F Di Fiore

Université de Rouen, Mont-Saint-Aignan, Haute-Normandie, France

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Publications (100)378.77 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The high failure rates in the radiotherapy (RT) target volume suggest that patients with locally advanced oesophageal cancer (LAOC) would benefit from increased total RT doses. High 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) uptake (hotspot) on pre-RT FDG positron emission tomography (PET)/CT has been reported to identify intra-tumour sites at increased risk of relapse after RT in non-small cell lung cancer and in rectal cancer. Our aim was to confirm these observations in patients with LAOC and to determine the optimal maximum standardized uptake value (SUVmax) threshold to delineate smaller RT target volumes that would facilitate RT dose escalation without impaired tolerance. The study included 98 consecutive patients with LAOC treated by chemoradiotherapy (CRT). All patients underwent FDG PET/CT at initial staging and during systematic follow-up in a single institution. FDG PET/CT acquisitions were coregistered on the initial CT scan. Various subvolumes within the initial tumour (30, 40, 50, 60, 70, 80 and 90 % SUVmax thresholds) and in the subsequent local recurrence (LR, 40 and 90 % SUVmax thresholds) were pasted on the initial CT scan and compared[Dice, Jaccard, overlap fraction (OF), common volume/baseline volume, common volume/recurrent volume]. Thirty-five patients had LR. The initial metabolic tumour volume was significantly higher in LR tumours than in the locally controlled tumours (mean 25.4 vs 14.2 cc; p = 0.002). The subvolumes delineated on initial PET/CT with a 30-60 % SUVmax threshold were in good agreement with the recurrent volume at 40 % SUVmax (OF = 0.60-0.80). The subvolumes delineated on initial PET/CT with a 30-60 % SUVmax threshold were in good to excellent agreement with the core volume (90 % SUVmax) of the relapse (common volume/recurrent volume and OF indices 0.61-0.89). High FDG uptake on pretreatment PET/CT identifies tumour subvolumes that are at greater risk of recurrence after CRT in patients with LAOC. We propose a 60 % SUVmax threshold to delineate high FDG uptake areas on initial PET/CT as reduced target volumes for RT dose escalation.
    European journal of nuclear medicine and molecular imaging 02/2015; DOI:10.1007/s00259-015-3004-y · 5.22 Impact Factor
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    ABSTRACT: It has been suggested that FDG PET has predictive value for the prognosis of treated oesophageal carcinoma. However, the studies reported in the literature have shown discordant results. The aim of this study was to determine whether pretherapy quantitative metabolic parameters correlate with patient outcomes.
    European journal of nuclear medicine and molecular imaging 07/2014; 41(11). DOI:10.1007/s00259-014-2839-y · 5.22 Impact Factor
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    ABSTRACT: Objective To assess the prognostic value of clinical and biological variables in the era of targeted therapies, especially induced toxicity in patients treated for metastatic renal cell carcinoma (RCC). Patients and methods A retrospective single-center study was performed in patients treated in our center from 2006 to 2012. The clinical and biological variables and toxicity data were retrospectively collected. Survival rates were calculated using the Kaplan-Meier method and compared by the Log-Rank test. Multivariate analysis was also performed using the Cox model. Results One hundred and two patients were included, with a median follow-up of 20 months. The median overall survival (OS) was 21 months, and 6 months for the progression free survival (PFS). As expected, the variables included in the Mozter prognostic score had a significant impact on OS (P < 0.0001) and PFS (P < 0.0001). However, hypoalbuminemia (P < 0.0001), brain metastasis (P = 0.003) and the absence of nephrectomy (P < 0.0001) were found as poor prognosis factors for OS. In addition, severe toxicity (grade 3-4) was significantly associated with higher OS (P < 0.0001) and PFS (P = 0.0003) and appeared as an independent factor in multivariate analysis for OS (P = 0.02) and PFS (P = 0.01). Conclusion Severe toxicity induced by targeted therapies was found as a prognostic factor increasing significantly the survival. Further studies are needed to assess the real value of this factor in the development of sequential therapies for the treatment of RCC.
    Progrès en Urologie 07/2014; DOI:10.1016/j.purol.2013.12.001 · 0.77 Impact Factor
  • European Urology Supplements 04/2014; 13(1):e287. DOI:10.1016/S1569-9056(14)60282-7 · 3.37 Impact Factor
  • Journal of Clinical Oncology 03/2014; DOI:10.1200/JCO.2013.49.9277 · 17.88 Impact Factor
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    ABSTRACT: The objective of this study is to investigate the feasibility and the additional interest of a parametric imaging (PI) method to monitor the early tumour metabolic response in a prospective series of oesophageal cancer patients who underwent positron emission tomography with fluoro-2-deoxy-d-glucose (FDG-PET/CT) before and during curative-intent chemo-radiotherapy. Fifty-seven patients with squamous cell carcinoma (SCC) of the oesophagus prospectively underwent FDG-PET/CT before chemo-radiotherapy (CRT) (PET1) and at 21 +/- 3 days after the beginning of CRT (PET2). The outcome was assessed at 3 months and 1 year after the completion of CRT (clinical examination, CT scan or FDG-PET/CT, biopsy). For each patient, PET1 and PET2 were registered using CT images. The 2 PET image sets were subtracted, so the voxels with significant changes in FDG uptake were identified. A model-based analysis of this graph was used to identify the tumour voxels in which significant changes occurred between the two scans and yielded indices characterising these changes (green and red clusters). Quantitative parameters were compared with clinical outcome at 3 months and at 1 year. The baseline tumour FDG uptake decreased significantly at PET2 (p < 0.0001). The tumour volume significantly decreased between PET1 and PET2 (p < 0.02). The initial functional volume of the lesion (TV1) was significantly lower (p < 0.02) in patients in clinical response (CR) at 3 months and 1 year. The volume of the lesion during the treatment (TV2) was significantly lower in patients identified as in CR at 3 months (p < 0.03), but did not predict the outcome at 1 year. Multivariate analyses of outcome at 3 months showed that the risk of failure/death increased with younger age (p = 0.001), larger metabolic volume on PET1 (p = 0.009) and larger volume with decreased FDG uptake (p = 0.047). As for outcome at 1 year, the risk of failure/death increased with younger age (p = 0.006), nodal involvement (p = 0.08) and larger volumes with increased uptake (p = 0.03). A parametric method to assess tumour response on serial FDG-PET performed during chemo-radiotherapy was evaluated. Early metabolic changes, i.e. variations in FDG uptake, provided additional prognostic information in multivariate analyses ClinicalTrials.gov NCT 00934505.Trial registration: Current Controlled Trials ISRCTN7824458.
    03/2014; 4(1):12. DOI:10.1186/2191-219X-4-12
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    ABSTRACT: Undernutrition is frequently observed in patients with a locally advanced oesophageal carcinoma. However, variations of nutritional parameters during chemoradiotherapy have not been thoroughly investigated. To evaluate the characteristics and the impact of nutritional variations during treatment. Weight loss, body mass index (BMI), serum albumin level and daily food intake at baseline and during treatment (T1=week 1; T2=week 5 or 8; T3=week 11) were retrospectively analyzed in 101 patients with oesophageal carcinoma. Significant variations occurred during chemoradiotherapy with a decrease in serum albumin level (p<0.001), body mass index (p<0.001) and weight (p<0.001). Response rate to treatment was significantly lower in patients with undernutrition at T1 (p=0.05), from T1 to T2 (p=0.01) and from T1 to T3 (p=0.04). Median overall survival was 25 months in patients with persistent undernutrition from T1 to T2 vs 42 months in wellnourished patients from T1 to T2 and those malnourished only at T1 or T2 (p=0.05). In responders, patients presenting with a lower weight or a lower food intake from T1 to T3 had worse survival (33 vs 59 months, p<0.001 and 29 vs 61 months, p=0.001, respectively). Significant variations of nutritional parameters occurred during chemoradiotherapy with a worse impact on response and survival.
    Digestive and Liver Disease 01/2014; 46(3). DOI:10.1016/j.dld.2013.10.016 · 2.89 Impact Factor
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    ABSTRACT: Background: Small bowel adenocarcinoma (SBA) is a rare tumour with a poor prognosis. Molecular biology data on SBA carcinogenesis are lacking. Methods: Expression of HER2, beta-catenin, p53 and mismatch repair (MMR) protein was assessed by immunohistochemistry. KRAS, V600E BRAF mutations and microsatellite instability were investigated. Results: We obtained samples from 63 SBA patients (tumour stages: I-II: 30%; III: 35%; IV: 32%; locally advanced: 3%). HER2 overexpression (3+) was observed in 2 out of 62 patients, overexpression of p53 in 26 out of 62, abnormal expression of beta-catenin in 12 out of 61, KRAS mutation in 21 out of 49, BRAF V600E mutation in 1 out of 40 patients, MMR deficiency (dMMR) in 14 out of 61 and was consistent with Lynch syndrome in 9 out of 14 patients. All of the dMMR tumours were in the duodenum or jejunum and only one was stage IV. Median overall survival (OS) was 36.6 months (95% CI, 26.9-72.2). For all patients, in univariate analysis, stages I-II (P<0.001), WHO PS 0-1 (P = 0.01) and dMMR phenotype (P = 0.02) were significantly associated with longer OS. In multivariate analysis, disease stage (P = 0.01) and WHO PS 0-1 (P = 0.001) independently predicted longer OS. For stage IV patients, median OS was 20.5 months (95% CI: 14.6; 36.6 months). In multivariate analysis, WHO PS 0-1 (P = 0.0001) and mutated KRAS status (P = 0.02) independently predicted longer OS. Conclusion: This large study suggests that molecular alterations in SBA are closer to those in colorectal cancer (CRC) than those in gastric cancer, with low levels of HER 2 overexpression and high frequencies of KRAS mutations. The seemingly higher frequency of dMMR than in CRC may be explained by the higher frequency of Lynch syndrome in SBA patients. A dMMR phenotype was significantly associated with a non-metastatic tumour (P = 0.02). A trend for a good prognosis and a duodenum or jejunum primary site was associated with dMMR.
    British Journal of Cancer 11/2013; 109(12). DOI:10.1038/bjc.2013.677 · 5.08 Impact Factor
  • Progrès en Urologie 11/2013; 23(13):1043. DOI:10.1016/j.purol.2013.08.060 · 0.77 Impact Factor
  • Progrès en Urologie 11/2013; 23(13):1044-1045. DOI:10.1016/j.purol.2013.08.063 · 0.77 Impact Factor
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    ABSTRACT: Sorafenib is a molecular-targeted therapy used in palliative treatment of advanced hepatocellular carcinoma (HCC) in Child-Pugh A patients. We describe the case of a patient who presented with a large HCC in the left liver associated with portal vein thrombosis (PVT). After 9 months of sorafenib treatment, reassessment showed that the tumors had decreased in size with recanalization of the portal vein. A lateral left hepatectomy was performed and pathology showed complete necrosis of the tumor. Sorafenib can downstage HCC in patients with cirrhosis allowing further surgical resection.
    World Journal of Surgical Oncology 08/2013; 11(1):171. DOI:10.1186/1477-7819-11-171 · 1.20 Impact Factor
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    ABSTRACT: BACKGROUND: A dramatic increase in the incidence of the diffuse form of gastric adenocarcinomas and particularly signet ring cell carcinomas has been observed in Western countries. Evidence is accruing that signet ring cell carcinomas may have inherent chemo resistance leaving many clinicians unsure of the benefits of delaying surgery to pursue a neoadjuvant approach.Methods/design: PRODIGE-19-FFCD1103-ADCI002 is a prospective multicentre controlled randomised phase II/III trial comparing current standard of care of perioperative chemotherapy (2x3 cycles of Epirubicin, cisplatin, 5-fluorouracil) with a strategy of primary surgery followed by adjuvant chemotherapy (6 cycles of Epirubicin, cisplatin, 5-fluorouracil) in patients with a stage IB-III gastric signet ring cell tumour. The principal objective of the phase II study (84 patients) is to determine if the experimental arm (primary surgery followed by adjuvant chemotherapy) has sufficient interest in terms of percentage of living patients at 24 months to be evaluated in a phase III trial. If 7 or less patients in the experimental arm are alive at 24 months, phase III will not be initiated. The primary objective of phase III (230 additional patients) is to demonstrate superiority of the experimental arm in terms of overall survival. Secondary endpoints include overall survival at 36 months, disease free survival at 24 and 36 months, R0 resection rates, treatment tolerance, postoperative mortality and morbidity evaluated by Clavien-Dindo severity index, the prognostic impact of positive peritoneal cytology and the assessment of quality of life. An ancillary study will assess the emotional and cognitive impact of surgery and perioperative chemotherapy for both the patient and their partner. DISCUSSION: As inherent chemo resistance of signet ring cell tumours and delay in definitive surgery may favour tumour progression we hypothesise that a policy of primary surgery followed by adjuvant chemotherapy will improve overall survival compared to a standard perioperative chemotherapeutic strategy. This randomised phase II/III trial is the first dedicated to this histological subtype. Whilst the development of new biomarkers and targeted therapies are awaited, the results of this trial should further help in devising individualised protocols of patient care in a tumour group whose diversity increasingly demands assessment of alternative strategies.Trial registration: NCT01717924 (ClinicalTrials.gov).
    BMC Cancer 06/2013; 13(1):281. DOI:10.1186/1471-2407-13-281 · 3.32 Impact Factor
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    ABSTRACT: 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).
    European Journal of Nuclear Medicine 05/2013; 40(9). DOI:10.1007/s00259-013-2450-7 · 4.53 Impact Factor
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    ABSTRACT: BACKGROUND: The EGFR 3[prime] untranslated region (UTR) harbors a polyadenine repeat which is polymorphic (A13/A14) and undergoes somatic deletions in microsatellite instability (MSI) colorectal cancer (CRC). These mutations could be oncogenic in colorectal tissue since they were shown to result into increased EGFR mRNA stability in CRC cell lines. METHODS: First, we determined in a case control study including 429 CRC patients corresponding to different groups selected or not on age of tumor onset and/or familial history and/or MSI, whether or not, the germline EGFR A13/A14 polymorphism constitutes a genetic risk factor for CRC; second, we investigated the frequency of somatic mutations of this repeat in 179 CRC and their impact on EGFR expression. RESULTS: No statistically significant difference in allelic frequencies of the EGFR polyA repeat polymorphism was observed between CRC patients and controls. Somatic mutations affecting the EGFR 3[prime]UTR polyA tract were detected in 47/80 (58.8%) MSI CRC versus 0/99 microsatellite stable (MSS) tumors. Comparative analysis in 21 CRC samples of EGFR expression, between tumor and non malignant tissues, using two independent methods showed that somatic mutations of the EGFR polyA repeat did not result into an EGFR mRNA increase. CONCLUSION: Germline and somatic genetic variations occurring within the EGFR 3[prime]UTR polyA tract have no impact on CRC genetic risk and EGFR expression, respectively. Genotyping of the EGFR polyA tract has no clinical utility to identify patients with a high risk for CRC or patients who could benefit from anti-EGFR antibodies.
    BMC Cancer 04/2013; 13(1):183. DOI:10.1186/1471-2407-13-183 · 3.32 Impact Factor
  • F. Di Fiore, P. Michel
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    ABSTRACT: Pretreatment assessment in patients with cancer of the gastroesophageal junction involves the evaluation of physiological status and tumor stage. Nutritional status is a prognostic and predictor factor of response to treatment; assessment involves the calculation of weight loss and the determination of serum albumin. Renal, cardiac, and pulmonary functions are evaluated (urea, creatinine, calculation of clearance, liver function tests, electrocardiogram, pulmonary function). The performance status (Karnofsky or WHO) is an important prognostic factor. The assessment of tumor stage involves the digestive endoscopy and endoscopic ultrasonography, CT thoraco-abdomino-pelvic injection, and PET-FDG. Laparoscopy is performed only when peritoneal involvement is suspected.
    Oncologie 03/2013; 15(3-4). DOI:10.1007/s10269-013-2266-x · 0.08 Impact Factor
  • The American Journal of Gastroenterology 01/2013; 108(1):152-5. DOI:10.1038/ajg.2012.367 · 9.21 Impact Factor
  • Urology 08/2012; 80(4):e37-8. DOI:10.1016/j.urology.2012.06.029 · 2.13 Impact Factor
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    ABSTRACT: The purpose of the study was to investigate the value of 18F-fluorodeoxyglucose-positron emission tomography performed after definitive chemoradiotherapy in patients with locally advanced oesophageal carcinoma. Forty consecutive patients underwent 18F-fluorodeoxyglucose-positron emission tomography at baseline and after chemoradiotherapy completion. Assessment of the clinical complete response to chemoradiotherapy included oesophagoscopy plus biopsies and computed tomography scan. Cox regression analysis was used to develop the univariate and multivariate models describing the association of the independent variables with survival and local control. A clinical complete response and 18F-fluorodeoxyglucose-positron emission tomography response were present in 29 patients (72.5%) and 13 patients (32.5%), respectively. A combined response was observed in 11 patients (27.5%). During follow-up, a local failure was detected in 27.2% of patients with 18F-fluorodeoxyglucose-positron emission tomography response versus 33.3% in non-responders (p=.9). In multivariate analysis, clinical complete response (HR 5.77, p=.009) and 18F-fluorodeoxyglucose-positron emission tomography response (HR 6.27, p=.031) were identified as independent prognostic factors of overall survival. In patients treated for an esophageal cancer, the present study suggested that 18F-fluorodeoxyglucose-positron emission tomography after chemoradiotherapy completion was an independent prognostic factor of overall survival without significant impact on local recurrence prediction.
    Digestive and Liver Disease 08/2012; 44(10):875-9. DOI:10.1016/j.dld.2012.04.017 · 2.89 Impact Factor
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    ABSTRACT: Definitive chemoradiotherapy (CRT) is considered curative intent treatment for locally advanced esophageal squamous cell carcinoma. Data concerning the usefulness of definitive CRT in patients with esophageal adenocarcinoma (ADC) are lacking. The aim of the study was to compare the results of definitive CRT versus surgery in patients with an ADC. All consecutive patients with a non-metastatic ADC treated between 1994 and 2008 were retrospectively assessed. Patients were divided into two groups: surgery group (±pre-operative treatment) versus definitive CRT group. In surgery and definitive CRT groups, 67 and 79 patients were evaluated, respectively. A complete resection was achieved in 92.5% of patients in surgery group and a clinical complete response was observed in 49.4% of patients in definitive CRT group. Overall survival was 36.2 ± 2.0 months in surgery group versus 16.5 ± 0.8 months in definitive CRT group (P = 0.02). The predictive factors of survival were age (P < 0.01), stage (P = 0.04), WHO performance status (P < 0.01), initial weight loss (P < 0.01), and the treatment group (P < 0.01). The results of the study do not support definitive CRT as an alternative to surgery in esophageal ADC treatment. Definitive CRT should be reserved for patients with a major operative risk.
    Journal of Surgical Oncology 06/2012; 105(8):761-6. DOI:10.1002/jso.22157 · 2.84 Impact Factor
  • P. Michel, F. Di Fiore
    06/2012; 7(3):1-4. DOI:10.1016/S1155-1968(12)53134-2

Publication Stats

2k Citations
378.77 Total Impact Points

Institutions

  • 2004–2014
    • Université de Rouen
      Mont-Saint-Aignan, Haute-Normandie, France
  • 2004–2013
    • Hôpital Charles-Nicolle
      Tunis-Ville, Tūnis, Tunisia
  • 2001–2013
    • Centre Hospitalier Universitaire Rouen
      • Service d'Urologie
      Rouen, Upper Normandy, France
  • 2009
    • Universitair Ziekenhuis Leuven
      Louvain, Flemish, Belgium
  • 2008
    • Centre Henri Becquerel
      Rouen, Haute-Normandie, France
  • 2005
    • Université du Havre
      El Havre, Haute-Normandie, France