Metabolic tumor volume as a prognostic imaging-based biomarker for head-and-neck cancer: pilot results from Radiation Therapy Oncology Group protocol 0522

Abstract

Purpose: 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 and materials: 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.

Conclusion: 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.

Conflict of interest statement

Conflicts of Interest: None

Conflicts of Interest: Dr. Robert Foote reports grant support from RTOG, personal fees from ASTRO for editorial services, and personal fees from UpToDate, all outside the scope of the submitted work. Dr. David Rosenthal reports personal fees from Bristol Myers during the conduct of the study.

Copyright © 2015 Elsevier Inc. All rights reserved.

Figures

Figure 1

Cumulative incidence estimates of local-regional relapse (Panel A) and distant metastasis (Panel B) and Kaplan-Meier estimates of progression-free survival (Panel C) and overall survival (Panel D) for patients with baseline primary MTV ≤ median or > median. Two-year local-regional relapse rates were 5.7% (95% CI: 0, 13.5) for patients with MTV ≤ median and 30.3% (95% CI: 14.3, 46.3) for patients with MTV > median. Two-year distant metastases rates were 2.9% (95% CI: 0, 8.5) for patients with MTV ≤ median and 12.1% (95% CI: 0.8, 23.4) for patients with MTV > median. Two-year progression-free survival rates were 88.6% (95% CI: 78.0, 99.1) for patients with MTV ≤ median and 63.6% (95% CI: 47.2, 80.0) for patients with MTV > median. Two-year overall survival rates were 94.3% (95% CI: 86.6, 100) for patients with MTV ≤ median and 84.9% (95% CI: 72.6, 97.1) for patients with MTV > median.