ERCC1 expression as a prognostic marker in N2(+) nonsmall-cell lung cancer patients treated with platinum-based neoadjuvant concurrent chemoradiotherapy.
BACKGROUND
Excision repair cross-complementation Group 1 (ERCC1) overexpression is associated with resistance to cisplatin-based chemotherapy in patients with nonsmall-cell lung cancer (NSCLC). A preliminary study also suggested that ERCC1 expression is associated with radioresistance in lung cancer cells. The aim of this study was to evaluate the clinical implications of ERCC1 expression in stage IIIA N2-positive NSCLC patients treated with platinum-based neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery.


METHODS
Sixty-eight patients with mediastinoscopy-proven N2-positive NSCLC were enrolled between August 1997 and September 2003. ERCC1 expression was assessed by immunohistochemistry from pretreatment mediastinoscopic biopsy specimens.


RESULTS
ERCC1 expression was positive in 31 of 68 specimens (46%). Among 14 patients who obtained pathologic complete response, 6 were positive for ERCC1 expression and 8 were negative (P = .818). On univariate analysis, with median follow-up of 61.8 months (range, 34.3-108.8 months), progression-free survival was 15.9 months for ERCC1-positive and 29.5 months for ERCC1-negative patients (P = .062), and there was a statistically significant difference in overall survival between ERCC1-negative tumors and ERCC1-positive tumors (89.2 vs 26.0 months, P = .014). On multivariate analysis, ERCC1 negativity (P = .041) and achieving mediastinal nodal clearance (downstage to pathological N0 or N1) after neoadjuvant CCRT followed by surgery (P = .005) were significant independent prognostic factors for the prolongation of survival.


CONCLUSIONS
These results suggest that N2-positive NSCLC patients with ERCC1 negative tumors show a survival benefit from neoadjuvant CCRT with a platinum-containing regimen.
Hwang
In Gyu
IG
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Ahn
Myung Ju
MJ
Park
Byeong Bae
BB
Ahn
Yong Chan
YC
Han
Joungho
J
Lee
Seungkoo
S
Kim
Jhingook
J
Shim
Young Mog
YM
Ahn
Jin Seok
JS
Park
Keunchil
K
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy / Q000556:secondary; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018572:Disease-Free Survival; D000077143:Docetaxel; D004720:Endonucleases / Q000378:metabolism*; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
D004268:DNA-Binding Proteins; D043823:Taxoids; D000077143:Docetaxel; D005047:Etoposide; D016190:Carboplatin; C071447:ERCC1 protein, human; D004720:Endonucleases; D017239:Paclitaxel; D002945:Cisplatin