Racial and ethnic differences in Alzheimer's disease (AD) and related dementias are well documented. Compared to Whites, Blacks/African Americans and Latinos/Hispanics have 50-100% higher rates of clinical AD, while Asians/Asian Americans have markedly lower rates. Progress toward better elucidating and addressing these disparities has been hampered by underrepresentation of minorities in clinical research, especially studies of neuroimaging, biomarkers and pharmacotherapies. Objective: The aim of this study was to compare rates of amyloid PET positivity and sociodemographic factors across racial and ethnic groups in a usual care setting. Imaging Dementia—Evidence for Amyloid Scanning (IDEAS) was a pragmatic, single arm, multi-site study of Medicare beneficiaries with mild cognitive impairment (MCI) or dementia. Participants were required to meet Appropriate Use Criteria for amyloid PET imaging including: etiology of cognitive impairment was unknown, AD was a diagnostic consideration and knowledge of PET results was expected to change diagnosis and management. IDEAS enrolled participants at 595 U.S. sites between February 2016 and September 2017. For the analyses, racial/ethnic categories were based on data collected at enrollment sites. 10% of the 18,550 participants were racial/ethnic minorities including 639 Blacks/African Americans, 848 Latinos/Hispanics and 328 Asian/Asian Americans. Whites were more likely to have a positive amyloid PET (62.7% [95% CI 62-63%]) versus Blacks/African Americans (53.8% [50-58%]), Latinos/Hispanics (54.1% [51-57%]) and Asian/Asian Americans (45.1% [40-51%]). See table for results by diagnosis. Compared to Whites, all minority groups were more likely to: have been diagnosed with dementia (vs MCI) prior to PET scan; consent by proxy; have Medicare Advantage and have diabetes. Blacks/African Americans were more likely to have hypertension and live alone, while Latinos/Hispanics and Asian/Asian Americans were less likely to live alone.

Health Care Utilization and Cost of Targeted Drug Delivery vs Conventional Management for Cancer Pain

We have previously reported that PET with 18F-fluoride (NaF PET) for assessment of osseous metastatic disease led to changes in intended management in a substantial fraction of patients with prostate or other types of cancer participating in the National Oncologic PET Registry. This study was performed to assess the concordance of intended patient management after NaF PET and inferred management based on analysis of Medicare claims. Methods: We analyzed linked post–NaF PET data of consenting National Oncologic PET Registry participants age 65 y or older from 2011 to 2014 and their corresponding Medicare claims. Post–NaF PET treatment plans, including combinations of 2 modes of therapy, were assessed for their concordance with clinical actions inferred from Medicare claims. NaF PET studies were stratified by indication (initial staging [IS] or suspected first osseous metastasis [FOM]) and cancer type (prostate, lung, or other cancers). Agreement was assessed between post–NaF PET intended management plans for treatment (surgery, radiotherapy, or systemic therapy) within 90 d for lung and 180 d for prostate or other cancers, and for watching (the absence of treatment claims for ≥60 d) as compared with claims-inferred care. Results: Actions after 9,898 scans were assessed. After NaF PET for IS, there was claims agreement for planned surgery in 76.0% (19/25) lung, 75.4% (98/130) other cancers, and 58.9% (298/506) prostate cancer. Claims confirmed chemotherapy plans after NaF PET done for IS or FOM in 81.0% and 73.5% for lung cancer (n = 148 and 136) and 69.4% and 67.5% for other cancers (n = 111 and 228). For radiotherapy plans, agreement ranged from 80.0% to 84.4% after IS and 68.4% to 74.0% for suspected FOM. Concordance was greatest for androgen deprivation therapy (ADT) (86.0%, n = 308) alone or combined with radiotherapy in prostate cancer IS (80.8%, n = 517). In prostate FOM, the concordance across all treatment plans was lower if the patients had ADT claims within 180 d before NaF PET. Agreement with nontreatment plans was high for FOM (87.2% in other cancers and 78.6% if no prior ADT in prostate) and low after IS (40.7%–62.5%). Conclusion: Concordance of post–NaF PET plans and claims was substantial and higher overall for IS than for FOM.

Introduction. We assessed the impact of [F-18]-fluorodeoxyglucose (FDG)-positron emission tomography (PET) on intended management of patients in the National Oncologic PET Registry (NOPR) for three different diagnostic indications: (a) determining whether a suspicious lesion is cancer (Dx), (b) detecting an unknown primary tumor site when there is confirmed or strongly suspected metastatic disease (cancer of unknown primary origin [CUP]), and (c) detecting a primary tumor site when there is a presumed paraneoplastic syndrome (PNS).Methods. We reviewed a sample of randomly selected reports of NOPR subjects who underwent PET for Dx and CUP and all reports for PNS to find subjects for analysis. For these studies, we evaluated the impact of PET on referring physicians' intended management, based on their management plans reported before and after PET.Results. Intended management was changed more frequently in the CUP group (43.1%) than in the Dx (23.9%) and PNS (25.4%) groups (CUP vs. Dx, p < .0001; PNS vs. Dx, p < .0001; CUP vs. PNS, p < .0002). Referring physicians reported that, in light of PET results, they were able to avoid further testing in approximately three-fourths of patients (71.8%-74.6%). At the time when the post-PET forms were completed, biopsies of suspicious sites had been performed in 21.2%, 32.4%, and 23.2%, respectively, of Dx, CUP, and PNS cases.Conclusion. Our analysis of NOPR data shows that PET appears to have a substantial impact on intended management when used for three common diagnostic indications.

In its 2013 National Coverage Decision on amyloid-beta PET imaging, the U.S. Centers for Medicare & Medicaid Services (CMS) indicated that one-time reimbursement would be considered under coverage with evidence development (CED) as part of research studies to evaluate the scan's impact on patient-oriented outcomes. A national CED protocol for amyloid PET was developed in response to the CMS decision. The protocol was written under the sponsorship of the Alzheimer's Association and in partnership with the American College of Radiology and the Society for Nuclear Medicine and Molecular Imaging. Key input on the protocol was provided by thought leaders in amyloid PET, CMS and industry stakeholders. Imaging Dementia—Evidence for Amyloid Scanning (IDEAS) is an open-label, longitudinal cohort study to assess the impact of amyloid PET in patients meeting Appropriate Use Criteria (AUC) for amyloid imaging (Johnson et al. 2013). The primary hypothesis is that in diagnostically uncertain cases of MCI and atypical dementia, knowledge of amyloid status will lead to significant changes in patient management, and this will translate into improved medical outcomes. Approximately 18,500 Medicare beneficiaries will be enrolled in a registry from sites across the U.S. Participants will be selected by dementia experts in partnership with PET facilities certified to perform and interpret amyloid PET. Aim 1 investigates the impact of amyloid PET on short-term patient management (90 days after the scan) in a cumulative endpoint consisting of: AD drug therapy, other drug therapy, and counselling about safety and future planning. Aim 2 utilizes Medicare claims data to construct a matched control group of amyloid PET naïve patients and compare 12-month rates of hospitalization and emergency room visits between registry and control Outcomes in both aims will be assessed separately in MCI and dementia. The study will further investigate how the scan impacts health care resource utilization. IDEAS was approved by CMS in April 2015, and aims to launch enrollment in early 2016 and complete analysis in 2020. The IDEAS cohort can serve as a foundation for developing further studies in this population.

Economic assessment of evolving technologies is assuming increasing importance worldwide. One form of economic assessment uses decision analysis, a simulation technique, to determine whether performing a clinical trial is worthwhile. This type of assessment may streamline data collection within a clinical trial, and can aid in the interpretation of a trial result with substantial benefits and toxicities. Although second-line chemotherapy for patients with metastatic breast cancer is in common use, its benefit is unclear and it is associated with substantial cost. A database search of currently active or recently closed randomised phase III comparative trials for metastatic breast cancer found only 6 trials involving a comparison of chemotherapies. Only 1 trial allowed prior chemotherapy for metastatic disease. Given the paucity of forthcoming clinical data, decision analysis is an appropriate tool for estimating the effectiveness of potential treatments with second-line agents for metastatic breast cancer. The findings of the Battelle decision analysis model, described in this issue, identified response rates and 1-year mortality as the key areas of focus for comparative trials. Decision analysis can improve the design and efficacy of prospective, comparative trials but cannot replace them.

6566 Background: A variety of case series have consistently reported an increased incidence of venous thromboembolism (VTE) and/ or pulmonary embolism (PE) during induction and consolidation therapy for acute leukemia (AL). Low (or standard) dose coumadin (with target INR 2-3) has been shown to be ineffective. To date there are no reported randomized controlled trials (RCT) investigating the efficacy of low molecular weight heparin (LMWH) vs. placebo in reducing VTE in AL. Our purpose is to make sample size projections for a RCT and to inform practitioners of the frequency of VTE. Methods: Medline literature search from years 2004 to 2009 of English language reports with abstracts using key words such as acute leukemia, heparin, venous thromboembolism and major hemorrhage. For sample size estimation the relative efficacy of LMWH was assumed to reduce incidence of VTE and PE by 50% and increase serious bleeding by 50%, Results: 7 series were found. The sample size range was 71 to 7876 (median 379 patients). The studies did distinguish between AL initial therapies vs. relapsed/recurrent disease. The incidence of VTE was consistently found to be highest in the first month of therapy. The median VTE incidence of VTE was 5.6% (range 2.1-12.0%) in the first 3 months. VTE appears to be even more common with promyelocytic leukemia. In 1 series involving 255 patients, warfarin showed no evidence of benefit. Our sample size and event projection suggest that serious bleeding with LMWH would be increased from 0.2% (no therapy) to 0.3% (LMWH). A RCT comparing LMWH to placebo would require at least 318 patients to show a reduction of VTE from 5.6% to < 2.8%. Conclusions: AL has the highest rate of VTE within first 3 months of diagnosis. The risks of major hemorrhage associated with LMWH in AL appear to be ~20 fold lower then the risk of VTE. Our sample size calculation suggests that a multi-center RCT would be required. For guidance in absence of evidence, our standard practice is to use LMWH until the platelet count falls below 50,000/mm3.

PURPOSE:To update the recommendations on the role of bone-modifying agents in the prevention and treatment of skeletal-related events (SREs) for patients with metastatic breast cancer with bone metastases.METHODS:A literature search using MEDLINE and the Cochrane Collaboration Library identified relevant studies published between January 2003 and November 2010. The primary outcomes of interest were SREs and time to SRE. Secondary outcomes included adverse events and pain. An Update Committee reviewed the literature and re-evaluated previous recommendations.RESULTS:Recommendations were modified to include a new agent. A recommendation regarding osteonecrosis of the jaw was added.RECOMMENDATIONS:Bone-modifying agent therapy is only recommended for patients with breast cancer with evidence of bone metastases; denosumab 120 mg subcutaneously every 4 weeks, intravenous pamidronate 90 mg over no less than 2 hours, or zoledronic acid 4 mg over no less than 15 minutes every 3 to 4 weeks is recommended. There is insufficient evidence to demonstrate greater efficacy of one bone-modifying agent over another. In patients with a calculated serum creatinine clearance of more than 60 mg/min, no change in dosage, infusion time, or interval of bisphosphonate administration is required. Serum creatinine should be monitored before each dose. All patients should receive a dental examination and appropriate preventive dentistry before bone-modifying agent therapy and maintain optimal oral health. Current standards of care for cancer bone pain management should be applied at the onset of pain, in concert with the initiation of bone-modifying agent therapy. The use of biochemical markers to monitor bone-modifying agent use is not recommended.

In the U.S., medical oncology as a profession is wrestling with conflicting and often unrealistic clinical and financial expectations. Office-based practitioners face an environment of low reimbursement for cognitive care, high but declining reimbursement for chemotherapy and supportive care, and high income expectations of oncology professionals. As a field, there has been little incentive to assess or improve the quality of cancer care. Current incentives are often misaligned to reward doing the most aggressive and expensive actions, as long as patients are satisfied, because this leads to the highest return to the practice. Some consequences include U.S. cancer treatment costs that are twice that of any other nation with no or minimal differences in survival, late referrals (if at all) to hospice, and 14%-20% of patients receiving chemotherapy within 14 days of their death when it is highly likely to harm and cause complications. This pattern of care may lead to a significant risk for stress and burnout, as well as being economically unsustainable. Systematic change to reward value requires realignment of incentives to provide episode-based care free from incentives to give expensive chemotherapy or supportive care drugs without good evidence, and an external board to determine appropriate patterns of care. The only ways to reduce the cost of care are to reduce either the amount of care or the cost of care, and either has dramatic consequences in a field that has been built on high expectations. These actions will likely control costs, but in the short term will cause significant distress among patients, families, and health care practitioners.

Source Citation Kelly CM, Juurlink DN, Gomes T, et al. Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study. BMJ. 2010;340;c693. 20142325

BACKGROUND:Positron emission tomography (PET) performed during cancer therapy (treatment monitoring) has shown promise for predicting treatment outcome. However, when used for this purpose, PET generally is not considered standard care. Under the Medicare 'coverage with evidence development' policy, PET (and integrated PET/computed tomography) became a covered service for treatment monitoring if prospective registry data were collected. METHODS:The National Oncologic PET Registry collected questionnaire data on intended patient management before and after PET. Data were available from 8240 patients who had 10,497 treatment-monitoring PET scans at 946 centers; these studies were used to monitor chemotherapy alone (82%), radiation therapy alone (6%), or combined-modality treatment (12%). Ovarian, pancreatic, and lung cancers accounted for 37% of the cohort. In 54% of scans, the pre-PET summary stage was metastatic disease. RESULTS:If PET had not been available, then the pre-PET plan would have been other imaging (53%), ongoing treatment (41%), or biopsy or watching (6%). Change in the post-PET intended management was similar in the imaging and treatment groups: 26% to 28% of scans to switching to another therapy, and 16% to 19% scans led to adjustment of the dose or duration of therapy. Changes in management were more frequent if the referring physician judged that the post-PET prognosis was worse rather than improved or unchanged (78% vs 40%). The physicians indicated that PET enabled 91% of their patients to avoid future tests. CONCLUSIONS:Physicians often report plans to modify their therapeutic plans in elderly cancer patients when PET is used for treatment monitoring.

T he age to begin screening women by mammography to reduce breast cancer mortality remains controversial. A recent metaanalysis showed a significant 15% reduction in breast cancer mortality in women screened at 40–49 years of age. The effectiveness of screening younger women may be due to screening after they reach age 50. The US Preventive Services Task Force’s recommendation is notable for its evasive tone, ‘‘The precise age at which the benefits from screening justify the potential harms is a subjective judgment and should take into account patient preferences.’’ Screening in the Age trial used a 2 view mammogram initially, then a single mediolateral oblique view thereafter. One focus of criticism is the single view, as this is not standard practice in North America. 32% of women did not respond to the initial invitation, and 19% of women did not have 1 routine screen. The trial was underpowered (72%) to meet its effect size of a 20% reduction in breast cancer mortality. This was diminished by the lower breast cancer mortality in the control group (2.35 per 1000). The key results of this trial were (1) using the intent to treat approach, a 17% non-statistically significant reduction in breast cancer mortality; (2) a larger benefit of 24% (relative risk 0.76, CI 0.51 to 1.01) for women who attended mammography; and (3) 23% of regular attendees had at least 1 false positive result for which 5% required an invasive procedure over 10 years. The non-significant number needed to screen to prevent 1 breast cancer death over 10 years is 2512. In conclusion, the non-significant reduction in breast cancer mortality is probably due to the trial being underpowered. The reviewer anticipates that health policy decision makers will be surprised and disappointed to learn how many women need to be screened for 10 years to prevent 1 breast cancer. Both sides of the controversy can use these data to support their argument about the initial age for screening mammography. Bruce E Hillner, MD Virginia Commonwealth University Richmond, Virginia, USA