Setup for meV-resolution inelastic X-ray scattering measurements and X-ray diffraction at the Matter in Extreme Conditions endstation at the Linac Coherent Light Source.

We describe a setup for performing inelastic X-ray scattering and X-ray diffraction measurements at the Matter in Extreme Conditions (MEC) endstation of the Linac Coherent Light Source. This technique is capable of performing high-, meV-resolution measurements of dynamic ion features in both crystalline and non-crystalline materials. A four-bounce silicon (533) monochromator was used in conjunction with three silicon (533) diced crystal analyzers to provide an energy resolution of ∼50 meV over a range of ∼500 meV in single shot measurements. In addition to the instrument resolution function, we demonstrate the measurement of longitudinal acoustic phonon modes in polycrystalline diamond. Furthermore, this setup may be combined with the high intensity laser drivers available at MEC to create warm dense matter and subsequently measure ion acoustic modes.

Colorectal Cancer: Cost-effectiveness of Colonoscopy versus CT Colonography Screening with Participation Rates and Costs.

Purpose To compare the cost-effectiveness of computed tomographic (CT) colonography and colonoscopy screening by using data on unit costs and participation rates from a randomized controlled screening trial in a dedicated screening setting. Materials and Methods Observed participation rates and screening costs from the Colonoscopy or Colonography for Screening, or COCOS, trial were used in a microsimulation model to estimate costs and quality-adjusted life-years (QALYs) gained with colonoscopy and CT colonography screening. For both tests, the authors determined optimal age range and screening interval combinations assuming a 100% participation rate. Assuming observed participation for these combinations, the cost-effectiveness of both tests was compared. Extracolonic findings were not included because long-term follow-up data are lacking. Results The participation rates for colonoscopy and CT colonography were 21.5% (1276 of 5924 invitees) and 33.6% (982 of 2920 invitees), respectively. Colonoscopy was more cost-effective in the screening strategies with one or two lifetime screenings, whereas CT colonography was more cost-effective in strategies with more lifetime screenings. CT colonography was the preferred test for willingness-to-pay-thresholds of €3200 per QALY gained and higher, which is lower than the Dutch willingness-to-pay threshold of €20 000. With equal participation, colonoscopy was the preferred test independent of willingness-to-pay thresholds. The findings were robust for most of the sensitivity analyses, except with regard to relative screening costs and subsequent participation. Conclusion Because of the higher participation rates, CT colonography screening for colorectal cancer is more cost-effective than colonoscopy screening. The implementation of CT colonography screening requires previous satisfactory resolution to the question as to how best to deal with extracolonic findings. © RSNA, 2018 Online supplemental material is available for this article.

Cost-effectiveness of High-performance Biomarker Tests vs Fecal Immunochemical Test for Noninvasive Colorectal Cancer Screening.

BACKGROUND & AIMS: Biomarker assays could increase the accuracy of noninvasive detection of colorectal cancer (CRC); fecal immunochemical tests (FITs) are estimated to miss 27%-47% of CRCs and 70%-80% of advanced adenomas per round of screening. We investigated the conditions under which biomarker screens would be cost-effective compared with FIT screens of average-risk individuals. METHODS: We used the MISCAN-Colon microsimulation model to estimate the effects of various CRC screening test characteristics on life-years gained (LYG) and; age-specific all-cause mortality was based on the 2010 Dutch life tables. Simulated CRC incidence rate and CRC stage distribution were calibrated to observed data in The Netherlands from 1999 through 2003 (before opportunities for screening). Survival rates after diagnosis of CRC at an age younger than 75 years were based on CRC relative survival data from 1985 through 2004; survival for individuals diagnosed at an age of 75 years or older was adjusted to fit the observed age-increasing mortality/incidence ratio. We modeled FIT along with hypothetical biomarker tests with different test performance levels. For each biomarker test we calculated the maximum unit cost for the test to be cost-effective compared with FIT, assuming a willingness-to-pay threshold of €50,000 ($56,000) per LYG. RESULTS: Biennial FIT screening of subjects 55-75 years old provided 84.9 LYG at a cost of €122,000 ($137,000) per 1000 participants. Considering a unit cost of €7 ($8) for FIT (including kit and analysis only, excluding organizational costs), a biomarker test that detects CRC with higher levels of specificity and sensitivity (100%) and advanced adenomas at a proportionally higher level of sensitivity (53%) should never exceed a cost of €51 ($57). The threshold cost could increase to more than €200 ($224) for high-performing biomarker tests in cases of limited colonoscopy capacity or higher uptake of this test. CONCLUSIONS: By using the MISCAN-Colon microsimulation model to estimate effects of CRC screening tests, we found that for a biomarker test with increased overall performance to be cost-effective, it should not exceed 7-fold the unit cost of FIT. This maximum would increase substantially if colonoscopy becomes more expensive or scarce, or if the new test has higher screening uptake. These values could be used to estimate the added value of new biomarkers compared with current FIT screening.

Harms, benefits and costs of fecal immunochemical testing versus guaiac fecal occult blood testing for colorectal cancer screening.

BACKGROUND: The ColonCancerCheck screening program for colorectal cancer (CRC) in Ontario, Canada, is considering switching from biennial guaiac fecal occult blood test (gFOBT) screening between age 50-74 years to the more sensitive, but also less specific fecal immunochemical test (FIT). The aim of this study is to estimate whether the additional benefits of FIT screening compared to gFOBT outweigh the additional costs and harms. METHODS: We used microsimulation modeling to estimate quality adjusted life years (QALYs) gained and costs of gFOBT and FIT, compared to no screening, in a cohort of screening participants. We compared strategies with various age ranges, screening intervals, and cut-off levels for FIT. Cost-efficient strategies were determined for various levels of available colonoscopy capacity. RESULTS: Compared to no screening, biennial gFOBT screening between age 50-74 years provided 20 QALYs at a cost of CAN$200,900 per 1,000 participants, and required 17 colonoscopies per 1,000 participants per year. FIT screening was more effective and less costly. For the same level of colonoscopy requirement, biennial FIT (with a high cut-off level of 200 ng Hb/ml) between age 50-74 years provided 11 extra QALYs gained while saving CAN$333,300 per 1000 participants, compared to gFOBT. Without restrictions in colonoscopy capacity, FIT (with a low cut-off level of 50 ng Hb/ml) every year between age 45-80 years was the most cost-effective strategy providing 27 extra QALYs gained per 1000 participants, while saving CAN$448,300. INTERPRETATION: Compared to gFOBT screening, switching to FIT at a high cut-off level could increase the health benefits of a CRC screening program without considerably increasing colonoscopy demand.

High resolution x-ray Thomson scattering measurements from cryogenic hydrogen jets using the linac coherent light source.

We present the first spectrally resolved measurements of x-rays scattered from cryogenic hydrogen jets in the single photon counting limit. The 120 Hz capabilities of the LCLS, together with a novel hydrogen jet design [J. B. Kim et al., Rev. Sci. Instrum. (these proceedings)], allow for the ability to record a near background free spectrum. Such high-dynamic-range x-ray scattering measurements enable a platform to study ultra-fast, laser-driven, heating dynamics of hydrogen plasmas. This measurement has been achieved using two highly annealed pyrolytic graphite crystal spectrometers to spectrally resolve 5.5 keV x-rays elastically and inelastically scattered from cryogenic hydrogen and focused on Cornell-SLAC pixel array detectors [S. Herrmann et al., Nucl. Instrum. Methods Phys. Res., Sect. A 718, 550 (2013)].

State disparities in colorectal cancer rates: Contributions of risk factors, screening, and survival differences.

BACKGROUND: Northeastern states of the United States have shown more progress in reducing colorectal cancer (CRC) incidence and mortality rates than Southern states, and this has resulted in considerable disparities. This study quantified how the disparities in CRC rates between Louisiana (a Southern state) and New Jersey (a Northeastern state) would be affected if differences in risk factors, screening, and stage-specific CRC relative survival between the states were eliminated. METHODS: This study used the Microsimulation Screening Analysis Colon microsimulation model to estimate age-adjusted CRC incidence and mortality rates in Louisiana from 1995 to 2009 under the assumption that 1) Louisiana had the same smoking and obesity prevalence observed in New Jersey, 2) Louisiana had the same CRC screening uptake observed in New Jersey, 3) Louisiana had the same stage-specific CRC relative survival observed in New Jersey, or 4) all the preceding were true. RESULTS: In 2009, the observed CRC incidence and mortality rates in Louisiana were 141.4 cases and 61.9 deaths per 100,000 individuals, respectively. With the same risk factors and screening observed in New Jersey, the CRC incidence rate in Louisiana was reduced by 3.5% and 15.2%, respectively. New Jersey's risk factors, screening, and survival reduced the CRC mortality rate in Louisiana by 3.0%, 10.8%, and 17.4%, respectively. With all trends combined, the modeled rates per 100,000 individuals in Louisiana became lower than the observed rates in New Jersey for both incidence (116.4 vs 130.0) and mortality (44.7 vs 55.8). CONCLUSIONS: The disparities in CRC incidence and mortality rates between Louisiana and New Jersey could be eliminated if Louisiana could attain New Jersey's levels of risk factors, screening, and survival. Priority should be given to enabling Southern states to improve screening and survival rates.

Public health impact of achieving 80% colorectal cancer screening rates in the United States by 2018.

BACKGROUND: The National Colorectal Cancer Roundtable, a national coalition of public, private, and voluntary organizations, has recently announced an initiative to increase colorectal cancer (CRC) screening rates in the United States to 80% by 2018. The authors evaluated the potential public health benefits of achieving this goal. METHODS: The authors simulated the 1980 through 2030 United States population of individuals aged 50 to 100 years using microsimulation modeling. Test-specific historical screening rates were based on National Health Interview Survey data for 1987 through 2013. The effects of increasing screening rates from approximately 58% in 2013 to 80% in 2018 were compared to a scenario in which the screening rate remained approximately constant. The outcomes were cancer incidence and mortality rates and numbers of CRC cases and deaths during short-term follow-up (2013-2020) and extended follow-up (2013-2030). RESULTS: Increasing CRC screening rates to 80% by 2018 would reduce CRC incidence rates by 17% and mortality rates by 19% during short-term follow-up and by 22% and 33%, respectively, during extended follow-up. These reductions would amount to a total of 277,000 averted new cancers and 203,000 averted CRC deaths from 2013 through 2030. CONCLUSIONS: Achieving the goal of increasing the uptake of CRC screening in the United States to 80% by 2018 may have a considerable public health impact by averting approximately 280,000 new cancer cases and 200,000 cancer deaths within <20 years. Cancer 2015;121:2281-2285. © 2015 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Colorectal cancer deaths attributable to nonuse of screening in the United States.

PURPOSE: Screening is a major contributor to colorectal cancer (CRC) mortality reductions in the United States but is underused. We estimated the fraction of CRC deaths attributable to nonuse of screening to demonstrate the potential benefits from targeted interventions. METHODS: The established microsimulation screening analysis colon model was used to estimate the population attributable fraction (PAF) in people aged ≥50 years. The model incorporates long-term patterns and effects of screening by age and type of screening test. PAF for 2010 was estimated using currently available data on screening uptake. PAF was also projected assuming constant future screening rates to incorporate lagged effects from past increases in screening uptake. We also computed PAF using Levin's formula to gauge how this simpler approach differs from the model-based approach. RESULTS: There were an estimated 51,500 CRC deaths in 2010, about 63% (N ∼ 32,200) of which were attributable to nonscreening. The PAF decreases slightly to 58% in 2020. Levin's approach yielded a considerably more conservative PAF of 46% (N ∼ 23,600) for 2010. CONCLUSIONS: Most of the current United States CRC deaths are attributable to nonscreening. This underscores the potential benefits of increasing screening uptake in the population. Traditional methods of estimating PAF underestimated screening effects compared with model-based approaches.

Adherence to surveillance guidelines after removal of colorectal adenomas: a large, community-based study.

OBJECTIVE: To determine adherence to recommended surveillance intervals in clinical practice. DESIGN: 2997 successive patients with a first adenoma diagnosis (57% male, mean age 59 years) from 10 hospitals, who underwent colonoscopy between 1998 and 2002, were identified via Pathologisch Anatomisch Landelijk Geautomatiseerd Archief: Dutch Pathology Registry. Their medical records were reviewed until 1 December 2008. Time to and findings at first surveillance colonoscopy were assessed. A surveillance colonoscopy occurring within ± 3 months of a 1-year recommended interval and ± 6 months of a recommended interval of 2 years or longer was considered appropriate. The analysis was stratified by period per change in guideline (before 2002: 2-3 years for patients with 1 adenoma, annually otherwise; in 2002: 6 years for 1-2 adenomas, 3 years otherwise). We also assessed differences in adenoma and colorectal cancer recurrence rates by surveillance timing. RESULTS: Surveillance was inappropriate in 76% and 89% of patients diagnosed before 2002 and in 2002, respectively. Patients eligible under the pre-2002 guideline mainly received surveillance too late or were absent (57% of cases). For patients eligible under the 2002 guideline surveillance occurred mainly too early (48%). The rate of advanced neoplasia at surveillance was higher in patients with delayed surveillance compared with those with too early or appropriate timed surveillance (8% vs 4-5%, p<0.01). CONCLUSIONS: There is much room for improving surveillance practice. Less than 25% of patients with adenoma receive appropriate surveillance. Such practice seriously hampers the effectiveness and efficiency of surveillance, as too early surveillance poses a considerable burden on available resources while delayed surveillance is associated with an increased rate of advanced adenoma and especially colorectal cancer.

The appropriateness of more intensive colonoscopy screening than recommended in Medicare beneficiaries: a modeling study.

IMPORTANCE: Many Medicare beneficiaries undergo more intensive colonoscopy screening than recommended. Whether this is favorable for beneficiaries and efficient from a societal perspective is uncertain. OBJECTIVE: To determine whether more intensive colonoscopy screening than recommended is favorable for Medicare beneficiaries (ie, whether it results in a net health benefit) and whether it is efficient from a societal perspective (ie, whether the net health benefit justifies the additional resources required). DESIGN, SETTING, AND PARTICIPANTS: Microsimulation modeling study of 65-year-old Medicare beneficiaries at average risk for colorectal cancer (CRC) and with an average life expectancy who underwent a screening colonoscopy at 55 years with negative results. INTERVENTIONS: Colonoscopy screening as recommended by guidelines (ie, at 65 and 75 years) vs scenarios with a shorter screening interval (5 or 3 instead of 10 years) or in which screening was continued to 85 or 95 years. MAIN OUTCOMES AND MEASURES: Quality-adjusted life-years (QALYs) gained (measure of net health benefit); additional colonoscopies required per additional QALY gained and additional costs per additional QALY gained (measures of efficiency). RESULTS: Screening previously screened Medicare beneficiaries more intensively than recommended resulted in only small increases in CRC deaths prevented and life-years gained. In comparison, the increases in colonoscopies performed and colonoscopy-related complications experienced were large. As a result, all scenarios of more intensive screening than recommended resulted in a loss of QALYs, rather than a gain (ie, a net harm). The only exception was shortening the screening interval from 10 to 5 years, which resulted in 0.7 QALYs gained per 1000 beneficiaries. However, this scenario was inefficient because it required no less than 909 additional colonoscopies and an additional $711 000 per additional QALY gained. Results in previously unscreened beneficiaries were slightly less unfavorable, but conclusions were identical. CONCLUSIONS AND RELEVANCE: Screening Medicare beneficiaries more intensively than recommended is not only inefficient from a societal perspective; often it is also unfavorable for those being screened. This study provides evidence and a clear rationale for clinicians and policy makers to actively discourage this practice.

Random comparison of repeated faecal immunochemical testing at different intervals for population-based colorectal cancer screening.

OBJECTIVE: Colorectal cancer screening by means of faecal immunochemical tests (FITs) requires successive screening rounds for an optimal preventive effect. However, data on the influence of the length of the screening interval on participation and diagnostic yield are lacking. Repeated FIT screening was therefore performed in a population-based trial comparing various repeat intervals. DESIGN: 7501 Dutch individuals aged 50-74 years were randomly selected and invited for two 1-sample FIT screening rounds (haemoglobin (Hb) concentration ≥ 50 ng/ml, corresponding to 10 µg Hb/g faeces) with intervals of 1 (group I), 2 (group II) or 3 years (group III). RESULTS: In group I, participation was 64.7% in the first screening round and 63.2% in the second. The corresponding percentages for groups II and III were 61.0% vs 62.5% and 62.0% vs 64.0%. Triennial screening resulted in a higher participation rate in the second screening round compared with annual screening (p=0.04). The overall positivity rate in the second screening round was significantly lower compared with the first round (6.0% vs 8.4%; OR 0.69, 95% CI 0.58 to 0.82) and did not depend on interval length (p=0.23). Similarly, the overall detection rate of advanced neoplasia was significantly lower in the second round compared with the first screening round (1.9% vs 3.3%; OR 0.57, 95% CI 0.43 to 0.76) and also did not depend on interval length (p=0.62). The positive predictive value of the FIT did not significantly change over time (41% vs 33%; p=0.07). CONCLUSION: The total number of advanced neoplasia found at repeat FIT screening is not influenced by the interval length within a range of 1-3 years. Furthermore, there is a stable and acceptably high participation in the second screening round. This implies that screening intervals can be tailored to local resources.

Cost-effectiveness of one versus two sample faecal immunochemical testing for colorectal cancer screening.

OBJECTIVE: The sensitivity and specificity of a single faecal immunochemical test (FIT) are limited. The performance of FIT screening can be improved by increasing the screening frequency or by providing more than one sample in each screening round. This study aimed to evaluate if two-sample FIT screening is cost-effective compared with one-sample FIT. DESIGN: The MISCAN-colon microsimulation model was used to estimate costs and benefits of strategies with either one or two-sample FIT screening. The FIT cut-off level varied between 50 and 200 ng haemoglobin/ml, and the screening schedule was varied with respect to age range and interval. In addition, different definitions for positivity of the two-sample FIT were considered: at least one positive sample, two positive samples, or the mean of both samples being positive. RESULTS: Within an exemplary screening strategy, biennial FIT from the age of 55-75 years, one-sample FIT provided 76.0-97.0 life-years gained (LYG) per 1000 individuals, at a cost of € 259,000-264,000 (range reflects different FIT cut-off levels). Two-sample FIT screening with at least one sample being positive provided 7.3-12.4 additional LYG compared with one-sample FIT at an extra cost of € 50,000-59,000. However, when all screening intervals and age ranges were considered, intensifying screening with one-sample FIT provided equal or more LYG at lower costs compared with two-sample FIT. CONCLUSION: If attendance to screening does not differ between strategies it is recommended to increase the number of screening rounds with one-sample FIT screening, before considering increasing the number of FIT samples provided per screening round.

Annual report to the nation on the status of cancer, 1975-2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates.

BACKGROUND: The American Cancer Society, the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updated information regarding cancer occurrence and trends in the United States. This year's report includes trends in colorectal cancer (CRC) incidence and death rates and highlights the use of microsimulation modeling as a tool for interpreting past trends and projecting future trends to assist in cancer control planning and policy decisions. METHODS: Information regarding invasive cancers was obtained from the NCI, CDC, and NAACCR; and information on deaths was obtained from the CDC's National Center for Health Statistics. Annual percentage changes in the age-standardized incidence and death rates (based on the year 2000 US population standard) for all cancers combined and for the top 15 cancers were estimated by joinpoint analysis of long-term trends (1975-2006) and for short-term fixed-interval trends (1997-2006). All statistical tests were 2-sided. RESULTS: Both incidence and death rates from all cancers combined significantly declined (P < .05) in the most recent time period for men and women overall and for most racial and ethnic populations. These decreases were driven largely by declines in both incidence and death rates for the 3 most common cancers in men (ie, lung and prostate cancers and CRC) and for 2 of the 3 leading cancers in women (ie, breast cancer and CRC). The long-term trends for lung cancer mortality in women had smaller and smaller increases until 2003, when there was a change to a nonsignificant decline. Microsimulation modeling demonstrates that declines in CRC death rates are consistent with a relatively large contribution from screening and with a smaller but demonstrable impact of risk factor reductions and improved treatments. These declines are projected to continue if risk factor modification, screening, and treatment remain at current rates, but they could be accelerated further with favorable trends in risk factors and higher utilization of screening and optimal treatment. CONCLUSIONS: Although the decrease in overall cancer incidence and death rates is encouraging, rising incidence and mortality for some cancers are of concern.