Publications by authors named "Anthony Turpin"

44 Publications

[Pembrolizumab as first-line therapy in microsatellite instability metastatic colorectal cancers].

Bull Cancer 2021 Mar 23;108(3):229-231. Epub 2021 Feb 23.

CHU Lille, service d'oncologie médicale, 59000 Lille, France; Université. Lille, CNRS, Inserm, UMR9020-UMR-S 1277, CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies, 59000 Lille, France.

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http://dx.doi.org/10.1016/j.bulcan.2021.01.004DOI Listing
March 2021

Biomarkers of Response to Etoposide-Platinum Chemotherapy in Patients with Grade 3 Neuroendocrine Neoplasms.

Cancers (Basel) 2021 Feb 5;13(4). Epub 2021 Feb 5.

Université de Paris, Department of Gastroenterology-Pancreatology, ENETS Centre of Excellence, Beaujon University Hospital (APHP), 92110 Clichy, France.

Etoposide-platinum (EP) chemotherapy has long been the reference treatment for grade 3 neuroendocrine neoplasms (G3 NEN). However, G3 NEN are heterogeneous, including well-differentiated tumors (NET) and poorly differentiated large (LCNEC) or small (SCNEC) cell carcinomas, whose response to EP chemotherapy varies considerably. Our aim was to evaluate predictive biomarkers for the response to EP chemotherapy in G3 NEN. We retrospectively studied 89 patients with lung (42%) and digestive (58%) G3 NEN treated by EP chemotherapy between 2006 and 2020. All cases were centrally reviewed for cytomorphology/Ki-67 and immunohistochemistry of retinoblastoma protein (Rb)/p53/p16, analyzed using a semi-quantitative score. The absence of Rb staining (Rb) or the absence of very intense p53 staining (p53) were considered inappropriate. Rb staining was also studied as a quantitative marker, the best threshold being determined by ROC curve. Intense p16 staining (p16) also suggested cell cycle dysregulation. Our primary endpoint was the objective response rate (ORR). We included 10 G3 NET, 31 LCNEC and 48 SCNEC, which showed ORR of 20%, 32% and 75%, respectively (NET vs. NEC, = 0.040; LCNEC vs. SCNEC, < 0.001). The ORR was significantly higher in NEN presenting with Rb (63% vs. 42%, = 0.025) and p16 (66% vs. 35%, = 0.006). Rb < 150 optimally identified responders (AUC = 0.657, < 0.001). The ORR was 67% in Rb < 150 (vs. 25%, = 0.005). On multivariate analysis, only Rb < 150 was independently associated with ORR (OR 4.16, 95% CI 1.11-15.53, = 0.034). We confirm the heterogeneity of the response to EP treatment in G3 NEN. Rb < 150 was the best predictive biomarker for the response to EP, and p53 immunostaining had no additional value.
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http://dx.doi.org/10.3390/cancers13040643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915900PMC
February 2021

Does bevacizumab increase joint pain in patients with cancer? Results of the prospective observational BEVARTHRALGIA study.

Cancer Chemother Pharmacol 2021 Apr 12;87(4):533-541. Epub 2021 Jan 12.

CNRS, Inserm, Institut Pasteur de Lille, UMR9020, UMR-S 1277, Canther, Cancer Heterogeneity, Plasticity and Resistance To Therapies, Medical Oncology Department, University of Lille, CHU Lille, Lille, France.

Purpose: The occurrence of arthralgia and myalgia during treatment with bevacizumab (Bev) has been described but not spontaneously reported. We aimed to evaluate the frequency of arthralgia in patients treated with Bev and identify the risk factors.

Methods: In this observational prospective study, a self-administered questionnaire was distributed to patients at the initiation of Bev and at 3 and 6 months of treatment. Bev (5-15 mg/kg) was administered every 2 or 3 weeks, with or without chemotherapy.

Results: A total of 71 patients (42 with colorectal cancer, 22 with ovarian cancer, and 7 with lung cancer) were enrolled from January to November 2018. All patients completed the questionnaire at initiation, while only 56 (78.9%) and 36 (50.7%) patients completed the questionnaire at 3 and 6 months, respectively. The frequency of joint pain was 29.6% before Bev treatment and increased to 41.8% and 50% at 3 and 6 months, respectively, without reaching significance. The evolution of pain was significant according to the Common Terminology Criteria for Adverse Events grades (P = 0.032). No significant increase in the impact of pain on instrumental or elementary activities was observed over time. The frequency of arthralgia significantly increased at 3 months in patients with ovarian cancer versus those with colorectal cancer (odds ratio: 19.50; 95% confidence interval 4.53-83.98; P < 0.001).

Conclusions: Bev‑including regimens tend to be associated with a significant increase in the frequency of arthralgia in women treated for ovarian cancer. Physicians should be aware of this side effect.

Clinical Trial Number: NCT03455907, date of registration: March 7, 2018.
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http://dx.doi.org/10.1007/s00280-020-04226-6DOI Listing
April 2021

Adjuvant Pancreatic Cancer Management: Towards New Perspectives in 2021.

Cancers (Basel) 2020 Dec 21;12(12). Epub 2020 Dec 21.

Service d'Oncologie Digestive et Médicale, Hôpital Paul Brousse (AP-HP), 12 Avenue Paul Vaillant Couturier, F-94800 Villejuif, France.

Adjuvant chemotherapy is currently used in all patients with resected pancreatic cancer who are able to begin treatment within 3 months after surgery. Since the recent publication of the PRODIGE 24 trial results, modified FOLFIRINOX has become the standard-of-care in the non-Asian population with localized pancreatic adenocarcinoma following surgery. Nevertheless, there is still a risk of toxicity, and feasibility may be limited in heavily pre-treated patients. In more frail patients, gemcitabine-based chemotherapy remains a suitable option, for example gemcitabine or 5FU in monotherapy. In Asia, although S1-based chemotherapy is the standard of care it is not readily available outside Asia and data are lacking in non-Asiatic patients. In patients in whom resection is not initially possible, intensified schemes such as FOLFIRINOX or gemcitabine-nabpaclitaxel have been confirmed as options to enhance the response rate and resectability, promoting research in adjuvant therapy. In particular, should oncologists prescribe adjuvant treatment after a long sequence of chemotherapy +/- chemoradiotherapy and surgery? Should oncologists consider the response rate, the R0 resection rate alone, or the initial chemotherapy regimen? And finally, should they take into consideration the duration of the entire sequence, or the presence of limited toxicities of induction treatment? The aim of this review is to summarize adjuvant management of resected pancreatic cancer and to raise current and future concerns, especially the need for biomarkers and the best holistic care for patients.
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http://dx.doi.org/10.3390/cancers12123866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767489PMC
December 2020

Impact of the IDEA Collaboration Study Results on Clinical Practice in France for Patients With Stage III Colon Cancer: A National GERCOR - PRODIGE Survey.

Clin Colorectal Cancer 2021 Mar 14;20(1):79-83.e4. Epub 2020 Nov 14.

Sorbonne University and Medical Oncology Department, Saint-Antoine hospital, AP-HP, Paris, France. Electronic address:

Background: The IDEA collaboration showed that the type and duration of adjuvant chemotherapy in stage III colon cancer (CC) could be adjusted according to the schedule of chemotherapy and the level of risk. We aimed at evaluating the implementation of IDEA's results in real-life practice for stage III CC.

Material And Methods: All clinicians registered in the French oncology cooperative groups GERCOR, FFCD, and UNICANCER GI mailing lists were invited to participate to an online anonymized nationwide survey from January 30, 2019 to March 31, 2019. Proportions were compared using the χ test.

Results: A total of 213 physicians answered the survey. Of these, 173 (81%) considered that 3 months of adjuvant chemotherapy was the new standard of care for low-risk (pT1-3/N1) stage III CC, and 99% considered that 6 months remained the standard of care for high-risk (pT4 and/or pN2) stage III CC. In patients under 70 years, capecitabine and oxaliplatin (CAPOX) for 3 months was prescribed by 74% of the participants in low-risk CC, whereas 6 months of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) was preferred for high-risk CC in 94% of cases. For patients over 70 years with good performance status and no comorbidities, 172 (81%) physicians prescribed oxaliplatin-based chemotherapy for low-risk CC (3 months, 144 of 172%; 88%), and 200 (94%) physicians prescribed oxaliplatin-based adjuvant chemotherapy for high-risk CC (6 months, 199 of 200%; 99.5%).

Conclusions: The IDEA results have been practice-changing as French physicians have implemented 3 months of CAPOX for patients with low-risk stage III CC, substituting from 6 months of FOLFOX, which remains the preferred regimen for high-risk patients.
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http://dx.doi.org/10.1016/j.clcc.2020.11.004DOI Listing
March 2021

Triplet combination of durvalumab, tremelimumab, and paclitaxel in biliary tract carcinomas: Safety run-in results of the randomized IMMUNOBIL PRODIGE 57 phase II trial.

Eur J Cancer 2021 Jan 3;143:55-63. Epub 2020 Dec 3.

GERCOR, Paris, France; Department of Medical Oncology, Institut Curie - Site Saint Cloud, Versailles Saint-Quentin University, Paris Saclay University, Saint-Cloud, France. Electronic address:

Background: The IMMUNOBIL PRODIGE 57 trial is a non-comparative randomized phase II study assessing the efficacy and safety of the durvalumab (an anti-PD-L1) and tremelimumab (an anti-CTLA4) combination with or without weekly paclitaxel in patients with advanced biliary tract carcinoma (BTC) after failure of platinum-based chemotherapy. Taxanes have already been safely combined with immune checkpoint inhibitors in other tumors. We report results of the 20-patient safety run-in.

Methods: Patients received durvalumab (1500 mg at day 1 [D1] of each cycle)/tremelimumab (75 mg at D1 for 4 cycles; Arm A) or durvalumab/tremelimumab with paclitaxel (80 mg/m at D1, D8, D15; Arm B) every 28 days.

Results: Twenty patients were enrolled (Arm A/B: 10/10). There were no dose-limiting toxicities (DLTs) in Arm A. Six DLTs were observed in five patients (50%) in Arm B, meeting a stopping rule for the trial inclusions. DLTs included three serious anaphylactic reactions (with one cardiac arrest), two enterocolitis, and one infectious pneumopathy with septic shock. There were no patients with history of personal or familial auto-immune disease.

Conclusion: The safety run-in part of IMMUNOBIL PRODIGE 57 raised concerns regarding co-administration of paclitaxel with durvalumab and tremelimumab in BTC, with an unexpected increase in anaphylactic adverse events. Phase II of the study will only evaluate the durvalumab and tremelimumab combination arm.

Clinicaltrials Registration: NCT03704480.
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http://dx.doi.org/10.1016/j.ejca.2020.10.027DOI Listing
January 2021

Professional and Psychological Impacts of the COVID-19 Pandemic on Oncology Residents: A National Survey.

JCO Glob Oncol 2020 10;6:1674-1683

Association pour l'Enseignement et la Recherche des Internes d'Oncologie, Paris, France.

Purpose: The COVID-19 pandemic has severely affected clinical practice in oncology, leading to organizational, ethical, and medical issues. In particular, it has raised challenges in the context of competing care priorities between COVID-19 and cancer treatment. Residents on the front line face difficulties related to increasing care needs and urgent reorganization of health care systems while managing psychological stress and uncertainty. We aimed to evaluate the impact of the COVID-19 pandemic on oncology residents.

Methods And Materials: We conducted a national survey (39 questions) in France among oncology and radiation therapy residents to determine the psychological impact and professional difficulties (eg, reassignment, training/research time, supervision, teleworking, management of patients) associated with the first peak of the COVID-19 pandemic.

Results: Overall, 222 residents (medical oncologists, 61%; radiation therapists, 39%) participated in our survey, representing approximately one third of all residents and fellows in France. One third of respondents had been reassigned to a COVID-19 ward. Training and research activity decreased for 89% and 41% of respondents, respectively. Two thirds (70%) of respondents declared that they had faced ethical issues, 35% felt worried about their own health, and 23% experienced psychological distress. According to the Hospital Anxiety and Depression Scale, 32% were anxious and 17% depressed. Consumption of tobacco, psychostimulants, and alcohol increased in 31%, 24%, and 29% of respondents, respectively.

Conclusion: French oncology residents were highly affected by the first peak of the COVID-19 pandemic in terms of professional activity and psychological impact. This national survey can be used as a basis for improved management, medical reorganization, and training of residents during the ongoing COVID-19 pandemic.
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http://dx.doi.org/10.1200/GO.20.00376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713519PMC
October 2020

Risk factors for Coronavirus Disease 2019 (COVID-19) severity and mortality among solid cancer patients and impact of the disease on anticancer treatment: A French nationwide cohort study (GCO-002 CACOVID-19).

Eur J Cancer 2020 12 8;141:62-81. Epub 2020 Oct 8.

Department of Gastroenterology, Saint Louis Hospital, APHP, Université de Paris, Paris, FFCD, France.

Background: Cancer patients are thought to have an increased risk of developing severe Coronavirus Disease 2019 (COVID-19) infection and of dying from the disease. In this work, predictive factors for COVID-19 severity and mortality in cancer patients were investigated.

Patients And Methods: In this large nationwide retro-prospective cohort study, we collected data on patients with solid tumours and COVID-19 diagnosed between March 1 and 11th June 2020. The primary end-point was all-cause mortality and COVID-19 severity, defined as admission to an intensive care unit (ICU) and/or mechanical ventilation and/or death, was one of the secondary end-points.

Results: From April 4 to 11th June 2020, 1289 patients were analysed. The most frequent cancers were digestive and thoracic. Altogether, 424 (33%) patients had a severe form of COVID-19 and 370 (29%) patients died. In multivariate analysis, independent factors associated with death were male sex (odds ratio 1.73, 95%CI: 1.18-2.52), The Eastern Cooperative Oncology Group Performance Scale (ECOG PS) ≥ 2 (OR 3.23, 95%CI: 2.27-4.61), updated Charlson comorbidity index (OR 1.08, 95%CI: 1.01-1.16) and admission to ICU (OR 3.62, 95%CI 2.14-6.11). The same factors, age along with corticosteroids before COVID-19 diagnosis, and thoracic primary tumour site were independently associated with COVID-19 severity. None of the anticancer treatments administered within the previous 3 months had any effect on mortality or COVID-19 severity, except for cytotoxic chemotherapy in the subgroup of patients with detectable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcriptase polymerase chain reaction (RT-PCR), which was associated with a slight increase of the risk of death (OR 1.53; 95%CI: 1.00-2.34; p = 0.05). A total of 431 (39%) patients had their systemic anticancer treatment (such as chemotherapy, targeted or immune therapy) interrupted or stopped following diagnosis of COVID-19.

Conclusions: Mortality and COVID-19 severity in cancer patients are high and are associated with general characteristics of patients. We found no deleterious effects of recent anticancer treatments, except for cytotoxic chemotherapy in the RT-PCR-confirmed subgroup of patients. In almost 40% of patients, the systemic anticancer therapy was interrupted or stopped after COVID-19 diagnosis.
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http://dx.doi.org/10.1016/j.ejca.2020.09.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543792PMC
December 2020

Creating scripted video-vignettes in an experimental study on two empathic processes in oncology: Reflections on our experience.

Patient Educ Couns 2021 Mar 6;104(3):654-662. Epub 2020 Sep 6.

Univ. Lille, CNRS, UMR 9193 - SCALab - Sciences Cognitives et Sciences Affectives, F-59000 Lille, France. Electronic address:

Objective: The aims were to: (1) apply the guidelines to develop and test the validity of video-vignettes manipulating empathy and context in oncology; (2) compare lay people's and patients' assessments of validity; (3) reflecting on our experiment METHODS: Guidelines were followed: (1) deciding whether video-vignettes were appropriate; (2) developing a valid script; (3) designing valid manipulations; (4) converting the scripted consultations into videos. One hundred sixteen lay people and 46 cancer patients filled in the Video Engagement Scale, the CARE, and ad hoc questionnaires on realism and emotions.

Results: The video-vignettes are valid for experimental use. Differences appeared in the emotions participants reported. The empathic processes were successfully manipulated and perceived. Lay people's and patients' assessments were equivalent, except for video-vignettes in neutral consultations. Participants' comments on nonverbal behavior, camera perspective, scripts and empathy assessment were reported.

Conclusion: Patients' assessments are impacted by their personal experiences. Researchers should control for this in analogue patient studies.

Practice Implications: Based on this experience, we reflect on: (1) adopting congruent nonverbal behavior throughout the video-vignettes; (2) alternating camera perspectives; (3) avoiding the sole use of written scripts; (4) using quantitative and qualitative analysis to validate scripts and video-vignettes.
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http://dx.doi.org/10.1016/j.pec.2020.08.041DOI Listing
March 2021

FOLFIRINOX De-Escalation in Advanced Pancreatic Cancer: A Multicenter Real-Life Study.

Oncologist 2020 11 17;25(11):e1701-e1710. Epub 2020 Sep 17.

Oncology Multidisciplinary Research Group (GERCOR), Paris, France.

Background: Our study describes the feasibility and efficacy of a first-line FOLFIRINOX (5-fluorouracil [5FU], folinic acid, irinotecan, and oxaliplatin) induction chemotherapy (CT) followed by de-escalation as a maintenance strategy for advanced pancreatic cancer.

Materials And Methods: This multicenter retrospective study was conducted from January 2011 to December 2018. FOLFIRINOX de-escalation was defined as stopping oxaliplatin and/or irinotecan after at least four cycles of FOLFIRINOX, without evidence of disease progression. Maintenance schedules were fluoropyrimidine monotherapy (intravenous or oral [capecitabine]), FOLFOX (5FU, oxaliplatin), or FOLFIRI (5FU, irinotecan). Primary endpoint was overall survival (OS). Secondary endpoints were first progression-free survival (PFS1), second progression-free survival (PFS2), and toxicity.

Results: Among 321 patients treated with FOLFIRINOX, 147 (45.8%) were included. Median OS was 16.1 months (95% confidence interval [CI], 13.7-20.3) and median PFS1 was 9.4 months (95% CI, 8.5-10.4). The preferred maintenance regimen was FOLFIRI in 66 (45%) patients versus 5FU monotherapy in 52 (35%) and FOLFOX in 25 (17%) patients. Among 118 patients who received maintenance CT with FOLFIRI or 5FU, there was no difference in PFS1 (median, 9.0 vs. 10.1 months, respectively; p = .33) or OS (median, 16.6 vs. 18.7 months; p = .86) between the two maintenance regimens. Reintroduction of FOLFIRINOX was performed in 20.2% of patients, with a median PFS2 of 2.8 months (95% CI, 2.0-22.3). The rates of grade 3-4 toxicity were significantly higher with FOLFIRI maintenance CT than with 5FU (41% vs. 22%; p = .03), especially for neuropathy (73% vs. 9%).

Conclusion: 5FU monotherapy maintenance appeared to be as effective as FOLFIRI, in a FOLFIRINOX de-escalation strategy, which is largely used in France.

Implications For Practice: FOLFIRINOX de-escalation and maintenance is a feasible strategy in advanced pancreatic cancer that decreases chemotherapy toxicity to improve both survival and quality of life. Survivals in patients with maintenance therapy are clinically meaningful. Fluoropyrimidine monotherapy maintenance seems to be as efficient as FOLFIRI and should be a reference arm in future pancreatic cancer maintenance trials.
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http://dx.doi.org/10.1634/theoncologist.2020-0577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648331PMC
November 2020

The Impact of Modern Chemotherapy and Chemotherapy-Associated Liver Injuries (CALI) on Liver Function: Value of 99mTc-Labelled-Mebrofenin SPECT-Hepatobiliary Scintigraphy.

Ann Surg Oncol 2021 Apr 24;28(4):1959-1969. Epub 2020 Aug 24.

Department of Digestive Surgery and Transplantation, Univ. Lille, CHRU Lille, Lille, France.

Background: Chemotherapy is increasingly used before hepatic resection, with controversial impact regarding liver function. This study aimed to assess the capacity of 99mTc-labelled-mebrofenin SPECT-hepatobiliary scintigraphy (HBS) to predict liver dysfunction due to chemotherapy and/or chemotherapeutic-associated liver injuries (CALI), such as sinusoidal obstruction syndrome (SOS) and nonalcoholic steatohepatitis (NASH) activity score (NAS).

Methods: From 2011 to 2015, all consecutive noncirrhotic patients scheduled for a major hepatectomy (≥ 3 segments) gave informed consent for preoperative SPECT-HBS allowing measurements of segmental liver function. As primary endpoint, HBS results were compared between patients with versus without (1) preoperative chemotherapy (≤ 3 months); and (2) CALI, mainly steatosis, NAS (Kleiner), or SOS (Rubbia-Brandt). Secondary endpoints were (1) other factors impairing function; and (2) impact of chemotherapy, and/or CALI on hepatocyte isolation outcome via liver tissues.

Results: Among 115 patients, 55 (47.8%) received chemotherapy. Sixteen developed SOS and 35 NAS, with worse postoperative outcome. Overall, chemotherapy had no impact on liver function, except above 12 cycles. In patients with CALI, a steatosis ≥ 30% significantly compromised function, as well as NAS, especially grades 2-5. Conversely, SOS had no impact, although subjected to very low patients number with severe SOS. Other factors impairing function were diabetes, overweight/obesity, or fibrosis. Similarly, chemotherapy in 73 of 164 patients had no effect on hepatocytes isolation outcome; regarding CALI, steatosis ≥ 30% and NAS impaired the yield and/or viability of hepatocytes, but not SOS.

Conclusions: In this first large, prospective study, HBS appeared to be a valuable tool to select heavily treated patients at risk of liver dysfunction through steatosis or NAS.
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http://dx.doi.org/10.1245/s10434-020-08988-4DOI Listing
April 2021

Maintenance treatment with fluoropyrimidine plus bevacizumab versus fluoropyrimidine alone after induction chemotherapy for metastatic colorectal cancer: The BEVAMAINT - PRODIGE 71 - (FFCD 1710) phase III study.

Dig Liver Dis 2020 10 31;52(10):1143-1147. Epub 2020 Jul 31.

University hospital Saint Louis, APHP, Paris, France.

Background: Maintenance treatments with fluoropyrimidine alone or combined with bevacizumab after induction chemotherapy are two standard options in first-line metastatic colorectal cancer (mCRC). However, no trial has compared these two maintenance regimens.

Methods: BEVAMAINT is a multicenter, open-label, randomized phase III trial comparing fluoropyrimidine alone or plus bevacizumab as maintenance treatment after induction polychemotherapy in mCRC. The primary endpoint is the time-to-treatment failure (TTF), calculated from date of randomization to first radiological progression, death, start of a new chemotherapy regimen (different from induction or maintenance chemotherapy) or end of maintenance treatment without introduction of further chemotherapy. We expect a 2-month TTF improvement from 6 months in the monotherapy arm to 8 months in the combination arm (hazard ratio [HR], 0.75). Based on a two-sided α risk of 5% and a power of 80%, using Schoenfeld method, 379 events are required (planned enrolment, 400 patients). Patients with mCRC, whose disease is measurable according to RECIST 1.1 criteria and controlled (objective response or stable disease) - but remains unresectable - after 4 to 6 months of induction polychemotherapy (doublet or triplet chemotherapy with or without anti-EGFR or bevacizumab), and who have recovered from limiting adverse events of induction polychemotherapy are eligible for randomization. Randomization is stratified according to center, response to induction chemotherapy (objective response vs stable disease), ECOG performance status (0-1 vs 2), maintenance fluoropyrimidine (5-fluorouracil vs capecitabine) and primary tumor status (resected vs not). Capecitabine or bolus and infusional 5-fluorouracil plus folinic acid (simplified LV5FU2 regimen) are both accepted for maintenance chemotherapy, at investigator's discretion. Clinical evaluation, tumor imaging, carcinoembryonic antigen and circulating tumor DNA dosages are planned at enrolment and every 9 weeks. The maintenance treatment will be discontinued in the event of unbearable toxicity, progression or patient refusal. After maintenance discontinuation, reintroduction of induction polychemotherapy is recommended; otherwise a second-line treatment is started. The enrolment has begun in January 2020.
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http://dx.doi.org/10.1016/j.dld.2020.06.034DOI Listing
October 2020

Maintenance therapies in metastatic pancreatic cancer: present and future with a focus on PARP inhibitors.

Ther Adv Med Oncol 2020 9;12:1758835920937949. Epub 2020 Jul 9.

GI Oncology, Medical Oncology Department, Institut Curie Saint-Cloud, Versailles Saint-Quentin University, Saint-Cloud, France.

Metastatic pancreatic ductal adenocarcinomas (PDACs) are now more effectively controlled using chemotherapy combinations such as FOLFIRINOX and gemcitabine plus nab-paclitaxel (NabP) regimens with a subset of patients who achieve a sustained tumor stabilization or response. The next challenge is to design maintenance therapies that result in continued tumor control with minimal toxicity. Quality of life should always be a priority in these patients with prolonged survival. Gradually tapering off the intensity of chemotherapy by suppressing drug(s) in the combination is one option. Thus, maintenance with 5-fluorouracil or gemcitabine as single agents after FOLFIRINOX or gemcitabine-NabP induction, respectively, seems to be a promising approach to minimize neurotoxicity while maintaining efficacy. Another option is to introduce maintenance drug(s) with different anti-tumoral actions. The recent example of olaparib in patients with BRCA mutated PDAC provides a promising proof-of-concept of a switch maintenance strategy in this setting.
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http://dx.doi.org/10.1177/1758835920937949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350045PMC
July 2020

A comprehensive overview of promising biomarkers in stage II colorectal cancer.

Cancer Treat Rev 2020 Aug 23;88:102059. Epub 2020 Jun 23.

University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020 - UMR-S 1277 - Canther - Cancer Heterogeneity, Plasticity and Resistance to Therapies, Lille, France; Medical Oncology Department, CHU Lille, University of Lille, Lille, France; Department of Gastroenterology and Gastrointestinal Oncology, Georges-Pompidou European Hospital, 20 Rue Leblanc, 75015 Paris, France; AP-HP, Sorbonne Paris Cité, University of Paris, 2 rue Albert Einstein, 75013 Paris, France; Department of Medical Oncology, Claude Huriez Hospital, Rue Michel Polonovski, 59000 Lille, France. Electronic address:

Colon cancer (CC) has the highest incidence rate among gastrointestinal cancers and ranks the third in mortality among all cancers, which contributes to the current CC burden and constitutes a major public health issue. While therapeutic strategies for stage I, III, and IV CC are standardized, those for stage II CC remain debatable. The choice of adjuvant chemotherapy for patients with stage II CC depends on stage (pT4) and grade (high) of the disease, the presence of venous, perinervous, and/or lymphatic emboli, or the need of suboptimal surgery (tumor with initial occlusion or perforation needing emergency surgeries, <12 lymph nodes harvested). Several prognostic factors that have been validated in retrospective studies can potentially define a population of CC patients at low and high-risk for reccurence. The role of biomarkers is becoming increasingly important for the future personalized treatment options. We conducted a systematic overview of potential prognostic biomarkers with possible clinical implications in stage II CC.
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http://dx.doi.org/10.1016/j.ctrv.2020.102059DOI Listing
August 2020

Liver transarterial chemoembolization and sunitinib for unresectable hepatocellular carcinoma: Results of the PRODIGE 16 study.

Clin Res Hepatol Gastroenterol 2020 Jun 21:101464. Epub 2020 Jun 21.

Department of Medical Oncology, University Hospital, Lille, France.

Background: Trans-arterial chemoembolization (TACE) is one first-line option therapy for patients with hepatocellular carcinoma (HCC) not suitable for surgical resection.

Aims: We evaluated the effects of sunitinib plus doxorubicin-TACE on bleeding or liver failure.

Methods: Seventy-eight patients with HCC were included in this randomized, double-blind study. They received one to three TACE plus either sunitinib or placebo four weeks out of six for one year. The occurrence of severe bleeding or liver failure was assessed during the week after the TACE. The safety and survival outcomes were evaluated.

Results: No bleeding complication was reported. One and two liver failures were respectively observed in sunitinib and placebo patients. Compliance to sunitinib treatment was acceptable. Sunitinib dose reduction occurred in 37% of patients due to acute toxicity. Main grade 3-4 toxicities were: thrombocytopenia, neutropenia, increased bilirubin, increased ALT and asthenia. In the sunitinib group, the median PFS and OS were 9.05 [5.81;11.63] and 25.0 [13.5;36.8] months, respectively. In the placebo group, the median PFS and OS were 5.51 [4.14;7.79] and 20.5 [15.1;30.6] months, respectively.

Conclusions: TACE plus sunitinib in the first-line therapy for patients with HCC not suitable for surgical resection was feasible. CLINICALTRIALS.

Gov Number: NCT01164202.
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http://dx.doi.org/10.1016/j.clinre.2020.05.012DOI Listing
June 2020

[COVID 19 and cancer: What are the consequences of the cancer care reorganization?]

Bull Cancer 2020 05 23;107(5):538-540. Epub 2020 Apr 23.

CHRU de Lille, département d'oncologie médicale, Lille, France; Université de Lille, Lille, France.

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http://dx.doi.org/10.1016/j.bulcan.2020.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177151PMC
May 2020

FOLFOXIRI FOLFIRINOX as first-line chemotherapy in patients with advanced pancreatic cancer: A population-based cohort study.

World J Gastrointest Oncol 2020 Mar;12(3):332-346

University Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon F-25000, France.

Background: FOLFIRINOX regimen is the first-line reference chemotherapy (L1) in advanced pancreatic ductal adenocarcinoma (aPDAC). FOLFOXIRI, a schedule with a lower dose of irinotecan and no bolus 5-fluorouracil, has demonstrated efficacy and feasibility in colorectal cancer.

Aim: To investigate the potential clinical value of FOLFOXIRI in patients with aPDAC in routine clinical practice.

Methods: Analyses were derived from all consecutive aPDAC patients treated in L1 between January 2011 and December 2017 in two French institutions, with either FOLFOXIRI ( = 165) or FOLFIRINOX ( = 124) regimens. FOLFOXIRI consisted of irinotecan (165 mg/m), oxaliplatin (85 mg/m), leucovorin (200 mg/m) and 5-fluorouracil (3200 mg/m as a 48-h continuous infusion) every 2 wk. Ninety-six pairs of patients were selected through propensity score matching, and clinical outcomes of the two treatment regimens were compared.

Results: Median overall survival was 11.1 mo in the FOLFOXIRI and 11.6 mo in the FOLFIRINOX cohorts, respectively. After propensity score matching, survival rates remained similar between the two regimens in terms of overall survival (hazard ratio = 1.22; = 0.219) and progression-free survival (hazard ratio = 1.27; = 0.120). The objective response rate was 37.1% in the FOLFOXIRI group 47.8% in the FOLFIRINOX group ( = 0.187). Grade 3/4 toxicities occurred in 28.7% of patients in the FOLFOXIRI cohort 19.5% in the FOLFIRINOX cohort ( = 0.079). FOLFOXIRI was associated with a higher incidence of grade 3/4 digestive adverse events. Hematopoietic growth factors were used after each chemotherapy cycle and the low hematological toxicity rates were below 5% with both regimens.

Conclusion: FOLFOXIRI is feasible in L1 in patients with aPDAC but does not confer any therapeutic benefit as compared with FOLFIRINOX. The low hematological toxicity rates strengthened the relevance of primary prophylaxis with hematopoietic growth factors.
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http://dx.doi.org/10.4251/wjgo.v12.i3.332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081111PMC
March 2020

Imaging for Metastasis in Prostate Cancer: A Review of the Literature.

Front Oncol 2020 31;10:55. Epub 2020 Jan 31.

Department of Medical Oncology, CHU Lille, Lille, France.

Initial staging and assessment of treatment activity in metastatic prostate cancer (PCa) patients is controversial. Indications for the various available imaging modalities are not well-established due to rapid advancements in imaging and treatment. We conducted a critical literature review of the main imaging abnormalities that suggest a diagnosis of metastasis in localized and locally advanced PCa or in cases of biological relapse. We also assessed the role of the various imaging modalities available in routine clinical practice for the detection of metastases and response to treatment in metastatic PCa patients. In published clinical trials, the most commonly used imaging modalities for the detection and evaluation of therapeutic response are bone scan, abdominopelvic computed tomography (CT), and pelvic and bone magnetic resonance imaging (MRI). For the detection and follow-up of metastases during treatment, modern imaging techniques i.e., choline-positron emission tomography (PET), fluciclovine-PET, or Prostate-specific membrane antigen (PSMA)-PET provide better sensitivity and specificity. This is particularly the case of fluciclovine-PET and PSMA-PET in cases of biochemical recurrence with low values of prostate specific antigen. In routine clinical practice, conventional imaging still have a role, and communication between imagers and clinicians should be encouraged. Present and future clinical trials should use modern imaging methods to clarify their usage.
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http://dx.doi.org/10.3389/fonc.2020.00055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005012PMC
January 2020

Bone Metastasis: Current State of Play.

Transl Oncol 2020 Feb 23;13(2):308-320. Epub 2019 Dec 23.

Department of Rheumatology, CHU de Lille, 59037 Lille, France; Department of supportive care, Centre Oscar Lambret, 59000 Lille, France.

Bone metastasis (BM) in cancer remains a critical issue because of its associated clinical and biological complications. Moreover, BM can alter the quality of life and survival rate of cancer patients. Growing evidence suggests that bones are a fertile ground for the development of metastasis through a "vicious circle" of bone resorption/formation and tumor growth. This review aims to outline the current major issues in the diagnosis and management of BM in the most common types of osteotropic cancers and describe the mechanisms and effects of BM. First, we discuss the incidence of BM through the following questions: Are we witnessing an increase in incidence, and are we now better equipped with modern imaging techniques? Is the advent of efficient bone resorption inhibitors affecting the bigger picture of BM management? Second, we discuss the potential effects of cancer progression and well-prescribed drugs, such as multitarget tyrosine kinase inhibitors, inhibitors of the mammalian target of rapamycin, and immune checkpoint inhibitors, on BM. Finally, we examine the duality of the effects of some therapies that may help in cancer treatment but may also contribute to further BM.
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http://dx.doi.org/10.1016/j.tranon.2019.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6931192PMC
February 2020

Should all pancreatic surgery be centralized regardless of patients' comorbidity?

HPB (Oxford) 2020 07 26;22(7):1057-1066. Epub 2019 Nov 26.

Department of Digestive Surgery and Transplantation, Lille University Hospital, Lille, France; University of LilleLille, France.

Background: It remains to be established whether centralization to high volume centers is essential for all patients undergoing pancreatic surgery. The aims of this study were to identify the optimal cut-off volume to optimize patient outcomes and to determine if patient comorbidity affected the volume-outcome relationship.

Methods: Patients undergoing pancreatectomy from 2012 to 2015 were retrospectively identified (n = 12 333) in the French nationwide database. The 90-day Post-Operative Mortality (POM) was analyzed according to hospital volume of pancreatectomy (very low:<10, Low:10-19, High:20-49 and very high:≥50 resections/year) and Charlson Comorbidity Index (ChCI).

Results: The overall POM was 6.9%. The cut-off of 20 pancreatic resections per year was identified as predictor of POM. Compared to high volume centers, POM was significantly higher in low and very low volume centers whatever the ChCl. Regarding surgical procedures, there was a significant decrease in POM with increasing hospital volume only after pancreaticoduodenectomy regardless of the ChCl. On multivariable analysis, low and very low volume centers were independently associated with increased mortality rates.

Conclusion: The optimal cut-off of annual caseload was 20 pancreatic resections. POM following pancreaticoduodenectomy is high in low and very low volume centers independently of ChCl, suggesting that this procedure should be centralized.
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http://dx.doi.org/10.1016/j.hpb.2019.10.2443DOI Listing
July 2020

ASO Author Reflections: Fong's Score in the Era of Modern Strategies for Metastatic Colorectal Cancer.

Ann Surg Oncol 2020 Mar 12;27(3):886. Epub 2019 Nov 12.

Department of Medical Oncology, Lille University Hospital, Lille, France.

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http://dx.doi.org/10.1245/s10434-019-08059-3DOI Listing
March 2020

Asymmetric kinetics of volume and function of the remnant liver after major hepatectomy as a key for postoperative outcome - A case-matched study.

HPB (Oxford) 2020 06 25;22(6):855-863. Epub 2019 Oct 25.

Department of Digestive Surgery and Transplantation, CHU, Univ Nord de France, F-59000 Lille, France.

Background: The kinetics of remnant liver (RL) function is unknown after major hepatectomy (MH), especially in case of post-hepatectomy liver failure (PHLF). This study investigated the change in RL function after MH using 99mTc-labelled-mebrofenin SPECT-scintigraphy and its correlation with RL volume and PHLF.

Methods: From 2011 to 2015, 125 patients undergoing MH had volumetric assessment by CT and functional SPECT-scintigraphy preoperatively and at day 7 (POD7) and 1 month (1M). RL volume and function changes were compared in (i) overall population and (ii) 17 patients with vs. 42 without PHLF (ISGLS) matched on preoperative RL function.

Results: Increase in RL function correlated poorly with volume increase at POD7 (r = 0.035, p = 0.43) and 1M (r = 0.394, p < 0.0001). Overall, function increase on POD7 (+38.8%) was lower than volume (+49.4%), but comparable at 1M (+78.8% vs. +73%). PHLF patients showed lower function increase on POD7 (+2.1% [-89%-77.8%] vs. +50% [-39%-218%]; p = 0.006). At 1M, 4 PHLF patients died with no function increase despite significant volumetric gain.

Conclusions: We first showed via sequential SPECT-scintigraphy that RL function increase after MH is slower than volume increase. A poor kinetic of function was correlated with PHLF as early as POD7, contrasting with substantial volume gain in PHLF patients.
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http://dx.doi.org/10.1016/j.hpb.2019.10.008DOI Listing
June 2020

Fong's Score in the Era of Modern Perioperative Chemotherapy for Metastatic Colorectal Cancer: A Post Hoc Analysis of the GERCOR-MIROX Phase III Trial.

Ann Surg Oncol 2020 Mar 22;27(3):877-885. Epub 2019 Oct 22.

Department of Medical Oncology, Lille University Hospital, Lille, France.

Background: Despite improvement in colorectal liver metastasis (CLM) treatment, survival after liver surgery remains highly variable. Several clinicopathologic prognostic factors have been reported, but their validity in the era of more effective perioperative chemotherapy remains to be defined. The aim of this study is to analyze the prognostic factors associated with survival after CLM resection.

Methods: Clinicopathologic data of patients included in the MIROX phase III trial who underwent surgery for isolated CLMs were analyzed. The primary endpoints were 5-year overall survival (OS) and disease-free survival (DFS). Univariate Cox analysis was performed to identify associations with OS and DFS and select variables for inclusion in a multivariate model to determine their independent prognostic value.

Results: A total of 181 patients were analyzed. The median follow-up period was 6.42 years [95% confidence interval (CI) 5.15-8.71 years], and the 5-year OS and DFS rates were 67.1% and 35.4%, respectively. On multivariate analysis, Fong's clinical risk score (CRS) as a categorical variable (CRS 0-1 vs. 2-3 vs. 4-5, p = 0.036) and polymorphonuclear neutrophil (PMN) count (> 6000/mm vs. ≤ 6000/mm, p = 0.006) before chemotherapy were found to be independent prognostic factors for OS. However, only Fong's CRS remained significantly associated with DFS (p = 0.027). The final OS model was used to establish a nomogram that allows individual OS estimations at 1, 3, 5, and 10 years.

Conclusions: Fong's CRS was independently associated with DFS and poor OS after CLM resection with FOLFOX-based chemotherapy regimen. It could be useful in daily practice and future trials to select patients more accurately.
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http://dx.doi.org/10.1245/s10434-019-07976-7DOI Listing
March 2020

Spatial heterogeneity of mutations in colorectal cancers in northern France.

Cancer Manag Res 2019 13;11:8337-8344. Epub 2019 Sep 13.

Medical oncology unit, Hôpital Claude Huriez, F-59000 Lille, France.

Background: Somatic mutations in the gene are the most common oncogenic mutations found in human cancers. However, no clinical features have been linked to KRAS mutations in colorectal cancer [CRC].

Purpose: In this study, we attempted to identify the potential geographical population clusters of mutations in CRC patients in northern France.

Patients And Methods: All patients with CRC who were identified to have mutations between 2008 and 2014 at the Regional Molecular Biology Platform at Lille University Hospital were included. 2,486 patients underwent a status available, with 40.9% of CRC with KRAS mutations in northern France. We retrospectively collected demographic and geographic data from these patients. The proportions of mutation were smoothed to take into account the variability related to low frequencies and spatial autocorrelation. Geographical clusters were searched using spatial scan statistical models.

Results: A mutation at codon 12 or 13 was found in 1,018 patients [40.9%]. We report 5 clusters of over-incidence but only one elongated cluster that was statistically significant [Cluster 1; proportion of mutation among CRC: 0.4570; RR=1.29; P=0.0314]. We made an ecological study which did not highlight a significant association between mutations and the distance to the Closest Waste Incineration Plant, and between mutations and The French Ecological Deprivation Index but few socio-economic and environmental data were available.

Conclusion: There was a spatial heterogeneity and a greater frequency of mutations in some areas close to major highways and big cities in northern France. These data demand deeper epidemiological investigations to identify environmental factors such as air pollution as key factors in the occurrence of mutations.
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http://dx.doi.org/10.2147/CMAR.S211119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6750880PMC
September 2019

Prognostic factors in patients with stage II colon cancer: Role of E-selectin gene polymorphisms.

Dig Liver Dis 2019 08 18;51(8):1198-1201. Epub 2019 Jun 18.

Department of Medical Oncology, Hôpital Claude Huriez, France. Electronic address:

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http://dx.doi.org/10.1016/j.dld.2019.05.019DOI Listing
August 2019

[Minimum activity threshold for digestive cancer surgery in France: What are the issues?]

Bull Cancer 2019 Jun 15;106(6):512-513. Epub 2019 May 15.

CHRU de Lille, département de chirurgie digestive et transplantation, 59000 Lille, France; Université de Lille, 59000 Lille, France.

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http://dx.doi.org/10.1016/j.bulcan.2019.03.018DOI Listing
June 2019

[A GERCOR-AERIO national survey of oncology residents in France: Current setting and expectations regarding post-internship and research].

Bull Cancer 2019 May 12;106(5):407-420. Epub 2019 Apr 12.

Institut Curie, université Versailles Saint-Quentin (UVSQ), département d'oncologie médicale, 35, rue Dailly, 92210 Saint-Cloud, France; GERCOR, 151, rue du Faubourg Saint-Antoine, 75011 Paris, France.

Introduction: The demographics of oncology residents has changed since 2010 with the increase in the size of promotions. The evolution of the residents' aspirations towards research and their future exercise in parallel with these demographic changes has not been assessed.

Methods: A questionnaire was developed by a working group from GERCOR (cooperative group in oncology), involving clinicians, researchers, GERCOR members, and residents. It consisted of 62 questions divided into 7 sections: demographics, medical thesis, post-residency, mobility, publication activity, basic research, and clinical/translational research. The national survey was published online by the Association d'enseignement et de recherche des internes en oncologie (AERIO).

Results: In total, 143 residents participated, of which 116 (81.1%) completed the questionnaire entirely. The population was representative of the current demographics, with a majority of women (65.0%), a median age of 28 years, and 39.7% of residents from Paris region. The unsupervised analysis revealed four profiles of residents, including one group strongly committed to research (16.8%), one group with moderate involvement (41.3%) and one group that did not seem interested in research (14.7%). Uncertainty about future position and lack of time and interaction with researchers appeared to be the main barriers to involvement of residents in research.

Discussion: This national survey provided useful information about the residents' perspective to academic research. It may serve as a basis for proposing measures adapted to their expectations.
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http://dx.doi.org/10.1016/j.bulcan.2019.02.009DOI Listing
May 2019

[Before seasonal influenza, vaccination of cancer patients and healthcare givers].

Bull Cancer 2019 Feb 30;106(2):94-96. Epub 2019 Jan 30.

Centre Oscar-Lambret, service de soins palliatifs, 3, rue Combemale, 59020 Lille cedex, France.

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http://dx.doi.org/10.1016/j.bulcan.2019.01.006DOI Listing
February 2019

[Adjuvant chemotherapy for upper tract urothelial cancer: Level of evidence IA].

Bull Cancer 2018 Oct 17;105(10):853-854. Epub 2018 Sep 17.

Centre Oscar-Lambret, département de cancérologie générale, 3, rue Combemale, 59020 Lille cedex, France; Hôpital Claude-Huriez, service universitaire d'oncologie médicale, rue Michel-Polonowski, 59037 Lille cedex, France. Electronic address:

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http://dx.doi.org/10.1016/j.bulcan.2018.07.017DOI Listing
October 2018