma.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 432-432
Author(s):  
Gabriel Malouf ◽  
Jianping Zhang ◽  
Nizar M. Tannir ◽  
Erika Thompson ◽  
Jean-Philippe Spano ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Renal Cell ◽  
Clear Cell ◽  
Cpg Islands ◽  
Genomic Analysis ◽  
The Cancer Genome Atlas ◽  
Cell Physiology ◽  
Cell Renal Cell Carcinoma ◽  
Primary Tumors ◽  
Cancer Subtypes

432 Background: Long non-coding RNAs (lncRNA) play a key role in regulating cell physiology through different mechanisms including the recruitment of histone-modifying enzymes. Recently, lncRNA classification of clear-cell renal cell carcinomas (cc-RCC) established four subtypes with different clinico-pathological features. However, the interplay between those lncRNA and DNA methylation patterns remains unknown. Methods: We performed a genomic analysis of GENCODE lncRNAs in cc-RCC using The Cancer Genome Atlas (TCGA) molecular RNAseq profiles of 471 primary tumors. Furthermore, we reannotated data of DNA methylation combining 27K (n=173) and 450K (n=298) Infinium arrays. We described global correlations between lncRNA expression and DNA methylation and established lncRNA methylation subtypes based on distinct signatures. In addition, we identified lncRNA regulated by DNA methylation and associated with poor outcome. Results: We identified 2,138 lncRNAs which contain promoters located in CpG islands (CGI). Out of those, 59 (2.8%) lncRNAs showed DNA methylation in both normal and cancer as compared to 1,487 (69.5%) lncRNA which were unmethylated in both of them. Importantly, 592 (27.7%) lncRNAs gained DNA methylation in ccRCC and this was associated with the repression of the expression of 70 of them. Unsupervised clustering of lncRNA using the most variable DNA methylation probes revealed three robust subtypes associated with distinct outcome. Finally, by integrating cancer subtypes data with clinical information, we identified several lncRNAs which promoter methylation was associated with patient outcome. Conclusions: Our study represents the first integrative analysis of lncRNA and DNA methylation in ccRCC and provides new insights in the role of epigenetic alterations in kidney cancer. Furthermore, we identified a subset of lncRNA regulated epigenetically which may represent potential therapeutic targets.

Tissue levels of steroid hormones and their receptors, prolactin, and SHBG in patients with gastric cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 448-448
Author(s):  
Oleg Ivanovich Kit ◽  
Elena M. Frantsiyants ◽  
Yuriy A. Gevorkyan ◽  
Natalya V. Soldatkina ◽  
Nikolay S. Samoylenko
Keyword(s):  
Gastric Cancer ◽  
Estrogen Receptors ◽  
Cancer Patients ◽  
Steroid Hormones ◽  
Primary Tumor ◽  
Free Testosterone ◽  
Peritoneal Metastases ◽  
Control Group ◽  
Primary Tumors ◽  
Tumor Tissues

448 Background: Hormones and their receptors are important effectors providing interconnection between the primary tumor and metastatic niches. The aim of the study was to determine levels of steroid hormones and their receptors, prolactin (PRL) and SSBG in tissues of gastric cancer (GC), omentum and peritoneum. Methods: Levels of steroid hormones and their receptors, PRL and SSBG were determined by ELISA in tissues of primary tumors, omentum and peritoneum in main groups: 1 (M0) – GC T3-4аN0-3M0 (n = 24) and 2 (M1) – GC T3-4аN0-3M1 (n = 21); in tissues of the stomach, omentum and peritoneum – in the control group (non-cancer patients, n = 17). Results: In GC (М1), estradiol was reduced in primary tumors, omentum and peritoneum by 4.2, 4.0 and 8.6 times, respectively; increased levels of free testosterone (by 18.9, 2.0 and 2.8 times) and PRL (by 8.0, 7.6 and 1.7 times) were observed (p < 0.05). GC (М0) was characterized by high levels of estrogen receptors (ER) α – by 1.2 times (p < 0.05), progesterone (PR) – by 3.5 times and SSBG – by 1.4 times (p < 0.05); tissues of the omentum and peritoneum showed increased levels of ERα – by 2.4 and 3.9 times, ERβ – by 1.5 (p < 0.05) and 2.5 times, РR – by 2.2 and 1.5 times (p < 0.05). GC (М1) had low ERα levels. Conclusions: Decreased levels of estradiol, together with elevated levels of free testosterone and prolactin, in tumor tissues can be considered marking for peritoneal metastases. Correlation between the content of these hormones in the omentum and peritoneum and the presence of metastasis in the organs confirms the “seed and soil” principle.

Feasibility of multiple immunoexpression assay for immune tumor micrornvironment (I-TME) on matched metastatic and primary renal cell carcinoma (RCC) for patient prognostication and predictiveness to immunotherapy (preliminary analyses of the Meet URO 18 study).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16545-e16545
Author(s):  
Matteo Brunelli ◽  
Sara Elena Rebuzzi ◽  
Valerio Gaetano Vellone ◽  
Marta Sbaraglia ◽  
Gabriele Gaggero ◽  
...  
Keyword(s):  
Nk Cells ◽  
Primary Tumor ◽  
Progression Free Survival ◽  
Tissue Expression ◽  
Tissue Level ◽  
Antibody Testing ◽  
Tissue Samples ◽  
Primary Tumors ◽  
Cd8 Cells ◽  
Primary Renal Cell Carcinoma

e16545 Background: The Meet-URO 18 study is ongoing to assess the prognostic role of I-TME in advanced RCC patients treated with ≥second line nivolumab divided into two cohorts according to clinical benefit [progression-free survival ≥ 12 and ≤ 3 months]. We primarily assessed the feasibility of multiple antibody testing related to I-TME on matched metastases and primary tumor. Methods: Immunohistochemical analyses were used for the TME assessment of T-lineage (CD3, CD4, CD8), FOXP-3, granulocytes (CD15), macrophage-lineage (CD68), natural killer (NK)-cells (CD56), tumor cells (TCs) (CD56), B-lineage (CD20) and phosphorylated mTOR (phmTOR). TCs were quantitatively assessed for CD15, CD56 and phmTOR positivity. For T-, B- and CD68 cells within TC nests, the number of immunoreactive cells were counted with a microscopic field of x200 (0.933 mm2). Results: Overall, 42 tumor tissue samples (primary tumors, metastases) were available and for 17 patients both metastatic and primary tumor tissues were assessable for matched analyses. Among these patients, 12 had clear cell, 1 papillary and 4 mucinous tubular and spindle cell histotype according to WHO 2016 classification. Intratumoral T/CD8 cells ranged from 32 to >400 spots (mean 240; >400 in 7 samples) and intratumoral T/CD4 cells from 4 to >400 spots (mean 168; >400 in 5 samples). Nine samples showed absence of phmTOR expression, while 8 ranged from 10% to 90% of positive TCs. We did not observe countable NK-cells, whereas CD56 was visible in 5 samples (mean 55% of positive TCs). Intratumoral CD68 cells ranged from 34 to >400 spots (mean 175, >400 in 3 patients). Agreement of CD15 method of reporting granulocytic presence was high, thus only CD15 neoplastic expression was reported and ranged from 12% to 55% (mean 30%) in 15 patients. TME multiple analysis resulted equally clustered in 8 patients (<20% variability of single immuno-test) whereas the remaining 9 patients showed significant differences as percentage of immuno-tissue expression in at least one of the 5 immuno-indicators (T/CD8-CD4, C15, CD68, CD56, phmTOR). The remaining 8 samples of patients without matched analyses were used to test the feasibility of multiple analyses; among all antibodies exclusion of the CD20 and FOXP-3 final evaluation was needed, due to technical standardization. According to the 5 immuno-indicators, double-triple positive or penta-positive TME indicators may be identified and graded. Conclusions: Providing multiple immunoexpression platforms on a single specimen may be used as routine workflow. Profiling I-TME, especially CD56, CD15 on TCs and CD68 cells and phmTOR, deserves investigation with extensive control groups. A validation cohort will be tested at tissue level and in correlation with peripheral blood markers.

P14.03 Shifting trends and entity-specific aspects in patients with brain metastasis: real-life analysis from 6031 individuals over an observation period of 30 years

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii38-ii38
Author(s):  
A Steindl ◽  
T J Brunner ◽  
K Heimbach ◽  
K Schweighart ◽  
G M Moser ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Brain Metastasis ◽  
Primary Tumor ◽  
Renal Cell ◽  
Cell Cancer ◽  
Real Life ◽  
Neurosurgical Procedures ◽  
Primary Tumors ◽  
Observation Period

Abstract BACKGROUND We aimed to investigate the changing clinical characteristics of patients with brain metastases (BM) over the last three decades as the foundation for modern BM specific clinical trial planning. MATERIAL AND METHODS 6031 patients with newly diagnosed BM from different solid tumors treated between 1986–2020 were identified from the Vienna Brain Metastasis Registry. RESULTS The fraction of BM originating from the most common BM causing primary tumors (lung cancer, breast cancer and melanoma) was stable over the observation period from 1986–2020. BM from renal cell carcinoma, colorectal cancer and cancer of unknown primary (CUP) decreased over time (p&lt;0.001). Synchronous diagnosis of BM and primary tumor was more frequently observed in lung cancer and CUP patients compared to breast cancer patients (p&lt;0.001). An increasing fraction of patients presented with asymptomatic BM (1986–1999: 20.2% vs. 2010–2020: 30.4%; p&lt;0.001), specifically in lung cancer (p&lt;0.001), melanoma (p&lt;0.001) and renal cell cancer (p=0.004). A decrease of neurosurgical procedures (1986–1999: 39.3% vs. 2010–2020: 20.4%) and an increase of radiation treatments (1986–1999: 56.5% vs. 2010–2020: 73.0%) and systemic therapies (1986–1999: 0.6% vs. 2010–2020: 2.4%; p&lt;0.001) was observed. Furthermore, median overall survival significantly increased across entities (1986–1999: 5 months vs. 2010–2020: 7 months; p=0.001). Intracranial progression as the cause of death increased across entities (p&lt; 0.001). The prognostic DS-GPA (Hazard ratio [HR] 1.42; p&lt; 0.001) and the Lung-molGPA (HR 1.67; p&lt;0.001) could be validated. CONCLUSION We observed changes of BM presentation and clinical parameters during the observation period depending on primary tumor origins. Future BM studies should follow an entity-specific approach and address the characteristics of modern BM cohorts.

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