Despite recent advances in chemotherapy for gastrointestinal cancer, a crucial factor related to lớn poor prognosis is reduced tolerance lớn chemotherapy induced by cancer cachexia. Fish oil (FO)-derived eicosapentaenoic acid (EPA) modulates inflammation in patients with various malignancies; however, the impact of FO-enriched nutrition as a combined modality therapy on clinical outcomes remains controversial. We systemically analysed chronological changes in biochemical and physiological status using bioelectrical impedance analysis in 128 gastrointestinal cancer patients provided with or without FO-enriched nutrition during chemotherapy. Furthermore, we evaluated the clinical significance of FO-enriched nutrition & clarified appropriate patient groups that receive sầu prognostic benefits from FO-enriched nutrition during treatment of gastrointestinal cancer. The control group showed significant up-regulation of serum CRP) levels và no significant difference in both skeletal muscle mass & lean body toàn thân mass. In contrast, the FO-enriched nutrition group showed no changes in serum CRP concentration và significantly increased skeletal muscle mass và lean body toàn thân mass over time. Furthermore, high CRPhường. levels significantly correlated with reduced tolerance to lớn chemotherapy, và FO-enriched nutrition improved chemotherapy tolerance and prognosis, particularly in gastrointestinal cancer patients with a modified Glasgow prognostic score (mGPS) of 1 or 2. We conclude that FO-enriched nutrition may improve the prognosis of patients with cancer cachexia và systemic inflammation (i.e., those with a mGPS of 1 or 2).

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Gastrointestinal (GI) cancer is the most common & lethal malignancy worldwide1. Of the top ten cancers leading khổng lồ cancer-related death, five sầu were classified as GI cancers, including oesophageal, gastric, colorectal, hepatobiliary & pancreatic cancers2. Furthermore, despite recent progress in surgical and medical treatments for GI cancer, these malignancies still result in 35% of all cancer deaths globally, và patients with advanced GI cancer still have sầu a poor prognosis2. Treatment for GI cancer patients is critically important in the current clinical situation.

Cancer cachexia occurs in up to 80% of patients with advanced cancer3, 4, especially those with gastrointestinal and pancreatic malignancies, and it is a major obstacle in terms of the morbidity and mortality of patients with advanced GI cancer5. Cancer cachexia is defined as a “multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment”3. Accumulating evidence has suggested that systemic inflammation related to lớn cancer is a pivotal mediator for the progression of cancer cachexia, & several pro-inflammatory cytokines released by both tumours & the host’s immune system, including interleukins (IL) 1, 2 & 6, interferon γ and TNF-α, have sầu been implicated in the pathogenesis of cachexia in GI cancer.

Accumulating evidence has revealed a strong correlation between cancer cachexia/sarcopenia and chemotherapeutic toxithành phố in patients with various types of cancer6,7,8. Pravày and colleagues analysed the association between the status of sarcopenia và chemotherapeutic toxicity in 55 women with advanced breast cancer resistant to lớn anthracycline and/or taxane treatment & clarified that sarcopenia was a predictor for capecitabine toxiđô thị in patients with metastatic breast cancer6. Similarly, two other studies demonstrated that decreased muscle mass was associated with an increased risk of grade 3–4 toxiđô thị for adjuvant and palliative chemotherapy in colon cancer patients7, 8. Furthermore, the status of systemic inflammation could be used as a marker for predicting chemotherapeutic outcome & prognosis in patients with various types of cancers9, 10. Collectively, cancer cachexia, induced by the systemic inflammatory response to lớn disease progression, increases the toxicity of chemotherapeutic treatment và exacerbates prognosis in GI cancer patients.

N-3 (omega-3) polyunsaturated fatty acids (FAs) from fish oil (FO) have plausible immune-modulating effects, partly caused by the formation of 3-series prostanoids and 5-series leukotrienes, with a low pro-inflammatory và immunosuppressive sầu effect11, 12. Specifically, eicosapentaenoic acid (EPA) is a naturally occurring omega-3 fatty acid found in FO & certain marine products và has been shown to have anti-genotoxic, antioxidant, & anti-inflammatory properties through suppressing IL-6 production, down-regulating the adễ thương phase response and reducing serum concentrations of C-reactive protein (CRP) in various types of cancer13. Despite evidence showing the anti-tumour and anti-cachexic activity of FO treatment in an animal mã sản phẩm of cachexia14, the potential advantages of FO-enriched supplementation in nutrition parameters, quality of life, compliance with chemotherapeutic treatment, và prognosis remain controversial. These advantages have not been clarified in previous clinical trials due to lớn several limitations, including little chronological biochemical and physiological evidence showing an alteration during nutritional intervention with FO, heterogeneous patient characteristics, little relevant nutritional support, & inadequate patient selection15, 16.

Previous work from our group has shown that several cytokines and serum markers reflecting the systemic inflammatory response, including IL-1b, IL-1ra, IL-6, IL-10, CRPhường, & albumin (Alb), are differentially expressed in serum from patients with advanced GI cancer và can be used as predictive biomarkers for postoperative sầu nutritional status, morbidity and mortality in GI cancer patients17,18,19,đôi mươi. To clarify the potential advantages of FO-enriched nutritional therapy in the treatment course of advanced GI cancer, we systemically investigated chronological alterations in biochemical và physiological status during chemotherapeutic treatment with or without FO-enriched nutrition in patients with advanced GI cancer. Furthermore, we analysed not only the association between FO-enriched nutritional therapy và tolerance of chemotherapeutic treatment but also the impact of FO-enriched nutrition on the long-term survival of these patients khổng lồ identify appropriate subgroups eligible for FO-enriched nutrition during the treatment of advanced GI cancer.

Serum CRPhường. levels increased along with tumour progression in patients with GI cancer

First, we analysed the serum concentrations of CEA (carcino-embryonic antigen), carbohydrate antigene 19–9 (CA19–9) and CRP in GI cancer patients over a treatment course with or without FO-enriched nutrition therapy (Supplementary Table 1, Fig. 1). Along with tumour progression, the serum concentrations of CEA và CA19-9 significantly increased in a time-dependent manner over both treatment courses (CEA: p = 0.003, 0.06; CA19-9: p = 0.046, 0.009, Supplementary Table 1). Furthermore, serum CRP.. levels were positively correlated with serum CEA levels in GI cancer patients (r = 0.27, p = 0.006, Supplementary Figure 1a).

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Figure 1


Chronological alterations in biochemical và physiological status during systemic chemotherapy in patients with GI cancer. (Upper line) Box plots are used to lớn represent the biochemical (serum CRP and CEA levels) and physiological status (skeletal muscle mass and lean body mass) of GI patients who received FO-enriched nutrition during systemic chemotherapy. Serum CRP levels were not significantly changed in the FO-enriched nutrition group of patients with GI cancer (p = 0.26), và there was a significant improvement in the skeletal muscle mass & lean body mass of this group (p = 0.0002 and p Full size image

Table 2 Multivariate analysis lớn identify predictors of tolerance to chemotherapeutic treatment in GI cancer patients.

Next, we focused on high-risk patients with elevated serum CRP.. levels (modified Glasgow prognostic score (mGPS) of 1 or 2) to lớn assess whether FO-enriched nutrition could affect the tolerance khổng lồ chemotherapy in these patients. Interestingly, analysis with the chi-square kiểm tra revealed that tolerance lớn chemotherapy tended to correlate with FO-enriched nutrition in GI cancer patients with an mGPS of 1 or 2 (p = 0.05, Table 3). Based on the chronological changes in biochemical và physiological factors observed in all patients, FO-enriched nutrition may not only suppress inflammatory responses along with disease progression but also improve the nutritional status of cancer cachexia. These changes are expected khổng lồ improve compliance with chemotherapeutic treatment, especially in patients with a systemic inflammatory response.

Table 3 Association between tolerance khổng lồ chemotherapy & clinicopathological factors in patients with GI cancer and an mGPS of 1 or 2.

FO-enriched nutrition significantly improved prognosis in GI cancer patients with an mGPS of 1 or 2

Finally, we evaluated the prognostic impact of FO-enriched nutrition in GI cancer patients. Survival curve analysis showed no significant differences between the patient groups with or without FO-enriched nutrition aước ao the total cohort (p = 0.84, Fig. 2a). However, the patients with an mGPS of 1 or 2 had a significantly better prognosis when they received FO-enriched nutrition (p = 0.0096, Fig. 2b). In addition, analysis using a Cox proportional hazards Model demonstrated that FO-enriched nutrition is an independent predictor for improvement of prognosis in patients with an mGPS of 1 or 2 (HR:0.24, 95%CI: 0.06–0.98, p = 0.045, Table 4). Collectively, our data clearly show that FO-enriched nutrition could improve sầu chemotherapeutic treatment compliance and prognosis in patients with an mGPS of 1 or 2.

Figure 2


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The mGPS was determined as previously described31, 32. Briefly, patients with elevated CRPhường (>0.5 mg/dl) were given a score of 1 or 2 depending on the absence or presence of hypoalbuminemia (



Edge SB BD, C. C., Fritz AG, Greene FL, Trotti A, eds. AJCC Cancer Staging Manual. 7th ed. New York: Springer. (2010).