Turpin
@chu-lille.fr
Medical Oncology Department
Lille University hospital
RESEARCH, TEACHING, or OTHER INTERESTS
Medicine, Cancer Research, Molecular Biology
Scopus Publications
Scopus Publications
Charles Poiraud, Xavier Lenne, Amélie Bruandet, Didier Theis, Nicolas Bertrand, Anthony Turpin, Stephanie Truant, and Mehdi El Amrani
Springer Science and Business Media LLC
Abstract Background Adjuvant chemotherapy (AC) improves the prognosis after pancreatic ductal adenocarcinoma (PDAC) resection. However, previous studies have shown that a large proportion of patients do not receive or complete AC. This national study examined the risk factors for the omission or interruption of AC. Methods Data of all patients who underwent pancreatic surgery for PDAC in France between January 2012 and December 2017 were extracted from the French National Administrative Database. We considered “omission of adjuvant chemotherapy” (OAC) all patients who failed to receive any course of gemcitabine within 12 postoperative weeks and “interruption of AC” (IAC) was defined as less than 18 courses of AC. Results A total of 11 599 patients were included in this study. Pancreaticoduodenectomy was the most common procedure (76.3%), and 31% of the patients experienced major postoperative complications. OACs and IACs affected 42% and 68% of the patients, respectively. Ultimately, only 18.6% of the cohort completed AC. Patients who underwent surgery in a high-volume centers were less affected by postoperative complications, with no impact on the likelihood of receiving AC. Multivariate analysis showed that age ≥ 80 years, Charlson comorbidity index (CCI) ≥ 4, and major complications were associated with OAC (OR = 2.19; CI95%[1.79–2.68]; OR = 1.75; CI95%[1.41–2.18] and OR = 2.37; CI95%[2.15–2.62] respectively). Moreover, age ≥ 80 years and CCI 2–3 or ≥ 4 were also independent risk factors for IAC (OR = 1.54, CI95%[1.1–2.15]; OR = 1.43, CI95%[1.21–1.68]; OR = 1.47, CI95%[1.02–2.12], respectively). Conclusion Sequence surgery followed by chemotherapy is associated with a high dropout rate, especially in octogenarian and comorbid patients.
Mathilde Moreau, Emily Alouani, Clémence Flecchia, Antoine Falcoz, Claire Gallois, Edouard Auclin, Thierry André, Romain Cohen, Antoine Hollebecque, Anthony Turpin,et al.
Elsevier BV
Gael S. Roth, Loic Verlingue, Matthieu Sarabi, Jean-Frédéric Blanc, Emmanuel Boleslawski, Karim Boudjema, Anne-Laure Bretagne-Bignon, Marine Camus-Duboc, Romain Coriat, Gilles Créhange,et al.
Elsevier BV
Rémy Nicolle, Jean-Baptiste Bachet, Alexandre Harlé, Juan Iovanna, Pascal Hammel, Vinciane Rebours, Anthony Turpin, Meher Ben Abdelghani, Alice Wei, Emmanuel Mitry,et al.
American Society of Clinical Oncology (ASCO)
PURPOSE GemPred, a transcriptomic signature predictive of the efficacy of adjuvant gemcitabine (GEM), was developed from cell lines and organoids and validated retrospectively. The phase III PRODIGE-24/CCTG PA6 trial has demonstrated the superiority of modified folinic acid, fluorouracil, irinotecan, and oxaliplatin (mFOLFIRINOX) over GEM as adjuvant therapy in patients with resected pancreatic ductal adenocarcinoma at the expense of higher toxicity. We evaluated the potential predictive value of GemPred in this population. PATIENTS AND METHODS Routine formalin-fixed paraffin-embedded surgical specimens of 350 patients were retrieved for RNA sequencing and GemPred prediction (167 in the GEM arm and 183 in the mFOLFIRINOX [mFFX] arm). Survival analyses were stratified by resection margins, lymph node status, and cancer antigen 19-9 level. RESULTS Eighty-nine patients' tumors (25.5%) were GemPred+ and were thus predicted to be gemcitabine-sensitive. In the GEM arm, GemPred+ patients (n = 50, 30%) had a significantly longer disease-free survival (DFS) than GemPred– patients (n = 117, 70%; median 27.3 v 10.2 months, hazard ratio [HR], 0.43 [95% CI, 0.29 to 0.65]; P < .001) and cancer-specific survival (CSS; median 68.4 v 28.6 months, HR, 0.42 [95% CI, 0.27 to 0.66]; P < .001). GemPred had no prognostic value in the mFFX arm. DFS and CSS were similar in GemPred+ patients who received adjuvant GEM and mFFX (median 27.3 v 24.0 months, and 68.4 v 51.4 months, respectively). The statistical interaction between GEM and GemPred+ status was significant for DFS ( P = .008) and CSS ( P = .004). GemPred+ patients had significantly more adverse events of grade ≥3 in the mFFX arm (76%) compared with those in the GEM arm (40%; P = .001). CONCLUSION This ancillary study of a phase III randomized trial demonstrates that among the quarter of patients with a GemPred-positive transcriptomic signature, survival was comparable with that of mFOLFIRINOX, whereas those receiving adjuvant gemcitabine had fewer adverse events.
Alessandro Parisi, Blandine Delaunay, Giada Pinterpe, Antoine Hollebecque, Jean Frederic Blanc, Mohamed Bouattour, Eric Assenat, Meher Ben Abdelghani, Matthieu Sarabi, Monica Niger,et al.
Elsevier BV
Nicolas Bertrand, Marie Bridoux, Cédric Gaxatte, Henry Abi Rached, Anthony Turpin, Jean-Guillaume Letarouilly, and Marie-Hélène Vieillard
Elsevier BV
Massih Ningarhari, Marlène Bertez, Anne Ploquin, Nicolas Bertrand, Christophe Desauw, Stéphane Cattan, Pascale Catala, Hélène Vandamme, Claire Cheymol, Stéphanie Truant,et al.
Wiley
AbstractBackground & AimsProgresses in management make a higher proportion of cirrhotic patients with gastrointestinal (GI) cancer candidates to chemotherapy. Data are needed on the safety and liver‐related events associated with the use of chemotherapy in these patients.MethodsForty‐nine patients with cirrhosis receiving chemotherapy against GI cancer from 2013 to 2018 were identified in the French Health Insurance Database using ICD‐10 codes K70‐K74, and matched 1:2 to non‐cirrhotic controls (n = 98) on age, tumour type and type of treatment. Adverse events (AE), dose tapering, discontinuation rate, liver‐related events and survival rate were compared.ResultsPatients with cirrhosis (Child–Pugh A 91%) more often received lower doses (38.8% vs 7.1%, p < .001), without significant differences in terms of grade 3/4 AE or dose tapering rates (29.6% vs. 36.7%; 22.3% vs 24.4%, respectively). Treatment discontinuation rate was higher in patients with cirrhosis (23.3% vs. 11.3%, p = .005). Child–Pugh (p = .007) and MELD (p = .025) scores increased under chemotherapy. Five patients with cirrhosis (10.2%) had liver decompensation within 12 months, and 17.2% of deaths in the cirrhosis group were liver‐related versus 0% in matched controls. WHO‐PS stage > 1 (HR 3.74, CI95%: 2.13–6.57, p < .001), TNM‐stage M1 (HR 3.61, CI 95%: 1.82–7.16, p < .001), non‐colorectal cancer (HR 1.73, CI 95%: 1.05–2.86, p = .032) and bilirubin higher than 5 mg/dL (HR 2.26, CI 95%: 1.39–3.70, p < .001) were independent prognostic factors of 2‐year mortality, whereas cirrhosis was not.ConclusionsChemotherapy should be proposed only in patients with compensated cirrhosis with close monitoring of liver function. Dose management remains challenging. Multidisciplinary management is warranted to improve these patients' outcomes.
Clémence Flecchia, Edouard Auclin, Emily Alouani, Mathilde Mercier, Antoine Hollebecque, Anthony Turpin, Thibault Mazard, Simon Pernot, Marie Dutherage, Romain Cohen,et al.
Springer Science and Business Media LLC
Charlène J. van der Zijden, Sjoerd M. Lagarde, Bianca Mostert, Joost J. M. E. Nuyttens, Manon C. W. Spaander, Bas P. L. Wijnhoven, Johanna W. van Sandick, Jolanda M. van Dieren, Francine E. M. Voncken, Jean-Pierre E. N. Pierie,et al.
Springer Science and Business Media LLC
Abstract Background Recent developments in esophageal cancer treatment, including studies exploring active surveillance following chemoradiotherapy, have led to a need for clear terminology and definitions regarding different multimodal treatment options. Objective The aim of this study was to reach worldwide consensus on the definitions and semantics of multimodal esophageal cancer treatment. Methods In total, 72 experts working in the field of multimodal esophageal cancer treatment were invited to participate in this Delphi study. The study comprised three Delphi surveys sent out by email and one online meeting. Input for the Delphi survey consisted of terminology obtained from a systematic literature search. Participants were asked to respond to open questions and to indicate whether they agreed or disagreed with different statements. Consensus was reached when there was ≥75% agreement among respondents. Results Forty-nine of 72 invited experts (68.1%) participated in the first online Delphi survey, 45 (62.5%) in the second survey, 21 (46.7%) of 45 in the online meeting, and 39 (86.7%) of 45 in the final survey. Consensus on neoadjuvant and definitive chemoradiotherapy with or without surgery was reached for 27 of 31 items (87%). No consensus was reached on follow-up after treatment with definitive chemoradiotherapy. Conclusion(s) Consensus was reached on most statements regarding terminology and definitions of multimodal esophageal cancer treatment. Implementing uniform criteria facilitates comparison of studies and promotes international research collaborations.
Antoine Lebeaud, Leony Antoun, Jane‐Rose Paccard, Julien Edeline, Hélène Bourien, Nadim Fares, Christophe Tournigand, Thierry Lecomte, David Tougeron, Vincent Hautefeuille,et al.
Wiley
AbstractBackground & AimsAccumulating data has shown the rising incidence and poor prognosis of early‐onset gastrointestinal cancers, but few data exist on biliary tract cancers (BTC). We aimed to analyse the clinico‐pathological, molecular, therapeutic characteristics and prognosis of patients with early onset BTC (EOBTC, age ≤50 years at diagnosis), versus olders.MethodsWe analysed patients diagnosed with intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder adenocarcinoma between 1 January 2003 and 30 June 2021. Baseline characteristics and treatment were described in each group and compared. Progression‐free survival, overall survival and disease‐free survival were estimated in each group using the Kaplan‐Meier method.ResultsOverall, 1256 patients were included, 188 (15%) with EOBTC. Patients with EOBTC demonstrated fewer comorbidities (63.5% vs. 84.5%, p < .0001), higher tumour stage (cT3–4: 50.0% vs. 32.3%, p = .0162), bilobar liver involvement (47.8% vs. 32.1%, p = .0002), and metastatic disease (67.6% vs. 57.5%, p = .0097) compared to older. Patients with EOBTC received second‐line therapy more frequently (89.5% vs. 81.0% non‐EOBTC, p = .0224). For unresectable patients with BTC, median overall survival was 17.0 vs. 16.2 months (p = .0876), and median progression‐free survival was 5.8 vs. 6.0 months (p = .8293), in EOBTC vs. older. In advanced stages, fewer actionable alterations were found in EOBTC (e.g., IDH1 mutations [7.8% vs. 16.6%]; FGFR2‐fusion [11.7% vs. 8.9%]; p = .029).ConclusionsPatients with EOBTC have a more advanced disease at diagnosis, are treated more heavily at an advanced stage but show similar survival. A distinctive molecular profile enriched for FGRF2 fusions was found.
Anne-Esther Frydman, Antoine Drouillard, Emilie Soularue, Olivier Dubreuil, Aziz Zaanan, Anthony Turpin, David Tougeron, Solène Doat, and Jean-Baptiste Bachet
Elsevier BV
Anthony Turpin, Carine Delliaux, Pauline Parent, Hortense Chevalier, Carmen Escudero-Iriarte, Franck Bonardi, Nathalie Vanpouille, Anne Flourens, Jessica Querol, Aurélien Carnot,et al.
Springer Science and Business Media LLC
Abstract Background Neuroendocrine prostate cancer (NEPC) is an aggressive form of prostate cancer, arising from resistance to androgen-deprivation therapies. However, the molecular mechanisms associated with NEPC development and invasiveness are still poorly understood. Here we investigated the expression and functional significance of Fascin-1 (FSCN1), a pro-metastasis actin-bundling protein associated with poor prognosis of several cancers, in neuroendocrine differentiation of prostate cancer. Methods Differential expression analyses using Genome Expression Omnibus (GEO) database, clinical samples and cell lines were performed. Androgen or antagonist’s cellular treatments and knockdown experiments were used to detect changes in cell morphology, molecular markers, migration properties and in vivo tumour growth. Chromatin immunoprecipitation-sequencing (ChIP-Seq) data and ChIP assays were analysed to decipher androgen receptor (AR) binding. Results We demonstrated that FSCN1 is upregulated during neuroendocrine differentiation of prostate cancer in vitro, leading to phenotypic changes and NEPC marker expression. In human prostate cancer samples, FSCN1 expression is restricted to NEPC tumours. We showed that the androgen-activated AR downregulates FSCN1 expression and works as a transcriptional repressor to directly suppress FSCN1 expression. AR antagonists alleviate this repression. In addition, FSCN1 silencing further impairs in vivo tumour growth. Conclusion Collectively, our findings identify FSCN1 as an AR-repressed gene. Particularly, it is involved in NEPC aggressiveness. Our results provide the rationale for the future clinical development of FSCN1 inhibitors in NEPC patients.
Aziz Zaanan, Julie Henriques, Anthony Turpin, Sylvain Manfredi, Romain Coriat, Eric Terrebonne, Jean-Louis Legoux, Thomas Walter, Christophe Locher, Olivier Dubreuil,et al.
Oxford University Press (OUP)
Abstract Background Small bowel adenocarcinoma is a rare cancer, and the role of adjuvant chemotherapy for localized disease is still debated. Methods This retrospective multicenter study included all consecutive patients who underwent curative surgical resection for localized small bowel adenocarcinoma between 1996 and 2019 from 3 French cohort studies. Prognostic and predictive factors of adjuvant chemotherapy efficacy were analyzed for disease-free survival and overall survival. The inverse probability of treatment weighting method was applied in the Cox regression model using the propensity score derived from multivariable logistic regression. Results A total of 354 patients were included: median age, 63.5 years; duodenum location, 53.5%; and tumor stage I, II, and III in 31 (8.7%), 144 (40.7%), and 179 (50.6%) patients, respectively. The adjuvant chemotherapy was administered in 0 (0%), 66 (48.5%), and 143 (80.3%) patients with stage I, II, and III, respectively (P &lt; .0001). In the subgroup analysis by inverse probability of treatment weighting method, a statistically significant disease-free survival and overall survival benefit in favor of adjuvant chemotherapy was observed in high-risk stage II (T4 and/or &lt;8 lymph nodes examined) and III (T4 and/or N2) but not for low-risk stage II (T3 and ≥8 lymph nodes examined) and III (T1-3/N1) tumors (Pinteraction &lt; .05). Furthermore, tumor location in jejunum and ileum was also a statistically significant predictive factor of response to adjuvant chemotherapy in stage II and III tumors (Pinteraction &lt; .05). Conclusion In localized small bowel adenocarcinoma, adjuvant chemotherapy seems to provide a statistically significant survival benefit for high-risk stage II and III tumors and for jejunum and ileum tumor locations.
Mathias Brugel, Thibault Marulier, Camille Evrard, Claire Carlier, David Tougeron, Guillaume Piessen, Stéphanie Truant, Anthony Turpin, Nicolas Williet, Damien Botsen,et al.
Elsevier BV
Julien Taïeb, Lina Sayah, Kathrin Heinrich, Volker Kunzmann, Alice Boileve, Geert Cirkel, Sara Lonardi, Benoist Chibaudel, Anthony Turpin, Tamar Beller,et al.
Elsevier BV
Nicolas Bertrand, Marie Bridoux, Cédric Gaxatte, Henry Abi Rached, Anthony Turpin, Jean-Guillaume Letarouilly, and Marie-Hélène Vieillard
Elsevier BV
E. Alouani, M. Mercier, C. Flecchia, E. Auclin, A. Hollebecque, T. Mazard, A. Turpin, S. Pernot, R. Cohen, M. Dutherage,et al.
Elsevier BV
Marie Bridoux, Marie-Cécile Le Deley, Nicolas Bertrand, Nicolas Simon, Dienabou Sylla, Xavier Mirabel, and Anthony Turpin
Springer Science and Business Media LLC
Marie Auvray Kuentz, Vincent Hautefeuille, Louis de Mestier, Clélia Coutzac, Thierry Lecomte, Victor Nardon, Pascal Artru, Anthony Turpin, Antoine Drouillard, David Malka,et al.
Wiley
AbstractPancreatic adenosquamous carcinoma (PASC) account for <5% of pancreatic malignancies. The efficacy of modern chemotherapy regimens in patients with advanced PASC is unknown. Patients with advanced PASC from 2008 to 2021 were consecutively included in this retrospective multicenter study. Overall survival (OS) and progression‐free survival (PFS) were evaluated by Kaplan‐Meier method. Ninety‐four PASC from 16 French centers were included (median age, 67.3 years; males, 56.4%; metastatic disease, 85.1%). The first‐line treatment was chemotherapy for 79 patients (84.0%) (37 FOLFIRINOX (FX), 7 Gemcitabine‐nab paclitaxel (GN) and 35 for all other regimen) or best supportive care (BSC) alone for 15 patients (16.0%). No significant difference was observed between FX and GN in terms of PFS (P = .67) or OS (P = .5). Modern regimens pooled together (FX and GN) as compared to all others chemotherapy regimens showed an improvement of overall response rate (39.5% and 9.7%, P = .002), PFS (median, 7.8 vs 4.7 months, P = .02) and OS (median, 12.7 vs 9.2 months, P = .35). This large study evaluating first‐line treatment regimens in advanced PASC suggests that modern regimens as FX or GN may be preferable to all other chemotherapy regimens. These results deserve confirmation in prospective studies.
Alexandre De Moura, Anthony Turpin, and Cindy Neuzillet
Elsevier BV
Margaret A. Tempero, Uwe Pelzer, Eileen M. O'Reilly, Jordan Winter, Do-Youn Oh, Chung-Pin Li, Giampaolo Tortora, Heung-Moon Chang, Charles D. Lopez, Tanios Bekaii-Saab,et al.
American Society of Clinical Oncology (ASCO)
PURPOSE This randomized, open-label trial compared the efficacy and safety of adjuvant nab-paclitaxel + gemcitabine with those of gemcitabine for resected pancreatic ductal adenocarcinoma (ClinicalTrials.gov identifier: NCT01964430 ). METHODS We assigned 866 treatment-naive patients with pancreatic ductal adenocarcinoma to nab-paclitaxel (125 mg/m2) + gemcitabine (1,000 mg/m2) or gemcitabine alone to one 30-40 infusion on days 1, 8, and 15 of six 28-day cycles. The primary end point was independently assessed disease-free survival (DFS). Additional end points included investigator-assessed DFS, overall survival (OS), and safety. RESULTS Two hundred eighty-seven of 432 patients and 310 of 434 patients completed nab-paclitaxel + gemcitabine and gemcitabine treatment, respectively. At primary data cutoff (December 31, 2018; median follow-up, 38.5 [interquartile range [IQR], 33.8-43 months), the median independently assessed DFS was 19.4 ( nab-paclitaxel + gemcitabine) versus 18.8 months (gemcitabine; hazard ratio [HR], 0.88; 95% CI, 0.729 to 1.063; P = .18). The median investigator-assessed DFS was 16.6 (IQR, 8.4-47.0) and 13.7 (IQR, 8.3-44.1) months, respectively (HR, 0.82; 95% CI, 0.694 to 0.965; P = .02). The median OS (427 events; 68% mature) was 40.5 (IQR, 20.7 to not reached) and 36.2 (IQR, 17.7-53.3) months, respectively (HR, 0.82; 95% CI, 0.680 to 0.996; P = .045). At a 16-month follow-up (cutoff, April 3, 2020; median follow-up, 51.4 months [IQR, 47.0-57.0]), the median OS (511 events; 81% mature) was 41.8 ( nab-paclitaxel + gemcitabine) versus 37.7 months (gemcitabine; HR, 0.82; 95% CI, 0.687 to 0.973; P = .0232). At the 5-year follow-up (cutoff, April 9, 2021; median follow-up, 63.2 months [IQR, 60.1-68.7]), the median OS (555 events; 88% mature) was 41.8 versus 37.7 months, respectively (HR, 0.80; 95% CI, 0.678 to 0.947; P = .0091). Eighty-six percent ( nab-paclitaxel + gemcitabine) and 68% (gemcitabine) of patients experienced grade ≥ 3 treatment-emergent adverse events. Two patients per study arm died of treatment-emergent adverse events. CONCLUSION The primary end point (independently assessed DFS) was not met despite favorable OS seen with nab-paclitaxel + gemcitabine.
Thomas Aparicio, Olivier Bouché, Pierre-Luc Etienne, Emilie Barbier, Laurent Mineur, Romain Desgrippes, Véronique Guérin-Meyer, Fayçal Hocine, Jean Martin, Valérie Le Brun-Ly,et al.
Elsevier BV
Aurélie Mailliez, Camille Ternynck, Alain Duhamel, Audrey Mailliez, Anne Ploquin, Christophe Desauw, Madleen Lemaitre, Nicolas Bertrand, Anne Vambergue, and Anthony Turpin
Wiley
AbstractDiabetes mellitus (DM) is a common comorbidity among cancer patients, but its impact on chemotherapy tolerance has not been widely studied. We aimed to compare the occurrence of severe grade 3/4 adverse events (G3/4 AEs) within 90 days of starting chemotherapy between patients with and without diabetes. We conducted a retrospective single‐center study in Lille University Hospital Oncology Department, France. Patients who received the first cycle of chemotherapy for gastrointestinal, gynecological or cancer of unknown primary source between 1 May 2013 and 1 May 2016, were included. Overall, 609 patients were enrolled: 490 patients without diabetes (80.5%) and 119 patients with diabetes (19.5%). Within 90 days of starting chemotherapy, patients with diabetes had a significantly higher occurrence of AEs G3/4 compared to those with no diabetes (multivariate odds ratio [OR]: 1.57 [1.02‐2.42], P = .04). More frequent G3/4 AEs in patients with diabetes were infection (26%), hematological disorders (13%), endocrine disorders (13%) and deterioration of the general condition (13%). In the year following the beginning of chemotherapy, patients with diabetes were twice as likely to be hospitalized as those without diabetes (univariate OR: 2.1 [1.40‐3.15], P = .0003). After multivariate adjustment, diabetes was no longer significantly associated with the risk of hospitalization (P = .051). There were no differences between patients with and without diabetes regarding dose reduction and chemotherapy treatment delays (P = .61 and P = .30, respectively). Our study suggests the need for better consideration of DM in the personalized care plan to improve chemotherapy tolerance and quality of life of patients with DM.
Anthony Turpin, Clotilde Descarpentries, Valérie Grégoire, Olivier Farchi, Alexis B Cortot, and Philippe Jamme
Oxford University Press (OUP)
Abstract Cholangiocarcinoma is the second most common liver cancer after hepatocellular carcinoma. In case of metastatic or unresectable disease, the recommended first-line treatment is gemcitabine-based doublet, most commonly gemcitabine and cisplatin. There is no standard treatment for further lines. MET fusions are rare alterations described in many cancers. The efficacy of specific MET inhibitors is poorly studied. We present the case of a patient with chemotherapy-refractory metastatic cholangiocarcinoma harboring a CAPZA-2-MET fusion along with MET amplification who dramatically responded to capmatinib, a specific MET tyrosine kinase inhibitor.