P. Mazzocco (1), G. Kaloshi, D. Ricard, J.Y. Delattre, F. Ducray, B.Ribba (1)
(1) INRIA Grenoble Rhône-Alpes, Numed Project Team, 655 avenue de l’Europe, 38330 Montbonnot-Saint-Martin, France
Objectives: To develop a model able to predict tumor size dynamics and overall survival (OS) in patients with low-grade gliomas (LGG) treated with temozolomide between 1999 and 2012.
Methods: We used tumor size measurements from 120 patients treated at Salpêtrière hospital (Paris) between 1999 and 2012 representing 1434 observations in total [1]. During this study, 60 patients (50%) died and the median survival time was 7 years. Biomolecular data including 1p19q codeletion, p53 and IDH mutation status were also available for 42 patients (35%). We first extended the tumor-growth-inhibition (TGI) model from [2] distinguishing proliferative and quiescent cells by 1) incorporating a resistance term as consequence of the observation that tumor regrows during treatment for 45 patients (38%) and 2) including biomolecular data as potential model covariates. Parameters were estimated with MONOLIX (Lixoft). Survival data were then described in a parametric model through the screening of relevant TGI model outputs.
Results:The model with the resistance term and covariates correctly fitted individual profiles. As expected, it was found that p53 mutation leads to faster tumor proliferation. IDH mutation was found to induce higher sensitivity of quiescent cells to apoptosis resulting in better tumor shrinkage. Tumor growth velocity before treatment, tumor size at treatment and relative change in tumor size after 8 weeks were found as best predictors for survival data.
Conclusions:The developed model can potentially be used to optimize temozolomide delivery in LGG patients as regards of tumor shrinkage and survival. Interestingly, as previously found for lung and thyroid cancer, the relative change after 8 weeks is a relevant predictor for low-grade gliomas.
References:
[1] Ricard,D., Kaloshi,G., Amiel-Benouaich,A., Lejeune,J., Marie,Y., Mandonnet,E., Kujas,M., et al. (2007). Dynamic history of lowgrade gliomas before and after temozolomide treatment. Ann Neurol, 61(5):484{490.
[2] Ribba, B., Kaloshi, G., Peyre, M., Ricard, D., Calvez, V., Tod, M., Cajavec Bernard, B., et al. (2012). A Tumor Growth Inhibition Model For Low-Grade Glioma Treated With Chemotherapy or Radiotherapy. Clinical Cancer Research, 18(18), 5071–80. doi:10.1158/1078-0432.CCR-12-0084
Reference: PAGE 22 () Abstr 2936 [www.page-meeting.org/?abstract=2936]
Poster: Oncology