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Stochastic and (distributionally) robust optimization problems often become computationally challenging as the number of scenarios or data points increases. Scenario reduction is therefore a key technique for improving tractability. We…

最优化与控制 · 数学 2026-03-10 Kevin-Martin Aigner , Sebastian Denzler , Frauke Liers , Sebastian Pokutta , Kartikey Sharma

Precision medicine aims to tailor therapeutic decisions to individual patient characteristics. This objective is commonly formalized through dynamic treatment regimes, which use statistical and machine learning methods to derive sequential…

机器学习 · 统计学 2026-03-23 Sophia Yazzourh , Erica E. M. Moodie

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…

医学物理 · 物理学 2025-04-22 Ivar Bengtsson

An important tool to evaluate the performance of any design is an optimal benchmark proposed by O'Quigley and others (2002, Biostatistics 3(1), 51-56) that provides an upper bound on the performance of a design under a given scenario. The…

统计理论 · 数学 2018-03-06 Pavel Mozgunov , Thomas Jaki , Xavier Paoletti

In this paper, a methodology is proposed that enables to analyze the sensitivity of the outcome of a therapy to unavoidable high dispersion of the patient specific parameters on one hand and to the choice of the parameters that define the…

系统与控制 · 电气工程与系统科学 2022-05-17 Mazen Alamir

Drug discovery is a multi-stage process that comprises two costly major steps: pre-clinical research and clinical trials. Among its stages, lead optimization easily consumes more than half of the pre-clinical budget. We propose a combined…

机器学习 · 计算机科学 2020-11-30 Leili Zhang , Giacomo Domeniconi , Chih-Chieh Yang , Seung-gu Kang , Ruhong Zhou , Guojing Cong

Purpose: We present a framework for robust automated treatment planning using machine learning, comprising scenario-specific dose prediction and robust dose mimicking. Methods: The scenario dose prediction pipeline is divided into the…

医学物理 · 物理学 2022-10-12 Oskar Eriksson , Tianfang Zhang

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…

医学物理 · 物理学 2015-04-28 Thomas Bortfeld , Jagdish Ramakrishnan , John N. Tsitsiklis , Jan Unkelbach

The fields of therapeutic application and drug research and development (R&D) both face substantial challenges, i.e., the therapeutic domain calls for more treatment alternatives, while numerous promising pre-clinical drugs have failed in…

Proton therapy is a modality in fast development. Characterized by a maximum dose deposition at the end of the proton trajectory followed by a sharp fall-off, proton beams can deliver a highly conformal dose to the tumor while sparing…

医学物理 · 物理学 2022-05-18 François Smekens , Nicolas Freud , Bruno Sixou , Guillaume Beslon , Jean M Létang

In phase I dose escalation studies for dual-agent combinations, at least one drug often has an established monotherapy dose. Consequently, substantial prior clinical safety data often exist for one or more monotherapies, allowing the study…

统计方法学 · 统计学 2026-05-07 Yuxuan Chen , Haiming Zhou , Keiko Nakajima , Philip He

Traditionally, optimization of radiation therapy (RT) treatment plans has been done before the initiation of RT course, using population-wide estimates for patients' response to therapy. However, recent technological advancements have…

医学物理 · 物理学 2021-02-15 Stefan C. M. ten Eikelder , Ali Ajdari , Thomas Bortfeld , Dick den Hertog

The primary objective of phase I oncology studies is to establish the safety profile of a new treatment and determine the maximum tolerated dose (MTD). This is motivated by the development of cytotoxic agents based on the underlying…

应用统计 · 统计学 2023-02-10 Yiding Zhang , Zhixing Xu , Hui Quan , Ji Lin

Proton pencil beam scanning (PBS) treatment planning for head and neck (H&N) cancers is a time-consuming and experience-demanding task where a large number of planning objectives are involved. Deep reinforcement learning (DRL) has recently…

定量方法 · 定量生物学 2024-09-19 Qingqing Wang , Chang Chang

Dose-finding studies in oncology often include an up-and-down dose transition rule that assigns a dose to each cohort of patients based on accumulating data on dose-limiting toxicity (DLT) events. In making a dose transition decision, a key…

统计方法学 · 统计学 2025-01-30 Zhiwei Zhang

A prototype for a web application was designed and implemented as a guide to be used by clinicians when designing the best drug therapy for a specific cancer patient, given biological data derived from the patients tumor tissue biopsy. A…

分子网络 · 定量生物学 2014-05-15 Elinor Velasquez , Jorge Soto-Andrade , Ben Bongalon

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…

统计方法学 · 统计学 2024-02-20 Chang Wang , Lu Wang

Purpose: The early identification of maximum tolerated dose (MTD) in phase I trial leads to faster progression to a phase II trial or an expansion cohort to confirm efficacy. Methods: We propose a novel adaptive design for identifying MTD…

统计方法学 · 统计学 2021-10-07 Masahiro Kojima

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…

统计方法学 · 统计学 2025-05-21 José L. Jiménez , Mourad Tighiouart

Studies often report estimates of the average treatment effect. While the ATE summarizes the effect of a treatment on average, it does not provide any information about the effect of treatment within any individual. A treatment strategy…

统计方法学 · 统计学 2025-06-13 Nicholas T. Williams , Katherine L. Hoffman Iván Díaz , Kara E. Rudolph