Systemic inflammation is recognized as one of the key driving factors for cancer development recurrence and death. Increasingly, studies are reporting that we can use simple lab tests as prognostic tools to help us better predict which patients will have favorable or unfavorable cancer outcomes by assessing simple indices of systemic inflammation.
Red Cell Distribution (RDW)
An inexpensive blood test result called red cell distribution (RDW) is becoming increasingly recognized as a prognostic tool in helping to predict which patients are at a greater risk of having cancer (especially having a higher stage cancer) and having worse cancer outcomes (higher recurrence and cancer mortality rates).
The RDW is a measure of the variability in size within the red blood cell population (also known as “anisocytosis”). The RDW is commonly reported as one of the components of the complete blood count (CBC) lab test.
It is believed that systemic inflammation increases RDW.
Most studies have found that having an RDW of greater than >13-15% increases one’s risk of:
- having cancer
- having a more advanced stage cancer
- lower overall survival (47% lower)
- lower cancer specific survival (46%)
- lower disease-free (recurrence-free) survival (91% lower)
- lower progression free survival (321% lower)
Systemic Immune Inflammatory Index (SII)
The SII is a calculated value based on the lymphocyte (L), neutrophil (N) and platelet (P) counts, which are included in most CBC lab tests:
SII = P x N/L
Neutrophils secrete circulating growth factors promoting cancer cells adhesion and seeding in distant organ sites, as well as assisting cancer cells in evading immune surveillance.
Lymphocytes play a vital role in tumor defense by inhibiting tumor cell proliferation and migration and inducing cytotoxic cell death.
Platelets have emerged as a vital player in the systemic and local response to tumor growth by facilitating tumor cell survival and metastasis.
A compilation of studies has found that having an SII >330 x 109 is associated with worse outcomes.
The SII is associated with a:
- lower overall survival (80% lower)
- lower cancer specific survival (44% lower)
- shorter time to cancer recurrence (91% lower)
- lower progression free survival (18% lower)
Neutrophil-to-Lymphocyte Ratio (NLR)
Neutrophils have been shown to inhibit the cancer killing effects of natural killer cells and suppress T-cell proliferation. The ratio of neutrophils (pro-tumor) and lymphocytes (anti-tumor) is a simple prognostic tool that can predict cancer outcomes.
The neutrophil (N) and lymphocyte (L) numbers are commonly reported as components of the complete blood count (CBC) lab test.
NLR = N/L
Studies report that
NLR of >4 is associated with a lower overall survival (81% lower)
NLR of >3.85 is associated with a lower cancer specific survival (61% lower)
NLR of >3.0 is associated with a lower progression free survival (63% lower)
NLR of >5.0 is associated with a disease-free (recurrence-free) specific survival (227% lower)
IL-6 is a protein produced by a variety of cells (i.e. white blood cells, fibroblasts, endothelial cells, etc.) that helps regulate immune responses, which makes the IL-6 test useful as a marker of immune activation and inflammation. IL-6 is a one of a large group of molecules called cytokines, which direct the body’s “inflammatory cascade.”
The majority of studies report that elevated levels of IL-6 are associated with worse cancer outcomes.
The median IL-6 cut-off, above which the overall survival rates decrease with a variety of cancer types is >10 pg/mL.
The table below shows the specific cut-off IL-6 values above which the survival rates for patients with the indicated cancers decreased:
- Example: on the first line (Advanced pancreatic cancer), those patients with an IL-6 lab value of greater than 17.5 pg/ML had a worse survival (median survival: 3.8 months) than those with a lower IL-6 level.