Cerebral relapse of metastatic gastrointestinal stromal tumor during treatment with imatinib mesylate: Case report

Abstract

BackgroundThe management of unresectable or metastatic gastrointestinal stromal tumors (GISTs) has previously been difficult as they are resistant to conventional chemotherapy and radiation. The development of imatinib mesylate has made a major impact on the management of advanced GISTs. It is apparent that there are sanctuary sites such as the central nervous system where imatinib does not achieve adequate concentrations. We describe the case of a man with metastatic GIST who experienced multiple cerebral relapses of disease while systemic disease progression appeared to be controlled by imatinib.Case presentationA 47-year-old man presented in July 1999 with a jejunal GIST with multiple hepatic metastases. The jejunal primary was resected and after unsuccessful cytoreductive chemotherapy, the liver metastases were also resected in December 1999. The patient subsequently relapsed in August 2001 with symptomatic hepatic, subcutaneous gluteal, left choroidal and right ocular metastases all confirmed on CT and PET scanning. Biopsy confirmed recurrent GIST. MRI and lumbar puncture excluded central nervous system involvement. The patient was commenced on imatinib 400 mg bd in September 2001 through a clinical trial.The symptoms improved with objective PET and CT scan response until December 2002 when the patient developed a right-sided foot drop. MRI scan showed a left parasagittal tumor which was resected and confirmed histologically to be metastatic GIST. Imatinib was ceased pre-operatively due to the trial protocol but recommenced in February 2003 on a compassionate use program. The left parasagittal metastasis recurred and required subsequent re-excision in September 2003 and January 2004. Control of the systemic GIST was temporarily lost on reduction of the dose of imatinib (due to limited drug supply) but on increasing the dose back to 800 mg per day, systemic disease was stabilized for a period of time before generalised progression occurred.ConclusionThis case illustrates that the brain can be a sanctuary site to treatment of GISTs with imatinib. Maintaining dosing of imatinib in the face of isolated sites of disease progression is also important, as other metastatic sites may still be sensitive.

Clinical responses observed with imatinib or sorafenib in melanoma patients expressing mutations in KIT

“…The increased rates of CNS metastases in this series may be explained by the limited penetration of small molecule kinase inhibitors into the brain, as documented in other imatinibsensitive malignancies such as chronic myeloid leukaemia, Philadelphia chromosome-positive acute lymphocytic leukaemia and GIST in which relapse within the CNS has been reported (Takayama et al, 2002;Hughes et al, 2004;Altintas et al, 2007). This is likely to represent a significant clinical problem as the brain is a frequent site of relapse in melanoma.…”

Gastrointestinal cancer and brain metastasis

“…The median survival was 10 months among this group (range, 3-28 months), although they did not differentiate between tumors of the small intestine and the colon and rectum. Survival among patients with ileal carcinoids 37 and GIST 38 brain metastasis has been reported as 9 and 19 months, respectively. The mean bDFI for these tumors was 24 months (range, 8-52 months), 14 months, and 42 months among adenocarcinomas (no differentiation between small intestine and colon/rectum), 34 ileal carcinoids, 37 and GIST cases, 38 respectively.…”

“…Survival among patients with ileal carcinoids 37 and GIST 38 brain metastasis has been reported as 9 and 19 months, respectively. The mean bDFI for these tumors was 24 months (range, 8-52 months), 14 months, and 42 months among adenocarcinomas (no differentiation between small intestine and colon/rectum), 34 ileal carcinoids, 37 and GIST cases, 38 respectively. The clinical presentation of brain metastases associated with small intestinal malignancies is variable and includes hemiparesis, extremity weakness, headache, blurry vision, cranial nerve palsies, and foot drop.…”

“…38 Survival after diagnosis of brain metastases is dependent upon tumor type with adenocarcinoma having the poorest prognosis and a 5-year survival rate of 15% to 20%. 1 Salvati et al 34 reported 34 cases of solitary cerebral metastases from 24 tumors originating in the colon-rectum and 10 tumors in the small intestine.…”

“…The clinical presentation of brain metastases associated with small intestinal malignancies is variable and includes hemiparesis, extremity weakness, headache, blurry vision, cranial nerve palsies, and foot drop. [35][36][37][38] Neurologic symptoms from brain metastasis were the first manifestations of small intestine cancer in only 3 patients, 32,35,36 including 2 patients with no additional systemic metastases. 32,36 Unlike other small intestinal malignancies, the metastatic potential of a carcinoid tumor (regardless of the primary location) is directly correlated to the size of the primary tumor.…”