Integrated Epigenetic and Transcriptomic Analysis Identifies DNA Methylation Signature of Malignant Peripheral Nerve Sheath Tumor Progression and Metastasis.

Purpose: Sarcomas are a complex group of highly aggressive and metastatic tumors with over 100 distinct subtypes. Because of their diversity and rarity, it is challenging to generate multisarcoma signatures that are predictive of patient outcomes.

Materials And Methods: Here, we identify a DNA methylation signature for progression and metastasis of numerous sarcoma subtypes using multiple epigenetic and genomic patient data sets.

Superoxide Dismutase Mimetic Avasopasem Manganese Enhances Radiation Therapy Effectiveness in Soft Tissue Sarcomas and Accelerates Wound Healing.

Soft tissue sarcomas (STSs) are mesenchymal malignant lesions that develop in soft tissues. Despite current treatments, including radiation therapy (RT) and surgery, STSs can be associated with poor patient outcomes and metastatic recurrences. Neoadjuvant radiation therapy (nRT), while effective, is often accompanied by severe postoperative wound healing complications due to damage to the surrounding normal tissues.

T* Imaging Assessment of Neoadjuvant Radiation Therapy Combined With Pharmacological Ascorbate in Extremity Soft-Tissue Sarcomas: A Pilot Study.

Background: Extremity soft-tissue sarcomas (STS) are commonly treated with neoadjuvant radiation therapy followed by surgical resection. However, the pathological near-complete response rate is low (9-25%). Noninvasive imaging assessment that predicts treatment response before and during treatment is desirable to optimize treatment regimens.

Three-Year Overall Survival with Tebentafusp in Metastatic Uveal Melanoma.

Background: Tebentafusp, a T-cell receptor-bispecific molecule that targets glycoprotein 100 and CD3, is approved for adult patients who are positive for HLA-A*02:01 and have unresectable or metastatic uveal melanoma. The primary analysis in the present phase 3 trial supported a long-term survival benefit associated with the drug.

Methods: We report the 3-year efficacy and safety results from our open-label, phase 3 trial in which HLA-A*02:01-positive patients with previously untreated metastatic uveal melanoma were randomly assigned in a 2:1 ratio to receive tebentafusp (tebentafusp group) or the investigator's choice of therapy with pembrolizumab, ipilimumab, or dacarbazine (control group), with randomization stratified according to the lactate dehydrogenase level.

Clinical diagnostic and radiographic features of recurrent intracranial malignant triton tumor in an adult: illustrative case.

Background: Malignant triton tumors (MTTs) are a rare and aggressive type of malignant peripheral nerve sheath tumor identified histologically by focal rhabdomyoblastic differentiation.

Observations: A 37-year-old female with a prior history of Hodgkin lymphoma presented with acute-onset confusion, cognitive deficits, and weakness. Brain magnetic resonance imaging revealed a hemorrhagic intracranial mass later confirmed to be a malignant triton tumor.

Clinical Activity of Combined Telomerase Vaccination and Pembrolizumab in Advanced Melanoma: Results from a Phase I Trial.

Purpose: Cancer vaccines represent a novel treatment modality with a complementary mode of action addressing a crucial bottleneck for checkpoint inhibitor (CPI) efficacy. CPIs are expected to release brakes in T-cell responses elicited by vaccination, leading to more robust immune responses. Increased antitumor T-cell responses may confer increased antitumor activity in patients with less immunogenic tumors, a subgroup expected to achieve reduced benefit from CPIs alone.

Talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone for advanced melanoma: 5-year final analysis of a multicenter, randomized, open-label, phase II trial.

Talimogene laherparepvec (T-VEC) plus ipilimumab has demonstrated greater antitumor activity versus ipilimumab alone, without additional toxicity, in patients with advanced melanoma. Here, we report the 5-year outcomes from a randomized phase II study. These data provide the longest efficacy and safety follow-up for patients with melanoma treated with a combination of an oncolytic virus and a checkpoint inhibitor.

Hypopigmented Mycosis Fungoides in an 11-Year-Old Palestinian Boy.

Cutaneous T-cell lymphoma (CTCL) is a lymphoproliferative disorder of the skin. The most common subtype of CTCL in pediatrics is mycosis fungoides (MF). There are multiple variants of MF.

Postoperative Echography for Optimization of Radiation Dosimetry in Patients with Uveal Melanoma Treated with Plaque Brachytherapy.

Purpose: (1) To describe the technique of postoperative echography to confirm the intended treatment dose to the tumor apex in patients with uveal melanoma treated with plaque brachytherapy. (2) To describe the local tumor control rate and visual outcomes with the brachytherapy strategies used at our institution.

Design: Retrospective review.

The Impact of TSC-1 and -2 Mutations on Response to Therapy in Malignant PEComa: A Multicenter Retrospective Analysis.

Background: Perivascular epithelioid cell neoplasms (PEComas) are a diverse family of mesenchymal tumors with myomelanocytic differentiation that disproportionately affect women and can be associated with tuberous sclerosis (TS). Although mTOR inhibition is widely used as first-line treatment, it is unclear what genomic alterations exist in these tumors and how they influence the response to therapy.

Methods: This was a multicenter study conducted at five sites within the US.

Patient reported quality of life in young adults with sarcoma receiving care at a sarcoma center.

Background: Sarcomas are a diverse group of neoplasms that vary greatly in clinical presentation and responsiveness to treatment. Given the differences in the sites of involvement, rarity, and treatment modality, a multidisciplinary approach is required. Previous literature suggests patients with sarcoma suffer from poorer quality of life (QoL) especially physical and functional wellbeing.

A randomised phase II trial of a trivalent ganglioside vaccine targeting GM2, GD2 and GD3 combined with immunological adjuvant OPT-821 versus OPT-821 alone in metastatic sarcoma patients rendered disease-free by surgery.

Background: Recurrence after resection of metastatic sarcoma is common. The gangliosides GM2, GD2 and GD3 are strongly expressed across sarcoma subtypes. We hypothesised that generation of anti-ganglioside antibodies would control micrometastases and improve outcomes in sarcoma patients who were disease-free after metastasectomy.

Detection of Ferritin Expression in Soft Tissue Sarcomas With MRI: Potential Implications for Iron Metabolic Therapy.

Background: Cancer cells often have altered iron metabolism relative to non-malignant cells with increased transferrin receptor and ferritin expression. Targeting iron regulatory proteins as part of a cancer therapy regimen is currently being investigated in various malignancies. Anti-cancer therapies that exploit the differences in iron metabolism between malignant and non-malignant cells (e.

Olutasidenib (FT-2102) in patients with relapsed or refractory IDH1-mutant glioma: A multicenter, open-label, phase Ib/II trial.

Background: Olutasidenib (FT-2102) is a highly potent, orally bioavailable, brain-penetrant and selective inhibitor of mutant isocitrate dehydrogenase 1 (IDH1). The aim of the study was to determine the safety and clinical activity of olutasidenib in patients with relapsed/refractory gliomas harboring an IDH1R132X mutation.

Methods: This was an open-label, multicenter, nonrandomized, phase Ib/II clinical trial.

Epigenetic modulation in sensitizing metastatic sarcomas to therapies and overcoming resistance.

Sarcomas are a class of rare malignancies of mesenchymal origin with a heterogeneous histological spectrum. They are classically associated with poor outcomes, especially once metastasized. A path to improving clinical outcomes may be made through modifying the epigenome, where a variety of sarcomas demonstrate changes that contribute to their oncogenic phenotypes.

Presumed Melanoma of Unknown Primary Origin Metastatic to the Choroid Mimics Primary Uveal Melanoma.

We describe the case of a 69-year-old woman who presented with a decline in vision in the left eye and was found to have a choroidal lesion with clinical and echographic features concerning for primary uveal melanoma. Systemic imaging identified numerous metastases to the liver, kidneys, paratracheal lymph nodes, lung, and brain. The hepatic lesion was biopsied, and genetic analysis identified a Val600Glu (c.

Surgical management for giant bladder leiomyosarcoma.

While urothelial carcinoma is the most common histologic type of bladder cancer in the United States, leiomyosarcoma is a rare and aggressive variant. The rarity of bladder leiomyosarcoma results in uncertainty regarding the optimal treatment pathway. We report on a patient with a giant non-metastatic bladder leiomyosarcoma effectively managed with primary surgical intervention without chemoradiation.

Intralesional SD-101 in Combination with Pembrolizumab in Anti-PD-1 Treatment-Naïve Head and Neck Squamous Cell Carcinoma: Results from a Multicenter, Phase II Trial.

Purpose: To determine whether SD-101, a Toll-like receptor 9 agonist, potentiates the antitumor activity of anti-PD-1 antibodies in patients with anti-PD-1/PD-L1 naïve, recurrent/metastatic head and neck squamous cell carcinoma (HNSCC).

Patients And Methods: Patients with PD-1 Ab-naïve HNSCC received either 2 mg SD-101 injected in one to four lesions or 8 mg SD-101 injected into a single lesion weekly × 4 doses then every 3 weeks × 7 doses. Pembrolizumab was administered at 200 mg every 3 weeks.

An Open-Label, Randomized, Multi-Center Study Comparing the Sequence of High Dose Aldesleukin (Interleukin-2) and Ipilimumab (Yervoy) in Patients with Metastatic Melanoma.

Combination immunotherapy with sequential administration may enhance metastatic melanoma (MM) patients with long-term disease control. High Dose Aldesleukin/Recombinant Interleukin-2 (HD rIL-2) and ipilimumab (IPI) offer complementary mechanisms against MM. This phase IV study assessed the sequenced use of HD rIL-2 and IPI in MM patients.