Angela Esposito1, Antonio Marra2, Vincenzo Bagnardi3, Samuele Frassoni3, Stefania Morganti2, Giulia Viale1, Paola Zagami2, Gianluca M Varano4, Giorgio Buccimazza5, Franco Orsi4, Konstantinos Venetis6, Luca Mazzarella7, Giuseppe Viale6, Nicola Fusco6, Carmen Criscitiello2, Giuseppe Curigliano8. 1. Division of Early Drug Development for Innovative Therapies, IEO, European Institute of Oncology IRCCS, Milan, Italy. 2. Division of Early Drug Development for Innovative Therapies, IEO, European Institute of Oncology IRCCS, Milan, Italy; Department of Oncology and Haemato-Oncology, University of Milano, Milan, Italy. 3. Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy. 4. Division of Interventional Radiology, IEO, European Institute of Oncology IRCCS, Milan, Italy. 5. Division of Interventional Radiology, IEO, European Institute of Oncology IRCCS, Milan, Italy; University of Milano, Milan, Italy. 6. Department of Oncology and Haemato-Oncology, University of Milano, Milan, Italy; Division of Pathology, IEO, European Institute of Oncology IRCCS, Milan, Italy. 7. Division of Early Drug Development for Innovative Therapies, IEO, European Institute of Oncology IRCCS, Milan, Italy; Department of Experimental Oncology, IEO, European Institute of Oncology IRCSS, Milan, Italy. 8. Division of Early Drug Development for Innovative Therapies, IEO, European Institute of Oncology IRCCS, Milan, Italy; Department of Oncology and Haemato-Oncology, University of Milano, Milan, Italy. Electronic address: giuseppe.curigliano@ieo.it.
Abstract
BACKGROUND: We performed a multi-parametric analysis investigating the association between adiposity (as measured using body mass index [BMI] and computed tomography [CT]-based body composition), tumour infiltrating lymphocytes (TILs) and clinical outcomes in patients with advanced-stage cancer treated with immunotherapy in phase I clinical trials. MATERIAL AND METHODS: All consecutive patients (N = 153) with metastatic solid tumours treated within immunotherapy-based phase I clinical trials between August 2014 and May 2019 at our institution were included. Baseline characteristics, BMI, TILs value and CT-assessed fat indices (total fat area [TFA], subcutaneous fat area [SFA] and visceral fat [VFA]) were collected. The primary endpoints were to evaluate the impact of these parameters on overall survival (OS) and progression-free survival (PFS). Kaplan-Meier method and Cox proportional-hazards model were used for survival analyses. RESULTS: At both univariate and multivariate analyses, BMI was not associated with PFS neither when considered as continuous variable (HR 0.90, 95% CI 0.74-1.09, P = 0.28) nor as dichotomous variable (underweight/normal versus overweight/obese) (HR 0.79, 95% CI 0.55-1.14, P = 0.21). Interestingly, patients diagnosed with 'immunogenic' tumours and higher VFA/SFA ratio (1st and 2nd tertile versus 3rd tertile) presented an increased OS (HR 0.88, 95% CI 0.78-1.00, P = 0.047). CONCLUSION: Our analysis showed that patients with tumours that are already known as responsive to ICIs with higher VFA/SFA ratio presented an increased OS. Further studies are needed to elucidate the effect of adiposity on the host immune response to immunotherapy.
BACKGROUND: We performed a multi-parametric analysis investigating the association between adiposity (as measured using body mass index [BMI] and computed tomography [CT]-based body composition), tumour infiltrating lymphocytes (TILs) and clinical outcomes in patients with advanced-stage cancer treated with immunotherapy in phase I clinical trials. MATERIAL AND METHODS: All consecutive patients (N = 153) with metastatic solid tumours treated within immunotherapy-based phase I clinical trials between August 2014 and May 2019 at our institution were included. Baseline characteristics, BMI, TILs value and CT-assessed fat indices (total fat area [TFA], subcutaneous fat area [SFA] and visceral fat [VFA]) were collected. The primary endpoints were to evaluate the impact of these parameters on overall survival (OS) and progression-free survival (PFS). Kaplan-Meier method and Cox proportional-hazards model were used for survival analyses. RESULTS: At both univariate and multivariate analyses, BMI was not associated with PFS neither when considered as continuous variable (HR 0.90, 95% CI 0.74-1.09, P = 0.28) nor as dichotomous variable (underweight/normal versus overweight/obese) (HR 0.79, 95% CI 0.55-1.14, P = 0.21). Interestingly, patients diagnosed with 'immunogenic' tumours and higher VFA/SFA ratio (1st and 2nd tertile versus 3rd tertile) presented an increased OS (HR 0.88, 95% CI 0.78-1.00, P = 0.047). CONCLUSION: Our analysis showed that patients with tumours that are already known as responsive to ICIs with higher VFA/SFA ratio presented an increased OS. Further studies are needed to elucidate the effect of adiposity on the host immune response to immunotherapy.
Authors: Sven H Loosen; Joao Gorgulho; Markus S Jördens; Maximilian Schulze-Hagen; Fabian Beier; Mihael Vucur; Anne T Schneider; Christiane Koppe; Alexander Mertens; Jakob N Kather; Frank Tacke; Verena Keitel; Tim H Brümmendorf; Christoph Roderburg; Tom Luedde Journal: Front Oncol Date: 2021-04-01 Impact factor: 6.244