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Multidisciplinary molecular tumour board: a tool to improve clinical practice and selection accrual for clinical trials in patients with cancer

BACKGROUND: The complexity of delivering precision medicine to oncology patients has led to the creation of molecular tumourboards (MTBs) for patient selection and assessment of treatment options. New technologies like the liquid biopsy are augmenting available therapeutic opportunities. This report...

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Autores principales: Rolfo, Christian, Manca, Paolo, Salgado, Roberto, Van Dam, Peter, Dendooven, Amelie, Machado Coelho, Andreia, Ferri Gandia, Jose, Rutten, Annemie, Lybaert, Willem, Vermeij, Joanna, Gevaert, Thomas, Weyn, Christine, Lefebure, Anneke, Metsu, Sofie, Van Laere, Steven, Peeters, Marc, Pauwels, Patrick
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6069914/
https://www.ncbi.nlm.nih.gov/pubmed/30094075
http://dx.doi.org/10.1136/esmoopen-2018-000398
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author Rolfo, Christian
Manca, Paolo
Salgado, Roberto
Van Dam, Peter
Dendooven, Amelie
Machado Coelho, Andreia
Ferri Gandia, Jose
Rutten, Annemie
Lybaert, Willem
Vermeij, Joanna
Gevaert, Thomas
Weyn, Christine
Lefebure, Anneke
Metsu, Sofie
Van Laere, Steven
Peeters, Marc
Pauwels, Patrick
author_facet Rolfo, Christian
Manca, Paolo
Salgado, Roberto
Van Dam, Peter
Dendooven, Amelie
Machado Coelho, Andreia
Ferri Gandia, Jose
Rutten, Annemie
Lybaert, Willem
Vermeij, Joanna
Gevaert, Thomas
Weyn, Christine
Lefebure, Anneke
Metsu, Sofie
Van Laere, Steven
Peeters, Marc
Pauwels, Patrick
author_sort Rolfo, Christian
collection PubMed
description BACKGROUND: The complexity of delivering precision medicine to oncology patients has led to the creation of molecular tumourboards (MTBs) for patient selection and assessment of treatment options. New technologies like the liquid biopsy are augmenting available therapeutic opportunities. This report aims to analyse the experience of our MTB in the implementation of personalised medicine in a cancer network. MATERIALS AND METHODS: Patients diagnosed with solid tumours progressing to standard treatments were referred to our Phase I unit. They underwent comprehensive next generation sequencing (NGS) of either tumour tissue or cell-free circulating tumour DNA (ctDNA) or both. The MTB expressed either a positive or negative opinion for the treatment of the patients with discovered druggable alterations inside a clinical trial, in an expanded access programme, with a compassionate use. Afterwards, discovered alterations were matched with OncoKB levels of evidence for the choice of alteration-specific treatments in order to compare MTB outcomes with a standardised set of recommendations. RESULTS: NGS was performed either on ctDNA or tumour tissue or in both of them in 204 patients. The MTB evaluated 173 of these cases. Overall, the MTB proposed alteration-specific targeted therapy to 72 patients (41.6%). 49 patients (28.3% of the total evaluated) were indicated to enter a clinical trial. In 29 patients with matched liquid biopsy NGS (lbNGS), tumour tissue NGS (ttNGS) and MTB evaluation, the MTB changed the treatment strategy coming from standardised recommendations based on lbNGS and ttNGS alone in 10 patients (34.5%), thanks to the evaluation of other clinical parameters. In our cohort, lbNGS was more likely, compared with ttNGS, to detect point mutations (OR 11, 95% CI 2.9 to 24.1, p<0.001) and all-type alterations (OR 13.6, 95% CI 5.5 to 43.2, p<0.001) from the same genes of matched patients. CONCLUSIONS: Our MTB allows patients with refractory cancer to be included in clinical trials and improves the precision of clinical decisions compared with a standardised set of mutation-driven recommendations.
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spelling pubmed-60699142018-08-09 Multidisciplinary molecular tumour board: a tool to improve clinical practice and selection accrual for clinical trials in patients with cancer Rolfo, Christian Manca, Paolo Salgado, Roberto Van Dam, Peter Dendooven, Amelie Machado Coelho, Andreia Ferri Gandia, Jose Rutten, Annemie Lybaert, Willem Vermeij, Joanna Gevaert, Thomas Weyn, Christine Lefebure, Anneke Metsu, Sofie Van Laere, Steven Peeters, Marc Pauwels, Patrick ESMO Open Original Research BACKGROUND: The complexity of delivering precision medicine to oncology patients has led to the creation of molecular tumourboards (MTBs) for patient selection and assessment of treatment options. New technologies like the liquid biopsy are augmenting available therapeutic opportunities. This report aims to analyse the experience of our MTB in the implementation of personalised medicine in a cancer network. MATERIALS AND METHODS: Patients diagnosed with solid tumours progressing to standard treatments were referred to our Phase I unit. They underwent comprehensive next generation sequencing (NGS) of either tumour tissue or cell-free circulating tumour DNA (ctDNA) or both. The MTB expressed either a positive or negative opinion for the treatment of the patients with discovered druggable alterations inside a clinical trial, in an expanded access programme, with a compassionate use. Afterwards, discovered alterations were matched with OncoKB levels of evidence for the choice of alteration-specific treatments in order to compare MTB outcomes with a standardised set of recommendations. RESULTS: NGS was performed either on ctDNA or tumour tissue or in both of them in 204 patients. The MTB evaluated 173 of these cases. Overall, the MTB proposed alteration-specific targeted therapy to 72 patients (41.6%). 49 patients (28.3% of the total evaluated) were indicated to enter a clinical trial. In 29 patients with matched liquid biopsy NGS (lbNGS), tumour tissue NGS (ttNGS) and MTB evaluation, the MTB changed the treatment strategy coming from standardised recommendations based on lbNGS and ttNGS alone in 10 patients (34.5%), thanks to the evaluation of other clinical parameters. In our cohort, lbNGS was more likely, compared with ttNGS, to detect point mutations (OR 11, 95% CI 2.9 to 24.1, p<0.001) and all-type alterations (OR 13.6, 95% CI 5.5 to 43.2, p<0.001) from the same genes of matched patients. CONCLUSIONS: Our MTB allows patients with refractory cancer to be included in clinical trials and improves the precision of clinical decisions compared with a standardised set of mutation-driven recommendations. BMJ Publishing Group 2018-07-23 /pmc/articles/PMC6069914/ /pubmed/30094075 http://dx.doi.org/10.1136/esmoopen-2018-000398 Text en © European Society for Medical Oncology 2018. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Original Research
Rolfo, Christian
Manca, Paolo
Salgado, Roberto
Van Dam, Peter
Dendooven, Amelie
Machado Coelho, Andreia
Ferri Gandia, Jose
Rutten, Annemie
Lybaert, Willem
Vermeij, Joanna
Gevaert, Thomas
Weyn, Christine
Lefebure, Anneke
Metsu, Sofie
Van Laere, Steven
Peeters, Marc
Pauwels, Patrick
Multidisciplinary molecular tumour board: a tool to improve clinical practice and selection accrual for clinical trials in patients with cancer
title Multidisciplinary molecular tumour board: a tool to improve clinical practice and selection accrual for clinical trials in patients with cancer
title_full Multidisciplinary molecular tumour board: a tool to improve clinical practice and selection accrual for clinical trials in patients with cancer
title_fullStr Multidisciplinary molecular tumour board: a tool to improve clinical practice and selection accrual for clinical trials in patients with cancer
title_full_unstemmed Multidisciplinary molecular tumour board: a tool to improve clinical practice and selection accrual for clinical trials in patients with cancer
title_short Multidisciplinary molecular tumour board: a tool to improve clinical practice and selection accrual for clinical trials in patients with cancer
title_sort multidisciplinary molecular tumour board: a tool to improve clinical practice and selection accrual for clinical trials in patients with cancer
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6069914/
https://www.ncbi.nlm.nih.gov/pubmed/30094075
http://dx.doi.org/10.1136/esmoopen-2018-000398
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