C Hill

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

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Publications (34)217.38 Total impact

  • C Hill, F Doyon
    07/2012; 13(10):1172. DOI:10.4267/10608/525
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    ABSTRACT: Predicting the efficacy of antiangiogenic therapy would be of clinical value in patients (pts) with metastatic renal cell carcinoma (mRCC). We tested the hypothesis that circulating endothelial cell (CEC), bone marrow-derived CD45(dim)CD34(+)VEGFR2(+) progenitor cell or plasma angiogenic factor levels are associated with clinical outcome in mRCC pts undergoing treatment with tyrosine kinase inhibitors (TKI). Fifty-five mRCC pts were prospectively monitored at baseline (day 1) and day 14 during treatment (46 pts received sunitinib and 9 pts received sorafenib). Circulating endothelial cells (CD45(-)CD31(+)CD146(+)7-amino-actinomycin (7AAD)(-) cells) were measured in 1 ml whole blood using four-color flow cytometry (FCM). Circulating CD45(dim)CD34(+)VEGFR2(+)7AAD(-) progenitor cells were measured in progenitor-enriched fractions by four-color FCM. Plasma VEGF, sVEGFR2, SDF-1α and sVCAM-1 levels were determined by ELISA. Correlations between baseline CEC, CD45(dim)CD34(+)VEGFR2(+)7AAD(-) progenitor cells, plasma factors, as well as day 1-day 14 changes in CEC, CD45(dim)CD34(+)VEGFR2(+)7AAD(-) progenitor, plasma factor levels, and response to TKI, progression-free survival (PFS) and overall survival (OS) were examined. No significant correlation between markers and response to TKI was observed. No association between baseline CEC, plasma VEGF, sVEGFR-2, SDF-1α, sVCAM-1 levels with PFS and OS was observed. However, baseline CD45(dim)CD34(+)VEGFR2(+)7AAD(-) progenitor cell levels were associated with PFS (P=0.01) and OS (P=0.006). Changes in this population and in SDF-1α levels between day 1 and day 14 were associated with PFS (P=0.03, P=0.002). Changes in VEGF and SDF-1α levels were associated with OS (P=0.02, P=0.007). Monitoring CD45(dim)CD34(+)VEGFR2(+) progenitor cells, plasma VEGF and SDF-1α levels could be of clinical interest in TKI-treated mRCC pts to predict outcome.
    British Journal of Cancer 03/2011; 104(7):1144-50. DOI:10.1038/bjc.2011.72 · 4.82 Impact Factor
  • Cancer Research 01/2011; 70(8 Supplement):372-372. DOI:10.1158/1538-7445.AM10-372 · 9.28 Impact Factor
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    ABSTRACT: Between 1966 and 1974, France conducted 41 atmospheric nuclear tests in Polynesia, but their potential health effects have not previously been investigated. In a case-control study, we compared the radiation exposure of almost all the French Polynesians diagnosed with differentiated thyroid carcinoma between 1981 and 2003 (n=229) to the exposure of 373 French Polynesian control individuals without cancer from the general population. Radiation exposures were estimated using measurements after the nuclear tests, age at time of each test, residential and dietary information. The average thyroid dose before 15 years of age was about 1.8 mGy, and 5% of the cases and 3% of the controls received a dose above 10 mGy. Despite this low level of dose, and after adjusting for ethnic group, level of education, body surface area, family history of thyroid cancer and number of pregnancies for women, we observed an increasing risk (P=0.04) of thyroid cancer with increasing thyroid dose received before age of 15 years, which remained after excluding non-aggressive differentiated thyroid micro-carcinomas. This increase of risk per unit of thyroid radiation dose was higher (P=0.03) in women who later experienced four or more pregnancies than among other women. The risk estimate is low, but is based on limited exposure data. The release of information on exposure, currently classified, would greatly improve the reliability of the risk estimation.
    British Journal of Cancer 09/2010; 103(7):1115-21. DOI:10.1038/sj.bjc.6605862 · 4.82 Impact Factor
  • S Guérin, C Hill
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    ABSTRACT: In 2007, a total number of 149,000 cancer deaths were observed in France, 89,100 in the male population and 60,600 in the female population, and in 2009, the number of new diagnoses of cancer is estimated to be 346,500, 197,500 among men and 149,000 among women. The most frequent cancers are prostate, lung and colorectal cancers in men, and breast, colorectal and lung cancers in women. Cancer mortality is higher in France than in the USA for men and lower for women. The largest differences between the two countries are observed for lung cancer and for head and neck (mouth, pharynx, larynx and oesophagus) cancers in men. Lung cancer mortality is higher in the USA than in France for men and much higher for women. These differences are explained by the difference in past tobacco consumption. For head and neck cancers in men, despite a very large decrease in France due mostly to the reduction in alcohol consumption, mortality remains today higher in France than in the USA.
    Bulletin du cancer 12/2009; 97(1):47-54. DOI:10.1684/bdc.2010.1013 · 0.64 Impact Factor
  • S Guérin, F Doyon, C Hill
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    ABSTRACT: In 2006, a total number of 149,000 cancer deaths were observed in France, 88,500 in the male population and 60,500 in the female population. In 2005, the number of new diagnoses of cancer is estimated to be 319,000, 183,000 among men and 136,000 among women. Age-standardised mortality rates are decreasing for most frequent cancer sites, at least in recent years, the main exceptions being lung in the female population, and pancreas in both male and female populations. Age-standardised incidence rate has increased by 38% between 1980 and 2005, when one takes demographic changes into account. This trend is the consequence of the increase in prostate cancer incidence among men and mostly of the increases in breast and lung cancers incidence, among women.
    Bulletin du cancer 03/2009; 96(1):51-7. DOI:10.1684/bdc.2008.0795 · 0.64 Impact Factor
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    ABSTRACT: To analyse the effect of external radiation exposure on the mortality of French nuclear workers. A cohort of 29 204 workers employed between 1950 and 1994 at the French Atomic Energy Commission (Commissariat à l'Energie Atomique (CEA)) or at the General Company of Nuclear Fuel (COmpagnie GEnérale des MAtières nucléaires (Cogema, now Areva NC)) was followed up for an average of 17.8 years. Standardised mortality ratios (SMRs) were computed with reference to French mortality rates. Dose-effect relationship were analysed through trend tests and Poisson regression, with linear and log-linear models. The mean exposure to X and gamma radiation was 8.3 mSv (16.9 mSv for exposed worker population). A total of 1842 deaths occurred between 1968 and 1994. A healthy worker effect was observed, the number of deaths in the cohort being 59% of the number expected from national mortality statistics. Among the 21 main cancer sites studied, a statistically significant excess was observed only for skin melanoma, and an excess of borderline statistical significance was observed for multiple myeloma. A dose-effect relationship was observed for leukaemia after exclusion of chronic lymphoid leukaemia (CLL). The relative risk observed for non-CLL leukaemia, n = 20, was 4.1 per 100 mSv (90% CI 1.4 to 12.2), linear model and 2.2 per 100 mSv (90% CI 1.2 to 3.3), log-linear model. Significant dose-effect relationship were also observed for causes of deaths associated with alcohol consumption: mouth and pharynx cancer, cirrhosis and alcoholic psychosis and external causes of death. The risk of leukaemia increases with increasing exposure to external radiation; this is consistent with published results on other nuclear workers cohorts.
    Occupational and environmental medicine 11/2007; 64(10):694-700. DOI:10.1136/oem.2007.032631 · 3.23 Impact Factor
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    ABSTRACT: Microarray studies aim at identifying homogeneous subtypes of cancer patients, searching for differentially expressed genes in tumours with different characteristics, or predicting the prognosis of patients. Using breast cancer as an example, we discuss the hypotheses underlying these studies, their power, and the validity and the clinical usefulness of the findings.
    British Journal of Cancer 05/2007; 96(8):1155-8. DOI:10.1038/sj.bjc.6603673 · 4.82 Impact Factor
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    ABSTRACT: Radiation protection standards are based mainly on risk estimates from studies of atomic bomb survivors in Japan. The validity of extrapolations from the relatively high-dose acute exposures in this population to the low-dose, protracted or fractionated environmental and occupational exposures of primary public health concern has long been the subject of controversy. A collaborative retrospective cohort study was conducted to provide direct estimates of cancer risk after low-dose protracted exposures. The study included nearly 600,000 workers employed in 154 facilities in 15 countries. This paper describes the design, methods and results of descriptive analyses of the study. The main analyses included 407,391 nuclear industry workers employed for at least 1 year in a participating facility who were monitored individually for external radiation exposure and whose doses resulted predominantly from exposure to higher-energy photon radiation. The total duration of follow-up was 5,192,710 person-years. There were 24,158 deaths from all causes, including 6,734 deaths from cancer. The total collective dose was 7,892 Sv. The overall average cumulative recorded dose was 19.4 mSv. A strong healthy worker effect was observed in most countries. This study provides the largest body of direct evidence to date on the effects of low-dose protracted exposures to external photon radiation.
    Radiation Research 05/2007; 167(4):361-79. DOI:10.1667/RR0554.1 · 2.45 Impact Factor
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    ABSTRACT: A 15-Country collaborative cohort study was conducted to provide direct estimates of cancer risk following protracted low doses of ionizing radiation. Analyses included 407,391 nuclear industry workers monitored individually for external radiation and 5.2 million person-years of follow-up. A significant association was seen between radiation dose and all-cause mortality [excess relative risk (ERR) 0.42 per Sv, 90% CI 0.07, 0.79; 18,993 deaths]. This was mainly attributable to a dose-related increase in all cancer mortality (ERR/Sv 0.97, 90% CI 0.28, 1.77; 5233 deaths). Among 31 specific types of malignancies studied, a significant association was found for lung cancer (ERR/Sv 1.86, 90% CI 0.49, 3.63; 1457 deaths) and a borderline significant (P = 0.06) association for multiple myeloma (ERR/Sv 6.15, 90% CI <0, 20.6; 83 deaths) and ill-defined and secondary cancers (ERR/Sv 1.96, 90% CI -0.26, 5.90; 328 deaths). Stratification on duration of employment had a large effect on the ERR/Sv, reflecting a strong healthy worker survivor effect in these cohorts. This is the largest analytical epidemiological study of the effects of low-dose protracted exposures to ionizing radiation to date. Further studies will be important to better assess the role of tobacco and other occupational exposures in our risk estimates.
    Radiation Research 05/2007; 167(4):396-416. DOI:10.1667/RR0553.1 · 2.45 Impact Factor
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    C. Hill, P. This, F. Doyon
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    ABSTRACT: Objectifs pédagogiques Connaître la fréquence du cancer du sein. Définir risque relatif et risque absolu. Connaître les facteurs de risque de cancer du sein. Savoir évaluer le risque de cancer du sein chez une patiente. Connaître la fréquence du cancer du sein en France. Comprendre les difficultés à mesurer un risque : savoir la différence entre risque absolu et risque relatif, savoir qu’il faut toujours préciser la durée sur laquelle on évalue le risque. Connaître les facteurs de risque du cancer du sein et savoir par combien ils multiplient le risque. Avoir compris les enjeux de la détermination du risque individuel du cancer du sein (adaptation de la surveillance, aide à la décision (ex. du THS de la ménopause, chirurgie prophylactique). Connaître les facteurs cliniques pertinents pour déterminer le niveau de risque en pratique, pour une patiente : âge, antécédents chirurgicaux (HCA, néoplasie lobulaire in situ, antécédents familiaux de cancer du sein ou de l’ovaire, autres facteurs de risque). Connaître les indications et les modalités des consultations d’oncogénétique. Savoir distinguer les femmes à très haut risque génétique et les femmes à risque familial. Connaître l’existence des tables de déterminations du risque (tables de Claus) et des modèles disponibles (modèle de Gail ou de Tyrer).
    Journal de Radiologie 10/2005; 86(10):1186-1186. DOI:10.1016/S0221-0363(05)74910-6 · 0.57 Impact Factor
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    ABSTRACT: To provide direct estimates of risk of cancer after protracted low doses of ionising radiation and to strengthen the scientific basis of radiation protection standards for environmental, occupational, and medical diagnostic exposures. Multinational retrospective cohort study of cancer mortality. Cohorts of workers in the nuclear industry in 15 countries. 407 391 workers individually monitored for external radiation with a total follow-up of 5.2 million person years. Estimates of excess relative risks per sievert (Sv) of radiation dose for mortality from cancers other than leukaemia and from leukaemia excluding chronic lymphocytic leukaemia, the main causes of death considered by radiation protection authorities. The excess relative risk for cancers other than leukaemia was 0.97 per Sv, 95% confidence interval 0.14 to 1.97. Analyses of causes of death related or unrelated to smoking indicate that, although confounding by smoking may be present, it is unlikely to explain all of this increased risk. The excess relative risk for leukaemia excluding chronic lymphocytic leukaemia was 1.93 per Sv (< 0 to 8.47). On the basis of these estimates, 1-2% of deaths from cancer among workers in this cohort may be attributable to radiation. These estimates, from the largest study of nuclear workers ever conducted, are higher than, but statistically compatible with, the risk estimates used for current radiation protection standards. The results suggest that there is a small excess risk of cancer, even at the low doses and dose rates typically received by nuclear workers in this study.
    BMJ (online) 07/2005; 331(7508):77. DOI:10.1136/bmj.38499.599861.E0 · 16.38 Impact Factor
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    The Lancet 05/2005; 365(9472):1684–1685. DOI:10.1016/S0140-6736(05)66539-7 · 39.21 Impact Factor
  • C Hill, F Doyon
    Revue d Épidémiologie et de Santé Publique 05/2005; 53(2):205-8. · 0.66 Impact Factor
  • C Hill, F Doyon
    Revue d Épidémiologie et de Santé Publique 05/2005; 53(2):209-10. · 0.66 Impact Factor
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    ABSTRACT: The aim of this multicenter trial was to evaluate the role of ovarian suppression in patients with early breast cancer previously treated with local surgery and adjuvant chemotherapy. Nine hundred and twenty-six premenopausal patients with completely resected breast cancer and either axillary node involvement or histological grade 2 or 3 tumors were randomized after surgery to adjuvant chemotherapy alone (control arm) or adjuvant chemotherapy plus ovarian suppression (ovarian suppression arm). Ovarian suppression was obtained by either radiation-induced ovarian ablation or triptorelin for 3 years. The analyses were performed with Cox models stratified by center. Median follow-up was 9.5 years. Mean age was 43 years. Ninety per cent of patients had histologically proven positive axillary nodes, 63% positive hormonal receptors and 77% had received an anthracycline-based chemotherapy regimen. Ovarian suppression was by radiation-induced ovarian ablation (45% of patients) or with triptorelin (48%). At the time of randomization, all patients had regular menses or their follicle-stimulating hormone and estradiol levels indicated a premenopausal status. The 10-year disease-free survival rates were 49% [95% confidence interval (CI) 44% to 54%] in both arms (P = 0.51). The 10-year overall survival rates were 66% (95% CI 61% to 70%) for the ovarian suppression arm and 68% (95% CI 63% to 73%) for the control arm (P = 0.19). There were no variations in the treatment effect according to age, hormonal receptor status or ovarian suppression modality. However, in patients <40 years of age and with estrogen receptor-positive tumors, ovarian suppression significantly decreased the risk of recurrence (P = 0.01). The results of this trial, after at least 10 years of follow-up, do not favor the use of ovarian suppression after adjuvant chemotherapy. The potential beneficial effect in younger women with hormono-dependent tumors should be further assessed.
    Annals of Oncology 04/2005; 16(3):389-96. DOI:10.1093/annonc/mdi085 · 6.58 Impact Factor
  • Revue d Épidémiologie et de Santé Publique 04/2005; 66(2):179-180. DOI:10.1016/S1775-8785(05)79062-7 · 0.66 Impact Factor
  • C. Hill, F. Doyon
    Revue d Épidémiologie et de Santé Publique 04/2005; 53(2):209-210. DOI:10.1016/S0398-7620(05)84590-0 · 0.66 Impact Factor
  • C. Hill, F. Doyon
    Revue d Épidémiologie et de Santé Publique 04/2005; 53(2):205-208. DOI:10.1016/S0398-7620(05)84589-4 · 0.66 Impact Factor
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    ABSTRACT: We studied the effect of adjuvant anthracycline-based chemotherapy in postmenopausal patients with resected early breast cancer treated with adjuvant tamoxifen. The trial included 835 patients with either axillary lymph node involvement, or tumors with histological grade II or III. They were randomized after local surgery to receive either tamoxifen (TAM group) or tamoxifen plus chemotherapy (TAM-CT group) consisting of six courses of 5-fluorouracil, doxorubicin and cyclophosphamide (FAC), or 5-fluorouracil, epidoxorubicin and cyclophosphamide (FEC). Radiotherapy was given after completion of adjuvant chemotherapy in the TAM-CT group and after surgery in the TAM group. The 5-year disease-free survival (DFS) rates were 73% in the TAM group and 79% in the TAM-CT group (log-rank test, P = 0.06). The 5-year overall survival rates were 82% and 87%, respectively (P = 0.06). The 5-year distant metastasis rates were 22% and 16% (P = 0.02), and the 5-year local recurrence rates were 6% and 4%, respectively (P = 0.23). There were no significant differences for contralateral breast cancer or other new primary malignancies. Chemotherapy tended to be more effective for patients who had tumors without estrogen receptors (trend test, P = 0.05). Anthracycline-based chemotherapy administered to postmenopausal patients receiving adjuvant tamoxifen gave a borderline significant benefit on overall and DFS, mainly by a reduction in distant metastases. Delaying radiotherapy after six courses of chemotherapy did not affect local control after up to 10 years of follow-up.
    Annals of Oncology 10/2002; 13(9):1378-86. DOI:10.1093/annonc/mdf299 · 6.58 Impact Factor