Periosteal Ewing Sarcoma with Distant Metastases: Report of Two Patients and Review of the Literature.

Periosteal Ewing sarcoma (ES) is an exceedingly rare topographic subtype of the ES. To our knowledge, only 60 patients have been reported in the medical English language literature. It predominantly affects men in the second decade of life and arises in the long tubular bone diaphysis. PES rarely develops distant metastases. We report two patients of this rare ES location that were found on the distal tibial shaft and proximal femoral diaphysis of a 21-year-old man and an 8-year-old boy, respectively. Both patients were treated with neoadjuvant chemotherapy, wide resection, and adjuvant chemotherapy. One of our patients had lung metastases at the time of diagnosis and died 5 years later. The other patient presented intramedullary humeral bone metastasis 19 years after diagnosis. There has been no evidence of disease in the 26 years of follow-up. Close follow-up of periosteal ES is recommended because distant metastases may exceptionally occur, even several years after diagnosis.

Economic evaluation of percutaneous cryoablation vs conventional surgery in extra-abdominal desmoid tumours in the Spanish healthcare system.

BACKGROUND: Desmoid tumours (DTs) or deep fibromatosis are benign soft-tissue tumours, sometimes locally aggressive, requiring intervention on some cases. Surgery has been the gold standard, but new less invasive techniques such as percutaneous cryoablation have proved their effectiveness, reducing health resources and complications. The study aimed to compare the total cost of percutaneous cryoablation and conventional surgery for patients with extra-abdominal and/or abdominal wall DTs, candidates for local ablative treatment in Spain. METHODS: A cost-analysis model was developed. An expert panel provided data about resource consumption for the percutaneous cryoablation technique and validated the epidemiology used for target population estimation. Unitary resources cost (€ 2022) derived from local cost databases. A retrospective analysis of 54 surgical cases in 3 Spanish hospitals was performed to estimate the cost of conventional surgery based on the cost of the Diagnosis-Related group (DRG) codes identified on this patient sample, weighted by each DRG proportion. The total cost for each alternative included intervention cost and complications cost, considering debridement required in 4.5% of cases with percutaneous cryoablation and minor surgery for surgical site infection in 18.0% for conventional surgery. RESULTS: The total cost for percutaneous cryoablation (€ 5774.78/patient-year) was lower than the total cost for conventional surgery (€ 6780.98/patient-year), yielding cost savings up to € 80,002 in 1 year for the entire cohort of 80 patients with DTs eligible for intervention estimated in Spain. One-way sensitivity analyses confirmed the results' robustness. CONCLUSION: Percutaneous cryoablation versus conventional surgery would yield cost savings for the management of DT patients in Spain. CRITICAL RELEVANCE STATEMENT: This manuscript provides insight into the economic impact derived from the savings related to the use of percutaneous cryoablation for desmoid-type tumours from the perspective of the Spanish National Healthcare System, providing useful information for the health decision-making process. KEY POINTS: • Desmoid tumours are locally aggressive and may require local therapy. • Percutaneous cryoablation procedure is less invasive than the conventional surgery. • Cost comparison shows savings associated to percutaneous cryoablation use.

Soft Tissue Aneurysmal Bone Cyst in the Sartorius Muscle of a 13-Year-Old Boy Mimicking Myositis Ossificans: Case Report.

INTRODUCTION: A soft tissue aneurysmal bone cyst is an extremely rare tumor. The objective of the article is to present the clinical, radiological, and histopathological features of a very unusual neoplasm of soft tissues. CASE REPORT: A 13-year-old male patient presented a painful, mobile, and rapidly growing mass on the posteromedial aspect of his left knee. Imaging studies revealed a mass that arose from the medial surface of the distal sartorius muscle, with extension to the subcutaneous fat tissue. It was a well-circumscribed solid tumor with a peripheral rim calcification on plain film, computerized tomography, and ultrasound (zonal phenomenon). On magnetic resonance imaging, a heterogenous mass on T1-weighted images (WI) and T2-WI was seen, with a peripheral hypointense rim in both sequences. An outstanding edema on T2-WI extending to the soft tissue and muscles of the medial compartment of the knee was detected. The mass was resected, and the "tumoral mimickers" histopathological and molecular (next-generation sequencing) diagnoses confirmed a soft tissue aneurysmal bone cyst. A follow-up showed that the patient was free of disease 12 months after surgery. CONCLUSION: Soft tissue aneurysmal bone cyst is a rare tumor. Appropriate clinical and radiological correlation should be performed to differentiate it from other tumor mimickers.

Peripheral Inflammatory Indexes Neutrophil/Lymphocyte Ratio (NLR) and Red Cell Distribution Width (RDW) as Prognostic Biomarkers in Advanced Solitary Fibrous Tumour (SFT) Treated with Pazopanib.

Pazopanib was assessed prospectively in the GEIS-32 phase II study (NCT02066285) on advanced solitary fibrous tumour (SFT), resulting in a longer progression-free survival (PFS) and overall survival (OS) compared with historical controls treated with chemotherapy. A retrospective analysis of peripheral inflammatory indexes in patients enrolled into GEIS-32 was performed to evaluate their prognostic and predictive value. Patients received pazopanib 800 mg/day as the first antiangiogenic line. The impacts of baseline neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and red cell distribution width (RDW) on PFS, OS, and Choi response were evaluated by univariate and multivariate analysis. Metastasis-free interval (MFI), mitotic count, and ECOG were also included as potential prognostic factors. Sixty-seven SFT patients, enrolled in this study, showed a median age of 63 years and a female/male distribution of 57/43. The median follow-up from treatment initiation was 16.8 months. High baseline NLR, PLR, and standardised RDW were significantly associated with worse PFS and OS. NLR, RDW, MFI, and mitotic count were independent variables for PFS, while RDW and ECOG were independent for OS. Further, NLR and mitotic count were independent factors for Choi response. High baseline NLR and RDW values were independent prognostic biomarkers for worse outcome in advanced SFT patients treated with pazopanib.

Eribulin activity in soft tissue sarcoma monolayer and three-dimensional cell line models: could the combination with other drugs improve its antitumoral effect?

BACKGROUND: Eribulin has shown antitumour activity in some soft tissue sarcomas (STSs), but it has only been approved for advanced liposarcoma (LPS). METHODS: In this study, we evaluated the effect of eribulin on proliferation, migration and invasion capabilities in LPS, leiomyosarcoma (LMS) and fibrosarcoma (FS) models, using both monolayer (2D) and three-dimensional (3D) spheroid cell cultures. Additionally, we explored combinations of eribulin with other drugs commonly used in the treatment of STS with the aim of increasing its antitumour activity. RESULTS: Eribulin showed activity inhibiting proliferation, 2D and 3D migration and invasion in most of the cell line models. Furthermore, we provide data that suggest, for the first time, a synergistic effect with ifosfamide in all models, and with pazopanib in LMS as well as in myxoid and pleomorphic LPS. CONCLUSIONS: Our results support the effect of eribulin on LPS, LMS and FS cell line models. The combination of eribulin with ifosfamide or pazopanib has shown in vitro synergy, which warrants further clinical research.

Uncommon and peculiar soft tissue sarcomas: Multidisciplinary review and practical recommendations. Spanish Group for Sarcoma research (GEIS -GROUP). Part II.

Among all Soft Tissue sarcomas there are some subtypes with low incidence and/or peculiar clinical behaviour, that need to be consider separately. Most of them are orphan diseases, whose biological characteristics imply a clearly different diagnostic and therapeutic approach from other more common sarcoma tumors. We present a brief and updated multidiciplinary review, focused on practical issues, aimed at helping clinicians in decision making. In this second part we review these subtypes: Alveolar Soft Part Sarcoma, Epithelioid Sarcoma, Clear Cell Sarcoma, Desmoplastic Small Round Cell Tumor, Rhabdoid Tumor, Phyllodes Tumor, Tenosynovial Giant Cell Tumors, Myoepithelial Tumor, Perivascular Epithelioid Cell Neoplasms (PEComas), Extraskeletal Myxoid Chondrosarcoma, NTRK-fusions Sarcomas. Most of them present their own radiological and histopathological feautures, that are essential to know in order to achieve early diagnosis. In some of them, molecular diagnosis is mandatory, not only in the diagnosis, but also to plan the treatment. On the other hand, and despite the low incidence, a great scientific research effort has been made to achieve new treatment opportunities for these patients even with approved indications. These include new treatments with targeted therapies and immunotherapy, which today represent possible therapeutic options. It is especially important to be attentive to new and potential avenues of research, and to promote the conduct of specific clinical trials for rare sarcomas.

Pazopanib for treatment of typical solitary fibrous tumours: a multicentre, single-arm, phase 2 trial.

BACKGROUND: Solitary fibrous tumour is an ultra-rare sarcoma, which encompasses different clinicopathological subgroups. The dedifferentiated subgroup shows an aggressive course with resistance to pazopanib, whereas in the malignant subgroup, pazopanib shows higher activity than in previous studies with chemotherapy. We designed a trial to test pazopanib activity in two different cohorts of solitary fibrous tumour: the malignant-dedifferentiated cohort, which was previously published, and the typical cohort, which is presented here. METHODS: In this single-arm, phase 2 trial, adult patients (aged ≥18 years) diagnosed with confirmed metastatic or unresectable typical solitary fibrous tumour of any location, who had progressed in the previous 6 months (by Choi criteria or Response Evaluation Criteria in Solid Tumors [RECIST]) and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 were enrolled at 11 tertiary hospitals in Italy, France, and Spain. Patients received pazopanib 800 mg once daily, taken orally, until progression, unacceptable toxicity, withdrawal of consent, non-compliance, or a delay in pazopanib administration of longer than 3 weeks. The primary endpoint was proportion of patients achieving an overall response measured by Choi criteria in patients who received at least 1 month of treatment with at least one radiological assessment. All patients who received at least one dose of the study drug were included in the safety analyses. This study is registered in ClinicalTrials.gov, NCT02066285, and with the European Clinical Trials Database, EudraCT 2013-005456-15. FINDINGS: From June 26, 2014, to Dec 13, 2018, of 40 patients who were assessed, 34 patients were enrolled and 31 patients were included in the response analysis. Median follow-up was 18 months (IQR 14-34), and 18 (58%) of 31 patients had a partial response, 12 (39%) had stable disease, and one (3%) showed progressive disease according to Choi criteria and central review. The proportion of overall response based on Choi criteria was 58% (95% CI 34-69). There were no deaths caused by toxicity, and the most frequent adverse events were diarrhoea (18 [53%] of 34 patients), fatigue (17 [50%]), and hypertension (17 [50%]). INTERPRETATION: To our knowledge, this is the first prospective trial of pazopanib for advanced typical solitary fibrous tumour. The manageable toxicity and activity shown by pazopanib in this cohort suggest that this drug could be considered as first-line treatment for advanced typical solitary fibrous tumour. FUNDING: Spanish Group for Research on Sarcomas (GEIS), Italian Sarcoma Group (ISG), French Sarcoma Group (FSG), GlaxoSmithKline, and Novartis.

Magnetic resonance imaging assessment in patients with axial spondyloarthritis: development of checklists for use in clinical practice.

The objective of our study was to standardize magnetic resonance imaging (MRI) assessment of spine and sacroiliac joints in patients with axial spondyloarthritis (axSpA) and/or inflammatory spinal pain, by creating checklists and templates based on the opinions of rheumatologists and radiologists. A scientific committee developed a series of questionnaires with multiple items regarding MRI in patients with axial inflammatory pain and/or axSpA. Then an expert panel of rheumatologists and radiologists rated all items in a 9-point Likert scale. Finally, the scientific committee and the expert panel met to create the definitive documents. Several definitive checklists and templates were generated for rheumatologist-requested MRI and for radiologist-requested MRI reports of sacroiliac joint and spinal examinations. A technical requirement protocol was also agreed on. Our results could be useful in increasing understanding between rheumatologists and radiologists regarding MRI in axSpA diagnosis and follow-up.

Pazopanib for treatment of advanced extraskeletal myxoid chondrosarcoma: a multicentre, single-arm, phase 2 trial.

BACKGROUND: Extraskeletal myxoid chondrosarcoma is a rare sarcoma with low sensitivity to cytotoxic chemotherapy. Retrospective evidence suggests that antiangiogenic drugs could be a treatment option. We aimed to investigate the activity of pazopanib, an antiangiogenic drug, in patients with advanced extraskeletal myxoid chondrosarcoma. METHODS: In this single-arm, open-label phase 2 trial, three parallel independent cohorts of different histotypes of advanced sarcomas were recruited (extraskeletal myxoid chondrosarcoma, typical solitary fibrous tumour, and malignant-dedifferentiated solitary fibrous tumour). In each cohort, patients received pazopanib. In this Article, we report the results of the cohort of patients with advanced extraskeletal myxoid chondrosarcoma. Separate reporting of the three cohorts was prespecified in the study protocol. In this cohort, adult patients (aged ≥18 years) with a diagnosis of NR4A3-translocated, metastatic, or unresectable extraskeletal myxoid chondrosarcoma, who had Response Evaluation Criteria in Solid Tumors (RECIST) progression in the previous 6 months, and had an Eastern Cooperative Oncology Group performance status of 0-2, were enrolled at 11 study sites of the Spanish, Italian, and French sarcoma groups. Patients received oral pazopanib (800 mg/day) continuously, until disease progression, unacceptable toxicity, death, non-compliance, patient refusal, or investigator's decision. The primary endpoint was the proportion of patients achieving an objective response according to RECIST 1·1 in the modified intention-to-treat population (patients who provided consent and had a central molecularly confirmed diagnosis of extraskeletal myxoid chondrosarcoma). The safety analysis included all patients who received at least one dose of pazopanib. This study is registered with ClinicalTrials.gov, number NCT02066285. FINDINGS: Between June 24, 2014, and Jan 17, 2017, 26 patients entered the study and started pazopanib. Of these, 23 met the eligibility criteria for the modified intention-to-treat analysis. Median follow-up was 27 months (IQR 18-30). 22 patients (one patient died before the primary analysis) were evaluable for the primary endpoint: four (18% [95% CI 1-36]) had a RECIST objective response. No deaths or grade 4 adverse events occurred. The most frequent grade 3 adverse events were hypertension (nine [35%] of 26 patients), increased concentration of alanine aminotransferase (six [23%]), and increased aspartate aminotransferase (five [19%]). INTERPRETATION: Pazopanib had clinically meaningful antitumour activity in patients with progressive and advanced extraskeletal myxoid chondrosarcoma, and could be considered a suitable option after failure to respond to first-line anthracycline-based chemotherapy in these patients. FUNDING: Spanish Group for Research on Sarcomas, Italian Sarcoma Group, French Sarcoma Group, GlaxoSmithKline, and Novartis.

Pazopanib for treatment of advanced malignant and dedifferentiated solitary fibrous tumour: a multicentre, single-arm, phase 2 trial.

BACKGROUND: A solitary fibrous tumour is a rare soft-tissue tumour with three clinicopathological variants: typical, malignant, and dedifferentiated. Preclinical experiments and retrospective studies have shown different sensitivities of solitary fibrous tumour to chemotherapy and antiangiogenics. We therefore designed a trial to assess the activity of pazopanib in a cohort of patients with malignant or dedifferentiated solitary fibrous tumour. The clinical and translational results are presented here. METHODS: In this single-arm, phase 2 trial, adult patients (aged ≥ 18 years) with histologically confirmed metastatic or unresectable malignant or dedifferentiated solitary fibrous tumour at any location, who had progressed (by RECIST and Choi criteria) in the previous 6 months and had an ECOG performance status of 0-2, were enrolled at 16 third-level hospitals with expertise in sarcoma care in Spain, Italy, and France. Patients received pazopanib 800 mg once daily, taken orally without food, at least 1 h before or 2 h after a meal, until progression or intolerance. The primary endpoint of the study was overall response measured by Choi criteria in the subset of the intention-to-treat population (patients who received at least 1 month of treatment with at least one radiological assessment). All patients who received at least one dose of the study drug were included in the safety analyses. This study is registered with ClinicalTrials.gov, number NCT02066285, and with the European Clinical Trials Database, EudraCT number 2013-005456-15. FINDINGS: From June 26, 2014, to Nov 24, 2016, of 40 patients assessed, 36 were enrolled (34 with malignant solitary fibrous tumour and two with dedifferentiated solitary fibrous tumour). Median follow-up was 27 months (IQR 16-31). Based on central radiology review, 18 (51%) of 35 evaluable patients had partial responses, nine (26%) had stable disease, and eight (23%) had progressive disease according to Choi criteria. Further enrolment of patients with dedifferentiated solitary fibrous tumour was stopped after detection of early and fast progressions in a planned interim analysis. 51% (95% CI 34-69) of 35 patients achieved an overall response according to Choi criteria. Ten (29%) of 35 patients died. There were no deaths related to adverse events and the most frequent grade 3 or higher adverse events were hypertension (11 [31%] of 36 patients), neutropenia (four [11%]), increased concentrations of alanine aminotransferase (four [11%]), and increased concentrations of bilirubin (three [8%]). INTERPRETATION: To our knowledge, this is the first trial of pazopanib for treatment of malignant solitary fibrous tumour showing activity in this patient group. The manageable toxicity profile and the activity shown by pazopanib suggests that this drug could be an option for systemic treatment of advanced malignant solitary fibrous tumour, and provides a benchmark for future trials. FUNDING: Spanish Group for Research on Sarcomas (GEIS), Italian Sarcoma Group (ISG), French Sarcoma Group (FSG), GlaxoSmithKline, and Novartis.

Malignant bone tumors (other than Ewing's): clinical practice guidelines for diagnosis, treatment and follow-up by Spanish Group for Research on Sarcomas (GEIS).

Primary malignant bone tumors are uncommon and heterogeneous malignancies. This document is a guideline developed by the Spanish Group for Research on Sarcoma with the participation of different specialists involved in the diagnosis and treatment of bone sarcomas. The aim is to provide practical recommendations with the intention of helping in the clinical decision-making process. The diagnosis and treatment of bone tumors requires a multidisciplinary approach, involving as a minimum pathologists, radiologists, surgeons, and radiation and medical oncologists. Early referral to a specialist center could improve patients' survival. The multidisciplinary management of osteosarcoma, chondrosarcoma, chordoma, giant cell tumor of bone and other rare bone tumors is reviewed in this guideline. Ewing's sarcoma will be the focus of a separate guideline because of its specific biological, clinical and therapeutic features. Each statement has been accompanied by the level of evidence and grade of recommendation on the basis of the available data. Surgical excision is the mainstay of treatment of a localized bone tumor, with various techniques available depending on the histologic type, grade and location of the tumor. Chemotherapy plays an important role in some chemosensitive subtypes (such as high-grade osteosarcoma). In other subtypes, historically considered chemoresistant (such as chordoma or giant cell tumor of bone), new targeted therapies have emerged recently, with a very significant efficacy in the case of denosumab. Radiation therapy is usually necessary in the treatment of chordoma and sometimes of other bone tumors.

Experiencia en los campamentos de refugiados saharauis, perspectiva cultural de la salud / Experience in the Saharawi refugee camps, cultural perspective of health

Desde el proyecto de Cooperación Internacional para el Desarrollo "Mejora del nivel de salud de la población saharaui mediante el fortalecimiento de la formación continuada de los profesionales sanitarios y docentes", se realiza una expedición a los campamentos de refugiados saharauis, ramificada en las vertientes sanitaria, académica, institucional y sociosanitaria. Su objetivo principal es promocionar la salud de la población asentada en los campamentos. Como resultado, se obtuvo el cumplimiento del objetivo principal de la expedición, promocionando la salud a partir de la educación. La experiencia permite concluir que la responsabilidad de transmitir y concienciar al conjunto de la población recae, casi de manera exclusiva, al personal sanitario, a las promotoras de salud y al colectivo femenino en general, por lo que es necesario continuar ofreciéndoles apoyo

From the International Development Cooperation project "Improvement of the health of the Sahrawi people by strengthening the continuing education of health professionals and teachers", it made an expedition to the Saharawi refugee camps, branched takes place in the health, academic, institutional and socio aspects. Its main objective is to promote the health of the population is living in the camps. As a result, it compliance with the main objective of the expedition was obtained from promoting health education. The experience lead to the conclusion that the responsibility of transmitting and educate the whole population lies almost exclusively, medical personnel, the promoters of health and the general female population, so it is necessary to continue providing support