Background: Patients with advanced solitary fibrous tumors (SFTs) have a poor prognosis; treatment options for recurrent disease are particularly limited. Several novel targeted agents have recently shown promise against advanced SFTs, but the relative efficacy of new agents is difficult to assess because data on the efficacy of conventional chemotherapy for SFTs are limited. We thus sought to estimate the efficacy of conventional chemotherapy for SFTs by reviewing data on tumor response to therapy and progression-free survival from SFT patients who received this therapy. Methods: We retrospectively analyzed the clinical outcomes of 21 patients with grossly measurable, advanced SFTs (unresectable metastatic disease or potentially resectable primary tumors) who received conventional chemotherapy and follow-up at The University of Texas MD Anderson Cancer Center between January 1994 and June 2007. Best tumor response to therapy was assessed using the Response Evaluation Criteria In Solid Tumors 1.1. The Kaplan-Meier method was used to estimate median progression-free survival (PFS) duration. Results: Of 21 patients, 4 received more than 1 regimen of chemotherapy, for a total of 25 treatments. Doxorubicin-based chemotherapy was given in 15 cases (60%), gemcitabine-based therapy in 5 cases (20%), and paclitaxel in 5 cases (20%). First-line chemotherapy was delivered in 18 cases (72%). No patients had a complete or partial response, 16 (89%) had stable disease, and 2 (11%) had disease progression. Five patients (28%) maintained stable disease for at least 6 months after first-line treatment. The median PFS duration was 4.6 months. The median overall survival from diagnosis was 10.3 years. Conclusion: Conventional chemotherapy is effective in controlling or stabilizing locally advanced and metastatic SFTs. Our findings can serve as a reference for tumor response and clinical outcomes in the assessment of novel treatments for SFTs.

Oncologic patients who are extreme responders to molecularly targeted therapy provide an important opportunity to better understand the biologic basis of response and, in turn, inform clinical decision making. Malignant neoplasms with an uncertain histologic and immunohistochemical characterization present challenges both on initial diagnostic workups and then later in management, as current treatment algorithms are based on a morphologic diagnosis. Herein, we report a case of a difficult to characterize sarcoma-like lesion for which genomic profiling with clinical next generation sequencing (NGS) identified the molecular underpinnings of arrested progression(stable disease) under combination targeted therapy within a phase I clinical trial.

Background: Myxoid liposarcoma (MLS) is a soft tissue sarcoma with adipocytic differentiation characterized by a unique chromosome rearrangement, t(12;16)(q13;p11). The exact efficacy of chemotherapy in MLS has not been clearly established. Patients and methods: We retrospectively analyzed the records of 37 histologically confirmed MLS patients who were treated at the University of Texas MD Anderson Cancer Center from January 2000 to December 2009 with doxorubicin 75-90 mg/m² over 72 hours combined with ifosfamide 10 gm/m² in the first-line setting. Response was assessed using RECIST and Choi criteria. The Kaplan-Meier method and log-rank test was used to estimate clinical outcomes. Results: The median follow-up period was 50.1 months. The overall response rates were 43.2% using RECIST and 86.5% using the Choi criteria. The 5-year disease-free survival rate was 90% for patients with resectable tumors. Median time to progression and overall survival time for the advanced-disease group were 23 and 31.1 months, respectively. Conclusion: Our study demonstrates that doxorubicin-ifosfamide combination therapy has a role in the treatment of MLS. The Choi criteria may be more sensitive in evaluating response to chemotherapy in MLS.

Background. The prognosis and clinical characteristics of head and neck synovial sarcomas (HNSS) are unclear. Herein, we present an update using a cohort of patients treated at our institution.Methods. We performed a retrospective chart review of 44 patients diagnosed with primary HNSS between March 1990 and June 2012. Overall survival (OS) and progression-free survival (PFS) curves were estimated and hazard ratios (HRs) were calculated.Results. The entire cohort’s median PFS was 4.6 years, and 20 of the 44 (45%) patients developed either local or distant recurrence. Tumor size ≥ 5 cm (p=0.008, HR = 4.69; 95% CI = 1.34–16.38) and a primary presentation in the soft tissues of the neck (p=0.04, HR = 2.41; 95% CI = 1.003–5.82) were associated with significantly worse PFS. The OS and PFS of patients who received definitive local therapy versus those who received additional adjuvant systemic therapy did not differ significantly.Conclusion. Despite the treatment challenges associated with HNSS, our cohort of patients had a better prognosis than one might expect in this unfavorable anatomical location. Our findings suggest that tumor size and site are predictive of PFS and that wide surgical excision is of vital importance, since traditional cytotoxic chemotherapy has limited efficacy at this site.

Background. Synovial sarcoma can present morphologically in multiple forms, including biphasic and monophasic subtypes. As a result, the histological diagnosis can sometimes be challenging. Transducin-Like Enhancer 1 (TLE1) is a transcriptional corepressor that normally is involved in embryogenesis and hematopoiesis but is also expressed in certain tumors. This systematic review examines the potential role of TLE1 as a diagnostic biomarker for the synovial sarcoma. Materials and Methods. A literature review and meta-analysis were conducted using the electronic databases Pubmed, the Cochrane Library, and Google Scholar. Thirteen studies met our eligibility criteria and were selected for in-depth analysis. Results. The mean sensitivity and specificity of TLE1 in detecting synovial sarcoma were 94% (95% CI 91%–97%) and 81% (95% CI 72%–91%), respectively, when all studies were aggregated together. The mean positive predictive value (PPV) of TLE1 was 75% (95% CI 62%–87%), whereas the negative predictive value (NPV) was 96% (95% CI 93%–98%). Conclusion. TLE1 is a sensitive and specific marker for synovial sarcoma that can aid in its diagnosis. Due to its involvement in several relevant signaling pathways, TLE1 might have direct relevance to the pathophysiology of the disease.

Background : Ten to fourteen percent of Ewing sarcoma (ES) study participants treated nationwide with IGF-1 receptor (IGF-1R)-targeted antibodies achieved tumor regression. Despite this success, low response rates and short response durations (approximately 7-weeks) have slowed the development of this therapy. Methods: We performed a meta-analysis of five phase-1b/2 ES-oriented trials that evaluated the anticancer activity of IGF-1R antibodies +/− mTOR inhibitors (mTORi). Our meta-analysis provided a head-to-head comparison of the clinical benefits of IGF-1R antibodies vs. the IGF-1R/mTOR-targeted combination. Available pretreatment clinical samples were semi-quantitatively scored using immunohistochemistry to detect proteins in the IGF-1R/PI3K/AKT/mTOR pathway linked to clinical response. Early PET/CT imaging, obtained within the first 2 weeks (median 10 days), were examined to determine if reduced FDG avidity was predictive of progression-free survival (PFS). Results: Among 56 ES patients treated at MD Anderson Cancer Center (MDACC) with IGF-1R antibodies, our analysis revealed a significant ~two-fold improvement in PFS that favored a combination of IGF-1R/mTORi therapy (1.6 vs. 3.3-months, p = 0.042). Low pIGF-1R in the pretreatment specimens was associated with treatment response. Reduced total-lesion glycolysis more accurately predicted the IGF-1R response than other previously reported radiological biomarkers. Conclusion: Synergistic drug combinations, and newly identified proteomic or radiological biomarkers of IGF-1R response, may be incorporated into future IGF-1R-related trials to improve the response rate in ES patients.