Between 1992 and 1999, we treated 350 patients with skeletal metastases. A multivariable analysis of the patients was conducted using the Cox proportional hazards model. We identified five significant prognostic factors for survival, namely, the site of the primary lesion, the performance status (Eastern Cooperative Oncology Group status 3 or 4), the presence of visceral or cerebral metastases, any previous chemotherapy, and multiple skeletal metastases. The score for each significant factor was derived from the corresponding estimated regression coefficients (natural logarithm of the hazard ratio). The prognostic score was calculated by adding all the scores for individual factors. The rate of survival was 31% at six months and 11% at one year for the patients with a prognostic score of 6 or more. By contrast, patients with a prognostic score of 2 or less had a rate of survival of 98% at six months and 89% at one year. This scoring system can be used to determine the optimal treatment for patients with pathological fractures or epidural compression.

The MR features described in this study are useful for distinguishing malignant peripheral nerve sheath tumors from neurofibromas. If a tumor has two or more of the four statistically significant features, it can be considered to be highly suspicious of malignancy and should be subjected to a biopsy for early diagnosis.

The prognosis of patients with bone metastasis from lung cancer has not been well documented. We assessed the survival rates after bone metastasis and prognostic factors in 118 patients with bone metastases from lung cancer. The cumulative survival rates after bone metastasis from lung cancer were 59.9% at 6 months, 31.6% at 1 year, and 11.3% at 2 years. The mean survival was 9.7 months (median, 7.2 months; range, 0.1-74.5 months). A favorable prognosis was more likely in women and patients with adenocarcinoma, solitary bone metastasis, no metastases to the appendicular bone, no pathologic fractures, performance status 1 or less, use of systemic chemotherapy, and use of an epithelial growth factor receptor inhibitor. Analyses of single and multiple variables indicated better prognoses for patients with adenocarcinoma, no evidence of appendicular bone metastases, and treatment with an epithelial growth factor receptor inhibitor. The mean survival period was longer in a small group treated with an epithelial growth factor receptor inhibitor than in the larger untreated group. The data preliminarily suggest treatment with an epithelial growth factor receptor inhibitor may improve survival after bone metastasis.

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BACKGROUNDBecause the efficacy and safety of pazopanib in Japanese patients with soft tissue sarcoma (STS) had not been evaluated previously in a large‐scale cohort, the authors investigated the efficacy and safety of pazopanib in 156 Japanese patients with relapsed STS. This was a retrospective study based on the collection of real‐life, postmarketing surveillance data.METHODSPatients received pazopanib with the objective of treating local recurrence (n = 20), metastasis (n = 104), and both (n = 32). The patient median age was 53.8 years. The primary objective of this study was to clarify the efficacy of pazopanib for patients with STS.RESULTSThe median treatment duration was 28.7 weeks, and the average dose intensity of pazopanib was 609 mg. Adverse events occurred in 127 patients (81.4%). In addition to the main common toxicities, such as hypertension and liver disorder, pneumothorax (n = 11) and thrombocytopenia (n = 16) also were observed. The median progression‐free survival for all patients was 15.4 weeks. The median progression‐free survival for patients with leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma, and liposarcoma was 18.6 weeks, 16.4 weeks, 15.3 weeks, and 8 weeks, respectively. The median survival for all patients was 11.2 months. The median survival for patients with leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma, and liposarcoma was 20.1 months, 10.6 months, 9.5 months, and 7.3 months, respectively.CONCLUSIONSThere were apparent differences in the efficacy of pazopanib treatment among histologic types of STS. Pazopanib treatment is a new treatment option; however, adverse events like pneumothorax and thrombocytopenia, which did not occur frequently in the PALETTE study (pazopanib for metastatic soft‐tissue sarcoma), should be taken into consideration. Cancer 2016;122:1408‐16. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

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Germ-line point mutations of the RET gene are responsible for multiple endocrine neoplasia (MEN) type 2A and 2B that develop medullary thyroid carcinoma and pheochromocytoma. We performed a differential display analysis of gene expression using NIH 3T3 cells expressing the RET-MEN2A or RET-MEN2B mutant proteins. As a consequence, we identified 10 genes induced by both mutant proteins and eight genes repressed by them. The inducible genes include cyclin D1, cathepsins B and L, and cofilin genes that are known to be involved in cell growth, tumor progression, and invasion. In contrast, the repressed genes include type I collagen, lysyl oxidase, annexin I, and tissue inhibitor of matrix metalloproteinase 3 (TIMP3) genes that have been implicated in tumor suppression. In addition, six RET-MEN2A-and five RET-MEN2B-inducible genes were identified. Among 21 genes induced by RET-MEN2A and/or RET-MEN2B, six genes including cyclin D1, cathepsin B, cofilin, ring finger protein 11 (RNF11), integrin-␣6, and stanniocalcin 1 (STC1) genes were also induced in TGW human neuroblastoma cells in response to glial cell line-derived neurotrophic factor stimulation. Because the STC1 gene was found to be highly induced by both RET-MEN2B and glial cell line-derived neurotrophic factor stimulation, and the expression of its product was detected in medullary thyroid carcinoma with the MEN2B mutation by immunohistochemistry, this may suggest a possible role for STC1 in the development of MEN 2B phenotype. The RET proto-oncogene encodes a receptor tyrosine kinase with a cadherin-related motif and a cysteine-rich domain in the extracellular domain and is located on chromosome 10q11.2.1,2 It has been demonstrated that RET is a functional receptor for four related neurotrophic factors including glial cell line-derived neurotrophic factor (GDNF), neurturin, artemin, and persephin. These factors are known to require glycosylphosphatidylinositol-anchored co-receptors, GFR-␣s, as ligand-binding components and to promote the survival of various central and peripheral neurons in culture.1,2 In addition, gene knockout studies revealed that the GDNF/RET signaling plays a crucial role in the development of the enteric nervous system and the kidney. [3][4][5][6] Germline mutations of the RET gene cause dominant inherited cancer syndromes; multiple endocrine neoplasia (MEN) type 2A and 2B.7-10 MEN 2A is characterized by the development of medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid hyperplasia. MEN 2B shows a more complex phenotype with association of MTC, pheochromocytoma, and developmental abnormalities such as mucosal neuroma, hyperganglionosis of the intestinal tract, and marfanoid skeletal changes. The MEN2A mutations were identified in cysteine residues of the RET extracellular domain, leading to ligand-independent RET dimerization. 11,12 The MEN2B mutations were detected in methionine at codon 918 or in alanine at codon 883 in the tyrosine kinase domain and appear to activate RET without dimerization. 12,13 A variety of si...

BACKGROUND When skeletal metastasis is the presenting problem and the primary site is occult, there is a need to identify the primary site as soon as possible. However, the search for the primary tumor is often time‐consuming and difficult. The purpose of this study was to analyze the efficacy of particular diagnostic approaches and to devise an efficient and optimal diagnostic strategy. METHODS Among 213 patients with skeletal metastasis treated between 1990 and 1996 were 64 in whom skeletal lesions were the first manifestation of malignancy. The authors retrospectively analyzed both the final diagnosis and the process by which it was made in these 64 cases. RESULTS The primary cancer was identified antemortem in 56 (88%) of the 64 patients by examination and in 3 patients at autopsy. Lung carcinoma, the most frequently observed primary lesion, was identified in 23 patients. Other primary lesions were prostate carcinoma in 11 patients, breast carcinoma in 5, and hepatocellular carcinoma in 5. The primary malignancy was not determined in 5 patients. Thoracic and abdominal computed tomography (CT) scans were useful, especially in the diagnosis of patients with lung, hepatocellular, renal cell, and pancreatic carcinomas. Tumor markers were abnormally elevated in 73% of patients with carcinomas. CONCLUSIONS Although thoracic and abdominal CT scans were useful, examination of the gastrointestinal tract and pelvic CT scan seldom revealed the primary lesion and therefore should not be performed as an initial routine study in the absence of abdominal symptoms. Tumor markers are useful in differentiating carcinoma from hematologic malignancy and primary bone tumor. Cancer 1999;86:533–7. © 1999 American Cancer Society.