Abstract 4334: Elevated lactic acid is a negative prognostic factor in metastatic lung cancer

Abstract

Abstract Introduction: Hyperlactatemia with or without type B lactic acidosis is a rare complication of malignancy, previously observed most often in hematological malignancies. Underlying pathophysiology involves reduced lactic acid metabolism from metastatic liver dysfunction as well as overproduction of lactic acid from aberrant glycolytic metabolism of tumors. Clinical data to evaluate the potential value of arterial or venous lactic acid (LA) level assessment as a predictor of overall survival (OS) or/and response to treatment are lacking. The aim of this study was to assess the prognostic value of LA in patients with metastatic lung cancer. Methods: Patients diagnosed with stage IV non-small cell lung cancer (NSCLC) or extensive stage small cell lung cancer (SCLC) from 2012 to present, were included in this single center, retrospective study. Patients with sepsis or acute exacerbation of heart failure were excluded from the study. Arterial and venous LA level, bicarbonate, anion gap, urine ketones, serum LDH were recorded for each patient and their associations with demographic and clinical data and OS were analyzed with the Chi-square test, Kaplan-Meier's actuarial method (log-tank test) and Cox proportional hazard model. Results: 85 patients (43 males, mean age 73.1, range 45-96 years) were studied. The maximal levels of arterial or venous LA were significantly associated with presence of ≥2 metastatic sites (p = 0.001), ICU admission or transfer (p = 0.016), intubation (p = 0.029), elevated serum anion gap (p<0.001) and LDH levels (p<0.001). No significant associations emerged between LA level and gender, age, smoking status, histology, tumor size or grade, previous lung resection, location of metastases, COPD, previous metformin use, ketonuria, and previous or ongoing palliative chemotherapy. Hyperlactatemia (p<0.001), histologic subtype (p = 0.019), ICU admission or transfer (p = 0.014), intubation (p = 0.026), number of metastatic sites (p = 0.01), AG (p<0.01) and LDH (p<0.001) were univariately associated with OS. LDH was the only independent prognostic factor [OR = 0.162 (95% CI: 0038-0.687), p = 0.014]. Conclusion: Our results suggest that elevated LA is a predictor of poor OS in metastatic lung cancer patients, irrespective of chemotherapy. Here lie implications for targeting tumor-derived LA production via manipulation of glycolytic enzymes or lactate transporters, with use of LA as a surrogate marker of response. Citation Format: Panagiotis J. Vlachostergios, Nirav Parikh, Katerina Oikonomou, Eugene Gibilaro, George Apergis. Elevated lactic acid is a negative prognostic factor in metastatic lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4334. doi:10.1158/1538-7445.AM2015-4334