Discordance Between Child-Pugh and National Cancer Institute Classifications for Hepatic Dysfunction: Implications on Dosing Recommendations for Oncology Compounds.

Guidance from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency recommends using Child-Pugh classification for pharmacokinetic evaluation in noncancer subjects with hepatic impairment (HI). Therefore, dosing recommendations for oncology compounds for patients with HI are commonly based on Child-Pugh classification. In oncology clinical practice, National Cancer Institute classification (NCIc), is commonly used for evaluating hepatic function and dosing decisions for oncology patients. This work evaluated the discordance between the 2 systems and the impact on dosing recommendations. The classification system in HI studies was reviewed for FDA-approved oncology compounds. Discordance between Child-Pugh and NCIc was evaluated for sunitinib, dacomitinib, palbociclib, bosutinib, and axitinib. Pharmacokinetic (PK) analyses were conducted based on Child-Pugh classification and NCIc. Review of 117 approved oncology compounds showed prevalent use of Child-Pugh classification for dedicated HI studies in noncancer subjects. NCIc is commonly used in cancer patient studies. NCIc tended to classify subjects as less impaired versus Child-Pugh (64.9%, 73.7%, and 61.5% of subjects with mild, moderate, and severe HI, respectively, via Child-Pugh were classified as at least 1 category less impaired via NCIc). PK analyses by NCIc were consistent with Child-Pugh for sunitinib, dacomitinib, and palbociclib. For bosutinib, NCIc showed less impact of HI than Child-Pugh; an opposite trend was observed for axitinib. The impact of this considerable discordance between the 2 systems on dosing decisions bears consideration. When Child-Pugh is used for HI study enrollment, exploratory PK analyses based on NCIc should be conducted. Prescribers should attempt to use the same classification system in the product label for dosing decisions.

Specific absorbed fractions for a revised series of the UF/NCI pediatric reference phantoms: internal electron sources.

In both the International Commission on Radiological Protection (ICRP) and Medical Internal Radiation Dose (MIRD) schemata of internal dosimetry, the S-value is defined as the absorbed dose to a target organ per nuclear decay of the radionuclide in a source organ. Its computation requires data on the energies and yields of all radiation emissions from radionuclide decay, the mass of the target organ, and the value of the absorbed fraction-the fraction of particle energy emitted in the source organ that is deposited in the target organ. The specific absorbed fraction (SAF) is given as the ratio of the absorbed fraction and the target mass. Historically, in the early development of both schemata, computational simplifications were made to the absorbed fraction in considering both organ self-dose ([Formula: see text]) and organ cross-dose ([Formula: see text]). In particular, the value of the absorbed fraction was set to unity for all 'non-penetrating' particle emissions (electrons and alpha particles) such that they contributed only to organ self-dose. As radiation transport codes for charged particles became more widely available, it became increasingly possible to abandon this distinction and to explicitly consider the transport of internally emitted electrons in a manner analogous to that for photons. In this present study, we report on an extensive series of electron SAFs computed in a revised series of the UF/NCI pediatric phantoms. A total of 28 electron energies-0-10 MeV-along a logarithmic energy grid are provided in electronic annexes, where 0 keV is associated with limiting values of the SAF. Electron SAFs were computed independently for collisional energy losses (SAFCEL) and radiation energy losses (SAFREL) to the target organ. A methodology was employed in which values of SAFREL were compiled by first assembling organ-specific and electron energy-specific bremsstrahlung x-ray spectra, and then using these x-ray spectra to re-weight a previously established monoenergetic database of photon SAFs for all phantoms and source-target combinations. Age-dependent trends in the electron SAF were demonstrated for the majority of the source-target organ pairs, and were consistent to values given for the ICRP adult phantoms. In selected cases, however, anticipated age-dependent trends were not seen, and were attributed to anatomical differences in relative organ positioning at specific phantom ages. Both the electron SAFs of this study, and the photon SAFs from our companion study, are presently being used by ICRP Committee 2 in its upcoming pediatric extension to ICRP Publication 133.

Specific absorbed fractions for a revised series of the UF/NCI pediatric reference phantoms: internal photon sources.

Assessment of radiation absorbed dose to internal organs of the body from the intake of radionuclides, or in the medical setting through the injection of radiopharmaceuticals, is generally performed based upon reference biokinetic models or patient imaging data, respectively. Biokinetic models estimate the time course of activity localized to source organs. The time-integration of these organ activity profiles are then scaled by the radionuclide S-value, which defines the absorbed dose to a target tissue per nuclear transformation in various source tissues. S-values are computed using established nuclear decay information (particle energies and yields), and a parameter termed the specific absorbed fraction (SAF). The SAF is the ratio of the absorbed fraction-fraction of particle energy emitted in the source tissue that is deposited in the target tissue-and the target organ mass. While values of the SAF may be computed using patient-specific or individual-specific anatomic models, they have been more widely available through the use of computational reference phantoms. In this study, we report on an extensive series of photon SAFs computed in a revised series of the University of Florida and the National Cancer Institute pediatric reference phantoms which have been modified to conform to the specifications embodied in the ICRP reference adult phantoms of Publication 110 (e.g. organs modeled, organ ID numbers, blood contribution to elemental compositions). Following phantom anatomical revisions, photon radiation transport simulations were performed using MCNPX v2.7 in each of the ten phantoms of the series-male and female newborn, 1 year old, 5 year old, 10 year old, and 15 year old-for 60 different tissues serving as source and/or target regions. A total of 25 photon energies were considered from 10 keV to 10 MeV along a logarithm energy grid. Detailed analyses were conducted of the relative statistical errors in the Monte Carlo target tissue energy deposition tallies at low photon energies and over all energies for source-target combinations at large intra-organ separation distances. Based on these analyses, various data smoothing algorithms were employed, including multi-point weighted data smoothing, and log-log interpolation at low energies (1 keV and 5 keV) using limiting SAF values based upon target organ mass to bound the interpolation interval. The final dataset is provided in a series of ten electronic supplemental files in MS Excel format. The results of this study were further used as the basis for assessing the radiative component of internal electron source SAFs as described in our companion paper (Schwarz et al 2021) for this same pediatric phantom series.

The World of Clinical Trial Development Post COVID-19: Lessons Learned from a Global Pandemic.

The novel coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a global health threat (1). Patients with cancer are one of the most vulnerable populations. During this pandemic, clinical trial accrual to NCI studies has fallen dramatically. Investigators quickly turned to regulatory bodies to simplify treatment schedules, facilitate telemedicine, and decrease required data collection. Going forward, the oncology research community must use the lessons learned to focus on redesigning studies to ensure that critical scientific questions are answered safely while expanding access and increasing partnerships with community physicians. These changes will accelerate clinical progress while protecting our patients.

Utilization and impact of immunotherapy in stage IV melanoma using the National Cancer Database.

To evaluate factors affecting the utilization of immunotherapy and to stratify results based on the approval of ipilimumab in 2011 and PD-1 inhibitors in 2014, an analysis of available data from the National Cancer Database (NCDB) was performed. Stage IV melanoma patients were identified. Effects of immunotherapy on overall survival (OS) were assessed using Kaplan-Meier curves and Cox proportional hazards model. A total of 19 233 patients were analyzed and 1998 received immunotherapy. Between 2011 and 2013, and in 2014, 18.6 and 28.9% of patients received immunotherapy, respectively. Patients who received immunotherapy from 2011 to 2013 had a 33% (95% CI, 30-35%) 3-year OS compared to 23% (95% CI, 21-24%). In 2014, 3-year OS was 37% (95% CI, 32-43%) for those who received immunotherapy compared to 22% (95% CI, 18-26%) for those who did not (P < 0.0001). This is the first analysis of a large cancer database for melanoma patients with stratification based on utilization and availability of immunotherapy. Immunotherapy increased yearly and improved OS. With combination immunotherapy now more widely employed, it is expected these results will continue to improve. This is the first analysis of a large cancer database for melanoma patients with stratification based on utilization and availability of immunotherapy demonstrating that immunotherapy increased yearly and improved OS.

Interrater Reliability in Toxicity Identification: Limitations of Current Standards.

PURPOSE: The National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0 is the standard for oncology toxicity encoding and grading, despite limited validation. We assessed interrater reliability (IRR) in multireviewer toxicity identification. METHODS AND MATERIALS: Two reviewers independently reviewed 100 randomly selected notes for weekly on-treatment visits during radiation therapy from the electronic health record. Discrepancies were adjudicated by a third reviewer for consensus. Term harmonization was performed to account for overlapping symptoms in CTCAE. IRR was assessed based on unweighted and weighted Cohen's kappa coefficients. RESULTS: Between reviewers, the unweighted kappa was 0.68 (95% confidence interval, 0.65-0.71) and the weighted kappa was 0.59 (0.22-1.00). IRR was consistent between symptoms noted as present or absent with a kappa of 0.6 (0.66-0.71) and 0.6 (0.65-0.69), respectively. CONCLUSIONS: Significant discordance suggests toxicity identification, particularly retrospectively, is a complex and error-prone task. Strategies to minimize IRR, including training and simplification of the CTCAE criteria, should be considered in trial design and future terminologies.

Global Consultation on Cancer Staging: promoting consistent understanding and use.

Disease burden is the most important determinant of survival in patients with cancer. This domain, reflected by the cancer stage and codified using the tumour-node-metastasis (TNM) classification, is a fundamental determinant of prognosis. Accurate and consistent tumour classification is required for the development and use of treatment guidelines and to enable clinical research (including clinical trials), cancer surveillance and control. Furthermore, knowledge of the extent and stage of disease is frequently important in the context of translational studies. Attempts to include additional prognostic factors in staging classifications, in order to facilitate a more accurate determination of prognosis, are often made with a lack of knowledge and understanding and are one of the main causes of the inconsistent use of terms and definitions. This effect has resulted in uncertainty and confusion, thus limiting the utility of the TNM classification. In this Position paper, we provide a consensus on the optimal use and terminology for cancer staging that emerged from a consultation process involving representatives of several major international organizations involved in cancer classification. The consultation involved several steps: a focused literature review; a stakeholder survey; and a consultation meeting. This aim of this Position paper is to provide a consensus that should guide the use of staging terminology and secure the classification of anatomical disease extent as a distinct aspect of cancer classification.

Evaluating the Strength of the Association Between Industry Payments and Prescribing Practices in Oncology.

BACKGROUND: Financial relationships between physicians and the pharmaceutical industry are common, but factors that may determine whether such relationships result in physician practice changes are unknown. MATERIALS AND METHODS: We evaluated physician use of orally administered cancer drugs for four cancers: prostate (abiraterone, enzalutamide), renal cell (axitinib, everolimus, pazopanib, sorafenib, sunitinib), lung (afatinib, erlotinib), and chronic myeloid leukemia (CML; dasatinib, imatinib, nilotinib). Separate physician cohorts were defined for each cancer type by prescribing history. The primary exposure was the number of calendar years during 2013-2015 in which a physician received payments from the manufacturer of one of the studied drugs; the outcome was relative prescribing of that drug in 2015, compared with the other drugs for that cancer. We evaluated whether practice setting at a National Cancer Institute (NCI)-designated Comprehensive Cancer Center, receipt of payments for purposes other than education or research (compensation payments), maximum annual dollar value received, and institutional conflict-of-interest policies were associated with the strength of the payment-prescribing association. We used modified Poisson regression to control confounding by other physician characteristics. RESULTS: Physicians who received payments for a drug in all 3 years had increased prescribing of that drug (compared with 0 years), for renal cell (relative risk [RR] 1.81, 95% confidence interval [CI] 1.58-2.07), CML (RR 1.22, 95% CI 1.08-1.39), and lung (RR 1.69, 95% CI 1.58-1.82), but not prostate (RR 0.97, 95% CI 0.93-1.02). Physicians who received compensation payments or >$100 annually had increased prescribing compared with those who did not, but NCI setting and institutional conflict-of-interest policies were not consistently associated with the direction of prescribing change. CONCLUSION: The association between industry payments and cancer drug prescribing was greatest among physicians who received payments consistently (within each calendar year). Receipt of payments for compensation purposes, such as for consulting or travel, and higher dollar value of payments were also associated with increased prescribing. IMPLICATIONS FOR PRACTICE: Financial payments from pharmaceutical companies are common among oncologists. It is known from prior work that oncologists tend to prescribe more of the drugs made by companies that have given them money. By combining records of industry gifts with prescribing records, this study identifies the consistency of payments over time, the dollar value of payments, and payments for compensation as factors that may strengthen the association between receiving payments and increased prescribing of that company's drug.

Advancing Tobacco Product Warning Labels Research Methods and Theory: A Summary of a Grantee Meeting Held by the US National Cancer Institute.

BACKGROUND: The World Health Organization's Framework Convention on Tobacco Control recommends prominent pictorial health warnings on tobacco products. To advance research methods, theory and understanding of how tobacco product warning labels (TPWLs) work, the US National Cancer Institute convened a grantee meeting. Our article describes the key insights that emerged from the meeting, situated within the context of the scientific literature. RESULTS & RECOMMENDATIONS: First, presentations confirmed that large, pictorial TPWLs motivate people to try to quit and encourage smoking cessation. Second, pictorial TPWLs increase attention, knowledge, negative affect, and thinking about the warning. Third, TPWL studies have primarily used brief-exposure laboratory studies and observational studies of sustained exposure through national policy implementation, with a few randomized trials involving several weeks of exposure-with generally consistent results found across study designs. Fourth, novel assessment methods include brain imaging, eye tracking and "best-worst" discrete choice experiments. To make TPWL even more effective, research is needed to confirm the mechanisms of their influence, their impact across vulnerable populations, and their effect on social media posts about tobacco products. Research is also needed on the effect of trial design choices, the predictive validity of new measurement approaches, and warning labels for non-cigarette tobacco products. IMPLICATIONS: To improve scientific understanding of TPWL effects, this grantee meeting summary describes emerging research methods, theory and study results. Directions for future research include examination of the mechanisms of how warning labels work across diverse tobacco products and across different populations and contexts.

A New Framework for Patient Engagement in Cancer Clinical Trials Cooperative Group Studies.

For the past two decades, the National Cancer Institute (NCI) has supported the involvement of patient advocates in both internal advisory activities and funded research projects to provide a patient perspective. Implementation of the inclusion of patient advocates has varied considerably, with inconsistent involvement of patient advocates in key phases of research such as concept development. Despite this, there is agreement that patient advocates have improved the patient focus of many cancer research studies. This commentary describes our experience designing and pilot testing a new framework for patient engagement at SWOG, one of the largest cancer clinical trial network groups in the United States and one of the four adult groups in the NCI's National Clinical Trials Network (NCTN). Our goal is to provide a roadmap for other clinical trial groups that are interested in bringing the patient voice more directly into clinical trial conception and development. We developed a structured process to engage patient advocates more effectively in the development of cancer clinical trials and piloted the process in four SWOG research committees, including implementation of a new Patient Advocate Executive Review Form that systematically captures patient advocates' input at the concept stage. Based on the positive feedback to our approach, we are now developing training and evaluation metrics to support meaningful and consistent patient engagement across the SWOG clinical trial life cycle. Ultimately, the benefits of more patient-centered cancer trials will be measured in the usefulness, relevance, and speed of study results to patients, caregivers, and clinicians.

Critique of the IARC 100F Working Group Evaluation of Occupational Benzene Exposure: Suggestions for the October 2017 Benzene-Only Working Group Meeting.

Health agencies and institutions utilize International Agency for Research on Cancer (IARC) monographs because they are said to represent authoritative cancer evaluations and scientific references. The United States National Cancer Institute has provided support for the IARC Monographs Program for more than three decades. The Volume 100F Monograph, which was published in 2012, reports the evaluations of benzene and more than two dozen other agents performed by the IARC Working Group (WG) that met in Lyon, France from 20 to 27 October 2009. All had already been judged to be human carcinogens. This commentary discusses errors in the occupational exposure section (1.1.3) of the 100F Benzene Monograph ("monograph"). Millions of workers in developed and developing countries have long been known to be routinely exposed to benzene. Since exposures may exceed occupational exposure limits, the hope is that this commentary will be considered by the IARC benzene-only WG at its meeting in October 2017.

Qualification of National Cancer Institute-Designated Cancer Centers for Quantitative PET/CT Imaging in Clinical Trials.

The National Cancer Institute developed the Centers for Quantitative Imaging Excellence (CQIE) initiative in 2010 to prequalify imaging facilities at all of the National Cancer Institute-designated comprehensive and clinical cancer centers for oncology trials using advanced imaging techniques, including PET. Here we review the CQIE PET/CT scanner qualification process and results in detail. Methods: Over a period of approximately 5 y, sites were requested to submit a variety of phantoms, including uniform and American College of Radiology-approved phantoms, PET/CT images, and examples of clinical images. Submissions were divided into 3 distinct time periods: initial submission (T0) and 2 requalification submissions (T1 and T2). Images were analyzed using standardized procedures, and scanners received a pass or fail designation. Sites had the opportunity to submit new data for scanners that failed. Quantitative results were compared across scanners within a given time period and across time periods for a given scanner. Results: Data from 65 unique PET/CT scanners across 56 sites were submitted for CQIE T0 qualification; 64 scanners passed the qualification. Data from 44 (68%) of those 65 scanners were submitted for T2. From T0 to T2, the percentage of scanners passing the CQIE qualification on the first attempt rose from 38% for T1 to 67% for T2. The most common reasons for failure were SUV outside specifications, incomplete submission, and uniformity issues. Uniform phantom and American College of Radiology-approved phantom results between scanner manufacturers were similar. Conclusion: The results of the CQIE process showed that periodic requalification may decrease the frequency of deficient data submissions. The CQIE project also highlighted the concern within imaging facilities about the burden of maintaining different qualifications and accreditations. Finally, for quantitative imaging-based trials, further evaluation of the relationships between the level of the qualification (e.g., bias or precision) and the quality of the image data, accrual rates, and study power is needed.

Relating Complexity and Error Rates of Ontology Concepts. More Complex NCIt Concepts Have More Errors.

OBJECTIVES: Ontologies are knowledge structures that lend support to many health-information systems. A study is carried out to assess the quality of ontological concepts based on a measure of their complexity. The results show a relation between complexity of concepts and error rates of concepts. METHODS: A measure of lateral complexity defined as the number of exhibited role types is used to distinguish between more complex and simpler concepts. Using a framework called an area taxonomy, a kind of abstraction network that summarizes the structural organization of an ontology, concepts are divided into two groups along these lines. Various concepts from each group are then subjected to a two-phase QA analysis to uncover and verify errors and inconsistencies in their modeling. A hierarchy of the National Cancer Institute thesaurus (NCIt) is used as our test-bed. A hypothesis pertaining to the expected error rates of the complex and simple concepts is tested. RESULTS: Our study was done on the NCIt's Biological Process hierarchy. Various errors, including missing roles, incorrect role targets, and incorrectly assigned roles, were discovered and verified in the two phases of our QA analysis. The overall findings confirmed our hypothesis by showing a statistically significant difference between the amounts of errors exhibited by more laterally complex concepts vis-à-vis simpler concepts. CONCLUSIONS: QA is an essential part of any ontology's maintenance regimen. In this paper, we reported on the results of a QA study targeting two groups of ontology concepts distinguished by their level of complexity, defined in terms of the number of exhibited role types. The study was carried out on a major component of an important ontology, the NCIt. The findings suggest that more complex concepts tend to have a higher error rate than simpler concepts. These findings can be utilized to guide ongoing efforts in ontology QA.

Cancer Center Website Rankings in the USA: Expanding Benchmarks and Standards for Effective Public Outreach and Education.

The 68 National Cancer Institute (NCI)-designated comprehensive and cancer centers have been tasked with leading the campaign in the fight against cancer, as well as providing education and outreach to the public. Therefore, it is important for these organizations to have an effective online presence to disseminate information and engage patients. The purpose of this study was to assess both the functionality and usability of cancer centers' websites. The 68 center web domains were evaluated using two separate but complementary approaches. First, a webcrawler was used to score each website on five dimensions: accessibility, content, marketing, technology, and usability. Rankings on each dimension and an average ranking were calculated for all 68 centers. Second, a three-reader system was used to determine a list of all functionalities present on the websites. Both webcrawler scores and functionality prevalence were compared across center type. No differences were observed in webcrawler scores between comprehensive and cancer centers. Mean scores on all dimensions ranged between 5.47 and 7.09. For the functionality assessment, 64 unique functions were determined and categorized into 12 domains, with the average center possessing less than 50 % of the functions. This census assessment of NCI centers' websites suggests the need for improvement to capitalize on new dissemination platforms available online. Progress in development of this technology can help achieve the goals of public education and outreach to a broad audience. This paper presents performance guidelines evaluated against best-demonstrated practice to facilitate social media use improvement.

Challenges in evaluating cancer as a clinical outcome in postapproval studies of drug safety.

Pharmaceuticals approved in the United States are largely not known human carcinogens. However, cancer signals associated with pharmaceuticals may be hypothesized or arise after product approval. There are many study designs that can be used to evaluate cancer as an outcome in the postapproval setting. Because prospective systematic collection of cancer outcomes from a large number of individuals may be lengthy, expensive, and challenging, leveraging data from large existing databases are an integral approach. Such studies have the capability to evaluate the clinical experience of a large number of individuals, yet there are unique methodological challenges involved in their use to evaluate cancer outcomes. To discuss methodological challenges and potential solutions, the Food and Drug Administration and the National Cancer Institute convened a two-day public meeting in 2014. This commentary summarizes the most salient issues discussed at the meeting.

Results From the Imaging and Radiation Oncology Core Houston's Anthropomorphic Phantoms Used for Proton Therapy Clinical Trial Credentialing.

PURPOSE: The purpose of this study was to summarize the findings of anthropomorphic proton phantom irradiations analyzed by the Imaging and Radiation Oncology Core Houston QA Center (IROC Houston). METHODS AND MATERIALS: A total of 103 phantoms were irradiated by proton therapy centers participating in clinical trials. The anthropomorphic phantoms simulated heterogeneous anatomy of a head, liver, lung, prostate, and spine. Treatment plans included those for scattered, uniform scanning, and pencil beam scanning beam delivery modalities using 5 different treatment planning systems. For every phantom irradiation, point doses and planar doses were measured using thermoluminescent dosimeters (TLD) and film, respectively. Differences between measured and planned doses were studied as a function of phantom, beam delivery modality, motion, repeat attempt, treatment planning system, and date of irradiation. RESULTS: The phantom pass rate (overall, 79%) was high for simple phantoms and lower for phantoms that introduced higher levels of difficulty, such as motion, multiple targets, or increased heterogeneity. All treatment planning systems overestimated dose to the target, compared to TLD measurements. Errors in range calculation resulted in several failed phantoms. There was no correlation between treatment planning system and pass rate. The pass rates for each individual phantom are not improving over time, but when individual institutions received feedback about failed phantom irradiations, pass rates did improve. CONCLUSIONS: The proton phantom pass rates are not as high as desired and emphasize potential deficiencies in proton therapy planning and/or delivery. There are many areas for improvement with the proton phantom irradiations, such as treatment planning system dose agreement, range calculations, accounting for motion, and irradiation of multiple targets.

Variations in cancer centers' use of cytology for the diagnosis of small cell lung carcinoma in the National Cancer Data Base.

BACKGROUND: Cytology is an accurate, safe, cost-effective, and guideline-recommended method for the diagnosis of small cell lung carcinoma (SCLC), but little is known about whether its use varies by treatment facility and patient characteristics. METHODS: Methods of diagnosis (cytology vs histology) for 86,830 patients with SCLC from 1314 facilities that contributed data to a nationwide registry and associations of diagnostic methods with patient and facility characteristics were studied in bivariate and multivariate analyses. RESULTS: The percentages of SCLC cases diagnosed by cytology in community cancer programs, comprehensive community cancer programs, academic cancer programs, and National Cancer Institute-designated cancer centers were 13.2%, 15.4%, 23.3%, and 31.3%, respectively (P < .0001). The corresponding prevalence ratios (and 95% confidence intervals [CIs]) of cytologic diagnosis using multivariate marginal logistic regression models and National Cancer Institute-designated cancer centers as the referent category were 0.45 (95% CI, 0.36-0.57), 0.52 (95% CI, 0.42-0.64), and 0.78 95% CI, (0.62-0.96), respectively. In contrast, the use of cytology varied little by patient demographic and clinical factors. CONCLUSIONS: The substantial variation among different types of cancer centers in their use of cytology for the diagnosis of SCLC suggests a need for additional research to study reasons for these differences as well as quality-improvement interventions to encourage adherence to guidelines for SCLC diagnosis.

Intakes of Calcium and Phosphorus and Calculated Calcium-to-Phosphorus Ratios of Older Adults: NHANES 2005-2006 Data.

BACKGROUND: High intakes of dietary phosphorus (P), relative to calcium (Ca) intake, are associated with a lower calcium:phosphorus ratio (Ca:P) ratio which potentially has adverse health effects, including arterial calcification, bone loss, and death. A substantial percentage of older adults (50 to 70 and 71 plus years) who have a higher risk of fracture rate than younger adults typically have low intakes of dietary Ca that are dominated by higher intakes of dietary P from natural and fortified foods, and lower Ca:P ratios than desirable. OBJECTIVE: This investigation was undertaken to examine Ca and P intakes and the resulting Ca:P ratios (by mass) across gender and older adult age groups, using data from the National Health and Nutrition Examination Survey (NHANES) 2005-2006. DESIGN: NHANES data are based on a cross-sectional sample of the non-institutionalized United States (US) population within various regions. This sample is selected to be representative of the entire US population at all ages. National Cancer Institute (NCI) methods and SAS survey procedures were used for analyses. Ca:P ratios were calculated using total Ca from both foods and supplements, whereas P intakes were calculated from food composition values and supplements. The amounts of P additives in processed foods are not available. RESULTS: Mean Ca and P intakes demonstrated lower intakes of Ca and higher intakes of P compared to current Recommended Dietary Allowances (RDAs). The Ca:P ratios in older male and female adults were influenced by both low-Ca and high-P dietary consumption patterns. CONCLUSIONS: Both low total Ca intakes and high P amounts contribute to lower Ca:P ratios, i.e., ~0.7:1.0, in the consumption patterns of older adults than is recommended by the RDAs, i.e., ~1.5:1.0. Whether Ca:P ratios lower than recommended contribute to increased risk of bone loss, arterial calcification, and all-cause mortality cannot be inferred from these data. Additional amounts of chemical P additives in the food supply may actually reduce even further the Ca:P ratios of older adults of both genders, but, without P additive data from the food industry, calculation of more precise ratios from NHANES 2005-2006 data is not possible.