Lung cancer, which contributes 11.4% of cases and 18.0% deaths among cancer patients worldwide in 2020. Despite the approval of various treatments like immunotherapy drugs, chemotherapy, radiation therapy, tumor-specific vaccination, and surgery over the past three decades, challenges still persist. Notably, lung cancer patients frequently face issues like involuntary weight loss and nutrition risks.10–54 Patients at nutrition risk not only experience malnutrition but also face a compromised prognosis, leading to increased hospitalization rates, in-hospital complications, longer stays, sarcopenia, cachexia, and a considerable decline in quality of life. Numerous studies highlight the significant impact of nutrition status on disease progression. Luo J and others retrospectively analyzed the relationship between nutritional status and prognosis in 110 newly diagnosed NSCLC patients, finding that nutritional status independently influences NSCLC overall survival (OS). Sánchez-Lara K assessed nutritional parameters, including C-reactive protein, blood cell count, ALB, IL-6, TNF-α levels, confirming malnutrition as an independent factor affecting prognosis for advanced NSCLC patients.16–17 Besides, various clinical studies indicate a close association between late-stage malignancy, nutritional status, and quality of life. Many studies have reported that malnourished patients spent on more days in the hospital than those with good nutrition.20–23 Malnutrition is an independent risk factor for complications, mortality, increased hospitalization time, and costs; hospitalization expenses for malnourished patients are over three times higher. In a prospective study in Mexico, it was observed that lung cancer patients with poor nutritional status (SGA B and C groups) had significantly lower quality of life and a shorter median overall survival (OS) compared to patients with relatively better nutritional status (SGA A group).24 Arrieta et al. conducted a study on 100 stage IV NSCLC patients treated with paclitaxel combined with cisplatin chemotherapy, revealing that patients experiencing malnutrition and hypoalbuminemia after chemotherapy had a significant increase in chemotherapy adverse drug reactions (ADR), including anemia, fatigue, and lack of appetite. 19 Researches also indicate that over 20% of malignant tumor patients ultimately die from malnutrition rather than end-stage tumors. Tumor patients are prone to malnutrition, and anti-tumor treatment can exacerbate nutritional loss, intensifying its impact on the body, as well as plays a vital role on the microenvironment of cancer, which involved in the development of cancer process.20–24 For example, the popular immune checkpoint inhibitor treatment, which may interacted with nutrition support.25–34 Therefore, appropriate nutritional intervention in clinical practice can improve patient nutritional status, benefit tumor treatment outcomes, and extend patient overall survival (OS). 35–39 Based on these studies and real-world data, this research aims to further explore the impact of enteral nutrition (EN) support therapy on the treatment efficacy and OS of advanced lung cancer patients, as relevant research data both domestically and internationally is still relatively scarce.
This study first aims to further explore the impact of enteral nutrition (EN) support therapy on the treatment efficacy and OS of advanced lung cancer patients, given the current lack of sufficient related research data globally. Results showed a statistically significant difference in OS distribution between the EN group (34 months) and the control group (24 months), emphasizing the positive impact of EN support therapy on prognosis.
The study also conducted a COX regression analysis on various factors that may affect patient prognosis. Factors like gender, smoking history, pathology, molecular targeted therapy, anti-angiogenic therapy, baseline WBC levels, baseline Hb levels, baseline ALB levels, and EN support therapy were found to have a statistically significant impact on OS (P < 0.05). The multifactorial Cox proportional hazards model was constructed, revealing that EN support therapy significantly impacts OS (HR = 0.501, 95% CI 0.267–0.941, P = 0.032). Additionally, better nutritional status (increased baseline ALB levels) can reduce the risk of death for late-stage lung cancer patients with nutritional risk/malnutrition (HR = 0.954, 95% CI 0.919–0.990, P = 0.013). These findings suggest that EN support therapy not only provides support but also holds substantial therapeutic value, becoming a crucial component of comprehensive multidisciplinary treatment for lung cancer. Improving patient nutrition significantly reduces the risk of death.
Additionally, it was found that the histopathological type (SCLC vs. NSCLC) has a statistically significant impact on OS (HR = 1.655, 95%CI:1.131–2.420, P = 0.009). The death risk for SCLC patients is 1.655 times that of NSCLC. Pathological classification, TNM staging, treatment plans, and nutritional status are identified as key indicators for predicting OS in advanced lung cancer patients. Mainly stage IIIb to IVb lung cancer patients were included, with the majority being in stage IVa (51.12%) and 78.73% having NSCLC. The baseline characteristics between the two groups showed no statistically significant differences. The median OS in the study was 25 months (95% CI: 22.06–27.94), and the 1-year survival rate was 79.17%, notably higher than reported in the literature, possibly due to the inclusion of some stage III patients and the widespread use of molecular targeted and immunotherapy.
Additionally, the study included patients with nutritional risk/malnutrition during diagnosis and first-line treatment, comparing nutritional and laboratory parameter changes between an EN group and a control group. The differences in variables such as Δweight, ΔBMI, ΔWBC, ΔRBC, ΔPLT, ΔLY, ΔHb, ΔTP, and ΔALB were found to be statistically insignificant. Survival analysis indicated a median progression-free survival (PFS) of 15 months in the EN group compared to 11 months in the control group, but the difference was not statistically significant. Safety analysis revealed that 73.18% of patients experienced adverse drug reactions (ADR) during hospitalization, with differences in overall ADR rate, bone marrow suppression rate, and gastrointestinal ADR rate between the EN and control groups. EN support therapy was associated with lower overall ADR and bone marrow suppression rates but a higher incidence of gastrointestinal ADR, potentially linked to increased gastrointestinal intolerance. Consider the potential bias, which may brought in by the study's retrospective design, further prospective cohort studies are needed to validate these results.
Combining above all, on one hand, our study confirmed that malnutrition is a common clinical issue and an important contributing factor on mortality in lung cancer patients. With the improvement for nutritional status could significantly reduce the risk of death for these patients. For advanced lung cancer patients under nutritional risk/malnutrition, EN support can markable decrease the incidence of adverse drug reactions (ADR) during anticancer treatment, extend OS, reduce mortality, ultimately enhancing the prognosis. Therefore, for advanced lung cancer patients with nutritional risk/malnutrition, EN goes beyond mere nutritional support and holds significant therapeutic value, warranting its elevation to nutritional support treatment.
On the other hand, throughout this study, it is evident that there is a considerable gap between domestic clinical practice and guidelines. Due to many “insurmountable” reasons, such as regional disparities, variations in nutritional awareness, economic conditions, and even patient compliance, most lung cancer patients didn’t receive adequate nutritional support treatment, leading to a decline for their prognosis, especially in quality of life or a shortened OS.40–45 In fact, research on the prevention and treatment of tumor-related malnutrition is not only a clinical necessity but also a major national policy requirement. Take China for example, with the acceleration of aging population and urbanization, the country is facing the grim reality of rising cancer incidence and mortality rates, a large number of cancer patients, and low five-year survival rates. The National Nutrition Plan (2017–2030) issued by the State Council explicitly emphasizes clinical nutrition administration, advocating for the establishment of standardized clinical nutrition support treatment pathway, including the basic procedures: nutrition screening, assessment, diagnosis, and treatment. This initiative aims to promote nutritional prevention and treatment of nutrition-related chronic diseases, including cancer. Despite the introduction of the policies and guidelines hope to standardize the management of clinical nutrition support, the current situation in the country remains challenging. Even in many large tertiary hospitals, the implementation is not entirely satisfactory. Therefore, the popularization and standardization of nutritional management for advanced lung cancer patients remain a daunting task.46–48 Clinical practitioners should heighten their awareness of nutritional risk/malnutrition in lung cancer patients, implement targeted preventive and therapeutic measures, and improve patient prognosis.
Due to the design of the observatory real world research shortages, this study has the following limitation: (1) natural limitations inherent in observational design, such as confounding bias and limited data; (2) selection bias and information bias introduced by retrospective research methods, making it difficult to trace external data due to the long research time; (3) the small sample size of the observation group and the lack of subgroup analysis on patients due to limited research time, including early nutrition group, late nutrition group, standard nutrition group, and non-standard nutrition group mentioned in the study design; (4) inconsistency in the criteria for nutritional risk/malnutrition entry, where nutritional risk is primarily determined based on NRS2002 scores, while four different methods were utilized, including malnutrition-related diagnoses, PG-SGA scores ≥ 4 points, BMI < 18.5 kg/m2 (in advanced lung cancer patients with poor general condition), and weight loss greater than 5% in the last 3 months or greater than 10% in the last 6 months. Due to these different tools of nutrition evaluation, this leads to inconsistent patient entry criteria and potential mismatches in baseline characteristics. Based on the above, a prospective cohort study is needed in the future, also based on real-world data, aim to expand the sample size, avoid the limitations of retrospective studies, then clarify the impact of EN treatment on the prognosis of patients with advanced lung and breast cancer undergoing internal medicine treatment. This includes the effects on patients' nutritional status, immune function, quality of life, and disease remission rate, ultimately advancing the completeness of the overall evidence chain.
Furthermore, despite the recognized importance of nutrition support during cancer treatment, standardized support protocols are lacking due to the complexity of cancer types. A comprehensive nutrition support approach in lung cancer care shall be carried out based on the data from real world research.
In conclusion, this study suggests that: 1. EN therapy significantly reduces ADR occurrence, prolongs OS, and decreases mortality, ultimately improving patient prognosis; 2. EN therapy may increase the occurrence of gastrointestinal ADRs; 3. Maintaining a good albumin level significantly reduces the risk of death; 4. The widespread and standardized implementation of nutritional management in late-stage lung cancer patients requires further improvement.