title: The predictive value of treatment response using FDG PET performed on day 21 of chemoradiotherapy in patients with oesophageal squamous cell carcinoma. A prospective, multicentre study (RTEP3).
abstract: OBJECTIVE
  FDG PET has been suggested to have predictive value in the prognosis of oesophageal carcinoma. However, the retrospective studies reported in the literature have shown discordant results. Additionally, only four studies have evaluated FDG PET during chemoradiotherapy (CRT) in patients with different histological lesions. The purpose of this study was to investigate the predictive value of FDG PET performed early during CRT (on day 21) in a population of patients with oesophageal squamous cell carcinoma.
  
  
  METHODS
  Included in this prospective study were 57 patients with a histological diagnosis of squamous cell carcinoma of the oesophagus. Of these 57 patients, 48 (84%) were evaluated (aged 63 ± 11 years; 44 men, 4 women). Each patient underwent FDG PET (4.5 MBq/kg) before CRT, according to the Herskovic protocol (t0; PET₁) and on day 21 ± 3 from the start of CRT (d21; PET₂). The response assessment included a clinical examination, CT scan or FDG PET and histological analysis 3 months and 1 year after PET₁. The patients were classified as showing a complete response (CR) or a noncomplete response. A quantitative analysis was carried out for PET₁ and PET₂ using the following parameters: SUVmax, SUVmean (with SUVmean40 as the 3-D volume at an SUVmax threshold of 40% and SUVmeanp as that defined by a physician), tumour volume (TV, with TV40 defined as the TV at 40% of SUVmax, and TVp as that defined by a physician); and the total lesion glycolysis (TLG, SUVmean × TV, with TLG₄₀ defined as the TLG at 40% of SUVmax, and TLGp as that defined by a physician). The differences in responses at 3 months and 1 year between PET₁ (t0) and PET₂ (d21) were assessed in terms of variations in SUV, TV and TLG using a repeated measures of variance (ANOVA).
  
  
  RESULTS
  SUVmax, SUVmean and TLG decreased significantly between PET₁ (t0) and PET₂ (d21; p < 0.0001). The TV significantly decreased only when assessed as TVp (p = 0.02); TV₄₀ did not decrease significantly. With respect to the predictive value of PET₁, only TV40_1 and TVp_1 values, and therefore TLG40_1 and TLGp_1, but not the SUV values, were significantly lower in patients with CR at 3 months. SUVmax1, TVp_1 and TLGp_1 were significantly lower in patients with CR at 1 year. With respect to the predictive value of PET₂, only TV40_2 and TVp_2 values, and therefore TLG40_2 and TLGp_2, but not the SUV values, were significantly lower in patients with CR at 3 months. None of the PET₂ parameters had significant value in predicting patient outcome at 1 year. The changes in SUVmax, TV₄₀, TVp, TLG₄₀ and TLGp between PET₁ and PET₂ had no relationship to patient outcome at 3 months or 1 year.
  
  
  CONCLUSIONS
  This prospective, multicentre study performed in a selected population of patients with oesophageal squamous cell cancer demonstrates that the parameters derived from baseline PET₁ are good predictors of response to CRT. Specifically, a high TV and TLG are associated with a poor response to CRT at 3 months and 1 year, and a high SUVmax is associated with a poor response to CRT at 1 year. FDG PET performed during CRT on day 21 appears to have less clinical relevance. However, patients with a large functional TV on day 21 of CRT have a poor clinical outcome (ClinicalTrials.gov NCT 00934505).
authors.affiliation: Department of Nuclear Medicine, Faculty of Medicine, Henri Becquerel Cancer Center and Rouen University Hospital, & QuantIF - LITIS (EA 4108), University of Rouen, Rouen, France.
authors.forename: Odré
authors.initials: O
authors.lastname: Palie
authors.forename: Pierre
authors.initials: P
authors.lastname: Michel
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Ménard
authors.forename: Caroline
authors.initials: C
authors.lastname: Rousseau
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Rio
authors.forename: Boumédiene
authors.initials: B
authors.lastname: Bridji
authors.forename: Ahmed
authors.initials: A
authors.lastname: Benyoucef
authors.forename: Marc-Etienne
authors.initials: ME
authors.lastname: Meyer
authors.forename: Khadija
authors.initials: K
authors.lastname: Jalali
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bardet
authors.forename: Che Mabubu
authors.initials: CM
authors.lastname: M'vondo
authors.forename: Pierre
authors.initials: P
authors.lastname: Olivier
authors.forename: Guillaume
authors.initials: G
authors.lastname: Faure
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Itti
authors.forename: Christian
authors.initials: C
authors.lastname: Diana
authors.forename: Claire
authors.initials: C
authors.lastname: Houzard
authors.forename: Françoise
authors.initials: F
authors.lastname: Mornex
authors.forename: Frederic
authors.initials: F
authors.lastname: Di Fiore
authors.forename: Pierre
authors.initials: P
authors.lastname: Vera
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000628:therapy; D059248:Chemoradiotherapy; D004938:Esophageal Neoplasms / Q000000981:diagnostic imaging* / Q000628:therapy; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D011446:Prospective Studies; D019275:Radiopharmaceuticals; D016896:Treatment Outcome
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18