bluuebunny/crossref_metadata_2025_split huggingface dataset:
Projection of cancer incidence and death to 2040 in the US: Impact of cancer screening and a changing demographic.
Authors: Rahib Lola , Wehner Mackenzie , Matrisian Lynn McCormick , Nead Kevin Thomas 
Published: May 2020

1566 Background: Coping with the current and future burden of cancer requires an in-depth understanding of cancer incidence and death trends. As of 2020, breast, lung, prostate, and colorectal cancer are the most incident cancers, while lung, colorectal, pancreas, and breast cancer result in the most deaths. Here we integrate observed cancer statistics and trends with observed and estimated US demographic data to project cancer incidences and deaths to the year 2040. Methods: Demographic cancer-specific delay-adjusted incidence and death rates from the Surveillance, Epidemiology, and End Results Program (2014-2016) were combined with US Census Bureau population growth projections (2016) and average annual percentage changes in incidence (2011-2015) and death (2012-2016) rates to project cancer incidences and deaths through the year 2040. We examined the 10 most incident and deadly cancers as of 2020. We utilized Joinpoint analysis to examine changes in incidence and death rates over time relative to changes in screening guidelines. Results: We predict the most incident cancers in 2040 in the US will be breast (322,000 diagnoses in 2040) and lung (182,000 diagnoses in 2040) cancer. Continuing decades long observed incident rate trends we predict that melanoma (173,000 diagnoses in 2040) will become the 3rd most common cancer while prostate cancer (63,000 diagnoses in 2040) will become the 5th most common cancer after colorectal cancer (139,000 diagnoses in 2040). Lung cancer (61,000 deaths in 2040) is predicted to continue to be the leading cause of cancer related death, with pancreas (45,000 deaths in 2040) and liver & intrahepatic bile duct (38,000 deaths in 2040) cancer surpassing colorectal cancer (34,000 deaths in 2040) to become the second and third most common causes of cancer related death, respectively. Breast cancer deaths (29,000 in 2040) are predicted to continue to decrease and become the fifth most common cause of cancer death. Joinpoint analysis of incidence and death rates supports a significant past, present, and future impact of cancer screening programs on the number of cancer diagnoses and deaths, particularly for prostate, thyroid, melanoma incidences, and lung cancer deaths. Conclusions: We demonstrate marked changes in the predicted landscape of cancer incidence and deaths by 2040. Our analysis reveals an influence of cancer screening programs on the number of cancer diagnoses and deaths in future years. These projections are important to guide future research funding allocations, healthcare planning, and health policy efforts.
Is there a genomic fingerprint of Radon (Rn)-induced lung cancer (LC)? Comparison of genomic alterations in LC specimens from high and low Rn zones.
Authors: Khan Hina , Saiganesh Harish , Olszewski Adam J. , Baca Yasmine , Kastura Michaela , Vatkevich John , Patel Nimesh , Khurshid Humera , Birnbaum Ariel E. , Liu Stephen V. , Mamdani Hirva , Kim Chul , Vanderwalde Ari M. , Raez Luis E. , Socinski Mark A. , Lopes Gilberto , Pai Sachin Gopalkrishna , Nieva Jorge J. , Azzoli Christopher G. , Safran Howard 
Published: May 2020

1572 Background: Rn-222 is a radioactive gas found in rocks and soil. It emits alpha particles that cause dsDNA breaks and increase potential for carcinogenesis. Rn is the 2nd leading cause of LC in the US after smoking. EPA estimates >15,000 deaths/yr (9% of LC deaths) from Rn. We hypothesize that the impact of Rn exposure may be reflected in LC gene mutation (mut) profiles. Methods: Using commercial NGS assays, we retrospectively analyzed genomic DNA alterations in FFPE specimens from 159 LC patients (pts) from the Lifespan Cancer Institute in Rhode Island (2014- 2019), followed by validation in a larger cohort of 5,532 pts using Caris platform. Based on EPA Rn maps, we identified counties with high indoor Rn levels (>4 pci/L; HR), and compared gene mut patterns with those from low Rn zones (<4 pci/L; LR). Based on pt’s zip code of residence, we categorized them to HR and LR. In the validation cohort, p values adjusted for multiple comparison (q) of < .05 were considered significant. Results: In the pilot cohort, 35 pts (22%) were in HR and 124 (78%) in LR zones. Adenocarcinoma histology was most frequent (73%) and smoking prevalence was high (75%) in both groups. Most prevalent alterations were TP53, KRAS and CDKN2A muts. In the HR, we noted more frequent recurrent muts in 2 DNA repair genes (DDR): ATM (11 vs 1%, p= .00086) and CHEK2 (6 vs 0%, p= .047) when compared to LR group. When classified into major pathways implicated in lung carcinogenesis, higher frequency of mutations were seen in DDR in HR zones vs. LR (29 vs 13%, p= .038). In the validation cohort, 1,433 (26%) pts were in HR and 4099 (74%) in LR zones. Among the DDR genes, ATM muts in HR group tended to be more frequent (4.7 vs 3.4% in LR, p= .03) as well as PALB2 (0.9 vs 0.4%, p= .02) while no difference seen in CHEK2. Other genes with significantly higher prevalence in HR were TP53, SMARCA4 and NFE2L2 (q< .05); while KMT2D, KEAP1, CDKN2A, MET, NF2, DNMT3A, CCND1 and FAS show a trend (p< .05). EGFR muts were significantly more frequent in LR zones (8.4 vs 14.6%, q= .001). Similar to the pilot cohort, DDR pathway alterations trend to be higher in HR zones (14 vs 12%, p= .05). Using a high TMB cut-off >10, tumors from HR zones had significantly higher TMB when compared to LR zones (56 vs 48%, q= .0005). Conclusions: To our knowledge, this is the first attempt to elucidate the pathobiology of Rn induced LC using gene mut analyses. Our observations suggest that LC associated with higher Rn exposure may have disabled DNA repair pathways and higher TMB. Assuming uniform tobacco smoke exposure, higher Rn was not associated with EGFR mut.
Video vs. in-person genetic counseling for men considering germline prostate cancer testing: A patient-choice study.
Authors: Giri Veda N. , Bowler Nicholas , Hegarty Sarah , Gross Laura , Hyatt Colette , Kelly William Kevin , Gomella Leonard G. 
Published: May 2020

1577 Background: Germline testing (GT) for prostate cancer (PCA) is rapidly increasing with higher demand for genetic counseling (GC). Alternate GC strategies need to be studied to address pretest informed consent. Here we conducted a patient-choice study of pretest video-based genetic education (VBGE) or in-person GC (IPGC) and assessed men’s preference and patient-reported outcomes from the first cohort of the Evaluation and Management for Prostate Oncology, Wellness, and Risk (EMPOWER) study. Methods: Eligibility for EMPOWER includes any male with PCA or at-risk for PCA based on family history or African American race. Men may choose pretest IPGC or VBGE. All receive results by a genetic professional. Demographics and PCA features were collected at baseline. The following outcomes and scales were assessed: baseline anxiety (GAD-7 scale), change in cancer genetics knowledge from baseline (Giri 2019), decisional conflict for GT (O’Connor 1993), and satisfaction (DeMarco 2004). Understanding of personal GT results was assessed after disclosure (Giri 2019). Descriptive statistics summarized results with counts and percentages for categorical variables and mean and standard deviation for continuous variables. Data were compared with Fisher’s exact, Chi-squared, or Wilcoxon two-sample tests, as appropriate. Mean change in cancer genetics knowledge was compared with t-tests. Significance level was set a priori at 0.05. All analyses were performed with SAS 9.4 (Cary, NC). Results: At the time of this analysis, 94 men were enrolled. Characteristics of the cohort were: White (88.3%), bachelor’s degree (67%), PCA diagnosis (93%), mean age of consent 59 years (IPGC) and 61 years (VBGE), Gleason > = 8 (32%), and > = T3 (31%). The majority preferred VBGE (77%) vs. IPGC (23%). Men who opted for IPGC had lower educational levels ( < = high school/GED) (18% IPGC vs 7% VBGE) and reported higher baseline anxiety (45% IPGC vs. 24% VBGE). Cancer genetics knowledge improved significantly with IPGC vs. VBGE (+2.5 vs +0.8; p < 0.01). No differences were observed in decisional conflict, satisfaction, or understanding of personal GT results between IPGC vs. VBGE. Both groups had high rates of GT uptake (IPGC 91%, VBGE 93%). Pathogenic mutations were identified in 15% in IPGC group and 10.4% in VBGE group. Conclusions: A substantial proportion of men opted for VBGE, and results suggest that VBGE is comparable to IPGC for men considering PCA GT. IPGC may be more suitable for men with lower knowledge of cancer genetics and greater levels or anxiety. Further study is warranted.
Genetic testing and referral patterns of non-BRCA mutation carriers at increased or uncertain risk of ovarian cancer.
Authors: Lee Sarah S. , Baumann Katherine , Bhuptani Bhoomi , Turecamo Sarah , Smith Julia Anne , Pothuri Bhavana 
Published: May 2020

1585 Background: While the management of BRCA1/2 is clear, management of non-BRCA mutations with increased risk or uncertain risk of ovarian cancer (OC) is not well established. Previously, we reported that referral to a gynecologic oncologist (GO) resulted in a 30-fold increased uptake of risk reducing surgery (RRS). We aimed to identify trends in genetic testing (GT) and referral to a GO of patients (pts) with such mutations. Methods: In this retrospective cohort study at 3 satellite sites within 1 institution from 2014 to 2018, pts were identified by ICD-10 codes Z15.01, Z15.02, Z15.09, Z15.89, C50.919, Q99.8, and C54.1. Pts with mutations with increased risk of OC ( MLH1, MSH2/6, PMS2, EPCAM (LS genes) , RAD51C/D, BRIP1, STK11) and uncertain risk of OC ( PALB2, ATM, BARD1, NBN) were included; BRCA1/2 and variants of uncertain significance were excluded . Outcomes of interest were patterns of GT and referral to a GO. Chi square and logistic regression were used with p < 0.05. Results: Of 20,000 pts with above ICD-10 codes, 240 pts had genes of interest. Mutations in increased risk of OC included: LS genes, 131; BRIP1, 14; RAD51D, 8; RAD51C, 5; STK11, 1. Mutations associated with uncertain risk of OC were: ATM, 43; PALB2, 23; NBN, 10; BARD1, 5. Pts with known mutations prior establishing care at our institution (N = 69) were less likely to be referred to a GO (22% vs 78%, p = 0.015). Pts with LS genes were more likely to be referred to a GO (52% vs. 25%, p < 0.001), to be tested by a GC (52% vs 25%, p < 0.001), and to be tested for family history (FH) of known mutation (69% vs 30%, p < 0.001). Provider performing GT included: genetic counselor (GC), 66 (28%); medical oncologist, 44 (18%); general obstetrician-gynecologist, 44 (18%); breast surgeon, 6 (3%), and primary care provider, 5 (2%). Of 66 pts tested by a GC, 46 (70%) were referred to GO, vs 48/105 (45%) pts who underwent GT by non-GC (p = 0.001). Reasons for GT among pts were: FH of cancer, 113 (47%); personal history of cancer, 56 (23%); known FH of a mutation, 49 (20%); and unknown indication, 22 (9%). When controlling for age, parity, race, insurance, GT provider, and reasons for GT, mutations with increased risk of OC were associated with referral to a GO (OR 3.55, 95% CI 1.88-6.72), along with pts who were tested by a GC (OR 2.65, 95% CI 1.27-5.51). Conclusions: Only ~30% of pts underwent GT by a GC, which was associated with increased referral to a GO. LS genes are better known and were associated with higher uptake of GO referral. Education of OC risks of these newer mutations among providers performing GT may increase referral to a GO and uptake of RRS.
Prospective agnostic germline testing in pediatric cancer patients.
Authors: Fiala Elise , Kennedy Jennifer , Kemel Yelena , Mauguen Audrey , Mandelker Diana , Zehir Ahmet , Birsoy Ozge , Bouvier Nancy , Maio Anna , Latham Alicia , Carlo Maria Isabel , Cadoo Karen Anne , Stadler Zsofia Kinga , Robson Mark E. , Shukla Neerav Narendra , Roberts Stephen S. , Kung Andrew , Offit Kenneth , Walsh Michael Francis 
Published: May 2020

1589 Background: We report our large cohort of pediatric cancer patients undergoing prospective agnostic germline sequencing. Our dataset is a significant addition to the 1,573 children reported to date who have undergone agnostic germline sequencing in previous large sequencing studies, each with ascertainment bias. Methods: 676 patients with pediatric solid tumors underwent matched tumor-normal targeted DNA sequencing from July 2015 to February 2020. At least 76 genes associated with cancer predisposition were analyzed in the germline, and variants were classified per American College of Medical Genetics guidelines. Pathogenic and likely pathogenic (P/LP) variants were reported to patients/families, who were offered genetic counseling and cascade testing with screening recommendations and referral to a surveillance clinic as appropriate. Results: One or more P/LP variants were found in 17% (115/676) of individuals when including low, moderate and high penetrance mutations in recessive and dominant genes, or 12% (81/676) when including moderate and high penetrance mutations in dominant genes. P/LP variants were detected in 40% (21/53) of patients with retinoblastomas, 8% (13/161) with neuroblastomas/ganglioneuroblastomas, 13% (14/112) with brain/spinal tumors, 8% (20/245) with sarcomas, and 12% (13/105) with other solid tumors. The most frequent mutations were in RB1 (n = 28) and TP53 (n = 8) in patients with associated tumors. Of patients with moderate/high penetrance mutations, 30% (24/81) had unexpected tumor types, with potential therapeutic relevance in 58% (14/24) including BRCA1 n = 2, BRCA2 n = 3, RAD51D n = 1, ATM n = 1 MLH1 n = 1, MSH2 n = 1, MSH6 n = 1, PMS2 n = 3, and SUFU n = 1. Two patients received immunotherapy based on their germline finding. Conclusions: P/LP germline variants are frequently present in patients with pediatric cancer. We are contributing significantly to the cohort size of agnostic sequencing in pediatric cancers. Our experience is similar to other studies with a ~12% detection rate of moderate and high penetrance mutations. Moderate/high penetrance mutations were concordant with the patient’s cancer history in 70% of cases, higher than previously reported, likely due to an enrichment of retinoblastoma. While many mutations are identified in patients with associated tumor types, a large proportion of mutations are unexpected based on the patient’s history. Clinical actionability of these findings may include screening, risk reduction, family planning, and increasingly targeted therapies.
Barriers to prescribing targeted therapies for NSCLC patients with highly actionable gene variants in the VA National Precision Oncology Program.
Authors: Vashistha Vishal , Armstrong Jenna , Winski David , Price Meghan , Hintze Bradley J. , Poonnen Pradeep , Snowdon Jane , Jackson Gretchen Purcell , Weeraratne Dilhan , Brotman David , Spector Neil L. , Kelley Michael J. 
Published: May 2020

2005 Background: Next-Generation Sequencing (NGS) gene panels are often completed to guide therapeutic decisions for patients with advanced stage non-small cell lung cancer (NSCLC). Patients with highly-actionable gene variants may experience improved therapeutic treatments and reduced toxicities with use of targeted agents. Ensuring appropriate prescription of targeted therapies is therefore of high importance. We sought to identify barriers to targeted agent use within the Veterans Health Affairs’ (VHA) National Precision Oncology Program (NPOP). Methods: A retrospective evaluation examined the cohort of NSCLC patients who underwent NGS multi-gene panels through NPOP between July 2015 and February 2019. A level of evidence for drug actionability was assigned to each observed oncogenic gene variant using an artificial intelligence offering (IBM Watson for Genomics: WfG). WfG level 1 and 2A evidence was reviewed by NPOP staff to exclude gene variants that did not conform to NPOP level 1 and 2A definitions. Anti-neoplastic drug prescriptions and oncology provider notes were obtained for all included patients from the VHA Corporate Data Warehouse. Review of clinical notes of patients who did not receive targeted agents was performed to categorize the reason(s). Results: Of 1764 NSCLC patients who successfully underwent NGS gene panel testing, 156 (8.9%) received therapeutic level 1 (7.3%) or 2A (1.6%) options for targeted agents based on WfG evidence analysis. In total, 117 (6.6%) patients had NPOP level 1 and 2A gene variants, all within ALK, BRAF, EGFR, ERBB2, MET, and RET. Of these, 49 (41.2%) patients were not prescribed available targeted agents. The three most common reasons were: (1) treating provider did not comment on NGS results (30.7%), (2) patient did not carry a diagnosis of advanced stage disease (18.4%), and (3) patient had begun an alternative systemic therapy prior to completion of sequencing (16.3%). No patient was denied access to a level 1 or 2A targeted drug due to utilization-management review. Conclusions: A substantial minority of patients with advanced NSCLC bearing highly-actionable gene variants are not prescribed available targeted agents. Further provider- and pathologist-directed educational effort are needed, as well as implementation of health informatics systems to provide near real-time decision support for test ordering and interpretation.
Are ED visits in cancer patients preventable? Care patterns before an ED visit.
Authors: Hong Arthur , Fullington Hannah , Sadeghi Navid , Cox John V. , Hobbs Stephanie Clayton , Sweetenham John W. , Courtney D. Mark , Lee Simon Craddock , Halm Ethan 
Published: May 2020

2023 Background: Medicare’s Oncology Care Model alternative payment program participation requires 24-hr patient access to clinician phone advice. Many participating practices have established oncology urgent care clinics to reduce the frequent ED visits in the early phase after cancer diagnosis. However, little is known about patients’ use of pre-ED visit clinical advice via phone. We combined EHR data on phone/secure messaging encounters, outpatient visits, and regional ED visits, to assess how often patients visit the ED without prior clinical advice, and to compare ED visit severity between those with and without preceding clinical advice. Methods: We linked adults ages 18+ from Parkland Health and Hospital System (PHHS), the Dallas County public safety net system, and UT Southwestern (UTSW) NACR Gold-certified cancer registry (2012-2018), to their respective EHR, and identifiably linked patients to a regional health information exchange of ED and hospital encounters. Exchange data included hospital name, ED disposition, diagnoses, and ED Severity Of Illness. We tallied ED visits within 6 months (180 days) after cancer diagnosis and EHR clinical contacts for 24 hours prior to ED visit (telephone/secure messaging, outpatient visits). After descriptive statistics, we used mixed-effects multivariate logistic regression clustering at patient level to model ED disposition after a pre-ED clinical contact. Results: We matched 8,289 Parkland (54% female, 78% Medicaid/charity assistance) and 10,817 UTSW patients (50% female, 12% Medicaid), who generated 21,009 and 22,696 ED visits, respectively. Two-thirds of all ED visits occurred without preceding clinical contact (70.2% PHHS, 66.7% UTSW); large shares of ED visits were to 67 other regional hospitals (22.2% PHHS, 69.5% UTSW). Telephone encounters and outpatient visits to any specialty were the most common contact before ED visit (UTSW: 28.2 and 12.4%; PHHS: 8.7 and 16.1%), but while nearly all UTSW clinic visits were to oncology, only 30% of PHHS clinic visits were to oncology. Though ED visit severity was slightly higher for ED visits without preceding clinical contact (46% vs. 43% ≥Major severity, p < 0.01), patients were discharged home more often if clinical contact preceded ED visits (aOR of hospitalization 0.82, 95% CI: 0.74 – 0.90). Conclusions: Two-thirds of ED visits occurred without prior clinical contact, and though these no-contact ED visits had higher severity of illness, they were more often discharged home from the ED. Future work should identify patient-oriented options to optimize the use of clinical care and the ED.
Integrating breast cancer screening into a cervical cancer screening program in three rural districts in Rwanda.
Authors: Pace Lydia E. , Dusengimana Jean Marie Vianney , Balinda Jean Paul , Benewe Origene , Rugema Vestine , Shyirambere Cyprien , Bigirimana Jean Bosco , Huang Chuan-Chin , Mpunga Tharcisse , Keating Nancy Lynn , Shulman Lawrence N. , Uwinkindi Francois 
Published: May 2020

2025 Background: In low-income countries where mammography is not widely available, optimal strategies to facilitate earlier breast cancer detection are not known. We previously conducted a cluster randomized clinical trial of clinician trainings in Burera District in rural Rwanda to facilitate earlier diagnosis among symptomatic women; 1.3% of women evaluated at intervention health centers (HCs) were diagnosed with cancer. Early stage breast cancer incidence was higher in intervention areas. Subsequently, Rwanda Biomedical Centre, Rwanda’s national health implementation agency, adapted the program in 3 other districts, offering screening clinical breast exams (CBE) to all women aged 30-50 years receiving cervical cancer screening and any other woman requesting CBE. A navigator facilitated patient tracking. We sought to examine patient volume, service provision and cancer detection rate in the adapted program. Methods: We abstracted data from weekly HC reports, facility registries, and the referral hospital’s electronic medical record to determine numbers of patients seen, referrals made, biopsies, and cancer diagnoses from July 2018-December 2019. Results: CBE was performed at 17,239 visits in Rwamagana, Rubavu and Kirehe Districts (total population 1.34 million) over 18, 17 and 7 months of program implementation respectively. At 722 visits (4.2%), CBE was abnormal. 571 patients were referred to district hospitals (DH); their average age was 35 years. Of those referred, 388 (68.0%) were seen at DH; 32% were not. Of those seen, 142 (36.6%) were referred to a referral facility; 121 of those referred (85.2%) actually went to the referral facility. Eighty-eight were recommended to have biopsies, 83 (94.3%) had biopsies, and 29 (34.9% of those biopsied; 0.17% of HC visits) were diagnosed with breast cancer. Conclusions: Integrating CBE screening into organized cervical cancer screening in rural Rwandan HCs led to a large number of patients receiving CBE. As expected, patients were young and the cancer detection rate was much lower than in a trial focused on symptomatic women. Even with navigation efforts, loss-to-follow-up was high. Analyses of stage, outcomes, patient and provider experience and cost are planned to characterize CBE screening’s benefits and harms in Rwanda. However, these findings suggest building health system capacity to facilitate referrals and retain patients in care are needed prior to further screening scaleup. In the interim, early diagnosis programs targeting symptomatic women may be more efficient and feasible.