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We present a 65-year-old female smoker who presented with acute bilateral blurred vision. Investigations led to an endobronchial ultrasound-guided fine-needle aspiration resulting in an early diagnosis of limited stage small cell lung cancer. Positive recoverin antibodies supported the diagnosis of cancer-associated retinopathy (CAR). CAR was the first manifestation of systemic malignancy in our patient and early diagnosis enabled curative intent systemic treatment with chemotherapy and radiotherapy. Ocular-specific treatment is required in CAR, although no standardised treatment exists. Current treatment options include steroids and immunosuppressive agents. Our patient was administered bilateral intravitreal dexamethasone implants, resulting in significant visual field and electroretinogram improvement at 8 weeks post-intervention. To our knowledge, this represents the first reported successful use of intravitreal dexamethasone implants as first-line therapy, in conjunction with chemoradiotherapy. Intravitreal dexamethasone implants therefore may provide an effective and safe treatment for CAR by reducing intraocular inflammation without systemic effects.

In cancer, human cells lose the ability to properly control the series of events that occur constantly during cell growth and division, including protein expression, stability, and dynamics. Heat shock proteins (Hsps) are key molecules in these events, constitutively expressed at high levels and could furthermore be induced by the response to cancer-induced stress. In tumor cells, Hsps have been shown to be implicated in the regulation of apoptosis, immune responses, angiogenesis and metastasis; in some cases, they can be overexpressed and dysregulated, representing important cancer hallmarks. In the past few years, it has been demonstrated that Hsps can be released by tumor cells through several secreting pathways, including the extracellular vesicles (EVs), thus modulating the tumor microenvironment as well as long-distance intercellular communication and metastatization. In this review, we discuss the role of extracellular Hsps in cancer, with a particular interest in Hsps in EVs. We would also like to highlight the importance of fully understanding of the role of extracellular Hsps released by EVs and encourage further research in this field the use of Hsps as early cancer biomarkers and therapeutic targets.

PURPOSE The purpose of this study was to examine differences between urban and rural primary care clinics in the use of colorectal cancer (CRC) screening methods and evidence-based interventions to promote CRC screening. METHODS This was a cross-sectional survey of primary care clinics in Nebraska. Surveys in paper form were sent out and followed up with telephone interviews to nonrespondents. Of the 375 facilities, 263 (70.1%) responded to the survey. FINDINGS Over 30% of urban clinics indicated that 80% or more of their patients were meeting the CRC guidelines compared to 18.3% of rural clinics (P = .03). Rural clinics were more likely than urban clinics to prefer the use of colonoscopy alone or in combination with stool tests (P = .02). The most common interventions for CRC screening included one-on-one patient education and use of computer-based pop-ups to remind providers. CONCLUSIONS In conclusion, we found some important differences between rural and urban primary care clinics in the implementation of CRC screening. Given that there is evidence for differences in preference for CRC screening methods (colonoscopy vs stool-based tests) between rural and urban community members, it is important to assess the effectiveness of different types of CRC screening interventions by comparing rural and urban primary care clinic patient populations.

BACKGROUND Models estimating risk for advanced proximal colorectal neoplasia (APN) may be used to select colorectal cancer (CRC) screening test, either prior to knowing distal colorectal findings or afterward. Current models have only fair discrimination and nearly all require knowing distal findings. OBJECTIVE Derive and test risk prediction models for APN with and without distal findings. SETTING Selected endoscopy centers within central Indiana, USA. PARTICIPANTS Average-risk persons undergoing first-time screening colonoscopy. INTERVENTIONS Demographics, personal and family medical history, lifestyle factors and physical measures were linked to the most advanced finding in proximal and distal colorectal segments. For both models, logistic regression identified factors independently associated with APN on a derivation set. Based on equation coefficients, points were assigned to each factor, and risk for APN was examined for each score. Scores with comparable risks were collapsed into risk categories. Both models and their scoring systems were tested on the validation set. MAIN OUTCOME APN, defined as any adenoma or sessile serrated lesion ≥1 cm, one with villous histology or high-grade dysplasia, or CRC proximal to the descending colon. RESULTS Among 3025 subjects in the derivation set (mean age 57.3 ± 6.5 years; 52% women), APN prevalence was 4.5%; 2859 (94.5%) had complete data on risk factors. Independently associated with APN were age, sex, cigarette smoking, cohabitation status, metabolic syndrome, non-steroidal anti-inflammatory drug use and physical activity. This model (without distal findings) was well-calibrated (P = 0.62) and had good discrimination (c-statistic = 0.73). In low-, intermediate- and high-risk groups that comprised 21, 58 and 21% of the sample, respectively, APN risks were 1.47% (95% CI, 0.67-2.77%), 3.09% (CI, 2.31-4.04%) and 11.6% (CI, 9.10-14.4%), respectively (P

RATIONALE Future optimization of CT lung cancer screening algorithms will depend on clinical outcomes data. OBJECTIVES To report the outcomes of positive and suspicious findings in a clinical CT lung cancer screening program. METHODS We retrospectively reviewed results for patients from our institution undergoing lung cancer screening from 1/2012 through 12/2018, with follow-up through 12/2019. All exams were retrospectively re-scored using Lung-RADS® v1.1. Metrics assessed included positive, probably benign and suspicious exam rates, frequency/nature of care escalation, and lung cancer detection rates following a positive, probably benign, and suspicious exam result and overall. We calculated time required to resolve suspicious exams as malignant or benign. Results were broken down by subcategories, reason for positive/suspicious designation, and screening round. RESULTS During the study period 4301 individuals underwent a total of 10897 exams. The number of positive (13.9%), suspicious (5.5%), and significant incidental (6.4%) findings were significantly higher at baseline screening. Cancer detection and false positive rates were 2.0% and 12.3% at baseline vs 1.3% and 5.1% across subsequent screening rounds respectively. Baseline solid nodule(s) 6 to < 8 mm were the only probably benign findings resulting in lung cancer detection within 12 months. New solid nodules 6 to < 8 mm were the only Lung-RADS® 4A findings falling within the Lung-RADS® predicted cancer detection range of 5-15% (12.8%). 38.5% of Lung-RADS® 4A cancers were detected within three months. CONCLUSIONS Modification of the definition and suggested workup of positive and suspicious lung cancer screening findings appears warranted.

PurposePoor oral health is associated with head and neck cancer (HNC). We evaluated whether a national oral health screening program (OHSP) could reduce the risk of HNC.Materials and MethodsData from 408,247 healthy individuals aged ≥ 40 years from the National Health Insurance System-National Health Screening program during 2003 and 2004 in Korea were analyzed. The risk of HNC was compared between subjects who underwent OHSP (HEALS-Dental+, n=165,292) and routine health check-ups only (HEALS-Dental‒, n=242,955). The impact of individual oral health-related factors on HNC risk was evaluated in HEALS-Dental+.ResultsA total of 1,650 HNC cases were diagnosed. The 10-year HNC-free rate was 99.684% with a median follow-up of 11 years. The risk of all HNC (hazard ratio [HR], 1.16; 95% confidence interval [CI], 1.03 to 1.29; p=0.011) and oropharyngeal cancer (HR, 1.48; 95% CI, 1.13 to 1.94; p=0.005) was significantly higher in HEALS-Dental‒ than in HEALS-Dental+. In HEALS-Dental+, oral cavity cancer was marginally reduced (p=0.085), and missing teeth was a significant factor for HNC (HR, 1.24; 95% CI, 1.02 to 1.50; p=0.032). Toothbrushing was a significant factor in univariate analysis (p=0.028), but not in multivariate analysis (p=0.877).ConclusionThe National OHSP significantly reduced the long-term HNC risk, particularly the incidence of oropharyngeal cancer. Routine OHSP should be considered at the population level.

The increasing incidence and mortality of young-onset colorectal cancer has drawn increasing attention. However, screening for young adults is controversial given the limited evidence regarding its effectiveness.We aimed to clarify the characteristics of young-onset colorectal cancer and to compare long-term outcomes of screening-detected colorectal cancer and non-screening-detected colorectal cancer.This was a retrospective cohort study.This study evaluated data from a colorectal cancer registry and medical records at a tertiary Japanese cancer center.All patients with colorectal cancer who were registered at a Japanese tertiary cancer center between January 2007 and December 2016 were included.The colorectal cancer cases were categorized as screening-detected colorectal cancer and non-screening-detected colorectal cancer, and patients were categorized into 3 age groups:50 years (young-onset), 50 to 75 years, and75 years. The baseline characteristics and survival outcomes of the groups were compared using Cox regression models.A total of 4345 patients were identified, with a median follow-up of 4.6 years. Relative to 50- to 75-year-old individuals, young-onset colorectal cancer was linked to a higher proportion of rectal cancer (50.4% vs 43.3%), a lower proportion of screening-detected colorectal cancer (29.4% vs 35.8%), a lower proportion of stage I colorectal cancer (15.2% vs 30.3%), and a higher proportion of stage III to IV colorectal cancer (64.0% vs 49.4%). Among patients who were50 years old, screening-detected colorectal cancer was associated with a 50% lower risk of mortality relative to non-screening-detected colorectal cancer (HR, 0.50; 95% CI, 0.26-0.95).The findings were limited by the retrospective analysis from a single center.Young-onset colorectal cancer was more likely to present at an advanced stage and had a lower rate of screening-detected colorectal cancer. Nevertheless, young-onset screening-detected colorectal cancer was associated with better overall survival than non-screening-detected colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B829 .ANTECEDENTES:La creciente incidencia y mortalidad del cáncer colorrectal en paciente joven ha atraído una atención cada vez mayor. Sin embargo, el cribado para adultos jóvenes es controvertido, dado la evidencia limitada con respecto a su efectividad.OBJETIVO:Nuestro objetivo fue identificar las características del cáncer colorrectal en paciente joven y comparar los resultados a largo plazo del cáncer colorrectal detectado por cribado y el cáncer colorrectal no detectado por cribado.DISEÑO:Este fue un estudio de cohorte retrospectivo.ESCENARIO:Este estudio evaluó datos de un registro de cáncer colorrectal y registros médicos en un centro oncológico terciario japonés.PACIENTES:Se incluyeron todos los pacientes con cáncer colorrectal registrados en un centro oncológico terciario japonés entre enero de 2007 y diciembre de 2016.PRINCIPALES MEDIDAS DE RESULTADO:Los casos de cáncer colorrectal se categorizaron como cáncer colorrectal detectado mediante cribado y cáncer colorrectal no detectado mediante cribado, y los pacientes se clasificaron en tres grupos de edad:50 años (joven), 50-75 años y75 años. Las características basales y los resultados de supervivencia de los grupos se compararon mediante modelos de regresión de Cox.RESULTADOS:Se identificaron un total de 4345 pacientes, con una mediana de seguimiento de 4,6 años. En relación con las personas de 50 a 75 años, el cáncer colorrectal de inicio en la juventud se relacionó con una mayor proporción de cáncer de recto (50,4% frente a 43,3%), una menor proporción de cáncer colorrectal detectado mediante exámenes de cribado (29,4% frente a 35,8%), una menor proporción de cáncer colorrectal en estadio I (15,2% frente a 30,3%) y una mayor proporción de cáncer colorrectal en estadio III-IV (64,0% frente a 49,4%). Entre los pacientes menores de 50 años, el cáncer colorrectal detectado mediante cribado se asoció con un 50% menos de riesgo de mortalidad, en comparación con el cáncer colorrectal no detectado mediante cribado (HR: 0,50; IC 95%: 0,26-0,95).LIMITACIONES:Los hallazgos fueron limitados por el análisis retrospectivo de un solo centro.CONCLUSIONES:El cáncer colorrectal en paciente joven presenta más probabilidades de presentarse en una etapa avanzada y con una tasa más baja de detección mediante cribado. No obstante, el cáncer colorrectal detectado por cribado de aparición temprana se asoció con una mejor supervivencia general que el cáncer colorrectal no detectado por cribado. Consulte Video Resumen en http://links.lww.com/DCR/B829 . (Traducción-Dr. Felipe Bellolio ).

Lung cancer screening with low-dose computed tomography has demonstrated at least a 20% decrease in lung cancer-specific mortality, but it has the potential harm of unnecessary invasive procedures performed because of false-positive results. This study reports the outcomes of a structured multidisciplinary lung cancer screening program in an area of endemic histoplasmosis.A retrospective review of patients undergoing lung cancer screening from December 2012 to March 2019 was conducted. Findings suggestive of lung cancer were presented to a multidisciplinary thoracic tumor board. Patients were assigned to interval imaging follow-up, additional diagnostic imaging, or referral for an invasive procedure. Invasive procedures were then compared between benign and malignant diseases.A total of 4087 scans were performed on 2129 patients; 372 (9.1%) were suspicious and were presented to a multidisciplinary thoracic tumor board. Ultimately, 108 procedures were performed: 55 bronchoscopies, 7 percutaneous biopsies, and 46 operations. A total of 25 patients (1.2%) underwent bronchoscopy resulting in benign pathologic findings, significantly associated with an indication of an endobronchial lesion (P = .01). All percutaneous biopsy specimens revealed malignancy. Five patients (0.2%) who underwent resection had benign disease. Lung cancer was diagnosed in 67 patients (3.1% of the entire cohort), 46 of whom had stage I or II disease.Lung cancer screening in a structured, multidisciplinary program successfully identifies patients with early-stage lung cancer with limited unnecessary surgical interventions. Patients with isolated endobronchial lesions should undergo short interval imaging follow-up to avoid bronchoscopy for benign disease. Future studies to minimize unnecessary procedures could incorporate biomarkers and advanced imaging analysis into risk assessment models.

PURPOSE Accurate risk assessment is essential for the success of population screening programs in breast cancer. Models with high sensitivity and specificity would enable programs to target more elaborate screening efforts to high-risk populations, while minimizing overtreatment for the rest. Artificial intelligence (AI)-based risk models have demonstrated a significant advance over risk models used today in clinical practice. However, the responsible deployment of novel AI requires careful validation across diverse populations. To this end, we validate our AI-based model, Mirai, across globally diverse screening populations. METHODS We collected screening mammograms and pathology-confirmed breast cancer outcomes from Massachusetts General Hospital, USA; Novant, USA; Emory, USA; Maccabi-Assuta, Israel; Karolinska, Sweden; Chang Gung Memorial Hospital, Taiwan; and Barretos, Brazil. We evaluated Uno's concordance index for Mirai in predicting risk of breast cancer at one to five years from the mammogram. RESULTS A total of 128,793 mammograms from 62,185 patients were collected across the seven sites, of which 3,815 were followed by a cancer diagnosis within 5 years. Mirai obtained concordance indices of 0.75 (95% CI, 0.72 to 0.78), 0.75 (95% CI, 0.70 to 0.80), 0.77 (95% CI, 0.75 to 0.79), 0.77 (95% CI, 0.73 to 0.81), 0.81 (95% CI, 0.79 to 0.82), 0.79 (95% CI, 0.76 to 0.83), and 0.84 (95% CI, 0.81 to 0.88) at Massachusetts General Hospital, Novant, Emory, Maccabi-Assuta, Karolinska, Chang Gung Memorial Hospital, and Barretos, respectively. CONCLUSION Mirai, a mammography-based risk model, maintained its accuracy across globally diverse test sets from seven hospitals across five countries. This is the broadest validation to date of an AI-based breast cancer model and suggests that the technology can offer broad and equitable improvements in care.

BACKGROUND: Racial/ethnic minorities face stark inequalities in lung cancer incidence, treatment, survival, and mortality compared with U.S. born non-Hispanic Whites. Lung cancer screening (LCS) with low-dose computed tomography (LDCT) is effective at reducing lung cancer mortality in high-risk current and former smokers and is recommended by the U.S. Preventive Services Task Force (USPSTF). This study sought to assess primary care providers’ (PCPs’) knowledge, attitudes, beliefs, and practice related to LCS and the recent USPSTF guidelines in five high risk immigrant communities in New York City. METHODS: We surveyed 83 eligible PCPs between December 2016 and January 2018 through surveys sent by mail, email, and fax, administered by phone or in-person. The survey included questions about providers’ clinical practice, knowledge, attitudes and beliefs related to LCS and the USPSTF guidelines. Information about patient demographics, PCPs’ training background and practice type were also collected. RESULTS: Sixty-seven percent of respondents reported that they did not have established guidelines for LCS at their practice and 52% expressed that “vague” screening criteria influenced their referral processes for LCS. Barriers to LCS with LDCT included concerns that LDCT is not covered by insurance, patients’ fears of screening results, and patients’ concerns regarding radiation exposure. DISCUSSION: Targeted educational interventions for both PCPs and patients may increase access to recommended LCS, especially for populations at disproportionate risk for lung cancer.

ObjectiveDespite some progress in recent years, colorectal cancer (CRC) screening adherence in the United States is still suboptimal, particularly among disadvantaged groups. In this study, we assessed the association between socioeconomic status (SES) and self-reported screening non-adherence (SNA) in a sample of racial/ethnic minorities living in San Francisco, California.Design/methodsA total of 376 participants of the San Francisco version of the Health Information National Trends Survey (SF-HINTS) with ages 50-75 years were included in this cross-sectional study. SNA was defined as not reporting blood stool test within the past year and not reporting sigmoidoscopy/colonoscopy within the past 10 years. Poisson regression models with robust variance estimators were used to evaluate the relation of SES with SNA, adjusting for measured confounders. Results are reported as prevalence ratios (PR) and 95% confidence intervals (95% CI).ResultsOverall SNA was 40%. In multivariable models including all respondents, retired participants had significantly lower SNA prevalence than employed participants (PR = 0.46, 95% CI = 0.26 0.83). In stratified analyses by race/ethnicity, Black respondents with less than high school (PR = 1.93, 95% CI = 1.09, 3.43) and those with high school or equivalent (PR = 1.88, 95% CI = 1.16, 3.04) had significantly higher SNA prevalence than those with at least some college. Among non-Hispanic Asian/Pacific Islanders, those disabled had significantly higher prevalence of SNA as compared to employed people (PR = 4.26, 95% CI = 2.11, 8.60). None of the SES indicators were significantly associated to SNA among Hispanics.ConclusionsParticipants with lower SES characteristics were less likely to adhere to CRC screening guidelines and being retired was a predictor of compliance. There was evidence of heterogeneity in associations between SES and CRC screening by race/ethnicity. Life circumstances of retired people could provide insights for designing interventions aimed to improve CRC screening uptake in these priority groups. Future efforts should consider mechanisms underlying differences by race/ethnicity.

Objectives People who are referred for colonoscopy, following an abnormal colorectal cancer (CRC) screening result, are at increased risk of CRC. Despite this, many individuals decline the procedure. The aim of this study was to investigate why. Methods As little is currently known about non-attendance at follow-up colonoscopy, and follow-up of abnormal screening results is a nurse-led process, we decided to conduct key informant interviews with Specialist Screening Practitioners ([SSPs] nurses working in the English Bowel Cancer Screening Program). Interviews were conducted online. Transcripts were assessed using inductive and deductive coding techniques. Results 21 SSPs participated in an interview. Five main types of barriers and facilitators to colonoscopy were described, namely: Sociocultural, Practical, Psychological, Health-related and COVID-related. Key psychological and sociocultural factors included: ‘Fear of pain and discomfort associated with the procedure’ and ‘Lack of support from family and friends’. Key practical, health-related and COVID-related factors included: ‘Family and work commitments’, ‘Existing health conditions as competing priorities’ and ‘Fear of getting COVID-19 at the hospital'. Conclusions A range of barriers and facilitators to follow-up colonoscopy exist. Future studies conducted with patients are needed to further explore barriers to colonoscopy. Practice implications Strategies to reduce non-attendance should adopt a multifaceted approach.

Background: Screening mammography facilities closed during the COVID-19 pandemic in spring 2020. Recovery of screening volumes has varied across patient subgroups and facilities. Objective: We compared screening mammography volumes, as well as patient and facility characteristics, between pre-COVID-19 periods and early and later post-closure recovery periods. Methods: This retrospective study included screening mammograms performed in the same 2-month period (May 26-July 26) in 2019 (pre-COVID-19), 2020 (early recovery) and 2021 (late recovery, following targeted interventions to expand access), across multiple facility types (urban, suburban, community health center). Suburban sites had highest proportion of White patients as well as greatest scheduling flexibility and expanded appointments during initial reopening. Findings were compared across years. Results: For White patients, volumes decreased 36.6% from 6550 in 2019 to 4384 in 2020, and then increased 61.0% to 6579 in 2021; for patients with races other than White, volumes decreased 53.9% from 1321 in 2019 to 609 in 2020, and then increased 136.8% to 1442 in 2021. Percentage of mammograms in patients with races other than White was 16.9% in 2019, 12.2% in 2020, and 18.0% in 2021. Proportion performed at the urban center was 55.3% in 2019, 42.2% in 2020, and 45.9% in 2021; proportion at suburban sites was 34.0% in 2019, 49.2% in 2020, and 43.5% in 2021. Pre-COVID-19 volumes were reached by the sixth week after reopening for suburban sites, but not reached during early recovery for other sites. Proportion performed on Saturdays for suburban sites was similar across periods, while for the urban site was 7.6% in 2019, 5.3% in 2020, and 8.8% in 2021; the community health center did not offer Saturday appointments during recovery. Conclusion: After reopening, screening shifted from urban to suburban settings, with disproportionate screening decrease in patients with races other than White. Initial delayed access at facilities serving underserved populations exacerbated disparities. Interventions to expand access resulted in late recovery volumes exceeding prepandemic volumes in patients with races other than White. Clinical Impact: Interventions to support equitable access across facilities serving diverse patient populations may mitigate potential widening disparities in breast cancer diagnosis during the pandemic.

Background: There are no established methods for pancreatic cancer (PAC) screening, but the NCI and the Pancreatic Cancer Action Network (PanCAN) are investigating risk-based screening strategies in patients with new-onset diabetes (NOD), a group with elevated PAC risk. Preliminary estimates of the cost-effectiveness of these strategies can provide insights about potential value and inform supplemental data collection. Using data from the Enriching New-Onset Diabetes for Pancreatic Cancer (END-PAC) risk model validation study, we assessed the potential value of CT screening for PAC in those determined to be at elevated risk, as is being done in a planned PanCAN Early Detection Initiative trial. Methods: We created an integrated decision tree and Markov state-transition model to assess the cost-effectiveness of PAC screening in patients aged ≥50 years with NOD using CT imaging versus no screening. PAC prevalence, sensitivity, and specificity were derived from the END-PAC validation study. PAC stage distribution in the no-screening strategy and PAC survival were derived from the SEER program. Background mortality for patients with diabetes, screening and cancer care expenditure, and health state utilities were derived from the literature. Life-years (LYs), quality-adjusted LYs (QALYs), and costs were tracked over a lifetime horizon and discounted at 3% per year. Results are presented in 2020 US dollars, and we took a limited US healthcare perspective. Results: In the base case, screening resulted in 0.0055 more LYs, 0.0045 more QALYs, and $293 in additional expenditures for a cost per QALY gained of $65,076. In probabilistic analyses, screening resulted in a cost per QALY gained of 25% of screen-detected PAC cases needed to be resectable for the cost per QALY gained with screening to be Conclusions: We found that risk-based PAC screening in patients with NOD is likely to be cost-effective in the United States if even a modest fraction (>25%) of screen-detected patients with PAC are resectable. Future studies should reassess the value of this intervention once clinical trial data become available.

Background: Non-contrast chest CTs (NCCT) are performed routinely for coronary artery calcium (CAC) scoring and lung cancer screening. However, a large amount of noncoronary and nonpulmonary data from these scans remain unassessed. We aimed to validate a deep learning model to automatically segment and measure left atrial (LA) volumes from routine NCCT and evaluate prediction for cardiovascular outcomes. Methods: We retrospectively evaluated 273 patients (median age 69 years, 55.5% male) who underwent a routine non-ECG gated NCCT for lung cancer screening. LA volumes were quantified by three expert cardiothoracic radiologists and a prototype AI algorithm. LA volumes were then indexed to the body surface area (BSA). Expert and AI LA volume index (LAVi) were compared and used to predict cardiovascular outcomes within five years. Logistic regression with appropriate univariate statistics were used for modelling outcomes. Findings: There was excellent correlation between AI and expert results with an LAV intraclass correlation of 0.950 (0.936-0.960). Bland-Altman plot demonstrated the AI underestimated LAVi by a mean 5.86 mL/m 2 . AI-LAVi was associated with new-onset atrial fibrillation (AUC 0.86; OR 1.12, 95% CI 1.08-1.18, p

Background: Major depression is found in around ten percent of patients attending cancer clinics. One of the symptoms of major depression, defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM), is ‘thoughts of death or suicide’. In order to implement depression screening programs for patients with cancer, we need to know the prevalence not only of this broadly defined symptom, but also of more specific suicidal thoughts, as only the latter clearly indicates the need for specialist psychiatric assessment and management of suicide risk. Methods: We analyzed data from a routine two-stage depression screening program that operated in three UK cancer centers, linked with demographic and clinical data obtained from a national cancer registry. We included data on 2,217 patients with common cancers and comorbid, interview-diagnosed, major depression. We determined the percentage of patients with: (a) the DSM-IV symptom ‘thoughts of death or suicide’ and (b) suicidal thoughts, defined as an affirmative response to the question ‘have you had thoughts of ending your life?’ We investigated the associations of patients’ demographic and clinical characteristics with each of these using logistic regression models. Results: We found that 29% (641/2,217) of patients had the DSM symptom ‘thoughts of death or suicide’ and 9% (207/2,217) had suicidal thoughts. Of the demographic and clinical characteristics that we studied, none had statistically significant associations with having the DSM symptom. Only younger age and primary cancer were associated with having suicidal thoughts. Conclusions: We found that almost one third of patients with cancer and comorbid major depression, have the DSM symptom ‘thoughts of death or suicide’. However, only a third of the patients with this symptom report suicidal thoughts. These findings suggest that around one in ten patients found by a screening program to have major depression will have suicidal thoughts requiring a psychiatric assessment. The staffing of depression screening programs should be designed with these data in mind.

Background Women who received a COVID-19 vaccination may display subclinical unilateral axillary lymphadenopathy on screening mammography, which can appear suspicious for malignancy, leading to additional diagnostic evaluation. Purpose To evaluate the prevalence of subclinical unilateral axillary lymphadenopathy (sLAD) on screening mammogram in women who received either the first or second dose of the Pfizer-BioNTech (Pfizer) or Moderna COVID-19 vaccines compared to women who have not. Materials and Methods In this IRB-approved, HIPAA complaint study from 12/14/2020 to 4/14/2021, 1027 patients presented for screening mammography and met study inclusion criteria. Patients with history of baseline lymphadenopathy or prior cancer diagnosis were excluded. Results : Of the 1027 women, 43 were recalled for unilateral sLAD. 34 women received a COVID-19 vaccination ipsilateral to the sLAD (Pfizer n=19, 44.2%; Moderna n=15, 34.9%), 9 did not (20.9%). Incidence of unilateral axillary sLAD was significantly higher (p-value

Objective A genomic test to predict personal risk of colorectal cancer (CRC) that targets screening and could be feasibly implemented in primary care. We explored informed decision-making and attitudes towards genomic testing in this setting. Methods A CRC genomic test was offered to 150 general practice patients with brief discussion of its implications. We measured informed choice about the test, consisting knowledge, attitudes and test uptake. Sixteen purposively-sampled participants were interviewed. Results Of 150, 142 (95%) completed the informed choice measure and of 27 invited, 16 (59%) completed an interview. 73% made an informed choice about the test. Interviews revealed that participants with inadequate knowledge on the informed choice scale still understood the gist of the test. While positive attitudes were most prevalent, some had concerns, and many were indifferent to the test. Positive attitudes included: that risk information could facilitate risk reduction; negative attitudes included: that risk results could cause worry and be used for insurance discrimination; indifferent attitudes included: that the test seemed benign and it was easy to do. Conclusions Our study adds to the evidence that genomic tests for CRC risk do not pose significant concern to patients in community settings. Practice implications As genomic tests become more prevalent, this study’s findings can be used to facilitate informed decision-making and ensure equitable access.

Incidental respiratory disease-related findings are frequently observed on low-dose CT (LDCT) lung cancer screenings. This study analyzed data from the National Lung Screening Trial (NLST) to assess the relationship between such findings and respiratory disease mortality (RDM), excluding lung cancer.Are incidental respiratory findings on LDCT scanning associated with increased RDM?Subjects in the NLST LDCT arm received three annual screens. Trial radiologists noted findings related to possible lung cancer, as well as respiratory-related incidental findings. Demographic characteristics, smoking history, and medical history were captured in a baseline questionnaire. Kaplan-Meier curves were used to assess cumulative RDM. Multivariate proportional hazards models were used to assess risk factors for RDM; in addition to incidental CT scan findings, variables included respiratory disease history (COPD/emphysema, and asthma), smoking history, and demographic factors (age, race, sex, and BMI).Of 26,722 subjects in the NLST LDCT arm, 25,002 received the baseline screen and a subsequent LDCT screen. Overall, 59% were male, 26.5% were aged ≥ 65 years at baseline, and 10.6% reported a history of COPD/emphysema. Emphysema on LDCT scanning was reported in 30.7% of subjects at baseline and in 44.2% at any screen. Of those with emphysema on baseline LDCT scanning, 18% reported a history of COPD/emphysema. Median mortality follow-up was 10.3 years. There were 3,639 deaths, and 708 were from respiratory diseases. Among subjects with no history of COPD/emphysema, 10-year cumulative RDM ranged from 3.9% for subjects with emphysema and reticular opacities to 1.1% for those with neither condition; the corresponding range among subjects with a COPD/emphysema history was 17.3% (both) to 3.7% (neither). Emphysema on LDCT imaging was associated with a significantly elevated RDM hazard ratio (2.27; 95% CI, 1.92-2.7) in the multivariate model. Reticular opacities (including honeycombing/fibrosis/scar) also had a significantly elevated hazard ratio (1.39; 95% CI, 1.19-1.62).Incidental respiratory disease-related findings observed on NLST LDCT screens were frequent and associated with increased mortality from respiratory diseases.

INTRODUCTION/BACKGROUND: The USPSTF (United States Preventive Service Task Force) guidelines suggest criteria centering on smoking status and age to select patients for lung cancer screening. Despite the significant advances in screening with low-dose computed tomography (LDCT), cancer detection rate is low (1.1%), highlighting the need to investigate possible ways to refine the current lung cancer screening strategy. Our aim was to determine clinical risk factors predictive of lung cancer in an urban safety-net hospital. MATERIALS AND METHODS: We performed a retrospective chart review of 2847 patients who received LDCT screening for lung cancer between 3/1/2015 and 12/31/2019. Patient demographics and medical history were collected. A bivariate logistic regression was used to evaluate predictors of lung cancer. RESULTS: Compared to the National Lung Cancer Screening Trial (NLST) population, our screening cohort had significantly more African Americans (38.2% vs 4.5%, p

Introduction Mammographic breast density (MBD) is a known risk factor for breast cancer and older women have higher incidence rates of breast cancer occurrence. The Breast Imaging Reporting and Data System (BI-RADS) is a commonly used MBD classification tool for mammogram reporting. However, they have limitations since there are reading inconsistencies between different radiologists with the visual assessment of breast density. Methods Digitised film-screen mammographic images were extracted from the Digital Database for Screening Mammography (DDSM). A machine learning project was developed using commercially available software with several predictive models applied to classify different amount of MBD on mammograms into different density groups. The effectiveness of different predictive models used in classifying the mammograms were tested by receiver operator characteristics (ROC) curve with comparison to the gold standard of BI-RADS classification. Results Three predictive models, Decision Tree (Tree), Support Vector Model (SVM) and k-Nearest Neighbour (kNN) showed high AUC values of 0.801, 0.805 and 0.810 respectively. High AUC values for the three predictive models indicates that the accuracy of the model is approaching that of the BI-RADS method. Discussion Our machine learning project showed to have capabilities to be potentially used in the clinical settings to help categorise mammograms into extremely dense breasts (BI-RADS Group A) from entirely fatty breasts (BI-RADS Group D). Conclusion Findings from the present study suggest that the machine learning method is potentially useful to quantify the amount of MBD in mammograms.

Objective This study aimed to explore Australian women’s current knowledge, perspectives and attitudes about breast density (BD); and information needs to inform effective evidence-based communication strategies. Methods Fourteen online focus group sessions with a total of 78 women in New South Wales and Queensland, Australia aged 40–74 years without a personal diagnosis of breast cancer were conducted. Audio-recorded data was transcribed and analysed thematically. Results Women had a very limited knowledge of BD. Overall, women expressed a preference for more frequent mammograms and/or supplemental screening should they be told they had dense breasts, despite being presented with information on potential downsides of additional testing. The majority of women were supportive of the notion of BD notification, often suggesting they had a ‘right to know’ and they would prefer to be educated and informed about it. Conclusion The potential of being informed and notified of BD is found to be of interest and importance to Australian women of breast screening age despite lacking current knowledge. Practice Implications This study highlights that policy makers and screening services need to consider how to weigh up these views and preferences of women with current evidence surrounding BD in deciding about implementing population-based BD notification.

The spread of early-stage (T1 and T2) adenocarcinomas to locoregional lymph nodes is a key event in disease progression of colorectal cancer (CRC). The cellular mechanisms behind this event are not completely understood and existing predictive biomarkers are imperfect. Here, we used an end-to-end deep learning algorithm to identify risk factors for lymph node metastasis (LNM) status in digitized histopathology slides of the primary CRC and its surrounding tissue. In two large population-based cohorts, we show that this system can predict the presence of more than one LNM in pT2 CRC patients with an area under the receiver operating curve (AUROC) of 0.733 (0.67-0.758) and patients with any LNM with an AUROC of 0.711 (0.597-0.797). Similarly, in pT1 CRC patients, the presence of more than one LNM or any LNM was predictable with an AUROC of 0.733 (0.644-0.778) and 0.567 (0.542-0.597), respectively. Based on these findings, we used the deep learning system to guide human pathology experts towards highly predictive regions for LNM in the whole slide images. This hybrid human observer and deep learning approach identified inflamed adipose tissue as the highest predictive feature for LNM presence. Our study is a first proof of concept that artificial intelligence (AI) systems may be able to discover potentially new biological mechanisms in cancer progression. Our deep learning algorithm is publicly available and can be used for biomarker discovery in any disease setting. © 2021 The Pathological Society of Great Britain and Ireland. Published by John WileySons, Ltd.

We compare the results of delay in oral cancer diagnosis before and after a campaign directed toward dentists and raising awareness of the population to achieve early diagnosis of oral cancer in Córdoba, Argentina. The campaign included training dentists in diagnostic skills and a public awareness program through media and networks.Clinical records (period 1: before intervention program, n = 70; period 2: after intervention program, n = 60) of patients presenting with oral squamous cell carcinoma treated in 2 referral centers were analyzed. Records included first symptoms, first consultation with a health professional, and the time when treatment was formulated.Oral cancer diagnosis at early stages increased from 27% (period 1) to 40% (period 2). Biopsy at first consultation was indicated in 6% of patients in period 1 and in 23.3% in period 2 (odds ratio = 4.68; 95% confidence interval, 1.87-11.73; P.05). Professional delay at early stage decreased from 72% in period 1 to 36.8% in period 2. During period 1, for initial stage cancer, the average patient and professional delays were 2.7 and 2.9 months, respectively (P = .06); in period 2, patient delay was 2.67 months and professional delay was 1.34 months (P = .005).The intervention program helped to improve early-stage diagnosis from 27% to 40% by reducing professional delays.

Background/Aims: Studies have reported an association between fecal occult blood and increased all-cause, non-colorectal cancer (CRC) as well as CRC mortality. This study aimed to determine whether positive fecal immunochemistry test (FIT) results are associated with death from various causes in the South Korean population.Methods: Using the Korean National Cancer Screening Program database, we collected data on patients who underwent FIT between 2009 and 2011.Results: Of the 5,932,544 participants, 380,789 (6.4%) had positive FIT results. FIT-positive participants had a higher mortality rate than FIT-negative participants from CRC (1.33 and 0.21 per 1,000 person-years, p < 0.001, respectively) and non-CRC causes (10.40 and 7.50 per 1,000 person-years, p < 0.001, respectively). Despite adjusting for age, sex, smoking status, alcohol consumption habits, body mass index, comorbidity, and aspirin use, FIT positivity was associated with an increased risk of dying from all non-CRC causes (adjusted hazard ratio [aHR], 1.17; 95% confidence interval [CI], 1.15 to 1.18) and CRC (aHR, 5.61; 95% CI, 5.40 to 5.84). Additionally, FIT positivity was significantly associated with increased mortality from circulatory disease (aHR, 1.14; 95% CI, 1.11 to 1.17), respiratory disease (aHR, 1.14; 95% CI, 1.09 to 1.19), digestive disease (aHR, 1.57; 95% CI, 1.48 to 1.66), neuropsychological disease (aHR, 1.08; 95% CI, 1.01 to 1.16), blood and endocrine diseases (aHR, 1.10; 95% CI, 1.04 to 1.17), and external factors (aHR, 1.16; 95% CI, 1.11 to 1.20).Conclusions: Positive FIT results are associated with an increased risk of mortality from CRC and various other chronic diseases, suggesting that it could be a predictor of mortality independent of its association with CRC.

A WHO global strategy launched in November 2020 sets out an ambitious pathway towards the worldwide elimination of cervical cancer as a public health problem within the next 100 years. Achieving this goal will require investment in innovative approaches. This review aims to describe integrated approaches that combine human papillomavirus (HPV) vaccination and cervical cancer screening in low- and middle-income countries (LMIC), and their efficacy in increasing uptake of services. A systematic review was conducted analyzing relevant papers from Embase, Medline, CINAHL and CAB Global Health databases, as well as grey literature. Narrative synthesis was performed on the included studies. Meta-analysis was not appropriate due to the heterogeneity and nature of included studies. From 5,278 titles screened, 11 uncontrolled intervention studies from four countries (from Africa and east Asia) were included, all from the past 12 years. Four distinct typologies of integration emerged that either increased awareness of HPV and/or cervical cancer screening, and/or coupled the delivery of HPV vaccination and cervical cancer screening programs. The synthesis of findings suggests that existing HPV vaccination programs can be a useful pathway for educating mothers and other female caregivers about cervical cancer screening; through in person conversations with care providers (preferred) or take-home communications products. Integrated service delivery through outreach and mobile clinics may overcome geographic and economic barriers to access for both HPV vaccination and cervical cancer screening, however these require significant program and system resources. One study promoted HPV vaccination as part of integrated service delivery, but there were no other examples found that examined use of cervical cancer screening platforms to promote or educate on HPV vaccination. This review has demonstrated gaps in published literature on attempts to integrate HPV vaccination and cervical cancer screening. The most promising practices to date seem to relate to integrated health communications for cervical cancer prevention. Future research should further explore the opportunities for integrated health communications to support the efforts towards the new global cervical cancer elimination agenda, and costs and feasibility of integrated service delivery for underserved populations.

Background The impact of a faecal immunochemical test-based colorectal cancer (CRC) screening program in terms of patient prognosis could be affected by lead-time bias, which artificially increases the survival of screen-detected patients due to the early diagnosis. Aims To provide a description of the impact of the CRC screening program in the Trentino Region (Italy), including the Cure Fraction (CF), a prognostic indicator not affected by lead-time bias. Methods The program started in 2008, inviting the resident population aged 50–69 years. In this retrospective cohort study, 1,697 CRC diagnosed between 2003 and 2014 in patients aged 50–69 years were classified as pre-screening (PS), screen-detected (SD), interval cancers (IC) and not-screen-detected (NSD). We compared groups by stage at diagnosis and CF. Trends in CRC mortality were reported. Results The proportion of stage I among SD cases was 51%, higher than PS (19%; OR 4.66, 95%CI 3.50–6.20), NSD (20.6%; OR 3.96, 95%CI 2.95–5.32) and IC (33.3%; OR 2.11, 95%CI 1.10–4.04). The CF of PS, NSD and SD cases was respectively 57% (95%CI 54–60%), 60% (95%CI 58–63%) and 93% (95%CI 89–96%). CRC mortality dropped from 40.7 to 25.6\100,000. Conclusion The program significantly improved the prognosis of patients, decreasing CRC mortality and incidence of advanced CRCs.

Objectives We sought to determine if implementation of low dose computed tomography (LDCT) screening for lung cancer in the United States had led to changes in patients being diagnosed with metastatic lung cancer over time. Materials Methods The Surveillance, Epidemiology, and End Result (SEER) database was utilized to determine the proportion of lung cancers diagnosed as stage I-III and stage IV from 2009-2018. Changes in lung cancer stage distribution were compared in the overall population and by race. Results From 2009 to 2018, the proportion of stage I-III lung cancers increased from 52% (51.3%-53.2%) in 2009 to 56% (54.0%-55.8%) in 2018 (p Conclusion Since the implementation of LDCT screening, the proportion of early-stage lung cancers increased in the general population. These changes in stage distribution were not present in black patients. Micro Abstract The SEER database was utilized to assess the impact of CT screening on lung cancer stage distribution from 2009-2018. The percentage of patients diagnosed with metastatic disease decreased overall, but there were no significant changes for black patients. These results associate CT screening to changes in lung cancer stage distribution, but potential racial disparities exist.

Background To recognize fully the benefit of lung cancer screening (LCS), annual adherence must approach the high levels seen in the National Lung Screening Trial. Emerging data suggest that annual adherence is poor and that a centralized approach to screening improves adherence. Research Questions Do differences in adherence exist between a centralized and decentralized approach to LCS within a hybrid program and what are predictors of adherence? Study Design A retrospective evaluation of a single-center hybrid LCS program was conducted to compare outcomes including patient eligibility and adherence between the centralized and decentralized approaches. Methods Patient demographics and outcomes were compared between those screened with a centralized and decentralized approach and between adherent and nonadherent patients using two-sample t tests, χ 2 tests, or analyses of variance, as appropriate. Annual adherence analysis was conducted using data from patients who remained eligible for screening with a baseline Lung CT Screening Reporting and Data System (Lung-RADS) score of 1 or 2. Logistic regression was used to estimate the association between adherence and the primary exposure, adjusting for potential confounders. Results A cohort of 1,117 patients underwent baseline low-dose CT imaging. Two hundred eleven patients (19%) were ineligible by United States Preventative Services Task Force criteria and most (90%) were screened with the decentralized approach. After exclusions, 765 patients with Lung-RADS score of 1 or 2 remained eligible for annual screening. Overall adherence was 56%; however, adherence in the centralized program was 70%, compared with 41% with the decentralized approach (P Interpretation Those screened using a centralized approach were more likely to meet eligibility criteria for LCS and more likely to return for annual screening than those screened using a decentralized approach.

Background:Artificial Intelligence (AI)-based automatic lung nodule detection system improves the detection rate of nodules. It is important to evaluate the clinical value of the AI system by comparing AI-assisted nodule detection with actual radiology reports.Objective:To compare the detection rate of lung nodules between the actual radiology reports and AI-assisted reading in lung cancer CT screening.Methods:Participants in chest CT screening from November to December 2019 were retrospectively included. In the real-world radiologist observation, 14 residents and 15 radiologists participated in finalizing radiology reports. In AI-assisted reading, one resident and one radiologist reevaluated all subjects with the assistance of an AI system to locate and measure the detected lung nodules. A reading panel determined the type and number of detected lung nodules between these two methods.Results:In 860 participants (57±7 years), the reading panel confirmed 250 patients with >1 solid nodule, while radiologists observed 131, lower than 247 by AI-assisted reading (p1 non-solid nodule, whereas radiologist observation identified 28, lower than 110 by AI-assisted reading (pConclusion:Comparing with the actual radiology reports, AI-assisted reading greatly improves the accuracy and sensitivity of nodule detection in chest CT, which benefits lung nodule detection, especially for non-solid nodules.

Appropriate screening of early asymptomatic cases can reduce the disease burden and mortality rate of sporadic colorectal cancer (CRC) significantly. Currently, fecal occult blood testing (FOBT) is able to detect up to 80% of asymptomatic cases in the population aged 50+. Therefore, there is still a demand for new screening tests that would complement FOBT, mainly by detecting at least a part of the FOBT-negative CRC and adenoma cases, or possibly by identifying person at increased risk of sporadic CRC in order to offer them tailored follow-up. Among the potential markers studied, our knowledge has advanced at most in toxigenic gram-negative bacteria. In this review, we assess their potential critically and recommend those best suited for prospective evaluation of their true ability to increase the sensitivity of FOBT when combined during general population screening. In our opinion, colibactin and Bacteroides fragilis toxin are the best candidates, possibly complemented by the cytotoxic necrotizing factor (CNF).

Patients with lung cancer are especially vulnerable to coronavirus disease 2019 (COVID-19) with a greater than sevenfold higher rate of becoming infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19, a greater than threefold higher hospitalization rate with high complication rates, and an estimated case fatality rate of more than 30%. The reasons for the increased vulnerability are not known. In addition, beyond the direct impact of the pandemic on morbidity and mortality among patients with lung cancer, COVID-19, with its disruption of patient care, has also resulted in substantial impact on lung cancer screening and treatment/management.COVID-19 vaccines are safe and effective in people with lung cancer. On the basis of the available data, patients with lung cancer should continue their course of cancer treatment and get vaccinated against the SARS-CoV-2 virus. For unknown reasons, some patients with lung cancer mount poor antibody responses to vaccination. Thus, boosting vaccination seems urgently indicated in this subgroup of vulnerable patients with lung cancer. Nevertheless, many unanswered questions regarding vaccination in this population remain, including the magnitude, quality, and duration of antibody response and the role of innate and acquired cellular immunities for clinical protection. Additional important knowledge gaps also remain, including the following: how can we best protect patients with lung cancer from developing COVID-19, including managing care in patient with lung cancer and the home environment of patients with lung cancer; are there clinical/treatment demographics and tumor molecular demographics that affect severity of COVID-19 disease in patients with lung cancer; does anticancer treatment affect antibody production and protection; does SARS-CoV-2 infection affect the development/progression of lung cancer; and are special measures and vaccine strategies needed for patients with lung cancer as viral variants of concern emerge.

Colorectal cancer (CRC) screening has been demonstrated to reduce CRC incidence and mortality. However, besides such benefits, CRC screening is also associated with potential harmful effects. In an ideal world, screening would only be directed to the small proportion of the population that might potentially benefit. Risk-based screening can be seen as a first step towards this ideal world, by redistributing screening resources from low-risk to high-risk individuals. In theory, this should result in scarce resources being used in individuals who benefit most, while intensity of screening is reduced in individuals who benefit less, hence improving the benefit-harm ratio among all invitees. Available strategies that have been proposed for risk-based CRC screening include using information on age, sex, prior screening history, lifestyle and/or genetic information. Implementation of risk-based screening requires careful consideration of reliable risk prediction models, participation with screening and informed decision-making. While it is important to recognise the limitations of current approaches, available evidence suggests that it might be feasible to start planning the introduction of tailored strategies within screening programmes. Implementing risk-based screening based on age, sex and prior screening history alone would already represent a substantial improvement over current uniform screening approaches. We propose that it is time that screening programmes start there and continue striving towards more comprehensive approaches embedding primary prevention as an effective approach to lower risk for everyone.

Background: Cervical cancer screening with high-risk human papillomavirus (HrHPV) testing is being introduced. Most HrHPV infections are transient, requiring triage tests to identify individuals at highest risk for progression to cervical cancer. Head-to-head comparisons of available strategies for screening and triage are needed. Endometrial and ovarian cancers could be amenable to similar testing. Methods: Between 2016 and 2020, discarded cervical cancer screening specimens from women ages 25 to 65 undergoing screening at Kaiser Permanente Northern California were collected. Specimens were aliquoted, stabilized, and stored frozen. Human papillomavirus (HPV), cytology, and histopathology results as well as demographic and cofactor information were obtained from electronic medical records (EMR). Follow-up collection of specimens was conducted for 2 years, and EMR-based data collection was planned for 5 years. Results: Collection of enrollment and follow-up specimens is complete, and EMR-based follow-up data collection is ongoing. At baseline, specimens were collected from 54,957 HPV-positive, 10,215 HPV-negative/Pap-positive, and 12,748 HPV-negative/Pap-negative women. Clinical history prior to baseline was available for 72.6% of individuals, of which 53.9% were undergoing routine screening, 8.6% recently had an abnormal screen, 30.3% had previous colposcopy, and 7.2% had previous treatment. As of February 2021, 55.7% had one or more colposcopies, yielding 5,563 cervical intraepithelial neoplasia grade 2 (CIN2), 2,756 cervical intraepithelial neoplasia grade 3 (CIN3), and 146 cancer histopathology diagnoses. Conclusions: This robust population-based cohort study represents all stages of cervical cancer screening, management, and posttreatment follow-up. Impact: The IRIS study is a unique and highly relevant resource allowing for natural history studies and rigorous evaluation of candidate HrHPV screening and triage markers, while permitting studies of biomarkers associated with other gynecologic cancers.

Objectives We propose a risk-tailored approach for management of lung cancer screening results. This approach incorporates individual risk factors and low-dose computed tomography (LDCT) image features into calculations of immediate and next-screen (1-y) risks of lung cancer detection, which in turn can recommend short-interval imaging or 1-year or 2-year screening intervals. Methods We first extended the "LCRAT+CT" individualized risk calculator to predict lung cancer risk after either a negative or abnormal LDCT screen result. To develop the abnormal screen portion, we analyzed 18,129 abnormal LDCT results in the National Lung Screening Trial (NLST), including lung cancers detected immediately (n = 649) or at the next screen (n = 235). We estimated the potential impact of this approach among NLST participants with any screen result (negative or abnormal). Results Applying the draft National Health Service (NHS) England protocol for lung screening to NLST participants referred 76% of participants to a 2-year interval, but delayed diagnosis for 40% of detectable cancers. The Lung Cancer Risk Assessment Tool+Computed Tomography (LCRAT+CT) risk model, with a threshold of less than 0.95% cumulative lung cancer risk, would also refer 76% of participants to a 2-year interval, but would delay diagnosis for only 30% of cancers, a 25% reduction versus the NHS protocol. Alternatively, LCRAT+CT, with a threshold of less than 1.7% cumulative lung cancer risk, would also delay diagnosis for 40% of cancers, but would refer 85% of participants for a 2-year interval, a 38% further reduction in the number of required 1-year screens beyond the NHS protocol. Conclusions Using individualized risk models to determine management in lung cancer screening could substantially reduce the number of screens or increase early detection.

PURPOSE Lung cancer screening (LCS) decreases lung cancer mortality; however, that reduction depends upon screening adherence. The purpose of this study was to determine factors associated with adherence rate for LCS among patients with negative baseline CT results in a multi-integrated health care network. METHODS A retrospective analysis was conducted among patients with negative baseline CT results in a multi-integrated health care network LCS program between January 2015 and January 2020. The two outcomes were adherence for the first and second subsequent LCS studies. Negative baseline result was defined as a Lung CT Screening Reporting and Data System score 0, 1, or 2. Adherence was defined as undergoing a follow-up study within 11 to 15 months of a prior scan. Multivariable logistic regression was used to determine significant predictors of adherence, adjusting for patient demographics, median household income (on the basis of geocoding ZIP codes from the US Census Bureau), smoking history, screening sites, and provider specialty. RESULTS A total of 30.7% (512 of 1,668) and 16.3% (270 of 1,660) of patients were adherent for the first two annual subsequent screens, respectively. First-year adherence was higher among former smokers and varied by site and provider specialty. Second-year adherence was higher among former smokers and varied by site, provider specialty, and pack-years smoked. CONCLUSIONS Adherence to LCS in a multihospital integrated health care network was poor and even lower at year 2. The identified factors associated with adherence may serve as targets to increase LCS adherence and decrease lung cancer mortality.

In the setting of cancer pathology, molecular characterization of tumors providing diagnostic and predictive information is acquiring more and more relevance. Moreover, the advent of innovative technologies continuously improves the knowledge of the molecular landscape of tumors and strengthens the links between clinics, tumor pathology and molecular features. In the clinical management of patients with thyroid nodules and thyroid tumors, the aid of molecular testing is encouraged but still not strongly recommended by current guidelines. Also for this reason this field of study is attracting much interest. The nCounter system is a relatively new technology based on a direct hybridization of fluorescent probes to specific nucleic acid targets, followed by digital measurement of signals; the reaction is highly multiplexable and results are robust and reproducible. This review reports and discusses the available data related to the application of this specific technique to thyroid nodules and thyroid tumors samples. The available data indicate that nCounter system represents a solid approach for the research of relevant diagnostic and prognostic biomarkers in thyroid pathology.

Purpose To identify factors influencing the likelihood of a false positive lung cancer screening (LCS) computed tomography (CT), which may lead to increased costs and patient anxiety. Materials and Methods In this retrospective study, we examined all LCS CTs performed across our healthcare network from 2014 to 2018, recording Lung-RADS category and diagnosis of lung cancer. A false positive was defined by Lung-RADS 3-4X and no diagnosis of lung cancer within 1 year. Patient demographics and smoking history, presence of emphysema, diagnosis of chronic obstructive pulmonary disease, radiologist years of experience and annual volume, income level by patient zip code, and screening institution were evaluated in a multivariate logistic regression model for false positive exams. Results A total of 5835 LCS CTs were included from 3735 patients. Lung cancer was diagnosed in 142 cases (2%). Of the LCS CTs, 905 (16%) were positive by Lung-RADS, and 766 (13%) represented false positives. Logistic regression analysis showed that screening institution (odds ratios [OR] 0.91 – 2.43), baseline scan (OR 1.43), radiologist experience (OR 0.59), patient age (OR 2.08), diagnosis of chronic obstructive pulmonary disease (OR 1.34), presence of emphysema (OR 1.32), and income level (OR 0.43) were significant predictors of false positives. Conclusion A number of patient-specific and site/radiologist-specific factors influence the false positive rate in CT LCS. In particular, radiologists with less experience had a higher false positive rate. Screening programs may wish to develop quality assurance programs to compare the false positive rates of their radiologists to national benchmarks.

Universal screening of endometrial cancer for underlying Lynch syndrome (LS) using DNA mismatch repair immunohistochemistry (MMR IHC) has been recommended. The objective of this study was to assess the feasibility and outcomes of using office endometrial samplings in a community LS screening program.A community laboratory adopted Cancer Care Ontario's LS screening recommendations. All new endometrial cancers in women aged70 years were screened for LS using MMR IHC and MLH1 promoter methylation testing cascade for MLH1/PMS2-deficient cases. This retrospective validation study analyzes the first year's results.Of 693 new endometrial cancers, 467 (67.4%) were eligible for LS screening. Both MMR IHC and MLH1 promoter methylation testing were conclusive in98% of cases. MMR deficiency (MMRd), which includes LS screen-positive cases, was identified in 25.9% of patients (121/467). LS screen-positive tumours comprised 5.9% (27/467) of all cases.Endometrial samplings from community practice are suitable for pre-operative LS screening. This testing can identify MMRd endometrial cancers with significant prognostic implications. Approximately 1 in 20 Ontario women70 years of age with endometrial cancer screen positive for LS. Pre-operative and/or operative assessment for co-existent colonic neoplasms needs to be considered in this high-risk group. In addition, these women should be referred to genetic counselling.

Background: Adherence-to-colonoscopy in cascade screening of colorectal cancer (CRC) is crucial to the effectiveness of screening, but it has not been systematically evaluated. We aimed to evaluate the colonoscopy adherence among average-risk populations globally. Methods: We searched Pubmed, Embase, Web of Science, and Cochrane Library for observational and experimental studies published in English up to December 31, 2018 and reporting the colonoscopy adherence following positive initial screening. We calculated pooled adherence with its 95% confidence intervals (CIs) using a random-effects meta-analysis. Subgroup and mixed-effects meta-regression analysis were performed to evaluate heterogeneous factors for adherence. Findings: Of 9,772 articles identified, 191 (313 studies) were included in the systematic review. The pooled adherence-to-colonoscopy was 81·6% (95% CI: 79·6-83·4), with the estimates varying substantially by continents, CRC incidence, GDP per capita, recruitment method, screening round and type of initial test. Type of initial test was the most modifiable heterogeneous factor for adherence across studies (Q=53·00, P

Hepatocellular carcinoma (HCC) continues to have a dismal prognosis, with 5-year survival below 20%. This poor prognosis can be in part attributed to failures along the cancer screening process continuum such as underuse of screening in at risk patients and appropriate treatments for patients with HCC. Better understanding these process failures, and how they compare to those seen in other cancer types, can help inform potential intervention targets and strategies to reduce HCC-related mortality. Herein, we outline a conceptual model with several discrete steps in the HCC screening process continuum including risk assessment, screening initiation, follow-up of screening results, diagnostic evaluation, and treatment evaluation. The conceptual model illustrates how each step in the screening process is prone to delays or failure, resulting in worse outcomes such as late stage diagnosis or poor survival, and how factors at the patient, provider, and health care system levels can contribute to these failures. We compare cancer screening processes for HCC with those employed in breast and colorectal cancer screening to identify opportunities for improvement. The Translational Liver Cancer consortium was recently established by the National Cancer Institute with the goal of improving early detection of HCC. Studies designed to address failures in the HCC screening process continuum will help accomplish this goal.

Rationale and Objectives Mobile mammography units provide preventive health care to patients facing barriers to annual screening. This study reviews the outcomes of a mobile mammography service during a recent 5-year period. Materials and Methods This retrospective study analyzed the examinations by mobile mammography during a 5-year period (9327 examinations). The patients recalled, biopsies performed, and cancers detected were tallied. The race, age, breast cancer size, lymph node involvement, and metastases were recorded. The positive predictive value (PPV) and cancer detection rate metrics were calculated as outlined by the American College of Radiology Breast Imaging Reporting and Data System Atlas. Results The program identified cancer in 14 cases (cancer detection rate = 1.5 per 1000 examinations [95% confidence interval [CI], 0.9–2.5]) with 11 being invasive. The majority of these cancers were small and of low stage. Lymph node status was determined in 11 of the 14 cases (1 as N1mi, 5 as N0, 4 as N1,1 as N2a). Abnormalities led to 1686 examinations recalled (Recall Rate = 17.8%; PPV 1 = 0.8% [95% CI, 0.5%–1.4%]). One hundred and one were recommended for biopsy (PPV 2 = 13.9% [95% CI, 8.4%–21.9%]), and 98 pursued biopsy (PPV 3 = 14.3% [95% CI, 8.7%–22.6%]). Patient age ranged from 41 to 67 years with an average of 50.6 years. Conclusion The program detected many cancers in an asymptomatic population facing barriers to breast cancer screening. These findings are underscored by the cancers detected at an early stage with a favorable prognosis and support the need for the development of similar programs.

Introduction Colorectal cancer (CRC) is the third most common malignancy worldwide, with the second highest mortality rate among all malignancies. In this review, we describe the current utility of stool diagnostic biomarkers for CRC. Methods We reviewed stool-related tests and biomarker candidates for the diagnosis of CRC. The guaiac-based fecal occult blood test (gFOBT), fecal immunochemical test (FIT), and multitarget stool DNA test (MT-sDNA) have been used as clinical CRC screening tools. Although microRNAs, protein biomarkers, and microbiota have not yet been used in clinical CRC screening, there is growing evidence that they have the potential to function as CRC screening tools. Results According to the literature, the sensitivity of MT-sDNA for detecting CRC was 87.0%-100%, 32.7%-82.0% for advanced adenomas, and the specificity was 86.1%-95.2%. The sensitivity of individual biomarkers of fecal microRNAs for detecting CRC was 34.2%-88.2%, 73.0% for advanced adenomas, and the specificity was 68%-100%. The sensitivity of fecal protein markers for detecting CRC was 63.6-93.0%, 47.7%-69.4% for advanced adenomas, and the specificity was 38.3%-97.5%. The sensitivity of fecal microbiota for detecting CRC was 54.0-100.0%, 32.0%-48.3% for advanced adenomas, and the specificity was 61.3%-90.0%. Conclusion MT-sDNA is the most sensitive CRC screening test, and its sensitivity is the highest for advanced adenomas; however, its detection cost is high. MT-sDNA was more sensitive to CRC and advanced precancerous lesions than FIT, but compared to three years of MT-sDNA, annual FIT as the first non-invasive screening test for CRC seemed to be more effective.

There is mounting evidence that Black patients develop more advanced liver cancers with less advanced liver disease. These findings have important implications for the future of liver cancer screening.

OBJECTIVES This study aimed to evaluate the most updated worldwide distribution, risk factors, and temporal trends of cervical cancer for different countries and age groups. METHODS The Global Cancer Observatory database was retrieved for the age-standardized rates (ASRs, per 100,000 persons) for incidence and mortality of cervical cancer in 2018. The associations with risk factors were examined by multivariable regression analysis, adjusting for human development index (HDI) and gross domestic products (GDP) per capita. Joinpoint regression analysis was used to calculate the 10-year annual average percent change (AAPC) for incidence and mortality. RESULTS A total of 568,847 new cases (ASR, 13.1) and 311,365 deaths (ASR, 6.9) of cervical cancer were reported globally in 2018. The highest incidence and mortality were observed in Southern Africa (ASRs, 43.1 and 20.0) and countries with low HDI (ASRs, 29.8 and 23.0). Countries with higher incidence and mortality had lower HDI (β = -8.19, 95% CI -11.32 to -5.06, p

Objective Our objective is to develop a site-specific proteomic-based screening test for ovarian cancer(OC) using the mucus of the cervix and vagina and evaluate a potential means for home testing. Methods Cervicovaginal fluid samples were obtained from ovarian cancer and normal control patients for LC-mass spectrometry(MS) proteomic evaluation. Statistical modeling determined the protein panel with the highest penetrance across ovarian cancer samples. A subcohort of patients consented to provide self-collected vaginal samples at home with questionnaire on feasibility. Cohen's kappa methodology was utilized to determine agreement between physician-collected and patient-collected samples. Results A total of 83 consecutive patient samples were collected prospectively (33 ovarian cancer & 50 controls). Thirty patients consented for self-collection. Using LC-MS, 30 peptides demonstrated independent statistical significance for detecting ovarian cancer. Using statistical modeling, the protein panel that determined the best predictor for detecting OC formed a “fingerprint” consisting of 5 proteins: s erine proteinase inhibitor A1; periplakin; profilin1; apolipoprotein A1; and thymosin beta4-like protein. These peptides demonstrated a significant increase probability of detecting ovarian cancer with the ROC curve having an AUC of 0.86 (p = 0.00001). Physician-collected and patient-collected specimens demonstrated moderate agreement with kappa average of 0.6 with upper bound of 0.75. Conclusions Using novel site-specific collection methods, we identified an OC “fingerprint” with adequate sensitivity and specificity to warrant further evaluation in a larger cohort. Agreement of physician-collected and patient-collected samples were encouraging and could improve access to screening with a home self-collection if this screening test is validated in future studies.

Introduction Comprehensive geriatric assessment (CGA) has been shown to reduce frailty in older patients in general. In older patients with cancer, frailty affects quality of life (QoL), physical function, and survival. However, few studies have examined the effect of CGA as an additional intervention to antineoplastic treatment. This protocol presents a randomized controlled trial, which aims to evaluate the effects of CGA-based interventions in older patients with cancer and Geriatric 8 (G8) identified frailty. Materials and Methods This randomized controlled trial will include patients, age 70+ years, with solid malignancies and G8 frailty (G8 ≤ 14). Patients will be separated into two groups, with different primary endpoints, depending on palliative or curative antineoplastic treatment initiation, and subsequently randomized 1:1 to either CGA with corresponding interventions or standard of care, along with standardized antineoplastic treatment. A geriatrician led CGA with corresponding interventions and clinical follow-up will be conducted within one month of antineoplastic treatment initiation. The interdisciplinary CGA will cover multiple geriatric domains and employ a standard set of validated assessment tools. Primary endpoints will be physical decline measured with the 30-s Chair-Stand-Test at three months (palliative setting) and unplanned hospital admissions at six months (curative setting). Additional outcomes include QoL, treatment toxicity and adherence, occurrence of polypharmacy, potential drug interactions, potential inappropriate medications, and survival. The primary outcomes will be analyzed using a mixed model regression analysis (30-s chair stand test) and linear regression models (unplanned hospitalizations), with an intention to treat approach. Power calculations reveal the need to enroll 134 (palliative) and 188 (curative) patients. Discussion The present study will examine whether CGA, as an additional intervention to antineoplastic treatment, can improve endpoints valued by older patients with cancer. Inclusion began November 2020 and is ongoing, with 37 and 29 patients recruited April 15th, 2021. Registration: NCT04686851

The study aimed to compare the performance of human papillomavirus (HPV)-based strategies to cytology for detecting cervical intraepithelial neoplasia grade 3 or worse (CIN3+) in routine program in China. The study included 50,434 women ages 30–64 years from January 2015 to December 2019, to assess four strategies: cytology with HPV triage (strategy 1), primary HPV testing with reflex cytology (strategy 2), primary HPV testing with HPV-16/18 genotyping and reflex cytology for non-16–18 high-risk HPV genotypes (strategy 3), and co-testing (strategy 4). The main outcomes were sensitivity for CIN3+ and colposcopy referral rate. Overall, the rates of HPV positivity and cytologic abnormality were 7.0% [95% confidential interval (CI), 6.8–7.2] and 3.5% (95% CI, 3.3–3.6], respectively. The sensitivity for CIN3+ were 88.5% for strategy 4, 83.2% for strategy 3, 64.6% for strategy 1, and 60.1% for strategy 2. The relative sensitivity of strategy 4 and strategy 3 compared with strategy 1 for detecting CIN3+ were 1.38 (95% CI, 1.24–1.54) and 1.29 (95% CI, 1.14–1.46), respectively. The colposcopy referral rates of strategies 4 and 3 were significantly higher than that of strategy 1 (2.4% and 2.2% vs. 1.4%, P < 0.001). In conclusion, co-testing and primary HPV testing with HPV-16/18 genotyping and reflex cytology improved the sensitivity for CIN3+ compared with cytology but increased the colposcopy referral rate. Long-term negative predicted value for HPV-negative women should be studied to determine the screening interval. Our study provides further evidence to the introduction of HPV-based strategies in China. Prevention Relevance: Both co-testing and primary HPV testing with HPV-16/18 genotyping and reflex cytology triage provided higher sensitivity for detecting CIN3+; however, the number of colposcopy referrals also increased compared with cytology in a routine program. It has great public health implications for the introduction of HPV-based screening strategies in China.

Aims: To review the patterns of early-onset (