Critique of Proposed Study: NLR as Predictor of Malnutrition Risk in Cancer Patients
Overall Assessment
This study design has significant methodological limitations that undermine its potential clinical utility, primarily because NLR reflects systemic inflammation rather than nutritional status per se, and using NRS-2002 as the reference standard creates a circular validation problem when inflammation is already embedded in disease severity scoring.
Critical Design Flaws
Fundamental Conceptual Problem
NLR measures systemic inflammation, not malnutrition directly. While inflammation and malnutrition frequently coexist in cancer patients, they represent distinct pathophysiological processes 1.
The NRS-2002 already incorporates disease severity (which correlates with inflammation) into its scoring system, creating a tautological relationship where you're essentially validating one inflammation marker against a tool that already accounts for inflammatory disease burden 1.
Total lymphocyte count (the denominator of NLR) decreases during acute inflammation, infection, sepsis, trauma, and radiation exposure—all independent of nutritional status 2, 3. This makes NLR an unreliable standalone nutritional marker in the heterogeneous cancer population you're studying.
Methodological Weaknesses
Retrospective chart review design cannot establish causality and is highly dependent on documentation quality, which you acknowledge is "variably performed" in your setting 4.
Cross-sectional design captures only a single time point, missing the dynamic nature of both inflammation and nutritional status in cancer patients undergoing active treatment 1.
No control for confounding variables: The study design doesn't account for active infection, sepsis, recent chemotherapy/radiation, tumor type, stage, or treatment modality—all of which independently affect NLR 5, 6, 7.
Using a single NLR cutpoint across all cancer types ignores substantial variation in inflammatory burden between different malignancies 6, 7.
Evidence Contradicting the Approach
What Guidelines Actually Recommend
ESPEN explicitly recommends NRS-2002 as the validated screening tool for hospitalized cancer patients because it has been independently associated with postoperative complications and overall survival 1.
The 2025 Advances in Nutrition guidelines state that "NRS-2002 being more specific and the SGA more sensitive for patients with cancer," making these the appropriate first-line tools rather than inflammatory markers 1.
Guidelines recommend measuring inflammation (CRP, NLR) alongside validated nutritional tools to interpret results correctly—not as replacement screening tools 4, 3, 6.
What Research Actually Shows
The 2021 cross-sectional study you're essentially replicating found NLR ≥5.0 associated with nutritional risk (NRS-2002 ≥3), but this association doesn't establish NLR as a superior or equivalent screening tool—it simply confirms that inflammation and malnutrition coexist 5.
More sophisticated 2023 research demonstrates that inflammation markers (including NLR) should supplement GLIM criteria, not replace validated screening tools 6. The study showed inflammation marker-based GLIM criteria had better prognostic accuracy than original GLIM, but this was for prognosis, not screening.
A 2019 study of 5,363 cancer patients found NLR's prognostic value varies dramatically by cancer type, stage, and treatment modality (HRs ranging from 1.58 overall to >2.0 in specific subgroups), making a single cutpoint approach problematic 7.
Specific Problems with Your Rationale
The "Resource-Limited Setting" Argument Doesn't Hold
NRS-2002 requires only BMI, weight history, food intake assessment, and disease severity—no laboratory tests needed 1, 4. It's actually more accessible than obtaining and calculating NLR from complete blood counts.
Your rationale states NRS-2002 "may not always be readily available or consistently documented," but the solution is improving documentation of this validated tool, not substituting an unvalidated inflammatory marker 4.
Complete blood counts (needed for NLR) are not universally available in all resource-limited settings either, and when available, the turnaround time may delay nutritional intervention 3.
Misunderstanding of What NLR Actually Reflects
Low lymphocyte counts in cancer patients reflect: immune suppression from chemotherapy, radiation-induced lymphopenia, tumor-induced immunosuppression, sepsis, and systemic inflammation—not primarily malnutrition 2, 3.
High neutrophil counts reflect: active infection, tumor-associated inflammation, corticosteroid use, and stress response 5, 6.
The 2025 Praxis Medical Insights explicitly states: "If inflammation is present (elevated CRP), TLC should not be interpreted as a nutritional marker because albumin, prealbumin, and TLC all decrease during inflammation regardless of nutritional status" 2.
What This Study Could Actually Contribute (If Redesigned)
Potentially Valuable Research Questions
Does adding NLR to NRS-2002 improve prognostic stratification? This would be more clinically useful than attempting to replace NRS-2002 6, 8.
What NLR cutpoints predict mortality or complications in specific cancer types (e.g., gastrointestinal malignancies undergoing surgery) after controlling for nutritional status? 7, 9.
Can NLR identify which malnourished patients (already identified by NRS-2002) have inflammation-driven cachexia requiring multimodal intervention versus simple nutritional support? 6, 8.
Recommended Design Modifications
Make this a prospective cohort study with standardized NRS-2002 assessment at admission, NLR measurement, and follow-up for clinical outcomes (complications, length of stay, mortality) 1, 4.
Stratify analysis by cancer type, stage, and treatment modality given the known variation in NLR's prognostic value across these subgroups 7.
Measure CRP alongside NLR to distinguish inflammatory from non-inflammatory states, as recommended by guidelines 3, 6.
Include validated outcome measures beyond NRS-2002: postoperative complications, 30-day mortality, length of stay, and readmission rates 1.
Test whether NLR adds incremental predictive value to NRS-2002 using C-index comparison and decision curve analysis, as done in the 2023 study 6.
Common Pitfalls You Must Avoid
Statistical Analysis Concerns
Don't report only sensitivity/specificity from ROC curves. The 2021 study found NLR >5.0 had only 60.9% sensitivity and 76.4% specificity—inadequate for a screening tool 5.
Avoid claiming NLR "predicts" malnutrition when you're really showing association with an inflammation-inclusive scoring system 5, 6.
Don't ignore the base rate problem: If malnutrition prevalence is 40-50% in your population (typical for hospitalized cancer patients), even modest specificity will generate many false positives 1.
Clinical Interpretation Errors
Don't recommend NLR as a standalone screening tool based on cross-sectional association data 4, 5.
Don't ignore that albumin, prealbumin, and total lymphocyte count are all negative acute phase reactants that decrease during inflammation regardless of nutritional status 1, 2, 3.
Don't assume that identifying "nutritional risk" via NLR will lead to appropriate intervention when the underlying problem may be inflammation-driven cachexia requiring multimodal therapy 6, 8.
Alternative Approaches That Would Be More Valuable
What Your Institution Actually Needs
Implementation study of systematic NRS-2002 screening with audit of documentation compliance and barriers to use 4.
Validation of NRS-2002 in your specific population with outcomes data (complications, mortality, length of stay) to demonstrate local relevance 1.
Quality improvement project training staff on proper NRS-2002 administration and documentation 4.
Development of a combined inflammation-nutrition risk score that incorporates both NRS-2002 and inflammatory markers (NLR, CRP) for prognostic stratification, similar to the 2023 inflammation marker-based GLIM criteria study 6.
Bottom Line Recommendation
Do not proceed with this study as designed. The fundamental premise—that NLR can serve as a "reliable predictor of malnutrition risk" to "support early nutritional assessment"—is not supported by current guidelines or high-quality evidence 1, 4. Instead, focus on implementing and validating the evidence-based NRS-2002 tool in your setting, then explore whether adding inflammatory markers improves prognostic accuracy for clinical outcomes 1, 6. This approach would generate clinically actionable data while avoiding the methodological and conceptual flaws inherent in your current design 4, 5.