DNA-adduct levels as a predictor of outcome for NSCLC patients receiving daily cisplatin and radiotherapy

Int J Cancer. 2000 Mar 20;89(2):160-6.


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.

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis
  • Carcinoma, Non-Small-Cell Lung / chemistry
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / radiotherapy
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Cisplatin / therapeutic use*
  • Combined Modality Therapy
  • DNA Adducts / analysis*
  • DNA, Neoplasm / analysis*
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / analysis
  • Lung Neoplasms / chemistry
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / radiotherapy
  • Lung Neoplasms / therapy*
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Radiation-Sensitizing Agents / therapeutic use
  • Radiotherapy Dosage
  • Tumor Suppressor Protein p53 / analysis


  • Antineoplastic Agents
  • DNA Adducts
  • DNA, Neoplasm
  • Ki-67 Antigen
  • Proto-Oncogene Proteins c-bcl-2
  • Radiation-Sensitizing Agents
  • Tumor Suppressor Protein p53
  • Cisplatin