Publications by authors named "William Tap"

DICER1-associated sarcoma is an emerging entity, defined by either somatic or germline dicer 1, ribonuclease III (DICER1) mutations and sharing characteristic morphologic features irrespective of the site of origin. In addition to the DICER1 driver mutation, concurrent genomic alterations, including tumor protein 53 (TP53) inactivation and RAS pathway activation, are frequently detected. Tumors that morphologically resemble malignant peripheral nerve sheath tumor (MPNST) have rarely been reported among DICER1 sarcomas and often pose diagnostic challenges.

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Purpose: The cancer/testis antigen New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a promising target in myxoid/round cell liposarcoma (MRCLS).

Methods: In this pilot study, we assessed the adoptive T-cell therapy NY-ESO-1cT letetresgene autoleucel (lete-cel) in patients with human leukocyte antigen (HLA)-A*02:01-, HLA-A*02:05-, and/or HLA-A*02:06-positive advanced/metastatic NY-ESO-1-expressing MRCLS. Patients underwent a reduced-dose (cohort 1) or standard-dose (cohort 2) lymphodepletion regimen (LDR).

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  • Pexidartinib is a drug used for treating tenosynovial giant cell tumor (TGCT) in patients where surgery isn't an option, and this study looked at the effects of stopping and then restarting the medication.
  • It was a phase 4 global study involving patients who had benefited from pexidartinib, allowing them to either continue treatment or stop with the option to restart later, monitoring their tumor progression and quality of life.
  • Results showed that while about 54.5% of patients who stopped the drug experienced disease progression, none of those who continued treatment saw their condition worsen over a 24-month period.
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Purpose: Survival of patients with metastatic sarcoma remains poor, and there is a pressing need for new therapies. Most sarcoma subtypes are not responsive to immune checkpoint inhibition alone. Lenvatinib, a multireceptor tyrosine kinase inhibitor targeting tumor vasculature, has an immunomodulatory activity that contributes to its antitumor effects.

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  • This phase II study (Alliance A091401) evaluates the effectiveness of nivolumab (N) alone and in combination with ipilimumab (N+I) on patients with different types of sarcomas, focusing on treatment responses and biomarkers.
  • The study involved 66 patients with various sarcoma types, and while neither N nor N+I showed positive responses in gastrointestinal stromal tumors (GIST), N+I had a better response in dedifferentiated liposarcoma (DDLPS) and undifferentiated pleomorphic sarcoma (UPS).
  • Results highlighted that traditional biomarkers did not predict immunotherapy response, but genomic instability markers correlated with better clinical outcomes, emphasizing the need for more research in
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  • Epithelioid hemangioendothelioma (EHE) is difficult to treat with traditional chemotherapy, prompting researchers to explore new therapies such as sirolimus and identify biomarkers for tumor aggressiveness.
  • Scientists created a patient-derived xenograft (PDX) model from an advanced EHE patient to test sirolimus and to study serum levels of Growth/Differentiation Factor 15 (GDF-15) as a potential biomarker.
  • The results indicated sirolimus was more effective than doxorubicin in reducing tumor growth and GDF-15 levels, establishing GDF-15 as a promising biomarker for EHE aggressiveness and potentially indicating the effectiveness of sirolimus in patients.
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The objective of this study is to develop a multimodal neural network (MMNN) model that analyzes clinical variables and MRI images of a soft tissue sarcoma (STS) patient, to predict overall survival and risk of distant metastases. We compare the performance of this MMNN to models based on clinical variables alone, radiomics models, and an unimodal neural network. We include patients aged 18 or older with biopsy-proven STS who underwent primary resection between January 1st, 2005, and December 31st, 2020 with complete outcome data and a pre-treatment MRI with both a T1 post-contrast sequence and a T2 fat-sat sequence available.

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  • Leiomyosarcomas (LMS) are a type of cancer that can happen by chance or be linked to genetic conditions, and scientists are studying how genetic changes might affect them.
  • In a study of 285 LMS cases, about 27% had harmful genetic changes that could influence the cancer, with most of these changes found in soft tissue LMS.
  • The findings suggest that certain genetic changes are more common in younger patients with soft tissue LMS, and knowing about these genetic changes can help with future testing and treatment plans.
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Limited guidance exists on streamlining cancer therapy for adolescent and young adult (AYA) patients 15-39 years of age, as much of the current data are extrapolated from pediatric or adult counterparts and can differ significantly between the two care models. Harmonization of standard treatment approaches has the potential to improve outcomes and establish a foundation for the development of future clinical trials. We present our experience harmonizing treatment and supportive care regimens for AYA patients with osteosarcoma receiving treatment with methotrexate, doxorubicin, and cisplatin (MAP) therapy on the pediatric and adult sarcoma services at the Memorial Sloan Kettering Cancer Center.

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  • TGCT is a challenging tumor to treat, primarily managed through surgery, but there are few options for patients who can't have surgery; this study investigates vimseltinib, a new oral medication targeting the CSF1 receptor.
  • Conducted as a phase I/II trial with 69 patients (37 with various malignant tumors and 32 with TGCT), the study aimed to evaluate the safety, tolerability, and pharmacokinetics of vimseltinib, while looking at its potential effectiveness.
  • The results showed that vimseltinib was generally well tolerated with a recommended dose of 30 mg taken twice a week, and achieved a 72% objective response rate in TGCT patients, demonstrating promising
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Background: Current guidelines recommend use of adjuvant imatinib therapy for many patients with gastrointestinal stromal tumours (GISTs); however, its optimal treatment duration is unknown and some patient groups do not benefit from the therapy. We aimed to apply state-of-the-art, interpretable artificial intelligence (ie, predictions or prescription logic that can be easily understood) methods on real-world data to establish which groups of patients with GISTs should receive adjuvant imatinib, its optimal treatment duration, and the benefits conferred by this therapy.

Methods: In this observational cohort study, we considered for inclusion all patients who underwent resection of primary, non-metastatic GISTs at the Memorial Sloan Kettering Cancer Center (MSKCC; New York, NY, USA) between Oct 1, 1982, and Dec 31, 2017, and who were classified as intermediate or high risk according to the Armed Forces Institute of Pathology Miettinen criteria and had complete follow-up data with no missing entries.

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Dysregulated epigenetic states are a hallmark of cancer and often arise from genetic alterations in epigenetic regulators. This includes missense mutations in histones, which, together with associated DNA, form nucleosome core particles. However, the oncogenic mechanisms of most histone mutations are unknown.

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Background: Craniofacial osteosarcomas (CFOS) are uncommon malignant neoplasms of the head and neck with different clinical presentation, biological behavior and prognosis from conventional osteosarcomas of long bones. Very limited genetic data have been published on CFOS.

Methods: In the current study, we performed comprehensive genomic studies in 15 cases of high-grade CFOS by SNP array and targeted next generation sequencing.

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  • Tenosynovial giant cell tumour (TGCT) is a locally aggressive tumor with limited treatment options, leading this study to assess vimseltinib, a CSF1R inhibitor, in patients whose TGCT symptoms prevent surgery.
  • The MOTION trial, a phase 3 randomized study, involved 123 adults from 35 hospitals globally, comparing vimseltinib to a placebo over 24 weeks, focusing on the objective response rate determined by independent radiological review.
  • Results showed a significant objective response rate of 40% for vimseltinib compared to 0% for placebo, with most side effects being mild (grade 1 or 2), highlighting vimseltinib's
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ALL cures require many MRD therapies. This strategy should drive experiments and trials in metastatic bone sarcomas.

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Both primary and secondary breast angiosarcoma (AS) are characterized by multifocal presentation and aggressive behavior. Despite multimodality therapy, local and distant relapse rates remain high. Therefore, neoadjuvant chemotherapy (NACT) is employed to improve the R0 resection rates and survival, but its benefits remain controversial.

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Pleomorphic rhabdomyosarcoma (PRMS) is a rare and highly aggressive sarcoma, occurring mostly in the deep soft tissues of middle-aged adults and showing a variable degree of skeletal muscle differentiation. The diagnosis is challenging as pathologic features overlap with embryonal rhabdomyosarcoma (ERMS), malignant Triton tumor, and other pleomorphic sarcomas. As recurrent genetic alterations underlying PRMS have not been described to date, ancillary molecular diagnostic testing is not useful in subclassification.

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Purpose: Alterations of the tumor suppressor gene is the second most frequent genetic event in embryonal rhabdomyosarcoma (ERMS), but its associations with clinicopathologic features, outcome, or coexisting molecular events are not well defined. Additionally, alterations, mostly in the setting of neurofibromatosis type I (NF1), drive the pathogenesis of most malignant peripheral nerve sheath tumor with divergent RMS differentiation (also known as malignant triton tumor [MTT]). Distinguishing between these entities can be challenging because of their pathologic overlap.

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Background: Afamitresgene autoleucel (afami-cel) showed acceptable safety and promising efficacy in a phase 1 trial (NCT03132922). The aim of this study was to further evaluate the efficacy of afami-cel for the treatment of patients with HLA-A*02 and MAGE-A4-expressing advanced synovial sarcoma or myxoid round cell liposarcoma.

Methods: SPEARHEAD-1 was an open-label, non-randomised, phase 2 trial done across 23 sites in Canada, the USA, and Europe.

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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.

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Purpose: Leiomyosarcomas (LMS) are clinically and molecularly heterogeneous tumors. Despite recent large-scale genomic studies, current LMS risk stratification is not informed by molecular alterations. We propose a clinically applicable genomic risk stratification model.

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Alterations in the tumor suppressor ATRX are recurrently observed in mesenchymal neoplasms. ATRX has multiple epigenetic functions including heterochromatin formation and maintenance and regulation of transcription through modulation of chromatin accessibility. Here, we show in murine mesenchymal progenitor cells (MPCs) that Atrx deficiency aberrantly activated mesenchymal differentiation programs.

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Background: Epithelioid hemangioendothelioma (EHE) is an ultra-rare, vascular sarcoma with clinical presentation ranging from an indolent to an aggressive form. Over 50% of patients present with metastatic disease, requiring systemic therapy, although no systemic therapies are specifically approved for EHE. Retrospective evidence supports the activity of mTOR inhibitors (e.

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