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Pancreatic Neoplasms: HELP
Articles by Florence Huguet
Based on 27 articles published since 2008
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Between 2008 and 2019, F. Huguet wrote the following 27 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline [Radiation therapy of pancreatic cancer]. 2016

Huguet, F / Mornex, F / Orthuon, A. ·Service d'oncologie radiothérapie, hôpital Tenon, 4, rue de la Chine, 75020 Paris, France. Electronic address: florence.huguet@aphp.fr. · Département d'oncologie radiothérapie, centre hospitalier Lyon Sud, 69000 Pierre-Bénite, France; EMR 3738, université Claude-Bernard Lyon 1, 69000 Lyon, France. · Unité de radiophysique, service de radiothérapie, hôpital Tenon, AP-HP, 75020 Paris, France. ·Cancer Radiother · Pubmed #27523418.

ABSTRACT: Currently, the use of radiation therapy for patients with pancreatic cancer is subject to discussion. In adjuvant setting, the standard treatment is 6 months of chemotherapy with gemcitabine and capecitabine. Chemoradiation (CRT) may improve the survival of patients with incompletely resected tumors (R1). This should be confirmed by a prospective trial. Neoadjuvant CRT is a promising treatment especially for patients with borderline resectable tumors. For patients with locally advanced tumors, there is no a standard. An induction chemotherapy followed by CRT for non-progressive patients reduces the rate of local relapse. Whereas in the first trials of CRT large fields were used, the treated volumes have been reduced to improve tolerance. Tumor movements induced by breathing should be taken in account. Intensity modulated radiation therapy allows a reduction of doses to the organs at risk. Whereas widely used, this technique is not recommended.

2 Guideline Radiotherapy technical considerations in the management of locally advanced pancreatic cancer: American-French consensus recommendations. 2012

Huguet, Florence / Goodman, Karyn A / Azria, David / Racadot, Severine / Abrams, Ross A. ·Department of Radiation Oncology, Tenon Hospital, APHP, University Paris VI, Paris, France. florence.huguet@tnn.aphp.fr ·Int J Radiat Oncol Biol Phys · Pubmed #22768988.

ABSTRACT: Pancreatic carcinoma is a leading cause of cancer-related mortality. Approximately 30% of pancreatic cancer patients present with locally advanced, unresectable nonmetastatic disease. For these patients, two therapeutic options exist: systemic chemotherapy or chemoradiotherapy. Within this context, the optimal technique for pancreatic irradiation is not clearly defined. A search to identify relevant studies was undertaken using the Medline database. All Phase III randomized trials evaluating the modalities of radiotherapy in locally advanced pancreatic cancer were included, as were some noncontrolled Phase II and retrospective studies. An expert panel convened with members of the Radiation Therapy Oncology Group and GERCOR cooperative groups to review identified studies and prepare the guidelines. Each member of the working group independently evaluated five endpoints: total dose, target volume definition, radiotherapy planning technique, dose constraints to organs at risk, and quality assurance. Based on this analysis of the literature, we recommend either three-dimensional conformal radiation therapy or intensity-modulated radiation therapy to a total dose of 50 to 54 Gy at 1.8 to 2 Gy per fraction. We propose gross tumor volume identification to be followed by an expansion of 1.5 to 2 cm anteriorly, posteriorly, and laterally, and 2 to 3 cm craniocaudally to generate the planning target volume. The craniocaudal margins can be reduced with the use of respiratory gating. Organs at risk are liver, kidneys, spinal cord, stomach, and small bowel. Stereotactic body radiation therapy should not be used for pancreatic cancer outside of clinical trials. Radiotherapy quality assurance is mandatory in clinical trials. These consensus recommendations are proposed for use in the development of future trials testing new chemotherapy combinations with radiotherapy. Not all of these recommendations will be appropriate for trials testing radiotherapy dose or dose intensity concepts.

3 Review Pancreatic cancer: French clinical practice guidelines for diagnosis, treatment and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, AFC). 2018

Neuzillet, Cindy / Gaujoux, Sébastien / Williet, Nicolas / Bachet, Jean-Baptiste / Bauguion, Lucile / Colson Durand, Laurianne / Conroy, Thierry / Dahan, Laetitia / Gilabert, Marine / Huguet, Florence / Marthey, Lysiane / Meilleroux, Julie / de Mestier, Louis / Napoléon, Bertrand / Portales, Fabienne / Sa Cunha, Antonio / Schwarz, Lilian / Taieb, Julien / Chibaudel, Benoist / Bouché, Olivier / Hammel, Pascal / Anonymous2561138 / Anonymous2571138 / Anonymous2581138 / Anonymous2591138 / Anonymous2601138 / Anonymous2611138 / Anonymous2621138 / Anonymous2631138 / Anonymous2641138 / Anonymous2651138. ·Department of Medical Oncology, Curie Institute, Versailles Saint-Quentin University (UVSQ), Saint-Cloud, France. Electronic address: cindy.neuzillet@gmail.com. · Department of Digestive, Hepato-Biliary and Pancreatic Surgery, Cochin Hospital, AP-HP, Paris Descartes Faculty of Medicine, Paris Descartes University, Sorbonne Paris Cité, Paris, France. · Hepato-Gastroenterology Department, University Hospital of Saint-Etienne, Saint Priest en Jarez, France. · Hepato-Gastroenterology Department, Pitié Salpétrière University Hospital, AP-HP, Paris Cedex 13, France. · Hepato-Gastroenterology Department, Departmental Hospital Center, La Roche sur Yon, France. · Department of Radiotherapy, Henri Mondor Hospital, AP-HP, Université Paris Est Creteil, Créteil, France. · Department of Medical Oncology, Lorraine Institute of Oncology and Lorraine University, Vandoeuvre-lès-Nancy Cedex, France. · Digestive Oncology Department, "DACCORD" (Digestif, Anatomie pathologique, Chirurgie, CISIH, Oncologie, Radiothérapie, Dermatologie) pole, CHU Timone, Marseille Cedex 05, France. · Paoli Calmettes Institute, Department of Medical Oncology and Cancer Research Center of Marseille (CRCM), INSERM U1068 Stress Cell, Aix-Marseille University, Marseille, France. · Department of Oncology and Radiotherapy, Tenon Hospital, East Paris University Hospitals, AP-HP, Paris Sorbonne University, Paris, France. · Gastroenterology Department, Béclère Hospital, AP-HP, Clamart, France. · Pathology Department, Toulouse University Hospital, Toulouse, France. · Department of Gastroenterology-Pancreatology, Beaujon Hospital, APHP, Paris 7 University, Clichy, France. · Jean Mermoz Private Hospital, Ramsay Générale de Santé, Lyon, France. · Digestive Oncology Department, Regional Institute of Cancer, Montpellier, France. · INSERM UMR 935, Paul Brousse Hospital, Hepatobiliary Center, AP-HP, Université Paris-Sud, Université Paris-Saclay, Villejuif, France. · Department of Digestive Surgery, Hôpital Charles Nicolle, Rouen University Hospital, Rouen, France and Genomic and Personalized Medicine in Cancer and Neurological Disorders, UMR 1245 INSERM, Rouen University, France. · Hepato-Gastroenterology and Digestive Oncology Department, Georges Pompidou European Hospital, AP-HP, Paris, France. · Department of Medical Oncology, Franco-British Institute, Levallois-Perret, France. · Hepato-Gastroenterology and Digestive Oncology Department, Robert Debré University Hospital, Avenue Général Koenig, 51092 Reims Cedex, France. · Department of Digestive Oncology, Beaujon University Hospital (AP-HP), Paris VII Diderot University, Clichy-la-Garenne, France. Electronic address: pascal.hammel@aphp.fr. ·Dig Liver Dis · Pubmed #30219670.

ABSTRACT: BACKGROUND: This document is a summary of the French intergroup guidelines regarding the management of pancreatic adenocarcinoma (PA), updated in July 2018. DESIGN: This collaborative work was produced under the auspices of all French medical and surgical societies involved in the management of PA. It is based on the previous guidelines, recent literature review and expert opinions. Recommendations were graded in three categories, according to the level of evidence. RESULTS: Over the last seven years, significant changes in PA management have been implemented in clinical practice. Imaging/staging: diffusion magnetic resonance imaging is useful before surgery to rule out small liver metastases. SURGERY: centralization of pancreatic surgery in expert centers is associated with a decreased postoperative mortality. Adjuvant chemotherapy: modified FOLFIRINOX in fit patients, or gemcitabine, or 5-FU, or gemcitabine plus capecitabine, to be discussed on a case-by-case basis. Locally advanced PA: no survival benefit of chemoradiotherapy. Metastatic PA: FOLFIRINOX and gemcitabine plus nab-paclitaxel combination are first-line standards in fit patients; second-line with 5FU/nal-IRI or 5FU/oxaliplatin combination after first-line gemcitabine. CONCLUSION: Guidelines for management of PA are continuously evolving and need to be regularly updated. This constant progress is made possible through clinical and translational research. However, as each individual case is particular, they cannot substitute to multidisciplinary tumor board discussion.

4 Review [Role of radiation therapy in the management of pancreatic cancer]. 2018

Huguet, F / Rivin Del Campo, E / Antoni, D / Vendrely, V / Hammel, P. ·Service d'oncologie radiothérapie, hôpital Tenon, hôpitaux universitaires Est Parisien, 4, rue de la Chine, 75020 Paris, France; Université Paris Sorbonne, 4, rue de la Chine, 75020 Paris, France. Electronic address: florence.huguet@aphp.fr. · Service d'oncologie radiothérapie, hôpital Tenon, hôpitaux universitaires Est Parisien, 4, rue de la Chine, 75020 Paris, France; Université Paris Sorbonne, 4, rue de la Chine, 75020 Paris, France. · Département universitaire de radiothérapie, centre Paul-Strauss, Unicancer, 3, rue de la Porte-de-l'Hôpital, 67065 Strasbourg cedex, France. · Service d'oncologie radiothérapie, hôpital Haut-Lévêque, CHU de Bordeaux, avenue de Magellan, 33604 Pessac, France. · Service d'oncologie digestive et médicale, hôpital Beaujon, AP-HP, 100, boulevard du Géneral-Leclerc, 92110 Clichy, France; Université Paris Diderot, 100, boulevard du Géneral-Leclerc, 92110 Clichy, France. ·Cancer Radiother · Pubmed #30100126.

ABSTRACT: At diagnosis, about 15% of patients with pancreatic cancer present with a resectable tumour, 50% have a metastatic tumour, and 25% a locally advanced tumor (non-metastatic but unresectable due to vascular invasion) or borderline resectable. Despite the technical progress made in the field of radiation therapy and the improvement of the efficacy of chemotherapy, the prognosis of these patients remains very poor. Recently, the role of radiation therapy in the management of pancreatic cancer has been much debated. This review aims to evaluate the role of radiation therapy for these patients.

5 Review Clinical applications of circulating tumor DNA and circulating tumor cells in pancreatic cancer. 2016

Riva, Francesca / Dronov, Oleksii I / Khomenko, Dmytro I / Huguet, Florence / Louvet, Christophe / Mariani, Pascale / Stern, Marc-Henri / Lantz, Olivier / Proudhon, Charlotte / Pierga, Jean-Yves / Bidard, Francois-Clement. ·Institut Curie, PSL Research University, SiRIC, Laboratory of Circulating Tumor Biomarkers, Paris, France; San Gerardo Hospital, Department of Medical Oncology, Monza, Italy. · Bogomolets National Medical University, Department of General Surgery No. 1, Kiev, Ukraine. · Hopital Tenon, Pierre and Marie Curie Paris VI University, Department of Radiation Oncology, Paris, France. · Institut Mutualiste Montsouris, Department of Medical Oncology, Paris, France. · Institut Curie, PSL Research University, Department of Surgery, Paris, France. · Institut Curie, PSL Research University, INSERM U830, Paris, France. · Institut Curie, PSL Research University, INSERM U932, Paris, France. · Institut Curie, PSL Research University, SiRIC, Laboratory of Circulating Tumor Biomarkers, Paris, France. · Institut Curie, PSL Research University, SiRIC, Laboratory of Circulating Tumor Biomarkers, Paris, France; Institut Curie, PSL Research University, Department of Medical Oncology, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France. · Institut Curie, PSL Research University, SiRIC, Laboratory of Circulating Tumor Biomarkers, Paris, France; Institut Curie, PSL Research University, Department of Medical Oncology, Paris, France. Electronic address: francois-clement.bidard@curie.fr. ·Mol Oncol · Pubmed #26856794.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is the most frequent pancreatic cancer type and is characterized by a dismal prognosis due to late diagnosis, local tumor invasion, frequent distant metastases and poor sensitivity to current therapy. In this context, circulating tumor cells and circulating tumor DNA constitute easily accessible blood-borne tumor biomarkers that may prove their clinical interest for screening, early diagnosis and metastatic risk assessment of PDAC. Moreover these markers represent a tool to assess PDAC mutational landscape. In this review, together with key biological findings, we summarize the clinical results obtained using "liquid biopsies" at the different stages of the disease, for early and metastatic diagnosis as well as monitoring during therapy.

6 Review Current standards and new innovative approaches for treatment of pancreatic cancer. 2016

Conroy, Thierry / Bachet, Jean-Baptiste / Ayav, Ahmet / Huguet, Florence / Lambert, Aurélien / Caramella, Caroline / Maréchal, Raphaël / Van Laethem, Jean-Luc / Ducreux, Michel. ·Department of Medical Oncology, Institut de Cancérologie de Lorraine and Lorraine University, 6 avenue de Bourgogne, CS 30519, 54519, Vandoeuvre-lès-Nancy, France. Electronic address: t.conroy@nancy.unicancer.fr. · Department of Hepato-Gastroenterology, Pitié-Salpétrière University Hospital, 47-83 boulevard de l'hôpital, 75651, Paris Cedex 13, France. · Department of Surgery, Nancy University Hospital Lorraine and Lorraine University, rue du Morvan, 54511, Vandoeuvre-lès Nancy, France. · Department of Radiation Therapy, Tenon Hospital, Paris Est University Hospitals, 4 rue de la Chine, 75020, Paris, France. · Department of Medical Oncology, Institut de Cancérologie de Lorraine and Lorraine University, 6 avenue de Bourgogne, CS 30519, 54519, Vandoeuvre-lès-Nancy, France. · Gustave Roussy Cancer Campus Grand Paris, 114 rue Edouard-Vaillant, 94805, Villejuif Cedex, France. · Department of Gastroenterology, Erasme University Hospital-ULB-Brussels, Lennikstreet 808, 1070, Brussels, Belgium. ·Eur J Cancer · Pubmed #26851397.

ABSTRACT: Pancreatic adenocarcinoma remains a devastating disease with a 5-year survival rate not exceeding 6%. Treatment of this disease remains a major challenge. This article reviews the state-of-the-art in the management of this disease and the new innovative approaches that may help to accelerate progress in treating its victims. After careful pre-therapeutic evaluation, only 15-20% of patients diagnosed with a pancreatic cancer (PC) are eligible for upfront radical surgery. After R0 or R1 resection in such patients, evidence suggests a significantly positive impact on survival of adjuvant chemotherapy comprising 6 months of gemcitabine or fluorouracil/folinic acid. Delayed adjuvant chemoradiation is considered as an option in cases of positive margins. Borderline resectable pancreatic cancer (BRPC) is defined as a tumour involving the mesenteric vasculature to a limited extend. Resection of these tumours is technically feasible, yet runs the high risk of a R1 resection. Neoadjuvant treatment probably offers the best chance of achieving successful R0 resection and long-term survival, but the best treatment options should be determined in prospective randomised studies. Gemcitabine has for 15 years been the only validated therapy for advanced PC. Following decades of negative phase III studies, increasing evidence now suggests that further significant improvements to overall survival can be achieved via either Folfirinox or gemcitabine + nab-paclitaxel regimens. Progress in systemic therapy may improve the chances of resection in borderline resectable pancreatic cancer (BRPC) or locally advanced PC. This requires first enhancing knowledge of the genetic events driving carcinogenesis, which may then be translated into clinical studies.

7 Review Locally advanced pancreatic cancer: the role of definitive chemoradiotherapy. 2014

Huguet, F / Mukherjee, S / Javle, M. ·Service d'Oncologie Radiothérapie, Hôpital Tenon, Hôpitaux Universitaires Est Parisien, Paris, France. Electronic address: florence.huguet@tnn.aphp.fr. · Gray Institute for Radiation Oncology and Biology, University of Oxford, NIHR Oxford Biomedical Research Centre, Oxford, UK. · Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. ·Clin Oncol (R Coll Radiol) · Pubmed #25001636.

ABSTRACT: At the time of diagnosis, around 20% of patients with pancreatic cancer present at a resectable stage, 50% have metastatic disease and 30% have locally advanced tumour, non-metastatic but unresectable because of superior mesenteric artery or coeliac encasement. Despite advances in chemoradiotherapy and improved systemic chemotherapeutic agents, patients with locally advanced pancreatic cancer suffer from high rates of distant metastatic failure and from local progression, with a median survival time ranging from 5 to 11 months. In the past 30 years, modest improvements in median survival have been attained for these patients treated by chemoradiotherapy or chemotherapy protocols. The optimal therapy for patients with locally advanced pancreatic carcinoma remains controversial. This review aims to evaluate the role of radiotherapy for these patients.

8 Review [Disseminated and circulating tumor cells in gastrointestinal oncology]. 2012

Vegas, Hélène / André, Thierry / Bidard, François-Clément / Ferrand, François-Régis / Huguet, Florence / Mariani, Pascale / Pierga, Jean-Yves. ·Institut Curie, 26, rue d'Ulm, 75005 Paris, France. helene.vegas@yahoo.com ·Bull Cancer · Pubmed #22531892.

ABSTRACT: Circulating (CTC) and disseminated tumor cells (DTC) represent two different steps of the metastatic process. As with other types of cancer, the recent development of techniques for the detection of CTC and DTC respectively in the blood and bone marrow of patients generated many results in digestive cancers. However, the interpretation of these results and of the prognostic value of CTC/DTC is often limited by the small cohort size and the heterogeneity of detection methods. The aim of this article is to review the different results and their clinical impact, and discuss the possible use of CTC and DTC as new biomarkers. First of all, it is important to take into account the variability of epithelial markers used for the initial stage of immunoselection of CTC/DTC as well as that of molecular or cytological markers used for the second stage of detection. In esophageal, gastric, pancreatic and hepatocellular carcinomas, and in the ileal and pancreatic neuroendocrine tumors, some studies showed a correlation between the detection of CTC and/or DTC and a clinical pejorative course, whether these tumors were at localized or metastatic stages. On colorectal cancer in the adjuvant setting, a recent meta-analysis showed an association between the detection of CTC in peripheral blood and disease-free survival or overall survival. These results are consistent with those of a study that identified detection of CTC as a prognostic factor for relapse in stage II. This last study concluded that it was necessary to achieve long-term evaluation of CTC as a biomarker to guide the decisions of chemotherapy for stage II. In metastatic colorectal cancer, the FDA approved in 2007 the use of pretherapeutic levels of CTC and its variations per-treatment, determined by CellSearch(®) technology, as a tool in treatments management. However, the modalities of this monitoring have to be specified and clinical benefit or the cost-effectiveness of a treatment based on this new biomarker has to be evaluated. Finally, the qualitative and quantitative monitoring of CTC could be a non-invasive tool to monitor changes in tumor biology throughout the disease, and thereby improve the understanding of the processes of dissemination and therapeutic resistance.

9 Review [New perspectives for radiosensitization in pancreatic carcinoma: a review of mechanisms involved in pancreatic tumorigenesis]. 2011

Huguet, F / Fernet, M / Monnier, L / Touboul, E / Favaudon, V. ·Service d'oncologie-radiothérapie, hôpital Tenon, Assistance publique-Hôpitaux de Paris, 4 rue de la Chine, Paris, France. florence.huguet@tnn.aphp.fr ·Cancer Radiother · Pubmed #21664851.

ABSTRACT: Pancreatic carcinoma is the fifth leading cause of cancer-related mortality. The 5-year overall survival is less than 5 %. This very poor prognosis can be explained both by late diagnosis and by treatment resistance, including resistance to radiation therapy. A better understanding of the pancreatic tumorigenesis and knowledge of the most frequent mutations in pancreatic adenocarcinoma (KRAS, p16, TP53, Smad4) open new perspectives for the development of more effective treatments. This review presents the major genetic and molecular alterations in pancreatic cancer that could be targeted to improve radiosensitization.

10 Review Chemoradiotherapy in the management of locally advanced pancreatic carcinoma: a qualitative systematic review. 2009

Huguet, Florence / Girard, Nicolas / Guerche, Clotilde Séblain-El / Hennequin, Christophe / Mornex, Françoise / Azria, David. ·Groupe Coopérateur Multidisciplinaire en Oncologie, Service d'Oncologie Radiothérapie, Hôpital Tenon, 4 rue de Chine, 75020 Paris, France. florence.huguet@tnn.aphp.fr ·J Clin Oncol · Pubmed #19307501.

ABSTRACT: PURPOSE: Pancreatic carcinoma is one of the leading causes of cancer-related mortality. At time of diagnosis, 30% of patients present with a locally advanced unresectable but nonmetastatic pancreatic carcinoma (LAPC). The French program Standards, Options, and Recommendations was promoted to conduct a qualitative systematic review to evaluate the role of radiotherapy in patients with LAPC. METHODS: A search to identify eligible studies was undertaken using the MEDLINE database. All phase III randomized trials and systematic reviews evaluating the role of radiotherapy in LAPC were included, together with some noncontrolled studies if no phase III trials were retrieved. The quality and clinical relevance of the studies were evaluated using validated checklists, which allowed associating each result with a level of evidence. RESULTS: Twenty-one studies were included, as follows: two meta-analyses, 13 randomized trials, and six nonrandomized trials. Chemoradiotherapy increases overall survival when compared with best supportive care (level of evidence C) or with exclusive radiotherapy (level B1), but is more toxic (level B1). Chemoradiotherapy is not superior to chemotherapy in terms of survival (level B1) and increases toxicity (level A). Recent data favor limited irradiation to the tumor volume (level C). Fluorouracil is still the reference chemotherapy in association with radiotherapy (level B1). Induction chemotherapy before chemoradiotherapy improves survival (level C). CONCLUSION: No standard treatment exists, but there are two options for treatment of LAPC; these are gemcitabine-based chemotherapy and chemoradiotherapy. Induction chemotherapy followed by a chemoradiotherapy is a promising strategy for selection of patients without early metastatic/progressing disease.

11 Review [The value of chemoradiotherapy in the management of locally advanced pancreatic adenocarcinoma: systematic review]. 2008

Azria, D / Seblain-El-Guerche, C / Girard, N / Hennequin, C / Huguet, F. ·Centre Val-d'Aurelle, 34298 Montpellier, France. ·Bull Cancer · Pubmed #19036684.

ABSTRACT: INTRODUCTION: At the request of the National Thesaurus of Gastrointestinal Cancer (TNCD), the SOR program undertaken by the French Federation of Cancer Centers (FNCLCC) and now led by the French National Cancer Institute (INCa), completed a systematic review to evaluate the value of chemoradiotherapy (CRT) in the management of locally advanced pancreatic adenocarcinoma in collaboration with clinician experts. METHODS: Results of a systematic literature search using Medline (from 1980 to 2008) were completed by a consult of evidence-based medicine websites. All phase III randomized trials and systematic reviews concerning non resectable locally advanced pancreatic adenocarcinoma and non metastatic (stage III) were included in the study. Some phase II trials were also included if no phase III trials were retrieved. The following interventions were compared: CRT versus best supportive care (BSC), CRT versus radiotherapy, and CRT versus chemotherapy. The modalities of CRT regimens and the sequences of chemotherapy-CRT versus CRT were also studied. The quality and clinical relevance of the trials were evaluated using validated checklists, allowing associating each result with a level of evidence. Data synthesis was performed considering both efficacy and toxicity outcomes for each intervention. RESULTS: Nineteen references were included in this systematic review: 2 meta-analyses, 11 randomized trials, 5 non-randomized trials and 1 randomized trial only published in abstract form. After a clinical and methodological critical appraisal, compared to the alternative BSC, concomitant CRT increases overall survival (C). Concomitant CRT compared to the radiotherapy alone increases the overall survival (B1) but is more toxic (B1). Concomitant CRT compared to chemotherapy alone is not superior in terms of survival (B1) and increases toxicity (A). Concerning administration modalities of radiotherapy, recent data are in favour to a limited irradiation to the tumoral volume (C) and to a total dose of 50-60 Gy in association with 5-FU. The study of radiotherapy associated drugs shows that 5-FU is the reference (B1) and the value of gemcitabine must be proved in randomized trials. Finally, the study of sequences chemotherapy-CRT has recently showed that induction chemotherapy before CRT improves survival (C). Validation of this strategy in a randomized trial is warranted. CONCLUSION: The use of CRT for locally advanced pancreatic adenocarcinoma is based on a few randomized trials even if this treatment appears superior in terms of survival compared to BSC and radiotherapy alone. This review shows the need to conduct other specific randomized trials in order to validate the value of CRT, especially compared to chemotherapy alone.

12 Clinical Trial Prognostic nomogram and score to predict overall survival in locally advanced untreated pancreatic cancer (PROLAP). 2016

Vernerey, Dewi / Huguet, Florence / Vienot, Angélique / Goldstein, David / Paget-Bailly, Sophie / Van Laethem, Jean-Luc / Glimelius, Bengt / Artru, Pascal / Moore, Malcolm J / André, Thierry / Mineur, Laurent / Chibaudel, Benoist / Benetkiewicz, Magdalena / Louvet, Christophe / Hammel, Pascal / Bonnetain, Franck. ·Methodological and Quality of Life in Oncology Unit, EA 3181, University Hospital of Besançon, 3 Boulevard Alexandre Fleming, Besançon 25030, France. · Oncology Multidisciplinary Research Group (GERCOR), 151 rue du Faubourg Saint Antoine, Paris 75011, France. · Department of Radiotherapy, Tenon Hospital (AP-HP), 4 rue de la Chine, Paris 75020, France. · Department of Gastroenterology, University Hospital of Besançon, 3 Boulevard Alexandre Fleming, Besançon 25030, France. · Department of Medical Oncology, Prince of Wales hospital and Prince of Wales Clinical school, UNSW, Sydney, New South Wales 2031, Australia. · AGITG (Australasian Gastrointestinal Trials Group), 119-143 Missenden Rd, Camperdown, New South Wales 2050, Australia. · Department of Gastroenterology, Erasme University Hospital, Route de Lennik 808, Brussels 1070, Belgium. · Department of Radiology, Oncology and Radiation Science, University of Uppsala, Uppsala 75105, Sweden. · Department of Gastroenterology, Jean Mermoz Hospital, 55 avenue Mermoz, Lyon 69008, France. · Department of Medical Oncology, Princess Margaret Hospital, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada. · Department of Medical Oncology, Saint-Antoine Hospital (AP-HP), 184 rue du Faubourg Saint Antoine, Paris 75011, France. · Department of Radiotherapy and Medical Oncology, Sainte-Catherine Institute, 250 Chemin de Baigne Pieds, Avignon 84918, France. · Department of Medical Oncology, Franco-British Hospital Institute, 3 Rue Barbès, Levallois-Perret 92300, France. · Department of Medical Oncology, Institute Mutualiste Montsouris, 42 Boulevard Jourdan, Paris 75014, France. · Department of Digestive Oncology, Beaujon Hospital (AP-HP), 100 boulevard du General Leclerc, Clichy 92110, France. ·Br J Cancer · Pubmed #27404456.

ABSTRACT: BACKGROUND: The management of locally advanced pancreatic cancer (LAPC) patients remains controversial. Better discrimination for overall survival (OS) at diagnosis is needed. We address this issue by developing and validating a prognostic nomogram and a score for OS in LAPC (PROLAP). METHODS: Analyses were derived from 442 LAPC patients enrolled in the LAP07 trial. The prognostic ability of 30 baseline parameters was evaluated using univariate and multivariate Cox regression analyses. Performance assessment and internal validation of the final model were done with Harrell's C-index, calibration plot and bootstrap sample procedures. On the basis of the final model, a prognostic nomogram and a score were developed, and externally validated in 106 consecutive LAPC patients treated in Besançon Hospital, France. RESULTS: Age, pain, tumour size, albumin and CA 19-9 were independent prognostic factors for OS. The final model had good calibration, acceptable discrimination (C-index=0.60) and robust internal validity. The PROLAP score has the potential to delineate three different prognosis groups with median OS of 15.4, 11.7 and 8.5 months (log-rank P<0.0001). The score ability to discriminate OS was externally confirmed in 63 (59%) patients with complete clinical data derived from a data set of 106 consecutive LAPC patients; median OS of 18.3, 14.1 and 7.6 months for the three groups (log-rank P<0.0001). CONCLUSIONS: The PROLAP nomogram and score can accurately predict OS before initiation of induction chemotherapy in LAPC-untreated patients. They may help to optimise clinical trials design and might offer the opportunity to define risk-adapted strategies for LAPC management in the future.

13 Clinical Trial Are fiducial markers useful surrogates when using respiratory gating to reduce motion of gastroesophageal junction tumors? 2016

Liu, Fenghong / Ng, Shu / Huguet, Florence / Yorke, Ellen D / Mageras, Gikas S / Goodman, Karyn A. ·a Department of Medical Physics , Memorial Sloan Kettering Cancer Center , New York , New York , USA ; · b Department of Radiation Oncology , Memorial Sloan Kettering Cancer Center , New York , New York , USA ; · c Department of Radiation Oncology , Hôpital Tenon , Paris , France. ·Acta Oncol · Pubmed #27152887.

ABSTRACT: BACKGROUND: Radiation therapy (RT) is an integral component of the management of gastroesophageal junction (GEJ) tumors. We evaluated the use of implanted radiopaque fiducials as tumor surrogates to allow for more focal delivery of RT to these mobile tumors when using respiratory gating (RG) to reduce motion. MATERIAL AND METHODS: We analyzed four-dimensional computed tomography scans of 20 GEJ patients treated with RG and assessed correlation between tumor and implanted fiducial motion over the whole respiratory cycle and within a clinically realistic gate around end-exhalation. We evaluated fiducial motion concordance in 11 patients with multiple fiducials. RESULTS: Gating reduced anterior-posterior (AP) and superior-inferior (SI) mean tumor and fiducial motions by over 50%. Fiducials and primary tumor motions were moderately correlated: R(2) for AP and SI linear fits to the entire group were 0.54 and 0.68, respectively, but the correlation had strong inter-patient variation. For all patients with multiple fiducials, relative in-gate displacements were below 3 mm; results were similar for eight of 11 patients over the whole cycle. CONCLUSION: Implanted fiducial and gross tumor volume (GTV) motions correlate well but the correlation is patient-specific and may be dependent on the location of the fiducials with respect to the GTV.

14 Clinical Trial Effect of Chemoradiotherapy vs Chemotherapy on Survival in Patients With Locally Advanced Pancreatic Cancer Controlled After 4 Months of Gemcitabine With or Without Erlotinib: The LAP07 Randomized Clinical Trial. 2016

Hammel, Pascal / Huguet, Florence / van Laethem, Jean-Luc / Goldstein, David / Glimelius, Bengt / Artru, Pascal / Borbath, Ivan / Bouché, Olivier / Shannon, Jenny / André, Thierry / Mineur, Laurent / Chibaudel, Benoist / Bonnetain, Franck / Louvet, Christophe / Anonymous6180866. ·Department of Digestive Oncology, Beaujon Hospital (AP-HP), Clichy, France. · Department of Radiotherapy, Tenon Hospital (AP-HP), Paris, France. · Department of Gastroenterology, Erasme University Hospital, Brussels, Belgium. · Department of Medical Oncology, Prince of Wales Hospital, Sydney, Australia5Australasian Gastrointestinal Trials Group (AGITG), Camperdown, Australia6Prince of Wales Clinical School, University of New South Wales, Sydney, Australia. · Department of Radiology, Oncology, and Radiation Science, University of Uppsala, Uppsala, Sweden. · Department of Gastroenterology, Jean Mermoz Hospital, Lyon, France. · Department of Gastroenterology, Saint-Luc University Clinics, Brussels, Belgium. · Department of Gastroenterology, Robert Debré Hospital, Reims, France. · Australasian Gastrointestinal Trials Group (AGITG), Camperdown, Australia6Prince of Wales Clinical School, University of New South Wales, Sydney, Australia11Department of Medical Oncology, Nepean Hospital NSW, Sydney, Australia. · Department of Medical Oncology, Saint-Antoine Hospital (AP-HP), Paris, France. · Department of Radiotherapy and Medical Oncology, Sainte-Catherine Institute, Avignon, France. · Department of Medical Oncology, Franco-British Hospital Institute, Levallois-Perret, France15Oncology Multidisciplinary Research Group (GERCOR), Paris, France. · Department of Methodology and Quality of Life in Oncology, Hospital Minjoz, Besançon, France. · Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France. ·JAMA · Pubmed #27139057.

ABSTRACT: IMPORTANCE: In locally advanced pancreatic cancer, the role of chemoradiotherapy is controversial and the efficacy of erlotinib is unknown. OBJECTIVES: To assess whether chemoradiotherapy improves overall survival of patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine-based induction chemotherapy and to assess the effect of erlotinib on survival. DESIGN, SETTING, AND PARTICIPANTS: In LAP07, an international, open-label, phase 3 randomized trial, 449 patients were enrolled between 2008 and 2011. Follow-up ended in February 2013. INTERVENTIONS: In the first randomization, 223 patients received 1000 mg/m2 weekly of gemcitabine alone and 219 patients received 1000 mg/m2 of gemcitabine plus 100 mg/d of erlotinib. In the second randomization involving patients with progression-free disease after 4 months, 136 patients received 2 months of the same chemotherapy and 133 underwent chemoradiotherapy (54 Gy plus capecitabine). MAIN OUTCOMES AND MEASURES: The primary outcome was overall survival from the date of the first randomization. Secondary outcomes were the effect of erlotinib and quality assurance of radiotherapy on overall survival, progression-free survival of gemcitabine-erlotinib and erlotinib maintenance with gemcitabine alone at the second randomization, and toxic effects. RESULTS: A total of 442 of the 449 patients (232 men; median age, 63.3 years) enrolled underwent the first randomization. Of these, 269 underwent the second randomization. Interim analysis was performed when 221 patients died (109 in the chemoradiotherapy group and 112 in the chemotherapy group), reaching the early stopping boundaries for futility. With a median follow-up of 36.7 months, the median overall survival from the date of the first randomization was not significantly different between chemotherapy at 16.5 months (95% CI, 14.5-18.5 months) and chemoradiotherapy at 15.2 months (95% CI, 13.9-17.3 months; hazard ratio [HR], 1.03; 95% CI, 0.79-1.34; P = .83). Median overall survival from the date of the first randomization for the 223 patients receiving gemcitabine was 13.6 months (95% CI, 12.3-15.3 months) and was 11.9 months (95% CI, 10.4-13.5 months) for the 219 patients receiving gemcitabine plus erlotinib (HR, 1.19; 95% CI, 0.97-1.45; P = .09; 188 deaths vs 191 deaths). Chemoradiotherapy was associated with decreased local progression (32% vs 46%, P = .03) and no increase in grade 3 to 4 toxicity, except for nausea. CONCLUSIONS AND RELEVANCE: In this open-label, randomized trial involving patients with locally advanced pancreatic cancer with disease controlled after 4 months of induction chemotherapy, there was no significant difference in overall survival with chemoradiotherapy compared with chemotherapy alone and there was no significant difference in overall survival with gemcitabine compared with gemcitabine plus erlotinib used as maintenance therapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00634725.

15 Clinical Trial Circulating tumor cells in locally advanced pancreatic adenocarcinoma: the ancillary CirCe 07 study to the LAP 07 trial. 2013

Bidard, F C / Huguet, F / Louvet, C / Mineur, L / Bouché, O / Chibaudel, B / Artru, P / Desseigne, F / Bachet, J B / Mathiot, C / Pierga, J Y / Hammel, P. ·Department of Medical Oncology, Institut Curie, Paris, France. fcbidard@curie.fr ·Ann Oncol · Pubmed #23676420.

ABSTRACT: BACKGROUND: Pancreatic carcinoma is one of the leading causes of cancer-related mortality. At the time of diagnosis, 30% of patients present with a locally advanced pancreatic carcinoma (LAPC). As circulating tumor cells (CTCs) count may be a surrogate of the cancer metastatic abilities, CTC detection rates and prognostic value were studied in a prospective cohort of LAPC patients. PATIENTS AND METHODS: An LAP07 international multicenter randomized study assesses in patients whose LAPC is controlled after 4 months of chemotherapy whether chemoradiotherapy could increase survival versus continuation of chemotherapy. A subgroup of patients included in the LAP07 trial was screened for CTCs (CellSearch®) before the start of the chemotherapy and after 2 months of treatment. Patient characteristics and survival were obtained prospectively and were correlated with CTC detection. RESULTS: Seventy-nine patients were included. One or more CTCs/7.5 ml were detected in 5% of patients before treatment and in 9% of patients after 2 months of treatment (overall detection rate: 11% of patients). CTC positivity was associated with poor tumor differentiation (P = 0.04), and with shorter overall survival (OS) in multivariable analysis (RR = 2.5, P = 0.01), together with anemia. CONCLUSIONS: The evaluation of micrometastatic disease using CTC detection appears as a promising prognostic tool in LAPC patients.

16 Clinical Trial Concomitant administration of weekly oxaliplatin, fluorouracil continuous infusion, and radiotherapy after 2 months of gemcitabine and oxaliplatin induction in patients with locally advanced pancreatic cancer: a Groupe Coordinateur Multidisciplinaire en Oncologie phase II study. 2008

Moureau-Zabotto, Laurence / Phélip, Jean-Marc / Afchain, Pauline / Mineur, Laurent / André, Thierry / Vendrely, Veronique / Lledo, Gerard / Dupuis, Olivier / Huguet, Florence / Touboul, Emmanuel / Balosso, Jacques / Louvet, Christophe. ·Hôpital Tenon, service de radiothérapie, 4 rue de la Chine, 75020 Paris, France. moureaul@marseille.fnclcc.fr ·J Clin Oncol · Pubmed #18309942.

ABSTRACT: BACKGROUND: According to previously reported Groupe Coordinateur Multidisciplinaire en Oncologie (GERCOR) studies in locally advanced pancreatic cancer (LAPC), concomitant chemoradiotherapy (CCRT) may be recommended for patients who do not experience disease progression after systemic induction chemotherapy (CT). To further improve patient outcome with classical fluorouracil (FU)-based CCRT, this study was designed to prospectively investigate a CCRT with FU infusion and weekly oxaliplatin after 2 months of gemcitabine and oxaliplatin (GEMOX) induction chemotherapy. PATIENTS AND METHODS: Nonpretreated patients with LAPC having WHO performance status (PS) of 0 to 2 received four induction cycles of GEMOX (gemcitabine 1 g/m(2) on day 1 and oxaliplatin 100 mg/m(2) on day 2; day 1 of a 15-day cycle). One month after cycle 4, patients who did not experience disease progression with PS 0 to 2 received 45 Gy over 5 weeks + 10 Gy (as a concomitant boost during the last 2 weeks) of radiotherapy (RT), with daily 250 mg/m(2) FU as a continuous infusion and 60 mg/m(2)of oxaliplatin weekly. RESULTS: Of 59 patients, 50 patients (84.7%) received CCRT, whereas nine patients did not because of disease progression (seven patients), CT toxicity (one patient), or personal decision (one patient). Forty-four patients (74.5%) completed the fully planned CCRT. Median progression-free survival and overall survival durations were 7.6 and 12.2 months, respectively, for the whole population and 9.4 and 12.6 months, respectively, for patients who completed CCRT. CCRT grade 3 to 4 toxicities (National Cancer Institute Common Toxicity Criteria) were neutropenia (10.4%), thrombocytopenia (8.4%), nausea and vomiting (16.7%), and diarrhea (12.5%). CONCLUSION: Concomitant administration of weekly oxaliplatin, continuous-infusion FU, and RT in patients with LAPC is feasible, with an acceptable acute and late safety profile. The encouraging results observed despite a nonoptimal patient selection (owing to the short induction time) indicates that further randomized evaluation to better define the specific role of oxaliplatin in CCRT is deserved.

17 Article How Does Chemoradiotherapy Following Induction FOLFIRINOX Improve the Results in Resected Borderline or Locally Advanced Pancreatic Adenocarcinoma? An AGEO-FRENCH Multicentric Cohort. 2019

Pietrasz, Daniel / Turrini, Olivier / Vendrely, Véronique / Simon, Jean-Marc / Hentic, Olivia / Coriat, Romain / Portales, Fabienne / Le Roy, Bertrand / Taieb, Julien / Regenet, Nicolas / Goere, Diane / Artru, Pascal / Vaillant, Jean-Christophe / Huguet, Florence / Laurent, Christophe / Sauvanet, Alain / Delpero, Jean-Robert / Bachet, Jean Baptiste / Sa Cunha, Antonio. ·Department of Hepato-Bilio-Pancreatic Surgery, Liver Transplant Center, Paul Brousse Hospital, Université Paris-Sud, Université Paris-Saclay, Villejuif, France. daniel.pietrasz@wanadoo.fr. · Department of Digestive and Hepatobiliary Surgery, Pitié-Salpêtrière Hospital, Sorbonne University, UPMC University, Paris 06, France. daniel.pietrasz@wanadoo.fr. · Surgical Oncology Department, Institut Paoli Calmette, Marseille, France. · Departement of Radiotherapy, Hopital Haut Lévêque, CHU de Bordeaux, Pessac, France. · Radiation Oncology, Pitié-Salpêtrière Hospital, Paris, France. · Pancreato-Gastroenterology Department, Beaujon Hospital, Clichy, France. · Gastroenterology Unit, Cochin Hospital, Paris, France. · Institut du Cancer de Montpellier, Montpellier, France. · CHU Estaing, Service de Chirurgie Digestive, Université Clermont Auvergne, Clermont-Ferrand, France. · Hepatogastroenterology and Digestive Oncology Department, Georges Pompidou Hospital, Paris, France. · Department of Digestive Surgery, Nantes Hospital, Nantes, France. · Surgical Oncology Department, Gustave Roussy, Villejuif, France. · Department of Gastroenterology, Hôpital Privé Jean Mermoz, Lyon, France. · Department of Digestive and Hepatobiliary Surgery, Pitié-Salpêtrière Hospital, Sorbonne University, UPMC University, Paris 06, France. · Department of Radiation Oncology, Tenon Hospital, Hôpitaux Universitaires Est Parisien, Assistance Publique-Hôpitaux de Paris, Paris, France. · Department of Hepatobiliopancreatic Surgery and Liver Transplantation, Hôpital Haut Lévêque, CHU de Bordeaux, Pessac, France. · Department of Digestive Surgery and Transplantation, Beaujon Hospital, Clichy, France. · Gastroenterology and Digestive Oncology Department, Pitié-Salpêtrière Hospital, Sorbonne University, UPMC University, Paris, France. · Department of Hepato-Bilio-Pancreatic Surgery, Liver Transplant Center, Paul Brousse Hospital, Université Paris-Sud, Université Paris-Saclay, Villejuif, France. ·Ann Surg Oncol · Pubmed #30362063.

ABSTRACT: BACKGROUND: Patients with borderline (BR) or locally advanced (LA) pancreatic adenocarcinoma (PAC) are often treated with induction FOLFIRINOX (FLX). However, the role of additional preoperative chemoradiotherapy (CRT) is controversial. The aim of this study is to evaluate its impact in patients who underwent resection after induction FLX. PATIENTS AND METHODS: Retrospective analysis of prospective consecutive surgical BR or LA PAC patients after induction FLX in 23 French centers between November 2010 and December 2015, treated with or without preoperative additional CRT (FLX vs FLX + CRT groups). RESULTS: Two hundred three patients were included (106 BR, 97 LA PAC). Median number of FLX cycles was 6 (range 1-30); 50% (n = 102) of patients received additional CRT. Median duration between diagnosis and surgery was 5.4 and 8.7 months (P = 0.001) in the FLX and FLX + CRT group, respectively. The 90-day mortality, major complications, and pancreatic fistula rates were 4.4%, 17.7%, and 5.4%, respectively. After 45.1 months follow-up, overall survival (OS) and disease-free survival were 45.4 months and 16.2 months, respectively. Patients with additional CRT had higher R0 resection rate (89.2% vs 76.3%; P = 0.017), ypN0 rate (76.2% vs 48.5%; P < 0.001), and higher rate of pathologic major response (33.3% vs 12.9%; P = 0.001). In the FLX + CRT group, patients had lower rate of locoregional relapse (28.3% vs 50.7%; P = 0.004). Patients with additional CRT had longer OS than those receiving FLX alone (57.8 vs 35.5 months; P = 0.007). CONCLUSIONS: Pathological results and survival data argue for interest in additional CRT. Prospective studies on an intention-to-treat basis are needed to confirm these results.

18 Article Chemoradiation for Unresectable Pancreatic Cancer Can Improve Quality of Life and Does Not Exclude Potential Resection. 2017

Huguet, Florence / Vendrely, Véronique. ·Department of Radiation Oncology, Tenon Hospital, Hôpitaux Universitaires Est Parisien, Assistance Publique-Hôpitaux de Paris, Paris, France. · Department of Radiation Oncology, Haut-Lévêque Hospital, Pessac, France. ·Int J Radiat Oncol Biol Phys · Pubmed #28871976.

ABSTRACT: -- No abstract --

19 Article 3rd St. Gallen EORTC Gastrointestinal Cancer Conference: Consensus recommendations on controversial issues in the primary treatment of pancreatic cancer. 2017

Lutz, Manfred P / Zalcberg, John R / Ducreux, Michel / Aust, Daniela / Bruno, Marco J / Büchler, Markus W / Delpero, Jean-Robert / Gloor, Beat / Glynne-Jones, Rob / Hartwig, Werner / Huguet, Florence / Laurent-Puig, Pierre / Lordick, Florian / Maisonneuve, Patrick / Mayerle, Julia / Martignoni, Marc / Neoptolemos, John / Rhim, Andrew D / Schmied, Bruno M / Seufferlein, Thomas / Werner, Jens / van Laethem, Jean-Luc / Otto, Florian. ·CaritasKlinikum St. Theresia, Saarbrücken, Germany. Electronic address: m.lutz@caritasklinikum.de. · Department of Epidemiology and Preventive Medicine, School of Public Health, Monash University, The Alfred Centre, Melbourne, Australia. · Institut Gustave Roussy, Villejuif, France. · Department of Pathology, Universitätsklinikum Carl Gustav Carus, Dresden, Germany. · Department of Gastroenterology & Hepatology, Erasmus Medical Center, University Medical Center Rotterdam, The Netherlands. · Chirurgische Universitätsklinik, Heidelberg, Germany. · Department of Surgery, Institut Paoli Calmettes, Marseille, France. · Klinik für Viszerale und Transplantationschirurgie, Inselspital, Bern, Switzerland. · Department of Medical Oncology, Mount Vernon Cancer Centre, Northwood, UK. · Department of General, Visceral and Transplantation Surgery, Klinikum der Universität München, Munich, Germany. · Radiooncology Service, Hôpital Tenon (Hôpitaux Universitaires Est Parisien), Paris Cedex 20, France. · Université René Descartes, UFR Biomédicale des Saints-Pères, Paris, France. · University Cancer Center Leipzig (UCCL), University Medicine Leipzig, Germany. · Istituto Europeo di Oncologia, Divisione di Epidemiologia e Biostatistica, Milan, Italy. · Klinik und Poliklinik für Innere Medizin A, Universitätsmedizin, Greifswald, Germany; Medizinische Klinik und Poliklinik II, Klinikum der Universität München, Munich, Germany. · Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, TU München, Munich, Germany. · Department of Surgery, Liverpool University, Liverpool, UK. · University of Michigan, Ann Arbor, MI, USA. · Klinik für Chirurgie, Kantonsspital St. Gallen, St. Gallen, Switzerland. · Department of Internal Medicine I, Ulm University, Ulm, Germany. · Hopital Erasme, Anderlecht, Belgium. · Tumor- und Brustzentrum ZeTuP, St. Gallen, Switzerland. ·Eur J Cancer · Pubmed #28460245.

ABSTRACT: The primary treatment of pancreatic cancer was the topic of the 3rd St. Gallen Conference 2016. A multidisciplinary panel reviewed the current evidence and discussed controversial issues in a moderated consensus session. Here we report on the key expert recommendations. It was generally accepted that radical surgical resection followed by adjuvant chemotherapy offers the only evidence-based treatment with a chance for cure. Initial staging should classify localised tumours as resectable or unresectable (i.e. locally advanced pancreatic cancer) although there remains a large grey-zone of potentially resectable disease between these two categories which has recently been named as borderline resectable, a concept which was generally accepted by the panel members. However, the definition of these borderline-resectable (BR) tumours varies between classifications due to their focus on either (i) technical hurdles (e.g. the feasibility of vascular resection) or (ii) oncological outcome (e.g. predicting the risk of a R1 resection and/or occult metastases). The resulting expert discussion focussed on imaging standards as well as the value of pretherapeutic laparoscopy. Indications for biliary drainage were seen especially before neoadjuvant therapy. Following standard resection, the panel unanimously voted for the use of adjuvant chemotherapy after R0 resection and considered it as a reasonable standard of care after R1 resection, even though the optimal pathologic evaluation and the definition of R0/R1 was the issue of an ongoing debate. The general concept of BR tumours was considered as a good basis to select patients for preoperative therapy, albeit its current impact on the therapeutic strategy was far less clear. Main focus of the conference was to discuss the limits of surgical resection and to identify ways to standardise procedures and to improve curative outcome, including adjuvant and perioperative treatment.

20 Article Chemotherapy and intensity-modulated radiation therapy for locally advanced pancreatic cancer achieves a high rate of R0 resection. 2017

Huguet, Florence / Hajj, Carla / Winston, Corrine B / Shi, Weiji / Zhang, Zhigang / Wu, Abraham J / O'Reilly, Eileen M / Reidy, Diane L / Allen, Peter / Goodman, Karyn A. ·a Department of Radiation Oncology , Tenon Hospital, Hôpitaux Universitaires Est Parisien, University Pierre and Marie Curie Paris VI , Paris , France. · b Department of Radiation Oncology at Memorial Sloan-Kettering Cancer Center , New York , NY , USA. · c Department of Radiology at Memorial Sloan-Kettering Cancer Center , New York , NY , USA. · d Department of Biostatistics at Memorial Sloan-Kettering Cancer Center , New York , NY , USA. · e Department of Medical Oncology at Memorial Sloan-Kettering Cancer Center , New York , NY , USA. · f Department of Surgery at Memorial Sloan-Kettering Cancer Center , New York , NY , USA. · g Department of Radiation Oncology , University of Colorado School of Medicine , Aurora , CO , USA. ·Acta Oncol · Pubmed #27796165.

ABSTRACT: BACKGROUND: To assess local control, survival and conversion to resectability among locally advanced pancreatic cancer (LAPC) patients treated with induction chemotherapy (ICT) followed by chemoradiotherapy treatment using intensity-modulated radiation therapy (IMRT). MATERIAL AND METHODS: Between 2007 and 2012, 134 LAPC patients were treated with ICT followed by IMRT. After chemoradiotherapy, 40 patients received maintenance chemotherapy. RESULTS: With a median follow-up of 20 months, median overall survival (OS) was 23 months. One- and two-year OS was 85% and 47%, respectively. On multivariate analysis, progression of disease after IMRT was associated with worse OS. Cumulative incidence of local failure was 10% at one year and 36% at two years. Twenty-six patients (19%) underwent resection after chemoradiotherapy including 22 patients (85%) with negative margins. On multivariate analysis, response to IMRT was associated with surgery (p = .01). Acute grade 3-4 hematologic and non-hematologic toxicity rates were 26% and 4.5%, respectively. CONCLUSION: IMRT is safe in patients with LAPC. Patients with non-progressive LAPC after ICT and who received IMRT had high rates of local control and prolonged survival.

21 Article Afatinib, an Irreversible EGFR Family Inhibitor, Shows Activity Toward Pancreatic Cancer Cells, Alone and in Combination with Radiotherapy, Independent of KRAS Status. 2016

Huguet, Florence / Fernet, Marie / Giocanti, Nicole / Favaudon, Vincent / Larsen, Annette K. ·Institut Curie, Centre de Recherche, 91405, Orsay, France. florence.huguet@tnn.aphp.fr. · Institut National de la Santé et de la Recherche Médicale (INSERM) U612, 91405, Orsay, France. florence.huguet@tnn.aphp.fr. · Institut Universitaire de Cancérologie, Université Pierre et Marie Curie, Sorbonne Universités, 75005, Paris, France. florence.huguet@tnn.aphp.fr. · Assistance Publique - Hôpitaux de Paris, Hôpitaux Universitaires Est Parisien, Hôpital Tenon, Service d'Oncologie Radiothérapie, 75020, Paris, France. florence.huguet@tnn.aphp.fr. · Laboratory of Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine, 75012, Paris, France. florence.huguet@tnn.aphp.fr. · Institut National de la Santé et de la Recherche Médicale (INSERM) U938, 75012, Paris, France. florence.huguet@tnn.aphp.fr. · Institut Curie, Centre de Recherche, 91405, Orsay, France. · Institut National de la Santé et de la Recherche Médicale (INSERM) U612, 91405, Orsay, France. · Institut Universitaire de Cancérologie, Université Pierre et Marie Curie, Sorbonne Universités, 75005, Paris, France. · Laboratory of Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine, 75012, Paris, France. · Institut National de la Santé et de la Recherche Médicale (INSERM) U938, 75012, Paris, France. ·Target Oncol · Pubmed #26668065.

ABSTRACT: BACKGROUND: Pancreatic adenocarcinoma is characterized by a high frequency of KRAS mutations and frequent deregulation of the epidermal growth factor receptor (EGFR) and other EGFR family members such as HER2/ErbB2. The EGFR inhibitor erlotinib is approved for treatment of pancreatic cancer, but has shown modest activity in most patients. OBJECTIVE: Here we investigated the activity of afatinib, a second-generation irreversible pan-EGFR family kinase inhibitor, alone or in combination with ionizing radiation, toward pancreatic cancer cells. METHODS: The influence of afatinib on cell proliferation, cell cycle distribution, clonogenic survival, nuclear fragmentation, ploidy, and centrosome amplification following irradiation was determined. Expression and phosphorylation of HER receptors, Akt, DNA-PKcs, and ERK1/2 was characterized by Western blot analysis. RESULTS: Afatinib was growth-inhibitory for all three cell lines but cytotoxic only toward BxPC3 (KRAS (wt)) and Capan-2 (KRAS (mut)) cells, both of which express high levels of EGFR, HER2, and HER3 receptors. Afatinib increased the radiosensitivity of BxPC3 and Capan-2 cells, prevented the radio-induced phosphorylation of Akt, and induced mitotic catastrophe following irradiation. In comparison, Panc-1 cells (KRAS (mut)) expressing low levels of EGFR family receptors were resistant to afatinib-induced radiosensitization. LIMITATIONS: These results must be confirmed in vivo. CONCLUSIONS: Afatinib showed cytotoxic and radiosensitizing effects toward a subset of pancreatic cancer cells which was closely correlated with expression of EGFR, HER2, and HER3 receptors, but not with KRAS status.

22 Article Intensity modulated radiation therapy reduces gastrointestinal toxicity in locally advanced pancreas cancer. 2016

Prasad, Shreya / Cambridge, Lajhem / Huguet, Florence / Chou, Joanne F / Zhang, Zhigang / Wu, Abraham J / O'Reilly, Eileen M / Allen, Peter J / Goodman, Karyn A. ·Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Radiation Oncology, Tenon Hospital, APHP, University Paris VI, Paris, France. · Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. Electronic address: karyn.goodman@ucdenver.edu. ·Pract Radiat Oncol · Pubmed #26577010.

ABSTRACT: PURPOSE: We compared gastrointestinal (GI) and hematologic toxicity in patients with locally advanced pancreas cancer (LAPC) undergoing definitive chemoradiation using intensity modulated radiation therapy (IMRT) or 3-dimensional conformal radiation therapy (3D-CRT) planning. METHODS AND MATERIALS: We retrospectively studied 205 patients with LAPC undergoing IMRT (n = 134) and 3D-CRT (n = 71) between May 2003 and March 2012. Patient, tumor, and treatment characteristics and acute GI/hematology toxicity according to the Common Terminology Criteria for Adverse Events, version 3.0, were recorded. Multivariable logistic regression models were used to test association between acute grade 2+ GI and hematologic toxicity outcomes and predictors. Propensity score analysis for grade 2+ GI toxicity was performed to reduce bias for confounding variables: age, gender, radiation dose, field size, and chemotherapy type. RESULTS: Median follow-up time for survivors was 22 months and was similar between groups. Median RT dose was significantly higher for IMRT versus 3D-CRT (5600 cGy vs 5040 cGy, P < .001); concurrent chemotherapy was mainly gemcitabine (56%) or 5-fluorouracil (38%). Grade 2+ GI toxicity occurred in 34% (n = 24) of 3D-CRT compared with 16% (n = 21) of IMRT patients. Using propensity score analysis, 3D-CRT had significantly higher grade 2+ GI toxicity (odds ratio, 1.26; 95% confidence interval, 1.08-1.45; P = .001). Grade 2+ hematologic toxicity was similar between IMRT and 3D-CRT groups, but was significantly greater in recipients of concurrent gemcitabine than in 5-fluorouracil (62% vs 29%, P < .0001). CONCLUSIONS: IMRT is associated with significant lower grade 2+ GI toxicity versus 3D-CRT for patients undergoing definitive chemoradiation therapy for LAPC. Because IMRT is better tolerated at higher doses and may allow further dose escalation, potentially improving local control for this aggressive disease. Further prospective studies of dose-escalated chemoradiation using IMRT are warranted.

23 Article Modeling pancreatic tumor motion using 4-dimensional computed tomography and surrogate markers. 2015

Huguet, Florence / Yorke, Ellen D / Davidson, Margaret / Zhang, Zhigang / Jackson, Andrew / Mageras, Gig S / Wu, Abraham J / Goodman, Karyn A. ·Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Radiation Oncology, Hôpitaux Universitaires Paris Est, Hôpital Tenon, University Paris VI, Paris, France. · Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. Electronic address: GoodmanK@mskcc.org. ·Int J Radiat Oncol Biol Phys · Pubmed #25680600.

ABSTRACT: PURPOSE: To assess intrafractional positional variations of pancreatic tumors using 4-dimensional computed tomography (4D-CT), their impact on gross tumor volume (GTV) coverage, the reliability of biliary stent, fiducial seeds, and the real-time position management (RPM) external marker as tumor surrogates for setup of respiratory gated treatment, and to build a correlative model of tumor motion. METHODS AND MATERIALS: We analyzed the respiration-correlated 4D-CT images acquired during simulation of 36 patients with either a biliary stent (n=16) or implanted fiducials (n=20) who were treated with RPM respiratory gated intensity modulated radiation therapy for locally advanced pancreatic cancer. Respiratory displacement relative to end-exhalation was measured for the GTV, the biliary stent, or fiducial seeds, and the RPM marker. The results were compared between the full respiratory cycle and the gating interval. Linear mixed model was used to assess the correlation of GTV motion with the potential surrogate markers. RESULTS: The average ± SD GTV excursions were 0.3 ± 0.2 cm in the left-right direction, 0.6 ± 0.3 cm in the anterior-posterior direction, and 1.3 ± 0.7 cm in the superior-inferior direction. Gating around end-exhalation reduced GTV motion by 46% to 60%. D95% was at least the prescribed 56 Gy in 76% of patients. GTV displacement was associated with the RPM marker, the biliary stent, and the fiducial seeds. The correlation was better with fiducial seeds and with biliary stent. CONCLUSIONS: Respiratory gating reduced the margin necessary for radiation therapy for pancreatic tumors. GTV motion was well correlated with biliary stent or fiducial seed displacements, validating their use as surrogates for daily assessment of GTV position during treatment. A patient-specific internal target volume based on 4D-CT is recommended both for gated and not-gated treatment; otherwise, our model can be used to predict the degree of GTV motion.

24 Article Does pre-operative chemoradiation for initially unresectable or borderline resectable pancreatic adenocarcinoma increase post-operative morbidity? A case-matched analysis. 2013

Araujo, Raphael L C / Gaujoux, Sébastien / Huguet, Florence / Gonen, Mithat / D'Angelica, Michael I / DeMatteo, Ronald P / Fong, Yuman / Kingham, T Peter / Jarnagin, William R / Goodman, Karyn A / Allen, Peter J. ·Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. ·HPB (Oxford) · Pubmed #23458208.

ABSTRACT: BACKGROUND: Neoadjuvant chemoradiation therapy for locally unresectable and borderline resectable pancreatic cancer may allow some patients to a undergo a resection, but whether or not this increases post-operative morbidity remains unclear. METHODS: The post-operative morbidity of 29 patients with initially locally unresectable/borderline pancreatic cancer who underwent a resection were compared with 29 patients with initially resectable tumours matched for age, gender, the presence of comorbidities (yes/no), American Society of Anesthesiology (ASA) score, tumour location (head/body-tail), procedure (pancreaticoduodenectomy/distal pancreatectomy) and vascular resection (yes /no). Wilcoxon's signed ranks test was used for continuous variables and McNemar's chi-square test for categorical variables. RESULTS: Compared with patients with initially resectable tumours, patients who underwent a resection after pre-operative chemoradiation therapy had similar rates of overall post-operative complications (55% versus 41%, P = 0.42), major complications (21% versus 21%, P = 1), pancreatic leaks and fistulae (7% versus 10%, P = 1) and mortality (0% versus 1.7%, P = 1). CONCLUSION: Although some previous studies have suggested differences in post-operative morbidity after chemoradiation, our case-matched analysis did not find statistical differences in surgical morbidity and mortality associated with pre-operative chemoradiation therapy.

25 Article [Pancreatic cancer]. 2010

Huguet, F / Orthuon, A / Touboul, E / Marseguerra, R / Mornex, F. ·Service d'oncologie radiothérapie, hôpital Tenon, Assistance-Publique-Hôpitaux de Paris, Université Paris VI, 4, rue de la Chine, 75020 Paris, France. florence.huguet@tnn.aphp.fr ·Cancer Radiother · Pubmed #21129675.

ABSTRACT: About 7200 new cases of pancreatic adenocarcinomas are diagnosed each year in France. At the time of diagnosis, an efficient carcinologic surgery will not be possible for nearly 80% of patients, in relation to loco-regional extension or metastatic dissemination. After surgical resection, the median survival of resected patients ranges from 12 to 20 months, with a high rate of relapses. Currently, the use of radiotherapy for patients with pancreatic cancer is controversial. In adjuvant setting, the standard treatment is six months of chemotherapy with FUFOL or gemcitabine. Chemoradiation (CRT) may improve the survival of patients with incompletely resected tumors (R1). This must be validated in a prospective trial. Neoadjuvant CRT is a promising treatment but always under evaluation. For the treatment of patients with locally advanced tumors, there is not a standart treatment. A strategy of initial chemotherapy followed by CRT for non progressive patients is under evaluation. Whereas in the first trials of CRT large fields were used, the current trend is to reduce the treated volumes to improve tolerance. The delineation of target volumes has been improved by the use of simulation CT. The aims of this work are to precise the radio-anatomical particularities, the pattern of spread of pancreatic cancer and the principles of 3D conformal radiotherapy illustrated with a clinical case.

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