Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Central nervous system metastases are a common complication of disseminated germ cell tumors of the testis. They occurred in 16% of 242 patients treated and in 25% of the patients who died in our VAB chemotherapy series. Pulmonary metastases preceded or coincided with the development of brain metastases. The frequency of brain metastases differed with the histology of the primary tumor. They occurred in 13% of pure embryonal carcinomas, 18% of mixed tumors containing embryonal or choriocarcinoma elements, and 83% of pure choriocarcinomas. Embryonal carcinoma and choriocarcinoma were the principle histologies found in brain metastases. Characteristically, pure choriocarcinoma deposits in the brain were multiple (8/9) and cerebellar involvement was common (5/9). Pure embryonal carcinoma CNS metastases were typically single (6/8) or very few and cerebellar involvement was not observed. The interval from the diagnosis of malignancy to the diagnosis of brain metastases was longer for embryonal carcinoma than for pure choriocarcinoma (23 mos. vs. 6.5 mos.). Survival following the diagnosis of brain metastases was poor. There was a tendency toward longer survival for histologically pure embryonal carcinoma deposits in the brain than for the pure choriocarcinomas (6.5 mos. vs. 1 mo.).
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PMID:Neurological complications of malignant germ cell tumors of testis: biology of brain metastases (I). 22 44

Gonadal germ cell tumors respond favorably to chemotherapy either at diagnosis or when they recur. Histologically similar tumors may arise in the CNS usually in the pineal or suprasellar regions. Although radiation therapy may produce a 5 year disease-free survival in excess of 60% in localized pure germinoma, germ cell tumors of other histology tend to recur. We have conducted 14 chemotherapy trials in 8 patients with recurrent CNS germ cell tumors using 3 different single agent and 2 multi-agent chemotherapy regimens. The histologic diagnoses of the patients were germinoma (4), endodermal sinus tumor (2), embryonal carcinoma (1), and mixed tumor - germinoma plus choriocarcinoma (1). There were 7 males and 1 female with a median age of 13 years. The primary tumor arose in the pineal region in 6 and was multicentric in 2. Seven patients had local recurrences and one developed an initial recurrence in the spinal canal. Three patients had CNS metastases at relapse and 2 had systemic metastases. Objective responses were documented in 7 of 14 trials (50%). Responses were observed with cyclophosphamide (80 mg/kg) in 3 of 4 patients for 2+, 3, and 5 mos, cisplatin (120 mg/m2) in 1 of 2 patients for 2+ mos, and the VAB 6 protocol (vinblastine, bleomycin, cyclophosphamide, actinomycin-d, cisplatin) in 3 of 5 patients for 5, 8, and 18 mos. The median duration of response was 5 mos. (2+-18). High doses of single chemotherapy agents such as cyclophosphamide and cisplatin as well as VAB 6 regimen have definite activity in recurrent CNS germ cell tumors, especially germinoma. Good palliation may be achieved with chemotherapy alone with acceptable morbidity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chemotherapy trials in recurrent primary intracranial germ cell tumors. 389 72

A report is presented on 12 patients with extrapulmonary small cell carcinoma. In 9 patients the primary tumor could be localized (cervix in 3, esophagus in 3, prostate in 2, pancreas in 1) whereas no primary was found in 3. Seven of 12 patients presented with distant metastases and four developed metastases later. Five of 12 had CNS metastases (brain metastases in 4, spinal cord compression in 1). Six patients were initially treated by surgery or radiotherapy (2 and 4 respectively). All six developed distant metastases during or shortly after local treatment. Five of 6 patients initially treated with chemotherapy responded to the treatment. Three of 12 patients are surviving 18+, 80+ and 81+ months after the initial diagnosis without evidence of disease. The biology and clinical course of extrapulmonary small cell carcinoma are similar to those of its pulmonary counterpart. In planning therapy for extrapulmonary small cell carcinoma, particular importance should be attached to systemic treatment.
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PMID:[Extrapulmonary small-cell carcinoma - a rarity with important therapeutic consequences]. 632 92

Osteosarcoma patients free of CNS metastases are at risk for acquiring leukoencephalopathy after receiving multiple courses of high dose intravenous methotrexate followed by oral leucovorin rescue (MTX-LV). A prospective study of the adequacy of CNS rescue of MTX biochemical toxicity by oral leucovorin was undertaken in newly diagnosed neurologically normal osteosarcoma patients. Prior to surgical resection of the primary tumor, ten patients received 4 weekly courses of MTX-LV. During the fourth weekly MTX-LV treatment, 0 and 72 hr serum and CSF determinations of MTX, 5-methyl-tetrahydrofolate (5-MTHF) and LV were made. No CSF MTX was detectable at 0 hr in any patient, but a significant elevation in CSF MTX occurred in 9/9 patients at 72 hr (mean 47.2 +/- 31.8 ng/ml or 1.04 +/- 0.7 X 10(-7) M). There was no significant change in mean CSF 5-MTHF over 72 hr despite a rise in serum 5-MTHF. MTX exceeded 5-MTHF in 6/9 patients in CSF, whereas only 3/8 patients had higher MTX in the serum at 72 hr. No acute systemic or neurotoxicity was seen. The failure of oral leucovorin to consistently elevate CSF 5-MTHF levels at 72 hr in the context of significant levels of CSF MTX may result in intermittent CNS folate deficiency. The clinical and pathological syndrome of leukoencephalopathy may be related to this phenomenon and may evolve after repeated MTX-LV treatments.
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PMID:The inability of oral leucovorin to elevate CSF 5-methyl-tetrahydrofolate following high dose intravenous methotrexate therapy. 661 87

Eighteen of 78 patients (23%) with metastatic colorectal cancer developed clinically significant metastases to the central nervous system (CNR). The patients developing CNS metastases had a decreased likelihood of associated liver metastases compared to the patients without CNS metastases (22% versus 80%). Pulmonary metastases were present in 55% of patients with CNS lesions and in 25% of those without CNS lesions. Overall survival from diagnosis of the primary tumor was comparable (median, 28 months) for patients with or without CNS lesions. The incidence of CNS metastases was comparable irrespective of Duke stage at presentation. For early lesions (Duke B or C), CNS metastases were associated with a shorter survival (31 versus 42 months). For advanced disease (Duke D lesions) at presentation, the overall survival of the group with CNS metastases was longer (24 versus nine months). Therefore, the longer survivorship of patients with advanced disease may contribute to a greater likelihood of CNS metastases.
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PMID:Metastasis to the central nervous system from colorectal cancer. 746 89

The objectives of this population-based study were to assess putative prognostic factors for central nervous system (CNS) metastases among patients with cutaneous malignant melanoma, to assess the cumulative risk of CNS metastases in different subsets of patients with recurrent disease, and to describe patient outcome. At a median follow-up of 11 years, 201/2516 patients with melanoma had developed CNS metastases, corresponding to a cumulative risk at 5 years of 7%. In 41 of these 201 patients the CNS metastases were recorded as the first site of recurrence. In a Cox's multivariate model, primary tumor thickness and ulceration in stage I patients were independent risk factors. The cumulative rates of incidence of CNS metastases 5 years after local or regional recurrence as first event were 5 and 42%, respectively. These results may help to form an individually based risk assessment, which might be of value for melanoma patients in certain occupations.
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PMID:Central nervous system metastases of cutaneous malignant melanoma--a population-based study. 983 75

Thyroid transcription factor-1 (TTF-1) is used as an immunohistochemical marker for the identification of the lungs or thyroid gland as the site of origin in patients with metastatic disease and unknown primary tumor. In this study the reliability of anti-TTF-1 was assessed in 65 metastases of the central nervous system (CNS), among which there were also small stereotactic biopsies (n = 22) and poorly preserved specimens. Eight out of nine CNS metastases of patients with known adenocarcinoma of the lungs, as well as seven adenocarcinoma metastases of patients with radiologically detected or anamnestically presumed pulmonary carcinoma, expressed TTF-1 immunohistochemically. One CNS metastasis from a follicular thyroid carcinoma was positive and one from an anaplastic thyroid carcinoma was negative. All CNS metastases from patients with known primary tumors outside the lungs or thyroid gland were negative. TTF-1 is a sensitive (up to 90%) and specific (100%) immunohistochemical marker for CNS metastases of adenocarcinomas of the lungs and also functions reliably on small or stereotactic biopsies and poorly preserved samples.
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PMID:[Diagnostic value of the monoclonal antibody to thyroid transcription factor -1(TTF-1) in CNS metastases. An immunohistochemical study of 65 cases]. 1218 82

Brain metastasis occurs in 15-40% of cancer patients and is present in approximately 10-16% of patients with metastatic breast disease. However, little is known about prognostic factors enabling the early identification of breast cancer patients at risk of CNS metastases. Therapy for brain metastases should be based on several parameters, such as the assessment of prognostic variables, the extent of neurological and systemic disease, and its chemo-sensitivity to previously administered chemotherapy treatments. In view of the known close correlation between metastatic and primary tumor chemosensitivity, the type of chemotherapy chosen should depend more on the tumor histology than on the cerebral distribution of the single drug. More recent drugs with a high impact on the clinical outcome of metastatic breast cancer patients, such as taxanes or trastuzumab, play only a limited role in the treatment of brain metastases.
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PMID:Chemotherapy in breast cancer patients with brain metastases: have new chemotherapic agents changed the clinical outcome? 1855 Mar 83

Metastatic spread of melanoma to the central nervous system (CNS) is associated with dismal prognosis. Preclinical testing of novel therapeutic approaches would be aided by the development of appropriate models of spontaneous CNS metastasis arising from primary tumors. A highly metastatic variant of the WM239A human melanoma cell line, designated 113/6-4L, was generated and used to test the efficacy of long-term, low-dose metronomic cyclophosphamide and vinblastine chemotherapy on advanced established metastatic disease in sites such as liver, lungs, and lymph node. This treatment resulted in control of advanced, systemic disease and prolongation of survival. Among long-term surviving mice, 20% showed the presence of spontaneous brain metastases. Two cell lines (131/4-5B1 and 131/4-5B2) were generated from such metastases, which were found to spontaneously metastasize to brain parenchyma with occasional localization to leptomeninges, after orthotopic transplantation and removal of the primary tumor. The cell lines were found to have increased ability to proliferate in brain-conditioned medium and displayed enhanced adhesion to lung and brain endothelial cells. These findings represent the first report of spontaneous CNS metastases generated from primary tumors of any human cancer in mice, which heritably maintains this phenotype, and as such, the variant cell lines generated should aid studies in the biology and treatment of CNS metastases, especially of melanoma origin.
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PMID:Development of a preclinical model of spontaneous human melanoma central nervous system metastasis. 1914 91

Benefit of adjuvant trastuzumab in breast cancer has been reported in four randomized trials of phase III, and these results are consistent in showing improvement in disease-free survival (DFS). Current evidence for homogeneity of this DFS benefit in subgroups of patients with the different size of the primary HER2-positive tumor treated according to the HERA trial is reviewed. It is evident that current published evidence is insufficient to rule out that there is a cohort of patients with HER2-positive disease who do not achieve a reduction in the risk of recurrence by adjuvant treatment with trastuzumab after completion of previous adjuvant chemo- and radiotherapy. An alternative interpretation of results of the HERA trial currently available in two primary reports (1-year, and 2-year median follow- up, respectively) is discussed. The risk factors of central nervous system (CNS) metastases in breast cancer and problem of CNS metastases in HER2-positive tumors are briefly reviewed. A hypothesis on the relations between brain metastases, their risk factors, the size of the primary tumor, and their impact on the DFS in patients with HER2-positive tumors treated with adjuvant trastuzumab is proposed based on the results of the HERA trial. Altogether, some direct evidence is presented here based on the published results of the HERA trial, and still more indirect evidence based on the information on related topics in literature, to show that current clinical practice of adjuvant trastuzumab in mono-therapy, which is based on assumption that there is a homogeneous benefit as for disease-free survival for all sizes of primary HER2-positive tumors above 1 cm, may not be based on such firm evidence as is commonly presented.
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PMID:Is there a qualitative interaction between adjuvant trastuzumab and size of the primary tumor in breast cancer? 1866 46


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