DNA-adduct levels as a predictor of outcome for NSCLC patients receiving daily cisplatin and radiotherapy.
We aimed to investigate whether biological factors related to radiosensitivity and chemosensitivity have prognostic significance in non-small-cell-lung-cancer (NSCLC) patients treated with daily low doses of cisplatin and radiotherapy. We treated 27 NSCLC patients with concomitant daily low-dose cisplatin and radiotherapy between 1993 and 1995. Tumour specimens were analyzed for p53 and bcl-2 expression, and for cell proliferation using antibodies against ki-67. In addition, apoptosis was measured by an end-labeling technique (TUNEL). Finally, cisplatin-induced DNA modification in buccal cells was assessed immunocytochemically using a specific anti-serum. Univariate and multivariate analyses were performed to assess the association between the different variables and survival. The median follow-up was 41 months, and 21 patients (78%) have died. In a univariate analysis, age, tumour stage and cisplatin-DNA-adduct staining were the only factors significantly associated with survival (p < 0.05, log-rank test). p53, bcl-2, Ki-67 and apoptosis showed no relationship with outcome. Multivariate analysis revealed that cisplatin-DNA-adduct staining remained an independent prognostic factor (hazard ratio, 0.10, 95% CI, 0.02-0.49), with shorter survival times for patients with low adduct staining.
van de Vaart
P J
PJ
Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Belderbos
J
J
de Jong
D
D
Sneeuw
K C
KC
Majoor
D
D
Bartelink
H
H
Begg
A C
AC
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy / Q000628:therapy*; D002945:Cisplatin / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D018736:DNA Adducts / Q000032:analysis*; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008175:Lung Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use; D011879:Radiotherapy Dosage; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D000970:Antineoplastic Agents; D018736:DNA Adducts; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D011838:Radiation-Sensitizing Agents; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin