Incidence Of CNS Involvement Research Articles

THER-05. SOLITARY CEREBRAL METASTASIS FROM TRANSITIONAL CELL CARCINOMA OF THE BLADDER

INTRODUCTION: Brain metastasis is the most common neurological neoplasia seen in adults. They typically metastasize from primary lung or breast but very seldom is bladder cancer the culprit. Transitional cell carcinoma (TCC) of the bladder accounts for less than 1% of brain metastasis and few cases have been reported in literature. Here we present a rare case of TCC presenting with signs of neurological impairment. CASE DESCRIPTION: A 75-year-old male with history of TCC presented to the emergency department with right upper extremity hemiparesis and dysarthria of 5 hours duration. He had undergone cystoscopy with resection of tumor 3 years prior followed by gemcitabine chemotherapy and combination radiotherapy/immunotherapy. CT imaging revealed a hyperdense 3.3 cm mass in the left frontoparietal region with internal hemorrhage measuring 1.4 cm and surrounding vasogenic edema. He was immediately treated with high dose corticosteroids and antiepileptics which did not result in improvement of his symptoms. Metastatic workup which included contrast enhanced CT of chest, abdomen and pelvis revealed no evidence of local or metastatic recurrence. Due to rapid worsening of his status, respiratory failure and encephalopathy, family did not want to pursue additional treatment and decided on inpatient hospice. The patient died 3 weeks later due to rapid neurological decline. DISCUSSION: According to literature, CNS involvement of disseminated TCC varies from 0.6% - 8%, and bladder carcinoma accounts for 0.5% of all intracranial metastases. Incidence of CNS involvement without evidence of recurrence or disseminated disease is extremely uncommon. Aggressive multitherapeutic regimens, which include gemcitabine, have been favored for its penetration of the blood-brain barrier but even with its use disease may present years later with an unfavorable prognosis. Although metastasis from TCC of the bladder is rare any decline in neurological status should warrant further investigation in these patients.

Medical management of brain metastases and leptomeningeal disease in patients with breast carcinoma.

Breast cancer is the most common malignancy among women and accounts for the second highest number of cancer-related deaths. With patients surviving longer due to advances in systemic control, the incidence of CNS involvement is increasing; however, the management of CNS metastases has not undergone parallel advancements. The blood-brain barrier limits the efficacy of most systemic chemotherapies, and the utilization of surgery and radiation beyond first-line therapy is limited. We will explore the recent developments in the medical management of breast cancer brain metastasis. Beyond traditional chemotherapy, we will also discuss targeted therapies and immunotherapies which may provide a survival benefit to this population and thus, offer further treatment options and a path for future research and treatment advances.

Brain metastases in metastatic breast cancer patients receiving trastuzumab-based therapies

CNS metastases mean a great challenge. It has been suggested that the brain metastases incidence could be high in metastasic breast cancer patients receiving trastuzumab based-therapies. We performed a descriptive analysis of our experience in this setting. 86 patients met the criteria (From Oct/99 to Oct/03). CNS progression occurred in 17 patients (19.5%). Mean age of CNS progression disease patients was 45.4 years while mean age for all the patients was 50.5 years. Response rate for the entire group of patients was: OR 39.7%; CB (OR + SD) 69%. Response rate to trastuzumab based-therapy was OR 82.4% and CB 88.2 at the time of CNS progression. Median time from the start of trastuzumab therapy up to the CNS progression was 10 months. OS was 23.4 weeks. The incidence of CNS involvement is high in young metastasic breast cancer women responding to trastuzumab-based therapies. This may lead to prophylactic cranial irradiation strategies or to the early detection in asymptomatic patients to improve surgery or radiosurgery results in these patients.

Acute myeloid leukemia with inv(16)(p13q22): involvement of cervical lymph nodes and tonsils is common and may be a negative prognostic sign.

Acute myeloid leukemia (AML) with inv(16)(p13q22) or the variant t(16;16)(p13;q22), is strongly associated with the FAB subtype M4Eo. A high incidence of CNS involvement was reported in the 1980s, but otherwise little is known about the pattern of extamedullary leukemia (EML) manifestations in this AML type. We have compiled clinical and cytogenetic data on 27 consecutive AML cases with inv(16)/t(16;16) from southern Sweden. In general, these AMLs displayed the clinical features that have previously been described as characteristic for this disease entity: low median age, hyperleukocytosis, M4Eo morphology, and a favorable prognosis. However, CNS leukemia was only seen in relapse in one patient diagnosed in 1980, whereas the most common EML manifestation in our series was lymphadenopathy (5/27, 19%), most often cervical with or without gross tonsillar enlargement. A review of previously published, clinically informative cases corroborates that lymphadenopathy, with preference for the cervical region, is the most common EML at diagnosis in inv(16)-positive AML (58/175, 33%). CNS leukemia, on the other hand, has been reported in only 17% of the cases, mostly in the relapse setting, with a diminishing frequency over time, possibly due to protective effects of high-dose cytarabine. Other reported EML sites include the scalp, ovaries, and the intestine. Cervicotonsillar EML was in our series associated with a shorter duration of first remission, (P < 0.05), and may hence prove to be an important clinical parameter when deciding treatment strategies in AML with inv(16)/t(16;16).

Prognostic significance of CD34 expression in childhood B-precursor acute lymphocytic leukemia: a Pediatric Oncology Group study.

We studied the blasts from 795 children greater than 1 year of age with newly diagnosed, untreated B-precursor acute lymphoblastic leukemia (ALL) for expression of the hematopoietic stem cell-associated antigen CD34. All cases were confirmed as B-lineage lymphoblastic leukemia by virtue of expression of CD19 and/or CD22, lack of T-cell antigens, and lack of surface-membrane immunoglobulin (Ig). The CD34 antigen was present in at least 10% of blast cells in 587 (73.8%) of the patients. There was no significant difference in presenting clinical characteristics between CD34+ and CD34- patients save for an increased incidence of CNS involvement at diagnosis in the latter. Patients with CD34+ leukemia were more likely to have blasts expressing CD22, CD9, and CD13 antigens but were less likely to coexpress CD20. Patients with pre-B (cytoplasmic mu) ALL were significantly more likely to lack CD34 on their blasts, while children with hyperdiploid ALL were more likely to be CD34+. Although remission induction rates were not significantly different between patients with CD34+ and CD34-ALL (P = .23), event-free survival was shorter for patients with CD34- leukemia (P = .0014). Even though CD34 expression was associated with certain other known prognostically favorable variables including hyperdiploidy and lack of cytoplasmic Ig, it had an independent favorable effect on treatment outcome, even after adjusting for competing prognostic factors.

Central nervous system complications of a newly recognized subtype of leukemia: AMML with a pericentric inversion of chromosome 16.

Ten patients with acute myelomonocytic leukemia (AMML) and inversion of chromosome 16 who had CNS involvement were identified at M.D. Anderson Hospital between January 1972 and December 1984. The nervous system signs and symptoms were evaluated in detail. CT scans, CSF cytologies, and treatment modalities were reviewed. Two patients underwent biopsies of lesions that proved to be granulocytic sarcomas. AMML with inversion 16 carries a much higher (33%) incidence of CNS involvement in the form of leptomeningeal metastasis and/or granulocytic sarcoma than all other acute nonlymphocytic leukemias (5%). The reason for this appears to be related to the chromosomal aberration and not to prolonged survival.

Sternberg's lymphoma: effect of treatment regimen upon prognosis in 38 cases.

Thirty-eight cases of diffuse poorly differentiated lymphoma with an anterior mediastinal mass were reviewed. Nine patients had stage I disease, 11 stage II, one stage III and 17 stage IV. Survival was prolonged in those stage III and IV cases whose treatment had commenced with chemotherapy rather than with radiotherapy. Survival and relapse-free interval were prolonged in all cases when chemotherapy had begun within a week of diagnosis and had continued with intervals of not more than 21 d between courses. Although patients whose chemotherapy had been delayed while radiotherapy was given fared worse overall, the incidence of mediastinal relapse was significantly increased when mediastinal irradiation had been omitted altogether or had been given in fractions of less than 100 rads. Prophylactic cranial irradiation and intrathecal chemotherapy reduced the incidence of CNS involvement in all stages of the disease. Testicular involvement occurred in three patients, two of them detected only at post-mortem, and occult ovarian involvement was also found in two post-mortems. Therapeutic principles are proposed including immediate systemic chemotherapy followed by mediastinal irradiation and CNS prophylaxis as soon as practicable after chemotherapy is begun and, later, testicular biopsy, or CT scan or ultrasound assessment of pelvic organs.