Higher Risk for Development of Brain Metastases in Long-Survivors from Colorectal Cancer with Concomitant Lung Metastases and KRAS Mutations
Future studies to address the impact on survival and the cost/effectiveness ratio of neuroimaging screening
An Italian study met its primary endpoint of reporting an high incidence of brain metastases in patients with metastatic colorectal cancer and concomitant KRAS mutations, lung metastases and a survival time from the first occurrence of metastases ≥ 10 months. The authors found 11% incidence of brain metastases and pointed out that neuroimaging screening may be considered in the follow-up of “at risk” patients. The study (Abst. O-0010) was presented by Dr Federica Zoratto of the Oncology Department, Santa Maria Goretti Hospital, University of Rome, Latina, Italy at the ESMO 15th World Congress in Gastrointestinal Cancer (3-6 July 2013, Barcelona, Spain).
Brain metastases occur in 1-4% of patients with metastatic colorectal cancer. Retrospective series showed that patients with a long survival from the diagnosis of metastatic colorectal cancer are more frequently affected. Moreover, brain metastases seem to be associated with lung metastases and KRAS activating mutations. The identification of clinical and molecular features correlated with brain metastases may allow the definition of a subgroup of patients more likely to develop brain metastases, thus to benefit from neuroimaging follow-up and early treatment.
The objective of the current study was to prospectively test the hypothesis that a a clinically relevant, higher incidence of brain metastases occurs in a population of patients with a survival time from the diagnosis of metastatic colorectal cancer ≥10 months, lung metastases and KRAS exons 2 and 3 mutations.
Given a reported incidence of brain metastases in unselected patients with metastatic colorectal cancer of around 3% (H0) and expecting an incidence in an “at risk” population selected on the basis of the 3 above reported features of 10% (H1), the study authors set α and β errors to 0.05 and 0.10 respectively. Furthermore, the Italian researchers adopted the Fleming single-stage design for calculating the sample size in their analysis. They planned that the null hypothesis would be rejected if at least 7 out of 104 “at risk” patients develop brain metastases.
A total of 623 patients, enrolled in clinical trials and treated with first-line chemotherapy and bevacizumab, were included in the overall study population. The authors identified 105 (16.9%) patients who simultaneously had a survival time from the diagnosis of metastatic colorectal cancer ≥10 months, lung metastases and KRAS exons 2 and 3 mutations.
In this study 26 (4.2%) out of 623 patients developed brain metastases. Among not “at risk” patients 14 out of 518 (2.7%) presented with brain metastases, while 12 out of 105 (11.4%) “at risk” patients developed brain metastases. The incidence of brain metastases in the two groups differed significantly (p = 0.0004). The null hypothesis was rejected according to the original design.
This analysis confirms the hypothesis that the concomitant presence of the 3 analysed risk factors increases the probability of developing brain metastases in patients with metastatic colorectal cancer. Based on the study data, the authors stressed on opportunity of considering a neuroimaging examination, such as brain CT scan or MRI, in this specific patient population in order to provide an early diagnosis of brain metastases and therefore the most appropriate therapy in an asymptomatic phase of the disease. They concluded that 11% incidence of brain metastases is clinically relevant finding. They plan to publish their findings in the scientific journal and future studies that should address the impact on survival and the cost/effectiveness ratio of neuroimaging screening.
This study elaborates on factors behind a clinically relevant problem in oncology. It has been conducted as a collaborative effort of several cancer institutions from central Italy.
Zoratto F, Loupakis F, Cremolini C, et al. Long-survivors with lung metastases and KRAS mutations have an increased risk to develop brain metastases from colorectal cancer. Ann Oncol 2013; 24 (Suppl 4): iv15.
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