Initial Steps in Creating a Patient-Centric Addendum to Clinical Trial Informed Consent Forms.

Introduction: The purpose of the informed consent form (ICF) is to outline the risks and benefits of an interventional clinical trial to potential participants. The aim of this study was to explore the feasibility of a short addendum to the ICF, summarizing key points most relevant to potential participants. Methods: A sample of 20 ICFs was reviewed against the requirements of the U.S. federal regulation documents and assessed for readability. Alongside the ICF review, we conducted focus groups and one-on-one interviews with people with lung cancer (n = 9) to learn what information was most important when considering participation in a clinical trial using a hypothetical phase 3 ICF. Results: The 20 ICFs reviewed were from phases 1 to 3, expanded-access, and single-patient trials covering predominantly NSCLC; 60% were global. The mean length of the ICFs was 21 (range: 15-34) pages. The average reading level was tenth grade whereas the average U.S. reading level was eighth grade. Readability varied by section, the "purpose of the study" section had the highest reading level. In the qualitative research component, participants were "overwhelmed" by the hypothetical ICF. Participants were also asked to list information for the addendum; their suggestions broadly map to federal regulations. An addendum with reference to sections in the ICF for additional details was well received. Conclusions: The variations in ICF architecture and readability make it difficult for patients to make an informed decision to participate in a clinical trial. Implications extend beyond lung cancer, highlighting key areas for ICF improvements and providing a roadmap for developing a patient-centric addendum.

Patient Report on the Impact of Coronavirus Disease 2019 and Living With Lung Cancer.

Introduction: Several studies have highlighted coronavirus disease 2019 (COVID-19)-related disruptions in treatment and care in people living with lung cancer. However, few studies have assessed patient-reported perspectives on treatment disruption. This study aims to report the patient perspectives on the impact of COVID-19, vaccination access, and coverage on people living with lung cancer. Methods: Data are from a larger online longitudinal study being run by a lung cancer nonprofit organization, LUNGevity Foundation. The survey is open to all patients living with lung cancer and their caregivers. These analyses focus on data captured in the COVID-19 module and the vaccine questionnaire. Descriptive statistics were computed for categorical and ordinal variables. Results: Overall, 164 people living with lung cancer completed the COVID-19 module. Of these, 54% reported disruption in access to treatment, appointments, participating in research and clinical trials. Participants living with stage IV disease were likely to be more concerned about COVID-19 (35%) compared with those with stage I, II, and III. More than half (66%) had tested for COVID-19 of this group 88% tested negative. There was a correlation among participants testing positive for COVID-19 and the number of household members who also tested positive for COVID-19. In the sample who completed the vaccine survey, almost all (98%) were vaccinated against COVID-19. When a recommendation came from a health care professional, an oncologist was the most likely referral source (33%). Conclusions: An integrative patient-reported view on the impact of COVID-19 is important for adequate preparation to ensure undisrupted treatment and allocation of resources.

Plain language summary and patient perspective of the 2020 lung cancer screening recommendations by the US Preventive Services Task Force.

WHAT IS THIS SUMMARY ABOUT?: This summary describes the research carried out by the United States Preventive Services Task Force (USPSTF for short) during a review and update of their lung cancer screening recommendations made in 2013. The USPSTF reviewed the results of clinical studies that used a type of scan called low dose computed tomography (LDCT for short). They wanted to see how successful LDCT was at finding lung cancers in people ho hadn't shown any physical signs of lung cancer, but had a history of smoking and were over 50 years of age. WHAT WERE THE RESULTS?: The review found that performing yearly LDCT scans in people who are at high risk of developing lung cancer is beneficial, as it means that some patients will be diagnosed earlier than they would be without this type of screening. People considered to be at high risk of developing lung cancer include: Adults aged 50 to 80 years who have smoked a pack of 20 cigarettes per day for 20 years or two packs per day for 10 years; OR Adults aged 50 to 80 years who currently smoke or have stopped smoking within the last 15 years. WHAT DO THE RESULTS OF THE STUDY MEAN?: The information gained from reviewing the research enabled the USPSTF to update their lung cancer screening recommendations.

Plain language summary and patient perspective of the European Society for Medical Oncology expert consensus statements on treating EGFR-positive non-small-cell lung cancer.

WHAT IS THIS SUMMARY ABOUT?: This article provides a plain language summary and patient perspective of a new set of recommendations made by the European Society for Medical Oncology (ESMO for short). These recommendations are also called expert consensus statements. They cover the management of people with a type of lung cancer called epidermal growth factor receptor-positive non-small-cell lung cancer (EGFR-positive NSCLC for short). WHY WERE THE RECOMMENDATIONS DEVELOPED?: The ESMO Clinical Practice Guidelines are used by healthcare professionals when treating people with cancer, but they don't necessarily have all the information healthcare professionals need to make decisions for with people with EGFR-positive NSCLC. So, in 2021, 32 healthcare professionals who are experts in treating people with EGFR-positive NSCLC worked together to produce recommendations to fill these gaps about EGFR-positive NSCLC. This was called a consensus-building process and it also included patient advocates. WHAT RECOMMENDATIONS DID THEY MAKE?: The experts discussed four main topics including how people with different stages of EGFR-positive NSCLC are diagnosed and treated, and how clinical studies are done. They reviewed the scientific information that exists on these subjects. They reached an agreement and developed the recommendations that are summarized here.

Plain language summary and patient perspective of the American Society for Clinical Oncology guideline: management of stage 3 non-small-cell lung cancer.

WHAT IS THIS SUMMARY ABOUT?: This is a plain language summary of a guideline on the management of stage 3 non-small-cell lung cancer, also known as NSCLC. This guideline was written by the American Society for Clinical Oncology (ASCO for short) and published in the Journal of Clinical Oncology. WHY WERE THE GUIDELINES DEVELOPED?: The purpose of the ASCO guideline is to provide recommendations to healthcare professionals in the US including oncologists, surgeons, pathologists, radiologists, and nurses on how best to diagnose and treat people with stage 3 NSCLC. HOW WERE THE GUILDEINES DEVELOPED?: The ASCO guideline is based on the latest research and scientific evidence to make certain the recommendations are up to date and based on reliable data and best practice. In 2021, a group of experts were asked by ASCO to form an Expert Panel. The Expert Panel reviewed the results of 127 clinical research studies on NSCLC that were done between 1990 and 2021. They looked at how NSCLC had been diagnosed and treated in these studies, as well as at patients' survival and quality of life. The Expert Panel used these findings and their own expertise to form their recommendations and produce the 2021 ASCO Guideline called 'Management of Stage 3 Non-Small-Cell Lung Cancer: ASCO Guideline'. WHAT INFORMATION DOES THE GUIDELINE CONTAIN?: The guideline aims to answer the following questions: What are the most precise ways to confirm and stage NSCLC in people suspected of having a stage 3 disease? Which patients with stage 3 NSCLC can be treated most successfully with surgery? Which patients who can be treated with surgery could also have an additional therapy before their surgery? Which patients who can be treated with surgery could also have an additional treatment after their surgery? Which treatment and/or management is most suitable for patients who cannot have surgery?

2022 cancer statistics: Focus on lung cancer.

WHAT IS THIS SUMMARY ABOUT?: This is a plain language summary of a medical journal article called 'Cancer statistics, 2022'. The data in this summary provides detailed information about lung cancer and less detailed information about other cancers. The researchers from the original study used data gathered from previous years to produce a cancer forecast, predicting the number of new cancer diagnoses and deaths in the United States in 2022. WHAT WERE THE RESULTS?: The review of the data up to 2019 found that compared to previous years: Advanced lung cancer diagnoses had decreased Local stage lung cancer diagnoses had increased Deaths had slowed for lung cancer Deaths continued to reduce for breast cancer, but the rate of this reduction had slowed down Female breast cancer diagnoses were slowly increasing each year Prostate cancer diagnoses stayed similar Local stage prostate cancer diagnoses stayed similar Advanced prostate cancer diagnoses had increased each year The researchers estimated that over 1.9 million new cancer cases would be diagnosed and over half a million cancer deaths would occur in the United States in 2022. This figure includes approximately 350 deaths per day from lung cancer, which was found to be the leading cause of cancer death in the United States. WHAT DO THE RESULTS OF THE STUDY MEAN?: The study found that progress in reducing the number of people being diagnosed with breast and prostate cancer has stalled. Although there were fewer lung cancers diagnosed, this reduction was likely caused by changes in screening and advancements in lung cancer treatments. The American Cancer Society recommended that investing more funds in detecting cancers early as well as developing targeted treatments would help to reduce cancer death rates. This would also help to address the differences in access to cancer care that exist based on racial, social and economic inequalities.

Plain language summary and patient perspective of the revised STARS study: long-term results of a study that compared the effectiveness of radiotherapy to surgery in people with non-small-cell lung cancer.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of a research study called revised STARS. The STARS study involved people with non-small-cell lung cancer, also known as NSCLC. The cancer was less than 5 cm in size and had not spread to other parts of the body (known as stage 1 cancer). The study compared the effectiveness of surgery versus a type of radiotherapy treatment, called stereotactic ablative radiotherapy (also known as SABR) as a treatment for people with NSCLC. Researchers wanted to find out how likely people were to be alive after treatment or if their cancer had grown or spread to other parts of their body (also known as progressed). WHAT WERE THE RESULTS?: The study found that the long term outcomes were similar between SABR and surgery. People with NSCLC were as likely to be alive 3 years after treatment with SABR compared to surgery. WHAT DO THE RESULTS OF THE STUDY MEAN?: SABR may be an alternative to surgery for people with stage 1 NSCLC which is less than 5 cm in size and has not spread to other parts of the body Clinical Trial Registration: NCT02357992 (ClinicalTrials.gov).

The 2021 Global Lung Cancer Therapy Landscape.

INTRODUCTION: The lung cancer treatment landscape has substantially evolved over the past decade. However, a systematic analysis of the current global drug development landscape has not been conducted. METHODS: We curated and analyzed a comprehensive list of therapeutic entities (TEs) in preclinical development and clinical trials for lung cancer. RESULTS: On the basis of our analysis of 707 TEs, we found a consistent forward trajectory in the development pipeline for both NSCLC and SCLC. Most of the TEs were in the advanced stages of clinical trials. Targeted therapies continue to dominate in the non-immuno-oncology space. Immuno-oncology targets are expanding beyond inhibitors of the programmed death-ligand 1 axis. CONCLUSIONS: Our analysis highlights a robust portfolio of both preclinical and clinical TEs and suggests that lung cancer treatment is going to become even more biomarker-driven.

International Association for the Study of Lung Cancer Study of the Impact of Coronavirus Disease 2019 on International Lung Cancer Clinical Trials.

INTRODUCTION: To evaluate the effects of the global coronavirus disease 2019 (COVID-19) pandemic on lung cancer trials, we surveyed investigators and collected aggregate enrollment data for lung cancer trials across the world before and during the pandemic. METHODS: A Data Collection Survey collected aggregate monthly enrollment numbers from 294 global lung cancer trials for 2019 to 2020. A 64-question Action Survey evaluated the impact of COVID-19 on clinical trials and identified mitigation strategies implemented. RESULTS: Clinical trial enrollment declined from 2019 to 2020 by 14% globally. Most reductions in enrollment occurred in April to June where we found significant decreases in individual site enrollment (p = 0.0309). Enrollment was not significantly different in October 2019 to December of 2019 versus 2020 (p = 0.25). The most frequent challenges identified by the Action Survey (N = 172) were fewer eligible patients (63%), decrease in protocol compliance (56%), and suspension of trials (54%). Patient-specific challenges included access to trial site (49%), ability to travel (54%), and willingness to visit the site (59%). The most frequent mitigation strategies included modified monitoring requirements (47%), telehealth visits (45%), modified required visits (25%), mail-order medications (25%), and laboratory (27%) and radiology (21%) tests at nonstudy facilities. Sites that felt the most effective mitigation strategies were telehealth visits (85%), remote patient-reported symptom collection (85%), off-site procedures (85%), and remote consenting (89%). CONCLUSIONS: The COVID-19 pandemic created many challenges for lung cancer clinical trials conduct and enrollment. Mitigation strategies were used and, although the pandemic worsened, trial enrollment improved. A more flexible approach may improve enrollment and access to clinical trials, even beyond the pandemic.

Knowledge and Practice Patterns Among Pulmonologists for Molecular Biomarker Testing in Advanced Non-small Cell Lung Cancer.

BACKGROUND: Targeted therapies for advanced non-small cell lung cancer (NSCLC) with oncogenic drivers have caused a paradigm shift in care. Biomarker testing is needed to assess eligibility for these therapies. Pulmonologists often perform bronchoscopy, providing tissue for both pathologic diagnosis and biomarker analysis. We performed this survey to define the existing knowledge and practices regarding the pulmonologists' role in biomarker testing for advanced NSCLC. RESEARCH QUESTION: What is the current knowledge and practice of pulmonologists regarding biomarker testing and targeted therapies in advanced NSCLC? STUDY DESIGN AND METHODS: This cross-sectional study was performed using an electronic survey of a random sample of 7,238 pulmonologists. Questions focused on diagnostic steps and biomarker analyses for NSCLC. RESULTS: A total of 453 pulmonologists responded. Respondents vary by reported lung cancer patient volume, ranging from 51% evaluating one to four new cases per month to 19% evaluating > 10 cases per month. Interventional training, academic practice setting, and higher volume of endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) were associated with increased knowledge of practice guidelines for the number of recommended passes during EBUS-TBNA (P < .05). Academic pulmonologists more commonly performed or referred for EBUS-TBNA than community pulmonologists (96% and 83%, respectively; P < .0005). Higher testing rates were associated with interventional training, academic setting, and the presence of an institutional policy, whereas lower testing rates were associated with general pulmonologists, practice in community settings, and lack of a guiding institutional policy (P < .05). INTERPRETATION: Substantial differences among pulmonologists' evaluation of advanced NSCLC, variation in knowledge of available biomarkers and the importance of targeted therapies, and differences in institutional coordination likely lead to underutilization of biomarker testing. Interventional training appears to drive improved knowledge and practice for biomarker testing more than practice setting. Improvements are needed in tissue acquisition and interdisciplinary coordination to ensure universal and comprehensive testing for eligible patients.

US Cancer Centers of Excellence Strategies for Increased Inclusion of Racial and Ethnic Minorities in Clinical Trials.

PURPOSE: Participation of racial and ethnic minority groups (REMGs) in cancer trials is disproportionately low despite a high prevalence of certain cancers in REMG populations. We aimed to identify notable practices used by leading US cancer centers that facilitate REMG participation in cancer trials. METHODS: The National Minority Quality Forum and Sustainable Healthy Communities Diverse Cancer Communities Working Group developed criteria by which to identify eligible US cancer centers-REMGs comprise 10% or more of the catchment area; a 10% to 50% yearly accrual rate of REMGs in cancer trials; and the presence of formal community outreach and diversity enrollment programs. Cancer center leaders were interviewed to ascertain notable practices that facilitate REMG accrual in clinical trials. RESULTS: Eight cancer centers that met the Communities Working Group criteria were invited to participate in in-depth interviews. Notable strategies for increased REMG accrual to cancer trials were reported across five broad themes: commitment and center leadership, investigator training and mentoring, community engagement, patient engagement, and operational practices. Specific notable practices included increased engagement of health care professionals, the presence of formal processes for obtaining REMG patient/caregiver input on research projects, and engagement of community groups to drive REMG participation. Centers also reported an increase in the allocation of resources to improving health disparities and increased dedication of research staff to REMG engagement. CONCLUSION: We have identified notable practices that facilitate increased participation of REMGs in cancer trials. Wide implementation of such strategies across cancer centers is essential to ensure that all populations benefit from advances in an era of increasingly personalized treatment of cancer.

Myeloid Zinc Finger 1 and GA Binding Protein Co-Operate with Sox2 in Regulating the Expression of Yes-Associated Protein 1 in Cancer Cells.

The transcription factor (TF) yes-associated protein 1 (YAP1) is a major effector of the tumor suppressive Hippo signaling pathway and is also necessary to maintain pluripotency in embryonic stem cells. Elevated levels of YAP1 expression antagonize the tumor suppressive effects of the Hippo pathway that normally represses YAP1 function. High YAP1 expression is observed in several types of human cancers and is particularly prominent in cancer stem cells (CSCs). The stem cell TF Sox2, which marks and maintains CSCs in osteosarcomas (OSs), promotes YAP1 expression by binding to an intronic enhancer element and YAP1 expression is also crucial for the maintainance of OS stem cells. To further understand the regulation of YAP1 expression in OSs, we subjected the YAP1 intronic enhancer to scanning mutagenesis to identify all DNA cis-elements critical for enhancer function. Through this approach, we identified two novel TFs, GA binding protein (GABP) and myeloid zinc finger 1 (MZF1), which are essential for basal YAP1 transcription. These factors are highly expressed in OSs and bind to distinct sites in the YAP1 enhancer. Depletion of either factor leads to drastically reduced YAP1 expression and thus a reversal of stem cell properties. We also found that YAP1 can regulate the expression of Sox2 by binding to two distinct DNA binding sites upstream and downstream of the Sox2 gene. Thus, Sox2 and YAP1 reinforce each others expression to maintain stemness and tumorigenicity in OSs, but the activity of MZF1 and GABP is essential for YAP1 transcription. Stem Cells 2017;35:2340-2350.

Early onset of craniosynostosis in an Apert mouse model reveals critical features of this pathology.

Activating mutations of FGFRs1-3 cause craniosynostosis (CS), the premature fusion of cranial bones, in man and mouse. The mechanisms by which such mutations lead to CS have been variously ascribed to increased osteoblast proliferation, differentiation, and apoptosis, but it is not always clear how these disturbances relate to the process of suture fusion. We have reassessed coronal suture fusion in an Apert Fgfr2 (S252W) mouse model. We find that the critical event of CS is the early loss of basal sutural mesenchyme as the osteogenic fronts, expressing activated Fgfr2, unite to form a contiguous skeletogenic membrane. A mild increase in osteoprogenitor proliferation precedes but does not accompany this event, and apoptosis is insignificant. On the other hand, the more apical coronal suture initially forms appropriately but then undergoes fusion, albeit at a slower rate, accompanied by a significant decrease in osteoprogenitor proliferation, and increased osteoblast maturation. Apoptosis now accompanies fusion, but is restricted to bone fronts in contact with one another. We correlated these in vivo observations with the intrinsic effects of the activated Fgfr2 S252W mutation in primary osteoblasts in culture, which show an increased capacity for both proliferation and differentiation. Our studies suggest that the major determinant of Fgfr2-induced craniosynostosis is the failure to respond to signals that would halt the recruitment or the advancement of osteoprogenitor cells at the sites where sutures should normally form.