Apparent diffusion coefficient histogram metrics correlate with survival in diffuse intrinsic pontine glioma: a report from the Pediatric Brain Tumor Consortium.
Diffuse intrinsic pontine glioma (DIPG) is associated with poor survival regardless of therapy. We used volumetric apparent diffusion coefficient (ADC) histogram metrics to determine associations with progression-free survival (PFS) and overall survival (OS) at baseline and after radiation therapy (RT).



Baseline and post-RT quantitative ADC histograms were generated from fluid-attenuated inversion recovery (FLAIR) images and enhancement regions of interest. Metrics assessed included number of peaks (ie, unimodal or bimodal), mean and median ADC, standard deviation, mode, skewness, and kurtosis.



Based on FLAIR images, the majority of tumors had unimodal peaks with significantly shorter average survival. Pre-RT FLAIR mean, mode, and median values were significantly associated with decreased risk of progression; higher pre-RT ADC values had longer PFS on average. Pre-RT FLAIR skewness and standard deviation were significantly associated with increased risk of progression; higher pre-RT FLAIR skewness and standard deviation had shorter PFS. Nonenhancing tumors at baseline showed higher ADC FLAIR mean values, lower kurtosis, and higher PFS. For enhancing tumors at baseline, bimodal enhancement histograms had much worse PFS and OS than unimodal cases and significantly lower mean peak values. Enhancement in tumors only after RT led to significantly shorter PFS and OS than in patients with baseline or no baseline enhancement.



ADC histogram metrics in DIPG demonstrate significant correlations between diffusion metrics and survival, with lower diffusion values (increased cellularity), increased skewness, and enhancement associated with shorter survival, requiring future investigations in large DIPG clinical trials.
Department of Radiology, Boston Children's Hospital, Boston, Massachusetts (T.Y.P., S.V., K.I.R.); Department of Radiology, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (A.P.); Department of Diagnostic Imaging, St Jude Children's Research Hospital, Memphis, Tennessee (L.E.K.); Department of Biostatistics, St Jude Children's Research Hospital, Memphis, Tennessee (M.K., J.M.B.); Department of Neurosurgery, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania (I.F.P.); Neuro-Oncology Program, Cincinnati Children's Hospital, Cincinnati, Ohio (M.F.).
Tina Young
TY
Poussaint
Department of Radiology, Boston Children's Hospital, Boston, Massachusetts (T.Y.P., S.V., K.I.R.); Department of Radiology, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (A.P.); Department of Diagnostic Imaging, St Jude Children's Research Hospital, Memphis, Tennessee (L.E.K.); Department of Biostatistics, St Jude Children's Research Hospital, Memphis, Tennessee (M.K., J.M.B.); Department of Neurosurgery, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania (I.F.P.); Neuro-Oncology Program, Cincinnati Children's Hospital, Cincinnati, Ohio (M.F.).
Sridhar
S
Vajapeyam
Department of Radiology, Boston Children's Hospital, Boston, Massachusetts (T.Y.P., S.V., K.I.R.); Department of Radiology, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (A.P.); Department of Diagnostic Imaging, St Jude Children's Research Hospital, Memphis, Tennessee (L.E.K.); Department of Biostatistics, St Jude Children's Research Hospital, Memphis, Tennessee (M.K., J.M.B.); Department of Neurosurgery, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania (I.F.P.); Neuro-Oncology Program, Cincinnati Children's Hospital, Cincinnati, Ohio (M.F.).
Kelsey I
KI
Ricci
Department of Radiology, Boston Children's Hospital, Boston, Massachusetts (T.Y.P., S.V., K.I.R.); Department of Radiology, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (A.P.); Department of Diagnostic Imaging, St Jude Children's Research Hospital, Memphis, Tennessee (L.E.K.); Department of Biostatistics, St Jude Children's Research Hospital, Memphis, Tennessee (M.K., J.M.B.); Department of Neurosurgery, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania (I.F.P.); Neuro-Oncology Program, Cincinnati Children's Hospital, Cincinnati, Ohio (M.F.).
Ashok
A
Panigrahy
Department of Radiology, Boston Children's Hospital, Boston, Massachusetts (T.Y.P., S.V., K.I.R.); Department of Radiology, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (A.P.); Department of Diagnostic Imaging, St Jude Children's Research Hospital, Memphis, Tennessee (L.E.K.); Department of Biostatistics, St Jude Children's Research Hospital, Memphis, Tennessee (M.K., J.M.B.); Department of Neurosurgery, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania (I.F.P.); Neuro-Oncology Program, Cincinnati Children's Hospital, Cincinnati, Ohio (M.F.).
Mehmet
M
Kocak
Department of Radiology, Boston Children's Hospital, Boston, Massachusetts (T.Y.P., S.V., K.I.R.); Department of Radiology, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (A.P.); Department of Diagnostic Imaging, St Jude Children's Research Hospital, Memphis, Tennessee (L.E.K.); Department of Biostatistics, St Jude Children's Research Hospital, Memphis, Tennessee (M.K., J.M.B.); Department of Neurosurgery, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania (I.F.P.); Neuro-Oncology Program, Cincinnati Children's Hospital, Cincinnati, Ohio (M.F.).
Larry E
LE
Kun
Department of Radiology, Boston Children's Hospital, Boston, Massachusetts (T.Y.P., S.V., K.I.R.); Department of Radiology, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (A.P.); Department of Diagnostic Imaging, St Jude Children's Research Hospital, Memphis, Tennessee (L.E.K.); Department of Biostatistics, St Jude Children's Research Hospital, Memphis, Tennessee (M.K., J.M.B.); Department of Neurosurgery, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania (I.F.P.); Neuro-Oncology Program, Cincinnati Children's Hospital, Cincinnati, Ohio (M.F.).
James M
JM
Boyett
Department of Radiology, Boston Children's Hospital, Boston, Massachusetts (T.Y.P., S.V., K.I.R.); Department of Radiology, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (A.P.); Department of Diagnostic Imaging, St Jude Children's Research Hospital, Memphis, Tennessee (L.E.K.); Department of Biostatistics, St Jude Children's Research Hospital, Memphis, Tennessee (M.K., J.M.B.); Department of Neurosurgery, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania (I.F.P.); Neuro-Oncology Program, Cincinnati Children's Hospital, Cincinnati, Ohio (M.F.).
Ian F
IF
Pollack
Department of Radiology, Boston Children's Hospital, Boston, Massachusetts (T.Y.P., S.V., K.I.R.); Department of Radiology, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (A.P.); Department of Diagnostic Imaging, St Jude Children's Research Hospital, Memphis, Tennessee (L.E.K.); Department of Biostatistics, St Jude Children's Research Hospital, Memphis, Tennessee (M.K., J.M.B.); Department of Neurosurgery, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania (I.F.P.); Neuro-Oncology Program, Cincinnati Children's Hospital, Cincinnati, Ohio (M.F.).
Maryam
M
Fouladi
D020295:Brain Stem Neoplasms / Q000401:mortality / Q000473:pathology* / Q000532:radiotherapy; D002648:Child; D038524:Diffusion Magnetic Resonance Imaging; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005910:Glioma / Q000401:mortality / Q000473:pathology* / Q000532:radiotherapy; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D053208:Kaplan-Meier Estimate; D008297:Male; D011379:Prognosis
ADC histogram; MR diffusion; brain tumor; brainstem glioma; pediatric