Jean-Pierre Gérard's research while affiliated with Université Côte d'Azur and other places

Publications (163)

Article
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Background and Purpose Breast intra operative radiation therapy has been evaluated with different systems delivering 20 - 21 Gy with treatment times around 30 minutes. Papillon + TM Contact X-ray machine was designed to produce a 50 kVp beam with a high dose rate ≥ 15 Gy/minute. A pilot study with the first prototype was conducted in Nice. Materia...
Article
Background The impact of the tumour volume or size on achieving clinical complete response (cCR) after radio(chemo)therapy is poorly understood. Materials and methods A literature search was performed to gather data on the predictive value of baseline tumour volume or size in achieving cCR. Results In total, nine reports were identified. In two o...
Article
3512 Background: The OPERA trial was testing the hypothesis that Contact x-ray brachytherapy (CXB) 50 kV boost will increase the rectal preservation rate in early T2-T3ab rectal adenocarcinoma. We present the 3 years clinical results. Methods: Inclusion criteria were: Age > 18 years, PS: 0-1, adenocarcinoma, distal - middle rectum, cT2-T3ab cN0-N1...
Article
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Background and Purpose Tumor recurrence, a characteristic of malignant tumors, is the biggest concern for rectal cancer survivors. The epidemiology of the disease calls for a pressing need to improve healthcare quality and patient outcomes. Prediction models such as Bayesian networks, which can probabilistically reason under uncertainty, could assi...
Article
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Rectal adenocarcinoma is a quite radioresistant tumor. In order to achieve non-operative management (NOM) radiotherapy plays a major role. Targeted radiotherapy aiming at high precision 3D radiotherapy uses stereotactic image-guided external beam radiotherapy machines. To further safely increase the tumor dose, endocavitary brachytherapy (ECB) is a...
Article
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Purpose To issue consensus recommendations for contact X-Ray brachytherapy (CXB) for rectal cancer covering pre-treatment evaluation, treatment, dosimetric issues and follow-up. These recommendations cover CXB in the definitive and palliative setting. Methods Members of GEC ESTRO with expertise in rectal contact X-Ray brachytherapy issued consensu...
Article
Multimodal treatment strategies for patients with rectal cancer are increasingly including the possibility of organ preservation, through nonoperative management or local excision. Organ preservation strategies can enable patients with a complete response or near-complete clinical responses after radiotherapy with or without concomitant chemotherap...
Article
Introduction Early rectal cancers are increasingly diagnosed through screening programmes and are often treated using local excision (LE). In the case of adverse pathological features completion total mesorectal excision surgery (TME) is the standard recommendation. The morbidity and mortality risks of TME have stimulated the use of adjunctive trea...
Article
12 Background: Non-operative modality (NOM) treatment of rectal cancer is gaining popularity as it avoids extirpative TME surgery and a stoma. OPERA trial was set up to evaluate the role of dose escalation using Contact X-ray brachytherapy [CXB] in improving the chance of organ preservation compared to the standard of care (EBCRT and TME surgery)....
Article
Background Watch and wait is a novel management strategy in patients with rectal cancer who have a clinical complete response after neoadjuvant chemoradiotherapy. Surveillance of these patients is generally intensive, because local regrowth (with the potential for salvage) occurs in 25% of patients, and distant metastases occur in 10% of patients....
Article
Purpose: Optimal timing of surgery after neoadjuvant chemoradiotherapy (Nad-CRT) is still controversial in locally advanced rectal cancer (LARC). The primary goal of this study was to determine the best surgical interval (SI) to achieve the highest rate of pathological complete response (pCR) and secondly to evaluate the effect on surgical complic...
Article
Purpose: No biomarker to personalize treatment in locally advanced rectal cancer (LARC) is currently available. We assessed in LARC whether a diagnostic biopsy-adapted Immunoscore (ISB) could predict response to neoadjuvant treatment (nT) and better define patients eligible to an organ preservation strategy ("Watch-and-Wait"). Experimental design...
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Introduction A neoadjuvant treatment aimed at rectal preservation should achieve a clinical complete response. This study comparing neoadjuvant treatment initiated with Contact X-ray (CXB) or External Beam radiotherapy (EBRT) is evaluating the influence of the time/dose parameter on clinical response during the first six months. Materials and meth...
Article
4074 Background: Neoadjuvant CRT with fluoropyrimidine (FP) is standard treatment for LARC, which is increasing in younger patients (pts). RCTs examining the addition of OX are still controversial. A post hoc analysis of the CAO/ARO/AIO-04 trial showed significant benefit in pts < 60y. We hypothesised that younger pts with LARC might have improved...
Article
We examined whether 66 germline single nucleotide polymorphisms (SNPs) in 10 candidate genes would predict clinical outcome in 316 patients with resectable locally advanced rectal cancer (LARC) enrolled in the ACCORD‐12 phase III trial who were randomly treated with preoperative radiotherapy plus capecitabine (CAP45; n=155) or dose‐intensified radi...
Article
2628 Background: We investigated whether an adaptation to rectal biopsies of the recently validated consensus Immunoscore, could predict the response to neoadjuvant treatment and delineate clinical responders that could benefit from a “Watch and Wait” (W&W) strategy with acceptable outcomes. Methods: Initial biopsies from 273 patients with locally...
Article
Background Neoadjuvant chemoradiotherapy (nCRT) and watch-and-wait policy as reported by Habr-Gama are references for organ preservation in rectal cancer. To increase the clinical complete response (cCR) and reduce the local recurrence rates, we report a retrospective analysis of a prospective cohort of selected T2-3 tumours treated in three French...
Article
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Purpose: The aim of this study was to evaluate the efficacy and toxicity of high-dose-rate brachytherapy (HDR-BT) boost in anal squamous cell carcinoma (ASCC). Material and methods: This was a monocentric retrospective study involving patients treated by external irradiation (± chemotherapy), with HDR-BT boost, for a localized ASCC. Clinical eva...
Article
Purpose A clinical complete response is seen after neoadjuvant chemoradiation for rectal tumors in 15%–20% of patients. These patients can potentially be spared mutilating total mesorectal excision surgery through a watch-and-wait policy. Recent studies show that dose escalation by a radiation boost increases the clinical complete response rate. Th...
Article
With an expanding elderly population and median rectal cancer detection age of 70 years, the prevalence of rectal cancer in elderly patients is increasing. Management is based on evidence from younger patients, resulting in substandard treatments and poor outcomes. Modern management of rectal cancer in the elderly demands patient-centered treatment...
Article
Background: The strategy of watch and wait (W&W) in patients with rectal cancer who achieve a complete clinical response (cCR) after neoadjuvant therapy is new and offers an opportunity for patients to avoid major resection surgery. However, evidence is based on small-to-moderate sized series from specialist centres. The International Watch & Wait...
Article
751 Background: The Lyon R96-02 randomized trial has demonstrated in T2-3 rectal cancer that external beam radiotherapy (EBRT) with Contact X Ray brachytherapy (CXB) boost was increasing clinical complete response, sphincter preservation and in early cases organ preservation. We report French experience in 3 radiotherapy departments using CXB boost...
Article
e15151 Background: We examined whether 133 germline polymorphisms (SNPs) in 15 candidate genes (CSF1R, IL8RA, TLR4, IL10, IL10RA, CTLA4, IL2, IL2RA, TGF b1, ICOS, IL13, IL13RA2, IFNgR, IL15 and IL15RA) would predict clinical outcome in the ACCORD-12 phase III trial which randomly compared neoadjuvant radiotherapy (RT) plus capecitabine (CAP45) with...
Article
Background: Contact X-ray brachytherapy (CXB) has been used at Centre Antoine Lacassagne since 2002 to increase the chance of conservative treatment (organ or sphincter preservation) in rectal cancer. A consecutive series of 112 patients (pts) is reported. Methods: Three protocols were used in selected rectal adenocarcinomas. Group 1: T1 N0 trea...
Article
Introduction: This document is a summary of the French Intergroup guidelines regarding the management of rectal adenocarcinoma published in February 2016. Method: This collaborative work, under the auspices of most of the French medical societies involved in the management of rectal cancer, is based on the previous guidelines published in 2013....
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The authors regret that the name of the co-author Salvatore Pucciarelli was misspelt in the original version of this article. The correct spelling is Salvatore Pucciarelli as given here. The authors would like to apologise for any inconvenience caused.
Article
Introduction: Patients with metastatic colorectal cancer (CRC) may present with oligometastatic lung lesions for which stereotactic ablative radiotherapy (SABR) can be utilized. This study aims to report efficacy and prognostic factors associated with colorectal lung metastases treated with SABR. Material and methods: This is a retrospective stu...
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Primary treatment of rectal cancer was the focus of the second St. Gallen European Organisation for Research and Treatment of Cancer (EORTC) Gastrointestinal Cancer Conference. In the context of the conference, a multidisciplinary international expert panel discussed and voted on controversial issues which could not be easily answered using publish...
Data
An increase in population of cells in G2/M phase caused by raising Fas expression level requires the phenolic hydroxyl group of Y232. SW480 cells stably overexpressing V5-tagged Fas wild type and Y232 mutant proteins with equivalent Fas surface expression were subjected to cell cycle analysis based on DNA content. Data shown are mean ± SEM values o...
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Demonstrations of both pro-apoptotic and pro-survival abilities of Fas (TNFRSF6/CD95/APO-1) have led to a shift from the exclusive "Fas apoptosis" to "Fas multisignals" paradigm and the acceptance that Fas-related therapies face a major challenge, as it remains unclear what determines the mode of Fas signaling. Through protein evolution analysis, w...
Data
FasL-induced proliferation is promoted by Y291D mutation. (A) Cell viability assay showing that FasL can activate cell proliferation. SW480 cells were synchronized to G1 phase by serum deprivation for 24 h and then left untreated or treated with indicated sublethal doses of soluble FasL (sFasL) for 48 h before viability measurement by WST-1 assay....
Data
Y283F mutation in murine Fas did not inhibit Fas/FasL complex uptake in murine T cells. L1210 cells stably expressing wild type or Y283F murine Fas were subjected to synchronized internalization assay as described previously [22,43]. Briefly, crosslinked FasL was allowed to bind to the cell surface at 4°C before the internalization was triggered by...
Data
Y232 and Y291 residues of Fas can be phosphorylated by SFKs, Src and Yes-1. Phospho-protein mobility shift detection that separated phospho-proteins based on their charges showed that overexpressing Src (left panels) or Yes-1 (right panels) in SW480 cells increased pY232 and pY291 Fas levels. SW480 cells were transiently transfected with control ve...
Data
Features of amino acids used in the site-directed mutagenesis. (TIF)
Data
Numerical values underlying the quantitative summary in the main and supplementary figures. Numerical values for Figs 2B, 2D, 3A–3D, 4A, 4C, 4E, 5A–5C, 6A, 6B, 6D, 6E, 7A–7D, S1B, S1C, S6A–S6C, S9 and S10 are presented. The data are shown for each figure panel in a separate worksheet. (XLSX)
Data
Supplementary Information. Lists of materials and methods, information concerning rectal cancer biopsies, and accession numbers of proteins referred to in the main text. (DOCX)
Article
490 Background: The ACCORD 12 randomized trial was aiming at improving ypCR by increasing the radiation dose and adding oxaliplatin (OX) to a standard RT 45 Gy with concurrent capecitabine. On short term benefit of OX was not demonstrated (Gérard JP et al. J Clin Oncol. 2010;28:1638-44) at 3 years no significant difference in clinical outcome was a...
Article
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Local excision for early rectal cancer allows rectal conservation without morbidity compared to total mesorectal excision. This strategy is indicated in patients with tumors selected on clinical and EUS criteria (usTis and usT1). Different surgical and endoscopic procedures are currently used to perform local excision with an advantage to TEM. The...
Chapter
Over the past century, surgery has been the mainstay of rectal cancer management and will remain so for the foreseeable future. However, surgical mortality and morbidity is high, especially for the elderly patients. The population is ageing globally, the effect being more pronounced in Western countries. It is important to avoid extirpative surgery...
Article
Purpose: The Lyon R90-01 randomized trial investigated whether the interval between preoperative radiation therapy and surgery influenced rectal cancer outcome. Long-term results are reported here after a median follow-up of 17 years. Methods and materials: Between February 1991 and December 1995, 210 patients from 29 French centers were randoml...
Article
Rectal cancers stages II–III are presenting many various clinical situations. Neoadjuvant chemoradiotherapy is a standard of care in many cases, and in association with TME surgery, local relapses are becoming uncommon. None of these neoadjuvant treatments have so far improved survival, and quality of life remains non-optimal after abdomino-perinea...
Article
Depending on its location or stage, rectal cancer may differ significantly. Before any treatment decision a careful work up is mandatory relying mainly on endoscopy and imaging (MRI). Surgery according to the TME principle is the cornerstone of treatment. Most of the time surgery is associated with external beam radiotherapy often combined with con...
Article
During the ACCORD 12 randomized trial, an evaluation of the clinical tumor response was prospectively performed after neoadjuvant chemoradiotherapy. The correlations between clinical complete response and patient characteristics and treatment outcomes are reported. Between 2005 and 2008 the Accord 12 trial accrued 598 patients with locally advanced...
Article
In France, around 400,000 persons are occupationaly exposed to ionizing radiations especially in the field of medicine or industry (nuclear plant or other). Outside of accident the effective doses received are low and below the natural annual exposure dose in Paris (2,5 mSv). Epidemiological studies show that in the occupational environment the exc...
Article
676 Background: Organ preservation (avoiding TME surgery) for T2 T3 a-b rectal cancer is a field of active clinical research. Contact X Ray CXB combined with external beam radiotherapy (EBRT) ± concurrent chemotherapy (CRT) is an attractive method to achieve clinical complete response (cCR) and consequently rectal preservation. We report an overvie...
Chapter
This chapter provides a literature overview and several clinical examples illustrating the different radiological presentations of rectal cancer. Contouring and treatment planning approaches are reviewed and dose distributions for common scenarios are presented.
Article
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AimTo assess clinical outcomes of patients treated with a high-dose rate brachytherapy boost for anal canal cancer (ACC).Methods From August 2005 to February 2013, 28 patients presenting an ACC treated by split-course external beam radiotherapy (EBRT) and HDR brachytherapy with or without chemotherapy in a French regional cancer center in Nice were...
Article
Introduction Les cancers du bas rectum sont considérés de moins bon pronostic que ceux du moyen rectum, mais les raisons restent controversées. Le but du travail était de comparer le pronostic des cancers du moyen et du bas rectum, et de déterminer les facteurs pronostiques à partir des données de l’essai ACCORD12/0405 PRODIGE2. Patients et méthod...
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In locally advanced rectal cancer a preoperative predictive biomarker is necessary to adjust treatment specifically for those patients expected to suffer relapse. We applied whole genome methylation CpG island array analyses to an initial set of patients (n=11) to identify differentially methylated regions (DMRs) that separate a good from a bad pro...
Article
This study aimed to determine the candidate genes and chromosomal imbalances capable of predicting occurrences of metastasis in patients with rectal cancer. Fresh frozen tumor tissues from 80 patients with rectal cancer were prospectively collected and analyzed using Affymetrix HG-U133 Plus 2.0 gene expression arrays and high-resolution Illumina si...
Article
Rectal cancer predominantly affects the elderly. Unfortunately, this age category is under-represented in clinical trials because clinicians are loath to include patients with a high risk of comorbidity. An exploratory analysis of the ACCORD12/PRODIGE 2 phase III trial was carried out to retrospectively compare the benefit of neoadjuvant chemothera...
Article
The treatment of anal cancer is based on concomitant radiotherapy and chemotherapy and is associated with a nonnegligible rate of local severe toxicities that can strongly impair the quality of life. A retrospective analysis was performed to screen the following factors as potential predictive factors for local skin and digestive toxicities, and as...
Article
Purpose: To evaluate the efficacy of irradiation of internal mammary nodes (IMN) on 10-year overall survival in breast cancer patients after mastectomy. Methods and patients: This multicenter phase 3 study enrolled patients with positive axillary nodes (pN+) or central/medial tumors with or without pN+. Other inclusion criteria were age <75 and...
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Abstract | Radiotherapy has been driven by constant technological advances since the discovery of X‑rays in 1895. Radiotherapy aims to sculpt the optimal isodose on the tumour volume while sparing normal tissues. The benefits are threefold: patient cure, organ preservation and cost-efficiency. The efficacy and tolerance of radiotherapy were demonst...
Article
PURPOSEThe ACCORD 12 trial investigated the value of two different preoperative chemoradiotherapy (CT-RT) regimens in T3-4 Nx M0 resectable rectal cancer. Clinical results are reported after follow-up of 3 years. PATIENTS AND METHODS Between November 2005 and July 2008, a total of 598 patients were randomly assigned to preoperative CT-RT with CAP45...
Chapter
Brachytherapy is a generic term to describe radionuclide “curietherapy,” usually performed with iridium 192 or contact X-ray 50 kV (CXRT) to deliver radiation dose with a short (brachy) FSD (focus skin distance) of 6 cm or less for rectal cancer. Iridium 192 can be used either with an endoluminal approach or with an interstitial perineal implant. C...
Article
Circumferential resection margin (CRM) appears as a new powerful prognostic factor of survival after surgery for rectal cancer. We aimed to evaluate predictive factors of positive CRM following preoperative radiochemotherapy in a French trial. Patients with rectal cancer were randomised in long course preoperative radiotherapy 45Gy plus capecitabin...
Article
A differential responsiveness of patients to ionizing radiation is observed after preoperative radiotherapy for rectal adenocarcinoma that might be related, in part, to an apoptosis defect. To establish if proteins of the apoptotic cascades [pro-apoptotic: active caspase 3, 8, and 9 and DIABLO (direct inhibitor of apoptosis-binding protein with low...
Article
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Surgery remains the standard of care for most rectal cancer as it offers the best chance of cure. However, for patients with early stage low rectal cancers there are several treatment options available using novel radiotherapy techniques. Good responders to novel radiotherapy can avoid surgery. Poor responders need salvage surgery. Patient selectio...
Article
Full-text available
Surgery remains the standard of care for most rectal cancer as it offers the best chance of cure. However, for patients with early stage low rectal cancers there are several treatment options available using novel radiotherapy techniques. Good responders to novel radiotherapy can avoid surgery. Poor responders need salvage surgery. Patient selectio...
Article
Full-text available
Concomitant radiochemotherapy (RCT) is the standard for locally advanced anal canal carcinoma (LAACC). Questions regarding the role of induction chemotherapy (ICT) and a higher radiation dose in LAACC are pending. Our trial was designed to determine whether dose escalation of the radiation boost or two cycles of ICT before concomitant RCT lead to a...
Article
556 Background: This trial was designed to test the role of a radiation dose escalation to increase conservative treatment in distal rectal cancer. The early results showed a significant increase of sphincter saving surgery (Gerard JP et al. J Clin Oncol. 2004;22:2404-2409). We present here clinical results with a 10 years follow up. Methods: Betwe...
Article
667 Background: Treatment of anal cancer is based on combined radiotherapy and chemotherapy (CT). Some patients present early (<2 months) and late (>2 months) toxicities of grade 3 or greater which can strongly impair quality of life. We aimed to identify predictive factors of toxicities in 106 patients treated in a single center between January 20...
Article
465 Background: Some studies have suggested colon and rectal cancer as two different entities when considering DNA mutations or chromosomal imbalances. We therefore wondered if two colon gene expression signatures could predict specific survival. We also tested the influence of chromosomal imbalancies on prognosis in rectal cancer. Methods: Between...
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389 Background: The main end point of this trial was pathological response and published in 2010. We present the main clinical outcome after 3 years follow up. Methods: A total of 598 patients were included by 56 different French institutions between 2005 and 2008. Inclusion criteria were: resectable rectal adenocarcinoma accessible to digital exam...
Article
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The purpose of this study was to develop accurate models and nomograms to predict local recurrence, distant metastases, and survival for patients with locally advanced rectal cancer treated with long-course chemoradiotherapy (CRT) followed by surgery and to allow for a selection of patients who may benefit most from postoperative adjuvant chemother...
Article
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Contact x-ray therapy (CXRT) with 50 kV has proven to be an efficient radiation therapy technique to achieve local control and rectal preservation for early rectal adenocarcinoma. Despite these results, CXRT has not been used due to the shortage of the no longer manufactured Philips RT 50™ unit. Recently, a new CXRT machine (Papillon 50™) became av...
Article
To retrospectively assess the clinical outcome in anal cancer patients treated with split-course radiation therapy and boosted through external-beam radiation therapy (EBRT) or brachytherapy (BCT). From January 2000 to December 2004, a selected group (162 patients) with invasive nonmetastatic anal squamous cell carcinoma was studied. Tumor staging...
Article
To evaluate the benefit of prophylactic inguinal irradiation (PII) in anal canal squamous cell carcinoma (ASCC). This retrospective study analyzed the outcome of 208 patients presenting with ASCC treated between 2000 and 2004 in four cancer centers of the south of France. The population study included 35 T1, 86 T2, 59 T3, 20 T4, and 8 T stage unkno...
Chapter
Radical cystectomy, with a pelvic lymph-node dissection, is considered the standard treatment for invasive bladder cancer. The optimal goals of treatment for any invasive bladder cancer should include long-term survival, prevention of both pelvic relapse and development of metastases and an excellent quality of life. This treatment has achieved exc...
Article
A common hypothesis is that neo-adjuvant treatment in rectal cancer, is able to increase sphincter saving surgery. This review studies data relevant to this question. A total of 17 randomized trials were analysed. Since 1976, the rate of sphincter saving surgery increased from 20% to 75%. In none of the 17 trials it was possible to demonstrate a si...
Article
Full-text available
Contact x-ray therapy (CXRT) with 50 kV has proven to be an efficient radiation therapy technique to achieve local control and rectal preservation for early rectal adenocarcinoma. Despite these results, CXRT has not been used due to the shortage of the no longer manufactured Philips RT 50™ unit. Recently, a new CXRT machine (Papillon 50™) became av...
Article
Surgery is the main treatment of rectal adenocarcinoma. After careful digital examination, rectoscopy and work-up, treatment decision is taken, in agreement with an informed patient according to the tumor stage. Early T1-2 tumors are treated with surgery first. Advanced T3-4 tumors are treated with pre-operative chemo-radiation often using the "CAP...
Article
Neoadjuvant chemoradiotherapy is considered a standard approach for T3-4 M0 rectal cancer. In this situation, we compared neoadjuvant radiotherapy plus capecitabine with dose-intensified radiotherapy plus capecitabine and oxaliplatin. We randomly assigned patients to receive 5 weeks of treatment with radiotherapy 45 Gy/25 fractions with concurrent...