scholarly journals Disease relapses after radical radiotherapy of prostate cancer: Analysis of prognostic factors

2008 ◽  
Vol 136 (7-8) ◽  
pp. 373-378
Author(s):  
Tatjana Josifovski ◽  
Ljiljana Radosevic-Jelic ◽  
Cane Tulic ◽  
Aleksandar Milosevic
Keyword(s):  
Prostate Cancer ◽  
Prognostic Factors ◽  
Locally Advanced ◽  
Tumor Grade ◽  
Tumor Stage ◽  
Advanced Tumor Stage ◽  
Radical Radiotherapy ◽  
Disease Relapse ◽  
Grade Ii ◽  
The Impact

INTRODUCTION Although there is no consensus on which is the best option in prostate cancer treatment, these patients could be successfully treated with radiotherapy. Regarding some prognostic factors, it is possible today to classify prostate cancer patients into several risk groups for clinical and biochemical relapse, and therefore to choose the right treatment modality. OBJECTIVE The objective in our study was to analyze the impact of tumor stage and grade, previous transurethral resection of the prostate (TUR), initial prostate specific antigen (PSA) level and age on disease relapse after radical radiotherapy of the prostate cancer. METHOD Between January 1991 and December 2005, a clinical, retrospective study was performed at the Radiotherapy Department of the Institute for Oncology and Radiology of Serbia, which included 283 patients with prostate cancer treated only with radical radiotherapy. During regular follow-up we analyzed response to treatment and disease relapse. RESULTS After radical radiotherapy disease relapse more often occurred (with statistical significance) in patients with locally advanced tumor (stage C 35% vs. A 13% vs. B 19%), low tumor grade (grade III 38% vs. grade II 23% vs. grade I 17%), initial PSA level over 10 ng/ml (29%) and over 20 ng/ml (37%) compared to 11% in the patients with initial PSA level below10 ng/ml, and patients of lower age (less than 55 years 50% vs. 16% in patients over 70 years). CONCLUSION Tumor stage C, low tumor grade (grade II-III), initial PSA level over 10 ng/ml (over 20 ng/ml) and younger age are poor prognostic factors for disease relapse. In this case, radiotherapy as monotherapy is not an adequate approach, and it needs to be combined with other therapeutic modalities.

The impact of comorbidity on survival among men with localized prostate cancer.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 8-8 ◽  
Author(s):  
G. L. Lu-Yao ◽  
D. Moore ◽  
W. Shih ◽  
Y. Lin ◽  
H. Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gleason Score ◽  
Tumor Grade ◽  
Tumor Stage ◽  
Localized Prostate Cancer ◽  
Medicare Program ◽  
Co Morbidity ◽  
Underlying Causes ◽  
Morbidity Index ◽  
The Impact

8 Background: To provide patients and clinicians more accurate estimates of co-morbidity specific survival stratified by patient age, tumor stage and tumor grade. Methods: We conducted a ten year competing risk analysis of 19,639 men age 66 years and older identified by the Surveillance, Epidemiology and End Results (SEER) program linked to Medicare program files. All men were diagnosed with localized prostate cancer and received no surgery or radiation within 180 days of diagnosis. The analysis was stratified by tumor grade and stage and by age and co-morbidity at diagnosis classified using the Charlson co-morbidity index. Underlying causes of death were obtained from SEER. Results: During the first ten years following diagnosis men with moderately and poorly differentiated prostate cancer were more likely to die from causes other than their disease. For men age 66-74 years with stage T1c Gleason score 5-7 disease at diagnosis, ten year overall mortality rates and prostate cancer specific rates were 28.8%, 50.5%, 83.1% and 4.8%, 2.0%, 5.3% respectively for men with Charlson scores 0, 1 and > 2. For men age 66-74 years with T1c Gleason score 8-10 disease at diagnosis, the corresponding rates were 55.0%, 52.0%, 64.3% and 25.7%, 20.2%, 13.7% respectively for men with Charlson scores 0, 1, > 2. Death from competing medical hazards was roughly comparable for men with stage T2 disease and higher for all men over age 75. Conclusions: Patients and clinicians should consider using co-morbidity specific data to estimate the threat posed by localized prostate cancer. No significant financial relationships to disclose.

scholarly journals Epithelial splicing regulatory protein 1 and 2 (ESRP1 and ESRP2) upregulation predicts poor prognosis in prostate cancer

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Morton Freytag ◽  
Martina Kluth ◽  
Elena Bady ◽  
Claudia Hube-Magg ◽  
Georgia Makrypidi-Fraune ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Regulatory Protein ◽  
Tumor Stage ◽  
Molecular Data ◽  
Prognostic Impact ◽  
Advanced Tumor Stage ◽  
Nuclear Staining ◽  
Prognostic Features ◽  
Advanced Tumor ◽  
The Impact

Abstract Background Epithelial splicing regulatory protein 1 (ESRP1) and 2 (ESRP2) regulate alternative splicing events of various pre-mRNAs. Some of these targets play a role in cancer-associated processes, including cytoskeleton reorganization and DNA-repair processes. This study was undertaken to estimate the impact of ESRP1 and ESRP2 alterations on prostate cancer patient prognosis. Methods A tissue microarray made from 17,747 individual cancer samples with comprehensive, pathological, clinical and molecular data was analyzed by immunohistochemistry for ESRP1 and ESRP2. Results Nuclear staining for ESRP1 was seen in 38.6% (36.0% low, 2.6% high) of 12,140 interpretable cancers and in 41.9% (36.4% low, 5.3% high) of 12,962 interpretable cancers for ESRP2. Nuclear protein expression was linked to advanced tumor stage, high Gleason score, presence of lymph node metastasis, early biochemical recurrence, and ERG-positive cancers (p < 0.0001 each). Expression of ESRPs was significantly linked to 11 (ESRP1)/9 (ESRP2) of 11 analyzed deletions in all cancers and to 8 (ESRP1)/9 (ESRP2) of 11 deletions in ERG-negative cancers portending a link to genomic instability. Combined ESRPs expression analysis suggested an additive effect and showed the worst prognosis for cancers with high ESRP1 and ESRP2 expression. Multivariate analyses revealed that the prognostic impact of ESRP1, ESRP2 and combined ESRP1/ESRP2 expression was independent of all established pre- and postoperative prognostic features. Conclusions Our data show a striking link between nuclear ESRP expression and adverse features in prostate cancer and identifies expression of ESRP1 and/or ESRP2 as independent prognostic markers with a potential for routine application.

scholarly journals Upregulation of the heterogeneous nuclear ribonucleoprotein hnRNPA1 is an independent predictor of early biochemical recurrence in TMPRSS2:ERG fusion-negative prostate cancers

2020 ◽  
Vol 477 (5) ◽  
pp. 625-636
Author(s):  
Katharina Möller ◽  
Anna Lena Wecker ◽  
Doris Höflmayer ◽  
Christoph Fraune ◽  
Georgia Makrypidi-Fraune ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Cell ◽  
Gleason Score ◽  
Biochemical Recurrence ◽  
Independent Predictor ◽  
Prognostic Impact ◽  
Advanced Tumor Stage ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Nuclear Ribonucleoprotein ◽  
The Impact

Abstract Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) is a ubiquitous RNA splicing factor that is overexpressed and prognostically relevant in various human cancer types. To study the impact of hnRNPA1 expression in prostate cancer, we analyzed a tissue microarray containing 17,747 clinical prostate cancer specimens by immunohistochemistry. hnRNPA1 was expressed in normal prostate glandular cells but often overexpressed in cancer cells. hnRNPA1 immunostaining was interpretable in 14,258 cancers and considered strong in 33.4%, moderate in 45.9%, weak in 15.3%, and negative in 5.4%. Moderate to strong hnRNPA1 immunostaining was strongly linked to adverse tumor features including high classical and quantitative Gleason score, lymph node metastasis, advanced tumor stage, positive surgical margin, and early biochemical recurrence (p < 0.0001 each). The prognostic impact of hnRNPA1 immunostaining was independent of established preoperatively or postoperatively available prognostic parameters (p < 0.0001). Subset analyses revealed that all these associations were strongly driven by the fraction of cancers lacking the TMPRSS2:ERG gene fusion. Comparison with other key molecular data that were earlier obtained on the same TMA showed that hnRNPA1 overexpression was linked to high levels of androgen receptor (AR) expression (p < 0.0001) as well as presence of 9 of 11 chromosomal deletions (p < 0.05 each). A strong association between hnRNPA1 upregulation and tumor cell proliferation that was independent from the Gleason score supports a role for tumor cell aggressiveness. In conclusion, hnRNPA1 overexpression is an independent predictor of poor prognosis in ERG-negative prostate cancer. hnRNPA1 measurement, either alone or in combination, might provide prognostic information in ERG-negative prostate cancer.

scholarly journals Meta-analysis of prognostic factors of overall survival in patients undergoing oesophagectomy for oesophageal cancer

2020 ◽  
Vol 33 (11) ◽  
Author(s):  
Sivesh K Kamarajah ◽  
Ella J Marson ◽  
Dengyi Zhou ◽  
Freddie Wyn-Griffiths ◽  
Aaron Lin ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Oesophageal Cancer ◽  
Meta Analysis ◽  
Staging System ◽  
Tumor Grade ◽  
Pooled Analysis ◽  
Prognostic Models ◽  
Biological Variables ◽  
The Impact

ABSTRACT Introduction Currently, the American Joint Commission on Cancer (AJCC) staging system is used for prognostication for oesophageal cancer. However, several prognostically important factors have been reported but not incorporated. This meta-analysis aimed to characterize the impact of preoperative, operative, and oncological factors on the prognosis of patients undergoing curative resection for oesophageal cancer. Methods This systematic review was performed according to PRISMA guidelines and eligible studies were identified through a search of PubMed, Scopus, and Cochrane CENTRAL databases up to 31 December 2018. A meta-analysis was conducted with the use of random-effects modeling to determine pooled univariable hazard ratios (HRs). The study was prospectively registered with the PROSPERO database (Registration: CRD42018157966). Results One-hundred and seventy-one articles including 73,629 patients were assessed quantitatively. Of the 122 factors associated with survival, 39 were significant on pooled analysis. Of these. the strongly associated prognostic factors were ‘pathological’ T stage (HR: 2.07, CI95%: 1.77–2.43, P &lt; 0.001), ‘pathological’ N stage (HR: 2.24, CI95%: 1.95–2.59, P &lt; 0.001), perineural invasion (HR: 1.54, CI95%: 1.36–1.74, P &lt; 0.001), circumferential resection margin (HR: 2.17, CI95%: 1.82–2.59, P &lt; 0.001), poor tumor grade (HR: 1.53, CI95%: 1.34–1.74, P &lt; 0.001), and high neutrophil:lymphocyte ratio (HR: 1.47, CI95%: 1.30–1.66, P &lt; 0.001). Conclusion Several tumor biological variables not included in the AJCC 8th edition classification can impact on overall survival. Incorporation and validation of these factors into prognostic models and next edition of the AJCC system will enable personalized approach to prognostication and treatment.

Prognostic analysis of the patients with operable gastric cancer and the importance of tolerability of therapy: Study of Anatolian Society of Medical Oncology.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14526-e14526
Author(s):  
Mehmet Kucukoner ◽  
Erkan Arpaci ◽  
Abdurrahman Isikdogan ◽  
Mehmet Bilici ◽  
Dogan Uncu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Prognostic Factors ◽  
Univariate Analysis ◽  
Tumor Grade ◽  
Tumor Stage ◽  
Adjuvant Chemoradiotherapy ◽  
Lauren Classification ◽  
Prognostic Analysis ◽  
Medical Centers ◽  
Laurén Classification

e14526 Background: The aims of this study were to evaluate the tolerability and toxicity with adjuvant chemoradiotherapy (CRT) and prognostic analysis of patients with operable gastric cancer. Methods: The retrospective analysis included 723 patients with operable gastric cancer, stage IB-IV (M0), received adjuvant CRT from 8 Medical Centers in Turkey between 2003 and 2010. Patients’ age, sex, tumor localization, Lauren classification, grade, stage, type of dissection, toxicity and tolerability status were analyzed. Results: 73.9% of the patients were with stage III- IVM0. 61.0% of the patients were in the intestinal type, 51.1% of the patients were with the distal type of gastric cancer and 61.4% of the patients had undergone D2 dissection. 545 (75.4%) of patients completed the entire of adjuvant CRT. The median follow-up period was 20.8 months. Overall Survival (OS) rates were 80% and 52% while relapse free survival (RFS) rates were 75% and 48%, at 1, 3 years, respectively. In univariate analysis of groups, according to the group under the age of 65 and above (p=0.16 / p=0.003), Lauren classification (p=0.004 / p<0.001), localization of tumor (p=0.02 / p=0.04), tumor grade (p=0.06 / p=0.003), stage (p<0.001 / p<0.001), type of dissection (p=0.445 / p=0.043), toxicity (p=0.062 / p=0.077), tolerability of therapy (p=0.002 / p=0.001) were significantly different in both RFS and OS. In multivariate analysis, three independent prognostic factors were identified on RFS / OS; stage (ods ratio (OR)=3.0, 95% confidence interval (CI):1.8-5.0, / OR=3.2, CI=1.8-5.4), for Lauren classification (OR=1.5, CI=0.9-2.2 / OR=1.5, CI= 1.1-2.2), for tolerability of therapy (OR=2.0, CI=1.0-3.8 / OR=1.9, CI=1.0-3.6). Conclusions: We found a new independent prognostic factor whether or not tolerate adjuvant CRT because of toxicity, except for the known prognostic factors like tumor stage and Lauren classification. We suggest that the treatment of the patients with intolerable to adjuvant CRT, is to change with less toxic adjuvant therapies.

scholarly journals HSD17B6 downregulation predicts poor prognosis and drives tumor progression via activating Akt signaling pathway in lung adenocarcinoma

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Tian Tian ◽  
Fu Hong ◽  
Zhiwen Wang ◽  
Jiaru Hu ◽  
Ni Chen ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Lung Adenocarcinoma ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Grade ◽  
Tumor Stage ◽  
Advanced Tumor Stage ◽  
Large Tumor ◽  
Mesenchymal Transition ◽  
Advanced Tumor

AbstractLung adenocarcinoma is one of the most frequent tumor subtypes, involving changes in a variety of oncogenes and tumor suppressor genes. Hydroxysteroid 17-Beta Dehydrogenase 6 (HSD17B6) could synthetize dihydrotestosterone, abnormal levels of which are associated with progression of multiple tumors. Previously, we showed that HSD17B6 inhibits malignant progression of hepatocellular carcinoma. However, the mechanisms underlying inhibiting tumor development by HSD17B6 are not clear. Moreover, its role in lung adenocarcinoma (LUAD) is yet unknown. Here, we investigated its expression profile and biological functions in LUAD. Analysis of data from the LUAD datasets of TCGA, CPTAC, Oncomine, and GEO revealed that HSD17B6 mRNA and protein expression was frequently lower in LUAD than in non-neoplastic lung tissues, and its low expression correlated significantly with advanced tumor stage, large tumor size, poor tumor differentiation, high tumor grade, smoking, and poor prognosis in LUAD. In addition, its expression was negatively regulated by miR-31-5p in LUAD. HSD17B6 suppressed LUAD cell proliferation, migration, invasion, epithelial–mesenchymal transition (EMT), and radioresistance. Furthermore, HSD17B6 overexpression in LUAD cell lines enhanced PTEN expression and inhibited AKT phosphorylation, inactivating downstream oncogenes like GSK3β, β-catenin, and Cyclin-D independent of dihydrotestosterone, revealing an underlying antitumor mechanism of HSD17B6 in LUAD. Our findings indicate that HSD17B6 may function as a tumor suppressor in LUAD and could be a promising prognostic indicator for LUAD patients, especially for those receiving radiotherapy.

scholarly journals The Impact of Whole Genome Data on Therapeutic Decision-Making in Metastatic Prostate Cancer: A Retrospective Analysis

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1178 ◽  
Author(s):  
Megan Crumbaker ◽  
Eva K. F. Chan ◽  
Tingting Gong ◽  
Niall Corcoran ◽  
Weerachai Jaratlerdsiri ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Precision Medicine ◽  
Metastatic Prostate Cancer ◽  
Parp Inhibitor ◽  
Locally Advanced ◽  
Genomic Data ◽  
Whole Genome ◽  
Genomic Alterations ◽  
Therapeutic Decision Making ◽  
The Impact

Background: While critical insights have been gained from evaluating the genomic landscape of metastatic prostate cancer, utilizing this information to inform personalized treatment is in its infancy. We performed a retrospective pilot study to assess the current impact of precision medicine for locally advanced and metastatic prostate adenocarcinoma and evaluate how genomic data could be harnessed to individualize treatment. Methods: Deep whole genome-sequencing was performed on 16 tumour-blood pairs from 13 prostate cancer patients; whole genome optical mapping was performed in a subset of 9 patients to further identify large structural variants. Tumour samples were derived from prostate, lymph nodes, bone and brain. Results: Most samples had acquired genomic alterations in multiple therapeutically relevant pathways, including DNA damage response (11/13 cases), PI3K (7/13), MAPK (10/13) and Wnt (9/13). Five patients had somatic copy number losses in genes that may indicate sensitivity to immunotherapy (LRP1B, CDK12, MLH1) and one patient had germline and somatic BRCA2 alterations. Conclusions: Most cases, whether primary or metastatic, harboured therapeutically relevant alterations, including those associated with PARP inhibitor sensitivity, immunotherapy sensitivity and resistance to androgen pathway targeting agents. The observed intra-patient heterogeneity and presence of genomic alterations in multiple growth pathways in individual cases suggests that a precision medicine model in prostate cancer needs to simultaneously incorporate multiple pathway-targeting agents. Our whole genome approach allowed for structural variant assessment in addition to the ability to rapidly reassess an individual’s molecular landscape as knowledge of relevant biomarkers evolve. This retrospective oncological assessment highlights the genomic complexity of prostate cancer and the potential impact of assessing genomic data for an individual at any stage of the disease.

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