Metastatic colon cancer to the liver or the lung traditionally carried a poor prognosis with a median survival of 12 months. The incorporation of surgical resection of the metastases, neoadjuvant and adjuvant chemotherapy
, ablative and targeted radiotherapies have transformed the management in such patients from a palliative to a curative approach [9
]. Management of liver and lung metastases with CRC is now well established, with surgical resection for curative intent being the treatment of choice in selected patients with distant metastases and recurrences in whom the primary tumor is well controlled [10
]. Complete resection can increase 5-year survival to 30-50% in liver metastases and 40% in lung metastases [8
]. In contrast, BM in patients with CRC still carries a dismal prognosis, with a median survival of two months from the date of diagnosis [12
] that extends up to 5.4 months with treatment. This is in part secondary to their late presentation, and presence of concomitant lung and liver metastases when discovered. Management of BM is still unclear and is usually determined by the extracranial disease progression and response to chemotherapy, since most of the patients die from their extracranial disease [14
]. The management of locoregional recurrent colon cancer is more clearly defined, with surgical resection in appropriate candidates offering an opportunity for curative therapy [16
Treatment goals in presence of BM range from a conservative/palliative approach to an aggressive/curative one. In such cases where few or no randomized trials are available, it is reasonable to make clinical decisions based on the patient’s life expectancy, treatment options currently available, and on the main prognostic factors identified in the literature. Among those, are the Karnofsky performance status (KPS) (≥70), age (≤65 years), control of primary tumor, absence of extracranial metastases and number of brain lesions [17
]. Recursive partitioning analysis (RPA) has been used to evaluate patient survival when patients were classified in three prognostic classes. RPA Class I patients with KPS of 70 or greater, age 65 years or younger, controlled primary tumor and absence of systemic metastases, had a median survival of 7.1 months [14
].Considering these prognostic factors, our patient would be classified as RPA class I and was a good candidate for a curative treatment regimen.
Multiple approaches have been tried to manage BM. Surgical resection has the benefit of providing tissue for diagnosis and prolonging survival in patients with BM from CRC, with the main drawback being neurologic deficits [11
]. Initial treatment strategies combined surgery with whole brain radiation therapy (WBRT) in efforts to decrease recurrence rates, however studies did not improve overall survival [10
]. In addition, the complications incurred by WBRT included an increase in long-term neurotoxicity and decrease quality of life [21
]. These complications of WBRT and advancement in the field of radiation therapy have led to alternative radiation treatment modalities such as stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (hfSRT) that focus therapy on the tumor bed and spare normal brain tissue from potential toxicity.
In our case, SRS was chosen as an adjuvant therapy due to concern for initial incomplete resection, obtaining the local control benefit of combined radiation and surgery, but avoiding the toxicity of WBRT. To our knowledge, no randomized controlled trials have compared surgery with WBRT to surgery with SRS in patients with BM from CRC. However, several retrospective studies on patients BM and varying primary malignancies treated with surgery and adjuvant SRS are available, and have demonstrated similar outcomes in survival and local intracranial recurrence similar to WBRT although with higher rates of distant brain recurrences [22
]. In patients who do develop intracranial recurrence, studies showed that salvage SRS provided an extended survival in selected patients in whom the major prognostic factors such as RPA class are favorable [25
Hypofractionated stereotactic radiotherapy can be an alternative to SRS in large or anatomically challenging lesions allowing higher cumulative radiation doses to the tumor. Although the use of hypofractionated radiation as a salvage therapy has not been rigorously evaluated, there have been similar results between use of SRS and hfSRT as adjuvant therapies in terms of local and distant control, survival and recurrences, and need for salvage therapy [26
Chemotherapy is indicated for patients with CRC and high-risk features, local or distant metastatic spread [28
]. Although its benefit in BM was initially thought to be limited because of the anatomic barriers: the blood-tumor and blood-brain barriers, a recent retrospective study showed that administration of chemotherapy after local control of BM in patients with CRC was associated with a statistically significant increase in overall survival, and was the most powerful independent prognostic factor for survival after BM [31
]. These results are encouraging, and will hopefully prompt additional studies with a prospective design to further clarify the role of chemotherapy in relation to brain metastases beyond the well documented benefit for reduction in risk of systemic metastases.