Cracking frailty to improve its diagnosis in the cancer set

Abstract

Continuous advancements along the cancer care continuum have provided substantial improvements to cancer morbidity and mortality. Nevertheless, surgery remains at the core of curative solid tumour treatment, which in newer regimens is combined with other forms of therapy; this strategy leads to improved treatment efficacy, but not without the cost of increased treatment burden to the patient. In a world of dwindling resources in healthcare, allocation of specialised strategies to the patients that most require it assumes the spotlight. Thus, it becomes imperative to stratify patients into proper risk groups. One emergent tool for risk assessment in gastric cancer patients is the frailty syndrome, but several gaps exist in the literature. In an attempt to tackle some of the gaps, this thesis was conceptualised, consisting of one literature review, three systematic reviews and two experimental studies, aimed at on one hand solidifying the role of frailty as a risk assessment tool, while at the same time advancing knowledge on its molecularity and exploring risk assessment in patients undergoing perioperative chemotherapy with the FLOT regimen. Our results indicate that despite frailty having potential as a risk assessment tool, integrating molecular markers with current clinical tools is still at a distant length, with research hampered by enormous heterogeneity in study design and lack of standardisation of frailty conceptualisation and operationalisation. At the same time, we were able to demonstrate the substantial impact that the FLOT treatment has on patients, which entails a constant degradation of patients' physiological reserve from neoadjuvancy through surgery. We also identified robust predictive associations between hematological parameters and certain forms of treatment intolerance/toxicity; similar associations with physical fitness parameters were lost upon adjustment to confounders. Calf circumference and probable sarcopenia emerged as independent predictors of postoperative complications, as well as of prolonged length of stay. Due to low statistical power, we could not analyse the role of frailty as a risk assessment tool. These results demonstrate the importance of a new frailty consensus that standardises once and for all the conceptual and operational definition of frailty, while also opening the door to the use of physical fitness markers as predictors of risk of developing poor treatment outcomes in patients undergoing perioperative chemotherapy with FLOT.