Prognostic impact of erythropoietin expression and erythropoietin receptor expression on locoregional control and survival of patients irradiated for stage II/III non-small-cell lung cancer.
OBJECTIVE
Prognostic factors can guide the physician in selecting the optimal treatment for an individual patient. This study investigates the prognostic value of erythropoietin (EPO) and EPO receptor (EPO-R) expression of tumor cells for locoregional control and survival in non-small-cell lung cancer (NSCLC) patients.


METHODS
Fourteen factors were investigated in 62 patients irradiated for stage II/III NSCLC, as follows: age, gender, Karnofsky performance score (KPS), histology, grading, TNM/American Joint Committee on Cancer (AJCC) stage, surgery, chemotherapy, pack years (average number of packages of cigarettes smoked per day multiplied by the number of years smoked), smoking during radiotherapy, hemoglobin levels during radiotherapy, EPO expression, and EPO-R expression. Additionally, patients with tumors expressing both EPO and EPO-R were compared to those expressing either EPO or EPO-R and to those expressing neither EPO nor EPO-R.


RESULTS
On univariate analysis, improved locoregional control was associated with AJCC stage II cancer (p < 0.048), surgery (p < 0.042), no smoking during radiotherapy (p = 0.024), and no EPO expression (p = 0.001). A trend was observed for a KPS of >70 (p = 0.08), an N stage of 0 to 1 (p = 0.07), and no EPO-R expression (p = 0.10). On multivariate analysis, AJCC stage II and no EPO expression remained significant. No smoking during radiotherapy was almost significant. On univariate analysis, improved survival was associated with N stage 0 to 1 (p = 0.009), surgery (p = 0.039), hemoglobin levels of ≥12 g/d (p = 0.016), and no EPO expression (p = 0.001). On multivariate analysis, N stage 0 to 1 and no EPO expression maintained significance. Hemoglobin levels of ≥12 g/d were almost significant. On subgroup analyses, patients with tumors expressing both EPO and EPO-R had worse outcomes than those expressing either EPO or EPO-R and those expressing neither EPO nor RPO-R.


CONCLUSIONS
EPO expression of tumor cells was an independent prognostic factor for locoregional control and survival in patients irradiated for NSCLC. EPO-R expression showed a trend. Patients with tumors expressing both EPO and EPO-R have an unfavorable prognosis.
Rades
Dirk
D
Department of Radiation Oncology, University of Lubeck, Germany. Rades.Dirk@gmx.net
Setter
Cornelia
C
Dahl
Olav
O
Schild
Steven E
SE
Noack
Frank
F
D000367:Age Factors; D000368:Aged; D000704:Analysis of Variance; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D004921:Erythropoietin / Q000378:metabolism*; D005260:Female; D006441:Hemoglobin A / Q000032:analysis; D006801:Humans; D017567:Karnofsky Performance Status; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D011379:Prognosis; D020266:Radiotherapy, Conformal; D017467:Receptors, Erythropoietin / Q000378:metabolism*; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects
D009363:Neoplasm Proteins; D017467:Receptors, Erythropoietin; D004921:Erythropoietin; D006441:Hemoglobin A