Incidentally Discovered Endocarditis Leading to the Diagnosis of an Epidermal Growth Factor Receptor Mutant Metastatic Pulmonary Malignancy of Occult Primary Tumor.

Introduction: Non-bacterial thrombotic endocarditis is well documented in the literature to occur in patients with known malignancies. It is, however, much less common for patients to be diagnosed with marantic endocarditis as the presenting sign of an unknown primary malignancy. Case Presentation: We discuss a case in which a patient was undergoing routine surveillance for his known heart failure with a transthoracic echocardiogram when an aortic valve vegetation was discovered. After further investigation, he was found to have metastatic adenocarcinoma of the lung. Next-generation sequencing was utilized to identify an EGFR mutation, which led to the patient being treated with osimertinib. Conclusion: Adequate treatment of his primary malignancy, along with anticoagulation, led to overall clinical improvement of the patient.

Predictive risk score for isolated brain metastasis in non-small cell lung cancer.

Background: Brain metastasis is common with non-small cell lung cancer (NSCLC). Patients with some early-stage cancers don't benefit from routine brain imaging. Currently clinical stage alone is used to justify additional brain imaging. Other clinical and demographic characteristics may be associated with isolated brain metastasis (IBM). We aimed to define the most salient clinical features associated with synchronous IBM, hypothesizing that clinical and demographic factors could be used to determine the risk of brain metastasis. Methods: The National Cancer Database was used to identify patients with NSCLC from 2016-2020. Primary outcome was the presence of IBM relative to patients without evidence of any metastasis. Cohorts were divided into test and validation. The test cohort was used to identify risk factors for IBM using multivariable logistic regression. Using the regression, a scoring system was created to estimate the rate of synchronous IBM. The accuracy of the scoring system was evaluated with receiver operating characteristic (ROC) analysis using the validation cohort. Results: Study population consisted of 396,113 patients: 25,907 IBM and 370,206 without metastatic disease. IBM was associated with age, clinical T stage, clinical N stage, Charlson/Deyo comorbidity score, histology, and grade. A scoring system using these factors showed excellent accuracy in the test and validation cohort in ROC analysis (0.806 and 0.805, respectively). Conclusions: Clinical and demographic characteristics can be used to stratify the risk of IBM among patients with NSCLC and provide an evidence-based method to identify patients who require dedicated brain imaging in the absence of other metastatic disease.

A Pilot Trial of Proton Based Cardiac Sparing Accelerated Fractionated RadioTherapy in Unresectable Non-Small Cell Lung Cancer with Extended Durvalumab Therapy (PARTICLE-D).

PURPOSE: Concurrent chemoradiotherapy is the current non-surgical standard of care for locally advanced non-small cell lung cancer (NSCLC). However, this is a difficult regimen to tolerate especially for those who are elderly, have multiple comorbidities or poor performance status. Alternative treatment regimens are needed for this vulnerable population. We report initial results of concurrent durvalumab, an immune checkpoint inhibitor, and hypofractionated, dose-escalating, proton external beam radiotherapy (EBRT). PATIENTS AND METHODS: This phase I, pilot dose-escalation trial enrolled seven patients with newly diagnosed stage IIIA-IIIC NSCLC who were unable or unwilling to undergo concurrent chemoradiotherapy. Patients previously treated with immunotherapy were excluded. Five patients in the initial phase of this 3+3 study design received a fixed dose of durvalumab each 28-day cycle plus hypofractionated proton EBRT 60 Gy in 20 fractions while two patients received the escalation dose of 69 Gy in 23 fractions. The primary objective assessed safety while secondary objectives assessed feasibility and adverse events. RESULTS: All patients experienced treatment-related adverse events, primarily grades 1-2. Pneumonitis and anemia were the most common. Only one dose limiting toxicity occurred, in arm one, which was a grade 3 pneumonitis leading to grade 5 pneumonia. Additionally, two delayed-onset grade 5 tracheal necrosis events occurred > 13 months after treatment initiation. CONCLUSIONS: Concurrent durvalumab plus hypofractionated proton EBRT was well tolerated in the short term. However, three treatment-related deaths, including two delayed-onset grade 5 tracheal necroses negatively impacted overall safety. A dose de-escalation protocol of proton-based radiotherapy plus durvalumab is warranted.

Racial and Ethnic Characteristics and Outcomes of Patients Diagnosed with CLL/SLL in the USA.

INTRODUCTION: This study was designed to compare outcomes among patients by race and ethnicity in the post-covalent Bruton tyrosine kinase inhibitor (cBTKi) treatment era. METHODS: A nationwide electronic health record (EHR)-derived de-identified database was utilized that included patients diagnosed with CLL from 2013 to 2022 who received systemic therapy for their disease. Use of cBTKi therapy, time to next treatment or death (TTNT-D), and overall survival (OS) were compared by race in unadjusted (Kaplan-Meier method) and adjusted analyses (Cox proportional hazards regression). RESULTS: This study included 4,572 White (71.8%) and 558 Black (8.8%) patients with CLL; 270 were Hispanic or Latino (4.2%). Patients who were Black were significantly younger, more were female, had later stage disease, were of lower socioeconomic status (SES), and were more likely to have unmutated immunoglobulin heavy chain gene (IGHV) and to have received cBTKi therapy than White patients (all p ≤ 0.002). SES was also significantly different by ethnicity. TTNT-D and OS were not different by race in either unadjusted or adjusted analyses (all p > 0.05). CONCLUSION: In unadjusted and adjusted analyses, TTNT-D and OS were not different by race. These data did not identify racial healthcare disparities in the era following the introduction of cBTKi therapy despite differences in baseline characteristics.

Non-Small Cell Lung Cancer, Version 4.2024, NCCN Clinical Practice Guidelines in Oncology

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommendations for the treatment of patients with NSCLC, including diagnosis, primary disease management, surveillance for relapse, and subsequent treatment. The panel has updated the list of recommended targeted therapies based on recent FDA approvals and clinical data. This selection from the NCCN Guidelines for NSCLC focuses on treatment recommendations for advanced or metastatic NSCLC with actionable molecular biomarkers.

Impact of Clinical Trial Design on Recruitment of Racial and Ethnic Minorities.

Knowledge related to how oncology treatment trial design influences enrollment of racial and ethnic minorities is limited. Rigorous identification of clinical trial design parameters that associate favorably with minority accrual provides educational opportunities for individuals interested in designing more representative treatment trials. We identified oncology trials with a minimum of 10 patients at an NCI-Designated Comprehensive Cancer Center from 2010 to 2021. We defined a study endpoint of racial and ethnic minority accrual greater than zero. Multivariable logistic regression was used to determine whether co-variables predicted our study endpoint. P-values of less than 0.05 were considered significant. A total of 352 cancer trials met eligibility criteria. These studies enrolled a total of 7981 patients with a total of 926 racial and ethnic minorities leading to a median enrollment of 10%. Trials open in community sites (yes versus no) were more likely to have a minority patient (OR, 2.21; 95% CI, 1.02-4.96) as well as pilot/phase I studies compared to phase II/III (OR, 3.19; 95% CI, 1.34-8.26). Trials incorporating immunotherapy (yes versus no) were less likely to have a minority patient (OR, 0.47; 95% CI, 0.23-0.94). Trials open in community sites as well as early phase treatment studies were more likely to accrue minority patients. However, studies including immunotherapy were less likely to accrue racial and ethnic minorities. Knowledge gained from our analysis may help individuals design oncology treatment trials that are representative of more diverse populations.

Biomarker Testing, Targeted Therapy and Clinical Trial Participation by Race Among Patients With Lung Cancer: A Real-World Medicaid Database Study.

Introduction: Biomarker testing in oncology is fundamental for targeted therapy use and clinical trial participation. Factors contributing to previously identified racial disparities in biomarker testing remain unclear. This study investigated biomarker testing, clinical trial participation, and targeted therapy by race among patients with metastatic lung cancer with Medicaid coverage in the United States. Methods: The Merative MarketScan Medicaid claims database was used for this study to identify patients diagnosed with having metastatic lung cancer between 2017 and 2019 with at least 121 days of follow-up. Racial differences in biomarker testing, clinical trial enrollment, and targeted therapy use were analyzed using chi-square/t tests followed by logistic regression for confounding covariates. Results: A total of 3845 patients were eligible. A total of 970 (25.2%) patients included in this study were Black. Biomarker testing was observed among 57.0%, targeted therapy among 4.6%, and 2.6% of the study cohort had evidence of clinical trial participation. No significant disparities between Black and White races were identified. Younger age and metastatic disease at initial diagnosis were the strongest independent factors associated with increased biomarker testing. Biomarker testing was positively associated with targeted therapy use (OR = 1.69, p = 0.005). Conclusions: Patients with metastatic lung cancer with Medicaid coverage were found to have exceedingly low biomarker testing rates; only 57% had evidence of any biomarker testing. Although no consistent differences between Black and White races were identified, this study calls attention to care experienced by socioeconomically disadvantaged patients with metastatic lung cancer in the United States.

NCCN Guidelines® Insights: Mesothelioma: Pleural, Version 1.2024.

Mesothelioma is a rare cancer that originates from the mesothelial surfaces of the pleura and other sites, and is estimated to occur in approximately 3,500 people in the United States annually. Pleural mesothelioma is the most common type and represents approximately 85% of these cases. The NCCN Guidelines for Mesothelioma: Pleural provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pleural mesothelioma. These NCCN Guidelines Insights highlight significant updates to the NCCN Guidelines for Mesothelioma: Pleural, including revised guidance on disease classification and systemic therapy options.