Publications by authors named "Gregory P Kalemkerian"

Article Synopsis
  • This clinical trial aimed to improve treatment outcomes for patients with locally advanced non-small cell lung cancer (NSCLC) by using adaptive radiation therapy that tailors the treatment based on the patient's response, while minimizing side effects like lung and esophageal toxicity.
  • A total of 47 patients participated, receiving personalized radiation doses based on imaging techniques (FDG-PET and SPECT) to maximize the dose to the tumor while sparing healthy lung tissue.
  • Results showed manageable toxicity levels after one year, with 21.3% experiencing grade 2 pneumonitis and 66.0% grade 2 esophagitis, while striving for better local control and overall survival.
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Background: Postimmunotherapy (IO) treatment options for stage IV non-small-cell lung cancer (NSCLC) remain limited. Docetaxel alone or in combination with ramucirumab remains a standard of care, but response rates and survival benefit are suboptimal. Cullin-RING ligases (CRL) catalyze degradation of tumor suppressor proteins and are overactivated in NSCLC.

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Introduction: In the phase 3 KEYNOTE-604 study (NCT03066778), pembrolizumab plus etoposide and platinum chemotherapy (EP) significantly ( = 0.0023) improved progression-free survival versus placebo plus EP in previously untreated extensive-stage SCLC (ES-SCLC). We present health-related quality of life (HRQoL) results from KEYNOTE-604.

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Purpose: To provide evidence-based recommendations to practicing clinicians on the management of patients with small-cell lung cancer.

Methods: An Expert Panel of medical oncology, thoracic surgery, radiation oncology, pulmonary, community oncology, research methodology, and advocacy experts were convened to conduct a literature search, which included systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2022. Outcomes of interest included response rates, overall survival, disease-free survival or recurrence-free survival, and quality of life.

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Background:: Malignant pleural mesothelioma (MPM) is a disease for which there remains an unmet need for better therapeutic options. Nintedanib is an oral multikinase inhibitor impacting VEGF, FGF, PDGFR, and other kinase activity such as TGFß signaling pathways. We conducted a phase II trial of nintedanib in patients with recurrent MPM.

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Introduction: Improving the clinical outcomes of patients with -mutated non-small cell lung cancer (NSCLC), the majority of whom are current or former smokers, has been a barrier to improving population-level outcomes in NSCLC. Novel and effective inhibitors are emerging, and sotorasib is the first member of that class to achieve commercial availability.

Areas Covered: In this review, we survey the epidemiology of -mutated NSCLC, as well as sotorasib's chemistry, pharmacology, and clinical trial data.

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Article Synopsis
  • Oncogenic RET fusions are found in various cancers, and pralsetinib is a selective drug targeting the RET receptor tyrosine kinase designed to treat these cases.
  • The ongoing ARROW trial enrolled 29 patients with advanced RET fusion-positive solid tumors, excluding non-small-cell lung and thyroid cancers, who had not responded to standard treatments.
  • The study showed a 57% overall response rate, with median responses lasting 12 months, and identified manageable side effects like neutropenia and anemia, suggesting pralsetinib could be an effective treatment for a range of RET-altered cancers.
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Article Synopsis
  • Immune checkpoint inhibitors (ICI), particularly anti-PD-1/PD-L1 agents, significantly enhance survival rates in patients with metastatic non-small cell lung cancer (mNSCLC), although tumor PD-L1 expression alone is not a reliable indicator of treatment response.
  • Researchers used multiplex fluorescent immunohistochemistry (mfIHC) to assess the tumor microenvironment (TME) in 68 samples from 52 mNSCLC patients, finding specific cellular interactions crucial for predicting ICI response.
  • The study discovered that lower levels of cytotoxic T lymphocyte (CTL) engagement with epithelial tumor cells (EC) and helper T lymphocytes (HTL), alongside reduced PD-L1 expression in EC, were strong predictors of non-response to
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Background: Bone metastases and skeletal-related events (SREs) are a frequent cause of morbidity in patients with metastatic non-small cell lung cancer (mNSCLC). Data are limited on bone metastases and SREs in patients with mNSCLC treated using immune checkpoint inhibitors (ICIs), and on the efficacy of bone-modifying agents (BMAs) in this setting. Here we report the incidence, impact on survival, risk factors for bone metastases and SREs, and impact of BMAs in patients with mNSCLC treated with ICIs in a multi-institutional cohort.

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Background: Lung cancer death rates and incidence in both men and women have decreased over the past two decades. However, certain subsets of non-small cell lung cancer (NSCLC) have arisen with poor outcomes. Identifying factors which contribute to poorer outcomes as well as those that inform early detection strategies remain unmet needs.

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Introduction: Small cell lung cancer (SCLC) is an aggressive malignancy that accounts for 15% of all lung cancers. It is characterized by initial responsiveness to therapy followed by rapid disease progression that is relatively resistant to further treatment. Recently, the addition of an immune checkpoint inhibitor (ICI) to chemotherapy has improved survival in patients with advanced disease, the first advance in systemic therapy in SCLC in over 30 years.

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Purpose: Pembrolizumab monotherapy has shown antitumor activity in patients with small-cell lung cancer (SCLC). The randomized, double-blind, phase III KEYNOTE-604 study compared pembrolizumab plus etoposide and platinum (EP) with placebo plus EP for patients with previously untreated extensive-stage (ES) SCLC.

Methods: Eligible patients were randomly assigned 1:1 to pembrolizumab 200 mg once every 3 weeks or saline placebo for up to 35 cycles plus 4 cycles of EP.

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Introduction: Cyclin-dependent kinases (CDKs) are critical regulators of cell cycle progression in both normal and malignant cells, functioning through complex molecular interactions. Deregulation of CDK-dependent pathways is commonly found in both non-small cell and small cell lung cancer, and these derangements suggest vulnerabilities that can be exploited for clinical benefit.

Areas Covered: In this review, the authors present an overview of the biology of CDKs in normal and malignant cells, with a focus on lung cancer, followed by an assessment of preclinical work that has demonstrated the vital role of CDKs in lung cancer development and progression, and the activity of CDK inhibitors in a variety of lung cancer models.

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(1) Background: Circulating tumor cell (CTC) clusters are emerging as clinically significant harbingers of metastases in solid organ cancers. Prior to engaging these CTC clusters in animal models of metastases, it is imperative for technology to identify them with high sensitivity. These clusters often present heterogeneous surface markers and current methods for isolation of clusters may fall short.

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Purpose: Preclinical data and subset analyses from immunotherapy clinical trials indicate that prior radiation therapy was associated with better progression-free survival and overall survival when combined with immune checkpoint inhibitors in patients with non-small cell lung cancer. We present a prospective study of hypofractionated image guided radiation therapy (HIGRT) to a single site of metastatic disease concurrently with atezolizumab in patients with metastatic non-small cell lung cancer.

Methods And Materials: Patients meeting eligibility criteria received 1200 mg of atezolizumab intravenously every 3 weeks with concurrent 3- or 5-fraction HIGRT starting no later than the second cycle.

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Purpose: Immunotherapy is a relatively new treatment modality for advanced non-small cell lung cancer following platinum-based chemotherapy. Nivolumab, pembrolizumab, and atezolizumab demonstrated superior outcomes and improved tolerability compared to standard treatment in randomized controlled trials; however, these studies vary significantly in inclusion criteria and study design. To our knowledge, the efficacy and safety of nivolumab and atezolizumab following platinum-based chemotherapy have not been directly compared to one another in a real-world clinic setting.

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Purpose: Radiation-induced cardiac toxicity (RICT) is an increasingly well-appreciated source of morbidity and mortality in patients receiving thoracic radiotherapy (RT). Currently available methods to predict RICT are suboptimal. We investigated circulating microRNAs (c-miRNAs) as potential biomarkers of RICT in patients undergoing definitive RT for non-small-cell lung cancer (NSCLC).

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Background And Purpose: Higher cardiac dose was associated with worse overall survival in the RTOG0617 study. Pericardial effusion (PCE) is a common cardiac complication of thoracic radiation therapy (RT). We investigated whether doses of radiation to the heart and pericardium are associated with PCE and overall survival in patients treated with thoracic radiation for non-small cell lung cancer (NSCLC).

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: Almost all patients with EGFR-driven lung cancer who are treated with EGFR tyrosine kinase inhibitors (TKI) develop resistance to treatment. A single base (c.2369C>T) transition mutation, T790M, is the most frequent resistance event after first-generation exposure to EGFR TKIs.

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The NCCN Guidelines for Small Cell Lung Cancer (SCLC) address all aspects of disease management. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for SCLC regarding immunotherapy, systemic therapy, and radiation therapy. For the 2018 update, new sections were added on "Signs and Symptoms of SCLC" and "Principles of Pathologic Review.

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The NCCN Guidelines for Neuroendocrine and Adrenal Tumors provide recommendations for the management of adult patients with neuroendocrine tumors (NETs), adrenal gland tumors, pheochromocytomas, and paragangliomas. Management of NETs relies heavily on the site of the primary NET. These NCCN Guidelines Insights summarize the management options and the 2018 updates to the guidelines for locoregional advanced disease, and/or distant metastasis originating from gastrointestinal tract, bronchopulmonary, and thymus primary NETs.

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