bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
Interest in cessation treatment and survival among smokers in a community-based multidisciplinary thoracic oncology program.
Authors: Meadows Meghan , Ward Kenneth Daniel , Faris Nicholas Ryan , Smeltzer Matthew , Fehnel Carrie , Ariganjoye Folabi , Smith Jessica , McHugh Laura , Fulford Angela , Osarogiagbon Raymond U.
Published: May 2020

2028

Background: Tobacco cessation is essential to high quality oncology care. Many patients smoke when diagnosed and continue to smoke during treatment, which adversely affects treatment response and survival. Although most patients are motivated to quit, few receive effective cessation therapy. The multidisciplinary clinic (MDC), where patients, their caregivers, and key specialists coordinate care, is an ideal setting to integrate a cessation program. To assess the need for cessation services within a MDC setting, we surveyed incoming patients about their smoking status, interest in quitting, and willingness to participate in a clinic-based cessation program. Methods: The study was conducted in the Multidisciplinary Thoracic Oncology Program at Baptist Cancer Center, Memphis TN. We evaluated sociodemographic/clinical characteristics, smoking status, and tobacco dependence of consecutive new patients diagnosed with lung cancer from 2014-2019, who completed a social history questionnaire. Current smokers reported their interest in quitting and their willingness to participate in a cessation program. Chi square tests and logistic regression models were used to compare characteristics of those who would participate vs. those who would not/were unsure. Kaplan-Meier curves and multivariable Cox regression were used to evaluate the association between willingness to participate in a cessation program and overall survival, adjusted for age, sex, race, and total pack-years of smoking. Results: Of 641 patients, the average age was 69 years (range: 32-95), 47% were men, 64% white/34% black, and 17% college graduates; 90% had ever smoked, 34% currently smoked, and 24% quit smoking within the past year. Among current smokers, 60% were very interested in quitting and 37% would participate in a clinic-based cessation program. Willingness to participate was associated with greater interest in quitting (p = 0.0010) and greater overall survival (log rank p = 0.01;HR: 0.48, 95% CI: 0.24-0.95) but was not associated with any sociodemographic, clinical, or smoking-related characteristics. Conclusions: Over half (58%) of patients in a community-based MDC program were current smokers/recent quitters. Willingness to participate in a cessation program was associated with improved survival, suggesting patients with favorable prognoses are especially interested in receiving cessation support. There is considerable need for cessation services and relapse-prevention support within a coordinated, MDC lung cancer care setting.
Implementation of Symptom Care Clinic (SCC) for acute symptoms management at outpatient oncology ambulatory centers.
Authors: Xiao Han , Fahy Rosanna , Salvaggio Rori , OSullivan Maryellen , Sokoli Desiree , Murray Cheryl , Majeed Jibran , Mao Jun J. , Groeger Jeffrey S.
Published: May 2020

2030

Background: With improved overall cancer survival, increasing number of cancer patients are undergoing active treatment. This, in return, add burden in acute symptom management related to disease and treatment. This has resulted in increasing unplanned emergency room (ER) visits and negatively impacted patients experience and health cost. We establish Symptom Care Clinic (SCC) embedded in suburban ambulatory oncology centers to reduce unplanned ER lists and to improve patient experience. Methods: Together with all stakeholders, we developed six SCCs at regional ambulatory centers in NY and NJ. Clearly defined work flow and algorithm were developed to ensure appropriate patient referral. On-site radiology and laboratory services are available. The SCCs are staffed with combination of Advanced Practice Provided (APP) and physicians or APP alone supported by on site medical oncologist or remote central Urgent Care Center Attendings. We evaluated clinic volumes, reduction ins unplanned ER visits and patient experience. Results: From October 2017 to December 2019, total of 17,542 SCC visits were documented. Total of 17,479 lab and 5,355 radiology tests as well as 3,915 infusions were performed. The top five most common laboratory tests are CBC, blood cultures, CMP, respiratory panel and urine culture. The most common symptoms are fever, nausea/vomiting/dehydration, rash and pain. Among all SCC visits during this period, 83% were discharged home and 17% were transferred to ER or hospitals. During 2019, total 10,736 SCC visits were recored, APP evaluated 73.7% of visits and physicians 16.3% with comaprable recidivism rate, 2.52% and 2.75%, respectively. Conservatively, we estimated that approximately 40% of visits would have been Er visits based on numbers of CBC and other testes performed. Qualitative feedbacks from patients indicated positive experience in convenient access, cohesive care coordination and time saving from traveling to and waiting in ER. Conclusions: We successfully implemented an effective acute symptom management system in busy ambulatory oncology centers that is patient centric. Out data showed that SCC reduced unplanned ER visits and that APP/physician model has low recidivism rate.
Effect of a supportive medicine program for cancer patients on patient connectivity to care and health care utilization.
Authors: Worster Brooke , Garber Gregory D. , Cammy Rebecca , Yocavitch Liana , Shimada Ayako , Csik Valerie Pracilio , Chapman Andrew E. , Leader Amy
Published: May 2020

2034

Background: The benefits of supportive medicine (SM) for cancer patients include improved quality of life, increased patient satisfaction, improved symptom management, increased cost savings and improved survival rates. At one NCI-designated cancer center, all patients were screened for distress; those who screened positive or were directly referred by a provider were enrolled into our multi-disciplinary SM program. Here, we document the impact of the supportive medicine program on outcomes of emergency department (ED) visits, hospital readmission, and non-billable touchpoints associated with patient navigation and resource referrals. Methods: The program systematically screened for biopsychosocial distress utilizing the National Comprehensive Cancer Center Distress Thermometer (DT) and the Problem Checklist (PC) to identify practical, emotional, spiritual and physical issues. Patients were categorized into three types: screened and enrolled in the SM program, and screened and not enrolled in the SM program, or provider referral into the SM program. Data included patient’s age, number of hospital admissions, emergency department visits, and non-billable touchpoints at 90 and 180 days after the distress screening or referral. Descriptive data were analyzed with counts and percentages for categorical variables and summarized with mean and standard deviation for numerical variables. For investigation of the effects of time and patient type on the change in utilization rate, generalized estimation equations for Poisson regression were conducted for each outcome. Results: In all, 2,738 patients were included in the analysis. Patients who were referred from a provider tended to be younger (p < .01) and more likely to die within 90 days (p < .001). At 180 days, ED visits decreased 18% for patients referred to the SM program and 42% for patients screened into the SM program, compared to a 3% decrease in ED visits among those not enrolled in the SM program (p < .01). Similarly, hospital admissions decreased 34% for patients referred to and 39% screened into the SM program, compared to a 4% increase for patients not enrolled in the SM program (p < .01). Non-billable touchpoints increased among all types of patients. Conclusions: An SM program reduces hospital admissions and ED visits, therefore improving outcomes and potentially reducing the cost of care for cancer patients. Future research should link this data to claims data to definitely evaluate the impact of SM programs on cost.
Model selection applied to 750 outpatient ICD-9 codes identifies hazards important for all-cause cancer mortality in 2 million veterans with 14 years of follow-up.
Authors: McMahon Benjamin , Dhaubhadel Sayera , Hengartner Nicolas , Danciu Ioana , Janet Tate , Justice Amy
Published: May 2020

2053

Background: Cost-benefit analysis before undergoing cancer treatments can involve a broad array of factors, yet existing statistical algorithms are limited to a few of the most commonly observed competing risks. Using 20 years of Veteran medical records from the Veteran’s Administration, we identify a broad array of outpatient descriptors providing contributions to computed mortality comparable in size to common cancers. Methods: 1,911,632 Veterans born between 1927 and 1968 with medical records extending from October 1, 2000 until either recorded death after October 1, 2005 (47%) or observation during CY 2019 were split equally into age-matched test and training sets. The 20 year-long record was split into three intervals: 5 years during which ICD codes were tallied, 14 years of waiting, and establishment of continuation in care during 2019. The 750 most common outpatient ICD9 codes were recorded as present/absent for each patient and used in a generalized linear model to predict subsequent mortality, subject to LASSO model selection and 10-fold cross validation. Gender was included as a covariate as well as age at time of prediction, up to the 4th power. Results: The C-statistic for predicting mortality in 14 years of follow-up was 0.835 on training data and 0.833 on test data when using the 498 codes selected by LASSO. Prevalent codes with the largest model coefficients were (ICD 9 code: model coefficient, # alive/# deceased in test set) congestive heart failure (428.0: 0.66, 9k/48k), chronic airway obstruction (496.: 0.60, 42k/105k), and tobacco use disorder (305.1: 0.54, 107k/123k), while the prevalent codes most protective in comparison to baseline were hyperlipidemia (272.4: -0.21, 211k/225k) and colon cancer screening (V76.51: -0.16, 49k/39k). In comparison, observed cancer ICD 9 coefficients were lung (162.9: 1.03, 1k/7k), colon (153.9: 0.18, 3.1k/7.0k), and prostate (185.: 0.06, 16k/32k). 74 predictors contribute with coefficients greater than colon cancers, such as ‘no household member able to render care’ (V60.4: 0.28, 1.1k/4.2k). Conclusions: A wide variety of structured data contribute at a similar level of importance in prediction of 14-year mortality. While various selection biases, co-linearity of predictors, differences in treatments, and missing data are significant impediments to utilization of predictive models in clinical practice, we have demonstrated an ability to identify and quantify predictors from a large data set with model selection techniques.
Core limitations in clinical trials leading to anticancer drug approvals by the U.S. Food and Drug Administration.
Authors: Hilal Talal , Gonzalez-Velez Miguel , Prasad Vinay
Published: May 2020

2057

Background: To date, a comprehensive evaluation of core limitations in clinical trials leading to anti-cancer drug approvals by the US Food and Drug Administration (FDA) has not been undertaken.The aim of this analysis was to assess the percentage of clinical trials with core limitations, defined as lack of randomization, lack of overall survival data, inappropriate use of crossover, and use of sub-optimal control arms that led to FDA approvals from 2014 to 2019. Methods: This observational analysis included all approved anti-cancer drug indications by the FDA from July 2014 through July 2019. All indications were investigated and each clinical trial evaluated for design, enrollment period, primary endpoints, and presence of core limitations. The standard of care therapy was determined by evaluating the literature and published guidelines 1-year prior to start of clinical trial enrollment. Crossover was examined and evaluated for optimal use. We then calculated the percentage of approvals based on clinical trials with any or all core limitations. Results: A total of 187 anti-cancer approvals were evaluated. The number of anti-cancer drug approvals doubled over time with 68 in first half of study period (June 2014 to December 2016) to 119 in second half of study period (January 2017 to July 2019). Of those, 125 (67%) were based on a clinical trial with at least one core limitation. 64 (34%) approvals were based on a single-arm clinical trial. Of the remaining 123 approvals based on randomized trials, 60 (32%) had a core limitation. Of all randomized trials, 37 (30%) lacked overall survival benefit, 31 (25%) had a sub-optimal control, and 17 (14%) used crossover inappropriately. Conclusions: The majority of cancer drugs are approved based on clinical trials with core limitations. Efforts to minimize core limitations at the time of clinical trial design are essential to ensure that new anti-cancer drugs being marketed truly improve patient outcomes over current standards.
Gender-based disparities in clinical trials supporting FDA approval of oncology drugs.
Authors: Zettler Marjorie , Feinberg Bruce A. , Kish Jonathan , Gajra Ajeet
Published: May 2020

2058

Background: Adequate gender representation in clinical trials of new drugs is critical in order to accurately detect possible differences in response and toxicity (Özdemir et al, JCO 2018). The under-representation of women in oncology clinical trials has been previously described, however data on registrational trials, which are the basis for drug approval and inform the prescribing information, is lacking. We conducted an analysis of the trials supporting Food and Drug Administration approval of oncology drugs over a 5-year period to evaluate the representation of women vs. men. Methods: Prescribing information for novel new drugs approved from 2014-2018 was reviewed for the proportions of men and women in the evaluable population of the supporting clinical trials. Sex-specific cancers were excluded. Prevalence estimates for the indications were obtained from the Surveillance, Epidemiology and End Results database and the published literature. A participation to prevalence ratio (PPR) was calculated for each trial by dividing the percentage of women in the trial by the percentage of women in the disease population. A PPR value closer to unity represents even gender distribution and the range 0.8-1.2 is considered to reflect an acceptable representation of women. Data are presented using descriptive statistics. Results: A total of 46 oncology drugs were approved based on 56 trials enrolling 13,862 patients (7941 [57%] men; 5,921 [43%] women). Of the 56 trials, 38 (68%) had a PPR within the 0.8-1.2 range, 15 (27%) fell between 0.4-0.7, and 3 (5%) had a PPR of 1.3. The proportion of trials with unbalanced gender representation was comparable for hematological malignancy and solid tumor indications and did not improve over time. Fewer unbalanced trials were Phase III or employed a randomized design. Nine of the 18 (50%) unbalanced trials enrolled <100 subjects, compared to 3 of the 38 (8%) balanced trials. Conclusions: A third of registrational trials for oncology drugs lacked balanced gender distribution. Of the trials lacking balance, the vast majority (80%) had under-representation of women. Phase I-II trials and smaller trials had greater gender disparity, a concerning finding in a precision medicine environment where an increasing number of registration trials have double digit accrual. Further research is needed to understand the implications of unbalanced gender accrual in registrational trials, and to develop strategies for preventing disparities.
Home ePRO compliance in prostate cancer clinical studies.
Authors: Gary Sarah Tressel , Dias Nadeeka , Conrad Elisa , Faulkner Kenneth G
Published: May 2020

2063

Background: Patient-reported outcomes (PRO) and electronic PRO (ePRO) play an important role in the development and approval of cancer products. Regulatory agencies are encouraging the inclusion of PRO-based endpoints that are indicative of clinical benefit in terms of patient symptoms and overall quality of life (QOL). Compliance with completion of ePRO assessments is an important component for obtaining accurate and high-quality data when conducting clinical trials. Traditionally, ePRO data in oncology trials has been collected mainly at clinic visits due to concerns over poor compliance at home. However, since symptoms and QOL can vary widely through a treatment course, it is often necessary to collect ePRO data more frequently in between clinic visits. It has been hypothesized that home completion, length of time in a study, and number of assessments may affect compliance. Methods: To address this hypothesis, ePRO compliance data was analyzed from two clinical studies in prostate cancer. Both studies used a handheld smartphone that contained an application to collect ePRO data. At the randomization visit, subjects completed ePRO assessments in clinic (2-3 questionnaires). Subsequently, all assessments were completed at home, including a daily diary and 1-4 questionnaires completed every 4-8 weeks for up to 14 months. Compliance was calculated as the number of assessments received divided by the number of assessments expected in a given assessment period. To evaluate assessment burden, each assessment period was categorized as requiring a lower number (daily diary and 1 questionnaire) or higher number (daily diary and 2-4 questionnaires) of assessments. Results: A total of 1,040 patients were included in the analysis. Overall compliance at the single clinic visit was 100%, which was expected since it was a required randomization visit. Overall compliance at home over 14 months was 80%. Compliance ranged from 78% to 89% over the duration of the studies, with no effect of time in the study on compliance. Compliance remained high even as patient numbers declined. Compliance when patients were required to complete a lower number of assessments (80%) was similar to compliance when patients were required to complete a higher number of assessments (79%). Compliance by region varied from 72% (Middle East) to 87% (Asia and Eastern Europe). Conclusions: The collection of ePRO at home provided high compliance that did not vary with length of time in the study or due to assessment burden. At home ePRO assessments provide an effective and feasible approach for recording symptoms and QOL in prostate cancer patients.
Timing of US Food and Drug Administration (FDA) cancer drug approvals relative to publication of clinical trial results.
Authors: Khaki Ali Raza , Desai Aakash , Schoen Martin W. , Gyawali Bishal , Chen Eddy J. , Yang Peter C. , Warner Jeremy Lyle
Published: May 2020

2071

Background: Publication of clinical trial results in peer reviewed literature is essential to inform clinicians regarding the use of new anti-cancer treatments, which often have a low therapeutic ratio and require careful assessment of risks and benefits. Publication of registration trials should precede FDA approval to facilitate evaluation and implementation of new therapies. The timing of trial publication relative to FDA drug approvals has not been systematically investigated. Methods: We collected all FDA drug approvals for a cancer indication between 2000-19. Trials were identified using FDA labels as well as drugs and publications indexed on HemOnc.org. Approvals for generics/biosimilars, non-oncology indications and label revisions without supportive evidence were excluded. Dates of approval, the approval pathway, approval type (new vs expansion), and the first full publication related to the registration were recorded. Trials and approvals were matched using available metadata. We calculated the proportion of drugs approved prior to publication overall and for those receiving accelerated approval (AA). We used logistic regression to compare rates of pre-publication approval by approval pathway and by new vs expanded approval. Results: Among a total of 378 drug approvals, 139 (37%) had pre-publication approval. Of these, the median overall time from approval to publication was 140 days (IQR 64-281 days). For those with approval after publication, median time from publication to approval was 157 days (IQR 72-359 days). The number of drugs approved pre-publication rose by 27% between the first and last quarters of the study period, though, the proportion decreased as more anti-cancer drugs have been approved in recent years (Table). More drugs were approved pre-publication through AA than regular approval (46% vs 34%, OR 1.66 [95% CI 1.03-2.70], p=0.04) and as new approvals vs. expanded approvals (45% vs 32%, OR 1.76 [95% CI 1.15-2.70], p=0.01). Conclusions: A substantial minority of FDA approvals occur before trial results are published, with the odds being higher for drugs receiving AA and for new approvals. Since clinicians rely upon published results to inform risk/benefit decisions, efforts are needed to ensure trial results are published by the time of FDA approval of new cancer drugs and indications. [Table: see text]
The clinical impact of ASCO “choosing wisely” recommendations on staging imaging for early stage breast cancers: An interrupted time-series analysis utilizing SEER-Medicare data.
Authors: Baltz Alan , Makhoul Issam , Siegel Eric R
Published: May 2020

2078

Background: The “Choosing Wisely” (CW) list, released by the American Society for Clinical Oncology (ASCO), highlights low-value procedures. In 2012, the CW recommendations advised against the use of staging imaging, including Positron Emission Tomography (PET), Computerized Tomography (CT) and radionuclide bone scans, for the staging of early breast cancer at low risk for metastasis. The objective of this study was therefore to assess the impact of the ASCO CW recommendations on staging imaging among early stage breast cancers. Methods: Women above the age of 66 with an early stage incident breast cancer diagnoses between 2010 and 2015 were identified within the linked SEER-Medicare data. The primary outcome of interest was the proportion of patients with a claim for staging imaging in the six months following the breast cancer diagnosis. Negative binomial regression, adjusting for pre-recommendation trends, was performed to estimate the changes in the rate of imaging staging within each year following the release of the recommendation. Results: A total of 50,004 women were identified during the study period. Prior to the release of the recommendations in 2012, the staging imaging rates among women newly diagnosed with early stage breast cancers were 5% greater in 2010 (p<.01) and 4% greater in 2011 (p<.01). Following the release of the recommendations, staging imaging rates did not decrease significantly in 2013 (2%;p=0.18). Imaging rates did, however, significantly decrease by 13% in 2014 (p<0.01) and by 16% in 2015 (p<0.01). Conclusions: The CW recommendation was associated with a significant decrease in unadvised staging imaging among incident early stage breast cancer diagnosis in the second and third year following its release. These findings demonstrate an improvement in the proportion of potentially inappropriate staging imaging in early stage breast cancers. The creation and dissemination of resources, such as the CW recommendations, serves as a powerful tool to improve clinical practice, quality of care, and patient safety from secondary malignancies, anxiety, and overdiagnosis.
Adoption of behavioral restrictions as anti-infective measures: A survey among solid tumor patients.
Authors: Shachar Eliya , Ferro Leora , Peleg Hasson Shira , Emmanuel Waller , Wolf Ido
Published: May 2020

2081

Background: Despite lack of evidence, a wide range of rigorous behavioral and social restrictions are recommended in various guidelines and websites in an attempt to mitigate infections. These include patient guided sites. We aimed to study the practices of patients with solid tumors treated with active therapy. Methods: We conducted an anonymous survey among cancer patients treated at a tertiary care center, addressing behavioral approach to infection prevention, by assessing adopted social (seven items), environmental (five items), and dietary (eight items) limitations, as well as compliance to influenza vaccinations. Clinical data included neutropenic fever (NF), and therapy myelosuppressive potential. Multivariable Poisson regression adjusted for sex, age, disease status, therapy to estimate the impact of these restrictions. Results: 214 patients with solid tumors responded to the survey, the majority female (59%), with a median age of 63. The most common tumor types included breast (28%), lung (14%), and colon (9.3%). Most (68%) were treated with chemotherapy, 17% with immunotherapy, 11% with biologicals and 3% with chemo-immunotherapy. Only 6% were admitted for NF. Sources of information regarding restrictions included physicians (4%), nurses (32.9%), and internet (9.8%); the majority were self-imposed. 53% maintained environmental limitations (traveling, sun exposure, hair dying), 37% adopted social restrictions (abstained from children, public places), and 21% affirmed dietary constraints (raw vegetables, tap water consumption). Females practiced stricter environmental and dietary restraint (p < 0.05), with a numerical trend reflecting stricter female social measures (p < 0.4). With no difference in practices among patients treated for a malignant disease and curative intent, and no difference in practice across therapies, in those treated with chemotherapy and immuno-therapy. 37% affirmed difficulty in adherence to these limitations. Conclusions: Our findings indicate that despite lack of evidence, cancer patients adopt anti-infective behavioral measures, which have a deleterious impact on quality of life. These practices are being used even among patients at low or no risk of NF. These findings call for implementation of an education program and development of practical instructions enabling patients to resume their normal life
MGMT methylation as a prognostic factor in IDH wild type anaplastic gliomas.
Authors: Franceschi Enrico , Tosoni Alicia , Di Nunno Vincenzo , Mura Antonella , Asioli Sofia , Pession Annalisa , Agati Raffaele , Paccapelo Alexandro , Bartolini Stefania , Brandes Alba Ariela
Published: May 2020

2523

Background: Anaplastic gliomas are classified according to the presence of IDH-mutation. IDH wild type (IDH wt) is associated with poor prognosis and limited effectiveness of treatments.The aim of this study was to find out if MGMT methylation represents a prognostic factor in this setting. Methods: Anaplastic gliomas are classified according to the presence of IDH-mutation. IDH wild type (IDH wt) is associated with poor prognosis and limited effectiveness of treatments.The aim of this study was to find out if MGMT methylation represents a prognostic factor in this setting. Results: The analysis included 73 pts with grade III, IDH wt (19.3%) gliomas. Median follow-up time was 69.9 months. Median age was 50 (Range: 18-75), M/F ratio was 40(54.8%)/33(45.2%).MGMT promoter was methylated in 34 pts (46.6%) and unmethylated in 39 pts (53.4%). After surgery, 9 pts (12.3%) received RT alone, 57 pts (78.1%) received both RT and CT (sequential, concomitant or both). Median survival was 26.2 months. In multivariate analysis age (HR = 1.064, 95%CI: 1.030-1.099; P < 0.001) and MGMT methylation (HR = 0.422, 95%CI: 0.210-0.848; P = 0.015) were independently associated with risk for death. Conclusions: IDH wild type confers a dismal prognosis in patients with grade III gliomas. MGMT methylation, as was demonstrated in glioblastoma, represents a prognostic factor that correlated with lower risk for death. Further studies will investigate potential correlations with treatments.
Leptomeningeal disease after surgical resection and radiosurgery for brain metastases and neurologic death: A multi-institutional analysis.
Authors: Prabhu Roshan Sudhir , Turner Brandon E , Asher Anthony L , Marcrom Samuel , Fiveash John B. , Foreman Paul M , Press Robert H. , Buchwald Zachary , Curran Walter J , Patel Kirtesh R. , Breen William , Brown Paul D. , Jethwa Krishan , Grills Inga S. , Arden Jessica , Foster Lauren M , Manning Matthew A. , Vaslow Zachary , Burri Stuart , Soltys Scott G.
Published: May 2020

2524

Background: Postoperative radiosurgery (SRS) has been associated with up to 30% risk of subsequent leptomeningeal disease (LMD). We previously demonstrated that radiographic pattern of LMD (classical “sugarcoating” [cLMD] vs. nodular [nLMD]) in this setting is prognostic. The association between radiographic pattern of LMD, type of salvage treatment (tx), and neurologic death (ND) has not been well described. Methods: The records of patients (pts) with brain metastases (BM), of which 1 was resected and treated with adjunctive SRS, and who subsequently developed LMD were combined from 7 tertiary care centers. Pts with classically radiosensitive tumors or prior or planned whole brain radiotherapy (WBRT) were excluded. ND was defined as symptomatic CNS progression around the time of death without life threatening systemic symptoms or progression. Salvage radiotherapy (RT) for LMD was categorized according to use of WBRT vs. focal cranial RT. Results: The study cohort consisted of 147 pts, of which 125 had died with known cause, 107 also received LMD salvage tx, and 82 also had cranial MRI follow-up. The ND rate in the 125 pts who died with known cause was 79%; the rate in pts who underwent LMD salvage tx (n = 107) was 76%. Univariate logistic regression demonstrated radiographic pattern of LMD (cLMD vs. nLMD, odds ratio [OR] 2.9, p = 0.04) and 2nd LMD failure after salvage tx (OR 3.9, p = 0.02) as significantly associated with ND. The ND rate was 86% for cLMD vs. 68% for nLMD pattern. WBRT was used in 95% of pts with cLMD vs. 52% of pts with nLMD. In the nLMD cohort (n = 58), there was no difference in ND rate based on type of salvage RT (WBRT: 67% vs. focal cranial RT: 68%, p = 0.92). Second LMD failure (vs. not) was associated with higher ND in the nLMD cohort (77% vs. 52%, p = 0.02). Of the 26 pts with nLMD who experienced 2nd LMD failure, 7 had classical 2nd LMD, of which 100% experienced ND, and 19 had nodular 2nd LMD, of which 68% experienced ND (p = 0.09). Conclusions: LMD after surgery and SRS for brain metastases is a clinically significant event with high rates of neurologic death. Classical LMD pattern (vs. nodular) and 2nd LMD failure after salvage tx were significantly associated with higher risk of neurologic death. In the nodular LMD cohort, radiographic pattern of 2nd LMD may be associated with risk of subsequent neurologic death. Pts with nodular LMD treated with salvage focal cranial RT or WBRT had similar risk of neurologic death. Methods to decrease LMD and the subsequent high risk of neurologic death in this setting warrant investigation.