An official website of the United States government
Summary Precision medicine is an emerging scientific topic for disease treatment and prevention that takes into account individual patient characteristics. It is an important direction for clinical research, and many statistical methods have been proposed recently. One of the primary goals of precision medicine is to obtain an optimal individual treatment rule (ITR), which can help make decisions on treatment selection according to each patient's specific characteristics. Recently, outcome weighted learning (OWL) has been proposed to estimate such an optimal ITR in a binary treatment setting by maximizing the expected clinical outcome. However, for ordinal treatment settings, such as individualized dose finding, it is unclear how to use OWL. In this article, we propose a new technique for estimating ITR with ordinal treatments. In particular, we propose a data duplication technique with a piecewise convex loss function. We establish Fisher consistency for the resulting estimated ITR under certain conditions, and obtain the convergence and risk bound properties. Simulated examples and an application to a dataset from a type 2 diabetes mellitus observational study demonstrate the highly competitive performance of the proposed method compared to existing alternatives.
more »
« less
Organic Field‐Effect Transistors as Flexible, Tissue‐Equivalent Radiation Dosimeters in Medical Applications
Abstract Radiation therapy is one of the most prevalent procedures for cancer treatment, but the risks of malignancies induced by peripheral beam in healthy tissues surrounding the target is high. Therefore, being able to accurately measure the exposure dose is a critical aspect of patient care. Here a radiation detector based on an organic field‐effect transistor (RAD‐OFET) is introduced, an in vivo dosimeter that can be placed directly on a patient's skin to validate in real time the dose being delivered and ensure that for nearby regions an acceptable level of low dose is being received. This device reduces the errors faced by current technologies in approximating the dose profile in a patient's body, is sensitive for doses relevant to radiation treatment procedures, and robust when incorporated into conformal large‐area electronics. A model is proposed to describe the operation of RAD‐OFETs, based on the interplay between charge photogeneration and trapping.
more »
« less
- PAR ID:
- 10446496
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Science
- Volume:
- 7
- Issue:
- 18
- ISSN:
- 2198-3844
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Radiation damage mitigation in electronics remains a challenge because the only established technique, thermal annealing, does not guarantee a favorable outcome. In this study, a non-thermal annealing technique is presented, where electron momentum from very short duration and high current density pulses is used to target and mobilize the defects. The technique is demonstrated on 60 Co gamma irradiated (5 × 10 6 rad dose and 180 × 10 3 rad h −1 dose rate) GaN high electron mobility transistors. The saturation current and maximum transconductance were fully and the threshold voltage was partially recovered at 30 °C or less. In comparison, thermal annealing at 300 °C mostly worsened the post-irradiation characteristics. Raman spectroscopy showed an increase in defects that reduce the 2-dimensional electron gas (2DEG) concentration and increase the carrier scattering. Since the electron momentum force is not applicable to the polymeric surface passivation, the proposed technique could not recover the gate leakage current, but performed better than thermal annealing. The findings of this study may benefit the mitigation of some forms of radiation damage in electronics that are difficult to achieve with thermal annealing.more » « less
-
Abstract A 3-D dosimeter fills the need for treatment plan and delivery verification required by every modern radiation-therapy method used today. This report summarizes a proof-of-concept study to develop a water-equivalent solid 3-D dosimeter that is based on novel radiation-hard scintillating material. The active material of the prototype dosimeter is a blend of radiation-hard peroxide-cured polysiloxane plastic doped with scintillating agent P-Terphenyl and wavelength-shifter BisMSB. The prototype detector was tested with 6 MV and 10 MV x-ray beams at Ohio State University’s Comprehensive Cancer Center. A 3-D dose distribution was successfully reconstructed by a neural network specifically trained for this prototype. This report summarizes the material production procedure, the material’s water equivalency investigation, the design of the prototype dosimeter and its beam tests, as well as the details of the utilized machine learning approach and the reconstructed 3-D dose distributions.more » « less
-
PURPOSE: Identify Oropharyngeal cancer (OPC) patients at high-risk of developing long-term severe radiation-associated symptoms using dose volume histograms for organs-at-risk, via unsupervised clustering. MATERIAL AND METHODS: All patients were treated using radiation therapy for OPC. Dose-volume histograms of organs-at-risk were extracted from patients’ treatment plans. Symptom ratings were collected via the MD Anderson Symptom Inventory (MDASI) given weekly during, and 6 months post-treatment. Drymouth, trouble swallowing, mucus, and vocal dysfunction were selected for analysis in this study. Patient stratifications were obtained by applying Bayesian Mixture Models with three components to patient’s dose histograms for relevant organs. The clusters with the highest total mean doses were translated into dose thresholds using rule mining. Patient stratifications were compared against Tumor staging information using multivariate likelihood ratio tests. Model performance for prediction of moderate/severe symptoms at 6 months was compared against normal tissue complication probability (NTCP) models using cross-validation. RESULTS: A total of 349 patients were included for long-term symptom prediction. High-risk clusters were significantly correlated with outcomes for severe late drymouth (p <.0001, OR = 2.94), swallow (p = .002, OR = 5.13), mucus (p = .001, OR = 3.18), and voice (p = .009, OR = 8.99). Simplified clusters were also correlated with late severe symptoms for drymouth (p <.001, OR = 2.77), swallow (p = .01, OR = 3.63), mucus (p = .01, OR = 2.37), and voice (p <.001, OR = 19.75). Proposed cluster stratifications show better performance than NTCP models for severe drymouth (AUC.598 vs.559, MCC.143 vs.062), swallow (AUC.631 vs.561, MCC.20 vs -.030), mucus (AUC.596 vs.492, MCC.164 vs -.041), and voice (AUC.681 vs.555, MCC.181 vs -.019). Simplified dose thresholds also show better performance than baseline models for predicting late severe ratings for all symptoms. CONCLUSION: Our results show that leveraging the 3-D dose histograms from radiation therapy plan improves stratification of patients according to their risk of experiencing long-term severe radiation associated symptoms, beyond existing NTPC models. Our rule-based method can approximate our stratifications with minimal loss of accuracy and can proactively identify risk factors for radiation-associated toxicity.more » « less
-
Abstract Cold atmospheric plasma (CAP) technology, a relatively novel technique mainly investigated as a stand-alone cancer treatment method in vivo and in vitro, is being proposed for application in conjunction with chemotherapy. In this study, we explore whether CAP, an ionized gas produced in laboratory settings and that operates at near room temperature, can enhance Temozolomide (TMZ) cytotoxicity on a glioblastoma cell line (U87MG). Temozolomide is the first line of treatment for glioblastoma, one of the most aggressive brain tumors that remains incurable despite advancements with treatment modalities. The cellular response to a single CAP treatment followed by three treatments with TMZ was monitored with a cell viability assay. According to the cell viability results, CAP treatment successfully augmented the effect of a cytotoxic TMZ dose (50 μM) and further restored the effect of a non-cytotoxic TMZ dose (10 μM). Application of CAP in conjunction TMZ increased DNA damage measured by the phosphorylation of H2AX and induced G2/M cell cycle arrest. These findings were supported by additional data indicating reduced cell migration and increased αvβ3 and αvβ5 cell surface integrin expression as a result of combined CAP–TMZ treatment. The data presented in this study serve as evidence that CAP technology can be a suitable candidate for combination therapy with existing chemotherapeutic drugs. CAP can also be investigated in future studies for sensitizing glioblastoma cells to TMZ and other drugs available in the market.more » « less
