P Lasser

Institut de Cancérologie Gustave Roussy, Villejuif, Île-de-France, France

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Publications (276)680.41 Total impact

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    ABSTRACT: Background:To test the prognostic value of tumour protein and genetic markers in colorectal cancer (CRC) and examine whether deficient mismatch repair (dMMR) tumours had a distinct profile relative to proficient mismatch repair (pMMR) tumours.Methods:This prospective multicentric study involved 251 stage I-III CRC patients. Analysed biomarkers were EGFR (binding assay), VEGFA, thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) expressions, MMR status, mutations of KRAS (codons 12-13), BRAF (V600E), PIK3CA (exons 9 and 20), APC (exon 15) and P53 (exons 4-9), CpG island methylation phenotype status, ploidy, S-phase, LOH.Results:The only significant predictor of relapse-free survival (RFS) was tumour staging. Analyses restricted to stage III showed a trend towards a shorter RFS in KRAS-mutated (P=0.005), BRAF wt (P=0.009) and pMMR tumours (P=0.036). Deficient mismatch repair tumours significantly demonstrated higher TS (median 3.1 vs 1.4) and TP (median 5.8 vs 3.5) expression relative to pMMR (P<0.001) and show higher DPD expression (median 14.9 vs 7.9, P=0.027) and EGFR content (median 69 vs 38, P=0.037) relative to pMMR.Conclusions:Present data suggesting that both TS and DPD are overexpressed in dMMR tumours as compared with pMMR tumours provide a strong rationale that may explain the resistance of dMMR tumours to 5FU-based therapy.British Journal of Cancer advance online publication 6 May 2014; doi:10.1038/bjc.2014.213 www.bjcancer.com.
    British Journal of Cancer 05/2014; DOI:10.1038/bjc.2014.213 · 5.08 Impact Factor
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    ABSTRACT: Abdominoperineal resections (APR) for anorectal tumors are associated with a high rate of perineal wound complications. The aim of this study was to evaluate the impact of pseudocontinent perineal colostomy (PPC) following APR on perineal wound healing. All patients undergoing APR between 2000 and 2009 were retrospectively reviewed. Perineal wound healing was compared between patients with PPC and those with perineal closure alone. APR was performed in 132 patients, including 31 with PPC and 101 with no PPC. Risk factors such as radiotherapy, smoking, diabetes mellitus, and obesity were not different between the two groups. The PPC group had significantly fewer cases of omentoplasty and adenocarcinoma histology. The overall perineal complication rate, perineal infection, or wound dehiscence was similar in the two groups, but the perineal healing rate at 6 and 12 weeks was significantly increased in the PPC group than in the non-PPC group (70.9% vs. 50%, P = 0.04, at 6 weeks; 90.3% vs. 73%, P = 0.04, at 12 weeks). PPC accelerates perineal wound healing after APR without decreasing the overall perineal complication rate.
    Journal of Surgical Oncology 06/2012; 105(7):628-31. DOI:10.1002/jso.22105 · 2.84 Impact Factor
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    ABSTRACT: After curative resection, the prognosis of gastroesophageal adenocarcinoma is poor. This phase III trial was designed to evaluate the benefit in overall survival (OS) of perioperative fluorouracil plus cisplatin in resectable gastroesophageal adenocarcinoma. Overall, 224 patients with resectable adenocarcinoma of the lower esophagus, gastroesophageal junction (GEJ), or stomach were randomly assigned to either perioperative chemotherapy and surgery (CS group; n = 113) or surgery alone (S group; n = 111). Chemotherapy consisted of two or three preoperative cycles of intravenous cisplatin (100 mg/m(2)) on day 1, and a continuous intravenous infusion of fluorouracil (800 mg/m(2)/d) for 5 consecutive days (days 1 to 5) every 28 days and three or four postoperative cycles of the same regimen. The primary end point was OS. Compared with the S group, the CS group had a better OS (5-year rate 38% v 24%; hazard ratio [HR] for death: 0.69; 95% CI, 0.50 to 0.95; P = .02); and a better disease-free survival (5-year rate: 34% v 19%; HR, 0.65; 95% CI, 0.48 to 0.89; P = .003). In the multivariable analysis, the favorable prognostic factors for survival were perioperative chemotherapy (P = .01) and stomach tumor localization (P < .01). Perioperative chemotherapy significantly improved the curative resection rate (84% v 73%; P = .04). Grade 3 to 4 toxicity occurred in 38% of CS patients (mainly neutropenia) but postoperative morbidity was similar in the two groups. In patients with resectable adenocarcinoma of the lower esophagus, GEJ, or stomach, perioperative chemotherapy using fluorouracil plus cisplatin significantly increased the curative resection rate, disease-free survival, and OS.
    Journal of Clinical Oncology 03/2011; 29(13):1715-21. DOI:10.1200/JCO.2010.33.0597 · 17.88 Impact Factor
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    ABSTRACT: In theory, perioperative detection of lymph nodes with the injection of isosulfan blue dye should provide lymph road mapping (LRM) able to direct the resection. However, there is no supporting evidence for this theory in cases of colon cancer. We reanalysed all operative reports using the sentinel lymph node technique with blue dye injection. The retrospective study included 140 patients who underwent the sentinel lymph node (SLN) procedure between February 2001 and November 2007, including 70 cases in which the in vivo technique was used. In 8 cases (11%), LRM was used by the surgeon to determine the extent of resection. In 5 cases, including limited or extended resection, the final pathological stage was II at the end of the follow-up period, and the patients had no recurrent disease. However, findings for 3 cases of stage III cancer were more relevant to the aims of this study. In these 3 patients, one with cancer (T3N1(3/22)) located at the hepatic flexure, and 2 with cancers (T3N2(7/41) and T2N2 (4/15)) at the splenic flexure, the middle colic artery was conserved as a result of LRM information. Of these 3 patients, 1 was alive without disease at 6-year follow-up and 2 at 5-year follow-up. LRM obtained via blue sentinel node detection makes it possible to avoid middle colic artery resection for selected colon cancer cases. LRM seems particularly suitable in cases of colonic flexure location or prior colon surgery.
    Techniques in Coloproctology 09/2010; 14(3):237-40. DOI:10.1007/s10151-010-0603-2 · 1.54 Impact Factor
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    ABSTRACT: Surgical treatment for epidermoid carcinoma of the anus is reserved for patients after failure of primary chemoradiotherapy and consists of abdominoperineal resection with permanent iliac colostomy. The purpose of this study was to analyze the oncologic and the functional outcomes after abdominoperineal resection and pseudocontinent perineal colostomy for epidermoid carcinoma of the anus after external radiation at maximal doses (60 Gy). Between 1990 and 2006, 95 patients underwent abdominoperineal resection for an epidermoid carcinoma of the anus. Eighteen (19 percent) underwent construction of a pseudocontinent perineal colostomy. Functional results were evaluated prospectively at regular intervals. Complete resection (R0) was obtained in 17 of 18 patients. After a median follow-up of 33 (range, 12-198) months, 15 of 18 patients were alive, and 11 were disease free. Five-year overall and disease-free survival rates were 67 and 53 percent, respectively. Functional outcomes were available for 16 patients. According to the Kirwan score, 15 were continent, and 13 did not require pad protection. Overall, 15 of 16 patients were satisfied. Pelvic reconstruction with a pseudocontinent perineal colostomy does not compromise the beneficial effect of salvage surgery, seems to be safe and feasible even after a high dose of radiotherapy, and provides a high degree of satisfaction.
    Diseases of the Colon & Rectum 06/2009; 52(5):958-63. DOI:10.1007/DCR.0b013e31819f2a4b · 3.20 Impact Factor
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    ABSTRACT: IntroductionWhen radiation therapy fails to control cancer of the anal canal, the only therapeutic alternative is salvage abdomino-perineal resection (APR). Its role remains debatable since very few long-term survivals have been reported. No prognostic factors have yet been identified in the limited series of reported cases.Patients95 APR’s performed over a 20 year period are reviewed and analyzed.ResultsMedian follow-up was 5.5 years. Only one prognostic factor was identified: an R0 resection (n=76) versus either R1 (n=9) or R2 (n=9) resection. Median survival for R0 APR was more than 10 years versus 1 year for R1 and R2 resections (p=0.001). There was no prognostic difference between salvage APR for disease progression (n=55) or for late recurrence (n=40). The sub-group of women < 45 years of age (n=5) had a particularly poor prognosis with no survivors beyond 2 years.Conclusion When anal cancer recurs after radiation therapy, a salvage APR is indicated. If an R0 resection can be achieved, median survival is greater than 10 years. However, the justification for APR when only an R1 or R2 resection can be achieved is much less clear; in such cases there was no survival beyond 3 years.
    Journal de Chirurgie 08/2008; 145(4):335-340. DOI:10.1016/S0021-7697(08)74312-6 · 0.50 Impact Factor
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    ABSTRACT: All patients with metastatic (ovarian and extraovarian) CRC who underwent resection of ovarian metastases in our institution from April 1988 to August 2006 were analyzed and the response to preoperative chemotherapy was evaluated according to the RECIST criteria, and analyzed with respect to the sites of metastases (ovarian and extraovarian). The studied population consisted of 23 women. At presentation, 20 patients had symptoms. Preoperative chemotherapy resulted in tumor control of measurable extraovarian metastases in 65% of cases. In contrast, no objective tumor response of ovarian metastases was observed, disease stabilization was obtained in only 3 patients (13%), and progression or occurrence of new ovarian metastases were observed in 20 patients (87%) (p=0.0005). With a median follow-up of 54 months [15-229], median overall survival was 30 months, and 3-year overall survival was 18%. Ovarian metastases are less responsive to chemotherapy compared to other sites. As these "metastatic sanctuaries" often cause symptoms, surgical resection should always be considered for ovarian metastases, even in the case of associated extraovarian metastases.
    European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 06/2008; 34(12):1335-9. DOI:10.1016/j.ejso.2008.03.010 · 2.56 Impact Factor
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  • P. Lasser, D. Goéré
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    ABSTRACT: Las pelvectomías se realizan en los cánceres que se encuentran en ginecología y en las neoplasias rectales localmente avanzadas, de estadio T4, que se definen por una extensión a los órganos vecinos, así como en las recidivas locorregionales de los cánceres ginecológicos y del recto, la vagina y el conducto anal. Se trata de intervenciones difíciles, responsables de una mortalidad y una morbilidad significativas, que requieren maniobras complejas de exéresis y reconstrucción, así como experiencia en cirugía digestiva, ginecológica, urinaria, plástica e incluso ortopédica. El factor pronóstico esencial es el carácter radical de la exéresis (R0), por lo que la decisión de estas intervenciones se toma durante una reunión multidisciplinaria (oncólogo y radiólogo), tras un estudio clínico y morfológico completo que permita descartar una extensión locorregional inaccesible a la resección o una extensión a distancia. La presencia de carcinomatosis peritoneal, metástasis viscerales (hepáticas o pulmonares), metástasis ganglionares lumboaórticas, invasión de los vasos ilíacos primitivos o externos, invasión del sacro en S1-S2 o una extensión tumoral hacia la escotadura ciática son contraindicaciones absolutas para la pelvectomía. La mortalidad y la morbilidad tras esta intervención varían según el cáncer primario, la realización o no de radioterapia preoperatoria, el tipo y extensión de la pelvectomía, la edad y el estado general del paciente, así como en función de la experiencia del cirujano. Tras una resección R0 de un cáncer primario ginecológico o rectal, se han descrito tasas prolongadas de supervivencia (20-60% a los 5 años), aunque son inferiores tras una resección de una recidiva pélvica de un cáncer rectal.
    01/2008; 24(4):1–24. DOI:10.1016/S1282-9129(08)70138-7
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    ABSTRACT: When radiation therapy fails to control cancer of the anal canal, the only therapeutic alternative is salvage abdomino-perineal resection (APR). Its role remains debatable since very few long-term survivals have been reported. No prognostic factors have yet been identified in the limited series of reported cases. 95 APR's performed over a 20 year period are reviewed and analyzed. Median follow-up was 5.5 years. Only one prognostic factor was identified: an R0 resection (n=76) versus either R1 (n=9) or R2 (n=9) resection. Median survival for R0 APR was more than 10 years versus 1 year for R1 and R2 resections (p=0.001). There was no prognostic difference between salvage APR for disease progression (n=55) or for late recurrence (n=40). The sub-group of women<45 years of age (n=5) had a particularly poor prognosis with no survivors beyond 2 years. When anal cancer recurs after radiation therapy, a salvage APR is indicated. If an R0 resection can be achieved, median survival is greater than 10 years. However, the justification for APR when only an R1 or R2 resection can be achieved is much less clear; in such cases there was no survival beyond 3 years.
    Journal de Chirurgie 01/2008; 145(4):335-40. · 0.50 Impact Factor
  • P. Lasser, D. Goéré
    01/2008; 3(3):1-24. DOI:10.1016/S0246-0424(08)36212-8
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    ABSTRACT: Transfusion of red blood cells (RBCs) has been associated with immunomodulatory effects. Persistence of donor cells in the recipient may be contributive. A randomized single-center trial was conducted to compare microchimerism and immune responses in 35 patients undergoing cancer surgery and transfused perioperatively with either unmodified RBCs (UN-RBCs, n = 18) or leukoreduced RBCs (LR-RBCs, n = 17). Biologic parameters included microchimerism assessment peripheral blood mononuclear cell (PBMNC) phenotyping, cytokine production by stimulated PBMNCs, FoxP3 gene expression, and T-cell repertoire (TCR) analysis. Microchimerism was documented in 8 of 18 patients after UN-RBC transfusion while absent after LR-RBC transfusion (0/17; p = 0.001). After UN-RBC transfusion, microchimerism was associated with increased interleukin (IL)-10 production (p = 0.02), reduced TCR alteration (p = 0.04), and reduced CD56+ cell counts (p = 0.02) when compared to recipients without evidence for microchimerism. FoxP3 gene expression did not differ significantly between both treatment groups nor with the presence or absence of microchimerism in the UN-RBC group. Finally, after an initial early decrease after surgery and transfusion, IL-12 production increased and more significantly so after UN-RBC transfusion versus LR-RBC transfusion (p = 0.05). UN-RBC-induced microchimerism is associated with specific immunomodulatory effects in cancer patients who received transfusions during surgery.
    Transfusion 10/2007; 47(9):1691-9. DOI:10.1111/j.1537-2995.2007.01344.x · 3.57 Impact Factor
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    ABSTRACT: The aim of this study was to compare functional results and quality of life (QoL) of two salvage techniques: coloanal anastomosis (CAA) or perineal reconstruction after abdominoperineal resection for very low rectal cancer. Between 1991 and 2001, 50 patients were operated for a very low rectal adenocarcinoma and analyzed after a follow-up greater than one year and because there was no relapse or no treatment, they were included in the analysis. Thirty-eight patients had a CAA, including: straight anastomosis (n=23), J pouch (n=10), coloplasty (n=2) and intersphincteric resection (n=3). Twelve patients underwent a PC. Vaizey's incontinence score was equivalent for the two groups: CAA 12 (0-22) versus PC 11 (8-13). The only differences were more frequent fractioned stools for the CAA group and increased pad soiling for the PC group. Overall QoL scores (QLQ C-30) were equivalent for CAA and PC. For very low rectal tumors, the choice of surgical technique must be based on oncologic rather than future functional or QoL criteria, because both approaches seem to provide similar results.
    European Journal of Surgical Oncology 06/2007; 33(4):459-62. DOI:10.1016/j.ejso.2006.10.023 · 2.89 Impact Factor
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    ABSTRACT: Results concerning the usefulness of the sentinel lymph node (SLN) in colorectal carcinoma have been discordant. The SLN technique may be used to guide surgical resection (lymph mapping), restrict the lymph node analysis solely to the SLN (accuracy) and upgrade tumor staging when micrometastases are specifically detected in the SLN. The blue dye injection technique was used. Serial sections of the SLNs were analyzed after hematoxylin-eosin (HES) staining. The SLN technique was tested in 123 patients, successfully in 112/118 (feasibility 95%) (five intraoperative exclusions). On average, twenty lymph nodes (range: 5-74) and two SLNs (range: 1-5) were identified. Lymph mapping was used in 11% of patients to guide surgical resection; the SLN was negative in 14 of 36 N+ patients (39% false-negatives); HES staining enabled detection of micrometastases in 8 of 84 initially N0 patients (10% secondary upgrading to N+). Limiting node analysis to the SLN cannot replace a complete pathology examination of all resected lymph nodes. Careful examination of serial sections of the SLN can however affect therapeutic decision making since staging may be upgraded in up to 10% of initially N0 patients.
    Gastroentérologie Clinique et Biologique 03/2007; 31(3):281-5. DOI:10.1016/S0399-8320(07)89374-2 · 1.14 Impact Factor
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    ABSTRACT: We reported the case of a patient presenting a rectal cancer of the upper part with a BMI at 59 which was previously considered as a contraindication to surgery. To perform the operation we had to make as first step of the procedure a panniculectomy. The technique made possible the rectal resection under good conditions, without blood transfusion. The post-operative course was uneventful except a pulmonary embolism controlled with medical treatment. This procedure is feasible in colorectal surgery.
    Annales de Chirurgie 12/2006; 131(9):556-8. DOI:10.1016/j.anchir.2006.03.022 · 0.35 Impact Factor
  • European Journal of Surgical Oncology 11/2006; 32. DOI:10.1016/S0748-7983(06)70673-4 · 2.89 Impact Factor
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    ABSTRACT: Objective This randomized study compared two neoadjuvant treatments in patients with a low rectal cancer less than 2 cm from the anal verge that would have required APR before radiotherapy.Method A total of 207 patients (71% uT3) with a rectal carcinoma at 0.5 cm from the anal verge were randomized in two groups. The group HDR received a high dose of radiotherapy (45 Gy + boost 18 Gy). The group RCT received 45 Gy with concomitant chemotherapy (5FU). Surgery was performed 6 weeks after treatment, surgeons were trained with TME, APR and intersphincteric resection.Results The rate of sphincter preserving surgery was 83% after HDR and 86% after RCT (P = 0.69). There was no difference in morbidity, clinical tumour regression (80% vs. 87%) and complete pathological response (8% vs. 15%) between HDR and RCT. Overall, the rate of R0 resection was 78%. After a follow-up of 23 months, the rates of local and distant recurrence were 6% and 19% respectively and the disease-free survival was 77%. Survival was better after sphincter preservation than after APR.Conclusion Sphincter preservation was achieved in 85% of ultra-low rectal carcinomas without compromising oncological prinicples. No difference was observed between HDR and RCT. Further follow-up is necessary to confirm this conservative approach.
    Colorectal Disease 09/2006; 8:1-1. DOI:10.1111/j.1463-1318.2006.01082_1.x · 2.02 Impact Factor
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    ABSTRACT: To report our experience of peritoneal carcinomatosis (PC) discovered during abdominal exploration in patients with liver metastases (LM). Liver resection plus cytoreductive surgery were combined in 24 patients with LM and moderate PC from colorectal origin treated with a curative intent between January 1993 and November 2003. The mean operative time was 357+/-112 min and median blood loss was 719 ml. One postoperative death occurred and postoperative morbidity was 58%. The mean hospital stay was 21.4+/-4.2 days. Three-year overall and disease-free survival rates were respectively 41.5% (confidence interval [CI]: 23-63) and 23.6% (CI: 11-45). Seven patients are disease-free with a mean follow-up of 27.8 months after their last surgery, 3 having a repeated hepatectomy. Three patients developed a peritoneal recurrence and 13 had recurrence in the liver. The only significant prognostic factor was a number of LMs of less than 3 (p < 0.01). A combined treatment of LM plus PC is feasible and is beneficial in selected patients presenting three or fewer metastases.
    European Journal of Surgical Oncology 09/2006; 32(6):632-6. DOI:10.1016/j.ejso.2006.03.013 · 2.89 Impact Factor
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    ABSTRACT: Advances in the understanding of tumor biology have led to the development of targeted therapies allowing progress in colorectal cancer treatment. One of the most promising targets is the epidermal growth factor receptor (EGFR). The presence and distribution of high- and low-affinity EGFR was investigated retrospectively in a group of 82 colorectal cancer samples (43 normal colon-colon cancer paired samples) using a specific ligand binding assay (Scatchard Analysis). A large majority of tumor samples exhibited one class of high-affinity binding sites (78%). Eighteen cases (22%) exhibited both high- and low-affinity binding sites. A wide interpatient variability was observed for the site number, with physiologically-relevant high-affinity sites ranging from 7 to 310 fmol/mg protein in tumors and from 6 to 313 fmol/mg protein in normal mucosa. A significant positive correlation was demonstrated between tumor and normal mucosa for the high-affinity Kd values and for the number of high-affinity sites, suggesting a common regulation for both tumor and normal tissue. These observations (i) could explain recently-reported clinically-active EGFR targeting in colorectal tumors apparently negative for EGFR, and (ii) may offer a plausible explanation for the link observed between toxicity in normal tissue (cutaneous rash) and clinical outcome of patients treated with anti-EGFR drugs. Present data extends our understanding of EGFR identity in colorectal cancer which could be useful in reconsidering the predictive tools for the identification of tumors putatively responsive to EGFR targeted therapy.
    Annals of Oncology 07/2006; 17(6):962-7. DOI:10.1093/annonc/mdl037 · 6.58 Impact Factor
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    ABSTRACT: Only a few drugs are active in the treatment of well-differentiated endocrine carcinomas (WDEC). We evaluated the combination of the so-called 'de Gramont schedule' and irinotecan in these tumors in a phase II study. 20 patients were enrolled in the study. The combination regimen included irinotecan, 180 mg/m(2) on day 1, followed by 200 mg/m(2) folinic acid in a 2-hour infusion, an intravenous 10-min bolus of 400 mg/m(2) 5-fluorouracil (5FU) and finally 600 mg/m(2) 5FU in a 22-hour infusion. Folinic acid and 5FU were repeated on day 2. Clinical, biological and morphological parameters were assessed by CT every 8 weeks. The site of the primary tumor was the pancreas in 10 cases, the lung in 3 cases and other sites in 7 cases. Sixteen patients had previously received chemotherapy, and 6 of them had had two lines of treatment. Six patients had previously been treated with chemoembolization. The median number of cycles administered was 8. Grade 3-4 neutropenia was observed in 8 patients, and 1 patient experienced febrile neutropenia. There was no toxicity-related death. No complete symptomatic response was observed in 7 evaluable patients; 4 patients had an objective biological response. One patient achieved a morphological objective response, stabilization was observed in 15, but progression occurred in 3 patients. Median survival was 15 months. The above-mentioned combination of LV5FU2 + irinotecan does not yield major activity in heavily pretreated unresectable metastatic gastroenteropancreatic WDEC, and significant toxicity was observed.
    Oncology 02/2006; 70(2):134-40. DOI:10.1159/000093004 · 2.61 Impact Factor

Publication Stats

6k Citations
680.41 Total Impact Points


  • 1985–2014
    • Institut de Cancérologie Gustave Roussy
      • • Department of Radiotherapy
      • • Department of Medical Imaging
      • • Department of General Surgery
      Villejuif, Île-de-France, France
  • 2007
    • Centre Hospitalier Universitaire Rouen
      Rouen, Upper Normandy, France
  • 2002
    • Sapienza University of Rome
      • Department of Surgery "Pietro Valdoni"
      Roma, Latium, Italy
  • 2001
    • Institut Bergonié
      Burdeos, Aquitaine, France
  • 2000
    • Institut Paoli Calmettes
      Marsiglia, Provence-Alpes-Côte d'Azur, France