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. Int. J. Cancer (Pred. Oncol.) 89:160–166, 2000. © 2000 Wiley‐Liss, Inc.