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Phase I dose-finding trials in oncology seek to find the maximum tolerated dose (MTD) of a drug under a specific schedule. Evaluating drug-schedules aims at improving treatment safety while maintaining efficacy. However, while we can…

A fundamental model of tumor growth in the presence of cytotoxic chemotherapeutic agents is formulated. The model allows to study the role of the Norton-Simon hypothesis in the context of dose-dense chemotherapy. Dose-dense protocols aim at…

Populations and Evolution · Quantitative Biology 2018-12-05 Álvaro G. López , Kelly C. Iarosz , Antonio M. Batista , Jesús M. Seoane , Ricardo L. Viana , Miguel A. F. Sanjuán

Robust optimization is a commonly employed method to mitigate uncertainties in the planning of intensity-modulated proton therapy (IMPT). In certain contexts, the large number of uncertainty scenarios makes the robust problem impractically…

Medical Physics · Physics 2025-04-22 Ivar Bengtsson

Background: Phase I trials desire to identify the maximum tolerated dose (MTD) early and proceed quickly to an expansion cohort or phase II trial for efficacy. We propose an early completion method based on multiple dosages to accelerate…

Quantitative Methods · Quantitative Biology 2021-10-04 Masahiro Kojima

One of the mechanisms that ensure cancer robustness is tumor heterogeneity, and its effects on tumor cells dynamics have to be taken into account when studying cancer progression. There is no unifying theoretical framework in mathematical…

Tissues and Organs · Quantitative Biology 2007-05-23 Georgy P. Karev , Artem S. Novozhilov , Eugene V. Koonin

Cancer and healthy cells have distinct distributions of molecular properties and thus respond differently to drugs. Cancer drugs ideally kill cancer cells while limiting harm to healthy cells. However, the inherent variance among cells in…

Other Quantitative Biology · Quantitative Biology 2013-08-07 Patrick N. Lawlor , Tomer Kalisky , Stephen Quake , Robert Rosner , Marsha Rich Rosner , Konrad P. Kording

Radiation therapy is an important tool in the treatment of breast cancer and can play a crucial role in improving patient outcomes. For breast cancer, if the technique has been for a long time the use of 3DCRT, clinicians have seen the…

With the advancement of high-throughput biotechnologies, we increasingly accumulate biomedical data about diseases, especially cancer. There is a need for computational models and methods to sift through, integrate, and extract new…

Quantitative Methods · Quantitative Biology 2020-07-03 Thomas Gaudelet , Noel Malod-Dognin , Natasa Przulj

In Oncology, trials evaluating drug combinations are becoming more common. While combination therapies bring the potential for greater efficacy, they also create unique challenges for ensuring drug safety. In Phase-I dose escalation trials…

Applications · Statistics 2023-02-23 Lukas A. Widmer , Andrew Bean , David Ohlssen , Sebastian Weber

Any process in which competing solutions replicate with errors and numbers of their copies depend on their respective fitnesses is the evolutionary optimization process. As during carcinogenesis mutated genomes replicate according to their…

Populations and Evolution · Quantitative Biology 2009-12-15 B. Brutovsky , D. Horvath

Phase I dose escalation trials in oncology generally aim to find the maximum tolerated dose (MTD). However, with the advent of molecular targeted therapies and antibody drug conjugates, dose limiting toxicities are less frequently observed,…

Methodology · Statistics 2025-08-19 Ayon Mukherjee , Jonathan L. Moscovici , Zheng Liu

Phase I early-phase clinical studies aim at investigating the safety and the underlying dose-toxicity relationship of a drug or combination. While little may still be known about the compound's properties, it is crucial to consider…

Methodology · Statistics 2022-09-13 Christian Röver , Moreno Ursino , Tim Friede , Sarah Zohar

In this paper, we studied phase-space analysis of a certain mathematical model of tumor growth with an immune responses and chemotherapy therapy. Mathematical modelling of this process is viewed as a potentially powerful tool in the…

Dynamical Systems · Mathematics 2018-03-15 Veli Shakhmurov , Akif Maharramov , Bunyad Shahmurzada

In this article, we propose a phase I-II design in two stages for the combination of molecularly targeted therapies. The design is motivated by a published case study that combines a MEK and a PIK3CA inhibitors; a setting in which higher…

Methodology · Statistics 2025-05-21 José L. Jiménez , Mourad Tighiouart

The essence of precision oncology lies in its commitment to tailor targeted treatments and care measures to each patient based on the individual characteristics of the tumor. The inherent heterogeneity of tumors necessitates gathering…

Quantitative Methods · Quantitative Biology 2024-07-01 Huajun Zhou , Fengtao Zhou , Chenyu Zhao , Yingxue Xu , Luyang Luo , Hao Chen

The conventional more-is-better dose selection paradigm, which targets the maximum tolerated dose (MTD), is not suitable for the development of targeted therapies and immunotherapies as the efficacy of these novel therapies may not increase…

Methodology · Statistics 2023-08-31 Peng Yang , Daniel Li , Ruitao Lin , Bo Huang , Ying Yuan

Early phase, personalized dose-finding trials for combination therapies seek to identify patient-specific optimal biological dose (OBD) combinations, which are defined as safe dose combinations which maximize therapeutic benefit for a…

Methodology · Statistics 2024-04-18 James Willard , Shirin Golchi , Erica EM Moodie

Health policy decisions regarding patient treatment strategies require consideration of both treatment effectiveness and cost. Optimizing treatment rules with respect to effectiveness may result in prohibitively expensive strategies; on the…

Methodology · Statistics 2021-10-20 Nicholas Illenberger , Andrew J. Spieker , Nandita Mitra

Geometric uncertainty can degrade treatment quality in radiation therapy. While margins and robust optimization mitigate these effects, they provide only implicit control over clinical goal fulfillment probability. We therefore develop a…

Medical Physics · Physics 2026-01-14 Albin Fredriksson , Erik Engwall , Jenneke de Jong , Johan Sundström

Intensity-modulated radiation therapy (IMRT) allows for the design of customized, highly-conformal treatments for cancer patients. Creating IMRT treatment plans, however, is a mathematically complex process, which is often tackled in…

Optimization and Control · Mathematics 2022-03-18 Danielle A. Ripsman , Thomas G. Purdie , Timothy C. Y. Chan , Houra Mahmoudzadeh
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