Dataset Information

Chareyron2009 - Mixed immunotherapy and chemotherapy of tumors Feedback design and model updating schemes

ABSTRACT: Mixed immunotherapy and chemotherapy of tumors: feedback design and model updating schemes. Chareyron S1, Alamir M. Author information Abstract In this paper, a recently developed model governing the cancer growth on a cell population level with combination of immune and chemotherapy is used to develop a reactive (feedback) mixed treatment strategy. The feedback design proposed here is based on nonlinear constrained model predictive control together with an adaptation scheme that enables the effects of unavoidable modeling uncertainties to be compensated. The effectiveness of the proposed strategy is shown under realistic human data showing the advantage of treatment in feedback form as well as the relevance of the adaptation strategy in handling uncertainties and modeling errors. A new treatment strategy defined by an original optimal control problem formulation is also proposed. This new formulation shows particularly interesting possibilities since it may lead to tumor regression under better health indicator profile.

SUBMITTER: Mohammad Umer Sharif Shohan

PROVIDER: MODEL2001160002 | BioModels | 2020-01-16

REPOSITORIES: BioModels

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Mixed immunotherapy and chemotherapy of tumors: feedback design and model updating schemes.

Chareyron S S Alamir M M

Journal of theoretical biology 20080705 3

In this paper, a recently developed model governing the cancer growth on a cell population level with combination of immune and chemotherapy is used to develop a reactive (feedback) mixed treatment strategy. The feedback design proposed here is based on nonlinear constrained model predictive control together with an adaptation scheme that enables the effects of unavoidable modeling uncertainties to be compensated. The effectiveness of the proposed strategy is shown under realistic human data sho ...[more]

PMID: 18655792

Publication: 1/2

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Project description:Background: Neoadjuvant chemotherapy (NAC) is the standard treatment for muscle-invasive bladder cancer (MIBC), yet 40% of patients progress, emphasizing the need for biomarkers predictive for response or chemoresistance. Gene expression-based subtypes may serve as biomarkers, though which subtypes will respond, notably when it comes to the basal subtype, remains contentious. Patients and methods: This post hoc study analyzed 300 NAC-treated patients enrolled in the GETUG/AFU VESPER trial, with transurethral diagnostic formalin-ﬁxed parafﬁn-embedded which underwent pathological review before being sequenced. ‘Mixed’ subtype was deﬁned for tumors displaying at least two different Consensus molecular subtypes in separate regions. We evaluated the association between molecular subtypes and outcome after NAC. Tumors with remaining tissue at cystectomy (n ¼ 83) were compared with pre-treatment tumors. Results: Cases were classiﬁed basal/squamous (Ba/Sq) (n ¼ 84), luminal unstable (n = 57), stroma-rich (n = 53), mixed (n = 48), luminal papillary (n ¼ 39), luminal non-speciﬁc (n = 18), and neuroendocrine-like (n ¼ 1), with 30/48 mixed cases including a Ba/Sq component. Compared with other molecular subtypes in a multivariate Cox model, Ba/Sq (pure or mixed) patients had an increased hazard ratio (HR) of progression-free survival [HR 2.0, 95% conﬁdence interval (CI) 1.36-3.0]. Mixed tumors were associated with decreased metabolic activity that could account for chemoresistance. Ba/Sq and mixed non-responders mostly maintained their subtype at cystectomy and have fewer myeloid dendritic cells after NAC. Tumors classiﬁed luminal papillary at transurethral resection of the urinary bladder tumor exhibited an increase in T CD4þ and macrophage signatures after NAC. Other subtypes did not show signiﬁcant immune changes after NAC. Our study design relied on detailed pathological review, which precluded evaluating the mixed subtype in published datasets. Furthermore, the sample size for post-NAC analyses constrained the statistical power of these ﬁndings. Conclusions: Our ﬁndings underscore the importance of recognizing intra-tumor heterogeneity in MIBC and its role in chemoresistance associated with Ba/Sq subtype, and provide valuable insights that could help future treatment development and improve patient outcomes.