Oncotarget. 2018 Apr 17;9(29):20282-20293. doi: 10.18632/oncotarget.24757. eCollection 2018 Apr 17.
The clinical impact of using complex molecular profiling strategies in routine oncology practice.
Laes JF1, Aftimos P2, Barthelemy P1, Bellmunt J2,3, Berchem G4, Camps C5, Peñas RL6, Finzel A1, García-Foncillas J7, Hervonen P8, Wahid I9, Joensuu T8, Kathan L10, Kong A11, Mackay J12, Mikropoulos C13, Mokbel K14, Mouysset JL15, Odarchenko S16, Perren TJ17, Pienaar R10, Regonesi C18, Alkhayyat SS19, El Kinge AR20, Abulkhair O20, Galal KM21, Ghanem H22, El Karak F23, Garcia A24, Ghitti G1, Sadik H1.
Molecular profiling and functional assessment of signalling pathways of advanced solid tumours are becoming increasingly available. However, their clinical utility in guiding patients' treatment remains unknown. Here, we assessed whether molecular profiling helps physicians in therapeutic decision making by analysing the molecular profiles of 1057 advanced cancer patient samples after failing at least one standard of care treatment using a combination of next-generation sequencing (NGS), immunohistochemistry (IHC) and other specific tests. The resulting information was interpreted and personalized treatments for each patient were suggested. Our data showed that NGS alone provided the oncologist with useful information in 10-50% of cases (depending on cancer type), whereas the addition of IHC/other tests increased extensively the usefulness of the information provided. Using internet surveys, we investigated how therapy recommendations influenced treatment choice of the oncologist. For patients who were still alive after the provision of the molecular information (76.8%), 60.4% of their oncologists followed report recommendations. Most treatment decisions (93.4%) were made based on the combination of NGS and IHC/other tests, and an approved drug- rather than clinical trial enrolment- was the main treatment choice. Most common reasons given by physicians to explain the non-adherence to recommendations were drug availability and cost, which remain barriers to personalised precision medicine. Finally, we observed that 27% of patients treated with the suggested therapies had an overall survival > 12 months. Our study demonstrates that the combination of NGS and IHC/other tests provides the most useful information in aiding treatment decisions by oncologists in routine clinical practice.
molecular profiling; next-generation sequencing; precision medicine; solid tumour; therapeutic decision making in oncology