EGFR V834L and L858R Comutation Is Associated With Response to Osimertinib in Non-Small-Cell Lung Cancer.

Up-front osimertinib leads to clinical benefit in EGFR V834L and L858R comutated NSCLC.

A Multistakeholder Qualitative Study to Inform Sexual Orientation and Gender Identity Data Collection in the Cancer Care Setting.

Purpose: Sexual and gender minoritized (SGM) populations face health disparities along the cancer care continuum, although attempts to define these disparities are limited by a lack of comprehensive sexual orientation and gender identity (SOGI) data collection. The objective of this study was to interview a diverse group of stakeholders to understand attitudes, barriers, and facilitators to inform data collection approaches in a cancer care setting. Methods: This was a qualitative study conducted from March to July 2023 with paired surveys of stakeholders including patients, caregivers, providers, and cancer registry staff. Twenty participants across these categories, including half who identified as SGM, completed surveys and interviews. Qualitative data were reduced to themes with exemplar quotations using rapid qualitative analysis methods and compared to survey data. Results: Themes revealed general support for SOGI data collection as part of holistic cancer care, and all participants acknowledged that specific SOGI-related information, particularly correct pronoun usage, was essential to inform patient-centered care. Themes revealed tensions around optimal SOGI data collection methods, mixed opinions on the relevance of sexual orientation, experiences of discrimination and discomfort related to SOGI, and limited acknowledgment of population benefits of SOGI data collection. Conclusion: Themes demonstrated overall support for SOGI data collection but also revealed several barriers, such as a lack of recognition of population benefits and experiences of discrimination and discomfort, that will need to be addressed to comprehensively collect these data. Based on diverse preferences and limitations of all methods of collection, a multimodal approach may be needed to optimize completion.

A Tailored Decision Aid Improves Understanding of Lung Cancer Screening in People With HIV.

BACKGROUND: People with HIV are at increased risk for lung cancer and multimorbidity, complicating the balance of risks and benefits of lung cancer screening. We previously adapted Decision Precision (screenlc.com) to guide shared decision-making for lung cancer screening in people with HIV. RESEARCH QUESTION: Does an HIV-adapted and personally tailored decision aid improve shared decision-making regarding lung cancer screening in people with HIV as measured by knowledge, decisional conflict, and acceptability? STUDY DESIGN AND METHODS: This was a single-arm pilot trial of the decision aid in 40 participants with HIV eligible for lung cancer screening. The decision aid included personalized screening recommendations and HIV-specific, 5-year risk estimates of lung cancer and all-cause mortality. Participants reviewed the decision aid at shared decision-making visits and completed previsit and postvisit surveys with measures of knowledge about lung cancer screening, acceptability, and decisional conflict. RESULTS: The 40 enrolled participants were a median 62 years old, 60% were currently smoking, and they had median 5-year risks of lung cancer and all-cause mortality of 2.0% (IQR, 1.4%-3.3%) and 4.1% (IQR, 3.3%-7.9%), respectively. Personalized recommendations included "Encourage Screening" for 53% of participants and "Preference Sensitive" recommendations for the remainder. Participants showed improvement in 2 validated knowledge measures with relative improvement of 60% (P < 0.001) on the 12-question lung cancer screening knowledge test and 27% (P < .001) on the 7-question lung cancer screening knowledge score, with significant improvement on questions regarding false-positive and false-negative findings, incidental findings, lung cancer-specific mortality benefit, and the possible harms of screening. Participants reported low scores on the decisional conflict scale (median score, 0; IQR, 0-5) and high acceptability. Ninety percent of patients ultimately underwent screening within 1 month of the visit. INTERPRETATION: This HIV-adapted and personally tailored decision aid improved participants' knowledge of risks, benefits, and characteristics of screening with low decisional conflict and high acceptability. This decision aid can enable high-quality shared decision-making in this high-risk population. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04682301; URL: www. CLINICALTRIALS: gov.

Lung Cancer Screening in People With HIV: A Mixed-Methods Study of Patient and Provider Perspectives.

INTRODUCTION: People with HIV are at higher risk of lung cancer; however, there is limited research on attitudes, barriers, and facilitators to lung cancer screening in people with HIV. The objective of this study was to understand the perspectives on lung cancer screening among people with HIV and their providers. METHODS: Surveys of people with HIV and HIV-care providers were complemented by qualitative focus groups and interviews designed to understand the determinants of lung cancer screening in people with HIV. Participants were recruited through an academic HIV clinic in Seattle, WA. Qualitative guides were developed by integrating the Consolidated Framework for Implementation Research and the Tailored Implementation of Chronic Diseases checklist. Themes that emerged from thematic analyses of qualitative data were compared with surveys in joint displays. All study components were conducted between 2021 and 2022. RESULTS: Sixty-four people with HIV completed surveys, and 43 participated in focus groups. Eleven providers completed surveys, and 10 were interviewed for the study. Themes from joint displays show overall enthusiasm for lung cancer screening among people with HIV and their providers, particularly with a tailored and evidence-based approach. Facilitators in this population may include longstanding engagement with providers and health systems and an emphasis on survivorship through preventive healthcare interventions. People with HIV may also face barriers acknowledged by providers, including a high level of medical comorbidities and competing issues such as substance abuse, mental health concerns, and economic instability. CONCLUSIONS: This study reveals that people with HIV and their providers have overall enthusiasm toward screening. However, tailored interventions may be needed to overcome specific barriers, including complex decision making in the setting of medical comorbidity and patient competing issues.

Development of Neuropathic Arthropathy With Entrectinib: Case Report.

TRK inhibition can lead to on-target neurologic adverse events. Two cases illustrate the development of neuropathic arthropathy as a side effect of entrectinib. After starting entrectinib, both patients developed foot pain, swelling, and sensory changes with magnetic resonance imaging revealing marrow edema. Providers should have a low threshold to investigate foot pain or gait abnormalities thoroughly with magnetic resonance imaging and referral to specialists to aid in the diagnosis of neuropathic arthropathy, with consideration to transition to an alternative agent.

Recognizing Prognostic and Predictive Biomarkers in the Treatment of Non-Small Cell Lung Cancer (NSCLC) with Immune Checkpoint Inhibitors (ICIs).

Immunotherapy plays a central role in the treatment of NSCLC and biomarkers predicting response to ICIs are valuable therapeutic tools. Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) is integral in therapy selection as its positive predictive nature to ICIs in the metastatic setting is well documented. Tumor mutational burden (TMB) has undergone much study and, while results are somewhat mixed, there is evidence for its positive predictive value with ICI use. Additional markers such as tumor-infiltrating lymphocytes (TILs), gene expression profiling (GEP), mismatch repair (MMR) and microsatellite instability (MSI), somatic mutations, neutrophil to leukocyte ratio (NLR), smoking history, medication history, and immune-related adverse event (irAE) development can further guide clinicians.

An overview of alectinib hydrochloride as a treatment option for ALK positive non-small cell lung cancer.

Introduction: Alectinib is a second-generation inhibitor of anaplastic lymphoma kinase (ALK) and RET. Phase III clinical trials have established its superiority to crizotinib in the first-line ALK inhibitor-naïve setting. Studies also support its use over chemotherapy in the post-crizotinib setting. It is currently one of several FDA- and EMA-approved ALK inhibitors, and it is listed as a preferred initial therapy for treatment-naïve ALK-positive non-small cell lung cancer (NSCLC).Areas covered: Herein, the authors provide the reader with details of the chemical structure, pharmacologic properties, resistance mutations, phase I, II, and III clinical trials, and safety profile of alectinib. Furthermore, the authors provide the reader with the expert opinion and future perspectives on the drug.Expert opinion: Alectinib compares favorably to other second-generation ALK inhibitors with regards to safety, tolerability, and efficacy. Based on currently available data, it is an appropriate first-line option. Ongoing studies will better resolve the ideal sequencing of ALK inhibitors in the treatment of ALK-positive NSCLC.

Capillary electrophoretic development of aptamers for a glycosylated VEGF peptide fragment.

The emergence of functional genomics and proteomics has added to the growing need for improved analysis methods that can detect and distinguish between protein variants resulting from allelic variation, mutation, or post-translational modification. Aptamers, single-stranded DNA or RNA molecules that fold into three-dimensional structures conducive to binding targets, have become an attractive alternative to antibodies for this type of analysis. Although aptamers have been developed for a wide range of target species, very few sequences have been identified that bind selectively to proteins with specific post-translational modifications. Using capillary electrophoresis-based selection, we have developed DNA aptamer sequences that selectively bind an N-glycosylated peptide fragment of vascular endothelial growth factor (VEGF). The selection method incorporates alternating positive- and counter-selection steps in free solution in order to obtain aptamers with both high affinity toward the glycosylated target and high selectivity versus a non-glycosylated variant. Affinity capillary electrophoresis and surface plasmon resonance binding assays indicate these sequences have low-µM dissociation constants and preferentially bind the glycosylated peptide with as much as 50-fold specificity. Such aptamers could serve as tools for rapid and simple monitoring of disease-linked functional changes in proteins, with potential applications in drug screening and disease diagnosis.

ROS1-rearranged Non-small Cell Lung Cancer.

ROS1-rearranged non-small cell lung cancer (NSCLC) makes up approximately 1% to 2% of all NSCLC, is oncogenically driven by a constitutively activated ROS1 kinase paired with certain fusion partners, and can be detected by several different assays. These patients are initially treated with tyrosine kinase inhibitors (TKIs), which target the activated ROS1 kinase. Eventually these tumors develop resistance to initial TKI treatment through secondary kinase mutations that block TKI binding or activation of bypass signaling pathways, which subvert ROS1 as the driver of the malignancy. Investigation of several TKIs that have shown efficacy in secondary resistant patients is underway.

Advances in Treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer: Targeted Therapy.

The treatment of metastatic non-small cell lung cancer (NSCLC) is constantly evolving. Although the advent of immunotherapy has played an important role in the treatment of patients with NSCLC, the identification of driver mutations and the subsequent specific treatment of these targets often lead to durable responses while maintaining quality of life. This review delves into targeted therapies available for epidermal growth factor receptor, anaplastic lymphoma kinase, ROS1, neurotrophic tropomyosin receptor kinase, and BRAF- mutated NSCLC patients, as well as other mutations with promising novel drugs under clinical investigation.

Tenosynovial giant cell tumor: case report of a patient effectively treated with pexidartinib (PLX3397) and review of the literature.

BACKGROUND: Tenosynovial giant cell tumors (TGCTs) or giant cell tumors of tendon sheath are neoplasms that arise in the synovium. They can be categorized as nodular (localized) or diffuse type (D-TGCT). Historically, surgery has been the mainstay of therapy, but diffuse type disease recurs at a high rate and treatment often requires increasingly morbid procedures. Elucidation of the importance of the colony-stimulating factor (CSF1)/CSF1 receptor (CSF1R) pathway in the pathogenesis of this disease has created significant interest in targeting this pathway as a novel TGCT treatment approach. Pexidartinib, a selective tyrosine kinase inhibitor against CSF1R, showed an 83% disease control rate (52% with partial response and 31% with stable disease) in a recent phase 1 study of patients with TGCT. CASE PRESENTATION: We present an illustrative example of a TGCT patient who would have required a morbid operation who derived considerable clinical benefit from pexidartinib treatment. Her tumor volume decreased by 48% after 4 months of treatment, and 55 months after starting treatment the patient exhibits continued disease stability with minimal clinical symptoms, and significant improvement in functional status. CONCLUSIONS: This case illustrates the effectiveness of systemic therapy in controlling a disease associated with high surgical morbidity. This approach may be especially useful in the treatment of extra-articular disease which often invades neurovascular bundles; as the effectiveness in metastatic disease is still unknown. In the future, systemic treatment for TGCT may be appropriate for the neoadjuvant setting to decrease disease burden prior to surgery with the aim of decreasing recurrence rates. However, properly designed prospective studies will need to be carried out to answer these questions.