This retrospective study aimed to identify potential predictors of AC incompletion in patients with stage III CRC, with a specific focus on the role of AAC as an indicator of AC incompletion. A notable finding was that high AAC volume was a significant predictor of AC incompletion in patients with stage III CRC. This finding underscores the comprehensive reflection of systemic conditions such as advanced age and comorbidities by AAC. Importantly, AAC was robustly associated with the critical outcomes of chemotherapy discontinuation in patients with CRC. This association suggests that AAC could effectively bridge the clinical gap by identifying risk factors that may impede AC completion prior to its initiation. Additionally, an increased risk of AC incompletion in patients with stage III CRC as both age and AAC volume increased. Finally, our results suggested that AC incompletion was associated with poor prognosis in patients with stage III CRC, as previously reported [2, 3]. To the best of our knowledge, this is the first study to establish a direct link between AAC and AC incompletion in patients with stage III CRC who commenced AC. These findings present AAC as a straightforward and immediately applicable metric in clinical settings.
The identification of clinically effective biomarkers for exploring the sustainability of AC in the older population presents a significant challenge to clinical practice. One study reported that there was no age requirement for postoperative AC, and aggregated analyses of randomized-controlled trials conducted in both the United States and Europe have demonstrated comparable effectiveness in terms of recurrence prevention and survival extension between patients aged ≥ 70 years and those aged < 60 years [20]. Our previous study also indicated that completion of AC may contribute to improved long-term prognosis, even in patients aged ≥ 80 years with stage III CRC [21]. However, older age is considered an important factor in the introduction and continuation of AC by many clinicians and patients [22, 23]. Increased age may also be associated with increased frailty and decreased tolerance to chemotherapy [24]. Although the decision on AC introduction or discontinuation should be made carefully, considering not only age, but also major organ functions, general health, and condition, no clinically useful biomarkers have yet been identified. Recently, geriatric assessment (GA) has been shown a useful method for measuring physical function, cognitive function, nutritional status, social factors, and family environment and has been reported to predict the completion of chemotherapy [25, 26]. Although GA has proven useful for characterizing health and functional impairments potentially associated with oncological outcomes [27], it requires considerable time and human resources [28]. Therefore, it is necessary to establish a simpler biomarker for predicting AC completion than that for predicting GA. AAC is a well-known risk marker of cardiovascular diseases and is associated with hyperphosphatemia, diabetes, chronic inflammation, and chronic kidney disease [29]. A recent study indicated that AAC severity independently correlated with an increased risk of pre-frailty or frailty in a dose-responsive relationship [9]. Furthermore, AAC volume can be calculated and quantified accurately, automatically, and rapidly using preoperative CT-based examination [30]. Our findings indicate that AAC volume is a specific predictor of AC completion as well as chronological age. This distinction is critical, as even among older patients, there is considerable variation in the overall health status and vulnerability, which are influenced by factors such as the extent of comorbidities and tumor progression. However, these variations cannot be accurately gauged using age alone. Consequently, measurement of AAC volume is anticipated to offer a more objective reflection of the systemic condition and tolerance to AC in patients.
There may be several complex underlying mechanisms and reasons why patients cannot complete AC. Several reports have described the predictive role of inflammatory markers and nutritional factors in severe complications with chemotherapy [31–33]. In the field of head and neck oncology, nutritional factors such as the prognostic nutritional index, mGPS, and the C-reactive protein to albumin ratio (CAR) are useful markers for predicting severe AEs [31, 33]. In CRC, CAR is also a useful tool for AEs (≥ grade 3) of the AC [32]. Contrary to expectations, high AAC was not associated with the severity of AEs, but the risk of AC incompletion in stage III CRC patients in this study. High AAC can be related to the patients’ adverse condition that cannot be assessed by the Common Terminology Criteria for Adverse Events (CTCAE) after AC introduction. Therefore, we focused on the association of AAC with alterations in nutritional status and inflammatory markers following the introduction of AC. Our findings suggest that higher levels of AAC are linked to a reduced improvement in nutritional status or inflammatory markers after the administration of AC, which can potentially contribute to AC incompletion independent of the AE severity. Thus, AAC could serve as an indicative marker of patient-specific susceptibility to the tolerance of AC.
This study had some limitations that should be considered when interpreting our findings. Specifically, the retrospective and non-randomized study design must be mentioned. The small sample size of patients at a single center may also weaken the conclusion. Future prospective studies involving a larger number of patients with high AAC are required to analyze the effects of AC on clinical outcomes.
In conclusion, high AAC volume may help us to more closely follow-up patients who have a potential risk of AC incompletion before AC introduction.