A gene expression signature to predicit overall, prostate cancer, and non–prostate cancer survival.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 51-51
Author(s):  
Chunde Li ◽  
Zhuochun Peng ◽  
Lambert Skoog ◽  
Henrik Hellborg ◽  
Inga-lill Wingmo ◽  
...  

51 Background: For prostate cancer patients, prostate cancer specific and non-prostate cancer specific survival have the same importance. This study aimed at identifying expression biomarkers that can predict prostate cancer specific, non-prostate cancer specific and overall survival at diagnosis. Methods: Selected ESCGPs (embryonic stem cell gene predictors) and control genes were analyzed by multiplex quantitative PCR using prostate fine-needle aspiration samples taken at diagnosis from a Swedish cohort of 189 prostate cancer patients diagnosed between 1986 and 2000. Of all patients, 97.9% had overall and cancer-specific survival data and 77.9% were primarily treated only by hormone therapy. The cohort was divided into one discovery and two validation subsets. Univariate and multivariate Cox proportional hazard ratios and Kaplan-Meier plots were used for the survival analysis. A published dataset was used for external validation. Results: An expression signature of F3, VGLL3 and IGFBP3, was sufficient to categorize the patients into high-risk, intermediate-risk and low-risk subtypes. The median overall survival of the subtypes was 3.23, 4.00 and 9.85 years respectively. The difference corresponded to HRs of 5.86 (95% CI 2.91-11.78, P<0.001) for the high-risk and 3.45 (95% CI 1.79-6.66, P<0.001) for the intermediate-risk compared to the low-risk subtype. This signature is significant in correlation to overall, cancer-specific and non-cancer specific survival in both univariate and multivariate analyses including common clinical parameters. Conclusions: These results suggest that these novel expression biomarkers and the expression signature could be used to improve the accuracy of the currently available clinical tools for predicting overall, cancer-specific and non-cancer specific survival and selecting patients with potential survival benefit from hormone treatment.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4561-4561 ◽  
Author(s):  
Chunde Li ◽  
Zhuochun Peng ◽  
Lambert Skoog ◽  
Henrik Hellborg ◽  
Gustaf Jonstam ◽  
...  

4561 Background: Current clinical parameters are not accurate in the prediction of overall survival of prostate cancer patients. Methods: Driven by cancer stem cell hypothesis and by using a simple bioinformatics analysis, we identified 641 genes with either consistently high or low level of expression in human embryonic stem cells. We showed that these 641 genes had strong power to classify cancers into different biological subtypes and named them as embryonic stem cell gene predictors (ESCGPs). Nineteen selected ESCGPs and five control genes were analyzed by multiplex quantitative PCR in prostate fine needle aspiration (FNA) samples taken at diagnosis. The cohort included 189 patients diagnosed during 1986-2001. Of these patients, 97.9% had overall and cancer specific survival data and 77.9% were treated by medical or surgical castration as the primary treatment. The cohort was divided into a discovery and two validation subsets. The univariate and multivariate Cox proportional hazards and Kaplan-Meier plots were used in the survival analysis. A published dataset was used for an external validation. Results: Ten gene markers F3, WNT5B, VGLL3, CTGF, IGFBP3, c-MAF-a, c-MAF-b, AMACR, MUC1 and EZH2, showed a significant correlation to overall or cancer specific survival. Four of these genes, F3, IGFBP3, CTGF and AMACR, were independent of all clinical parameters. An expression signature of F3, VGLL3 and IGFBP3 characterized patients into three subtypes. The median overall survival was 2.60 years in the high risk, 3.85 years in the intermediate risk and 7.98 years in the low risk subtype, corresponding to a HR of 5.86 (95% CI 2.91-11.78, p<0.001) for the high risk and 3.45 (95% CI 1.79-6.66, p<0.001) for the intermediate risk over the low risk subtype. Two gene markers, F3 and EZH2, were further verified by the external validation. Conclusions: The new ESCGP gene markers and the expression signatures can be used to predict the overall and cancer specific survival of prostate cancer patients.


2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 54-54 ◽  
Author(s):  
Shiro Hinotsu ◽  
Hideyuki Akaza ◽  
Osamu Ogawa ◽  
Mototsugu Oya ◽  
Tadaichi Kitamura ◽  
...  

54 Background: In Japan, the J-CaP database was established in 2001 when the Japan Study Group of Prostate Cancer (J-CaP Study Group), commenced a study to gather information about hormone therapy administered to Japanese patients and to analyze the outcomes of treatment. From the results of prostate cancer registry conducted by Japanese Urological Association revealed that 45% of localized prostate cancer patients diagnosed in the year of 2000 treated by hormonal therapy in Japan. The J-CaP database is the largest cohort of over 20,000 prostate cancer patients treated by hormonal therapy. Therefore, the objective of the current study was to estimate the outcome of hormonal therapy for the localized prostate cancer patients in the J-CaP database. Methods: The study cohort included 9,127 men with localized prostate cancer who treated by hormonal therapy. All patients were diagnosed by biopsy as having prostate cancer and began to receive hormonal therapy between January 2001 and December 2003. In this study, initial hormonal treatment contained anti-androgen monotherapy, surgical castration only, LHRH agonist monothrerapy, LHRH agonist plus short-term anti-androgen, surgical castration plus anti-androgen, and LHRH agonist plus anti-androgen. All patients evaluated risk category of D’Amico classification. The percentage of Low-risk, intermediate-risk, and high-risk was 19%, 22%, and 59% of men, respectively. Prognosis analyses were performed using Kaplan–Meier methods. Progression-free survival and overall survival were estimated for each risk classification. Results: After a median follow-up of 2.9 years (interquartile range, 1.5-5.3 years) and five year progression-free survival of low-risk, intermediate-risk and high risk were 74.5%, 68.1%, and 57.1%, respectively. The five-year overall survival of low-risk, intermediate-risk, and high risk were 90.0%, 87.2%, and 81.8%, respectively. Conclusions: Comparing the results of radical prostatectomy in US, the five-year progression free survival was 54.6% in high-risk patients. Japanese patients with localized prostate cancer who treated hormonal therapy were comparable outcome of radical treatment in US considering the patients’ risk classification.


Author(s):  
Abeer Al-Battashi ◽  
Ameera Al-Rahbi ◽  
Adbulhakeem Al-Rawahi ◽  
Mohammed Mamdouh ◽  
Ibrahim Al-Ghaithi ◽  
...  

Objectives: Neuroblastoma is a common childhood malignancy with limited number of publications from the middle east. This study describes the clinical characteristics and the survival outcome of Omani children with neuroblastoma who are treated at the National Oncology Center from 2010 to 2017. Methods: Data was retrospectively collected for Omani Children aged less than thirteen-years with neuroblastoma from January 2010 to December 2017. The survival data were statistically correlated with known prognostic factors including age, stage of disease, MYCN profile and presence of metastasis. Results: Fifty-six Omani children were included. The male to female ratio was 1:1. The mean age at presentation was one year and ten months. The two most common presenting complaints were body masses (48.2%) and constitutional symptoms (33.9%). About 54.5% were high-risk, 35.7% were intermediate risk and 9.8% were low-risk. High-risk neuroblastoma was mainly in children older than one year (76.6%), with low-risk being mainly observed in less than one year of age (80%). The overall survival of all groups combined was 74% (p value < 0.05); and the event free survival was 67% (p value < 0.05). The five years overall survival for the high-risk, intermediate-risk and low-risk was 60%, 88% and 100% respectively. Moreover, the event free survival was 51%, 79% and 100% respectively. Conclusion: Omani children with neuroblastoma mainly presented with masses or constitutional symptoms. The majority of Omani children with neuroblastoma had an advanced disease at presentation which was associated with inferior survival. The survival outcomes were reasonably similar to published international data. Keywords: Neuroblastoma, Oman, Survival


2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Neda Gholizadeh ◽  
Peter B. Greer ◽  
John Simpson ◽  
Jonathan Goodwin ◽  
Caixia Fu ◽  
...  

Abstract Background Current multiparametric MRI (mp-MRI) in routine clinical practice has poor-to-moderate diagnostic performance for transition zone prostate cancer. The aim of this study was to evaluate the potential diagnostic performance of novel 1H magnetic resonance spectroscopic imaging (MRSI) using a semi-localized adiabatic selective refocusing (sLASER) sequence with gradient offset independent adiabaticity (GOIA) pulses in addition to the routine mp-MRI, including T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI) and quantitative dynamic contrast enhancement (DCE) for transition zone prostate cancer detection, localization and grading. Methods Forty-one transition zone prostate cancer patients underwent mp-MRI with an external phased-array coil. Normal and cancer regions were delineated by two radiologists and divided into low-risk, intermediate-risk, and high-risk categories based on TRUS guided biopsy results. Support vector machine models were built using different clinically applicable combinations of T2WI, DWI, DCE, and MRSI. The diagnostic performance of each model in cancer detection was evaluated using the area under curve (AUC) of the receiver operating characteristic diagram. Then accuracy, sensitivity and specificity of each model were calculated. Furthermore, the correlation of mp-MRI parameters with low-risk, intermediate-risk and high-risk cancers were calculated using the Spearman correlation coefficient. Results The addition of MRSI to T2WI + DWI and T2WI + DWI + DCE improved the accuracy, sensitivity and specificity for cancer detection. The best performance was achieved with T2WI + DWI + MRSI where the addition of MRSI improved the AUC, accuracy, sensitivity and specificity from 0.86 to 0.99, 0.83 to 0.96, 0.80 to 0.95, and 0.85 to 0.97 respectively. The (choline + spermine + creatine)/citrate ratio of MRSI showed the highest correlation with cancer risk groups (r = 0.64, p < 0.01). Conclusion The inclusion of GOIA-sLASER MRSI into conventional mp-MRI significantly improves the diagnostic accuracy of the detection and aggressiveness assessment of transition zone prostate cancer.


2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 233-233
Author(s):  
David-Dan Nguyen ◽  
Lorine Haeuser ◽  
Marco Paciotti ◽  
Chanan Reitblat ◽  
Jacqueline Cellini ◽  
...  

233 Background: Prostate cancer (PCa) is an indolent disease, especially when detected at a localized stage. Unlike other tumors that may benefit from timely receipt of definitive therapy, it is generally accepted that treatment delays for localized PCa are acceptable, especially for low-risk PCa. We sought to determine if treatment delays for intermediate-risk and high-risk PCa negatively impacted oncological outcomes. Methods: We conducted a systematic review of the literature with searches of Medline, EMBASE, and the Cochrane Database of Systematic Reviews, from inception to June 30, 2020. General study characteristics as well as study population and delay information were collected. The outcomes of interest extracted included biochemical recurrence (BCR), pathological features (positive surgical margins, upgrading, extracapsular extension, and other pathological features), cancer-specific survival, and overall survival. Due to significant heterogeneity between studies, a meta-analysis was not possible. Results: After identifying 1793 unique references, 24 manuscripts met criteria for data extraction, 15 of which were published after 2013. Based on our review, delays up to 3 months are safe for all PCa and are not associated with worse oncological outcomes. Some studies identified worse oncological outcomes as a result of delays beyond 6 to 9 months. However, these studies are counterbalanced by others finding no statistically significant association with delays up to 12 months. Studies that did find worse outcomes as a result of delays identified a higher risk of BCR and pathological findings, but not worse survival. Conclusions: Definitive treatment for intermediate-risk and high-risk PCa can be delayed up to 3 months without any oncological consequences. Some evidence suggests that delays beyond 6-9 months are associated with a higher risk of BCR and varying worse pathological findings; as such, care should be given to provide definitive treatment within 9 months. To date, there is no evidence of worse cancer-specific or overall survival as a result of delayed treatment for intermediate-risk and high-risk PCa.


2020 ◽  
Author(s):  
Mo Chen ◽  
Tian-en Li ◽  
Pei-zhun Du ◽  
Junjie Pan ◽  
Zheng Wang ◽  
...  

Abstract Background and aims: In this research, we aimed to construct a risk classification model to predict overall survival (OS) and locoregional surgery benefit in colorectal cancer (CRC) patients with distant metastasis.Methods: We selected a cohort consisting of 12741 CRC patients diagnosed with distant metastasis between 2010 and 2014, from the Surveillance, Epidemiology and End Results (SEER) database. Patients were randomly assigned into training group and validation group at the ratio of 2:1. Univariable and multivariable Cox regression models were applied to screen independent prognostic factors. A nomogram was constructed and assessed by the Harrell’s concordance index (C-index) and calibration plots. A novel risk classification model was further established based on the nomogram.Results: Ultimately 12 independent risk factors including race, age, marriage, tumor site, tumor size, grade, T stage, N stage, bone metastasis, brain metastasis, lung metastasis and liver metastasis were identified and adopted in the nomogram. The C-indexes of training and validation groups were 0.77 (95% confidence interval [CI] 0.73-0.81) and 0.75 (95% CI 0.72-0.78), respectively. The risk classification model stratified patients into three risk groups (low-, intermediate- and high-risk) with divergent median OS (low-risk: 36.0 months, 95% CI 34.1-37.9; intermediate-risk: 18.0 months, 95% CI 17.4-18.6; high-risk: 6.0 months, 95% CI 5.3-6.7). Locoregional therapies including surgery and radiotherapy could prognostically benefit patients in the low-risk group (surgery: hazard ratio [HR] 0.59, 95% CI 0.50-0.71; radiotherapy: HR 0.84, 95% CI 0.72-0.98) and intermediate risk group (surgery: HR 0.61, 95% CI 0.54-0.68; radiotherapy: HR 0.86, 95% CI 0.77-0.95), but not in the high-risk group (surgery: HR 1.03, 95% CI 0.82-1.29; radiotherapy: HR 1.03, 95% CI 0.81-1.31). And all risk groups could benefit from systemic therapy (low-risk: HR 0.68, 95% CI 0.58-0.80; intermediate-risk: HR 0.50, 95% CI 0.47-0.54; high-risk: HR 0.46, 95% CI 0.40-0.53).Conclusion: A novel risk classification model predicting prognosis and locoregional surgery benefit of CRC patients with distant metastasis was established and validated. This predictive model could be further utilized by physicians and be of great significance for medical practice.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1577-1577
Author(s):  
Deesha Sarma ◽  
So Yeon Kim ◽  
David H. Henry

1577 Background: Venous thromboembolism (VTE) poses a significant health risk to cancer patients and is one of the leading causes of death among this population. The most effective way to prevent VTE and reduce its prominence as a public health burden is by identifying high-risk patients and administering prophylactic measures. In 2008, Khorana et al. developed a model that classified patients by risk based on clinical factors. Methods: We conducted a retrospective study to test this model’s efficacy, on 150 patients with cancer receiving chemotherapy at an outpatient oncology clinic between January 1 and August 1, 2011. We aggregated data and assigned points based on the five factors in the Khorana model: site of cancer with 2 points for very high-risk site and 1 point for high-risk site, 1 point each for leukocyte counts more than 11 x 109/L, platelet counts greater than 350 X 109/L, hemoglobin levels less than 100 g/L and/or the use of erythropoiesis-stimulating agents, and BMI greater than 35 kg/m2 (Khorana et al., Blood 2008). Based on this scoring system, patients with 0 points were grouped into the low-risk category, those with 1-2 points were considered intermediate-risk, and those with 3-4 points were classified as high-risk. Results: As shown in the table, VTE incidence for the low-risk group was 1.9%, intermediate-risk group was 3.9%, and high-risk group was 9.1%. Conclusions: High-risk patients were about 4.5 times more likely to develop a VTE than low risk patients. These results provide valuable insight in determining which patients might benefit from prophylaxis and in motivating the design of prospective clinical trials that assess the VTE predictive model in various ambulatory cancer settings. [Table: see text]


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