Publications by authors named "Marie-Cécile Le Deley"

120 Publications

Effects of Proton Pump Inhibitors Intake During Chemoradiotherapy for Rectal Cancer: a Retrospective Cohort Study.

J Gastrointest Cancer 2022 May 14. Epub 2022 May 14.

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

Purpose: Proton pump inhibitors (PPIs) are one of the most widely used drugs worldwide and are involved in several drug interactions. Recently, several studies have suggested that PPIs may interfere with the efficacy of capecitabine. This study primarily aimed to investigate the effects of PPI intake on the pathologic response rate of patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy with capecitabine.

Method: A retrospective study was conducted at a French Comprehensive Cancer Center. Patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by surgery were included in the study. Demographic parameters, treatment characteristics, survival data, and PPI intake data were collected. Frequencies and percentages were reported for categorical variables and medians and interquartile ranges for continuous variables. Distribution of variables was compared according to PPI treatment using the chi-square test or Fisher's exact test for categorical data and nonparametric Wilcoxon tests for continuous variables. Survival data were estimated using the Kaplan-Meier method and compared using the log-rank test.

Results: In total, 215 patients were included, of whom 135 (62.8%) were men. The PPI intake frequency was 16.1%. The rate of complete pathological response was not significantly lower in patients on PPIs than in those not on PPIs (8.7% vs. 19%, p = 0.36). PPI intake was not associated with a statistically significant decrease in recurrence-free survival (hazard ratio [HR] = 1.26, 95% confidence interval [CI] 0.61-2.60, p = 0.54) or overall survival (HR = 0.95, 95% CI 0.33-2.76, p = 0.93).

Conclusion: No significant association was observed between PPI co-medication and complete pathological response or survival in patients treated for locally advanced rectal cancer. However, the safety of PPIs could not be confirmed. Further ancillary studies of prospective clinical trials or studies using the Health Data Hub are necessary to explore the effects of PPIs on rectal cancer more accurately.
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http://dx.doi.org/10.1007/s12029-022-00825-zDOI Listing
May 2022

MRI and Molecular Characterization of Pediatric High-Grade Midline Thalamic Gliomas: The HERBY Phase II Trial.

Radiology 2022 Apr 12:211464. Epub 2022 Apr 12.

From the Department of Medical Physics and Clinical Engineering (D.R., P.S.M.) and Department of Radiology (R.A.D., T.J.), Nottingham University Hospitals Trust, Derby Rd, Nottingham NG7 2UH, England; Mental Health & Clinical Neurosciences Unit, University of Nottingham, Nottingham, England (D.R., R.A.D., P.S.M.); Department of Pediatric Radiology, Necker Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France (R.C.); Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands (E.S.A.); Department of Radiology, Leeds Teaching Hospitals, Leeds, England (D.W.); Institute for Diagnostic and Interventional Neuroradiology, Würzburg University, Würzburg, Germany (M.W.M.); Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, London, England (C.J., A.M.); Department of Pathological Anatomy and Cytology, Centre Hospitalier Sainte Anne, Paris, France (P.V.); Department of Biostatistics, Centre Oscar Lambret, Lille, France (M.C.L.D.); Department of Haematology and Oncology, Great Ormond Street Hospital, London, England (D.H.); Pediatric Oncology and Hematology Unit, Hospital La Fe, Valencia, Spain (A.C.); Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy (M.M.); Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Medical University of Vienna, Vienna, Austria (A.A.A.); Auckland Radiation Oncology, Auckland City Hospital, New Zealand. (F.S.); F. Hoffmann-La Roche, Basel, Switzerland (G.Z., J. Garcia); Department of Pediatric and Adolescent Oncology and Unit 981 from the Institut National de la Santé et de la Recherche Médicale, Gustave Roussy, Université Paris-Saclay, Université Paris-Sud, Villejuif, France (G.V., J. Grill); and Institute of Cancer and Genomic Sciences, University of Birmingham, and Birmingham Children's Hospital, Birmingham, England (A.P.).

Background Diffuse midline gliomas (DMG) are characterized by a high incidence of mutations and poorer outcome. The HERBY trial has provided one of the largest cohorts of pediatric DMGs with available radiologic, histologic-genotypic, and survival data. Purpose To define MRI and molecular characteristics of DMG. Materials and Methods This study is a secondary analysis of a prospective trial (HERBY; ClinicalTrials.gov identifier, NCT01390948) undertaken between October 2011 and February 2016. Among 121 HERBY participants, 50 had midline nonpontine-based tumors. Midline high-grade gliomas were reclassified into DMG mutant, wild type with enhancer of zest homologs inhibitory protein overexpression, epidermal growth factor receptormutant, or not otherwise stated. The epicenter of each tumor and other radiologic characteristics were ascertained from MRI and correlated with the new subtype classification, histopathologic characteristics, surgical extent, and outcome parameters. Kaplan-Meier curves and log-rank tests were applied to determine and describe survival differences between groups. Results There were 42 participants (mean age, 12 years ± 4 [SD]; 23 girls) with radiologically evaluable thalamic-based DMG. Eighteen had partial thalamic involvement (12 thalamopulvinar, six anteromedial), 10 involved a whole thalamus, nine had unithalamic tumors with diffuse contiguous extension, and five had bithalamic tumors (two symmetric, three partial). Twenty-eight participants had DMG mutant tumors; there were no differences in outcome compared with other DMGs ( = 4). Participants who underwent major debulking or total or near-total resection had longer overall survival (OS): 18.5 months vs 11.4 months ( = .02). Enrolled participants who developed leptomeningeal metastatic dissemination before starting treatment had worse outcomes (event-free survival, 2.9 months vs 8.0 months [ = .02]; OS, 11.4 months vs 18.5 months [ = .004]). Conclusion Thalamic involvement of diffuse midline gliomas ranged from localized partial thalamic to holo- or bithalamic with diffuse contiguous spread and had poor outcomes, irrespective of subtype alterations. Leptomeningeal dissemination and less than 50% surgical resection were adverse risk factors for survival. Clinical trial registration no. NCT01390948 © RSNA, 2022 . See also the editorial by Widjaja in this issue.
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http://dx.doi.org/10.1148/radiol.211464DOI Listing
April 2022

Lack of prognostic value of CTNNB1 mutation profile in desmoid-type fibromatosis.

Clin Cancer Res 2022 Mar 16. Epub 2022 Mar 16.

Gustave Roussy Cancer Institute, Villejuif, France.

Purpose: This prospective nationwide cohort study aimed to investigate desmoid-type fibromatosis (DF) outcomes, focusing on the prognostic value of CTNNB1 mutations.

Experimental Design: ALTITUDES (NCT02867033) was a nationwide prospective cohort study of DF diagnosed between January 2016 and December 2020. At diagnosis, CTNNB1 molecular alterations were identified using next-generation sequencing or Sanger sequencing. The primary endpoint was event-free survival (EFS) (progression, relapse, or death). We enrolled 628 patients managed by active surveillance (AS), surgical resection (SR), or systemic treatment as front-line therapy.

Results: Overall, 516 (82.2%) patients (368 females [71.3%], median age 40.3 years [range, 1-89]) were eligible for analysis. In 435 (84.3%) cases, there was one CTNNB1 molecular alteration: p.T41A, p.S45F, or p.S45P. The front-line management was AS in 352 (68.2%), SR in 120 (23.3%), and systemic treatments in 44 (8.5%) patients. CTNNB1 mutation distribution was similar across the three therapeutic groups. The median follow-up period was 24.7 (range, 0.4-59.7) months. The estimated 3-year EFS rate was 66.2% (95%CI, 60.5%-71.2%). DF harboring p.S45F was significantly associated with male sex (p=0.03), non-abdominal wall sites (p=0.05), pain (p=0.007), and large tumor size (p=0.025). CTNNB1 p.S45F mutation was not significantly associated with EFS, either in univariate (hazard ratio [HR]=1.06; 95% confidence interval [CI], 0.65-1.73; p=0.81), or in multivariate analysis (HR=0.91; 95% CI, 0.55-1.49; p=0.71).

Conclusions: We found that CTNNB1 mutation profile was associated with unfavorable prognostic factors but was not a prognostic factor for EFS.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-4235DOI Listing
March 2022

Reply to H. B et al.

J Clin Oncol 2022 03 7;40(9):1030-1032. Epub 2022 Feb 7.

Anne-Sophie Defachelles, MD, and Emilie Bogart, MD, Centre Oscar Lambret, Lille, France; Michela Casanova, MD, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy; Johannes H.M. Merks, MD, Princess Maxima Center for Pediatric Oncology, Utrecht, the Netherlands; Gianni Bisogno, MD, PhD, Department of Women and Children Health, University Hospital of Padova, Padova, Italy; Giuseppina Calareso, MD, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy; Soledad Gallego Melcon, MD, PhD, University Hospital Vall d'Hebron, Barcelona, Spain; Susanne Andrea Gatz, MD, Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom; Marie-Cécile Le Deley, MD, Centre Oscar Lambret, Lille, France; Kieran McHugh, MD, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom; Alicia Probst, MSc, and Nathalie Rocourt, MD, Centre Oscar Lambret, Lille, France; Rick R. van Rijn, MD, PhD, Amsterdam University Medical Centers, Amsterdam, the Netherlands; Véronique Minard-Colin, MD, PhD, Department of Pediatric and Adolescent Oncology, INSERM U1015, Gustave Roussy, Université Paris-Saclay, Villejuif, France; and Julia C. Chisholm, MD, Children and Young People's Unit, The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, United Kingdom.

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http://dx.doi.org/10.1200/JCO.21.02612DOI Listing
March 2022

Head and neck Ewing sarcoma: French surgical practice analysis pleads for surgery centralization.

J Craniomaxillofac Surg 2021 Feb 6. Epub 2021 Feb 6.

Unit of Maxillofacial and Plastic Surgery, APHP, Necker-Enfants Malades, 149 Rue de Sèvres, Paris, 75015, France; University Paris Descartes, 12 Rue de l'École de Médecine, 75006, Paris, France.

This study aimed to analyze surgical procedures for head and neck Ewing sarcoma (HNES) with regard to oncological, functional, and esthetic outcomes. A blinded multidisciplinary retrospective chart review of operated French HNES patients (Euro-EWING 99 trial, 1999-2014) was performed to assess patient/tumor characteristics, treatment details, and outcomes. Primary surgery without reconstruction was undertaken in 13 patients (emergency context/misdiagnosis). However, because of contaminated surgical margins, all patients had to undergo systematic postoperative radiotherapy. Twenty-six patients underwent multidisciplinary evaluation and were scheduled to undergo postchemotherapy surgery, with 19 patients scheduled for immediate reconstruction. All cases showed R0 margins after postchemotherapy surgery of the initial tumor bed by multidisciplinary surgical teams, while n = 3/4 of local relapses (very poor prognosis) had R1a margins after surgery of the residual tumor volume following chemotherapy. Only three surgical expertise centers operated on ≥ 4 patients over the 15-year period. Thirty patients developed long-term sequelae, with increased complications following radiotherapy. Referring patients to surgical expertise centers following a suspected diagnosis, with planned postchemotherapy surgery of the initial tumor bed at these centers, might limit the need for intralesional resections, allowing radical R0 resections and thus reducing long-term sequelae as well as the risk of secondary radio-induced malignancy by limiting the need for postoperative radiotherapy.
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http://dx.doi.org/10.1016/j.jcms.2021.01.030DOI Listing
February 2021

Long-Term Outcomes and Prognostic Factors of Patients with Metastatic Solid Tumors Admitted to the Intensive Care Unit.

Oncology 2022 20;100(3):173-181. Epub 2022 Jan 20.

Department of Medical Oncology, Centre Oscar Lambret, Lille, France.

Introduction: Admission of metastatic cancer patients to the intensive care unit (ICU) poses medical and ethical challenges in the absence of reliable prognostic tools to guide decision-making.

Material And Methods: We retrospectively analyzed the medical charts of 129 consecutive patients with metastatic solid tumors admitted to the ICU between January and September 2014 and identified prognostic factors (PFs) using Cox models.

Results: The mean patient age at ICU admission was 58.9 years (range, 25-81 years; males, 51%). Performance status (PS) was 0-1 and 2-3 in 61% and 39% of the patients, respectively. The most prevalent cancers were lung cancer (20%), sarcoma (17%), and breast cancer (16%). ICU admission was attributable to the cancer itself (53%), cancer treatment toxicity (43%), and comorbidities (37%). The median overall survival (OS) after ICU admission was 2.6 months; 15% of the patients died during the ICU stay. Poor PFs for OS were PS >1 before ICU admission (p = 0.007) and ICU admission for the cancer itself (p < 10-3). After ICU discharge, 58% and 42% of the patients received systemic treatment within 12 months and showed good PS recovery, respectively. Multiple organ failure and a multidisciplinary decision to limit therapeutic efforts were poor PFs for reinitiation of systemic treatment (p = 0.2 and 0.006, respectively), and the latter was also a poor PF for PS recovery (p = 0.004).

Discussion: In the ICU, the OS of adult patients with solid tumors was similar to that of the noncancer population. For ICU admissions related to the cancer itself, the prognosis is poor.
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http://dx.doi.org/10.1159/000520097DOI Listing
March 2022

Is ovarian recovery after chemotherapy in young patients with early breast cancer influenced by controlled ovarian hyperstimulation for fertility preservation or tumor characteristics? Results of a prospective study in 126 patients.

Int J Cancer 2022 06 7;150(11):1850-1860. Epub 2022 Feb 7.

Centre d'Assistance Médicale à la Procréation et de Préservation de la Fertilité, Hôpital Jeanne de Flandre, Centre Hospitalier Universitaire de Lille, Lille, France.

Young individuals, aged <40 years, represent 7% of all patients with early breast cancer (EBC), most of whom receive chemotherapy. Preserving future fertility in these patients has become a major concern. This prospective study assessed ovarian function during and after chemotherapy according to patient and tumor characteristics and evaluated the outcome of controlled ovarian hyperstimulation (COH). Ovarian reserve was evaluated in terms of amenorrhea duration and by longitudinal serum anti-Müllerian hormone (AMH) level variations measured at study entry, during treatment and until 24 months thereafter. COH has been proposed for patients receiving adjuvant chemotherapy. We studied the association between clinical factors and ovarian function using Cox models and logistic regression. In this young population (age < 38 years, median = 32), 85 of 90 evaluable patients (94%) experienced chemo-induced amenorrhea, including six persistent amenorrhea and one chemotherapy-induced definitive ovarian failure. Overall, 33% of patients still had undetectable AMH values 12 months after the end of chemotherapy, although most had recovered spontaneous and regular menstrual function. No specific factor was associated with clinical or biological late ovarian dysfunction, except for age and baseline AMH value. Overall, 58 patients underwent COH. The mean number of total retrieved oocytes and metaphase II oocytes were of 11.7 and 6.9, respectively. Thus, our study confirms the importance of fertility preservation in young patients with EBC. Our findings indicate that sequential chemotherapy is associated with a higher risk of persistent amenorrhea. There was no significant association between tumor characteristics, fertility preservation or recovery of ovarian reserve.
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http://dx.doi.org/10.1002/ijc.33933DOI Listing
June 2022

Functional Cerebral MRI Evaluation of Integration of Breast Reconstruction into the Body Schema.

Ann Surg Oncol 2022 Apr 27;29(4):2652-2661. Epub 2021 Nov 27.

Imagering Department of Adolphe Rothschild Fondation, Paris, France.

Background: The objective of breast reconstruction (BR) is to erase the after-effects of total mastectomy by allowing patients to restore their breast shape. The aim of our study was to investigate the body map integration of different types of BR using functional magnetic resonance (fMRI).

Patients And Methods: We prospectively enrolled all women undergoing BR for breast cancer to the Remasco study (NCT02553967). Participants were categorized into four groups according to the standard of care they required: immediate BR (IBR), delayed BR (DBR), flap (autologous), or implant BR. Each patient performed sensorimotor tasks during the fMRI acquisition.

Results: Data of 38 patients were analyzed. We identified the cingulate region as the area of interest in the brain. In the case of DBR, the brain area activated during palpation of the total mastectomy scar (before BR) was different from the brain area activated during palpation of the reconstructed breast (Brodmann areas 31 versus 32). Palpation of the native breast and reconstructed breast activated the same Brodmann area 32. Comparing the brain activation signal during palpation of the native breast and the reconstructed breast did not reveal any significant difference in the overall population (P = 0.41) or in the groups: autologous (P = 0.32), implant (P = 0.10), IBR (P = 0.72), or DBR (P = 0.10).

Conclusions: This experimental study allowed us to describe and understand the brain plasticity processes that accompany BR. The results suggest that the reconstructed breast is integrated into the body schema, regardless of the type of BR or the timing.
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http://dx.doi.org/10.1245/s10434-021-11048-0DOI Listing
April 2022

A New Paradigm in Managing Advanced Ovarian Cancer: Differentiating Patients Requiring Neoadjuvant Treatment from Primary Cytoreduction.

Cancers (Basel) 2021 Sep 30;13(19). Epub 2021 Sep 30.

Department of Gynecologic Oncology, Oscar Lambret Center, 59000 Lille, France.

Our study aims to evaluate the comparability of primary debulking surgery (PDS) and neoadjuvant chemotherapy (NACT) patients. This single-center retrospective study includes all patients treated for advanced stages high-grade serous ovarian carcinomas (HGSOC) between 2007 and 2017. Preoperative characteristics and postoperative outcomes were compared after a propensity score matching analysis. Of the 221 patients included, 38% underwent PDS, and 62% received NACT. There was no age difference at diagnosis; however, CA125 levels, PCI score levels, and rates of stage IV were higher in the NACT group. There were no differences concerning the rate and the severity of complications ( = 0.29). The propensity score distribution showed a broad distinction between PDS patients and NACT patients with no significant overlap. Survival analyses demonstrate, after a median follow-up of 66.5 months, an overall survival (OS) of 105.9 and progression-free survival (PFS) of 29.2 months in the PDS group, compared to OS of 52.8 and PFS of 18.9 months in the NACT group. Advanced HGSOC is a heterogeneous population, in which inoperable patients should be differentiated from PDS patients based on many factors, primarily tumor burden.
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http://dx.doi.org/10.3390/cancers13194925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508489PMC
September 2021

Use of a Biodegradable, Contrast-Filled Rectal Spacer Balloon in Intensity-Modulated Radiotherapy for Intermediate-Risk Prostate Cancer Patients: Dosimetric Gains in the BioPro-RCMI-1505 Study.

Front Oncol 2021 26;11:701998. Epub 2021 Aug 26.

Academic Department of Radiation Oncology, Centre Oscar Lambret, Lille, France.

Background/purpose: Dose-escalated external beam radiotherapy (RT) is effective in the control of prostate cancer but is associated with a greater incidence of rectal adverse events. We assessed the dosimetric gain and safety profile associated with implantation of a new biodegradable rectal spacer balloon.

Materials/methods: Patients scheduled for image-guided, intensity-modulated RT for intermediate-risk prostate cancer were prospectively included in the French multicenter BioPro-RCMI-1505 study (NCT02478112). We evaluated the dosimetric gain, implantation feasibility, adverse events (AEs), and prostate-cancer-specific quality of life associated with use of the balloon spacer.

Results: After a scheduled review of the initial recruitment target of 50 patients by the study's independent data monitoring committee (IDMC), a total of 24 patients (including 22 with dosimetry data) were included by a single center between November 2016 and May 2018. The interventional radiologist who implanted the balloons considered that 86% of the procedures were easy. 20 of the 24 patients (83.3%) received IMRT and 4 (16.7%) received volumetric modulated arc therapy (78-80 Gy delivered in 39 fractions). The dosimetric gains associated with spacer implantation were highly significant (p<0.001) for most variables. For the rectum, the median (range) relative gain ranged from 15.4% (-9.2-47.5) for D20cc to 91.4% (36.8-100.0) for V70 Gy (%). 15 patients (62%) experienced an acute grade 1 AE, 8 (33%) experienced a late grade 1 AE, 1 (4.2%) experienced an acute grade 2 AE, and 3 experienced a late grade 2 AE. No grade 3 AEs were reported. Quality of life was good at baseline (except for sexual activity) and did not markedly worsen during RT and up to 24 months afterwards.

Conclusion: The use of a biodegradable rectal spacer balloon is safe, effective and associated with dosimetric gains in modern RT for intermediate-risk prostate cancer.
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http://dx.doi.org/10.3389/fonc.2021.701998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427159PMC
August 2021

FOLFIRINOX relative dose intensity and disease control in advanced pancreatic adenocarcinoma.

Ther Adv Med Oncol 2021 16;13:17588359211029825. Epub 2021 Jul 16.

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.

Background: Most patients with advanced pancreatic adenocarcinoma (PA) treated with FOLFIRINOX experience adverse events requiring dose reduction. We aimed to assess the association between relative dose intensity (RDI) and disease control in a European setting.

Methods: We retrospectively included patients with advanced PA treated with three or more cycles of FOLFIRINOX between 2011 and 2018 in six French centers. We computed the cumulative single-agent RDI (csRDI) before the first reassessment for each FOLFIRINOX agent (oxaliplatin, irinotecan, 5FU bolus, and 5FU intravenous infusion) and the cumulative multi-drug RDI (cmRDI) of their combination. The association between RDI and disease control or objective response at first reassessment was evaluated using multivariable logistic regression models controlling for performance status, liver metastases, and center.

Results: We included 243 patients. Median csRDIs were 81%, 79%, 75%, and 85% for oxaliplatin, irinotecan, 5FU bolus, and 5FU intravenous infusion, respectively. Median cmRDI was 80%. None of the RDIs was significantly associated with disease control or objective response. Including RDI in a clinical model did not improve its ability to predict disease control; the area under the curve was 0.79 (95% CI: 0.73-0.85) with RDI 0.78 (95% CI: 0.72-0.85) without. Similar results were observed for the objective response.

Conclusion: Pragmatic dose adjustments of FOLFIRINOX should be made by oncologists without considering a loss of effect.
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http://dx.doi.org/10.1177/17588359211029825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287268PMC
July 2021

Randomized Phase II Trial of Vincristine-Irinotecan With or Without Temozolomide, in Children and Adults With Relapsed or Refractory Rhabdomyosarcoma: A European Paediatric Soft Tissue Sarcoma Study Group and Innovative Therapies for Children With Cancer Trial.

J Clin Oncol 2021 09 3;39(27):2979-2990. Epub 2021 Aug 3.

Children and Young People's Unit, The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, United Kingdom.

Purpose: The VIT-0910 trial was conducted to evaluate efficacy and safety of the vincristine-irinotecan combination with and without temozolomide (VIT and VI, respectively) in relapsed or refractory rhabdomyosarcoma (RMS).

Methods: In this randomized European phase II trial, patients age 0.5-50 years received 21-day cycles combining vincristine (1.5 mg/m once a day on day 1 and day 8) and irinotecan (50 mg/m once a day from day 1 to day 5) with and without temozolomide (125 mg/m once a day from day 1 to day 5 and 150 mg/m once a day from cycle 2), until progression or unacceptable toxicity. The primary end point was objective response rate after two cycles. Secondary end points included best response, progression-free survival, overall survival, and adverse events. A Simon 2-stage design was initially planned to separately analyze 40 patients/arm. After amendment, the trial sample size was increased to 120 and a comparison between arms, adjusted for confounding factors, was added to the statistical plan (ClinicalTrials.gov, NCT01355445).

Results: Overall, 120 patients (60 per arm) were recruited in 37 European centers. The median age was 11 years (range, 0.75-45); 89% of patients had a relapsed RMS. The objective response rate was 44% (24 of 55 evaluable patients) for VIT versus 31% (18 of 58) for VI (adjusted odds ratio, 0.50; 95% CI, 0.22 to 1.12; = .09). The VIT arm achieved significantly better overall survival (adjusted hazard ratio, 0.55; 95% CI, 0.35 to 0.84; = .006) compared with VI, with consistent progression-free survival results (adj-hazard ratio, 0.68; 95% CI, 0.46 to 1.01; = .059). Overall, patients experienced adverse events ≥ grade 3 more frequently with VIT than VI (98% 78%, respectively; = .009), including a significant excess of hematologic toxicity (81% 61%; = .025).

Conclusion: The addition of temozolomide to VI improved chemotherapy efficacy for patients with relapsed RMS, with manageable increase in toxicity. VIT is considered the new standard treatment in these patients in the European paediatric Soft Tissue Sarcoma Group and will be the control arm in the next randomized trial.
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http://dx.doi.org/10.1200/JCO.21.00124DOI Listing
September 2021

Studies of Intra-Fraction Prostate Motion During Stereotactic Irradiation in First Irradiation and Re-Irradiation.

Front Oncol 2021 14;11:690422. Epub 2021 Jul 14.

Academic Department of Radiation Oncology, Oscar Lambret Comprehensive Cancer Center, Lille, France.

Background: Understanding intra-fractional prostate motions is crucial for stereotactic body radiation therapy (SBRT). No studies have focused on the intra-fractional prostate motions during re-irradiation with SBRT. The objective was to evaluate these translational and rotational motions in primary treated patients and in the context of re-irradiation.

Methods: From January 2011 to March 2020, 162 patients with histologically proven prostate cancer underwent prostate SBRT, including 58 as part of a re-irradiation treatment. We used the continuous coordinates of the fiducial markers collected by an orthogonal X-ray dual-image monitoring system. The translations and rotations of the prostate were calculated. Prostate deviations representing overall movement was defined as the length of the 3D-vectors.

Results: A total of 858 data files were analyzed. The deviations over time in the group of primary treated patients were significantly larger than that of the group of re-irradiation, leading to a mean deviation of 2.73 mm (SD =1.00) versus 1.90 mm (SD =0.79), <0.001. In the re-irradiation group, we identified displacements of -0.05 mm (SD =1.53), 0.20 mm (SD =1.46); and 0.42 mm (SD =1.24) in the left-right, superior-inferior and anterior-posterior planes. Overall, we observed increasing deviations over the first 30 min followed by a stabilization related to movements in the three translational axes.

Conclusion: This is the first study to focus on intrafraction prostate motions in the context of re-irradiation. We observed that intra-fraction prostate motions persisted in the setting of re-irradiation, although they showed a significant reduction when compared with the first irradiation. These results will help to better estimate random errors during SBRT treatment of intra-prostatic recurrence after irradiation.
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http://dx.doi.org/10.3389/fonc.2021.690422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316636PMC
July 2021

"TNM" at study entry in phase I trials.

Bull Cancer 2021 06 7;108(6):671-672. Epub 2021 May 7.

University Bordeaux, Inserm, Bordeaux Population Health Research Center, ISPED, Université de Bordeaux, Case 11, 146, rue Léo-Saignat, 33076 Bordeaux cedex, France; Institut Bergonie, Inserm CIC 1401, Clinical and Epidemiological Research Unit, 351 cours de la Libération, 33405 Talence cedex, France.

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http://dx.doi.org/10.1016/j.bulcan.2021.01.020DOI Listing
June 2021

Successive Osteosarcoma Relapses after the First Line O2006/Sarcome-09 Trial: What Can We Learn for Further Phase-II Trials?

Cancers (Basel) 2021 Apr 2;13(7). Epub 2021 Apr 2.

Department of Oncology for Child and Adolescent, Gustave Roussy, Paris-Saclay University, 94800 Villejuif, France.

The purpose was to describe first and subsequent relapses in patients from the OS2006/Sarcome-09 trial, to help future trial design. We prospectively collected and analysed relapse data of all French patients included in the OS2006/Sarcome-09 trial, who had achieved a first complete remission. 157 patients experienced a first relapse. The median interval from diagnosis to relapse was 1.7 year (range 0.5-7.6). The first relapse was metastatic in 83% of patients, and disease was not measurable according to RECIST 1.1 criteria in 23%. Treatment consisted in systemic therapy (74%) and surgical resection (68%). A quarter of the patients were accrued in a phase-II clinical trial. A second complete remission was obtained for 79 patients. Most of them had undergone surgery (76/79). The 3-year progression-free and overall survival rates were 21% and 37%, respectively. In patients who achieved CR2, the 3y-PFS and OS rates were 39% and 62% respectively. Individual correlation between subsequent PFS durations was poor. For osteosarcoma relapses, we recommend randomised phase-II trials, open to patients from all age categories (children, adolescents, adults), not limited to patients with measurable disease (but stratified according to disease status), with PFS as primary endpoint, response rate and surgical CR as secondary endpoints.
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http://dx.doi.org/10.3390/cancers13071683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038261PMC
April 2021

Home hospitalization for palliative cancer care: factors associated with unplanned hospital admissions and death in hospital.

BMC Palliat Care 2021 Jan 26;20(1):24. Epub 2021 Jan 26.

Direction of Research and Innovation, Oscar Lambret Center, 3 rue Frédéric Combemale, 59020, Lille, France.

Background: Home hospitalization at the end of life can sometimes be perturbed by unplanned hospital admissions (UHAs, defined as any admission that is not part of a preplanned care procedure), which increase the likelihood of death in hospital. The objectives were to describe the occurrence and causes of UHAs in cancer patients receiving end-of-life care at home, and to identify factors associated with UHAs and death in hospital.

Methods: A retrospective, single-center study (performed at a regional cancer center in the city of Lille, northern France) of advanced cancer patients discharged to home hospitalization between January 2014 and December 2017. We estimated the incidence of UHA over time using Kaplan-Meier method and Kalbfleish and Prentice method. We investigated factors associated with the risk UHA in cause-specific Cox models. We evaluated factors associated with death in hospital in logistic regressions.

Results: One hundred and forty-two patients were included in the study. Eighty-two patients (57.7 %) experienced one or more UHAs, a high proportion of which occurred within 1 month after discharge to home. Most UHAs were related to physical symptoms and were initiated by the patient's family physician. A post-discharge palliative care consultation was associated with a significantly lower incidence of UHAs. Sixty-five patients (47.8 % of the deaths) died in hospital. In a multivariate analysis, living alone and the presence of one or more children at home were associated with death in hospital.

Conclusions: More than 40 % of cancer patients receiving end of life home hospitalization were not readmitted to hospital, reflecting the effectiveness of this type of palliative care setting. However, over half of the UHAs were due to an acute intercurrent event. Our results suggest that more efforts should be focused on anticipating these events at home - primarily via better upstream coordination between hospital physicians and family physicians.
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http://dx.doi.org/10.1186/s12904-021-00720-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839201PMC
January 2021

Characterization of Macrophages and Osteoclasts in the Osteosarcoma Tumor Microenvironment at Diagnosis: New Perspective for Osteosarcoma Treatment?

Cancers (Basel) 2021 Jan 23;13(3). Epub 2021 Jan 23.

Pôle Os-Articulations-Chirurgie Plastique, University of Nantes, INSERM UMR 1238, 44035 Nantes, France.

Biological and histopathological techniques identified osteoclasts and macrophages as targets of zoledronic acid (ZA), a therapeutic agent that was detrimental for patients in the French OS2006 trial. Conventional and multiplex immunohistochemistry of microenvironmental and OS cells were performed on biopsies of 124 OS2006 patients and 17 surgical ("OSNew") biopsies respectively. CSF-1R (common osteoclast/macrophage progenitor) and TRAP (osteoclast activity) levels in serum of 108 patients were correlated to response to chemotherapy and to prognosis. TRAP levels at surgery and at the end of the protocol were significantly lower in ZA+ than ZA- patients (p = 0.0011; 0.0132). For ZA+-patients, an increase in the CSF-1R level between diagnosis and surgery and a high TRAP level in the serum at biopsy were associated with a better response to chemotherapy ( = 0.0091; = 0.0251). At diagnosis, high CD163+ was associated with good prognosis, while low TRAP activity was associated with better overall survival in ZA- patients only. Multiplex immunohistochemistry demonstrated remarkable bipotent CD68+/CD163+ macrophages, homogeneously distributed throughout OS regions, aside osteoclasts (CD68+/CD163-) mostly residing in osteolytic territories and osteoid-matrix-associated CD68-/CD163+ macrophages. We demonstrate that ZA not only acts on harmful osteoclasts but also on protective macrophages, and hypothesize that the bipotent CD68+/CD163+ macrophages might present novel therapeutic targets.
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http://dx.doi.org/10.3390/cancers13030423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866157PMC
January 2021

Systematic review of phase-I/II trials enrolling refractory and recurrent Ewing sarcoma: Actual knowledge and future directions to optimize the research.

Cancer Med 2021 03 15;10(5):1589-1604. Epub 2021 Jan 15.

Department of Oncology for Child and Adolescent, Gustave Roussy Cancer Campus, Villejuif cedex, France.

Background: Optimal Phase-II design to evaluate new therapies in refractory/relapsed Ewing sarcomas (ES) remains imperfectly defined.

Objectives: Recurrent/refractory ES phase-I/II trials analysis to improve trials design.

Methods: Comprehensive review of therapeutic trials registered on five databases (who.int/trialsearch, clinicaltrials.gov, clinicaltrialsregister.eu, e-cancer.fr, and umin.ac.jp) and/or published in PubMed/ASCO/ESMO websites, between 2005 and 2018, using the criterion: (Ewing sarcoma OR bone sarcoma OR sarcoma) AND (Phase-I or Phase-II).

Results: The 146 trials identified (77 phase-I/II, 67 phase-II, and 2 phase-II/III) tested targeted (34%), chemo- (23%), immune therapies (19%), or combined therapies (24%). Twenty-three trials were ES specific and 48 had a specific ES stratum. Usually multicentric (88%), few trials were international (30%). Inclusion criteria cover the recurrent ES age range for only 12% of trials and allowed only accrual of measurable diseases (RECIST criteria). Single-arm design was the most frequent (88%) testing mainly single drugs (61%), only 5% were randomized. Primary efficacy outcome was response rate (RR=CR+PR; Complete+Partial response) (n = 116/146; 79%), rarely progression-free or overall survival (16% PFS and 3% OS). H0 and H1 hypotheses were variable (3%-25% and 20%-50%, respectively). The 62 published trials enrolled 827 ES patients. RR was poor (10%; 15 CR=1.7%, 68 PR=8.3%). Stable disease was the best response for 186 patients (25%). Median PFS/OS was of 1.9 (range 1.3-14.7) and 7.6 months (5-30), respectively. Eleven (18%) published trials were considered positive, with median RR/PFS/OS of 15% (7%-30%), 4.5 (1.3-10), and 16.6 months (6.9-30), respectively.

Conclusion: This review supports the need to develop the international randomized phase-II trials across all age ranges with PFS as primary endpoint.
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http://dx.doi.org/10.1002/cam4.3712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940237PMC
March 2021

Assessing Prognostic and Predictive Biomarkers of Regorafenib Response in Patients with Advanced Soft Tissue Sarcoma: REGOSARC Study.

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

Direction of Research and Innovation, Centre Oscar Lambret, 59000 Lille, France.

Regorafenib significantly prolonged progression-free survival (PFS) in pretreated patients with advanced non-adipocytic sarcoma (HR = 0.46; < 0.001) in a placebo-controlled, randomized, phase-II trial (NCT01900743). Thus, here, we assessed the prevalence of 57 biomarkers and their prognostic and predictive values for PFS and overall survival (OS). We analyzed 134/182 patients included in this trial, treated with regorafenib ( = 71, 53%) or placebo ( = 63, 47%). Mutational analyses were performed via full coding sequence analysis for 10 genes, and mutation hotspot panel for 50 genes (four genes in common). H19 was studied with RNA in-situ hybridization. The prognostic and predictive biomarkers' values were studied only for biomarkers found positive/mutated in at least 10 patients. Overall, 25 out of 57 studied biomarkers, including five out of seven genes involved in angiogenesis, were found mutated/positive in at least one patient, of which 23 biomarkers had low prevalence (fewer than eight out of 134 patients), contrasting with H19 ( = 24, 18%), and TP53 ( = 35, 26%). However, in multivariable models of PFS and OS, including treatment effects and interactions, no significant prognostic or predictive values of the tested biomarkers were observed. Though several promising biomarkers were found to be positive/mutated, none of them were identified as viable predictive and prognostic biomarkers.
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http://dx.doi.org/10.3390/cancers12123746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763753PMC
December 2020

Is the survival of patients treated with ipilimumab affected by antibiotics? An analysis of 1585 patients from the French National hospital discharge summary database (PMSI).

Oncoimmunology 2020 11 22;9(1):1846914. Epub 2020 Nov 22.

CERIM, ULR 2694 METRICS, Univ. Lille, CHU Lille, Lille, France.

: The gut microbiota has a key role in the regulation of the immune system. Disruption of the gut microbiota's composition by antibiotics might significantly affect the efficacy of immune checkpoint inhibitors. In a study of patients treated with ipilimumab, we sought to assess the relationship between overall survival and in-hospital antibiotic administration. : Patients having been treated with ipilimumab between January 2012 and November 2014 were selected from the French National Hospital Discharge Summary Database. Exposure to antibiotics was defined as the presence of a hospital stay with a documented systemic bacterial infection in the 2 months before or the month after initiation of the patient's first ever course of ipilimumab. The primary outcome was overall survival. : We studied 43,124 hospital stays involving 1585 patients from 97 centers. All patients had received ipilimumab monotherapy for advanced melanoma. Overall, 117 of the 1585 patients (7.4%) were documented as having received systemic antibiotic therapy in hospital during the defined exposure period. The median overall survival time was shorter in patients with infection (6.3 months, vs. 15.4 months in patients without an infection; hazard ratio (HR) = 1.88, 95% confidence interval [1.46; 2.43], = 10). In a multivariate analysis adjusted for covariates, infection was still significantly associated with overall survival (HR = 1.68, [1.30; 2.18], = 10). : In patients treated with ipilimumab for advanced melanoma, infection, and antibiotic administration in hospital at around the time of the patient's first ever course of ipilimumab appears to be associated with significantly lower clinical benefit.
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http://dx.doi.org/10.1080/2162402X.2020.1846914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714497PMC
November 2020

Role of radiotherapy and chemotherapy in the risk of leukemia after childhood cancer: An international pooled analysis.

Int J Cancer 2021 05 9;148(9):2079-2089. Epub 2020 Nov 9.

Radiation Epidemiology Group, Unit 1018 INSERM-CESP, Villejuif, France.

Childhood cancer survivors are at increased risk for second primary leukemia (SPL), but there is little consensus on the magnitude of some risk factors because of the small size of previous studies. We performed a pooled analysis of all published studies with detailed treatment data, including estimated active bone marrow (ABM) dose received during radiation therapy and doses of specific chemotherapeutic agents for childhood cancer diagnosed from 1930 through 2000, in order to more thoroughly investigate treatment-related risks of SPL. A total of 147 SPL cases (of which 69% were acute myeloid leukemia [AML]) were individually matched to 522 controls, all from four case-control studies including patients from six countries (France, United Kingdom, United States, Canada, Italy and Netherlands). Odds ratios (OR) and corresponding 95% confidence intervals (CIs) were calculated using conditional logistic regression, and the excess OR per Gray (EOR/Gy) was also calculated. After accounting for the other therapies received, topoisomerase II inhibitor was associated with an increased SPL risk (highest tertile vs none: OR = 10.0, 95% CI: 3.7-27.3). Radiation dose to the ABM was also associated with increased SPL risk among those not receiving chemotherapy (EOR/Gy = 1.6, 95% CI: 0.1-14.3), but not among those who received chemotherapy (CT). SPL were most likely to occur in the first decade following cancer treatment. Results were similar when analyses were restricted to AML. The evidence of interaction between radiation and CT has implications for leukemogenic mechanism. The results for topoisomerase II inhibitors are particularly important given their increasing use to treat childhood cancer.
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http://dx.doi.org/10.1002/ijc.33361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174089PMC
May 2021

Prognostic Factors in Childhood Anaplastic Large Cell Lymphoma: Long Term Results of the International ALCL99 Trial.

Cancers (Basel) 2020 Sep 24;12(10). Epub 2020 Sep 24.

Pediatric Hematology, Oncology and Stem Cell Transplant Division, Padua University Hospital, 35128 Padua, Italy.

With the aim of describing the long-term follow-up and to define the prognostic role of the clinical/pathological/molecular characteristics at diagnosis for childhood, adolescent and young adults affected by anaplastic large cell lymphoma (ALCL), we analyzed 420 patients aged up to 22 years homogeneously treated within the international ALCL99 trial. The 10-year progression free survival (PFS) was 70% and overall survival was 90%, rare late relapses occurred but no secondary malignancies were reported. Among clinical/pathological characteristics, only patients presenting a small cell/lymphohistiocytic (SC/LH) pattern were independently associated with risk of failure (hazard ratio = 2.49). Analysis of minimal disseminated disease (MDD), available for 162 patients, showed that both SC/LH pattern (hazard ratio = 2.4) and MDD positivity (hazard ratio = 2.15) were significantly associated with risk of failure in multivariate analysis. Considering MDD and SC/LH results, patients were separated into three biological/pathological (bp) risk groups: a high-risk group (bpHR) including MDD-positive patients with SC/LH pattern; a low-risk group (bpLR) including MDD-negative patients without SC/LH pattern; and an intermediate-risk group (bpIR) including remaining patients. The 10-year PFS was 40%, 75% and 86% for bpHR, bpIR and bpLR, respectively ( < 0.0001). These results should be considered in the design of future ALCL trials to tailor individual treatments.
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http://dx.doi.org/10.3390/cancers12102747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598675PMC
September 2020

[Dosimetric factors related to postoperative pulmonary complications in locally advanced esophageal cancers treated with preoperative chemoradiotherapy: Literature review].

Bull Cancer 2020 Oct 22;107(10):982-990. Epub 2020 Sep 22.

Centre Oscar-Lambret, département universitaire de radiothérapie, 3, rue F.-Combemale, 59020 Lille, France; Université de Lille, CRIStAL UMR 9189, Lille, France.

Introduction: Preoperative chemoradiotherapy is an option for locally advanced esophageal cancer. Radiation therapy may increase postoperative pulmonary complications. Usual lungs dose constraints in radiotherapy are old and used by extrapolation of lung cancer management. Our objective is to review the literature on correlations between postoperative lung toxicity and dosimetric factors.

Method: This literature review identified and selected studies published between 1987 and 2019 using the PRISMA method. The articles were identified on the basis of a PubMed search and the author's knowledge, using the following terms: "esophageal cancer"; "chemoradiotherapy"; "dosimetric factors"; "postoperative pulmonary complications".

Results: Fourteen articles were selected, and five did not demonstrate a correlation between dosimetric factors and the postoperative pulmonary complications rate. The V20 (lung volume receiving more than 20Gy) was identified in three studies, like the V10, V15 and mean lung dose (around 10Gy) in two studies. The V30≥20% was identified in one study.

Discussion: The most frequently identified dosimetric predictors for postoperative pulmonary complications are the V20 and the mean lung dose. Results of prospective studies would lead us to specify which of these parameters is most relevant for predicting the risk of postoperative pulmonary complications.
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http://dx.doi.org/10.1016/j.bulcan.2020.07.001DOI Listing
October 2020

DEPOSEIN-how meaningful was the benefit from intrathecal chemotherapy?

Neuro Oncol 2020 11;22(11):1710-1711

Department of Biostatistics, Oscar Lambret Center, Lille, France.

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http://dx.doi.org/10.1093/neuonc/noaa195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690348PMC
November 2020

Phase I study of vinblastine in combination with nilotinib in children, adolescents, and young adults with refractory or recurrent low-grade glioma.

Neurooncol Adv 2020 Jan-Dec;2(1):vdaa075. Epub 2020 Jun 9.

Department of Pediatric and Adolescent Oncology, Gustave Roussy, Villejuif, France.

Background: New rescue regimens are needed for pediatric refractory/recurrent low-grade glioma. Nilotinib is a tyrosine kinase inhibitor that has potential synergistic effects with vinblastine on angiogenesis, tumor cell growth, and immunomodulation.

Methods: This phase I trial aimed to determine the recommended doses of this combination for phase II trials (RP2D) using the dual-agent Bayesian continual reassessment method. Nilotinib was given orally twice daily (BID) in combination with once-weekly vinblastine injections for a maximum of 12 cycles of 28 days (clinicaltrials.gov, NCT01884922).

Results: Thirty-five pediatric patients were enrolled across 4 dose levels. The median age was 7 years and 10 had neurofibromatosis type 1. Patients had received a median of 3 prior treatment lines and 25% had received more than 4 previous treatment lines. Dose-limiting toxicity (DLT) during cycle 1 was hematologic, dermatologic, and cardiovascular. The RP2D was identified at 3 mg/m weekly for vinblastine with 230 mg/m BID for nilotinib (estimated probability of DLT = 18%; 95% credibility interval, 7-29%). Fifteen patients completed the 12 cycles; 2 stopped therapy prematurely due to toxicity and 18 due to disease progression. Three patients achieved a partial response leading to an objective response rate of 8.8% (95% confidence interval [CI], 1.9-23.7), and the disease control rate was 85.3% (95% CI, 68.9-95.1). The 12-month progression-free survival was 37.1% (95% CI, 23.2-53.67).

Conclusions: Vinblastine and nilotinib combination was mostly limited by myelosuppression and dermatologic toxicity. The efficacy of the combination at the RP2D is currently evaluated in a randomized phase II trial comparing this regimen to vinblastine alone.
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http://dx.doi.org/10.1093/noajnl/vdaa075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344116PMC
June 2020

Neuro-meningeal relapse in anaplastic large-cell lymphoma: incidence, risk factors and prognosis - a report from the European intergroup for childhood non-Hodgkin lymphoma.

Br J Haematol 2021 03 9;192(6):1039-1048. Epub 2020 Jul 9.

Department of Children and Adolescents Oncology, Gustave Roussy Cancer Center, Paris-Saclay University, Villejuif, France.

Relapses involving the central nervous system (CNS) are rare in children and adolescents with ALK+ anaplastic large cell lymphoma (ALCL) treated with regimens including CNS prophylaxis. Early identification of patients at high-risk for CNS relapse would enable stratification and better adaptation of initial treatment especially in the light of the upcoming targeted therapies with limited CNS penetration. We analyzed clinical and histological data of all ALK+ALCL patients with CNS relapse registered in ALCL99-database with the aim to describe risk factors and outcome. Characteristics of patients with no relapse, relapse without CNS involvement and CNS relapse were compared. At a median follow-up of 8 years (0.05-18 years), a CNS involvement was reported at first or subsequent relapse in 26/618 patients. Median interval between initial diagnosis and first CNS relapse was 8 months (IQR 5.55-10.61/range 1.31-130.69). The 5-year cumulative risk of CNS relapse was 4% (95% CI 2.9-5.5). Bone marrow involvement, peripheral blasts and CNS involvement at diagnosis were more frequent in patients with CNS relapse than in patients with no relapse or with relapse with no CNS involvement. The treatment of CNS relapse was heterogeneous. The median survival after CNS relapse was 23.7 months. Eleven patients were alive at last follow-up. Three-year overall survival after CNS relapse was 48.70% (95% CI 30.52-67.23).
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http://dx.doi.org/10.1111/bjh.16755DOI Listing
March 2021

Severe perioperative morbidity after robot-assisted versus conventional laparoscopy in gynecologic oncology: Results of the randomized ROBOGYN-1004 trial.

Gynecol Oncol 2020 08 25;158(2):382-389. Epub 2020 May 25.

Institut Paoli Calmettes Cancer Center, Marseille, France.

Objective: In gynecologic oncology, minimally invasive surgery using conventional laparoscopy (CL) decreases the incidence of severe morbidity compared to open surgery. In 2005, robot-assisted laparoscopy (RL) was approved for use in gynecology in the US. This study aimed to assess whether RL is superior to CL in terms of morbidity incidence.

Methods: ROBOGYN-1004 (ClinicalTrials.gov, NCT01247779) was a multicenter, phase III, superiority randomized trial that compared RL and CL in patients with gynecologic cancer requiring minimally invasive surgery. Patients were recruited between 2010 and 2015. The primary endpoint was incidence of severe perioperative morbidity (severe complications during or 6 months after surgery).

Results: Overall, 369 of 385 patients were included in the as-treated analysis: 176 and 193 underwent RL and CL, respectively. The median operating time for RL was 190 (range, 75-432) minutes and for CL was 145 (33-407) minutes (p < 0.001). The blood loss volumes for the corresponding procedures were 100 (0-2500) and 50 (0-1000) mL (p = 0.003), respectively. The overall rates of conversion to open surgery for the corresponding procedures were 7% (10/176) and 5% (10/193), respectively (p = 0.52). Severe perioperative morbidity occurred in 28% (49/176) and 21% (41/192) of patients who underwent RL and CL, respectively (p = 0.15). At a median follow-up of 25.1 months (range, 0.6-78.2), no significant differences in overall and disease-free survival were observed between the groups.

Conclusions: RL was not found superior to CL with regard to the incidence of severe perioperative morbidity in patients with gynecologic cancer. In addition, RL involved a longer operating time than CL.
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http://dx.doi.org/10.1016/j.ygyno.2020.05.010DOI Listing
August 2020

Reducing the seroma volume by quilting suture after breast reconstruction with a latissimus dorsi flap: Single institutional experience.

Bull Cancer 2020 May 28;107(5):543-550. Epub 2020 Apr 28.

Centre Oscar Lambret, breast surgery unit, 3, rue Combemale, 59020 Lille cedex, France. Electronic address:

Introduction: After breast reconstruction (BR) with latissimus dorsi flap (LDF) postoperative seroma is a frequent source of functional discomfort. The aim of this study was to evaluate the quilting suture on reducing the seroma volume by reducing the dead space created by LDF harvest for BR.

Material And Methods: This retrospective monocenter study was designed to compare patients who underwent BR using LDF with or without quilting suture. The primary endpoint was the seroma volume drained during hospitalization and percutaneous puncture. Complications and painful or functional sequelae were also evaluated in both groups.

Results: One hundred eight patients were included in the study. The mean (standard deviation, SD) age of our population was 49.7 years (9.3) and the mean body mass index (BMI) 26.9kg/m (4.1). Sixty-nine patients (63%) underwent quilting suturing in the latissimus dorsi compartment, 41% with overedge and 59% with simple stitches. The mean total volume of fluid drainage was 1238mL (1111). In multivariate analysis, the use of quilting suture was associated with a significant reduction in the total volume of drainage (-502mL, P=0.03); reduction was greater using overedge stitches than simple stitches (P=0.02). The beneficial effect of quilting suture appears to be more important in patients with a BMI greater than 30kg/m2 (interaction test, P=0.01).

Conclusion: This study shows the efficacy of quilting suture in reducing postoperative seroma formation in BR using LDF. Efficacy was greater when overedge stitches were used. Obese patients benefited more from quilting suture than patients with BMI<25.
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http://dx.doi.org/10.1016/j.bulcan.2020.03.006DOI Listing
May 2020

Curative Irradiation Treatment of Hepatocellular Carcinoma: A Multicenter Phase 2 Trial.

Int J Radiat Oncol Biol Phys 2020 05 28;107(1):116-125. Epub 2020 Jan 28.

Département Universitaire de Radiothérapie, Centre Oscar Lambret, Lille, France.

Purpose: Liver transplantation is the standard definitive treatment for nonmetastatic hepatocellular carcinoma (HCC). However, less than 5% of patients are ultimately candidates as a result of frequent comorbidities and graft shortage. The aim of this study was to evaluate stereotactic body radiation therapy (SBRT) as an ablative treatment for inoperable HCC.

Methods And Materials: A prospective phase 2 trial included newly diagnosed single HCC lesions that were without extrahepatic extension and that were deemed unsuitable for standard locoregional therapies, with a tumor size ranging from 1 to 6 cm. The SBRT dose was 45 Gy in 3 fractions. Primary endpoint was the local control of irradiated HCC at 18 months, defined by Response Evaluation Criteria in Solid Tumors.

Results: Forty-three patients were treated and evaluable. Median follow-up was 4.0 years (range, 1.2-4.6 years). All 43 patients had cirrhosis; 37 (88%) were Child-Pugh grade A and 5 (12%) grade B (1 missing data). No patients had received prior local treatment. Thirteen patients (31%) presented grade ≥3 acute adverse events, including 8 patients with an abnormality of the liver function tests (19%). Three patients (10%) experienced a decline in Child-Pugh at 3 months post-SBRT. The 18-month local control rate was 98% (95% confidence interval, 85%-99%). The 18-month overall survival rate was 72% (range, 56%-83%). Median overall survival was 3.5 years.

Conclusions: Local control and overall survival after SBRT for untreated solitary HCC were excellent despite candidates being unfit for transplantation, resection, ablation, or embolization treatments. SBRT should be considered as a bridge to transplant or as definitive therapy for those ineligible for transplant.
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http://dx.doi.org/10.1016/j.ijrobp.2019.12.004DOI Listing
May 2020
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