Curing Stage IV Melanoma: Where Have We Been and Where Are We?

Little more than 10 years ago, metastatic melanoma was considered to have one of the poorest cancer outcomes, associated with a median overall survival of 6-8 months. Cytotoxic chemotherapy offered modest response rates of 20%-30%, but no clear survival benefit. Patients were routinely enrolled in clinical trials as their first-line therapy in the search for effective novel therapeutics. Remarkable developments in molecular biology, cancer genomics, immunology, and drug discovery have dominated the early part of the 21st century, and nowhere have the benefits been better realized than in the transformation of outcomes for patients with metastatic melanoma: since 2011, 14 new agents have been approved that significantly increase survival, with long-term remissions and, possibly now, potential for cure. Even so, there is still much work to be done, given that most treated patients still die of their disease. Although most survival gains have so far been realized for cutaneous melanoma, improving treatment options for those 10% of patients with rarer, noncutaneous melanomas is a high priority. Key novel therapeutic approaches aimed at improving outcomes with potential for curing patients with melanoma are considered.

Racial and Socioeconomic Equity of Tecovirimat Treatment during the 2022 Mpox Emergency, New York, New York, USA.

We assessed tecovirimat treatment equity for 3,740 mpox patients in New York, New York, USA, during the 2022 mpox emergency; 32.4% received tecovirimat. Treatment rates by race/ethnicity were 38.8% (White), 31.3% (Black/African American), 31.0% (Hispanic/Latino), and 30.1% (Asian/Pacific Islander/other). Future public health emergency responses must prioritize institutional and structural racism mitigation.

Early intervention and special education in New York City: Patterns of service use and disparities affecting children of colour.

BACKGROUND: Compliance with the requirements of the Individuals with Disabilities Education Act (IDEA) in the United States is monitored through review of cross-sectional reports from three discrete, age-defined programmes (early intervention [EI], early childhood special education [ECSE)] and school-age special education [SE]) to promote the timely, efficient and effective delivery of appropriate services to all eligible children. Analysis of longitudinal data is required to discern how children use services across programmes to provide the necessary context for IDEA oversight and to identify areas for programme or policy interventions to reduce barriers to service use and promote equity. METHODS: We applied sequence analysis to a data linkage across five public record systems among 15 626 New York City children born in 1998 who had records from birth through third grade. RESULTS: Five predominant patterns of service use were identified: (1) multiple therapies across EI/ECSE/SE (13%), (2) EI without transition to Department of Education schools or services (24%), (3) EI and intermittent ECSE/SE (16%), (4) older entry into EI and both speech and occupational therapy throughout ECSE/SE (9%) and (5) limited EI use and mostly speech therapy in ECSE/SE (38%). Each pattern had distinct demographics (e.g., pattern 2 was disproportionately White and from low poverty neighbourhoods; pattern 4 was disproportionately male and Black; pattern 5 was disproportionately Latino) and academic outcomes (e.g., pattern 1 had largest proportion in a SE school and not tested in third grade; pattern 3 had third grade tests scores that were similar to overall citywide mean scores). CONCLUSIONS: The differences in demographic profiles across the five patterns of service use illustrate the systemic inequities in the delivery of these important services. Delayed entry and limited use of EI services among children of colour underscore the need for equity goals to increase early referral and optimize service use.

A Phase 1 study of ADI-PEG20 (pegargiminase) combined with cisplatin and pemetrexed in ASS1-negative metastatic uveal melanoma.

Metastatic uveal melanoma (UM) is a devastating disease with few treatment options. We evaluated the safety, tolerability and preliminary activity of arginine depletion using pegylated arginine deiminase (ADI-PEG20; pegargiminase) combined with pemetrexed (Pem) and cisplatin (Cis) chemotherapy in a phase 1 dose-expansion study of patients with argininosuccinate synthetase (ASS1)-deficient metastatic UM. Eligible patients received up to six cycles of Pem (500 mg/m2 ) and Cis (75 mg/m2 ) every 3 weeks plus weekly intramuscular ADI (36 mg/m2 ), followed by maintenance ADI until progression (NCT02029690). Ten of fourteen ASS1-deficient patients with UM liver metastases and a median of one line of prior immunotherapy received ADIPemCis. Only one ≥ grade 3 adverse event of febrile neutropenia was reported. Seven patients had stable disease with a median progression-free survival of 3.0 months (range, 1.3-8.1) and a median overall survival of 11.5 months (range, 3.2-36.9). Despite anti-ADI-PEG20 antibody emergence, plasma arginine concentrations remained suppressed by 18 weeks with a reciprocal increase in plasma citrulline. Tumour rebiopsies at progression revealed ASS1 re-expression as an escape mechanism. ADIPemCis was well tolerated with modest disease stabilisation in metastatic UM. Further investigation of arginine deprivation is indicated in UM including combinations with immune checkpoint blockade and additional anti-metabolite strategies.

The use of electronic health records to inform cancer surveillance efforts: a scoping review and test of indicators for public health surveillance of cancer prevention and control.

INTRODUCTION: State cancer prevention and control programs rely on public health surveillance data to set objectives to improve cancer prevention and control, plan interventions, and evaluate state-level progress towards achieving those objectives. The goal of this project was to evaluate the validity of using electronic health records (EHRs) based on common data model variables to generate indicators for surveillance of cancer prevention and control for these public health programs. METHODS: Following the methodological guidance from the PRISMA Extension for Scoping Reviews, we conducted a literature scoping review to assess how EHRs are used to inform cancer surveillance. We then developed 26 indicators along the continuum of the cascade of care, including cancer risk factors, immunizations to prevent cancer, cancer screenings, quality of initial care after abnormal screening results, and cancer burden. Indicators were calculated within a sample of patients from the New York City (NYC) INSIGHT Clinical Research Network using common data model EHR data and were weighted to the NYC population using post-stratification. We used prevalence ratios to compare these estimates to estimates from the raw EHR of NYU Langone Health to assess quality of information within INSIGHT, and we compared estimates to results from existing surveillance sources to assess validity. RESULTS: Of the 401 identified articles, 15% had a study purpose related to surveillance. Our indicator comparisons found that INSIGHT EHR-based measures for risk factor indicators were similar to estimates from external sources. In contrast, cancer screening and vaccination indicators were substantially underestimated as compared to estimates from external sources. Cancer screenings and vaccinations were often recorded in sections of the EHR that were not captured by the common data model. INSIGHT estimates for many quality-of-care indicators were higher than those calculated using a raw EHR. CONCLUSION: Common data model EHR data can provide rich information for certain indicators related to the cascade of care but may have substantial biases for others that limit their use in informing surveillance efforts for cancer prevention and control programs.

Neighborhood-Level Chronic Disease Surveillance: Utility of Primary Care Electronic Health Records and Emergency Department Claims Data.

CONTEXT: Disease burden may vary substantively across neighborhoods in an urban setting. Yet, data available for monitoring chronic conditions at the neighborhood level are scarce. Large health care data sets have potential to complement population health surveillance. Few studies have examined the utility of health care data for neighborhood-level surveillance. OBJECTIVE: We examined the use of primary care electronic health records (EHRs) and emergency department (ED) claims for identifying neighborhoods with higher chronic disease burden and neighborhood-level prevalence estimation. DESIGN: Comparison of hypertension and diabetes estimates from EHRs and ED claims with survey-based estimates. SETTING: Forty-two United Hospital Fund neighborhoods in New York City. PARTICIPANTS: The EHR sample comprised 708 452 patients from the Hub Population Health System (the Hub) in 2015, and the ED claim sample comprised 1 567 870 patients from the Statewide Planning and Research Cooperative System in 2015. We derived survey-based estimates from 2012 to 2016 Community Health Survey (n = 44 189). MAIN OUTCOME MEASURE: We calculated hypertension and diabetes prevalence estimates by neighborhood from each data source. We obtained Pearson correlation and absolute difference between EHR-based or claims-based estimates and survey-based estimates. RESULTS: Both EHR-based and claims-based estimates correlated strongly with survey-based estimates for hypertension (0.91 and 0.72, respectively) and diabetes (0.83 and 0.82, respectively) and identified similar neighborhoods of higher burden. For hypertension, 10 and 17 neighborhoods from the EHRs and ED claims, respectively, had an absolute difference of more than 5 percentage points from the survey-based estimate. For diabetes, 15 and 4 neighborhoods from the EHRs and ED claims, respectively, differed from the survey-based estimate by more than 5 percentage points. CONCLUSIONS: Both EHRs and ED claims data are useful for identifying neighborhoods with greater disease burden and have potential for monitoring chronic conditions at the neighborhood level.

Successful, Easy to Access, Online Publication of COVID-19 Data During the Pandemic, New York City, 2020.

Making public health data easier to access, understand, and use makes it more likely that the data will be influential. Throughout the COVID-19 pandemic, the New York City (NYC) Department of Health and Mental Hygiene's Web-based data communication became a cornerstone of NYC's response and allowed the public, journalists, and researchers to access and understand the data in a way that supported the pandemic response and brought attention to the deeply unequal patterns of COVID-19's morbidity and mortality in NYC. (Am J Public Health. 2021;111(S3):S193-S196. https://doi.org/10.2105/AJPH.2021.306446).

Phase 1, pharmacogenomic, dose-expansion study of pegargiminase plus pemetrexed and cisplatin in patients with ASS1-deficient non-squamous non-small cell lung cancer.

INTRODUCTION: We evaluated the arginine-depleting enzyme pegargiminase (ADI-PEG20; ADI) with pemetrexed (Pem) and cisplatin (Cis) (ADIPemCis) in ASS1-deficient non-squamous non-small cell lung cancer (NSCLC) via a phase 1 dose-expansion trial with exploratory biomarker analysis. METHODS: Sixty-seven chemonaïve patients with advanced non-squamous NSCLC were screened, enrolling 21 ASS1-deficient subjects from March 2015 to July 2017 onto weekly pegargiminase (36 mg/m2 ) with Pem (500 mg/m2 ) and Cis (75 mg/m2 ), every 3 weeks (four cycles maximum), with maintenance Pem or pegargiminase. Safety, pharmacodynamics, immunogenicity, and efficacy were determined; molecular biomarkers were annotated by next-generation sequencing and PD-L1 immunohistochemistry. RESULTS: ADIPemCis was well-tolerated. Plasma arginine and citrulline were differentially modulated; pegargiminase antibodies plateaued by week 10. The disease control rate was 85.7% (n = 18/21; 95% CI 63.7%-97%), with a partial response rate of 47.6% (n = 10/21; 95% CI 25.7%-70.2%). The median progression-free and overall survivals were 4.2 (95% CI 2.9-4.8) and 7.2 (95% CI 5.1-18.4) months, respectively. Two PD-L1-expressing (≥1%) patients are alive following subsequent pembrolizumab immunotherapy (9.5%). Tumoral ASS1 deficiency enriched for p53 (64.7%) mutations, and numerically worse median overall survival as compared to ASS1-proficient disease (10.2 months; n = 29). There was no apparent increase in KRAS mutations (35.3%) and PD-L1 (<1%) expression (55.6%). Re-expression of tumoral ASS1 was detected in one patient at progression (n = 1/3). CONCLUSIONS: ADIPemCis was safe and highly active in patients with ASS1-deficient non-squamous NSCLC, however, survival was poor overall. ASS1 loss was co-associated with p53 mutations. Therapies incorporating pegargiminase merit further evaluation in ASS1-deficient and treatment-refractory NSCLC.

Persistent disparities in SARS-CoV-2 test percent positivity by neighborhood in New York City, March 1-July 25, 2020.

PURPOSE: To examine neighborhood-level disparities in SARS-CoV-2 molecular test percent positivity in New York City (NYC) by demographics and socioeconomic status over time to better understand COVID-19 inequities. METHODS: Across 177 neighborhoods, we calculated the Spearman correlation of neighborhood characteristics with SARS-CoV-2 molecular test percent positivity during March 1-July 25, 2020 by five periods defined by trend in case counts: increasing, declining, and three plateau periods to account for differential testing capacity and reopening status. RESULTS: Percent positivity was positively correlated with neighborhood racial and ethnic characteristics and socioeconomic status, including the proportion of the population who were Latino and Black non-Latino, uninsured, Medicaid enrollees, transportation workers, or had low educational attainment. Correlations were generally consistent over time despite increasing testing rates. Neighborhoods with high proportions of these correlates had median percent positivity values of 62.6%, 28.7%, 6.4%, 2.8%, and 2.2% in the five periods, respectively, compared with 40.6%, 11.7%, 1.7%, 0.9%, and 1.0% in neighborhoods with low proportions of these correlates. CONCLUSIONS: Disparities in SARS-CoV-2 molecular test percent positivity persisted in disadvantaged neighborhoods during multiple phases of the first few months of the COVID-19 epidemic in NYC. Mitigation of the COVID-19 burden is still urgently needed in disproportionately affected communities.

ActionHealthNYC: Effectiveness of a Health Care Access Program for the Uninsured, 2016-2017.

Objectives. To evaluate the effectiveness of a novel health care access program (ActionHealthNYC) for uninsured immigrants. Methods. The evaluation was conducted as a randomized controlled trial in New York City from May 2016 through June 2017. Using baseline and follow-up survey data, we assessed health care access, patient experience, and health status. Results. At baseline, 25% of participants had a regular source of care; two thirds had visited a doctor in the past year and reported 2.5 visits in the past 12 months, on average. Nine to 12 months later, intervention participants were 1.2 times more likely to report having a primary care provider (58% vs 46%), were 1.2 times more likely to have seen a doctor in the past 9 months (91% vs 77%), and had 1.5 times more health care visits (4.1 vs 2.9) compared with control participants. Conclusions. ActionHealthNYC increased health care access among program participants. Public Health Implications. State and local policymakers should build on the progress that has been made over the last decade to expand and improve access to health care for uninsured immigrants.

COVID-19 Outbreak - New York City, February 29-June 1, 2020.

New York City (NYC) was an epicenter of the coronavirus disease 2019 (COVID-19) outbreak in the United States during spring 2020 (1). During March-May 2020, approximately 203,000 laboratory-confirmed COVID-19 cases were reported to the NYC Department of Health and Mental Hygiene (DOHMH). To obtain more complete data, DOHMH used supplementary information sources and relied on direct data importation and matching of patient identifiers for data on hospitalization status, the occurrence of death, race/ethnicity, and presence of underlying medical conditions. The highest rates of cases, hospitalizations, and deaths were concentrated in communities of color, high-poverty areas, and among persons aged ≥75 years or with underlying conditions. The crude fatality rate was 9.2% overall and 32.1% among hospitalized patients. Using these data to prevent additional infections among NYC residents during subsequent waves of the pandemic, particularly among those at highest risk for hospitalization and death, is critical. Mitigating COVID-19 transmission among vulnerable groups at high risk for hospitalization and death is an urgent priority. Similar to NYC, other jurisdictions might find the use of supplementary information sources valuable in their efforts to prevent COVID-19 infections.

ctDNA monitoring using patient-specific sequencing and integration of variant reads.

Circulating tumor-derived DNA (ctDNA) can be used to monitor cancer dynamics noninvasively. Detection of ctDNA can be challenging in patients with low-volume or residual disease, where plasma contains very few tumor-derived DNA fragments. We show that sensitivity for ctDNA detection in plasma can be improved by analyzing hundreds to thousands of mutations that are first identified by tumor genotyping. We describe the INtegration of VAriant Reads (INVAR) pipeline, which combines custom error-suppression methods and signal-enrichment approaches based on biological features of ctDNA. With this approach, the detection limit in each sample can be estimated independently based on the number of informative reads sequenced across multiple patient-specific loci. We applied INVAR to custom hybrid-capture sequencing data from 176 plasma samples from 105 patients with melanoma, lung, renal, glioma, and breast cancer across both early and advanced disease. By integrating signal across a median of >105 informative reads, ctDNA was routinely quantified to 1 mutant molecule per 100,000, and in some cases with high tumor mutation burden and/or plasma input material, to parts per million. This resulted in median area under the curve (AUC) values of 0.98 in advanced cancers and 0.80 in early-stage and challenging settings for ctDNA detection. We generalized this method to whole-exome and whole-genome sequencing, showing that INVAR may be applied without requiring personalized sequencing panels so long as a tumor mutation list is available. As tumor sequencing becomes increasingly performed, such methods for personalized cancer monitoring may enhance the sensitivity of cancer liquid biopsies.

Identifying demographic and health profiles of young adults with frequent jail incarceration in New York City during 2011-2017.

PURPOSE: The purpose of this study was to investigate incarceration patterns among young adults in New York City jails from mid-2011 through 2017, with an aim that identification of frequently incarcerated young "hot spotters" may inform early interventions. METHODS: We examined electronic health records for 3114 individuals with no known prior jail admission and admitted within 4.5 years after turning age 18 years. We used group-based trajectory analysis to identify hot spotters and compared their characteristics with those of other trajectory groups. We repeated the analysis for three older adult groups for additional comparison. RESULTS: Five percent of the young individuals became hot spotters (mean = 7.7 incarcerations). They were more likely to be homeless (27.1% vs. 7.2%-16.4% in other trajectory groups), have substance use disorders (95.2% vs. 73.2%-89.8%), and mental health needs (65.7% vs. 28.5%-53.3%), and be incarcerated for theft-related charges (52.7% vs. 32.0%-49.6%) and misdemeanors (34.8 vs. 25.5%-29.4%). They differed in charge profile and homelessness compared with older hot spotters. CONCLUSIONS: Some young adults are at risk of frequent incarceration. Tailored health- and behavior-related interventions may preclude cyclical incarceration and address barriers to well-being and stability.

The seasonality of suicide attempts: a single poison control center perspective.

Introduction: Suicide attempts by poisoning are increasing and suicide occurrence may be associated with seasonality. We performed a retrospective analysis of poisoning exposure data from a single Poison Control Center (PCC) to determine if suicide attempts were associated with season, day of the week, and/or US holidays.Methods: We analyzed exposure cases identified as "intentional overdose - suspected suicide attempt" over 2009-2012. We used singular spectrum analysis (SSA) to detect cyclic patterns in the data and then performed Poisson regression and t-tests to determine if the number of cases were associated with season, day of the week, and US holidays.Results: There were 42,578 cases of "intentional overdose - suspected suicide" during the study period. Singular Spectrum Analysis (SSA) showed that the number of cases associated with poisoning suicide attempts peaked in the Spring and dipped in the Fall. Regression analysis showed higher numbers of suspected suicide attempts from intentional overdose in spring compared with winter by 1.07 times (p = 0.003), and on Sunday (p < 0.001), Monday (p < 0.001), and Thursday (p = 0.02) compared with Saturday by at least 1.09 times. No significant difference was seen for most holidays except for lower numbers of cases around Christmas (3 days before and after; 22.0 vs. 32.3 on control dates, p < 0.001).Conclusions: Suicide attempts by poisoning are associated with season of the year and some days of the week. Further research is required determine reasons for these associations and implementation of public health interventions.

Birth characteristics of children who used early intervention and special education services in New York City.

BACKGROUND: Early intervention (EI) and special education (SE) are beneficial for children with developmental disabilities and/or delays and their families, yet there are disparities in service use. We sought to identify the birth characteristics that predict EI/SE service use patterns. METHODS: We conducted a retrospective cohort study using linked administrative data from five sources for all children born in 1998 to New York City resident mothers. Multinomial regression was used to identify birth characteristics that predicted predominant patterns of service use. RESULTS: Children with service use patterns characterized by late or limited/no EI use were more likely to be first-born children and have Black or Latina mothers. Children born with a gestational age ≤31 weeks were more likely to enter services early. Early term gestational age was associated with patterns of service use common to children with pervasive developmental delay, and maternal obesity was associated with the initiation of speech therapy at the time of entry into school. CONCLUSIONS: Maternal racial disparities existed for patterns of EI/SE service use. Specific birth characteristics, such as parity and gestational age, may be useful to better identify children who are at risk for suboptimal EI use.

Noninvasive Detection of Clinically Significant Prostate Cancer Using Circulating Tumor Cells.

PURPOSE: Prostate specific antigen testing results in unnecessary biopsy and over diagnosis with consequent overtreatment. Tissue biopsy is an invasive procedure associated with significant morbidity. More accurate noninvasive or minimally invasive diagnostic approaches should be developed to avoid unnecessary prostate biopsy and over diagnosis. We investigated the potential of using circulating tumor cell analysis in cancer diagnosis, particularly to predict clinically significant prostate cancer in prebiopsy cases. MATERIALS AND METHODS: We enrolled 155 treatment naïve patients with prostate cancer and 98 before biopsy for circulating tumor cell enumeration. RNA was extracted from circulating tumor cells of 184 patients for gene expression analysis. The Kruskal-Wallis and Spearman rank tests, multivariate logistic regression and the random forest method were applied to assess the association of circulating tumor cells with aggressive prostate cancer. RESULTS: Of patients with localized prostate cancer 54% were scored as having positive circulating tumor cells, which was associated with a higher Gleason score (p=0.0003), risk group (p <0.0001) and clinically significant prostate cancer (p <0.0001). In the prebiopsy group a positive circulating tumor cell score combined with prostate specific antigen predicted clinically significant prostate cancer (AUC 0.869). A 12-gene panel prognostic for clinically significant prostate cancer was also identified. When combining the prostate specific antigen level, the circulating tumor cell score and the 12-gene panel, the AUC of clinically significant prostate cancer prediction was 0.927. Adding those data to cases with available multiparametric magnetic resonance imaging data significantly increased prediction accuracy (AUC 0.936 vs 0.629). CONCLUSIONS: Circulating tumor cell analysis has the potential to significantly improve patient stratification by prostate specific antigen and/or multiparametric magnetic resonance imaging for biopsy and treatment.

Using Calibration to Reduce Measurement Error in Prevalence Estimates Based on Electronic Health Records.

INTRODUCTION: Increasing adoption of electronic health record (EHR) systems by health care providers presents an opportunity for EHR-based population health surveillance. EHR data, however, may be subject to measurement error because of factors such as data entry errors and lack of documentation by physicians. We investigated the use of a calibration model to reduce bias of prevalence estimates from the New York City (NYC) Macroscope, an EHR-based surveillance system. METHODS: We calibrated 6 health indicators to the 2013-2014 NYC Health and Nutrition Examination Survey (NYC HANES) data: hypertension, diabetes, smoking, obesity, influenza vaccination, and depression. We classified indicators into having low measurement error or high measurement error on the basis of whether the proportion of misclassification (ie, false-negative or false-positive cases) was greater than 15% in 190 reviewed charts. We compared bias (ie, absolute difference between NYC Macroscope estimates and NYC HANES estimates) before and after calibration. RESULTS: The health indicators with low measurement error had the same bias after calibration as before calibration (diabetes, 2.5 percentage points; smoking, 2.5 percentage points; obesity, 3.5 percentage points; hypertension, 1.1 percentage points). For indicators with high measurement error, bias decreased from 10.8 to 2.5 percentage points for depression, and from 26.7 to 8.4 percentage points for influenza vaccination. CONCLUSION: The calibration model has the potential to reduce bias of prevalence estimates from EHR-based surveillance systems for indicators with high measurement errors. Further research is warranted to assess the utility of the current calibration model for other EHR data and additional indicators.

Impact of residential displacement on healthcare access and mental health among original residents of gentrifying neighborhoods in New York City.

OBJECTIVES: As gentrification continues in New York City as well as other urban areas, residents of lower socioeconomic status maybe at higher risk for residential displacement. Yet, there have been few quantitative assessments of the health impacts of displacement. The objective of this paper is to assess the association between displacement and healthcare access and mental health among the original residents of gentrifying neighborhoods in New York City. METHODS: We used 2 data sources: 1) 2005-2014 American Community Surveys to identify gentrifying neighborhoods in New York City, and 2) 2006-2014 Statewide Planning and Research Cooperative System. Our cohort included 12,882 residents of gentrifying neighborhoods in 2006 who had records of emergency department visits or hospitalization at least once every 2 years in 2006-2014. Rates of emergency department visits and hospitalizations post-baseline were compared between residents who were displaced and those who remained. RESULTS: During 2006-2014, 23% were displaced. Compared with those who remained, displaced residents were more likely to make emergency department visits and experience hospitalizations, mainly due to mental health (Rate Ratio = 1.8, 95% confidence interval = 1.5, 2.2), after controlling for baseline demographics, health status, healthcare utilization, residential movement, and the neighborhood of residence in 2006. CONCLUSIONS: These findings suggest negative impacts of displacement on healthcare access and mental health, particularly among adults living in urban areas and with a history of frequent emergency department visits or hospitalizations.

The Novel Association of Circulating Tumor Cells and Circulating Megakaryocytes with Prostate Cancer Prognosis.

Purpose: To develop an approach for the investigation of different subtypes of circulating tumor cells (CTC) and other cells to evaluate their potential prognostic value of prostate cancer.Experimental Design: Malignancy of CTCs undergoing epithelial-to-mesenchymal transition (EMT) was confirmed by repeated FISH. Subgroups of CTCs in 81 patients with prostate cancer (43 castration resistant and 38 untreated localized) were correlated to disease aggressiveness parameters. AUC analysis was applied to compare the performance for metastasis prediction between serum PSA level alone and a combined risk score using both PSA and EMTing CTC count. Circulating megakaryocytes and cancer patient survival association was performed using Cox model.Results: The majority of vimentin (VIM)+/CD45- cells were malignant, with genomic alterations in several genomic regions. The number of cytokeratin (CK)-/VIM+/CD45- CTCs correlated with disease burden, tumor aggressiveness, and poorer survival. Meanwhile, CK+/VIM+/CD45- CTCs were associated with metastases better than other subtypes of CTCs in these limited samples. Combination of PSA level and the number of CK+/VIM+/CD45- CTCs enhanced the prediction of cancer metastases [AUC, 0.921; 95% confidence interval (CI), 0.858-0.985]. The number of circulating megakaryocytes was potentially associated with good patient survival in advanced prostate cancer (HR, 0.849; 95% CI, 0.628-1.146, per cell increase), and the difference between the number of mesenchymal CTCs and megakaryocytes strongly correlated to poor survival (HR, 10.17; 95% CI, 2.164-47.789, if score ≥2.0).Conclusions: This CTC analysis approach and the potential association of megakaryocytes with cancer prognosis may greatly enhance our ability to investigate the cancer metastasis process and to predict/monitor cancer progression. Clin Cancer Res; 23(17); 5112-22. ©2017 AACR.