High transposable element expression in sarcomas is associated with increased immune infiltrates and improved outcomes including after immunotherapy.

Background: Response to immune checkpoint inhibition (ICI) in sarcomas is overall low and heterogeneous. Understanding determinants of ICI outcomes may improve efficacy and patient selection. Thus, we investigated whether the expression of transposable elements (TEs), which are epigenetically silenced and can stimulate antitumor immunity, influence ICI outcomes and immune infiltrates in common sarcoma subtypes.

Clinical Patterns and Prognostic Outcomes of Asian Ocular Adnexal Marginal Zone Lymphoma.

Background: Ocular adnexal marginal zone lymphoma (OAMZL) is the most common subtype of primary ocular lymphoma and has been rising in incidence in Asian populations.

Methods: We conducted a retrospective review of 95 patients diagnosed with OAMZL within a multi-ethnic cohort from Singapore. Clinical characteristics, survival outcomes including overall survival (OS) and progression-free survival (PFS), and maximum standardized uptake value (SUVmax) on staging F-18 fluorodeoxyglucose positron emission tomography/computed tomography (18-FDG-PET/CT) were investigated.

Prevalence of Long-Term Dysphagia in Head and Neck Cancer Survivors Not Receiving Dysphagia Treatment.

Objective: In head and neck cancer (HNC) survivors not actively receiving dysphagia care, long-term dysphagia prevalence, dysphagia-related complications, and quality of life outcomes remain poorly understood. Understanding these outcomes is critical for creating effective HNC survivorship programs.

Methods: HNC survivors who completed cancer treatment > 2 years prior who had not undergone a swallow evaluation or therapy for > 1 year completed the MD Anderson Dysphagia Inventory (MDADI) and reported dysphagia-related complications.

Surgical Outcomes of U-Shaped Incisions Versus Conventional Incisions in Parotidectomy.

ImportanceModified Blair and Facelift incisions are conventional approaches to parotid pathologies. However, they frequently result in prominent scars in cosmetically sensitive regions. A newer alternative, U-shaped incision offers a minimally visible scar along the contour of the pinna while enabling management of parotid pathologies.

IL-13/IL-13Rα2 axis promotes proliferation of angiosarcoma cells.

Angiosarcoma is a rare and aggressive soft tissue sarcoma with a poor prognosis and limited treatment options. The role of interleukin-13 (IL-13) and its receptors in angiosarcoma pathogenesis has been largely unknown. We first reanalyzed transcriptomic data from a published angiosarcoma cohort and found IL13RA2 mRNA elevated in angiosarcoma versus normal tissue.

Outcomes of primary CNS lymphoma treated with combined immunochemotherapy with whole-brain radiotherapy.

Purpose: Given that most PCNSL cases are diagnosed at a late age, they may be unsuitable for consolidation therapy with autologous stem cell transplantation (HDC-ASCT). We thus examine the outcomes of PCNSL in a multiethnic Asian population treated with HD-MTX-based chemotherapy and consolidation WBRT, so as to benchmark current treatment outcomes.

Methods: We conducted a retrospective study involving patients (n = 129) diagnosed with PCNSL at the National Cancer Centre Singapore from 2000 to 2019.

Outcome Evaluation of Volume-Staged Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations.

Background And Objectives: Single-session stereotactic radiosurgery (SRS) has limited role for large arteriovenous malformations (AVM). Volume-staged SRS (VS-SRS) is used to optimize outcomes, but studies reporting results are limited.

Methods: This multicenter retrospective cohort of 378 patients from 21 centers reports results of VS-SRS for the entire AVM nidus.

Role of Data in Development and Application of Quantitative Systems Pharmacology Models.

Quantitative systems pharmacology (QSP) is an interdisciplinary approach that integrates mathematical modeling, biological knowledge, and experimental data to gain insights into the complex dynamics of drug action and disease progression on the human physiological system. Different types of data from multiple and often disparate sources are used throughout all phases of QSP model development. Herein, we explore the various types of data used to inform the development and application of QSP models, their sources, and how the quality of data impacts the interpretation of model-derived results.

Establishment and characterization of a novel patient-derived TP63-rearranged anaplastic large-cell lymphoma model PTCL-S1.

Anaplastic large-cell lymphoma (ALCL) accounts for 15% of all peripheral T-cell lymphomas globally and can be further divided into subcategories, of which patients with ALK-negative ALCL have dismal prognosis and overall survival. We established a patient-derived xenograft (PDX) and in vitro model (designated PTCL-S1) of TP63-rearranged ALK-negative ALCL from the primary tumour site of a 55-year old Chinese woman. Whole genome sequencing of the patient's tumour identified various mutations including AKT1 and NOTCH1, as well as the TP63-TBL1XR1 gene fusion.

Prospective Clinical Validation of a Combinatorial Functional Precision Medicine Platform in Relapsed/Refractory Non-Hodgkin's Lymphoma.

Purpose: Despite initially responding to first-line treatment, many patients with non-Hodgkin's lymphoma (NHL) eventually relapse or are refractory. These patients are empirically subjected to salvage therapies that may not be efficacious. We had previously presented feasibility evidence of an ex vivo functional precision medicine (FPM) platform, quadratic phenotypic optimization platform (QPOP), being potentially useful in identifying alternative therapeutic options for patients with relapsed/refractory (R/R)-NHL.

Circulating tumor DNA as a molecular biomarker in the phase II trial of imatinib plus binimetinib in patients with advanced gastrointestinal stromal tumors.

Purpose: This study investigated factors that affected ctDNA detection and ctDNA as a molecular biomarker in a phase II trial of imatinib and binimetinib in newly diagnosed advanced GIST, including patients exposed to imatinib within 4 weeks of trial enrollment.

Experimental Design: Plasma and tumor tissue samples were collected at baseline, on-treatment, and upon progression. DNAs extracted from plasma and tumor tissue were analyzed using genomic assays, MSK-ACCESS and MSK-IMPACT, respectively.

Computer vision to predict cell seeding coverage in re-endothelialized mouse lungs.

Transplantation of donor grafts recellularized with recipient-derived or non-immunogenic universal cells is a potential means of reducing the graft rejection and post-transplant complications in lung transplantation. Achieving a fully recellularized lung, however, remains a far-off goal and has several limitations, including inadequate cell coverage of the acellular scaffold. A key parameter for evaluating recellularization efficacy is the cell seeding coverage (CSC); the ratio of seeded cell area to the total area of the lung scaffold.

Decoding subclonal anti-tumor immunity.

Subclonal evolution allows tumors to evade the immune system. In this issue of Cancer Cell, Dijkstra et al. combine the TRACERx cohort with co-cultures of autologous tumors and immune cells to functionally profile subclonal immune escape at the single-clone resolution.

PARP inhibitor augments anti-tumor efficacy of DNMT inhibitor by inducing senescence in cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an aggressive, heterogeneous malignancy with limited effective treatment options. One of the key epigenetic dysregulations in CCA is aberrant DNA hypermethylation, suggesting that targeted DNA methylation is a promising therapeutic strategy for this disease. However, there is still limited information on how effective DNA demethylating agents are in the treatment of CCA in the clinical setting, and further studies are urgently needed to evaluate their potential benefits.

Macular Hole Closure by Internal Limiting Membrane Flap without Gas Tamponade versus Conventional Surgery: A Comparative Study.

Purpose: To compare the effectiveness and safety of the novel internal limiting membrane (ILM) flap with no gas tamponade technique and conventional surgery in repairing macular hole (MH).

Design: Retrospective comparative study.

Participants: Consecutive patients with OCT confirmed full-thickness MH who underwent MH repair surgery by either conventional surgery or the ILM flap with no gas tamponade technique at the Hong Kong Eye Hospital from November 1, 2021, to July 31, 2024.

Phase II study of rucaparib and nivolumab in patients with leiomyosarcoma.

Background: Objective responses to immune checkpoint inhibitors (ICI) in leiomyosarcoma (LMS) are rare. Response rates may be increased by combination with other drugs known to promote immune infiltration, such as poly(ADP-ribose) polymerase (PARP) inhibitors, which have led to benefit in -altered uterine LMS. We therefore evaluated the combination of a PARP inhibitor, rucaparib, and the anti-programmed death receptor-1 monoclonal antibody, nivolumab, in patients with advanced LMS and investigated its effects on the tumor immune microenvironment.

Real-time gated proton therapy: Introducing clinical workflow and failure modes and effects analysis (FMEA).

Introduction: Real-Time Gated Proton Therapy (RGPT) has been used in proton therapy to mitigate respiratory motion challenges. This study presents the first comprehensive description of the RGPT clinical workflow at the National Cancer Centre Singapore (NCCS) and introduces a novel Failure Modes and Effects Analysis (FMEA) for RGPT.

Methods: We detail the workflow for prostate and liver/lung proton treatments.

Interpolated Retrieval of Relevant Material, Not Irrelevant Material, Enhances New Learning of a Video Lecture In-Person and Online.

Interpolated retrieval enhances the learning of new information-a finding known as the forward testing effect. The context change account suggests that learning benefits are due to a shift in internal context, which can be triggered through the retrieval of either content-relevant or content-irrelevant information. In two experiments, we examined whether interpolated episodic, autobiographical, and semantic retrieval would enhance new learning of a video lecture, compared to interpolated review.

Swallowing Function Outcomes in Head and Neck Cancer Survivors Followed by a Long-Term Dysphagia Surveillance Protocol.

Background: This study aimed to evaluate swallow outcomes in head and neck cancer (HNC) survivors enrolled in a long-term dysphagia surveillance protocol following curative intent radiotherapy (RT).

Methods: We conducted a retrospective review of videofluoroscopic swallow studies from 2015 to 2023 in HNC patients treated with RT. Swallow kinematics and function were assessed at baseline, 0-1, 1-2, 2-5, and 5+ years post-RT.

BCG response and oncological outcomes in high risk nonmuscle invasive bladder cancer following previously treated upper tract urothelial carcinoma: A propensity-matched analysis.

Introduction: Metachronous bladder recurrences after prior treatment for primary upper tract urothelial carcinoma (UTUC) can occur in ∼3% to 50% of patients. Because UTUC demonstrated distinct molecular alterations, bladder recurrences in these patients may be molecularly and phenotypically different compared to primary bladder carcinoma. We aim to study the BCG efficacy in patients with primary high risk nonmuscle invasive bladder cancer (P-NMIBC) and metachronous bladder recurrences after previous nephroureterectomy for UTUC (M-NMIBC).

The burden of intracranial atherosclerosis on cerebral small vessel disease: A community cohort study.

Objective: Exploring the prevalence and association between intracranial atherosclerosis (ICAS) and cerebral small vessel diseases (CSVD), this study delved beyond the current scope, utilising high-resolution vessel wall MRI (HRVW-MRI) to investigate how subtle changes in intracranial atherosclerotic features influence the various burdens of CSVD.

Methods: Stroke-free Chinese adult participants were recruited from our ongoing community-based MRI cohort. HRVW-MRI technique with a T1-weighted 3D SPACE sequence was used to assess atherosclerotic plaque features: plaque load, degree of stenosis, remodelling index, eccentricity.

Genetic landscape of uveal melanoma in Southeast Asia: high 1q gains and unique patterns of metastasis risk.

Purpose: This retrospective cohort study aims to investigate chromosomal aberrations in Southeast Asian (SEA) uveal melanoma (UM) patients, evaluate their impact on clinical outcomes, and compare findings with the TCGA-Uveal Melanoma (TCGA-UM) dataset to explore potential genetic differences.

Methods: Formalin-fixed paraffin-embedded (FFPE) tumour samples from 20 UM patients diagnosed between 2004 and 2018 were initially analysed using the OncoScan™ CNV Array to detect chromosomal aberrations, with 14 samples yielding valid results for cytogenetic analysis. BAP1 immunohistochemistry was performed on all 20 samples to assess BAP1 protein expression using automated immunostaining techniques validated in the Clinical Pathology Laboratory of the Singapore General Hospital.

In-lecture quizzes improve online learning for university and community college students.

Online classes are now integral to higher education, particularly for students at two-year community colleges, who are profoundly underrepresented in experimental research. Here, we provided a rigorous test of using interpolated retrieval practice to enhance learning from an online lecture for both university and community college students (N = 703). We manipulated interpolated activity (participants saw review slides or answered short quiz questions) and onscreen distractions (control, memes, TikTok).