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  • 1
    In: JCO Precision Oncology, American Society of Clinical Oncology (ASCO), , No. 5 ( 2021-11), p. 370-377
    Type of Medium: Online Resource
    ISSN: 2473-4284
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
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  • 2
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 4534-4534
    Abstract: Introduction: With the increasing complexity of current diagnostic investigations, the integration of clinical, pathological and molecular characteristics is crucial for the management of patients (pts) with cancers of unknown primary (CUP). A national multidisciplinary tumor board (NatCUPMTB) was created 2 years ago in France to discuss the diagnostic and therapeutic management of CUP pts. The objective of this study was to evaluate its diagnostic, prognostic and therapeutic impact after 2 years of activity. Methods: This was a multicenter retrospective study with prospective follow-up. All pts discussed at least once in the NatCUPMTB between June 2020 and August 2022 were included. Pts and tumors characteristics, pathological and molecular analyses including WGS, WES and RNAseq performed on SEQOIA and AURAGEN national large-scale sequencing platforms, multidisciplinary tumor board (MTB) conclusions, and follow-up after MTB were collected. Results: 76 pts for whom a long-term follow-up was available were included. The median age at diagnosis was 57 yo, 54% were female, and the median number of metastatic sites at diagnosis was 2. The median time between diagnosis and first MTB presentation was 3.8 months (0.2-55). MTB investigations enabled to identify a likely primary origin in 44/76 (58%) pts, and the MTB recommended a personalized therapeutic strategy in 50/76 patients (66%). MTB recommendations were based on the combination of clinical, pathological and molecular investigations in 55% of pts. After a median follow-up of 6.2 months, the median overall survival (OS) was 17.7 months from diagnosis and 11.0 months from the 1st MTB presentation. Pts for which the MTB had a diagnostic impact, and having received a treatment following MTB recommendation (based on putative origin or targetable alteration) had increased OS compared to pts with no diagnostic orientation (median OS 18.4 months vs 5.6 months, p=0.003) or having received other treatments (median OS 18.4 vs 4.4 months, p=0.0001). Conclusion: NatCUPMTB provides significant diagnostic and therapeutic benefit in pts with CUP. Early presentation of pts at NatCUPMTB as soon as CUP diagnosis is suspected should be recommended. Citation Format: Nicolas Jacquin, Maud Kamal, Ivan Bieche, Célia Dupain, Isabelle Guillou, Linda Larbi-Chérif, Etienne Rouleau, Julien Masliah Planchon, Isabelle Soubeyran, Christelle de la Fouchardière, Camille Tlemsani, Hélène Blons, Fabienne Escande, Michel Vidaud, Jennifer Wong, Pierre Saintigny, Sandrine Boyault, Adrien Buisson, Yves Allory, Anne Vincent-Salomon, Vincent Cockenpot, Janick Selves, Christophe Le Tourneau, Sarah Watson. National Multidisciplinary Tumor Board improves diagnostic stratification and therapeutic management in Cancers of Unknown Primary: the French Experience. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4534.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
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  • 3
    In: Neuro-Oncology, Oxford University Press (OUP), ( 2023-06-28)
    Abstract: The prognosis for Li–Fraumeni syndrome (LFS) patients with medulloblastoma (MB) is poor. Comprehensive clinical data for this patient group is lacking, challenging the development of novel therapeutic strategies. Here, we present clinical and molecular data on a retrospective cohort of pediatric LFS MB patients. Methods In this multinational, multicenter retrospective cohort study, LFS patients under 21 years with MB and class 5 or class 4 constitutional TP53 variants were included. TP53 mutation status, methylation subgroup, treatment, progression free- (PFS) and overall survival (OS), recurrence patterns, and incidence of subsequent neoplasms were evaluated. Results The study evaluated 47 LFS individuals diagnosed with MB, mainly classified as DNA methylation subgroup “SHH_3” (86%). The majority (74%) of constitutional TP53 variants represented missense variants. The 2- and 5-year (y-) PFS were 36% and 20%, and 2- and 5y-OS were 53% and 23%, respectively. Patients who received postoperative radiotherapy (RT) (2y-PFS: 44%, 2y-OS: 60%) or chemotherapy before RT (2y-PFS: 32%, 2y-OS: 48%) had significantly better clinical outcome then patients who were not treated with RT (2y-PFS: 0%, 2y-OS: 25%). Patients treated according to protocols including high-intensity chemotherapy and patients who received only maintenance-type chemotherapy showed similar outcomes (2y-PFS: 42% and 35%, 2y-OS: 68% and 53%, respectively). Conclusions LFS MB patients have a dismal prognosis. In the presented cohort use of RT significantly increased survival rates, whereas chemotherapy intensity did not influence their clinical outcome. Prospective collection of clinical data and development of novel treatments are required to improve the outcome of LFS MB patients.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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  • 4
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 24, No. Supplement_1 ( 2022-06-03), p. i107-i107
    Abstract: PURPOSE: The prognosis for SHH-medulloblastoma (MB) patients with Li-Fraumeni syndrome (LFS) is poor. Due to lack of comprehensive data for these patients, it is challenging to establish effective therapeutic recommendations. We here describe the largest retrospective cohort of pediatric LFS SHH-MB patients to date and their clinical outcomes. PATIENTS AND METHODS: N=31 patients with LFS SHH-MB were included in this retrospective multicenter study. TP53 variant type, clinical parameters including treatment modalities, event-free survival (EFS) and overall survival (OS), as well as recurrence patterns and incidence of secondary neoplasms, were evaluated. RESULTS: All LFS-MBs were classified as SHH subgroup, in 30/31 cases based on DNA methylation analysis. The majority of constitutional TP53 variants (72%) represented missense variants, and all except two truncating variants were located within the DNA-binding domain. 54% were large cell anaplastic, 69% gross totally resected and 81% had M0 status. The 2-(y)ear and 5-(y)ear EFS were 26% and 8,8%, respectively, and 2y- and 5y-OS 40% and 12%. Patients who received post-operative radiotherapy (RT) followed by chemotherapy (CT) showed significantly better outcomes (2y-EFS:43%) compared to patients who received CT before RT (30%) (p & lt;0.05). The 2y-EFS and 2y-OS were similar when treated with protocols including high-dose chemotherapy (EFS:22%, OS:44%) compared to patients treated with maintenance-type chemotherapy (EFS:31%, OS:45%). Recurrence occurred in 73.3% of cases independent of resection or M-status, typically within the radiation field (75% of RT-treated patients). Secondary malignancies developed in 12.5% and were cause of death in all affected patients. CONCLUSIONS: Patients with LFS-MBs have a dismal prognosis. This retrospective study suggests that upfront RT may increase EFS, while intensive therapeutic approaches including high-dose chemotherapy did not translate into increased survival of this patient group. To improve outcomes of LFS-MB patients, prospective collection of clinical data and development of treatment guidelines are required.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 5
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 25, No. Supplement_1 ( 2023-06-12), p. i64-i65
    Abstract: Patients with Li-Fraumeni syndrome (LFS) who develop medulloblastoma (MB) have a very poor prognosis. The development of novel therapeutic strategies is challenged by the lack of clinical data for this patient group. We here present clinical and molecular data on a retrospective cohort of pediatric patients with LFS-associated MB. This is an international, retrospective, multicenter cohort study. Patients with LFS-associated MB under 21 years and class 5 (pathogenic) or class 4 (likely pathogenic) constitutional TP53 variants were included. We evaluated TP53 mutation status (constitutional and somatic), DNA methylation subgroup, treatment modalities, event-free (EFS) and overall survival (OS), patterns of recurrence, as well as occurrence of secondary neoplasms. Forty-seven individuals with LFS-associated MB were included. MBs were classified mainly as Sonic Hedgehog (SHH) group (87%). TP53 variants were classified as class 5 (70%) and class 4 (30%). The majority (74%) of TP53 variants represented missense variants. The 2-year (y-) EFS and -OS were 33% and 53%, respectively. A significantly better outcome was seen in patients who received post-operative radiotherapy (RT) (2y-EFS: 44%, 2y-OS: 60%) or chemotherapy before RT (2y-EFS: 24%, 2y-OS: 48%) compared with patients who received no RT (2y-EFS: n.a., 2y-OS: 25%). No significantly different outcomes were seen between patients treated either according to protocols including high-intensity chemotherapy or receiving only maintenance-type chemotherapy (2y-EFS: 42% and 31%, 2y-OS: 68% and 53%, respectively). Patients with LFS-associated MB have a dismal prognosis. Use of RT in LFS-associated MB significantly increased survival rates in the presented cohort, but choice of chemotherapy regimen did not influence their clinical outcome. To improve the outcome of patients with LFS-associated MB, prospective collection of clinical data and development of novel treatments are required.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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  • 6
    In: Journal of Pediatric Surgery, Elsevier BV, Vol. 53, No. 3 ( 2018-03), p. 567-571
    Type of Medium: Online Resource
    ISSN: 0022-3468
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
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  • 7
    In: Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 22, No. 12_Supplement ( 2023-12-01), p. A113-A113
    Abstract: Introduction: With the increasing complexity of current diagnostic investigations, the integration of clinical, pathological and genomic characteristics is crucial for the management of patients (pts) with cancers of unknown primary (CUP). A national multidisciplinary tumor board (NatCUPMTB) was created in July 2020 in France to discuss the diagnostic and therapeutic management of CUP pts. The objective of this study was to evaluate the diagnostic, prognostic and therapeutic impact of this NatCUPMTB after 30 months of activity. Methods: This was a multicenter retrospective study with prospective follow-up. All pts discussed at least once in the NatCUPMTB between July 2020 and January 2023 were included. Pts and tumors characteristics, pathological and genomic analyses including WGS, WES and transcriptome analysis performed on the two PFMG2025 (French Genomic Medecine Plan 2025) national sequencing laboratories, multidisciplinary tumor board (MTB) conclusions, and follow-up after MTB were collected. Results: 151 pts were included. The median age at diagnosis was 58 yo, 55% were female, and the majority of patients had an OMS status & lt;2. The median number of metastatic sites at diagnosis was 2, with a majority located in the lymph nodes (63%). The median time between diagnosis and first MTB presentation was 4 months (1-20). At the time of analysis, NatCUPMTB conclusions and long-term follow up (30 months) were available for 93 pts alive at the second MTB presentation. MTB investigations enabled to identify a likely primary origin in 62/93 (67%) pts, the most frequent being renal carcinoma (N=10), lung carcinoma (N=9) and breast carcinoma (N=8). The most frequently molecular alterations found were in TP53 (37%), KRAS (19%), CDKN2A (18%), NF2 (12%), KMT2C (10%), CDKN2B (9%), PBRM1 (9%) genes. MTB diagnoses were based on the combination of clinical, pathological and genomic investigations in 34/93 (37%) of pts. The others were based on pathological and genomic investigations in 15/93 pts (16%), genomic in 4/93 pts (4%), clinical and genomic in 3/93 pts (3%), clinical and pathological in 3/93 pts (3%) and pathological in 3/93 pts (3%). After a median follow-up of 11.2 months, the median overall survival (OS) was 11.9 months from the 2nd MTB presentation. Importantly, a personalized therapeutic strategy was recommended by NatCUPMTB in 79/93 (85%) of pts. Among these recommendations, 38/79 (49%) were based on the diagnosis of tissue of origin (TOO), 12/79 (15%) on an actionable molecular alteration, 24/79 (30%) on both the TOO and an actionable molecular alteration, and 5/79 (6%) were based on an unguided clinical trial. Conclusion: NatCUPMTB provides significant diagnostic and therapeutic benefit in 85% of pts with CUP. Early presentation of pts at NatCUPMTB as soon as CUP diagnosis is suspected should be recommended. Citation Format: Ivan Bieche, Maud Kamal, Nicolas Jacquin, Célia Dupain, Isabelle Guillou, Etienne Rouleau, Julien Masliah Planchon, Isabelle Soubeyran, Christelle De La Fouchardière, Camille Tlemsani, Hélène Blons, Laëtitia Marisa, Anna Patrikidou, Fabienne Escande, Pierre Blanc, Jennifer Wong, Pierre Saintigny, Sandrine Boyault, Adrien Buisson, Yves Allory, Anne Vincent-Salomon, Vincent Cockenpot, Janick Selves, Christophe Le Tourneau, Sarah Watson. National multidisciplinary tumor board improves diagnostic stratification and therapeutic management in cancers of unknown primary [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A113.
    Type of Medium: Online Resource
    ISSN: 1538-8514
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
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  • 8
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 3363-3363
    Abstract: Introduction: Cell-free tumor DNA (ctDNA) is an emerging biomarker in head and neck squamous cell carcinoma (HNSCC) for disease staging, patients’ recurrence risk stratification and early detection of relapse. We aimed to compare variants identified in ctDNA versus surgical tumor specimen, and to study the evolution of the mutational landscape of ctDNA over time in HNSCC. Patients and Method: Forty-one HNSCC patients treated with curative-intent primary surgery from SCANDARE cohort (NCT03017573) were evaluated for longitudinal ctDNA-based NGS. Overall, 28 patients were treated with adjuvant (chemo)radiotherapy, and 31 experienced recurrence. Formalin-fixed paraffin-embedded tumor tissues at surgery were available for 41 patients. Serial contributive ctDNA were retrieved from all 41 patients at the date of surgery, 36 patients within 19 weeks after surgery, 20 patients at six months after surgery, and 22 patients at recurrence. Tissue DNA was personalized detected with a custom NGS panel of 571 genes (DRAGON) and ctDNA was sequenced using another personalized dedicated NGS panel including up to 15 genes (OncoFOLLOW). Results: Most frequently mutated genes in tissue included TP53 (15.9%), FAT1 (6.7%), NOTCH1 (5.5%) and PIK3CA (4.3%) with similar allelic ratio to ctDNA at baseline surgery. Higher prevalence of KRAS and TP53 mutations was found in ctDNA at recurrence in comparison with ctDNA and tissue, respectively, at baseline surgery (KRAS: 6.3% versus 1.6% and 0.6%; TP53: 31.2% versus 21.1% and 15.9%). Additional variants in NRAS, HRAS, TP53, JAK2 and SDHA were detected in 6 patients in ctDNA at surgery and were not found in tissue, suggesting spatial intratumor heterogeneity. Twenty-three/36 patients (64%) had detected ctDNA within 19 weeks after surgery among whom, 17/23 patients (74%) had disease recurrence. Eleven/20 patients (including 10 with adjuvant treatment) had detected ctDNA at six months after surgery among whom 6 patients (55%) had disease recurrence. Fifteen/22 patients (68%) had detected ctDNA at recurrence. Emerging pathogenic variants were found in patients with detected ctDNA after surgery (n=7/23; 30%), at six months after surgery (n=1/11; 9%) and at recurrence (n=4/15; 27%). Conclusion: Our study suggests spatial and longitudinal tumor heterogeneity and reports emerging mutations in ctDNA over time in HNSCC. Prognostic significance characterization of the ctDNA dominant clone allele frequency is ongoing. Citation Format: Grégoire Marret, Constance Lamy, Sophie Vacher, Mathieu Séné, Ladidi Ahmanache, Laura Courtois, Zakhia El Beiano, Jerzy Klijanienko, Charlotte Martinat, Nicolas Servant, Choumouss Kamoun, Linda Larbi Chérif, Thierry Bronzini, Cédric Balsat, Jean-François Laes, Aubray Prévot, Sébastien Sauvage, Maxime Lienard, Emmanuel Martin, Bérengère Genin, Nathalie Badois, Maria Lesnik, Antoine Dubray-Vautrin, Olivier Choussy, Wahib Ghanem, Rabah Taouachi, Julien Masliah Planchon, Ivan Bièche, Maud Kamal, Christophe Le Tourneau. Spatial and longitudinal tumor heterogeneity in head and neck squamous cell carcinoma patients treated with primary surgery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3363.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
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  • 9
    In: Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 22, No. 12_Supplement ( 2023-12-01), p. B005-B005
    Abstract: Introduction: The European Society of Medical Oncology Scale of Actionability of molecular Targets (ESCAT) classification system provides a standardized framework for categorizing genomic alterations (GA) of advanced cancer patients. We aimed to analyze the impact of matched therapies administered based on GAs identified through Institut Curie Molecular Tumor Board (MTB) between January 2018 and December 2022, according to ESCAT classification. Patients and methods: Between 2018 and 2022, 1,445 patients were discussed at Institut Curie MTB. Inclusion criteria were pre-defined as: adult patients ( & gt;18 years) with advanced or rare cancers. Tumors characteristics, pathological and genomic analyses, MTB conclusions, and follow-up after MTB were collected. Molecular analyses included a custom in-house NGS panel of 571 genes (DRAGON) and targeted RNAseq (ARCHER FusionPlex® CTL panel) or WGS, WES and RNAseq performed on the SEQOIA platform as part of the French Genomic Medecine Plan 2025. Clinical endpoints were Objective Response Rates (ORR), Progression-Free Survival (PFS) and Overall Survival (OS). ORR, PFS and OS of the population of patients receiving matched therapies were analyzed according to ESCAT Tiers. Results: Median patients age was 59 in the global MTB population (range=18-95; n=1,445) and mostly females (968/1,445; 67%). Most frequent tumors were from breast (20%), head and neck (10%), pancreas (10%), colon/rectum (9%), ovary (7%), lung (7%), soft tissue (7%), uterus (6%) or uveal melanoma (5%). Of the 1,445 patients, 995 had a tumor molecular profiling (69%). Actionable GAs were found in 576/995 (58%) of patients and 211/995 (21%) patients were oriented towards matched therapy. Simultaneously, some patients have also been referred to a genetic consultation when GA may correspond to a known predisposition gene. Among the 211 patients oriented towards matched therapy and after clinical evaluation for each patient, 101/211 (47%) representing 101/995 (10%) of the total patients actually received a matched therapy according to 102 actionable GAs identified through MTB analysis. The main actionable GAs detected were found in PIK3CA (12%), ERBB2 (11%), BRCA2 (6%) and FGFR3 (5%) genes. Among these, 40/102 GAs (40%) were classified as tier I, 4 (4%) as tier II, 35 (35%) as tier III, 18 (18%) as tier IV and 5 (5%) as tier X according to ESCAT. For those patients, PFS and OS were significantly improved when treatment was administered based on ESCAT tiers I/II (p=0.0486 for PFS, and p=0.0224 for OS). Worst clinical outcomes were observed for hypothetical targets classified as Tiers III and IV. Conclusions: High throughput screening was feasible for a majority of patients enrolled in the MTB. Among the patients screened, actionable GAs are identified in 58% of the patients. Yet 21% were oriented to matched therapy. Finally, 10% of patients were eventually treated with matched therapy, with a favorable outcome observed in patients with ESCAT Tiers I/II. Citation Format: Maud Kamal, Kimya Rahmani Narj Abadi, Raphaël Sanchez, Célia Dupain, Isabelle Guillou, Grégoire Marret, Zahra Castel Ajgal, Marie Paule Sablin, Cindy Neuzillet, Amani Asnacios Lecerf, Edith Borcoman, Ségolène Hescot, Florence Coussy, Manuel Rodrigues, Nicolas Girard, Sarah Watson, Julien Masliah Planchon, Jennifer Wong, Abderaouf Hamza, Celine Callens, Olfa Trabelsi Grati, Samia Melaabi, Keltouma Driouch, Emmanuelle Mouret-Fourme, Chrystelle Colas, Samantha Antonio, Odette Mariani, Michèle Nijnikoff, Anne Vincent-Salomon, Yves Allory, Ivan Bieche, Christophe Le Tourneau. Impact of molecular profiling and ESCAT classification on patient outcome: The experience of Institut Curie Molecular Tumor Board [abstract] . In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr B005.
    Type of Medium: Online Resource
    ISSN: 1538-8514
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
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  • 10
    In: European Urology, Elsevier BV, Vol. 69, No. 6 ( 2016-06), p. 1055-1061
    Type of Medium: Online Resource
    ISSN: 0302-2838
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2016
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