Current Screening Guidelines Research Articles

Abstract LB219: Methods to improve representation of racial and ethnic minorities in lung cancer screening programs: A systematic review

Abstract Background: Most lung cancer screening trials to date and current screening guidelines overlook vulnerable populations with disproportionate lung cancer burden such as racial and ethnic minorities. Given the barriers, perceptions, and socioeconomic burden of these underserved populations, uptake of lung cancer screening has minimal. To develop and implement better methods of recruitment underserved populations, concerted efforts to understand the barriers and perceptions of these population are needed. Objective: Conduct a systematic review of methods for recruitment of racial and ethnic minorities into lung cancer screening trials or programs. Methods: We searched for studies that reported methods of recruitment and racial and ethnic minorities into lung cancer screening from 2010 to June 2020, using Ovid MEDLINE and Embase databases. Full-text screening and data extraction were completed independently by two reviewers and adjudication was performed by a third, independent reviewer. We compared referral rates of the recruitment modalities by racial/ethnic subgroups and by sex. Results: We identified 525 studies of which 25 were included in the systematic review corresponding to 291,329 patients. The most frequent methods of recruitment were referral, physical mail, community-based strategies, targeted strategies, phone, advertisement, and social media. Referral (n=7; 2,510 patients) was the most effective method of recruitment with response rates ranging from 31% to 97%. Direct mail (n=8 studies; 189,799 patients) was the second most extensively used recruitment method with response rates of 28% to 79%. Direct mail to Hispanic patients (2,995 total) for lung cancer screening programs was more effective than other methods of recruitment. Direct mail was more effective in recruiting African American patients (8,331 total) compared to referral (1,083 total). Conclusion: This review identified recruitment modalities that were more successful and less unsuccessful in recruiting racial and ethnic minorities into lung cancer screening trials and programs. This work highlights priorities and next steps required to improve recruitment of racial and ethnic minorities in lung cancer screening. There is a need to develop culturally relevant lung cancer screening interventions for Hispanics/Latino patients and to create targeted intervention for African American patients. Citation Format: Tiffany J. Gilliard, Jaileene Perez-Morales, Matthew Schabath, Mary Katherine Haver. Methods to improve representation of racial and ethnic minorities in lung cancer screening programs: A systematic review [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB219.

A Good Way to Reduce Screening for Retinopathy of Prematurity: Development of the ROP Model in a China Preterm Population.

Importance: Retinopathy of prematurity (ROP) is a preventable cause of blindness in children. Without treatment, more than 45% of eyes may suffer permanent vision loss. Current ROP screening guidelines, which include a range of birth weights (BWs) and gestational ages (GAs), may require screening many low-risk preemies who might develop severe ROP.Method: All high-risk infants in the neonatal intensive care unit (NICU) of the First Affiliated Hospital of Zhengzhou University from 2017 to 2021 were included in this retrospective cohort study. Each of the 27 candidate risk factors was evaluated in univariate analysis and adjusted for known risk factors (i.e., GA and BW). The significant results were analyzed in a backward selection multivariate logistic regression model. Receiver operating characteristic (ROC) curves and a nomogram were drawn.Results: The study included 2,040 infants who underwent ROP screening. The weight gain rate [OR, 2.65; 95% confidence interval (CI), 1.49–1.21 ≤ 12 g/d vs. > 18 g/d; P = 0.001], blood transfusion (OR, 2.03; 95% CI, 1.14–3.64; P = 0.017), invasive mechanical ventilation (OR, 1.74; 95% CI, 1.15–2.66; P = 0.009) and N-terminal segment of pro-B-type natriuretic peptide (NT-proBNP) ≥ 25,000 ng/L (OR, 1.51; 95% CI, 1.00–2.28; P = 0.048) were four new statistically independent risk factors in addition to GA and BW. The area under the curve (AUC) of the final multivariate model was 0.90 (95% CI, 0.88–0.92; P < 0.001).Conclusions and Relevance: These findings add to our understanding of ROP screening because they include all eligible infants rather than only high-risk infants, as in previous studies. Under the control of BW and GA, low weight gain rate, increased number of blood transfusion, invasive mechanical ventilation and NT-proBNP ≥ 25,000 ng/L were “new” statistically independent risk factors for ROP. The ROP risk can be calculated manually or represented by a nomogram for clinical use.

Young breast cancer and the influence of ethnicity in Sandakan: A 3-year retrospective cross-sectional study.

Breast cancer (BC) is the most common cancer in Malaysia, with incidence increasing with age. There have been demonstrated differences in age of presentation and tumour biology when comparing ethnicities. Twenty percent of Caucasian women present before 50 years old, but almost 50% of Southeast Asian (SEA) women present before 50. However, BC in Indigenous sub-groups has not yet been studied. Sandakan is a city in Sabah with a large Indigenous population. Current nationwide screening guidelines are based on the U.S. Preventive Task Force 2009 Guidelines, which may not represent our population. We aim to examine the age of incidence for our local population, for local screening recommendations. Retrospective cross-sectional study, including all consecutive cases of epithelial invasive tumours, from January 2016 to December 2018. Other histological types were excluded. Univariate and multivariate analyses were performed. A total of 115 breast tumours were identified. Ten tumours were excluded (five ductal carcinoma in situ, four phyllodes, and one sarcoma), leaving a study population of 105 patients. Median age of presentation was 53 years (min 30; max 97). A total of 41.9% presented before the age of 50. Patients of Indigenous ethnic origins were 11years younger at presentation than non-Indigenous women. Tumour grade was more likely to be higher among Indigenous women. Median age of presentation of BC in Sandakan matches regional data; however, patients of Indigenous ethnic groups present even earlier. Screening guidelines should consider the growing evidence of young BC in SEA.

Improving prostate biopsy decision making in Mexican patients: Still a major public health concern

BackgroundProstate cancer screening has reduced its mortality in 21%. However, this has also led to an increased number of biopsies in order to establish the diagnosis, many of them unnecessary. Current screening guidelines prioritize use of prostatic magnetic resonance and new biomarkers to reduce unnecessary biopsies, however, their implementation in developing countries screening programs is mainly limited by its costs. ObjectiveWe aimed to evaluate Prostate Biopsy Risk Collaborative Group (PBCG) and Prostate Cancer Prevention Trial Risk Calculator (PCPTRC) 2.0 predictions accuracy in Mexican patients in order to guide prostate biopsy decision making and reduce unnecessary biopsies. Materials and methodsWe retrospectively analyzed patients between 55 and 90 years old who underwent prostate biopsy in a high-volume center in Mexico between January 2017 and June 2020. Clinical utility of PBCG and PCPTRC 2.0 to predict high-grade prostate cancer (HGPCa) biopsy outcomes was evaluated using decision curve analysis and compared to actual biopsy decision making. Receiver operating characteristics area under the curve (AUC) was used to measure discrimination and external validation. ResultsFrom 687 patients eligible for prostate biopsy, 433 met selections criteria. One hundred and thirty-five (31.17%) patients were diagnosed with HGPCa, 63 (14.54%) with low-grade disease and 235 (54.27%) had a negative biopsy. PCPTRC 2.0 ≥15% threshold got a standardized net benefit (sNB) of 0.70, while PBCG ≥30% and ≥35% had a sNB of 0.27 and 0.15, respectively. Use of both models for guiding prostate biopsy decision resulted in no statistical difference for HGCPa detection rates, while achieved a significant difference in reducing total and unnecessary biopsies. However, this difference was lower (better) for PCPTRC 2.0, being statistically significative when compared against PBCG thresholds. Both models were well calibrated (AUC 0.79) and achieved external validation compared with international cohorts. ConclusionsOur study is the first to effectively validate both PCPTRC 2.0 and PBCG predictions for the Mexican population, proving that their use in daily practice improves biopsy decision making by accurately predicting HGPCa and limit unnecessary biopsies without representing additional costs to screening programs.

Global guidelines for cervical cancer screening: a systematic review

Objective: To systematically summarize and evaluate the current cervical cancer screening guidelines worldwide. Methods: "Cervical cancer/cervical intraepithelial neoplasia", "screening", and "guidelines/recommendations" were searched as keywords in PubMed, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Data for cervical cancer screening guidelines. The language was limited to Chinese and English. A total of 29 guidelines were included before September 1, 2020. The basic information and recommendations of the guidelines issued were summarized. Results: Among the 29 cervical cancer screening guidelines, most guidelines targeted on the population aged 25-65 years. Cytology and human papillomavirus (HPV) testing are two commonly used methods for the cervical cancer screening, and HPV testing is increasingly recommended as the primary screening methods. Most guidelines recommended five years interval for the HPV testing-based screening or co-testing (HPV testing and cytology) based screening and three years for the cytology-based. For managing population with abnormal cervical cancer screening, triage or screening repeatedly to identify high-risk populations were more recommended. Direct colposcopy or treatment were allowed for women with higher risk of cervical intraepithelial neoplasia (CIN) during the screening procedure. Several guidelines involving HPV vaccination population recommended them the same strategy as the general population without vaccination. Conclusion: Currently, most of the cervical cancer screening guidelines applied to the population with the average risk of the CINs and were issued by the developed countries. Primary methods for the cervical cancer screening have gradually changed from the cytology to the HPV testing. There is a lack of recommendations targeting special population on cervical cancer screening in the current guidelines.

Impact of Pan-Ethnic Expanded Carrier Screening in Improving Population Health Outcomes: Proceedings from a Multi-Stakeholder Virtual Roundtable Summit, June 25, 2020.

Impact of Pan-Ethnic Expanded Carrier Screening in Improving Population Health Outcomes: Proceedings from a Multi-Stakeholder Virtual Roundtable Summit, June 25, 2020.

State of the Science: Screening, Surveillance, and Epidemiology of HPV-Related Malignancies.

Oropharyngeal, cervical, vulvar, and anal cancers share a common risk factor of HPV infection. HPV vaccination is currently recommended at age 11 or 12 to prevent new HPV infections for all genders with catch-up vaccination recommened up to age 26. Despite the known effectiveness of HPV vaccination to prevent HPV-related cancer, there is continued low uptake in the United States; only 40% of eligible persons were vaccinated in 2018, though rates are 70% among teenagers. Current American Cancer Society cancer screening guidelines recommend cervical cancer screening, but do not have specific recommendations for screening for other HPV-related cancers. Oropharyngeal cancer precursors have yet to be identified, and there are currently no routine screening tests for oropharyngeal cancer recommended by the U.S. Preventive Services Task Force. The U.S. Preventive Services Task Force and American Cancer Society recommend cervical cancer screening for women at average risk up to age 65, and screening guidelines do not currently differ by HPV vaccination status. Primary HPV DNA testing was first approved for cervical cancer screening in 2016 and was shown to be superior for cervical cancer prevention. Vulvar and anal cancer precursors have been identified, but optimal screening remains unclear. Examination of the anal canal and perianus is best performed by trained clinicians using high-resolution anoscopy, and effectiveness of using high-resolution anoscopy to detect and treat anal high-grade squamous intraepithelial lesions to prevent cancer is actively being researched. Current multistep approaches to control HPV-related malignancies include HPV vaccination coupled with cervical cancer screening or surveillance for oropharyngeal, vulvar, and anal cancers.

Human SHC-transforming protein 1 and its isoforms p66shc: A novel marker for prediabetes.

AimsPrediabetes is a multifactorial condition. Current guidelines for diabetes screening recommend either the use of glycated hemoglobin (HbA1c), or blood glucose level (BGL). This research aimed to identify if p66shc a component of the Human SHC‐Transforming Protein 1 (Shc1), a mitochondrial associated oxidative stress biomarker, is significantly altered in patients with elevated BGL. Furthermore, we evaluated if inflammatory and oxidative stress markers, such as p66shc, are a useful addition to the regularly used biomarkers to increase sensitivity for identification of prediabetes.MethodsAll participants attended the Diabetic Health Screening at Charles Sturt University (CSU), Australia. The cross‐sectional clinical study collected demographic and clinical variables from 346 participants and classified into control or prediabetes based on fasting BGL. Blood and urine samples were analyzed for oxidative stress and inflammation markers. Logistic regression was used to compare multidimensional diagnostic models for prediabetes, including p66shc/Shc1, to the current HbA1c‐only model in terms of sensitivity, specificity and predictive accuracy. Significance was set at P ≤ 0.05.ResultsA significant decrease of p66shc/Shc1 was determined in prediabetes compared to controls (P ≤ 0.05). HbA1c testing resulted in an accuracy of 62%, while adding p66shc and triglycerides increased predictive accuracy to 88.05%. When HbA1c was omitted and Shc1 was combined with 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG) and monocyte chemo‐attractant protein‐1 (MCP‐1), a predictive accuracy of 89.5% was achieved.ConclusionOur findings showed a major improvement of sensitivity to identify prediabetes by including oxidative stress and inflammatory biomarkers underlining beneficial diagnostic information, which most likely improves prevention and early treatment options in prediabetes.

Do the 2013 United States Preventive Services Task Force guidelines for lung cancer screening fail high-risk African American smokers? An institutional retrospective observational cohort study.

Lung cancer cause nearly 1.76 million deaths worldwide in 2018. In 2011, the National-Lung-Cancer-Screening-Trial showed 20% relative risk reduction with LDCT and subsequently led to the current USPSTF screening guidelines. However, the predominant focus on elderly, Caucasian questions its generalizability to communities with young, African Americans such as our institution. Hence, the objective of our study is to investigate the need to modify the current screening guidelines at our institution by assessing the applicability of newer individual risk-based prediction models for LDCT screening. This is a retrospective observational cohort study of newly diagnosed lung cancer patients at LSU Health Sciences Center Shreveport from 2011 to 2015. One-third of the patients did not meet the current USPSTF screening guidelines. We categorized them into high-risk (groups1 and 2), moderate-risk, and low-risk according to 2018 NCCN Lung Cancer Screening Guidelines Version 1.2020. The high-risk groups were differentiated using the Tammemagi lung cancer risk calculator. Among those who did not meet the screening guidelines, nearly 50% were African American, 95% with known smoking history, and 80% diagnosed at advanced stage at the time of diagnosis. After employing the Tammemagi Risk based calculator, 12.5% were categorized into high-risk group 2, who are also eligible for annual LDCT. The current USPSTF guidelines have failed in our population consisting of young African American smokers, questioning the health disparity in medicine. By employing individual risk-based prediction models, we could potentially identify tailored high-risk populations leading to appropriate use of LDCT screening.

Cervical cancer screening among sexual minority women: findings from a national survey.

Sexual minority women (SMW; lesbian, bisexual, and other women who have sex with women) are at risk for cervical cancer but less likely than non-SMW to receive regular cervical cancer screening (Pap- and/or HPV-testing). We examined factors contributing to receipt of guideline-based cervical cancer screening among SMW. During October 2019, we conducted an online survey of self-identified SMW aged 21-45years living in the United States (n = 435). We estimated risk differences (RD) in women's likelihood of being within current cervical cancer screening guidelines by sociodemographic and health-related characteristics. Overall, 75% of respondents were within current screening guidelines. Adjusting for other factors, SMW were more likely to be within guidelines if they were insured (aRD 0.26, 95% CI 0.13, 0.39), had a partner (aRD 0.18, 95% CI 0.09, 0.28), and were older (aRD 0.12, 95% CI 0.04, 0.20). Overall, the most common reasons for not being screened recently were lack of insurance/cost (42%) and perceiving it was unnecessary (28%). Many SMW are not being screened for cervical cancer according to guidelines. Findings can inform efforts to improve screening among this population.

Diabetic Ketoacidosis With Alpelisib

Background: Hyperglycemia is a frequently reported adverse effect of alpelisib, an isoform specific phosphoinositide 3 kinase inhibitor, which is recently approved for use in hormone receptor positive advanced or metastatic breast cancer. Though two patients in clinical trials with alpelisib developed diabetic ketoacidosis (DKA), there have been no case reports to date characterizing this complication after drug approval. We present the first case of DKA in patients on alpelisib therapy.Clinical Case: A 55-year-old woman with a history of hormone-receptor positive metastatic breast cancer was started on treatment with fulvestrant and alpelisib. The patient did not have any previous history of diabetes nor gestational diabetes, though she had evidence of prediabetes prior to starting treatment. Patient was non-obese and had a family history of type 2 diabetes. Baseline hemoglobin A1c was 5.6% (n <5.7%) with impaired fasting glucose of 108 mg/dl (n<105 mg/dL) immediately prior to starting therapy. One week after starting alpelisib, she presented to the emergency center in diabetic ketoacidosis. Initial laboratory evaluation showed serum glucose 690 mg/dl, anion gap metabolic acidosis, with undetectable serum bicarbonate and ketonuria. C-peptide on hospital day 1 was found to be 2.8 ng/ml (n 0.5 - 3.4 ng/ml) with a concurrent glucose of 479 mg/dl. GAD65 and Islet Antigen 2 antibodies were negative. Diabetic ketoacidosis quickly resolved with continuous insulin infusion and stopping alpelisib. The patient was able to come off all insulin therapy prior to discharge and was discharged on metformin with adequate glycemic control.Conclusions: Current manufacturer guidelines for alpelisib recommend screening for diabetes mellitus at baseline and monitoring blood glucose and/or fasting plasma glucose weekly for the first two weeks of treatment and monthly thereafter. However, patients with no pre-existing history of diabetes mellitus may be at risk for life-threatening hyperglycemic crises which may develop within a week of initiation of alpelisib and more frequent monitoring may be indicated. The hyperglycemic effect of alpelisib appears to be reversible upon stopping the drug.

Frequency of high-grade squamous cervical lesions among women over age 65 years living with HIV

Current US cervical cancer screening guidelines recommend screening cessation at the age of 65 years provided women have adequate previous screening and no history of precancer. Women living with HIV are at higher risk of cervical cancer than women living without HIV. Furthermore, limited data exists to quantify the risk of cervical cancer among women who otherwise would qualify for screening cessation. This study aimed to determine whether guidelines recommending women to discontinue cervical cancer screening at the age of 65 years are appropriate for women living with HIV. Semiannual Papanicolaou testing was performed as part of surveillance visits in the Women's Interagency HIV Study. Launched in October 1994, the Women's Interagency HIV Study is a federally funded US multisite cohort study that has enrolled 3678 women living with HIV and 1304 women living without HIV; we included data throughout September 2019 onward. Conventional Papanicolaou tests were collected at scheduled 6-month visits and read centrally according to the 1991 Bethesda System criteria. Results were analyzed among women at least 65 years of age. The primary endpoint was high-grade cytology, including high-grade squamous intraepithelial lesions; atypical glandular cells; atypical squamous cells, cannot exclude high-grade lesions; and malignant cytology. Wilcoxon rank-sum tests were used to compare the continuous variables, and Chi-square tests or the Fisher exact tests were used to compare the categorical variables. The Kaplan-Meier method was used to calculate the cumulative incidence. Poisson regression was used to compare 2 incidence rates. Of 169 eligible women (121 women living with HIV and 48 women living without HIV) who contributed 678.4 person-years of observation after reaching the age of 65 years, 2.2% had high-grade cytologic abnormalities. However, no cancer was found. Furthermore, 20 women had previous precancer results, and 74 women had abnormal Papanicolaou test results in the previous decade. Among 50 women (38 women living with HIV and 12 women living without HIV) with a previous hysterectomy and no history of cervical precancer, the cumulative incidence rates of high-grade squamous intraepithelial lesions were 0.6 (95% confidence interval, 0.0-3.2) per 100 person-years for women living with HIV and 0.0 (95% confidence interval, 0.0-8.1) per 100 person-years for women living without HIV (P=.61). Only 48 women (27 women living with HIV and 21 women living without HIV) had cervices and met the current guidelines to discontinue screening; their risk of experiencing high-grade squamous intraepithelial lesions was 2.2 (95% confidence interval, 0.6-5.5) per 100 person-years overall and did not vary by HIV status (2.3 [95% confidence interval, 0.5-6.8] per 100 person-years for women living with HIV and 1.8 [95% confidence interval, 0.0-9.8] per 100 person-years for women living without HIV; P=.81). Most women living with HIV do not meet the criteria for cervical cancer screening cessation and will need to continue screening over the age of 65 years; however, women who meet the criteria for screening cessation have risks of high-grade squamous lesions similar to women living without HIV and may choose to discontinue.

Screening of Newborns and Infants for Developmental Dysplasia of the Hip: A Systematic Review.

Developmental dysplasia of hip (DDH) is a common disorder of childhood and has a good prognosis when treated at an early age. In spite of being a significant concern, many children with DDH are not picked early and present late at walking age. In our country, it is presumed to be due to absence of a national policy for screening of DDH. Screening programmes including the combination of clinical and radiological methods in different ways have been suggested. However, the exact method of screening is controversial. To analyze effectiveness and cost-effectiveness of various screening methods for DDH. Systematic review. This review was conducted in accordance with PRISMA guidelines. Medline database was explored for original case series and randomized clinical trials. Inclusion criteria were English language, screening for DDH in neonates, sample size more than 500, and studies with minimum duration of one year. Thirty-four studies were selected to write the manuscript. This included 23 studies looking for effectiveness of a screening programme and 11 studies comparing various outcomes of different screening strategies. A trend favoring universal ultrasound screening was observed. The literature supports universal ultrasound screening and has proved its cost-effectiveness. However, considering the logistic and financial challenges in our country, immediate implementation of universal ultrasound screening seems impractical. In the absence of any current guidelines for screening for DDH in India, we suggest professional organizations involved in the care of children and public health policy-makers to come together to develop national screening guidelines for DDH.

Latent iron deficiency and iron deficiency anemia in pregnancy: effects on maternal and fetal health, possible ways to solve the problem

Iron deficiency with or without anemia in pregnant women is quite common today. In fact, anemia affects nearly 30% of women of reproductive age, and its prevalence among pregnant women is estimated to be 38% worldwide. Although iron deficiency (IR) is not the only cause of anemia, it is the most prevalent one. Anemia-reduction strategies among pregnant women are often ineffective, and severe anemia can greatly increase the risk of maternal mortality, as reported by WHO. Now therefore, the current guidelines for screening and treatment of ID-anemia (IDA) in pregnant women and new-borns require change. Severe anemia can greatly increase the risk of maternal death and adversely affect a developing fetus and new-born. In this review, we analyse the available data on the epidemiology and the effects of iron deficiency on mothers and infants, current treatment strategies and screening recommendations, as well as examine the treatment of IDA in pregnant women and newborns and the problem of poor compliance in patients with latent iron deficiency. A continuous long-term course of administration of oral iron supplements is one of the components of success in the treatment of IDA, and particularly latent forms of iron deficiency in pregnant women. It is often the case that poor patients’ compliance with therapy leads to poor treatment outcomes and misleading conclusions about the ineffectiveness of oral iron dosage forms in the battle against IDA. The data we have analysed suggest the possibility of increasing compliance with IDA treatment in pregnant women.

Disparities in Meeting USPSTF Breast, Cervical, and Colorectal Cancer Screening Guidelines Among Women in the United States.

IntroductionMany sociodemographic factors affect women’s ability to meet cancer screening guidelines. Our objective was to examine which sociodemographic characteristics were associated with women meeting US Preventive Services Task Force (USPSTF) guidelines for breast, cervical, and colorectal cancer screening.MethodsWe used 2018 Behavioral Risk Factor Surveillance System data to examine the association between sociodemographic variables, such as race/ethnicity, rurality, education, and insurance status, and self-reported cancer screening for breast, cervical, and colorectal cancer. We used multivariable log-binomial regression models to estimate adjusted prevalence ratios and 95% CIs.ResultsOverall, the proportion of women meeting USPSTF guidelines for breast, cervical, and colorectal cancer screening was more than 70%. The prevalence of meeting screening guidelines was 6% to 10% greater among non-Hispanic Black women than among non-Hispanic White women across all 3 types of cancer screening. Women who lacked health insurance had a 26% to 39% lower screening prevalence across screening types than women with health insurance. Compared with women with $50,000 or more in annual household income, women with less than $50,000 in annual household income had a 3% to 8% lower screening prevalence across all 3 screening types. For colorectal cancer, the prevalence of screening was 7% less among women who lived in rural counties than among women in metropolitan counties.ConclusionMany women still do not meet current USPSTF guidelines for breast, cervical, and colorectal cancer screening. Screening disparities are persistent among socioeconomically disadvantaged groups, especially women with low incomes and without health insurance. To increase the prevalence of cancer screening and reduce disparities, interventions must focus on reducing economic barriers and improving access to care.

A Prospective Pilot Study of Lung Cancer Screening in Patients at High Risk for Lung Cancer Who do not Meet Current Screening Guidelines

Abstract Purpose: To describe the results of a lung cancer screening (LCS) study of high-risk individuals ineligible for screening by Medicare (CMS) guidelines and prospectively selected by 6-year risk score. Methods: Study inclusion criteria included individuals 40–82 years old, with a 6-yr risk score of ≥1.5% for &amp;lt;77 years or age or &amp;gt;4% for 78–82 years of age, calculated by the PLCOm2012 model, no symptoms of lung cancer, and willingness to sign a consent form. Enrollment was offered to eligible individuals referred for screening through the University of Colorado Hospital LCS program that did not meet CMS screening guidelines (55–77 years old, ≥30 pack year smoking history, current smoker or quit within the past 15 years). Enrolled participants completed a shared design making visit with a LCS clinic provider, underwent a LDCT read in Lung-RADs (LR) by thoracic radiologists, and received follow-up and additional referrals, if indicated, from the LCS clinic. Individuals could undergo up to 3 LDCTs as part of the study. Results: The study completed 66 LDCTs on 48 participants. Screened individuals were 52% male, 85% white, 52% former smokers, had a mean baseline age of 69(±9) years, and a mean 6-year risk score of 5.6%(±5.9%). LR results of the index LDCTs included 46% LRs 1, 44% LRs 2, 4% LRs 3, and 6% LRs 4. 35% of screened participants had a significant incidental finding; 59% were coronary calcifications. Reasons screened individuals were ineligible by CMS guidelines included: 12% &amp;lt;55 years, 21% &amp;gt;77 years, 27% &amp;lt;30 pack year smoking history, and 40% quit smoking &amp;gt;15 years prior. The study diagnosed two lung cancers, a stage 1A adenocarcinoma diagnosed in 74 yr old white female with a 3.3% 6-yr risk score and a carcinoid diagnosed in a 77 yr old white male with a risk score of 7.5%. Both individuals had quit smoking &amp;gt;15 years prior. Conclusions: Early stage lung cancers can be detected in asymptomatic individuals who are prospectively selected by risk calculators and fall outside current CMS guidelines. However, the two cancers were diagnosed in people that would not qualify for the proposed expanded US Preventive Service Task Force guidelines, lowering eligibility to 50 years of age and tobacco exposure to 20 pack years.

Colorectal Cancer in People with Cystic Fibrosis under the Age of 40: A Case Series

Introduction Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), a disease which affects primarily the respiratory and gastrointestinal (GI) tracts. The lifetime risk of colorectal cancer (CRC) in patients with CF is approximately 5-10 times that of the general population. In 2018, the CF Foundation CRC Screening Task Force recommended initiating CRC screening in adults with CF at age 40. Case Presentations In this case series, we present three cases of females with CF younger than age 40 diagnosed with CRC with variable presentations and stages. We discuss the data supporting current CRC screening guidelines in CF in an effort to raise awareness among clinicians regarding young-onset CRC in this population. Furthermore, we aim for this case series to help drive further investigation into the mechanisms underlying CF-related CRC and to open the door to changes in current screening practices. Conclusion People with CF are at substantially higher risk of development of CRC relative to the general population. While current CRC screening practices advocate for earlier screening in this population compared to average-risk patients, this case series highlights potential limitations to current screening guidelines.

Validation of multivariable lung cancer risk prediction models for the personalized assignment of optimal screening frequency: a retrospective analysis of data from the German Lung Cancer Screening Intervention Trial (LUSI).

BackgroundCurrent guidelines for lung cancer screening via low-dose computed tomography recommend annual screening for all candidates meeting basic eligibility criteria. However, lung cancer risk of eligible screening participants can vary widely, and further risk stratification could be used to individually optimize screening intervals in view of expected benefits, possible harms and financial costs. To this effect, models have been developed in the US National Lung Screening Trial based on self-reported lung cancer risk factors and imaging data. We evaluated these models using data from an independent screening trial in Germany.MethodsWe examined the Polynomial model by Schreuder et al., the Lung Cancer Risk Assessment Tool extended by CT characteristics (LCRAT + CT) by Robbins et al., and a criterion of presence vs. absence of pulmonary nodules ≥4 mm (Patz et al.), applied to sub-sets of screening participants according to eligibility criteria. Discrimination was evaluated via the receiver operating characteristic curve. Delayed diagnoses and false positive results were calculated at various thresholds of predicted risk. Model calibration was assessed by comparing mean predicted risk versus observed incidence.ResultsOne thousand five hundred and six participants were eligible for the validation of the LCRAT + CT model, and 1,889 for the validation of the Polynomial model and Patz criterion, yielding areas under the receiver operating characteristic curve of 0.73 (95% CI: 0.63, 0.82), 0.75 (0.67, 0.83), and 0.56 (0.53, 0.72) respectively. Skipping 50% annual screenings (participants within the 5 lowest risk deciles by LCRAT + CT in any round or by the Polynomial model; baseline screening round), would have avoided 75% (21.9%, 98.7%) and 40% (21.8%, 61.1%) false positive screen tests and delayed 10% (1.8%, 33.1%) or no (0%, 32.1%) diagnoses, respectively. Using the Patz criterion, referring 63.2% (61.0% to 65.4%) of participants to biennial screening would have avoided 4% (0.2% to 22.3%) of false positive screen tests but delayed 55% (24.6% to 81.9%) diagnoses.ConclusionsIn this German trial, the LCRAT + CT and Polynomial models showed useful discrimination of screening participants for one-year lung cancer risk following CT examination. Our results illustrate the remaining heterogeneity in risk within screening-eligible subjects and the trade-off between a low-frequency screening approach and delayed detection.

Incorporating both genetic and tobacco smoking data to identify high-risk smokers for lung cancer screening.

The US Preventive Services Task Force (USPSTF) recently proposed to widen the current lung cancer screening guideline to include less-heavy smokers. We sought to incorporate both genetic and tobacco smoking data to evaluate the proposed new guideline in white smokers. We constructed a polygenic risk score (PRS) using lung cancer risk variants. Using data from 308 490 participants of European descent in the UK Biobank, a population-based cohort study, we estimated hazard ratios of lung cancer associated with both tobacco smoking and PRS to identify individuals at a similar or higher risk than the group of heavy smokers who are recommended for screening under the USPSTF-2014 guideline (≥30 pack-years, either current or former smokers who quit within 15 years). During a median follow-up of 5.8 years, 1449 incident cases of lung cancer were identified. We found a similar lung cancer risk for current smokers with 20-29 pack-years [hazard ratio = 20.7, 95% confidence interval: 16.3-26.4] and the 'heavy smoker group' defined above (hazard ratio = 19.9, 95% confidence interval: 16.8-23.6) compared with never smokers. Current smokers with 20-29 pack-years did not reach a 6-year absolute risk of 0.0151, a suggested risk threshold for using low-dose computed tomography screening, until the age of 55 years. However, these smokers at high genetic risk (PRS ≥ 80%) reached this risk level at the age of 50. Our findings support the USPSTF proposal to lower the smoking pack-year eligibility to 20 pack-years for current smokers and suggest that PRS for lung cancer could be considered to identify high-risk smokers for screening.

Abstract PD10-05: Universal genetic testing in breast cancer patients: A multi-center prospective study

Abstract Background: Hereditary factors play a key role in the risk of developing breast cancers. Identification of a germline predisposition can have important implications for treatment decisions, risk-reducing interventions, cancer screening, and testing for family members. Aim: To determine the prevalence of pathogenic or likely pathogenic germline mutations (P/LP) using a “universal” testing approach and uptake of no-cost cascade family testing in patients with breast cancer. Methods: We undertook a prospective multi-site study of germline genetic alterations among breast cancer patients receiving care at Mayo Clinic cancer centers in Rochester, MN; Eau Claire, WI; Jacksonville, FL and Phoenix, AZ between April 1, 2018 and March 31, 2020. Patients with a new or active breast cancer diagnosis (all stages) irrespective of cancer family history were tested with a &amp;gt;80-gene next generation sequencing panel.Results: Of 390 patients, the median age was 58 years (SD 12.3), 1% were male, 85% were white and 28% had advanced (stage 3-4) disease. P/LP were found in 12.1% (n=47) of patients, including 29 in moderate and high penetrance cancer susceptibility genes. 13 (3.3%) patients had mutations in BRCA1 or 2, while 33 (8.4%) had mutations in BRCAness (ATM, BAP1, BARD1, BLM, BRCA1, BRCA2, BRIP1, CHEK2, NBN, PALB2, RAD50, RAD51C, RAD51D, WRN) associated genes. Of the P/LP findings the most frequent aberrations were in BRCA2 (13.5%), BRCA1 (11.5%), CHEK2 (11.5%), MUTYH (11.5%), and WRN (9.6%). Variants of uncertain significance were found in 209 (53.6%) including 26 (6.6%) with concurrent P/LP and VUS. 37 (9.4%) patients had mutations associated with published management recommendations, precision therapies and/or clinical trial eligibility. 10 (2.6%) patients had P/LP that would not have met current screening guidelines, including 4 with moderate or high penetrance mutations. Patients with younger age of diagnosis were less likely than patients with older age of diagnosis to have a P/LP mutation (OR= 0.47, 95%CI: 0.25-0.90 p = 0.020). Only 10 (21%) patients with P/LP had family members undergo familial site- specific testing at no cost.Conclusions: In this prospective multi-center study of unselected breast cancer patients, universal multi-gene panel testing found that 1 in 8 patients harbor P/LP germline variants. Current guidelines were able to identify the majority of patients with P/LP mutations. Familial site specific testing is greatly under-utilized even when cost is not a barrier. Multigene panels impact cancer patient care by identifying precision medicine treatment interventions, and guiding long-term medical management and preventive surveillance. Citation Format: Brenda Ernst, Natalie Ertz-Archambault, Deborah J Rhodes, Donald W Northfelt, Myra Wick, Douglas L Riegert-Johnson, Scott Okuno, Katie Kunze, Michael Golafshar, Cindy M Azevedo, PLS Uson Junior, ED Esplin, Robert Nussbaum, Margaret Klint, Sarah Mantia, Megan Hager, Keith Stewart, Niloy Jewel Samadder. Universal genetic testing in breast cancer patients: A multi-center prospective study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD10-05.