External validation of a prognostic CT-based radiomic signature in oropharyngeal squamous cell carcinoma.
BACKGROUND
Oropharyngeal squamous cell carcinoma (OPSCC) is one of the fastest growing disease sites of head and neck cancers. A recently described radiomic signature, based exclusively on pre-treatment computed tomography (CT) imaging of the primary tumor volume, was found to be prognostic in independent cohorts of lung and head and neck cancer patients treated in the Netherlands. Here, we further validate this signature in a large and independent North American cohort of OPSCC patients, also considering CT artifacts.


METHODS
A total of 542 OPSCC patients were included for which we determined the prognostic index (PI) of the radiomic signature. We tested the signature model fit in a Cox regression and assessed model discrimination with Harrell's c-index. Kaplan-Meier survival curves between high and low signature predictions were compared with a log-rank test. Validation was performed in the complete cohort (PMH1) and in the subset of patients without (PMH2) and with (PMH3) visible CT artifacts within the delineated tumor region.


RESULTS
We identified 267 (49%) patients without and 275 (51%) with visible CT artifacts. The calibration slope (β) on the PI in a Cox proportional hazards model was 1.27 (H0: β = 1, p = 0.152) in the PMH1 (n = 542), 0.855 (H0: β = 1, p = 0.524) in the PMH2 (n = 267) and 1.99 (H0: β = 1, p = 0.002) in the PMH3 (n = 275) cohort. Harrell's c-index was 0.628 (p = 2.72e-9), 0.634 (p = 2.7e-6) and 0.647 (p = 5.35e-6) for the PMH1, PMH2 and PMH3 cohort, respectively. Kaplan-Meier survival curves were significantly different (p < 0.05) between high and low radiomic signature model predictions for all cohorts.


CONCLUSIONS
Overall, the signature validated well using all CT images as-is, demonstrating a good model fit and preservation of discrimination. Even though CT artifacts were shown to be of influence, the signature had significant prognostic power regardless if patients with CT artifacts were included.
a Department of Radiation Oncology (MAASTRO) , GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre (MUMC+) , Maastricht , The Netherlands.
Ralph T H
RT
Leijenaar
a Department of Radiation Oncology (MAASTRO) , GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre (MUMC+) , Maastricht , The Netherlands.
Sara
S
Carvalho
a Department of Radiation Oncology (MAASTRO) , GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre (MUMC+) , Maastricht , The Netherlands.
Frank J P
FJ
Hoebers
a Department of Radiation Oncology (MAASTRO) , GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre (MUMC+) , Maastricht , The Netherlands.|b Departments of Radiation Oncology and Radiology , Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School , Boston , MA , USA.
Hugo J W L
HJ
Aerts
a Department of Radiation Oncology (MAASTRO) , GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre (MUMC+) , Maastricht , The Netherlands.
Wouter J C
WJ
van Elmpt
c Department of Radiation Oncology , Princess Margaret Cancer Center, University of Toronto , Toronto, Ontario , Canada.
Shao Hui
SH
Huang
c Department of Radiation Oncology , Princess Margaret Cancer Center, University of Toronto , Toronto, Ontario , Canada.
Biu
B
Chan
c Department of Radiation Oncology , Princess Margaret Cancer Center, University of Toronto , Toronto, Ontario , Canada.
John N
JN
Waldron
c Department of Radiation Oncology , Princess Margaret Cancer Center, University of Toronto , Toronto, Ontario , Canada.
Brian
B
O'sullivan
a Department of Radiation Oncology (MAASTRO) , GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre (MUMC+) , Maastricht , The Netherlands.
Philippe
P
Lambin
D016477:Artifacts; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000401:mortality* / Q000628:therapy; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D009959:Oropharyngeal Neoplasms / Q000000981:diagnostic imaging* / Q000401:mortality* / Q000628:therapy; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D036542:Tomography, Spiral Computed