Publications by authors named "Simon Pernot"

47 Publications

Skeletal muscle loss during chemotherapy and its association with survival and systemic treatment toxicity in metastatic colorectal cancer: An AGEO prospective multicenter study.

Clin Res Hepatol Gastroenterol 2021 Mar 1;45(6):101603. Epub 2021 Mar 1.

Sorbonne Paris Cite, Paris Descartes University, Siric CARPEM, Assistance Publique-Hôpitaux de Paris, Department of Gastroenterology and Digestive Oncology, Hôpital Européen Georges Pompidou, Paris, France. Electronic address:

Purpose: We showed in a previous study that the PG-SGA score is associated with survival and chemotherapy-related toxicities in metastatic colorectal cancer (mCRC) patients. The objective was to evaluate the association between pretherapeutic sarcopenia and variation in skeletal muscle index (SMI) during treatment with these outcomes in the same population.

Methods: This prospective, multicenter, observational study enrolled non-pretreated mCRC patients. SMI was measured on routine CT scan at day 0 (D0) and day 60 (D60). Nutritional factors were collected at D0. Progression-free survival (PFS) and overall survival (OS) were calculated from treatment start.

Results: 149 patients were included from 7/2013 to 11/2016. Pretherapeutic sarcopenia was not significantly associated with survival or chemotherapy-related toxicities. The decrease in SMI > 14% was significantly associated with shorter PFS (6 vs 9 mo; HR 1.8, 95% CI 1.1-3.1, p = 0.02) and OS (8.5 vs 26 mo; HR 2.6, 95% CI 1.4-4.8, p = 0.002), independently of hypoalbuminemia and malnutrition defined by PG-SGA. Patients with a SMI decrease > 14% had a higher rate of grade ≥ 2 clinical toxicities (40% vs 22%, OR 3.0, 95% CI 1.2-7.7, p = 0.02), but the difference was not statistically significant in multivariable analysis.

Conclusion: To our knowledge, this is the first study to assess prospectively the association of skeletal muscle loss with survival and treatment toxicities in non-pretreated patients with mCRC. Pretherapeutic sarcopenia was not associated with poor outcomes, but the loss of skeletal muscle mass within 60 days from treatment start was highly prognostic, independently of other prognostic and nutritional factors.
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http://dx.doi.org/10.1016/j.clinre.2020.101603DOI Listing
March 2021

Episomal HPV16 responsible for aggressive and deadly metastatic anal squamous cell carcinoma evidenced in peripheral blood.

Sci Rep 2021 Feb 25;11(1):4633. Epub 2021 Feb 25.

Laboratoire de virologie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, 20-40 rue Leblanc, 75015, Paris, France.

Archival tissue samples collected longitudinally from a patient who died from HPV16-induced high-grade anal intraepithelial squamous cell carcinoma with vertebral HPV16-positive metastasis were retrospectively analyzed by the Capture-HPV method (Capt-HPV) followed by Next-Generation Sequencing (NGS). Full length nucleotide sequences of the same HPV16 were identified from the initial and second anal biopsy samples, from plasma sample and from vertebral metastasis biopsy. Remarkably, HPV was episomal in each sample. The HPV genome sequence was closest to the HPV16 Qv18158E variant subtype (A1 lineage) exhibiting base substitutions and deletions in 7 and 2 HPV loci, respectively. In conclusion, the powerful Capt-HPV followed by NGS allows evidencing the detailed cartography of tumoral and circulating HPV DNA, giving rise to a unique and unexpected episomal virus molecular status in a context of aggressive carcinoma, underlying the importance of HPV status and its association with clinical features for further prospective studies.
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http://dx.doi.org/10.1038/s41598-021-84110-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907240PMC
February 2021

Regorafenib-Avelumab Combination in Patients with Microsatellite Stable Colorectal Cancer (REGOMUNE): A Single-arm, Open-label, Phase II Trial.

Clin Cancer Res 2021 Jan 25. Epub 2021 Jan 25.

Early Phase Trials Unit, Institut Bergonié, Bordeaux, France.

Purpose: Regorafenib is synergistic with immune checkpoint inhibition in colorectal cancer preclinical models.

Patients And Methods: This was a single-arm, multicentric phase II trial. Regorafenib was given 3 weeks on/1 week off, 160 mg every day; avelumab 10 mg/kg i.v. was given every 2 weeks, beginning at cycle 1, day 15 until progression or unacceptable toxicity. The primary endpoint was the confirmed objective response rate under treatment, as per RECIST 1.1. The secondary endpoints included a 1-year nonprogression rate, progression-free survival (PFS), and overall survival (OS), safety and biomarkers studies performed on sequential tumor samples obtained at baseline and at cycle 2 day 1.

Results: Forty-eight patients were enrolled in four centers. Forty-three were assessable for efficacy after central radiological review. Best response was stable disease for 23 patients (53.5%) and progressive disease for 17 patients (39.5%). The median PFS and OS were 3.6 months [95% confidence interval (CI), 1.8-5.4] and 10.8 months (95% CI, 5.9-NA), respectively. The most common grade 3 or 4 adverse events were palmar-plantar erythrodysesthesia syndrome ( = 14, 30%), hypertension ( = 11, 23%), and diarrhea ( = 6, 13%). High baseline infiltration by tumor-associated macrophages was significantly associated with adverse PFS (1.8 vs. 3.7 months; = 0.002) and OS (3.7 months vs. not reached; = 0.002). Increased tumor infiltration by CD8 T cells at cycle 2, day 1 as compared with baseline was significantly associated with better outcome.

Conclusions: The combination of regorafenib + avelumab mobilizes antitumor immunity in a subset of patients with microsatellite stable colorectal cancer. Computational pathology through quantification of immune cell infiltration may improve patient selection for further studies investigating this approach.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-3416DOI Listing
January 2021

Pooled analysis of 115 patients from updated data of Epitopes-HPV01 and Epitopes-HPV02 studies in first-line advanced anal squamous cell carcinoma.

Ther Adv Med Oncol 2020 4;12:1758835920975356. Epub 2020 Dec 4.

Centre Hospitalier Universitaire de Besançon, Besançon, France.

Aims: The addition of docetaxel to cisplatin and 5-fluorouracil (DCF) has shown promising efficacy in advanced squamous cell carcinoma of the anus (SCCA). Preliminary results of Epitopes-HPV01 study showed a high rate of long-lasting complete response to DCF. The prospective, multicenter, Epitopes-HPV02 trial then confirmed the high efficacy of the modified DCF (mDCF) regimen in terms of complete response rate and long-term survival in metastatic or non-resectable locally advanced recurrent SCCA. Here, we present updated results of the Epitopes-HPV01 and Epitopes-HPV02 studies.

Patients & Methods: Epitopes-HPV01 is a prospective study performed by the regional cancer network of Franche-Comté, France. Epitopes-HPV02 is a phase II study supported by two French collaborative oncological groups, performed in 25 centers. Both studies included patients with metastatic, or with unresectable local recurrent SCCA, treated with DCF regimen.

Results: In Epitopes-HPV01, 51 patients were enrolled between September 2012 and January 2019, and 49 patients were included for analysis; while 69 patients were included between September 2014 and December 2016 in Epitopes-HPV02, and 66 patients for analysis. Pooled analysis of 115 patients showed a median progression-free survival of 12.2 months [95% confidence interval (CI) 10.6-16.1] [11.0 months (9.3-16.0) in -HPV02, and 15.6 months (11.2-34.5) in -HPV01, ( = 0.06)]. The median overall survival was 39.2 months (26.0-109.1) [36.3 in -HPV02 (25.2-NR), and 61.1 months (21.4-120.0) in -HPV01 ( = 0.62)]. Objective response rate was 87.7% (90.9% in -HPV02 and 83.3% in -HPV01) with 40.3% of complete response (45.5% in -HPV02 and 33.3% in -HPV01). No differences were observed between standard DCF ( = 54) and mDCF ( = 58) in terms of OS ( = 0.57) and PFS ( = 0.99). 5-years PFS and OS rates were 24.5% and 44.4%, respectively, in the whole population. No treatment-related death was observed.

Conclusion: Updated results of Epitopes-HPV01 and 02 studies, as well as the pooled analysis, confirm mDCF as a standard treatment in patients with advanced SCCA.
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http://dx.doi.org/10.1177/1758835920975356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720302PMC
December 2020

Aflibercept in Combination With FOLFIRI as First-line Chemotherapy in Patients With Metastatic Colorectal Cancer (mCRC): A Phase II Study (FFCD 1302).

Clin Colorectal Cancer 2020 Dec 12;19(4):285-290. Epub 2020 Jun 12.

Department of Gastroenterology and Digestive Oncology, Hopital European George Pompidou, Paris, France. Electronic address:

Background: FOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) + aflibercept improves median overall survival (OS) and progression-free survival (PFS) in patients with previously treated metastatic colorectal cancer (mCRC). Our aim was to investigate efficacy and tolerability of this combination in the first line.

Patients And Methods: Patients with untreated documented mCRC received aflibercept plus FOLFIRI every 14 days until progression or unacceptable toxicity in an open, phase II single-arm, multicenter trial. The primary endpoint was the 6-month PFS rate. Secondary endpoints were OS and tolerability. A 2-step Simon design was used with H: 55% and H= 75%. Data were analyzed in intention to treat.

Results: Forty-one patients were included, and 40 were analyzed (1 consent withdrawal) in 9 French centers between October 2014 and February 2017. The median age was 65 years (range, 46-81 years), 55% had ≥ 2 metastatic sites, and 50% and 15% had RAS and BRAF mutations, respectively. Twenty-two (54.5%; 95% confidence interval, 38.9%-68.5%) patients were alive and non-progressive at 6 months. FOLFIRI + aflibercept was considered ineffective, resulting in the cessation of inclusions. The median follow-up was 34 months. The overall response rate was 55%, and the disease control rate was 80%. The median duration of treatment was 5.3 months; the median PFS and OS were 8.2 and 18.6 months, respectively. Grade 3 to 4 adverse events were mainly gastrointestinal (47.5%) and vascular (32.5%). Of the patients, 87.5% had at least 1 dose modification.

Conclusion: Although the primary objective was not met, first-line FOLFIRI + aflibercept for mCRC leads to median PFS and OS close to those reported with classical doublet and targeted agents, but with significant toxicities needing dose reduction.
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http://dx.doi.org/10.1016/j.clcc.2020.06.003DOI Listing
December 2020

Intra-arterial hepatic beads loaded with irinotecan (DEBIRI) with mFOLFOX6 in unresectable liver metastases from colorectal cancer: a Phase 2 study.

Br J Cancer 2020 08 8;123(4):518-524. Epub 2020 Jun 8.

Département de Gastroentérologie et d'Oncologie Digestive, Hôpital Européen George Pompidou, Paris, France.

Background: Chemo-embolisation with drug-eluting beads loaded with irinotecan (DEBIRI) increased survival as compared with intravenous irinotecan in chemorefractory patients with liver-dominant metastases from colorectal cancer (LMCRC). First-line DEBIRI with systemic chemotherapy may increase survival and secondary resection.

Methods: In the FFCD-1201 single-arm Phase 2 study, patients with untreated, non-resectable LMCRC received DEBIRI plus mFOLFOX6. Four courses of DEBIRI were performed alternating right and left lobe or two sessions with both lobes treated during the same session.

Results: Fifty-seven patients were enrolled. Grade 3-5 toxicities were more frequent when both lobes were treated during the same session (90.5% versus 52.8%). Nine-month PFS rate was 53.6% (95% CI, 41.8-65.1%). The objective response rate (RECIST 1.1) was 73.2%, and the secondary R0 surgery was 33%. With a median follow-up of 38.3 months, median OS was 37.4 months (95% CI, 25.7-45.8), and median PFS 10.8 months (95% CI, 8.2-12.3).

Conclusions: Front-line DEBIRI + mFOLFOX6 should not be recommended as the hypothesised 9-month PFS was not met. However, high response rate, deep responses, and prolonged OS encourage further evaluation in strategies integrating biologic agent, in particular in patients with secondary surgery as the main goal.

Clinical Trial Registration: NCT01839877.
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http://dx.doi.org/10.1038/s41416-020-0917-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435188PMC
August 2020

Does Bead Size Affect Patient Outcome in Irinotecan-Loaded Beads Chemoembolization Plus Systemic Chemotherapy Regimens for Liver-Dominant Colorectal Cancer? Results of an Observational Study.

Cardiovasc Intervent Radiol 2020 Jun 26;43(6):866-874. Epub 2020 Feb 26.

Interventional Radiology Department, Hôpital Européen Georges Pompidou, 20 Rue Leblanc, 75015, Paris, France.

Purpose: We investigated the clinical effects of bead size in irinotecan-loaded beads chemoembolization (DEBIRI) used for treating liver-dominant colorectal cancer.

Materials And Methods: Between March 2009 and January 2018, all consecutive patients with colorectal cancer liver metastases referred for DEBIRI at our tertiary center were included in an observational study. Patients were treated exclusively with either 100-mg irinotecan-loaded DC beads of 70-150 μm (small bead group or SB) or 100-300 μm (large bead group or LB) in diameter, in addition to systemic therapy. Liver tumor response rate at 3 months, liver and overall progression-free survival (PFS) and overall survival were estimated.

Results: In total, 84 patients with liver-dominant progressive disease underwent 232 DEBIRI sessions. Fifty-four patients were treated in the SB group and 30 patients in the LB group. Liver progression-free rates at 3 months were 86.7% for the LB group and 79.6% for the SB group (NS). Median liver-PFS and overall PFS were, respectively, 7.15 months and 7.15 months for the LB group and 7.65 and 7.55 months for the SB group (NS). Median overall survival was 13.04 months for the LB group and 15.59 months for the SB group (p = 0.04). Specific treatment grade 3 + 4 toxicity occurrence was 5 (17%) in the LB group and 20 (37%) in the SB group.

Conclusion: No significant difference in patient outcome was observed between DEBIRI bead sizes of 70-150 μm and 100-300 μm. A trend toward higher treatment-specific toxicity was observed with the smaller beads.
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http://dx.doi.org/10.1007/s00270-020-02438-0DOI Listing
June 2020

Human Epidermal Growth Factor Receptor 2 (HER2) in Advanced Gastric Cancer: Current Knowledge and Future Perspectives.

Drugs 2020 Mar;80(4):401-415

Department of Gastroenterology and Digestive Oncology, European Georges Pompidou Hospital, AP-HP, Paris Descartes University, 20 rue Leblanc, 75015, Paris, France.

The discovery of human epidermal growth factor receptor 2 (HER2) overexpression in 15-20% of gastric adenocarcinomas has been a key advance in the global care of this disease. Validated by the ToGA trial in the first-line setting of advanced HER2-positive (+) gastric cancer (GC), trastuzumab, an anti-HER2 monoclonal antibody (mAb), was the first therapeutic agent to significantly improve the prognosis of these patients. Since these results, many attempts have been made to improve the clinical outcomes of patients with HER2+ GC. However, all the other HER2-targeting molecules have failed to show a survival benefit in large phase III studies. The value of continuing trastuzumab after disease progression has been suggested by several retrospective studies. However, recent results of a randomized phase II trial showed no benefit from this strategy. On the other hand, novel therapeutic methods, such as immunotherapy, are emerging as new tools in the strategy of care of advanced GC, even if their benefit in the specific HER2+ population remains undetermined. Furthermore, substantial progress has been made in the understanding of the mechanisms leading to resistance to anti-HER2 therapies, and in the screening methods to detect them, thus opening new perspectives. The aim of this review was firstly to summarize the existing data on the specific strategy of care of HER2+ advanced GC, and secondly, to describe current knowledge regarding the potential mechanisms of resistance to HER2-targeting therapies. Lastly, we report the prospects for overcoming these potential obstacles, from future therapeutic strategies to new detection methods.
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http://dx.doi.org/10.1007/s40265-020-01272-5DOI Listing
March 2020

Withholding the Introduction of Anti-Epidermal Growth Factor Receptor: Impact on Outcomes in RAS Wild-Type Metastatic Colorectal Tumors: A Multicenter AGEO Study (the WAIT or ACT Study).

Oncologist 2020 02 2;25(2):e266-e275. Epub 2019 Oct 2.

Department of Gastroenterology, Cochin Hospital, Paris, France.

Background: Patients with RAS wild-type (WT) nonresectable metastatic colorectal cancer (mCRC) may receive either bevacizumab or an anti-epidermal growth factor receptor (EGFR) combined with first-line, 5-fluorouracil-based chemotherapy. Without the RAS status information, the oncologist can either start chemotherapy with bevacizumab or wait for the introduction of the anti-EGFR. Our objective was to compare both strategies in a routine practice setting.

Materials And Methods: This multicenter, retrospective, propensity score-weighted study included patients with a RAS WT nonresectable mCRC, treated between 2013 and 2016 by a 5-FU-based chemotherapy, with either delayed anti-EGFR or immediate anti-vascular endothelial growth factor (VEGF). Primary criterion was overall survival (OS). Secondary criteria were progression-free survival (PFS) and objective response rate (ORR).

Results: A total of 262 patients (129 in the anti-VEGF group and 133 in the anti-EGFR group) were included. Patients receiving an anti-VEGF were more often men (68% vs. 56%), with more metastatic sites (>2 sites: 15% vs. 9%). The median delay to obtain the RAS status was 19 days (interquartile range: 13-26). Median OS was not significantly different in the two groups (29 vs. 30.5 months, p = .299), even after weighting on the propensity score (hazard ratio [HR] = 0.86, 95% confidence interval [CI], 0.69-1.08, p = .2024). The delayed introduction of anti-EGFR was associated with better median PFS (13.8 vs. 11.0 months, p = .0244), even after weighting on the propensity score (HR = 0.74, 95% CI, 0.61-0.90, p = .0024). ORR was significantly higher in the anti-EGFR group (66.7% vs. 45.6%, p = .0007).

Conclusion: Delayed introduction of anti-EGFR had no deleterious effect on OS, PFS, and ORR, compared with doublet chemotherapy with anti-VEGF.

Implications For Practice: For RAS/RAF wild-type metastatic colorectal cancer, patients may receive 5-fluorouracil-based chemotherapy plus either bevacizumab or an anti-epidermal growth factor receptor (EGFR). In daily practice, the time to obtain the RAS status might be long enough to consider two options: to start the chemotherapy with bevacizumab, or to start without a targeted therapy and to add the anti-EGFR at reception of the RAS status. This study found no deleterious effect of the delayed introduction of an anti-EGFR on survival, compared with the introduction of an anti-vascular endothelial growth factor from cycle 1. It is possible to wait one or two cycles to introduce the anti-EGFR while waiting for RAS status.
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http://dx.doi.org/10.1634/theoncologist.2019-0328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011620PMC
February 2020

Efficacy and Safety of Aflibercept in Combination With Chemotherapy Beyond Second-Line Therapy in Metastatic Colorectal Carcinoma Patients: An AGEO Multicenter Study.

Clin Colorectal Cancer 2020 03 4;19(1):39-47.e5. Epub 2019 Sep 4.

Department of Digestive Oncology, European Georges Pompidou Hospital, René Descartes University, Paris, France. Electronic address:

Background: Although no data have been reported beyond second-line therapy, aflibercept is approved in this setting in many countries. We conducted a multicenter study to analyze the efficacy and safety of a aflibercept-chemotherapy regimen beyond second-line therapy in patients with metastatic colorectal cancer.

Patients And Methods: Metastatic colorectal cancer patients treated with aflibercept beyond second-line therapy were included. Objective response rate, overall survival (OS), and progression-free survival (PFS) were assessed.

Results: A total of 130 patients were included. Median OS and PFS were 7.6 months (95% confidence interval, 6.2-9.3) and 3.3 months (95% confidence interval, 2.7-3.8), respectively. The best response rates were partial response 6.9%, stable disease 38.5%, progressive disease 42.5%, and not evaluable 12%. According to whether patients received previous FOLFIRI (leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin)-bevacizumab or not, OS was 7.7 and 8.1 months (P = .31), and PFS was 2.9 and 3.9 months (P = .02), respectively. Interestingly, PFS and OS were both significantly improved by 4% and 5% per month, respectively, without antiangiogenic treatment before the initiation of the aflibercept regimen. The negative effect of prior FOLFIRI-bevacizumab or shorter time since last bevacizumab was maintained in multivariate analysis for both OS and PFS.

Conclusion: The aflibercept-chemotherapy regimen is a therapeutic option in patients with chemorefractory disease beyond second-line therapy, in particular in patients with an antiangiogenic-free interval.
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http://dx.doi.org/10.1016/j.clcc.2019.08.003DOI Listing
March 2020

Three fluoropyrimidine-based regimens in routine clinical practice after nab-paclitaxel plus gemcitabine for metastatic pancreatic cancer: An AGEO multicenter study.

Clin Res Hepatol Gastroenterol 2020 06 10;44(3):295-301. Epub 2019 Oct 10.

Department of Gastroenterology and Digestive Oncology, Georges-Pompidou European Hospital, Assistance publique-Hôpitaux de Paris (AP-HP), Sorbonne Paris Cité Paris Descartes University, Paris, France.

Background: A combination of nab-paclitaxel plus gemcitabine (N+G) has recently become a standard first-line treatment in patients with metastatic pancreatic adenocarcinoma (MPA), but there are currently no published data concerning second-line treatment after N+G. The aim of this study was to evaluate the survival outcomes and tolerability of three usual fluoropyrimidine-based regimens FOLFOX, FOLFIRI and FOLFIRINOX after N+G failure in MPA patients.

Methods: Patients receiving N+G as first-line regimen were prospectively identified in 11 French centers between January 2014 and January 2017. After disease progression or unacceptable toxicity, patients eligible for second-line therapy were enrolled in the study. The primary endpoint was overall survival following the second-line regimen. Secondary endpoints were objective response, progression-free survival and safety.

Results: Out of 137 patients treated with N+G as first-line regimen, 61 (44.5%) received second-line chemotherapy, including FOLFOX (39.4%), FOLFIRI (34.4%) or FOLFIRINOX (26.2%). Baseline characteristics were not different between the 3 groups. In particular, median age was 71.7 years, sex ratio was 1/1, and performance status (PS) was 0 in 11.5% of case. Main grade 3 toxicities were neutropenia (4.9%) and nausea (3.3%), without major differences between the groups. No toxic death was observed. Median second-line progression-free survival (PFS) and overall survival (OS) were 2.95 (95% CI: 2.3-5.4) and 5.97 months (95% CI: 4.0-8.0), respectively, with no difference between the 3 groups. Median OS from the start of first-line chemotherapy was 12.7 months (10.4-15.1) and was significantly better in patients receiving FOLFIRI after N+G failure, 18.4 months (95% CI: 11.7-24.1, P<0.05), as compared with FOLFOX or FOLFIRINOX (10.4 and 12.3 months, respectively).

Conclusion: This study suggests that second-line fluoropyrimidine-based regimens after N+G failure are feasible, have a manageable toxicity profile in selected patients with MPA, and are associated with promising clinical outcomes, in particular when combined with irinotecan. Randomized phase 3 trials are needed to confirm this trend.
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http://dx.doi.org/10.1016/j.clinre.2019.08.009DOI Listing
June 2020

Folfirinox gemcitabine/nab-paclitaxel as first-line therapy in patients with metastatic pancreatic cancer: a comparative propensity score study.

Therap Adv Gastroenterol 2019 25;12:1756284819878660. Epub 2019 Sep 25.

Department of Gastroenterology and Gastro-intestinal Oncology, Hôpital Européen Georges-Pompidou, APHP, Paris Descartes University, Sorbonne Paris Cité, Paris, France.

Background: Folfirinox (FFX) and gemcitabine/nab-paclitaxel (GN) are both standard first-line treatments in patients with metastatic pancreatic cancer (mPC). However, data comparing these two chemotherapeutic regimens and their sequential use remain scarce.

Methods: Data from two independent cohorts enrolling patients treated with FFX ( = 107) or GN ( = 109) were retrospectively pooled. Primary endpoint was overall survival (OS). Progression-free survival (PFS) was the secondary endpoint. A propensity score based on age, gender, performance status (PS), and presence of liver metastases was used to make groups comparable.

Results: In the whole study population, OS was significantly higher in FFX (14 months; 95% CI: 10-21) than in GN groups (9 months; 95% CI: 8-12) before ( = 0.008) and after ( = 0.021) adjusting for age, number of metastatic sites, liver metastases, peritoneal carcinomatosis and CA19.9 level at baseline. PFS tends to be higher in FFX (6 months) than GN groups (5 months;  = 0.053). After matching ( = 49/group), patients were comparable for all baseline characteristics including PS. In the matched population, there was a trend toward greater OS in patients treated with FFX (HR = 0.67;  = 0.097). However, survival in each group was not solely a result of the first-line regimen. The proportion of patients who were fit for GN after FFX failure (FFX-GN sequence) was higher (46.9%) than the reverse sequence (20.4%;  = 0.01), which suggests a higher feasibility for the FFX-GN sequence. Corresponding median OS were 19 months 9.5 months, respectively ( = 0.094).

Conclusion: This study shows greater OS with FFX than with GN in patients with mPC. GN after FFX failure appears more feasible than the reverse sequence.
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http://dx.doi.org/10.1177/1756284819878660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764033PMC
September 2019

Plasma clearance of RAS mutation under therapeutic pressure is a rare event in metastatic colorectal cancer.

Int J Cancer 2020 Aug 12;147(4):1185-1189. Epub 2019 Oct 12.

Centre de Recherche des Cordeliers, INSERM, CNRS, Sorbonne Université, USPC, Université Paris Descartes, Université Paris Diderot, F-75006, Paris, France.

In metastatic colorectal cancer (mCRC), circulating tumor DNA (ctDNA) monitoring can be used to genotype tumors and track clonal evolution. We investigated the clearance of RAS mutated clones under chemotherapy pressure by ctDNA analysis in patients with a RAS mutated mCRC. Patients with a RAS mutated tumor included in the prospective PLACOL study were monitored for ctDNA. Analyses were based on optimized targeted next-generation sequencing and/or droplet-based digital polymerase chain reaction (ddPCR). For plasma samples without detectable mutations at progression disease, we tested the methylation status of WIF1 and NPY genes using methylation-ddPCR (met-ddPCR) to validate the presence of ctDNA. Among the 36 patients with positive plasma samples for RAS mutations at inclusion, 28 (77.8%) remained RAS positive at disease progression and 8 (22.2%) became negative. Subsequent met-ddPCR for methylated markers showed that only two out of the eight patients with RAS negative plasma had detectable ctDNA at progression. Therefore, only 2 samples among 36 were confirmed for clearance of RAS mutation in our series. In conclusion, this study suggests that the clearance of RAS mutations in patients treated by chemotherapy for a RAS mutated mCRC is a rare event. Monitoring tumor mutations in plasma samples should be combined with a strict control of the presence of ctDNA. The therapeutic impacts of RAS clearance need to be further explored.
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http://dx.doi.org/10.1002/ijc.32657DOI Listing
August 2020

Evaluation of two nutritional scores' association with systemic treatment toxicity and survival in metastatic colorectal cancer: an AGEO prospective multicentre study.

Eur J Cancer 2019 09 12;119:35-43. Epub 2019 Aug 12.

Sorbonne Paris Cite, Paris Descartes University, Siric CARPEM, Assistance Publique-Hôpitaux de Paris, Department of Gastroenterology and Digestive Oncology, Hôpital Européen Georges Pompidou, Paris, France. Electronic address:

Introduction: The Patient-Generated Subjective Global Assessment (PG-SGA) is currently the standard nutritional assessment tool for patients with cancer. In a retrospective assessment of a prospective cohort, we showed that the Nutritional Risk Index (NRI) seemed to be associated with treatment toxicity and survival in patients with metastatic colorectal cancer (mCRC).

Objective: The objective of this study was to compare these two nutritional tools (PG-SGA and NRI) on their correlation with chemotherapy-related toxicity and survival in non-pre-treated patients with mCRC.

Methods: This prospective multicentre observational study enrolled non-pre-treated patients with mCRC. PG-SGA and NRI were performed at the onset of first-line chemotherapy. Treatment-related toxicities were registered according to National Cancer Institute Common Toxicity Criteria Adverse Event version 4.0. Progression-free survival (PFS) and overall survival (OS) were calculated from the start of treatment.

Results: A total of 168 patients were included from eight French centres. Patients were considered malnourished in 41% of cases according to PG-SGA and 56% of cases according to the NRI. In multivariate analysis, malnutrition according to PG-SGA was significantly associated with chemotherapy-related grade ≥2 clinical toxicities (odds ratio: 3.7; 95% confidence interval [CI]: 1.7-8.4; p = 0.001) and OS (hazard ratio [HR]: 2.6; 95% CI: 1.3-5.3; p = 0.006), but not with PFS (HR: 1.5; 95% CI: 0.8-2.6; p = 0.2). Conversely, malnutrition according to the NRI was not significantly associated with these tolerance and efficacy parameters.

Conclusion: Although more complex to perform in daily oncology practice, the PG-SGA score appears to be the best nutritional assessment tool because of its strong association with clinically relevant oncological outcomes such as OS and treatment-related toxicities in patients with mCRC.
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http://dx.doi.org/10.1016/j.ejca.2019.07.011DOI Listing
September 2019

Inclusion of Older Patients with Cancer in Clinical Trials: The SAGE Prospective Multicenter Cohort Survey.

Oncologist 2019 12 19;24(12):e1351-e1359. Epub 2019 Jul 19.

Clinical Epidemiology and Ageing Unit, Institut Mondor de Recherche Biomédicale, Paris-Est University, Créteil, France.

Background: The primary objective was to evaluate the rates of older patients with colorectal cancer (CRC) who were eligible for a clinical trial, invited to participate, and, ultimately, included. The secondary objective was to assess the reasons for ineligibility, noninvitation, and noninclusion and factors associated.

Materials And Methods: The Sujets AGés dans les Essais Cliniques (SAGE; Older Subjects in Clinical Trials) multicenter prospective cohort was established in seven centers (10 departments of medical oncology, digestive oncology, and digestive surgery) between 2012 and 2016. All patients with CRC aged 65 or older were studied. The endpoints were clinical trial availability, patient's eligibility, invitation, and enrollment in a trial.

Results: We included 577 older patients (mean age ± SD: 75.6 ± 7 years; males: 56%; metastasis: 41%). Thirty-seven trials were ongoing (one trial for older patients). Of the 474 patients with at least one available trial for their cancer stage and site, 127 (27%) were eligible; 84 of these 127 (66%) were invited to participate, and 70 of these 84 (83%) were included. In a multivariate analysis, noninvitation was found to be associated with older age ( = .016): adjusted relative risk (95% confidence interval), 0.14 (0.02-0.60) for ≥80 vs. 65-69; 0.54 (0.18-1.04) for 75-79 vs. 65-69; 0.47 (0.17-0.93) for 70-74 vs. 65-69.

Conclusion: Three-quarters of older patients with CRC were ineligible for a clinical trial. One-third of the eligible patients were not invited to participate in a trial, and 17% of invited patients were not included. Few trials are reserved for older patients. Patients aged 80 or older were significantly less likely to be eligible for a trial and invited to participate. : NCT01754636.

Implications For Practice: The results of this study suggest that barriers to participation of older patients in clinical trials are particularly marked at age 80 years or older. Secondly, the results emphasize the need for trials for older patients. Thirdly, there is also a need for more pragmatic "real-world" trials, rather than solely randomized trials performed in idealized settings with strictly selected patients. Large prospective observational cohorts with a precise follow-up of toxicity, functional decline, and quality of life may constitute one way of generating more data on the risk-benefit ratio for cancer treatments in older patients.
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http://dx.doi.org/10.1634/theoncologist.2019-0166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6975930PMC
December 2019

Factors associated with anal cancer screening uptake in men who have sex with men living with HIV: a cross-sectional study.

Eur J Cancer Prev 2020 01;29(1):1-6

Department of Biostatistics and Epidemiology, Cochin Hôtel-Dieu Hospital.

Most western countries have guidelines on anal cancer screening for men who have sex with men (MSM) living with HIV. However, adherence to these guidelines has been studied poorly. This cross-sectional study reports anal cancer screening uptake and identifies the factors associated with a previous screening in MSM living with HIV in a Paris Hospital (France). A total of 410 outpatients completed a self-administered questionnaire on anal cancer screening. The median age was 50 years and the median time from HIV diagnosis was 14.2 years. Overall, 82.2% of patients were aware of anal cancer screening and, of these, 56.7% had already undergone a screening test. The absence of history of screening (43.3%) was most often explained by lack of time (31.3%) or information (28.2%). Among patients familiar with the anal screening procedure, those older than 50 years (adjusted odds ratio=2.4, 95% confidence interval=1.3-4.7, P=0.007) and informed by healthcare providers (adjusted odds ratio=8.2, 95% confidence interval=2.5-32.0, P=0.001) were more likely to have already been screened. To date, adherence to anal cancer screening in MSM living with HIV appears to be inadequate to enable diagnosis of cancer at its early stages. Encouraging physicians to inform MSM living with HIV about anal cancer screening, irrespective of their age, could be an effective strategy to improve anal cancer screening uptake.
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http://dx.doi.org/10.1097/CEJ.0000000000000507DOI Listing
January 2020

Infiltrating and peripheral immune cell analysis in advanced gastric cancer according to the Lauren classification and its prognostic significance.

Gastric Cancer 2020 01 2;23(1):73-81. Epub 2019 Jul 2.

Université de Paris, PARCC, INSERM, 75015, Paris, France.

Background: The correlation between immune cells and the Lauren classification subtypes and their prognostic impact in advanced gastric cancer (AGC) are unknown.

Methods: Circulating natural killer (NK) cells, CD4 and CD8 T cells, regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) were quantified in peripheral blood mononuclear cells (PBMCs) from 67 patients with untreated AGC enrolled in the PRODIGE 17-ACCORD 20 trial. CD56 cells (NK), CD8, and FoxP3 (Treg) tumor-infiltrating lymphocytes (TILs) were assessed in tumor samples.

Results: Circulating NK and Treg proportions were significantly lower in patients with diffuse/mixed-type AGC (n = 27) than those with intestinal type (n = 40; median 6.3% vs 11.5%; p = 0.02 and median 3.3% vs 5.2%; p = 0.03, respectively). Proportions of circulating MDSC, CD4 and CD8 T cells were not associated with one pathological type. Among tumor-infiltrating cells, CD8 T cells, but not NK or FoxP3 cells, were significantly lower in diffuse/mixed-type AGC (median 21 vs 59 cells/field; p = 0.009). Patients with high circulating NK cell counts (> 17%) had a better overall survival than those with < 17% (HR 0.40; 95% CI [0.15-1.06]; p = 0.04). Patients with high CD8 TIL counts (> 31 cells/field) had significantly longer overall survival (HR 0.44; 95% CI [0.21-0.92]; p = 0.02). The prognostic value of CD8 TILs was maintained after adjustment for confounding factors, including the Lauren classification (HR = 0.42; 95% CI [0.18-0.96]; p = 0.039).

Conclusion: Diffuse/mixed-type AGC has lower rates of CD8 TILs and circulating NK cells and Tregs than the intestinal type. This "cold tumor" phenotype may be associated with a worse outcome.
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http://dx.doi.org/10.1007/s10120-019-00983-3DOI Listing
January 2020

Integration of elicited expert information via a power prior in Bayesian variable selection: Application to colon cancer data.

Stat Methods Med Res 2020 02 9;29(2):541-567. Epub 2019 Apr 9.

INSERM U1138, University Paris Descartes, Sorbonne University, Paris, France.

Background: Building tools to support personalized medicine needs to model medical decision-making. For this purpose, both expert and real world data provide a rich source of information. Currently, machine learning techniques are developing to select relevant variables for decision-making. Rather than using data-driven analysis alone, eliciting prior information from physicians related to their medical decision-making processes can be useful in variable selection. Our framework is electronic health records data on repeated dose adjustment of Irinotecan for the treatment of metastatic colorectal cancer. We propose a method that incorporates elicited expert weights associated with variables involved in dose reduction decisions into the Stochastic Search Variable Selection (SSVS), a Bayesian variable selection method, by using a power prior.

Methods: Clinician experts were first asked to provide numerical clinical relevance weights to express their beliefs about the importance of each variable in their medical decision making. Then, we modeled the link between repeated dose reduction, patient characteristics, and toxicities by assuming a logistic mixed-effects model. Simulated data were generated based on the elicited weights and combined with the observed dose reduction data via a power prior. We compared the Bayesian power prior-based SSVS performance to the usual SSVS in our case study, including a sensitivity analysis using the power prior parameter.

Results: The selected variables differ when using only expert knowledge, only the usual SSVS, or combining both. Our method enables one to select rare variables that may be missed using only the observed data and to discard variables that appear to be relevant based on the data but not relevant from the expert perspective.

Conclusion: We introduce an innovative Bayesian variable selection method that adaptively combines elicited expert information and real world data. The method selects a set of variables relevant to model medical decision process.
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http://dx.doi.org/10.1177/0962280219841082DOI Listing
February 2020

Is dual-phase C-arm CBCT sufficiently accurate for the diagnosis of colorectal cancer liver metastasis during liver intra-arterial treatment?

Eur Radiol 2019 Oct 1;29(10):5253-5263. Epub 2019 Apr 1.

INSERM U970, Paris, France.

Purpose: This study aimed to estimate the accuracy of dual-phase C-arm cone beam computed tomography (CBCT) for the detection of colorectal cancer liver metastases, as compared with multidetector computed tomography (MDCT).

Materials And Methods: Between March 2014 and December 2016, 49 consecutive patients referred for intra-arterial treatment for colorectal cancer liver metastases were enrolled in a single-center observational study. All patients were examined with MDCT and with dual-phase C-arm cone beam computed tomography performed after iodine injection in the proper hepatic artery before intra-arterial treatment. Two blinded observers independently reviewed all examinations. Diagnostic accuracy was determined using both a six-cell matrix method and a "worst-case scenario."

Results: Readers identified at MDCT 264 colorectal liver metastases and 43 other liver lesions. The early and late arterial phase showed 240 and 277 liver lesions respectively. A certainty of the diagnosis was obtained in 63% and 85% at the early (EAP) and late arterial phase (LAP), respectively. Streak artifacts or liver segment truncation, or inadequate enhancement was responsible for the inability to see or to correctly adjudicate a lesion to a diagnosis in 27% and 15% of the cases at the EAP and LAP. The "worst-case scenario" yielded a Se and Sp of 58% and 51%, respectively, at EAP and 84% and 70%, respectively, at LAP.

Conclusion: On CBCT, EAP showed limited accuracy. LAP provided the best tumor detectability.

Key Points: • The early arterial phase (EAP) yielded poor accuracy: Se = 58% and Sp = 51% (p < 0.0001). • The late arterial phase (LAP) phase yielded good accuracy: Se = 84% and Se = 70% (p = 0.02). • The probability of a correct diagnosis at the EAP was 60%.
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http://dx.doi.org/10.1007/s00330-019-06173-0DOI Listing
October 2019

HPV-circulating tumoural DNA by droplet-based digital polymerase chain reaction, a new molecular tool for early detection of HPV metastatic anal cancer? A case report.

Eur J Cancer 2019 05 22;112:34-37. Epub 2019 Mar 22.

Laboratoire de virologie, Hôpital Européen Georges Pompidou, Assistance Publique - Hôpitaux de Paris, France; Faculté de Médecine Paris Descartes, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; INSERM U970, PARCC, Hôpital Européen Georges Pompidou, Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.ejca.2019.02.012DOI Listing
May 2019

[A drug-resistant dyspepsia].

Rev Prat 2018 Jun;68(6):643-646

Service d'oncologie digestive, AP-HP, Hôpital européen Georges-Pompidou, Paris, France.

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June 2018

Can cone-beam CT tumor blood volume predicts the response to chemoembolization of colorectal liver metastases? Results of an observational study.

Eur Radiol 2019 Sep 20;29(9):5022-5031. Epub 2019 Feb 20.

INSERM U970, Paris, France.

Purpose: To determine whether intraprocedural C-arm cone-beam CT (CBCT) parenchymal blood volume (PBV) can predict the response of colorectal cancer liver metastases (CRCLM) 2 months after irinotecan drug-eluting bead (DEBIRI) chemoembolization.

Materials And Methods: This single-center observational study was compliant with the Helsinki Declaration and approved by our institutional review board. Thirty-four consecutive CRCLM patients referred for DEBIRI chemoembolization were enrolled between March 2015 and December 2016. Tumor size was assessed at baseline and 2 months after DEBIRI chemoembolization by multidetector CT (Response Evaluation Criteria in Solid Tumors RECIST 1.0), and PBV was measured before and after DEBIRI chemoembolization. Two independent readers reviewed all data. We determined the potential correlation (Spearman's rank correlation) between intraprocedural PBV values and tumor response at 2 months. The relationship between tumor response and PBV was studied using a mixed model. A logistic regression model was applied to study the relationship between patient "Responder/Non-responder" and PBV.

Results: There was a strong correlation between baseline PBV or the percent change of PBV and the 2-month tumor response (rho = - 0.8587 (p = 0.00001) and rho = 0.8027 (p = 0.00001), respectively). The mixed model showed that an increase of 1 ml/1000 ml in PBV of a tumor before DEBIRI chemoembolization led to a 0.54 mm decrease in diameter (p < 0.005). A 1% decrease in PBV after DEBIRI chemoembolization resulted in tumor shrinkage of 0.75 mm (p < 0.005). The logistic regression model showed that patients with a 1% smaller mean decrease of PBV after DEBIRI chemoembolization had a 10% lower likelihood of achieving disease control (OR = 0.9, 95% confidence interval (CI) = 0.81-1; p = 0.0493).

Conclusion: Intraprocedural PBV may predict tumor response to DEBIRI chemoembolization.

Key Points: • There is a strong relationship between the parenchymal blood volume (PBV) of colorectal liver metastases before DEBIRI chemoembolization and tumor response at 2 months. • Higher PBV values before DEBIRI chemoembolization correlate with greater tumor shrinkage, but only if the PBV decreases by more than 70% after DEBIRI chemoembolization. • Each increase of 1% in the mean decrease of PBV after DEBIRI chemoembolization resulted in a 10% lower likelihood of achieving disease control (OR = 0.9, 95% confidence interval (CI) = 0.81-1; p = 0.0493).
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http://dx.doi.org/10.1007/s00330-019-6007-4DOI Listing
September 2019

Pharmaceutical interventions to improve safety of chemotherapy-treated cancer patients: A cross-sectional study.

J Oncol Pharm Pract 2019 Jul 28;25(5):1195-1203. Epub 2019 Jan 28.

1 Pharmacy Department, Georges Pompidou European Hospital, Paris, France.

Purpose: Cancer chemotherapy is a high-risk process. To improve patient safety, a systematic pharmaceutical analysis of chemotherapy prescriptions is performed in our institution. The aim of this study was to assess the impact of pharmaceutical interventions (PIs) on the safety of patient chemotherapy prescriptions.

Methods: This prospective cross-sectional study was conducted in an 800-bed university hospital with oncology departments. All chemotherapy prescriptions were included and PIs were collected prospectively during one month. The clinical impact of PIs was scored by an expert panel of oncologists and pharmacists, using the Hatoum scale. Univariate and multivariate analysis were conducted to identify factors associated with a higher frequency of PIs.

Results: Of 1346 prescriptions included, 129 required a PI (9.6% (95% CI: 8.1-11.4)). Most PIs were scored as having at least a significant impact for patient safety (69.8% (95% CI: 60.4-76.9)). The frequency of PIs was significantly associated with tumour site (p = 0.04) and weekday of prescription (p = 0.005). Multivariate analysis identified factors independently associated with PI performance, including pancreas and biliary tract cancers (odds ratio = 2.8 (95% CI: 1.4-5.3)), ovary cancers (odds ratio = 2.4 (95% CI: 1.2-4.8)) and head and neck cancers (odds ratio = 2.4 (95% CI: 1.1-5.1)) and the day 1 of the protocol with a cytotoxic agent (odds ratio = 3.7 (95% CI: 1.1-11.1)).

Conclusions: Oncology pharmacists have a critical role in the safety of chemotherapy prescriptions. The coordination between healthcare professionals and access to patient data seem essential to improve the PIs' relevance and their clinical impact on patient safety.
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http://dx.doi.org/10.1177/1078155219826344DOI Listing
July 2019

Docetaxel, cisplatin, and fluorouracil chemotherapy for metastatic or unresectable locally recurrent anal squamous cell carcinoma (Epitopes-HPV02): a multicentre, single-arm, phase 2 study.

Lancet Oncol 2018 08 2;19(8):1094-1106. Epub 2018 Jul 2.

Department of Oncology, University Hospital of Besancon, Centre Hospitalier Universitaire de Besançon, Besançon, France; Department of Oncology and Radiotherapy, Hôpital Nord Franche Comté, Montbéliard, France; Clinical Investigational Center, CIC-1431, University Hospital of Besançon, Besançon, France; INSERM, Unit 1098, University of Bourgogne Franche-Comté, Besançon, France; Groupe Coopérateur Multidisciplinaire en Oncologie (GERCOR) Oncology Multidisciplinary Group, Paris, France; Fédération Francophone de Cancérologie Digestive (FFCD), Dijon, France.

Background: The incidence of anal squamous cell carcinoma has been increasing markedly in the past few decades. Currently, there is no validated treatment for advanced-stage anal squamous cell carcinoma. Therefore, we aimed to validate the clinical activity and safety of docetaxel, cisplatin, and fluorouracil (DCF) chemotherapy in patients with metastatic or unresectable locally recurrent anal squamous cell carcinoma.

Methods: We did a multicentre, single-arm, phase 2 study. We recruited patients from 25 academic hospitals, cancer research centres, and community hospitals in France who were aged 18 years or older with histologically confirmed anal squamous cell carcinoma, with metastatic disease or with unresectable local recurrence; an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; and with at least one evaluable lesion according to the Response Evaluation Criteria in Solid Tumors (version 1.1). Chemotherapy-naive patients received either six cycles of standard DCF (75 mg/m docetaxel and 75 mg/m cisplatin on day 1 and 750 mg/m per day of fluorouracil for 5 days, every 3 weeks) or eight cycles of modified DCF (40 mg/m docetaxel and 40 mg/m cisplatin on day 1 and 1200 mg/m per day of fluorouracil for 2 days, every 2 weeks), which were administered intravenously. The choice between the standard versus modified regimens was recommended based on, but not limited to, age (≤75 years vs >75 years) and ECOG performance status (0 vs 1). The primary endpoint was investigator-assessed progression-free survival at 12 months from the first DCF cycle; for the primary endpoint to be met, at least 11 (17%) of 66 enrolled patients had to be alive without disease progression at 12 months. Efficacy and safety analyses were done in a modified intention-to-treat population, defined as all patients who were evaluable for progression at 12 months who received at least one cycle of DCF. This trial is registered at ClinicalTrials.gov, number NCT02402842, and the final results are presented here.

Findings: Between Sept 17, 2014, and Dec 7, 2016, we enrolled 69 patients. Of these patients, three did not receive DCF. Of the 66 patients who received treatment, 36 received the standard DCF regimen and 30 received modified DCF. The primary endpoint was met: 31 (47%) of 66 patients were alive and progression free at 12 months. 22 (61%) of 36 patients who received the standard DCF regimen and 18 (60%) of 30 patients who received the modified DCF regimen had disease progression at data cutoff. 46 (70%) of 66 patients had at least one grade 3-4 adverse event (30 [83%] of 36 in the standard DCF regimen and 16 [53%] of 30 in the modified DCF regimen). The most common grade 3-4 adverse events were neutropenia (15 [23%]; eight [22%] for standard DCF vs seven [23%] for modified DCF), diarrhoea (12 [18%]; nine [25%] vs three [10%]), asthenia (ten [15%]; eight [22%] vs two [7%]), anaemia (ten [15%]; six [17%] vs four [13%]), lymphopenia (eight [12%]; three [8%] vs five [17%]), mucositis (seven [11%]; seven [19%] vs none), and vomiting (seven [11%]; five [14%] vs two [7%]). No grade 4 non-haematological adverse events and febrile neutropenia were observed with modified DCF, whereas three (8%) grade 4 non-haematological adverse events and five (14%) cases of febrile neutropenia were reported with standard DCF. 97 serious adverse events were reported (69 in patients who received the standard DCF regimen [61 drug-related] and 28 in those given the modified DCF regimen [14 drug-related]). No treatment-related deaths were recorded.

Interpretation: Compared with standard DCF, modified DCF provided long-lasting response with good tolerability in patients with metastatic or unresectable locally recurrent anal squamous cell carcinoma with ECOG performance status of 0-1 in the first-line setting, and therefore could be considered as a new standard of care for these patients. Regarding the elevated risk of high-grade and serious adverse events and febrile neutropenia, standard DCF cannot be recommended in this situation.

Funding: Besançon University Hospital and Ligue contre le cancer Grand-Est.
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http://dx.doi.org/10.1016/S1470-2045(18)30321-8DOI Listing
August 2018

Comparison of anal cancer screening strategies including standard anoscopy, anal cytology, and HPV genotyping in HIV-positive men who have sex with men.

Br J Cancer 2018 08 20;119(3):381-386. Epub 2018 Jul 20.

Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

Background: There is no consensus on screening strategy of high-grade intraepithelial neoplasia (HGAIN). Guidelines range from clinical examination with digital anorectal examination followed by standard anoscopy (SA), to anal cytology (Pap)+/- HPV genotyping. We compared screening strategy yields based on Pap, SA, and HPV-16 genotyping alone or in combination in HIV-MSM.

Methods: Pap, SA, and HPV-16 genotyping were performed in all HIV-MSM attending a first anal cancer screening consultation in Paris, France. High-resolution anoscopy, the gold standard to detect HGAIN, was performed in the case of HPV-16 positivity or abnormal cytology. Yield was defined as the number of patients with HGAIN relative to the total number of patients screened.

Results: On 212 patients, the complete strategy (SA + Pap + HPV genotyping) yield (12.7%) was significantly higher than that of SA (3.3%, p < 0.001) and HPV-16 alone (6.6%, p < 0.05). Although none of the other strategies were significantly different from the complete strategy, Pap + HPV-16 and Pap + SA had closer yields (about 11%), with OR = 0.83 (95% CI [0.44;1.57]) and 0.87 (95% CI [0.46;1.64]), respectively.

Conclusions: Pap combined with HPV-16 genotyping or SA tended towards higher yields compared to Pap alone, and closer to that of the complete strategy.
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http://dx.doi.org/10.1038/s41416-018-0176-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6068120PMC
August 2018

Efficacy of a docetaxel-5FU-oxaliplatin regimen (TEFOX) in first-line treatment of advanced gastric signet ring cell carcinoma: an AGEO multicentre study.

Br J Cancer 2018 08 6;119(4):424-428. Epub 2018 Jun 6.

Department of GI Oncology, Hôpital Européen Georges-Pompidou, APHP, Paris Descartes University, Sorbonne Paris Cité, Paris, France.

Background: Triplet chemotherapy, with docetaxel-5FU-oxaliplatin (TEFOX), has yielded promising results in patients with advanced and operable gastric adenocarcinoma. This may prove useful in treating signet ring cell carcinoma (SRCC), which is known to be chemoresistant and has a poor prognosis. We therefore evaluated TEFOX in patients with untreated advanced SRCC.

Methods: Patients with metastatic or locally advanced non-resectable SRCC were treated with TEFOX. Chemotherapy was administered every 14 days, with combined docetaxel (50 mg/m) and oxaliplatin (85 mg/m) followed by 5FU (2400 mg/m).

Results: Among 65 patients enrolled, including 17 with linitis plastica, ORR and DCR were 66.1% and 87.6%, respectively. Median PFS and OS were 9.7 months (95% CI [6.9-11.4]) and 14.3 months (95% CI [11.6-21.6]) respectively. Twenty-six patients (40%) initially considered as unresectable had secondary resection (n = 24) or radiotherapy (n = 2) with curative intent, with median PFS and OS of 12.4 and 26.2 months, respectively.

Conclusions: TEFOX appears to be effective as first-line treatment in advanced gastric SRCC and has an acceptable safety profile. It allowed a curative intent approach in 40% of patients. Considering the low chemosensitivity of SRCC reported with other chemotherapy regimens and pending for randomised studies, TEFOX might be an option in advanced gastric SRCC.
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http://dx.doi.org/10.1038/s41416-018-0133-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133962PMC
August 2018

Colorectal Cancer: Why Does Side Matter?

Drugs 2018 Jun;78(8):789-798

Department of Gastroenterology and Digestive Oncology, Assistance Publique-Hôpitaux De Paris, Hôpital Européen Georges Pompidou, Paris Descartes University, Paris, France.

Colorectal cancer (CRC) is a heterogeneous disease, and the search for clinical and molecular prognostic and predictive factors is thus necessary to better tailor each individual patient's management. Primary tumor location (PTL) seems to act as a master prognostic factor pooling different clinical, pathological, and molecular poor prognostic factors. In fact, right-sided (RS) CRC patients are more frequently female and elderly with microsatellite unstable, BRAF mutated, CpG island methylator phenotype (CIMP)-high, poorly differentiated tumors, compared to left-sided (LS) CRC patients. PTL does not seem to clearly influence disease-free survival (DFS) in localised colon cancer even though the opposite prognostic value of RS tumors on DFS depending on RAS/BRAF mutational status has been recently suggested in these patients. In metastatic CRC (mCRC), the poor prognosis associated with RS tumors is confirmed in the most recent publications in the era of double and triple chemotherapeutic regimens and targeted agents. Concerning the predictive value of PTL, in patients with RAS wild-type mCRC in the first-line setting, anti-epidermal growth factor receptor (EGFR) therapy combined with chemotherapy appears to be more effective than bevacizumab in LS CRC, while patients with RS CRC benefit less from anti-EGFR therapy, and intensive chemotherapy plus bevacizumab may be more appropriate but EGFR antibodies remain an option if objective response is needed. Due to the limitation of the current data (unplanned and retrospective analyses), these conclusions must be interpreted with caution. Clinical trials in RS CRC may be of interest to clarify what is the best treatment strategy in these patients.
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http://dx.doi.org/10.1007/s40265-018-0921-7DOI Listing
June 2018

[Papillomavirus, could we speak about cancer and prevention?]

Bull Cancer 2018 Feb 17;105(2):137-139. Epub 2018 Jan 17.

AP-HP, faculté de médecine Paris-Descartes, hôpital européen Georges-Pompidou, service d'anatomo-pathologie, Paris, 75015 France.

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http://dx.doi.org/10.1016/j.bulcan.2017.12.001DOI Listing
February 2018

5-FU or mitomycin C hepatic arterial infusion after failure of arterial oxaliplatin in patients with colorectal cancer unresectable liver metastases.

Clin Res Hepatol Gastroenterol 2018 06 7;42(3):255-260. Epub 2017 Dec 7.

Department of gastroenterology and digestive oncology depart, université Paris Descartes, Sorbonne Paris-cité, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France. Electronic address:

Introduction: Hepatic arterial infusion (HAI) chemotherapy with oxaliplatin is an accepted option in the management of colorectal cancer (CRC) with dominant liver metastases (LM). However, despite prolonged control, some patients experience disease progression. On the other hand, oxaliplatin leads to dose-limiting toxicity. In these cases, the use of a second-line HAI with an alternative drug has never been reported to date. We evaluated treatment outcomes in patients receiving second-line HAI with 5-FU or mitomycin C, after first-line HAI of oxaliplatin in heavily pretreated patients.

Material And Methods: Between March 2010 and June 2016, this observational study included 24 patients with unresectable CRC LM and treated with HAI of 5-FU (17 patients) or mitomycin C (7 patients), after HAI of oxaliplatin.

Results: Mean age was 61.7 years. Forty-two percent of patients (10/24) had extra-hepatic metastases and 75% (18/24) at least 8 liver metastases. Including HAI of oxaliplatin, all patients had previously received at least 2 lines of chemotherapy±targeted agents (100%) and 96% (23/24) received concomitant systemic therapies together with HAI of 5-FU or mitomycin C. The overall objective response rate and disease control rate were, respectively, 42% (10/24) and 71% (17/24). Median progression-free survival and overall survival (OS) were, respectively, 5.6 and 25.8 months; hepatic progression-free survival was 8.5months. Thirteen percent (3/24) of the patients received further curative intent treatment after HAI 5-FU and mitomycin C. No toxic death occurred and the toxicity profile was acceptable.

Conclusions: HAI of 5-FU or mitomycin C is an alternative option in patients with predominant CRC LM, when they experience disease progression or do not tolerate HAI of oxaliplatin.
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http://dx.doi.org/10.1016/j.clinre.2017.11.004DOI Listing
June 2018