Jason Lester - Academia.edu (original) (raw)

Papers by Jason Lester

Research paper thumbnail of POSTER PRESENTATION Open Access

Developing an intervention to support lung cancer patients and their clinicians when considering ... more Developing an intervention to support lung cancer patients and their clinicians when considering systemic anti-cancer therapy: pact study

Research paper thumbnail of Community Page Tracking Genomic Cancer Evolution for Precision Medicine: The Lung TRACERx Study

Research paper thumbnail of Geospatial immune variability illuminates differential evolution of lung adenocarcinoma

Research paper thumbnail of Using DNA sequencing data to quantify T cell fraction and therapy response

Nature, 2021

The immune microenvironment influences tumour evolution and can be both prognostic and predict re... more The immune microenvironment influences tumour evolution and can be both prognostic and predict response to immunotherapy 1,2. However, measuring tumour infiltrating lymphocytes (TILs) is restricted by lack of appropriate data. Whole exome sequencing (WES) of DNA is frequently performed to calculate tumour mutational burden and identify actionable mutations. Here we develop a method for T cell fraction estimation from WES samples, utilising a signal from T cell receptor excision circle (TRECs) loss during VDJ recombination of the T cell receptor alpha (TCRA) gene. This score significantly correlates with orthogonal TIL estimates and is agnostic to sample type. Blood TCRA T cell fraction is higher in females and correlates with both tumour immune infiltrate and presence of bacterial sequencing reads. Tumour TCRA T cell fraction is prognostic in lung adenocarcinoma and using a meta-analysis of immunotherapy-treated tumours, we show that this score predicts immunotherapy response, providing value beyond tumour mutational burden. Applying this score to a multi-sample pancancer cohort revealed high diversity in immune infiltration within tumours. Subclonal loss of 12q24.31-32, encompassing SPPL3, was associated with reduced TCRA T cell fraction. Our method, T cell ExTRECT (T cell Exome TREC Tool), quantifies the T cell infiltrate of WES samples. Here we propose a method for the estimation of the T cell fraction present in a WES sample. This method utilises a somatic copy number-based signal from VDJ recombination and the loss of TRECs. We explore the underlying features which predict T cell infiltrate in tumours and blood and evaluate determinants of immune heterogeneity within tumours. Finally, we demonstrate that our estimated T cell fraction can be used as a predictor of clinical response to CPI therapy. Results Inferring T cell fraction from WES data T cell diversity, which is required for immune system recognition of foreign antigens, is a product of VDJ recombination, where segments within the T cell receptor genes recombine. The alpha chain of the T cell receptor is encoded by the TCRA gene (also known as TRA) and the result of VDJ recombination is the excision of unselected gene segments from TCRA as TRECs, with the T cell undergoing a deletion event within TCRA. Tools to infer cancer somatic copy number alteration (SCNA) 6-9 rely on the read depth ratio (RDR), reflecting the log of the ratio of reads between the tumour sample and its matched control (e.g. buffy coat in a centrifuged blood sample). Deviation in the RDR from zero is assumed to reflect a tumour SCNA. However, within TCRA this assumption does not hold; a deviance in the RDR may reflect T cell specific deletion events and SCNA tools may thus erroneously infer tumour SCNA. Indeed, in the TRACERx100 cohort multiple SCNA within TCRA were inferred in 165/327 tumour regions (Extended Data Fig. 1a). The RDR deviated the most within segments frequently included within TRECs (Extended Data Fig. 1b-c). This suggests that most detected SCNAs within TCRA reflect a signal of relative T cell content rather than cancer SCNAs.

Research paper thumbnail of Publisher Correction: Spatial heterogeneity of the T cell receptor repertoire reflects the mutational landscape in lung cancer

Nature Medicine, 2020

In the version of this article initially published, the list of members and affiliations for the ... more In the version of this article initially published, the list of members and affiliations for the TRACERx Consortium was provided as a Supplementary Note. The list should have been provided in the online version. The error has been corrected in the HTML and PDF versions of the article.

Research paper thumbnail of Olaparib maintenance versus placebo monotherapy in patients with advanced non-small cell lung cancer (PIN): A multicentre, randomised, controlled, phase 2 trial

Research paper thumbnail of Active symptom control with or without oral vinorelbine in patients with relapsed malignant pleural mesothelioma (VIM): A randomised, phase 2 trial

Research paper thumbnail of Additional file 2: of CONFIRM: a double-blind, placebo-controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial

Informed Consent Form. (PDF 133 kb)

Research paper thumbnail of Additional file 1: of CONFIRM: a double-blind, placebo-controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial

SPIRIT Checklist. (DOC 121 kb)

Research paper thumbnail of Six versus three-weekly pembrolizumab: as well-tolerated?

Research paper thumbnail of Association of sarcopenia and observed physical performance with attainment of multidisciplinary team planned treatment in non-small cell lung cancer: an observational study protocol

BackgroundNon-small cell lung cancer (NSCLC) frequently presents in advanced stages. A significan... more BackgroundNon-small cell lung cancer (NSCLC) frequently presents in advanced stages. A significant proportion of those with reportedly good ECOG performance status (PS) fail to receive planned multidisciplinary team (MDT) treatment, often for functional reasons, but an objective decline in physical performance is not well described. Sarcopenia, or loss of muscle mass, is an integral part of cancer cachexia. However, changes in both muscle mass and physical performance may predate clinically overt cachexia, and may be present even with normal body mass index. Physical fitness for treatment is currently subjectively assessed by means of the PS score, which may be inadequate in predicting tolerance to treatment. This study aims to evaluate whether measuring physical performance and muscle mass at baseline in NSCLC patients, in addition to PS score, is able to predict commencement and successful completion of MDT-planned treatment.Methods/designThis is a prospective, single-centre explo...

Research paper thumbnail of Phylogenetic ctDNA analysis depicts early stage lung cancer evolution

The early detection of relapse following primary surgery for non-small-cell lung cancer and the c... more The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung c...

Research paper thumbnail of Retrospective Analysis of Real-World Treatment Patterns and Clinical Outcomes in Patients With Advanced Non-Small Cell Lung Cancer Starting First-Line Systemic Therapy in the United Kingdom

Background: The treatment landscape for advanced non-small cell lung cancer (aNSCLC) has evolved ... more Background: The treatment landscape for advanced non-small cell lung cancer (aNSCLC) has evolved rapidly since immuno-oncology (IO) therapies were introduced. This study used recent data to assess real-world treatment patterns and clinical outcomes in aNSCLC in the United Kingdom. Methods: Electronic prescribing records of treatment-naive patients starting first-line (1L) treatment for aNSCLC between June 2016 and March 2018 (follow-up until December 2018) in the United Kingdom were assessed retrospectively. Patient characteristics and treatment patterns were analyzed descriptively. Outcomes assessed included overall survival (OS), time to treatment discontinuation, time to next treatment, and real-world tumor response.Results: In all, 1003 patients were evaluated (median age, 68 years [range, 28-93 years]; 53.9% male). Use of 1L IO monotherapy (0%-25.9%) and targeted therapy (11.8%-15.9%) increased during the study period, but chemotherapy remained the most common 1L treatment at a...

Research paper thumbnail of Chemotherapy decision-making in advanced lung cancer: a prospective qualitative study

BMJ Supportive & Palliative Care

ObjectiveTo study how treatment decisions are made alongside the lung cancer clinical pathway.Met... more ObjectiveTo study how treatment decisions are made alongside the lung cancer clinical pathway.MethodsA prospective, multicentre, multimethods, five-stage, qualitative study. Mediated discourse, thematic, framework and narrative analysis were used to analyse the transcripts.Results51 health professionals, 15 patients with advanced lung cancer, 15 family members and 18 expert stakeholders were recruited from three UK NHS trusts. Multidisciplinary team (MDT) members constructed treatment recommendations around patient performance status, pathology, clinical information and imaging. Information around patients’ social context, needs and preferences were limited. The provisional nature of MDTs treatment recommendations was not always linked to future discussions with the patient along the pathway, that is, patients’ interpretation of their prognosis, treatment discussions occurring prior to seeing the oncologist. This together with the rapid disease trajectory placed additional stress on...

Research paper thumbnail of Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial

Research paper thumbnail of Retrospective Analysis of Real-World Treatment Patterns and Clinical Outcomes in Patients With Advanced Non-Small Cell Lung Cancer Starting First-Line Systemic Therapy in the United Kingdom

Background: The treatment landscape for advanced non-small cell lung cancer (aNSCLC) has evolved ... more Background: The treatment landscape for advanced non-small cell lung cancer (aNSCLC) has evolved rapidly since immuno-oncology (IO) therapies were introduced. This study used recent data to assess real-world treatment patterns and clinical outcomes in aNSCLC in the United Kingdom. Methods: Electronic prescribing records of treatment-naive patients starting first-line (1L) treatment for aNSCLC between June 2016 and March 2018 (follow-up until December 2018) in the United Kingdom were assessed retrospectively. Patient characteristics and treatment patterns were analyzed descriptively. Outcomes assessed included overall survival (OS), time to treatment discontinuation, time to next treatment, and real-world tumor response.Results: In all, 1003 patients were evaluated (median age, 68 years [range, 28-93 years]; 53.9% male). Use of 1L IO monotherapy (0%-25.9%) and targeted therapy (11.8%-15.9%) increased during the study period, but chemotherapy remained the most common 1L treatment at a...

Research paper thumbnail of 33 Development of an intervention to support lung cancer patients and their clinicians when considering systematic anti-cancer therapy: the pact study, a prospective multi-centre multi-methods five-stage qualitative study

BMJ Supportive & Palliative Care

BackgroundThe NHS aspires to place patients’ needs wishes and preferences at the heart of a clini... more BackgroundThe NHS aspires to place patients’ needs wishes and preferences at the heart of a clinical decision-making; however it is not clear how this can be routinely implemented. One example is the patient clinical care pathway for patients diagnosed with advanced non-small cell lung cancer (NSCLC) where there may be misunderstanding of the extent of disease prognosis and aims of treatment.AimTo understand how treatment decisions are made for NSCLC patients and map the decisions pathway.MethodologyPACT is a prospective multi-centre multi-methods five-stage qualitative study. Non-participant observation of MDT meetings (n=12) determined patients’ allocation to treatment. Non-participant observation of patient-clinician consultations (n=14) explored communication of treatment options and decision-making. Interviews with patients/companions and clinicians (n=27) explored perception of treatment options and involvement in decision-making. Mediated discourse thematic framework and narr...

Research paper thumbnail of A randomised phase II trial of carboplatin and gemcitabine +/- vandetanib in first line treatment of advanced urothelial cell cancer patients not suitable to receive cisplatin

Research paper thumbnail of Treatment and treatment outcomes of advanced NSCLC patients in routine clinical care: Results of the retrospective LUCEOR study

Journal of Clinical Oncology

6058 Background: Although NSCLC is the most common type of lung cancer, published data on both tr... more 6058 Background: Although NSCLC is the most common type of lung cancer, published data on both treatment patterns and outcomes in routine clinical care are scarce. Collecting this data systematically across countries will help to understand, compare and improve patient care. Methods: 1,490 patient charts were reviewed retrospectively from 40 sites in Australia, Belgium, Canada, France, Germany, Italy, Sweden, Turkey, the Netherlands and the UK, 1436 of those evaluable. Patients deceased before April 2010 were eligible if ≥18 years, diagnosed with advanced stage IIIb/IV NSCLC and had received active 1st line anti-cancer treatment. Demographic data, disease and, treatment history and resource use were collected from start of first line treatment until death. Results: Mean age at NSCLC diagnosis was 64 years [SD=10.6], 67% of patients had stage IV disease at diagnosis and 66% were male. Confirmed tumor histology was adenocarcinoma in 50% of patients, squamous and large cell carcinoma i...

Research paper thumbnail of Deciphering antitumour response and resistance with intratumour heterogeneity (DARWIN II)

Journal of Clinical Oncology

TPS9099 Background: The importance of intratumour heterogeneity (ITH) is increasingly recognised ... more TPS9099 Background: The importance of intratumour heterogeneity (ITH) is increasingly recognised as a driver of cancer progression and survival outcome. However understanding how tumour clonal heterogeneity impacts upon therapeutic outcome is still an area of unmet clinical and scientific need. The TRACERx trial (NCT01888601), a prospective study of patients with radically resected primary non-small cell lung cancer (NSCLC), aims to define the evolutionary trajectories of lung cancer in both space and time through genetic analysis of multi-region and longitudinal tumour sampling. DARWIN II is an investigator initiated study for patients who are enrolled within the TRACERx trial, or who have multi-region sequencing of their primary disease, but subsequently relapse with metastatic disease. This study will examine the role of intra-tumour heterogeneity and predicted neo-antigens on the anti-tumour activity of anti-PDL1 immunotherapy. Methods: This multicentre non-randomised phase II m...

Research paper thumbnail of POSTER PRESENTATION Open Access

Developing an intervention to support lung cancer patients and their clinicians when considering ... more Developing an intervention to support lung cancer patients and their clinicians when considering systemic anti-cancer therapy: pact study

Research paper thumbnail of Community Page Tracking Genomic Cancer Evolution for Precision Medicine: The Lung TRACERx Study

Research paper thumbnail of Geospatial immune variability illuminates differential evolution of lung adenocarcinoma

Research paper thumbnail of Using DNA sequencing data to quantify T cell fraction and therapy response

Nature, 2021

The immune microenvironment influences tumour evolution and can be both prognostic and predict re... more The immune microenvironment influences tumour evolution and can be both prognostic and predict response to immunotherapy 1,2. However, measuring tumour infiltrating lymphocytes (TILs) is restricted by lack of appropriate data. Whole exome sequencing (WES) of DNA is frequently performed to calculate tumour mutational burden and identify actionable mutations. Here we develop a method for T cell fraction estimation from WES samples, utilising a signal from T cell receptor excision circle (TRECs) loss during VDJ recombination of the T cell receptor alpha (TCRA) gene. This score significantly correlates with orthogonal TIL estimates and is agnostic to sample type. Blood TCRA T cell fraction is higher in females and correlates with both tumour immune infiltrate and presence of bacterial sequencing reads. Tumour TCRA T cell fraction is prognostic in lung adenocarcinoma and using a meta-analysis of immunotherapy-treated tumours, we show that this score predicts immunotherapy response, providing value beyond tumour mutational burden. Applying this score to a multi-sample pancancer cohort revealed high diversity in immune infiltration within tumours. Subclonal loss of 12q24.31-32, encompassing SPPL3, was associated with reduced TCRA T cell fraction. Our method, T cell ExTRECT (T cell Exome TREC Tool), quantifies the T cell infiltrate of WES samples. Here we propose a method for the estimation of the T cell fraction present in a WES sample. This method utilises a somatic copy number-based signal from VDJ recombination and the loss of TRECs. We explore the underlying features which predict T cell infiltrate in tumours and blood and evaluate determinants of immune heterogeneity within tumours. Finally, we demonstrate that our estimated T cell fraction can be used as a predictor of clinical response to CPI therapy. Results Inferring T cell fraction from WES data T cell diversity, which is required for immune system recognition of foreign antigens, is a product of VDJ recombination, where segments within the T cell receptor genes recombine. The alpha chain of the T cell receptor is encoded by the TCRA gene (also known as TRA) and the result of VDJ recombination is the excision of unselected gene segments from TCRA as TRECs, with the T cell undergoing a deletion event within TCRA. Tools to infer cancer somatic copy number alteration (SCNA) 6-9 rely on the read depth ratio (RDR), reflecting the log of the ratio of reads between the tumour sample and its matched control (e.g. buffy coat in a centrifuged blood sample). Deviation in the RDR from zero is assumed to reflect a tumour SCNA. However, within TCRA this assumption does not hold; a deviance in the RDR may reflect T cell specific deletion events and SCNA tools may thus erroneously infer tumour SCNA. Indeed, in the TRACERx100 cohort multiple SCNA within TCRA were inferred in 165/327 tumour regions (Extended Data Fig. 1a). The RDR deviated the most within segments frequently included within TRECs (Extended Data Fig. 1b-c). This suggests that most detected SCNAs within TCRA reflect a signal of relative T cell content rather than cancer SCNAs.

Research paper thumbnail of Publisher Correction: Spatial heterogeneity of the T cell receptor repertoire reflects the mutational landscape in lung cancer

Nature Medicine, 2020

In the version of this article initially published, the list of members and affiliations for the ... more In the version of this article initially published, the list of members and affiliations for the TRACERx Consortium was provided as a Supplementary Note. The list should have been provided in the online version. The error has been corrected in the HTML and PDF versions of the article.

Research paper thumbnail of Olaparib maintenance versus placebo monotherapy in patients with advanced non-small cell lung cancer (PIN): A multicentre, randomised, controlled, phase 2 trial

Research paper thumbnail of Active symptom control with or without oral vinorelbine in patients with relapsed malignant pleural mesothelioma (VIM): A randomised, phase 2 trial

Research paper thumbnail of Additional file 2: of CONFIRM: a double-blind, placebo-controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial

Informed Consent Form. (PDF 133 kb)

Research paper thumbnail of Additional file 1: of CONFIRM: a double-blind, placebo-controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial

SPIRIT Checklist. (DOC 121 kb)

Research paper thumbnail of Six versus three-weekly pembrolizumab: as well-tolerated?

Research paper thumbnail of Association of sarcopenia and observed physical performance with attainment of multidisciplinary team planned treatment in non-small cell lung cancer: an observational study protocol

BackgroundNon-small cell lung cancer (NSCLC) frequently presents in advanced stages. A significan... more BackgroundNon-small cell lung cancer (NSCLC) frequently presents in advanced stages. A significant proportion of those with reportedly good ECOG performance status (PS) fail to receive planned multidisciplinary team (MDT) treatment, often for functional reasons, but an objective decline in physical performance is not well described. Sarcopenia, or loss of muscle mass, is an integral part of cancer cachexia. However, changes in both muscle mass and physical performance may predate clinically overt cachexia, and may be present even with normal body mass index. Physical fitness for treatment is currently subjectively assessed by means of the PS score, which may be inadequate in predicting tolerance to treatment. This study aims to evaluate whether measuring physical performance and muscle mass at baseline in NSCLC patients, in addition to PS score, is able to predict commencement and successful completion of MDT-planned treatment.Methods/designThis is a prospective, single-centre explo...

Research paper thumbnail of Phylogenetic ctDNA analysis depicts early stage lung cancer evolution

The early detection of relapse following primary surgery for non-small-cell lung cancer and the c... more The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung c...

Research paper thumbnail of Retrospective Analysis of Real-World Treatment Patterns and Clinical Outcomes in Patients With Advanced Non-Small Cell Lung Cancer Starting First-Line Systemic Therapy in the United Kingdom

Background: The treatment landscape for advanced non-small cell lung cancer (aNSCLC) has evolved ... more Background: The treatment landscape for advanced non-small cell lung cancer (aNSCLC) has evolved rapidly since immuno-oncology (IO) therapies were introduced. This study used recent data to assess real-world treatment patterns and clinical outcomes in aNSCLC in the United Kingdom. Methods: Electronic prescribing records of treatment-naive patients starting first-line (1L) treatment for aNSCLC between June 2016 and March 2018 (follow-up until December 2018) in the United Kingdom were assessed retrospectively. Patient characteristics and treatment patterns were analyzed descriptively. Outcomes assessed included overall survival (OS), time to treatment discontinuation, time to next treatment, and real-world tumor response.Results: In all, 1003 patients were evaluated (median age, 68 years [range, 28-93 years]; 53.9% male). Use of 1L IO monotherapy (0%-25.9%) and targeted therapy (11.8%-15.9%) increased during the study period, but chemotherapy remained the most common 1L treatment at a...

Research paper thumbnail of Chemotherapy decision-making in advanced lung cancer: a prospective qualitative study

BMJ Supportive & Palliative Care

ObjectiveTo study how treatment decisions are made alongside the lung cancer clinical pathway.Met... more ObjectiveTo study how treatment decisions are made alongside the lung cancer clinical pathway.MethodsA prospective, multicentre, multimethods, five-stage, qualitative study. Mediated discourse, thematic, framework and narrative analysis were used to analyse the transcripts.Results51 health professionals, 15 patients with advanced lung cancer, 15 family members and 18 expert stakeholders were recruited from three UK NHS trusts. Multidisciplinary team (MDT) members constructed treatment recommendations around patient performance status, pathology, clinical information and imaging. Information around patients’ social context, needs and preferences were limited. The provisional nature of MDTs treatment recommendations was not always linked to future discussions with the patient along the pathway, that is, patients’ interpretation of their prognosis, treatment discussions occurring prior to seeing the oncologist. This together with the rapid disease trajectory placed additional stress on...

Research paper thumbnail of Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial

Research paper thumbnail of Retrospective Analysis of Real-World Treatment Patterns and Clinical Outcomes in Patients With Advanced Non-Small Cell Lung Cancer Starting First-Line Systemic Therapy in the United Kingdom

Background: The treatment landscape for advanced non-small cell lung cancer (aNSCLC) has evolved ... more Background: The treatment landscape for advanced non-small cell lung cancer (aNSCLC) has evolved rapidly since immuno-oncology (IO) therapies were introduced. This study used recent data to assess real-world treatment patterns and clinical outcomes in aNSCLC in the United Kingdom. Methods: Electronic prescribing records of treatment-naive patients starting first-line (1L) treatment for aNSCLC between June 2016 and March 2018 (follow-up until December 2018) in the United Kingdom were assessed retrospectively. Patient characteristics and treatment patterns were analyzed descriptively. Outcomes assessed included overall survival (OS), time to treatment discontinuation, time to next treatment, and real-world tumor response.Results: In all, 1003 patients were evaluated (median age, 68 years [range, 28-93 years]; 53.9% male). Use of 1L IO monotherapy (0%-25.9%) and targeted therapy (11.8%-15.9%) increased during the study period, but chemotherapy remained the most common 1L treatment at a...

Research paper thumbnail of 33 Development of an intervention to support lung cancer patients and their clinicians when considering systematic anti-cancer therapy: the pact study, a prospective multi-centre multi-methods five-stage qualitative study

BMJ Supportive & Palliative Care

BackgroundThe NHS aspires to place patients’ needs wishes and preferences at the heart of a clini... more BackgroundThe NHS aspires to place patients’ needs wishes and preferences at the heart of a clinical decision-making; however it is not clear how this can be routinely implemented. One example is the patient clinical care pathway for patients diagnosed with advanced non-small cell lung cancer (NSCLC) where there may be misunderstanding of the extent of disease prognosis and aims of treatment.AimTo understand how treatment decisions are made for NSCLC patients and map the decisions pathway.MethodologyPACT is a prospective multi-centre multi-methods five-stage qualitative study. Non-participant observation of MDT meetings (n=12) determined patients’ allocation to treatment. Non-participant observation of patient-clinician consultations (n=14) explored communication of treatment options and decision-making. Interviews with patients/companions and clinicians (n=27) explored perception of treatment options and involvement in decision-making. Mediated discourse thematic framework and narr...

Research paper thumbnail of A randomised phase II trial of carboplatin and gemcitabine +/- vandetanib in first line treatment of advanced urothelial cell cancer patients not suitable to receive cisplatin

Research paper thumbnail of Treatment and treatment outcomes of advanced NSCLC patients in routine clinical care: Results of the retrospective LUCEOR study

Journal of Clinical Oncology

6058 Background: Although NSCLC is the most common type of lung cancer, published data on both tr... more 6058 Background: Although NSCLC is the most common type of lung cancer, published data on both treatment patterns and outcomes in routine clinical care are scarce. Collecting this data systematically across countries will help to understand, compare and improve patient care. Methods: 1,490 patient charts were reviewed retrospectively from 40 sites in Australia, Belgium, Canada, France, Germany, Italy, Sweden, Turkey, the Netherlands and the UK, 1436 of those evaluable. Patients deceased before April 2010 were eligible if ≥18 years, diagnosed with advanced stage IIIb/IV NSCLC and had received active 1st line anti-cancer treatment. Demographic data, disease and, treatment history and resource use were collected from start of first line treatment until death. Results: Mean age at NSCLC diagnosis was 64 years [SD=10.6], 67% of patients had stage IV disease at diagnosis and 66% were male. Confirmed tumor histology was adenocarcinoma in 50% of patients, squamous and large cell carcinoma i...

Research paper thumbnail of Deciphering antitumour response and resistance with intratumour heterogeneity (DARWIN II)

Journal of Clinical Oncology

TPS9099 Background: The importance of intratumour heterogeneity (ITH) is increasingly recognised ... more TPS9099 Background: The importance of intratumour heterogeneity (ITH) is increasingly recognised as a driver of cancer progression and survival outcome. However understanding how tumour clonal heterogeneity impacts upon therapeutic outcome is still an area of unmet clinical and scientific need. The TRACERx trial (NCT01888601), a prospective study of patients with radically resected primary non-small cell lung cancer (NSCLC), aims to define the evolutionary trajectories of lung cancer in both space and time through genetic analysis of multi-region and longitudinal tumour sampling. DARWIN II is an investigator initiated study for patients who are enrolled within the TRACERx trial, or who have multi-region sequencing of their primary disease, but subsequently relapse with metastatic disease. This study will examine the role of intra-tumour heterogeneity and predicted neo-antigens on the anti-tumour activity of anti-PDL1 immunotherapy. Methods: This multicentre non-randomised phase II m...