title: Nodal parameters of FDG PET/CT performed during radiotherapy for locally advanced mucosal primary head and neck squamous cell carcinoma can predict treatment outcomes: SUVmean and response rate are useful imaging biomarkers.
abstract: OBJECTIVE
  To evaluate the prognostic utility of nodal metabolic parameters derived from FDG PET/CT performed before radiotherapy (prePET) and during the third week of radiotherapy (iPET) in patients with mucosal primary head and neck squamous cell carcinoma (MPHNSCC).
  
  
  METHODS
  This analysis included 75 patients with newly diagnosed locally advanced node-positive MPHNSCC treated with radical radiotherapy and concurrent systemic therapy who underwent prePET and iPET: N1 11 patients, N2a 38, N2b 12, N2c 9, N3 5. The median follow-up was 28 months (9 - 70 months). The maximum and mean standardized uptake values (SUVmax and SUVmean), metabolic tumour volume (MTV) and total lesional glycolysis (TLG) of the index lymph node (node with the highest TLG) and the combined total lymph nodes, and their percentage reductions on iPET were determined, and the results were correlated with 3-year Kaplan-Meier locoregional, regional and distant metastatic failure-free survival (FFS), disease-free survival (DFS) and overall survival (OS). Optimal cut-off values were derived from receiver operating characteristic curves. Cox regression univariate and multivariate analyses with clinical covariates were performed.
  
  
  RESULTS
  Based on assessment of residual nodal metabolic burden during treatment, the iPET index node SUVmean (optimal cut-off value 2.95 g/ml) and the total node SUVmean (optimal cut-off value 3.25) were the best independent predictors of outcome in the multivariate analysis: index node SUVmean for DFS and OS p = 0.033 and 0.003, respectively, and the total node SUVmean for locoregional FFS, DFS and OS p = 0.028, 0.025 and 0.014, respectively. Based on the assessment of response rates during treatment, a reduction of more than 50 % in the total node TLG was the best biomarker for locoregional and regional FFS, DFS and OS in the multivariate analysis (p = 0.001, 0.016, 0.001 and 0.004, respectively), and reduction in the total node MTV for locoregional FFS, DFS and OS (p = 0.026, 0.003 and 0.014, respectively). There were no significant correlations between oncological outcomes and prePET nodal parameters.
  
  
  CONCLUSIONS
  We demonstrated that the index node and total node SUVmean on iPET and a reduction of more than 50 % in MTV and TLG are useful imaging biomarkers, and can potentially identify those patients with MPHNSCC who have a high risk of locoregional metastatic failure and death.
authors.affiliation: Department of Nuclear Medicine and PET, Liverpool Hospital, Locked Bag 7103, Liverpool BC, NSW, Australia. peter.lin@sswahs.nsw.gov.au.|South Western Sydney Clinical School, University of New South Wales, Sydney, NSW, Australia. peter.lin@sswahs.nsw.gov.au.|Western Sydney University, Sydney, NSW, Australia. peter.lin@sswahs.nsw.gov.au.
authors.forename: Peter
authors.initials: P
authors.lastname: Lin
authors.affiliation: South Western Sydney Clinical School, University of New South Wales, Sydney, NSW, Australia.|Cancer Therapy Centre, Liverpool Hospital, Liverpool, NSW, Australia.|Ingham Institute of Applied Medical Research, Liverpool, NSW, Australia.
authors.forename: Myo
authors.initials: M
authors.lastname: Min
authors.affiliation: South Western Sydney Clinical School, University of New South Wales, Sydney, NSW, Australia.|Cancer Therapy Centre, Liverpool Hospital, Liverpool, NSW, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Lee
authors.affiliation: South Western Sydney Clinical School, University of New South Wales, Sydney, NSW, Australia.|Western Sydney University, Sydney, NSW, Australia.|Cancer Therapy Centre, Liverpool Hospital, Liverpool, NSW, Australia.|Ingham Institute of Applied Medical Research, Liverpool, NSW, Australia.
authors.forename: Lois
authors.initials: L
authors.lastname: Holloway
authors.affiliation: South Western Sydney Clinical School, University of New South Wales, Sydney, NSW, Australia.|Cancer Therapy Centre, Liverpool Hospital, Liverpool, NSW, Australia.|Ingham Institute of Applied Medical Research, Liverpool, NSW, Australia.
authors.forename: Dion
authors.initials: D
authors.lastname: Forstner
authors.affiliation: Cancer Therapy Centre, Liverpool Hospital, Liverpool, NSW, Australia.
authors.forename: Victoria
authors.initials: V
authors.lastname: Bray
authors.affiliation: Cancer Therapy Centre, Liverpool Hospital, Liverpool, NSW, Australia.
authors.forename: Allan
authors.initials: A
authors.lastname: Fowler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D005240:Feasibility Studies; D005260:Female; D019788:Fluorodeoxyglucose F18; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D000072078:Positron Emission Tomography Computed Tomography; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D019788:Fluorodeoxyglucose F18
keywords: FDG PET/CT; Imaging biomarkers; Mucosal primary head and neck squamous cell carcinoma; Positron emission tomography; Radiotherapy