scholarly journals Two-step feature selection for predicting survival time of patients with metastatic castrate resistant prostate cancer

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2678 ◽  
Author(s):  
Motoki Shiga

Metastatic castrate resistant prostate cancer (mCRPC) is the major cause of death in prostate cancer patients. Even though some options for treatment of mCRPC have been developed, the most effective therapies remain unclear. Thus finding key patient clinical variables related with mCRPC is an important issue for understanding the disease progression mechanism of mCRPC and clinical decision making for these patients. The Prostate Cancer DREAM Challenge is a crowd-based competition to tackle this essential challenge using new large clinical datasets. This paper proposes an effective procedure for predicting global risks and survival times of these patients, aimed at sub-challenge 1a and 1b of the Prostate Cancer DREAM challenge. The procedure implements a two-step feature selection procedure, which first implements sparse feature selection for numerical clinical variables and statistical hypothesis testing of differences between survival curves caused by categorical clinical variables, and then implements a forward feature selection to narrow the list of informative features. Using Cox’s proportional hazards model with these selected features, this method predicted global risk and survival time of patients using a linear model whose input is a median time computed from the hazard model. The challenge results demonstrated that the proposed procedure outperforms the state of the art model by correctly selecting more informative features on both the global risk prediction and the survival time prediction.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15174-e15174
Author(s):  
Bertha E. Sanchez ◽  
Nilesh Gupta ◽  
Meredith Mahan ◽  
Evelyn R Barrack ◽  
Prem-veer Reddy ◽  
...  

e15174 Background: Docetaxel is a tubulin-targeting cytotoxic that remains first-line therapy in metastatic castrate-resistant prostate cancer (mCRPC) patients (pts) even though half of pts are reported to be non-responders. A predictive marker to identify those who will benefit from docetaxel-therapy will assist clinical decision making. High βIII-tubulin (TUBB3) expression has previously been reported to correlate with lack of response to taxanes in other cancers. We evaluated TUBB3 expression as a predictor of docetaxel-resistance in mCRPC. Methods: mCRPC pts treated with at least 3 cycles of docetaxel between 1990 and 2011 were identified retrospectively. TUBB3 immunostaining was performed on archival formalin-fixed, paraffin-embedded tissue. Stain intensity was scored from 0 to 3; 2 and 3 were interpreted as positive. Rates of PSA response were compared between pts with positive (+) and negative (-) TUBB3 expression. Two definitions of PSA response were evaluated (any PSA decline and at least 50% decline). Overall survival (OS) distribution between TUBB3+ and TUBB3- pts was estimated by the Kaplan-Meier method. Results: Of 73 pts, 26 (35%) expressed TUBB3. At diagnosis, the mean age was 65.7 years and the median Gleason score was 8. At the time of docetaxel therapy, the mean age was 71.2 years, the median PSA level was 70.9 (range, 0.2-5253) and 76% had ECOG performance status ≤1. The median number of docetaxel cycles was 7 (range, 3-18). The total dose of docetaxel was not different between groups (p=0.705). The median OS was 19.2 mo. TUBB3 expression was not correlated with any clinical or pathological characteristic (age, Gleason score, stage, ECOG, PSA, LDH, alkaline phosphatase, hemoglobin, visceral disease or chemotherapy before docetaxel). 65% of TUBB3+ pts had any PSA decline compared to 89% of pts with TUBB3- (p=0.0267). 52% of TUBB3+ pts had a PSA decline of ≥ 50% compared to 70% of TUBB3- pts (p=0.0144). Median OS for TUBB3+ pts was 16.8 mo compared to 20.4 mo in TUBB3- pts (p=0.039). Conclusions: High TUBB3 expression was associated with shorter OS and lower PSA response rates in mCRPC pts treated with docetaxel. These findings need to be validated prospectively.


2021 ◽  
Vol 10 (5) ◽  
pp. 205846012110225
Author(s):  
Omer Aras ◽  
Stefan Harmsen ◽  
Richard Ting ◽  
Haluk B Sayman

Targeted radionuclide therapy has emerged as a promising and potentially curative strategy for high-grade prostate cancer. However, limited data are available on efficacy, quality of life, and pretherapeutic biomarkers. Here, we highlight the case of a patient with prostate-specific membrane antigen (PSMA)-positive metastatic castrate-resistant prostate cancer who displayed complete response to 225Ac-PSMA-617 after having been resistant to standard-of-care therapy, then initially partially responsive but later resistant to subsequent immunotherapy, and resistant to successive 177Lu-PSMA-617. In addition, the patient’s baseline germline mutation likely predisposed him to more aggressive disease.


The Prostate ◽  
2014 ◽  
Vol 74 (14) ◽  
pp. 1462-1464 ◽  
Author(s):  
Raya Leibowitz-Amit ◽  
Nimira Alimohamed ◽  
Francisco E. Vera-Badillo ◽  
Jo-An Seah ◽  
Arnoud J. Templeton ◽  
...  

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