The aim of the present study was to clarify the clinical impact of change in CAR in gastric cancer patients who received curative treatment. The major finding is that a change in CAR is a significant risk factor in gastric cancer patients. In addition, a higher change in CAR is related to postoperative complications and lymph node recurrence. Therefore, a change in CAR is a promising prognostic factor for gastric cancer patients.

In the present study, the high-change CAR (≥ 0.05) group had a significantly poorer prognosis in comparison to the low-change CAR (< 0.05) group (hazard ratio: 1.733, 95% confidence interval: 1.009–2.978, p = 0.0049). Moreover, the 5-year OS rates of the high-change CAR group and low-change CAR group were 77.5% and 87.6%, respectively. Although limited studies have evaluated the clinical impact in malignancies, similar results were observed in previous studies. Oshima et al. evaluated the changes and prognostic impact of inflammatory nutritional factors during neoadjuvant chemoradiation therapy in 49 patients with resectable pancreatic cancer [16]. They found that high change in CAR (≥ 0.077) after chemoradiation therapy were significantly associated with shorter OS. The median OS was 23.1 months in patients with a high change in CAR and 64.1 months in those with a low change in CAR. In addition, change in CAR after chemoradiation therapy were a prognostic factor (hazard ratio: 5.1842, p = 0.0036). Moreover, Ikoma et al. evaluated the clinical impact of change in CAR in 97 gastric cancer patients who received immune checkpoint inhibitor therapy [17]. They found that patients with low change in CAR (≤ 0.01) during immune checkpoint inhibitor therapy had better survival than those with high change in CAR (> 0.01). The median OS was 9.4 months in the patients with low change in CAR and 4.5 months in those with high change in CAR; the difference was statistically significant (p = 0.002). In addition, the univariate and multivariate analyses showed that low change in CAR was a prognostic factor (HR 0.59; 95% CI 0.37–0.93; p = 0.002). Considering our results and previous reports, the change in CAR during cancer treatment might be a promising prognostic factor.

Recently, the change in CAR during treatment might be not only a promising prognostic factor but also a promising nutritional assessment tool for nutritional intervention. To date, there have been various nutritional/anti-inflammatory treatment studies for malignancy patients during cancer treatment [18, 19]. However, limited studies have shown only positive results, and there are no definitive nutritional/anti-inflammatory treatments. One possible reason is the difficulty of setting an endpoint. Although previous studies, including our studies, focused on body weight or lean body mass, the effect of nutritional/anti-inflammation treatment during cancer treatment on weight and muscle was much smaller than expected, and the difference may not have been detectable. On the other hand, the change in CAR might indicate small change in nutritional/anti-inflammatory treatment during cancer treatment. For example, Silva et al. conducted a clinical trial to evaluate the systemic inflammatory response to eicosapentaenoic acid (EPA) in 29 colorectal cancer patients [20]. The patients who were assigned to the supplemental group received 2 g of fish oil containing 600 mg of EPA and docosahexaenoic acid (DHA). When the change in CAR between baseline and 9 weeks after chemotherapy was compared, the patients who received EPA showed a clinically relevant decrease in their C-reactive protein/albumin ratio (p = 0.005).

They found that low doses of fish oil supplementation can positively modulate the nutritional status and C-reactive protein/albumin ratio. Considering these factors, change in the CAR might become promising predictive markers of nutritional/anti-inflammatory treatment during cancer treatment.

To introduce change in CAR as a parameter in daily clinical practice, it is necessary to set the optimal cutoff value. In the present study, we set the cutoff value of change in CAR at 0.05 according to the 1-, 3-, and 5-year survival rates. Several values of the change in CAR have been described in previous studies. Oshima et al. set the cutoff value of change in CAR at 0.077, and Ikoma et al. set it at 0.01. These differences might be due to the following reasons. First, the number of patients and patient background factors were different. Our study (n = 458) evaluated resectable gastric cancer, Ikoma et al. evaluated unresectable gastric cancer (n = 97), and Oshima et al. evaluated pancreatic cancer (n = 49). Second, the methods used to evaluate change in CAR were different. Our study evaluated the cutoff value of change in CAR according to the survival rate, while other studies evaluated the cutoff value of change in CAR according to a receiver operating characteristic curve. These differences might have affected the cutoff value. Further studies are needed to establish the optimal evaluation method and optimal cutoff value of change in CAR.

The present study was associated with some limitations. First, this was a retrospective study with a small sample size from a single institution. Therefore, our study might have a selection bias. Second, there might be time bias in the present study. Our study included data from 2012 to 2017. During this period, perioperative care and perioperative adjuvant treatment were improved. Third, in the present study, the incidence of other-cause death was significantly higher in the high-change group than in the low-change group. However, the reason for this issue is unclear. Considering these factors, our results need to be validated in another large cohort.

In conclusion, change in CAR during treatment is a significant risk factor and in gastric cancer patients and is therefore a promising prognostic factor. In addition, the changes of inflammation status during perioperative periods might be a promising prognostic factor for gastrointestinal cancer patients.