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To promote precision medicine, individualized treatment regimes (ITRs) are crucial for optimizing the expected clinical outcome based on patient-specific characteristics. However, existing ITR research has primarily focused on scenarios…

Methodology · Statistics 2024-02-20 Chang Wang , Lu Wang

Neutropenia is an adverse event commonly arising during intensive chemotherapy of acute myeloid leukemia (AML). It is often associated with infectious complications. Mathematical modeling, simulation, and optimization of the treatment…

Quantitative Methods · Quantitative Biology 2020-04-21 Felix Jost , Enrico Schalk , Daniela Weber , Hartmut Doehner , Thomas Fischer , Sebastian Sager

With the advancement in drug development, multiple treatments are available for a single disease. Patients can often benefit from taking multiple treatments simultaneously. For example, patients in Clinical Practice Research Datalink (CPRD)…

Applications · Statistics 2018-04-17 Muxuan Liang , Ye Ting , Haoda Fu

With the development of novel therapies such as molecularly targeted agents and immunotherapy, the maximum tolerated dose paradigm that "more is better" does not necessarily hold anymore. In this context, doses and schedules of novel…

Heterogeneous treatment effect estimation is critical in oncology, particularly in multi-arm trials with overlapping therapeutic components and long-term survivors. These shared mechanisms pose a central challenge to identifying causal…

Methodology · Statistics 2025-10-29 Peter Chang , John Kairalla , Arkaprava Roy

We investigate the long-time dynamics and optimal control problem of a diffuse interface model that describes the growth of a tumor in presence of a nutrient and surrounded by host tissues. The state system consists of a Cahn-Hilliard type…

Analysis of PDEs · Mathematics 2023-07-28 Cecilia Cavaterra , Elisabetta Rocca , Hao Wu

Histopathological evidence supports the idea that the emergence of phenotypic heterogeneity and resistance to cytotoxic drugs can be considered as a process of adaptation, or evolution, in tumor cell populations. In this framework, can we…

Tissues and Organs · Quantitative Biology 2013-12-24 Alexander Lorz , Tommaso Lorenzi , Jean Clairambault , Alexandre Escargueil , Benoît Perthame

In this article, a well-known mathematical model of cancer immunotherapy is discussed and used to represent therapeutic protocols for cancer treatment. The optimal control problem is formulated based on the Pontryagin maximum principle to…

Quantitative Methods · Quantitative Biology 2020-08-04 Sima Sarv Ahrabi

We present a method for handling dose constraints as part of a convex programming framework for inverse treatment planning. Our method uniformly handles mean dose, maximum dose, minimum dose, and dose-volume (i.e., percentile) constraints…

Medical Physics · Physics 2019-03-05 Anqi Fu , Baris Ungun , Lei Xing , Stephen Boyd

To accurately verify the dose of intensity-modulated radiation therapy (IMRT), we have used a global optimization method to investigate a new dose-verification algorithm. In practical application of this quality assurance (QA) procedure,…

Medical Physics · Physics 2007-05-23 Dong Hyun Park , Sung-Yong Park , Dahl Park , Tae-Hyun Kim , Kyung Hwan Shin , Dae Yong Kim , Kwan-Ho Cho

Pharmacokinetic modeling using ordinary differential equations (ODEs) has an important role in dose optimization studies, where dosing must balance sustained therapeutic efficacy with the risk of adverse side effects. Such ODE models…

Methodology · Statistics 2025-06-30 Yuxuan Zhao , Samuel W. K. Wong

Progress in immunotherapy revolutionized the treatment landscape for advanced lung cancer, raising survival expectations beyond those that were historically anticipated with this disease. In the present study, we describe the methods for…

Applications · Statistics 2019-11-25 Lizet Sanchez , Patricia Lorenzo-Luaces , Claudia Fonte , Agustin Lage

Optimal treatment rules can improve health outcomes on average by assigning a treatment associated with the most desirable outcome to each individual. Due to an unknown data generation mechanism, it is appealing to use flexible models to…

Methodology · Statistics 2023-11-21 Lingjie Shen , Gijs Geleijnse , Maurits Kaptein

Many drugs used therapeutically or recreationally induce tolerance: the effect of the substance decreases with repeated use. This phenomenon may reduce the efficacy of the substance unless dosage is increased beyond what is healthy for the…

Dynamical Systems · Mathematics 2024-03-19 Golrokh Nouri , Paul Tupper

Phase Ib/II oncology trials, despite their small sample sizes, aim to provide information for optimal internal company decision-making concerning novel drug development. Hybrid controls (a combination of the current control arm and controls…

Significant evidence has become available that emphasizes the importance of personalization in medicine. In fact, it has become a common belief that personalized medicine is the future of medicine. The core of personalized medicine is the…

Methodology · Statistics 2020-04-30 Qiong Zhang , Amin Khademi , Yongjia Song

We analyze the effect of tumor repopulation on optimal dose delivery in radiation therapy. We are primarily motivated by accelerated tumor repopulation towards the end of radiation treatment, which is believed to play a role in treatment…

Medical Physics · Physics 2015-04-28 Thomas Bortfeld , Jagdish Ramakrishnan , John N. Tsitsiklis , Jan Unkelbach

Objective: We propose a semiautomatic pipeline for radiation therapy treatment planning, combining ideas from machine learning-automated planning and multicriteria optimization (MCO). Approach: Using knowledge extracted from historically…

Medical Physics · Physics 2022-02-16 Tianfang Zhang , Rasmus Bokrantz , Jimmy Olsson

Combination of several anti-cancer treatments has typically been presumed to have enhanced drug activity. Motivated by a real clinical trial, this paper considers phase I-II dose finding designs for dual-agent combinations, where one main…

Methodology · Statistics 2023-05-09 José L. Jiménez , Haiyan Zheng

We consider a system of two coupled integro-differential equations modelling populations of healthy and cancer cells under therapy. Both populations are structured by a phenotypic variable, representing their level of resistance to the…

Optimization and Control · Mathematics 2016-12-15 Camille Pouchol , Jean Clairambault , Alexander Lorz , Emmanuel Trélat