Prognostic value of 18F-FDG PET/CT in patients with oropharyngeal squamous cell carcinoma Leo Jia, BA1, Joyce Hsu, BS1, Eran Rotem, MD, MPH2, Hadyn Williams, MD3, Waleed Mourad, MD4, Stephen Scott, BA1, James Rawson, MD5, Darko Pucar, MD, PhD3 1Medical Scholars Program, 2Department of Radiology & Imaging - Vascular & Interventional Radiology, 3Department of Radiology & Imaging - Nuclear Medicine, 4Department of Radiology & Imaging - Radiation Oncology, 5Department of Radiology & Imaging - Body Imaging; Medical College of Georgia, Augusta University, Augusta, GA Introduction Materials and Methods Results (cont.) Worldwide there are over 550,000 new cases of head and neck cancers reported annually, including an estimated 130,000 oropharyngeal cancers (1, 2). In the United States alone, the estimated incidence and mortality of oropharyngeal squamous cell carcinomas (OPSCC) in 2015 was 45,780 and 8,650, respectively (3). To facilitate staging, clinical evaluation and computed tomography (CT) are widely supplemented with 2-deoxy-2-[18] fluoro-D-glucose (FDG) positron emission tomography (PET)/CT imaging that generates additional diagnostic information on the location, volume, and metabolic activity of OPSCC tumors. PET/CT is effective for the localization and staging of primary tumors and evaluation of radiotherapy and chemotherapy responses (4). PET/CT is particularly useful in the detection of distant metastases, which has been shown to be correlated with a poor prognosis and a major factor in limiting patient survival.   Presently, standardized uptake value (SUV) measurements identify areas of maximal glucose metabolic activity (SUV max). This value, in combination with particular knowledge about patterns of cancer spread (what nodes are typically involved for a tumor at a certain location), are routinely used for cancer detection and staging. However, due to the inhomogeneous metabolic patterns of OPSCC tumors, this detection method may not correlate with prognostic indices, and, as a result, the prognostic utility of SUV max is limited. Recently, metabolic tumor volume (MTV) and total lesional glycolysis (the product of MTV and mean SUV) have been proposed as potential additional prognostic markers in OPSCC, with the ultimate goal of improving the accuracy of risk stratification and treatment selection in individual patients. However, the utility of MTV and TLG in prognosis of OPSCC remains uncertain at this time. Subjects: Thirty-one (31) patients with non-metastatic (M0) OPSCC (90.3% male, 621.6 years old, 77.4% current or former tobacco smokers) had 18F-FDG PET/CT prior to radiation or chemoradiation at the Medical College of Georgia between 2006 and 2013. Data collection continued to time of last follow-up or death. Nine (9) of 31 patients died during the follow-up period.   Image analysis: PET, CT, and co-registered PET/CT images were displayed on a MIMvista™ (MIM Software Inc., Cleveland, OH) workstation/software and retrospectively interpreted by a board-certified radiologist/nuclear medicine physician (D.P.) with 6 years of experience. Reference SUV mean of the liver was determined by placing a 3 cm circular region-of-interest over the right liver lobe. SUV max, SUV mean, MTV, and TLG for primary tumor and regional lymph nodes were determined using fixed-percentage threshold-segmentation method. The voxels were included if they were greater than 40% of the maximum voxel within an operator-defined sphere. For calculating nodal MTV and TLG, regional nodes were considered measureable if their SUV max was 1.5 greater than liver SUV mean. Statistical analysis: Primary tumor imaging variables were SUV max, SUV mean, MTV, and TLG. Regional nodal imaging parameters were: total number of involved nodes, SUV max of the most active lymph node, and MTV and TLG of all active regional nodes. Clinical parameters were American Joint Committee on Cancer (AJCC) tumor stages. Demographic parameters were age, sex, and race. Univariate Cox Proportion Hazards regression model was used to determine the hazard ratio for each imaging and clinical variable. Fig. 2 Kaplan-Meier survival plot for 2-year OS of patients with SUV max of the most active lymph node below (green line) and above (blue line) the median of 8.08 was 78% and 60%, respectively. X-axis: Time to death (years) Y-axis: Overall Survival Conclusion The standard parameters, SUV max of the most active lymph node and clinical AJCC tumor stage were significant variables in predicting OS in OPSCC, while advanced imaging parameters, MTV and TLG, were not significant predictors of OS. Results References [1] Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90. [2] Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009;45:309–16. [3] Siegel, R. L., Miller, K. D. and Jemal, A. (2015), Cancer statistics, 2015. CA: A Cancer Journal for Clinicians, 65: 5–29. doi: 10.3322/caac.21254 [4] Soydal Ç, Yüksel C, Küçük NÖ, Ökten İ, Özkan E, Doğanay Erdoğan B. Prognostic Value of Metabolic Tumor Volume Measured by 18F-FDG PET/CT in Esophageal Cancer Patients. Molecular Imaging and Radionuclide Therapy. 2014;23(1):12-15. doi:10.4274/Mirt.07379.   Variables Coefficient Hazards ratio (95% CI) P-value 18FDG-PET/CT – Primary tumor SUVmax -0.099 0.906 (0.768-1.068) 0.238 SUVmean -0.212 0.809 (0.601-1.088) 0.809 MTV +0.017 1.017 (0.990-1.045) 0.217 TLG +0.001 1.001 (0.997-1.005) 0.719 18FDG-PET/CT – Regional lymph nodes (LN) # LN involved1 -0.261 0.770 (0.488-1.215) 0.261 SUVmax of most active LN (MALN) -0.117 0.889 (0.778-1.016) 0.084 MALN MTV -0.023 0.978 (0.903-1.058) 0.575 MALN TLG -0.006 0.994 (0.979 -1.009) 0.421 Demographic Age when diagnosed 0.048 1.049 (0.974-1.130) 0.205 Sex 0.467 1.594 (0.197-12.886) 0.662 Race 0.470 1.600 (0.399-6.418) 0.507 Clinical Stage -1.208 0.299 (0.140-0.638) 0.002 Fig. 1 18F-FDG PET/CT of patient with OPSCC in tongue base with bilateral lymphatic involvement. Primary tumor and involved lymph nodes were contoured using fixed-percentage threshold-segmentation. Acknowledgements Hypothesis Medical students Leo Jia and Joyce Hsu thank the Augusta University Medical Scholars Program and radiology and radiation oncology faculty for the opportunity to conduct this research. In particular, they acknowledge Dr. Darko Pucar for mentorship, Dr. Eran Rotem for statistical analysis, Dr. Hadyn Williams for manuscript review and Mrs. Yolanda Elam for research administration assistance. Table 1 Univariate Cox Proportional Hazards regression determined that the SUV max of the most active lymph node (p=0.084) and AJCC tumor staging (p=0.002) to be the only significant predictors of OS. Neither MTV nor TLG of the primary tumor nor of the most active lymph node were determined to be significant predictors of OS (p=0.217 and p=0.719, respectively). Pretreatment 18F-FDG PET/CT metabolic tumor parameters, SUV max, MTV, and TLG, can predict overall survival (OS) in patients with OPSCC treated with radiation or chemoradiation.