Phase II Study of Osimertinib in Patients With Epidermal Growth Factor Receptor Mutations: Results From the NCI-MATCH ECOG-ACRIN (EAY131) Trial Subprotocol E.

PURPOSE: The National Cancer Institute Molecular Analysis for Therapy Choice trial is a signal-finding genomically driven platform trial that assigns patients with any advanced refractory solid tumor, lymphoma, or myeloma to targeted therapies on the basis of next-generation sequencing results. Subprotocol E evaluated osimertinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in patients with EGFR mutations. METHODS: Eligible patients had EGFR mutations (T790M or rare activating) and received osimertinib 80 mg once daily. Patients with lung cancer with EGFR T790M were excluded. The primary end point was objective response rate (ORR), and the secondary end points were 6-month progression-free survival (PFS), overall survival, and toxicity. RESULTS: A total of 19 patients were enrolled: 17 were evaluable for toxicity and 13 for efficacy. The median age of the 13 included in the efficacy analysis was 63 years, 62% had Eastern Cooperative Oncology Group performance status 1, and 31% received >three previous systemic therapies. The most common tumor type was brain cancers (54%). The ORR was 15.4% (n = 2 of 13; 90% CI, 2.8 to 41.0) and 6-month PFS was 16.7% (90% CI, 0 to 34.4). The two confirmed RECIST responses were observed in a patient with neuroendocrine carcinoma not otherwise specified (EGFR exon 20 S768T and exon 18 G719C mutation) and a patient with low-grade epithelial carcinoma of the paranasal sinus (EGFR D770_N771insSVD). The most common (>20%) treatment-related adverse events were diarrhea, thrombocytopenia, and maculopapular rash. CONCLUSION: In this pretreated cohort, osimertinib did not meet the prespecified end point threshold for efficacy, but responses were seen in a neuroendocrine carcinoma with an EGFR exon 20 S768T and exon 18 G719C mutation and an epithelial carcinoma with an EGFR D770_N771insSVD mutation. Osimertinib was well tolerated and had a safety profile consistent with previous studies.

Evaluating implementation of a community-focused patient navigation intervention at an NCI-designated cancer center using RE-AIM.

BACKGROUND: Patient navigation is an evidence-based intervention that reduces cancer health disparities by directly addressing the barriers to care for underserved patients with cancer. Variability in design and integration of patient navigation programs within cancer care settings has limited this intervention's utility. The implementation science evaluation framework, RE-AIM, allows quantitative and qualitative examination of effective implementation of patient navigation programs into cancer care settings. METHODS: The Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework was used to evaluate implementation of a community-focused patient navigation intervention at an NCI-designated cancer center between June 2018 and October 2021. Using a 3-month longitudinal, non-comparative measurement period, univariate and bivariate analyses were conducted to examine associations between participant-level demographics and primary (i.e., barrier reduction) and secondary (i.e., patient-reported outcomes) effectiveness outcomes. Mixed methods analyses were used to examine adoption and delivery of the intervention into the cancer center setting. Process-level analyses were used to evaluate maintenance of the intervention. RESULTS: Participants (n = 311) represented a largely underserved population, as defined by the National Cancer Institute, with the majority identifying as Hispanic/Latino, having a household income of $35,000 or less, and being enrolled in Medicaid. Participants were diagnosed with a variety of cancer types and most had advanced staged cancers. Pre-post-intervention analyses indicated significant reduction from pre-intervention assessments in the average number of reported barriers, F(1, 207) = 117.62, p < .001, as well as significant increases in patient-reported physical health, t(205) = - 6.004, p < .001, mental health, t(205) = - 3.810, p < .001, self-efficacy, t(205) = - 5.321, p < .001, and satisfaction with medical team communication, t(206) = - 2.03, p = .029. Referral patterns and qualitative data supported increased adoption and integration of the intervention into the target setting, and consistent intervention delivery metrics suggested high fidelity to intervention delivery over time. Process-level data outlined a successful transition from a grant-funded community-focused patient navigation intervention to an institution-funded program. CONCLUSIONS: This study utilized the implementation science evaluation framework, RE-AIM, to evaluate implementation of a community-focused patient navigation program. Our analyses indicate successful implementation within a cancer care setting and provide a potential guide for other oncology settings who may be interested in implementing community-focused patient navigation programs.

NCI Cancer Research Data Commons: Resources to Share Key Cancer Data.

Since 2014, the NCI has launched a series of data commons as part of the Cancer Research Data Commons (CRDC) ecosystem housing genomic, proteomic, imaging, and clinical data to support cancer research and promote data sharing of NCI-funded studies. This review describes each data commons (Genomic Data Commons, Proteomic Data Commons, Integrated Canine Data Commons, Cancer Data Service, Imaging Data Commons, and Clinical and Translational Data Commons), including their unique and shared features, accomplishments, and challenges. Also discussed is how the CRDC data commons implement Findable, Accessible, Interoperable, Reusable (FAIR) principles and promote data sharing in support of the new NIH Data Management and Sharing Policy. See related articles by Brady et al., p. 1384, Pot et al., p. 1396, and Kim et al., p. 1404.

NCI Cancer Research Data Commons: Cloud-Based Analytic Resources.

The NCI's Cloud Resources (CR) are the analytical components of the Cancer Research Data Commons (CRDC) ecosystem. This review describes how the three CRs (Broad Institute FireCloud, Institute for Systems Biology Cancer Gateway in the Cloud, and Seven Bridges Cancer Genomics Cloud) provide access and availability to large, cloud-hosted, multimodal cancer datasets, as well as offer tools and workspaces for performing data analysis where the data resides, without download or storage. In addition, users can upload their own data and tools into their workspaces, allowing researchers to create custom analysis workflows and integrate CRDC-hosted data with their own. See related articles by Brady et al., p. 1384, Wang et al., p. 1388, and Kim et al., p. 1404.

NCI Cancer Research Data Commons: Lessons Learned and Future State.

More than ever, scientific progress in cancer research hinges on our ability to combine datasets and extract meaningful interpretations to better understand diseases and ultimately inform the development of better treatments and diagnostic tools. To enable the successful sharing and use of big data, the NCI developed the Cancer Research Data Commons (CRDC), providing access to a large, comprehensive, and expanding collection of cancer data. The CRDC is a cloud-based data science infrastructure that eliminates the need for researchers to download and store large-scale datasets by allowing them to perform analysis where data reside. Over the past 10 years, the CRDC has made significant progress in providing access to data and tools along with training and outreach to support the cancer research community. In this review, we provide an overview of the history and the impact of the CRDC to date, lessons learned, and future plans to further promote data sharing, accessibility, interoperability, and reuse. See related articles by Brady et al., p. 1384, Wang et al., p. 1388, and Pot et al., p. 1396.

NCI Cancer Research Data Commons: Core Standards and Services.

The NCI Cancer Research Data Commons (CRDC) is a collection of data commons, analysis platforms, and tools that make existing cancer data more findable and accessible by the cancer research community. In practice, the two biggest hurdles to finding and using data for discovery are the wide variety of models and ontologies used to describe data, and the dispersed storage of that data. Here, we outline core CRDC services to aggregate descriptive information from multiple studies for findability via a single interface and to provide a single access method that spans multiple data commons. See related articles by Wang et al., p. 1388, Pot et al., p. 1396, and Kim et al., p. 1404.

Authorship of Publications Supported by NCI-Funded Grants Involving Low- and Middle-Income Countries.

Importance: Scientific publication is an important tool for knowledge dissemination and career advancement, but authors affiliated with institutions in low- and middle-income countries (LMICs) are historically underrepresented on publications. Objective: To assess the country income level distribution of author affiliations for publications resulting from National Cancer Institute (NCI)-supported extramural grants between 2015 and 2019, with international collaborating institutions exclusively in 1 or more LMICs. Design and Setting: This cross-sectional study assessed authorship on publications resulting from NCI-funded grants between October 1, 2015, and September 30, 2019. Grants with collaborators in LMICs were identified in the National Institutes of Health (NIH) Query/View/Report and linked to publications using Dimensions for NIH, published between 2011 and 2020. Statistical analysis was performed from May 2021 to July 2022. Main Outcomes and Measures: Author institutional affiliation was used to classify author country and related income level as defined by the World Bank. Relative citation ratio and Altmetric data from Dimensions for NIH were used to compare citation impact measures using the Wilcoxon rank sum test. Results: In this cross-sectional study, 159 grants were awarded to US institutions with collaborators in LMICs, and 5 grants were awarded directly to foreign institutions. These 164 grants resulted in 2428 publications, of which 1242 (51%) did not include any authors affiliated with an institution in an LMIC. In addition, 1884 (78%) and 2009 (83%) publications had a first or last author, respectively, affiliated with a high-income country (HIC). Publications with HIC-affiliated last authors also demonstrated greater citation impact compared with publications with LMIC-affiliated last authors as measured by relative citation ratios and Altmetric Attention Scores; publications with HIC-affiliated first authors also had higher Altmetric Attention Scores. Conclusions and Relevance: This cross-sectional study suggests that LMIC-affiliated authors were underrepresented on publications resulting from NCI-funded grants involving LMICs. It is critical to promote equitable scientific participation by LMIC institutions in cancer research, including through current and planned programs led by the NCI.

Variability in expenses related to spine oncology care: comparison of payer-negotiated rates at National Cancer Institute-Designated Cancer Centers.

BACKGROUND: As of 2021, the Centers for Medicare and Medicaid Services (CMS) requires all hospitals to publish their commercially negotiated prices. To our knowledge, price variation of spine oncology diagnosis and treatments has not been previously investigated. PURPOSE: The aim of this study is to characterize the availability and variation of prices for spinal oncology services among National Cancer Institute-Designated Cancer Centers (NCI-DCC). STUDY DESIGN: Cross-sectional analysis. METHODS: Cancer centers were identified; those that did not provide patient care or participate in Medicare's Inpatient Prospective System were excluded. A cross-sectional analysis was conducted to gather commercially negotiated prices by searching online for "[center name] price transparency OR machine-readable file OR chargemaster." Data obtained was queried using 44 current procedural terminology (CPT) codes for imaging, procedures, and surgeries relevant to spine oncology. Comparison of prices was achieved by normalizing the median price for each service at each center to the estimated 2022 Medicare reimbursement for the center's Medicare Administrator Contractor. The ratios between the lowest and highest median commercial negotiated price within a center and across all centers were defined as "within-center ratio" and "across-center ratio" respectively. RESULTS: In total, 49 centers disclosed commercial payer-negotiated rates. Mean rate (±SD) for cervical corpectomy was $9,134 (±$10,034), thoracic laminectomy for neoplasm excision was $5,382 (±$5502), superficial bone biopsy was $1,853 (±$1,717), and single-photon emission computerized tomography (SPECT) was $813 (±$232). Within-center ratios ranged from 5.0 (SPECT scan) to 17.8 (radiofrequency bone ablation). Across-center ratios (for codes with > 10 centers reporting) ranged from 9.0 (corpectomy, thoracic, lateral extra-cavitary) to 418.7 (anterior approach cervical corpectomy). CONCLUSIONS: Price transparency for spinal oncology remains elusive despite recent CMS regulatory oversight, with marked heterogeneity in the quality of published rates complicating patients' ability to "shop" for care. Additionally, there continues to be significant variation in commercial rates for spine oncology diagnosis and treatment. CLINICAL SIGNIFICANCE: Despite regulation by CMS, prices for spinal oncology services are not uniformly available to patients and vary between NCI-DCC. The findings of this manuscript present potential barriers for patients to compare and obtain affordable care.

Engaging Communities in Cancer Prevention and Control Activity Prioritization through a Statewide Needs Assessment: A Case Study from Nebraska.

Community outreach and engagement (COE) activities are important in identifying catchment area needs, communicating these needs, and facilitating activities relevant to the population. The National Cancer Institute-designated cancer centers are required to conduct catchment-wide cancer needs assessments as part of their COE activities. The University of Nebraska Medical Center Buffett Cancer Center undertook a three-year-long process to conduct a needs assessment, identify priorities, and develop workgroups to implement cancer prevention and control activities. Activities were conducted through collaborations with internal and external partners. The needs assessment focused on prevention, early detection, and treatment of cancer and involved secondary data analysis and focus groups with identified underrepresented priority populations (rural, African American, Hispanic, Native American, and LGBTQ+ populations). Results were tailored and disseminated to specific audiences via internal and external reports, infographics, and presentations. Several workgroups were developed through meetings with the internal and external partners to address identified priorities. COE-specific initiatives and metrics have been incorporated into University of Nebraska Medical Center and Buffett Cancer Center strategic plans. True community engagement takes a focused effort and significant resources. A systemic and long-term approach is needed to develop trusted relationships between the COE team and its local communities.

Defining the Role of the Advanced Practice Provider Within the National Cancer Institute Community Oncology Research Program.

PURPOSE: Oncology advanced practice providers (APPs), including nurse practitioners, clinical nurse specialists, physician assistants, and clinical pharmacists, contribute significantly to quality cancer care. Understanding the research-related roles of APPs in the National Cancer Institute's (NCI) Community Oncology Research Program (NCORP) could lead to enhanced protocol development, trial conduct, and accrual. METHODS: The 2022 NCORP Landscape Assessment Survey asked two questions about the utilization and roles of APPs in the NCORP. RESULTS: A total of 271 practice groups completed the 2022 survey, with a response rate of 90%. Of the 259 nonpediatric exclusive practice groups analyzed in this study, 92% used APPs for clinical care activities and 73% used APPs for research activities. APPs most often provided clinical care for patients enrolled in trials (97%), followed by assistance with coordination (65%), presenting/explaining clinical trials (59%), screening patients (49%), ordering investigational drugs (37%), and consenting participants (24%). Some groups reported APPs as an enrolling investigator (18%) and/or participating in institutional oversight/selection of trials (15%). Only 5% of NCORP sites reported APPs as a site primary investigator for trials, and very few (3%) reported APPs participating in protocol development. CONCLUSION: Practice groups report involving APPs in clinical research within the NCORP network; however, opportunities for growth exists. As team-based care has enhanced clinical practice in oncology, this same approach can be used to enhance successful research. Suggested strategies include supporting APP research-related time, recognition, and education. The findings of this survey and subsequent recommendations may be applied to all adult oncology practices that participate in clinical research.

Disparities in National Cancer Institute and Nonprofit Organization Funding Disproportionately Affect Cancers With Higher Incidence Among Black Patients and Higher Mortality Rates.

PURPOSE: National Cancer Institute (NCI) and nonprofit organization (NPO) funding is critical for research and advocacy but may not be equitable across cancers. METHODS: This study evaluated funding from the NCI and NPOs supporting lung, breast, colorectal, pancreatic, hepatobiliary, prostate, ovarian, cervical and endometrial cancers, leukemia, lymphoma, and melanoma from 2015 to 2018. The primary objectives were to assess for funding disparities across different cancers compared with their incidence and mortality and across racial groups. We also determined if underfunding correlates with fewer clinical trials. Correlations between funding for each cancer and its incidence, mortality, and number of clinical trials were analyzed using descriptive statistics and Pearson correlation coefficients (CCs). RESULTS: Diseases with the largest combined NCI and NPO funding were breast cancer ($3.75 billion in US dollars [USD]) and leukemia ($1.99 billion USD). Those with the least funding were endometrial ($94 million USD), cervical ($292 million USD), and hepatobiliary cancers ($348 million USD). Disease-specific funding correlated well with incidence but correlated poorly with mortality (Pearson CCs, 0.74; P = .006 and .30, P = .346, respectively). Breast cancer, leukemia, and lymphoma were well-funded while colorectal, lung, hepatobiliary and uterine cancers were underfunded. Higher incidence among Black patients correlated with underfunding. The amount of funding for a particular cancer correlated strongly with the number of clinical trials for that disease (Pearson CC, 0.91; P < .0001). CONCLUSION: Many cancers with high incidence and mortality rates are underfunded. Cancers that affect Black patients at higher rates are also underfunded. Underfunding strongly correlates with fewer clinical trials, which could impede future advances in underfunded cancers.

Availability of cancer survivorship support services across the National Cancer Institute Community Oncology Research Program network.

BACKGROUND: National cancer organizations recommend provision of nutrition, physical activity, and mental health supportive services to cancer survivors. However, the availability of these services across diverse community oncology settings remains unclear. METHODS: The National Cancer Institute Community Oncology Research Program (NCORP) is a national network of community oncology practices engaged in cancer research. The 2022 NCORP Landscape Assessment (5UG1CA189824) assessed individual practices' establishment of survivorship clinics and nutrition, physical activity, and mental health services, resources, and/or referrals. Descriptive statistics summarized and logistic regression quantified the association between services, practice, and patient characteristics. RESULTS: Of 46 NCORP community sites, 45 (98%) responded to the survey, representing 259 adult practice groups. A total of 41% had a survivorship clinic; 96% offered mental health, 94% nutrition, and 53% physical activity services, resources, and/or referrals. All 3 services were offered in various formats (eg, in-house, referrals, education) by 51% and in-house only by 25% of practices. Practices with advanced practice providers were more likely to have a survivorship clinic (odds ratio [OR] = 3.19, 95% confidence interval [CI] = 1.04 to 9.76). Practices with at least 30% Medicare patients (OR = 2.54, 95% CI = 1.39 to 4.66) and more oncology providers (OR = 1.02, 95% CI = 1.01 to 1.04) were more likely to have all 3 services in any format. Practices with at least 30% Medicare patients (OR = 3.41, 95% CI = 1.50 to 7.77) and a survivorship clinic (OR = 2.84, 95% CI = 1.57 to 5.14) were more likely to have all 3 services in-house. CONCLUSIONS: Larger oncology practices and those caring for more survivors on Medicare provided more supportive services, resources, and/or referrals. Smaller practices and those without survivorship clinics may need strategies to address potential gaps in supportive services.

Pulmonary metastatectomy in pediatric cancer patients at National Cancer Institute, Egypt: prognostic factors and outcome.

BACKGROUND: Metastatic tumors account for 80% of all lung tumors in children. Wilms tumour and osteosarcoma are the most tumors of childhood that produce lung metastases. The aim of the current study is to assess the prognostic factors of pulmonary metastatectomy in pediatric solid tumours as age, number, size, site,laterality, resectability of pulmonary nodules, and number of Thoracotomies. Calculate overall survival among patients who underwent pulmonary metastatectomy. METHODS: It is a retrospective study including all pediatric patients with metastatic solid tumors to lungs treated at pediatric oncology department, National Cancer Institute, Cairo University from 2008 to 2014. Fifty-five patients were included, 43 (78.2℅) patients of them had Osteosarcoma. RESULTS: Thirty (54.5℅)patients were male. The mean age was 15 years ranging from (4.5- 23) years. The site of primary disease was at lower limbs in 43 (78.2%) patients. All patients underwent complete surgical resection of the primary disease with negative margin, 22(51.1%) of the osteosarcoma patients did amputation with tumor necrosis less than 90%. All patients received chemotherapy and only 9 received radiation therapy. The patients were classified into four groups according to time of diagnosis of pulmonary metastasis: at time of diagnosis in 13 (21.8%) patients, within treatment in 16 (30.9%) patients, within first year follow up in 18 (32.7%) patients and detected late in 8 (14.5%) patients. Bilateral lung metastasis diagnosed by CT chest were detected in 42 (76.4%) patients. Size of metastatic nodules was ranging from (0.5 to 10 cm) with mean 3.4 cm. Number of metastatic nodules was ranging from (1 to 28) median 4.Metastatic complications were detected in 19 patients. 5-year OS was 74.8% in the study group, and 68% in osteosarcoma patients. Effect of prognostic factors as sex, time of respectability, laterality, tumor necrosis of the 1ry disease, Timing of lung metastasis, size and site of the primary, Surgical approach of metastatectomy, postoperative complications on overall survival of the studied patients was done with significant P-value of tumor necrosis of the 1ry disease and Timing of lung metastasis 0.017, 0.001 respectively. CONCLUSION: Resection of pulmonary metastases of pediatric solid tumours is a safe and effective treatment that offers better survival.

A roadmap to establishing global oncology as a priority initiative within a National Cancer Institute-designated cancer center.

As the burden of cancers impacting low- and middle-income countries is projected to increase, formation of strategic partnerships between institutions in high-income countries and low- and middle-income country institutions may serve to accelerate cancer research, clinical care, and training. As the US National Cancer Institute and its Center for Global Health continue to encourage cancer centers to join its global mission, academic cancer centers in the United States have increased their global activities. In 2015, the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, responded to the call for international partnership in addressing the global cancer burden through the establishment of the Global Cancer Program as a priority initiative. In developing the Global Cancer Program, we galvanized institutional support to foster sustained, bidirectional, equitable, international partnerships in global cancer control. Our focus and intent in disseminating this commentary is to share experiences and lessons learned from the perspective of a US-based, National Cancer Institute-designated cancer center and to provide a roadmap for other high-income institutions seeking to strategically broaden their missions and address the complex challenges of global cancer control. Herein, we review the formative evaluation, governance, strategic planning, investments in career development, funding sources, program evaluation, and lessons learned. Reflecting on the evolution of our program during the first 5 years, we observed in our partners a powerful shift toward a locally driven priority setting, reduced dependency, and an increased commitment to research as a path to improve cancer outcomes in resource-constrained settings.

The role of community outreach and engagement in evaluation of NCI Cancer Center Support Grants.

PURPOSE: National Cancer Institute (NCI)-designated cancer centers are required to consider their impact on the catchment area they serve. These activities are facilitated by community outreach and engagement (COE) activities as specified in the Cancer Center Support Grant (CCSG) request for applications. While the critical importance of COE activities to NCI-designated cancer centers is well known, it is less clear what impact the COE component has on the overall CCSG merit descriptor and score. METHODS: We undertook an online survey of all 62 NCI-designated Comprehensive and Clinical centers who reported their COE merit descriptor and overall CCSG priority score as of Fall 2021. RESULTS: Of 48 (77%) of responding centers, we identified a strong correlation between the COE merit descriptor and the overall numerical CCSG score received by the center (Spearman's rank correlation coefficient r = 0.360, p = 0.0053). When stratifying this relationship by center type, we observed a very strong correlation between COE and CCSG ratings for comprehensive cancer centers (n = 40; r = 0.544; p = 0.0003) but not for non-comprehensive cancer centers (n = 8; r = 0.073; p = 0.864). CONCLUSION: COE component merit descriptors for comprehensive cancer center CCSG evaluations are strongly correlated with the overall cancer center review score.