26 results on '"Pudlarz, T."'
Search Results
2. Codon-specific KRAS mutations predict survival in advanced pancreatic cancer
- Author
-
Boilève, A., Rousseau, A., Hilmi, M., Tarabay, A., Mathieu, J.R.R., Cartry, J., Bedja, S., Goudarzi, N., Nicotra, C., Ngo-Camus, M., Boige, V., Valéry, M., Pudlarz, T., Bani, M.-A., Dartigues, P., Tselikas, L., Italiano, A., Cosconea, S., Gelli, M., Fernandez-de-Sevilla, E., Malka, D., Annereau, M., Jaulin, F., Smolenschi, C., Hollebecque, A., and Ducreux, M.
- Published
- 2024
- Full Text
- View/download PDF
3. 172P Early impact of a personalised cancer interception programme for women at non-genetic high risk of breast cancer (BC)
- Author
-
Veron, L., primary, Aupomerol, M., additional, Ouali, K., additional, Pudlarz, T., additional, Degousée, L., additional, Abdayem, P., additional, Caron, H., additional, Raynard, B., additional, Hesry, G., additional, Caron, O., additional, and Delaloge, S., additional
- Published
- 2023
- Full Text
- View/download PDF
4. 108P Assessing molecular characteristics in a large cohort of anal squamous cell carcinoma patients
- Author
-
Smolenschi, C., Sharaf, R., Hollebecque, A., Bani, M.A., Boige, V., Boileve, A., Valery, M., Italiano, A., Tarabay, A., Facchinetti, F., Pudlarz, T., Bahleda, R., Fuerea, A.C., Benhaim, L., Sourouille, I., Bayle, A., Gelli, M., Fernandez de Sevilla, E., Ducreux, M.P., and Vasseur, D.
- Published
- 2024
- Full Text
- View/download PDF
5. 1516P Lung-only metastatic PDAC: Another disease?
- Author
-
Mercier, L., Boileve, A., Ducreux, M.P., Lambert, A., Tarabay, A., Hollebecque, A., Smolenschi, C., Delaye, M., Valery, M., Pudlarz, T., Fuerea, A.C., and Boige, V.
- Published
- 2024
- Full Text
- View/download PDF
6. 1734P Early impact of a personalized lung cancer interception program for heavy smokers
- Author
-
Abdayem, P., Veron, L., Garcia, G., Berkane, K., Pradere, P., Pudlarz, T., Ouali, K., Caramella, C., Issard, J., Selhane, F., Ben Ahmed, T., Tardieu, A., Hanna, A., Ammar, D., Caron, H., Ortolan, B., Mercier, O., Planchard, D., Caron, O., and Delaloge, S.
- Published
- 2023
- Full Text
- View/download PDF
7. 1667P Clinical and molecular features of young onset pancreatic adenocarcinoma
- Author
-
Remond, M., Tarabay, A.A., Hollebecque, A., Gelli, M., Mouawia, A., Ben Ammar, I., Fernandez de Sevilla, E., Cosconea, S., Tselikas, L., Barbe, R., Fuerea, A.C., Bani, M.A., Deloger, M., Besse, B., Pudlarz, T., Valery, M., Boige, V., Smolenschi, C., Ducreux, M.P., and Boileve, A.
- Published
- 2023
- Full Text
- View/download PDF
8. 112P Clinical, genomic and transcriptomic characteristics of young-onset biliary tract cancers
- Author
-
Pudlarz, T., Antoun, L., Rousseau, A., Nicolle, R., Gelli, M., Fernandez de Sevilla, E., Cosconea, S., Tselikas, L., Barbe, R., Turpin, A., Deloger, M., Italiano, A., Valery, M., Tarabay, A.A., Boige, V., Malka, D., Smolenschi, C., Hollebecque, A., Ducreux, M.P., and Boileve, A.
- Published
- 2023
- Full Text
- View/download PDF
9. P-340 Bidirectional chemotherapy for patients with gastrointestinal peritoneal carcinomatosis
- Author
-
Smolenschi, C., Hollebecque, A., Valéry, M., Boileve, A., Antoun, L., Tarabay, A., Pudlarz, T., Eid, R., Benhaim, L., Sourrouille, I., Gelli, M., Fernandez de Sevilla, E., Ducreux, M., and Boige, V.
- Published
- 2023
- Full Text
- View/download PDF
10. PD-29 Could molecular profiling be helpful in daily practice in the treatment of anal carcinoma?
- Author
-
Smolenschi, C., Hollebecque, A., Valéry, M., Boileve, A., Boige, V., Bayle, A., Antoun, L., Tarabay, A., Lacroix, L., Pudlarz, T., Sourrouille, I., Benhaim, L., Labrunie, J. Durand, Fernandez de Sevilla, E., Gelli, M., Bahleda, R., Ngo-Camus, M., Nicotra, C., Ducreux, M., and Vasseur, D.
- Published
- 2023
- Full Text
- View/download PDF
11. 46P [18F]2-Fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18FDG-PET/CT) in patients treated with immune checkpoint inhibitors (ICI) for microsatellite instability-high metastatic colorectal cancer (MSI mCRC)
- Author
-
Pudlarz, T., primary, Montravers, F., additional, Garcia-Larnicol, M-L., additional, Kempf, E., additional, Bennouna, J., additional, de la Fouchardière, C., additional, Tougeron, D., additional, Borg, C., additional, Mazard, T., additional, Chibaudel, B., additional, Parc, Y., additional, Svrcek, M., additional, Menu, Y.M., additional, Cohen, R., additional, and Andre, T., additional
- Published
- 2020
- Full Text
- View/download PDF
12. AACR 2019 — Congrès de l’association américaine de recherche contre le cancer
- Author
-
Pudlarz, T., primary, Naoun, N., additional, Beinse, G., additional, Grazziotin-Soares, D., additional, and Lotz, J.-P., additional
- Published
- 2019
- Full Text
- View/download PDF
13. Professionals' Perceptions of the Colorectal Cancer Pathway: Results of a Co-Constructed Qualitative Study.
- Author
-
Delaye M, Polomeni A, Faiderbe S, Berlioz N, Benssekoum C, Guillemin A, Pudlarz T, and de Montgolfier S
- Subjects
- Humans, Female, Male, Critical Pathways, France, Health Personnel psychology, Patient Care Team, Middle Aged, Adult, Colorectal Neoplasms psychology, Colorectal Neoplasms therapy, Qualitative Research, Attitude of Health Personnel, Interviews as Topic
- Abstract
Introduction: Qualitative research on the perceptions of healthcare professionals involved in cancer care about their respective roles in the patient care pathway is limited. Therefore, the aim of this qualitative study was to document these perceptions., Methods: A multidisciplinary team that included patient researchers constructed a semi-structured interview guide on the perceptions of the colorectal cancer care pathway by professionals. Interviews were conducted with healthcare professionals from two French hospitals that manage patients with colorectal cancer. Then, the interviews were fully transcribed and analysed by the whole multidisciplinary team., Results: Thirteen healthcare professionals were interviewed (six nurses, four physicians, one psychologist, one social worker and one secretary). They described the colorectal care pathway using a great lexical diversity and listed a significant number of professionals as taking part in this pathway. Among the people mentioned were healthcare professionals working inside and outside the hospital, family members and non-conventional medicine practitioners. However, they did not spontaneously mention the patient. Their views on the role of the referring physician, the general practitioner and the patient were further explored. The interviews highlighted the coordination difficulties among the various professionals, particularly between general practitioners and hospital teams. These data provided interesting elements for developing a tool to help coordination among professionals., Conclusions: This preliminary study, with its participatory design, brings interesting elements of reflection on the care pathway for patients with colorectal cancer. It will continue through the creation of a larger participatory project., Patient or Public Contribution: Patient partners were included in all steps of this study. This transdisciplinary project was coordinated by a group composed of three patient partners, two healthcare professionals and two humanities and social sciences researchers. Their knowledge of the patient's perspective on the care pathway enriched discussions from the study design to results analysis., (© 2024 The Author(s). Health Expectations published by John Wiley & Sons Ltd.)
- Published
- 2024
- Full Text
- View/download PDF
14. Clinical and molecular features of early onset pancreatic adenocarcinoma.
- Author
-
Rémond M, Smolenschi C, Tarabay A, Gelli M, Fernandez-de-Sevilla E, Mouawia A, Cosconea S, Tselikas L, Barbe R, Fuerea A, Bani MA, Deloger M, Besse B, Pudlarz T, Valéry M, Boige V, Hollebecque A, Ducreux M, and Boilève A
- Subjects
- Humans, Male, Female, Middle Aged, Adult, Age of Onset, Aged, Adenocarcinoma genetics, Adenocarcinoma pathology, Adenocarcinoma mortality, Mutation, Biomarkers, Tumor genetics, Liver Neoplasms genetics, Liver Neoplasms secondary, Liver Neoplasms mortality, Liver Neoplasms pathology, Pancreatic Neoplasms pathology, Pancreatic Neoplasms genetics, Pancreatic Neoplasms mortality, Pancreatic Neoplasms epidemiology
- Abstract
Pancreatic adenocarcinoma (PDAC) is a major health burden and may become the second cause of death by cancer in developed countries. The incidence of early-onset pancreatic cancer (EOPC, defined by an age at diagnosis <50 years old) is increasing. Here, we conducted a study of all PDAC patients followed at our institution. Patients were classified as EOPC or non-early onset (nEOPC, >50). Eight hundred and seventy eight patients were included, of which 113 EOPC, exhibiting a comparable performance status. EOPC were more often diagnosed at the metastatic stage (70.0% vs 58.3%) and liver metastases were more prevalent at diagnosis (60.2% vs. 43.9%). The median overall survival (OS) from diagnosis was 18.1 months, similar between EOPC and nEOPC. Among patients who underwent surgery, recurrence-free survival was similar between age groups. Among metastatic patients, first line progression free survival was similar but EOPC received more treatment lines (72.3% vs. 58.1% received ≥2 lines). Regarding molecular alterations, the mean tumor mutational burden (TMB) was lower in EOPC (1.42 vs. 2.95 mut/Mb). The prevalence of KRAS and BRCA1/2 mutations was similar, but EOPC displayed fewer alterations in CNKN2A/B. Fifty eight patients (18.6%) had actionable alterations (ESCAT I-III) and 31 of them received molecularly matched treatments. On the transcriptomic level, despite its clinical aggressiveness, EOPC was less likely to display a basal-like phenotype. To conclude, EOPC were diagnosed more frequently at the metastatic stage. OS and 1st line PFS were similar to nEOPC. EOPC displayed specific molecular features, such as a lower TMB and fewer alterations in CDKN2A/B., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
- Published
- 2024
- Full Text
- View/download PDF
15. Role of molecular biology in the management of pancreatic cancer.
- Author
-
Boileve A, Smolenschi C, Lambert A, Boige V, Tarabay A, Valery M, Fuerea A, Pudlarz T, Conroy T, Hollebecque A, and Ducreux M
- Abstract
Pancreatic ductal adenocarcinoma (PDAC) presents significant challenges in patient management due to a dismal prognosis, increasing incidence, and limited treatment options. In this regard, precision medicine, which personalizes treatments based on tumour molecular characteristics, has gained great interest. However, its widespread implementation is not fully endorsed in current recommendations. This review explores key molecular alterations in PDAC, while emphasizing differences between KRAS -mutated and KRAS -wild-type tumours. It assesses the practical application of precision medicine in clinical settings and outlines potential future directions with respect to PDAC. Actionable molecular targets are examined with the aim of enhancing our understanding of PDAC molecular biology. Insights from this analysis may contribute to a more refined and personalized approach to pancreatic cancer treatment, ultimately improving patient outcomes., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
16. Case report: Microsatellite instability determination is not always black and white in Lynch syndrome diagnosis.
- Author
-
Rodriguez JE, Vasseur D, Bani MA, Cabaret O, Cotteret S, Muleris M, Golbarg V, Malka D, Pudlarz T, Caron O, and Smolenschi C
- Abstract
Introduction: Microsatellite instability (MSI) is a genetic marker that is useful in the detection and treatment of Lynch syndrome (Sd). Although conventional techniques such as immunohistochemistry (IHC) and polymerase chain reaction (PCR) are the standards for MSI detection, the advent of next-generation sequencing (NGS) has offered new possibilities, especially with circulating DNA., Case Report: We present the case of a 26-year-old patient with Lynch Sd and a BRAF -mutated metastatic colon cancer. The discordant MSI results between the conventional methods and NGS posed challenges in making treatment decisions. Subsequent NGS analysis revealed a high MSI status, leading to participation in an immunotherapy trial, with remarkable clinical response., Conclusion: This case emphasizes the importance of comprehensive molecular profiling and strong interdisciplinary collaborations, especially in cases with ambiguous MSI results., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Rodriguez, Vasseur, Bani, Cabaret, Cotteret, Muleris, Golbarg, Malka, Pudlarz, Caron and Smolenschi.)
- Published
- 2024
- Full Text
- View/download PDF
17. Exposure-response relationship of cabozantinib in patients with metastatic renal cell carcinoma treated in routine care.
- Author
-
Blanchet B, Xu-Vuilard A, Jouinot A, Puisset F, Combarel D, Huillard O, Le Louedec F, Thomas F, Teixeira M, Flippot R, Mourey L, Albiges L, Pudlarz T, Joly C, Tournigand C, Chauvin J, Puszkiel A, Chatelut E, Decleves X, Vidal M, Goldwasser F, Oudard S, Medioni J, and Vano YA
- Subjects
- Humans, Anilides adverse effects, Pyridines adverse effects, Retrospective Studies, Carcinoma, Renal Cell pathology, Kidney Neoplasms pathology
- Abstract
Background: Interindividual pharmacokinetic variability may influence the clinical benefit or toxicity of cabozantinib in metastatic renal cell carcinoma (mRCC). We aimed to investigate the exposure-toxicity and exposure-response relationship of cabozantinib in unselected mRCC patients treated in routine care., Methods: This ambispective multicenter study enrolled consecutive patients receiving cabozantinib in monotherapy. Steady-state trough concentration (Cmin,ss) within the first 3 months after treatment initiation was used for the PK/PD analysis with dose-limiting toxicity (DLT) and survival outcomes. Logistic regression and Cox proportional-hazards models were used to identify the risk factors of DLT and inefficacy in patients, respectively., Results: Seventy-eight mRCC patients were eligible for the statistical analysis. Fifty-two patients (67%) experienced DLT with a median onset of 2.1 months (95%CI 0.7-8.2). In multivariate analysis, Cmin,ss was identified as an independent risk factor of DLT (OR 1.46, 95%CI [1.04-2.04]; p = 0.029). PFS and OS were not statistically associated with the starting dose (p = 0.81 and p = 0.98, respectively). In the multivariate analysis of PFS, Cmin, ss > 336 ng/mL resulted in a hazard ratio of 0.28 (95%CI, 0.10-0.77, p = 0.014). By contrast, Cmin, ss > 336 ng/mL was not statistically associated with longer OS., Conclusion: Early plasma drug monitoring may be useful to optimise cabozantinib treatment in mRCC patients treated in monotherapy, especially in frail patients starting at a lower than standard dose., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2024
- Full Text
- View/download PDF
18. Precision medicine for KRAS wild-type pancreatic adenocarcinomas.
- Author
-
Ben-Ammar I, Rousseau A, Nicolle R, Tarabay A, Boige V, Valery M, Pudlarz T, Malka D, Gelli M, Fernandez-De-Sevilla E, Fuerea A, Tanguy ML, Rouleau E, Barbe R, Mathieu JRR, Jaulin F, Smolenschi C, Hollebecque A, Ducreux M, and Boileve A
- Subjects
- Female, Humans, Male, Middle Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Mutation, Precision Medicine, Proto-Oncogene Proteins p21(ras) genetics, Retrospective Studies, Aged, Adenocarcinoma drug therapy, Adenocarcinoma genetics, Adenocarcinoma pathology, Carcinoma, Pancreatic Ductal drug therapy, Carcinoma, Pancreatic Ductal genetics, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms genetics
- Abstract
Background: KRAS mutation is the most common molecular alteration in pancreatic adenocarcinoma (PDAC), and around 10% of patients harbor KRAS wild-type tumors (KRAS
WT )., Methods: A retrospective chart review of clinical/molecular data was performed including all PDAC patients with a determined KRAS status (tumor molecular profiling on tissue or liquid biopsy)., Results: 342 patients were included with 54 KRASWT PDAC (16%) compared to 288 patients with KRASm PDAC. Median age was 61 years [IQR:54.0;67.0] and 164 pts (48%) were female. At diagnosis, KRASWT patients (63%) were more frequently diagnosed at a non-metastatic stage compared to KRASm patients (41%) (p = 0.003). Regarding metastatic sites, liver was less frequent in KRASWT (39%, p < 0.0001). Median overall survival (mOS) from initial diagnosis was significantly higher in the KRASWT group compared to KRASm (50.8 months, CI95% [32.0-NR] vs 21.1 months, CI95% [18.9-23.4] (p < 0.004 after adjustment on age, ECOG and stage at diagnosis). In first-line systemic treatment, (mostly FOLFIRINOX) progression-free survival (PFS) was also higher in KRASWT . Based on ESCAT classification, a putative actionable alteration (ESCAT I-III) was identified in 19 (36%) KRASWT pts and 46 (16%) KRASm patients (p < 0.0001) with more alterations in FGFR2, BRAF(V600E), NRTK and more MSI tumors. KRASWT harbored also fewer alterations in TP53, CDKN2A, and SMAD4. 12 KRASWT patients received a molecularly-matched treatment with clinical benefit and improved outcomes compared to KRASm patients., Conclusions: KRASWT patients display distinct disease characteristics and outcomes with prolonged overall survival. KRASWT patients also harbor more actionable molecular alterations, leading to higher survival rates after receiving molecularly matched treatments., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Antoine Hollebecque: Amgen, AstraZeneca, Debiopharm, Eli Lilly and Company, Incyte Corporation, QED Therapeutics. David Malka: Roche, Amgen, Bayer, Sanofi, Merck Serono, Servier, Sanofi, Pierre Fabre, Viatris, Bristol Myers Squibb, MSD Oncology, LEO Pharma, Incyte, AstraZeneca, Taiho Oncology, Pfizer. Fanny Jaulin: ORAKL. Valérie Boige: Amgen, AstraZeneca, Bayer Schering Pharma, Ipsen, Merck Serono, MSD Oncology, Roche/Genentech. Michel Ducreux: Merck Serono, MSD, AMGEN, Roche, Bayer, Ipsen, Pfizer, Servier, Pierre Fabre, HalioDx, Lilly, Sanofi, BMS. Alice Boilève: Merck Serono, Ipsen. Other authors report no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)- Published
- 2024
- Full Text
- View/download PDF
19. Targetable Molecular Alterations in the Treatment of Biliary Tract Cancers: An Overview of the Available Treatments.
- Author
-
Valery M, Vasseur D, Fachinetti F, Boilève A, Smolenschi C, Tarabay A, Antoun L, Perret A, Fuerea A, Pudlarz T, Boige V, Hollebecque A, and Ducreux M
- Abstract
Biliary tract cancers (BTCs) are rare tumours, most often diagnosed at an unresectable stage, associated with poor prognosis, with a 5-year survival rate not exceeding 10%. Only first- and second-line treatments are well codified with the combination of cisplatin-gemcitabine chemotherapy and immunotherapy followed by 5-FU and oxaliplatin chemotherapy, respectively. Many studies have shown that BTC, and more particularly intrahepatic cholangiocarcinoma (iCCA), have a high rate of targetable somatic alteration. To date, the FDA has approved several drugs. Ivosidenib targeting IDH1 mutations, as well as futibatinib and pemigatinib targeting FGFR2 fusions, are approved for pre-treated advanced CCA. The combination of dabrafenib and trametinib are approved for BRAFV600E mutated advanced tumours, NTRK inhibitors entrectinib and larotrectinib for tumours bearing NTRK fusion and prembrolizumab for MSI-H advanced tumours, involving a small percentage of BTC in these three settings. Several other potentially targetable alterations are found in BTC, such as HER2 mutations or amplifications or KRAS G12C mutations and mutations in genes involved in DNA repair mechanisms. This review aims to clarify the specific diagnostic modalities for gene alterations and to summarize the results of the main trials and developments underway for the management of advanced BTC with targetable alterations.
- Published
- 2023
- Full Text
- View/download PDF
20. Neoadjuvant Nivolumab Plus Ipilimumab and Adjuvant Nivolumab in Localized Deficient Mismatch Repair/Microsatellite Instability-High Gastric or Esophagogastric Junction Adenocarcinoma: The GERCOR NEONIPIGA Phase II Study.
- Author
-
André T, Tougeron D, Piessen G, de la Fouchardière C, Louvet C, Adenis A, Jary M, Tournigand C, Aparicio T, Desrame J, Lièvre A, Garcia-Larnicol ML, Pudlarz T, Cohen R, Memmi S, Vernerey D, Henriques J, Lefevre JH, and Svrcek M
- Subjects
- Humans, Aged, Nivolumab therapeutic use, Ipilimumab therapeutic use, Neoadjuvant Therapy, Microsatellite Instability, DNA Mismatch Repair, Neoplasm Recurrence, Local drug therapy, Esophagogastric Junction pathology, Antineoplastic Combined Chemotherapy Protocols adverse effects, Adenocarcinoma drug therapy, Adenocarcinoma genetics, Adenocarcinoma pathology, Stomach Neoplasms drug therapy, Stomach Neoplasms genetics, Stomach Neoplasms pathology
- Abstract
Purpose: In patients with resectable gastric/gastroesophageal junction (GEJ) adenocarcinoma, surgery plus perioperative platinum-based chemotherapy is the standard of care. Perioperative chemotherapy remains debatable for gastric/GEJ adenocarcinoma with deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H)., Patients and Methods: NEONIPIGA (ClinicalTrials.gov identifier: NCT04006262) phase II study evaluated neoadjuvant nivolumab 240 mg once every two weeks ×6 and ipilimumab 1 mg/kg once every six weeks ×2, followed by surgery and adjuvant nivolumab 480 mg once every four weeks (nine injections) in patients with locally advanced resectable dMMR/MSI-H, clinical (c) tumor (T)2-T4 node (N)x metastasis (M)0 gastric/GEJ adenocarcinoma. The primary end point was a pathological complete response (pCR) rate., Results: Between October 2019 and June 2021, 32 patients with dMMR/MSI-H gastric/GEJ adenocarcinoma were enrolled. The median age was 65.5 years (range, 40-80). Clinical stages were cT2-T3N0 (n = 9), cT2-T3N1 (n = 22), and cT3N1M1 (n = 1, wrongly included). With a median follow-up of 14.9 months (95% CI, 10.6 to 17.6), 32 patients received neoadjuvant immunotherapy (27 patients completed all cycles). Neoadjuvant therapy-related grade 3/4 adverse events occurred in six patients (19%). Twenty-nine patients underwent surgery; three did not have surgery and had complete endoscopic response with tumor-free biopsies and a normal computed tomography scan (two refused surgery and one had metastasis at inclusion). The rate of surgical morbidity (Clavien-Dindo classification) was 55% (one postoperative death occurred). All 29 patients had an R0 resection, and 17 (58.6%; 90% CI, 41.8 to 74.1) had pCR (pathological T0N0). Becker tumor regression grades 1a, 1b, 2, and 3 were observed in 17 patients, three (including two pathological T0N1), two, and seven patients, respectively. Of the 29 patients with surgery, 23 received adjuvant nivolumab. At database lock, no patient had relapse and one died without relapse., Conclusion: Nivolumab and ipilimumab-based neoadjuvant therapy is feasible and associated with no unexpected toxicity and a high pCR rate in patients with dMMR/MSI-H resectable gastric/GEJ adenocarcinoma.
- Published
- 2023
- Full Text
- View/download PDF
21. Treatments after Immune Checkpoint Inhibitors in Patients with dMMR/MSI Metastatic Colorectal Cancer.
- Author
-
Bui QL, Mas L, Hollebecque A, Tougeron D, de la Fouchardière C, Pudlarz T, Alouani E, Guimbaud R, Taieb J, André T, Colle R, and Cohen R
- Abstract
Background: Several studies reported improved outcomes with conventional treatments (CT, i.e., chemotherapy ± targeted therapy) administered after immune checkpoints inhibitors (ICI) in certain tumor types. No data are available concerning patients (pts) with metastatic colorectal cancer (mCRC) harboring mismatch repair deficiency/microsatellite instability (dMMR/MSI). We aimed to assess the outcomes of dMMR/MSI mCRC pts receiving CT after ICI failure., Methods: We conducted a retrospective multicenter study investigating the outcomes of all dMMR/MSI mCRC pts who received post-ICI CT between 2015 and 2020., Results: 31 pts (male 61%, median age 56 years) were included. ICI was an anti-PD(L)1 monotherapy in 71% of pts, and 61% received >2 lines before post-ICI CT. The overall response rate and disease control rate were 13% and 45%, with a median progression-free survival (PFS) and overall survival of 2.9 and 7.4 months, respectively. No association of the outcomes with either ICI efficacy or anti-angiogenic agents was observed. Prolonged PFS (range 16.1-21.3 months) was observed in 4 pts (13%)., Conclusions: Although conducted on a limited number of patients, our results do not support an association of previous ICI treatment with an enhanced efficacy of CT in dMMR/MSI mCRC. However, prolonged disease control was observed in several cases, suggesting that some pts might derive an unexpected benefit from post-ICI treatments.
- Published
- 2022
- Full Text
- View/download PDF
22. Immune Checkpoint Inhibition in Metastatic Colorectal Cancer Harboring Microsatellite Instability or Mismatch Repair Deficiency.
- Author
-
Cohen R, Colle R, Pudlarz T, Heran M, Duval A, Svrcek M, and André T
- Abstract
Microsatellite instability (MSI) is a tumor phenotype related to a deficient DNA mismatch repair system (dMMR). This phenotype, observed in 5% of metastatic mCRC but 10-18% of localized CRC, is associated with high tumor mutational burden with highly immunogenic neoantigens. It has emerged as a major predictive biomarker for the efficacy of ICIs. In this review, we will present a comprehensive overview of the literature concerning the efficacy of ICIs in MSI/dMMR mCRC, with a focus on new developments in first-line metastatic setting. Then, we will present current and future challenges of immuno-oncology for patients with MSI/dMMR metastatic CRC.
- Published
- 2021
- Full Text
- View/download PDF
23. Nutrition and physical activity professional education in gastrointestinal oncology: a national multidisciplinary survey.
- Author
-
Hilmi M, Pellat A, Benoit O, Foucaut AM, Mino JC, Kauffmann A, Rochet F, Heuze E, Pudlarz T, Naoun N, Garcia-Larnicol ML, Delpeut C, Peschaud F, and Neuzillet C
- Subjects
- Adult, Clinical Competence, Female, France, Gastroenterology methods, Health Personnel education, Humans, Male, Middle Aged, Surveys and Questionnaires, Dietetics education, Education, Medical, Continuing methods, Gastroenterology education, Health Personnel psychology, Medical Oncology education, Physical and Rehabilitation Medicine education
- Abstract
Objectives: Sarcopenia, present in more than 50% of digestive oncology patients, has a negative impact on clinical outcomes. Nutrition and adapted physical activity are two major interventions for the management of sarcopenia. However, young hepato-gastroenterologists, oncologists and surgeons in France have limited awareness on these topics. We aimed to evaluate the need for training programmes of physicians (residents and senior doctors) involved in digestive oncology on nutrition and adapted physical activity., Methods: A 42-question survey was developed, by a working group of clinicians, dieticians and adapted physical activity teachers, to assess five areas related to demographics of respondents, nutrition practices, nutrition training, adapted physical activity practices and adapted physical activity training. The national survey was undertaken between April and July of 2019., Results: 230 physicians participated in the survey; 34% were hepato-gastroenterologists, 31% were oncologists, 23% were surgeons and 40% were residents. Sixty-one per cent of participants had received training in nutrition and only 21% in adapted physical activity. Ninety per cent of the physicians expressed their desire for more effective training on these two topics. Disparities in clinical practices were observed between hepato-gastroenterologists, oncologists and surgeons., Conclusions: More initial and continuing training on nutrition and adapted physical activity is needed for French physicians in the current digestive oncology clinical practice., Competing Interests: Competing interests: CN reports personal fees from Servier, Bristol-Myers Squibb, Amgen, Merck, MSD, Novartis, Incyte, Nutricia, Baxter, Fresenius Kabi, OSE Immunotherapeutics, Roche and AstraZeneca outside the submitted work. EH reports personal fees from Nutricia outside the submitted work., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2020
- Full Text
- View/download PDF
24. Molecular Targets for the Treatment of Metastatic Colorectal Cancer.
- Author
-
Cohen R, Pudlarz T, Delattre JF, Colle R, and André T
- Abstract
Over the past years, colorectal cancer (CRC) was subtyped according to its molecular and genetic characteristics, allowing the development of therapeutic strategies, based on predictive biomarkers. Biomarkers such as microsatellite instability (MSI), RAS and BRAF mutations, HER2 amplification or NTRK fusions represent major tools for personalized therapeutic strategies. Moreover, the routine implementation of molecular predictive tests provides new perspectives and challenges for the therapeutic management of CRC patients, such as liquid biopsies and the reintroduction of anti-EGFR monoclonal antibodies. In this review, we summarize the current landscape of targeted therapies for metastatic CRC patients, with a focus on new developments for EGFR blockade and emerging biomarkers (MSI, HER2 , NTRK ).
- Published
- 2020
- Full Text
- View/download PDF
25. [Localized MSI/dMMR gastric cancer patients, perioperative immunotherapy instead of chemotherapy: The GERCOR NEONIPIGA phase II study is opened to recruitment].
- Author
-
Cohen R, Pudlarz T, Garcia-Larnicol ML, Vernerey D, Dray X, Clavel L, Jary M, Piessen G, Zaanan A, Aparicio T, Louvet C, Tournigand C, Chibaudel B, Tougeron D, Guimbaud R, Benouna J, Adenis A, Sokol H, Borg C, Duval A, Svrcek M, and André T
- Subjects
- Adenocarcinoma genetics, Adenocarcinoma pathology, Adenocarcinoma surgery, Chemotherapy, Adjuvant, DNA Mismatch Repair, Disease-Free Survival, Humans, Microsatellite Instability, Multicenter Studies as Topic, Neoadjuvant Therapy methods, Patient Selection, Perioperative Care, Phenotype, Stomach Neoplasms genetics, Stomach Neoplasms pathology, Stomach Neoplasms surgery, Treatment Outcome, Adenocarcinoma drug therapy, Antineoplastic Agents, Immunological therapeutic use, Clinical Trials, Phase II as Topic, Ipilimumab therapeutic use, Nivolumab therapeutic use, Stomach Neoplasms drug therapy
- Abstract
Introduction: Perioperative chemotherapy is the standard strategy for localized gastric cancers. Nevertheless, this strategy seems to be inefficient, if not deleterious, for patients with tumors harboring microsatellite instability (MSI) and/or mismatch repair deficiency (dMMR), a tumor phenotype predictive for the efficacy of immune checkpoint inhibitors (ICKi)., Aim: The GERCOR NEONIPIGA single-arm phase II study (NCT04006262; EUDRACT 2018-004712-22) aims at evaluating the efficacy of a peri-operative strategy with nivolumab and ipilimumab in neoadjuvant setting, then nivolumab alone after surgery for patients with resectable MSI/dMMR gastric cancer., Material and Methods: Main inclusion criteria are: gastric and oesogastric junction adenocarcinoma (GOA), T2-T4, all N stage and M0, MSI/dMMR. Patients will be treated with nivolumab 240mg Q2W, 6 infusions, and ipilimumab 1mg/kg Q6W, 2 infusions in neoadjuvant setting. Following surgery, patients with TRG 1-2-3 (Mandard tumor regression grade), acceptable tolerance of neoadjuvant treatment and postoperative ECOG performance status 0-1, will be treated with adjuvant nivolumab 480mg Q4W, 9 infusions., Results: The primary endpoint is pathological complete response rate (pCR-R). Based on a Fleming design, with α=5% and β=20%, 27 patients have to be evaluated (H0=5%; H1=20%). Secondary endpoints include disease-free survival, overall survival and safety., Conclusion: This study is planned to include 32 patients to evaluate the pCR-R with the combination of nivolumab and ipilimumab in neoadjuvant setting for MSI/dMMR localized GOA. The MSI/MMR status should be systematically assessed on diagnostic biopsies of all GOA. If it meets its primary endpoint, the GERCOR NEONIPIGA study might mark a turning point in the management of localized MSI/dMMR GOA patients., (Copyright © 2020 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
26. [Going beyond microsatellite instability for immunotherapy in metastatic colorectal cancer: Consensus molecular subtypes and tumor mutational burden].
- Author
-
Cohen R, Heran M, Pudlarz T, Hilmi M, Tournigand C, André T, and Rousseau B
- Subjects
- Colorectal Neoplasms immunology, Humans, T-Lymphocytes immunology, Tumor Escape, Tumor Microenvironment immunology, Colorectal Neoplasms genetics, Colorectal Neoplasms therapy, DNA Mismatch Repair, Immunotherapy methods, Microsatellite Instability
- Abstract
Next generation immunotherapies have limited efficacy in colorectal cancer. Immune checkpoints inhibitors demonstrated their benefit in mismatch repair-deficient tumors, which also exhibit microsatellite instability (MSI). The Consensual Molecular Subtype (CMS) classification has been recently proposed and highlights specific immune escape mechanisms for each subtype. CMS1 "immune" subtype is hypermutated with a favorable immune microenvironment for immune checkpoints inhibitors activity. Importantly, CMS1 is not restricted to MSI tumors and includes also exonucleasic domain POLE mutated tumors which are good candidates for immunotherapy. The scope of this comprehensive review is to described immune anomalies and propose immunomodulating strategies for each CMS subtype in colorectal cancer. Finally, the potential interest of tumor mutation burden and the Immunoscore
® in colorectal cancer is discussed taking into account the molecular classification and obstacles to antitumoral immune activity., (Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)- Published
- 2019
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.