Abstract
Background
Malnutrition is common in patients with metastatic esophagogastric adenocarcinoma (EGA). However, the prognostic impact of nutritional risk screening (NRS) in advanced EGA remains underexplored. This preplanned analysis of the phase II AIO-MATEO trial evaluated the impact of NRS on clinical outcomes for patients with advanced EGA.
Patients and methods
Patients enrolled in the MATEO trial (exploring S-1 maintenance therapy) with an available baseline NRS before induction chemotherapy were included. Patients were stratified by their baseline NRS score (<3 versus ≥3). Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan–Meier and Cox regression methods.
Results
Of the 136 patients, 86 had an NRS score <3 and 50 had an NRS score ≥3 at baseline. Baseline median European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30) global health score was lower for the NRS ≥3 group (37.5 versus 58.3). Nutritional interventions were more frequent in the NRS ≥3 group (45.8% versus 10.6%; P < 0.001). Patients with NRS ≥3 had inferior median PFS (4.9 months versus 6.9 months; P = 0.025) and OS (8.2 months versus 13.2 months; P = 0.003). Patients whose NRS score improved during induction chemotherapy showed superior median PFS (7.4 months versus 4.1 months; P = 0.085) and OS (20.1 months versus 8.0 months; P = 0.054) compared with those without improvement. No significant differences in overall toxicity were observed.
Conclusions
Baseline NRS is a significant predictor of outcome in patients with metastatic EGA. Our findings underscore the importance of routinely assessing the nutritional status of patients with metastatic EGA and intervening early.
Key words: chemotherapy, malnutrition, metastatic esophagogastric adenocarcinoma, nutritional intervention, nutritional risk screening
Highlights
-
•
This is a preplanned analysis of a randomized trial evaluating the impact of NRS on survival in metastatic EGA.
-
•
Baseline NRS score <3 and improvement in NRS during induction therapy are associated with superior survival outcome.
-
•
Nutritional support was only provided to 45.8% of patients with an NRS score ≥3.
-
•
Baseline NRS is a powerful and independent predictor of outcome in patients with metastatic EGA.
-
•
Routine NRS screening and timely nutritional intervention are strongly recommended for patients with metastatic EGA.
Introduction
Esophagogastric adenocarcinoma (EGA) is a highly prevalent malignancy, with a global incidence of ∼9.2/100 000.1 While the incidence of gastric cancer has been declining in recent decades, there has been a marked increase in adenocarcinomas at the esophagogastric junction, particularly in high-income countries.2 Compared with other gastrointestinal tumors, malnutrition is common and often present at the time of diagnosis in EGA.3, 4, 5, 6, 7 Malnutrition, caused by the tumor disease itself or treatment-related toxicity, negatively impacts treatment tolerance, recovery, and overall survival (OS). This underscores the importance of an early nutritional assessment and intervention as a critical component of EGA management.8, 9, 10, 11, 12, 13, 14
The nutritional risk screening (NRS), developed by the European Society for Clinical Nutrition and Metabolism (ESPEN) in 2002, is a widely utilized tool for identifying patients at risk of malnutrition, particularly in hospitalized settings.15,16 The NRS score evaluates two key components: nutritional status and disease severity. Patients are assigned scores for each component, with an additional point for those over 70 years of age, due to the increased malnutrition risk in elderly patients (Supplementary Table S1, available at https://doi.org/10.1016/j.esmogo.2025.100297). A score of ≥3 indicates an increased nutritional risk and thus recommends a nutritional support intervention.16 This may include dietary counseling and monitoring, oral nutritional supplements, and enteral or parenteral nutrition.
Studies have shown that tailored nutritional support based on NRS scores improves clinical outcomes, including fewer post-operative complications and better quality of life (QoL) for patients with EGA.17, 18, 19 However, data on the impact of the NRS score on the outcomes of patients with metastatic EGA undergoing systemic treatment are limited. To the best of our knowledge, there are no randomized oncological trials that have included a preplanned analysis of the NRS during the treatment phase.
The international, randomized phase II AIO-MATEO study explored the efficacy and safety of S-1 maintenance therapy—an orally administered chemotherapy drug composed of tegafur, gimeracil, and oteracil—compared with continued platinum-based chemotherapy in Caucasian patients with human epidermal growth factor receptor 2 (HER2)-negative advanced EGA who had no disease progression after 3 months of induction chemotherapy.20 The MATEO study showed that S-1 maintenance therapy resulted in survival outcomes that were non-inferior compared with ongoing platinum-based combination chemotherapy, while offering better tolerability.21
This preplanned analysis of the MATEO trial investigates the impact of baseline nutritional risk, as assessed by NRS score, on progression-free survival (PFS), OS, treatment-related toxicity, and QoL in patients undergoing platinum-based combination chemotherapy as first-line treatment for metastatic EGA.
Patients and methods
Study design and treatment regimens
MATEO is an international, investigator-initiated, randomized phase II trial conducted within the Arbeitsgemeinschaft Internistische Onkologie (AIO) and registered at ClinicalTrials.gov (NCT02128243). The design and protocol of the MATEO study have been previously published.20 Briefly, patients with histologically confirmed HER2-negative metastatic or locally advanced irresectable EGA who have finished 12 weeks of platinum-based induction chemotherapy without disease progression were randomly assigned in a 2 : 1 ratio to either S-1 monotherapy (arm A) or continuation of platinum–fluoropyrimidine-based combination chemotherapy (arm B). Investigators selected polychemotherapy regimens from a predefined list of recommended doublet or triplet regimens. The trial design is illustrated in Supplementary Figure S1, available at https://doi.org/10.1016/j.esmogo.2025.100297.
This study was conducted in compliance with the Declaration of Helsinki. The trial protocol and all its amendments received approval from the responsible ethics committee. Written informed consent was obtained from all patients before any study-related procedures.
Quality of life, nutritional assessment, and nutritional interventions
QoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30). Clinically significant deterioration was defined as a decrease of ≥10 points in the global health status. QoL assessments were carried out at baseline (before start of induction therapy) and at randomization (week 12).
The local investigator assessed nutritional status using the NRS at the same time points (see Supplementary Table S1, available at https://doi.org/10.1016/j.esmogo.2025.100297). The NRS is a two-step screening tool Supplementary Table S1https://doi.org/10.1016/j.esmogo.2025.100297. In the first step, initial screening evaluates factors such as recent weight loss, body mass index (BMI), reduced dietary intake, and the severity of the underlying disease. If any of these factors are concerning, the second step (final screening) is carried out, assessing the score based on the presence of any nutritional deficiencies and the patient’s functional status influenced by disease severity. An additional point is added for patients aged ≥70 years. The NRS score ranges from 0 to 7, with higher scores indicating greater nutritional risk. For patients with a negative initial screening, an NRS score of 0 is assigned.
Nutritional interventions were categorized as follows: no nutritional intervention referred to standard oncologic care without any specific nutritional support. Nutritional counseling consisted of individualized dietary advice provided by trained staff. Additional oral high-calorie intake included the prescription of oral nutritional supplements to increase daily caloric and protein intake. Additional parenteral nutrition referred to supplemental intravenous nutrition administered in addition to oral intake. Total parenteral nutrition was defined as the exclusive intravenous nutrition without relevant oral intake. No specific protocol guidance was provided for nutritional interventions.
Statistical analysis
For the preplanned analysis presented in this article, patients were stratified into the NRS <3 group and NRS ≥3 group based on their NRS score at baseline. PFS and OS were estimated using the Kaplan–Meier method and P values between groups were assessed using the log-rank test. Since the primary objective of the MATEO trial was to demonstrate non-inferiority in OS for the S-1 maintenance group compared with the continuation of platinum-based chemotherapy, outcome results were reported with two-sided 80% confidence intervals (CIs), and two-sided P values < 0.2 were considered statistically significant. The Cox proportional hazards model was used for both univariate and multivariate analysis of risk factors. Only variables with a significant association to outcome in the univariate analysis were included in the final multivariate analysis. Comparisons of nutritional interventions and the incidence of adverse events (AEs) between NRS groups were carried out using the chi-square test for categorical variables. For these analyses, P values < 0.05 were considered statistically significant.
Patient population for subgroup analysis
Between November 2014 and April 2019, 221 patients were recruited across six European countries, with 162 patients registered before induction therapy. This analysis focuses on 136 eligible patients who completed induction therapy during the study and had an assessed NRS score at baseline before start of systemic treatment. A corresponding CONSORT diagram is shown in Supplementary Figure S2, available at https://doi.org/10.1016/j.esmogo.2025.100297.
Results
Patient characteristics and NRS score distribution
A total of 136 patients were included in this analysis. At screening, 86 patients had an NRS score of <3, while 50 patients had an NRS score of ≥3. The distribution of NRS scores at screening is detailed in Table 1. Baseline patient characteristics stratified by NRS groups (<3 versus ≥3) are presented in Table 2. Patients in the NRS ≥3 group were older (mean age 67.6 years) compared with those in the NRS <3 group (mean age 61.1 years) and had a lower mean body weight (71.5 kg versus 76.9 kg). Additionally, a higher proportion of patients in the NRS ≥3 group had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 1 (74.0% versus 44.2%). FLOT (docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil) as a triplet chemotherapy was used more frequently as induction regimen in the NRS <3 group (59.3% versus 34.0%). A higher proportion of patients in the NRS ≥3 group did not undergo randomization due to limiting toxicity or early disease progression (44.0% versus 32.6% in the NRS <3 group). Other characteristics including gender, ethnicity, BMI, histological subtype, M stage at initial diagnosis, prior chemotherapy, or radiotherapy for localized disease were balanced between the two groups.
Table 1.
Nutritional risk score at screening
| Nutritional risk score | n = 136, % (n) |
|---|---|
| 0 | 13.2 (18) |
| 1 | 19.1 (26) |
| 2 | 30.9 (42) |
| 3 | 21.3 (29) |
| 4 | 12.5 (17) |
| 5 | 1.5 (2) |
| 6 | 1.5 (2) |
Table 2.
Patient characteristics
| Characteristic | NRS < 3 n = 86 | NRS ≥ 3 n = 50 |
|---|---|---|
| Age, years | ||
| Mean (range) | 61.1 (35-83) | 67.6 (35-80) |
| Sex, % (n) | ||
| Male | 74.4 (64) | 64.0 (32) |
| Female | 25.6 (22) | 36.0 (18) |
| Ethnic group, % (n) | ||
| Caucasian | 100 (86) | 98.0 (49) |
| African | 0 | 2.0 (1) |
| ECOG PS, % (n) | ||
| 0 | 55.8 (48) | 26.0 (13) |
| 1 | 44.2 (38) | 74.0 (37) |
| Body weight, kg | ||
| Mean (range) | 76.9 (48-119) | 71.5 (38-106) |
| BMI, kg/m2 | ||
| Mean (range) | 25.8 (18-41) | 24.5 (15-37) |
| Tumor localization (primary tumor), % (n) | ||
| Distal esophagus (AEG I) | 19.8 (17) | 16.0 (8) |
| Cardia carcinoma (AEG II) | 36.0 (31) | 20.0 (10) |
| Subcardial carcinoma (AEG III) | 7.0 (6) | 20.0 (10) |
| Distal stomach | 37.2 (32) | 44.0 (22) |
| Histological subtype, % (n) | ||
| Intestinal type | 50.0 (43) | 40.0 (20) |
| Diffuse type | 24.4 (21) | 30.0 (15) |
| Mixed type | 5.8 (5) | 10.0 (5) |
| Unknown | 19.8 (17) | 20.0 (10) |
| M stage at initial diagnosis, % (n) | ||
| M0 | 23.3 (20) | 22.0 (11) |
| M1 | 75.6 (65) | 78.0 (39) |
| Prior chemotherapy, % (n) | 15.1 (13) | 16.0 (8) |
| Prior radiotherapy, % (n) | 4.7 (4) | 4.0 (2) |
| Induction regimen, % (n) | ||
| FLOT | 59.3 (51) | 34.0 (17) |
| FLO | 19.8 (17) | 48.0 (24) |
| Modified FOLFOX6 | 11.6 (10) | 12.0 (6) |
| Cisplatin/S1 | 7.0 (6) | 4.0 (2) |
| EOX/EOF | 0 | 2.0 (1) |
| Cisplatin/5-FU | 2.3 (2) | 0 |
| Study arm, % (n) | ||
| A | 47.7 (41) | 32.0 (16) |
| B | 19.8 (17) | 24.0 (12) |
| Not randomized | 32.6 (28) | 44.0 (22) |
5-FU, 5-fluorouracil; AEG, adenocarcinoma of esophagogastric junction; BMI, body mass index; ECOG PS, Eastern Cooperative Oncology Group performance status; EOF, epirubicin, oxaliplatin, 5-FU; EOX, epirubicin, oxaliplatin, capecitabine; FLO, oxaliplatin, folinic acid, 5-FU; FLOT, docetaxel, oxaliplatin, folinic acid, 5-FU; modified FOLFOX-6, oxaliplatin, folinic acid, 5-FU; NRS, nutritional risk screening.
Nutritional interventions
The frequency of nutritional interventions was significantly different between patients with NRS scores <3 and ≥3. At baseline, data were available for 85 patients in the NRS <3 group and 48 patients in the NRS ≥3 group. 45.8% of patients in the NRS ≥3 group compared with 10.6% in the NRS <3 group (P < 0.001) received nutritional interventions. The types of interventions varied. The NRS ≥3 group received nutritional counseling more frequently (8.3% versus 3.5%), as well as additional oral high-calorie intake (31.3% versus 4.7%) and parenteral nutrition (6.3% versus 1.2%). By the end of induction chemotherapy, nutritional intervention data were available for 57 patients in the NRS <3 group and 24 patients in the NRS ≥3 group. Nutritional interventions remained significantly more common in the NRS ≥3 group (45.8% versus 15.8%; P = 0.004), with continued higher use of additional oral high-calorie intake (20.8% versus 7.0%) and additional parenteral nutrition (12.5% versus 3.5%). Detailed data on nutritional intervention by NRS group are provided in Table 3.
Table 3.
Nutritional intervention
| NRS < 3 n = 85 | NRS ≥ 3 n = 48 | P value | |
|---|---|---|---|
| Nutritional intervention at baseline, % (n) | 10.6 (9) | 45.8 (22) | <0.001 |
| Type of nutritional intervention at baseline, % (n) | <0.001 | ||
| No nutritional intervention | 89.4 (76) | 54.2 (26) | |
| Nutritional counseling | 3.5 (3) | 8.3 (4) | |
| Additional oral high-calorie intake | 4.7 (4) | 31.3 (15) | |
| Additional parenteral nutrition | 1.2 (1) | 6.3 (3) | |
| Total parenteral nutrition | 1.2 (1) | 0 |
| NRS <3 n = 57 | NRS ≥3 n = 24 | P value | |
|---|---|---|---|
| Nutritional intervention at end of induction phase, % (n) | 15.8 (9) | 45.8 (11) | 0.004 |
| Type of nutritional intervention at end of induction phase, % (n) | 0.040 | ||
| No nutritional intervention | 84.2 (48) | 54.2 (13) | |
| Nutritional counseling | 5.3 (3) | 12.5 (3) | |
| Additional oral high-calorie intake | 7.0 (4) | 20.8 (5) | |
| Additional parenteral nutrition | 3.5 (2) | 12.5 (3) | |
| Total parenteral nutrition | 0 | 0 |
P values indicating statistical significance are printed in bold (standard practice).
NRS, nutritional risk screening.
Adverse events
No significant differences were observed between the groups regarding the overall incidence of any AE, serious AE (SAE), treatment-related AE or SAE, or the most frequent and clinically relevant AEs. Any AE occurred in 100% of patients in the NRS <3 group and 96.2% of patients in the NRS ≥3 group (P = 0.151). SAEs were reported in 26.4% of patients in the NRS <3 and 19.2% of patients in the NRS ≥3 group (P = 0.483). Treatment-related AEs were observed in 98.1% and 96.2% (P = 0.602), while treatment-related SAEs occurred in 15.1% and 11.5% of patients (P = 0.668), respectively.
Survival outcomes and post-study treatment
When analyzing all patients, regardless of the treatment arm assigned, PFS and OS were significantly longer in the NRS <3 group than in the NRS ≥3 group. Specifically, median PFS was 6.9 months (80% CI 6.6-7.5 months) in the NRS <3 group, compared with 4.9 months (80% CI 4.6-5.9 months) in the NRS ≥3 group (P = 0.025). Median OS was 13.2 months (80% CI 10.5-14.6 months) in the NRS <3 group, compared with 8.2 months (80% CI 6.8-8.8 months) in the NRS ≥3 group (P = 0.003) (Figure 1A and B). Among patients whose NRS score improved from ≥3 to <3 at the end of induction therapy, median PFS was 7.4 months (80% CI 5.9-10.8 months) compared with 4.1 months (80% CI 2.9-8.4 months) for those without improvement (P = 0.085), and median OS was 20.1 months (80% CI 8.4-24.3 months) versus 8.0 months (80% CI 4.0-9.8 months) (P = 0.054) (Figure 1C and D).
Figure 1.
Progression-free survival (PFS) and overall survival (OS) by Nutritional Risk Screening (NRS) group and by NRS change. (A) Kaplan–Meier estimates for PFS by NRS group since start of induction. (B) Kaplan–Meier estimates for OS by NRS group since start of induction. (C) Kaplan–Meier estimates for PFS by NRS change since start of induction. (D) Kaplan–Meier estimates for OS by NRS change since start of induction.
Consistent with the results of the main analysis of the MATEO trial,21 univariate Cox regression analysis comparing survival outcomes between study arms by NRS groups revealed no significant differences in PFS and OS between study arm B versus study arm A, whereas patients in both NRS groups who were not randomized due to limiting toxicity or early disease progression exhibited significantly worse outcomes. Data from univariate Cox regression are demonstrated in Supplementary Table S2, available at https://doi.org/10.1016/j.esmogo.2025.100297. Kaplan–Meier estimates for PFS and OS by study arm within each NRS group are depicted in Supplementary Figure S3, available at https://doi.org/10.1016/j.esmogo.2025.100297.
Regarding post-study treatments, no significant differences were observed between the NRS groups. Post-study treatment was initiated in 86.9% (n = 53/61) of patients in the NRS <3 group and 80.0% (n = 24/30) in the NRS ≥3 group (P = 0.392).
Quality of life outcomes
The median global health score at screening was significantly worse for the NRS ≥3 group with 37.5 compared with 58.3 for the NRS <3 group. The median time to further deterioration was shorter in the NRS <3 group with 5.9 months (80% CI 5.1-9.2 months), compared with the NRS ≥3 group, where it was not calculable (80% CI 7.4 months- not calculable) (P = 0.038) (Supplementary Figure S4, available at https://doi.org/10.1016/j.esmogo.2025.100297) according to the QLQ-C30 questionnaire.
Multivariate analysis
In the multivariate Cox regression analysis including gender, age, and baseline nutritional status as covariates, all three parameters were identified as independent predictors for OS. Patients with NRS ≥3 had a higher risk of death compared with those with NRS <3 [hazard ratio (HR) 1.61, 80% CI 1.15-2.27, P = 0.071]. Similarly, patients aged ≥70 years showed an increased mortality risk compared with those <70 years (HR 1.51, 80% CI 1.08-2.12, P = 0.120). Additionally, gender showed significance (P = 0.048), with female patients demonstrating a lower risk of mortality than males (HR 0.58, 80% CI 0.40-0.82).
Discussion
To the best of our knowledge, this is the first preplanned analysis of a randomized oncological trial evaluating the impact of nutritional risk on outcome in patients with metastatic EGA undergoing systemic treatment. This analysis of the phase II MATEO trial highlights the significant influence of baseline nutritional risk, assessed by the NRS 2002, on clinical outcomes in patients with HER2-negative metastatic EGA. Our findings underscore the critical role of nutritional status in determining survival, emphasizing the importance of early nutritional assessment and intervention in this patient population.
The groups were categorized into NRS <3 and ≥3, as the ESPEN guidelines recommend nutritional intervention for patients with NRS scores of ≥3.15,16
The NRS score ≥3 group tended to be older and had a lower mean body weight compared with the patients in the NRS <3 group, suggesting that older patients and patients with a lower body weight are at higher nutritional risk. Our results demonstrate that patients with a baseline NRS score ≥3 had significantly shorter PFS and OS compared with those with an NRS score <3. These findings are consistent with previous studies indicating that malnutrition adversely affects survival in cancer patients, likely due to reduced treatment tolerance, increased susceptibility to infections, and impaired recovery from therapy.8, 9, 10, 11, 12, 13, 14 However, most prior studies have focused on the impact of NRS in non-metastatic EGA, particularly on post-operative outcomes. To our knowledge, only one cohort study by Li et al. has evaluated the prognostic value of NRS in metastatic gastric cancer. In this study, patients were stratified into groups with NRS ≤3 and >3. Consistent with our findings, patients with an NRS >3 had a significantly shorter PFS and OS compared with those with an NRS ≤3.19
Notably, our analysis revealed that patients whose NRS score improved from ≥3 to <3 during the induction chemotherapy exhibited significantly better PFS and OS compared with those whose scores did not improve. One could speculate that improvement in the NRS score represents a surrogate marker for treatment response, but it may also demonstrate that timely nutritional interventions may reduce the negative impact of malnutrition on survival or treatment tolerance, highlighting the importance of early and effective nutritional support.
Nutritional interventions were significantly more frequent in the NRS ≥3 group, with nearly half of these patients requiring high-calorie oral or parenteral nutrition. However, despite the clear international guidelines recommending nutritional screening and support in patients with advanced EGA15,22, our analysis revealed that only 45.8% of this group of patients received such support. This discrepancy suggests that nutritional risk is often underestimated in daily clinical practice and that there may be substantial differences in how nutritional support is managed between institutions. Further data on the timing and intensity of the nutritional interventions were not assessed in this study. Consequently, the effects of the interventions themselves could not be reliably analyzed but only prognostic associations could be identified.
In general, no significant differences in treatment-related toxicity were observed between the NRS groups.
QoL assessments revealed that patients in the NRS <3 group surprisingly experienced a significantly shorter median time to deterioration in global health status compared with the NRS ≥3 group. However, the median global health score at screening was already significantly lower for the NRS ≥3 group, indicating poorer baseline QoL. This suggests that patients in the NRS <3 group started with a higher QoL, offering less potential for improvement, whereas those in the NRS ≥3 group may have already experienced substantial impairments. This difference in baseline QoL, along with potential ceiling as well as floor effects, may influence the observed time to deterioration and limit interpretation. Despite this, the shorter time to deterioration observed in the NRS <3 group highlights the importance of early QoL monitoring and supportive interventions, even among patients classified as having lower nutritional risk.
Multivariate analysis identified the NRS score at screening as an independent prognostic factor for OS, with patients in the NRS ≥3 group exhibiting a 1.61-fold higher risk of death compared with those in the NRS <3 group. This fact underscores that nutritional risk, as detected by NRS, is a critical determinant of survival in metastatic EGA, independent of other clinical and treatment-related factors. Additional significant prognostic factors included age and gender, with patients aged <70 years and females demonstrating more favorable survival outcomes.
This study has several limitations. The premature closure of the MATEO trial due to slow recruitment and changes in treatment approaches, such as the use of checkpoint inhibitors, may limit the generalizability of our findings. The NRS score was initially developed and validated for inpatients and not for patients in the outpatient setting. Furthermore, the NRS score incorporates factors that may be independent of nutrition such as age and comorbidities, which could act as potential confounders and may independently influence survival outcomes, irrespective of the nutritional status. We also acknowledge that a significantly higher proportion of patients in the NRS <3 group received triplet therapy compared with those in the NRS ≥3 group which likely impacted the observed survival outcomes. Additionally, the heterogeneity in the center-specific approach to provide nutritional support resulting in different types of nutritional interventions applied might have impacted the results we observed. Thus, the study design of the MATEO trial does not allow an estimation of the benefit of a nutritional intervention. During the study treatment, both improvements and deteriorations of the NRS score have been observed irrespective of the nutritional intervention applied, most likely reflecting the course of the disease.
In conclusion, this analysis of the MATEO trial demonstrates that the NRS is a powerful and independent predictor of survival in patients with metastatic EGA, highlighting the need for early and consistent nutritional interventions in high-risk patients. Despite recommendations of international guidelines, the limited implementation of nutritional support in patients in the NRS ≥3 group suggests variability in clinical practice across treatment centers. Future randomized studies focusing on standardizing nutritional interventions and evaluating their impact on survival and toxicity in this vulnerable patient population are warranted. Additionally, the influence of baseline NRS scores on the tolerability of targeted therapies or checkpoint inhibitors warrants further investigation. Integrating nutritional risk assessment and management into routine oncological care could offer a meaningful opportunity to improve outcomes in patients with metastatic EGA.
Acknowledgements
The authors greatly appreciate the support provided by the AIO Study gGmbH and the members of the Data and Safety Monitoring Board (DSMB) throughout the study.
Funding
The MATEO study was supported by a grant provided by Taiho Pharmaceutical, and study medication (S-1) was provided by Nordic Pharma [no grant number].
Disclosure
RS has received honoraria from Eisai, Amgen, and Pfizer, and has received travel support from Astellas, Ipsen, and BeiGene. MP and JLS are employees of P95, which was contracted by AIO to conduct the statistical analysis described in this manuscript. DJ has received consulting fees from Roche Pharma AG, OncoOne Research & Development Research GmbH, Amgen Inc., and CureVac AG; has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca GmbH, GRN Klinik Weinheim, BMS GmbH & Co KGaA, MSD, If-Kongress Management GmbH, Gruppe 5 Filmproduktion GmbH, The Norwegian Cancer Society, Department of Radiation Medicine, University of Kentucky, Centrum für Integrierte Onkologie Bonn; has received payment for expert testimony: expert opinions for courts, Wilhelm-Sander-Stiftung; has received support for attending meetings and/or travel: Amgen Inc., Oryx GmbH, Roche Glycart AG, Aex Congresse GmbH, Parexel, BMS Stiftung Immunonkologie, BMS GmbH & Co KGaA, and Bioevents-congress.com; participation on a data safety monitoring board or advisory board: CureVac AG, Definiens, F. Hoffmann-La Roche Ltd., VAXIMM AG, Oncolytics Biotech Inc., Genmab A-S, Life Science Inkubator GmbH, and OncoOne Research & Development Research GmbH; has a leadership or fiduciary role in other board, society, committee, or advocacy group paid or unpaid for BMS Stiftung Immunonkologie. FL reports research grants for his institution from AstraZeneca, BeiGene, BMS, Daiichi Sankyo, and Gilead, and personal fees from Amgen, ArtTempi. Astellas, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Iomedico, Daiichi Sankyo, Eli Lilly, Gilead, Elsevier, Incyte, Medscape, MedUpdate, Merck Serono, MSD, PAGE, Roche, Servier, StreamedUp!, and VJ Oncology, all outside the submitted work. GS reports personal fees from AstraZeneca, Amgen, Daiichi Sankyo, Pharmacosmos GmbH, and BMS, and travel grant from BeiGene. GMH received fees for an advisory role from Bristol Myers Squibb, MSD Sharp & Dohme, Lilly, Daiichi Sankyo, Servier, AstraZeneca, AbbVie, and BeiGene; he received speaker’s honoraria from Servier, MSD Sharp & Dohme, Lilly, Bristol Myers Squibb, AstraZeneca, Swiss Cancer League, Astellas, BeiGene, Deciphera, and StreamedUp; research funding is provided by DKFZ Heidelberg, MSD Sharp & Dohme, Bristol Myers Squibb, IKF Frankfurt, AstraZeneca, Leap Therapeutics, Daiichi Sankyo, and PMV Pharma; travel support was provided by Lilly, MSD Sharp & Dohme, Daiichi Sankyo, Amgen, BeiGene, and AstraZeneca. All other authors have declared no conflicts of interest.
Data sharing
The data that support the findings of this study are available from the corresponding authors upon reasonable request.
Supplementary Data
References
- 1.Bray F., Laversanne M., Sung H., et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229–263. doi: 10.3322/caac.21834. [DOI] [PubMed] [Google Scholar]
- 2.Arnold M., Laversanne M., Brown L.M., Devesa S.S., Bray F. Predicting the future burden of esophageal cancer by histological subtype: international trends in incidence up to 2030. Am J Gastroenterol. 2017;112(8):1247–1255. doi: 10.1038/ajg.2017.155. [DOI] [PubMed] [Google Scholar]
- 3.Zhang Z., Wan Z., Zhu Y., Zhang L., Zhang L., Wan H. Prevalence of malnutrition comparing NRS2002, MUST, and PG-SGA with the GLIM criteria in adults with cancer: a multi-center study. Nutrition. 2021;83 doi: 10.1016/j.nut.2020.111072. [DOI] [PubMed] [Google Scholar]
- 4.Guo Z.Q., Yu J.M., Li W., et al. Survey and analysis of the nutritional status in hospitalized patients with malignant gastric tumors and its influence on the quality of life. Support Care Cancer. 2020;28(1):373–380. doi: 10.1007/s00520-019-04803-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.von Meyenfeldt M. Cancer-associated malnutrition: an introduction. Eur J Oncol Nurs. 2005;9(suppl 2):S35–S38. doi: 10.1016/j.ejon.2005.09.001. [DOI] [PubMed] [Google Scholar]
- 6.Pressoir M., Desné S., Berchery D., et al. Prevalence, risk factors and clinical implications of malnutrition in French Comprehensive Cancer Centres. Br J Cancer. 2010;102(6):966–971. doi: 10.1038/sj.bjc.6605578. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Wie G.A., Cho Y.A., Kim S.Y., Kim S.M., Bae J.M., Joung H. Prevalence and risk factors of malnutrition among cancer patients according to tumor location and stage in the National Cancer Center in Korea. Nutrition. 2010;26(3):263–268. doi: 10.1016/j.nut.2009.04.013. [DOI] [PubMed] [Google Scholar]
- 8.Xu L.B., Mei T.T., Cai Y.Q., et al. Correlation between components of malnutrition diagnosed by global leadership initiative on malnutrition criteria and the clinical outcomes in gastric cancer patients: a propensity score matching analysis. Front Oncol. 2022;12 doi: 10.3389/fonc.2022.851091. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Xiao Q., Li X., Duan B., et al. Clinical significance of controlling nutritional status score (CONUT) in evaluating outcome of postoperative patients with gastric cancer. Sci Rep. 2022;12(1):93. doi: 10.1038/s41598-021-04128-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Wang H.M., Wang T.J., Huang C.-S., et al. Nutritional status and related factors in patients with gastric cancer after gastrectomy: a cross-sectional study. Nutrients. 2022;14(13):2634. doi: 10.3390/nu14132634. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.de Sousa I.M., Silva F.M., de Carvalho A.L.M., da Rocha I.M.G., Fayh A.P.T. Accuracy of isolated nutrition indicators in diagnosing malnutrition and their prognostic value to predict death in patients with gastric and colorectal cancer: a prospective study. JPEN J Parenter Enteral Nutr. 2022;46(3):508–516. doi: 10.1002/jpen.2199. [DOI] [PubMed] [Google Scholar]
- 12.Matsui R., Inaki N., Tsuji T. Effect of malnutrition as defined by the Global Leadership Initiative on Malnutrition criteria on compliance of adjuvant chemotherapy and relapse-free survival for advanced gastric cancer. Nutrition. 2023;109 doi: 10.1016/j.nut.2022.111958. [DOI] [PubMed] [Google Scholar]
- 13.Gil-Andrés D., Cabañas-Alite L. A narrative review comparing nutritional screening tools in outpatient management of cancer patients. Nutrients. 2024;16(5):752. doi: 10.3390/nu16050752. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Reim D., Friess H. Feeding challenges in patients with esophageal and gastroesophageal cancers. Gastrointest Tumors. 2016;2(4):166–177. doi: 10.1159/000442907. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Kondrup J., Allison S.P., Elia M., Vellas B., Plauth M., Educational and Clinical Practice Committee, European Society of Parenteral and Enteral Nutrition (ESPEN) ESPEN guidelines for nutrition screening 2002. Clin Nutr. 2003;22(4):415–421. doi: 10.1016/s0261-5614(03)00098-0. [DOI] [PubMed] [Google Scholar]
- 16.Kondrup J., Rasmussen H.H., Hamberg O., Stanga Z., Ad Hoc ESPEN Working Group Nutritional risk screening (NRS 2002): a new method based on an analysis of controlled clinical trials. Clin Nutr. 2003;22(3):321–336. doi: 10.1016/s0261-5614(02)00214-5. [DOI] [PubMed] [Google Scholar]
- 17.Guo W., Ou G., Li X., Huang J., Liu J., Wei H. Screening of the nutritional risk of patients with gastric carcinoma before operation by NRS 2002 and its relationship with postoperative results. J Gastroenterol Hepatol. 2010;25(4):800–803. doi: 10.1111/j.1440-1746.2009.06198.x. [DOI] [PubMed] [Google Scholar]
- 18.Bachmann J., Müller T., Schröder A., et al. Influence of an elevated nutrition risk score (NRS) on survival in patients following gastrectomy for gastric cancer. Med Oncol. 2015;32(7):204. doi: 10.1007/s12032-015-0631-x. [DOI] [PubMed] [Google Scholar]
- 19.Li Y.-F., Nie R.-C., Wu T., et al. Prognostic value of the Nutritional Risk Screening 2002 scale in metastatic gastric cancer: a large-scale cohort study. J Cancer. 2019;10(1):112–119. doi: 10.7150/jca.27729. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Haag G.-M., Stocker G., Quidde J., Jaeger D., Lordick F. Randomized controlled trial of S-1 maintenance therapy in metastatic esophagogastric cancer – the multinational MATEO study. BMC Cancer. 2017;17(1):509. doi: 10.1186/s12885-017-3497-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Stocker G., Lorenzen S., Ettrich T., et al. S-1 maintenance therapy in Caucasian patients with metastatic esophagogastric adenocarcinoma-final results of the randomized AIO MATEO phase II trial. ESMO Open. 2023;8(3) doi: 10.1016/j.esmoop.2023.101572. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Lordick F., Carneiro F., Cascinu S., et al. Gastric cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022;33(10):1005–1020. doi: 10.1016/j.annonc.2022.07.004. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.