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. 2018 Apr 17;9(29):20282-20293.
doi: 10.18632/oncotarget.24757.

The clinical impact of using complex molecular profiling strategies in routine oncology practice

Jean-François Laes  1 , Philippe Aftimos  2 , Philippe Barthelemy  1 , Joaquim Bellmunt  2   3 , Guy Berchem  4 , Carlos Camps  5 , Ramón de Las Peñas  6 , Ana Finzel  1 , Jesús García-Foncillas  7 , Petteri Hervonen  8 , Ibrahim Wahid  9 , Timo Joensuu  8 , Louis Kathan  10 , Anthony Kong  11 , James Mackay  12 , Christos Mikropoulos  13 , Kefah Mokbel  14 , Jean-Loup Mouysset  15 , Sergey Odarchenko  16 , Timothy J Perren  17 , Rika Pienaar  10 , Carlos Regonesi  18 , Shadi Salem Alkhayyat  19 , Abdul Rahman El Kinge  20 , Omalkhair Abulkhair  20 , Khaled Morsi Galal  21 , Hady Ghanem  22 , Fadi El Karak  23 , Angel Garcia  24 , Gregori Ghitti  1 , Helen Sadik  1
Affiliations

The clinical impact of using complex molecular profiling strategies in routine oncology practice

Jean-François Laes et al. Oncotarget. .

Abstract

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.

Keywords: molecular profiling; next-generation sequencing; precision medicine; solid tumour; therapeutic decision making in oncology.

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Conflict of interest statement

CONFLICTS OF INTEREST HS, AF, GG and J-FL are employees of OncoDNA. GG and J-FL report ownership of OncoDNA shares etc.

Figures

Figure 1
Figure 1. Variants identified by NGS
All the variants were stratified by potential functional impact and by cancer type.
Figure 2
Figure 2. Categorisation of samples analysed
(A) Number of samples rejected and processed; (B) Patients with treatment options (approved for the cancer type analysed, approved for other cancer types or under development) and without, according to test; (C) The potential or lack of potential or the unknown potential clinical benefit of samples, according to test and cancer type. PCB, potential clinical benefit.
Figure 3
Figure 3. Results of oncologist survey
(A) Survival status of patients 3 months after provision of molecular results; (B) Treatment choices according and against recommendations; (C) Treatment modification stratified based on the test type; (D) Treatment choices according to treatment approval status.
Figure 4
Figure 4. Overall survival of patients
For the cases where our recommendations were followed (n = 114), the overall survival was analysed.
See this image and copyright information in PMC

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