Characterizing tumor heterogeneity with functional imaging and quantifying high-risk tumor volume for early prediction of treatment outcome: cervical cancer as a model.
OBJECTIVE
Treatment response in cancer has been monitored by measuring anatomic tumor volume (ATV) at various times without considering the inherent functional tumor heterogeneity known to critically influence ultimate treatment outcome: primary tumor control and survival. This study applied dynamic contrast-enhanced (DCE) functional MRI to characterize tumors' heterogeneous subregions with low DCE values, at risk for treatment failure, and to quantify the functional risk volume (FRV) for personalized early prediction of treatment outcome.


METHODS
DCE-MRI was performed in 102 stage IB(2)-IVA cervical cancer patients to assess tumor perfusion heterogeneity before and during radiation/chemotherapy. FRV represents the total volume of tumor voxels with critically low DCE signal intensity (<2.1 compared with precontrast image, determined by previous receiver operator characteristic analysis). FRVs were correlated with treatment outcome (follow-up: 0.2-9.4, mean 6.8 years) and compared with ATVs (Mann-Whitney, Kaplan-Meier, and multivariate analyses).


RESULTS
Before and during therapy at 2-2.5 and 4-5 weeks of RT, FRVs >20, >13, and >5 cm(3), respectively, significantly predicted unfavorable 6-year primary tumor control (p = 0.003, 7.3 × 10(-8), 2.0 × 10(-8)) and disease-specific survival (p = 1.9 × 10(-4), 2.1 × 10(-6), 2.5 × 10(-7), respectively). The FRVs were superior to the ATVs as early predictors of outcome, and the differentiating power of FRVs increased during treatment.


CONCLUSIONS
Our preliminary results suggest that functional tumor heterogeneity can be characterized by DCE-MRI to quantify FRV for predicting ultimate long-term treatment outcome. FRV is a novel functional imaging heterogeneity parameter, superior to ATV, and can be clinically translated for personalized early outcome prediction before or as early as 2-5 weeks into treatment.
Department of Radiation Oncology, Ohio State University, Columbus, OH 43210, USA. Nina.Mayr@osumc.edu
Nina A
NA
Mayr
Zhibin
Z
Huang
Jian Z
JZ
Wang
Simon S
SS
Lo
Joline M
JM
Fan
John C
JC
Grecula
Steffen
S
Sammet
Christina L
CL
Sammet
Guang
G
Jia
Jun
J
Zhang
Michael V
MV
Knopp
William T C
WT
Yuh
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003287:Contrast Media; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D012372:ROC Curve; D012039:Regional Blood Flow / Q000502:physiology; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D047368:Tumor Burden; D059016:Tumor Microenvironment / Q000502:physiology*; D002583:Uterine Cervical Neoplasms / Q000098:blood supply* / Q000473:pathology / Q000628:therapy*
D003287:Contrast Media