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Oncology drug development starts with a dose escalation phase to find the maximal tolerable dose (MTD). Dose limiting toxicity (DLT) is the primary endpoint for dose escalation phase. Traditionally, model-based dose escalation trial designs…

Applications · Statistics 2024-04-18 Arnab Kumar Maity , Satrajit Roy Chowdhury , Ray Li , Lada Markovtsova , Roberto Bugarini

Decision-making in personalized medicine such as cancer therapy or critical care must often make choices for dosage combinations, i.e., multiple continuous treatments. Existing work for this task has modeled the effect of multiple…

Machine Learning · Computer Science 2023-10-30 Jonas Schweisthal , Dennis Frauen , Valentyn Melnychuk , Stefan Feuerriegel

Dose optimization in oncology clinical trials has shifted from seeking the maximum tolerated dose to identifying the Optimal Biological Dose (OBD) that balances therapeutic benefits and risks across multiple clinical attributes. Existing…

Methodology · Statistics 2025-05-07 Fanni Zhang , Kristine Broglio , Michael Sweeting , Gina D'Angelo

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…

Machine Learning · Computer Science 2020-11-30 Leili Zhang , Giacomo Domeniconi , Chih-Chieh Yang , Seung-gu Kang , Ruhong Zhou , Guojing Cong

In this article, we establish a class of new accelerated modulus-based iteration methods for solving the linear complementarity problem. When the system matrix is an $H_+$-matrix, we present appropriate criteria for the convergence…

Optimization and Control · Mathematics 2023-05-05 Bharat Kumar , Deepmala , A. K. Das

Fast and accurate dose predictions are one of the bottlenecks in treatment planning for microbeam radiation therapy (MRT). In this paper, we propose a machine learning (ML) model based on a 3D U-Net. Our approach predicts separately the…

We demonstrate the application of mixture density networks (MDNs) in the context of automated radiation therapy treatment planning. It is shown that an MDN can produce good predictions of dose distributions as well as reflect uncertain…

Medical Physics · Physics 2021-07-06 Viktor Nilsson , Hanna Gruselius , Tianfang Zhang , Geert De Kerf , Michaël Claessens

Code completion is widely used by software developers to provide coding suggestions given a partially written code snippet. Apart from the traditional code completion methods, which only support single token completion at minimal positions,…

Software Engineering · Computer Science 2021-06-29 Jingxuan Li , Rui Huang , Wei Li , Kai Yao , Weiguo Tan

We propose a two-stage design for a clinical trial with an early stopping rule for safety. We use different criteria to assess early stopping and efficacy. The early stopping rule is based on a criteria that can be determined more quickly…

Methodology · Statistics 2013-07-25 Daniel Zelterman

Treatment of cancer has rapidly evolved over time in quite dramatic ways, for example from chemotherapies, targeted therapies to immunotherapies and chimeric antigen receptor T-cells. Nonetheless, the basic design of early phase I trials in…

Applications · Statistics 2024-12-04 Lukas Andreas Widmer , Sebastian Weber , Yunnan Xu , Hans-Jochen Weber

An important task in early phase drug development is to identify patients, which respond better or worse to an experimental treatment. While a variety of different subgroup identification methods have been developed for the situation of…

Methodology · Statistics 2020-01-22 Marius Thomas , Björn Bornkamp , Heidi Seibold

Dose-finding trials for oncology studies are traditionally designed to assess safety in the early stages of drug development. With the rise of molecularly targeted therapies and immuno-oncology compounds, biomarker-driven approaches have…

Methodology · Statistics 2025-09-15 Xijin Chen , Pavel Mozgunov , Richard D. Baird , Thomas Jaki

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

Several recently developed methods have the potential to harness machine learning in the pursuit of target quantities inspired by causal inference, including inverse weighting, doubly robust estimating equations and substitution estimators…

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…

This study investigates the applicability of 3D dose predictions from a model trained on one modality to a cross-modality automated planning workflow. Additionally, we explore the impact of integrating a multi-criteria optimizer on adapting…

Medical Physics · Physics 2024-02-26 Gregory Szalkowski , Xuanang Xu , Shiva Das , Pew-Thian Yap , Jun Lian

The next great leap toward improving treatment of cancer with radiation will require the combined use of online adaptive and magnetic resonance guided radiation therapy techniques with automatic X-ray beam orientation selection.…

Medical Physics · Physics 2019-08-14 Ryan Neph , Yangsibo Huang , Youming Yang , Ke Sheng

Major advances have been made regarding the utilization of artificial intelligence in health care. In particular, deep learning approaches have been successfully applied for automated and assisted disease diagnosis and prognosis based on…

Methodology · Statistics 2020-03-24 Max Westphal , Antonia Zapf , Werner Brannath

Microbeam radiation therapy (MRT) utilizes coplanar synchrotron radiation beamlets and is a proposed treatment approach for several tumour diagnoses that currently have poor clinical treatment outcomes, such as gliosarcomas. Prescription…

Oncology dose-finding trials are shifting from identifying the maximum tolerated dose (MTD) to determining the optimal biological dose (OBD), driven by the need for efficient methods that consider both toxicity and efficacy. This is…

Methodology · Statistics 2025-04-01 Hao Sun , Jieqi Tu , Revathi Ananthakrishnan , Eunhee Kim
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