FDG PET during radiochemotherapy is predictive of outcome at 1 year in non-small-cell lung cancer patients: a prospective multicentre study (RTEP2).

PURPOSE: To assess prospectively the prognostic value of FDG PET/CT during curative-intent radiotherapy (RT) with or without concomitant chemotherapy in patients with non-small-cell lung cancer (NSCLC). METHODS: Patients with histological proof of invasive localized NSCLC and evaluable tumour, and who were candidates for curative-intent radiochemotherapy (RCT) or RT were preincluded after providing written informed consent. Definitive inclusion was conditional upon significant FDG uptake before RT (PET1). All included patients had a FDG PET/CT scan during RT (PET2, mean dose 43 Gy) and were evaluated by FDG PET/CT at 3 months and 1 year after RT. The main endpoint was death (from whatever cause) or tumour progression at 1 year. RESULTS: Of 77 patients preincluded, 52 were evaluable. Among the evaluable patients, 77% received RT with induction chemotherapy and 73% RT with concomitant chemotherapy. At 1 year, 40 patients (77 %) had died or had tumour progression. No statistically significant association was found between stage (IIIB vs. other), histology (squamous cell carcinoma vs. other), induction or concomitant chemotherapy, and death/tumour progression at 1 year. The SUVmax in the PET2 scan was the single variable predictive of death or tumour progression at 1 year (odds ratio 1.97, 95% CI 1.25 - 3.09, p = 0.003) in multivariate analysis. The area under the receiver operating characteristic curve was 0.85 (95% CI 0.73 - 0.94, p < 10(-4)). A SUVmax value of 5.3 in the PET2 scan yielded a sensitivity of 70% and a specificity of 92% for predicting tumour progression or death at 1 year. CONCLUSION: This prospective multicentre study demonstrated the prognostic value in terms of disease-free survival of SUVmax assessed during the 5th week of curative-intent RT or RCT in NSCLC patients (NCT01261598; RTEP2 study).

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).

PURPOSE: 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. CONCLUSION: 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).

Does the association of 18F-FDG uptake intensity and lesion topography reveal histological phenotype and tumor differentiation in esophageal cancer?

In daily clinical practice, the esophageal squamous cell cancer (ESCC) is considered to be more (18)F-FDG avid than adenocarcinoma (EAD). To date, the few studies concerning the existence of a real metabolic difference based on esophageal cancer (EC) histology, show divergent and not definitive results. A retrospective analysis of (18)F-FDG PET/CT of 87 patients with ESCC and EAD was performed to investigate the role played by both histopathological subtype and tumor differentiation in the characterization of glucose metabolic profile of EC. Esophageal squamous cell cancer was well differentiated (WD) in 42 cases and poorly differentiated (PD) in 12 patients. Twenty-one of the 33 patients had WD EAD, while 12 had a PD EAD. The (18)F-FDG maximal standardized uptake value (SUV(max)) was determined for all lesions and used for inter and intra-group comparison. In ESCC, the SUV(max) ranged from 4 to 31 with a mean value of 16±6. In EAD, the SUV(max) ranged from 2 to 25 with a mean value of 10±6. A statistically significant difference (P<0.0001) was found between ESCC and EAD. According to histological classification and tumor differentiation, we obtained the following results: a) the SUV(max) values of WD ESCC and WD EAD were 17±5 (range: 7-31) and 7±3 (range: 2-12) respectively (P<0.00001), b) the SUV(max) values of PD ESCC and PD EAD were 11±4 (range: 4-19) and 17±6 (range: 7-25) respectively (P<0.05). Moreover, a statistically significant difference of SUV(max) values was found between WD and PD ESCC (P<0.005) as well as between WD and PD differentiated EAD (P<0.0001). In order to predict tumor histology (ESCC, EAD) from both SUV(max) and lesion location, a multivariate discriminant analysis was performed on the whole population with a resulting diagnostic accuracy equal to 82% (P<0.00001). In conclusion, we provide additional arguments about (18)F-FDG uptake difference between ESCC and EAD as well as between poorly and well-differentiated forms of both EC histological subtypes.