Lymphocyte-to-monocyte ratio (LMR) is prognostic factor for selection of neoadjuvant treatment in locally advanced rectal cancer patients: Sub-set analysis of Polish-2 study

Abstract

Introduction: The prognostic role of blood morphology derrived parameters like neutrocyte-to-lymphocyte (NLR) or lymphocyte-to-monocyte (LMR) ratios was established in several cancers. Recent studies indicated that granulocyte-monocyte stimulating factors might boost the abscopal effect of radiotherapy in selected malignancies. In order to test if such parameters may be valuable in the treatment selection for locally advanced rectal cancer patients, we have analyzed a subset of patients treated in The M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (Warsaw, Poland) within Polish-2 study. This study was designed to test if short-course irradiation (5x5 Gy) combined with chemotherapy afterwards can boost the pathologic response rates (pCR) versus conventional chemoradiation in advanced rectal cancer patients (cT4 or bulky cT3 tumors). The primary endpoint was negative with similar pCR and disease-free survival. Surprisingly, the overall survival of patients treated with short-course irradiation was improved. The hypothesis of an immune-related phenomenon was raised, but this was not confirmed until now. Method(s): The cohort of 166 patients randomized to either 5x5 Gy radiotherapy combined with 3 cycles of chemotherapy or chemoradiation treated at the Maria Sklodowska-Curie Memorial Cancer Center was identified. The blood morphology parameters from the day of treatment allocation were derived from medical records. The parameters included in the model were calculated according standard formulas (NLR - neutrocyte-to-lymphocyte ratio, LMR - lymphocyte-to-monocyte ratio, PLR -platelet-to-lymphocyte ratio, dNLR= ANC/(WBC-ANC); where ANC = neutrocyte count, WBC=lymphocyte count). Various cut-offs were tested in this exploratory analysis according to the literature data. Prognostic and predictive value for particular parameters was assessed with log rank test. Result(s): All tested parameters were highly prognostic for patients with locally advanced rectal cancer. The optimized cut off values for improved prognosis were: NLR < 3, dNLR< 2.5, PLR < 200 and LMR> 2.6. Notable, the patients with LMR >2.6 (n=102) had improved prognosis when treated with short-course irradiation combined with chemotherapy (p=0.019) compare to those after chemoradiation. There is (Figure Presented) a trend for similar improvement of overall survival in NLR< 3 (p=0.1) and no other parameters had any predictive values. Conclusion(s): The study confirms several previous observations on prognostic value of simple parameters available for all patients prior to the treatment. The hypothesis on immune-related phenomenon in the hypofractionated radiotherapy of rectal cancer might be supported. Further studies are needed to confirm our observations.