4. Discussion
NSCLC, reduced skeletal muscle loss, colorectal cancer, muscle loss, gastrointestinal or lung cancer, CRC, taste and smell alterations, cancer, cachexia, toxicities, sarcopenia, lung cancer, cancer type, Anorexia
COLORECTAL CANCER, RECRUITMENT, CANCER, SARCOPENIA, RECRUITMENT, LUNG CANCER, STAGE II NSCLC, MALNOURISHED, NSCLC, ANOREXIA
Despite the challenges in patient recruitment and early termination of this study, we demonstrated that intervention twice daily with a high-protein, high-energy, low-volume ONS was effective at increasing protein intake in patients with CRC and NSCLC undergoing first-line systemic treatment with chemo-, concurrent chemoradio- or immunotherapy. Data from the literature suggest that 52–66% of patients undergoing systemic treatment fail to meet ESPEN minimum protein recommendations of >1.0 g/kg BW/day without specific nutritional support [Body weight changes showed a trend towards better weight maintenance at T1 and T2 in the IG compared to the CG; however, these changes did not reach statistical significance. At T3, both the IG and CG showed an increase in body weight compared to T0. An important factor for consideration in the current study is the nutritional status of subjects at baseline. Anorexia, inadequate nutritional intake and cachexia are highly prevalent in patients with gastrointestinal or lung cancer at diagnosis [A review of the literature highlighted that muscle loss is also prevalent in these cancer types with a median sarcopenia prevalence of 49% and 70% in CRC and lung cancer patients, respectively [Although no statistically significant increase in body weight was observed, the increase in protein intake seen in the IG may exert a positive influence on body composition with the potential to maintain or increase lean body mass [The study product had a low volume (125 mL) to support patient compliance throughout the course of the treatment. Overall compliance to the study product was high (73.4%, i.e., 1.5 servings per day with 2 servings being the prescribed dose) and remained stable over the 12-week intervention period. A previous study showed an average ONS compliance of around 50% in patients with stage III NSCLC during multimodality treatment [We observed no major differences in the other outcomes assessed such as quality of life, performance status, factors affecting dietary intake, taste and smell alterations, and treatment tolerance and toxicities between study groups, although the reporting of these parameters was significantly hindered by the small sample size. Data from other studies using ONS for three months, post-discharge, following colorectal cancer surgery have shown improvements in other outcomes such as reduced skeletal muscle loss and sarcopenia prevalence as well as improved chemotherapy tolerance compared with dietary advice alone in patients at nutritional risk [Despite the challenges in patient recruitment, this study was a well-designed, multi-centre, randomised controlled trial in which 42 patients were enrolled, and subsequent data on nutritional outcomes was successfully collected. The study adds to the existing literature by focusing on a cohort of patients that excluded the most malnourished subjects but represented an “at-risk” group based on their projected clinical course according to guidelines from the ESMO [In contrast to the strengths of this study, there are a few limitations. Recruitment challenges led to the study being terminated earlier than planned with 37 patients being included in the modified Intention-to-Treat (mITT) subject data set (subjects who completed the primary endpoint at T1). The study was also impacted by the COVID-19 pandemic, which meant that recruitment was paused for an extended period of time. This may have affected ongoing recruitment with subjects being less willing to have non-essential healthcare interactions during the pandemic given their clinical vulnerability. A review of the impact of COVID-19 on oncology clinical trials showed that patient enrolment in active clinical trials for cancer therapies was severely affected by the COVID-19 pandemic, and recruitment continued to be problematic in some countries [Despite using a 2:1 randomisation to offer subjects a greater chance of receiving the nutritional intervention, it is possible that the lack of a control product may have affected patients’ willingness to participate and/or continue in the study (contributing to higher attrition in the control arm). A 2:1 randomisation approach is more often used in oncology trials so that patients have a higher chance of receiving the intervention and thus the expected benefit from participation [A multi-centre international study design was selected for this trial for a number of reasons, namely to maximise recruitment in a population where recruitment can be difficult and to reflect the diverse practices and expertise that occur in real-world clinical practice to increase the generalisability of results. However, this can also represent a challenge since practices such as standard nutritional care can differ between study centres. The study was not stratified by centre due to more important covariates being prioritised, i.e., cancer type and cancer treatment. However, at study initiation a questionnaire about standard nutritional care was completed via interview with the relevant study site personnel. Heterogeneity in when, how and by whom patients were screened for nutritional risk and when and what nutritional intervention was used was identified. The prescription of ONS was found to be part of standard nutritional care but generally commenced relatively late in the patient journey, although this varied by country. For this reason, the use of ONS in the control group in the study was monitored. One subject in the control group received a prescription of ONS (one serving of 125 mL per day) on intervention Day 3 and 4, which is unlikely to have influenced the results.Despite a growing body of research demonstrating the benefits of nutritional intervention in cancer, there remains a gap in translating the available evidence into clinical practice. The provision of nutritional intervention is still an unmet need for many patients despite the availability of nutritional guidelines from expert professional groups. Research that considers the patients’ perspective shows that nutrition is rated as highly important in their cancer care [