Relevance of Reference Centers in Sarcoma Care and Quality Item Evaluation: Results from the Prospective Registry of the Spanish Group for Research in Sarcoma (GEIS).

BACKGROUND: Reference centers (RCs) are a key point for improving the survival of patients with soft-tissue sarcomas (STS). The aim of this study was to evaluate selected items in the management of patients with STS, comparing results between RC and local hospitals (LHs). MATERIALS AND METHODS: Diagnostic and therapeutic data from patients diagnosed between January 2004 and December 2011 were collected. Correlation with outcome was performed. RESULTS: A total of 622 sarcomas were analyzed, with a median follow-up of 40 months. Imaging of primary tumor preoperatively (yes vs. no) correlated with a higher probability of free surgical margins (77.4% versus 53.7%; p = .006). The provenance of the biopsy (RC vs. LH) significantly affected relapse-free survival (RFS; 3-year RFS 66% vs. 46%, respectively; p = .019). Likewise, 3-year RFS was significantly worse in cases with infiltrated (55.6%) or unknown (43.4%) microscopic surgical margins compared with free margins (63.6%; p < .001). Patients managed by RCs had a better 3-year overall survival compared with those managed by LHs (82% vs. 70.4%, respectively; p = .003). Perioperative chemotherapy in high-risk STS, more frequently administered in RCs than in LHs, resulted in significantly better 3-year RFS (66% vs. 44%; p = .011). In addition, patients with stage IV disease treated in RCs survived significantly longer compared with those in LHs (30.4 months vs. 18.5 months; p = .036). CONCLUSION: Our series indicate that selected quality-of-care items were accomplished better by RCs over LHs, all with significant prognostic value in patients with STS. Early referral to an RC should be mandatory if the aim is to improve the survival of patients with STS. IMPLICATIONS FOR PRACTICE: This prospective study in patients diagnosed with soft-tissue sarcoma shows the prognostic impact of reference centers in the management of these patients. The magnitude of this impact encompasses all steps of the process, from the initial management (performing diagnostic biopsy) to the advanced disease setting. This is the first prospective evidence showing improvement in outcomes of patients with metastatic disease when they are managed in centers with expertise. This study provides extra data supporting referral of patients with sarcoma to reference centers.

The Impact of Expert Pathology Review and Molecular Diagnostics on the Management of Sarcoma Patients: A Prospective Study of the Hellenic Group of Sarcomas and Rare Cancers.

Precise classification of sarcomas is crucial to optimal clinical management. In this prospective, multicenter, observational study within the Hellenic Group of Sarcoma and Rare Cancers (HGSRC), we assessed the effect of expert pathology review, coupled with the application of molecular diagnostics, on the diagnosis and management of sarcoma patients. Newly diagnosed sarcoma patients were addressed by their physicians to one of the two sarcoma pathologists of HGSRC for histopathological diagnostic assessment. RNA next-generation sequencing was performed on all samples using a platform targeting 86 sarcoma gene fusions. Additional molecular methods were performed in the opinion of the expert pathologist. Therefore, the expert pathologist provided a final diagnosis based on the histopathological findings and, when necessary, molecular tests. In total, 128 specimens from 122 patients were assessed. Among the 119 cases in which there was a preliminary diagnosis by a non-sarcoma pathologist, there were 37 modifications in diagnosis (31.1%) by the sarcoma pathologist, resulting in 17 (14.2%) modifications in management. Among the 110 cases in which molecular tests were performed, there were 29 modifications in diagnosis (26.4%) through the genomic results, resulting in 12 (10.9%) modifications in management. Our study confirms that expert pathology review is of utmost importance for optimal sarcoma diagnosis and management and should be assisted by molecular methods in selected cases.

The Sarcoma Immune Landscape: Emerging Challenges, Prognostic Significance and Prospective Impact for Immunotherapy Approaches.

Despite significant advances in multidisciplinary treatment strategies including surgery, radiotherapy, targeted therapy and chemotherapy there are yet no substantial improvements in the clinical benefit of patients with sarcomas. Current understanding of the underlying cellular and molecular pathways which govern the dynamic interactions between the tumor stroma, tumor cells and immune infiltrates in sarcoma tissues, led to the clinical development of new therapeutic options based on immunotherapies. Moreover, progress of the treatment of sarcomas also depends on the identification of biomarkers with prognostic and predictive values for selecting patients most likely to benefit from these new therapeutic treatments and also serving as potent therapeutic targets. Novel combinations with radiotherapy, chemotherapy, targeted therapy, vaccines, CAR-T cells and treatments targeting other immune components of the tumor microenvironment are underway aiming to bypass known resistance mechanisms. This review focuses on the role of tumor microenvironment in sarcoma, prognosis and response to novel immunotherapies.

Chemotherapy and targeted treatments of breast sarcoma by histologic subtype.

Introduction: Breast sarcomas (BS) are uncommon and often present both diagnostic and therapeutic challenges. Historically, radical surgery has been the mainstay of treatment for localized breast sarcomas. On the other hand, in advanced disease, since they are a heterogeneous group of neoplasms consisting of several different subtypes including angiosarcoma, phyllodes tumor, and pleomorphic undifferentiated sarcoma, there is a lack of proven specific therapy. As a result, their treatment is based on the soft tissue sarcoma (STS) paradigm, whereas histotype-tailored approaches apply to specific subtypes like dermatofibrosarcoma protuberans. To date, advanced stages constitute an incurable form of disease and chemotherapy remains the cornerstone of treatment with the aim of palliation of symptoms and increase in survival.Areas covered: In this manuscript, we review the clinicopathologic characteristics of the most common subtypes of BS, as well as the current treatment landscape of BS, with a particular focus on opportunities and challenges provided by new targeted molecules and immunotherapy.Expert opinion: The treatment approach of advanced BS is based on the pathologic subtype. A true breakthrough has still to be obtained, as the development of new agents in BS suffers from the same weaknesses as in other STS.

Primary Sarcoma of the Lung - Prognostic Value of Clinicopathological Characteristics of 26 Cases.

BACKGROUND/AIM: Primary sarcomas of the lung (PSL) represent a rare, largely unknown entity. We herein present a retrospective study of 26 patients diagnosed with PSL. PATIENTS AND METHODS: For a period of 10 years, the records of patients from 5 centers were gathered and analyzed. RESULTS: Median age at diagnosis was 61.96 years (range=31-75 years). Eight patients (33.33%) had mediastinal node invasion (MNI). From 17 patients (70.83%) with localized disease, 11 patients (64.70%) underwent surgery. Recurrence rate was 72.72%. Median disease-free interval was 15 months. The median overall survival (OS) of patients with metastatic disease was 4 months and 10 months for the whole population. Only surgery had an impact on survival. CONCLUSION: Prognosis of PSL is somber. The high proportion of patients with MNI at diagnosis may serve as an indication for surgical evaluation of mediastinum and raises the question whether patients with locoregional PSL should be treated with a more aggressive approach.

Soft tissue sarcomas of the upper extremities: Maximizing treatment opportunities and outcomes.

Soft tissue sarcomas (STS) are rare tumors; they do not even equate to 1% of all malignant tumor cases. One-fifth of all STS occur in the upper extremities, where epithelioid sarcoma, synovial sarcoma, clear cell sarcoma and malignant fibrohistiocytoma are the most frequent subtypes. Surgical resection is the cornerstone of treatment. However, accomplishment of optimal oncological and functional results of STS of the upper extremities may represent a challenge for hand surgeons, due to the complex anatomy. In several cases, preoperative therapies are needed to facilitate tumor resection and improve the oncological outcome. Oligometastatic disease may also be a challenging scenario as curative strategies can be applied. Radiotherapy and chemotherapy are commonly used for this purpose albeit with conflicting evidence. Novel drug combinations have also been approved in the metastatic setting, further improving the quality of life and survival of eligible patients. Thus, prior to any approach, every case should be individually discussed in sarcoma centers with specialized multidisciplinary tumor boards. The aim of the present review was to gather the multidisciplinary experiences of the available therapeutic strategies for STS of the upper extremities.

Pericardial Synovial Sarcoma: Case Report, Literature Review and Pooled Analysis.

BACKGROUND: Pericardial synovial sarcomas (PSS) are very rare tumors, with dismal prognosis and limited data. We describe the clinical features and identify prognostic factors of primary PSS. CASE REPORT: We describe the case of a 56-year-old male patient with PSS managed by the multidisciplinary team of thoracic oncology. The therapeutic plan comprised surgery, chemotherapy, stereotactic radiosurgery and targeted therapy, with excellent results. MATERIALS AND METHODS: Data from 37 cases reported in English during the past 20 years were gathered and analyzed. PSS was found to occur at a mean age of 36±17.082 (range=13-67) years. Survival analysis was performed on 20 cases with follow-up of at least 6 months. CONCLUSION: Only complete resection of the tumor seems to be an independent prognostic factor. To our knowledge, this is the first report on the safety and effectivity of pazopanib in PSS and may provide guidance for similar cases in the future.