Malnutrition is defined as an imbalance in nutritional compositions with negative effects on body functions and clinical outcomes in cancer patients, and it accounts for 20%–30% of deaths in terminal cancer patients (1–3). Over 80% of gastrointestinal cancer patients develop malnutrition (4). On the one hand, gastrointestinal cancers often cause digestive tract dysfunction and obstruction, which lead to insufficient nutrition and energy intake (5). On the other hand, antitumor therapy is likewise a factor of malnutrition that increases nutritional needs and develops inevitable side effects, including gastrointestinal symptoms that would further aggravate the nutritional problems of cancer patients (6).

Currently, the European Society for Parenteral and Enteral Nutrition (ESPEN) recommends that home parenteral nutrition (HPN) be administered to adult cancer patients who are unable to achieve nutritional requirements through oral food intake or enteral nutrition (EN) and are at risk of malnutrition death (7, 8). Patients with incurable gastrointestinal tumors may struggle to meet nutritional needs, whereas the use of supplemental HPN (sHPN) for heterogeneous cancer patients may result in a significant improvement in their quality of life, particularly in terms of physical and functional well-being, and even prolonged survival with manageable complications (5, 9–12). Studies also showed that appropriate nutrition support was related to better antitumor therapy tolerance and a reduction of therapy toxicity (13).

Nevertheless, the implementation of sHPN is still controversial. Despite the insufficient awareness and prompt treatment in daily clinical practice, some researchers believed that it is an expenditure of social resources with limited benefits (14, 15). In addition, it could increase the risk of infection, family burden, and generate additional costs, including costs of drugs, injections, training, complications, and readministrations (16). A recent randomized clinical trial (RCT) (NCT02066363) demonstrated the efficacy of sHPN in patients with incurable gastrointestinal cancers, suggesting an improvement in muscle condition [fat-free mass (FFM), fat-free mass index (FFMI)] and quality of life. However, it was a unilateral analysis without a consideration of social resources (17). Hence, we aimed to conduct a comprehensive analysis of the clinical effects and economic benefits of sHPN for incurable gastrointestinal cancer patients from the perspective of the Chinese healthcare system, with the goal of providing nutritional guidance to patients with advanced cancer.

For the primary outcome, cost-effectiveness analysis showed patients in the sHPN group spent $10,693.40, with a QALY of 0.6081, while patients in non-sHPN group spent $8,642.22, with a QALY of 0.5237. The incremental cost between the sHPN group and the non-sHPN group was $2,051.18, and the incremental QALY was 0.0844. The ICER was $24,289.17, which achieved an economic benefit for patients with HPN comparing with the WTP ($29,307/QALY) threshold in China. Results are shown in Figure 1 and Table 2 .

For the secondary outcomes, we explored the difference from the baseline of each effect parameter and further calculated the corresponding ICERs between the sHPN group and the non-sHPN group at each visit. Results showed that outcomes in the sHPN group were superior to those in the non-sHPN group except for the measurement of handgrip at the time of visit 2. At the time of visit 3, three analyses achieved the best economic results, including quality of life, BMI, and FFM parameters, with an ICER of $9,004.58, $600.31/kg h⁻², and $178.31/kg, respectively. Two analyses balancing FFMI and 6MWT parameters demonstrated the best economic benefits at the time of visit 2 with an ICER of $797.45/kg h⁻² and $13.62/m, respectively. When considering handgrip as the effect parameter, the most cost-effectiveness result was achieved at visit 5, with an ICER of $411.67/kg. Results are listed in Table 3 and Supplementary Table S2 .

In the one-way sensitivity analysis, results showed the most influential parameter was the utilities in the sHPN group, followed by transformation probabilities in the sHPN group ( Supplementary Figure S1 ). In the probabilistic sensitivity analysis, the cost-effectiveness acceptability curve ( Figure 2 ) showed the sHPN group achieved economic benefits even if the WTP was set at $2,500/QALY. The incremental cost-effectiveness scatter plot ( Supplementary Figure S2 ) showed that a Monte Carlo simulation with 1,000 iterations was stable.

The prevalence of HPN was reported to be approximately 5–79 per million inhabitants per year in western countries, and 25% of patients suffered from malignant diseases (20–22). However, HPN is not a routinely recommended method of nutritional support in China considering its actual burdens despite China’s high incidence of gastrointestinal cancers, especially gastric cancer and liver cancer (23). Thus, we explored the economic benefits of sHPN for incurable gastrointestinal cancer patients considering various effect parameters in the perspective of the Chinese health system. Through the combined analyses of clinical efficacy and economics, we hope to provide references for clinical applications and designations of Chinese national medical insurance policies, and also provide references for the pricing of their related costs in China.

In the current study, we conducted a cost-effectiveness analysis where we comprehensively analyzed cost, quality of life, and survival of incurable gastrointestinal cancer patients as the primary outcome. The ICER was $24,289.17, which showed the economic benefits of sHPN. Subsequently, we performed cost-effectiveness analyses based on the effect parameters provided in the clinical trial (17). Results showed that the economic benefits could be achieved on various clinical effects except for the handgrip parameter at the time of visit 2, and the period for the obtainment of the best economic benefits differs among effect parameters. It is noticeable that although we analyzed the differences between each parameter and their baseline values, it was improper for the comparison among parameters due to different units of effect parameters and ICERs. In summary, while obtaining clinical benefits, sHPN also achieved economic benefits and could be a recommended form of nutrition support for patients with incurable gastrointestinal tumors in China.

Previous economic analysis focused on patients with malignant inoperable bowel obstruction (IBO), which demonstrated that HPN was associated with poor economic benefits. The administration of HPN for patients with malignant intestinal failure should be under a comprehensive and careful consideration (24). Different inclusion criteria of patients might account for the result. In our analysis, HPN for incurable gastrointestinal cancer patients was used as a supplemental nutrition support, while for patients with malignant intestinal failure, parenteral nutrition support was the primary source of energy and nutrition. Thus, application dosage, complication rates, and corresponding costs all increased. It suggested that early supplemental nutrition support for advanced cancer patients with malnutrition could improve economic benefits and further confirmed the significance and feasibility of sHPN. Besides, in our study, sHPN was administrated at 25%–35% of the daily nutritional need for 2–4 days/week based on the NCT02066363 trial. Due to a lack of data, we did not explore the cost-effectiveness of different sHPN dosages or frequencies. Therfore, the best mode of sHPN administration still needs further exploration.

Since sHPN has not been extensively promoted in China yet, our research could be a reference for pricing. Costs were calculated according to current prices in China. We did not reckon on the cost of training for sHPN because free seminars and training were held regularly in Chinese hospitals for patients by doctors, nurses, and pharmacists. However, common complications of sHPN mainly include infections, catheter obstructions, and thrombosis, which raise the significance of catheter care training for patients and homecare nurses (12, 25). Therefore, when sHPN is widely accepted and applied in China, full-time personnel should be set up to take charge of training and be paid a corresponding fee. With a WTP of $29,307/QALY in China, economic benefits could still be achieved if the training fee was set as $423.75. Besides, if sHPN could be covered by Chinese national medical insurance, further cost reductions could be achieved by bearing the costs of more additional services such as dietitian, pharmacist, and other healthcare workers.

Our research has the following advantages. First, our study is the first cost-effectiveness analysis of sHPN for incurable gastrointestinal cancer patients. Previous economic analyses of nutrition support mainly focused on the effect indexes such as changes in hospitalization stays, complication rates, and related markers (26). Our study conducted cost-effectiveness analyses from multiple dimensions by evaluating sHPN on both long-term survival and short-term objective indicators, which provided nutritional options for clinical practice in China. In addition, our study focused on patients with incurable gastrointestinal cancers. Previous studies have shown that tumor type had little impact on the prognosis of incurable cancer patients receiving HPN, thus our economic analysis might also be suggestive for patients with other types of cancer (27, 28).

There are also several limitations. Firstly, despite the benefits of sHPN, there is still a lack of universally accepted standards for the application of sHPN. The current study was based on the NCT02066363 trial, and thus the indication of sHPN was consistent with the trial. However, considering the huge population base and rare medical resources in China, the specific indications and criteria of the sHPN application still need further exploration. Secondly, the current economic analysis was based on the Chinese healthcare perspective, since costs vary widely among regions, and thus our results were applicable to the Chinese healthcare system and were limited to other countries with different healthcare systems (7, 27). However, due to the lack of clinical data for Chinese patients, our analysis was based on a Danish unicentral open-label RCT, and thus ethnic heterogeneity should be taken into consideration as well. Despite the clinical characteristics and survival of patients in the NCT02066363 trial were comparable with those of Asian patients, differences in BMI existed among different populations. Patients in Europe had a slightly higher average value of BMI than Asian patients (25–26 vs. 23–24) (29–31). Besides, considering the limited sample size, clinical results should be further confirmed by large-scale clinical trials. The stability of the results should be considered, especially for 6MWT due to missing values (17). Thirdly, the accurate cost of best practice nutritional care for patients in the non-sHPN group was unavailable, while only the cost of EN was reckoned in. Finally, the impact of HPN on distinct individuals varies, depending on their underlying disease and performance state (32). Thus, individualized treatment should be applied to the administration of HPN.

In conclusion, malnutrition is a common comorbidity for patients with incurable gastrointestinal cancers. Considering the unmet nutritional needs, we conducted cost-effectiveness analyses on the application of sHPN for patients with incurable gastrointestinal cancer, which showed sHPN was cost-effective and worthy of further promotion in China.

The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author.

The manuscript has been read and approved by all the authors, that all journal requirements for authorship have been met, and that each author believes that the manuscript represents honest work.

This work was supported by the National Natural Science Foundation of China [grant number 81874052]; Jilin Province Department of Finance [grant number JLSWSRCZX2020-0023]; Technology Development Program of Jilin Province [grant number 20190303146SF].

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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