Baseline Circulating Tumor Cell Counts Significantly Enhance a Prognostic Score for Patients Participating in Phase I Oncology Trials

Abstract

Background: High circulating tumor cell (CTC) counts are associated with poor prognosis in several cancers. Enrollment of patients on phase I oncology trials requires a careful assessment of the potential risks and benefits. Many patients enrolled on such trials using established eligibility criteria have a short life expectancy and are less likely to benefit from trial participation. We hypothesized that the incorporation of CTC counts might improve patient selection for phase I trials.Methods: This retrospective analysis evaluated patients who had baseline CTCs enumerated prior to their starting on a phase I trial. CTCs were enumerated using the CellSearch System.Results: Between January 2006 and December 2009 a total of 128 patients enrolled in phase I trials had CTC counts evaluated. Higher CTC counts as a continuous variable independently correlated with risk of death in this patient population (P ¼ 0.006). A multivariate point-based risk model was generated using CTCs as a dichotomous variable (!3 or <3), and incorporated other established prognostic factors, including albumin <35 g/L, lactate dehydrogenase greater than upper limit of normal, and >2 metastatic sites. Comparison of receiver operating characteristic curves demonstrated that the addition of baseline CTC counts improved the performance of the prospectively validated Royal Marsden Hospital phase I prognostic score, which now identifies three risk groups (P < 0.0001): good prognosis [score 0-1, median overall survival (OS) 63.7 weeks], intermediate prognosis (score 2-3, median OS 37.3 weeks), and poor prognosis (score 4, median OS 13.4 weeks).Conclusion: CTC enumeration improved the performance of a validated prognostic score to help select patients for phase I oncology trials. Clin Cancer Res; 17(15); 5188-96. Ó2011 AACR.

Circulating Tumor Cells: Application as a Biomarker for Molecular Characterization and Predictor of Survival in an All-Comer Solid Tumor Phase I Clinical Study

“…Bidard and coworkers demonstrated detection of a single CTC in 7.5 ml of blood was associated with poor OS and development of metastasis in breast cancer patients [24]. Olmos et al showed that higher CTC count as a continuous variable was correlated with patient death in Phase I trials with various tumor types [25]. We separated the patients with detectable CTC into 2 groups (1-3 and >3 CTC) based on their CTC number at baseline.…”

“…Therefore, selection of patients with no CTC or a lower CTC count may reduce the patient loss and warrant a proper evaluation of investigational immunotherapeutic agents in early phase clinical trials. It has been reported that incorporation of the CTC count could improve the performance of prognostic score used for patient selection for phase I trials [25]. …”

Prediction of early death among patients enrolled in phase I trials: development and validation of a new model based on platelet count and albumin

“…It is likely to be difficult to improve on this level prediction using basic clinical and laboratory parameters. This suggests that the integration of more sophisticated parameters reflecting other dimensions than tumour burden and its consequences, such as tumour growth dynamics (Gomez-Roca et al , 2011) or the presence of circulating tumour cells (Olmos et al , 2011), may need to be incorporated if the predictive value of models is to improve.…”

“…To date, several models predictive of early death in this context have been proposed (Janisch et al , 1994; Yamamoto et al , 1999; Bachelot et al , 2000; Verweij, 2000; Han et al , 2003; Arkenau et al , 2008a, 2008b, 2009; Penel et al , 2008, 2009, 2010; Wheler et al , 2009; Olmos et al , 2011). Arkenau et al (2008a, 2008b) developed a score based on overall survival, which then was validated by logistic regression analysis for prediction of 90-day survival.…”

Relevance of Micrometastases and Targeting the Bone Marrow Niche with Zoledronic Acid in Breast Cancer

“…Both CTCs and DTCs may have prognostic potential as markers for survival and metastasis in patients with BC [12,[22][23][24][29][30][31][32][33][34][35][36][37][38][39] or prostate cancer (PC) [40][41][42][43] and for survival in colorectal cancer (CRC) [44,45]. Persistence of DTCs after radical prostatectomy was an independent predictor of disease recurrence in patients with PC, suggesting that DTCs also may be clinically significant in this patient population.…”