Publications by authors named "Yvonne Ang"

Purpose: Scalp cooling therapy (SCT) improves chemotherapy-induced alopecia (CIA), but there are few published data about its efficacy in an Asian-predominant population. We report our tertiary institution experience of SCT in patients with breast or gynaecological cancers undergoing chemotherapy.

Methods: The Paxman scalp cooling system was employed for eligible women with breast or gynaecological cancers receiving anthracycline or taxane-based chemotherapy.

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Introduction: High grade astrocytic glioma (HGG) is a lethal solid malignancy with high recurrence rates and limited survival. While several cytotoxic agents have demonstrated efficacy against HGG, drug sensitivity testing platforms to aid in therapy selection are lacking. Patient-derived organoids (PDOs) have been shown to faithfully preserve the biological characteristics of several cancer types including HGG, and coupled with the experimental-analytical hybrid platform Quadratic Phenotypic Optimization Platform (QPOP) which evaluates therapeutic sensitivity at a patient-specific level, may aid as a tool for personalized medical decisions to improve treatment outcomes for HGG patients.

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Article Synopsis
  • Patients with advanced non-small-cell lung cancer (NSCLC) and brain metastases are often treated with osimertinib, but the effectiveness of adding stereotactic radiosurgery (SRS) is uncertain.
  • This study proposes a meta-analysis of existing trials to determine if SRS combined with osimertinib improves control of brain metastases compared to osimertinib alone.
  • The research will evaluate various outcomes, including intracranial progression-free survival and overall survival, and will be shared with the medical community and patients through publications and presentations.*
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Despite the efficacy of immunotherapy in non-small cell lung cancer (NSCLC), the majority of the patients experience relapse with limited subsequent treatment options. Preclinical studies of various epithelial tumors, such as melanoma and NSCLC, have shown that harnessing the gut microbiome resulted in improvement of therapeutic responses to immunotherapy. Is this review, we summarize the role of microbiome, including lung and gut microbiome in the context of NSCLC, provide overview of the mechanisms of microbiome in efficacy and toxicity of chemotherapies and immunotherapies, and address current ongoing clinical trials for NSCLC including fecal microbiota transplantation (FMT) and live biotherapeutic products (LBPs).

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Introduction: Lung cancer remains an important cause of cancer-related mortality in Singapore, with a greater proportion of non-smokers diagnosed with non-small cell lung cancer (NSCLC) in the past 2 decades. The higher prevalence of targetable genomic alterations in lung cancer diagnosed in Singapore compared with countries in the West, as well as the expanding therapeutic landscape for NSCLC in the era of precision medicine, are both factors that underscore the importance of efficient and effective molecular profiling.

Method: This article provides consensus recommendations for biomarker testing for early-stage to advanced NSCLC.

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Background: The importance of the number of brain metastases (BM) when deciding between whole brain radiation treatment (WBRT) and radiosurgery is controversial. We hypothesized that the number of BM is of limited importance when deciding radiation strategy, and offered Gamma Knife surgery (GKS) also for selected patients with 20 or more BM.

Methods: The outcome following single session GKS for 75 consecutive patients harboring 20 or more (20+) BM was analyzed.

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Epidermal growth factor receptor () T790M mutations drive resistance in 50% of patients with advanced non-small cell lung cancer (NSCLC) who progress on first/second generation (1G/2G) EGFR tyrosine kinase inhibitors (TKIs) and are sensitive to Osimertinib. Tissue sampling is the gold-standard modality of T790M testing, but it is invasive. We evaluated the efficacy of Osimertinib in patients with EGFR mutant NSCLC and T790M in circulating tumour DNA (ctDNA).

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  • The study investigates the effectiveness of trifluridine/tipiracil (FTD/TPI) in treating metastatic breast cancer (MBC) patients, both with and without prior exposure to fluoropyrimidines, via a phase II clinical trial.
  • A total of 74 patients were enrolled, showing median progression-free survival (PFS) of 5.7 months for those with prior exposure and 9.4 months for those without, with response rates observed in both groups.
  • The treatment demonstrated acceptable safety, with side effects like neutropenia and fatigue, and concluded that FTD/TPI is a promising option for MBC patients.
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Article Synopsis
  • The study investigated factors that predict primary resistance to immune checkpoint inhibitors (ICIs) in patients with advanced non-small-cell lung cancer (NSCLC), defining resistance as disease progression within 6 months of treatment.
  • Out of 108 patients, over half (54.6%) exhibited primary resistance, with notable demographics including a majority being male, smokers, and predominantly Chinese with adenocarcinoma.
  • Key predictive factors for resistance included being female, having a neutrophil-to-lymphocyte ratio (NLR) of 3 or higher at 6 weeks, and receiving immunotherapy as a later treatment line (≥2 lines).
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Objective: To identify the independent risk factors for 30-day perioperative seizures, as well as to evaluate the effect of perioperative seizures on overall mortality and tumor recurrence among patients who underwent surgical resection of brain metastases.

Methods: Patients who underwent surgical resection of brain metastases at our institution between 2011 and 2019 were included. 30-day perioperative seizures were defined as the presence of any preoperative or postoperative seizures diagnosed by a neurosurgeon or neurologist within 30 days of metastases resection.

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Background: Durvalumab consolidation is associated with improved survival following concurrent chemoradiotherapy (CCRT) in patients with stage III non-small cell lung cancer (NSCLC). Given the heterogeneity of stage III NSCLC patients, in this study we evaluated the efficacy and safety of durvalumab in the real-world setting.

Method: Unresectable stage III NSCLC patients were retrospectively studied: one cohort received CCRT, another had CCRT-durvalumab.

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Background: Adding intraperitoneal paclitaxel (IP-PTX) to paclitaxel/5-fluoropyrimidine has shown promising results in patients with gastric cancer peritoneal metastases (GCPM) but has not been studied with standard-of-care platinum/fluoropyrimidine combinations. Our goal to was evaluate IP-PTX with capecitabine/oxaliplatin (XELOX) in GCPM.

Methods: Forty-four patients with GCPM received IP PTX (40 mg/m, Days 1, 8), oral capecitabine (1000 mg/m twice daily, Days 1-14) and intravenous oxaliplatin (100 mg/m, Day 1) in 21-day cycles.

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Background: Breast cancers are heterogeneous with variable clinical courses and treatment responses.

Objective: We sought to evaluate dynamic changes in the molecular landscape of HER2-negative tumors treated with chemotherapy and anti-angiogenic agents.

Patients And Methods: Newly diagnosed HER2-negative breast cancer patients received low-dose sunitinib or bevacizumab prior to four 2-weekly cycles of dose-dense doxorubicin and cyclophosphamide.

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Purpose: RET is an estrogen response gene with preclinical studies demonstrating cross-talk between the RET and estrogen receptor (ER) pathways. We investigate the role of lenvatinib, a multikinase inhibitor with potent activity against RET, in patients with metastatic breast cancer.

Patients And Methods: Patients with advanced ER+/HER2- breast cancer were treated with lenvatinib plus letrozole in a phase Ib/II trial.

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Purpose: Tumor angiogenesis controlled predominantly by vascular endothelial growth factor and its receptor (VEGF-VEGFR) interaction plays a key role in the growth and propagation of cancer cells. However, the newly formed network of blood vessels is disorganized and leaky. Pre-treatment with anti-angiogenic agents can "normalize" the tumor vasculature allowing effective intra-tumoral delivery of standard chemotherapy.

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Introduction: Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC), and provides a target for a dendritic cell (DC) vaccine. CD137 ligand (CD137L) expressed on antigen presenting cells, costimulates CD137-expressing T cells, and reverse CD137L signaling differentiates monocytes to CD137L-DC, a type of DC, which is more potent than classical DC in stimulating T cells.

Methods: In this phase I study, patients with locally recurrent or metastatic NPC were administered CD137L-DC pulsed with EBV antigens (CD137L-DC-EBV-VAX).

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Immune-related adverse events (IrAEs) of immune checkpoint inhibitors (ICIs) can be serious and unpredictable. We examine the incidence rate and risk factors for IrAEs in an Asian cohort of nonsmall cell lung cancer (NSCLC) patients treated with immunotherapy. Between June 2014 and August 2020, we retrospectively analysed IrAEs in NSCLC patients treated with anti-PD-1 or anti-PD-L1 inhibitors at the National University Cancer Institute, Singapore.

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A dose of 200 mg 3-weekly of pembrolizumab was approved by the Food and Drug Administration (FDA) as treatment for advanced non-small cell lung cancer (NSCLC) without oncogenic drivers. This is despite evidence showing no difference in efficacy with 2 mg/kg. Our study aimed to assess the efficacy of a lower fixed dose of 100 mg, which is closer to 2 mg/kg weight-based dose in an average-sized Asian patient.

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Background: The approved doses of the single agent nivolumab - an anti-programmed cell death protein 1 (PD-1) monoclonal antibody - for renal cell carcinoma (RCC) are 3 mg/kg and a 240-mg flat dose, despite efficacy shown at lower doses in earlier CheckMate trials. In view of financial constraints, the minimum dose of nivolumab required for efficacy remains a critical area of inquiry.

Methods: A retrospective review of RCC patients receiving single-agent anti-PD-1 treatment was conducted.

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Background: We previously reported that low-dose, short-course sunitinib prior to neoadjuvant doxorubicin-cyclophosphamide (AC) normalised tumour vasculature and improved perfusion, but resulted in neutropenia and delayed subsequent cycles in breast cancer patients. This study combined sunitinib with docetaxel, which has an earlier neutrophil nadir than AC.

Methods: Patients with advanced solid cancers were randomized 1:1 to 3-weekly docetaxel 75 mg/m, with or without sunitinib 12.

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Background: The importance of immune-checkpoint inhibitors (ICI) can no longer be understated since its move to front-line treatment in non-small cell lung cancer (NSCLC) in recent years. However, the safety and efficacy of ICI in special populations such as those with infections like tuberculosis (TB) and hepatitis B (HBV) remain unknown as they are routinely excluded from clinical trials.

Methods: Records of patients with advanced NSCLC who were treated with ICI from January 2014 to June 2019 at a single Asian centre were reviewed.

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Introduction: Lorlatinib, a next-generation central nervous system-penetrant ALK/ROS1 tyrosine kinase inhibitor (TKI), is approved to treat TKI-refractory ALK-positive (ALK+) NSCLC based on results from a phase 2 study.

Methods: A real-world analysis was performed on ALK+ or ROS1-positive (ROS1+) patients with NSCLC enrolled in lorlatinib early or expanded access programs in Hong Kong, Singapore, South Korea, Taiwan, Thailand, and the United States.

Results: A total of 95 patients with NSCLC (76 ALK+ and 19 ROS1+) were analyzed.

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