{
  "abstract": "The extreme therapeutic resistance of malignant gliomas motivates the development of multimodal treatment strategies. We present a mechanistic mathematical framework to investigate the coupled dynamics of radiotherapy, temozolomide, and chimeric antigen receptor (CAR) T-cell therapy. The model is formulated as a nine-dimensional impulsive dynamical system that captures proliferative-quiescent tumor states, treatment-specific resistance, tissue damage, TMZ pharmacokinetics, and the lymphotoxic interferences exerted by conventional regimens on engineered T cells. Mathematical analysis establishes the existence of biologically meaningful solutions, maps invariant structures, and identifies threshold conditions under which sustained therapy locally stabilizes the tumor-free equilibrium. After study-matched benchmarking against clinical trials, including the standard Stupp protocol, we deploy heterogeneous virtual patient cohorts to evaluate five combined CAR-T--Stupp sequences. At the population level, the immunotherapeutic adjunct yields a consistent but modest survival extension, increasing median overall survival by $0.8$--$0.9$ months with minimal sensitivity to temporal ordering or scheduling perturbations. Crucially, these population-level medians mask profound individual heterogeneity: under combined protocols, $19\\%$--$22\\%$ of virtual patients extend survival by more than $60$ days, and $\\sim 3\\%$ gain over a year. A low intrinsic tumor proliferation rate $r_1$ emerges as the primary determinant of response, bolstered by robust T-cell expansion and attenuated microenvironmental suppression. These findings suggest that the clinical promise of multimodal integration depends on identifying responsive tumor phenotypes for personalized treatments rather than searching for a single universally optimal timeline.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": "2609.39191",
  "author_total": 5,
  "authors": [
    {
      "name": "Dmitry Sinelshchikov"
    },
    {
      "name": "Nikols Amaru Mora Millán"
    },
    {
      "name": "Miguel Perales-Patón"
    },
    {
      "name": "Juan Belmonte-Beitia"
    },
    {
      "name": "Matteo Italia"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7pac914gmxzyf.bib",
  "cited_by": 0,
  "doi": "10.48550/arxiv.2609.39191",
  "fulltext_url": null,
  "id": "7pac914gmxzyf",
  "issns": [],
  "landing_url": "https://arxiv.org/abs/2609.39191",
  "language": null,
  "licence": "LicenseRef-arXiv-nonexclusive-1.0",
  "licence_label": "arXiv licence",
  "licence_source": "article",
  "licence_url": "http://arxiv.org/licenses/nonexclusive-distrib/1.0/",
  "metadata_licence": "CC0-1.0",
  "native_subjects": [
    [
      "arxiv",
      "math.DS"
    ],
    [
      "openalex",
      "2611|Mathematical Biology Tumor Growth"
    ]
  ],
  "openalex": "W7215082381",
  "pdf_url": "https://arxiv.org/pdf/2609.39191",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-30",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/7pac914gmxzyf.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:49Z",
      "native_id": "2609.39191",
      "source": "arxiv",
      "url": "https://arxiv.org/abs/2609.39191"
    }
  ],
  "subjects": [
    {
      "field": "mathematics",
      "origin": "arxiv:math.DS",
      "subfield": "dynamical-systems"
    }
  ],
  "title": "Combining standard chemoradiotherapy with CAR-T cell therapy in malignant gliomas: Insights from an impulsive mathematical framework and virtual trials",
  "title_text": "Combining standard chemoradiotherapy with CAR-T cell therapy in malignant gliomas: Insights from an impulsive mathematical framework and virtual trials",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:49Z",
  "url": "https://research.draconitic.com/paper/7pac914gmxzyf",
  "venue": "arXiv",
  "versions": []
}