90P - Clinical phenotyping of lung cancer-associated cachexia in relation to tumour volume in TRACERx

Background

Cancer-associated cachexia (CAC) is a debilitating syndrome of fat and/or muscle loss that affects up to 80% of patients with cancer, leading to progressive functional decline, reduced treatment response and survival. Despite its morbidity, there are no globally approved therapies or standardised diagnostic criteria. The dynamic changes in body composition (BC) - subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and skeletal muscle (SKM) from early to late stage disease in patients with non-small cell lung cancer (NSCLC) is poorly understood. Here, we analyse longitudinal BC changes in patients with NSCLC in the context of tumour burden.

Methods

TRACERx is a national prospective study that follows over 800 patients with NSCLC from diagnosis to death or end of follow up. Patients are recruited with early stage, operable disease and undergo surgical resection, followed by standard of care treatment. Computed tomography (CT) imaging is performed at diagnosis, post-surgery, relapse and post-relapse. Here, we analysed BC of two cohorts: patients who relapsed and patients in remission. DAFS (Data Analysis Facilitation Suite), a deep learning pipeline is used to derive BC measurements from CT scans. Tumour volume in matched CT images were evaluated via segmentation and contouring of visualised lesions to quantify metastatic burden volumetrically.

Results

As cachexia is not well defined, two approaches were utilised to identify patients who develop CAC. (1) The threshold loss approach uses the 5th percentile of BC changes in the non-relapse cohort as the cachectic loss threshold to identify patients who develop CAC. Patients who were CAC based on this approach have worse overall survival compared to non-CAC patients. (2) The trajectory approach uses latent class mixed models to identify distinct trajectories of BC changes. In some patients, BC changes were found to track with increasing or decreasing tumour volumes and were impacted by treatment.

Conclusions

Assessing longitudinal BC may help identify patients at risk of developing CAC during treatment and disease progression and guide early intervention. Correlating this to metastatic disease burden may reveal shared biological mechanisms driving CAC and the metastatic process.

Editorial acknowledgement

Clinical trial identification

NCT01888601.

Legal entity responsible for the study

Cancer Research UK.

Funding

Cancer Research UK.

Disclosure

C. Swanton: Financial Interests, Personal, Invited Speaker, Activity took place in 2016: Pfizer, Celgene; Financial Interests, Personal, Invited Speaker, October 26th 2020: Novartis; Financial Interests, Personal, Invited Speaker: Roche/Ventana, BMS, AstraZeneca, MSD, Illumina, GSK; Financial Interests, Personal, Advisory Board, Ad Board - November 12th, 2020: Amgen; Financial Interests, Personal, Advisory Board, Current - since 2018: Genentech; Financial Interests, Personal, Advisory Board: Sarah Canon Research Institute; Financial Interests, Personal, Advisory Board, Joined October 2020. Also have stock options: Bicycle Therapeutics; Financial Interests, Personal, Other, Consultancy: Medicxi; Financial Interests, Personal, Advisory Board, Member of the Science Advisory Board. Also had stock options until June 2021: GRAIL; Financial Interests, Personal, Other, Consultancy agreement: Roche Innovation Centre Shanghai; Financial Interests, Personal, Advisory Board, 29 November - 1 December 2022: Novartis; Financial Interests, Personal, Invited Speaker, Oncology Collective - 2nd Nov - 4 Nov 2022 - Atlanta, USA: Roche; Financial Interests, Personal, Advisory Board, ctDNA advisory Board - 24th March 2023: AstraZeneca; Financial Interests, Personal, Invited Speaker, Pfizer Oncology 'Leading the revolution for the future: Pfizer; Financial Interests, Personal, Advisory Board, Scientific Advisory Board and Stock options from September 2023: Relay Therapeutics; Financial Interests, Personal, Advisory Board, Member of the Scientific Advisory Board: SAGA Diagnostics; Financial Interests, Personal, Full or part-time Employment, Chief Clinician since October 2017: Cancer Research UK; Financial Interests, Personal, Ownership Interest, Co-Founder of Achilles Therapeutics. Also, have stock options in this company: Achilles Therapeutics; Financial Interests, Personal, Stocks/Shares, Stocks owned until June 2021: GRAIL, Apogen Biotechnologies; Financial Interests, Personal, Stocks/Shares: Epic Biosciences, Bicycle Therapeutics; Financial Interests, Personal, Stocks/Shares, Stock options: Relay Therapeutics; Financial Interests, Institutional, Research Grant, Funded RUBICON grant - October 2018 - April 2021: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant, Collaboration in minimal residual disease sequencing technologies: Archer Dx Inc; Financial Interests, Institutional, Research Grant: Pfizer, Boehringer Ingelheim; Financial Interests, Institutional, Invited Speaker, Chief Investigator for the MeRmaiD 1and 2 clinical trials and chair of the steering committee: AstraZeneca; Financial Interests, Institutional, Research Grant, Research grant from Oct 2019 - July 2023 - Genetics of CIN and SCNAs for Targeted Discovery (SCEPTRE): Ono Pharmaceutical; Financial Interests, Institutional, Research Grant, Research Grants from 2015: Roche; Financial Interests, Personal, Other, Co-chief investigator: NHS-Galleri Clinical Trial; Financial Interests, Institutional, Research Grant, from October 2022: Personalis; Non-Financial Interests, Personal, Principal Investigator, Chief Investigator for MeRmaiD 1 and 2 clinical trials: AstraZeneca; Non-Financial Interests, Personal, Member of Board of Directors, From 2019-2022: AACR; Non-Financial Interests, Personal, Other, Board of Directors: AACR; Non-Financial Interests, Personal, Advisory Role, EACR Advisory Council member: EACR. M. Jamal-Hanjani: Financial Interests, Personal, Invited Speaker, Invited speaker honorarium: Oslo Cancer Cluster, Astex Pharmaceutical; Financial Interests, Personal, Invited Speaker, Speaker honorarium: Pfizer, Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, Cancer cachexia research advisory board: Pfizer; Non-Financial Interests, Personal, Advisory Role, Scientific Advisory Board and Steering Committee member: Achilles Therapeutics; Other, Personal, Other, I am named as co-inventor on patent PCT/US2017/028013 relating to methods for lung cancer detection: Patent. All other authors have declared no conflicts of interest.