CARCINOMA OF UNKNOWN ORIGIN: Deep Genomic profile helps to achieve an accurate diagnosis.

Date 20 October 2018
Event ESMO 2018 Congress
Session Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Topics Translational Research
Carcinoma of Unknown Primary Site (CUP)
Presenter Amaya Fernandez Díaz
Citation Annals of Oncology (2018) 29 (suppl_8): viii649-viii669. 10.1093/annonc/mdy303
Authors A.B. Fernandez Díaz1, V. Iranzo Gonzalez-Cruz2, A.J. Cunquero Tomas3, C. Avila Andrade1, E. Jantus-Lewintre4, S. Calabuig Fariñas5, J.E. Ales6, M. Valero7, G. D'Errico8, R.A. Pazo Cid9, A. Gallego Martínez10, A. Viana11, S. Ponce Aix12, J.A. Pérez-Fidalgo13, A. Terradez14, A. Rodrigo14, L. Alvarez14, G. Beniuga15, M. Martorell16, C. Camps17
  • 1Medical Oncology Service, Dep. of Medical Oncology, Hospital General Universitario de Valencia, Valencia, Spain, 46018 - Valencia/ES
  • 2Medical Oncology Service, Dep. of Medical Oncology, Hospital General Universitario de Valencia, Valencia, Spain; Centro Investigación Biomédica en Red de Cáncer (CIBEROnc), 46018 - Valencia/ES
  • 3Medical Oncology, Hospital General Universitario Valencia, 46018 - Valencia/ES
  • 4Laboratorio De Oncología Molecular, Fundación Para La Investigación, Hospital General Universitario De Valencia-ciberonc, Valencia, Spain, Molecular Oncology Lab. Fundación Investigación Hospital General Universitario Valencia, Valencia, Spain; Centro Investigación Biomédica en Red de Cáncer (CIBEROnc), Madrid, Spain; Dep. of Biotechnology, Universitat Politècnica València, Valencia, Spain, 46014 - Valencia/ES
  • 5Medical Oncology Service, Molecular Oncology Lab. Fundación Investigación Hospital General Universitario Valencia, Valencia, Spain; Centro Investigación Biomédica en Red de Cáncer (CIBEROnc), Madrid, Spain; Dep. of Pathology, Universitat de València, Valencia, Spain, 46018 - Valencia/ES
  • 6Medical Oncology, Hospital Nuestra Señora de Sonsoles, 5004 - AVILA/ES
  • 7Medical Oncology, ONCOAVANZE, 41013 - SEVILLA/ES
  • 8Medical Oncology, Hospital Universitario Quirónsalud Madrid, 28223 - MADRID/ES
  • 9Medical Oncology, Hospital Miguel Servet, 50009 - Zaragoza/ES
  • 10Medical Oncology, Hospital Universitario La Paz, 28046 - Madrid/ES
  • 11Medical Oncology, Hospital Nuestra Señora del Prado, 45600 - TOLEDO/ES
  • 12Medical Oncology, University Hospital 12 De Octubre, 28041 - Madrid/ES
  • 13Medical Oncology, Hospital Clínico Universitario de Valencia, 46010 - Valencia/ES
  • 14Scientific Department, OncoDNA S.A., 6041 - Gosselies/BE
  • 15Pathology Department., Institute Pathology and Génétique, 6041 - Charleroi/BE
  • 16Pathology Department., Dep. of Pathology, Hospital General Universitario de Valencia, Valencia, Spain; Dep. of Pathology, Universitat de València, Valencia, Spain, 46014 - VALENCIA/ES
  • 17Medical Oncology, Dep. of Medical Oncology, Hospital General Universitario de Valencia, Valencia, Spain; Centro Investigación Biomédica en Red de Cáncer (CIBEROnc), Madrid, Spain; Dep. of Medicine, Universitat de València, Valencia, Spain, 46014 - Valencia/ES

Abstract

Background

Diagnosis and treatment of Cancer of Unknown Origin (CUP) continues to be a challenge. In the era of personalized medicine, genomic profile by Next-Generation-Sequencing (NGS) in addition to immunohistochemistry (IHC) tests may complement clinical features improving diagnosis and detecting targetable mutations. In the present study we have analysed the clinical utility of theOncoDEEP® CUP platformfor tissue of origin assessment and genotyping in a cohort of CUP patients.

Methods

We conducted this multicentric prospective exploratory study across 22 institutions (September 2017- March 2018). The cohort included 60 patients with histologically diagnosed metastatic CUP and available FFPE tumor samples. The molecular analysis was performed using the OncoDEEP® CUP platform, which includes a deep genomic tumor characterization as well as a panel of IHC tests.

Results

Patient’s median age was 60 years [24-80], 61.7% were females. At time of diagnosis,48% presented a single metastatic site whereas 52% has multimetastaticlocations. Predominant histology was adenocarcinoma (36.7%) followed by carcinoma NOS (25%), squamous cell carcinoma (13.3%) and others (25%). In 10% of the cases, the analysis could not be completed due to insufficient tumor samples. In the remaining 54 samples, a probable primary origin was assessed in 43 patients (80%). Potentially actionable mutations were found in 36 cases (61%). As expected, the most frequently mutated gene was TP53 (12/36), followed by KRAS, TPMT, ARID1A,BRAF, CDKN2A, PI3KCA, PTEN and STK11. During follow up 11 deaths have been recorded, whereas the rest of the patients remain in the study.

Conclusions

OncoDEEP® CUP may provide an opportunity for CUP patients to benefit from site-specific treatments and personalized therapies if druggable mutations are identified. Acknowledgments to the rest collaborating centers: H. U. de Ceuta, H. U. Virgen Macarena, H. Ramón y Cajal, H. U. Santa Lucía, HC Marbella International Hospital, H. Parc Taulí, H. U. La Ribera, H. Marina Baixa, H. Morales Meseger, H. U. Lucus Augusti and Instituto Valenciano de Oncología (IVO).

Clinical trial identification

Legal entity responsible for the study

Hospital General Universitario de Valencia, Valencia, Spain, Valencia.

Funding

The Spanish Institute for Foreign Trade (ICEX).

Editorial Acknowledgement

Disclosure

A. Terradez, A. Rodrigo, L. Alvarez, G. Beniuga: Employee: OncoDNA. All other authors have declared no conflicts of interest.