TY - JOUR
T1 - Obesity and Cancer Treatment Outcomes: Interpreting the Complex Evidence
AU - Slawinski, Corinna
AU - Barriuso, Jorge
AU - Guo, Hui
AU - Renehan, Andrew
N1 - Funding Information:
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. J. Barriuso reports grants and non-financial support from Ipsen, non-financial support from Novartis, personal fees and non-financial support from Pfizer, non-financial support from AAA, non-financial support from Nanostring, outside the submitted work. All other authors declare no competing interests.
Funding Information:
The authors acknowledge the support of statistical and support staff, and other researchers at the Centre for Biostatistics, University of Manchester and the Manchester Cancer Research Centre for the constant culture to attain high-quality research. This work was supported by CRUK via the funding to Cancer Research UK Manchester Centre: [C147/A18083] and [C147/A25254]. A.G. Renehan is supported by the Manchester NIHR Biomedical Research Centre (IS-BRC-1215-20007).
Publisher Copyright:
© 2020 The Royal College of Radiologists
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - A wealth of epidemiological evidence, combined with plausible biological mechanisms, present a convincing argument for a causal relationship between excess adiposity, commonly approximated as body mass index (BMI, kg/m
2), and incident cancer risk. Beyond this relationship, there are a number of challenges posed in the context of interpreting whether being overweight (BMI 25.0–29.9 kg/m
2) or obese (BMI ≥ 30.0 kg/m
2) adversely influences disease progression, cancer mortality and survival. Elevated BMI (≥ 25.0 kg/m
2) may influence treatment selection of, for example, the approach to surgery; the choice of chemotherapy dosing; the inclusion of patients into randomised clinical trials. Furthermore, the technical challenges posed by an elevated BMI may adversely affect surgical outcomes, for example, morbidity (increasing the risk of surgical site infections), reduced lymph node harvest (and subsequent risk of under-staging and under-treatment) and increased risk of margin positivity. Suboptimal chemotherapy dosing, associated with capping chemotherapy in obese patients as an attempt to avoid excess toxicity, might be a driver of poor prognostic outcomes. By contrast, the efficacy of immune checkpoint inhibition may be enhanced in patients who are obese, although in turn, this observation might be due to reverse causality. So, a central research question is whether being overweight or obese adversely affects outcomes either directly through effects of cancer biology or whether adverse outcomes are mediated through indirect pathways. A further dimension to this complex relationship is the obesity paradox, a phenomenon where being overweight or obese is associated with improved survival where the reverse is expected. In this overview, we describe a framework for evaluating methodological problems such as selection bias, confounding and reverse causality, which may contribute to spurious interpretations. Future studies will need to focus on prospective studies with well-considered methodology in order to improve the interpretation of causality.
AB - A wealth of epidemiological evidence, combined with plausible biological mechanisms, present a convincing argument for a causal relationship between excess adiposity, commonly approximated as body mass index (BMI, kg/m
2), and incident cancer risk. Beyond this relationship, there are a number of challenges posed in the context of interpreting whether being overweight (BMI 25.0–29.9 kg/m
2) or obese (BMI ≥ 30.0 kg/m
2) adversely influences disease progression, cancer mortality and survival. Elevated BMI (≥ 25.0 kg/m
2) may influence treatment selection of, for example, the approach to surgery; the choice of chemotherapy dosing; the inclusion of patients into randomised clinical trials. Furthermore, the technical challenges posed by an elevated BMI may adversely affect surgical outcomes, for example, morbidity (increasing the risk of surgical site infections), reduced lymph node harvest (and subsequent risk of under-staging and under-treatment) and increased risk of margin positivity. Suboptimal chemotherapy dosing, associated with capping chemotherapy in obese patients as an attempt to avoid excess toxicity, might be a driver of poor prognostic outcomes. By contrast, the efficacy of immune checkpoint inhibition may be enhanced in patients who are obese, although in turn, this observation might be due to reverse causality. So, a central research question is whether being overweight or obese adversely affects outcomes either directly through effects of cancer biology or whether adverse outcomes are mediated through indirect pathways. A further dimension to this complex relationship is the obesity paradox, a phenomenon where being overweight or obese is associated with improved survival where the reverse is expected. In this overview, we describe a framework for evaluating methodological problems such as selection bias, confounding and reverse causality, which may contribute to spurious interpretations. Future studies will need to focus on prospective studies with well-considered methodology in order to improve the interpretation of causality.
KW - Cancer
KW - chemotherapy
KW - immunotherapy
KW - obesity
KW - radiotherapy
KW - surgery
UR - http://www.scopus.com/inward/record.url?scp=85086947058&partnerID=8YFLogxK
U2 - 10.1016/j.clon.2020.05.004
DO - 10.1016/j.clon.2020.05.004
M3 - Article
SN - 0936-6555
VL - 32
SP - 591
EP - 608
JO - Clinical Oncology
JF - Clinical Oncology
IS - 9
ER -