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Volumetric Assessment of Imaging Response in the PNOC Pediatric Glioma Clinical Trials
Volumetric Assessment of Imaging Response in the PNOC Pediatric Glioma Clinical Trials
Volumetric Assessment of Imaging Response in the PNOC Pediatric Glioma Clinical Trials

상세정보

자료유형  
 학위논문 서양
최종처리일시  
20250211151059
ISBN  
9798382327563
DDC  
616
저자명  
Ramakrishnan, Divya.
서명/저자  
Volumetric Assessment of Imaging Response in the PNOC Pediatric Glioma Clinical Trials
발행사항  
[Sl] : Yale University, 2024
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2024
형태사항  
115 p
주기사항  
Source: Dissertations Abstracts International, Volume: 85-11, Section: B.
주기사항  
Advisor: Aboian, Mariam S.
학위논문주기  
Thesis (M.D.)--Yale University, 2024.
초록/해제  
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.
일반주제명  
Medical imaging
일반주제명  
Medicine
일반주제명  
Health sciences
키워드  
Brain tumors
키워드  
Neuro-oncology
키워드  
Neuroradiology
키워드  
Pediatric gliomas
키워드  
Response assessment
기타저자  
Yale University Yale School of Medicine
기본자료저록  
Dissertations Abstracts International. 85-11B.
전자적 위치 및 접속  
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■1001  ▼aRamakrishnan,  Divya.
■24510▼aVolumetric  Assessment  of  Imaging  Response  in  the  PNOC  Pediatric  Glioma  Clinical  Trials
■260    ▼a[Sl]▼bYale  University▼c2024
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2024
■300    ▼a115  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  85-11,  Section:  B.
■500    ▼aAdvisor:  Aboian,  Mariam  S.
■5021  ▼aThesis  (M.D.)--Yale  University,  2024.
■520    ▼aResponse  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.
■590    ▼aSchool  code:  0265.
■650  4▼aMedical  imaging
■650  4▼aMedicine
■650  4▼aHealth  sciences
■653    ▼aBrain  tumors
■653    ▼aNeuro-oncology
■653    ▼aNeuroradiology
■653    ▼aPediatric  gliomas
■653    ▼aResponse  assessment
■690    ▼a0574
■690    ▼a0564
■690    ▼a0566
■71020▼aYale  University▼bYale  School  of  Medicine.
■7730  ▼tDissertations  Abstracts  International▼g85-11B.
■790    ▼a0265
■791    ▼aM.D.
■792    ▼a2024
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17160680▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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