rPOP: Robust PET-only processing of community acquired heterogeneous amyloid-PET data.

The reference standard for amyloid-PET quantification requires structural MRI (sMRI) for preprocessing in both multi-site research studies and clinical trials. Here we describe rPOP (robust PET-Only Processing), a MATLAB-based MRI-free pipeline implementing non-linear warping and differential smoothing of amyloid-PET scans performed with any of the FDA-approved radiotracers (18F-florbetapir/FBP, 18F-florbetaben/FBB or 18F-flutemetamol/FLUTE). Each image undergoes spatial normalization based on weighted PET templates and data-driven differential smoothing, then allowing users to perform their quantification of choice. Prior to normalization, users can choose whether to automatically reset the origin of the image to the center of mass or proceed with the pipeline with the image as it is. We validate rPOP with n = 740 (514 FBP, 182 FBB, 44 FLUTE) amyloid-PET scans from the Imaging Dementia-Evidence for Amyloid Scanning - Brain Health Registry sub-study (IDEAS-BHR) and n = 1,518 scans from the Alzheimer's Disease Neuroimaging Initiative (n = 1,249 FBP, n = 269 FBB), including heterogeneous acquisition and reconstruction protocols. After running rPOP, a standard quantification to extract Standardized Uptake Value ratios and the respective Centiloids conversion was performed. rPOP-based amyloid status (using an independent pathology-based threshold of ≥24.4 Centiloid units) was compared with either local visual reads (IDEAS-BHR, n = 663 with complete valid data and reads available) or with amyloid status derived from an MRI-based PET processing pipeline (ADNI, thresholds of >20/>18 Centiloids for FBP/FBB). Finally, within the ADNI dataset, we tested the linear associations between rPOP- and MRI-based Centiloid values. rPOP achieved accurate warping for N = 2,233/2,258 (98.9%) in the first pass. Of the N = 25 warping failures, 24 were rescued with manual reorientation and origin reset prior to warping. We observed high concordance between rPOP-based amyloid status and both visual reads (IDEAS-BHR, Cohen's k = 0.72 [0.7-0.74], ∼86% concordance) or MRI-pipeline based amyloid status (ADNI, k = 0.88 [0.87-0.89], ∼94% concordance). rPOP- and MRI-pipeline based Centiloids were strongly linearly related (R2:0.95, p<0.001), with this association being significantly modulated by estimated PET resolution (ß= -0.016, p<0.001). rPOP provides reliable MRI-free amyloid-PET warping and quantification, leveraging widely available software and only requiring an attenuation-corrected amyloid-PET image as input. The rPOP pipeline enables the comparison and merging of heterogeneous datasets and is publicly available at https://github.com/leoiacca/rPOP.

Association of Amyloid Positron Emission Tomography With Subsequent Change in Clinical Management Among Medicare Beneficiaries With Mild Cognitive Impairment or Dementia.

Importance: Amyloid positron emission tomography (PET) detects amyloid plaques in the brain, a core neuropathological feature of Alzheimer disease. Objective: To determine if amyloid PET is associated with subsequent changes in the management of patients with mild cognitive impairment (MCI) or dementia of uncertain etiology. Design, Setting, and Participants: The Imaging Dementia-Evidence for Amyloid Scanning (IDEAS) study was a single-group, multisite longitudinal study that assessed the association between amyloid PET and subsequent changes in clinical management for Medicare beneficiaries with MCI or dementia. Participants were required to meet published appropriate use criteria stating that etiology of cognitive impairment was unknown, Alzheimer disease was a diagnostic consideration, and knowledge of PET results was expected to change diagnosis and management. A total of 946 dementia specialists at 595 US sites enrolled 16 008 patients between February 2016 and September 2017. Patients were followed up through January 2018. Dementia specialists documented their diagnosis and management plan before PET and again 90 (±30) days after PET. Exposures: Participants underwent amyloid PET at 343 imaging centers. Main Outcomes and Measures: The primary end point was change in management between the pre- and post-PET visits, as assessed by a composite outcome that included Alzheimer disease drug therapy, other drug therapy, and counseling about safety and future planning. The study was powered to detect a 30% or greater change in the MCI and dementia groups. One of 2 secondary end points is reported: the proportion of changes in diagnosis (from Alzheimer disease to non-Alzheimer disease and vice versa) between pre- and post-PET visits. Results: Among 16 008 registered participants, 11 409 (71.3%) completed study procedures and were included in the analysis (median age, 75 years [interquartile range, 71-80]; 50.9% women; 60.5% with MCI). Amyloid PET results were positive in 3817 patients with MCI (55.3%) and 3154 patients with dementia (70.1%). The composite end point changed in 4159 of 6905 patients with MCI (60.2% [95% CI, 59.1%-61.4%]) and 2859 of 4504 patients with dementia (63.5% [95% CI, 62.1%-64.9%]), significantly exceeding the 30% threshold in each group (P < .001, 1-sided). The etiologic diagnosis changed from Alzheimer disease to non-Alzheimer disease in 2860 of 11 409 patients (25.1% [95% CI, 24.3%-25.9%]) and from non-Alzheimer disease to Alzheimer disease in 1201 of 11 409 (10.5% [95% CI, 10.0%-11.1%]). Conclusions and Relevance: Among Medicare beneficiaries with MCI or dementia of uncertain etiology evaluated by dementia specialists, the use of amyloid PET was associated with changes in clinical management within 90 days. Further research is needed to determine whether amyloid PET is associated with improved clinical outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02420756.

Impact on Patient Management of [18F]-Fluorodeoxyglucose-Positron Emission Tomography (PET) Used for Cancer Diagnosis: Analysis of Data From the National Oncologic PET Registry.

INTRODUCTION: We assessed the impact of [(18)F]-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. IMPLICATIONS FOR PRACTICE: [(18)F]-fluorodeoxyglucose-positron emission tomography appears to have a substantial impact on intended management when used for three targeted diagnostic indications: (a) determining whether a suspicious lesion is cancer, (b) detecting an unknown primary tumor site in a patient with confirmed or strongly suspected metastatic disease, and (c) detecting a primary tumor site in a patient with a presumed paraneoplastic syndrome.

Intended versus inferred management after PET for cancer restaging: analysis of Medicare claims linked to a coverage with evidence development registry.

BACKGROUND: The National Oncologic PET Registry (NOPR) ascertained changes in the intended management of cancer patients using questionnaire data obtained before and after positron emission tomography (PET) under Medicare's coverage with evidence development policy. OBJECTIVE: To assess the concordance between intended care plans and care received as ascertained through administrative claims data. RESEARCH DESIGN: Analysis of linked data of NOPR participants from 2006 to 2008 and their corresponding Medicare claims. SUBJECTS: Consenting patients aged older than 65 years having their first PET for restaging of bladder, kidney, ovarian, pancreas, prostate, small cell lung, or stomach cancer. MEASURES: : Agreement (positive predictive values and κ) between NOPR post-PET intended management plans for treatment (systemic therapy, radiotherapy, surgery, or combinations), biopsy, or watching as compared to claims-inferred care 30 days after PET. RESULTS: A total of 8460 patients with linked data were assessed. A total of 43.5% had metastatic disease and 45.3% had treatment planned (predominantly systemic therapy only), 11.1% biopsy and 43.5% watching. Claims-confirmed intended plans (positive predictive value) for single-mode systemic therapy in 62.0%, radiation in 66.0%, surgery in 45.6%, and biopsy in 55.7%. A total of 25.7% of patients with a plan of watching had treatment claims. By cancer type, κ ranged for systemic therapy only from 0.17 to 0.40 and for watching from 0.21 to 0.41. Agreement rates varied by cancer types but were minimally associated with patient age, performance status, comorbidity, or stage. CONCLUSIONS: Among elderly cancer patients undergoing PET for restaging, there was moderate concordance between their physicians' planned management and claims-inferred actions within a narrow time window. When higher accuracy levels are required in future coverage with evidence development studies, alternative designs will be needed.

Amyloid Positron Emission Tomography and Subsequent Health Care Use Among Medicare Beneficiaries With Mild Cognitive Impairment or Dementia.

Importance: Results of amyloid positron emission tomography (PET) have been shown to change the management of patients with mild cognitive impairment (MCI) or dementia who meet Appropriate Use Criteria (AUC). Objective: To determine if amyloid PET is associated with reduced hospitalizations and emergency department (ED) visits over 12 months in patients with MCI or dementia. Design, Setting, and Participants: This nonrandomized controlled trial analyzed participants in the Imaging Dementia-Evidence for Amyloid Scanning (IDEAS) study, an open-label, multisite, longitudinal study that enrolled participants between February 2016 and December 2017 and followed up through December 2018. These participants were recruited at 595 clinical sites that provide specialty memory care across the US. Eligible participants were Medicare beneficiaries 65 years or older with a diagnosis of MCI or dementia within the past 24 months who met published AUC for amyloid PET. Each IDEAS study participant was matched to a control Medicare beneficiary who had not undergone amyloid PET. Data analysis was conducted on December 13, 2022. Exposure: Participants underwent amyloid PET at imaging centers. Main Outcomes and Measures: The primary end points were the proportions of patients with 12-month inpatient hospital admissions and ED visits. One of 4 secondary end points was the rate of hospitalizations and rate of ED visits in participants with positive vs negative amyloid PET results. Health care use was ascertained from Medicare claims data. Results: The 2 cohorts (IDEAS study participants and controls) each comprised 12 684 adults, including 6467 females (51.0%) with a median (IQR) age of 77 (73-81) years. Over 12 months, 24.0% of the IDEAS study participants were hospitalized, compared with 25.1% of the matched control cohort, for a relative reduction of -4.49% (97.5% CI, -9.09% to 0.34%). The 12-month ED visit rates were nearly identical between the 2 cohorts (44.8% in both IDEAS study and control cohorts) for a relative reduction of -0.12% (97.5% CI, -3.19% to 3.05%). Both outcomes fell short of the prespecified effect size of 10% or greater relative reduction. Overall, 1467 of 6848 participants (21.4%) with positive amyloid PET scans were hospitalized within 12 months compared with 1081 of 4209 participants (25.7%) with negative amyloid PET scans (adjusted odds ratio, 0.83; 95% CI, 0.78-0.89). Conclusions and Relevance: Results of this nonrandomized controlled trial showed that use of amyloid PET was not associated with a significant reduction in 12-month hospitalizations or ED visits. Rates of hospitalization were lower in patients with positive vs negative amyloid PET results.

Racial and Ethnic Differences in Amyloid PET Positivity in Individuals With Mild Cognitive Impairment or Dementia: A Secondary Analysis of the Imaging Dementia-Evidence for Amyloid Scanning (IDEAS) Cohort Study.

Importance: Racial and ethnic groups with higher rates of clinical Alzheimer disease (AD) are underrepresented in studies of AD biomarkers, including amyloid positron emission tomography (PET). Objective: To compare amyloid PET positivity among a diverse cohort of individuals with mild cognitive impairment (MCI) or dementia. Design, Setting, and Participants: Secondary analysis of the Imaging Dementia-Evidence for Amyloid Scanning (IDEAS), a single-arm multisite cohort study of Medicare beneficiaries who met appropriate-use criteria for amyloid PET imaging between February 2016 and September 2017 with follow-up through January 2018. Data were analyzed between April 2020 and January 2022. This study used 2 approaches: the McNemar test to compare amyloid PET positivity proportions between matched racial and ethnic groups and multivariable logistic regression to assess the odds of having a positive amyloid PET scan. IDEAS enrolled participants at 595 US dementia specialist practices. A total of 21 949 were enrolled and 4842 (22%) were excluded from the present analysis due to protocol violations, not receiving an amyloid PET scan, not having a positive or negative scan, or because of small numbers in some subgroups. Exposures: In the IDEAS study, participants underwent a single amyloid PET scan. Main Outcomes and Measures: The main outcomes were amyloid PET positivity proportions and odds. Results: Data from 17 107 individuals (321 Asian, 635 Black, 829 Hispanic, and 15 322 White) with MCI or dementia and amyloid PET were analyzed between April 2020 and January 2022. The median (range) age of participants was 75 (65-105) years; 8769 participants (51.3%) were female and 8338 (48.7%) were male. In the optimal 1:1 matching analysis (n = 3154), White participants had a greater proportion of positive amyloid PET scans compared with Asian participants (181 of 313; 57.8%; 95% CI, 52.3-63.2 vs 142 of 313; 45.4%; 95% CI, 39.9-50.9, respectively; P = .001) and Hispanic participants (482 of 780; 61.8%; 95% CI, 58.3-65.1 vs 425 of 780; 54.5%; 95% CI, 51.0-58.0, respectively; P = .003) but not Black participants (359 of 615; 58.4%; 95% CI, 54.4-62.2 vs 333 of 615; 54.1%; 95% CI, 50.2-58.0, respectively; P = .13). In the adjusted model, the odds of having a positive amyloid PET scan were lower for Asian participants (odds ratio [OR], 0.47; 95% CI, 0.37-0.59; P < .001), Black participants (OR, 0.71; 95% CI, 0.60-0.84; P < .001), and Hispanic participants (OR, 0.68; 95% CI, 0.59-0.79; P < .001) compared with White participants. Conclusions and Relevance: Racial and ethnic differences found in amyloid PET positivity among individuals with MCI and dementia in this study may indicate differences in underlying etiology of cognitive impairment and guide future treatment and prevention approaches.

Allocating cancer-directed expenditures: tensions between prevention, early detection and treatment is unnecessary.

In most countries, the allocation of financial resources for cancer prevention, early detection, and treatment come from different nonrelated "silos." Primary prevention benefits have the greatest economic return since the cancer benefits are intertwined with other major health conditions. Smoking alone accounts for about one-third cancer deaths. In most affluent countries, vaccines for selected viral caused cancers are (wisely) widely available if not optimally utilized. Estimating the additional cancer burden from obesity is still evolving. Age-targeted, less frequent but higher rates of participation in early detection of cervical, breast, and colorectal cancer will likely be prudent expenditures.The last 20 years in high-income countries, there has seen an explosion in demand and the costs of cancer drug or biologic therapy, a modest growth in some forms of radiation, yet minimal or declining surgical costs for primary disease control. Expenditures for cancer drugs are now the world leader of any medication category. While a few have truly led to marked benefits, all have been priced at levels that strain or break budgets. We comment on ten steps or principles that can be applied in most countries that can meaningfully reduce cancer care costs with minimal impact on survival and maintain or enhance quality of patient's life especially with advanced disease. We emphasize limiting systemic therapies for metastatic disease to fully ambulatory patients, those who previously responded to therapy, and earlier initiation of palliative care. Changing behaviors, incentives, expectations, and the framing of treatment effects are necessary to "bend" the current unrelenting cancer care cost curve.

Association Between Ambient Air Pollution and Amyloid Positron Emission Tomography Positivity in Older Adults With Cognitive Impairment.

Importance: Amyloid-ß (Aß) deposition is a feature of Alzheimer disease (AD) and may be promoted by exogenous factors, such as ambient air quality. Objective: To examine the association between the likelihood of amyloid positron emission tomography (PET) scan positivity and ambient air quality in individuals with cognitive impairment. Design, Setting, and Participants: This cross-sectional study used data from the Imaging Dementia-Evidence for Amyloid Scanning Study, which included more than 18 000 US participants with cognitive impairment who received an amyloid PET scan with 1 of 3 Aß tracers (fluorine 18 [18F]-labeled florbetapir, 18F-labeled florbetaben, or 18F-labeled flutemetamol) between February 16, 2016, and January 10, 2018. A sample of older adults with mild cognitive impairment (MCI) or dementia was selected. Exposures: Air pollution was estimated at the patient residence using predicted fine particulate matter (PM2.5) and ground-level ozone (O3) concentrations from the Environmental Protection Agency Downscaler model. Air quality was estimated at 2002 to 2003 (early, or approximately 14 [range, 13-15] years before amyloid PET scan) and 2015 to 2016 (late, or approximately 1 [range, 0-2] years before amyloid PET scan). Main Outcomes and Measures: Primary outcome measure was the association between air pollution and the likelihood of amyloid PET scan positivity, which was measured as odds ratios (ORs) and marginal effects, adjusting for demographic, lifestyle, and socioeconomic factors and medical comorbidities, including respiratory, cardiovascular, cerebrovascular, psychiatric, and neurological conditions. Results: The data set included 18 178 patients, of which 10 991 (60.5%) had MCI and 7187 (39.5%) had dementia (mean [SD] age, 75.8 [6.3] years; 9333 women [51.3%]). Living in areas with higher estimated biennial PM2.5 concentrations in 2002 to 2003 was associated with a higher likelihood of amyloid PET scan positivity (adjusted OR, 1.10; 95% CI, 1.05-1.15; z score = 3.93; false discovery rate [FDR]-corrected P < .001; per 4-µg/m3 increments). Results were similar for 2015 to 2016 data (OR, 1.15; 95% CI, 1.05-1.26, z score = 3.14; FDR-corrected P = .003). An average marginal effect (AME) of +0.5% (SE = 0.1%; z score, 3.93; 95% CI, 0.3%-0.7%; FDR-corrected P < .001) probability of amyloid PET scan positivity for each 1-µg/m3 increase in PM2.5 was observed for 2002 to 2003, whereas an AME of +0.8% (SE = 0.2%; z score = 3.15; 95% CI, 0.3%-1.2%; FDR-corrected P = .002) probability was observed for 2015 to 2016. Post hoc analyses showed no effect modification by sex (2002-2003: interaction term ß = 1.01 [95% CI, 0.99-1.04; z score = 1.13; FDR-corrected P = .56]; 2015-2016: ß = 1.02 [95% CI, 0.98-1.07; z score = 0.91; FDR-corrected P = .56]) or clinical stage (2002-2003: interaction term ß = 1.01 [95% CI, 0.99-1.03; z score = 0.77; FDR-corrected P = .58]; 2015-2016: ß = 1.03; 95% CI, 0.99-1.08; z score = 1.46; FDR-corrected P = .47]). Exposure to higher O3 concentrations was not associated with amyloid PET scan positivity in both time windows. Conclusions and Relevance: This study found that higher PM2.5 concentrations appeared to be associated with brain Aß plaques. These findings suggest the need to consider airborne toxic pollutants associated with Aß pathology in public health policy decisions and to inform individual lifetime risk of developing AD and dementia.

Concrete options and ideas for increasing value in oncology care: the view from one trench.

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.

Relationship between cancer type and impact of PET and PET/CT on intended management: findings of the national oncologic PET registry.

UNLABELLED: We previously reported aggregate data showing that PET was associated with a change in intended management for over one third of patients participating in the National Oncologic PET Registry (NOPR). Here, we present results for specific cancer types and indications for testing. METHODS: The NOPR collected questionnaire data from referring physicians on intended management before and after PET. Data were available from 40,863 PET studies done at 1,368 centers. The impact of PET was assessed for 18 cancer types in patients with pathologically confirmed cancer by type and indication for testing (initial staging, restaging, or detection of suspected recurrence), other than treatment monitoring. RESULTS: When intended management was classified as treatment or nontreatment, physicians changed their intended management for 38.0% of cases (95% confidence interval = 37.6%-38.5%). The frequencies of changes in management ranged from 48.7% for myeloma to 31.4% for nonmelanoma skin cancer. Comparisons across testing indications revealed that only in multiple myeloma did PET have a consistently greater impact on intended management. When the intended management plan before PET was treatment, a change in the intent of treatment (curative vs. palliative) or a major change in the modality of treatment occurred at similar frequencies across different cancer types. CONCLUSION: The impact of PET on physicians' intended management for patients with known cancer was consistent across cancer types.

A decision analysis study of the value of a liver biopsy in nonalcoholic steatohepatitis.

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is an increasingly prevalent clinical syndrome reflecting a mixture of pathological liver histology with the potential to progress to cryptogenic cirrhosis. Liver biopsy (LB) is the only way to determine the severity of disease. However, LB is invasive, has complications and financial costs. The aim of this study is to determine the benefits of early LB for diagnosis and early treatment. METHODS: A decision tree model tracked the potential outcomes of NAFLD between an LB-directed approach vs. no initial LB. Each specific biopsy category determined subsequent care actions. The baseline probabilities were determined by literature review and expert opinion. RESULTS: An initial LB strategy was projected to have a lower mortality compared with the no initial LB group and fewer transplant eligible patients after 5 years. If the prevalence of NAFLD is increased, the mortality increases in both the study groups. With improved efficacy of medical and/or surgical intervention, the mortality rate was decreased. CONCLUSION: This decision tree model provides a context for balancing the risk and benefit of LB in NAFLD. With early biopsy, and early intervention, the relative return of preventing advanced liver disease per LB was high.

Intended Versus Inferred Treatment After 18F-Fluoride PET Performed for Evaluation of Osseous Metastatic Disease in the National Oncologic PET Registry.

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.

Hospice Admission and Survival After 18F-Fluoride PET Performed for Evaluation of Osseous Metastatic Disease in the National Oncologic PET Registry.

We have previously reported that PET using 18F-fluoride (NaF PET) for assessment of osseous metastatic disease was associated with substantial changes in intended management in Medicare beneficiaries participating in the National Oncologic PET Registry (NOPR). Here, we use Medicare administrative data to examine the association between NaF PET results and hospice claims within 180 d and 1-y survival. Methods: We classified NOPR NaF PET results linked to Medicare claims by imaging indication (initial staging [IS]; detection of suspected first osseous metastasis [FOM]; suspected progression of osseous metastasis [POM]; or treatment monitoring [TM]) and type of cancer (prostate, lung, breast, or other). Results were classified as definitely positive scan findings versus probably positive scan findings versus negative scan findings for osseous metastasis for IS and FOM; more extensive disease versus no change or less extensive disease for POM; and worse prognosis versus no change or better prognosis for TM, based on the postscan assessment. Our study included 21,167 scans obtained from 2011 to 2014 of consenting NOPR participants aged 65 y or older. Results: The relative risk of hospice claims within 180 d of a NaF PET scan was 2.0-7.5 times higher for patients with evidence of new or progressing osseous metastasis than for those without, depending on indication and cancer type (all P < 0.008). The percentage difference in hospice claims for those with a finding of new or more advanced osseous disease ranged from 3.9% for IS prostate patients to 28% for FOM lung patients. Six-month survival was also associated with evidence of new or increased osseous disease; risk of death was 1.8-5.1 times as likely (all P ≤ 0.0001), with percentage differences of approximately 30% comparing positive and negative scans in patients with lung cancer imaged for IS or FOM. Conclusion: Our analyses demonstrated that NaF PET scan results are highly associated with subsequent hospice claims and, ultimately, with patient survival. NaF PET provides important information on the presence of osseous metastasis and prognosis to assist patients and their physicians when making decisions on whether to select palliative care and transition to hospice or whether to continue treatment.

The National Oncologic PET Registry (NOPR): design and analysis plan.

UNLABELLED: The Centers for Medicare and Medicaid Services (CMS) has provided a mechanism for expanded coverage of selected promising technologies under its "coverage with evidence development (CED)" policy. The National Oncologic PET Registry (NOPR) was designed to address the CED requirements for collection of clinical and demographic data to allow for CMS coverage of PET for previously noncovered cancer types and indications. The NOPR opened in May 2006. This report reviews the NOPR's data collection and analysis plan. METHODS: NOPR is a nationwide prospective internet-based registry. All PET facilities that are participating providers in the Medicare program may enroll in NOPR. The PET facility is responsible for collecting and entering patient data into the NOPR database through a Web application at: (http://www.cancerPETregistry.org/). Data are collected from the requesting physician on Pre-PET and Post-PET forms. The primary research goal is to assess the effect of PET on referring physicians' plans of intended patient management across the spectrum of expanded cancer indications (diagnosis, staging, restaging, suspected recurrence, and treatment monitoring). The NOPR investigators will have access to data only on cases in which both the patient and the referring physician have consented to allow their data to be used for research. Data will be analyzed and compared in aggregate for all cancers by category (e.g., staging) and then for specific high-impact types and indications (e.g., staging of pancreatic cancer) when 200 patients have been accrued to a specific combination or after the NOPR has been operational for 1 y. CONCLUSION: The NOPR will allow an accurate assessment of the impact of PET on intended patient management across a wide spectrum of cancer indications.

The National Oncologic PET Registry: expanded medicare coverage for PET under coverage with evidence development.

OBJECTIVE: The purpose of this article is to review the recent expansion of Medicare coverage for 18F-FDG PET for certain cancer indications under the Centers for Medicare & Medicaid Services' new Coverage with Evidence Development (CED) policy and to describe the specific operational mechanics of the National Oncologic PET Registry (NOPR). CONCLUSION: The NOPR will make possible a more accurate assessment of the actual influence of PET on patient management across a wide spectrum of cancer indications. By linking access to PET for virtually all Medicare beneficiaries to the collection of clinically valuable evidence, the NOPR represents the cutting edge of the CED approach.

Real-World Conundrums and Biases in the Use of White Cell Growth Factors.

We present the 2015 American Society of Clinical Oncology (ASCO) white cell growth factors, or colony-stimulating factor (CSF), guidelines, updated from 2006. One new indication has been added-dose-intense chemotherapy for bladder cancer-to accompany the existing use for dose-dense breast cancer chemotherapy. Colony-stimulating factors remain appropriate for any regimen where the risk of febrile neutropenia is about 20% per cycle and dose reduction is not appropriate. Based on new evidence from multiple trials, CSF use is no longer indicated in treatment of lymphoma unless there are special risk factors. The United States accounts for 78% of the sales of CSF. The panel approved the use of all biosimilars, but the cost savings will be small as the price is about 80% of the branded CSFs. More biosimilars at lower cost are awaited. Methods to reduce use without harm to patients, by requiring justification according to accepted guidelines, are ongoing.

Trends in clinical trials reports in common cancers between 1989 and 2000.

PURPOSE: Cancer clinical trials can be dichotomized into pilot (phase I and phase II) and randomized controlled clinical trials (RCTs). The best data source for evidence-based medicine is from RCTs. However, many patients prefer to enroll onto pilot trials, and many investigators prefer to conduct or refer their patients to pilot trials. This exploratory study sought to describe the epidemiologic patterns of clinical trial reports in common cancers. METHODS: A structured review was conducted of MEDLINE citations of all English clinical trials reports published between 1989 and 2000 in breast, lung, colorectal, prostate, and female genital cancers, plus leukemias and lymphomas. Each report was classified by design (RCT, pilot, or other) and country. The abstracts of RCTs were reviewed for sample size. Reports addressing screening or prevention were excluded. RESULTS: A total of 12,035 reports, of which 3,560 were from RCTs, were found. The annual growth in RCT reports in breast, colorectal, and prostate cancer was significant (range, 4.8% to 8.5% per year) but was insignificant in leukemias, lymphomas, and female genital and lung cancers (range, 0.1% to 4.3% per year). Within each cancer, the average sample size per report did not change during the 12 years. Nonrandomized trial reports increased on average 15.1% per year (range, 10.1% to 23.2%). The United States accounted for 30% of all RCT reports and 45% of pilot trial reports. CONCLUSION: The faster growth in nonrandomized compared with RCT reports may reflect rapid advances in cancer biology or different structural, commercial, and financial incentives, especially in the United States compared with Europe. Unless additional studies show evidence of an increase in their quality, the modest growth in RCT reports may limit future evidence-based cancer care.

Clinical decisions associated with positron emission tomography in a prospective cohort of patients with suspected or known cancer at one United States center.

PURPOSE: In 2001, Medicare approved reimbursement of F-18 fluorodeoxyglucose positron emission tomography (PET) for a variety of cancers. PET has been observed to be more accurate than other imaging in cancer patients, but the impact of PET on management in routine practice is uncertain. PATIENTS AND METHODS: We studied a prospective cohort having noninvestigational PET at one university center. Before and after PET, a questionnaire was administered to solicit information regarding each physician's preceding actions, intended management, and probability estimates. RESULTS: Seventy-one physicians provided data on 248 patients, of whom 40% had new or suspected cancer and 60% were undergoing restaging or had suspected recurrence. Lung, lymphoma, and head/neck cancers accounted for two thirds of cases. Sixteen physicians made 64% of requests. Physicians changed their intended management in 61% of patients (95% CI, 54% to 66%). For individual physicians ordering at least 10 scans, the average kappa was 0.16 (range, -0.04 to 0.36), reflecting only slight level of agreement between their before and after PET plan. PET was associated with a change in 90 (79%) of 114 patients if the pre-PET intended plan involved more testing or biopsy. In 32% of cases, physicians changed to a treatment from a nontreatment strategy. The therapeutic goal and mode changed in 22 (7%) and 21 cases (8%), respectively. CONCLUSION: This study confirms that physicians often change their decision making based on PET. This impact is likely due to combined effects of PET's improved accuracy and reduced physician uncertainty. Physicians may also be overconfident in interpreting PET and use it as the final arbiter after an extensive evaluation in lieu of tissue biopsy.