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Tools to Evaluate Tumour Response to Therapy: Tissue Biomarkers
Annals of Oncology 25 (Supplement 4): iv27–iv28, 2014 doi:10.1093/annonc/mdu307.3
special symposium: neuroendocrine tumours: the cutting edge and a glimpse into the future 76IN
TOOLS TO EVALUATE TUMOUR RESPONSE TO THERAPY: TISSUE BIOMARKERS
T. Meyer University College London, London, UK
abstracts
Neuroendocrine tumours are highly heterogeneous with respect to their clinical behaviour, ranging from highly aggressive small cell carcinomas to very indolent tumours with a prognosis measured in decades. Tissue biomarkers can inform clinical decision making in three ways; Firstly, they may provide prognostic information which helps to differentiate those who need treatment from those in which a wait-and-watch policy is reasonable. The best validated prognostic biomarker is grade, based on Ki67 and Mitotic Index (MI). While these are widely used, it is also recognised that tumours can be heterogeneous and a small, single site biopsy may be misleading. Furthermore
tumours can evolve and an historic biopsy may not be relevant years later. Blood based biomarkers such as chromogranin A, NSE, VEGF, IL-8 and circulating tumour cells (CTCs) are more immediate and have also been shown to be prognostic. Secondly, tissue biomarkers may predict response and help stratify patients for specific therapy. For cytotoxic chemotherapy, there is evidence that response rate correlates with Ki67 and MI although a cut-off cannot be clearly defined. Unlike other tumours, mutation rates are low in NETs and stratification for targeted therapy according to driver mutations is not established. Around 14% of Pancreatic NETs have mutations in mTOR pathway genes yet their presence has not been shown to be associated with a better response to everolimus. Epigenetic regulation of gene expression may be relevant and there is some data suggesting that low MGMT expression due to promoter hypermethylation may be associated with response to temozolomide but prospective trials are needed to confirm these observations. Finally, tissue biomarkers can provide a surrogate for long term outcome following therapy. Given the low rate of objective response and prolonged disease course, such markers are highly desirable. In blood, reduction in the numbers of CTCs, chromogranin A and NSE following therapy appears to predict a better outcome and for everolimus specifically, an increase in p-Akt T308 in post treatment biopsy has been linked with improved radiological response. As is the case in other tumours, there are no robust methods to select or predict response to VEGFR inhibitors such as sunitinib. Disclosure: T. Meyer: Advisory Board; Novartis, Keocyte Research Funding; Ipsen Lectures: Ipsen
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
special symposium: neuroendocrine tumours: the cutting edge and a glimpse into the future 76IN
TOOLS TO EVALUATE TUMOUR RESPONSE TO THERAPY: TISSUE BIOMARKERS
T. Meyer University College London, London, UK
abstracts
Neuroendocrine tumours are highly heterogeneous with respect to their clinical behaviour, ranging from highly aggressive small cell carcinomas to very indolent tumours with a prognosis measured in decades. Tissue biomarkers can inform clinical decision making in three ways; Firstly, they may provide prognostic information which helps to differentiate those who need treatment from those in which a wait-and-watch policy is reasonable. The best validated prognostic biomarker is grade, based on Ki67 and Mitotic Index (MI). While these are widely used, it is also recognised that tumours can be heterogeneous and a small, single site biopsy may be misleading. Furthermore
tumours can evolve and an historic biopsy may not be relevant years later. Blood based biomarkers such as chromogranin A, NSE, VEGF, IL-8 and circulating tumour cells (CTCs) are more immediate and have also been shown to be prognostic. Secondly, tissue biomarkers may predict response and help stratify patients for specific therapy. For cytotoxic chemotherapy, there is evidence that response rate correlates with Ki67 and MI although a cut-off cannot be clearly defined. Unlike other tumours, mutation rates are low in NETs and stratification for targeted therapy according to driver mutations is not established. Around 14% of Pancreatic NETs have mutations in mTOR pathway genes yet their presence has not been shown to be associated with a better response to everolimus. Epigenetic regulation of gene expression may be relevant and there is some data suggesting that low MGMT expression due to promoter hypermethylation may be associated with response to temozolomide but prospective trials are needed to confirm these observations. Finally, tissue biomarkers can provide a surrogate for long term outcome following therapy. Given the low rate of objective response and prolonged disease course, such markers are highly desirable. In blood, reduction in the numbers of CTCs, chromogranin A and NSE following therapy appears to predict a better outcome and for everolimus specifically, an increase in p-Akt T308 in post treatment biopsy has been linked with improved radiological response. As is the case in other tumours, there are no robust methods to select or predict response to VEGFR inhibitors such as sunitinib. Disclosure: T. Meyer: Advisory Board; Novartis, Keocyte Research Funding; Ipsen Lectures: Ipsen
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].