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Molecular profiling of advanced non-small cell lung cancer in the era of immunotherapy approach: a multicenter Italian observational prospective study of biomarker screening in daily clinical practice
  1. Tiziana Vavala1,2,
  2. Umberto Malapelle3,
  3. Claudia Veggiani4,
  4. Vienna Ludovini5,
  5. Mauro Papotti6,
  6. Alvaro Leone7,
  7. Paolo Graziano8,
  8. Roberta Minari9,
  9. Francesca Bono10,
  10. Anna Sapino11,12,
  11. Laura Manotti13,
  12. Giancarlo Troncone3,
  13. Pasquale Pisapia3,
  14. Salvatore Girlando14,
  15. Lucio Buffoni2,
  16. Luisella Righi2,
  17. Ida Colantonio15,
  18. Oscar Bertetto16,
  19. Silvia Novello2
  1. 1SC Oncology, ASL CN1, Saluzzo, Italy
  2. 2Department of Oncology, University of Turin, Torino, Italy
  3. 3Department of Public Health, University of Naples Federico II, Napoli, Campania, Italy
  4. 4Pathology Unit, Hospital Maggiore della Carità, Novara, Piemonte, Italy
  5. 5Molecular Biology Laboratory, Medical Oncology Division, Ospedale Santa Maria della Misericordia, Perugia, Umbria, Italy
  6. 6Department of Oncology, Unversity of Torino, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Torino, Italy
  7. 7Department of Pathology, San Camillo Forlanini Hospital, Rome, Italy
  8. 8Unit of Pathology, IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Puglia, Italy
  9. 9UO Medical Oncology, University Hospital of Parma, Parma, Italy
  10. 10UO Anatomo-Pathology, San Gerardo Hospital, Monza, Italy
  11. 11Department of Surgical Pathology, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Piemonte, Italy
  12. 12Department of Medical Sciences, University of Turin, Torino, Piemonte, Italy
  13. 13Department of Oncology, UO Anatomo-Pathology, Hospital of Cremona, Cremona, Lombardia, Italy
  14. 14Anatomo-pathology Unit, Santa Chiara Hospital, Trento, Italy
  15. 15Department of Oncologia, Azienda Ospedaliera S Croce e Carle Cuneo, Cuneo, Piemonte, Italy
  16. 16Rete Oncologica Piemonte e Valle d'Aosta Department, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Torino, Piemonte, Italy
  1. Correspondence to Dr Tiziana Vavala, SC of Oncology, ASL CN1, Saluzzo (Cuneo), Italy; tvavala{at}


Aims Heterogeneous implementation of molecular tests in current diagnostic algorithm at a European and international level is emerging as a major issue for efficient lung cancer molecular profiling.

Methods From May 2017 until October 2017, N=1612 patients referring to 13 Italian institutions were selected, at advanced stage non-small cell lung cancer (NSCLC), and prospectively evaluated. Principal endpoints were: the percentage of diagnoses performed on cytological and histological material, the proportion of requests for epidermal growth factor receptor (EGFR) mutational status, and resistance mutations detected on tissue and/or liquid biopsy samples after first-generation or second-generation tyrosine kinase inhibitors, the proportion of requests for anaplastic lymphoma kinase (ALK) gene rearrangements, ROS proto-oncogene 1 (ROS1) and Kirsten Rat Sarcoma (KRAS) determinations, the proportion of requests for programmed death-ligand1 (PD-L1) evaluation and, finally, the different assays used for the detection of EGFR mutations, ALK and ROS1 gene rearrangements and PD-L1 expression.

Results Of 1325 patients finally included, only 50.8% requests were related to driver mutations with target agents already available in first-line at that preplanned time, while 49.2% were associated with PD-L1, ROS1, KRAS and others. Multiplex genomic assays (such as next-generation sequencing) were considered by all participating centres.

Conclusions To the best of our knowledge, this is the first study in a ‘real-life daily practice’ involving both pathologists and oncologists evaluating routinely workflow and trends towards improvements in molecular requests. Collected data aim to describe the applied algorithms and evolution of molecular screening for stage IV NSCLC in clinical practice.

  • EGFR
  • molecular biology
  • lung neoplasms
  • pathology
  • molecular
  • immunohistochemistry

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  • Handling editor Runjan Chetty.

  • Twitter @PasqualePisapia

  • Contributors All authors concepted the design of the study, the acquisition of data, the final analysis and interpretation of data. All authors reviewed the manuscript and accepted to submit the paper in its present form.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests TV, PP, CV, VL, MP, AL, PG, RM, FB, AS, LM, SG, LB, IC, LR and OB: no competing interests. UM reports personal fees from Boehringer Ingelheim, AstraZeneca, Roche, MSD, Amgen, Merck and BMS for participation in speaker bureau and for acting in an advisory role, outside the submitted work. GT reports personal fees from Roche for participation in speaker bureau and personal fees from MSD and Pfizer for acting in an advisory role, outside the submitted work. SN reports personal fees from AstraZeneca, Boehringer Ingelheim, BMS, MSD, Eli Lilly, Takeda, Pfizer and Roche for acting in an advisory role and/or for participation in speaker bureau, outside the submitted work.

  • Patient consent for publication Not required.

  • Ethics approval The study protocol was approved by the Institutional Review Board of the Coordinating Center: Thoracic Oncology Unit, Department of Oncology, San Luigi Gonzaga University Hospital (Orbassano, Turin, Italy).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article. However, detailed datasets for this manuscript are not publicly available because of sensitive information of centres and patients. Requests to access the datasets is possible upon reasonable request.

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