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Breast Cancer is a major public health problem and the most common diagnosed malignancy in woman. There have been significant developments in clinical approaches and theoretical experimental to understand the interactions of cancer cells…

Dynamical Systems · Mathematics 2022-05-25 Hassnaa Akil , Nadia Idrissi Fatmi

Adaptive therapy is a recent paradigm in cancer treatment aiming at indefinite, safe containment of the disease when cure is judged unattainable. In modeling this approach, inherent limitations arise due to the structure of the vector…

Dynamical Systems · Mathematics 2025-03-20 Frederik J. Thomsen , Johan L. A. Dubbeldam

The traditional more-is-better dose selection paradigm, developed based on cytotoxic chemotherapeutics, is often problematic When applied to the development of novel molecularly targeted agents (e.g., kinase inhibitors, monoclonal…

Methodology · Statistics 2022-11-04 Liyun Jiang , Ying Yuan

Phase I-II cancer clinical trial designs are intended to accelerate drug development. In cases where efficacy cannot be ascertained in a short period of time, it is common to divide the study in two stages: i) a first stage in which dose is…

Methodology · Statistics 2022-12-13 José L. Jiménez , Mourad Tighiouart

We study an optimal control problem for a stochastic model of tumour growth with drug application. This model consists of three stochastic hyperbolic equations describing the evolution of tumour cells. It also includes two stochastic…

Optimization and Control · Mathematics 2024-08-30 Sakine Esmaili , M. R. Eslahchi , Delfim F. M. Torres

Fluence map optimization for intensity-modulated radiation therapy planning can be formulated as a large-scale inverse problem with competing objectives and constraints associated with the tumors and organs-at-risk. Unfortunately,…

Optimization and Control · Mathematics 2022-02-17 Kelsey Maass , Minsun Kim , Aleksandr Aravkin

Personalizing combination therapies in oncology requires navigating an immense space of possible drug and dose combinations, a task that remains largely infeasible through exhaustive experimentation. Recent developments in patient-derived…

Machine Learning · Computer Science 2025-09-10 Antoine de Mathelin , Christopher Tosh , Wesley Tansey

The US Food and Drug Administration launched Project Optimus with the aim of shifting the paradigm of dose-finding and selection towards identifying the optimal biological dose that offers the best balance between benefit and risk, rather…

Methodology · Statistics 2023-09-13 Ying Yuan , Heng Zhou , Suyu Liu

We establish a broad methodological foundation for mixed-integer optimization with learned constraints. We propose an end-to-end pipeline for data-driven decision making in which constraints and objectives are directly learned from data…

Optimization and Control · Mathematics 2023-10-30 Donato Maragno , Holly Wiberg , Dimitris Bertsimas , S. Ilker Birbil , Dick den Hertog , Adejuyigbe Fajemisin

While chemoresistance in primary tumors is well-studied, much less is known about the influence of systemic chemotherapy on the development of drug resistance at metastatic sites. In this work, we use a hybrid spatial model of tumor…

Tissues and Organs · Quantitative Biology 2016-03-04 Ami B. Shah , Katarzyna A. Rejniak , Jana L. Gevertz

Malignant gliomas (MGs), particularly glioblastoma, are among the most aggressive brain tumors, with limited treatment options and a poor prognosis. Maximal safe resection and the so-called Stupp protocol are the standard first-line…

We propose a new integrated phase I/II trial design to identify the most efficacious dose combination that also satisfies certain safety requirements for drug-combination trials. We first take a Bayesian copula-type model for dose finding…

Applications · Statistics 2011-08-09 Ying Yuan , Guosheng Yin

In parametric Bayesian designs of early phase cancer clinical trials with drug combinations exploring a discrete set of partially ordered doses, several authors claimed that there is no added value in including an interaction term to model…

Methodology · Statistics 2022-08-12 Mourad Tighiouart , José L. Jiménez , Marcio A. Diniz , André Rogatko

In this article, we focus on determining a minimum-cost treatment program aimed at maintaining the size of a cancerous tumor at a level that allows the patient to live comfortably. At each predetermined point in a treatment horizon, the…

Optimization and Control · Mathematics 2026-03-31 Alain Billionnet

Traditionally, the major objective in phase I trials is to identify a working-dose for subsequent studies, whereas the major endpoint in phase II and III trials is treatment efficacy. The dose sought is typically referred to as the maximum…

Methodology · Statistics 2016-08-14 Mourad Tighiouart , André Rogatko

Dual agent dose-finding trials study the effect of a combination of more than one agent, where the objective is to find the Maximum Tolerated Dose Combination (MTC), the combination of doses of the two agents that is associated with a…

Applications · Statistics 2025-02-10 Helen Barnett , Oliver Boix , Dimitris Kontos , Thomas Jaki

This paper deals with the classic radiotherapy dose fractionation problem for cancer tumors concerning the following goals: a) To maximize the effect of radiation on the tumor, restricting the effect produced to the organs at risk (healing…

Optimization and Control · Mathematics 2021-02-17 Luis Alberto Fernández , Lucía Fernández

It is increasingly common for therapies in oncology to be given in combination. In some cases, patients can benefit from the interaction between two drugs, although often at the risk of higher toxicity. A large number of designs to conduct…

Some clinical and pre-clinical data suggests that treating some tumors at a mild, patient-specific dose might delay resistance to treatment and increase survival time. A recent mathematical model with sensitive and resistant tumor cells…

Dynamical Systems · Mathematics 2022-12-01 Frank Alvarez , Yannick Viossat

Computational systems and methods are often being used in biological research, including the understanding of cancer and the development of treatments. Simulations of tumor growth and its response to different drugs are of particular…

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