Evaluation of a 3-month intervention with high protein, omega-3 LC-PUFA enriched oral nutritional supplement on body weight, inflammation, muscle strength and patient reported outcomes in patients with cancer

Evaluation of a 3-month intervention with high protein, omega-3 LC-PUFA enriched oral nutritional supplement on body weight, inflammation, muscle strength and patient reported outcomes in patients with cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Evaluation of a 3-month intervention with high protein, omega-3 LC-PUFA enriched oral nutritional supplement on body weight, inflammation, muscle strength and patient reported outcomes in patients with cancer Petra Beran Holeckova, Viktor Rosenberg, Vera Lanska, Marek Tomecka, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7453912/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose To compensate for reduced nutritional intake and altered metabolic needs in cancer, ESMO and ESPEN recommend higher than normal energy and protein intake, with omega-3 long chain polyunsaturated fatty acid (LC-PUFA) supplementation to target inflammation. Methods In this multi-center, single arm study adult outpatients with or at risk of malnutrition and requiring ONS were prescribed 2 x 125 ml high protein (HP), omega-3 LC-PUFA enriched ONS (Forticare Advanced, 18 g protein, 306 kcal, 1.1 g EPA, 0.7 g DHA, 10 µg vitamin D) daily for 3 months. Body weight (BW), adherence to ONS (primary outcomes), C-reactive protein (CRP), hand grip strength (HGS), 30-second chair stand test (CST) and patient reported outcomes were assessed at baseline (Day 0), 1 and 3 months. Results 761 patients (47.5% male, mean age 65 (SD 12) years) were included. At baseline, 77.9% of patients had > 5% weight loss (WL) and had higher CRP and lower albumin levels than patients with < 5% WL (p < 0.001). Average adherence to the ONS was 1.7 (85%) bottles/d, despite 34% of patients reporting altered taste/smell. Mean gain in BW was 1 kg (p < 0.0001) with 76% of patients gaining or stabilizing BW over 3 months. CRP levels decreased (mean − 7.5 mg/L (p < 0.0001), physical performance improved (increase in HGS (+ 1.2 kg, p < 0.0001) and CST (+ 1.4 stands, p < 0.0001)) and patients reported improved physical aspects of quality of life (p < 0.001) at 3 months. Conclusion In this study, patients with cancer prescribed HP, omega-3 LC-PUFA enriched ONS for 3-months gained weight, experienced reduced inflammation, and improved physical performance and patient reported outcomes. oral nutritional supplements high protein omega-3 LC-PUFA cancer strength patient reported outcomes Figures Figure 1 Figure 2 Figure 3 1. Introduction Malnutrition in cancer is highly prevalent affecting 14–67% of patients depending on disease site [ 23 ] with adverse consequences such as poorer tolerance of systemic chemotherapy, reduced performance status, quality of life (QOL) and survival [ 36 ]. Nutrition impact symptoms (e.g. appetite loss, nausea, dry mouth, early satiety and taste changes) are common in cancer [ 17 , 40 ], are known to progress over the cancer journey [ 16 , 32 ], are associated with reduced dietary intake [ 2 , 37 ], have an adverse effect on QOL and are associated with eating-related distress [ 2 , 7 , 14 , 40 ]. Low muscle mass, a key feature of malnutrition, has been shown to be an independent predictor of dose-limiting anti-cancer treatment toxicity, with muscle loss considered a strong predictor of survival [ 4 , 30 ]. Loss of muscle is not only detrimental to clinical outcome but also to outcomes that matter to patients such as QOL [ 22 ]. Meeting nutritional needs in cancer is challenging due to effects of cancer itself and the side effects of treatment including chemosensory alterations which negatively affect QOL [ 7 , 8 ]. Up to 70% of patients with cancer experience taste and smell changes during chemotherapy and radiotherapy and these sensory alterations may persist up to one year after treatment [ 39 ]. To compensate for reduced intake and altered metabolic needs, guidelines from The European Society for Clinical Nutrition and Metabolism (ESPEN) [ 30 ] and the European Society for Medical Oncology (ESMO) [ 5 ] on nutrition in cancer recommend higher than normal energy and protein intake; 25–30 kcal/kg/day (if energy expenditure is not measured individually) and protein intake of 1.0-1.5 g/kg/day. Likened to a wildfire, muscle loss is rapid and difficult to regain with diverse causes including inflammation [ 35 ]. Inflammation has detrimental effects on nutritional status through promoting anorexia (reducing nutrient intake), increasing muscle catabolism, increasing resting energy expenditure and blunting response to nutrition intervention and is one of the etiological criterion for the Global Leadership Initiative on Malnutrition (GLIM) diagnosis of malnutrition [ 3 , 11 ]. To target inflammation, the ESPEN guidelines recommend supplementation with omega-3 long chain polyunsaturated fatty acids (LC-PUFA) or fish oil to improve appetite and BW in patients with advanced cancer undergoing chemotherapy at risk of weight loss or who are malnourished [ 30 ], with ESMO recommending omega-3 LC-PUFA enriched ONS for patients undergoing chemotherapy, radiotherapy or chemoradiotherapy to increase BW, attenuate lean body mass and improve QOL [ 5 ]. Omega-3 LC-PUFA are known for their anti-inflammatory properties and it has been suggested that they may inhibit tumour growth through effects on membrane signaling [ 9 ]. Supplementation with omega-3 LC-PUFA has been shown to be safe, to reduce inflammatory markers and increase survival in patients with cancer (22). Increasing protein intake positively impacts muscle mass and function in patients with cancer [ 10 , 21 ]. For patients unable to meet nutritional needs through diet alone, expert guidance recognise oral nutritional supplements (ONS) as an effective and non-invasive part of nutritional care [ 5 , 30 ]. In patients undergoing cancer therapy high protein supplementation mitigates weight loss, improves muscle strength and reduces hospitalisation rates [ 33 ]. Despite expert guidance and evidence of benefit, in clinical practice nutrition intervention is often overlooked or delivered too late. Integration of structured processes for early management of malnutrition and cachexia in cancer offers the potential to intervene in the patient journey at a point when the intervention is likely to be effective in minimising the adverse effects of malnutrition and cachexia on anti-cancer therapy (1). To bridge the evidence-practice gap pragmatic trials that assess interventions in clinical settings that resemble standard of care and focus on patient-oriented outcomes are needed [ 34 ]. In this prospective, pragmatic, single-arm trial evaluating a 3-month nutrition intervention with a HP omega-3 LC-PUFA enriched ONS in patients with or at risk of malnutrition, the primary objective of the study was to observe patient outcomes in a real-world setting. To better understand the patients’ perspective patient-reported outcomes were collected, an often overlooked aspect in clinical trials [ 31 ]. 2. Materials and Methods 2.1 Study Design and Population This pragmatic, prospective, single-arm, longitudinal, interventional, multi-centre study was carried out in the Czech Republic and Slovakia in 69 outpatient centres. The schedule of assessments and study design are outlined in Fig. 1 . The inclusion criteria were: patients meeting the requirements for prescription of Oral Nutritional Supplements (ONS), patients undergoing active/radical oncological treatment (curative or palliative chemotherapy, radiotherapy and concomitant chemoradiotherapy) with newly diagnosed malnutrition, patients with a diagnosis of tumour types associated with high nutritional risk and aged between 18 and 80 years of age. Screening for malnutrition risk and assessment for prescription of ONS was undertaken according to the standard protocol in each country. In the Czech Republic the standard protocol developed by the Working Group on Nutritional Care in Oncology (Pracovní skupina nutriční péče v onkologii, PSNPO) was used. Patients were weighed and were asked to report previous weight (6 months ago), height and food intake. The patient’s healthcare professional (HCP) calculated percentage weight loss, BMI and in combination with details of age and diagnosis, assigned a risk of malnutrition score. In the Czech Republic if the malnutrition risk score was ≥ 2 (maximum score possible was 4) and required prescription of ONS the patient fulfilled the study eligibility criteria for risk of malnutrition. In Slovakia a similar protocol was employed, the ‘Protocol of the initial indication for ambulatory enteral nutrition for adult patients’ developed by the Ministry of Health in association with the local society for parenteral and enteral nutrition. The protocol was completed by the patient’s HCP and included a two-step process. If initial assessment of percentage weight loss, anthropometric measures and income resulted in a score of ≥ 1, the second step was completed which included a clinical evaluation of nutritional status and underlying clinical diagnosis. A score of ≥ 2 indicated the presence of malnutrition and the need for prescription of ONS. Patients were excluded if they i) were unable to provide information to enable the HCP to complete the study questionnaire, ii) could not have their weight or height measured, iii) had uncontrolled diabetes mellitus, iv) had a known allergy to milk protein and milk products, or v) were receiving full or partial enteral tube feeding or parenteral nutrition. The study was conducted according to the main principles of Good Clinical Practice. The protocol was submitted to the Bulovka University Hospital, Prague, Czech Republic Ethics Committee and approved prior to the start of the study (registration number: 10.1.2023/10711/EK-Z) on the 12th of January 2023. All patients provided informed written consent before any study procedures were performed. Figure 1 shows the study design and schedule of assessments. 2.2 Nutrition Intervention Patients were prescribed two bottles of a liquid, ready to drink, low volume, high protein (HP), energy dense, omega-3 long chain polyunsaturated fatty acid (LC-PUFA) enriched ONS (Forticare Advanced, Nutricia) daily for 3 months in addition to habitual food intake. Each 125 ml bottle contained 18 g of protein, 306 kcal, 1.1 g of eicosapentaenoic acid (EPA), 0.7 g of docosahexaenoic acid (DHA) and 10 µg of vitamin D. The study product flavours have previously been validated with patients with cancer and are specifically designed to address the needs of patients with taste alterations [ 25 ]. Patients were offered a choice of two flavours of the ONS (Cool Berry and Cool Mango Peach). Other than the provision of the ONS patients received the usual care provided by their outpatient centre. 2.3 Outcome Measures BW (kg), BMI (kg/m 2 ), C-reactive protein (CRP) (mg/L) and albumin (g/dL) were measured according to the outpatient clinic’s usual procedures. Hand grip strength (HGS) (kg) of the non-dominant hand was measured using a dynamometer (Saehan DHD-1 and KERN MAP 80K1 N/A) with oral training provided on measurement procedures. Due to the resources available only 18 centres received a dynamometer. The 30-second chair stand test (CST) was used to assess the number of times the patient was able to stand up from a chair in 30 seconds (see Online Resource 1 for instructions used). Patient reported outcomes of physical aspects of QOL were assessed by four answer categories (certainly no, almost no, almost yes, certainly yes) to three simple questions i) Are you able to walk for 20 minutes? ii) Did you need to rest during the day? and iii) Did you feel weak during the last week. The three questions were developed in consultation with oncologists and were designed to ensure that the protocol was feasible in clinical practice. Patients were asked to report the perceived benefits of the ONS at one month and three months, and at three months to report how they felt (themes relating to energy, strength, physical activity, ability to do activities, generally feeling better, appearance and BW) and about changes in their perception of taste and smell from before the beginning of their anti-cancer treatment. Details of these patient questions are available in the Online Resource 1. Adherence to the ONS was recorded at one month and three months and was based on patients’ reported average daily consumption of the ONS (i.e. 0, 0.5, 1, 1.5 or 2 bottles per day). At one month and three months patients were asked to indicate if they liked (Yes/No) the ONS. 2.4 Statistics and Data Analysis Patient recruitment for this study was conducted over a defined time period rather than being based on a pre-specified sample size calculation. The final sample size reflects the number of patients enrolled during the recruitment timeframe between February 2023 and March 2024. Statistical calculations were done by JMP®, Version 17.2.0. SAS Institute Inc., Cary, NC, 2022–2023. Normal distribution was tested by Shapiro-Wilk test. Continuous variables were described by mean and standard deviation. For discrete variables absolute and relative frequencies were used. Change in time was evaluated by paired t-test or Wilcoxon signed rank test for continuous variables and by McNemar’s test for discrete ones. Difference between two independent groups was tested by t-test or Mann-Whitney‘s test for continuous variables. All tests were two-sided and p less than 0.05 was considered statistically significant. 3. Results 3.1 Recruitment and patient characteristics A total of 880 patients were assessed for eligibility to participate, of whom 39 were excluded because they did not fulfil the inclusion criteria or declined to participate. Due to difficulties attending the clinic 55 patients did not start the study. A further 25 patients were lost to follow up. Therefore, data from 761 patients were included in the final per-protocol analysis (Figure S1 in the Online Resource 1). The baseline demographic characteristics of the 761 participating patients (47.5% male) are presented in Table 1 . Patients’ ages ranged from 29 to 95 years (mean 65 years, SD 12). At baseline although only 11.6% of patients had a BMI of less than 18.5 kg/m 2 , in total 77.9% of patients had experienced unplanned BW loss (WL) of greater than 5% (5–10% WL (53.5%) and > 10% WL (24.4%)) in the last six months. Eighty-seven per cent of patients had a CRP level of greater than 5 mg/L at baseline and 56.9% of patients had an albumin level below 35 g/dL at baseline. Patients with greater than 5% weight loss at baseline had higher CRP and lower albumin levels than patients with less than 5% weight loss at baseline (p < 0.001). Fifty-two per cent of patients were receiving anti-cancer treatment with palliative intent and 47.7% with curative intent. All major cancer types were represented. Table 1 Demographic and clinical characteristics of participating patients at baseline (n = 761). Parameter Mean (SD) Age (years) a 65 (12) n (%) Sex b Females Males 394 (52.5) 357 (47.5) Body Mass Index (kg/m 2 ) c 30 86 (11.6) 470 (63.4) 162 (21.9) 23 (3.1) Unplanned body weight loss in the last six months (kg) d 10% 166 (22.0) 403 (53.5) 184 (24.4) C-reactive protein (mg/L) e 100 93 (12.9) 155 (21.6) 398 (55.4) 48 (6.7) 25 (3.5) Albumin (g/dL) f 35 418 (56.9) 20 (2.7) 297 (40.4) Treatment intent g Curative Palliative 356 (47.7) 389 (52.2) Tumour site h Lower gastrointestinal Liver, pancreas, gallbladder, biliary tract Breast Oesophageal, stomach and duodenum Head and neck/ear, nose, throat Lung Urological Gynaecological Malignant melanoma and tumour of the skin Haematological Non-site specific/primary site unknown Thyroid and other endocrine Other j 135 (19.0) 113 (15.9) 94 (13.3) 82 (11.6) 78 (11.0) 67 (9.4) 51 (7.2) 32 (4.5) 15 (2.1) 14 (2.0) 12 (1.7) 7 (1.0) 9 (1.3) Numbers do not add up to n = 761 due to missing values. i Includes non-site specific/ill-defined or multiple independent primary sites or primary site unknown; j Includes tumours of the bone, joint, eye and abdominal cavity. 3.2 Anthropometrics and adherence (primary outcomes) A statistically significant increase in mean BW and mean BMI was observed from baseline to three months (Table 2 ). Overall, 76% of patients gained or stabilized BW (63% gained > 1 kg, 13% were weight stable i.e. ± 1 kg) and 24% of patients lost more than 1 kg BW. Average adherence to the ONS was 1.7 (85%) bottles per day at 1 month. There was no significant change in adherence between the first and third month of the study (1.7 vs 1.6 bottles/day, p = 0.1115, n = 733). The ONS received a positive response for overall liking, with 92% of respondents expressing overall liking in the first month and 90% in the third month (p = 0.073). 3.3 Laboratory parameters There was a statistically significant decrease in mean CRP of 7.5 mg/L from baseline to three months (p < 0.0001) and a statistically significant increase in mean albumin of 1.0 g/dL from baseline to three months (p < 0.0001) (Table 2 ) 3.4 Muscle strength There was a statistically significant improvement in muscle strength from baseline to three months, mean HGS increased by 1.2 kg (p < 0.0001) and the mean number of stand ups in the 30 second CST increased by 1.4 (p < 0.0001) (Table 2 ). Table 2 Mean BW, BMI, albumin, CRP, 30 second chair stand test and hand grip strength at baseline, 1 month and 3 months (per protocol). n Baseline (SD) 1 month (SD) 3 months (SD) Difference (0–3 months) Mean 95% CI p-value Body weight (kg) 743 66.0 (12.5) 66.1 (12.2) 67.0 (12.1) 1.0 0.76–1.25 < 0.0001 Body Mass Index (kg/m 2 ) 727 22.7 (3.8) 22.7 (3.6) 23.0 (3.6) 0.34 0.25–0.42 < 0.0001 C-reactive protein (mg/L) 687 22.6 (29.7) 18.1 (26.2) 15.1 (24.8) -7.5 -5.28- -9.66 < 0.0001 Albumin (g/dL) 709 34.2 (7.7) 34.6 (7.8) 35.2 (7.5) 1.0 0.71–1.29 < 0.0001 30 second chair stand test (number of stand ups) 706 6.7 (3.8) 7.3 (4.1) 8.0 (4.7) 1.4 1.19–1.53 < 0.0001 Hand grip strength (kg) 304 18.9 (10.5) 19.0 (10.6) 20.0 (11.1) 1.2 0.74–1.63 < 0.0001 Paired t-test used for all, with the exception of CRP for which the Wilcoxon test was used. 3.5 Patient reported physical aspects of QOL Physical performance aspects of QOL improved from baseline to 3 months. (Fig. 2 ). 3.6 Taste and smell changes At three months 34.5% of patients reported a change in taste and smell perception during anti-cancer treatment (data available for n = 754). Of the 260 patients who reported a change in taste and smell perception at 3 months compared to before the beginning of anti-cancer treatment, 94% reported changes to their sense of taste and 88% reported changes to their sense of smell. Details of the changes experienced are shown in Online Resource 1. 3.7 Perceived benefits reported by patients At either 1 month, 3 months or both, patients reported a perceived benefit of the ONS on a range of points (Table 3 ). Table 3 Perceived benefits of the ONS reported by patients at 1 month, 3 months or both. Perceived benefit reported by patients n Answered yes at either 1 month, 3 months or both (%) It supplemented my daily food intake 714 57 My physical condition has improved 726 44 I have gained weight 680 35 It supports my treatment 684 51 It gives me back my lost strength 712 44 I am more self-reliant 666 30 All of the above 737 55 No perceived benefit 738 1 At three months most patients reported improved feelings relating to energy, strength and ability to undertake activities, however feeling able to maintain a healthy weight was reported less (21%) (Fig. 3 ). 4. Discussion To our knowledge this prospective, pragmatic, single-arm, multi-centre interventional study is the first to investigate the effects of a low volume, HP, high energy, omega-3 enriched LC-PUFA ONS in outpatients with cancer reflecting real-world clinical settings, and in particular, to assess patient-reported outcomes. In this study, patients with cancer prescribed HP, omega-3 LC-PUFA enriched ONS for 3-months gained weight, experienced reduced inflammation and improved physical performance. Although one in three patients reported altered taste or smell, average adherence to the ONS was excellent and patients reported perceived benefits of the ONS. Reflecting increased understanding over time of the role of omega-3 LC-PUFA in modulating inflammation in cancer, many studies have investigated the effects of omega-3 LC-PUFA enriched ONS on outcomes in patients with cancer and have been included in wider reviews [ 15 , 18 , 26 , 42 ]. However, many included studies had small sample sizes (range n = 13 to 200) and short duration of intervention (range 1 to 12 weeks, majority (8/14) of studies ≤ 6 weeks) [ 15 , 18 , 26 , 42 ]. Similarly, studies conducted more recently had small sample sizes (n = 37 to 159) but, in some, intervention periods were longer (range 5 to 24 weeks, in 2/4 studies duration ≥ 12 weeks) [ 1 , 12 , 38 , 41 ]. In the present study the improvement in mean BW (n = 743) and mean BMI (n = 727) observed from baseline to three months is in line with Cereda et al. (2018) who demonstrated that the use of an omega-3 fatty acid enriched ONS (18% energy from protein, 2 kcal/ml) during radiotherapy and for 12 weeks post-radiotherapy in patients with head and neck cancer (n = 136) resulted in a significantly smaller loss of BW than nutritional counselling alone, with patients in the ONS group more likely to maintain BW during the intervention period [ 12 ]. Vidal Casariego et al. (2023) found that malnourished cancer outpatients (n = 37) supplemented with HP ONS enriched with omega-3 LC-PUFA and L-leucine (2 kcal/ml) over 8 weeks had a tendency to return to their initial BW at the first assessment and increase BW at the end of the follow-up period compared to a slight decrease in BW in a group supplemented with standard HP ONS, however neither of these observations reached statistical significance [ 41 ], possibly due to the short intervention time. In an RCT of HP EPA-enriched ONS (1.27 kcal/ml) vs normal diet in pre-operative patients with pancreatic cancer (n = 62) Akita et al. (2019) showed no difference in BMI pre to post intervention ratio, but noted that the control group showed a significant decline in BW during the study which was not seen in the intervention group [ 1 ]. The study duration was short (5 weeks) and adherence to the ONS was poor which may have contributed to the lack of positive effect on BW in the intervention group. Adherence to the ONS in the present study was excellent (85%), with no significant change in adherence or overall liking of the ONS across the 3-month duration of the study, likely due to the low volume (2.4 kcal/ml) of the ONS and flavours specifically tailored for and tested by patients with cancer (30). Good adherence rates (patient-reported) have also been observed in other studies, 80% in malnourished cancer outpatients taking a HP, omega-3 LC-PUFA, L-leucine enriched ONS (2 kcal/ml) [ 41 ] and 73.4% in well-nourished patients with lung and colorectal cancer taking a low volume HP ONS (2.4kcal/ml) [ 20 ]. A fair adherence rate of 60% of the ONS prescription target (recorded by care givers and dietitians) was reported by Cereda et al. (2018) [ 12 ]. ‘Disagreeable’ taste of the ONS was reported as a key reason for low adherence (55% subjects (17/31) consuming < 50%) to five weeks of supplementation with a HP, EPA-enriched ONS (1.27 kcal/ml) in pre-surgical patients with pancreatic cancer [ 1 ], illustrating that a combination of low volume and specifically tailored flavours may be key attributes to support adherence. Improvement in muscle strength, assessed using HGS and the 30 second CST, was statistically significant and patients reported improvements in physical performance aspects of QOL from baseline to 3 months. These objectives, easy to perform and low-cost methods were chosen as they can be feasibly implemented in clinical practice. HGS is correlated with muscle mass (MM) [ 29 ] and predicts survival [ 13 ] in patients with cancer and CST is patient-centered, safe, feasible and can also be used remotely [ 6 ]. The use of patient-reported outcomes are key to enhancing patient care [ 19 ]. Whilst previous studies have shown that supplementation with protein and omega-3 fatty acid fortified ONS increase MM and confer benefits on some measures of function and QOL, changes were not always seen in HGS [ 1 , 38 , 41 ]. Cereda et al. (2018) measured HGS in patients with head and neck cancer undergoing radiotherapy and showed a trend towards significance favouring the intervention group vs controls and, although they found no effect on change in Phase angle, they did observe a significant difference over time in favour of the intervention for recovery of QOL [ 12 ]. In the present study, statistically significant improvements in mean CRP and albumin from baseline to three months were observed. Shirai et al. (2017) showed that fish oil-enriched ONS inhibited increases in serum CRP levels compared to subjects in the control group in whom a significant increase in CRP was observed during intervention [ 38 ]. High baseline inflammatory status may hinder response to nutrition intervention [ 27 ] and should therefore be considered when selecting the most appropriate nutrition support [ 43 ]. Interestingly, a higher intake of a HP omega-3 LC-PUFA and L-leucine enriched ONS has been observed when patients’ nutritional and clinical condition worsened which was not observed in a group taking a standard HP ONS, possibly related to appetite-stimulating properties of Omega-3 LC-PUFA (45). The main strengths of this study include the large number of participating patients across a broad range of tumour types, the pragmatic nature of the study and the collection of nutritional outcome data, both objective and patient-reported, in real-world settings. Implementation of nutritional care in practice is often limited [ 23 ], hampered by lack of awareness, lack of nutrition education and lack of standard operating procedures, clearly defined responsibilities and healthcare professional collaboration [ 4 ]. Individualisation of nutritional care managed by nutrition experts is not always available to all patients and may be focused on the most complex cases due to resource constraints, however early and appropriate nutrition intervention delivered by the wider healthcare team that meets patient’s individual needs, preferences and goals is still achievable with the use of evidence-based protocols or pathways [ 24 ] and is preferable to lack of intervention. The present study contributes useful insights on the topic but also has some limitations. Although the single-arm design enabled all patients to receive intervention possibly encouraging participation, the lack of a control group means that the benefits observed may not be solely due to the ONS intervention. The number of participating centres was large showing extensive interest in nutritional care, however there was likely some variation in local procedures although nationally agreed protocols for screening for nutritional risk and for prescribing ONS were followed. Patient reported outcomes were gathered, in particular patients’ perceived benefits of ONS and feelings in relation to energy and ability to undertake activities, however the measures used were not validated which could be a focus for future work. Only eighteen centres (26%) had access to HGS due to limited resources, nevertheless the data obtained is promising and shows that use of HGS is acceptable in practice. Adherence to the ONS was self-reported but this is feasible in practice and is a frequently used method for reported adherence in studies of ONS [ 20 , 28 ]. Although dietary intake was not recorded and evaluated in the present study, a previous study of a low volume, HP ONS showed that intake from ONS increases protein intake in patients with cancer [ 20 ]. While the predefined inclusion criteria specified an age range of 18 to 80 years, a protocol deviation resulted in the inclusion of several individuals above this range, with the oldest patient being 95 years of age. Fifty-five eligible patients did not start the study due to issues with attendance at clinics and a further twenty-five were lost to follow up but it is likely that this reflects real-world practice. 5. Conclusions In this large, single-arm, pragmatic, interventional study, outpatients receiving anti-cancer treatment across a broad range of cancer types prescribed low volume, HP omega-3 LC-PUFA enriched ONS for 3-months gained weight, experienced reduced inflammation and improved physical performance. Average adherence to the ONS was excellent and patients reported perceived benefits of the ONS. The ONS was prescribed in real-world settings following nationally agreed protocols, which could be replicated elsewhere to ensure nutrition intervention is implemented in a timely way that meets patients’ needs. Declarations Funding This study was funded by Danone Research and Innovation. Writing and editorial services were supported by Danone Research and Innovation. Competing interests P. Holeckova, received research support, travel support and speaker honoraria from Danone Research and Innovation. V. Rosenberg and V. Lanska received research support from Danone Research and Innovation. M. Tomecka and J. Smitka are employees of Danone. The funders contributed to the design of the study; in the analyses and interpretation of data; in the writing of the manuscript; and in the decision to publish the results. Author Contributions Conceptualization: P. Holečková; Methodology: P. Holečková; Formal analysis and investigation: V. Lanska; Writing - review and editing: P. Holečková; Funding acquisition: M. Tomecka, J. Smitka; Supervision: V. Rosenberg. All authors read and approved the final manuscript. Ethics Approval The study was conducted according to the main principles of Good Clinical Practice. The protocol was submitted to the Bulovka University Hospital, Prague, Czech Republic Ethics Committee and approved prior to the start of the study (registration number: 10.1.2023/10711/EK-Z) on the 12th of January 2023. Consent to participate Informed consent was obtained from all subjects involved in the study. Data Availability Statement The datasets presented are available upon reasonable request. Any requests will be reviewed against adherence with ethical, scientific, regulatory, and legal requirements. Requests to access the datasets should be directed to [email protected] Supplementary Information The ‘Online Resource 1’ file contains the instructions used for the 30-second chair stand test, the questions used to gather patient reported measures, Figure S1 showing the flow diagram of patient recruitment and study participation and further Figures showing results for CRP, albumin, hand grip strength and chair stand test, and patient reported taste and smell changes. References Akita H, Takahashi H, Asukai K, Tomokuni A, Wada H, Marukawa S, Yamasaki T, Yanagimoto Y, Takahashi Y, Sugimura K, Yamamoto K, Nishimura J, Yasui M, Omori T, Miyata H, Ochi A, Kagawa A, Soh Y, Taniguchi Y, Ohue M, Yano M, Sakon M (2019) The utility of nutritional supportive care with an eicosapentaenoic acid (EPA)-enriched nutrition agent during pre-operative chemoradiotherapy for pancreatic cancer: Prospective randomized control study Clinical Nutrition ESPEN 33: 148–153 10.1016/j.clnesp.2019.06.003 Amano K, Baracos VE, Mori N, Okamura S, Yamada T, Miura T, Tatara R, Kessoku T, Matsuda Y, Tagami K, Otani H, Mori M, Taniyama T, Nakajima N, Nakanishi E, Kako J, Morita T, Miyashita M (2024) Associations of nutrition impact symptoms with dietary intake and eating-related distress in patients with advanced cancer Clinical Nutrition ESPEN 60: 313–319 https://doi.org/10.1016/j.clnesp.2024.02.027 Arends J, Baracos V, Bertz H, Bozzetti F, Calder PC, Deutz NEP, Erickson N, Laviano A, Lisanti MP, Lobo DN, McMillan DC, Muscaritoli M, Ockenga J, Pirlich M, Strasser F, de van der Schueren M, Van Gossum A, Vaupel P, Weimann A (2017) ESPEN expert group recommendations for action against cancer-related malnutrition Clin Nutr 36: 1187–1196 10.1016/j.clnu.2017.06.017 Arends J, Muscaritoli M, Anker S, Audisio R, Barazzoni R, Bosnjak S, Bossi P, Bowman J, Gijssels S, Krznarić Ž, Strasser F, Aapro M (2023) Overcoming barriers to timely recognition and treatment of cancer cachexia: Sharing Progress in Cancer Care Task Force Position Paper and Call to Action Critical Reviews in Oncology/Hematology 185: 103965 https://doi.org/10.1016/j.critrevonc.2023.103965 Arends J, Strasser F, Gonella S, Solheim TS, Madeddu C, Ravasco P, Buonaccorso L, de van der Schueren MAE, Baldwin C, Chasen M, Ripamonti CI (2021) Cancer cachexia in adult patients: ESMO Clinical Practice Guidelines ESMO Open 6: 100092 10.1016/j.esmoop.2021.100092 Bowman A, Denehy L, Benjemaa A, Crowe J, Bruns E, Hall T, Traill A, Edbrooke L (2023) Feasibility and safety of the 30-second sit-to-stand test delivered via telehealth: An observational study PM&R 15: 31–40 https://doi.org/10.1002/pmrj.12783 Bressan V, Bagnasco A, Aleo G, Catania G, Zanini MP, Timmins F, Sasso L (2017) The life experience of nutrition impact symptoms during treatment for head and neck cancer patients: a systematic review and meta-synthesis Support Care Cancer 25: 1699–1712 10.1007/s00520-017-3618-7 Brisbois TD, de Kock IH, Watanabe SM, Baracos VE, Wismer WV (2011) Characterization of chemosensory alterations in advanced cancer reveals specific chemosensory phenotypes impacting dietary intake and quality of life J Pain Symptom Manage 41: 673–683 10.1016/j.jpainsymman.2010.06.022 Calder PC (2012) Mechanisms of Action of (n-3) Fatty Acids1,2 The Journal of Nutrition 142: 592S-599S https://doi.org/10.3945/jn.111.155259 Capitão C, Coutinho D, Neves PM, Capelas ML, Pimenta NM, Santos T, Mäkitie A, Ravasco P (2022) Protein intake and muscle mass maintenance in patients with cancer types with high prevalence of sarcopenia: a systematic review Supportive Care in Cancer 30: 3007–3015 10.1007/s00520-021-06633-8 Cederholm T, Jensen GL, Ballesteros-Pomar MD, Blaauw R, Correia MITD, Cuerda C, Evans DC, Fukushima R, Ochoa Gautier JB, Gonzalez MC, van Gossum A, Gramlich L, Hartono J, Heymsfield SB, Jager-Wittenaar H, Jayatissa R, Keller H, Malone A, Manzanares W, McMahon MM, Mendez Y, Mogensen KM, Mori N, Muscaritoli M, Nogales GC, Nyulasi I, Phillips W, Pirlich M, Pisprasert V, Rothenberg E, de van der Schueren M, Shi HP, Steiber A, Winkler MF, Barazzoni R, Compher C (2024) Guidance for assessment of the inflammation etiologic criterion for the GLIM diagnosis of malnutrition: A modified Delphi approach Clinical Nutrition 43: 1025–1032 10.1016/j.clnu.2023.11.026 Cereda E, Cappello S, Colombo S, Klersy C, Imarisio I, Turri A, Caraccia M, Borioli V, Monaco T, Benazzo M, Pedrazzoli P, Corbella F, Caccialanza R (2018) Nutritional counseling with or without systematic use of oral nutritional supplements in head and neck cancer patients undergoing radiotherapy Radiother Oncol 126: 81–88 10.1016/j.radonc.2017.10.015 Cereda E, Tancredi R, Klersy C, Lobascio F, Crotti S, Masi S, Cappello S, Stobäus N, Tank M, Cutti S, Arcaini L, Bonzano E, Colombo S, Pedrazzoli P, Norman K, Caccialanza R (2022) Muscle weakness as an additional criterion for grading sarcopenia-related prognosis in patients with cancer Cancer Med 11: 308–316 10.1002/cam4.4362 Crowder SL, Douglas KG, Yanina Pepino M, Sarma KP, Arthur AE (2018) Nutrition impact symptoms and associated outcomes in post-chemoradiotherapy head and neck cancer survivors: a systematic review J Cancer Surviv 12: 479–494 10.1007/s11764-018-0687-7 de Aguiar Pastore Silva J, Emilia de Souza Fabre M, Waitzberg DL (2015) Omega-3 supplements for patients in chemotherapy and/or radiotherapy: A systematic review Clin Nutr 34: 359–366 10.1016/j.clnu.2014.11.005 de Oliveira Hinokuma AF, de Andrade PC, Höfelmann DA (2025) Progression of nutritional impact symptoms in cancer patients undergoing radiotherapy Support Care Cancer 33: 108 10.1007/s00520-025-09172-8 de Pinho NB, Martucci RB, Rodrigues VD, D'Almeida CA, Thuler LCS, Saunders C, Jager-Wittenaar H, Peres WAF (2020) High prevalence of malnutrition and nutrition impact symptoms in older patients with cancer: Results of a Brazilian multicenter study Cancer 126: 156–164 10.1002/cncr.32437 de van der Schueren MAE, Laviano A, Blanchard H, Jourdan M, Arends J, Baracos VE (2018) Systematic review and meta-analysis of the evidence for oral nutritional intervention on nutritional and clinical outcomes during chemo(radio)therapy: current evidence and guidance for design of future trials Annals of oncology 29: 1141–1153 10.1093/annonc/mdy114 Di Maio M, Basch E, Denis F, Fallowfield LJ, Ganz PA, Howell D, Kowalski C, Perrone F, Stover AM, Sundaresan P, Warrington L, Zhang L, Apostolidis K, Freeman-Daily J, Ripamonti CI, Santini D (2022) The role of patient-reported outcome measures in the continuum of cancer clinical care: ESMO Clinical Practice Guideline Annals of Oncology 33: 878–892 10.1016/j.annonc.2022.04.007 Dingemans AM, van Walree N, Schramel F, Soud MY, Baltruškevičienė E, Lybaert W, Veldhorst M, van den Berg CA, Kaasa S (2023) High Protein Oral Nutritional Supplements Enable the Majority of Cancer Patients to Meet Protein Intake Recommendations during Systemic Anti-Cancer Treatment: A Randomised Controlled Parallel-Group Study Nutrients 1510.3390/nu15245030 Ford KL, Sawyer MB, Ghosh S, Trottier CF, Disi IR, Easaw J, Mulder K, Koski S, Porter Starr KN, Bales CW, Arends J, Siervo M, Deutz N, Prado CM (2024) Feasibility of two levels of protein intake in patients with colorectal cancer: findings from the Protein Recommendation to Increase Muscle (PRIMe) randomized controlled pilot trial ESMO Open 9: 103604 https://doi.org/10.1016/j.esmoop.2024.103604 Hanna L, Nguo K, Furness K, Porter J, Huggins CE (2022) Association between skeletal muscle mass and quality of life in adults with cancer: a systematic review and meta-analysis Journal of Cachexia, Sarcopenia and Muscle 13: 839–857 https://doi.org/10.1002/jcsm.12928 Hébuterne X, Lemarié E, Michallet M, de Montreuil CB, Schneider SM, Goldwasser F (2014) Prevalence of malnutrition and current use of nutrition support in patients with cancer JPEN 38: 196–204 10.1177/0148607113502674 Holdoway A, Page F, Bauer J, Dervan N, Maier AB (2022) Individualised Nutritional Care for Disease-Related Malnutrition: Improving Outcomes by Focusing on What Matters to Patients Nutrients 1410.3390/nu14173534 Kwiecien C, Pouyet V, Daly LE, Fernandez Gonzalez I, Blanchard H, Bilman E, Mekers S, Boireau N (2023) EPA Enriched Oral Nutritional Supplements With A Tailored Sensory Design To Address Taste Alterations Are Appreciated By Patients With Cancer Clinical Nutrition ESPEN 54: 500 10.1016/j.clnesp.2022.09.129 Lam CN, Watt AE, Isenring EA, de van der Schueren MAE, van der Meij BS (2021) The effect of oral omega-3 polyunsaturated fatty acid supplementation on muscle maintenance and quality of life in patients with cancer: A systematic review and meta-analysis Clin Nutr 40: 3815–3826 10.1016/j.clnu.2021.04.031 Merker M, Felder M, Gueissaz L, Bolliger R, Tribolet P, Kagi-Braun N, Gomes F, Hoess C, Pavlicek V, Bilz S, Sigrist S, Brandle M, Henzen C, Thomann R, Rutishauser J, Aujesky D, Rodondi N, Donze J, Stanga Z, Mueller B, Schuetz P (2020) Association of Baseline Inflammation With Effectiveness of Nutritional Support Among Patients With Disease-Related Malnutrition: A Secondary Analysis of a Randomized Clinical Trial JAMA Netw Open 3: e200663 10.1001/jamanetworkopen.2020.0663 Milla SP, Luna PPG, Casariego AV, González FV, Folgueras TM, Jáuregui OI, Rey SG, Fernández AC, Plaza BL, Quintana TC, de Luis Román DA (2024) Adherence and impact of an oral nutritional supplement enriched in leucine, EVOO, EPA and DHA, and beta-glucans on the coverage of energy and protein requirements in patients with cancer and malnutrition: Alisenoc study Nutrition 120: 112355 10.1016/j.nut.2024.112355 Moreau J, Ordan M-A, Barbe C, Mazza C, Perrier M, Botsen D, Brasseur M, Portefaix C, Renard Y, Tallière B, Bertin E, Hoeffel C, Bouché O (2019) Correlation between muscle mass and handgrip strength in digestive cancer patients undergoing chemotherapy Cancer Medicine 8: 3677–3684 https://doi.org/10.1002/cam4.2238 Muscaritoli M, Arends J, Bachmann P, Baracos V, Barthelemy N, Bertz H, Bozzetti F, Hutterer E, Isenring E, Kaasa S, Krznaric Z, Laird B, Larsson M, Laviano A, Muhlebach S, Oldervoll L, Ravasco P, Solheim TS, Strasser F, de van der Schueren M, Preiser JC, Bischoff SC (2021) ESPEN practical guideline: Clinical Nutrition in cancer Clin Nutr 40: 2898–2913 10.1016/j.clnu.2021.02.005 Naqvi A, Matias N, Al-Khaffaf B (2024) Reporting of core outcomes in gastric cancer surgery trials over the past 25 years (systematic review) Journal of Surgical Oncology 129: 1274–1288 https://doi.org/10.1002/jso.27613 Neoh MK, Abu Zaid Z, Mat Daud ZA, Md Yusop NB, Ibrahim Z, Abdul Rahman Z, Jamhuri N (2020) Changes in Nutrition Impact Symptoms, Nutritional and Functional Status during Head and Neck Cancer Treatment Nutrients 1210.3390/nu12051225 Orsso CE, Caretero A, Poltronieri TS, Arends J, de van der Schueren MA, Kiss N, Laviano A, Prado CM (2024) Effects of high-protein supplementation during cancer therapy: a systematic review and meta-analysis The American Journal of Clinical Nutrition 120: 1311–1324 10.1016/j.ajcnut.2024.08.016 Orsso CE, Ford KL, Kiss N, Trujillo EB, Spees CK, Hamilton-Reeves JM, Prado CM (2023) Optimizing clinical nutrition research: the role of adaptive and pragmatic trials European Journal of Clinical Nutrition 77: 1130–1142 10.1038/s41430-023-01330-7 Prado CM, Anker SD, Coats AJS, Laviano A, von Haehling S Nutrition in the spotlight in cachexia, sarcopenia and muscle: avoiding the wildfire Journal of Cachexia, Sarcopenia and Muscle https://doi.org/10.1002/jcsm.12673 Ryan AM, Prado CM, Sullivan ES, Power DG, Daly LE (2019) Effects of weight loss and sarcopenia on response to chemotherapy, quality of life, and survival Nutrition 67–68: 110539 10.1016/j.nut.2019.06.020 Shakhshir MH, Salameh HT, Amer R, Zyoud SeH (2024) An evaluation of nutritional impact symptoms and their association with reduced dietary intake in patients with solid tumors at tertiary care hospitals: a multicenter, cross-sectional study from Palestine BMC Cancer 24: 524 10.1186/s12885-024-12289-4 Shirai Y, Okugawa Y, Hishida A, Ogawa A, Okamoto K, Shintani M, Morimoto Y, Nishikawa R, Yokoe T, Tanaka K, Urata H, Toiyama Y, Inoue Y, Tanaka M, Mohri Y, Goel A, Kusunoki M, McMillan DC, Miki C (2017) Fish oil-enriched nutrition combined with systemic chemotherapy for gastrointestinal cancer patients with cancer cachexia Sci Rep 7: 4826 10.1038/s41598-017-05278-0 Spotten LE, Corish CA, Lorton CM, Ui Dhuibhir PM, O'Donoghue NC, O'Connor B, Walsh TD (2017) Subjective and objective taste and smell changes in cancer Annals of Oncology:28: 969–984 10.1093/annonc/mdx018 Tong H, Isenring E, Yates P (2009) The prevalence of nutrition impact symptoms and their relationship to quality of life and clinical outcomes in medical oncology patients Support Care Cancer 17: 83–90 10.1007/s00520-008-0472-7 Vidal Casariego A, García Luna PP, Villazón González F, Martín Folgueras T, Palma Milla S, López Gómez JJ, González Navarro I, Calleja Fernández A, Casañas Quintana T, López Plaza B, de Luis Román DA (2023) Impact of an oral nutritional supplement enriched in leucine, EPA, DHA, and β-glucans on the increase of muscle mass in patients with cancer and malnutrition: The alisenoc trial Journal of Functional Foods 110: 105833 https://doi.org/10.1016/j.jff.2023.105833 Wang Y, Liu R, Chang M, Wei W, Guo Y, Jin Q, Wang X (2023) Does omega-3 PUFA-enriched oral nutritional intervention benefit cancer patients receiving chemo (radio) therapy? A systematic review and meta-analysis of randomized controlled trials Critical reviews in Food Science and Nutrition 63: 3081–3096 10.1080/10408398.2021.1984199 Wunderle C, Stumpf F, Schuetz P (2024) Inflammation and response to nutrition interventions JPEN 48: 27–36 https://doi.org/10.1002/jpen.2534 Additional Declarations No competing interests reported. Supplementary Files SupplementaryInformationOnlineResource114.07.2025.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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1","display":"","copyAsset":false,"role":"figure","size":228033,"visible":true,"origin":"","legend":"\u003cp\u003eStudy design and schedule of assessments.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7453912/v1/bb9594211cdbbed7cbf4c83d.png"},{"id":93730794,"identity":"d645304a-cb08-4587-8d17-85d78ab083a0","added_by":"auto","created_at":"2025-10-17 02:21:51","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":261698,"visible":true,"origin":"","legend":"\u003cp\u003ePatient reported physical aspects of QOL (McNemar’s test used).\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7453912/v1/41dc0753ef1f30990256f80c.jpeg"},{"id":93730797,"identity":"d6c3fcba-1174-477b-bc98-b73bca6b5333","added_by":"auto","created_at":"2025-10-17 02:21:52","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":74777,"visible":true,"origin":"","legend":"\u003cp\u003ePatient reported feelings at 3-months (n=746).\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7453912/v1/5d85980d0aa94e782e40707c.png"},{"id":102403984,"identity":"ecbc4cb5-1105-4913-bea4-e70a7a6cbe40","added_by":"auto","created_at":"2026-02-11 10:51:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1418037,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7453912/v1/f3e2d6d1-31d7-4008-af76-5ad95b8fe994.pdf"},{"id":93732307,"identity":"e0e12238-33e2-431e-ac6b-a2aa74b789af","added_by":"auto","created_at":"2025-10-17 02:29:51","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":295110,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryInformationOnlineResource114.07.2025.docx","url":"https://assets-eu.researchsquare.com/files/rs-7453912/v1/4045fe1e2bc407b33c1339b9.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Evaluation of a 3-month intervention with high protein, omega-3 LC-PUFA enriched oral nutritional supplement on body weight, inflammation, muscle strength and patient reported outcomes in patients with cancer","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eMalnutrition in cancer is highly prevalent affecting 14\u0026ndash;67% of patients depending on disease site [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] with adverse consequences such as poorer tolerance of systemic chemotherapy, reduced performance status, quality of life (QOL) and survival [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Nutrition impact symptoms (e.g. appetite loss, nausea, dry mouth, early satiety and taste changes) are common in cancer [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e], are known to progress over the cancer journey [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], are associated with reduced dietary intake [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e], have an adverse effect on QOL and are associated with eating-related distress [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Low muscle mass, a key feature of malnutrition, has been shown to be an independent predictor of dose-limiting anti-cancer treatment toxicity, with muscle loss considered a strong predictor of survival [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Loss of muscle is not only detrimental to clinical outcome but also to outcomes that matter to patients such as QOL [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eMeeting nutritional needs in cancer is challenging due to effects of cancer itself and the side effects of treatment including chemosensory alterations which negatively affect QOL [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Up to 70% of patients with cancer experience taste and smell changes during chemotherapy and radiotherapy and these sensory alterations may persist up to one year after treatment [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. To compensate for reduced intake and altered metabolic needs, guidelines from The European Society for Clinical Nutrition and Metabolism (ESPEN) [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] and the European Society for Medical Oncology (ESMO) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] on nutrition in cancer recommend higher than normal energy and protein intake; 25\u0026ndash;30 kcal/kg/day (if energy expenditure is not measured individually) and protein intake of 1.0-1.5 g/kg/day.\u003c/p\u003e\u003cp\u003eLikened to a wildfire, muscle loss is rapid and difficult to regain with diverse causes including inflammation [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Inflammation has detrimental effects on nutritional status through promoting anorexia (reducing nutrient intake), increasing muscle catabolism, increasing resting energy expenditure and blunting response to nutrition intervention and is one of the etiological criterion for the Global Leadership Initiative on Malnutrition (GLIM) diagnosis of malnutrition [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. To target inflammation, the ESPEN guidelines recommend supplementation with omega-3 long chain polyunsaturated fatty acids (LC-PUFA) or fish oil to improve appetite and BW in patients with advanced cancer undergoing chemotherapy at risk of weight loss or who are malnourished [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e], with ESMO recommending omega-3 LC-PUFA enriched ONS for patients undergoing chemotherapy, radiotherapy or chemoradiotherapy to increase BW, attenuate lean body mass and improve QOL [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Omega-3 LC-PUFA are known for their anti-inflammatory properties and it has been suggested that they may inhibit tumour growth through effects on membrane signaling [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Supplementation with omega-3 LC-PUFA has been shown to be safe, to reduce inflammatory markers and increase survival in patients with cancer (22).\u003c/p\u003e\u003cp\u003eIncreasing protein intake positively impacts muscle mass and function in patients with cancer [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. For patients unable to meet nutritional needs through diet alone, expert guidance recognise oral nutritional supplements (ONS) as an effective and non-invasive part of nutritional care [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. In patients undergoing cancer therapy high protein supplementation mitigates weight loss, improves muscle strength and reduces hospitalisation rates [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eDespite expert guidance and evidence of benefit, in clinical practice nutrition intervention is often overlooked or delivered too late. Integration of structured processes for early management of malnutrition and cachexia in cancer offers the potential to intervene in the patient journey at a point when the intervention is likely to be effective in minimising the adverse effects of malnutrition and cachexia on anti-cancer therapy (1). To bridge the evidence-practice gap pragmatic trials that assess interventions in clinical settings that resemble standard of care and focus on patient-oriented outcomes are needed [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. In this prospective, pragmatic, single-arm trial evaluating a 3-month nutrition intervention with a HP omega-3 LC-PUFA enriched ONS in patients with or at risk of malnutrition, the primary objective of the study was to observe patient outcomes in a real-world setting. To better understand the patients\u0026rsquo; perspective patient-reported outcomes were collected, an often overlooked aspect in clinical trials [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1 Study Design and Population\u003c/h2\u003e\u003cp\u003eThis pragmatic, prospective, single-arm, longitudinal, interventional, multi-centre study was carried out in the Czech Republic and Slovakia in 69 outpatient centres. The schedule of assessments and study design are outlined in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The inclusion criteria were: patients meeting the requirements for prescription of Oral Nutritional Supplements (ONS), patients undergoing active/radical oncological treatment (curative or palliative chemotherapy, radiotherapy and concomitant chemoradiotherapy) with newly diagnosed malnutrition, patients with a diagnosis of tumour types associated with high nutritional risk and aged between 18 and 80 years of age.\u003c/p\u003e\u003cp\u003eScreening for malnutrition risk and assessment for prescription of ONS was undertaken according to the standard protocol in each country. In the Czech Republic the standard protocol developed by the Working Group on Nutritional Care in Oncology (Pracovn\u0026iacute; skupina nutričn\u0026iacute; p\u0026eacute;če v onkologii, PSNPO) was used. Patients were weighed and were asked to report previous weight (6 months ago), height and food intake. The patient\u0026rsquo;s healthcare professional (HCP) calculated percentage weight loss, BMI and in combination with details of age and diagnosis, assigned a risk of malnutrition score. In the Czech Republic if the malnutrition risk score was \u0026ge;\u0026thinsp;2 (maximum score possible was 4) and required prescription of ONS the patient fulfilled the study eligibility criteria for risk of malnutrition. In Slovakia a similar protocol was employed, the \u0026lsquo;Protocol of the initial indication for ambulatory enteral nutrition for adult patients\u0026rsquo; developed by the Ministry of Health in association with the local society for parenteral and enteral nutrition. The protocol was completed by the patient\u0026rsquo;s HCP and included a two-step process. If initial assessment of percentage weight loss, anthropometric measures and income resulted in a score of \u0026ge;\u0026thinsp;1, the second step was completed which included a clinical evaluation of nutritional status and underlying clinical diagnosis. A score of \u0026ge;\u0026thinsp;2 indicated the presence of malnutrition and the need for prescription of ONS.\u003c/p\u003e\u003cp\u003ePatients were excluded if they i) were unable to provide information to enable the HCP to complete the study questionnaire, ii) could not have their weight or height measured, iii) had uncontrolled diabetes mellitus, iv) had a known allergy to milk protein and milk products, or v) were receiving full or partial enteral tube feeding or parenteral nutrition. The study was conducted according to the main principles of Good Clinical Practice. The protocol was submitted to the Bulovka University Hospital, Prague, Czech Republic Ethics Committee and approved prior to the start of the study (registration number: 10.1.2023/10711/EK-Z) on the 12th of January 2023. All patients provided informed written consent before any study procedures were performed. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the study design and schedule of assessments.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2 Nutrition Intervention\u003c/h2\u003e\u003cp\u003ePatients were prescribed two bottles of a liquid, ready to drink, low volume, high protein (HP), energy dense, omega-3 long chain polyunsaturated fatty acid (LC-PUFA) enriched ONS (Forticare Advanced, Nutricia) daily for 3 months in addition to habitual food intake. Each 125 ml bottle contained 18 g of protein, 306 kcal, 1.1 g of eicosapentaenoic acid (EPA), 0.7 g of docosahexaenoic acid (DHA) and 10 \u0026micro;g of vitamin D. The study product flavours have previously been validated with patients with cancer and are specifically designed to address the needs of patients with taste alterations [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Patients were offered a choice of two flavours of the ONS (Cool Berry and Cool Mango Peach). Other than the provision of the ONS patients received the usual care provided by their outpatient centre.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3 Outcome Measures\u003c/h2\u003e\u003cp\u003eBW (kg), BMI (kg/m\u003csup\u003e2\u003c/sup\u003e), C-reactive protein (CRP) (mg/L) and albumin (g/dL) were measured according to the outpatient clinic\u0026rsquo;s usual procedures. Hand grip strength (HGS) (kg) of the non-dominant hand was measured using a dynamometer (Saehan DHD-1 and KERN MAP 80K1 N/A) with oral training provided on measurement procedures. Due to the resources available only 18 centres received a dynamometer. The 30-second chair stand test (CST) was used to assess the number of times the patient was able to stand up from a chair in 30 seconds (see Online Resource 1 for instructions used). Patient reported outcomes of physical aspects of QOL were assessed by four answer categories (certainly no, almost no, almost yes, certainly yes) to three simple questions i) Are you able to walk for 20 minutes? ii) Did you need to rest during the day? and iii) Did you feel weak during the last week. The three questions were developed in consultation with oncologists and were designed to ensure that the protocol was feasible in clinical practice. Patients were asked to report the perceived benefits of the ONS at one month and three months, and at three months to report how they felt (themes relating to energy, strength, physical activity, ability to do activities, generally feeling better, appearance and BW) and about changes in their perception of taste and smell from before the beginning of their anti-cancer treatment. Details of these patient questions are available in the Online Resource 1. Adherence to the ONS was recorded at one month and three months and was based on patients\u0026rsquo; reported average daily consumption of the ONS (i.e. 0, 0.5, 1, 1.5 or 2 bottles per day). At one month and three months patients were asked to indicate if they liked (Yes/No) the ONS.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.4 Statistics and Data Analysis\u003c/h2\u003e\u003cp\u003ePatient recruitment for this study was conducted over a defined time period rather than being based on a pre-specified sample size calculation. The final sample size reflects the number of patients enrolled during the recruitment timeframe between February 2023 and March 2024. Statistical calculations were done by JMP\u0026reg;, Version 17.2.0. SAS Institute Inc., Cary, NC, 2022\u0026ndash;2023. Normal distribution was tested by Shapiro-Wilk test. Continuous variables were described by mean and standard deviation. For discrete variables absolute and relative frequencies were used. Change in time was evaluated by paired t-test or Wilcoxon signed rank test for continuous variables and by McNemar\u0026rsquo;s test for discrete ones. Difference between two independent groups was tested by t-test or Mann-Whitney\u0026lsquo;s test for continuous variables. All tests were two-sided and p less than 0.05 was considered statistically significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e3.1 Recruitment and patient characteristics\u003c/h2\u003e\u003cp\u003eA total of 880 patients were assessed for eligibility to participate, of whom 39 were excluded because they did not fulfil the inclusion criteria or declined to participate. Due to difficulties attending the clinic 55 patients did not start the study. A further 25 patients were lost to follow up. Therefore, data from 761 patients were included in the final per-protocol analysis (Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e in the Online Resource 1).\u003c/p\u003e\u003cp\u003eThe baseline demographic characteristics of the 761 participating patients (47.5% male) are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Patients\u0026rsquo; ages ranged from 29 to 95 years (mean 65 years, SD 12). At baseline although only 11.6% of patients had a BMI of less than 18.5 kg/m\u003csup\u003e2\u003c/sup\u003e, in total 77.9% of patients had experienced unplanned BW loss (WL) of greater than 5% (5\u0026ndash;10% WL (53.5%) and \u0026gt;\u0026thinsp;10% WL (24.4%)) in the last six months. Eighty-seven per cent of patients had a CRP level of greater than 5 mg/L at baseline and 56.9% of patients had an albumin level below 35 g/dL at baseline. Patients with greater than 5% weight loss at baseline had higher CRP and lower albumin levels than patients with less than 5% weight loss at baseline (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Fifty-two per cent of patients were receiving anti-cancer treatment with palliative intent and 47.7% with curative intent. All major cancer types were represented.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDemographic and clinical characteristics of participating patients at baseline (n\u0026thinsp;=\u0026thinsp;761).\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eParameter\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge (years)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSex\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eFemales\u003c/p\u003e\n \u003cp\u003eMales\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e394 (52.5)\u003c/p\u003e\n \u003cp\u003e357 (47.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBody Mass Index (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt;18.5\u003c/p\u003e\n \u003cp\u003e18.5\u0026ndash;24.9\u003c/p\u003e\n \u003cp\u003e25\u0026ndash;30\u003c/p\u003e\n \u003cp\u003e\u0026gt;30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e86 (11.6)\u003c/p\u003e\n \u003cp\u003e470 (63.4)\u003c/p\u003e\n \u003cp\u003e162 (21.9)\u003c/p\u003e\n \u003cp\u003e23 (3.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnplanned body weight loss in the last six months (kg)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt; 5%\u003c/p\u003e\n \u003cp\u003e5\u0026ndash;10%\u003c/p\u003e\n \u003cp\u003e\u0026gt;10%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e166 (22.0)\u003c/p\u003e\n \u003cp\u003e403 (53.5)\u003c/p\u003e\n \u003cp\u003e184 (24.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC-reactive protein (mg/L)\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt;5\u003c/p\u003e\n \u003cp\u003e5\u0026ndash;10\u003c/p\u003e\n \u003cp\u003e10.1\u0026ndash;50\u003c/p\u003e\n \u003cp\u003e50.1\u0026ndash;100\u003c/p\u003e\n \u003cp\u003e\u0026gt;100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e93 (12.9)\u003c/p\u003e\n \u003cp\u003e155 (21.6)\u003c/p\u003e\n \u003cp\u003e398 (55.4)\u003c/p\u003e\n \u003cp\u003e48 (6.7)\u003c/p\u003e\n \u003cp\u003e25 (3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAlbumin (g/dL)\u003csup\u003ef\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt;35\u003c/p\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003cp\u003e\u0026gt;35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e418 (56.9)\u003c/p\u003e\n \u003cp\u003e20 (2.7)\u003c/p\u003e\n \u003cp\u003e297 (40.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTreatment intent\u003csup\u003eg\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eCurative\u003c/p\u003e\n \u003cp\u003ePalliative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e356 (47.7)\u003c/p\u003e\n \u003cp\u003e389 (52.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTumour site\u003csup\u003eh\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eLower gastrointestinal\u003c/p\u003e\n \u003cp\u003eLiver, pancreas, gallbladder, biliary tract\u003c/p\u003e\n \u003cp\u003eBreast\u003c/p\u003e\n \u003cp\u003eOesophageal, stomach and duodenum\u003c/p\u003e\n \u003cp\u003eHead and neck/ear, nose, throat\u003c/p\u003e\n \u003cp\u003eLung\u003c/p\u003e\n \u003cp\u003eUrological\u003c/p\u003e\n \u003cp\u003eGynaecological\u003c/p\u003e\n \u003cp\u003eMalignant melanoma and tumour of the skin\u003c/p\u003e\n \u003cp\u003eHaematological\u003c/p\u003e\n \u003cp\u003eNon-site specific/primary site unknown\u003c/p\u003e\n \u003cp\u003eThyroid and other endocrine\u003c/p\u003e\n \u003cp\u003eOther\u003csup\u003ej\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e135 (19.0)\u003c/p\u003e\n \u003cp\u003e113 (15.9)\u003c/p\u003e\n \u003cp\u003e94 (13.3)\u003c/p\u003e\n \u003cp\u003e82 (11.6)\u003c/p\u003e\n \u003cp\u003e78 (11.0)\u003c/p\u003e\n \u003cp\u003e67 (9.4)\u003c/p\u003e\n \u003cp\u003e51 (7.2)\u003c/p\u003e\n \u003cp\u003e32 (4.5)\u003c/p\u003e\n \u003cp\u003e15 (2.1)\u003c/p\u003e\n \u003cp\u003e14 (2.0)\u003c/p\u003e\n \u003cp\u003e12 (1.7)\u003c/p\u003e\n \u003cp\u003e7 (1.0)\u003c/p\u003e\n \u003cp\u003e9 (1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eNumbers do not add up to n\u0026thinsp;=\u0026thinsp;761 due to missing values. \u003csup\u003ei\u003c/sup\u003eIncludes non-site specific/ill-defined or multiple independent primary sites or primary site unknown; \u003csup\u003ej\u003c/sup\u003eIncludes tumours of the bone, joint, eye and abdominal cavity.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003e3.2 Anthropometrics and adherence (primary outcomes)\u003c/h2\u003e\u003cp\u003eA statistically significant increase in mean BW and mean BMI was observed from baseline to three months (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Overall, 76% of patients gained or stabilized BW (63% gained\u0026thinsp;\u0026gt;\u0026thinsp;1 kg, 13% were weight stable i.e. \u0026plusmn; 1 kg) and 24% of patients lost more than 1 kg BW. Average adherence to the ONS was 1.7 (85%) bottles per day at 1 month. There was no significant change in adherence between the first and third month of the study (1.7 vs 1.6 bottles/day, p\u0026thinsp;=\u0026thinsp;0.1115, n\u0026thinsp;=\u0026thinsp;733). The ONS received a positive response for overall liking, with 92% of respondents expressing overall liking in the first month and 90% in the third month (p\u0026thinsp;=\u0026thinsp;0.073).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003e3.3 Laboratory parameters\u003c/h2\u003e\u003cp\u003eThere was a statistically significant decrease in mean CRP of 7.5 mg/L from baseline to three months (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and a statistically significant increase in mean albumin of 1.0 g/dL from baseline to three months (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003e3.4 Muscle strength\u003c/h2\u003e\u003cp\u003eThere was a statistically significant improvement in muscle strength from baseline to three months, mean HGS increased by 1.2 kg (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and the mean number of stand ups in the 30 second CST increased by 1.4 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMean BW, BMI, albumin, CRP, 30 second chair stand test and hand grip strength at baseline, 1 month and 3 months (per protocol).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"8\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003en\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eBaseline (SD)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 month (SD)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3 months (SD)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u003cp\u003eDifference (0\u0026ndash;3 months)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eMean\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBody weight (kg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e743\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e66.0 (12.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e66.1 (12.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e67.0 (12.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.76\u0026ndash;1.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBody Mass Index (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e727\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e22.7 (3.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e22.7\u003c/p\u003e\u003cp\u003e(3.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e23.0 (3.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.25\u0026ndash;0.42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eC-reactive protein (mg/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e687\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e22.6 (29.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e18.1 (26.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e15.1 (24.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-7.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-5.28- -9.66\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlbumin (g/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e709\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e34.2 (7.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e34.6 (7.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e35.2 (7.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.71\u0026ndash;1.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e30 second chair stand test (number of stand ups)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e706\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6.7 (3.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e7.3 (4.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e8.0 (4.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.19\u0026ndash;1.53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHand grip strength (kg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e304\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e18.9 (10.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e19.0 (10.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e20.0 (11.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.74\u0026ndash;1.63\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003ePaired t-test used for all, with the exception of CRP for which the Wilcoxon test was used.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003e3.5 Patient reported physical aspects of QOL\u003c/h2\u003e\u003cp\u003ePhysical performance aspects of QOL improved from baseline to 3 months. (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003e3.6 Taste and smell changes\u003c/h2\u003e\u003cp\u003eAt three months 34.5% of patients reported a change in taste and smell perception during anti-cancer treatment (data available for n\u0026thinsp;=\u0026thinsp;754). Of the 260 patients who reported a change in taste and smell perception at 3 months compared to before the beginning of anti-cancer treatment, 94% reported changes to their sense of taste and 88% reported changes to their sense of smell. Details of the changes experienced are shown in Online Resource 1.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003e3.7 Perceived benefits reported by patients\u003c/h2\u003e\u003cp\u003eAt either 1 month, 3 months or both, patients reported a perceived benefit of the ONS on a range of points (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePerceived benefits of the ONS reported by patients at 1 month, 3 months or both.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePerceived benefit reported by patients\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003en\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAnswered yes at either 1 month, 3 months or both (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIt supplemented my daily food intake\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e714\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e57\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMy physical condition has improved\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e726\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e44\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eI have gained weight\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e680\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e35\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIt supports my treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e684\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e51\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIt gives me back my lost strength\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e712\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e44\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eI am more self-reliant\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e666\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAll of the above\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e737\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e55\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo perceived benefit\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e738\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eAt three months most patients reported improved feelings relating to energy, strength and ability to undertake activities, however feeling able to maintain a healthy weight was reported less (21%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eTo our knowledge this prospective, pragmatic, single-arm, multi-centre interventional study is the first to investigate the effects of a low volume, HP, high energy, omega-3 enriched LC-PUFA ONS in outpatients with cancer reflecting real-world clinical settings, and in particular, to assess patient-reported outcomes. In this study, patients with cancer prescribed HP, omega-3 LC-PUFA enriched ONS for 3-months gained weight, experienced reduced inflammation and improved physical performance. Although one in three patients reported altered taste or smell, average adherence to the ONS was excellent and patients reported perceived benefits of the ONS.\u003c/p\u003e\u003cp\u003eReflecting increased understanding over time of the role of omega-3 LC-PUFA in modulating inflammation in cancer, many studies have investigated the effects of omega-3 LC-PUFA enriched ONS on outcomes in patients with cancer and have been included in wider reviews [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. However, many included studies had small sample sizes (range n\u0026thinsp;=\u0026thinsp;13 to 200) and short duration of intervention (range 1 to 12 weeks, majority (8/14) of studies\u0026thinsp;\u0026le;\u0026thinsp;6 weeks) [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Similarly, studies conducted more recently had small sample sizes (n\u0026thinsp;=\u0026thinsp;37 to 159) but, in some, intervention periods were longer (range 5 to 24 weeks, in 2/4 studies duration\u0026thinsp;\u0026ge;\u0026thinsp;12 weeks) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn the present study the improvement in mean BW (n\u0026thinsp;=\u0026thinsp;743) and mean BMI (n\u0026thinsp;=\u0026thinsp;727) observed from baseline to three months is in line with Cereda et al. (2018) who demonstrated that the use of an omega-3 fatty acid enriched ONS (18% energy from protein, 2 kcal/ml) during radiotherapy and for 12 weeks post-radiotherapy in patients with head and neck cancer (n\u0026thinsp;=\u0026thinsp;136) resulted in a significantly smaller loss of BW than nutritional counselling alone, with patients in the ONS group more likely to maintain BW during the intervention period [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Vidal Casariego et al. (2023) found that malnourished cancer outpatients (n\u0026thinsp;=\u0026thinsp;37) supplemented with HP ONS enriched with omega-3 LC-PUFA and L-leucine (2 kcal/ml) over 8 weeks had a tendency to return to their initial BW at the first assessment and increase BW at the end of the follow-up period compared to a slight decrease in BW in a group supplemented with standard HP ONS, however neither of these observations reached statistical significance [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e], possibly due to the short intervention time. In an RCT of HP EPA-enriched ONS (1.27 kcal/ml) vs normal diet in pre-operative patients with pancreatic cancer (n\u0026thinsp;=\u0026thinsp;62) Akita et al. (2019) showed no difference in BMI pre to post intervention ratio, but noted that the control group showed a significant decline in BW during the study which was not seen in the intervention group [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The study duration was short (5 weeks) and adherence to the ONS was poor which may have contributed to the lack of positive effect on BW in the intervention group.\u003c/p\u003e\u003cp\u003eAdherence to the ONS in the present study was excellent (85%), with no significant change in adherence or overall liking of the ONS across the 3-month duration of the study, likely due to the low volume (2.4 kcal/ml) of the ONS and flavours specifically tailored for and tested by patients with cancer (30). Good adherence rates (patient-reported) have also been observed in other studies, 80% in malnourished cancer outpatients taking a HP, omega-3 LC-PUFA, L-leucine enriched ONS (2 kcal/ml) [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e] and 73.4% in well-nourished patients with lung and colorectal cancer taking a low volume HP ONS (2.4kcal/ml) [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. A fair adherence rate of 60% of the ONS prescription target (recorded by care givers and dietitians) was reported by Cereda et al. (2018) [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. \u0026lsquo;Disagreeable\u0026rsquo; taste of the ONS was reported as a key reason for low adherence (55% subjects (17/31) consuming\u0026thinsp;\u0026lt;\u0026thinsp;50%) to five weeks of supplementation with a HP, EPA-enriched ONS (1.27 kcal/ml) in pre-surgical patients with pancreatic cancer [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], illustrating that a combination of low volume and specifically tailored flavours may be key attributes to support adherence.\u003c/p\u003e\u003cp\u003eImprovement in muscle strength, assessed using HGS and the 30 second CST, was statistically significant and patients reported improvements in physical performance aspects of QOL from baseline to 3 months. These objectives, easy to perform and low-cost methods were chosen as they can be feasibly implemented in clinical practice. HGS is correlated with muscle mass (MM) [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] and predicts survival [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] in patients with cancer and CST is patient-centered, safe, feasible and can also be used remotely [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The use of patient-reported outcomes are key to enhancing patient care [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Whilst previous studies have shown that supplementation with protein and omega-3 fatty acid fortified ONS increase MM and confer benefits on some measures of function and QOL, changes were not always seen in HGS [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. Cereda et al. (2018) measured HGS in patients with head and neck cancer undergoing radiotherapy and showed a trend towards significance favouring the intervention group vs controls and, although they found no effect on change in Phase angle, they did observe a significant difference over time in favour of the intervention for recovery of QOL [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn the present study, statistically significant improvements in mean CRP and albumin from baseline to three months were observed. Shirai et al. (2017) showed that fish oil-enriched ONS inhibited increases in serum CRP levels compared to subjects in the control group in whom a significant increase in CRP was observed during intervention [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. High baseline inflammatory status may hinder response to nutrition intervention [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] and should therefore be considered when selecting the most appropriate nutrition support [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. Interestingly, a higher intake of a HP omega-3 LC-PUFA and L-leucine enriched ONS has been observed when patients\u0026rsquo; nutritional and clinical condition worsened which was not observed in a group taking a standard HP ONS, possibly related to appetite-stimulating properties of Omega-3 LC-PUFA (45).\u003c/p\u003e\u003cp\u003eThe main strengths of this study include the large number of participating patients across a broad range of tumour types, the pragmatic nature of the study and the collection of nutritional outcome data, both objective and patient-reported, in real-world settings. Implementation of nutritional care in practice is often limited [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], hampered by lack of awareness, lack of nutrition education and lack of standard operating procedures, clearly defined responsibilities and healthcare professional collaboration [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Individualisation of nutritional care managed by nutrition experts is not always available to all patients and may be focused on the most complex cases due to resource constraints, however early and appropriate nutrition intervention delivered by the wider healthcare team that meets patient\u0026rsquo;s individual needs, preferences and goals is still achievable with the use of evidence-based protocols or pathways [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] and is preferable to lack of intervention.\u003c/p\u003e\u003cp\u003eThe present study contributes useful insights on the topic but also has some limitations. Although the single-arm design enabled all patients to receive intervention possibly encouraging participation, the lack of a control group means that the benefits observed may not be solely due to the ONS intervention. The number of participating centres was large showing extensive interest in nutritional care, however there was likely some variation in local procedures although nationally agreed protocols for screening for nutritional risk and for prescribing ONS were followed. Patient reported outcomes were gathered, in particular patients\u0026rsquo; perceived benefits of ONS and feelings in relation to energy and ability to undertake activities, however the measures used were not validated which could be a focus for future work. Only eighteen centres (26%) had access to HGS due to limited resources, nevertheless the data obtained is promising and shows that use of HGS is acceptable in practice. Adherence to the ONS was self-reported but this is feasible in practice and is a frequently used method for reported adherence in studies of ONS [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Although dietary intake was not recorded and evaluated in the present study, a previous study of a low volume, HP ONS showed that intake from ONS increases protein intake in patients with cancer [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. While the predefined inclusion criteria specified an age range of 18 to 80 years, a protocol deviation resulted in the inclusion of several individuals above this range, with the oldest patient being 95 years of age. Fifty-five eligible patients did not start the study due to issues with attendance at clinics and a further twenty-five were lost to follow up but it is likely that this reflects real-world practice.\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eIn this large, single-arm, pragmatic, interventional study, outpatients receiving anti-cancer treatment across a broad range of cancer types prescribed low volume, HP omega-3 LC-PUFA enriched ONS for 3-months gained weight, experienced reduced inflammation and improved physical performance. Average adherence to the ONS was excellent and patients reported perceived benefits of the ONS. The ONS was prescribed in real-world settings following nationally agreed protocols, which could be replicated elsewhere to ensure nutrition intervention is implemented in a timely way that meets patients\u0026rsquo; needs.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by Danone Research and Innovation. Writing and editorial services were supported by Danone Research and Innovation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eP. Holeckova, received research support, travel support and speaker honoraria from Danone Research and Innovation. V. Rosenberg and V. Lanska received research support from Danone Research and Innovation. M. Tomecka and J. Smitka are employees of Danone. The funders contributed to the design of the study; in the analyses and interpretation of data; in the writing of the manuscript; and in the decision to publish the results.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: P. Holečkov\u0026aacute;; Methodology: P. Holečkov\u0026aacute;; Formal analysis and investigation: V. Lanska; Writing - review and editing: P. Holečkov\u0026aacute;; Funding acquisition: M. Tomecka, J. Smitka; Supervision: V. Rosenberg. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted according to the main principles of Good Clinical Practice. The protocol was submitted to the Bulovka University Hospital, Prague, Czech Republic Ethics Committee and approved prior to the start of the study (registration number: 10.1.2023/10711/EK-Z) on the 12th of January 2023.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e Informed consent was obtained from all subjects involved in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u0026nbsp;\u003c/strong\u003eThe datasets presented are available upon reasonable request. Any requests will be reviewed against adherence with ethical, scientific, regulatory, and legal requirements. Requests to access the datasets should be directed to [email protected]\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary Information\u0026nbsp;\u003c/strong\u003eThe \u0026lsquo;Online Resource 1\u0026rsquo; file contains the instructions used for the 30-second chair stand test, the questions used to gather patient reported measures, Figure S1 showing the flow diagram of patient recruitment and study participation and further Figures showing results for CRP, albumin, hand grip strength and chair stand test, and patient reported taste and smell changes.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAkita H, Takahashi H, Asukai K, Tomokuni A, Wada H, Marukawa S, Yamasaki T, Yanagimoto Y, Takahashi Y, Sugimura K, Yamamoto K, Nishimura J, Yasui M, Omori T, Miyata H, Ochi A, Kagawa A, Soh Y, Taniguchi Y, Ohue M, Yano M, Sakon M (2019) The utility of nutritional supportive care with an eicosapentaenoic acid (EPA)-enriched nutrition agent during pre-operative chemoradiotherapy for pancreatic cancer: Prospective randomized control study Clinical Nutrition ESPEN 33: 148\u0026ndash;153 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.clnesp.2019.06.003\u003c/span\u003e\u003cspan address=\"10.1016/j.clnesp.2019.06.003\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAmano K, Baracos VE, Mori N, Okamura S, Yamada T, Miura T, Tatara R, Kessoku T, Matsuda Y, Tagami K, Otani H, Mori M, Taniyama T, Nakajima N, Nakanishi E, Kako J, Morita T, Miyashita M (2024) Associations of nutrition impact symptoms with dietary intake and eating-related distress in patients with advanced cancer Clinical Nutrition ESPEN 60: 313\u0026ndash;319 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.clnesp.2024.02.027\u003c/span\u003e\u003cspan address=\"10.1016/j.clnesp.2024.02.027\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eArends J, Baracos V, Bertz H, Bozzetti F, Calder PC, Deutz NEP, Erickson N, Laviano A, Lisanti MP, Lobo DN, McMillan DC, Muscaritoli M, Ockenga J, Pirlich M, Strasser F, de van der Schueren M, Van Gossum A, Vaupel P, Weimann A (2017) ESPEN expert group recommendations for action against cancer-related malnutrition Clin Nutr 36: 1187\u0026ndash;1196 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.clnu.2017.06.017\u003c/span\u003e\u003cspan address=\"10.1016/j.clnu.2017.06.017\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eArends J, Muscaritoli M, Anker S, Audisio R, Barazzoni R, Bosnjak S, Bossi P, Bowman J, Gijssels S, Krznarić Ž, Strasser F, Aapro M (2023) Overcoming barriers to timely recognition and treatment of cancer cachexia: Sharing Progress in Cancer Care Task Force Position Paper and Call to Action Critical Reviews in Oncology/Hematology 185: 103965 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.critrevonc.2023.103965\u003c/span\u003e\u003cspan address=\"10.1016/j.critrevonc.2023.103965\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eArends J, Strasser F, Gonella S, Solheim TS, Madeddu C, Ravasco P, Buonaccorso L, de van der Schueren MAE, Baldwin C, Chasen M, Ripamonti CI (2021) Cancer cachexia in adult patients: ESMO Clinical Practice Guidelines ESMO Open 6: 100092 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.esmoop.2021.100092\u003c/span\u003e\u003cspan address=\"10.1016/j.esmoop.2021.100092\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBowman A, Denehy L, Benjemaa A, Crowe J, Bruns E, Hall T, Traill A, Edbrooke L (2023) Feasibility and safety of the 30-second sit-to-stand test delivered via telehealth: An observational study PM\u0026amp;R 15: 31\u0026ndash;40 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/pmrj.12783\u003c/span\u003e\u003cspan address=\"10.1002/pmrj.12783\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBressan V, Bagnasco A, Aleo G, Catania G, Zanini MP, Timmins F, Sasso L (2017) The life experience of nutrition impact symptoms during treatment for head and neck cancer patients: a systematic review and meta-synthesis Support Care Cancer 25: 1699\u0026ndash;1712 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00520-017-3618-7\u003c/span\u003e\u003cspan address=\"10.1007/s00520-017-3618-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBrisbois TD, de Kock IH, Watanabe SM, Baracos VE, Wismer WV (2011) Characterization of chemosensory alterations in advanced cancer reveals specific chemosensory phenotypes impacting dietary intake and quality of life J Pain Symptom Manage 41: 673\u0026ndash;683 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jpainsymman.2010.06.022\u003c/span\u003e\u003cspan address=\"10.1016/j.jpainsymman.2010.06.022\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCalder PC (2012) Mechanisms of Action of (n-3) Fatty Acids1,2 The Journal of Nutrition 142: 592S-599S \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3945/jn.111.155259\u003c/span\u003e\u003cspan address=\"10.3945/jn.111.155259\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCapit\u0026atilde;o C, Coutinho D, Neves PM, Capelas ML, Pimenta NM, Santos T, M\u0026auml;kitie A, Ravasco P (2022) Protein intake and muscle mass maintenance in patients with cancer types with high prevalence of sarcopenia: a systematic review Supportive Care in Cancer 30: 3007\u0026ndash;3015 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00520-021-06633-8\u003c/span\u003e\u003cspan address=\"10.1007/s00520-021-06633-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCederholm T, Jensen GL, Ballesteros-Pomar MD, Blaauw R, Correia MITD, Cuerda C, Evans DC, Fukushima R, Ochoa Gautier JB, Gonzalez MC, van Gossum A, Gramlich L, Hartono J, Heymsfield SB, Jager-Wittenaar H, Jayatissa R, Keller H, Malone A, Manzanares W, McMahon MM, Mendez Y, Mogensen KM, Mori N, Muscaritoli M, Nogales GC, Nyulasi I, Phillips W, Pirlich M, Pisprasert V, Rothenberg E, de van der Schueren M, Shi HP, Steiber A, Winkler MF, Barazzoni R, Compher C (2024) Guidance for assessment of the inflammation etiologic criterion for the GLIM diagnosis of malnutrition: A modified Delphi approach Clinical Nutrition 43: 1025\u0026ndash;1032 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.clnu.2023.11.026\u003c/span\u003e\u003cspan address=\"10.1016/j.clnu.2023.11.026\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCereda E, Cappello S, Colombo S, Klersy C, Imarisio I, Turri A, Caraccia M, Borioli V, Monaco T, Benazzo M, Pedrazzoli P, Corbella F, Caccialanza R (2018) Nutritional counseling with or without systematic use of oral nutritional supplements in head and neck cancer patients undergoing radiotherapy Radiother Oncol 126: 81\u0026ndash;88 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.radonc.2017.10.015\u003c/span\u003e\u003cspan address=\"10.1016/j.radonc.2017.10.015\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCereda E, Tancredi R, Klersy C, Lobascio F, Crotti S, Masi S, Cappello S, Stob\u0026auml;us N, Tank M, Cutti S, Arcaini L, Bonzano E, Colombo S, Pedrazzoli P, Norman K, Caccialanza R (2022) Muscle weakness as an additional criterion for grading sarcopenia-related prognosis in patients with cancer Cancer Med 11: 308\u0026ndash;316 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/cam4.4362\u003c/span\u003e\u003cspan address=\"10.1002/cam4.4362\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCrowder SL, Douglas KG, Yanina Pepino M, Sarma KP, Arthur AE (2018) Nutrition impact symptoms and associated outcomes in post-chemoradiotherapy head and neck cancer survivors: a systematic review J Cancer Surviv 12: 479\u0026ndash;494 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s11764-018-0687-7\u003c/span\u003e\u003cspan address=\"10.1007/s11764-018-0687-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ede Aguiar Pastore Silva J, Emilia de Souza Fabre M, Waitzberg DL (2015) Omega-3 supplements for patients in chemotherapy and/or radiotherapy: A systematic review Clin Nutr 34: 359\u0026ndash;366 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.clnu.2014.11.005\u003c/span\u003e\u003cspan address=\"10.1016/j.clnu.2014.11.005\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ede Oliveira Hinokuma AF, de Andrade PC, H\u0026ouml;felmann DA (2025) Progression of nutritional impact symptoms in cancer patients undergoing radiotherapy Support Care Cancer 33: 108 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00520-025-09172-8\u003c/span\u003e\u003cspan address=\"10.1007/s00520-025-09172-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ede Pinho NB, Martucci RB, Rodrigues VD, D'Almeida CA, Thuler LCS, Saunders C, Jager-Wittenaar H, Peres WAF (2020) High prevalence of malnutrition and nutrition impact symptoms in older patients with cancer: Results of a Brazilian multicenter study Cancer 126: 156\u0026ndash;164 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/cncr.32437\u003c/span\u003e\u003cspan address=\"10.1002/cncr.32437\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ede van der Schueren MAE, Laviano A, Blanchard H, Jourdan M, Arends J, Baracos VE (2018) Systematic review and meta-analysis of the evidence for oral nutritional intervention on nutritional and clinical outcomes during chemo(radio)therapy: current evidence and guidance for design of future trials Annals of oncology 29: 1141\u0026ndash;1153 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/annonc/mdy114\u003c/span\u003e\u003cspan address=\"10.1093/annonc/mdy114\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDi Maio M, Basch E, Denis F, Fallowfield LJ, Ganz PA, Howell D, Kowalski C, Perrone F, Stover AM, Sundaresan P, Warrington L, Zhang L, Apostolidis K, Freeman-Daily J, Ripamonti CI, Santini D (2022) The role of patient-reported outcome measures in the continuum of cancer clinical care: ESMO Clinical Practice Guideline Annals of Oncology 33: 878\u0026ndash;892 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.annonc.2022.04.007\u003c/span\u003e\u003cspan address=\"10.1016/j.annonc.2022.04.007\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDingemans AM, van Walree N, Schramel F, Soud MY, Baltruškevičienė E, Lybaert W, Veldhorst M, van den Berg CA, Kaasa S (2023) High Protein Oral Nutritional Supplements Enable the Majority of Cancer Patients to Meet Protein Intake Recommendations during Systemic Anti-Cancer Treatment: A Randomised Controlled Parallel-Group Study Nutrients 1510.3390/nu15245030\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFord KL, Sawyer MB, Ghosh S, Trottier CF, Disi IR, Easaw J, Mulder K, Koski S, Porter Starr KN, Bales CW, Arends J, Siervo M, Deutz N, Prado CM (2024) Feasibility of two levels of protein intake in patients with colorectal cancer: findings from the Protein Recommendation to Increase Muscle (PRIMe) randomized controlled pilot trial ESMO Open 9: 103604 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.esmoop.2024.103604\u003c/span\u003e\u003cspan address=\"10.1016/j.esmoop.2024.103604\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHanna L, Nguo K, Furness K, Porter J, Huggins CE (2022) Association between skeletal muscle mass and quality of life in adults with cancer: a systematic review and meta-analysis Journal of Cachexia, Sarcopenia and Muscle 13: 839\u0026ndash;857 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/jcsm.12928\u003c/span\u003e\u003cspan address=\"10.1002/jcsm.12928\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eH\u0026eacute;buterne X, Lemari\u0026eacute; E, Michallet M, de Montreuil CB, Schneider SM, Goldwasser F (2014) Prevalence of malnutrition and current use of nutrition support in patients with cancer JPEN 38: 196\u0026ndash;204 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/0148607113502674\u003c/span\u003e\u003cspan address=\"10.1177/0148607113502674\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHoldoway A, Page F, Bauer J, Dervan N, Maier AB (2022) Individualised Nutritional Care for Disease-Related Malnutrition: Improving Outcomes by Focusing on What Matters to Patients Nutrients 1410.3390/nu14173534\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKwiecien C, Pouyet V, Daly LE, Fernandez Gonzalez I, Blanchard H, Bilman E, Mekers S, Boireau N (2023) EPA Enriched Oral Nutritional Supplements With A Tailored Sensory Design To Address Taste Alterations Are Appreciated By Patients With Cancer Clinical Nutrition ESPEN 54: 500 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.clnesp.2022.09.129\u003c/span\u003e\u003cspan address=\"10.1016/j.clnesp.2022.09.129\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLam CN, Watt AE, Isenring EA, de van der Schueren MAE, van der Meij BS (2021) The effect of oral omega-3 polyunsaturated fatty acid supplementation on muscle maintenance and quality of life in patients with cancer: A systematic review and meta-analysis Clin Nutr 40: 3815\u0026ndash;3826 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.clnu.2021.04.031\u003c/span\u003e\u003cspan address=\"10.1016/j.clnu.2021.04.031\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMerker M, Felder M, Gueissaz L, Bolliger R, Tribolet P, Kagi-Braun N, Gomes F, Hoess C, Pavlicek V, Bilz S, Sigrist S, Brandle M, Henzen C, Thomann R, Rutishauser J, Aujesky D, Rodondi N, Donze J, Stanga Z, Mueller B, Schuetz P (2020) Association of Baseline Inflammation With Effectiveness of Nutritional Support Among Patients With Disease-Related Malnutrition: A Secondary Analysis of a Randomized Clinical Trial JAMA Netw Open 3: e200663 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jamanetworkopen.2020.0663\u003c/span\u003e\u003cspan address=\"10.1001/jamanetworkopen.2020.0663\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMilla SP, Luna PPG, Casariego AV, Gonz\u0026aacute;lez FV, Folgueras TM, J\u0026aacute;uregui OI, Rey SG, Fern\u0026aacute;ndez AC, Plaza BL, Quintana TC, de Luis Rom\u0026aacute;n DA (2024) Adherence and impact of an oral nutritional supplement enriched in leucine, EVOO, EPA and DHA, and beta-glucans on the coverage of energy and protein requirements in patients with cancer and malnutrition: Alisenoc study Nutrition 120: 112355 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.nut.2024.112355\u003c/span\u003e\u003cspan address=\"10.1016/j.nut.2024.112355\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMoreau J, Ordan M-A, Barbe C, Mazza C, Perrier M, Botsen D, Brasseur M, Portefaix C, Renard Y, Talli\u0026egrave;re B, Bertin E, Hoeffel C, Bouch\u0026eacute; O (2019) Correlation between muscle mass and handgrip strength in digestive cancer patients undergoing chemotherapy Cancer Medicine 8: 3677\u0026ndash;3684 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/cam4.2238\u003c/span\u003e\u003cspan address=\"10.1002/cam4.2238\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMuscaritoli M, Arends J, Bachmann P, Baracos V, Barthelemy N, Bertz H, Bozzetti F, Hutterer E, Isenring E, Kaasa S, Krznaric Z, Laird B, Larsson M, Laviano A, Muhlebach S, Oldervoll L, Ravasco P, Solheim TS, Strasser F, de van der Schueren M, Preiser JC, Bischoff SC (2021) ESPEN practical guideline: Clinical Nutrition in cancer Clin Nutr 40: 2898\u0026ndash;2913 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.clnu.2021.02.005\u003c/span\u003e\u003cspan address=\"10.1016/j.clnu.2021.02.005\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNaqvi A, Matias N, Al-Khaffaf B (2024) Reporting of core outcomes in gastric cancer surgery trials over the past 25 years (systematic review) Journal of Surgical Oncology 129: 1274\u0026ndash;1288 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/jso.27613\u003c/span\u003e\u003cspan address=\"10.1002/jso.27613\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNeoh MK, Abu Zaid Z, Mat Daud ZA, Md Yusop NB, Ibrahim Z, Abdul Rahman Z, Jamhuri N (2020) Changes in Nutrition Impact Symptoms, Nutritional and Functional Status during Head and Neck Cancer Treatment Nutrients 1210.3390/nu12051225\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOrsso CE, Caretero A, Poltronieri TS, Arends J, de van der Schueren MA, Kiss N, Laviano A, Prado CM (2024) Effects of high-protein supplementation during cancer therapy: a systematic review and meta-analysis The American Journal of Clinical Nutrition 120: 1311\u0026ndash;1324 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ajcnut.2024.08.016\u003c/span\u003e\u003cspan address=\"10.1016/j.ajcnut.2024.08.016\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOrsso CE, Ford KL, Kiss N, Trujillo EB, Spees CK, Hamilton-Reeves JM, Prado CM (2023) Optimizing clinical nutrition research: the role of adaptive and pragmatic trials European Journal of Clinical Nutrition 77: 1130\u0026ndash;1142 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41430-023-01330-7\u003c/span\u003e\u003cspan address=\"10.1038/s41430-023-01330-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePrado CM, Anker SD, Coats AJS, Laviano A, von Haehling S Nutrition in the spotlight in cachexia, sarcopenia and muscle: avoiding the wildfire Journal of Cachexia, Sarcopenia and Muscle \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/jcsm.12673\u003c/span\u003e\u003cspan address=\"10.1002/jcsm.12673\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRyan AM, Prado CM, Sullivan ES, Power DG, Daly LE (2019) Effects of weight loss and sarcopenia on response to chemotherapy, quality of life, and survival Nutrition 67\u0026ndash;68: 110539 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.nut.2019.06.020\u003c/span\u003e\u003cspan address=\"10.1016/j.nut.2019.06.020\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShakhshir MH, Salameh HT, Amer R, Zyoud SeH (2024) An evaluation of nutritional impact symptoms and their association with reduced dietary intake in patients with solid tumors at tertiary care hospitals: a multicenter, cross-sectional study from Palestine BMC Cancer 24: 524 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12885-024-12289-4\u003c/span\u003e\u003cspan address=\"10.1186/s12885-024-12289-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShirai Y, Okugawa Y, Hishida A, Ogawa A, Okamoto K, Shintani M, Morimoto Y, Nishikawa R, Yokoe T, Tanaka K, Urata H, Toiyama Y, Inoue Y, Tanaka M, Mohri Y, Goel A, Kusunoki M, McMillan DC, Miki C (2017) Fish oil-enriched nutrition combined with systemic chemotherapy for gastrointestinal cancer patients with cancer cachexia Sci Rep 7: 4826 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41598-017-05278-0\u003c/span\u003e\u003cspan address=\"10.1038/s41598-017-05278-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSpotten LE, Corish CA, Lorton CM, Ui Dhuibhir PM, O'Donoghue NC, O'Connor B, Walsh TD (2017) Subjective and objective taste and smell changes in cancer Annals of Oncology:28: 969\u0026ndash;984 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/annonc/mdx018\u003c/span\u003e\u003cspan address=\"10.1093/annonc/mdx018\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTong H, Isenring E, Yates P (2009) The prevalence of nutrition impact symptoms and their relationship to quality of life and clinical outcomes in medical oncology patients Support Care Cancer 17: 83\u0026ndash;90 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00520-008-0472-7\u003c/span\u003e\u003cspan address=\"10.1007/s00520-008-0472-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVidal Casariego A, Garc\u0026iacute;a Luna PP, Villaz\u0026oacute;n Gonz\u0026aacute;lez F, Mart\u0026iacute;n Folgueras T, Palma Milla S, L\u0026oacute;pez G\u0026oacute;mez JJ, Gonz\u0026aacute;lez Navarro I, Calleja Fern\u0026aacute;ndez A, Casa\u0026ntilde;as Quintana T, L\u0026oacute;pez Plaza B, de Luis Rom\u0026aacute;n DA (2023) Impact of an oral nutritional supplement enriched in leucine, EPA, DHA, and β-glucans on the increase of muscle mass in patients with cancer and malnutrition: The alisenoc trial Journal of Functional Foods 110: 105833 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jff.2023.105833\u003c/span\u003e\u003cspan address=\"10.1016/j.jff.2023.105833\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang Y, Liu R, Chang M, Wei W, Guo Y, Jin Q, Wang X (2023) Does omega-3 PUFA-enriched oral nutritional intervention benefit cancer patients receiving chemo (radio) therapy? A systematic review and meta-analysis of randomized controlled trials Critical reviews in Food Science and Nutrition 63: 3081\u0026ndash;3096 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/10408398.2021.1984199\u003c/span\u003e\u003cspan address=\"10.1080/10408398.2021.1984199\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWunderle C, Stumpf F, Schuetz P (2024) Inflammation and response to nutrition interventions JPEN 48: 27\u0026ndash;36 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/jpen.2534\u003c/span\u003e\u003cspan address=\"10.1002/jpen.2534\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"oral nutritional supplements, high protein, omega-3 LC-PUFA, cancer, strength, patient reported outcomes","lastPublishedDoi":"10.21203/rs.3.rs-7453912/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7453912/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eTo compensate for reduced nutritional intake and altered metabolic needs in cancer, ESMO and ESPEN recommend higher than normal energy and protein intake, with omega-3 long chain polyunsaturated fatty acid (LC-PUFA) supplementation to target inflammation.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eIn this multi-center, single arm study adult outpatients with or at risk of malnutrition and requiring ONS were prescribed 2 x 125 ml high protein (HP), omega-3 LC-PUFA enriched ONS (Forticare Advanced, 18 g protein, 306 kcal, 1.1 g EPA, 0.7 g DHA, 10 \u0026micro;g vitamin D) daily for 3 months. Body weight (BW), adherence to ONS (primary outcomes), C-reactive protein (CRP), hand grip strength (HGS), 30-second chair stand test (CST) and patient reported outcomes were assessed at baseline (Day 0), 1 and 3 months.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003e761 patients (47.5% male, mean age 65 (SD 12) years) were included. At baseline, 77.9% of patients had\u0026thinsp;\u0026gt;\u0026thinsp;5% weight loss (WL) and had higher CRP and lower albumin levels than patients with \u0026lt;\u0026thinsp;5% WL (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Average adherence to the ONS was 1.7 (85%) bottles/d, despite 34% of patients reporting altered taste/smell. Mean gain in BW was 1 kg (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) with 76% of patients gaining or stabilizing BW over 3 months. CRP levels decreased (mean \u0026minus;\u0026thinsp;7.5 mg/L (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), physical performance improved (increase in HGS (+\u0026thinsp;1.2 kg, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and CST (+\u0026thinsp;1.4 stands, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001)) and patients reported improved physical aspects of quality of life (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) at 3 months.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eIn this study, patients with cancer prescribed HP, omega-3 LC-PUFA enriched ONS for 3-months gained weight, experienced reduced inflammation, and improved physical performance and patient reported outcomes.\u003c/p\u003e","manuscriptTitle":"Evaluation of a 3-month intervention with high protein, omega-3 LC-PUFA enriched oral nutritional supplement on body weight, inflammation, muscle strength and patient reported outcomes in patients with cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-17 02:21:46","doi":"10.21203/rs.3.rs-7453912/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ebc2d712-9edd-4e4d-ab08-c73e20d08063","owner":[],"postedDate":"October 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-21T23:23:46+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-17 02:21:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7453912","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7453912","identity":"rs-7453912","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}