Blood-Based Biomarkers Are Associated with Disease Recurrence and Survival in Gastrointestinal Stroma Tumor Patients after Surgical Resection

<div><p>Background</p><p>Inflammatory blood count biomarkers may improve recurrence risk stratification and inform long-term prognosis of cancer patients. Here, we quantify the prognostic impact of blood-based biomarkers on recurrence risk and long-term survival in a large cohort of gastrointestinal stroma tumor (GIST) patients after curative surgery.</p><p>Methods</p><p>One-hundred-forty-nine consecutive GIST patients were followed-up for a median period of 4.8 years. Local recurrence, distant metastasis, and death occurred in 9, 21, and 31 patients, respectively. Time-to-event and competing risk analysis were applied to study the association between haemoglobin (Hb) level, white blood cell count (WBC), neutrophil/lymphocyte ratio (NLR), derived NLR (dNLR), lymphocyte/monocyte ratio (LMR), and platelet/lymphocyte ratio (PLR) with risk of local or distant recurrence (RR), recurrence free survival (RFS), and overall survival (OS).</p><p>Results</p><p>A low Hb (p = 0.029), and elevations in the parameters WBC (p = 0.004), NLR (p = 0.015) and dNLR (p = 0.037) were associated with a poor OS in GIST patients in multivariate analysis. Moreover, a low Hb (p = 0.049) and an elevated WBC (p = 0.001), NLR (p = 0.007), dNLR (p = 0.043) and PLR (p = 0.024) were independently associated with decreased RFS after adjusting for Miettinen score. However, only an increase of dNLR/NLR showed a significant association to higher RR (p = 0.048). Inclusion of NLR or PLR to Miettinen risk score did not reasonably improve the clinical risk prediction of 2-year RFS.</p><p>Conclusion</p><p>Low Hb, elevated WBC, elevated dNLR, and elevated PLR are independent prognostic factors for a worse clinical outcome in GIST patients after curative resection.</p></div

Risk of recurrence according to the derived neutrophil lymphocyte ratio (dNLR) at baseline.

<p>Patients with an elevated dNLR at baseline had a significantly higher risk of developing recurrence. The risk of recurrence (defined as a composite of local recurrence and/or distant metastasis, whatever came first) was estimated using competing risk cumulative incidence estimators with death-from-any-cause as the competing event of interest. The boxed p-value was estimated using Gray’s test. The dNLR was dichotomized into a binary variable at its 75^th percentile (i.e. Q3, cut-off: 2.7 units).</p

Baseline Predictors of Oncologic Outcomes in GIST–Univariable Analysis.

<p>The endpoints overall survival and recurrence-free survival were analyzed with Cox proportional hazards models, whereas the endpoints local recurrence, distant metastasis, and recurrence were analyzed using Fine & Gray models. Abbreviations: HR–hazard ratio, SHR–subdistribution hazard ratio, 95%CI– 95% confidence interval, p–p-value, HPF–high power field, g/dL–grams per deciliter, G/L–giga per liter, NLR–neutrophil lymphocyte ratio, dNLR–derived NLR, LMR–lymphocyte monocyte ratio, PLR–platelet lymphocyte ratio.</p

Risk of all-cause mortality according to neutrophil lymphocyte ratio (NLR) at baseline.

<p>Patients with an elevated NLR at baseline had a significantly worse overall survival experience. The risk of death was estimated using the inverse Kaplan-Meier estimator, and the boxed p-value using a log-rank test. The NLR was dichotomized into a binary variable at its 75^th percentile (i.e. Q3, cut-off: 4.9 units).</p

Risk of all-cause mortality according to second primary malignancy status (SPM) at baseline.

<p>The presence of a second primary malignancy (SPM) or a history of a SPM at baseline was a significant contributor towards an increased risk of death-from-any-cause. The risk of death was estimated using the inverse Kaplan-Meier estimator, and the boxed p-value using a log-rank test.</p