Abstract
Undernourishment is reported to impair treatment response, further leading to poor prognosis for cancer patients. We aimed to investigate the role of nutritional status on the prognosis of squamous cell carcinoma (SCC) of the esophagus, and its correlation with anticancer immune responsiveness. We retrospectively reviewed 340 esophageal-SCC patients who completed curative treatment and received a nutrition evaluation by the Patient-Generated Subjective Global Assessment (PGSGA) score at the beginning and completion of neoadjuvant treatment at our hospital. The correlation between the nutritional status and various clinicopathological parameters and prognosis were examined. In addition, the role of nutritional status in the regulation of the anticancer immune response was also assessed in cancer patients and in a 4-nitroquinoline 1-oxide (4NQO)-induced esophageal tumor model. Our data revealed that malnutrition (patients with a high PGSGA score) was associated with advanced stage and reduced survival rate. Patients in the group with a high PGSGA score were correlated with the higher neutrophil-to-lymphocyte ratio, higher proportion of myeloid-derived-suppressor cells (MDSC) and increased IL-6 level. Furthermore, surgical resection brought the survival benefit to patients in the low PGSGA group, but not for the malnourished patients after neoadjuvant treatment. Using a 4NQO-induced tumor model, we found that nutrition supplementation decreased the rate of invasive tumor formation and attenuated the immune-suppressive microenvironment. In conclusion, malnutrition was associated with poor prognosis in esophageal-SCC patients. Nutritional status evaluated by PGSGA may be useful to guide treatment decisions in clinical practice. Nutritional supplementation is suggested to improve prognosis, and it might be related to augmented anticancer immune response.
Highlights
Malnutrition is a common problem in patients with aerodigestive tract malignancies [1,2]
We previously reported that the neutrophil-to-lymphocyte ratio (NLR) was relevant to IL-6 and myeloid-derived-suppressor cells (MDSC) levels, and that it was associated with poor prognosis in esophageal-squamous cell carcinoma (SCC) patients [15,16]
The high Pre-Tx Patient-Generated Subjective Global Assessment (PGSGA) group was significantly associated with more advanced disease, lower body mass index (BMI) and a higher risk of distant metastasis and death during follow-up
Summary
Malnutrition is a common problem in patients with aerodigestive tract malignancies [1,2]. Esophageal cancer is an aggressive malignancy with high recurrence rate and poor rate of survival [3]. The treatment outcome depends on patient characteristics, tumor status, and response to treatment [5]. It has been reported that undernourishment can impact tumor progression and survival in cancer patients [6]. Considering nutritional status is associated with prognosis, nutritional assessment should be integrated with the multimodal anticancer treatment [9]. We evaluated the nutritional status of esophageal-SCC patients by the Patient-Generated Subjective Global Assessment (PGSGA), and examined its role in the treatment response and prognosis
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