title: Head and neck PET/CT: therapy response interpretation criteria (Hopkins Criteria)-interreader reliability, accuracy, and survival outcomes.
abstract: There has been no established qualitative system of interpretation for therapy response assessment using PET/CT for head and neck cancers. The objective of this study was to validate the Hopkins interpretation system to assess therapy response and survival outcome in head and neck squamous cell cancer patients (HNSCC).
  
  
  METHODS
  The study included 214 biopsy-proven HNSCC patients who underwent a posttherapy PET/CT study, between 5 and 24 wk after completion of treatment. The median follow-up was 27 mo. PET/CT studies were interpreted by 3 nuclear medicine physicians, independently. The studies were scored using a qualitative 5-point scale, for the primary tumor, for the right and left neck, and for overall assessment. Scores 1, 2, and 3 were considered negative for tumors, and scores 4 and 5 were considered positive for tumors. The Cohen κ coefficient (κ) was calculated to measure interreader agreement. Overall survival (OS) and progression-free survival (PFS) were analyzed by Kaplan-Meier plots with a Mantel-Cox log-rank test and Gehan Breslow Wilcoxon test for comparisons.
  
  
  RESULTS
  Of the 214 patients, 175 were men and 39 were women. There was 85.98%, 95.33%, 93.46%, and 87.38% agreement between the readers for overall, left neck, right neck, and primary tumor site response scores, respectively. The corresponding κ coefficients for interreader agreement between readers were, 0.69-0.79, 0.68-0.83, 0.69-0.87, and 0.79-0.86 for overall, left neck, right neck, and primary tumor site response, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of the therapy assessment were 68.1%, 92.2%, 71.1%, 91.1%, and 86.9%, respectively. Cox multivariate regression analysis showed human papillomavirus (HPV) status and PET/CT interpretation were the only factors associated with PFS and OS. Among the HPV-positive patients (n = 123), there was a significant difference in PFS (hazard ratio [HR], 0.14; 95% confidence interval, 0.03-0.57; P = 0.0063) and OS (HR, 0.01; 95% confidence interval, 0.00-0.13; P = 0.0006) between the patients who had a score negative for residual tumor versus positive for residual tumor. A similar significant difference was observed in PFS and OS for all patients. There was also a significant difference in the PFS of patients with PET-avid residual disease in one site versus multiple sites in the neck (HR, 0.23; log-rank P = 0.004).
  
  
  CONCLUSIONS
  The Hopkins 5-point qualitative therapy response interpretation criteria for head and neck PET/CT has substantial interreader agreement and excellent negative predictive value and predicts OS and PFS in patients with HPV-positive HNSCC.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Charles
authors.initials: C
authors.lastname: Marcus
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Anthony
authors.initials: A
authors.lastname: Ciarallo
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Abdel K
authors.initials: AK
authors.lastname: Tahari
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Esther
authors.initials: E
authors.lastname: Mena
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland Department of Oncology, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Wayne
authors.initials: W
authors.lastname: Koch
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, Maryland Department of Oncology, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Wahl
authors.affiliation: Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland; and.
authors.forename: Ana P
authors.initials: AP
authors.lastname: Kiess
authors.affiliation: Department of Oncology, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Hyunseok
authors.initials: H
authors.lastname: Kang
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, Maryland Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland Department of Oncology, Johns Hopkins School of Medicine, Baltimore, Maryland Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland rsubram4@jhmi.edu.
authors.forename: Rathan M
authors.initials: RM
authors.lastname: Subramaniam
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000401:mortality / Q000628:therapy*; D005260:Female; D019788:Fluorodeoxyglucose F18; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging / Q000401:mortality / Q000628:therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D000077195:Squamous Cell Carcinoma of Head and Neck; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D019788:Fluorodeoxyglucose F18
keywords: Hopkins PET interpretation criteria; head and neck; therapy assessment