title: ¹⁸F-FDG PET/CT following chemoradiation of uterine cervix cancer provides powerful prognostic stratification independent of HPV status: a prospective cohort of 105 women with mature survival data.
abstract: OBJECTIVE
  To report 5-year outcomes of a prospective registry study investigating posttherapy FDG PET/CT in women with locally advanced cervical cancer. A secondary analysis assessing the prognostic significance of HPV infection was performed.
  
  
  METHODS
  Patients underwent definitive chemoradiation followed by a single FDG PET/CT scan for response assessment. A complete metabolic response (CMR) was defined as no evidence of FDG-avid disease. Patients were dichotomized according to HPV infection status into a 'higher-risk' group and a 'lower-risk' group, with the higher-risk group comprising those with alpha-7 strain HPV (subtypes 18, 39 and 45) and those who were HPV-negative and the lower-risk group comprising those with alpha-9 strain HPV (subtypes 16, 31, 33, 52 and 58) and those with mixed strains. Survival outcomes, patterns of failure and salvage therapy outcomes were investigated for their association with metabolic response and HPV status.
  
  
  RESULTS
  In 105 patients the median prospective follow-up was 5.2 years. The 5-year cancer-specific, overall and progression-free survival rates in patients with a CMR were 97 %, 93 % and 86 %, respectively. In patients without a CMR, the corresponding 5-year survival rates were 36 %, 22 % and 0 % respectively (p < 0.01). PET response was associated with patterns of failure (p < 0.01), with the 5-year freedom from local, nodal and distant failure in patients with a CMR being 94 %, 90 % and 94 %, respectively. Of 16 patients who underwent salvage therapy, 12 had disease detected on the surveillance PET scan, and 8 achieved a post-salvage CMR of whom all were alive at a median of 4.9 years. DNA adequate for HPV analysis was extracted in 68 patients. The likelihood of a PET metabolic response was not influenced by HPV infection status, with 71 % and 75 % of higher-risk and lower-risk patients, respectively, achieving CMR (p = 0.83). Higher-risk patients had a poorer OS (HR 2.6, range 1.0 - 6.6, p = 0.05) in univariable analysis but not multivariable analysis (p = 0.11).
  
  
  CONCLUSIONS
  At 5 years CMR remains a powerful factor predicting survival after initial and salvage therapy. Metabolic response was not associated with HPV infection risk. Further studies are required to establish the association with HPV infection risk and survival after chemoradiation.
authors.affiliation: Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, St Andrews Street, East Melbourne, 3002, Victoria, Australia. shankar.siva@petermac.org.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia. shankar.siva@petermac.org.
authors.forename: Shankar
authors.initials: S
authors.lastname: Siva
authors.affiliation: Department of Pathology, Peter MacCallum Cancer Centre, East Melbourne, Australia.
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Deb
authors.affiliation: Molecular Therapeutics and Biomarkers Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Australia.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Young
authors.affiliation: Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, St Andrews Street, East Melbourne, 3002, Victoria, Australia.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia.
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Hicks
authors.affiliation: Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, St Andrews Street, East Melbourne, 3002, Victoria, Australia.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia.
authors.forename: Jason
authors.initials: J
authors.lastname: Callahan
authors.affiliation: Department of Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, East Melbourne, Australia.
authors.forename: Mathias
authors.initials: M
authors.lastname: Bressel
authors.affiliation: Department of Cancer Medicine, Peter MacCallum Cancer Centre, East Melbourne, Australia.
authors.forename: Linda
authors.initials: L
authors.lastname: Mileshkin
authors.affiliation: Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia.|Department of Cancer Medicine, Peter MacCallum Cancer Centre, East Melbourne, Australia.
authors.forename: Danny
authors.initials: D
authors.lastname: Rischin
authors.affiliation: Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, St Andrews Street, East Melbourne, 3002, Victoria, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Bernshaw
authors.affiliation: Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, St Andrews Street, East Melbourne, 3002, Victoria, Australia.
authors.forename: Kailash
authors.initials: K
authors.lastname: Narayan
mesh_terms: D059248:Chemoradiotherapy; D018572:Disease-Free Survival; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D064847:Multimodal Imaging; D027383:Papillomaviridae / Q000502:physiology*; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D016879:Salvage Therapy; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy* / Q000821:virology
chemical_list: D019788:Fluorodeoxyglucose F18
keywords: Cervix; Human papilloma virus; PET; Patterns of failure; Positron emission; Radiotherapy; Salvage