Development of an Integrated Prostate Cancer Research Information System

Oh, William; Hayes, Julia H.; Evan, Carolyn; Manola, Judith; George, Daniel J.; Waldron, Helen; Donovan, Meaghan; Varner, John; Orechia, John A.; Katcher, Beth; Lu, Diana; Nevins, Arthur; Wright, Renée L.; Tormey, Lauren K.; Talcott, James A.; Rubin, Mark A.; Loda, Massimo; Sellers, William R.; Richie, Jerome P.; Kantoff, Philip W.; Weeks, Jane C.

doi:10.3816/cgc.2006.n.019

Cited by 59 publications

(48 citation statements)

References 4 publications

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“…The Prostate Clinical Research Information System (CRIS) database at Dana-Farber Cancer Institute was used to identify metastatic CRPC patients. The CRIS system comprises data-entry software, a central data repository, collection of patient data including comprehensive follow-up of all patients, and tightly integrated security measures, as previously described 33 . All patients provided written informed consent to allow the collection of tissue and blood and the analysis of clinical and genetic data for research purposes (DFCI Protocol # 01–045, IRB expiration date 3/20/2014).…”

Section: Methodsmentioning

confidence: 99%

Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer

et al. 2014

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Comprehensive analyses of cancer genomes promise to inform prognoses and precise cancer treatments. A major barrier, however, is inaccessibility of metastatic tissue. A potential solution is to characterize circulating tumor cells (CTCs), but this requires overcoming the challenges of isolating rare cells and sequencing low-input material. Here we report an integrated process to isolate, qualify and sequence whole exomes of CTCs with high fidelity, using a census-based sequencing strategy. Power calculations suggest that mapping of >99.995% of the standard exome is possible in CTCs. We validated our process in two prostate cancer patients including one for whom we sequenced CTCs, a lymph node metastasis and nine cores of the primary tumor. Fifty-one of 73 CTC mutations (70%) were observed in matched tissue. Moreover, we identified 10 early-trunk and 56 metastatic-trunk mutations in the non-CTC tumor samples and found 90% and 73% of these, respectively, in CTC exomes. This study establishes a foundation for CTC genomics in the clinic.

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Section: Methodsmentioning

confidence: 99%

Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer

et al. 2014

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“…The CRIS system consists of data-entry software, a central data repository, collection of patient data including comprehensive follow-up of all patients, and tightly integrated security measures as previously described. 14 All patients provided written informed consent to allow the collection of tissue and blood and the analysis of clinical and genetic data for research purposes. Patients with metastatic castration-resistant prostate cancer were identified for this trial based on (1) progression on a phase II study of abiraterone in combination with dutasteride or (2) Prostate-specific Antigen (PSA) > 20 ng ml −1 to enrich for patients likely to have detectable CTCs.…”

Section: Methodsmentioning

confidence: 99%

Functional analysis of single cells identifies a rare subset of circulating tumor cells with malignant traits

Yao

Choudhury

Yamanaka

et al. 2014

Integrative Biology

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Ample evidence supports genetic and functional heterogeneity in primary tumors, but it remains unclear whether circulating tumor cells (CTCs) also exhibit the same hierarchical organization. We examined the functional diversity of viable, single CTCs using an array of subnanoliter wells (nanowells). The compartmentalization of single cells by nanowells allowed clonal comparison and mapping of heterogeneity of single cells or preformed clusters of cells. By measuring the short-term viability, invasiveness and secretory profiles of individual CTCs, it was evident that only a rare subset of CTCs possessed malignant traits indicative of metastatic potential in late-stage, progressing metastatic castration-resistant prostate cancer (mCRPC) patients. These CTCs were resistant to anoikis after being in the circulation, were invasive in their epithelial state, or secreted proteases capable of cleaving peptide substrates. Every CTC observed, however, did not exhibit such metastatic potential, suggesting that enumeration of CTCs alone may be insufficient to understand metastasis or stratify patients.

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“…9 The DFCI Institutional Review Board approved this study. All patients provided written informed consent allowing analysis of clinical data for research purposes.…”

Section: Databasementioning

confidence: 99%

“…A total of 822 patients treated with 2eHT and/or chemotherapy for CRPC were identified in our database 9 ; 200 patients were excluded from further analysis for lack of documentation of 2eHT or chemotherapy (CT) for CRPC (N 5 56), absence of follow-up data (N 5 41), ADT start date in 1995 or before (N 5 75), or database error (N 5 28). The final cohort consisted of 622 patients.…”

Section: Study Cohortmentioning

confidence: 99%

Clinical predictors of survival in men with castration‐resistant prostate cancer

Nakabayashi

Hayes

Taplin

et al. 2013

Cancer

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BACKGROUND: This study sought to characterize Modern patients with castration-resistant prostate cancer (CRPC) and identify pretreatment clinical predictors of survival. METHODS: A cohort of men with CRPC with and without metastases (M) treated with secondary hormonal therapy (2eHT) and/or chemotherapy (CT) was identified from the authors' institutional database. Associations of patient and disease characteristics at diagnosis, at androgen-deprivation therapy (ADT) initiation, at CRPC index date, and survival were evaluated. CRPC index date was defined as the start date of either 2eHT or CT, whichever came first. RESULTS: In the cohort of 622 men, 434 men (70%) had M-positive disease; 552 men (89%) received 2eHT and 70 men (11%) received CT as their initial CRPC treatment. There were 410 deaths (66%) at the time of analysis. Median overall survival (OS) was 35 months (quartile 1, quartile 3: 21 months, 61 months). In multivariate analyses, higher biopsy Gleason score, the presence of M at ADT initiation, shorter time from ADT start to CRPC, higher prostate-specific antigen and poorer Eastern Cooperative Oncology Group performance status at CRPC and M at CRPC were predictive of shorter OS. Interestingly, whereas some men with biopsy Gleason scores of 6 died of their disease (N 5 42), they had a longer OS after CRPC compared with those with a Gleason score 7. CONCLUSIONS: This large retrospective study of patients with CRPC in a tertiary cancer center shows that biopsy Gleason score of 6 is associated with a less aggressive CRPC course, and the impact that M at ADT initiation and CRPC have on outcome is quantified.

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Development of an Integrated Prostate Cancer Research Information System

Cited by 59 publications

References 4 publications

Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer

Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer

Functional analysis of single cells identifies a rare subset of circulating tumor cells with malignant traits

Clinical predictors of survival in men with castration‐resistant prostate cancer

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