Nivolumab and sunitinib in patients with advanced bone sarcomas: A multicenter, single-arm, phase 2 trial.

Background: Herein, we present the results of the phase 2 IMMUNOSARC study (NCT03277924), investigating sunitinib and nivolumab in adult patients with advanced bone sarcomas (BS).

Methods: Progressing patients with a diagnosis of BS were eligible. Treatment was comprised of sunitinib (37.

Exploratory analysis of immunomodulatory factors identifies L1CAM as a prognostic marker in alveolar soft-part sarcoma.

Background: Alveolar soft-part sarcoma (ASPS) is a rare tumor driven by the ASPSCR1-TFE3 fusion protein, with a propensity for metastasis. Prognostic factors remain poorly understood, and traditional chemotherapies are largely ineffective. Recent interest lies in immune checkpoint inhibitors (ICIs), yet predictive biomarkers for treatment response are lacking.

Phase Ib Study for the Combination of Doxorubicin, Dacarbazine, and Nivolumab as the Upfront Treatment in Patients With Advanced Leiomyosarcoma: A Study by the Spanish Sarcoma Group (GEIS).

Purpose: Doxorubicin, alongside a select group of cytotoxic agents, is capable of inducing an adaptive immune response via a well-established peculiar type of tumor cell death called immunogenic cell death (ICD). We hypothesize that combining doxorubicin and dacarbazine with nivolumab may enhance therapeutic efficacy by exerting synergy in the ICD circuit. We hereby present a phase Ib trial with this combination.

Predictive and Dynamic Signature for Antiangiogenics in Combination with a PD1 Inhibitor in Soft-Tissue Sarcoma: Correlative Studies Linked to the IMMUNOSARC Trial.

Purpose: The IMMUNOSARC trial combined an antiangiogenic agent (sunitinib) with a PD1 inhibitor (nivolumab) in advanced sarcomas. Here, we present the first correlative studies of the soft-tissue sarcoma cohort enrolled in this trial.

Experimental Design: Formalin-fixed paraffin-embedded and peripheral blood samples were collected at baseline and week 13.

Shared germline genomic variants in two patients with double primary gastrointestinal stromal tumours (GISTs).

Background: Gastrointestinal stromal tumours (GISTs) are prevalent mesenchymal tumours of the gastrointestinal tract, commonly exhibiting structural variations in and genes. While the mutational profiling of somatic tumours is well described, the genes behind the susceptibility to develop GIST are not yet fully discovered. This study explores the genomic landscape of two primary GIST cases, aiming to identify shared germline pathogenic variants and shed light on potential key players in tumourigenesis.

HMGA1 regulates trabectedin sensitivity in advanced soft-tissue sarcoma (STS): A Spanish Group for Research on Sarcomas (GEIS) study.

HMGA1 is a structural epigenetic chromatin factor that has been associated with tumor progression and drug resistance. Here, we reported the prognostic/predictive value of HMGA1 for trabectedin in advanced soft-tissue sarcoma (STS) and the effect of inhibiting HMGA1 or the mTOR downstream pathway in trabectedin activity. The prognostic/predictive value of HMGA1 expression was assessed in a cohort of 301 STS patients at mRNA (n = 133) and protein level (n = 272), by HTG EdgeSeq transcriptomics and immunohistochemistry, respectively.

Combination treatment with PD1/PDL-1 inhibitors for sarcomas: state of the art, next questions.

Purpose Of Review: Only a small fraction of sarcomas exhibit recognized parameters of immune sensitivity, such as tumor mutational burden, PDL-1 expression, or microsatellite instability. Combined strategies aimed to modulate tumor microenvironment to increase the efficacy of PD1/PDL-1 inhibitors in sarcoma. Most explored prospective studies were based on combinations of PD1/PDL-1 inhibitors with antiangiogenics, other immune checkpoints, or chemotherapy.

Best Overall Response-Associated Signature to Doxorubicin in Soft Tissue Sarcomas: A Transcriptomic Analysis from ANNOUNCE.

Purpose: This exploratory analysis evaluated the tumor samples of the patients treated with doxorubicin (with or without olaratumab) in a negative phase III ANNOUNCE trial to better understand the complexity of advanced soft tissue sarcomas (STS) and to potentially identify its predictive markers.

Experimental Design: RNA sequencing was performed on pretreatment tumor samples (n = 273) from the ANNOUNCE trial to evaluate response patterns and identify potential predictive treatment markers for doxorubicin. A BOR-associated signature to doxorubicin (REDSARC) was created by evaluating tumors with radiographic response versus progression.

STAT6-targeting antisense oligonucleotides against solitary fibrous tumor.

Solitary fibrous tumor (SFT) is a rare, non-hereditary soft tissue sarcoma thought to originate from fibroblastic mesenchymal stem cells. The etiology of SFT is thought to be due to an environmental intrachromosomal gene fusion between NGFI-A-binding protein 2 (NAB2) and signal transducer and activator protein 6 (STAT6) genes on chromosome 12, wherein the activation domain of STAT6 is fused with the DNA-binding domain of NAB2 resulting in the oncogenesis of SFT. All NAB2-STAT6 fusion variations discovered in SFTs contain the C-terminal of STAT6 transcript, and thus can serve as target site for antisense oligonucleotides (ASOs)-based therapies.

Circulating TNF-RII, IP-10 and HGF are associated with severity of COVID-19 in oncologic patients.

The COVID-19 patients showed hyperinflammatory response depending on the severity of the disease but little have been reported about this response in oncologic patients that also were infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sixty-five circulating cytokines/chemokines were quantified in 15 oncologic patients, just after SARS-CoV-2 infection and fourteen days later, and their levels were compared in patients who required hospitalisation by COVID-19 versus non-hospitalised patients. A higher median age of 72 years (range 61-83) in oncologic patients after SARS-CoV-2 infection was associated with hospitalisation requirement by COVID-19 versus a median age of 49 years (20-75) observed in the non-hospitalised oncologic patients (p = 0.

Trabectedin and low-dose radiation therapy in patients with advanced leiomyosarcoma.

Background And Objectives: Dimensional response is an unmet need in second lines of advanced soft tissue sarcomas (STS). Indeed, the three approved drugs, pazopanib, trabectedin, and eribulin, achieved an overall response rate (ORR) of less than 10%. This fact potentially hinders the options for fast symptomatic relief or surgical rescue.

Delays in diagnosis and surgery of sarcoma patients during the COVID-19 outbreak in Spain.

Background And Objectives: Social distancing and quarantine implanted during the COVID-19 outbreak could have delayed the accession of oncologic patients to hospitals and treatments. This study analysed the management of sarcoma patients during this period in five Spanish hospitals.

Design And Methods: Clinical data from adult sarcoma patients, soft tissue and bone sarcomas, managed during the COVID-19 outbreak, from 15 March to 14 September 2020 (Covid cohort), were retrospectively collected and time for diagnosis, surgery and active treatments were compared with sarcoma patients managed during the same pre-pandemic period in 2018 (Control cohort).

Oromandibular Dystonia as a Side Effect of Methotrexate.

Oromandibular dystonia is a focal dystonia characterized by involuntary movements of the jaw, oropharynx, lips, and tongue. The diagnosis of oromandibular dystonia is clinical and can be complex. For effective treatment, it is essential to understand its underlying etiology.

Phase II trial of CDK4/6 inhibitor palbociclib in advanced sarcoma based on mRNA expression of CDK4/ CDKN2A.

Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors demonstrated activity in terms of progression-free survival (PFS) in advanced dedifferentiated liposarcoma (DD-LPS), a sarcoma with CDK4 amplification. CDK4 overexpression is by far more common than amplification in sarcomas and it might be a rational target for CDK inhibitors. Preclinical investigators of this study found that CDK4 overexpression, while not of CDKN2A, was the most consistent predictive factor for palbociclib efficacy in sarcomas.

REGISTRI: Regorafenib in first-line of KIT/PDGFRA wild type metastatic GIST: a collaborative Spanish (GEIS), Italian (ISG) and French Sarcoma Group (FSG) phase II trial.

Background: Approximately 15% of adult GIST patients harbor tumors that are wild-type for KIT and PDGFRα genes (KP-wtGIST). These tumors usually have SDH deficiencies, exhibit a more indolent behavior and are resistant to imatinib. Underlying oncogenic mechanisms in KP-wtGIST include overexpression of HIF1α high IGFR signaling through the MAPK pathway or BRAF activating mutation, among others.

Reduction of Tumor Growth with RNA-Targeting Treatment of the NAB2-STAT6 Fusion Transcript in Solitary Fibrous Tumor Models.

Solitary fibrous tumor (SFT) is a rare soft-tissue sarcoma. This nonhereditary cancer is the result of an environmental intrachromosomal gene fusion between NAB2 and STAT6 on chromosome 12, which fuses the activation domain of STAT6 with the repression domain of NAB2. Currently there is not an approved chemotherapy regimen for SFTs.

Platinum-Based Regimens Are Active in Advanced Pediatric-Type Rhabdomyosarcoma in Adults and Depending on HMGB1 Expression.

Rhabdomyosarcoma (RMS) in adults is a rare and aggressive disease, which lacks standard therapies for relapsed or advanced disease. This retrospective study aimed to describe the activity of BOMP-EPI (bleomycin, vincristine, methotrexate and cisplatin alternating with etoposide, cisplatin and ifosfamide), an alternative platinum-based regimen, in adult patients with relapsed/metastatic RMS. In the study, 10 patients with RMS with a median age at diagnosis of 20.

Efficacy of Eribulin Plus Gemcitabine Combination in L-Sarcomas.

Although the overall survival of advanced soft-tissue sarcoma (STS) patients has increased in recent years, the median progression-free survival is lower than 5 months, meaning that there is an unmet need in this population. Among second-line treatments for advanced STS, eribulin is an anti-microtubule agent that has been approved for liposarcoma. Here, we tested the combination of eribulin with gemcitabine in preclinical models of L-sarcoma.

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.

Expression of p53 as a biomarker of pazopanib efficacy in solitary fibrous tumours: translational analysis of a phase II trial.

Background: Solitary fibrous tumours (SFT) are soft tissue sarcomas molecularly defined by the presence of the NAB2::STAT6 intrachromosomal fusion gene. Recently, a prospective phase II trial evaluating the role of the antiangiogenic tyrosine kinase inhibitor pazopanib in SFT has been conducted (NCT02066285).

Methods: Here, we analysed the mRNA and protein expression levels of the tumour suppressor and angiogenesis regulator p53 () in pre-treatment tumour samples from 22 patients with low aggressive (or typical) SFT and 28 patients with high aggressive (26 malignant and 2 dedifferentiated) SFT enrolled in the aforementioned pazopanib phase II trial.

ISG15 as a prognostic biomarker in solitary fibrous tumour.

Background: Solitary fibrous tumour (SFT) is a rare mesenchymal malignancy that lacks robust prognostic and predictive biomarkers. Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like modifier, associated with tumour progression, and with poor survival of SFT patients, as previous published by our group. Here, we describe the role of ISG15 in the biology of this rare tumour.

Predictive Value of MRP-1 in Localized High-Risk Soft Tissue Sarcomas: A Translational Research Associated to ISG-STS 1001 Randomized Phase III Trial.

MRP-1 is implicated in multidrug resistance and was described as prognostic in high-risk patients with soft-tissue sarcoma (STS) in a previous study. The current research aimed to validate MRP-1 prognostic/predictive value in localized sarcomas treated with anthracyclines plus ifosfamide within the ISG-1001 phase III study. In addition, the inhibitory activity on MRP-1 was investigated in preclinical studies to identify new combinations able to increase the efficacy of standard chemotherapy in STS.