자료유형  

 학위논문

Control Number  

0017160680

International Standard Book Number  

9798382327563

Dewey Decimal Classification Number  

616

Main Entry-Personal Name  

Ramakrishnan, Divya.

Publication, Distribution, etc. (Imprint  

[S.l.] : Yale University., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

115 p.

General Note  

Source: Dissertations Abstracts International, Volume: 85-11, Section: B.

General Note  

Advisor: Aboian, Mariam S.

Dissertation Note  

Thesis (M.D.)--Yale University, 2024.

Summary, Etc.  

요약Response assessment in neuro-oncology relies on radiographic assessment of tumor burden on magnetic resonance (MR) imaging. The most widely used criteria were developed by the Response Assessment in Neuro-Oncology (RANO) group. The RANO criteria rely on bidimensional (2D) measurements of tumor on MR images. The RANO criteria were originally developed to assess response in adult high-grade glioma. However, the heterogeneous appearance of pediatric low-grade gliomas make application of RANO criteria challenging. Volumetric assessment of pediatric gliomas may offer a more comprehensive method for characterizing response.The goal of this thesis was to compare 2D and volumetric assessment methods in two pediatric glioma clinical trials from the Pacific Pediatric Neuro-Oncology Consortium (PNOC). The primary purpose of the thesis was to compare 2D and volumetric response to a clinical reference standard - neuroradiologist visual response assessment via the Brain Tumor Reporting and Data System (BT-RADS). A secondary aim was to determine optimal thresholds for categorizing volumetric response using BT-RADS as a reference standard. A third aim was to compare 2D and volumetric posttreatment trajectories in trial participants.Retrospective analyses of two pediatric glioma clinical trials (PNOC-001 and PNOC-002) were conducted. Changes in tumor 2D area, whole tumor volume, and solid tumor volume were compared to assess response. Follow-up images were assigned a response score on BT-RADS by two neuroradiologists. Empirical receiver operating characteristic (ROC) curves of changes in 2D area, whole, and solid tumor volume were constructed to classify partial response (PR) and progressive disease (PD) based on BT-RADS. In the PNOC-002 trial, a mathematical model was used to construct posttreatment trajectories of changes in 2D area and whole tumor volume in a subset of participants.Empirical ROC curves to classify BT-RADS PD among the 65 follow-up images assessed in the PNOC-001 trial yielded an AUC of 0.78 (95% CI: 0.66-0.90) for 2D area percent change, 0.84 (95% CI: 0.74-0.94) for whole volume percent change, and 0.96 (95% CI: 0.92-1.00) for solid volume percent change. DeLong tests revealed that there was a significant increase in AUC of the solid volume ROC curve compared to both 2D area (p = 0.005) and whole volume (p = 0.006). The empirical ROC curves to classify BT-RADS PR yielded an AUC of 0.87 (95% CI: 0.77-0.96) for 2D area percent change, 0.84 (95% CI: 0.70-0.99) for whole volume percent change, and 0.97 (95% CI: 0.94-1.00) for solid volume percent change. DeLong tests revealed that there was a significant increase in AUC of the solid volume ROC curve compared to 2D area (p = 0.02) but not whole volume (p = 0.08). The thresholds for solid volume percent change that included an 80% sensitivity in their 95% confidence intervals for classifying BT-RADS PD ranged from 15-25% and 15-20% for classifying BT-RADS PR.The empirical ROC curves for classification of BT-RADS PR in the 31 participants at the end of treatment or last available follow-up produced the following AUC values: 0.92 (95% CI: 0.80-1.00) for 2D area percent change, 0.99 (95% CI: 0.97- 1.00) for whole volume percent change, and 0.99 (95% CI: 0.97-1.00) for solid volume percent change. DeLong test revealed no statistically significant difference in AUC between 2D area and either solid (p = 0.17) or whole volume (p = 0.17) ROC curves. The empirical ROC curves for classification of BT-RADS PR at the first time of BTRADS PR detection produced the following AUC values: 0.84 (95% CI: 0.69-0.99) for 2D area percent change, 0.91 (95% CI: 0.80-1.00) for whole volume percent change, and 0.92 (95% CI: 0.82-1.00) for solid volume percent change. There was no statistically significant difference in AUC between the 2D area ROC curve and either solid (p = .34) or whole volume (p = .39) ROC curves based on DeLong tests. Based on mathematically modeled trajectories, there was no significant correlation in time to best response obtained from 2D area vs. whole volume posttreatment changes (ρ = 0.39, p = 0.054). Eight out of 25 participants (32%) had a difference of 90 days in transition time from partial response to stable disease between 2D area and whole volume trajectories. Moreover, of the 16 participants with tumor regrowth following stable disease, 50% had a difference of ≥ 90 days in transition time from stable disease to progressive disease between 2D area and whole volume trajectories.Solid tumor volume better predicted neuroradiologist assessment of partial response and progressive disease according to BT-RADS criteria in the PNOC-001 trial but performed as well as 2D measurements in classifying partial response in the PNOC-002 trial. Although volumetrics was not consistently superior to 2D measurements in detecting response in our study, there were differences in individual participant 2D and volumetric posttreatment trajectories. Future research comparing volumetric to 2D assessment in prospective trials is required to understand the significance of these differences to clinical management.

Subject Added Entry-Topical Term  

Medical imaging.

Subject Added Entry-Topical Term  

Medicine.

Subject Added Entry-Topical Term  

Health sciences.

Index Term-Uncontrolled  

Brain tumors

Index Term-Uncontrolled  

Neuro-oncology

Index Term-Uncontrolled  

Neuroradiology

Index Term-Uncontrolled  

Pediatric gliomas

Index Term-Uncontrolled  

Response assessment

Added Entry-Corporate Name  

Yale University Yale School of Medicine

Host Item Entry  

Dissertations Abstracts International. 85-11B.

Electronic Location and Access  

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Control Number  

joongbu:658565