Publications by authors named "Heather Wakelee"

Background: Thymic epithelial tumors (TETs), including thymoma and thymic carcinoma, are rare thoracic tumors of the anterior mediastinum. For those with advanced disease, platinum-based chemotherapy is used as first-line treatment. However, there is no standard regimen established for TET at progression after initial therapy, and treatment options for advanced/recurrent TETs are limited.

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Progressive leptomeningeal metastases (LM) are associated with intractable neurological symptoms and a poor prognosis, and effective treatment options are limited. Intrathecal (IT) pemetrexed has been shown to confer clinical benefit in lung adenocarcinoma, yet our understanding of the efficacy and safety of the treatment is limited. We report a patient with a long-standing history of leptomeningeal disease due to ALK-positive adenocarcinoma of the lung, previously controlled by increased doses of lorlatinib (125 mg/day).

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  • A study investigated the safety and efficacy of combining regorafenib and low-dose methotrexate for patients with advanced -mutant NSCLC, as there are limited treatment options available beyond G12C inhibitors.
  • The study included 18 patients, revealing a median progression-free survival of 3.7 months and a median overall survival of 10.4 months, with a 16.7% objective response rate.
  • The treatment caused notable toxicity, leading to dose adjustments and discontinuations; consequently, the study did not meet its primary goal of improving progression-free survival.
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  • Lung cancer is a major cause of death among Asian American females, including those from Chinese, Korean, Japanese, and Vietnamese backgrounds, even though smoking rates in this group are low.
  • Over 80% of Asian American females diagnosed with lung cancer have never smoked, contradicting general smoking-related lung cancer trends, and rates in non-smokers seem to be on the rise.
  • Key risk factors for lung cancer in this demographic include family history, pre-existing lung conditions, exposure to cooking fumes and second-hand smoke, and unique genetic mutations, indicating a need for further research tailored to this population.
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  • 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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Purpose: For metastatic non-small cell lung cancer, the addition of radiation therapy (RT) to immune checkpoint inhibitor (ICI) therapy could have synergistic anti-cancer effects and address the most threatening tumors. We posited that the addition of high-dose RT to ICI could prolong progression-free survival (PFS).

Methods And Materials: In this single-arm phase 2 trial, 45 patients with metastatic non-small cell lung cancer who had received an anti-PD-1/anti-PD-L1 ICI for 4+ weeks were enrolled from July 2017 to May 2021.

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Objective: Long-term breast cancer (BC) survivors are known to develop second malignancies, with second primary lung cancer (SPLC) one common type. Smoking was identified as a main risk factor for SPLC among BC survivors. These findings were limited to the U.

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  • The KEYNOTE-671 trial showed that adding pembrolizumab to neoadjuvant chemotherapy significantly enhanced event-free survival in patients with early-stage non-small-cell lung cancer (NSCLC).
  • The trial involved randomizing nearly 800 participants across 189 medical centers, comparing treatment with pembrolizumab plus chemotherapy against a placebo plus chemotherapy.
  • Results indicated that after 36 months, overall survival was higher in the pembrolizumab group (71%) compared to the placebo group (64%), suggesting a positive impact of the immunotherapy.
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Introduction: Patients with advanced ALK-positive NSCLC typically have poor response to immunotherapy; the benefit of consolidation durvalumab in patients with unresectable stage III ALK-positive NSCLC remains unclear. Herein, we compare the efficacy and safety of consolidation ALK tyrosine kinase inhibitor (TKI) versus durvalumab or observation after concurrent chemoradiation.

Methods: We conducted a retrospective study using a multicenter study of 17 institutions globally.

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Lung cancer is the leading cause of cancer death in the US and globally. The mortality from lung cancer has been declining, due to a reduction in incidence and advances in treatment. Although recent success in developing targeted and immunotherapies for lung cancer has benefitted patients, it has also expanded the complexity of potential treatment options for health care providers.

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  • Recent advancements in lung cancer treatments have led to increased survival rates for patients, but a higher risk of second primary lung cancer (SPLC) is now a concern, particularly in Hispanic populations whose SPLC risk remains unclear.
  • Using a dataset from the Multiethnic Cohort followed over several years, the study discovered that although Hispanics had a lower initial lung cancer incidence compared to Whites and Blacks, they exhibited a higher SPLC incidence following initial lung cancer diagnosis.
  • The findings indicate that Hispanics have a significantly higher SPLC incidence rate, likely due to better survival after initial lung cancer, prompting the need for ongoing monitoring to address racial disparities in lung cancer outcomes.
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  • - The study examined genomic alterations in non-small cell lung cancer (NSCLC) across a large sample of over 75,000 patients in the US and compared findings with a Japanese cohort to identify differences based on race, sex, and age.
  • - Significant variations in genetic alterations were observed: for example, EGFR mutations were more common in East Asian patients, while ALK mutations were prevalent in Admixed American, East Asian, and South Asian groups compared to others.
  • - Additionally, the analysis showed clear distinctions in mutation prevalence linked to sex and age, with certain mutations like EGFR and ALK being more frequent in females, while mutations such as TP53 and KEAP1 were more common in males; older patients
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Background: Prior research in non-small cell lung cancer (NSCLC) has shown that tumors with specific driver mutations may be less likely to respond to immune checkpoint inhibitors (ICI). In this analysis, we evaluated the characteristics of patients with durable clinical benefit (DCB) to ICI compared to those with no durable clinical benefit (NDB), with emphasis on the role of molecular alterations in EGFR, ALK, and ROS1 and pretreatment neutrophil-to-lymphocyte ratio (NLR).

Methods: We retrospectively collected clinical characteristics and outcomes for patients who initiated ICI monotherapy for advanced NSCLC at Stanford University between April 2015 and May 2018.

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Advances in the multidisciplinary care of early stage resectable NSCLC (rNSCLC) are emerging at an unprecedented pace. Numerous phase 3 trials produced results that have transformed patient outcomes for the better, yet these findings also require important modifications to the patient treatment journey trajectory and reorganization of care pathways. Perhaps, most notably, the need for multispecialty collaboration for this patient population has never been greater.

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Emerging data supporting the rise of perioperative immune checkpoint inhibitors (ICIs) as a standard of care in the treatment of early stage, surgically resectable non-small cell lung cancer (NSCLC) dominated the NSCLC news in 2023. Adjuvant pembrolizumab became the second adjuvant ICI to receive US Food and Drug Administration approval in early 2023 after the 2021 approval of adjuvant atezolizumab and the 2022 approval of neoadjuvant nivolumab with chemotherapy. Subsequently in 2023, multiple phase 3 trials examining perioperative ICIs were positive and demonstrated clinically meaningful outcomes by prolonging event-free survival, improving pathologic complete response rates, and trending toward improved overall survival in most.

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Purpose: Immune checkpoint inhibitors (ICI) used as cancer therapy have been associated with a range of cardiac immune-related adverse events (irAEs), including fulminant myocarditis with a high case fatality rate. Early detection through cardiotoxicity screening by biomarker monitoring can lead to prompt intervention and improved patient outcomes. In this study, we investigate the association between cardiotoxicity screening with routine serial troponin I monitoring in asymptomatic patients receiving ICI, cardiovascular adverse event (CV AE) detection, and overall survival (OS).

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Introduction: Targeting the tumor microenvironment may enhance response to immunotherapy (immune checkpoint inhibitors) and improve outcomes for patients. This study tested the safety and efficacy of vorolanib, a novel tyrosine kinase inhibitor of vascular endothelial growth factor, platelet-derived growth factor, and c-KIT, in combination with programmed cell death protein 1 blockade using nivolumab for refractory thoracic malignancies.

Methods: This single-arm multicenter study enrolled patients with extensive-stage SCLC, thymic carcinoma, and NSCLC, either naive or had progressed on previous chemotherapy or immune checkpoint inhibitors (either primary or acquired resistance).

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Introduction: Durvalumab improves survival when used as consolidation therapy after chemoradiation (CRT) in patients with stage III NSCLC. The optimal consolidation therapy for patients with EGFR-mutant (EGFRmut) stage III NSCLC remains unknown.

Methods: In this multi-institutional, international retrospective analysis across 24 institutions, we evaluated outcomes in patients with stage III EGFRmut NSCLC treated with concurrent CRT followed by consolidation therapy with osimertinib, durvalumab, or observation between 2015 and 2022.

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Malignant pleural effusions (MPEs) can be utilized as liquid biopsy for phenotyping malignant cells and for precision immunotherapy, yet MPEs are inadequately studied at the single-cell proteomic level. Here we leverage mass cytometry to interrogate immune and epithelial cellular profiles of primary tumors and pleural effusions (PEs) from early and late-stage non-small cell lung cancer (NSCLC) patients, with the goal of assessing epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) states in patient specimens. By using the EMT-MET reference map PHENOSTAMP, we observe a variety of EMT states in cytokeratin positive (CK+) cells, and report for the first time MET-enriched CK+ cells in MPEs.

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Purpose/objectives: Adoption of hypofractionated accelerated radiation therapy (HART) with concurrent chemotherapy has been limited by toxicity concerns. We aimed to describe outcomes of patients treated with HART and concurrent chemotherapy and to evaluate dosimetry to organs at risk to guide patient selection.

Materials/methods: We evaluated a retrospective cohort of NSCLC patients treated with concurrent chemotherapy with HART (>2.

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Introduction: Prior attempts to escalate radiation dose for non-small cell lung cancer (NSCLC) have not improved survival. Given the high risk for cardiopulmonary toxicity with treatment and heterogenous presentation of locally advanced NSCLC, it is unlikely that a single dose regimen is optimal for all patients. This phase I/II trial aims to evaluate a novel treatment approach where the level of accelerated hypofractionation is determined by the predicted toxicity from dose to organs at risk (OARs).

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Article Synopsis
  • 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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Background: Patients with thoracic malignancies who develop COVID-19 infection have a higher hospitalization rate compared to the general population and to those with other cancer types, but how this outcome differs by race and ethnicity is relatively understudied.

Methods: The TERAVOLT database is an international, multi-center repository of cross-sectional and longitudinal data studying the impact of COVID-19 on individuals with thoracic malignancies. Patients from North America with thoracic malignancies and confirmed COVID-19 infection were included for this analysis of racial and ethnic disparities.

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