We acknowledge Dr. Bernard North, part funded by the Imperial Experimental Cancer Medicine Centre (ECMC) grant from Cancer Research UK (CR-UK) and the UK Department of Health (DoH), for his statistical support as well as Farah Williams for her contribution to retrieving patient records.
Developing an objective marker to optimize patient selection and predict survival benefit in early-phase cancer trials
Article first published online: 8 OCT 2013
© 2013 American Cancer Society
Volume 120, Issue 2, pages 262–270, 15 January 2014
How to Cite
Stavraka, C., Pinato, D. J., Turnbull, S. J., Flynn, M. J., Forster, M. D., O'Cathail, S. M., Babar, S., Seckl, M. J., Kristeleit, R. S. and Blagden, S. P. (2014), Developing an objective marker to optimize patient selection and predict survival benefit in early-phase cancer trials. Cancer, 120: 262–270. doi: 10.1002/cncr.28381
The first 2 authors contributed equally to this work and should be considered joint first authors.
- Issue published online: 7 JAN 2014
- Article first published online: 8 OCT 2013
- Manuscript Accepted: 20 AUG 2013
- Manuscript Revised: 16 AUG 2013
- Manuscript Received: 24 MAY 2013
- prognostic score;
- phase 1 trial;
Several prognostic indices have been devised to optimize patient selection for phase 1 oncology trials with no consensus as to the optimal score and none qualifying as a marker of treatment response.
Multivariate predictors of overall survival (OS) were tested on 118 referred patients to develop the Hammersmith Score (HS). The score's ability to predict OS, progression-free survival (PFS), and 90-day mortality (90DM) was compared with other prognostic indices. Changes in HS were recalculated during treatment.
Albumin < 35 g/L, lactate dehydrogenase > 450 U/L, and sodium < 135 mmol/L emerged as independent prognostic factors. These were used with equal weighting to devise the HS, a compound prognostic index ranging from 0 to 3. High (HS = 2-3) score predicted worse OS (hazard ratio [HR] = 6.5, P < .001), PFS (HR = 2.8, P = .01), and 90DM (OR = 9.0, P < .001). HS was a more accurate multivariate predictor of OS (HR = 6.4, P < .001, C-index = 0.72), PFS (HR = 2.7, P = .03), and 90DM (area under the ROC curve 0.703) compared with other scores. Worsening of the HS during treatment predicted for shorter OS (P < .001). HS retained prognostic and predictive ability following external validation.
HS is a simple, validated index to optimize patient selection and predict survival benefit from phase 1 oncology treatments. Prospective validation is ongoing. Cancer 2014;120:262–270. © 2013 American Cancer Society.