R Maki

..Based on evidence of activity in preclinical and Phase I studies, the authors undertook a study of bortezomib, a reversible proteasome inhibitor, for patients with metastatic sarcomas...

..Examination of this novel approach using multiple dose levels is 1 approach to further investigate the immunogenicity and clinical utility of HSPPC-96 vaccination in this setting...

..To determine if the addition of docetaxel to gemcitabine improved clinical outcome of patients with metastatic soft tissue sarcomas, we compared a fixed dose rate infusion of gemcitabine versus a lower dose of gemcitabine with docetaxel...

..Imatinib may be useful for patients with locally advanced DFSP, when other options for local therapy are limited...

..Given the low response rate to docetaxel as a single agent, it is likely that there is true clinical synergy of the combination. Disclosure of potential conflicts of interest is found at the end of this article...

..The management of some of these rare tumors is discussed herein, including osteogenic sarcoma, Ewing sarcoma, and rhabdomyosarcoma...

..The data regarding the initial evidence of immune responses against sarcomas are reviewed in the context of current or potential clinical studies...

....

..To discuss advances in immunotherapy as pertaining to systemic therapy for sarcomas...

..Greater success with these agents clinically is expected when combining the agents with inhibitors of other cell signaling pathways in which cross-resistance has been observed...

..It is hoped that the intersection of cellular immunology and sarcoma molecular biology will lead to new modalities of therapy for this group of patients with this heterogeneous group of diseases...

..Given the lack of new agents for sarcoma therapy since the development of ifosfamide, these studies give hope that the term "effective systemic therapy for sarcoma" might become a reality...

..Further evaluation of sorafenib in these and possibly other sarcoma subtypes appears warranted, presumably in combination with cytotoxic or kinase-specific agents...

....

..The distinct gene expression profile suggests avenues for investigation of pathogenesis and potential therapeutic strategies...

..Our goal was to investigate the spectrum of pathologic response and molecular alterations in a group of GIST patients, clinically defined as having imatinib-stable/imatinib-responsive lesions, who underwent surgical resection...

....

..It also represents a novel mechanism of oncogenic transcription factor activation...

..The clinical benefit of sunitinib is genotype-dependent in regards to both primary and secondary mutations, with GIST patients harboring the KIT(AY502-3ins) exon 9 mutation being the most sensitive...

..A secondary V600E BRAF mutation could represent an alternative mechanism of imatinib resistance. Kinase inhibitors targeting BRAF may be effective therapeutic options in this molecular GIST subset...

..The pathology of GIST, surgical options for primary and metastatic disease, and findings leading to the use of imatinib and sunitinib for GIST are highlighted in this review...

..Pulmonary metastatectomy improved survival in selected patients. LEVEL OF EVIDENCE: Therapeutic study, Level III-1 (retrospective cohort study). See the Guidelines for Authors for a complete description of levels of evidence...

..We performed a phase I study of 5-fluorouracil (5-FU), cisplatin and irinotecan...

..Treatment with IF should be considered in patients with high-risk primary extremity liposarcoma...

..Treatment of metastatic GIST with imatinib mesylate results in a 2-year survival of approximately 72%. The outcome of patients with metastatic GIST not treated with tyrosine kinase inhibitors is not well defined...

..8 months for sites below the clavicle. DISCUSSION: Angiosarcoma is an aggressive malignancy characterized by biologic heterogeneity at different anatomic sites and relative sensitivity to paclitaxel and doxorubicin...

..We designed a phase I clinical trial of FU in combination with UCN-01...

..Preliminary correlations between the site of mutation and the clinical phenotype have been proposed, but the strength of these associations is not defined...

..Although the efficacy of tyrosine kinase inhibitors in metastatic GIST depends on tumor mutation status, there have been conflicting reports on the prognostic importance of KIT mutation in primary GIST...

..We observed that hypophosphatemia developed in some patients with either chronic myelogenous leukemia or gastrointestinal stromal tumors who were receiving imatinib...

..To evaluate the antitumor activity and tolerability of bevacizumab and doxorubicin in patients with metastatic soft-tissue sarcoma (STS)...

..We postulated that adjuvant treatment with imatinib would improve recurrence-free survival compared with placebo after resection of localised, primary gastrointestinal stromal tumour...

....

..To the authors' knowledge, few studies to date have examined the effect of chemotherapy in patients undergoing pulmonary resection for metastatic STS of the extremity...

..These data provide a basis for the activity of vascular endothelial growth factor receptor-directed therapy in the treatment of primary and radiation-induced AS...

..We tested the hypothesis that the gene expression profile in GISTs might be related to KIT genotype and possibly to other clinicopathological factors...

..Nearly all tumors have an activating mutation in the KIT or, less often, PDGFRalpha, gene. Therapy with tyrosine kinase inhibitors benefits over 80% of patients with advanced GIST, but most patients eventually develop drug resistance...

..This malignant tumor created numerous management dilemmas and therapeutic challenges related to the unstable airway and the need for tracheal stenting to bypass the airway obstruction...

..That acquired resistance to imatinib in GIST commonly occurs via secondary gene mutation in the KIT kinase domain has implications for strategies to delay or prevent imatinib resistance and to employ newer targeted therapies...

..We examine clinicopathologic factors associated with disease-free survival (DFS) in patients with primary and recurrent DFSP and evaluate responses to multimodality therapy...

..Finally, the ways in which these advances in basic science are translating into and redefining clinical practice are highlighted...

..We found a high prevalence of CK abnormalities in this group and believe that CKs should be monitored during therapy with imatinib...

..The patterns of failure and mechanisms of sarcoma-specific death are poorly characterized among the minority of patients with low-grade soft tissue sarcoma (STS) who succumb to disease...

..CONCLUSIONS: ET-743 was found to be well tolerated in heavily pretreated osteosarcoma patients but had limited antitumor activity as a single agent. The combination of ET-743 with cisplatin or doxorubicin should be considered...

..To the authors' knowledge, there are limited data examining chemotherapy outcomes as a guide to therapeutic decisions for unresectable disease...

..In the current study, the authors examined the outcomes of patients with desmoid tumors who received systemic therapy at a single institution to provide a basis for the examination of newer agents...

..In conclusion, we showed gene expression profiling to be useful in classification and diagnosis, providing insights into pathogenesis and pointing to potential new therapeutic targets of soft tissue sarcoma...

..In this review, we examine target selection for specific sarcoma subtypes, and demonstrate with a few examples new techniques being used to delineate novel therapeutic inroads for patients with sarcoma...

..Our results indicate that a degree of developmental maturity can be quantitatively assigned to solid tumors, supporting the notion that transformation of a solid tumor stem cell can occur at distinct stages of maturation...

..In this review, we will highlight the diverse effect of Wnt signaling on three types of tissue stem cells and their corresponding malignancies...

..Our results confirm LOI in several tumours expressing high levels of IGF2, which may explain the observed paraneoplastic hypoglycaemia...

..Our results provide mechanistic insights regarding the cell of origin of MFH, establish what we believe is a novel tumor suppressor role for Wnt signaling, and identify a potential therapeutic differentiation strategy for sarcomas...

..CT of the chest, abdomen and pelvis was negative for metastatic disease. At this point the patient was referred to a specialist oncology center for further management...

..To identify prognostic factors related to outcome in 255 patients with synovial sarcoma and to construct a preoperative nomogram to predict the risk of disease-specific death...

....

..These results suggest that caution should be used in the interpretation of randomized clinical trials of adjuvant chemotherapy that seem to demonstrate clinical benefits with relatively short-term follow-up...

..Optimizing dosing strategies to further enhance the therapeutic index of ET-743 may depend upon obtaining a better understanding of the metabolic fate of the drug in humans...

....

....

..As such, a complete accounting of potential risks and benefits is appropriate when discussing adjuvant chemotherapy with patients who have stage III disease...

..Research in stem-cell biology and nanotechnology holds promise for additional novel treatment options in the future...

..To determine if ifosfamide-based chemotherapy (IF) offers a survival benefit to adult patients with primary extremity synovial sarcoma...