Analysis Of Clinical Features In Lung Cancer Patients With Brain Metastases

Objective:This retrospective study attempts to evaluate the prognostic factors in lung cancer patients with brain metastases and to analyze the impact of multi-treatment modalities over survival of these patients. We also try to identify the relationship between the protein expression of p53, nm23 and VEGF in resected cancer tissues and the survival of these operation patients followed by brain metastases. The information in the study may be useful for the clinicians to make some decisions.Methods:We reviewed the clinical data of 352 lung cancer patients with brain metastases in our hospital from the year of 1997 to 2005. The multivariate analysis was performed with Cox's proportion risk model. Treatment modalities included palliative therapy, simple whole brain radiotherapy (WBRT) or chemotherapy, combined radiochemotherapy, stereotactic linac-based radiosurgery(SRS) plus chemotherapy/WBRT and neurosurgical resection plus chemotherapy/WBRT. A total of 92 specimens of resected lung cancer tissues were examined for the protein expressions of P53, nm23 and VEGF by immunohistochemical staining. Survival analysis was compared with Kaplan-Meier method and log-rank test was used respectively. Statistical significance was defined as P<0.05.Results:The univariate analysis showed that patients'performance status, age, the number of brain metastases, the absence or presence of extracranial metastases and metastatic symptoms were related to survival period. The multivariate analysis indicated that patients'performance status, age and the absence or presence of extracranial metastases were closely related to their prognosis. The median survival time (MST) of the patients receiving one of such treatments as palliative therapy, simple WBRT or chemotherapy, combined radiochemotherapy, SRS plus chemotherapy/ WBRT or neurosurgical resection plus chemotherapy/ WBRT was 1.7 months,3.2 months,9.0 months,11.6 months and 17.1 months respectively. The MST of the patients with SRS followed by WBRT and those with SRS alone was 12.1 months and 10.6 months respectively(P=0.3804).The MST of the patients with≥4 cycles chemotherapy and those with≤3 cycles chemotherapy was 14.2 months and 6.7 months respectively (P=0.0000).The MST of the operation patients with p53(+)/p53(-), nm23(+)/(-) and VEGF(+)/(-) was 11.0/11.9months (P=0.5179),13.0/10.1 months (P=0.1075) and 10.5/12.2 months (P=0.0231) respectively.Conclusions:Performance status, age and the absence or presence of extracranial metastases are the independent prognostic factors in lung cancer with brain metastases. The patients with PS score 0～1, age≤60 years and absence of extracranial metastases have longer survival time and they would benefit from multi-treatment modalities. Either combined radiochemotherapy or SRS plus chemotherapy/ WBRT is an effective treatment method. There may be a relatively longer survival trend in the patients with SRS plus chemotherapy/WBRT than those with combined radiochemotherapy. There is uncertain survival benefit over the patients undergoing SRS with or without WBRT. It is proper for the patients to receive no less than 4 cycles chemotherapy. The clinical significance of neurosurgical resection of brain metastases should be further confirmed. The protein expressionof VEGF in resected cancer tissues is related to the survival of these patients while the expressions of p53 and nm23 are unrelated to survival. The patients with positive VEGF expression in cancer tissues have shorter survival time. VEGF may be regarded as a predictor for survival of lung cancer patients with brain metastases.