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.

Aim: To investigate if the genetic information provided by sequencing of both solid and liquid biopsies can shed light on tumor heterogeneity, and to understand the clinical usefulness of adding blood profiling to standard tissue analysis in cancer care. Methods:Data from 351 patients with stage IV solid tumors for whom molecular profiling of their solid and liquid biopsies was available were studied, with a focus on the discrepant molecular information found between tissue and blood samples. Results:In 86% of patients, solid and liquid biopsies provided different molecular information. Discrepant gene mutations with a functional impact on the corresponding protein were studied in detail. In 97% of cases, these additional mutations provided clinical value, mainly predicting sensitivity or resistance to targeted therapies. Specifically, 42% of the mutations found only in the liquid biopsy were directly predictive of approved therapies (80% targeted therapies), while 54% were inclusion criteria for molecularly-matched trials. Conclusion:This study suggests that the addition of blood profiling should be considered in routine clinical oncology, especially for patients with metastatic disease where integrated analysis of solid and liquid biopsies provides a more complete characterization of tumor heterogeneity and provides valuable clinical information for patient treatment.

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