ABSTRACT
Colorectal cancer is one of the most common causes of death due to cancer. In the majority of patients, diagnosis of brain metastasis (80%) follows diagnosis of the systemic cancer (metachronous presentation). However, brain metastases can be diagnosed before primary tumour diagnosis (precocious presentation) or simultaneously (synchronous presentation). With this case report, we aim to share the experience we gained with these two cases of precocious brain metastasis. These cases demonstrate that tumour biology is one of the most important of the widely recognized prognostic factors of colorectal cancer.
Introduction
Colorectal cancer is currently one of the main causes of cancer mortality. Synchronized metastatic cancer is found at initial diagnosis in 10-15% of primary colorectal carcinoma patients. In adults, primary tumors responsible for brain metastases are pulmonary in 50%, breast in 15-30% and colon in 5% of cases, while no primary focus can be detected in 10-15%. The incidence of colorectal cancer with brain metastasis (0.4-2.3%) is low compared to the rates of colorectal cancer with liver (20-30%) and lung (10-20%) metastasis. However, there has been an increase in reported cases due to advances of magnetic resonance imaging (MRI) and systemic colorectal cancer therapy. For most patients with brain metastasis (80%), metastasis appears after the systemic cancer is diagnosed (metachronous presentation).1 However, in some cases, brain metastasis may be diagnosed before (precocious presentation) or at the same time (synchronized presentation) as the primary tumor.2,3,4 Brain metastases are the most common intracranial malignancies and occur at 10 times the frequency of primary brain tumors.5,6
The average survival after diagnosis of colorectal cancer with brain metastasis has been reported as 2.7-8.3 months.7 In patients with no detectable primary focus and brain metastasis as the sole finding, those with the best prognosis have an average survival of 13.4 months. Patients with brain metastasis of breast cancer have a better prognosis than patients with brain metastases of other primary tumors. In contrast, patients with brain metastasis of colorectal cancer tend to have a worse prognosis. This may be attributable to the higher prevalence of cerebellar metastasis in these patients, which has poor prognosis among intracranial tumors.8
In this study, we present two cases of colon cancer patients presenting with precocious brain metastasis and discuss their treatment and follow-up.
Discussion
Metastatic brain masses are not common and are usually associated with disease of another region. Although it was previously believed that 10-15% of intracranial tumors were metastatic, this rate has more recently been reported as 20-40%.1,2,3,4,5,9 Brain metastasis as the initial sign of primary colon cancer, without lung or liver metastasis is extremely rare, and only a few cases can be found in the literatüre.10,11,12 The intracranial spread pattern and focus number of a metastatic tumor depends on the origin and type of the primary tumor. There are several factors that affect the prognosis of central nervous system tumors. These include the size and number of metastatic foci, the extent of peritumoral edema and response to pharmacologic agents, whether the mass can be resected and the possibility of local recurrence on the same side as the metastatic tumor resection, radiosensitivity of the primary tumor, and timing of metastasis diagnosis (precocious vs metachronous presentation).3,4,8 In adults, the origin of brain metastasis is lung in 41% of cases, breast in 19%, malignant melanoma in 10%, GIS in 7%, colorectal in 4%, and genito-urinary system (kidney) in 3%.13
The frequency of intracranial metastasis of colorectal system cancers is 33% for rectum, 23% for sigmoid colon, 15% for cecum and ascending colon, 9% for rectosigmoid colon, 4% for descending colon, and 1% for transverse colon.14 Brain metastasis is present at diagnosis in 1-3% of colorectal cancer patients, while 10% develop metastasis during the course of disease.7,15 The management of brain metastasis of colorectal cancer is determined by several factors, including patient performance; location, grade, and type of the primary cancer; number and location of brain lesions, and the presence of leptomeningeal disease.16 Metastatic tumor cells reach the brain via hematogenous spread. Arterial circulation is the primary route to the brain, though a small proportion of cells from pelvic and retroperitoneal cancers may reach the brain via Batson’s plexus (vertebral venous system).4 Brain metastases are often found in the gray-white junction where the vascular structures narrow and embolism is more likely.17 Approximately 80% of brain metastases are found in the cerebral hemispheres, 15% in the cerebellum and 5% in the brain stem. In both of our cases, the lesions were located in the cerebral hemispheres. Molecular studies have demonstrated that brain metastases as associated with disruption of the blood-brain-barrier. Colon, breast, and renal cancer metastases are often single (37-50%), whereas malignant melanoma and lung cancer metastases are usually multifocal (63%).18,19 The most common presenting symptom for these patients is headache. The focal weakness, papillary edema, and focal and generalized seizures exhibited in our two cases are also common signs.20 Rarely, as in the two cases reported here, brain metastases may be detected incidentally while investigating other symptoms.
The best diagnostic method for brain metastases is contrast MRI and computed tomography examination. These methods allow metastasis to be differentiated from primary brain tumors, abscesses, cerebral infarcts, and hemorrhage. Angiography and/or biopsy are generally requried for definitive diagnosis. Stereotactic biopsy is a safe and appropriate approach for obtaining brain tissue.21 Untreated brain metastases have a poor prognosis, with an average survival of about 4 weeks.22
The best treatment approach for patients whose brain metastasis consists of a single focus is full brain radiotherapy, surgery and stereotactic radiosurgery.23,24 Surgical removal of metastatic brain lesions extends survival.25,26 Increased awareness, early diagnosis and aggressive treatment of brain metastases may increase survival in colorectal cancer patients with brain metastasis to 3.5-7.13 months. Although the development of brain metastasis usually indicates poor prognosis, it is now possible to alleviate most symptoms associated with brain metastasis and substantially improve patients’ quality of life. In a case series reported by Vagn-Hansen and Rafaelsen9, they reported that operated patients lived 1 month longer than patients who were not operated.Malafosse et al.3 reported that the survival of patients who underwent chemoradiotherapy and aggressive surgery with craniectomy was significantly longer than in those who did not undergo surgery (86.6±17.35 days or 2.9±0.59 months). Metastasectomy is a common practice in oncologic surgery.4,8 In rare cases, a metastatic lesion may be detected in the brain in the absence of any signs of disease. In these cases, metastasectomy (craniotomy of the metastatic lesions) is necessary to extend survival.5,27 Our first case survived for 15 years after the diagnosis of metastatic cancer. This period is remarkably long when compared to the literature. We attribute this to the biological behavior of the patient’s tumor. Another interesting aspect of this case is the secondary colon malignancy which appeared after 13 years. Our second case survived for 16 years after metastatic cancer diagnosis, which is consistent with the best prognosis reported in the literature.
In conclusion, although there are few case series of this kind and our own series comprises only two patients, several points must be kept in mind: albeit rare, the brain is a metastasis zone for colorectal cancers; during treatment, priority should be given to symptom-producing brain metastases and complete surgical resection is required; following neoadjuvant chemoradiotherapy, primary focus resection should be performed with reliable surgical margins and oncologic principles; and patients should be followed using a multidisciplinary approach.
On the other hand, we are rapidly acquiring new information about molecular oncogenetics and how malignant cells behave. Our experience with these two cases shows that, of the widely accepted prognostic factors for colon cancer, tumor biology is an important factor.
