Background: Breast cancer (BC) management in older women requires an individual approach and is b... more Background: Breast cancer (BC) management in older women requires an individual approach and is becoming increasingly topical given the aging population. Postoperative radiation therapy (RT) is a standard treatment of BC after breast-conserving-surgery in most patients but its relative benefit may be counteracted by potential side-effects, especially in elderly. The aim of this study was to assess acute and long-term radiation-induced toxicities and the impact of comorbidities on outcomes in the older women treated by RT for non-metastatic breast cancer. Materials and Methods: Women aged ≥ 70 years at diagnosis, who received exclusive or postoperative RT for primary non-metastatic breast cancer, including carcinoma in situ, between 2003 and 2009 were retrieved from the Institut Curie registry. We calculated the Charlson Comorbidity Index (CCI) for each patient and collected the cardiovascular risk factors other than age (hypertension, dyslipidemia, smoking status). We analyzed overa...
HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Distributed under a Creative Commons Attribution-NoDerivatives| 4.0 International License
s Ophthalmologica 2013;230(suppl 1):1–30 DOI: 10.1159/000354999 2 Main Session 2: Neovascular AMD... more s Ophthalmologica 2013;230(suppl 1):1–30 DOI: 10.1159/000354999 2 Main Session 2: Neovascular AMD A Clinical Understanding of Anti-VEGF Therapy
Background Outcome of HER2-positive metastatic breast cancer (MBC) patients has improved since th... more Background Outcome of HER2-positive metastatic breast cancer (MBC) patients has improved since the use of trastuzumab. However, most HER2-positive MBC patients will progress within 1 year of trastuzumab-based therapy. Only limited data are available concerning long-term responders. Methods The primary objective of this study was to compare overall survival (OS) of HER2+ MBC patients with long-term response to first-line trastuzumab with overall survival of those with non-long-term response, based on two institutional databases: the French Epidemiological Strategy and Medical Economics program and the Breast Database. Long-term responders (LTR) were defined as patients with non-progressive disease for ≥ 2 years on first-line trastuzumab. Secondary objectives included progression-free survival (PFS), and predictive factors for LTR status. Results From 2004 to 2014, 422 HER2-positive MBC patients received first-line trastuzumab. With a median follow-up of 48 months, median OS and PFS were 63 months (CI95%, 50-71), and 18 months (CI95%, 15-21) respectively. In 111 patients (26.3%) classified as LTR, median OS was 110 months (CI95%, 95-not reached) versus 56 months in non-LTR patients (CI95%, 47-68). In multivariate logistic regressions, the following factors were independently associated with LTR status: number of metastatic sites (≤ 2 versus > 2, p = 0.01); endocrine therapy for metastatic disease (p = 0.001) and taxane-based first-line chemotherapy (p = 0.003). Conclusion Several features are associated with long-term response to trastuzumab: few metastatic sites, taxane-based chemotherapy and maintenance endocrine therapy in HR+ patients. Further studies are needed to identify patients in whom trastuzumab can be stopped after several years of sustained response.
Purpose: To report the results of a randomised study comparing the efficacy of Hydrosorb® versus ... more Purpose: To report the results of a randomised study comparing the efficacy of Hydrosorb® versus control (water based spray) in the topical treatment of grade 1 and 2 radiation dermatitis in population of patients treated for early stage breast cancer (BC) with normo fractionated radiotherapy (RT). Patients and Methods: Breast cancer patients with grade 1-2 radio-induced dermatitis during normo fractionated postoperative radiotherapy were eligible (according to the CTCAE v3 scale). They were randomised to receive either Hydrosorb® (A) or water based spray (B). The primary endpoint was local treatment failure defined as interruption of radiotherapy because of skin radiotoxicity or and/or change of local cares for skin alteration. Secondary endpoints were the evaluation of skin colorimetry, pain, and quality of life. Pain was assessed according to two classes with a VAS cut-off of 2. Results: Two-hundred seventy eight patients were enrolled (A = 142, B = 136). There were 186 successfu...
Objectif de l'étude.-Analyser les cancers secondaires observés dans une série de 675 patients pri... more Objectif de l'étude.-Analyser les cancers secondaires observés dans une série de 675 patients pris en charge par une curiethérapie de prostate par implants permanents entre 1999 et 2003, et comparer leur incidence à celle attendue dans une population générale correspondante en France. Matériel et méthodes.-La cohorte étudiée a inclus des patients à bas risque et une sélection de patients de risque intermédiaire « favorable ». Tous ont été pris en charge de manière homogène par une curiethérapie prostatique par grains libres d'iode 125, utilisant une technique en temps réel. La dose prescrite était de 145 Gy. Le suivi moyen est de 132 mois. Résultats.-La probabilité de survie globale à 10 ans était de 92 % (intervalle de confiance [IC] à 95 % : 90-94). La survie sans récidive à 10 ans est de 82 % (IC 95 % : 79-85). Soixante-et-un cancers secondaires ont été observés. La comparaison avec une population franç aise de mêmes structure d'âge et sexe a montré un rapport d'incidence (standard incidence ratio [SIR]) pour le cancer de vessie de 1,02 (IC 95 % : 0,46-1,93). Pour le cancer colorectal, le rapport d'incidence était de 0,45 (IC 95 % : 0,19-0,89). Pour le cancer du poumon, le rapport d'incidence était de 0,38 (IC 95 % : 0,17-0,76). Le rapport d'incidence pour l'ensemble des cancers était de 0,61 (IC 95 % : 0,47-0,79). En excluant les cancers colorectaux et pulmonaires (tous les deux avec des rapports très bas), le rapport d'incidence était de 1,06 (IC 95 % : 0,77-1,29). Conclusion.-Avec un suivi moyen de plus de 11 ans, l'analyse de cette série n'a détecté aucun excès de risque de seconds cancers après une curiethérapie par implants permanents. Le manque de puissance statistique ne permet pas, cependant, d'éliminer formellement une discrète augmentation du risque de cancer secondaire.
Background: Despite of therapeutics progress in advanced breast cancer, brain metastases occurren... more Background: Despite of therapeutics progress in advanced breast cancer, brain metastases occurrence remain a frequent and delicate situation. The efficacy of whole-brain radiation therapy (WBRT), still considered as the standard local treatment in case of multiple brain metastases, is limited. Recently, several phase II studies have shown some efficacy of the association of WBRT and temozolomide (TMZ), an oral alkylating agent already known as a radiosensitizer, with improved brain control rate (44 to 96%). Patients with breast cancer were underrepresented and none of these trials have studied this combined treatment issue in this specific population. The aim of this study was to assess the efficacy and safety of WBRT combined with temozolomide in the treatment of brain metastases from breast cancer. Materials and Methods: A prospective randomized multicenter phase II study was developed, using a modified two-stage Fleming design. Patients with newly diagnosed intraparenchymal brain...
To describe the results of retinoblastoma treatment from 1995-2009 in a single institution. Retro... more To describe the results of retinoblastoma treatment from 1995-2009 in a single institution. Retrospective review of the charts of patients treated for retinoblastoma. Clinical characteristics at diagnosis, treatments and outcomes in terms of survival and ocular preservation are described. During the study period 826 children were referred for retinoblastoma and 730 were managed in our institution. Four hundred and eleven children presented with unilateral retinoblastoma and 319 with bilateral retinoblastoma. Median follow-up is of 93 months. Global survival is 98.5% of children, 10 children presented with second tumors, 11 children died (6 of tumor-related causes). Of the 411 children with unilateral retinoblastoma enucleation was needed at diagnosis for 324 (78.8%). Conservative treatments were attempted for 87 patients (21.2%) and ocular preservation obtained for 65 patients (74% of eyes). Three hundred and nineteen patients presented with bilateral retinoblastoma. Three hundred and ten could be treated conservatively for at least one eye. Initial intravenous chemotherapy was necessary for 75% of them. Ocular preservation without external beam radiation was possible for 221 patients (70%). The use of EBR decreased significantly after 2004 (9.1% of eyes vs 25.1%: P<0.001). Management and treatment of retinoblastoma are complex, adapted to the extent of the disease. Survival is good. Enucleation is still required for extensive ocular disease, especially for unilateral patients. Intravenous chemotherapy allows good tumor control and eye preservation and decrease the need of EBR. Retinoblastoma treatment with intravenous chemotherapy and ocular adjuvant therapies is very effective on the local tumor control and eye preservation.
(similar to grade 1) and one with a bad prognosis (similar to grade 3). We therefore also raised ... more (similar to grade 1) and one with a bad prognosis (similar to grade 3). We therefore also raised the question if a single proliferative factor, i.e. cyclin A, can be used for this purpose. Material and Methods: In 219 consecutive premenopausal node negative patients, cyclin A was determined with immunohistochemistry on tissue microarray. High cyclin A was defined as the 7 th decile of positive cells. Only 13% of the patients received adjuvant systemic therapy. Cox proportional hazards regression was used to model the impact of the prognostic factors on distant disease-free survival (DDFS). Due to nonproportional hazards, the analysis was restricted to the first five years after diagnosis, a time period during which 34 patients developed distant recurrences. Results: Cyclin A was associated to DDFS in univariate analysis (hazard ratio (HR) 3.6, 95% confidence interval (CI): 1.8−7.1, p < 0.001). Corresponding HR:s were 2.7 for Ki67 (95% CI: 1.3−5.5, p = 0.005) and 2.7 for grade 3 vs 1+2 (95% CI: 1.3−5.2, p = 0.004). HER2, age, ER and progesterone receptor were also significant factors, whereas tumor size was not. Cyclin A could divide histological grade 2 into two groups with significantly different DDFS (HR: 15, 95% CI: 4.3−52, p < 0.001). In the grade 1 and 3 subgroups, cyclin A was not a prognostic factor. When subdividing according to ER status, cyclin A was a prognostic factor in the ER positive subgroup, but not in the ER negative (HR: 5.8, 95% CI: 2.2−16, p < 0.001) vs. 1.5 (95% CI: 0.6−3.9, p = 0.44). In multivariate analysis, cyclin A was an independent prognostic factor for DDFS (HR: 2.9, 95% CI: 1.2−7.0, p = 0.018), together with HER2 and age. Due to colinearity, histological grade and Ki67 were not included in the same model. Conclusion: In this study cyclin A was an independent prognostic factor for premenopausal patients with node-negative breast cancer, but only in the ER positive subgroup. Similar to gene expression analyses, cyclin A can subdivide histological grade 2 breast cancer into two groups with different prognosis. Taken together, cyclin A may be an alternative or a complement to histological grade and Ki67 for prognostic considerations.
Background: Adjuvant! Online is a web-based application designed to provide 10 years survival pro... more Background: Adjuvant! Online is a web-based application designed to provide 10 years survival probability of patients with breast cancer. Several predictors have not been assessed in the original Adjuvant! Online study. We provide the validation of Adjuvant! Online algorithm on two breast cancer datasets, and we determined whether the accuracy of Adjuvant! Online is improved with other well-known prognostic factors. Patients and Methods: The French data set is composed of 456 women with early breast cancer. The Dutch data set is composed of 295 women less than 52 years of age. Agreement between observation and Adjuvant! Online prediction was checked, and logistic models were performed to estimate the prognostic information added by risk factors to Adjuvant! Online prediction. Results: Adjuvant! Online prediction was overall well-calibrated in the French data set but failed in some subgroups of such high grade and HER2 positive patients. HER2 status, Mitotic Index and Ki67 added significant information to Adjuvant! Online prediction. In the Dutch data set, the overall 10-year survival was overestimated by Adjuvant! Online, particularly in patients less than 40 years old. Conclusion: Adjuvant! Online needs to be updated to adjust overoptimistic results in young and high grade patients, and should consider new predictors such as Ki67, HER2 and Mitotic Index.
Purpose: To determine whether exclusive radiotherapy (ERT) could be an option after complete clin... more Purpose: To determine whether exclusive radiotherapy (ERT) could be an option after complete clinical response (cCR) to neoadjuvant chemotherapy (NCT) for early breast cancers (EBC).Patients and methods: Between 1985 and 1999, 1477 patients received NCT for EBC considered to be too large for primary conservative surgery. Of 165 patients with cCR, 65 were treated by breast surgery (with radiotherapy) and 100 by ERT.Results: The two groups were comparable in terms of baseline characteristics, except for larger initial tumor sizes in the ERT group. There were no significant differences in overall, disease-free and metastasis-free survivals. Five-year and 10-year overall survivals were 91% and 77% in the no surgery group and 82% and 79% in the surgery group, respectively (p = 0.9). However, a non-significant trend towards higher locoregional recurrence rates (LRR) was observed in the no surgery group (31% vs. 17% at 10 years; p = 0.06). In patients with complete responses on mammography...
Introduction: AdjuvantOnline is a web-based application designed to provide 10 years survival pro... more Introduction: AdjuvantOnline is a web-based application designed to provide 10 years survival probability patients with breast cancer. Few validation studies have underlined some limitations, particularly an overestimation of the prognosis among certain subgroups of patients. Moreover, several predictors such as HER2 over expression status and proliferation markers have not been assessed in Adjuvant! original study. We provide the validation of AdjuvantOnline algorithm on two breast cancer datasets collected from two large European cancer centres, and we determined whether the accuracy of AdjuvantOnline is improved by others well known prognostic factors. Material and Methods: The French data set is composed of 456 women with early breast cancer, treated at the Institut Curie between 1995 and 1996. The dutch data set is composed of 295 women less that 52 years treated at the Netherlands Cancer Institute between 1984 and 1995. Agreement between observation and Adjuvant! prediction wa...
Background: To identify ER+ve ERBB2-ve ductal T1T2N0 carcinomas associated with a poor prognosis ... more Background: To identify ER+ve ERBB2-ve ductal T1T2N0 carcinomas associated with a poor prognosis remains challenging. We have previously demonstrated that the number of chromosomal breakpoints assessed by CGH could be a marker of worse outcome for breast carcinomas. Our aim was to validate the CGH based signature in a series of luminal ductal and T1T2 N0 carcinoma patients with long-term clinical follow-up. Patients and methods: We analyzed 214 patients treated for an invasive ductal ER+ve ERBB2-ve carcinomas, smaller than 30mm. The training set was composed of 109 patients (10.9 years of median follow-up; 30 cases associated with a metastatic event within less than 4 years/79 control cases with no metastastic event at 5 years) and the validation set of 105 patients (10.5 years of median follow-up; 30 relapses including contra-lateral breast carcinomas, loco-regional relapses and 8 metastatic events). None of the patient received adjuvant chemotherapy. 16 received an adjuvant hormon...
This prospective study was designed to validate a questionnaire on patients&amp;amp;amp;amp;a... more This prospective study was designed to validate a questionnaire on patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; perception of care quality during respiratory-gated radiotherapy for breast or lung cancer. Psychometric tests were performed on selected patients. Confirmatory factorial analyses and capacity to discriminate the responses were achieved to validate the best model on 297 patients. Factorial analyses identified the following three scales: (a) perception of quality, (b) global satisfaction, and (c) physical or emotional experience. The scales were able to differentiate patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; responses according to radiotherapy modalities. The questionnaire presented adequate psychometric properties. This tool could be used for the assessment from the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s point of view.
ABSTRACT Purpose Since 2005 we have used more intensive chemotherapy, combined with intensive loc... more ABSTRACT Purpose Since 2005 we have used more intensive chemotherapy, combined with intensive local treatment started at the third cycle in case of bilateral group D or group D+E bilateral retinoblastoma. We report the results Methods All children identified with bilaterally advanced retinoblastoma were treated with 6 courses of 3 drugs. Local treatments including laser, cryotherapy and sometimes iodine plaque brachytherapy were started at the third cycle, synergistic with the chemotherapy. All tumors except the macular tumors were treated with laser during 5 to 20 minutes. The inferior periphery was treated with cryotherapy . After the end of the chemotherapy, close follow up was performed and additional local treatments were often necessary. Data concerning the initial findings, treatments and results were entered in the data base. Results : the follow up ranges from 3 to 8 years with a mean follow up of five years. Between 2005 and 2010 23 group D eyes were treated in 16 children.17 eyes are preserved without external beam (73%) One eye is lost to follow up. Visual acuity is available in 11 children ranging from counting fingers to 20/20 with a mean visual acuity of 20/50. Conclusion Intravenous chemotherapy associated with intensive local treatments allows preservation of the eye with usefull vision in a great pourcentage of group D eyes.
Estimating the prognostic effect of a time-dependent covariate could be tricky using a classical ... more Estimating the prognostic effect of a time-dependent covariate could be tricky using a classical Cox model, despite adjustment on other known prognostic factors. This study evaluated and compared the performance of a Cox model including the covariate occurring over time as a time-dependent covariate and the so-called 'illness-death' multistate model, which is usually used to describe event-history data. We assess breast cancer prognosis related to a subsequent pregnancy occurring over time after cancer treatment in young women. We generated simulations. We considered constant and time-varying prognostic hazard ratios (HR.t /) between patients undergoing the intermediate event and those who did not. We used both the classical Cox model and the multistate model to estimate the prognostic effect of the intermediate event HR.t /. We also used the latter to estimate the covariate effect on each transition .exp.ˇi j //, thus helping to interpret HR.t / by taking into account the disease history. We applied these approaches to a female cohort treated and followed up in eight French Hospitals since 1990.
Introduction In 2014, the RD IV should not be correlated to the output (OS) and affect the OS onl... more Introduction In 2014, the RD IV should not be correlated to the output (OS) and affect the OS only indirectly through its effect on the treatment. We used “Activity level of FCCC”, which represents the number of cases in the whole database per contributing FCCC as IV with five strata. Analysis was carried out with the two-stage residual inclusion method (2SRI). For the quasi-trial analysis, the idea is to use a “superficial” randomized trial using variables, for example centers, reflecting a definite preferences for certain treatment options. Indeed, comparisons of results between centers can be informative and it is likely such differential preferences exist in real-life practice. In this study, we have considered the percentage of patients with bevacizumab + paclitaxel in each center, regardless of treatment arm. Results In the first analysis published by Delaloge and al., the OS adjusted for major prognostic factors was significantly longer in the paclitaxel and bevacizumab group...
Background: Breast cancer (BC) management in older women requires an individual approach and is b... more Background: Breast cancer (BC) management in older women requires an individual approach and is becoming increasingly topical given the aging population. Postoperative radiation therapy (RT) is a standard treatment of BC after breast-conserving-surgery in most patients but its relative benefit may be counteracted by potential side-effects, especially in elderly. The aim of this study was to assess acute and long-term radiation-induced toxicities and the impact of comorbidities on outcomes in the older women treated by RT for non-metastatic breast cancer. Materials and Methods: Women aged ≥ 70 years at diagnosis, who received exclusive or postoperative RT for primary non-metastatic breast cancer, including carcinoma in situ, between 2003 and 2009 were retrieved from the Institut Curie registry. We calculated the Charlson Comorbidity Index (CCI) for each patient and collected the cardiovascular risk factors other than age (hypertension, dyslipidemia, smoking status). We analyzed overa...
HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Distributed under a Creative Commons Attribution-NoDerivatives| 4.0 International License
s Ophthalmologica 2013;230(suppl 1):1–30 DOI: 10.1159/000354999 2 Main Session 2: Neovascular AMD... more s Ophthalmologica 2013;230(suppl 1):1–30 DOI: 10.1159/000354999 2 Main Session 2: Neovascular AMD A Clinical Understanding of Anti-VEGF Therapy
Background Outcome of HER2-positive metastatic breast cancer (MBC) patients has improved since th... more Background Outcome of HER2-positive metastatic breast cancer (MBC) patients has improved since the use of trastuzumab. However, most HER2-positive MBC patients will progress within 1 year of trastuzumab-based therapy. Only limited data are available concerning long-term responders. Methods The primary objective of this study was to compare overall survival (OS) of HER2+ MBC patients with long-term response to first-line trastuzumab with overall survival of those with non-long-term response, based on two institutional databases: the French Epidemiological Strategy and Medical Economics program and the Breast Database. Long-term responders (LTR) were defined as patients with non-progressive disease for ≥ 2 years on first-line trastuzumab. Secondary objectives included progression-free survival (PFS), and predictive factors for LTR status. Results From 2004 to 2014, 422 HER2-positive MBC patients received first-line trastuzumab. With a median follow-up of 48 months, median OS and PFS were 63 months (CI95%, 50-71), and 18 months (CI95%, 15-21) respectively. In 111 patients (26.3%) classified as LTR, median OS was 110 months (CI95%, 95-not reached) versus 56 months in non-LTR patients (CI95%, 47-68). In multivariate logistic regressions, the following factors were independently associated with LTR status: number of metastatic sites (≤ 2 versus > 2, p = 0.01); endocrine therapy for metastatic disease (p = 0.001) and taxane-based first-line chemotherapy (p = 0.003). Conclusion Several features are associated with long-term response to trastuzumab: few metastatic sites, taxane-based chemotherapy and maintenance endocrine therapy in HR+ patients. Further studies are needed to identify patients in whom trastuzumab can be stopped after several years of sustained response.
Purpose: To report the results of a randomised study comparing the efficacy of Hydrosorb® versus ... more Purpose: To report the results of a randomised study comparing the efficacy of Hydrosorb® versus control (water based spray) in the topical treatment of grade 1 and 2 radiation dermatitis in population of patients treated for early stage breast cancer (BC) with normo fractionated radiotherapy (RT). Patients and Methods: Breast cancer patients with grade 1-2 radio-induced dermatitis during normo fractionated postoperative radiotherapy were eligible (according to the CTCAE v3 scale). They were randomised to receive either Hydrosorb® (A) or water based spray (B). The primary endpoint was local treatment failure defined as interruption of radiotherapy because of skin radiotoxicity or and/or change of local cares for skin alteration. Secondary endpoints were the evaluation of skin colorimetry, pain, and quality of life. Pain was assessed according to two classes with a VAS cut-off of 2. Results: Two-hundred seventy eight patients were enrolled (A = 142, B = 136). There were 186 successfu...
Objectif de l'étude.-Analyser les cancers secondaires observés dans une série de 675 patients pri... more Objectif de l'étude.-Analyser les cancers secondaires observés dans une série de 675 patients pris en charge par une curiethérapie de prostate par implants permanents entre 1999 et 2003, et comparer leur incidence à celle attendue dans une population générale correspondante en France. Matériel et méthodes.-La cohorte étudiée a inclus des patients à bas risque et une sélection de patients de risque intermédiaire « favorable ». Tous ont été pris en charge de manière homogène par une curiethérapie prostatique par grains libres d'iode 125, utilisant une technique en temps réel. La dose prescrite était de 145 Gy. Le suivi moyen est de 132 mois. Résultats.-La probabilité de survie globale à 10 ans était de 92 % (intervalle de confiance [IC] à 95 % : 90-94). La survie sans récidive à 10 ans est de 82 % (IC 95 % : 79-85). Soixante-et-un cancers secondaires ont été observés. La comparaison avec une population franç aise de mêmes structure d'âge et sexe a montré un rapport d'incidence (standard incidence ratio [SIR]) pour le cancer de vessie de 1,02 (IC 95 % : 0,46-1,93). Pour le cancer colorectal, le rapport d'incidence était de 0,45 (IC 95 % : 0,19-0,89). Pour le cancer du poumon, le rapport d'incidence était de 0,38 (IC 95 % : 0,17-0,76). Le rapport d'incidence pour l'ensemble des cancers était de 0,61 (IC 95 % : 0,47-0,79). En excluant les cancers colorectaux et pulmonaires (tous les deux avec des rapports très bas), le rapport d'incidence était de 1,06 (IC 95 % : 0,77-1,29). Conclusion.-Avec un suivi moyen de plus de 11 ans, l'analyse de cette série n'a détecté aucun excès de risque de seconds cancers après une curiethérapie par implants permanents. Le manque de puissance statistique ne permet pas, cependant, d'éliminer formellement une discrète augmentation du risque de cancer secondaire.
Background: Despite of therapeutics progress in advanced breast cancer, brain metastases occurren... more Background: Despite of therapeutics progress in advanced breast cancer, brain metastases occurrence remain a frequent and delicate situation. The efficacy of whole-brain radiation therapy (WBRT), still considered as the standard local treatment in case of multiple brain metastases, is limited. Recently, several phase II studies have shown some efficacy of the association of WBRT and temozolomide (TMZ), an oral alkylating agent already known as a radiosensitizer, with improved brain control rate (44 to 96%). Patients with breast cancer were underrepresented and none of these trials have studied this combined treatment issue in this specific population. The aim of this study was to assess the efficacy and safety of WBRT combined with temozolomide in the treatment of brain metastases from breast cancer. Materials and Methods: A prospective randomized multicenter phase II study was developed, using a modified two-stage Fleming design. Patients with newly diagnosed intraparenchymal brain...
To describe the results of retinoblastoma treatment from 1995-2009 in a single institution. Retro... more To describe the results of retinoblastoma treatment from 1995-2009 in a single institution. Retrospective review of the charts of patients treated for retinoblastoma. Clinical characteristics at diagnosis, treatments and outcomes in terms of survival and ocular preservation are described. During the study period 826 children were referred for retinoblastoma and 730 were managed in our institution. Four hundred and eleven children presented with unilateral retinoblastoma and 319 with bilateral retinoblastoma. Median follow-up is of 93 months. Global survival is 98.5% of children, 10 children presented with second tumors, 11 children died (6 of tumor-related causes). Of the 411 children with unilateral retinoblastoma enucleation was needed at diagnosis for 324 (78.8%). Conservative treatments were attempted for 87 patients (21.2%) and ocular preservation obtained for 65 patients (74% of eyes). Three hundred and nineteen patients presented with bilateral retinoblastoma. Three hundred and ten could be treated conservatively for at least one eye. Initial intravenous chemotherapy was necessary for 75% of them. Ocular preservation without external beam radiation was possible for 221 patients (70%). The use of EBR decreased significantly after 2004 (9.1% of eyes vs 25.1%: P&lt;0.001). Management and treatment of retinoblastoma are complex, adapted to the extent of the disease. Survival is good. Enucleation is still required for extensive ocular disease, especially for unilateral patients. Intravenous chemotherapy allows good tumor control and eye preservation and decrease the need of EBR. Retinoblastoma treatment with intravenous chemotherapy and ocular adjuvant therapies is very effective on the local tumor control and eye preservation.
(similar to grade 1) and one with a bad prognosis (similar to grade 3). We therefore also raised ... more (similar to grade 1) and one with a bad prognosis (similar to grade 3). We therefore also raised the question if a single proliferative factor, i.e. cyclin A, can be used for this purpose. Material and Methods: In 219 consecutive premenopausal node negative patients, cyclin A was determined with immunohistochemistry on tissue microarray. High cyclin A was defined as the 7 th decile of positive cells. Only 13% of the patients received adjuvant systemic therapy. Cox proportional hazards regression was used to model the impact of the prognostic factors on distant disease-free survival (DDFS). Due to nonproportional hazards, the analysis was restricted to the first five years after diagnosis, a time period during which 34 patients developed distant recurrences. Results: Cyclin A was associated to DDFS in univariate analysis (hazard ratio (HR) 3.6, 95% confidence interval (CI): 1.8−7.1, p < 0.001). Corresponding HR:s were 2.7 for Ki67 (95% CI: 1.3−5.5, p = 0.005) and 2.7 for grade 3 vs 1+2 (95% CI: 1.3−5.2, p = 0.004). HER2, age, ER and progesterone receptor were also significant factors, whereas tumor size was not. Cyclin A could divide histological grade 2 into two groups with significantly different DDFS (HR: 15, 95% CI: 4.3−52, p < 0.001). In the grade 1 and 3 subgroups, cyclin A was not a prognostic factor. When subdividing according to ER status, cyclin A was a prognostic factor in the ER positive subgroup, but not in the ER negative (HR: 5.8, 95% CI: 2.2−16, p < 0.001) vs. 1.5 (95% CI: 0.6−3.9, p = 0.44). In multivariate analysis, cyclin A was an independent prognostic factor for DDFS (HR: 2.9, 95% CI: 1.2−7.0, p = 0.018), together with HER2 and age. Due to colinearity, histological grade and Ki67 were not included in the same model. Conclusion: In this study cyclin A was an independent prognostic factor for premenopausal patients with node-negative breast cancer, but only in the ER positive subgroup. Similar to gene expression analyses, cyclin A can subdivide histological grade 2 breast cancer into two groups with different prognosis. Taken together, cyclin A may be an alternative or a complement to histological grade and Ki67 for prognostic considerations.
Background: Adjuvant! Online is a web-based application designed to provide 10 years survival pro... more Background: Adjuvant! Online is a web-based application designed to provide 10 years survival probability of patients with breast cancer. Several predictors have not been assessed in the original Adjuvant! Online study. We provide the validation of Adjuvant! Online algorithm on two breast cancer datasets, and we determined whether the accuracy of Adjuvant! Online is improved with other well-known prognostic factors. Patients and Methods: The French data set is composed of 456 women with early breast cancer. The Dutch data set is composed of 295 women less than 52 years of age. Agreement between observation and Adjuvant! Online prediction was checked, and logistic models were performed to estimate the prognostic information added by risk factors to Adjuvant! Online prediction. Results: Adjuvant! Online prediction was overall well-calibrated in the French data set but failed in some subgroups of such high grade and HER2 positive patients. HER2 status, Mitotic Index and Ki67 added significant information to Adjuvant! Online prediction. In the Dutch data set, the overall 10-year survival was overestimated by Adjuvant! Online, particularly in patients less than 40 years old. Conclusion: Adjuvant! Online needs to be updated to adjust overoptimistic results in young and high grade patients, and should consider new predictors such as Ki67, HER2 and Mitotic Index.
Purpose: To determine whether exclusive radiotherapy (ERT) could be an option after complete clin... more Purpose: To determine whether exclusive radiotherapy (ERT) could be an option after complete clinical response (cCR) to neoadjuvant chemotherapy (NCT) for early breast cancers (EBC).Patients and methods: Between 1985 and 1999, 1477 patients received NCT for EBC considered to be too large for primary conservative surgery. Of 165 patients with cCR, 65 were treated by breast surgery (with radiotherapy) and 100 by ERT.Results: The two groups were comparable in terms of baseline characteristics, except for larger initial tumor sizes in the ERT group. There were no significant differences in overall, disease-free and metastasis-free survivals. Five-year and 10-year overall survivals were 91% and 77% in the no surgery group and 82% and 79% in the surgery group, respectively (p = 0.9). However, a non-significant trend towards higher locoregional recurrence rates (LRR) was observed in the no surgery group (31% vs. 17% at 10 years; p = 0.06). In patients with complete responses on mammography...
Introduction: AdjuvantOnline is a web-based application designed to provide 10 years survival pro... more Introduction: AdjuvantOnline is a web-based application designed to provide 10 years survival probability patients with breast cancer. Few validation studies have underlined some limitations, particularly an overestimation of the prognosis among certain subgroups of patients. Moreover, several predictors such as HER2 over expression status and proliferation markers have not been assessed in Adjuvant! original study. We provide the validation of AdjuvantOnline algorithm on two breast cancer datasets collected from two large European cancer centres, and we determined whether the accuracy of AdjuvantOnline is improved by others well known prognostic factors. Material and Methods: The French data set is composed of 456 women with early breast cancer, treated at the Institut Curie between 1995 and 1996. The dutch data set is composed of 295 women less that 52 years treated at the Netherlands Cancer Institute between 1984 and 1995. Agreement between observation and Adjuvant! prediction wa...
Background: To identify ER+ve ERBB2-ve ductal T1T2N0 carcinomas associated with a poor prognosis ... more Background: To identify ER+ve ERBB2-ve ductal T1T2N0 carcinomas associated with a poor prognosis remains challenging. We have previously demonstrated that the number of chromosomal breakpoints assessed by CGH could be a marker of worse outcome for breast carcinomas. Our aim was to validate the CGH based signature in a series of luminal ductal and T1T2 N0 carcinoma patients with long-term clinical follow-up. Patients and methods: We analyzed 214 patients treated for an invasive ductal ER+ve ERBB2-ve carcinomas, smaller than 30mm. The training set was composed of 109 patients (10.9 years of median follow-up; 30 cases associated with a metastatic event within less than 4 years/79 control cases with no metastastic event at 5 years) and the validation set of 105 patients (10.5 years of median follow-up; 30 relapses including contra-lateral breast carcinomas, loco-regional relapses and 8 metastatic events). None of the patient received adjuvant chemotherapy. 16 received an adjuvant hormon...
This prospective study was designed to validate a questionnaire on patients&amp;amp;amp;amp;a... more This prospective study was designed to validate a questionnaire on patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; perception of care quality during respiratory-gated radiotherapy for breast or lung cancer. Psychometric tests were performed on selected patients. Confirmatory factorial analyses and capacity to discriminate the responses were achieved to validate the best model on 297 patients. Factorial analyses identified the following three scales: (a) perception of quality, (b) global satisfaction, and (c) physical or emotional experience. The scales were able to differentiate patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; responses according to radiotherapy modalities. The questionnaire presented adequate psychometric properties. This tool could be used for the assessment from the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s point of view.
ABSTRACT Purpose Since 2005 we have used more intensive chemotherapy, combined with intensive loc... more ABSTRACT Purpose Since 2005 we have used more intensive chemotherapy, combined with intensive local treatment started at the third cycle in case of bilateral group D or group D+E bilateral retinoblastoma. We report the results Methods All children identified with bilaterally advanced retinoblastoma were treated with 6 courses of 3 drugs. Local treatments including laser, cryotherapy and sometimes iodine plaque brachytherapy were started at the third cycle, synergistic with the chemotherapy. All tumors except the macular tumors were treated with laser during 5 to 20 minutes. The inferior periphery was treated with cryotherapy . After the end of the chemotherapy, close follow up was performed and additional local treatments were often necessary. Data concerning the initial findings, treatments and results were entered in the data base. Results : the follow up ranges from 3 to 8 years with a mean follow up of five years. Between 2005 and 2010 23 group D eyes were treated in 16 children.17 eyes are preserved without external beam (73%) One eye is lost to follow up. Visual acuity is available in 11 children ranging from counting fingers to 20/20 with a mean visual acuity of 20/50. Conclusion Intravenous chemotherapy associated with intensive local treatments allows preservation of the eye with usefull vision in a great pourcentage of group D eyes.
Estimating the prognostic effect of a time-dependent covariate could be tricky using a classical ... more Estimating the prognostic effect of a time-dependent covariate could be tricky using a classical Cox model, despite adjustment on other known prognostic factors. This study evaluated and compared the performance of a Cox model including the covariate occurring over time as a time-dependent covariate and the so-called 'illness-death' multistate model, which is usually used to describe event-history data. We assess breast cancer prognosis related to a subsequent pregnancy occurring over time after cancer treatment in young women. We generated simulations. We considered constant and time-varying prognostic hazard ratios (HR.t /) between patients undergoing the intermediate event and those who did not. We used both the classical Cox model and the multistate model to estimate the prognostic effect of the intermediate event HR.t /. We also used the latter to estimate the covariate effect on each transition .exp.ˇi j //, thus helping to interpret HR.t / by taking into account the disease history. We applied these approaches to a female cohort treated and followed up in eight French Hospitals since 1990.
Introduction In 2014, the RD IV should not be correlated to the output (OS) and affect the OS onl... more Introduction In 2014, the RD IV should not be correlated to the output (OS) and affect the OS only indirectly through its effect on the treatment. We used “Activity level of FCCC”, which represents the number of cases in the whole database per contributing FCCC as IV with five strata. Analysis was carried out with the two-stage residual inclusion method (2SRI). For the quasi-trial analysis, the idea is to use a “superficial” randomized trial using variables, for example centers, reflecting a definite preferences for certain treatment options. Indeed, comparisons of results between centers can be informative and it is likely such differential preferences exist in real-life practice. In this study, we have considered the percentage of patients with bevacizumab + paclitaxel in each center, regardless of treatment arm. Results In the first analysis published by Delaloge and al., the OS adjusted for major prognostic factors was significantly longer in the paclitaxel and bevacizumab group...
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Papers by A. Savignoni