Publications by authors named "Catherine Shu"

Introduction: Asian American, Native Hawaiian, and Pacific Islander (AANHPI) people represent one of the largest and most rapidly growing groups in the United States and are often aggregated as a homogeneous, rather than diverse, population in medical research and education. Currently, few educational interventions focus on the disaggregation of AANHPI patient populations and the improvement of knowledge about health disparities that affect AANHPI patients.

Methods: We developed, implemented, and facilitated a workshop for medical students to address AANHPI health disparities, adaptable for in-person and online formats.

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Introduction: Treatment options for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with disease progression on/after osimertinib and platinum-based chemotherapy are limited.

Methods: CHRYSALIS-2 Cohort A evaluated amivantamab+lazertinib in patients with EGFR exon 19 deletion- or L858R-mutated NSCLC with disease progression on/after osimertinib and platinum-based chemotherapy. Primary endpoint was investigator-assessed objective response rate (ORR).

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Introduction: Neoadjuvant chemoimmunotherapy has achieved overall survival (OS) benefit for patients with resectable non-small cell lung cancer (NSCLC). Here, we present outcomes after 3 years of follow-up from the first reported study of neoadjuvant atezolizumab+chemotherapy.

Methods: This open-label, multicenter single-arm investigator-initiated phase II study conducted at three US hospitals tested up to four cycles of atezolizumab, carboplatin, and nab-paclitaxel prior to surgery.

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Background: Cachexia is characterized by weight loss and decline in muscle mass and function and is a poor prognostic factor among patients with cancer. Patients with metastatic EGFR-mutant non-small cell lung cancer (NSCLC) derive remarkable survival benefits with osimertinib, a third-generation EGFR tyrosine kinase inhibitor. It is not known whether patients treated with osimertinib experience any weight loss or whether weight loss impacts patient outcomes.

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Article Synopsis
  • Dual immune checkpoint blockade (ICB) using CTLA4 and PD-(L)1 inhibitors shows improved anti-tumor effectiveness and immune toxicity compared to PD-(L)1 inhibitors alone in advanced non-small-cell lung cancer (NSCLC) patients.
  • Patients with mutations in STK11 and/or KEAP1 genes benefit more from the combination treatment compared to those receiving only PD-(L)1 inhibitors, as shown in the POSEIDON trial.
  • The loss of KEAP1 serves as a strong predictor for the success of dual ICB, as it leads to a more favorable outcome by changing the tumor's immune environment to better engage CD4 and CD8 T cells for anti-tumor activity. *
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  • Scientists found that using two medications together, one that stops cancer and another that helps blood vessels, can help people with a certain type of lung cancer live longer without their cancer getting worse.
  • They ran a study (called the RAMOSE trial) comparing one medication plus the blood vessel helper to just the medication alone.
  • The results showed that people taking both medications had better outcomes, living longer without cancer progression, even though both groups experienced side effects from the treatments.
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  • Amivantamab is an antibody approved for advanced non-small cell lung cancer with specific genetic variants, but it often causes skin-related side effects due to its effects on the epidermal growth factor receptor (EGFR).
  • A study analyzed how often and severely patients experienced these skin issues, focusing on conditions like rash and paronychia, after their disease progressed on platinum chemotherapy.
  • Out of 380 patients studied, a significant 78% experienced skin-related side effects, with paronychia and various rashes being the most common; healthcare providers worked together to manage these issues through dose adjustments and patient education.
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The spectrum of clinical and radiographic presentations of lung adenocarcinoma is increasingly broad, including in the metastatic setting. Here, we report on a patient who initially presented with a mild chronic cough that remained stable over a decade, with serial CT scans showing gradual worsening of multifocal areas of consolidation and ground-glass opacities of the bilateral lungs. The patient was ultimately diagnosed with rearranged lung adenocarcinoma and achieved a dramatic response with entrectinib.

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Purpose: Newer-generation tyrosine kinase inhibitors (TKIs) for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor () mutations and anaplastic lymphoma kinase () rearrangements have demonstrated high CNS activity. The optimal use of up-front stereotactic radiosurgery (SRS) for brain metastases (BM) in patients eligible for CNS-penetrant TKIs is controversial, and data to guide patient management are limited.

Materials And Methods: Data on TKI-naïve patients with EGFR- and ALK-driven NSCLC with BM treated with CNS-penetrant TKIs with and without up-front SRS were retrospectively collected from seven academic centers in the United States.

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  • Amivantamab-vmjw is a bispecific antibody approved for treating advanced non-small cell lung cancer (NSCLC) with EGFR exon 20 mutations, but its safety and efficacy in other EGFR mutations, especially when used with other therapies, are less understood.
  • A study analyzed data from multiple cancer centers for 61 NSCLC patients treated with amivantamab, focusing on factors like response rates, safety, and treatment duration alongside existing therapies.
  • Results indicated that 45.2% of patients had a clinical response, with higher success rates in atypical mutation cohorts, and adverse events were consistent with previous findings, suggesting amivantamab's potential effectiveness even in various EGFR mutations when combined with other treatments.
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Introduction: Pathologic response has been proposed as an early clinical trial end point of survival after neoadjuvant treatment in clinical trials of NSCLC. The International Association for the Study of Lung Cancer (IASLC) published recommendations for pathologic evaluation of resected lung cancers after neoadjuvant therapy. The aim of this study was to assess pathologic response interobserver reproducibility using IASLC criteria.

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Novel targeted therapy and immunotherapy drugs have recently been approved for use in patients with surgically resectable lung cancer. Accurate staging, early molecular testing, and knowledge of recent trials are critical to optimize oncologic outcomes in these patients.

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  • A study analyzed 424 patients with KRASG12C-mutant non-small cell lung cancer (NSCLC) and identified key genomic alterations (in KEAP1, SMARCA4, and CDKN2A) that lead to worse outcomes with KRASG12C inhibitors (KRASG12Ci).
  • These alterations allowed researchers to classify patients into different prognostic groups, indicating nearly 50% of those who experienced early disease progression.
  • The research suggests potential pathways not only associated with poor response (like PI3K/AKT/MTOR) but also hints that certain DNA damage response issues might improve KRASG12Ci effectiveness, paving the way for personalized treatment strategies.
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Unlabelled: Predicting in vivo response to antineoplastics remains an elusive challenge. We performed a first-of-kind evaluation of two transcriptome-based precision cancer medicine methodologies to predict tumor sensitivity to a comprehensive repertoire of clinically relevant oncology drugs, whose mechanism of action we experimentally assessed in cognate cell lines. We enrolled patients with histologically distinct, poor-prognosis malignancies who had progressed on multiple therapies, and developed low-passage, patient-derived xenograft models that were used to validate 35 patient-specific drug predictions.

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The advent of immune checkpoint inhibition has pushed the treatment paradigm for resectable non-small-cell lung cancer (NSCLC) toward neoadjuvant therapy. A growing number of promising trials have examined the utility of neoadjuvant immunotherapy, both alone and in combination with other modalities such as radiation therapy (RT) and chemotherapy. The phase II LCMC3 and NEOSTAR trials demonstrated a role for neoadjuvant immunotherapy in inducing meaningful pathologic responses, and another phase II trial established the feasibility of combining neoadjuvant durvalumab with RT.

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Background: Amivantamab, a fully humanized EGFR-MET bispecific antibody, has antitumor activity in diverse EGFR- and MET-driven non-small cell lung cancer (NSCLC) and a safety profile consistent with associated on-target activities. Infusion-related reaction(s) (IRR[s]) are reported commonly with amivantamab. We review IRR and subsequent management in amivantamab-treated patients.

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BRAF/MEK inhibition remains standard of care for treatment of BRAF-mutated non-small cell lung cancer (NSCLC). Although common adverse events (AEs) have been reported through clinical trials and ongoing clinical practice, only a handful of reports have detailed unusual adverse events associated with these medications. This report presents a patient with BRAF-mutated NSCLC treated with dabrafenib and trametinib who experienced 2 unusual AEs-Sweet syndrome and MEK-associated retinopathy-that responded to steroid treatment.

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Introduction: CD73 is overexpressed in EGFR-mutated NSCLC and may promote immune evasion, suggesting potential for combining CD73 blockers with EGFR tyrosine kinase inhibitors (TKIs). This phase 1b-2 study (NCT03381274) evaluated the anti-CD73 antibody oleclumab plus the third-generation EGFR TKI osimertinib in advanced EGFR-mutated NSCLC.

Methods: Patients had tissue T790M-negative NSCLC with TKI-sensitive EGFR mutations after progression on a first- or second-generation EGFR TKI and were osimertinib naive.

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Treatment with immune checkpoint blockade (ICB) often fails to elicit durable antitumor immunity. Recent studies suggest that ICB does not restore potency to terminally dysfunctional T cells, but instead drives proliferation and differentiation of self-renewing progenitor T cells into fresh, effector-like T cells. Antitumor immunity catalyzed by ICB is characterized by mobilization of antitumor T cells in systemic circulation and tumor.

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The efficacy of neoadjuvant treatment for NSCLC can be pathologically assessed in resected tissue. Major pathologic response (MPR) and pathologic complete response (pCR), defined as less than or equal to 10% and 0% viable tumor cells, respectively, are increasingly being used in NSCLC clinical trials to establish them as surrogate end points for efficacy to shorten time to outcome. Nevertheless, sampling and MPR calculation methods vary between studies.

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Unlabelled: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib has significantly prolonged progression-free survival (PFS) in patients with EGFR-mutant lung cancer, including those with brain metastases. However, despite striking initial responses, osimertinib-treated patients eventually develop lethal metastatic relapse, often to the brain. Although osimertinib-refractory brain relapse is a major clinical challenge, its underlying mechanisms remain poorly understood.

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Introduction: The 2018 updated molecular testing guidelines for patients with advanced lung cancer incorporated immunohistochemistry (IHC) analysis as an equivalent to fluorescence in situ hybridization (FISH) method recommended in 2013. Nevertheless, no specific recommendation for alternative methods was proposed owing to insufficient data. The aim of this study was to compare the results of IHC, FISH, RNA next-generation sequencing (NGS), and RNA in situ hybridization (ISH) with available clinical data.

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Hepatoid adenocarcinoma of the lung (HAL) is a rare extrahepatic tumor characterized by histologic features of hepatocellular carcinoma. The standard treatment for nonresectable HAL has not been established, though traditionally, these tumors have been treated with platinum-based chemotherapy. Here, we report the use of combination chemotherapy and immunotherapy in a patient presenting with metastatic HAL and an elevated alpha-fetoprotein.

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