Stereotactic Radiosurgery Plays a Critical Role in Enhancing Long-term Survival in a Patient with Pancreatic Cancer Metastatic to the Brain

Discussion

Brain metastases from pancreatic cancer are an extremely rare pathological entity. A recent literature review yielded only 12 published reports of metastatic pancreatic cancer to the brain (14). Overwhelmingly, outcomes were extremely poor, with the majority of patients dying within a year, most of them within weeks or months (14). Only recently have reports surfaced of long-term survival with this disease (5, 15). Three patients from these reports are described as living without tumor recurrence 20 months, six years, and 10 years after the diagnosis of brain metastases (5, 15). Our case is yet another exception to the rule that pancreatic cancer with brain metastases carries an extremely limited prognosis; however, our treatment approach differs in that we stress the extensive use of multiple treatments with SRS, while the cases mentioned above focus on surgical resection. Furthermore, our patient's brain metastases manifested as multiple small lesions rather than a solitary tumor.

Advances in medical oncology have created a sense of optimism that exceptions from the dismal prognosis with pancreatic cancer are indeed possible. However, a growing rate of cases with brain metastases is expected to result from the increased survival of these patients (2). Therefore, signs of suspicious neurological symptoms should lead to an early imaging study and prompt treatment of brain metastases. Closer and more vigilant patient surveillance may afford the chance of detecting these lesions at earlier stages, with obvious benefit to these patients. At the current time, serial MRI imaging every three months is generally accepted as adequate brain imaging follow-up (6).

Recently, a second long-term survivor of pancreatic cancer with metastatic disease to the brain cancer came to our attention. While the very recent diagnosis of this patient's metastatic disease excludes the possibility of our commenting on the treatment of this lesion, her clinical history is important in that it underlines the importance of vigilant patient surveillance. This 61-year-old white female with a history of breast cancer was diagnosed with pancreatic cancer in 2006. She underwent a Whipple procedure and was placed on a long-term chemotherapeutic regiment and was stable with pancreatic cancer for six years. She then presented with frontal headaches, a loss of peripheral vision, and blurred vision. An MRI of the brain did not show any abnormalities. However, persistent symptoms prompted a second MRI less than a month later, which revealed a small frontal metastasis and diffuse enhancement, consistent with leptomeningeal disease. In light of the extremely rare nature of these metastases, it is likely that important clinical clues are missed and these lesions are discovered too late. On this occasion, suspicious neurological symptoms were investigated adequately, affording the patient an earlier and potentially more effective treatment of her metastatic disease.

These brain metastases pose a special challenge compared to other systemic metastases since systemic chemotherapeutic regimens must overcome the blood-brain barrier (BBB). Therefore, the sole use of chemotherapy for brain metastases is not adequate and additional treatment modalities are commonly employed. The current trend in the treatment of a resectable brain metastasis in a patient with stable systemic disease is to consider surgical resection followed by whole-brain radiation therapy (WBRT) (Category 1 recommendation) or surgical resection followed by SRS (Category 2A recommendation) (6). Although both options are appropriate, the category 1 recommendation is based on high-level evidence compared to a lower level of evidence for category 2A. The treatment of recurrences includes SRS, or surgery, or WBRT, which are all category 2A options (6). The option of choosing SRS instead of WBRT in the first place has the advantage of a potential reduced rate of cognitive deficits that may be incurred with WBRT (8, 9, 12, 13). This remains a controversial issue as SRS also carries the risk of neurological complications (11). The brain's exposure to radiation is also less with SRS when compared to WBRT. Furthermore, should any recurrences emerge, the reduced radiation exposure allows for the use of multiple, subsequent SRS therapies for rapid succession treatment. An initial WBRT followed by subsequent SRSs would probably result in a higher risk of complications due to increased radiation levels within the brain.

The SRS approach instead of a WBRT regimen has the disadvantage that it lacks the prophylactic effect of WBRT in the development of recurrences. This is certainly an important consideration, but it is felt that newer, molecularly-targeted chemotherapeutic drugs that achieve a better penetration of the BBB may potentially substitute for the prophylactic effect of WBRT. Moreover, the increased relapse rate with the SRS approach compared to the combined use of WBRT does not negatively affect the survival or functional independence of the patient (7, 10).

A major advantage of utilizing SRS in the treatment of recurrences rests not only in its less invasive nature compared to surgery, but also in its ability to effectively and safely control any metastases in inaccessible or eloquent brain areas. To that end, SRS offers the patient a non-invasive procedure with minimal risk and considerably lower morbidity. Moreover, this facet of the treatment modality allows for the option of re-treatment if a recurrence is found and can be carried out within a short time frame if required.

Although our approach is generally considered appropriate, it is still not supported by a cohort-based evidence group. Further evidence from prospective studies is required in order to evaluate this approach for treating brain metastases in general. However, with the growing reported incidence of patients with pancreatic cancer with brain metastases, this treatment modality may be offered with a view to studying a regimen geared towards reaching a highly efficacious standard while minimizing morbidity for patients.

While the number of cases with brain metastases of pancreatic cancer continues to rise, there is a paucity of studies addressing the genetic composition of these distant metastases along with a lack of any targeted therapies for these specific metastases. To date, these tumors have not been characterized with a view to identifying potential molecular targets for therapy or to understanding why some pancreatic adenocarcinomas metastasize to the brain in the first place. Additionally, the molecular profiling of brain metastases from pancreatic cancer in patients with an unexpectedly long survival may contribute to the identification of more accurate markers of prognostication. The early identification of patients with a relatively favorable prognosis may lead to utilization of less invasive therapies that may augment surgical resection as was implemented in our case. Genomic profiling of cases of long-term survivors may also serve as a platform for the development of tailored therapies that target these tumors on the molecular level.