Citations

11570 Background: Intergroup Rhabdomyosarcoma Study Group (IRSG) protocols included treatment modifications, which may have ameliorated late health outcomes for rhabdomyosarcoma (RMS) survivors treated in more recent era. Methods: We evaluated chronic health conditions (CHCs) and late mortality ( > 5 years from diagnosis) among survivors treated 1970-1990 (IRSG I-III) and 1991-1999 (IRSG IV), and associations with specific treatments to identify treatment-related factors for adverse outcomes. Associations between treatments and CHCs and mortality were evaluated using Fine and Gray’s proportional hazards method accounting for competing risks. Results: 856 survivors treated 1970-90 (median diagnosis age 5.4 years [0- 20]) and 306 treated 1991-99 (median diagnosis age 5.5 years [0-20]) were included. Significant exposure differences between eras included higher percentage (53% vs. 17%, p < 0.01) receiving ≥ 20gm/m2 cumulative alkylators in 1991-99, but more receiving platinums (13% vs 5%, p < 0.01) and abdomen/ pelvis radiation (29% vs. 23%, p = 0.04) in 1970-90. 20-year cumulative incidence for any (40% vs. 28%, p < 0.01), ≥2 (16% vs. 7%, p < 0.01), and endocrine (8% vs. 2.5%, p < 0.01) grade 3-5 CHCs was higher in 1970-90 compared to 1991-99. The hazard ratio (HR) for any (HR 0.7, 95% Confidence Interval [CI] 0.55-0.9), ≥2 (HR 0.38, 95% CI 0.22-0.66) and endocrine (HR 0.25, 95% CI 0.09-0.67) grade 3-5 CHC was lower for 1991-99 survivors than 1970-90. The effect of era (1991-99 vs 1970-90, HR 0.73; 95% CI 0.59-0.91) on CHC was not attenuated when treatment variables were added to multivariable model. Exposures with increased risk of grade 3-5 CHC included platinums (hearing, HR 2, 95% CI 1.07-3.8), anthracycline ≥250mg/m2 (cardiovascular, HR 2.7, 95% CI 1.2-6) and abdomen/ pelvis radiation (second malignant neoplasms, HR 2.1, 95% CI 1.1-4, gastrointestinal, HR 7.4, 95% CI 3.5-16 and endocrine, HR 2.5, 95% CI 1.4-4.4). Gonadal dysfunction was the most common endocrine CHC. There was no difference in all cause or cause-specific mortality between the two cohorts. Conclusions: RMS survivors from the IRSG IV era are at reduced risk for late onset chronic health conditions compared to previous era.

Background: Uncontrolled blood pressure (BP) is a leading preventable cause of death that remains common in the US population despite the availability of effective medications. New technology and program innovation has high potential to improve BP but may be expensive and burdensome for patients, clinicians, health systems, and payers and may not produce desired results or reduce existing disparities in BP control. Methods and Results: The PCORnet Blood Pressure Control Laboratory is a platform designed to enable national surveillance and facilitate quality improvement and comparative effectiveness research. The platform uses PCORnet, the National Patient-Centered Clinical Research Network, for engagement of health systems and collection of electronic health record data, and the Eureka Research Platform for eConsent and collection of patient-reported outcomes and mHealth data from wearable devices and smartphones. Three demonstration projects are underway: BP track will conduct national surveillance of BP control and related clinical processes by measuring theory-derived pragmatic BP control metrics using electronic health record data, with a focus on tracking disparities over time; BP MAP will conduct a cluster-randomized trial comparing effectiveness of 2 versions of a BP control quality improvement program; BP Home will conduct an individual patient-level randomized trial comparing effectiveness of smartphone-linked versus standard home BP monitoring. Thus far, BP Track has collected electronic health record data from over 826 000 eligible patients with hypertension who completed ≈3.1 million ambulatory visits. Preliminary results demonstrate substantial room for improvement in BP control (<140/90 mm Hg), which was 58% overall, and in the clinical processes relevant for BP control. For example, only 12% of patients with hypertension with a high BP measurement during an ambulatory visit received an order for a new antihypertensive medication. Conclusions: The PCORnet Blood Pressure Control Laboratory is designed to be a reusable platform for efficient surveillance and comparative effectiveness research; results from demonstration projects are forthcoming.

11015 Background: Immune checkpoint inhibitors have demonstrated activity in multiple tumor types but their activity in soft tissue sarcomas remains limited. In the multicenter phase II study, SARC028, the anti-PD-1 antibody, P demonstrated objective responses that were largely restricted to UPS and LPS subtypes. We now report outcomes from 2 expansion cohorts of SARC 028 in advanced UPS and LPS. Methods: To further confirm the clinical activity of P in UPS and LPS, we enrolled an additional 30 pts in each of 2 expansion cohorts for a total of 40 UPS and 40 LPS pts. Primary endpoint was investigator-assessed response by RECIST v1.1. Secondary endpoints were safety, progression-free survival (PFS), 12-week PFS rate, and overall survival (OS). An ORR of 25% was considered clinically meaningful and < 10% was considered to show lack of efficacy. P was to be considered a success if 8 or more of 40 enrolled patients had a PR or better (1-sided α = 0.042, 82% power). Pts age ≥18 with advanced, refractory UPS or LPS received 200 mg of P IV every 3 weeks until progression or unacceptable toxicity. Results: Preliminary results from the first 10 pts in each of the UPS and LPS cohorts have been reported. We now present summary data after enrolling an additional 30 pts in each cohort. The ORR in the UPS cohort was 23% (9/40), with an additional 5/30 PRs observed in the expansion cohort (total 2 CRs, 7 PRs). In the LPS cohort, the ORR was 10% (4/39 evaluable pts), with an additional 2/30 PRs observed (total 4 PRs). Median PFS for the UPS group was 3 months [95% CI: 2, 5] and 2 months [95% CI: 2, 4] for the LPS group. 12-week PFS rate was 50% in UPS [95% CI: 35, 65] and 44% in LPS [95% CI: 28, 60]. The UPS group had a median OS of 12 months [95% CI: 7, 34] and 13 months [95% CI: 8, NR] for the LPS group. P was well tolerated with no unexpected toxicities. Conclusions: The UPS cohort achieved its primary endpoint, however the activity of P in UPS deserves further evaluation in a randomized study. The activity of P was not confirmed in the LPS cohort. Ongoing biomarker analyses may direct better patient selection and guide future combination strategies. Clinical trial information: NCT02301039.

AbstractImmune checkpoint inhibitor therapies targeting PD‐1/PD‐L1 are now the standard of care in oncology across several hematologic and solid tumor types, including triple negative breast cancer (TNBC). Patients with metastatic or locally advanced TNBC with PD‐L1 expression on immune cells occupying ≥1% of tumor area demonstrated survival benefit with the addition of atezolizumab to nab‐paclitaxel. However, concerns regarding variability between immunohistochemical PD‐L1 assay performance and inter‐reader reproducibility have been raised. High tumor‐infiltrating lymphocytes (TILs) have also been associated with response to PD‐1/PD‐L1 inhibitors in patients with breast cancer (BC). TILs can be easily assessed on hematoxylin and eosin–stained slides and have shown reliable inter‐reader reproducibility. As an established prognostic factor in early stage TNBC, TILs are soon anticipated to be reported in daily practice in many pathology laboratories worldwide. Because TILs and PD‐L1 are parts of an immunological spectrum in BC, we propose the systematic implementation of combined PD‐L1 and TIL analyses as a more comprehensive immuno‐oncological biomarker for patient selection for PD‐1/PD‐L1 inhibition‐based therapy in patients with BC. Although practical and regulatory considerations differ by jurisdiction, the pathology community has the responsibility to patients to implement assays that lead to optimal patient selection. We propose herewith a risk‐management framework that may help mitigate the risks of suboptimal patient selection for immuno‐therapeutic approaches in clinical trials and daily practice based on combined TILs/PD‐L1 assessment in BC. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Background: Grand rounds and named lectureships are forums in academic medicine for sharing research, scholarly achievements, and clinical expertise. An invitation to speak at grand rounds is regarded as an honor and is part of the pathway to academic promotion. We describe gender representation relative to the national academic medical workforce among invited speakers at departmental grand rounds and annual named lectures at a large academic medical center. Materials and Methods: Lists of external speakers for grand rounds from 2015 through 2017 were obtained from 18 departments and for annual named lectures from 2007 to 2017 from 7 departments. Results: Of the 783 invited speakers to the 25 speaker series, there were 178 women (22.7%). The proportion of women speakers for departmental grand rounds ranged from 0% to 59.3%; representation of women speakers was lower than representation in their specialty in 14 of the 18 departments and significantly lower in 4 of the 18 departments. In four departments, there was a higher proportion of women than available in the specialty-specific academic medicine workforce. The proportion of women who spoke at annual named lectures was significantly lower in two of seven lecture series and ranged from 0% to 21.2%. Three departments had no women speakers. Conclusions: The underrepresentation of women as speakers is a potential target to improve gender representation and role modeling and provide equitable opportunity for academic advancement. Solutions may include formal diversity and inclusion training, intentional overrepresentation of invited female speakers, and inclusion of women on grand rounds planning committees.

Background: The Patient-Centered Outcomes Research Institute (PCORI) funded National Blood Pressure Surveillance System (BP Track) is a new national system that generates quarterly metrics of blood pressure (BP) control and BP-related quality metrics for participating healthcare systems from electronic health record (EHR) data. Methods: Queries against standardized EHR data in the national Patient-Centered Clinical Research Network (PCORnet) Common Data Model format produce a set of quality metrics relevant to improving BP control, including Controlling High BP (NQF 0018) and Improvement in BP (CMS65v7), and eight process measures specific to clinical management and treatment practices for improving BP control ( Table ). The metrics, aggregated overall and by health system are reported back to health systems via user-friendly Tableau dashboards, and allow for observation of metric trends. Results: To date, 19 datamarts have contributed EHR data from 1,177,232 patients who met the eligibility criteria for the BP Control measure and 4,454,729 encounters that included a BP measurement during the measurement period. Average age was 62 years; 10% were young adults (<45 years), 17% were African American, 52% female, 28% had diabetes, 15% had coronary heart disease, and 14% had depression. Results demonstrate substantial opportunity for improvement in overall BP control (60% with BP<140/<90 mmHg, range: 42-72%), and many healthcare processes, including medication intensification (12%, 0.6-22%) and use of fixed dose combination medications (24%, 0-88%, Table ). Conclusion: Major opportunities exist for improving BP control, especially in improving the frequency and quality of BP medication prescribing for patients with high BP. The BP Track National BP Surveillance System will track these metrics, by demographic subgroup and over time, and will generate data that can guide and focus quality improvement initiatives aimed at effective BP management.

A major direction for future microbiome research is implementation of fecal sample collections in large-scale, prospective epidemiologic studies. Studying microbiome-disease associations likely requires microbial data to be pooled from multiple studies. Our findings suggest collection methods that are most optimal to be used standardly across future WGSS microbiome studies.

Introduction Population-level screening has been shown to reduce the incidence and mortality of colorectal cancer (CRC). Unfortunately, adherence to screening recommendations among eligible US adults remains below national goals. A relatively new non-invasive screening modality, the Food and Drug Administration–approved multi-target stool DNA (mt-sDNA) assay (commercialised as Cologuard), which combines the detection of haemoglobin and DNA abnormalities, has been completed by more than 3 million individuals. Given mt-sDNA’s recent availability, the effectiveness of mt-sDNA screening with respect to CRC incidence and mortality reduction has not yet been established. Methods and analysis Through an academic–industry collaboration, a prospective cohort study (Voyage) was designed with an initial enrolment target of 150 000 individuals with mt-sDNA ordered by their healthcare provider for CRC screening. Consented participants will be asked to complete a baseline questionnaire to collect sociodemographic and health information. Additional questionnaires will be provided after 1 year, and every 3 years thereafter, to collect data regarding CRC screening follow-up in order to estimate rates of CRC incidence and other health outcomes. Linkage to the National Death Index will be used to estimate mortality rates. Ethics and dissemination The Voyage study will be conducted in accordance with international guidelines and local regulatory requirements and laws. Data will be stored and retained at Mayo Clinic. Only limited data elements required for research purposes will be transmitted between Mayo Clinic and Exact Sciences Laboratories. Results of the Voyage study will be disseminated through scientific presentations and publications. Trial registration number NCT04124406.

39 Background: The excess risk of high-grade prostate cancer in the Prostate Cancer Prevention Trial (PCPT) among men randomized to finasteride raised concerns that a chemoprevention benefit would be offset by increased mortality. Two 2019 publications had contrasting results whether 5-ARIs increased prostate cancer mortality. In PCPT, there was no excess prostate cancer mortality. In a VA study, 5-ARI use was associated with later stage at diagnosis and 39% higher prostate cancer mortality risk. We studied men with regular access to health care and screening to address this conflicting evidence. Methods: We performed two parallel analyses in the Health Professionals Follow-up Study. 5-ARI use was reported on biennial questionnaires starting in 1996. In line with PCPT, we studied 38,047 men for cancer incidence and mortality through 2016. In line with the VA study, we undertook a case-only study of 4,225 patients with localized/locally advanced cancers followed similarly. We estimated hazard ratios (HR) and 95% confidence intervals accounting for screening patterns, lifestyle factors, and concomitant medications. Results: 5-ARI ever-users (n = 4,101; 10.7%) were more likely to have had regular PSA screening (74% vs. 57% nonusers) and a negative prostate biopsy before diagnosis. Neither ever 5-ARI use (HR 1.08, 0.73-1.60, 445 events) nor long-term use ( > 4 years, HR 1.03, 1.03-2.02) were associated with lethal prostate cancer. There was no difference in stage. Diagnostic PSA levels were lower in 5-ARIs users (10.0 vs. 16.0 ng/ml in never-users). Among nonmetastatic cases, 278 men died of prostate cancer; there was no association between 5-ARIs and prostate cancer survival (HR 0.85, 0.51-1.43). Conclusions: Our results align with PCPT and show no excess risk of lethal prostate cancer, no higher stage at diagnosis, and no excess mortality after diagnosis associated with 5-ARI. Men on 5-ARIs had more interactions with health care, which may have led to higher quality care. This contrasts with the VA study where men on 5-ARIs were diagnosed later due to suppressed PSA and had worse survival. These results show the importance of real-world data in framing the benefits and risks associated with 5-ARIs.