- C. Letellier, S. K. Sasmal, C. Draghi, F. Denis & D. Ghosh,
A chemotherapy combined with an anti-angiogenic drug applied to a cancer model including angiogenesis,
Chaos, Solitons & Fractals, 99, 297-311, 2017. Onine

- Abstract
Com­bined ther­apy made of a chemother­apy and an­tian­gio­genic agents is a clin­i­cal treat­ment rec­om­mended for its ef­fi­ciency. Since the op­ti­miza­tion of a treat­ment against can­cer re­lasp is still mostly based on on­col­o­gist’s know-how, it is de­sir­able to de­velop dif­fer­ent ap­proaches for such a task. Math­e­mat­i­cal mod­el­ling is one of the promis­ing ways. We here in­ves­ti­gated the ac­tion of a com­bined ther­apy in­serted to a math­e­mat­i­cal can­cer model in or­der to de­ter­mine how the dy­nam­ics un­der­ly­ing tu­mor growth is gov­erned by some key pa­ra­me­ters. We here re­tained a chemother­apy (for in­stance, pa­cli­taxel and car­bo­platin) com­bined with an an­tian­gio­genic drug (as be­va­cizumab) ap­plied to a can­cer model de­scrib­ing the in­ter­ac­tions be­tween host, im­mune, tu­mor and en­dothe­lial cells. The ef­fects of such a ther­apy are in­ves­ti­gated and the rel­e­vant role played by the “nor­mal” tis­sue of the tu­mor mi­cro-en­vi­ron­ment is ev­i­denced.

F. Denis, C. Lethrosne, N. Pourel, O. Molinier, Y. Pointreau, J. Domont, H. Bourgeois, H. Senellart, P. Trémolières, T. Lizée, J. Bennouna, T. Urban, C. El Khouri, A. Charron, A.-L. Septans, M. Balavoine, S. Landry, P. Solal-Céligny & C. Letellier
Randomized trial comparing a web-mediated follow-up with routine surveillance in lung cancer patients,
Journal of the National Cancer Institute, 109 (9), djx029, 2017. Online

- Abstract
Background : The use of web-based monitoring for lung cancer patients is growing in interest because of promising recent results suggesting improvement in cancer and resource utilization outcomes. It remains an open question whether the overall survival (OS) in these patients could be improved by using a web-mediated follow-up rather than classical scheduled follow-up and imaging.
Methods : Advanced-stage lung cancer patients without evidence of disease progression after or during initial treatment were randomly assigned in a multicenter phase III trial to compare a web-mediated follow-up algorithm (experimental arm), based on weekly self-scored patient symptoms, with routine follow-up with CT scans scheduled every three to six months according to the disease stage (control arm). In the experimental arm, an alert email was automatically sent to the oncologist when self-scored symptoms matched predefined criteria. The primary outcome was OS.
Results : From June 2014 to January 2016, 133 patients were enrolled and 121 were retained in the intent-to-treat analysis ; 12 deemed ineligible after random assignment were not subsequently followed. Most of the patients (95.1%) had stage III or IV disease. The median follow-up was nine months. The median OS was 19.0 months (95% confidence interval [CI] = 12.5 to noncalculable) in the experimental and 12.0 months (95% CI = 8.6 to 16.4) in the control arm (one-sided p = .001) (hazard ratio = 0.32, 95% CI = 0.15 to 0.67, one-sided p = .002). The performance status at first detected relapse was 0 to 1 for 75.9% of the patients in the experimental arm and for 32.5% of those in the control arm (two-sided p < .001). Optimal treatment was initiated in 72.4% of the patients in the experimental arm and in 32.5% of those in the control arm (two-sided p < .001).
Conclusions : A web-mediated follow-up algorithm based on self-reported symptoms improved OS due to early relapse detection and better performance status at relapse.

A comment on this paper can be found in [1] or here

D. Ghosh, S. Khajanchi, S. Mangiarotti, F. Denis, S. K. Dana & C. Letellier
How tumor growth can be influenced by delayed interactions between cancer cells and the microenvironment ?
Biosystems, in press Online

- Abstract
If recent advances in oncology emphasized the role of microenvironment in tumor growth, the role of delays for modeling tumor growth is still uncertain. In this paper, we considered a model, describing the interactions of tumor cells with their microenvironment made of immune cells and host cells, in which we inserted, as suggested by the clinicians, two time delays, one in the interactions between tumor cells and immune cells and, one in the action of immune cells on tumor cells. We showed analytically that the singular point associated with the co-existence of the three cell populations loses its stability via a Hopf bifurcation. We analytically calculated a range of the delays over which tumor cells are inhibited by immune cells and over which a period-1 limit cycle induced by this Hopf bifurcation is observed. By using a global modeling technique, we investigated how the dynamics observed with two delays can be reproduced by a similar model without delays. The effects of these two delays was thus interpreted in terms of interactions between the cell populations.

[1] R. Nipp &J. Temel,The patient knows best : Incorporating patient-reported outcomes into routine clinical care, Journal of the National Cancer Institute, 109 (9), djx044, 2017.

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