The Trifecta of Inflammation in Oncology
JANET MAENDEL DO(EUR), DNM
The Trifecta of Inflammation—hsCRP, ESR, and LDH—has become a foundational tool in metabolic oncology thanks to the clinical leadership of Dr. Nasha Winters. These three markers, when assessed together, reveal a powerful snapshot of inflammatory activity, tumor dynamics, and overall disease behavior. While each marker offers insight on its own, their combined interpretation often exposes patterns that would otherwise be missed—particularly in patients who are actively cancering, experiencing pseudo-progression, or showing signs of overtreatment.
High-Sensitivity C-Reactive Protein (hs-CRP)
hs-CRP is a highly sensitive marker of systemic inflammation, capable of detecting subtle shifts in inflammatory activity. In oncology, elevated hs-CRP can reflect the body’s inflammatory response to tumor growth or progression. Tracking this marker provides clinically useful information about tumor burden, treatment response, and overall prognosis.
Lactate Dehydrogenase (LDH/LD)
LDH is an enzyme central to energy production. Elevated levels typically indicate rapid cell turnover or tissue damage—both hallmarks of aggressive or metabolically active cancers. High LDH often correlates with greater tumor burden, poorer prognosis, and lower survival rates, making it a meaningful marker for monitoring disease activity and therapeutic response.
Erythrocyte Sedimentation Rate (ESR)
ESR measures the rate at which red blood cells settle in a test tube, offering a broad view of inflammatory activity. Although less specific than hs-CRP or LDH, ESR adds context—especially when seen alongside the other two markers. Elevated ESR may reflect tumor-driven inflammation or systemic effects of cancer on the body.
Interpreting the Trifecta
Inflammatory Response
Together, hs-CRP, LDH, and ESR reveal the inflammatory landscape surrounding the tumor and its treatments. Persistent elevations often indicate active inflammation driven by cancer biology or therapeutic stress.
Disease Monitoring
hs-CRP and LDH are particularly valuable for tracking tumor progression or regression. LDH, in particular, is strongly associated with aggressive disease patterns. ESR provides supportive context, helping differentiate between localized and systemic inflammatory activity.
Treatment Evaluation
Shifts in the trifecta can signal treatment effectiveness or insufficiency. Declining levels often reflect positive therapeutic response, whereas rising or persistently high levels may indicate progression, ineffective dosing, or the need for reevaluation.
Prognostic Indicators
Elevations in hs-CRP and LDH are well documented as predictors of poorer outcomes in many cancers. Although ESR is more nonspecific, in combination with the other markers it adds meaningful context for assessing risk and prognosis.
When the trifecta is elevated within functional ranges, the cancer process is in control. Using hs-CRP, LDH, and ESR together enhances clinical decision-making by providing a clearer view of inflammation, tumor behavior, and response to therapy. Their combined interpretation offers one of the most accessible and informative tools for monitoring cancer dynamics and guiding strategic interventions.