Metabolic tumor volume as a prognostic imaging-based biomarker for head-and-neck cancer: pilot results from Radiation Therapy Oncology Group protocol 0522.
OBJECTIVE
To evaluate candidate fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging biomarkers for head-and-neck chemoradiotherapy outcomes in the cooperative group trial setting.


METHODS
Radiation Therapy Oncology Group (RTOG) protocol 0522 patients consenting to a secondary FDG-PET/CT substudy were serially imaged at baseline and 8 weeks after radiation. Maximum standardized uptake value (SUVmax), SUV peak (mean SUV within a 1-cm sphere centered on SUVmax), and metabolic tumor volume (MTV) using 40% of SUVmax as threshold were obtained from primary tumor and involved nodes.


RESULTS
Of 940 patients entered onto RTOG 0522, 74 were analyzable for this substudy. Neither high baseline SUVmax nor SUVpeak from primary or nodal disease were associated with poor treatment outcomes. However, primary tumor MTV above the cohort median was associated with worse local-regional control (hazard ratio 4.01, 95% confidence interval 1.28-12.52, P=.02) and progression-free survival (hazard ratio 2.34, 95% confidence interval 1.02-5.37, P=.05). Although MTV and T stage seemed to correlate (mean MTV 6.4, 13.2, and 26.8 for T2, T3, and T4 tumors, respectively), MTV remained a strong independent prognostic factor for progression-free survival in bivariate analysis that included T stage. Primary MTV remained prognostic in p16-associated oropharyngeal cancer cases, although sample size was limited.


CONCLUSIONS
High baseline primary tumor MTV was associated with worse treatment outcomes in this limited patient subset of RTOG 0522. Additional confirmatory work will be required to validate primary tumor MTV as a prognostic imaging biomarker for patient stratification in future trials.
Department of Radiation Oncology, University of Texas Southwestern School of Medicine, Dallas, Texas. Electronic address: david.schwartz@utsw.edu.
David L
DL
Schwartz
Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania.
Jonathan
J
Harris
Department of Radiation Oncology, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Min
M
Yao
Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.
David I
DI
Rosenthal
American College of Radiology Imaging Network, Philadelphia, Pennsylvania.
Adam
A
Opanowski
American College of Radiology Imaging Network, Philadelphia, Pennsylvania.
Anthony
A
Levering
Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.
K Kian
KK
Ang
Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida.
Andy M
AM
Trotti
Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.
Adam S
AS
Garden
Sutter Medical Group, Sacramento, California.
Christopher U
CU
Jones
Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
Paul
P
Harari
Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.
Robert
R
Foote
Department of Radiation Medicine, Oregon Health & Science University, Portland, Oregon.
John
J
Holland
Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania.
Qiang
Q
Zhang
Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, California.
Quynh-Thu
QT
Le
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D059248:Chemoradiotherapy / Q000379:methods; D016001:Confidence Intervals; D018572:Disease-Free Survival; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D007822:Laryngeal Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000473:pathology; D010641:Phenotype; D049268:Positron-Emission Tomography / Q000295:instrumentation / Q000379:methods*; D011379:Prognosis; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014057:Tomography, X-Ray Computed / Q000295:instrumentation / Q000379:methods
D001786:Blood Glucose; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18