Streamlining the Conduct of Cancer Clinical Trials: New Standard Data Collection Practices for National Cancer Institute Late Phase Clinical Studies.

The increase in the complexity of cancer clinical trials over the past several decades has led to a dramatic growth in trial cost and operational burden. The extent and frequency of data collection, particularly in late phase trials which enroll many participants, have been major contributors to this problem. The Clinical Trials and Translational Research Advisory Committee of the National Cancer Institute (NCI) recently assessed the impact of these stressors on the NCI National Clinical Trials Network (NCTN) and recommended that data collection in late phase NCTN trials be limited to data elements essential to address the primary and secondary objectives of the trial.

Improving Access to Patient-Focused, Decentralized Clinical Trials Requires Streamlined Regulatory Requirements: An ASCO Research Statement.

Strategies to bring clinical trials closer to patients gained momentum during the COVID-19 pandemic, enabling more participants to receive treatment and/or testing in their local communities. Incorporation of decentralized trial elements presents both opportunities and challenges, spanning regulatory, technical, and operational aspects. This ASCO research statement includes timely consensus-driven recommendations and a call for engagement of all research stakeholders.

Approach for reporting master protocol study designs on ClinicalTrials.gov: qualitative analysis.

Objective: To describe an approach for reporting master protocol research programs (MPRPs) that is consistent with existing good reporting practices and that uses structured information to convey the overall master protocol and design of each substudy.

Design: Qualitative analysis.

Data Sources: ClinicalTrials.

Patterns of Enrollment in Cancer Treatment Trials During the COVID-19 Pandemic at National Cancer Institute-Designated Cancer Centers.

The COVID-19 pandemic posed unprecedented strain on enrollment to cancer clinical trials and their conduct. Here, we highlight an analysis using information from the National Cancer Institute (NCI) Clinical Trials Reporting Program database to describe enrollment patterns to interventional cancer treatment trials at NCI-Designated Cancer Centers during the pandemic. Enrollment to cancer treatment trials at NCI-Designated Cancer Centers decreased precipitously early in the pandemic and has not yet fully returned to the 2019 baseline as of mid-2021.

COVID-19, Social Justice, and Clinical Cancer Research.

The coronavirus disease 2019 (COVID-19) pandemic and related socioeconomic events have markedly changed the environment in which cancer clinical trials are conducted. These events have resulted in a substantial, immediate-term decrease in accrual to both diagnostic and therapeutic cancer investigations as well as substantive alterations in patterns of oncologic care. The sponsors of clinical trials, including the US National Cancer Institute, as well as the cancer centers and community oncology practices that conduct such studies, have all markedly adapted their models of care, usage of healthcare personnel, and regulatory requirements in the attempt to continue clinical cancer investigations while maintaining high levels of patient safety.

Characteristics of Breast Ducts in Normal-Risk and High-risk Women and Their Relationship to Ductal Cytologic Atypia.

Breast ductal cytologic atypia is an important risk factor for sporadic breast cancer. Characterization of the associated normal breast tissue is needed to develop additional methods of risk assessment and new targets for breast cancer prevention. We conducted a prospective clinical trial evaluating women at normal-risk or at high-risk for sporadic breast cancer.

The National Cancer Institute and Department of Veterans Affairs Interagency Group to Accelerate Trials Enrollment (NAVIGATE): A federal collaboration to improve cancer care.

Cancer clinical trials represent an important option for patients with a diagnosis of cancer and the clinician-investigators involved in their care who seek options for their disease. For all who are impacted by cancer, these studies offer opportunities for greater learning. Conducting these important studies involves several challenges, including recruiting eligible participants.

Research Priorities, Measures, and Recommendations for Assessment of Tobacco Use in Clinical Cancer Research.

There is strong evidence that cigarette smoking causes adverse outcomes in people with cancer. However, more research is needed regarding those effects and the effects of alternative tobacco products and of secondhand smoke, the effects of cessation (before diagnosis, during treatment, or during survivorship), the biologic mechanisms, and optimal strategies for tobacco dependence treatment in oncology. Fundamentally, tobacco is an important source of variation in clinical treatment trials.

An Improved Breast Epithelial Sampling Method for Molecular Profiling and Biomarker Analysis in Women at Risk for Breast Cancer.

Background: There is a strong need to define the molecular changes in normal at-risk breast epithelium to identify biomarkers and new targets for breast cancer prevention and to develop a molecular signature for risk assessment. Improved methods of breast epithelial sampling are needed to promote whole-genome molecular profiling, increase ductal epithelial cell yield, and reduce sample cell heterogeneity.

Methods: We developed an improved method of breast ductal sampling with ductal lavage through a 22-gauge catheter and collection of ductal samples with a microaspirator.

Relationships between computer-extracted mammographic texture pattern features and BRCA1/2 mutation status: a cross-sectional study.

Introduction: Mammographic density is similar among women at risk of either sporadic or BRCA1/2-related breast cancer. It has been suggested that digitized mammographic images contain computer-extractable information within the parenchymal pattern, which may contribute to distinguishing between BRCA1/2 mutation carriers and non-carriers.

Methods: We compared mammographic texture pattern features in digitized mammograms from women with deleterious BRCA1/2 mutations (n = 137) versus non-carriers (n = 100).

Implementation of timeline reforms speeds initiation of National Cancer Institute-sponsored trials.

Background: The National Cancer Institute (NCI) organized the Operational Efficiency Working Group in 2008 to develop recommendations for improving the speed with which NCI-sponsored clinical trials move from the idea stage to a protocol open to patient enrollment.

Methods: Given the many stakeholders involved, the Operational Efficiency Working Group advised a multifaceted approach to mobilize the entire research community to improve their business processes. New staff positions to monitor progress, protocol-tracking Web sites, and strategically planned conference calls were implemented.

Single-cell genetic analysis of ductal carcinoma in situ and invasive breast cancer reveals enormous tumor heterogeneity yet conserved genomic imbalances and gain of MYC during progression.

Ductal carcinoma in situ (DCIS) is a precursor lesion of invasive ductal carcinoma (IDC) of the breast. To understand the dynamics of genomic alterations in this progression, we used four multicolor fluorescence in situ hybridization probe panels consisting of the oncogenes COX2, MYC, HER2, CCND1, and ZNF217 and the tumor suppressor genes DBC2, CDH1, and TP53 to visualize copy number changes in 13 cases of synchronous DCIS and IDC based on single-cell analyses. The DCIS had a lower degree of chromosomal instability than the IDC.

Interphase cytogenetics of sputum cells for the early detection of lung carcinogenesis.

This perspective on Varella-Garcia et al. (beginning on p. 447 in this issue of the journal) examines the role of interphase fluorescence in situ hybridization for the early detection of lung cancer.

Mammographic density does not differ between unaffected BRCA1/2 mutation carriers and women at low-to-average risk of breast cancer.

Elevated mammographic density (MD) is one of the strongest risk factors for sporadic breast cancer. Epidemiologic evidence suggests that MD is, in part, genetically determined; however, the relationship between MD and BRCA1/2 mutation status is equivocal. We compared MD in unaffected BRCA1/2 mutation carriers enrolled in the U.

The prioritization of cancer antigens: a national cancer institute pilot project for the acceleration of translational research.

The purpose of the National Cancer Institute pilot project to prioritize cancer antigens was to develop a well-vetted, priority-ranked list of cancer vaccine target antigens based on predefined and preweighted objective criteria. An additional aim was for the National Cancer Institute to test a new approach for prioritizing translational research opportunities based on an analytic hierarchy process for dealing with complex decisions. Antigen prioritization involved developing a list of "ideal" cancer antigen criteria/characteristics, assigning relative weights to those criteria using pairwise comparisons, selecting 75 representative antigens for comparison and ranking, assembling information on the predefined criteria for the selected antigens, and ranking the antigens based on the predefined, preweighted criteria.

Recruitment to a physical activity intervention study in women at increased risk of breast cancer.

Background: Physical activity is being studied as a breast cancer prevention strategy. Women at risk of breast cancer report interest in lifestyle modification, but recruitment to randomized physical activity intervention studies is challenging.

Methods: We conducted an analysis of recruitment techniques used for a prospective, randomized pilot study of physical activity in women at risk of breast cancer.

Ductal lavage in women from BRCA1/2 families: is there a future for ductal lavage in women at increased genetic risk of breast cancer?

Purpose: Ductal lavage has been used for risk stratification and biomarker development and to identify intermediate endpoints for risk-reducing intervention trials. Little is known about patient characteristics associated with obtaining nipple aspirate fluid (NAF) and adequate cell counts (> or =10 cells) in ductal lavage specimens from BRCA mutation carriers.

Methods: We evaluated patient characteristics associated with obtaining NAF and adequate cell counts in ductal lavage specimens from the largest cohort of women from BRCA families yet studied (BRCA1/2 = 146, mutation-negative = 23, untested = 2).

The influence of a gene expression profile on breast cancer decisions.

Purpose: The Oncotype Dx Recurrence Score (RS), is often employed in patients with estrogen receptor-positive, node negative (ER+LN-) breast cancer. We investigated the impact of the RS on actual chemotherapy administration and the effect of the assay on a panel of breast oncology experts.

Patients And Methods: The prospective adjuvant chemotherapy recommendations (prior to RS) and actual adjuvant therapy (after RS) for consecutive patients with ER+LN- breast cancer were recorded.

Effect of raloxifene on mammographic density and breast magnetic resonance imaging in premenopausal women at increased risk for breast cancer.

Background: Mammographic density is a risk factor for breast cancer. Mammographic density and breast magnetic resonance imaging (MRI) volume (MRIV) assess the amount of fibroglandular tissue in the breast. Mammographic density and MRIV can be modulated with hormonal interventions, suggesting that these imaging modalities may be useful as surrogate endpoint biomarkers for breast cancer chemoprevention trials.

RAD51 135G-->C modifies breast cancer risk among BRCA2 mutation carriers: results from a combined analysis of 19 studies.

RAD51 is an important component of double-stranded DNA-repair mechanisms that interacts with both BRCA1 and BRCA2. A single-nucleotide polymorphism (SNP) in the 5' untranslated region (UTR) of RAD51, 135G-->C, has been suggested as a possible modifier of breast cancer risk in BRCA1 and BRCA2 mutation carriers. We pooled genotype data for 8,512 female mutation carriers from 19 studies for the RAD51 135G-->C SNP.

Randomized comparison of phone versus in-person BRCA1/2 predisposition genetic test result disclosure counseling.

Purpose: This study evaluated whether phone results were equivalent to in-person result disclosure for individuals undergoing BRCA1/2 predisposition genetic testing.

Methods: A total of 111 of 136 subjects undergoing education and counseling for BRCA1/2 predisposition genetic testing agreed to randomization to phone or in-person result disclosure. Content and format for both sessions were standardized.

Lack of association between sputum atypia and chronic obstructive pulmonary disease mortality.

Hypothesis: Chronic obstructive pulmonary disease (COPD) and lung cancer are thought to share common elements in pathogenesis. The authors hypothesized that sputum atypia would reflect the processes leading to progressive airflow obstruction and might be a novel biomarker of more rapidly progressive COPD.

Methods: The authors analyzed the association between COPD death and sputum cytologic atypia in an ongoing cohort of 2013 smokers with varying degrees of airflow obstruction during the period between January 1, 1993, and July 1, 2001.

Evolution of the colored eco-genetic relationship map (CEGRM) for assessing social functioning in women in hereditary breast-ovarian (HBOC) families.

The CEGRM was initially conceived as a simple, concise, visual representation of the social interaction domains of information, tangible services and emotional exchanges (Kenen, R., & Peters, J. (2001).