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The FACS, GILDA, and COLOFOL trials have cast doubt on the value of intensive extracolonic surveillance for resected nonmetastatic colorectal cancer and by extension metastasectomy. We reexamined this pessimistic interpretation. We evaluate an alternative explanation: insufficient power to detect a realistically sized survival benefit that may be clinically meaningful.A microsimulation model of postdiagnosis colorectal cancer was constructed assuming an empirically plausible efficacy for metastasectomy and thus surveillance. The model was used to predict the large-sample mortality reduction expected for each trial and the implied statistical power. A potential recurrence imbalance in the FACS trial was investigated. Goodness of fit between model predictions and trial results were evaluated. Downstream life expectancy was estimated and power calculations performed for future trials evaluating surveillance and metastasectomy.For all 3 trials, the model predicted a mortality reduction of ≤5% and power of10%. The FACS recurrence imbalance likely led to a large relative bias (2.5) in the hazard ratio for overall survival favoring control. After adjustment, both COLOFOL and FACS results were consistent with model predictions (P.5). A 2.6 (95% credible interval 0.5-5.1) and 3.6 (95% credible interval 0.8-7.0) month increase in life expectancy is predicted comparing intensive extracolonic surveillance-routine computed tomography scans and carcinoembryonic antigen assays-with 1 computed tomography scan at 12 months or no surveillance, respectively. An adequately sized surveillance trial is not feasible. A metastasectomy trial should randomize at least 200 to 300 patients.Recent trial results do not warrant de novo skepticism of metastasectomy nor targeted extracolonic surveillance. Given the potential for clinically meaningful life-expectancy gain and significant uncertainty, a trial of metastasectomy is needed.

Purpose Prostate cancer is the second leading cause of cancer death in men in the US. Since 2015, landmark studies have demonstrated improved survival outcomes with the use of docetaxel (DCT) or abiraterone (AA) in addition to androgen deprivation therapy (ADT) in the metastatic hormone-naive setting. These treatment strategies have not been prospectively compared but have similar overall survival benefits despite differing mechanisms of action, toxicity, and cost. We performed a cost-effectiveness analysis to provide insight into the value of AA vs. DCT in the first-line treatment of metastatic prostate cancer. Materials and Methods We developed Markov models by using a US-payer perspective and a 3-year time horizon to estimate costs (2018 US$) and progression-free quality-adjusted life years (PF-QALYs) for ADT alone, DCT, and AA. Health states were defined as initial state, treatment states according to experience of an adverse event, and progressed disease/death. State transition probabilities were derived from rates for drug discontinuation, frequency of adverse events, disease progression, and death from the randomized phase III trials ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) and LATITUDE. Univariate and probabilistic sensitivity analyses were conducted to evaluate model uncertainty. Results DCT resulted in an increase of 0.32 PF-QALYs and $16,100 in cost and AA resulted in an increase of 0.52 PF-QALYs and $215,800 in cost compared to ADT alone. The incremental cost-effectiveness ratio for DCT vs. ADT was $50,500/PF-QALY and for AA vs. DCT was $1,010,000/PF-QALY. Probabilistic sensitivity analysis demonstrated that at a willingness-to-pay threshold of $150,000/PF-QALY AA was highly unlikely to be cost-effective. Conclusion DCT is substantially more cost-effective than AA in the treatment of metastatic hormone naive prostate cancer.

To describe the needs of academic staff conducting non-communicable disease (NCD) research at the University of the West Indies, Mona Campus in Jamaica.Utilizing a cross-sectional design an online survey was created using the research electronic data capture application (REDCap); it was disseminated via email to 708 academic staff members in the Faculties of Medical Sciences and ScienceTechnology between September and November 2018. Participants were asked to indicate their level of access to expertise, training and equipment for conducting research. Descriptive analysis was conducted using STATA version 14.Most respondents were women (74.2%), predominantly scientists (33.1%) or specialist physicians (22.6%). Less than 2/3 of respondents reported publishing research findings in peer reviewed journals, with a quarter not disseminating their research findings in any medium. Resources for field research/data collection, epidemiological methods and principles, and data management/data analysis were generally available. However, there was limited access to training, expertise and equipment in emerging techniques for NCD research such as metabolomics, bioinformatics/analysis of large-scale data sets and health economics. Additional challenges included limited access to financing for research, inadequate workspace and poor administrative support for conducting research.There is a need for more local research seed funding, stronger administrative support for researchers, and opportunities for training in cutting edge NCD research techniques. Jamaican researchers could benefit from being part of a regional research centre of excellence with critical research skills and equipment that builds research networks and strengthens the NCD research response.Describir las necesidades del personal académico que investiga las enfermedades no transmisibles (ENT) en el Campus de Mona de la Universidad de las Indias Occidentales, en Jamaica.Mediante un diseño transversal, se elaboró una encuesta en línea con RedCap, una aplicación para la captura de datos electrónicos para la investigación, y se divulgó por correo electrónico a los 708 miembros del personal académico de las Facultades de Ciencias Médicas y Ciencia y Tecnología entre septiembre y noviembre del 2018. Se pidió a los participantes que indicaran su nivel de acceso a conocimientos, capacitación y equipo para llevar a cabo investigaciones. El análisis descriptivo se realizó con STATA, versión 14.La mayoría de los entrevistados fueron mujeres (74,2%), predominantemente científicas (33,1%) o médicas especialistas (22,6%). Menos de dos terceras partes de los entrevistados informó que publicaban los resultados de sus investigaciones en revistas arbitradas y una cuarta parte declaró que no divulgaba los resultados de sus investigaciones en ningún medio. Por lo general, tenían a su disposición recursos para la investigación de campo o la recopilación de datos, métodos y principios epidemiológicos, así como para la gestión y el análisis de datos. Sin embargo, tenían poco acceso a conocimientos, capacitación y equipo en las técnicas emergentes para la investigación sobre ENT como la metabolómica, la bioinformática o el análisis de conjuntos de datos a gran escala y economía de la salud. Otros retos incluyeron poco acceso al financiamiento para la investigación, espacios de trabajo inadecuados y un apoyo administrativo deficiente para investigar.Se necesita más capital inicial destinado a la investigación local, un mayor respaldo administrativo a los investigadores y oportunidades de capacitación en las técnicas más recientes de investigación de ENT. Los investigadores jamaiquinos podrían sacar provecho de formar parte de un centro regional de excelencia para la investigación con el equipo y las capacidades de investigación fundamentales para contribuir a la formación de redes de investigación y fortalecer la respuesta investigadora a las ENT.Descrever as carências enfrentadas pelo grupo acadêmico que realiza pesquisa em doenças não transmissíveis (DNT) na Universidade das Índias Ocidentais, campus de Mona, Jamaica.Uma pesquisa transversal online foi desenvolvida com o uso da plataforma de captura eletrônica de dados de pesquisa (RedCap) e distribuída por e-mail a 708 integrantes dos grupos acadêmicos nas Faculdades de Ciências Médicas e de Ciência e Tecnologia entre setembro e novembro de 2018. Foi pedido aos participantes que informassem o grau de acesso a conhecimento especializado, capacitação e equipamentos para a realização de pesquisa. Uma análise descritiva foi realizada com o uso do software STATA versão 14.Participaram, na sua maioria, mulheres (74,2%), com o predomínio de pesquisadores científicos (33,1%) ou médicos especialistas (22,6%). Menos de 2/3 informaram publicar os resultados de suas pesquisas em periódicos científicos com avaliação por pares e 25% disseram que não divulgavam seus resultados em nenhum veículo. Afirmaram que, em geral, havia recursos para realizar pesquisa de campo/coleta de dados, métodos e procedimentos básicos epidemiológicos e gerenciamento/análise de dados. Porém, era limitado o acesso a capacitação, conhecimentos especializados e equipamentos para empregar métodos emergentes de pesquisa de DNT como metabolômica, bioinformática/processamento em larga escala de grandes conjuntos de dados e economia da saúde. Outras dificuldades citadas foram limitação de financiamento para pesquisa, inadequação dos locais de trabalho e apoio administrativo deficiente à realização de pesquisas.Faz-se necessário mais financiamento para projetos iniciantes locais, firme apoio administrativo aos pesquisadores e oportunidades para capacitação em métodos de ponta de pesquisa de DNT. A situação dos pesquisadores jamaicanos poderia melhorar se fizessem parte de um centro de excelência regional com recursos e equipamentos essenciais para a realização de pesquisa que lhes permitisse formar redes de pesquisadores e fortalecer a resposta da pesquisa de DNT.

53 Background: Multiple phase III trials have proven that Abi and Doc both improve overall survival (OS) in men with mHSPC. No randomized trials have compared the two approaches. Methods: We conducted a retrospective, observational study to compare OS in de novo M1 men, treated with Abi vs. Doc using patient-level data from the Flatiron health EHR-derived de-identified database. We also compared this real-world OS to trial level data using extracted data points along the OS curves from CHAARTED and LATITUDE trials. OS was compared via Kaplan-Meier curves. Analyses were adjusted via propensity score weighting for age, Gleason score, PSA at diagnosis, race, ethnicity, ECOG PS, insurance type and treatment setting. Results: The cohort included 418 Abi pts and 807 Doc pts (Table). Median follow-up was 13.5 mo for Abi and 31.6 mo for Doc. Unadjusted median OS for Abi and Doc were 31.6 mo (95% CI 28.1-NA) and 41.8 mo (95% CI 37.4-46.3) respectively (P=0.09). Twelve mo and 24 mo OS for Abi was 86.3% and 69%; for Doc it was 89.8% and 72.1 %. Median adjusted OS for Abi and Doc were 31.6 mo (95% CI 28.0-undefined) and 38.8 mo (95% CI 33.1-46.3) respectively (P=0.4). Twelve mo and 24 mo adjusted OS for Abi was 86.6% and 69.4%; for Doc it was 87.9% and 69.2%. Based on extracted trial data, in LATITUDE, Abi treated pts had 12 mo and 24 mo OS of 93.5% and 77.0%; in CHAARTED, Doc treated pts had 12 mo and 24 mo OS of 94.3% and 83.6%. Conclusions: Utilizing real-world data, we demonstrate that 12 and 24-months OS are clinically and statistically similar between Abi and Doc in men with mHSPC. Median OS is also similar, although due to limited follow-up, the estimate of median OS for Abi has large variability. In addition, we show that clinical trial pts had superior outcomes to those in a real-world clinic population. Recent meta-analyses of trial data have not found significant differences in OS for Abi vs. Doc; this analysis of real-world data confirms these findings and indicates that they may be generalizable to a broader patient population. Although this observational study is subject to residual confounding and missing data, it provides further evidence to support the use of both Abi and Doc in men with mHSPC. Differentiating costs, side-effects and QOL can thus become more prominent when making decisions about therapy. [Table: see text]

ObjectiveSurveillance following colorectal cancer (CRC) resection uses optical colonoscopy (OC) to detect intraluminal disease and CT to detect extracolonic recurrence. CT colonography (CTC) might be an efficient use of resources in this situation because it allows for intraluminal and extraluminal evaluations with one test.DesignWe developed a simulation model to compare lifetime costs and benefits for a cohort of patients with resected CRC. Standard of care involved annual CT for 3 years and OC for years 1, 4 and every 5 years thereafter. For the CTC-based strategy, we replace CT+OC at year 1 with CTC. Patients with lesions greater than 6 mm detected by CTC underwent OC. Detection of an adenoma 10 mm or larger was followed by OC at 1 year, then every 3 years thereafter. Test characteristics and costs for CTC were derived from a clinical study. Medicare costs were used for cancer care costs as well as alternative test costs. We discounted costs and effects at 3% per year.ResultsFor persons with resected stage III CRC, the standard-of-care strategy was more costly (US$293) and effective (2.6 averted CRC cases and 1.1 averted cancer deaths per 1000) than the CTC-based strategy, with an incremental cost-effectiveness ratio of US$55 500 per quality-adjusted life-year gained. Our analysis was most sensitive to the sensitivity of CTC for detecting polyps 10 mm or larger and assumptions about disease progression.ConclusionIn a simulation model, we found that replacing the standard-of-care approach to postdiagnostic surveillance with a CTC-based strategy is not an efficient use of resources in most situations.

Purpose. As part of a clinical trial comparing the utility of computed tomographic colonography (CTC) and optical colonoscopy (OC) for post colorectal cancer resection surveillance, we explored the diagnostic yield and costs of a strategy of CTC followed by OC if a polyp is observed (abbreviated CTC_S), versus OC 1 year following curative bowel resection, using the detection of actionable polyps on OC as the criterion. Methods. Using data from 231 patients who underwent same-day CTC followed by OC, we created a decision tree that outlined the choices and outcomes at 1-year clinical follow-up. Colorectal polyp prevalence, sensitivity, and specificity of CTC were compared with five exemplary studies and meta-analyses. Detection criteria were derived for ≥6 mm or ≥10 mm polyps. OC was the gold standard. Costs were gleaned from cataloging components of the cases at the principal investigator’s institution. Analyses included marginal cost of the OC strategy to detect additional actionable polyps and number of polyps missed per 10,000 patients. Results. At our prevalence of 0.156 for ≥6 mm (0.043 ≥10 mm), CTC_S would miss 779 ≥6 mm actionable polyps per 10,000 patients (≥10 mm: 173 per 10,000). Cost to detect an additional ≥6 mm polyp in this cohort is $5,700 (≥10 mm: $28,000). Sensitivity analyses demonstrate that any improvement in performance characteristics would raise the cost of OC to detect more actionable polyps. Similar results were seen using Medicare costs, or when literature values were used for performance characteristics. Conclusion. At an action threshold of ≥6 mm, OC costs at least $5,700 per extra polyp detected relative to CTC_S in patients undergoing surveillance after colorectal cancer surgery, on the order of incremental cost-effectiveness ratios found for other clinical problems involving short-term events.

Background Comorbidity adjustment is an important component of health services research and clinical prognosis. When adjusting for comorbidities in statistical models, researchers can include comorbidities individually or through the use of summary measures such as the Charlson Comorbidity Index or Elixhauser score. We examined the conditions under which individual versus summary measures are most appropriate. Methods We provide an analytic proof of the utility of comorbidity summary measures when used in place of individual comorbidities. We compared the use of the Charlson and Elixhauser scores versus individual comorbidities in prognostic models using a SEER-Medicare data example. We examined the ability of summary comorbidity measures to adjust for confounding using simulations. Results We devised a mathematical proof that found that the comorbidity summary measures are appropriate prognostic or adjustment mechanisms in survival analyses. Once one knows the comorbidity score, no other information about the comorbidity variables used to create the score is generally needed. Our data example and simulations largely confirmed this finding. Conclusions Summary comorbidity measures, such as the Charlson Comorbidity Index and Elixhauser scores, are commonly used for clinical prognosis and comorbidity adjustment. We have provided a theoretical justification that validates the use of such scores under many conditions. Our simulations generally confirm the utility of the summary comorbidity measures as substitutes for use of the individual comorbidity variables in health services research. One caveat is that a summary measure may only be as good as the variables used to create it.

Background Most studies on human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (SCC) have been performed on white Americans. Our study examined the incidence of HPV in an African American oropharyngeal SCC cohort and its survival. Methods African American patients with oropharyngeal SCC in a combined tumor registry were identified. HPV16 testing was performed by polymerase chain reaction (PCR) from DNA extracted from tumor blocks. The p16 staining was performed using standard immunohistochemistry. Results Forty-four patients were identified for analysis. Seventy-three percent of the tumors were HPV-positive. Only 39% of the patients who were HPV-positive were also p16-positive. Survival between all 3 tumor types, patients who tested HPV-positive/p16, HPV-positive/p16-positive, and HPV-negative/p16-negative was significantly different (p = .03). HPV/p16 status was significant on univariate and multivariate analysis. Conclusion HPV oropharyngeal SCC is strongly present in this African American cohort. Two thirds of the patients who were HPV-positive were p16-negative. Greater study is needed to explain the high p16 negativity among this HPV-positive oropharyngeal SCC African American cohort. © 2015 Wiley Periodicals, Inc. Head Neck, 2015

Background/Aims: Diverse samples in clinical trials can make findings more generalizable. We sought to characterize the prevalence of clinical trials in the United States that required English fluency for participants to enroll in the trial. Methods: We randomly chose over 10,000 clinical trial protocols registered with ClinicalTrials.gov and examined the inclusion and exclusion criteria of the trials. We compared the relationship of clinical trial characteristics with English fluency inclusion requirements. We merged the ClinicalTrials.gov data with US Census and American Community Survey data to investigate the association of English-language restrictions with ZIP-code-level demographic characteristics of participating institutions. We used Chi-squared tests, t-tests, and logistic regression models for analyses. Results: English fluency requirements have been increasing over time, from 1.7% of trials having such requirements before 2000 to 9.0% after 2010 (p Conclusion: The proportion of clinical trials registered with ClinicalTrials.gov that have English fluency requirements for study inclusion has been increasing over time. English-language restrictions are associated with a number of characteristics, including the demographic characteristics of communities in which the sponsoring institutions are located.

Introduction: International research collaborations are a critical strategy in tackling immigrant and global prevention and control challenges. Available communications and data technology facilitates collaborations to address global cancer inequities. The purpose of the African Caribbean Cancer Consortium (AC3) is to develop and sustain partnerships to investigate and respond to the increasing cancer vulnerability among African descended peoples worldwide. In the Caribbean, cancer incidence and mortality are rising in persons of African ancestry. We will present preliminary outcomes from our NCI-P20 award. Methods: Our goal is to establish a Caribbean Regional Center of Research Excellence (CRCRE). The project started in Jamaica in partnership with the University of the West Indies-Mona. The CRCRE is building a sustainable research center at the Mona campus that will spread to other campuses throughout the University system. Using ZOOM, WhatsApp, YouTube, GoogleDocs, and REDCap, we will develop a sustainable research infrastructure in the Caribbean. Results: Regional Needs Assessment- Using REDCap, we were able to conduct a research needs assessment across the Caribbean. A survey was developed by the research team and administered within the Mona campus and Caribbean-wide through the AC3 member listserv. We had over 150 respondents representing key stakeholders who identified top priorities to develop sustainable research in the region. The REDCap database for the CRCRE will also house training webinars readily available for users. Mentor-Mentee Program was implemented to match junior faculty in the Caribbean to senior faculty within the AC3 network. Among Caribbean researchers, we are building capacity for basic, translational, clinical and behavioral research. Mentors and mentees will utilize ZOOM, e-mail, Googledocs, WhatsApp and YouTube to facilitate training, mentoring and study processes. Genetic Counseling Training was conducted between genetic counselors at Fox Chase Cancer Center (FCCC) and 3 Caribbean nurses based at Princess Margaret Hospital, Nassau, Bahamas. Nurses received virtual training via NCCN and ZOOM lectures. Nurses then shadowed FCCC genetic counselors. They will utilize ZOOM, WhatsApp and YouTube to facilitate ongoing training, mentoring, and supervision. Discussion: Using communication and data technologies are effective and cost effective platforms for developing and sustaining international cancer prevention and control research in low and middle-income countries including the Caribbean. Caribbeans account for 10% of all immigrants and 50% of all immigrant Blacks. Therefore, attending to and addressing cancer biologic, genetic, environmental and behavioral risk and disparate outcomes among Caribbeans will benefit the Region as well as inform strategies to reduce cancer disparities within U.S. Black population. Citation Format: Elizabeth Blackman, Kimlin Tam Ashing, Camille Ragin, Marshall Tulloch-Reid, J. Robert Beck, Althea Bailey, Ian Hambilton, Natalie Guthrie-Dixon, Georgia Williamson, Andrea Forman, Robin Roberts. Establishing sustainable research collaborations in the Caribbean through the utilization of multiple technology platforms [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4185.

Health care providers are accustomed to identifying populations for whom cost-related concerns may be a significant barrier, such as the poor, but few empiric data have been collected to substantiate such assumptions, particularly among insured patients.Patients with cancer from academic and community hospitals completed a questionnaire that included closed-ended items concerning demographic variables, optimism, numeracy, and concerns about present and future medical costs. In addition, they answered open-ended questions regarding cost concerns and medical expenses.Nearly all (99%) participants were insured. In response to the closed-ended questions, 30.3% of patients reported concern about paying for their cancer treatment, 22.3% reported that their family had made sacrifices to pay for their care, and 8.3% stated that their insurance adequately covered their current health care costs, and 17.3% reported concerns about coverage for their costs in the future. On open-ended questions, 35.3% reported additional expenses, and 47.5% reported concerns about health care costs. None of the assessed patient characteristics proved to be a robust predictor across all cost-related concerns. There was a strong association between the identification of concerns or expenses on the open-ended questions and concerns on closed-ended questions.Cost concerns are common among patients with cancer who have health insurance. Health care providers may alleviate concerns by discussing cost-related concerns with all patients, not only those of lower socioeconomic status or those without insurance. A closed-ended screening question may help to initiate these conversations. This may identify potential resources, lower distress, and enable patients to make optimal treatment decisions.

Time to surgery (TTS) is of concern to patients and clinicians, but controversy surrounds its effect on breast cancer survival. There remains little national data evaluating the association.To investigate the relationship between the time from diagnosis to breast cancer surgery and survival, using separate analyses of 2 of the largest cancer databases in the United States.Two independent population-based studies were conducted of prospectively collected national data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database and the National Cancer Database (NCDB). The SEER-Medicare cohort included Medicare patients older than 65 years, and the NCDB cohort included patients cared for at Commission on Cancer-accredited facilities throughout the United States. Each analysis assessed overall survival as a function of time between diagnosis and surgery by evaluating 5 intervals (≤30, 31-60, 61-90, 91-120, and 121-180 days) and disease-specific survival at 60-day intervals. All patients were diagnosed with noninflammatory, nonmetastatic, invasive breast cancer and underwent surgery as initial treatment.Overall and disease-specific survival as a function of time between diagnosis and surgery, after adjusting for patient, demographic, and tumor-related factors.The SEER-Medicare cohort had 94 544 patients 66 years or older diagnosed between 1992 and 2009. With each interval of delay increase, overall survival was lower overall (hazard ratio [HR], 1.09; 95% CI, 1.06-1.13; P.001), and in patients with stage I (HR, 1.13; 95% CI, 1.08-1.18; P.001) and stage II disease (HR 1.06; 95% CI, 1.01-1.11; P = .01). Breast cancer-specific mortality increased with each 60-day interval (subdistribution hazard ratio [sHR], 1.26; 95% CI, 1.02-1.54; P = .03). The NCDB study evaluated 115 790 patients 18 years or older diagnosed between 2003 and 2005. The overall mortality HR was 1.10 (95% CI, 1.07-1.13; P.001) for each increasing interval, significant in stages I (HR, 1.16; 95% CI, 1.12-1.21; P.001) and II (HR, 1.09; 95% CI, 1.05-1.13; P.001) only, after adjusting for demographic, tumor, and treatment factors.Greater TTS is associated with lower overall and disease-specific survival, and a shortened delay is associated with benefits comparable to some standard therapies. Although time is required for preoperative evaluation and consideration of options such as reconstruction, efforts to reduce TTS should be pursued when possible to enhance survival.

Objective To evaluate an entertainment-based patient decision aid for early stage breast cancer surgery in low health literacy patients. Methods Newly diagnosed female patients with early stage breast cancer from two public hospitals were randomized to receive an entertainment-based decision aid for breast cancer treatment along with usual care (intervention arm) or to receive usual care only (control arm). Pre-decision (baseline), pre-surgery, and 1-year follow-up assessments were conducted. Results Patients assigned to the intervention arm of the study were more likely than the controls to choose mastectomy rather than breast-conserving surgery; however, they appeared better informed and clearer about their surgical options than women assigned to the control group. No differences in satisfaction with the surgical decision or the decision-making process were observed between the patients who viewed the intervention and those assigned to the control group. Conclusions Entertainment education may be a desirable strategy for informing lower health literate women about breast cancer surgery options. Practice Implications Incorporating patient decision aids, particularly computer-based decision aids, into standard clinical practice remains a challenge; however, patients may be directed to view programs at home or at public locations (e.g., libraries, community centers).

Testing emerging technologies involves the evaluation of biologic plausibility, technical efficacy, clinical effectiveness, patient satisfaction, and cost-effectiveness. The objective of this study was to select an effective classification algorithm for optical spectroscopy as an adjunct to colposcopy and obtain preliminary estimates of its accuracy for the detection of CIN 2 or worse. We recruited 1,000 patients from screening and prevention clinics and 850 patients from colposcopy clinics at two comprehensive cancer centers and a community hospital. Optical spectroscopy was performed, and 4,864 biopsies were obtained from the sites measured, including abnormal and normal colposcopic areas. The gold standard was the histologic report of biopsies, read 2 to 3 times by histopathologists blinded to the cytologic, histopathologic, and spectroscopic results. We calculated sensitivities, specificities, receiver operating characteristic (ROC) curves, and areas under the ROC curves. We identified a cutpoint for an algorithm based on optical spectroscopy that yielded an estimated sensitivity of 1.00 [95% confidence interval (CI) = 0.92-1.00] and an estimated specificity of 0.71 [95% CI = 0.62-0.79] in a combined screening and diagnostic population. The positive and negative predictive values were 0.58 and 1.00, respectively. The area under the ROC curve was 0.85 (95% CI = 0.81-0.89). The per-patient and per-site performance were similar in the diagnostic and poorer in the screening settings. Like colposcopy, the device performs best in a diagnostic population. Alternative statistical approaches demonstrate that the analysis is robust and that spectroscopy works as well as or slightly better than colposcopy for the detection of CIN 2 to cancer.

6514Background: Therapies previously reserved for castration resistant prostate cancer (CRPC) have demonstrated improved progression-free (PFS) and overall survival (OS) in mHNPC. Four randomized t...

BACKGROUND: Since 1996, 6 new drugs have been introduced for the treatment of metastatic colorectal cancer. Although they are promising, these drugs frequently are given in the palliative and are much more expensive than older treatments. The objective of the current study was to measure the cost implications of treatment with sequential regimens that include chemotherapy and/or monoclonal antibodies. METHODS: A Markov model was used to evaluate a hypothetical cohort of 1000 patients with newly diagnosed, metastatic colorectal cancer. Patients supposedly received up to 3 lines of treatment before supportive care and subsequent death. Data were obtained from published, multicenter phase 2 and randomized phase 3 clinical trials. Sensitivity analyses were conducted on the efficacy, toxicity, and cost. RESULTS: Using drug costs alone, treatment that included new chemotherapeutic agents increased survival at an incremental cost-effectiveness ratio (ICER) of $100,000 per discounted life-year (DLY). The addition of monoclonal antibodies improved survival at an ICER of >$170,000 per DLY. The results were most sensitive to changes in the initial regimen. Even with significant improvements in clinical characteristics (efficacy and toxicity), treatment with the most effective regimens still had very high ICERs. CONCLUSIONS: Treatment of metastatic colorectal cancer with the most effective regimens came at very high incremental costs. The authors concluded that cost-effectiveness analyses should be a routine component of the drug-development process, so that physicians and patients are informed appropriately regarding the value of new innovations. Cancer 2009. © 2009 American Cancer Society.

We evaluated the performance of the Papanicolaou smear in screening and diagnostic settings.We analyzed Papanicolaou smear results of 1,850 women recruited into a clinical trial to evaluate an emerging technology for the detection of cervical cancer. Screening and diagnosis groups were based on the history of previous Papanicolaou smear results. We calculated sensitivities, specificities, positive and negative likelihood ratios (LR+ and LR-), receiver operating characteristic curves, and areas under the receiver operating characteristic curve (AUC).In the screening group, by defining disease as cervical intraepithelial neoplasia (CIN) 2,3/cancer or worse and using high-grade squamous intraepithelial lesion (HSIL) as the test cutpoint, the AUC was 0.689, and the LR+ and LR- were 39.25 and 0.67, respectively. In the diagnosis group, the AUC was 0.764, and the LR+ and LR- were 3.79 and 0.56, respectively. By defining disease as human papillomavirus/CIN 1 or worse and HSIL as the test cutpoint, the AUC was 0.586, and the LR+ and LR- were 17.01 and 0.92 in the screening group; in the diagnosis group, the AUC was 0.686, and the LR+ and LR- were 2.77 and 0.75, respectively.In a screening setting, a Papanicolaou smear result of HSIL or worse is 39 times more likely in a patient with CIN 2,3/cancer than in a patient without it. This compares to 4 times more likely in the diagnostic setting. The magnitude of the positive likelihood ratio observed in the screening group indicated that abnormal Papanicolaou smear results obtained in the screening setting should have more impact on clinical decision making than those from results obtained in the diagnostic setting.

A medical decision model is a representation of a healthcare decision process with observable outcomes enabling healthcare decision makers to choose among competing courses of action. Its credibility and value depend largely on three components: the plausibility of the structure as measured against the problem concept, the quality of the data that feed the model parameters, and the validity of the outcome structure. Health decision models in use today include decision trees, state-transition models (STM), and dynamic transmission models. Formal medical decision models are now almost exclusively represented as STMs which assume that an individual is always in one of a finite number of conditions (States) and events of interest to the problem are characterized as movements from one state to another (transition). Two common STMs are the Markov cohort, where a simulated group of patients begins in a particular health state and transitions within each time unit which are accomplished according to probabilities and the microsimulation, where a cohort of patients moves from state to state one at a time, using a random number based on probabilities to effect the state transitions. In this chapter best practices for modeling medical decisions will be highlighted, including the use of a worked example.

Purpose New treatments are introduced routinely into clinical practice without rigorous economic analysis. The specific aim of this study was to examine the cost effectiveness of proton beam radiation compared with current state-of-the art therapy in the treatment of patients with prostate cancer. Materials and Methods A Markov model was informed with cost, freedom from biochemical failure (FFBF), and utility data obtained from the literature and from patient interviews to compare the cost effectiveness of 91.8 cobalt gray equivalent (CGE) delivered with proton beam versus 81 CGE delivered with intensity-modulated radiation therapy (IMRT). The length of how many years the model was run, patient's age, probability of FFBF after treatment with proton beam therapy and IMRT, utility of patients treated with salvage hormone therapy, and treatment cost were tested in sensitivity analyses. Results Analysis at 15 years resulted in an expected mean cost of proton beam therapy and IMRT of $63,511 and $36,808, and $64,989 and $39,355 for a 70-year-old and 60-year-old man respectively, with quality-adjusted survival of 8.54 and 8.12 and 9.91 and 9.45 quality-adjusted life-years (QALY), respectively. The incremental cost effectiveness ratio was calculated to be $63,578/QALY for a 70-year-old man and $55,726/QALY for a 60-year-old man. Conclusion Even when based on the unproven assumption that protons will permit a 10-Gy escalation of prostate dose compared with IMRT photons, proton beam therapy is not cost effective for most patients with prostate cancer using the commonly accepted standard of $50,000/QALY. Consideration should be given to limiting the number of proton facilities to allow comprehensive evaluation of this modality.

Most studies on human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (SCC) have been performed on white Americans. Our study examined the incidence of HPV in an African American oropharyngeal SCC cohort and its survival.African American patients with oropharyngeal SCC in a combined tumor registry were identified. HPV16 testing was performed by polymerase chain reaction (PCR) from DNA extracted from tumor blocks. The p16 staining was performed using standard immunohistochemistry.Forty-four patients were identified for analysis. Seventy-three percent of the tumors were HPV-positive. Only 39% of the patients who were HPV-positive were also p16-positive. Survival between all 3 tumor types, patients who tested HPV-positive/p16, HPV-positive/p16-positive, and HPV-negative/p16-negative was significantly different (p = .03). HPV/p16 status was significant on univariate and multivariate analysis.HPV oropharyngeal SCC is strongly present in this African American cohort. Two thirds of the patients who were HPV-positive were p16-negative. Greater study is needed to explain the high p16 negativity among this HPV-positive oropharyngeal SCC African American cohort. © 2015 Wiley Periodicals, Inc. Head Neck 38: E867-E872, 2016.

Purpose: To evaluate the cost-effectiveness of adding hormone therapy to radiation for patients with locally advanced prostate cancer, using a Monte Carlo simulation of a Markov Model. Methods and Materials: Radiation Therapy Oncology Group (RTOG) protocol 86-10 randomized patients to receive radiation therapy (RT) alone or RT plus total androgen suppression (RTHormones) 2 months before and during RT for the treatment of locally advanced prostate cancer. A Markov model was designed with Data Pro (TreeAge Software, Williamstown, MA). The analysis took a payer's perspective. Transition probabilities from one state of health (i.e., with no disease progression or with hormone-responsive metastatic disease) to another were calculated from published rates pertaining to RTOG 86-10. Patients remained in one state of health for 1 year. Utility values for each health state and treatment were obtained from the literature. Distributions were sampled at random from the treatment utilities according to a second-order Monte Carlo simulation technique. Results: The mean expected cost for the RT-only treatments was $29,240 (range, $29,138–$29,403). The mean effectiveness for the RT-only treatment was 5.48 quality-adjusted life years (QALYs) (range, 5.47–5.50). The mean expected cost for RTHormones was $31,286 (range, $31,058–$31,555). The mean effectiveness was 6.43 QALYs (range, 6.42–6.44). Incremental cost-effectiveness analysis showed RTHormones to be within the range of cost-effectiveness at $2,153/QALY. Cost-effectiveness acceptability curve analysis resulted in a >80% probability that RTHormones is cost-effective. Conclusions: Our analysis shows that adding hormonal treatment to RT improves health outcomes at a cost that is within the acceptable cost-effectiveness range.

Robert S. Ledley, one of the founding fathers of the field of medical decision making and the man who applied computer science to medical judgment and diagnosis, died July 24, 2012, after a prolonged struggle with Alzheimer’s. Our community, as well as the medical field as a whole, has lost a pioneering genius. Bob Ledley’s legacy will live on through his magnum opus ‘‘Reasoning Foundations of Medical Diagnosis,’’ coauthored with Lee B. Lusted, MD, FACMI. Lee Lusted was one of the founders of the Society for Medical Decision Making and the founding editor of Medical Decision Making. In their seminal work, the authors showed how computers could help physicians with diagnoses and even taught medical workers how to use edge-notched cards to create diagnostic databases. Most important, this article addressed decision making under uncertainty and valuing outcomes. Citation analyses have demonstrated that this paper lies at the root of medical decision science. In fact, many readers may recall their introduction to our discipline through this article. We now explore the rest of his talent for technological innovation. Robert Steven Ledley was born in Flushing Meadows, New York, in 1926. While attending dental school at New York University College (at his parents’ strong behest, so that he could earn a living), he also pursued his interest in physics at Columbia University. He received his DDS in 1948 and his MS in theoretical physics the following year. One of his professors ‘‘joked that he was the only physicist who could pull a man’s tooth.’’ When the Korean War broke out, Ledley volunteered as a First Lieutenant in the US Army Dental Corps; as a result of his background in physics, he was assigned to research prosthetic dental devices at Walter Reed Army Medical Center in Washington, DC. His work optimizing denture fitting based on ‘‘angle of chew’’ earned him an article from the Associated Press titled ‘‘Mathematics Used to Keep False Teeth in Place.’’ After completing his service, Bob served as an investigator at the National Bureau of Standards and Johns Hopkins University and was an associate professor at George Washington University. While at the National Bureau of Standards, Ledley obtained for his wife (the former Terry Wachtell, a music major whom he convinced to switch to mathematics) a position as a programmer on the Standards Eastern Automatic Computer (SEAC). Bob was fascinated and spent a decade learning to program before using the computer to solve complex problems in his own research. He was an ardent believer in the prowess of computational research: ‘‘I had previously realized that although, conceptually, physics equations could be written to describe any biomedical phenomenon, such equations would be so complex that they could not feasibly be solved in closed form. Thus SEAC would be my panacea, because the equations would become tractable to numerical methods of solutions. Or so I truly believed at the time. That was to be my field, application of computers to biomedical problems.’’ It didn’t take long for Ledley to arrive at a natural starting point—computerizing the diagnostic process. He recalled, ‘‘I put together a deck of the McBee keysort cards (the cards with the holes around the margins) for diseases of the tongue. Each card was a disease, and symptoms related to the disease of the card were punched out to the card margin. Then, if needles were pushed through the edge holes From University of Illinois at Chicago, Chicago, IL (SS); Fox Chase Cancer Center, Philadelphia, PA (JRB); and Tufts Medical Center, Boston, MA (SGP).

To demonstrate how a researcher can investigate the appropriateness of a published comorbidity summary measure for use with a given sample.Surveillance, Epidemiology, and End Results linked to Medicare claims data.We examined Kaplan-Meier estimated survival curves for four diseases within strata of a comorbidity summary measure, the Charlson Comorbidity Index.We identified individuals with early-stage kidney cancer diagnosed from 1995 to 2009. We recorded comorbidities present in the year before diagnosis.The use of many comorbidity summary measures is valid under appropriate conditions. One condition is that the relationships of the comorbidities with the outcome of interest in a researcher's own population are comparable to the relationships in a published algorithm's population. The original comorbidity weights from the Charlson Comorbidity Index seemed adequate for three of the diseases in our sample. We found evidence that the Charlson Comorbidity Index might underestimate the impact of one disease in our sample.Examination of survival curves within strata defined by a comorbidity summary measure can be a useful tool for determining whether a published method appropriately accounts for comorbidities. A comorbidity score is only as good as those variables included.

Although initially approved for metastatic colorectal cancer (mCRC) tumors with epidermal growth factor receptor (EGFR) overexpression, the use of anti-EGFR antibodies is now restricted to wild-type KRAS tumors. Little is known about prescribers' response to new clinical data, practice guidelines, and US Food and Drug Administration (FDA) label change with regard to the use of anti-EGFR antibodies in clinical practice.Commercially insured patients with mCRC who received second-line therapy between 2004 and 2010 were identified by dusing the LifeLink Health Plan Claims Database. We calculated the fraction of patients receiving anti-EGFR antibody in 2-month intervals. χ(2) tests were used to compare treatment rates at four time points: time 1: June 2008, ASCO presentation of clinical data; time 2: February 2009, ASCO guidelines publication; time 3: August 2009, FDA label change; time 4: April 2010 to 8 months after FDA label change.Five thousand eighty-nine patients received second-line therapy; of these, 2,599 patients received an anti-EGFR antibody. Median age was 60 years (range, 20 to 97), with 57% male sex. The majority of patients (59.4%) received an anti-EGFR antibody at time 1, with significant decrease at each of the subsequent time points (time 2: 46.2% [P = .019]; time 3: 35.2% [P.001]; Time 4: 16.2% [P.001]). Multivariable logistic regression did not show any affect of age, sex, comorbidities, or region of the country on this pattern.The use of anti-EGFR antibodies for mCRC decreased after the presentation of clinical trial data, ASCO guidelines publication, and FDA label change. These data suggest that oncologists respond rapidly to new evidence and professional guidelines, and readily incorporate predictive biomarkers into clinical practice.

New computationally intensive tools for medical survival analyses include recursive patitioning (also called CART) and artificial neural networks. A challenge that remains is to better understand the behavior of these techniques in effort to know when they will be effective tools. Theoretically they may overcome limitations of the traditional multivariable survival technique, the Cox proportional hazards regression model. Experiments were designed to test whether the new tools would, in practice, overcome these limitations. Two datasets in which theory suggests CART and the neural network should outperform the Cox model were selected. The first was a published leukemia dataset manipulated to have a strong interaction that CART should detect. The second was a published cirrhosis dataset with pronounced nonlinear effects that a neural network should fit. Repeated sampling of 50 training and testing subsets was applied to each technique. The concordance index C was calculated as a measure of predictive accuracy by each technique on the testing dataset. In the interaction dataset, CART outperformed Cox (P < 0.05) with a C improvement of 0.1 (95% CI, 0.08 to 0.12). In the nonlinear dataset, the neural network outperformed the Cox model (P < 0.05), but by a very slight amount (0.015). As predicted by theory, CART and the neural network were able to overcome limitations of the Cox model. Experiments like these are important to increase our understanding of when one of these new techniques will outperform the standard Cox model. Further research is necessary to predict which technique will do best a priori and to assess the magnitude of superiority.

The optimal management strategy for men who have localized prostate cancer remains controversial. This study examines the extent to which suggested treatment based on the perspective of a group or society agrees with that derived from individual patients' preferences. A previously published decision analysis for localized prostate cancer was used to suggest the treatment that maximized quality-adjusted life expectancy. Two treatment recommendations were obtained for each patient: the first (group-level) was derived using the mean utilities of the cohort; the second (individual-level) used his own set of utilities. Group-level utilities misrepresented 25-48% of individuals' pref erences depending on the grade of tumor modeled. The best kappa measure achieved between group and individual preferences was 0.11. The average quality-adjusted life years lost due to misrepresentation of preference was as high as 1.7 quality-adjusted life years. Use of aggregated utilities in a group-level decision analysis can ignore the substantial variability at the individual level. Caution is needed when applying a group- level recommendation to the treatment of localized prostate cancer in an individual patient. Key words: decision analysis; utility assessment; prostate cancer; patient pref erences. (Med Decis Making 1998;18:376-380)

The question of when to choose surgery over watchful waiting for treatment of clinically localized prostate cancer is difficult. Recently, the Prostate Patient Outcomes Research Team (PORT) published a decision analysis that promoted watchful waiting as a reasonable alternative to invasive treatment for many men with localized prostatic carcinoma. Criticisms were leveled at the analysis itself, its structure, and especially the probabilities and utilities used in the model.We reexamine the PORT decision analysis. Structural sensitivity of the model was conducted, as were multi-way analyses incorporating data more recent than those used in the PORT analysis. The model structure is concluded to be sound and reasonable given the available literature on prostate cancer progression. However, recent data suggest that some probabilities used in the PORT analysis may be understated, causing life expectancy for surgical treatment to be understated. Using these recent data, the decision to operate on all gr...

To realize the advantages of advanced computing technology in medicine we will have to blend computing and communications facilities into a seamless entity that can support ubiquitous computing for medical use. Work-group computing applications, high speed networks linking a multiplicity of servers, and mobile computing platforms can provide the next generation of devices and services for the physician. Ultimately, the biggest challenge for communications and computing in medicine will be found in the requirement for standards in semantics and syntax in the highest levels of the OSI model. We present here our view of the functional requirements for physician communications and computing to meet standard medical practice in Western societies.

This article addresses use of the Internet and Web 2.0 technologies by racial and ethnic minorities and explores the potential opportunities and challenges in leveraging Web 2.0 approaches to impact health disparities. These opportunities and challenges include developing approaches and methods to (a) identify strategies for integrating social media into health promotion interventions focused on major health-related issues that affect members of medically underserved groups; (b) amalgamate techniques to leverage and connect social-media technologies to other evidence-informed online resources; (c) integrate health communication best practices, including addressing health literacy issues; (d) capitalize on social networking to enhance access and communication with health care providers; and (e) advance current efforts and ongoing expansion of research participation by individuals from underserved communities.

This chapter describes the Cancer Biomedical Informatics Grid (caBIG®) project, a collaboration among the National Cancer Institute (NCI) and numerous discovery organizations, mostly NCI-designated cancer centers. The rationale for the caBIG® project opens the review, followed by description and analysis of the pilot phase (2004–2007). Changes in caBIG® as it transitions to an enterprise phase are evaluated. The chapter concludes with a review of important papers that either describe caBIG® components or are based on the initiative.