Malnutrition increases the toxicity of chemotherapy and impairs quality of life of patients with cancer [33]. Our current findings suggest an association between nutrition risk classified by GNRI, and AENT in the early period, antibiotics use, and mortality in patients with unresectable CRC receiving cytotoxic chemotherapy. We calculated GNRI using three factors: height, body weight, and serum albumin levels. Therefore, GNRI is an accurate, objective, and time-saving tool for nutrition assessment [1, 10]. More patients in the risk group (GNRI <98) had AENT than in the no-risk group(GNRI ≥98). Furthermore, AENT may increase due to infection and malnutrition, which results in higher treatment costs for the patients in the risk group because of the need for antibiotic treatment and other supportive care forms.
Previous reports validated the association between malnutrition and the patient’s tolerability and vulnerability to cytotoxic chemotherapy due to severe chemotherapy-associated adverse events [1, 8]. However, in patients with CRC, the effect of body weight, BMI, or hypoalbuminemia alone on tolerability and vulnerability has remained controversial [25, 33-35]. The body weight of patients with CRC changes easily due to decreased food intake, ascites, pleural effusion, and dehydration [36]. Similarly, serum albumin levels are easily influenced by inflammation and dehydration [37]. Therefore, the association between BMI or albumin alone and the nutrition risk of patients with cancer may be controversial [4, 34].
In the GNRI calculation, body weight and serum albumin levels are inversely proportional. In other words, if the patient’s body weight increases due to ascites or pleural effusion, the patient’s serum albumin levels decrease by increasing body fluid volume unless intra-vascular dehydration occurs. Conversely, if the amount of body fluid decreases, the patient’s body weight decreases, but the patient’s serum albumin levels increase due to high blood concentration. However, our findings showed no correlation between body weight and albumin. Thus, GNRI calculation may reflect nutrition status and risk complementarity, although BMI, body weight, or albumin alone cannot reflect nutrition status and risk comprehensively because of unknown risk factors.
NRI is composed of basal weight and serum albumin levels. NRI seems useful for identifying malnutrition and nutrition risk. However, baseline body weight is uncertain because malnutrition occurs before cancer diagnosis. In addition, it is difficult to exclude the patient’s memory bias. Therefore, NRI may not comprehensively reflect nutrition status and risk [3]. In contrast, the body weight used in GNRI is obtained at just one point in time. Thus, GNRI may help identify nutrition status and risk before chemotherapy, enabling prediction concerning the tolerability to chemotherapy.
Malnutrition increases the risk of infection and hospitalization in patients with cancer [4]. Moderate or severe infection disease is critical in some cases. Prediction of patients’ immunocompromised status through a novel method can help patients exercise preventive measures, e.g., avoiding crowds, following hand wash practices, wearing a mask on the mouth, following a diet avoiding fresh vegetables and fermented food. Furthermore, we need to assess for the presence of comorbidities that lead to severe infection, such as diabetes mellitus, chronic obstructive pulmonary disease, and asthma. Therefore, nutrition risk assessment is essential in patients with cancer.
We consider that nutrition risk assessment can be used similarly to Geriatric Assessment (GA) to discover (diagnose) a missing problem, predict adverse events of treatment and disease prognosis, and determine treatment strategy [38]. Importantly, the diagnosis of unrecognized problems underlying malnutrition has benefits[39]. Patients with nutritional risk have metabolic, cardiovascular, and respiratory comorbidities and potential psychosocial and economic problems [40-42]. Thus, supportive care for physical comorbidities and psychosocial and economic difficulties is important in patients with cancer. GNRI is useful for assessing nutrition risk in patients with cancer, and the GNRI assessment enables the discovery of problems associated with malnutrition. Recognizing comorbidities and malnutrition-associated problems in patients with cancer will enhance supportive care [2]. Supportive care enhancement will reduce antibiotics use, admission treatment for adverse events, and mortality-associated excessive chemotherapy. Therefore, enhanced supportive care can reduce medical expenses [13, 43].
Another aspect of essential supportive care for patients with cancer involves identifying the patients requiring supportive care and what type of care they may benefit from. Our findings support the utilization of GNRI in predicting AENT. Recent studies reported that nutrition support might reduce adverse events associated with toxic chemotherapy [44]. Support for comorbidities that causes malnutrition is also important. However, nutrition intervention for all patients with cancer may not be practical and increase medical expenses [26, 41]. Therefore, before chemotherapy initiation, the GNRI nutrition risk assessment will help physicians identify patients who may benefit from nutrition support and comorbidity screening. If the patient with cancer has a GNRI lower than 98, we should introduce nutrition support and intervention practically as a part of the cancer treatment strategy. Nutrition support and intervention comprise nutrition education and counseling, exercise with rehabilitation therapists, and life support from medical social workers and care workers. However, the effect of nutrition support based on GNRI remains unexplored on patients with CRC of tolerance and vulnerability to chemotherapy. Thus, a prospective study is needed to validate the benefit of nutrition support for chemotherapy in patients with CRC.
We did not observe any association between GNRI and admission. Admission treatment is complicated. When the patients determine whether to be admitted for treatment, disease severity is not the only determinant. Many patients and families may have many other determinants, such as financial conditions, family situations, and insurance issues. Therefore, nutrition risk assessment alone may not reflect all essential issues. To expand upon the current findings, we intend to delve into issues concerning admission treatment.
The present study has some limitations. First, the present study enrolled only patients covered by a single center. Thus, it is undeniable there was bias regarding diet and exercise habits as regional culture, climate, and economy influence patients’ lifestyle. Second, most of the patient’s chemotherapy protocol was an oxaliplatin-based protocol. Japanese clinical physicians more commonly use an oxaliplatin-based protocol than an irinotecan-based protocol for the first-line chemotherapy [45]. Thus, we might have some selection bias. Finally, regarding treatment strategy, the chemotherapy protocol was determined by internal meetings within the department. We determined the treatment strategy based on the Japanese Society for Cancer of the Colon and Rectum guidelines and considering the patient’s age, PS, organ dysfunction status, and patient’s wishes. Although our strategy included more than one physician’s opinion, the inherent aspects of single-center studies may cause a degree of selection bias in the treatment strategy. Thus, a multi-center study is needed to resolve the biases.
In conclusion, in patients with CRC receiving chemotherapy, our study results indicate an association between nutrition risk classification by GNRI and AENT, antibiotic use, and mortality. GNRI may be a useful screening tool predicting tolerability and vulnerability to chemotherapy. Further prospective research is needed to validate nutrition support based on nutrition status and risk classification by GNRI in patients with CRC.