All times are listed in CET (Central European Time).
- Michael J. Seckl (London, United Kingdom)
- Antonia Digklia (Lausanne, Switzerland)
13O - Impact of surgery and chemotherapy in ovarian sex cord-stromal tumors from the multicentric Salomé study including 469 patients: A TMRG and GINECO group study
- Helene Vanacker (Lyon, France)
- Brunhilde Hanvic (Nancy, France)
- Fabrice Lecuru (Paris, France)
- Helene Vanacker (Lyon, France)
- Patricia Pautier (Villejuif, Cedex, France)
- Fabrice Narducci (Lille, France)
- Francois Cherifi (Caen, France)
- Anne Floquet (Bordeaux, France)
- Martina Aida Angeles (Toulouse, France)
- Dominique Berton-Rigaud (Saint-Herblain, France)
- Christophe Pomel (Clermont-Ferrand, France)
- Elsa Kalbacher (Besancon, France)
- Magali Provansal Gross (Marseille, France)
- Yolanda Fernandez (Vandoeuvre-lès-Nancy, France)
- Thibault De La Motte Rouge (Rennes, France)
- Frédéric Selle (Paris, France)
- Pierre Meeus (Lyon, France)
- Catherine Genestie (Villejuif, Cedex, France)
- Julia Salleron (Vandoeuvre-lès-Nancy, France)
- Isabelle L. Ray-Coquard (Lyon, France)
Abstract
Background
Identifying prognostic factors and measuring the impact of adjuvant chemotherapy in patients with sex cord stromal tumors (SCST) are challenging and must be addressed with large cohorts.
Methods
Data from 13 TMRG network centers were collected and retrospectively analysed. In 2021, a total of 469 adult patients with malignant SCST receiving upfront surgery were enrolled and survival analyses were performed.
Results
359 (75%) patients were diagnosed with adult Granulosa cell tumors, 61 (13%) Sertoli Leydig cell tumors, and 49 (10.4%) another rare sub-type. With 6.4 years of median follow up, 154 (32.8%) patients developed first recurrence. Of them, 82 (17.5%) a second recurrence and 49 (10.4%) a third recurrence. At initial diagnosis, adjuvant chemotherapy was administered in 67 (14.7%) patients. In the relapse setting, 125 (92.6%), 51 (71.8%) and 25 (59.5%) patients underwent surgery in the first, second and third relapse respectively. At recurrence, perioperative chemotherapy was administered in 79 (58.5%), 20 (28.2%) and 10 (23.8%) patients respectively in first, second and third relapse. In first-line therapy, age less than 70 years, FIGO stage and complete surgery were associated with longer PFS. Chemotherapy use had no impact on PFS in the early stage (FIGO I-II). PFS seemed similar using BEP or other chemotherapy regimens (HR 0.88 [0.43; 1.81]) in first-line, however, at relapse BEP regimen improves survival compared to all other regimens. In case of recurrence, PFS is statistically prolonged by complete surgery (HR 0.35 [0.18; 0.71]). Perioperative chemotherapy use did not impact on PFS.
Conclusions
Chemotherapy use has no impact on survival in the first-line or in the relapse setting. Only surgery and its quality demonstrate benefit for PFS in ovarian SCST in the first-line and in relapses. These data supported the need of randomized trial to confirm no benefice of Chemotherapy in SCT.
Legal entity responsible for the study
Centre Léon Bérard.
Funding
Has not received any funding.
Disclosure
P. Pautier: Financial Interests, Personal, Advisory Board, 2015, 2022: PharmaMar; Financial Interests, Institutional, Advisory Board, 2020: Roche, Clovis; Financial Interests, Institutional, Advisory Board, 2021: AstraZeneca; Financial Interests, Personal, Advisory Board, 2019-2020: AstraZeneca; Financial Interests, Institutional, Advisory Board: GSK; Financial Interests, Personal, Advisory Board, 2018-2019: Roche; Financial Interests, Institutional, Expert Testimony, 2022: MSD. A. Floquet: Financial Interests, Personal, Other, Consultancy: GSK; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Clovis Oncology; Financial Interests, Personal, Invited Speaker, French coordinator - Duo Trial: AstraZeneca; Financial Interests, Personal, Invited Speaker, French Coordinator - Mirasol Trial: Immunogen. C. Pomel: Financial Interests, Personal, Advisory Board: Roche, GSK, PharmaMar, MSD; Financial Interests, Personal, Invited Speaker: Roche, GSK, PharmaMar; Financial Interests, Personal, Expert Testimony: Roche. Y. Fernandez: Financial Interests, Personal, Advisory Board: Tesaro. T. De La Motte Rouge: Financial Interests, Personal, Advisory Board: Pfizer, AstraZeneca, GSK, Clovis Oncology, Roche, Mylan, Tesaro; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Research Grant: Novartis, Pfizer, MSD, Seagen; Financial Interests, Institutional, Invited Speaker: Roche, AstraZeneca, GSK, MSD, Pfizer, Netris Pharma; Non-Financial Interests, Personal, Advisory Role: French National Cancer Institute, Unicancer; Non-Financial Interests, Personal, Principal Investigator: Arcagy. F. Selle: Financial Interests, Institutional, Invited Speaker: AstraZeneca, MSD, GlaxoSmithKline-Tesaro. I.L. Ray-Coquard: Financial Interests, Personal, Advisory Board: Roche, GSK, AstraZeneca, Mersana, Deciphera, Amgen, Oxnea, Merck Serono, Agenus, Novartis, Macrogenics, Clovis, EQRX, Adaptimmune, Eisai, SUTRO, BMS, Adaptimmune, Daiichi Sankyo; Financial Interests, Institutional, Other, COLIBRI translational research: BMS; Financial Interests, Institutional, Advisory Board, translational research NEOPREMBROV trial: MSD; Non-Financial Interests, Personal, Principal Investigator: PAOLA1; Non-Financial Interests, Personal, Other, President: GINECO. All other authors have declared no conflicts of interest.
Invited discussant
- Michael J. Seckl (London, United Kingdom)
- Michael J. Seckl (London, United Kingdom)
8O - Outcomes for patients with appendix adenocarcinoma and the role of systemic chemotherapy
- Madeleine C. Strach (Manchester, United Kingdom)
- Madeleine C. Strach (Manchester, United Kingdom)
- Bipasha Chakrabarty (Manchester, United Kingdom)
- Raghavendar Nagaraju (Manchester, United Kingdom)
- Saifee Mullamitha (Manchester, United Kingdom)
- Michael Braun (Manchester, United Kingdom)
- Sarah O'Dwyer (Manchester, United Kingdom)
- Omer Aziz (Manchester, United Kingdom)
- Jorge Barriuso (Manchester, United Kingdom)
Abstract
Background
Appendix adenocarcinomas (AA) are rare aggressive tumours often presenting with peritoneal metastases. The role of systemic chemotherapy remains unclear. The aim of this study was to evaluate the outcomes of patients with AA and to evaluate the role of systemic chemotherapy.
Methods
Data were collected from a prospective database (2005-2021). Cytoreduction (CRS) was described: CC0 (no residual disease, RD), CC1 (<0.25cm RD), CC2 (0.25-2.5cm RD) or CC3 (>2.5cm RD). Chemotherapy was categorised as ‘prior’ (>6 months, m, before CRS); ‘neoadjuvant’ (<6m before CRS) or ‘adjuvant’ (<6m after CC0-1 CRS) and ‘palliative’ (after CC2-3 CRS, unresectable or recurrent disease). Analyses used descriptive statistics, Kaplan-Meier and Cox regression methods.
Results
We identified 216 patients with AA: 141 mucinous, 71 not otherwise specified, 4 signet ring cell. Median age was 59 (21-81) and 58% were female. 149 (69%) patients presented with metastatic disease. 182 (84%) patients had CRS/HIPEC (76% Mitomycin C), with CC0-1 achieved in 172/182 (95%). Systemic chemotherapy (29% oxaliplatin/fluoropyrimidine) was given to 97/216 (45%) of the whole cohort (10% prior, 6% neoadjuvant, 7% adjuvant and 24% palliative); 37/46 (80%) of patients with positive nodes and 28/44 (64%) those with CC2-3 CRS. After median follow-up of 56 months (1-286), median overall survival (OS) was 122m (95% confidence interval, CI, 61-182m) and median progression-free survival (PFS) was 41m (95% CI 27-54). For patients with positive nodes, median OS was NR for those who had no chemotherapy and neoadjuvant or adjuvant chemotherapy, 81m for prior chemotherapy and 28m for palliative chemotherapy (p<0.001). After multivariate analysis, chemotherapy was associated with reduced risk of death for patients with positive nodes compared to no chemotherapy (neoadjuvant or adjuvant p=0.005, prior p=0.011 and palliative p<0.001).
Conclusions
This study represents the single largest series of patients who have AA with long term follow-up data that evaluates the role of chemotherapy in multimodality treatment. This study suggests that positive node status identifies a subgroup of patients with AA who derive the most benefit from systemic chemotherapy.
Legal entity responsible for the study
The Christie NHS Foundation Trust.
Funding
Has not received any funding.
Disclosure
M.C. Strach: Financial Interests, Personal, Advisory Board: Specialised Therapeutics; Financial Interests, Personal, Other, Fellowship: ESMO; Financial Interests, Institutional, Research Grant: Royal Prince Alfred Hospital; Financial Interests, Personal, Funding, Travel Fellowship: The Royal Australasian College of Physicians; Financial Interests, Institutional, Funding: The Christie Charitable Funds; Financial Interests, Personal, Funding, PhD Scholarship: Australian Government RTP Scholarship. S. O'Dwyer: Financial Interests, Institutional, Funding: Cancer Research UK; Financial Interests, Personal, Member, Academy: R&D. O. Aziz: Financial Interests, Institutional, Funding: Cancer Research UK; Financial Interests, Personal, Member, Academy: R&D. J. Barriuso: Financial Interests, Personal, Invited Speaker: Pfizer, Ipsen, NanoString, Servier; Financial Interests, Personal, Advisory Board: Nutricia; Financial Interests, Personal, Expert Testimony: AAA; Non-Financial Interests, Personal, Project Lead: EORTC; Non-Financial Interests, Personal, Invited Speaker: GETNE; Non-Financial Interests, Personal, Principal Investigator: ENETS. All other authors have declared no conflicts of interest.
Invited discussant
- Antonia Digklia (Lausanne, Switzerland)
- Antonia Digklia (Lausanne, Switzerland)
27O - Master gene regulation activity and methylation data reveals common patterns in well differentiated neuroendocrine tumors (NETs) from different tumor sites
- Carlos Carretero-Puche (Madrid, Spain)
- Carlos Carretero-Puche (Madrid, Spain)
- Beatriz Antón Pascual (Madrid, Spain)
- Beatriz Gil-Calderón (Madrid, Spain)
- Marta Benavent (Seville, Spain)
- Lourdes Gomez-Izquierdo (Seville, Spain)
- Paula Jimenez-Fonseca (Oviedo, Spain)
- Ana Teijo (Madrid, Spain)
- Yolanda Rodríguez (Madrid, Spain)
- Beatriz Rubio-Cuesta (Madrid, Spain)
- Gonzalo Gomez-Lopez (Madrid, Spain)
- Fatima Al-Shahrour (Madrid, Spain)
- Beatriz Soldevilla (Madrid, Spain)
- Rocio Garcia-Carbonero (Madrid, Spain)
Abstract
Background
NENs are a heterogeneous family of tumors of wide anatomical distribution that share common clinical and biological traits. Although some studies have characterized the molecular landscape of specific primary locations, there is no cross-site molecular classification of NENs. The global purpose of our project is to improve our understanding of the biological basis of NETs and its impact on clinical outcome. We performed a multiomics factor integrative analysis (MOFA) with data from NETs of multiple anatomic sites and assessed the clinical relevance of inferred latent factors representing the underlying main axes of molecular heterogeneity across samples.
Methods
Transcriptomic and methylation data, were obtained from FFPE tumor samples of 194 patients with G1-G3 NETs from GEP, lung or other origins. Transcriptomic data was transformed into a master regulator activity (MRA) score matrix using the ARACNE and Viper, deeming as master regulators transcription factors, co-factors, cell surface receptors and main regulators of signalling pathways. MRA scores were combined with methylation information performing a MOFA modelling stratified by primary tumor site. All factors were associated to different molecular and clinical data, included tumor grade, site, functionality, and overall survival.
Results
MOFA identified 10 factors: 1, 2, 7, 8 and 10 were exclusively explained by MRA, 3 and 6 by methylation data, and 4, 5, 6 and 9 by both omics. All factors, except for factor 6, explained the variance by primary tumor site. Factor 6 elucidate differences between G1 and G2 tumors only in NETs from lung origin. Several factors were associated with grade (3,4,6 and 9), gender (1,6) and functionality (3,8 and 9), and factor 6 was also associated with a poor prognosis. Finally, we identified genes and pathways related to 10 factors included FGFR4 in factor 2 or several genes related to NETs in factor 4.
Conclusions
To our knowledge this is the largest series to date of comprehensively characterized NETs from a clinical and molecular perspective, and shall lay the ground to build a cross-site classification of NENs to identify unique and shared targetable vulnerabilities of potential clinical use.
Legal entity responsible for the study
Rocio Garcia-Carbonero.
Funding
Pfizer.
Disclosure
R. Garcia-Carbonero: Financial Interests, Personal, Advisory Board: AAA, Advanz Pharma, Amgen, Bayer, BMS, HMP, Ipsen, Merck, Midatech, MSD, Novartis, PharmaMar, Pierre Fabre, Servier; Financial Interests, Institutional, Research Grant: BMS, MSD, Pfizer; Non-Financial Interests, Personal, Leadership Role, Global PI of investigator-initiated clinical trials (AXINET, NICENEC, PEMBROLA): BMS, MSD, Pfizer; Other, Personal, Other, Honoraria received by spouse for advisory board or invited speaker roles: Abbie, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Genomica, Lilly, MSD, Merck, Novartis, Pfizer, PharmaMar, Roche, Sanofi, Servier, Takeda. All other authors have declared no conflicts of interest.
Invited discussant
- Lynnette Fernandez-Cuesta (Lyon, France)
- Lynnette Fernandez-Cuesta (Lyon, France)
22O - Sinonasal cancer: Molecular biomarkers for tumor classification and targeted treatment
- Mario A. Hermsen (Oviedo, Spain)
- Mario A. Hermsen (Oviedo, Spain)
Abstract
Background
The sinonasal cavities harbor a great variety of rare epithelial and neuroendocrine tumors. Many subtypes are poorly differentiated and difficult to diagnose, while their clinical behavior can differ greatly. In spite of advances with endoscopic surgery and radiotherapeutic, recurrences remain frequent and 5-year survival lies between 20-60% or lower. Therefore, there is an unmet clinical need for better diagnostic biomarkers and novel therapeutic approaches. Our aim was to apply whole exome sequencing (WES) to identify such biomarkers.
Methods
Tumor and germline DNA of 96 patients with 7 different subtypes of sinonasal cancer comprising 39 intestinal-type adenocarcinoma (ITAC), 22 squamous cell carcinoma (SNSCC), 15 mucosal melanoma (MMM), 10 undifferentiated carcinoma (SNUC), 7 olfactory neuroblastoma (ONB), 2 neuroendocrine carcinoma (SNEC) and 1 teratocarcinosarcoma (TCS) was obtained and analyzed by WES, selecting somatic variants. NF1 and FGFR1 gene copy number changes were studied by MLPA.
Results
All histological tumor subtypes carried distinct genetic profiles. Recurrent subtype-unique mutations included: APC, CTNNB1, PIK3CA and KRAS in ITAC; EGFR and CDKN2A in SNSCC; NRAS and NF1 in MMM, IDH2 in SNUC/SNEC/ONB, and ARID1A, SMARCB1 and SMARCA4 in SNUC/TCS. Alterations commonly observed in most subtypes were mutations in TP53, NOTCH1/2, BRCA1/2 and FANCA, and amplifications in FGFR1.
Conclusions
Our results confirm that classification of sinonasal cancer subtypes can be aided by genetic analysis to optimize patient care. Indeed the WHO Classification of Head and Neck Tumors already recognizes a number of subtypes solely based on specific mutation, protein expression or chromosomal translocation. In addition, recent DNA methylation profiling studies have shown great diagnostic potential. Our WES data also reveal molecular targets for personalized treatment strategies. Candidate therapies include inhibitors of PI3K/MTOR for ITAC, of EGFR and CDK4/6 for SNSCC, of MEK for MMM, of IDH2 for SNUC/SNEC/ONB, and of EZH2 for SNUC/TCS, while DNA repair and FGFR inhibitors may be considered for many of the sinonasal tumor subtypes.
Legal entity responsible for the study
The author.
Funding
Instituto de Salud Carlos III grant PI19/00191.
Disclosure
The author has declared no conflicts of interest.
Invited discussant
- Alessandro Franchi (Pisa, Italy)
- Alessandro Franchi (Pisa, Italy)
Q&A
- Michael J. Seckl (London, United Kingdom)
- Antonia Digklia (Lausanne, Switzerland)
- Michael J. Seckl (London, United Kingdom)
- Antonia Digklia (Lausanne, Switzerland)