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Chemotherapy treatment-related side effects are common and increase the risk of suboptimal outcomes. Exercise interventions during cancer treatment improve self-reported physical functioning, fatigue, anxiety, and depression, but it is unclear whether these interventions improve important clinical outcomes, such as chemotherapy relative dose intensity. The National Cancer Institute funded the Exercise and Nutrition to Improve Cancer Treatment-Related Outcomes (ENICTO) Consortium to address this knowledge gap. This article describes the mechanisms hypothesized to underpin intervention effects on clinically relevant treatment outcomes, briefly outlines each projects distinct research aims, summarizes the scope and organizational structure of ENICTO, and provides an overview of the integrated common data elements used to pursue research questions collectively. In addition, the article includes a description of consortium-wide activities and broader research community opportunities for collaborative research. Findings from the ENICTO Consortium have the potential to accelerate a paradigm shift in oncology care such that patients with cancer could receive exercise and nutrition programming as the standard of care in tandem with chemotherapy to improve relative dose intensity for a curative outcome.

BackgroundThe legal climate for cannabis use has dramatically changed with an increasing number of states passing legislation legalizing access for medical and recreational use. Among cancer patients, cannabis is often used to ameliorate adverse effects of cancer treatment. Data are limited on the extent and type of use among cancer patients during treatment and the perceived benefits and harms. This multicenter survey was conducted to assess the use of cannabis among cancer patients residing in states with varied legal access to cannabis.MethodsA total of 12 NCI-Designated Cancer Centers, across states with varied cannabis-access legal status, conducted surveys with a core questionnaire to assess cannabis use among recently diagnosed cancer patients. Data were collected between September 2021 and August 2023 and pooled across 12 cancer centers. Frequencies and 95% confidence intervals for core survey measures were calculated, and weighted estimates are presented for the 10 sites that drew probability samples.ResultsOverall reported cannabis use since cancer diagnosis among survey respondents was 32.9% (weighted), which varied slightly by state legalization status. The most common perceived benefits of use were for pain, sleep, stress and anxiety, and treatment side effects. Reported perceived risks were less common and included inability to drive, difficulty concentrating, lung damage, addiction, and impact on employment. A majority reported feeling comfortable speaking to health-care providers though, overall, only 21.5% reported having done so. Among those who used cannabis since diagnosis, the most common modes were eating in food, smoking, and pills or tinctures, and the most common reasons were for sleep disturbance, followed by pain and stress and anxiety with 60%-68% reporting improved symptoms with use.ConclusionThis geographically diverse survey demonstrates that patients use cannabis regardless of its legal status. Addressing knowledge gaps concerning benefits and harms of cannabis use during cancer treatment is critical to enhance patient-provider communication.

Precision medicine holds great promise for improving cancer outcomes. Yet, there are large inequities in the demographics of patients from whom genomic data and models, including patient-derived xenografts (PDX), are developed and for whom treatments are optimized. In this study, we developed a genetic ancestry pipeline for the Cancer Genomics Cloud, which we used to assess the diversity of models currently available in the National Cancer Institute-supported PDX Development and Trial Centers Research Network (PDXNet). We showed that there is an under-representation of models derived from patients of non-European ancestry, consistent with other cancer model resources. We discussed these findings in the context of disparities in cancer incidence and outcomes among demographic groups in the US, as well as power analyses for biomarker discovery, to highlight the immediate need for developing models from minority populations to address cancer health equity in precision medicine. Our analyses identified key priority disparity-associated cancer types for which new models should be developed.SignificanceUnderstanding whether and how tumor genetic factors drive differences in outcomes among U.S. minority groups is critical to addressing cancer health disparities. Our findings suggest that many additional models will be necessary to understand the genome-driven sources of these disparities.

Although patient-derived xenografts (PDX) are commonly used for preclinical modeling in cancer research, a standard approach to in vivo tumor growth analysis and assessment of antitumor activity is lacking, complicating the comparison of different studies and determination of whether a PDX experiment has produced evidence needed to consider a new therapy promising. We present consensus recommendations for assessment of PDX growth and antitumor activity, providing public access to a suite of tools for in vivo growth analyses. We expect that harmonizing PDX study design and analysis and assessing a suite of analytical tools will enhance information exchange and facilitate identification of promising novel therapies and biomarkers for guiding cancer therapy.

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.

Objectives: To descriptively assess cannabis perceptions and patterns of use among older adult cancer survivors in a state without a legal cannabis marketplace. Methods: This study used weighted prevalence estimates to cross-sectionally describe cannabis perceptions and patterns of use among older (65+) adults (N = 524) in a National Cancer Institute-designated center in a state without legal cannabis access. Results: Half (46 %) had ever used cannabis (18% following diagnosis and 10 % currently). Only 8% had discussed cannabis with their provider. For those using post-diagnosis, the most common reason was for pain (44%), followed by insomnia (43%), with smoking being the most common (40%) mode of use. Few (<3%) reported that cannabis had worsened any of their symptoms. Discussion: Even within a state without a legal cannabis marketplace, older cancer survivors might commonly use cannabis to alleviate health concerns but unlikely to discuss this with their providers. [ABSTRACT FROM AUTHOR]

The Health Communication and Informatics Research Branch at the U.S. National Cancer Institute was founded in 1999 in response to increasing evidence demonstrating a link between effective health communication and improved cancer-related outcomes and in recognition of the rapid and dramatic technological changes that were transforming health communication at the turn of the 21st century. For the past 25 years, the Health Communication and Informatics Research Branch has been conducting and supporting research at the forefront of emerging cancer communication trends and technologies, making numerous contributions to health communication science, public health, and cancer control practice. In this essay, we provide a brief history of the branch and the context that led to its establishment, discuss contributions made by the branch to health communication research and practice through key projects and initiatives, and conclude by highlighting health communication and informatics research priorities that offer opportunities for significant impact going forward in light of the challenges posed by the current communication environment. [ABSTRACT FROM AUTHOR]

PURPOSE: Cancer center clinical trial offices (CCTOs) support trial development, activation, conduct, regulatory adherence, data integrity, and compliance. In 2018, the Association of American Cancer Institutes (AACI) Clinical Research Innovation (CRI) Steering Committee conducted and published survey results to benchmark North American CCTOs, including trial volume, accrual, full time equivalents (FTEs), and budget. The survey was readministered in 2023 to assess contemporary CCTO performance and capacity with results presented here. METHODS: The 28 question 2023 survey was sent to directors of AACI's clinical member cancer centers. Survey participation was voluntary, no compensation was provided, and data requested covered operations during 2022. Definitions were consistent with National Cancer Institute (NCI) CCTO reporting requirements and AACI staff anonymously compiled results for descriptive statistical reporting. RESULTS: The survey response rate was 61% (60/99). The median annual CCTO budget was $11.5 million (M) US dollars (USD) versus $8.2M USD in 2018. These budgets support a median of 150 FTEs versus 104 previously, and a median total of 384 versus 280 interventional treatment trials and a median of 479 versus 531 interventional treatment accruals. Sources of support for CCTO annual budgets were primarily from industry revenue (45.3%) or institutional support (31.7%). Nearly 60% of centers reported activating NCI-sponsored studies within 90 days but only 9% reported meeting a 90-day activation timeline for industry sponsored studies. CONCLUSION: Contemporary benchmarks for CCTO operations through this survey demonstrate larger staff sizes, larger budgets, more trials supported, but fewer patients enrolled to interventional treatment trials in comparison with 2018. These data shine a critical light on the increasing complexity of cancer clinical trials, the importance of external funding sources, and necessary operational efficiency upgrades to provide cutting-edge cancer research and care. [ABSTRACT FROM AUTHOR]

An estimated 38 million people live with human immunodeficiency virus (HIV) worldwide and are at excess risk for multiple cancer types. Elevated cancer risks in people living with HIV (PLWH) are driven primarily by increased exposure to carcinogens, most notably oncogenic viruses acquired through shared transmission routes, plus acceleration of viral carcinogenesis by HIV-related immunosuppression. In the era of widespread antiretroviral therapy (ART), life expectancy of PLWH has increased, with cancer now a leading cause of co-morbidity and death. Furthermore, the types of cancers occurring among PLWH are shifting over time and vary in their relative burden in different parts of the world. In this context, the International Agency for Research on Cancer (IARC) and the US National Cancer Institute (NCI) convened a meeting in September 2022 of multinational and multidisciplinary experts to focus on cancer in PLWH. This report summarizes the proceedings, including a review of the state of the science of cancer descriptive epidemiology, etiology, molecular tumor characterization, primary and secondary prevention, treatment disparities and survival in PLWH around the world. A consensus of key research priorities and recommendations in these domains is also presented.

The optimal management of locally advanced rectal cancer is rapidly evolving. The National Cancer Institute Rectal-Anal Task Force convened an expert panel to develop consensus on the design of future clinical trials of patients with rectal cancer. A series of 82 questions and subquestions, which addressed radiation and neoadjuvant therapy, patient perceptions, rectal cancer populations of special interest, and unique design elements, were subject to iterative review using a Delphi analytical approach to define areas of consensus and those in which consensus is not established. The task force achieved consensus on several areas, including the following: 1) the use of total neoadjuvant therapy with long-course radiation therapy either before or after chemotherapy, as well as short-course radiation therapy followed by chemotherapy, as the control arm of clinical trials; 2) the need for greater emphasis on patient involvement in treatment choices within the context of trial design; 3) efforts to identify those patients likely, or unlikely, to benefit from nonoperative management or minimally invasive surgery; 4) investigation of the utility of circulating tumor DNA measurements for tailoring treatment and surveillance; and 5) the need for identification of appropriate end points and recognition of challenges of data management for patients who enter nonoperative management trial arms. Substantial agreement was reached on priorities affecting the design of future clinical trials in patients with locally advanced rectal cancer.

This is the American Cancer Society's biennial update of statistics on breast cancer among women based on high‐quality incidence and mortality data from the National Cancer Institute and the Centers for Disease Control and Prevention. Breast cancer incidence continued an upward trend, rising by 1% annually during 2012–2021, largely confined to localized‐stage and hormone receptor‐positive disease. A steeper increase in women younger than 50 years (1.4% annually) versus 50 years and older (0.7%) overall was only significant among White women. Asian American/Pacific Islander women had the fastest increase in both age groups (2.7% and 2.5% per year, respectively); consequently, young Asian American/Pacific Islander women had the second lowest rate in 2000 (57.4 per 100,000) but the highest rate in 2021 (86.3 per 100,000) alongside White women (86.4 per 100,000), surpassing Black women (81.5 per 100,000). In contrast, the overall breast cancer death rate continuously declined during 1989–2022 by 44% overall, translating to 517,900 fewer breast cancer deaths during this time. However, not all women have experienced this progress; mortality remained unchanged since 1990 in American Indian/Alaska Native women, and Black women have 38% higher mortality than White women despite 5% lower incidence. Although the Black‐White disparity partly reflects more triple‐negative cancers, Black women have the lowest survival for every breast cancer subtype and stage except localized disease, with which they are 10% less likely to be diagnosed than White women (58% vs. 68%), highlighting disadvantages in social determinants of health. Progress against breast cancer could be accelerated by mitigating racial, ethnic, and social disparities through improved clinical trial representation and access to high‐quality screening and treatment. [ABSTRACT FROM AUTHOR]

The objectives of this study were to assess the feasibility of utilizing computational calculations and the simulation of the National Cancer Institute computed tomography (NCICT) dosimetry system to obtain size-specific dose estimate (SSDE) and effective dose values resulting from the most common CT examinations in Thai pediatric patients and to evaluate age- and size-specific k conversion factor. For the calculation methods, SSDEs were calculated using the American Association of Physicists in Medicine Report No. 220 and 293 methodologies. The results revealed that SSDEs derived from CT scans of the body, obtained through the two different methods, varied by within 10%. The size of the patient and the scanning distance had an impact on the variability of E values derived from NCICT. Age- and size-specific k conversion factors may be used as a first line to estimate risk for the pediatric patients. [ABSTRACT FROM AUTHOR]

Clinical ethics consultation services (CECS) can be particularly complex in oncology, and widespread misconceptions exist about their nature. As a result, visibility and accessibility of information regarding CECS is critical. We investigated the availability and content of information regarding CECS on websites of NCI-designated comprehensive cancer centers and cancer centers (CCs). Each website was reviewed for information on CECS and reviewed for benchmarks partially derived from the American Society of Bioethics and Humanities recommendations for CECS. Our analysis revealed that of 70 NCI-designated center websites, 38 had information on CECS, and 17 were found directly on these sites. When CECS information was available, most websites provided a mission statement (71%) and an explanation of what constitutes an ethics consult (74%). Few provided a description of the consult process (45%) or service membership (39%). Our findings reveal a significant gap in CECS visibility on the websites of NCI-designated CCs. [ABSTRACT FROM AUTHOR]

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PURPOSE: Routine collection of sexual orientation (SO) and gender identity (GI; collectively SOGI) in cancer clinics advances cancer care equity. METHODS: In 2022, NCI Community Oncology Research Program (NCORP) practice groups were asked about routine collection of SOGI data in the electronic health record. The proportions of practice groups reporting collection of SO and/or GI data were calculated, and practice group characteristics were assessed for associations. RESULTS: Of 271 practice groups nationwide, 42% (n = 112) collect SO data, 58% (n = 157) collect GI data, and 35% (n = 96) collect both. In multivariate analyses, SO data collection was associated with practice groups having minority outreach staff (odds ratio [OR], 2.07 [95% CI, 1.12 to 3.81]; P =.02); GI data collection was associated with practice groups located in the Northeastern United States (OR, 2.08 [95% CI, 0.73 to 5.91]; P =.045), and those with a higher proportion of new patients who were White (OR, 1.02 [95% CI, 1.01 to 1.04]; P <.001). Practice groups in the South were least likely to collect SOGI data (OR, 0.49 [95% CI, 0.26 to 0.94]; P =.004). There were no statistically significant differences in SO and/or GI collection on the basis of the practice group's proportion of Medicaid/Medicare patients, number of new patients with cancer per year, or practice ownership. CONCLUSION: Slightly over one third of NCORP practice groups report routinely collecting SOGI data. There are regional differences in data collection, underscoring the need to craft targeted, region-specific interventions focused on boosting the capture and recording of SOGI data in an affirming manner. [ABSTRACT FROM AUTHOR]

Important progress has been made over the last decade in the classification, imaging, and treatment of neuroendocrine neoplasm (NENs), with several new agents approved for use. Although the treatment options available for patients with well-differentiated neuroendocrine tumors (NETs) have greatly expanded, the rapidly changing landscape has presented several unanswered questions about how best to optimize, sequence, and individualize therapy. Perhaps the most important development over the last decade has been the approval of 177Lu-DOTATATE for treatment of gastroenteropancreatic-NETs, raising questions around optimal sequencing of peptide receptor radionuclide therapy (PRRT) relative to other therapeutic options, the role of re-treatment with PRRT, and whether PRRT can be further optimized through use of dosimetry among other approaches. The NET Task Force of the National Cancer Institute GI Steering Committee convened a clinical trial planning meeting in 2021 with multidisciplinary experts from academia, the federal government, industry, and patient advocates to develop NET clinical trials in the era of PRRT. Key clinical trial recommendations for development included 1) PRRT re-treatment, 2) PRRT and immunotherapy combinations, 3) PRRT and DNA damage repair inhibitor combinations, 4) treatment for liver-dominant disease, 5) treatment for PRRT-resistant disease, and 6) dosimetry-modified PRRT.

Data-driven basic, translational, and clinical research has resulted in improved outcomes for children, adolescents, and young adults (AYAs) with pediatric cancers. However, challenges in sharing data between institutions, particularly in research, prevent addressing substantial unmet needs in children and AYA patients diagnosed with certain pediatric cancers. Systematically collecting and sharing data from every child and AYA can enable greater understanding of pediatric cancers, improve survivorship, and accelerate development of new and more effective therapies. To accomplish this goal, the Childhood Cancer Data Initiative (CCDI) was launched in 2019 at the National Cancer Institute. CCDI is a collaborative community endeavor supported by a 10-year, $50-million (in US dollars) annual federal investment. CCDI aims to learn from every patient diagnosed with a pediatric cancer by designing and building a data ecosystem that facilitates data collection, sharing, and analysis for researchers, clinicians, and patients across the cancer community. For example, CCDIs Molecular Characterization Initiative provides comprehensive clinical molecular characterization for children and AYAs with newly diagnosed cancers. Through these efforts, the CCDI strives to provide clinical benefit to patients and improvements in diagnosis and care through data-focused research support and to build expandable, sustainable data resources and workflows to advance research well past the planned 10 years of the initiative. Importantly, if CCDI demonstrates the success of this model for pediatric cancers, similar approaches can be applied to adults, transforming both clinical research and treatment to improve outcomes for all patients with cancer.

Brain metastases are an increasing global public health concern, even as survival rates improve for patients with metastatic disease. Both metastases and the sequelae of their treatment are key determinants of the inter-related priorities of patient survival, function, and quality of life, mandating a multidimensional approach to clinical care and research. At a virtual National Cancer Institute Workshop in September, 2022, key stakeholders convened to define research priorities to address the crucial areas of unmet need for patients with brain metastases to achieve meaningful advances in patient outcomes. This Policy Review outlines existing knowledge gaps, collaborative opportunities, and specific recommendations regarding consensus priorities and future directions in brain metastases research. Achieving major advances in research will require enhanced coordination between the ongoing efforts of individual organisations and consortia. Importantly, the continual and active engagement of patients and patient advocates will be necessary to ensure that the directionality of all efforts reflects what is most meaningful in the context of patient care.

As the immuno-oncology field continues the rapid growth witnessed over the past decade, optimising patient outcomes requires an evolution in the current response-assessment guidelines for phase 2 and 3 immunotherapy clinical trials and clinical care. Additionally, investigational tools-including image analysis of standard-of-care scans (such as CT, magnetic resonance, and PET) with analytics, such as radiomics, functional magnetic resonance agents, and novel molecular-imaging PET agents-offer promising advancements for assessment of immunotherapy. To document current challenges and opportunities and identify next steps in immunotherapy diagnostic imaging, the National Cancer Institute Clinical Imaging Steering Committee convened a meeting with diverse representation among imaging experts and oncologists to generate a comprehensive review of the state of the field.

BACKGROUND: Literature on advanced practice providers (APPs) prescribing chemotherapy independently, without physician cosignature, is limited. OBJECTIVES: This project assessed safety and provider satisfaction for an existing independent APP chemotherapy prescribing privilege at a National Cancer Institute-designated comprehensive cancer center. METHODS: Rate of Reporting to Improve Safety and Quality events associated with APPs with independent chemotherapy prescribing privileges was compared to that of physicians during a threeyear period. Satisfaction of APPs with independent chemotherapy prescribing privileges was evaluated. FINDINGS: The odds of a reported event were higher for physicians than for APPs. APP survey responses were positive for readiness, confidence, and satisfaction with independent chemotherapy prescribing privilege. [ABSTRACT FROM AUTHOR]

Background: Bortezomib and dexamethasone (BD) regimen offers a promising therapeutic approach in multiple myeloma (MM) by inhibiting the proteolytic pathway of tumor cells. Aims and Objectives: This study aims to assess the safety profile and treatment outcomes of MM patients undergoing the BD regimen. Materials and Methods: This prospective observational study included MM patients who received BD regimen. Patients received bortezomib (1.3 mg/m2 intravenous) weekly for 4 weeks along with dexamethasone (40 mg orally) weekly for 4 weeks. Clinical assessments were performed after each cycle, and adverse drug reactions were graded according to National Cancer Institute criteria. Treatment outcomes were evaluated after the 4th cycle based on specific parameters. Results: Thirtyseven patients, with a mean age of 56.2 years, predominantly male (56.8%), were included. Common symptoms included bone pain, fatigue, weight loss, and appetite loss. Toxicities were mainly grade 1 and 2, with peripheral neuropathy (PN) being the most prevalent. The BD regimen exhibited a response rate of 65%, accompanied by significant improvements in bone marrow plasma cells, β2 microglobulin, immunoglobulin assay, and erythrocyte sedimentation rate. In addition, treatment improved performance status, in 51.4% of patients achieving scores above 90 on the Karnofsky scale. Conclusion: The BD regimen demonstrated notable efficacy and tolerability in MM treatment. However, it is associated with a higher risk of PN. [ABSTRACT FROM AUTHOR]

Outcomes are poor for patients with large B-cell lymphoma who relapse after CD19-directed chimeric antigen receptor (CAR) T-cell therapy (CAR19). CD22 is a nearly universally expressed B-cell surface antigen and the efficacy of a CD22-directed CAR T-cell therapy (CAR22) in large B-cell lymphoma is unknown, which was what we aimed to examine in this study. In this single centre, open-label, dose-escalation phase 1 trial, we intravenously administered CAR22 at two dose levels (1 million and 3 million CAR22-positive T cells per kg of bodyweight) to adult patients (aged ≥18 years) who relapsed after CAR19 or had CD19-negative large B-cell lymphoma. The primary endpoints were manufacturing feasibility, safety measured by the incidence and severity of adverse events and dose-limiting toxicities, and identification of the maximum tolerated dose (ie, the recommended phase 2 dose). This study is registered with ClinicalTrials.gov (NCT04088890) and is active, but closed for enrolment. From Oct 17, 2019, to Oct 19, 2022, a total of 41 patients were assessed for eligibility; however, one patient withdrew. 40 patients underwent leukapheresis and 38 (95%) had CAR T-cell products manufactured successfully. The median age was 65 years (range 25–84), 17 (45%) were women, 32 (84%) had elevated pretreatment lactate dehydrogenase, 11 (29%) had refractory disease to all previous therapies, and patients had received a median of four lines of previous therapy (range 3–8). Of the 38 patients treated, 37 (97%) had relapsed after previous CAR19. The identified maximum tolerated dose was 1 million CAR T cells per kg. Of 29 patients who received the maximum tolerated dose, no patients developed a dose-limiting toxicity or grade 3 or higher cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or immune effector cell-associated haemophagocytic lymphohistiocytosis-like syndrome. This trial identifies CD22 as an immunotherapeutic target in large B-cell lymphoma and demonstrates the durable clinical activity of CAR22 in patients with disease progression after CAR19 therapy. Although these findings are promising, it is essential to recognise that this is a phase 1 dose-finding study. Further investigations are warranted to establish the long-term efficacy and to delineate the patient subgroups that will derive the most benefit from this therapeutic approach. National Cancer Institute, National Institutes of Health, Stanford Cancer Institute, Leukemia & Lymphoma Society, Parker Institute for Cancer Immunotherapy, Lymph & Co, and the European Hematology Association. [ABSTRACT FROM AUTHOR]

Jointpoint Regression Software from the National Cancer Institute was used to model age-adjusted male and female pleural and peritoneal mesothelioma rates in the surveillance, epidemiology, and end results (SEER) 8, SEER 12, and SEER 22 cancer registries. Linear mixed models were then used to determine if there was a statistical association between U.S. cosmetic talc consumption and the 30-year lagged age-adjusted mesothelioma rates (1) over the reporting period for each registry and (2) for the periods of time identified by the jointpoint model where changes in the rate of mesothelioma occurred. Regardless of the SEER registry used, from the early-1980s through 2020, rates of peritoneal mesothelioma have remained steady or declined. Female pleural mesothelioma rates were unchanged from the early-1980s until 2017 when rates declined, while male rates peaked in the early 1990s and have since declined. Cosmetic talc consumption was not statistically associated with an increased rate of pleural or peritoneal mesothelioma in males or females, suggesting that the use of cosmetic talc products is not associated with the development of mesothelioma. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this review is to summarize the impact of the multidisciplinary tumor board as a tool or mechanism for orthopedic oncology care, to highlight its evolution and changing role over time, to assess its strengths and weaknesses, and to report our institutional experience as an NCI-Designated Comprehensive Cancer Center. Methods: We reviewed the relevant literature about multidisciplinary tumor boards in orthopedic oncology, and summarized the articles to provide a summary of the topic. Additionally, we retrospectively reviewed our electronic medical records to analyze the distribution, characteristics, and numbers of the cases that were discussed. Results: Our retrospective institutional review revealed a total of 1178 individual patients discussed between August 2018 and August 2023. There was an even distribution of patients by sex, with 549 female (50.2%) patients and 544 male (49.8%). Diagnoses peaked in the second and sixth decades of life (189 and 175 patients, respectively). The majority of patients were discussed once (55%) or twice (21%). The most common neoplastic diagnosis that was presented in these meetings was giant cell tumor of bone (n = 51). Osteosarcoma (n = 41) was the most common diagnosis among the primary malignant bone tumors, and liposarcomas (n = 41) were the most frequently discussed soft tissue sarcoma histology. Conclusion: Tumor boards have played a central role in cancer care for almost a century. Our experience at an NCI-designated comprehensive cancer center has yielded a review of over a thousand individual cases in only a 5-year span of time. [ABSTRACT FROM AUTHOR]

Systematic evaluations of cancer risk in people living with HIV or AIDS (PLHIV) and solid organ transplant recipients provide unique insights into the role of the immune system in cancer development. In this systematic review and meta-analysis, we expand previous analyses of cancer risk for these two immunocompromised populations. We considered studies published in English and listed on PubMed or Embase up to July 1, 2022. Studies were eligible for inclusion if they used population-based registries and compared cancer incidence in PLHIV or solid organ transplant recipients with the general population in the same geographical area. We extracted the number of observed site-specific cancers and expected cases and calculated meta-standardised incidence ratios for cancer within PLHIV and solid organ transplant recipients. In solid organ transplant recipients meta-standardised incidence ratios were compared by organ type. This project is registered on PROSPERO, CRD42022366679. 46 studies in PLHIV and 67 in solid organ transplant recipients were included in the analysis. Meta-standardised incidence ratios for cancers associated with human papillomavirus were increased in both populations; the highest meta-standardised incidence ratio in PLHIV was anal cancer (37·28 [95% CI 23·65–58·75], I 2=97·4%), and in solid organ transplant recipients was cutaneous squamous cell carcinoma (45·87 [31·70–66·38], I 2=99·0%). Meta-standardised incidence ratios were significantly increased for most non-HPV viral-infection-related cancers in both populations; the highest standard incidence ratios were for Kaposi sarcoma (PLHIV: 801·52 [95% CI 200·25–3208·13], I 2=100·0%; solid organ transplant recipients: 47·31 [23·09–96·95], I 2=87·7%) and non-Hodgkin lymphoma (32·53 [19·64–53·87], I 2=99·8%; 10·24 [8·48–12·35], I 2=94·9%). Eight types of cancer with no known viral cause showed an increased risk in solid organ transplant recipients only; no cancer type showed increased risk in PLHIV only. Cancer risk was increased for a range of infection-related cancers in both PLHIV and solid organ transplant recipients, but divergent results in these and other cancers have emerged. The cancer risk patterns probably reflect variances in the degree of impaired immunity, exposure to carcinogenic viruses, and perhaps exposure to carcinogenic immunosuppressive agents. US National Cancer Institute, National Institutes of Health. [ABSTRACT FROM AUTHOR]

Background: Survivors of rectal cancer experience persistent bowel dysfunction after treatments. Dietary interventions may be an effective approach for symptom management and posttreatment diet quality. SWOG S1820 was a pilot randomized trial of the Altering Intake, Managing Symptoms in Rectal Cancer (AIMS‐RC) intervention for bowel dysfunction in survivors of rectal cancer. Methods: Ninety‐three posttreatment survivors were randomized to the AIMS‐RC group (N = 47) or the Healthy Living Education attention control group (N = 46) after informed consent and completion of a prerandomization run‐in. Outcome measures were completed at baseline and at 18 and 26 weeks postrandomization. The primary end point was total bowel function score, and exploratory end points included low anterior resection syndrome (LARS) score, quality of life, dietary quality, motivation, self‐efficacy, and positive/negative affect. Results: Most participants were White and college educated, with a mean age of 55.2 years and median time since surgery of 13.1 months. There were no statistically significant differences in total bowel function score by group, with the AIMS‐RC group demonstrating statistically significant improvements in the exploratory end points of LARS (p =.01) and the frequency subscale of the bowel function index (p =.03). The AIMS‐RC group reported significantly higher acceptability of the study. Conclusions: SWOG S1820 did not provide evidence of benefit from the AIMS‐RC intervention relative to the attention control. Select secondary end points did demonstrate improvements. The study was highly feasible and acceptable for participants in the National Cancer Institute Community Oncology Research Program. Findings provide strong support for further refinement and effectiveness testing of the AIMS‐RC intervention. In this feasibility and preliminary efficacy randomized trial, the Altering Intake, Managing Symptoms in Rectal Cancer (AIMS‐RC) diet modification intervention did not significantly improve total bowel function among survivors of rectal cancer but demonstrated improvements in the frequency of bowel movements and low anterior resection syndrome. SWOG S1820 and the AIMS‐RC intervention were highly feasible and acceptable for participants enrolled via the National Cancer Institute Community Oncology Research Program. [ABSTRACT FROM AUTHOR]

First-line biparametric magnetic resonance imaging (bpMRI) screening has been proposed as an alternative to prostate-specific antigen (PSA) testing for prostate cancer screening. This decision analysis used a microsimulation model to evaluate the comparative effectiveness and cost-effectiveness of first-line bpMRI versus PSA-based screening among U.S. men aged 55 years with no prior screening or prostate cancer diagnosis. Visual Abstract. Lifetime Health and Economic Outcomes of Biparametric Magnetic Resonance Imaging as First-Line Screening for Prostate Cancer: First-line biparametric magnetic resonance imaging (bpMRI) screening has been proposed as an alternative to prostate-specific antigen (PSA) testing for prostate cancer screening. This decision analysis used a microsimulation model to evaluate the comparative effectiveness and cost-effectiveness of first-line bpMRI versus PSA-based screening among U.S. men aged 55 years with no prior screening or prostate cancer diagnosis. Background: Contemporary prostate cancer (PCa) screening uses first-line prostate-specific antigen (PSA) testing, possibly followed by multiparametric magnetic resonance imaging (mpMRI) for men with elevated PSA levels. First-line biparametric MRI (bpMRI) screening has been proposed as an alternative. Objective: To evaluate the comparative effectiveness and cost-effectiveness of first-line bpMRI versus PSA-based screening. Design: Decision analysis using a microsimulation model. Data Sources: Surveillance, Epidemiology, and End Results database; randomized trials. Target Population: U.S. men aged 55 years with no prior screening or PCa diagnosis. Time Horizon: Lifetime. Perspective: U.S. health care system. Intervention: Biennial screening to age 69 years using first-line PSA testing (test-positive threshold, 4 µg/L) with or without second-line mpMRI or first-line bpMRI (test-positive threshold, PI-RADS [Prostate Imaging Reporting and Data System] 3 to 5 or 4 to 5), followed by biopsy guided by MRI or MRI plus transrectal ultrasonography. Outcome Measures: Screening tests, biopsies, diagnoses, overdiagnoses, treatments, PCa deaths, quality-adjusted and unadjusted life-years saved, and costs. Results of Base-Case Analysis: For 1000 men, first-line bpMRI versus first-line PSA testing prevented 2 to 3 PCa deaths and added 10 to 30 life-years (4 to 11 days per person) but increased the number of biopsies by 1506 to 4174 and the number of overdiagnoses by 38 to 124 depending on the biopsy imaging scheme. At conventional cost-effectiveness thresholds, first-line PSA testing with mpMRI followed by either biopsy approach for PI-RADS 4 to 5 produced the greatest net monetary benefits. Results of Sensitivity Analysis: First-line PSA testing remained more cost-effective even if bpMRI was free, all men with low-risk PCa underwent surveillance, or screening was quadrennial. Limitation: Performance of first-line bpMRI was based on second-line mpMRI data. Conclusion: Decision analysis suggests that comparative effectiveness and cost-effectiveness of PCa screening are driven by false-positive results and overdiagnoses, favoring first-line PSA testing with mpMRI over first-line bpMRI. Primary Funding Source: National Cancer Institute. [ABSTRACT FROM AUTHOR]

Cancer mortality rates have declined during the last 28 years, but that process is not equitably shared. Disparities in cancer outcomes by race, ethnicity, socioeconomic status, sexual orientation and gender identity, and geographic location persist across the cancer care continuum. Consequently, community outreach and engagement (COE) efforts within National Cancer Institute‐Designated Cancer Center (NCI‐DCC) catchment areas have intensified during the last 10 years as has the emphasis on COE and catchment areas in NCI's Cancer Center Support Grant applications. This review article attempts to provide a historic perspective of COE within NCI‐DCCs. Improving COE has long been an important initiative for the NCI, but it was not until 2012 and 2016 that NCI‐DCCs were required to define their catchment areas rigorously and to provide specific descriptions of COE interventions, respectively. NCI‐DCCs had previously lacked adequate focus on the inclusion of historically marginalized patients in cancer innovation efforts. Integrating COE efforts throughout the research and operational aspects of the cancer centers, at both the patient and community levels, will expand the footprint of COE efforts within NCI‐DCCs. Achieving this change requires sustained commitment by the centers to adjust their activities and improve access and outcomes for historically marginalized communities. [ABSTRACT FROM AUTHOR]

BACKGROUND The identification of oncogenic mutations in diffuse large B-cell lymphoma (DLBCL) has led to the development of drugs that target essential survival pathways, but whether targeting multiple survival pathways may be curative in DLBCL is unknown. METHODS We performed a single-center, phase 1b-2 study of a regimen of venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide (ViPOR) in relapsed or refractory DLBCL. In phase 1b, which included patients with DLBCL and indolent lymphomas, four dose levels of venetoclax were evaluated to identify the recommended phase 2 dose, with fixed doses of the other four drugs. A phase 2 expansion in patients with germinal-center B-cell (GCB) and non-GCB DLBCL was performed. ViPOR was administered every 21 days for six cycles. RESULTS In phase 1b of the study, involving 20 patients (10 with DLBCL), a single dose-limiting toxic effect of grade 3 intracranial hemorrhage occurred, a result that established venetoclax at a dose of 800 mg as the recommended phase 2 dose. Phase 2 included 40 patients with DLBCL. Toxic effects that were observed among all the patients included grade 3 or 4 neutropenia (in 24% of the cycles), thrombocytopenia (in 23%), anemia (in 7%), and febrile neutropenia (in 1%). Objective responses occurred in 54% of 48 evaluable patients with DLBCL, and complete responses occurred in 38%; complete responses were exclusively in patients with non-GCB DLBCL and high-grade B-cell lymphoma with rearrangements of MYC and BCL2 or BCL6 (or both). Circulating tumor DNA was undetectable in 33% of the patients at the end of ViPOR therapy. With a median follow-up of 40 months, 2-year progression-free survival and overall survival were 34% (95% confidence interval [CI], 21 to 47) and 36% (95% CI, 23 to 49), respectively. CONCLUSIONS Treatment with ViPOR was associated with durable remissions in patients with specific molecular DLBCL subtypes and was associated with mainly reversible adverse events. (Funded by the Intramural Research Program of the National Cancer Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health and others; ClinicalTrials.gov number, NCT03223610.) [ABSTRACT FROM AUTHOR]

BACKGROUND The risk of second tumors after chimeric antigen receptor (CAR) T-cell therapy, especially the risk of T-cell neoplasms related to viral vector integration, is an emerging concern. METHODS We reviewed our clinical experience with adoptive cellular CAR T-cell therapy at our institution since 2016 and ascertained the occurrence of second tumors. In one case of secondary T-cell lymphoma, a broad array of molecular, genetic, and cellular techniques were used to interrogate the tumor, the CAR T cells, and the normal hematopoietic cells in the patient. RESULTS A total of 724 patients who had received T-cell therapies at our center were in- cluded in the study. A lethal T-cell lymphoma was identified in a patient who had received axicabtagene ciloleucel therapy for diffuse large B-cell lymphoma, and both lymphomas were deeply profiled. Each lymphoma had molecularly distinct immunophenotypes and genomic profiles, but both were positive for Epstein-Barr virus and were associated with DNMT3A and TET2 mutant clonal hematopoiesis. No evidence of oncogenic retroviral integration was found with the use of multiple techniques. CONCLUSIONS Our results highlight the rarity of second tumors and provide a framework for defining clonal relationships and viral vector monitoring. (Funded by the National Cancer Institute and others.). [ABSTRACT FROM AUTHOR]

Background: Adolescents and young adults (AYAs) commonly receive cancer care in the community setting, but the availability of treatment options, resources, and support services for this population is not well known. The National Cancer Institute Community Oncology Research Program (NCORP) funds a network of practices whose mission is to increase access to cancer care and clinical trials in the community setting. We describe our interdisciplinary methodological approach to identify and characterize NCORP practices where AYAs receive cancer care. Methods: NCORP practices completed a cross-sectional Landscape Assessment to describe resources and practice characteristics. We established an interdisciplinary team of stakeholders to analyze the Landscape Assessment data relating to AYAs. Through an iterative process, we assessed NCORP practice responses to questions assessing AYA cancer care capacity, determined a threshold to define practices treating AYAs, and characterized these practices. Results: We determined that practices provide cancer care to AYAs if the following criteria were met: (1) endorsed having an AYA program (n = 20), (2) AYAs comprised ≥5% of annual cancer cases (n = 55), or (3) the practice treated ≥50 AYA cancer cases annually (n = 70). Of 271 NCORP practices, 100 (37%) met any criteria, whereas 87 (32%) did not; 84 (31%) could not be classified due to missing or unknown data. Conclusion: Using an interdisciplinary process, we define practices that treat AYAs in the community. We posit a uniform approach to examine resources and practice capacity for AYAs receiving cancer care across the United States to guide future AYA-focused cancer care delivery research development. [ABSTRACT FROM AUTHOR]

Background The majority of patients with cancer seek care at community oncology sites; however, most clinical trials are available at National Cancer Institute (NCI)–designated sites. Although the NCI National Cancer Oncology Research Program (NCORP) was designed to address this problem, little is known about the county-level characteristics of NCORP site locations. Methods This cross-sectional analysis determined the association between availability of NCORP or NCI sites and county-level characteristic theme percentile scores from the Center for Disease Control and Prevention's Social Vulnerability Index themes. Health Resources and Services Administration's Area Health Resource Files were used to determine contiguous counties. We estimated risk ratios and 95% confidence intervals (CIs) using modified Poisson regression models to evaluate the association between county-level characteristics and site availability within singular and singular and contiguous counties. Results Of 3141 included counties, 14% had an NCORP, 2% had an NCI, and 1% had both sites. Among singular counties, for a standard deviation increase in the racial and ethnic theme score, there was a 22% higher likelihood of NCORP site availability (95% CI = 1.10 to 1.36); for a standard deviation increase in the socioeconomic status theme score, there was a 24% lower likelihood of NCORP site availability (95% CI = 0.67 to 0.87). Associations were of smaller magnitude when including contiguous counties. NCI sites were located in more vulnerable counties. Conclusions NCORP sites were more often in racially diverse counties and less often in socioeconomically vulnerable counties. Research is needed to understand how clinical trial representation will increase if NCORP sites strategically increase their locations in more vulnerable counties. [ABSTRACT FROM AUTHOR]

BackgroundThe National Cancer Institute (NCI) method has been used widely by researchers to make inferences about usual dietary intake distributions of foods and nutrients based on a limited number of 24-hour dietary recalls (24HRs). Although the NCI method does not provide individual estimates of usual intake, it can be used to address many research questions, including modeling effects of nutrition interventions on population distributions of usual intake. Software for implementing the NCI method and corresponding code examples is publicly available in the form of SAS macros, but little formal guidance exists for conducting advanced analyses.ObjectivesWe aim to present advanced techniques for working with NCI macros to conduct both basic and advanced dietary analyses and modeling.MethodWe first present the three basic building blocks of analyses using the NCI method: 1) dataset preparation; 2) application of the MIXTRAN macro to estimate parameters of the usual intake distribution, including effects of covariates, after transformation of 24HRs to approximate normality; and 3) application of the DISTRIB macro to estimate the distribution of usual nutrient intake. Then, we illustrate how researchers can employ these building blocks to answer questions beyond typical descriptive analyses.ResultsResearchers can adapt the building blocks to 1) account for factors such as demographic changes or nutrition interventions such as food fortification, 2) estimate the prevalence of dietary inadequacy via the full probability method, 3) incorporate nutrient intake from sources not always captured by 24HRs, such as dietary supplements and human milk, and 4) carry out multiple subgroup analyses. This paper describes the theoretical basis and operational guidance for these techniques.ConclusionWith this paper as a detailed resource, researchers can leverage the basic NCI building blocks to investigate a wide range of questions about usual dietary intake distribution.

PURPOSE: Major adverse cardiac events (MACEs) because of immune checkpoint inhibitors (ICIs) are infrequent immune-related adverse events (irAEs) that comprise a spectrum of cardiac toxicities with variable manifestations. ICI-related MACEs can lead to significant morbidity and mortality, hence the need to better define presentations of MACEs and their association with noncardiac irAEs in ICI-treated patients. METHODS: We conducted a retrospective pooled analysis of MACE captured in the serious adverse events reporting database of the National Cancer Institute-Cancer Therapy Evaluation Program for National Cancer Institute-sponsored investigational clinical trials between June 2015 and December 2019. Patients were eligible if they had been treated with anti-programmed cell death protein-1 (anti-PD-1)/programmed cell death-ligand 1 (anti-PD-L1) alone or with additional anticancer therapies. RESULTS: A total of 6,925 participants received anti-PD-(L)1-based therapies; 48% (n = 3,354) were treated with single-agent anti-PD-(L)1 therapy. Of 6,925 patients, 0.6% (n = 40) qualified as ICI-related MACE, with 77.5% (n = 31 of 40) being ≥ grade 3. Myocarditis accounted for 45% (n = 18 of 40) of total ICI-MACEs. Concurrent multisystem involvement with other noncardiac irAEs was seen in 65% (n = 26 of 40). Most patients with myocarditis (83%, n = 15 of 18) had one or more noncardiac irAEs associated. Incidence of MACE was higher with anti-PD-(L)1 + targeted therapies compared with anti-PD-(L)1 + anti-cytotoxic T-cell lymphocyte-4 combinations (2.1% v 0.9%, P = .08). There was a higher incidence of myocarditis with anti-PD-(L)1-based combination therapies versus single-agent anti-PD-(L)1 therapies (0.36%, n = 13 of 3,571 v 0.15%, n = 5 of 3,354, P = .08). Deaths related to myocarditis were identified in 22.5% (n = 4 of 18). All four patients who died had concurrent myositis. CONCLUSION: Increasing patient and prescriber awareness in understanding patterns of ICI-MACE and associated noncardiac irAEs should be emphasized. Better characterization of the risk of MACE with the concurrent use of non-ICI-based anticancer therapies with anti-PD-(L)1 treatments is needed.

PURPOSE: Despite therapeutic advances in the treatment of ovarian cancer (OC), 5-year survival remains low, and patients eventually die from recurrent, chemotherapy-resistant disease. The National Cancer Gynecologic Cancer Steering Committee identified the integration of scientifically defined subgroups as a top strategic priority in clinical trial planning. METHODS: A group of experts was convened to review the scientific literature in OC to identify validated predictive biomarkers that could inform patient selection and treatment stratification. Here, we report on these findings and their potential for use in future clinical trial design on the basis of hierarchal evidence grading. RESULTS: The biomarkers were classified on the basis of mechanistic targeting, including DNA repair and replication stress, immunotherapy and tumor microenvironment, oncogenic signaling, and angiogenesis. Currently, BRCA mutations and homologous recombination deficiency to predict poly (ADP-ribose) polymerase inhibitor response are supported in OC by the highest level of evidence. Additional biomarkers of response to agents targeting the pathways above have been identified but require prospective validation. CONCLUSION: Although a number of biomarkers of response to various agents in OC have been described in the literature, high-level evidence for the majority is lacking. This report highlights the unmet need for identification and validation of predictive biomarkers to guide therapy and future trial design in OC.

BackgroundLocally advanced cervical cancer (CC) remains lethal in the United States. We investigate the effect of receiving care at an National Cancer Institute-designated cancer center (NCICC) on survival.MethodsData for women diagnosed with CC from 2004 to 2016 who received radiation treatment were extracted from the California Cancer Registry (n = 4250). Cox proportional hazards regression models assessed whether (1) receiving care at NCICCs was associated with risk of CC-specific death, (2) this association remained after multivariable adjustment for age, race/ethnicity, and insurance status, and (3) this association was explained by receipt of guideline-concordant treatment.ResultsMedian age was 50 years (interquartile range [IQR] 41-61 years), with median follow-up of 2.7 years (IQR 1.3-6.0 years). One-third of patients were seen at an NCICC, and 29% died of CC. The hazard of CC-specific death was reduced by 20% for those receiving care at NCICCs compared with patients receiving care elsewhere (HR = .80; 95% CI, 0.70-0.90). Adjustment for guideline-concordant treatment and other covariates minimally attenuated the association to 0.83 (95% CI, 0.74-0.95), suggesting that the survival advantage associated with care at NCICCs may not be due to receipt of guideline-concordant treatment.ConclusionsThis study demonstrates survival benefit for patients receiving care at NCICCs compared with those receiving care elsewhere that is not explained by differences in guideline-concordant care. Structural, organizational, or provider characteristics and differences in patients receiving care at centers with and without NCI designation could explain observed associations. Further understanding of these factors will promote equality across oncology care facilities and survival equity for patients with CC.

Children and adolescents diagnosed with cancer can now expect an average 85% 5-year overall survival, with significant improvements in longer-term morbidity and mortality reported over the past several decades. However, the long-term impact of therapeutic agents and modalities introduced in recent years remains unclear and will require dedicated follow-up in the years ahead. The Children's Oncology Group (COG), a part of the NCI's National Clinical Trials Network, with over 200 sites across North America and beyond, enrolls more than 10,000 patients onto research protocols annually, inclusive of first-line clinical trials and nontherapeutic studies. COG provides a platform to conduct survivorship research with several unique strengths: (i) a huge catchment to ascertain relatively rare but important adverse events, (ii) study populations that are otherwise too rare to study in smaller consortia, including access to highly diverse patient populations, (iii) long-term follow-up of clinical trial populations linked to the original trial data, and (iv) a natural platform for intervention research. Enhancements in COG infrastructure facilitate survivorship research, including a COG patient registry (Project:EveryChild), availability of a long-term follow-up tracking resource, and successful deployment of various remote-based study procedures to reduce the burden on participants and participating institutions.

Angiosarcoma is a rare subtype of malignant neoplasm originating from vascular or lymphatic endothelial cells; its low incidence has posed significant challenges for comprehensive investigations into its pathogenic mechanisms and the development of innovative treatment modalities through in vitro and in vivo models. Recent endeavors spearheaded by patient-partnered research initiatives have aimed to elucidate the intricacies of angiosarcomas by leveraging biological omics approaches, with the overarching objective of enhancing prognostic indicators and therapeutic options for this uncommon pathology. To bridge the gap between preclinical research and translational applications, we engineered angiosarcoma-derived organoids from surgically resected primary tumors, hereafter referred to as "sarconoids," as a proof-of-concept model. A novel protocol for the establishment of these sarconoids has been developed and validated. To ensure that the sarconoids faithfully recapitulate the heterogeneity and complexities of the patients' original tumors, including transcriptomic signatures, cell-type specificity, and morphological traits, exhaustive histological and transcriptomic analyses were conducted. Subsequently, we expanded the scope of our study to include an evaluation of a sarconoid-based drug screening platform; for this purpose, a drug library (AOD IX), supplied by the National Cancer Institute's Developmental Therapeutics Program, was screened using 96-well plates. Our findings suggest that sarconoids can be reliably generated from angiosarcoma patient-derived tissues and can serve as accurate models for evaluating therapeutic responses, thereby holding far-reaching implications for translational research and clinical applications aimed at advancing our understanding and treatment of angiosarcoma. [ABSTRACT FROM AUTHOR]

Background: Lymph node metastasis in vulvar cancer is a critical prognostic factor associated with higher recurrence and decreased survival. A survival benefit is reported with adjuvant radiotherapy but with potential significant morbidity. We aim to clarify whether there is high-quality evidence to support the use of adjuvant radiotherapy in this setting. Objectives: The aim of the study was to assess the effectiveness and safety of adjuvant radiotherapy to locoregional metastatic nodal areas. Search Methods: We conducted a comprehensive and systematic literature search of MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Google Scholar, ClinicalTrials.gov, and the National Cancer Institute. We considered only randomized controlled trials (RCTs). Main Results: We identified 1,760 records and finally retrieved only one eligible RCT (114 participants with positive inguinofemoral lymph nodes). All women had undergone radical vulvectomy and bilateral inguinal lymphadenectomy and had been randomized to adjuvant radiotherapy or to intraoperative ipsilateral pelvic lymphadenectomy without adjuvant radiotherapy. At 6 years, the overall survival (OS) was 51% versus 41% in favor of radiotherapy (HR 0.61; 95% CI 0.30--1.3) without significance and with very low certainty of evidence. At 6 year, the cumulative incidence of cancer-related deaths was 29% versus 51% in favor of adjuvant radiotherapy (HR 0.49; 95% CI 0.28--0.87). Recurrence-free survival at 6 years was 59% after adjuvant radiotherapy versus 48% after pelvic lymphadenectomy (HR 0.39; 95% CI 0.17--0.88). Three (5.3%) versus 13 (24.1%) groin recurrences were noted, respectively, in the adjuvant radiotherapy and pelvic lymphadenectomy groups. There was no significant difference in acute toxicities for pelvic lymphadenectomy compared to radiotherapy. In women with positive pelvic lymph nodes (20%), the OS at 6 year was 36% compared with 13% in favor of adjuvant radiotherapy. Late cutaneous toxicity rate appeared to be greater after radiotherapy (19% vs. 15%) but with less chronic lymphedema (16% vs. 22%). Conclusion: There is only very low-quality evidence on administering adjuvant radiotherapy for inguinal lymph node metastases. Although the identified study was a multicenter RCT, there was a reasonable imprecision and inconsistency because of small study numbers, wide confidence intervals in the data, and early trial closure, resulting in downgrading of the evidence. [ABSTRACT FROM AUTHOR]

Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare and aggressive cancer predisposition syndrome. Because a scarcity of data on this condition contributes to management challenges and poor outcomes, we aimed to describe the clinical spectrum, cancer biology, and impact of genetics on patient survival in CMMRD. In this cohort study, we collected cross-sectional and longitudinal data on all patients with CMMRD, with no age limits, registered with the International Replication Repair Deficiency Consortium (IRRDC) across more than 50 countries. Clinical data were extracted from the IRRDC database, medical records, and physician-completed case record forms. The primary objective was to describe the clinical features, cancer spectrum, and biology of the condition. Secondary objectives included estimations of cancer incidence and of the impact of the specific mismatch-repair gene and genotype on cancer onset and survival, including after cancer surveillance and immunotherapy interventions. We analysed data from 201 patients (103 males, 98 females) enrolled between June 5, 2007 and Sept 9, 2022. Median age at diagnosis of CMMRD or a related cancer was 8·9 years (IQR 5·9–12·6), and median follow-up from diagnosis was 7·2 years (3·6–14·8). Endogamy among minorities and closed communities contributed to high homozygosity within countries with low consanguinity. Frequent dermatological manifestations (117 [93%] of 126 patients with complete data) led to a clinical overlap with neurofibromatosis type 1 (35 [28%] of 126). 339 cancers were reported in 194 (97%) of 201 patients. The cumulative cancer incidence by age 18 years was 90% (95% CI 80–99). Median time between cancer diagnoses for patients with more than one cancer was 1·9 years (IQR 0·8–3·9). Neoplasms developed in 15 organs and included early-onset adult cancers. CNS tumours were the most frequent (173 [51%] cancers), followed by gastrointestinal (75 [22%]), haematological (61 [18%]), and other cancer types (30 [9%]). Patients with CNS tumours had the poorest overall survival rates (39% [95% CI 30–52] at 10 years from diagnosis; log-rank p<0·0001 across four cancer types), followed by those with haematological cancers (67% [55–82]), gastrointestinal cancers (89% [81–97]), and other solid tumours (96% [88–100]). All cancers showed high mutation and microsatellite indel burdens, and pathognomonic mutational signatures. MLH1 or MSH2 variants caused earlier cancer onset than PMS2 or MSH6 variants, and inferior survival (overall survival at age 15 years 63% [95% CI 55–73] for PMS2 , 49% [35–68] for MSH6 , 19% [6–66] for MLH1 , and 0% for MSH2 ; p<0·0001). Frameshift or truncating variants within the same gene caused earlier cancers and inferior outcomes compared with missense variants (p<0·0001). The greater deleterious effects of MLH1 and MSH2 variants as compared with PMS2 and MSH6 variants persisted despite overall improvements in survival after surveillance or immune checkpoint inhibitor interventions. The very high cancer burden and unique genomic landscape of CMMRD highlight the benefit of comprehensive assays in timely diagnosis and precision approaches toward surveillance and immunotherapy. These data will guide the clinical management of children and patients who survive into adulthood with CMMRD. The Canadian Institutes for Health Research, Stand Up to Cancer, Children's Oncology Group National Cancer Institute Community Oncology Research Program, Canadian Cancer Society, Brain Canada, The V Foundation for Cancer Research, BioCanRx, Harry and Agnieszka Hall, Meagan's Walk, BRAINchild Canada, The LivWise Foundation, St Baldrick Foundation, Hold'em for Life, and Garron Family Cancer Center. [ABSTRACT FROM AUTHOR]

Prior research has defined cancer service areas (CSAs) anchored by major cancer centers in the U.S., such as members of the Association of American Cancer Institutes (AACI). Those CSAs have discrete boundaries and may not capture the increasingly interwoven cancer care markets. This is the first attempt to delineate possible overlapping CSAs. Specifically, we integrate the concept of shared memberships and other spatial attributes into the Speaker‐Listener Label Propagation (SLPA) algorithm, termed the spatially constrained SLPA (or ScSLPA), and apply it to six representative areas in the U.S. The results show that overlapping CSAs tend to form in areas that are more urbanized, with higher localization index (LI) values, larger populations, and shorter travel times than discrete CSAs. Two CSAs in Los Angeles and San Diego are consistent with the catchment areas (CAs) of the National Cancer Institute (NCI)‐designated cancer centers, and other CSAs are much smaller than the CAs of their anchoring cancer centers. The study has important implications for public health policy to advance cancer control and prevention efforts. [ABSTRACT FROM AUTHOR]

This population-based assessment suggests that diagnosis of high-grade serous tubo-ovarian carcinoma has been rapidly shifting from high-grade serous ovarian to fallopian tubal carcinoma in recent years in the United States. OBJECTIVE: To assess population-level trends, characteristics, and outcomes of high-grade serous tubo-ovarian carcinoma in the United States. METHODS: This retrospective cohort study queried the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The study population was 27,811 patients diagnosed with high-grade serous tubo-ovarian carcinoma from 2004 to 2020. The exposure was the primary cancer site (ovary or fallopian tube). Main outcome measures were temporal trends, clinical characteristics, and overall survival associated with primary cancer site assessed in multivariable analysis. RESULTS: The study population comprised 23,967 diagnoses of high-grade serous ovarian carcinoma and 3,844 diagnoses of high-grade serous fallopian tubal carcinoma. The proportion of diagnoses of high-grade serous fallopian tubal carcinoma increased from 365 of 7,305 (5.0%) in 2004–2008 to 1,742 of 6,663 (26.1%) in 2017–2020. This increase was independent in a multivariable analysis (adjusted odds ratio [aOR] vs 2004–2008, 2.28 [95% CI, 1.98–2.62], 3.27 [95% CI, 2.86–3.74], and 6.65 [95% CI, 5.84–7.57] for 2009–2012, 2013–2016, and 2017–2020, respectively). This increase in high-grade serous fallopian tubal carcinoma was seen across age groups (4.3–5.8% to 22.7–28.3%) and across racial and ethnic groups (4.1–6.0% to 21.9–27.5%) (all P for trend <.001). Among the cases of tumors smaller than 1.5 cm, the increase was particularly high (16.9–67.6%, P for trend <.001). Primary-site tumors in the high-grade serous fallopian tubal carcinoma group were more likely to be smaller than 1.5 cm (aOR 8.26, 95% CI, 7.35–9.28) and unilateral (aOR 7.22, 95% CI, 6.54–7.96) compared with those in high-grade serous ovarian carcinoma. At the cohort level, the diagnosis shift to high-grade serous fallopian tubal carcinoma was associated with narrowing differences in survival over time between the two malignancy groups: adjusted hazard ratio 0.84 (95% CI, 0.74–0.96), 0.91 (95% CI, 0.82–1.01), 1.01 (95% CI, 0.92–1.12), and 1.12 (95% CI, 0.98–1.29) for 2004–2008, 2009–2012, 2013–2016, and 2017–2020, respectively. CONCLUSION: This population-based assessment suggests that diagnoses of high-grade serous tubo-ovarian carcinoma in the United States have been rapidly shifting from high-grade serous ovarian to fallopian tubal carcinoma in recent years, particularly in cases of smaller, unilateral tumors. [ABSTRACT FROM AUTHOR]

Despite decades of declining mortality rates, lung cancer remains the leading cause of cancer death in the United States. This article examines lung cancer incidence, stage at diagnosis, survival, and mortality using population‐based data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries. Over the past 5 years, declines in lung cancer mortality became considerably greater than declines in incidence among men (5.0% vs. 2.6% annually) and women (4.3% vs. 1.1% annually), reflecting absolute gains in 2‐year relative survival of 1.4% annually. Improved outcomes likely reflect advances in treatment, increased access to care through the Patient Protection and Affordable Care Act, and earlier stage diagnosis; for example, compared with a 4.6% annual decrease for distant‐stage disease incidence during 2013–2019, the rate for localized‐stage disease rose by 3.6% annually. Localized disease incidence increased more steeply in states with the highest lung cancer screening prevalence (by 3%–5% annually) than in those with the lowest (by 1%–2% annually). Despite progress, disparities remain. For example, Native Americans have the highest incidence and the slowest decline (less than 1% annually among men and stagnant rates among women) of any group. In addition, mortality rates in Mississippi and Kentucky are two to three times higher than in most western states, largely because of elevated historic smoking prevalence that remains. Racial and geographic inequalities highlight longstanding opportunities for more concerted tobacco‐control efforts targeted at high‐risk populations, including improved access to smoking‐cessation treatments and lung cancer screening, as well as state‐of‐the‐art treatment. Recent declines in lung cancer mortality have outpaced those for incidence, reflecting gains in relative survival that are partly due to recent shifts to earlier stage at diagnosis. Persistent racial and geographic disparities reflect longstanding opportunities for public health intervention to reduce smoking and improve health care access. [ABSTRACT FROM AUTHOR]

The current standard of care of screening and referring patients for treatment for symptoms, such as depression, pain, and fatigue, is not effective. This trial aimed to test the efficacy of an integrated screening and novel stepped collaborative care intervention versus standard of care for patients with cancer and at least one of the following symptoms: depression, pain, or fatigue. This randomised, parallel, phase 3 trial was conducted in 29 oncology outpatient clinics associated with the UPMC Hillman Cancer Center in the USA. Patients (aged ≥21 years) with any cancer type and clinical levels of depression, pain, or fatigue (or all of these) were eligible. Eligible family caregivers were aged 21 years or older and providing care to a patient diagnosed with cancer who consented for this study. Patients were randomly assigned (1:1) to stepped collaborative care or standard of care using a central, permuted block design (sizes of 2, 4, and 6) stratified by sex and prognostic status. The biostatistician, oncologists, and outcome assessors were masked to treatment assignment. Stepped collaborative care was once-weekly cognitive behavioural therapy for 50–60 min from a care coordinator via telemedicine (eg, telephone or videoconferencing). Pharmacotherapy for symptoms might be initiated or changed if recommended by the treatment team or preferred by the patient. Standard of care was screening and referral to a health-care provider for treatment of symptoms. The primary outcome was health-related quality of life in patients at 6 months. Maintenance of the treatment benefits was assessed at 12 months. Participants included in the primary analysis were per intention to treat, which included patients missing one or both follow-up assessments. This trial was registered with ClinicalTrials.gov (NCT02939755). Between Dec 5, 2016, and April 8, 2021, 459 patients and 190 family caregivers were enrolled. 222 patients were assigned to standard of care and 237 to stepped collaborative care. Of 459 patients, 201 (44%) were male and 258 (56%) were female. Patients in the stepped collaborative care group had a greater 0–6-month improvement in health-related quality of life than patients in the standard-of-care group (p=0·013, effect size 0·09). Health-related quality of life was maintained for the stepped collaborative care group (p=0·74, effect size 0·01). Patients in the stepped collaborative care group had greater 0–6-month improvements than the standard-of-care group in emotional (p=0·012), functional (p=0·042), and physical (p=0·033) wellbeing. No adverse events were reported by patients in either group and deaths were considered unrelated to the study. An integrated screening and novel stepped collaborative care intervention, compared with the current standard of care, is recommended to improve health-related quality of life. The findings of this study will advance the implementation of guideline concordant care (screening and treatment) and has the potential to shift the practice of screening and treatment paradigm nationwide, improving outcomes for patients diagnosed with cancer. US National Cancer Institute. [ABSTRACT FROM AUTHOR]

Background: The National Cancer Institute issued a Request for Information (RFI; NOT-CA-23-007) in October 2022, soliciting input on using and reusing metabolomics data. This RFI aimed to gather input on best practices for metabolomics data storage, management, and use/reuse. Aim of review: The nuclear magnetic resonance (NMR) Interest Group within the Metabolomics Association of North America (MANA) prepared a set of recommendations regarding the deposition, archiving, use, and reuse of NMR-based and, to a lesser extent, mass spectrometry (MS)-based metabolomics datasets. These recommendations were built on the collective experiences of metabolomics researchers within MANA who are generating, handling, and analyzing diverse metabolomics datasets spanning experimental (sample handling and preparation, NMR/MS metabolomics data acquisition, processing, and spectral analyses) to computational (automation of spectral processing, univariate and multivariate statistical analysis, metabolite prediction and identification, multi-omics data integration, etc.) studies. Key scientific concepts of review: We provide a synopsis of our collective view regarding the use and reuse of metabolomics data and articulate several recommendations regarding best practices, which are aimed at encouraging researchers to strengthen efforts toward maximizing the utility of metabolomics data, multi-omics data integration, and enhancing the overall scientific impact of metabolomics studies. [ABSTRACT FROM AUTHOR]

The U.S. Government is committed to maintaining a robust research program that supports a portfolio of scientific experts who are investigating the biological effects of radiation exposure. On August 17 and 18, 2023, the Radiation and Nuclear Countermeasures Program, within the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), partnered with the National Cancer Institute, NIH, the National Aeronautics and Space Administration, and the Radiation Injury Treatment Network to convene a workshop titled, Advanced Technologies in Radiation Research (ATRR), which focused on the use of advanced technologies under development or in current use to accelerate radiation research. This meeting report provides a comprehensive overview of the research presented at the workshop, which included an assembly of subject matter experts from government, industry, and academia. Topics discussed during the workshop included assessments of acute and delayed effects of radiation exposure using modalities such as clustered regularly interspaced short palindromic repeats (CRISPR) – based gene editing, tissue chips, advanced computing, artificial intelligence, and immersive imaging techniques. These approaches are being applied to develop products to diagnose and treat radiation injury to the bone marrow, skin, lung, and gastrointestinal tract, among other tissues. The overarching goal of the workshop was to provide an opportunity for the radiation research community to come together to assess the technological landscape through sharing of data, methodologies, and challenges, followed by a guided discussion with all participants. Ultimately, the organizers hope that the radiation research community will benefit from the workshop and seek solutions to scientific questions that remain unaddressed. Understanding existing research gaps and harnessing new or re-imagined tools and methods will allow for the design of studies to advance medical products along the critical path to U.S. Food and Drug Administration approval. [ABSTRACT FROM AUTHOR]

PURPOSE: Individuals diagnosed with cancer between 15 and 39 years (adolescent and young adult [AYA]) face unique vulnerability. Detail is lacking about care delivery for these patients, especially those with ALL. We address these knowledge gaps by describing AYA ALL care delivery details at National Cancer Institute Community Oncology Research Program (NCORP) (sub)affiliates by model of care. METHODS: Participating institutions treated at least one AYA with ALL from 2012 to 2016. Study-specific criteria were used to determine the number of unique clinical facilities (CFs) per NCORP and their model of care (adult/internal medicine [IM], pediatric, mixed [both]). Surveys completed by NCORPs for each CF by model of care captured size, resources, services, and communication. RESULTS: Among 84 participating CFs (adult/IM, n=47; pediatric, n=15; mixed, n=24), 34% treated 5-10 AYAs with ALL annually; adult/IM CFs more often treated <5 (adult/IM, 60%; pediatric, 40%; mixed, 29%). Referral decisions were commonly driven by an age/diagnosis combination (58%), with frequent ALL-specific age minimums (87%) or maximums (80%). Medical, navigational, and social work services were similar across models while psychology was available at more pediatric CFs (pediatric, 80%; adult/IM, 40%; mixed, 46%-54%). More pediatric or mixed CFs reported oncologists interacting with pediatric/adult counterparts via tumor boards (pediatric, 93%; adult/IM, 26%; mixed, 96%) or initiating contact (pediatric, 100%; adult/IM, 77%; mixed 96%); more pediatric CFs reported an affiliated counterpart (pediatric, 53%; adult, 19%). Most CFs reported no AYA-specific resources (79%) or meetings (83%-98%). CONCLUSION: System-level aspects of AYA ALL care delivery have not been examined previously. At NCORPs, these characteristics differ by models of care. Additional work is ongoing to investigate the impact of these facility-level factors on guideline-concordant care in this population. Together, these findings can inform a system-level intervention for diverse practice settings. Many community sites treat <5 AYAs with acute lymphoblastic #leukemia each year. #concerning [ABSTRACT FROM AUTHOR]

The conect4children (c4c) initiative was established to facilitate the development of new drugs and other therapies for paediatric patients. It is widely recognised that there are not enough medicines tested for all relevant ages of the paediatric population. To overcome this, it is imperative that clinical data from different sources are interoperable and can be pooled for larger post hoc studies. c4c has collaborated with the Clinical Data Interchange Standards Consortium (CDISC) to develop cross-cutting data resources that build on existing CDISC standards in an effort to standardise paediatric data. The natural next step was an extension to disease-specific data items. c4c brought together several existing initiatives and resources relevant to disease-specific data and analysed their use for standardising disease-specific data in clinical trials. Several case studies that combined disease-specific data from multiple trials have demonstrated the need for disease-specific data standardisation. We identified three relevant initiatives. These include European Reference Networks, European Joint Programme on Rare Diseases, and Pistoia Alliance. Other resources reviewed were National Cancer Institute Enterprise Vocabulary Services, CDISC standards, pharmaceutical company-specific data dictionaries, Human Phenotype Ontology, Phenopackets, Unified Registry for Inherited Metabolic Disorders, Orphacodes, Rare Disease Cures Accelerator-Data and Analytics Platform (RDCA-DAP), and Observational Medical Outcomes Partnership. The collaborative partners associated with these resources were also reviewed briefly. A plan of action focussed on collaboration was generated for standardising disease-specific paediatric clinical trial data. A paediatric data standards multistakeholder and multi-project user group was established to guide the remaining actions—FAIRification of metadata, a Phenopackets pilot with RDCA-DAP, applying Orphacodes to case report forms of clinical trials, introducing CDISC standards into European Reference Networks, testing of the CDISC Pediatric User Guide using data from the mentioned resources and organisation of further workshops and educational materials. [ABSTRACT FROM AUTHOR]

Adjuvant durvalumab after definitive chemoradiotherapy (CRT) for unresectable stage III non-small cell lung cancer (NSCLC) is well-tolerated in clinical trials. However, pneumonitis rates outside of clinical trials remain poorly defined with CRT followed by durvalumab. We aimed to describe the influence of durvalumab on pneumonitis rates among a large cohort of patients with stage III NSCLC. We studied patients with stage III NSCLC in the national Veterans Health Administration from 2015 to 2021 who received concurrent CRT alone or with adjuvant durvalumab. We defined pneumonitis as worsening respiratory symptoms with radiographic changes within 2 years of CRT and graded events according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. We used Cox regression to analyze risk factors for pneumonitis and the effect of postbaseline pneumonitis on overall survival. Among 1994 patients (989 CRT alone, 1005 CRT followed by adjuvant durvalumab), the 2-year incidence of grade 2 or higher pneumonitis was 13.9% for CRT alone versus 22.1% for CRT plus durvalumab (unadjusted P <.001). On multivariable analysis, durvalumab was associated with higher risk of grade 2 pneumonitis (hazard ratio, 1.45; 95% CI, 1.09-1.93; P =.012) but not grade 3 to 5 pneumonitis (P =.2). Grade 3 pneumonitis conferred worse overall survival (hazard ratio, 2.51; 95% CI, 2.06-3.05; P <.001) but grade 2 pneumonitis did not (P =.4). Adjuvant durvalumab use was associated with increased risk of low-grade but not higher-grade pneumonitis. Reassuringly, low-grade pneumonitis did not increase mortality risk. We observed increased rates of high-grade pneumonitis relative to clinical trials; the reasons for this require further study. [ABSTRACT FROM AUTHOR]