Citations

4009 Background: An ∼65% 5-year disease-free-survival (DFS) rate from 5-FU/mitomycin/radiation for anal carcinoma needs improvement. Methods: A phase III randomized trial compared 5-FU (1,000mg/m2 days 1–4 and 29–32) plus mitomycin (10mg/m2 days 1 and 29) and radiation (45 to 59 Gy) (Arm A) to 5-FU (1,000mg/m2 days 1–4, 29–32, 57–60 and 85–88) plus cisplatin (75mg/m2 on days 1, 29, 57 and 85) and radiation (45 to 59 Gy; start day=57) (Arm B) in anal carcinoma patients. Stratification included gender, clinical N status and tumor diameter. Primary endpoint was DFS. Statistical power was 80% with two-sided test to detect 10% DFS increase for Arm B. Results: Of 682 patients accrued, 598 were analyzable. Most unanalyzed patients’ data are early. Patient characteristics were balanced. Median age was 55 years, women predominated (69%), 27.5% had >5 cm tumor diameter and 26% had clinically N+ cancer. Preliminary 5-year estimated DFS was 56% for Arm A and 48% for Arm B (p=0.28) and 5-year estimated overall survival was 69% for both arms (p=0.24). Men(p=0.04), clinically N+ cancer (p<0.0001) and tumor diameter >5 cm (p=0.005) independently prognosticated DFS in a multivariate analysis. 5-year colostomy rate was 10% for Arm A and 20% for arm B(p=0.12). Grade 3/4 toxicity rates: non-hematologic=76% for Arm A and 75% for Arm B but hematologic=67% for Arm A and 47% for Arm B(p=0.0004). Conclusions: In Intergroup-98–11, induction 5-FU/cisplatin followed by 5-FU/cisplatin/radiation failed to improve DFS compared to the standard treatment, 5-FU/mitomycin/radiation. Supported by RTOG U10 CA21661, CCOP U10 CA37422, Stat U10 CA32115. No significant financial relationships to disclose.

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.

PURPOSE To determine the sensitivity and specificity of genetic testing criteria for the detection of germline pathogenic variants in women with breast cancer. MATERIALS AND METHODS Women with breast cancer enrolled in a breast cancer registry at a tertiary cancer center between 2000 and 2016 were evaluated for germline pathogenic variants in 9 breast cancer predisposition genes ( ATM , BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, and TP53). The performance of the National Comprehensive Cancer Network (NCCN) hereditary cancer testing criteria was evaluated relative to testing of all women as recommended by the American Society of Breast Surgeons. RESULTS Of 3,907 women, 1,872 (47.9%) meeting NCCN criteria were more likely to carry a pathogenic variant in 9 predisposition genes compared with women not meeting criteria (9.0% v 3.5%; P < .001). Of those not meeting criteria (n = 2,035), 14 (0.7%) had pathogenic variants in BRCA1 or BRCA2. The sensitivity of NCCN criteria was 70% for 9 predisposition genes and 87% for BRCA1 and BRCA2, with a specificity of 53%. Expansion of the NCCN criteria to include all women diagnosed with breast cancer at ≤ 65 years of age achieved > 90% sensitivity for the 9 predisposition genes and > 98% sensitivity for BRCA1 and BRCA2. CONCLUSION A substantial proportion of women with breast cancer carrying germline pathogenic variants in predisposition genes do not qualify for testing by NCCN criteria. Expansion of NCCN criteria to include all women diagnosed at ≤ 65 years of age improves the sensitivity of the selection criteria without requiring testing of all women with breast cancer.

Background: Avoiding early hospital readmission after a diagnosis of atrial fibrillation (AF) lowers healthcare costs. Purpose: This investigation pilot tested the process of using a Connected Health (CH) communication platform in AF care management. Subjects: A self-selected group of patients (n=18, 56% male, mean age=69 years, SD =12.6) diagnosed with hemodynamically stable AF and an uncontrolled ventricular response with heart rates > 110 bpm were recruited. MethodS: Eligibility criteria included a recent AF related emergency department or outpatient clinic visit and the new prescription of a rate control medication. This included AV node modifying medications (either a beta blocker or nondihydropyradine calcium channel blocker) at a starting dose determined by the supervising physician. A care management team (CMT) coordinated by a nurse practitioner provided individualized telephone medical management with no planned clinical visits during a period of early recovery. Patients were equipped with the AliveCor TM Kardia electrocardiogram (ECG) home monitoring device and a supporting mobile device application. Patients returned home with medical guidance from the CMT and ECG recording instructions. Heart rate and rhythm were monitored remotely by the NP and the medication dose was adjusted to reach a target resting heart rate <110 bpm. Patients were managed for 3-weeks before being discharged back to primary care or outpatient cardiology for consideration of a rate versus rhythm control strategy if spontaneous restoration of sinus rhythm had not occurred. ResultS: Patients recorded an average of 50 ( SD =40.0) ECG tracings with a mean of 13 ( SD =3.79) related CMT telephone contacts. The mean resting heart rate was significantly lower ( p <0.05) at the completion of the intervention (72.9 bpm, SD =17.31) compared to baseline (102.3 bpm, SD =27.17). All of the AF patients achieved adequate heart rate control or spontaneously returned to sinus rhythm. However, 4 patients (22%) required a related emergency room visit and unplanned hospitalization. Conclusion: In this small feasibility study, an electronic healthcare device (biosensor) paired with a mobile-heath application provided a practical remote monitoring communication platform to support tele-management, but the intervention did not prevent hospital readmission. Future Directions: Further research is needed to identify factors that will improve the process of applying CH to AF care management.

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.

Background: The National Comprehensive Cancer Network and American Society of Clinical Oncology recommend consideration of the use of echocardiography 6 to 12 months after completion of anthracycline-based chemotherapy in at-risk populations. Assessment of BNP (B-type natriuretic peptide) has also been suggested by the American College of Cardiology/American Heart Association/Heart Failure Society of America for the identification of Stage A (at risk) heart failure patients. The real-world frequency of the use of these tests in patients after receipt of anthracycline therapy, however, has not been studied previously. Methods and Results: In this retrospective study, using administrative claims data from the OptumLabs Data Warehouse, we identified 31 447 breast cancer and lymphoma patients (age ≥18 years) who were treated with an anthracycline in the United States between January 1, 2008 and January 31, 2018. Continuous medical and pharmacy coverage was required for at least 6 months before the initial anthracycline dose and 12 months after the final dose. Only 36.1% of patients had any type of cardiac surveillance (echocardiography, BNP, or cardiac imaging) in the year following completion of anthracycline therapy (29.7% echocardiography). Surveillance rate increased from 37.5% in 2008 to 42.7% in 2018 (25.6% in 2008 to 40.5% echocardiography in 2018). Lymphoma patients had a lower likelihood of any surveillance compared with patients with breast cancer (odds ratio, 0.79 [95% CI, 0.74–0.85]; P <0.001). Patients with preexisting diagnoses of coronary artery disease and arrhythmia had the highest likelihood of cardiac surveillance (odds ratio, 1.54 [95% CI, 1.39–1.69] and odds ratio, 1.42 [95% CI, 1.3–1.53]; P <0.001 for both), although no single comorbidity was associated with a >50% rate of surveillance. Conclusions: The majority of survivors of breast cancer and lymphoma who have received anthracycline-based chemotherapy do not undergo cardiac surveillance after treatment, including those with a history of cardiovascular comorbidities, such as heart failure.

TPS586 Background: Chemoradiotherapy(CRT) is a SOC for patients with muscle invasive bladder cancer (MIBC) who refuse or are not fit for radical cystectomy. Radiotherapy and chemotherapy are known to increases the PD-L1 expression in bladder cancer. Based on these observations, we hypothesized that addition of atezolizumab to CRT will increase its efficacy. Methods: This is a randomized phase III trial testing CRT with and without atezolizumab for 6 months in 475 patients with MIBC. Pts will be stratified on performance status (0-1 vs. 2); clinical stage (T2 vs T3/T4a, chemotherapy(cisplatin vs 5FU+mitomycin vs gemcitabine); and radiation field (bladder only vs small pelvis). Patients will undergo biopsy 18 week from registration. If they have residual disease they will be taken off protocol treatment and can proceed with alternative SOC option including radical cystectomy. Patients will be followed for 5 years. The primary end point of the study is bladder intact event –free survival (BIEFS). The event is comprised of: recurrence or residual muscle-invasive bladder cancer at 18 weeks or later, clinical evidence of nodal or metastatic disease, radical cystectomy, or death due to any cause. This composite endpoint is reflective of the intent of bladder preservation strategy with radical cystectomy included as one of the outcomes. Secondary end points include overall survival, modified event free survival, pathologic response at 18 weeks, metastasis free survival, cancer specific survival, rate of salvage cystectomy, rate of adverse event and QOL & PRO end points. The expected 3 year BIEFS for the control arm is 52%. The study leadership concluded that a 12% improvement in this endpoint is meaningful for this patient population. With a sample size of 475 patients the study has 85% power to detect the improvement from 52% to 64% in the BIEFS at 3 years (hazard ratio=0.68). The study team will perform translational studies evaluating tumor tissue, whole blood and urine for molecular and immunologic markers of immune response and response to RT. Successful completion of this trial could lead to a new treatment paradigm for patients with muscle invasive bladder cancer. Clinical trial information: NCT03775265.

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.

PURPOSE To develop recommendations concerning the management of male breast cancer. METHODS ASCO convened an Expert Panel to develop recommendations based on a systematic review and a formal consensus process. RESULTS Twenty-six descriptive reports or observational studies met eligibility criteria and formed the evidentiary basis for the recommendations. RECOMMENDATIONS Many of the management approaches used for men with breast cancer are like those used for women. Men with hormone receptor–positive breast cancer who are candidates for adjuvant endocrine therapy should be offered tamoxifen for an initial duration of five years; those with a contraindication to tamoxifen may be offered a gonadotropin-releasing hormone agonist/antagonist plus aromatase inhibitor. Men who have completed five years of tamoxifen, have tolerated therapy, and still have a high risk of recurrence may be offered an additional five years of therapy. Men with early-stage disease should not be treated with bone-modifying agents to prevent recurrence, but could still receive these agents to prevent or treat osteoporosis. Men with advanced or metastatic disease should be offered endocrine therapy as first-line therapy, except in cases of visceral crisis or rapidly progressive disease. Targeted systemic therapy may be used to treat advanced or metastatic cancer using the same indications and combinations offered to women. Ipsilateral annual mammogram should be offered to men with a history of breast cancer treated with lumpectomy regardless of genetic predisposition; contralateral annual mammogram may be offered to men with a history of breast cancer and a genetic predisposing mutation. Breast magnetic resonance imaging is not recommended routinely. Genetic counseling and germline genetic testing of cancer predisposition genes should be offered to all men with breast cancer.