title: Metastatic renal cell carcinoma: relationship between initial metastasis hypoxia, change after 1 month's sunitinib, and therapeutic response: an 18F-fluoromisonidazole PET/CT study.
abstract: The aims of this cohort study were to evaluate initial tumor hypoxia in metastatic renal cell carcinoma (mRCC) and its changes after sunitinib treatment, using (18)F-fluoromisonidazole PET/CT, and investigate the possible prognostic value of initial tumor hypoxia or its changes under sunitinib therapy.
  
  
  METHODS
  Antiangiogenic-naive patients with mRCC were prospectively enrolled in this cohort study. Before initiation of sunitinib, CT defined up to 10 targets that were assessed at 1 and 6 mo according to the response evaluation criteria in solid tumors (RECIST). Pretreatment target uptake of (18)F-fluoromisonidazole was compared with uptake at 1 mo. Targets were considered hypoxic when their maximal standard uptake value was above mean blood value + 2 SDs. Hypoxic volumes were also computed. Relationships between initial hypoxia status, initial degree of hypoxia, its change at 1 mo, and overall or progression-free survival (OS and PFS, respectively) were assessed by survival analysis.
  
  
  RESULTS
  Fifty-three patients were included. Median follow-up was 16.8 mo. (18)F-fluoromisonidazole uptake significantly decreased in initially hypoxic target metastases but did not change in others (-22%, P < 10(-4), vs. +1.5%, P = 0.77; P = 10(-3) between groups). Seventy-five percent of patients with hypoxic metastases were free of progressive disease at 4.8 mo (95% confidence interval, 2.99-11.83), compared with 11.3 mo (95% confidence interval, 3.08-36.9) for other patients (P = 0.02), whereas OS was not significantly different. Changes in tumor hypoxia were not related to PFS or OS.
  
  
  CONCLUSIONS
  Sunitinib reduced hypoxia in initially hypoxic RECIST target metastases but did not induce significant hypoxia in nonhypoxic RECIST target metastases. Patients with initially hypoxic targets have shorter PFS than others.
authors.affiliation: Department of Nuclear Medicine, Georges Pompidou European Hospital, Assistance Publique–Hôpitaux de Paris, Paris Descartes University, Paris, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Hugonnet
authors.forename: Laure
authors.initials: L
authors.lastname: Fournier
authors.forename: Jacques
authors.initials: J
authors.lastname: Medioni
authors.forename: Corinne
authors.initials: C
authors.lastname: Smadja
authors.forename: Elif
authors.initials: E
authors.lastname: Hindié
authors.forename: Virginie
authors.initials: V
authors.lastname: Huchet
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Itti
authors.forename: Charles-André
authors.initials: CA
authors.lastname: Cuenod
authors.forename: Gilles
authors.initials: G
authors.lastname: Chatellier
authors.forename: Stéphane
authors.initials: S
authors.lastname: Oudard
authors.forename: Marc
authors.initials: M
authors.lastname: Faraggi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D015687:Cell Hypoxia / Q000187:drug effects; D015331:Cohort Studies; D018450:Disease Progression; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D008920:Misonidazole / Q000031:analogs & derivatives*; D009362:Neoplasm Metastasis; D049268:Positron-Emission Tomography; D011379:Prognosis; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D000077210:Sunitinib; D016019:Survival Analysis; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007211:Indoles; D011758:Pyrroles; C031843:fluoromisonidazole; D008920:Misonidazole; D000077210:Sunitinib