The role of CEACAMs in neutrophil function.

Background: In addition to the long-known antibacterial actions of neutrophils, neutrophils are recognized to have a variety of other effects and are functionally diverse. Neutrophils can either stimulate or inhibit B cells and T cells, regulate NK development and activity, augment or direct the resolution of inflammation, act as myeloid-derived suppressor cells, modulate tumour growth and metastasis and trigger autoimmune diseases. CEACAMs 1, 3, 6 and 8 are expressed on human neutrophils.

RAD51C and MYST3 Mutations in a Case of Desmoid-Type Fibromatosis With No Mutation in CTNNB1 or APC.

Most cases of desmoid-type fibromatosis (DTF) exhibit a mutation in APC or CTNNB1. We report a case of mesenteric DTF in which no mutation in APC or CTNNB1 was found, but a germline variant of uncertain significance (VUS) in RAD51C and a subclonal mutation in MYST3 were identified. Whether these genetic changes are important in DTF in this case, or whether genetically conventional DTF cells were present at a density below detection is unknown; it will be of interest to see results in further studies of wild-type APC/CTNNB1 cases.

Multifocal Desmoid-Type Fibromatosis: Case Series and Potential Relationship to Neuronal Spread.

Multifocal desmoid-type fibromatosis (DTF) is very rare and usually regional. We report three cases that initially appeared to be multifocal, but subsequent detailed imaging revealed unsuspected tracking along nerves in two cases. This neural spread is reminiscent of neuromuscular choristoma (NMC), a rare developmental lesion in which mature skeletal muscle cells, or rarely smooth muscle cells, infiltrate and enlarge peripheral nerves.

Patched Homolog 1 (PTCH1) Mutation in a CIC-Rearranged Sarcoma: Lack of Response to the Smoothened (SMO) Vismodegib.

Next-generation sequencing (NGS) to identify potential targets is becoming a common approach to refractory tumors. We describe a patient with a CIC-DUX4 sarcoma that harbored a patched homolog 1 (PTCH1) mutation, a mutation not previously reported in so-called Ewing family tumors. PTCH1 is part of the hedgehog signaling pathway.

A Novel Tongue-Based Tumor With an RREB1-MRTFB Fusion: Variant Rhabdomyosarcoma or Aggressive Variant of Ectomesenchymal Chondromyxoid Tumor.

The presence of a fusion in a tumor is one of the most important prognostic factors in rhabdomyosarcoma. Most histologically defined alveolar rhabdomyosarcomas bear a fusion. We discuss a case that was initially thought to be a rhabdomyosarcoma but was later discovered to have an fusion.

Biclonal Desmoid-Type Fibromatosis With Two Beta-Catenin Mutations: Evidence for the Recruitment of Normal Myofibroblasts.

Sporadic aggressive fibromatosis, or desmoid-type fibromatosis, is characterized by oncogenic mutations in CTNNB1. The clonal cell is a myofibroblast-like cell, and it has been hypothesized that the recruitment of normal myofibroblasts could contribute significantly to the tumor. We describe a case in which a CTNNB1 p.

Prospective Trial of Neutrophil/Lymphocyte Ratio and Other Blood Counts as Biomarkers of Survival among Patients with High-Grade Soft Tissue Sarcomas Treated with Pegylated Liposomal Doxorubicin and Ifosfamide.

Several studies have reported an association between levels of circulating blood cells, in particular the neutrophil to lymphocyte ratio (absolute neutrophil count (ANC)/absolute lymphocyte count (ALC)) and outcomes in patients with cancer. In the current study, the association between lymphocyte, neutrophil, monocyte, and platelet counts and survival was examined in a prospective trial of preoperative pegylated-liposomal doxorubicin and ifosfamide for high-grade soft-tissue sarcomas. A statistically significant association between overall survival, but not progression free-survival, was observed with the ANC/ALC ratio at a cutoff value of ≥2 and a statistically significant trend using a cutoff of ≥5.

Prospective Trial of Monocyte Count as a Biomarker of Hand-Foot Syndrome Among Patients With Soft Tissue Sarcomas Treated With Pegylated Liposomal Doxorubicin and Ifosfamide.

Pegylated liposomal doxorubicin (PLD) is widely used and can be used for prolonged periods, with the limiting toxicity usually being hand-foot syndrome (HFS). The pharmacokinetics of PLD is variable between patients, leading to variability in the risk of developing HFS. Dosing based on body surface area does not decrease variability in PLD clearance; thus, other predictive markers could be useful.

Multiple malignant tumors in a patient with familial chordoma, a case report.

Background: Chordoma is a rare bone tumor that is typically resistant to chemotherapy and is associated with genetic abnormalities of the T-box transcription factor T (TBXT) gene, which encodes the transcription factor brachyury. Brachyury is felt to be a major contributor to the development of chordomas.

Case Presentation: We describe a 67-year-old woman who developed an undifferentiated pleomorphic sarcoma in her thigh.

Pegylated liposomal doxorubicin-induced renal toxicity in retroperitoneal liposarcoma: a case report and literature review.

Doxorubicin is one of the most active drugs for sarcoma. Pegylated liposomal doxorubicin (PLD) is a unique formulation of doxorubicin, which carries a more favorable toxicity profile in comparison with free doxorubicin. The main toxicity of PLD is hand-foot syndrome.

A Retrospective Analysis of the Efficacy of Immunotherapy in Metastatic Soft-Tissue Sarcomas.

Although checkpoint inhibitors have been approved in multiple cancers, they are still under investigation in soft tissue sarcoma (STS). We conducted a retrospective review to report the safety, efficacy, and prognostic factors related to checkpoint inhibitors in STS. A sequential cohort of metastatic STS patients from four institutions treated with checkpoint inhibitors was assembled.

Inhibition of Ovarian Cancer Cell Spheroid Formation by Synthetic Peptides Derived from Nectin-4.

The formation of 3D multicellular spheroids in the ascites fluid of ovarian cancer patients is an understudied component of the disease progression. Spheroids are less sensitive to chemotherapy, in part due to the protection afforded by their structure, but also due to their slower proliferation rate. Previous studies suggest that the cell adhesion molecule Nectin-4 plays a key role in the formation of ovarian cancer spheroids.

Development of cutaneous squamous cell carcinoma after prolonged exposure to pegylated liposomal doxorubicin and hand-foot syndrome: a newly recognized toxicity.

Pegylated liposomal doxorubicin (PLD) can be administered for prolonged periods with minimal toxicity. The risk of cutaneous squamous cell carcinoma (SCC) with this therapy has not been reported. We describe cutaneous SCC of the plantar foot in two patients exposed to high doses of PLD.

Effect of chemotherapy on cancer stem cells and tumor-associated macrophages in a prospective study of preoperative chemotherapy in soft tissue sarcoma.

Background: Cancer stem cells (CSC) may respond to chemotherapy differently from other tumor cells.

Methods: This study examined the expression of the putative cancer stem cell markers ALDH1, CD44, and CD133; the angiogenesis marker CD31; and the macrophage marker CD68 in soft tissue sarcomas (STS) before and after 4 cycles of chemotherapy with doxorubicin and ifosfamide in 31 patients with high-grade soft tissue sarcoma in a prospective clinical trial.

Results: None of the markers clearly identified CSCs in STS samples.

Cardiotoxicity Monitoring in Patients Treated with Tyrosine Kinase Inhibitors.

Tyrosine kinase inhibitors (TKIs) can cause cardiotoxicity, and some suggest routine monitoring of cardiac function during TKI use. We describe two cases of TKI-induced heart failure (HF) that suggest the utility of monitoring with laboratory tests is questionable. One patient developed HF 5 days after starting pazopanib.

Long-term cure of soft tissue sarcoma with pegylated-liposomal doxorubicin after doxorubicin and ifosfamide failure.

Background: Doxorubicin is one of the most active drugs available for the treatment of sarcoma. Pegylated-liposomal doxorubicin (PLD) is a formulation of doxorubicin in which the doxorubicin is encapsulated in liposomes coated with methoxypoly (ethylene glycol); this formulation results in decreased uptake by the reticuloendothelial system, higher concentrations of drug in tumor, and less toxicity, including reduced cardiotoxicity, nausea, alopecia, and myelosuppression. No premedication is necessary.

Long-term Outcome After Doxorubicin and Ifosfamide Overdose in a Patient With Osteosarcoma and BARD1 Mutation.

Current treatment of high-grade osteosarcoma consists of preoperative chemotherapy, typically using some combination of doxorubicin, cisplatin, ifosfamide, and/or high-dose methotrexate followed by surgical resection. In this report, we present a case of a 21-year-old woman with high-grade osteosarcoma of the chest wall who received 5 times the planned dose of doxorubin and 4 times the planned dose of ifosfamide. She survived this chemotherapy overdose after administration of dimethyl sulfoxide and phenobarbital.

Cardiac safety profile of patients receiving high cumulative doses of pegylated-liposomal doxorubicin: use of left ventricular ejection fraction is of unproven value.

Purpose: One of the great conundrums for both oncologists and cardiologists is how to best monitor the potential and actual cardiotoxicity of doxorubicin. Pegylated-liposomal doxorubicin (PLD) has a safer cardiotoxicity profile than bolus administration of doxorubicin. Although ejection fraction (EF) is commonly performed to monitor doxorubicin-induced cardiotoxicity, evidence for its predictive utility is limited.

Results of a prospective phase 2 study of pazopanib in patients with advanced intermediate-grade or high-grade liposarcoma.

Background: This phase 2, single-arm, multicenter study was designed to determine the treatment activity and safety of single-agent pazopanib in patients with unresectable or metastatic liposarcoma.

Methods: Eligible patients had high-grade or intermediate-grade liposarcoma with measurable tumors that were unresectable or metastatic, documented disease progression, and had received any number of prior treatments, excluding previous treatment with a vascular endothelial growth factor inhibitor or a tyrosine kinase inhibitor. Patients received oral pazopanib 800 mg once daily for 28-day cycles.

Biology and Treatment of Aggressive Fibromatosis or Desmoid Tumor.

Aggressive fibromatosis, also known as desmoid-type fibromatosis (DTF) or desmoid tumor, is an uncommon locally invasive tumor. Because of its low incidence and variable behavior, DTF is often first seen by physicians who are not familiar with it, and recent advances in understanding this disease have led to changes in treatment approaches. The Wnt (β-catenin) pathway appears to play a key role in DTF pathogenesis, and recent studies of DTF biology suggest a possible model of DTF pathogenesis.

Gene expression identifies heterogeneity of metastatic behavior among gastrointestinal stromal tumors.

Background: Adjuvant imatinib is useful in patients with gastrointestinal stromal tumors (GIST) at high risk of recurrence. At present, the risk of recurrence is determined based on tumor size, mitotic rate, tumor site, and tumor rupture. Previous studies using various biochemical pathways identified gene expression patterns that distinguish two subsets of aggressive fibromatosis (AF), serous ovarian carcinoma (OVCA), and clear cell renal cell carcinoma (RCC).

Response of Aneurysmal Bone Cyst to Denosumab.

Study Design: Case report and literature review.

Objective: To describe a unique case of large sacral aneurysmal bone cysts (ABCs) treated with denosumab and review the literature on this rare entity.

Summary And Background Data: ABCs are expansile osteolytic lesions that typically contain blood-filled spaces separated by fibrous septa.

Gene expression identifies heterogeneity of metastatic behavior among high-grade non-translocation associated soft tissue sarcomas.

Background: The biologic heterogeneity of soft tissue sarcomas (STS), even within histological subtypes, complicates treatment. In earlier studies, gene expression patterns that distinguish two subsets of clear cell renal carcinoma (RCC), serous ovarian carcinoma (OVCA), and aggressive fibromatosis (AF) were used to separate 73 STS into two or four groups with different probabilities of developing metastatic disease (PrMet). This study was designed to confirm our earlier observations in a larger independent data set.

Effects of denosumab on pain and analgesic use in giant cell tumor of bone: interim results from a phase II study.

Background: Giant cell tumor of bone (GCTB) is an aggressive primary osteolytic tumor. GCTB often involves the epiphysis, usually causing substantial pain and functional disability. Denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor κΒ ligand (RANKL), is an effective treatment option for patients with advanced GCTB.