Cumulative Incidence Of Brain Metastases Research Articles

Factors associated with the development of brain metastases

The risk of developing brain metastases after definitive treatment of locally advanced nonsmall cell lung cancer (NSCLC) is approximately 30%-50%. The risk for patients with early stage disease is less defined. The authors sought to investigate this further and to study potential risk factors. The records of all patients who underwent surgery for T1-T2 N0-N1 NSCLC at Duke University between the years 1995 and 2005 were reviewed. The cumulative incidence of brain metastases and distant metastases was estimated by using the Kaplan-Meier method. A multivariate analysis assessed factors associated with the development of brain metastases. Of 975 consecutive patients, 85% were stage I, and 15% were stage II. Adjuvant chemotherapy was given to 7%. The 5-year actuarial risk of developing brain metastases and distant metastases was 10%(95% confidence interval [CI], 8-13) and 34%(95% CI, 30-39), respectively. Of patients developing brain metastases, the brain was the sole site of failure in 43%. On multivariate analysis, younger age (hazard ratio [HR], 1.03 per year), larger tumor size (HR, 1.26 per cm), lymphovascular space invasion (HR, 1.87), and hilar lymph node involvement (HR, 1.18) were associated with an increased risk of developing brain metastases. In this large series of patients treated surgically for early stage NSCLC, the 5-year actuarial risk of developing brain metastases was 10%. A better understanding of predictive factors and biological susceptibility is needed to identify the subset of patients with early stage NSCLC who are at particularly high risk.

Brain Metastases in Women with Inflammatory Breast Cancer (IBC): Incidence, Treatment and Outcome.

Abstract Background: Brain metastases are an uncommon metastatic recurrence site in breast cancer with a median incidence of approximately 6% in unselected populations. Inflammatory breast cancer (IBC) is an aggressive disease associated with dismal outcome. The purpose of this study was to determine the incidence of and survival following brain metastases among women with IBC.Material and Methods: Two hundred and six women with newly diagnosed stage III or IV IBC diagnosed between the period of between 2003 and 2008 were identified in a prospectively maintained IBC database at the MD Anderson Cancer Center. Cumulative incidence of brain metastases was computed. Cox proportional hazards models were fitted to explore factors that predict for the development of brain metastases. Survival was computed using the Kaplan-Meier product limit method.Results: Median follow-up was 20 months. Eighty three (40.3%) women had de-novo stage IV disease and 123 (59.7%) had stage III disease at diagnosis. Thirty-three (16%) patients developed brain metastases with a cumulative incidence at 1 and 3 years of 2.7% and 22% respectively. Eleven (5.3%) patients developed brain metastases as the first site of recurrence with cumulative incidence at 1 and 3 years of 1.6% and 6.7% respectively. In the multivariable model, no specific factor was observed to be significantly associated with time to brain metastases, including HER-2 status. Median overall survival for the whole cohort was not reached. 3-year overall survival for the whole cohort was 78% (95% CI 69%-86%). Median survival following a diagnosis of brain metastases for all women who developed brain metastases or those who developed brain metastases as the first site of recurrence was 6 months.Conclusion: In this single-institutional study, women with IBC demonstrated a high early incidence of brain metastases associated with poor survival. As such IBC may be an ideal cohort to target screening procedures for brain metastases and/or enrollment of these women in clinical trials evaluating additional adjuvant preventive strategies. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2102.

Survival among women with triple receptor-negative breast cancer and brain metastases

BackgroundThe purpose of this study was to determine the incidence of and survival following brain metastases among women with triple receptor-negative breast cancer. Patients and methodsIn all, 679 patients with nonmetastatic triple receptor-negative breast cancer diagnosed from 1980 to 2006 were identified. Cumulative incidence of brain metastases was computed. Cox proportional hazards models were fitted to explore factors that predict for development of brain metastases. Survival was computed using the Kaplan–Meier product limit method. ResultsMedian follow-up was 26.9 months. In all, 42 (6.2%) patients developed brain metastases with a cumulative incidence at 2 and 5 years of 5.6% [95% confidence interval (CI) 3.8% to 7.9%] and 9.6% (95% CI 6.8% to 13%), respectively. A total of 24 (3.5%) patients developed brain metastases as the first site of recurrence with cumulative incidence at 2 and 5 years of 2.0% (95% CI 2.6% to 6.0%) and 4.9% (95% CI 3.2% to 7.0%), respectively. In the multivariable model, no specific factor was observed to be significantly associated with time to brain metastases. Median survival for all patients who developed brain metastases and those who developed brain metastases as the first site of recurrence was 2.9 months (95% CI 2.0–7.6 months) and 5.8 months (95% CI 1.7–11.0 months), respectively. ConclusionIn this single-institutional study, patients with nonmetastatic triple receptor-negative breast tumors have a high early incidence of brain metastases associated with poor survival and maybe an ideal cohort to target brain metastases preventive strategies.

Survival among women with triple receptor-negative breast cancer and brain metastases.

Abstract Abstract #6077 Background
 The purpose of this study was to determine the incidence of brain metastases in a cohort of women with early stage triple-receptor negative breast cancer and to evaluate the survival outcomes of these patients.
 Method
 Six hundred and seventy nine patients with early stage triple-receptor negative breast cancer diagnosed between 1980 and 2006 were identified. Cumulative incidence of brain metastases at 2- and 5-years following a diagnosis of early-stage triple receptor-negative breast cancer considering death as a competing risk was computed. Time to brain metastases was computed from the date of breast cancer diagnosis to the date of development of brain metastases. Cox proportional hazards models, adjusted for various patient and tumor characteristics, were then fitted to explore factors that could predict for the subsequent development of brain metastases in this cohort. Survival following a diagnosis of brain metastases was measured from the date of brain metastases diagnosis to the date of death from any cause. All survival outcomes were computed using the Kaplan – Meier product limit method and compared across groups using log rank statistic.
 Results
 Median age was 50 years (range 22 to 97 years) and median follow-up was 26.9 months (range 1.1 to 321.3 months. Overall 42 (6.2%) patients developed brain metastases of whom 16 (38.1%) had 3 brain lesions or less, 19 (45.2%) had more than 3 brain lesions and number of brain lesions was unknown in 7 (16.7%) patients. Overall cumulative incidence at 2- and 5-years was 5.6% (95% CI 3.8%-7.9%) and 9.6% (95% CI 6.8% - 13%) respectively. Twenty –four (3.5%) patients developed brain metastases as the first site of recurrence with cumulative incidence at 2- and 5-years observed to be 2.0% (95% CI 2.6% -6.0%) and 4.9% (95% CI 3.2%-7.0%) respectively. In the multivariable model factors such as age at primary tumor diagnosis, initial clinical stage, histological tumor grade, number of lymph nodes examined and tumor lymph-vascular invasion were not significantly associated with time to brain metastases. For the whole group of patients who developed brain metastases median survival was 2.9 months (95% CI 2.0 – 7.6 months). Among those who developed brain metastases as the first site of recurrence median survival was 5.8 months (95% CI 1.7 – 11.0 months).
 Conclusion
 Data from published studies have reported a 5-year cumulative incidence of brain metastases of approximately 5 % in an unselected breast cancer population. In our large single institutional study patients with triple-receptor-negative breast tumors we report higher early cumulative incidence compared to historical controls associated with poor survival. Patients with triple-receptor negative breast tumors may be an ideal cohort to target brain metastases preventive strategies. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6077.

Factors affecting the risk of brain metastases after chemoradiotherapy for locally advanced non-small-cell lung cancer (LA-NSCLC)

17019 Background: With an improvement in treatment outcome in patients with LA-NSCLC undergoing radical chemoradiotherapy, brain metastasis has become a greater problem. We assessed the cumulative incidence of brain metastases and its risk factors in such patients with LA-NSCLC. Methods: Between 1993 and 2003, 85 consecutive patients with stage IIIA or IIIB NSCLC underwent chemoradiotherapy in our institution. The characteristics of these patients were as follows: median age, 64 years (range, 39 to 74 years); stage IIIA/IIIB, 30/55 patients; squamous-cell/nonsquamous-cell histologies, 39/46 patients. Concurrent and sequential chemoradiotherapy were administered for 78 and 7 patients, respectively. Only two patients underwent surgical resection after chemoradiotherapy. Fifty-seven patients received conventional thoracic radiotherapy with a total dose of 59.5 ± 1.4 Gy (range, 40 to 70 Gy), and 28 received twice-daily radiotherapy with a total dose of 71.5 ± 6.5 Gy (range, 43 to 86 Gy). Thirty-eight patients received a combination chemotherapy consisting of cisplatin and docetaxel, and the remaining 47 received the other platinum-based regimens. Results: At a median follow-up time of 51 months (range, 9 to 131 months), median survival time was 25 months, with a 3-year survival rate of 36.9%. The median disease-free survival time was 13 months. During treatment and observation periods, 21 (24.7%) patients had developed brain metastases. Thirteen (15.3%) patients experienced brain metastases as the first site of relapse, and in nine (10.6%), brain was the sole site of relapse. The cumulative risk of brain metastases was 15.4% at 1-year, 21.1% at 2-year, and 25.7% at 3-year, respectively. In a multivariate analysis using Cox proportional hazard model, T-factor (T4 vs. T1–3) was the most predictive of brain failure (hazard ratio, 3.51; 95% confidence interval, 1.35 to 9.13; p = 0.01). Conclusions: In patients with LA-NSCLC undergoing chemoradiotherapy, brain was one of the most common sites of failure when locoregional control was achieved. Although efficacy of prophylactic cranial irradiation (PCI) on survival remains unclear for such patients with NSCLC, identification of patients more likely to have a benefit from PCI would be useful. No significant financial relationships to disclose.

Late Brain Metastases from Colorectal Cancer a Case Report and Review of the Literature

Metastatic brain tumors from colorectal cancer are relatively rare. In previous reports the incidence ranged from 1.9 to 3.5 percent of all metastatic brain tumors. In another recent article the cumulative incidence of brain metastasis was estimated at 1.2%. The prognosis for patients with even a single resectable brain metastasis is poor. This paper presents the case report of a 72-year-old woman with a solitary brain metastasis 16 years after a diagnosis of colorectal cancer. She remained asymptomatic for 16 years. The first sign of a secondary tumor was diplopia. Brain scan demonstrated a space-occupying lesion in the occipital area. A solitary tumor was removed by craniotomy. Histological examination showed that it was a metastasis from the intestinal primary tumor. The patient subsequently underwent whole brain radiotherapy for a total dose of 30 Gy in 10 fractions.

Rationale for a phase III study of erythropoietin as a neurocognitive protectant in patients with lung cancer receiving prophylactic cranial irradiation

Recent meta-analysis of patients with small cell lung cancer has confirmed the effectiveness of prophylactic cranial irradiation in reducing the cumulative incidence of brain metastases and contributing to a significant increase in 3-year survival. Likewise, with increased median survivals being documented in patients with stage IIIA/B non–small cell lung cancer, there is evidence that the brain is emerging as a significant metastatic target site. Although prophylactic cranial irradiation is a reasonable option to explore, the potential for long-term neuropsychologic adverse effects is of concern in both diagnostic groups. Radiation-induced reactive oxygen intermediates and reactive nitrogen intermediates appear to play a major role in mediating this toxicity. Hypoxic stress results in a significant increase in erythropoietin (EPO) mRNA in mouse brain and, in two models, the administration of EPO improves performance function and prevents cognitive impairment. With the demonstration of EPO receptors in astrocytes, neurons, and brain capillary endothelial cells as well as the ability of EPO to cross the blood-brain barrier, a potential for EPO-mediated central nervous system radioprotection is postulated. The rationale and preliminary design for a phase III study of EPO as a neurocognitive protectant in patients with lung cancer receiving prophylactic cranial irradiation is presented. Semin Oncol 29 (suppl 19):47-52. Copyright 2002, Elsevier Science (USA). All rights reserved.

Rationale for a phase III study of erythropoietin as a neurocognitive protectant in patients with lung cancer receiving prophylactic cranial irradiation.

Recent meta-analysis of patients with small cell lung cancer has confirmed the effectiveness of prophylactic cranial irradiation in reducing the cumulative incidence of brain metastases and contributing to a significant increase in 3-year survival. Likewise, with increased median survivals being documented in patients with stage IIIA/B non-small cell lung cancer, there is evidence that the brain is emerging as a significant metastatic target site. Although prophylactic cranial irradiation is a reasonable option to explore, the potential for long-term neuropsychologic adverse effects is of concern in both diagnostic groups. Radiation-induced reactive oxygen intermediates and reactive nitrogen intermediates appear to play a major role in mediating this toxicity. Hypoxic stress results in a significant increase in erythropoietin (EPO) mRNA in mouse brain and, in two models, the administration of EPO improves performance function and prevents cognitive impairment. With the demonstration of EPO receptors in astrocytes, neurons, and brain capillary endothelial cells as well as the ability of EPO to cross the blood-brain barrier, a potential for EPO-mediated central nervous system radioprotection is postulated. The rationale and preliminary design for a phase III study of EPO as a neurocognitive protectant in patients with lung cancer receiving prophylactic cranial irradiation is presented.

Prophylactic Cranial Irradiation for Patients with Small-Cell Lung Cancer in Complete Remission

Prophylactic cranial irradiation reduces the incidence of brain metastasis in patients with small-cell lung cancer. Whether this treatment, when given to patients in complete remission, improves survival is not known. We performed a meta-analysis to determine whether prophylactic cranial irradiation prolongs survival. We analyzed individual data on 987 patients with small-cell lung cancer in complete remission who took part in seven trials that compared prophylactic cranial irradiation with no prophylactic cranial irradiation. The main end point was survival. The relative risk of death in the treatment group as compared with the control group was 0.84 (95 percent confidence interval, 0.73 to 0.97; P= 0.01), which corresponds to a 5.4 percent increase in the rate of survival at three years (15.3 percent in the control group vs. 20.7 percent in the treatment group). Prophylactic cranial irradiation also increased the rate of disease-free survival (relative risk of recurrence or death, 0.75; 95 percent confidence interval, 0.65 to 0.86; P<0.001) and decreased the cumulative incidence of brain metastasis (relative risk, 0.46; 95 percent confidence interval, 0.38 to 0.57; P<0.001). Larger doses of radiation led to greater decreases in the risk of brain metastasis, according to an analysis of four total doses (8 Gy, 24 to 25 Gy, 30 Gy, and 36 to 40 Gy) (P for trend=0.02), but the effect on survival did not differ significantly according to the dose. We also identified a trend (P=0.01) toward a decrease in the risk of brain metastasis with earlier administration of cranial irradiation after the initiation of induction chemotherapy. Prophylactic cranial irradiation improves both overall survival and disease-free survival among patients with small-cell lung cancer in complete remission.