Changes In Treatment Recommendations Research Articles

The REMAR (Rhein-Main-Registry) real-world study: prospective evaluation of the 21-gene breast recurrence score® assay in addition to Ki-67 for adjuvant treatment decisions in early-stage breast cancer

PurposeKi-67 is recommended by international/national guidelines for risk stratification in early breast cancer (EBC), particularly for defining “intermediate risk,” despite inter-laboratory/inter-observer variability and cutoff uncertainty. We investigated Ki-67 (> 10%– < 40%, determined locally) as a prognostic marker for intermediate/high risk in EBC, pN0-1 patients.MethodsThis prospective, non-interventional, real-world study included females ≥ 18 years, with pN0/pN1mi/pN1, HR+ , HER2-negative EBC, and locally determined Ki-67 ranging 10%–40%. The primary outcome was changes in treatment recommendations after disclosing the Oncotype DX Breast Recurrence Score®(RS) assay result.ResultsThe analysis included 567 patients (median age, 57 [range, 29–83] years; 70%/1%/29%/ with pN0/pN1mi/pN1 disease; 81% and 19% with RS results 0–25 and 26–100, respectively). The correlations between local and central Ki-67, local Ki-67, and the RS, and central Ki-67 and the RS results were weak (r = 0.35, r = 0.3, and r = 0.46, respectively), and discrepancies were noted in both directions (e.g., local Ki-67 was lower or higher than central Ki-67). After disclosing the RS, treatment recommendations changed for 190 patients (34%). Changes were observed in pN0 and pN1mi/pN1 patients and in patients with centrally determined Ki-67 ≤ 10% and > 10%. Treatment changes were aligned with RS results (adding chemotherapy for patients with higher RS results, omitting it for lower RS results), and their net result was 8% reduction in adjuvant chemotherapy use (from 32% pre-RS results to 24% post-RS results).ConclusionThe Oncotype DX® assay is a tool for individualizing treatments that adds to classic treatment decision factors. The RS result and Ki-67 are not interchangeable, and Ki-67, as well as nodal status, should not be used as gatekeepers for testing eligibility, to avoid under and overtreatment.

298 (PB-114) Poster - Changes in treatment recommendations for patients with ductal carcinoma in situ using a 7-gene predictive biosignature: Analysis of the Australian PREDICT registry

298 (PB-114) Poster - Changes in treatment recommendations for patients with ductal carcinoma in situ using a 7-gene predictive biosignature: Analysis of the Australian PREDICT registry

Looking Back: International Practice Patterns in Breast Radiation Oncology From a Case-Based Survey Across 54 Countries During the First Surge of the COVID-19 Pandemic.

The COVID-19 pandemic has profoundly affected cancer care worldwide, including radiation therapy (RT) for breast cancer (BC), because of risk-based resource allocation. We report the evolution of international breast RT practices during the beginning of the pandemic, focusing on differences in treatment recommendations between countries. Between July and November 2020, a 58-question survey was distributed to radiation oncologists (ROs) through international professional societies. Changes in RT decision making during the first surge of the pandemic were evaluated across six hypothetical scenarios, including the management of ductal carcinoma in situ (DCIS), early-stage, locally advanced, and metastatic BC. The significance of changes in responses before and during the pandemic was examined using chi-square and McNemar-Bowker tests. One thousand one hundred three ROs from 54 countries completed the survey. Incomplete responses (254) were excluded from the analysis. Most respondents were from the United States (285), Japan (117), Italy (63), Canada (58), and Brazil (56). Twenty-one percent (230) of respondents reported treating at least one patient with BC who was COVID-19-positive. Approximately 60% of respondents reported no change in treatment recommendation during the pandemic, except for patients with metastatic disease, for which 57.7% (636/1,103; P < .0005) changed their palliative practice. Among respondents who noted a change in their recommendation during the first surge of the pandemic, omitting, delaying, and adopting short-course RT were the most frequent changes, with most transitioning to moderate hypofractionation for DCIS and early-stage BC. Early in the COVID-19 pandemic, significant changes in global RT practice patterns for BC were introduced. The impact of published results from the FAST FORWARD trial supporting ultrahypofractionation likely confounded the interpretation of the pandemic's independent influence on RT delivery.

American College of Allergy, Asthma and Immunology members' preferred steps 1 to 3 asthma maintenance and reliever therapy and incomplete insurance coverage indicated as main practice hurdle

BackgroundNew asthma guidelines (GINA, 2022; NAEPP EPR-4, 2020) include considerable changes in treatment recommendations, specifically regarding anti-inflammatory rescue and Single MAintenance and Reliever Therapy (SMART). ObjectiveTo explore American College of Allergy, Asthma and Immunology members’ preferred treatment and perceived hurdles. MethodsA survey (SurveyMonkey) regarding steps 1 to 3 asthma therapy was e-mailed to American College of Allergy, Asthma and Immunology members. ResultsThe allergists completed 147 surveys (46% with >20 years of experience; 98% from United States; 29% academic, 75% [also] private practice). In addition, 69% follow the National Asthma Education and Prevention Program and 81% the Global Initiative for Asthma recommendations. Of 147 allergists, 117 (80%) indicated correctly what SMART strategy is; 21%/36%/50%/39% would use SMART in step 3 treatment of a below 5-year-old/5- to 11-year-old/12- to 65-year-old/above 65-year-old patient, respectively. In this group, 11% to 14% incorrectly chose inhaled corticosteroid (ICS) plus salmeterol and 9% ICS plus vilanterol for SMART. In a 4-year-old needing step 1 therapy (N = 129), 55% of the respondents would add anti-inflammatory therapy; for step 2 treatment, most would prescribe ICS 100 to 200 µg budesonide equivalent daily; in step 3, 49% would prescribe ICS plus long-acting beta-agonist (LABA). In a 7-year-old needing step 1 treatment (N = 134), 40% would prescribe only short-acting beta-agonist; in step 3, 45% would institute SMART strategy, but only 8 of 135 (6%) chose very-low dose ICS plus formoterol (as recommended in Global Initiative for Asthma); most (39%) use low-dose ICS plus formoterol. As for rescue therapy, 59% is now instituting some form of anti-inflammatory rescue. Finally, in a 25-year-old patient (N = 144): in step 1, 39% would prescribe exclusively short-acting beta-agonist; in step 2, 4% only anti-inflammatory rescue and the rest prescribes ICS maintenance; one-third begins SMART strategy at step 2 and 50% in step 3.Major hurdles for prescribing one's preferred strategy included incomplete insurance coverage, insurance not approving more than one canister of ICS-formoterol per month, and cost. ConclusionAsthma therapy varies among physicians, with respondents suggesting underutilization of the recommended anti-inflammatory rescue and SMART therapy. A major hurdle is lack of insurance coverage of medication in line with the guidelines.

Multidisciplinary prostate cancer consultation at home: Does the virtual visit platform adversely affect care for elderly patients or impact treatment recommendations?

1521 Background: Amidst the COVID-19 pandemic, Hartford Healthcare (HHC) implemented a multidisciplinary virtual visit prostate cancer clinic (MDVV) to allow patients to receive cancer consultations at home. This clinic has shown significant logistical advantages for provision of coordinated cancer care. To evaluate concerns regarding usability of the telehealth platform for elderly patients, and the absence of in person physical exam at initial consult, we evaluated the MDVV in terms of patient satisfaction based on age, as well as for differences in treatment recommendations after patients were seen in-person at a pre-treatment follow up visit. Methods: Patients with newly diagnosed or progressive prostate cancer were offered a MDVV consultation. Those who assented had sequential virtual consultations with a urologic surgeon, a radiation oncologist, and a medical oncologist, followed by a group conference with all 3 specialists, and were guided through the visit by a nurse navigator. Patients then completed a 7 item satisfaction survey using a 5 point Likert scale evaluating their perception of the efficacy, efficiency, coordination, and overall value of the clinic. Responses were stratified by age group and compared. Chart review determined the impact of subsequent in person office visit on treatment recommendations, and the proportion of patients who underwent staging imaging according to NCCN guidelines. This was compared with a cohort of consecutive patients who completed traditional consults with two high volume prostate cancer surgeons immediately before the pandemic. Results: A total of 161 patients with newly diagnosed or progressive prostate cancer received a MDVV consultation from August 2020 – February 2023. Patient age ranged from 47-84 years (9% &lt; 60 yrs, 52% 60-70 yrs, 34% 70-80 yrs, 5% &gt;80 yrs). The median score for patient satisfaction on all 7 domains was 1 (strongly agree), and did not differ between age groups. There were no instances of a change in treatment recommendation after follow up in person office visit. While 100% of the MDVV cohort received multidisciplinary consultation before treatment, only 14/50 traditional cohort patients (28%) ultimately received the same (p&lt;.001). 100% of MDVV patients underwent imaging according to NCCN guidelines, compared with 33/50 (66%) of traditional patients (p&lt;.001). Conclusions: A virtual format for a multidisciplinary prostate cancer clinic is a logistically advantageous, effective means of offering in-home consultation to prostate cancer patients, leading to high patient satisfaction, regardless of age. The absence of in-person physical examination at initial consultation did not ultimately impact treatment recommendations. This format also improved access to multidisciplinary consultation and increased adherence to imaging guidelines.

Abstract OT3-11-03: The PREDICT Registry Australia: A prospective registry to evaluate the clinical utility of a 7-gene predictive biosignature on treatment decisions in patients with ductal carcinoma in situ

Abstract Background: For women with ductal carcinoma in situ (DCIS) treated with breast conserving surgery (BCS), the benefit of adjuvant radiation therapy (RT) remains controversial. Since there is level 1 evidence supporting the role of RT in reducing the risk of local recurrence, current guidelines generally recommend RT for all women having BCS even though the absolute benefit is variable. In response to the need for prognostic and predictive tools to better assess risk and RT benefit, a 7-gene predictive biosignature (DCISionRT, PreludeDx, Laguna Hills, CA) was developed. The test provides a validated score (DS) for assessing 10-year risk of recurrence and RT benefit using individual tumor biology, as assessed by clinical and pathologic biomarkers. The primary objective of the PREDICT registries is to understand the decision impact such a tool has on treatment decisions. Prospective Clinical Trial Design: This is a multicenter, prospective, observational registry for women diagnosed with DCIS in Australia. After DCIS diagnosis, sites will send the most representative tissue block or sections mounted on charged slides to the PreludeDx lab for biosignature testing. Treating physicians will complete a treatment recommendation survey before and after receiving the biosignature test results. Test results, treatment recommendations, patient preferences and clinicopathologic features will be stored in a de-identified registry for participating institutions from a variety of geographic regions across Australia. Women will then be followed for up to 10 years with completion of a follow-up form. The study has been approved by the North Shore Local Health District Human Research Ethics Committee, St Leonards, NSW, Australia. Universal Trial Number (UTN): U1111-1266-0439; ANZCTR: ACTRN12621000695808; ClinicalTrials.gov: NCT04916808. Eligibility Criteria: The study includes females age 26 or older who are candidates for BCS and eligible for RT and/or systemic treatment. Subjects must not have been previously treated for DCIS or have previous or current invasive or micro-invasive breast cancer. Specific Aims: The primary endpoints are changes in treatment recommendations for surgical, radiation and hormonal therapy. Secondary endpoints are identification of key drivers for treatment recommendations, including age, size, grade, necrosis, hormone receptor status, patient preference and biosignature status. Statistical Methods: Changes in pre- and post-DCISionRT treatment recommendations will be analyzed using McNemar’s test (alpha level = 0.05). Multivariate logistic regression will be used to determine odds ratios of clinicopathologic factors leading to pre- and post-test treatment recommendations. Pre-test covariates include patient age, tumor size, palpability, margin status, hormone receptor status, nuclear grade, tumor necrosis, family history of breast cancer, race, ethnicity and patient preference, as well as physician specialty (surgeons vs. radiation oncologists) and post-test covariates will also include the DCISionRT Decision Score (DS). Differences in recurrence-free and overall survival will be assessed by Kaplan-Meier survival analysis using the log-rank test and/or the Cox Proportional Hazards model. Statistical analyses will be carried out using R (https://www.r-project.org) or SAS. An early interim analysis based on the first 200 enrolled patients is currently underway. Present and Planned Accrual: We are planning to enroll up to 1,500 women from up to 100 sites across Australia. A similar registry has recently completed enrollment of 2,500 women from 68 sites in the US. Citation Format: Yvonne Zissiadis, G Bruce Mann, David Speakman, Christobel Saunders, Christopher Pyke, Daniel De Viana, Melissa Bochner, James R. French, Marcus Dreosti, Sally Baron-Hay, Alexandra Feetham, Kim Kirkham, Shane Ryan, Karuna Mittal, Steven C. Shivers, Troy Bremer. The PREDICT Registry Australia: A prospective registry to evaluate the clinical utility of a 7-gene predictive biosignature on treatment decisions in patients with ductal carcinoma in situ [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-11-03.

Step 1-3 Asthma Treatment Among Allergists Affected By Reduced Insurance Coverage

New asthma guidelines (GINA, 2022; NAEPP EPR-4, 2020), include considerable changes in treatment recommendations, specifically regarding anti-inflammatory rescue and MAintenance and Reliever Therapy (MART). We wanted to explore ACAAI members’ preferred treatment and perceived hurdles.

The impact of ankle haemarthropathy in patients with moderate haemophilia.

Moderate haemophilia has traditionally been associated with less complications than severe haemophilia. Changes in treatment recommendations have highlighted the burden of moderate haemophilia with a subset of patients with a severe bleeding phenotype. The ankle joint is disproportionally affected by ankle haemarthropathy however the impact has not been evaluated in moderate haemophilia, nor the effect on health related quality of life (HRQoL) or foot and ankle outcomes. To establish the impact of ankle haemarthropathy in patients with moderate haemophilia. A multicentre questionnaire study recruited patients from 11 haemophilia centres in England, Scotland and Wales. The HAEMO-QoL-A and Manchester-Oxford foot and ankle questionnaire (MOXFQ) with total and domain scores measured impact. Measures of pain and ankle haemophilia joint health (HJHS) scores were also collected. Twenty-nine participants were recruited. HAEMO-QoL A mean (SD) total scores of 10.8 (5.2) of 100 (best health) and foot and ankle specific MOXFQ total scores of 45.5 (24.7) above zero (best outcome) indicate poor HRQoL and foot and ankle outcomes. Average ankle pain over past 6 months of (0-10) 5.5 (SD2.5) was reported and median (IQR) ankle HJHS of 3.0 (1;12.5) to 4.5 (0;9.5) for the left and right ankles. HRQoL and foot and ankle specific outcomes are poor in patients with moderate haemophilia and ankle haemarthropathy, driven by chronic levels of ankle joint pain. Despite moderate haemophilia being considered less affected by haemarthrosis and haemarthropathy, patients with a bleeding or haemarthropathy phenotype are clinically similar to patients with severe haemophilia A.

What Primary Care Practitioners Need to Know about the New NICE Guideline for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Adults.

The new NICE guideline for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), published in October 2021, makes significant changes in treatment recommendations. It acknowledges the complexity of this chronic medical condition, which always impacts quality of life and can be profoundly disabling, recognising the prejudice and stigma that people with ME/CFS often experience in the absence of any specific diagnostic test. The guideline outlines steps for accurate diagnosis, recognising post-exertional malaise as a core symptom; importantly, ME/CFS can now be diagnosed after just 3 months in a bid to improve long-term health outcomes. It recommends the need for individual, tailored management by a multi-disciplinary team, ensuring that the wellbeing of the individual is paramount. The guideline makes clear that any programme based on fixed incremental increases in physical activity or exercise, for example, graded exercise therapy (GET), should not be offered as a treatment for ME/CFS and emphasises that cognitive behavioural therapy (CBT) should only be offered as a supportive intervention. Because of the rigorous methodology required by NICE Committee review and the inclusion of the testimony of people with lived experience as committee members, this guideline will influence the future diagnosis and management of ME/CFS in the UK and beyond.

The PREDICT Registry Australia: A Prospective Registry to Evaluate the Clinical Utility of a Biomarker Assay on Treatment Decisions in Patients with DCIS Following Breast Conserving Surgery

<h3>Purpose/Objective(s)</h3> The benefit of adjuvant radiation therapy (RT) for women with ductal carcinoma in situ (DCIS) treated with breast conserving surgery (BCS) remains controversial. Although level-I evidence supports the role of RT in reducing the risk of local recurrence, the absolute benefit of RT is variable and so it is important to develop better prognostic and predictive tools. The assay under evaluation is a biologic signature that provides a validated decision score (DS) for assessing 10-year risk of recurrence and RT benefit using individual tumor biology as assessed by clinical and pathologic biomarkers. The primary objective of the PREDICT registries is to understand the decision impact such a tool has on treatment decisions. The hypothesis is that the biomarker assay is associated with changes in treatment recommendations for surgical, hormonal and/or radiation therapy. <h3>Materials/Methods</h3> This is a multi-center, prospective, observational study for women diagnosed with DCIS of the breast. After diagnosis, sites will send the most representative tissue block or sections for testing. Treating physicians complete a treatment recommendation survey before and after receiving test results. Test results, treatment recommendations, patient preferences and clinicopathologic features will be stored in a de-identified registry for participating institutions from a variety of geographic regions across Australia. Women will be followed for up to 10 years with completion of a follow-up form. The study includes females age 26 or older who are candidates for BCS and eligible for RT and/or systemic treatment. Subjects must not have been previously treated for DCIS or have previous or current invasive or micro-invasive breast cancer. The primary endpoints are changes in treatment recommendations for surgical, radiation and hormonal therapy. Secondary endpoints are identification of key drivers for treatment recommendations, including clinicopathologic factors and patient preference. Changes in pre- and post-test treatment recommendations will be analyzed using McNemar's test (alpha level = 0.05). Multivariate logistic regression will be used to determine odds ratios of clinicopathologic factors leading to pre- and post-test treatment recommendations. Pre-test covariates include patient age, tumor size, palpability, margin status, hormone receptor status, nuclear grade, tumor necrosis, family history, race, ethnicity and patient preference, as well as physician specialty and post-test covariates will also include the DS. Differences in recurrence-free and overall survival will be assessed by Kaplan-Meier survival analysis using the log-rank test and/or the Cox Proportional Hazards model. We are planning to enroll up to 1,500 women from up to 100 sites across Australia. A similar registry in the US has enrolled 2,500 women from 67 sites. <h3>Results</h3> TBD <h3>Conclusion</h3> TBD

162P MammaPrint 10-year follow up results from a German breast cancer cohort study

MammaPrint (MP) is a 70-gene signature, which has been validated in multiple studies and has proven to be a powerful predictor of risk of recurrence in patients with breast cancer (BC). In a German validation study using samples from the Patients Tumor Bank of Hope (PATH), the degree of concordance between MP and clinical risk classifications valid at that time has been determined retrospectively. MP use was shown to be feasible in a German study population revealing a change in treatment recommendation in 40% of patients (Gevensleben H et al.

The Impact of a Dedicated Chronic Total Occlusion PCI Program on Heart Team Decision Making.

Guidelines endorse a heart team (HT) approach to standardize the decision-making process for patients with complex coronary artery disease (CAD). With percutaneous treatment options for complex CAD increasing, we hypothesized that practice had changed over the past decade-and that more individuals, previously deemed too high risk for intervention, would now be referred for either surgical or percutaneous revascularization. This observational study was conducted at St Thomas' Hospital (London, United Kingdom). All patients discussed at HT meetings were recorded and treatment recommendations audited. A subset of historic cases was selected for blinded, repeat discussion. From April 2018 to 2019, a total of 52 HT meetings discussing 375 cases were held. Patients tended to be male, with a majority demonstrating multivessel CAD in the context of preserved left ventricular function. SYNTAX scores were balanced across the tertiles. Thirty-five percent of patients had at least 1 chronic total occlusion (mean J-CTO, 3 [interquartile range, 2-3]), affecting the right coronary artery in 60%. Fifteen historic patients with isolated CTOs were re-presented an average of 8 years later; only 3 patients received the same outcome, with 80% now receiving a recommendation for revascularization over medical therapy. A dedicated program supporting complex coronary intervention is associated with a change in treatment recommendations issued by the local HT. In line with international guidelines, this might indicate that any complex or multivessel CAD should be discussed at HT meetings with, ideally, the presence of CTO operators.

Burnout Among Respiratory Therapists Amid the COVID-19 Pandemic.

Burnout is a major challenge in health care and is associated with poor overall well-being, increased medical errors, worse patient outcomes, and low job satisfaction. There is scant literature focused on the respiratory therapist's (RT) experience of burnout, and a thorough exploration of RTs' perception of factors associated with burnout has not been reported. The aim of this qualitative study was to understand the factors associated with burnout as experienced by RTs amid the COVID-19 pandemic. We performed a post hoc, qualitative analysis of free-text responses from a survey of burnout prevalence in RTs. There were 1,114 total and 220 free-text responses. Five overarching themes emerged from the analysis: staffing, workload, physical/emotional consequences, lack of effective leadership, and lack of respect. Respondents discussed feelings of anxiety, depression, and compassion fatigue as well as concerns that lack of adequate staffing, high workload assignments, and inadequate support from leadership contributed to feelings of burnout. Specific instances of higher patient acuity, surge in critically ill patients, rapidly evolving changes in treatment recommendations, and minimal training and preparation for an extended scope of practice were reported as stressors that led to burnout. Some respondents stated that they felt a lack of respect for both the RT profession and the contribution of RTs to patient care. Themes associated with burnout in RTs included staffing, workload, physical and emotional exhaustion, lack of effective leadership, and lack of respect. These results provide potential targets for interventions to combat burnout among RTs.

Impact of the 21-Gene Recurrence Score Assay on Treatment Decisions and Cost in Patients with Node-Positive Breast Cancer: A Multicenter Study in Quebec.

BackgroundThe 21-gene Breast Recurrence Score (RS) assay, “the assay”, has led to a paradigm shift for patients with hormone receptor-positive, node-negative early breast cancer and is emerging as an important tool to assist physician-patient decisions in foregoing chemotherapy in node-positive patients. We wanted to better understand the impact of the RS assay in node-positive patients upon physician treatment decisions and treatment cost in Quebec, Canada.Patients and MethodsWe conducted a multicenter, prospective observational trial for Estrogen/Progesterone Receptor (ER/PR)- positive, Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer patients with 1-3 positive lymph nodes. Physicians completed a questionnaire indicating treatment choice prior to and post availability of RS results. The primary endpoint was change in the physician’s recommendation for chemotherapy prior to and post assay results. Secondary endpoints included change in physician’s expressed level of confidence, and changes in estimated cost of recommended treatments prior to and post assay results.ResultsFor the entire cohort, physician recommendation for chemotherapy was reduced by an absolute 67.1% by knowledge of the RS assay result (P < .0001). Physician recommendation of chemotherapy was decreased by 75.9% for patients RS result <14 (P < .0001); and 67.5% for patients with RS result 14-25 (P < .0001). Changes in treatment recommendations were associated with an overall reduction in cost by 73.7% per patient, and after incorporating the cost of the RS test, a cost benefit of $823 CAN at 6-month follow-up.ConclusionAltogether, we established that the assay led to a two-third reduction in the use of chemotherapy, and was a cost-effective approach for hormone receptor-positive, node-positive breast cancer.

The Effect of Changes in Treatment Recommendations for Gestational Diabetes on Perinatal Morbidity [A191

INTRODUCTION: Evidence about the lack of efficacy of glyburide prompted the American College of Obstetricians and Gynecologists (ACOG) to recommend insulin as first-line treatment and metformin as an alternative for treatment of gestational diabetes (GDMA2) in February 2018. This study compared the treatments and perinatal outcomes in women before and after the ACOG recommendations. METHODS: This was a retrospective study of patients treated for GDMA2. Patients were divided into two groups (group 1: February 2016 to January 2018; group 2: February 2018 to January 2020). The primary outcome was comparison of perinatal outcomes between the groups during those two periods. The secondary outcome was comparison of the effect of glyburide, metformin, and insulin on perinatal outcomes regardless of the time frame. Outcomes were also compared between insulin glargine and insulin NPH. Maternal outcomes included rates of primary cesarean delivery, preeclampsia, and ICU admission. Neonatal outcomes included large for gestational age, shoulder dystocia, NICU admission, hypoglycemia, hyperbilirubinemia, and stillbirth. Institutional review board approval was obtained. RESULTS: A total of 160 patients received medications. Baseline characteristics were similar. Insulin was the most common medication used in both groups (58%). In group 1, 21 patients received glyburide versus seven in group 2 (P=.01). There was no difference regarding insulin or metformin use between groups (P&gt;.05). Perinatal outcomes were similar in both groups (P&gt;.05). Regardless of time frame, NICU admissions (P=.01) and shoulder dystocia (P=.04) were higher with glyburide. Preeclampsia rates were lower in women receiving insulin NPH (P=.03). CONCLUSION: Glyburide use decreased after ACOG recommendations. Decline in use of glyburide is not accompanied by significant improvements in perinatal morbidity. Regardless of time frame, glyburide is associated with higher neonatal adverse outcomes and NPH with decrease in maternal adverse outcomes.

Artificial Intelligence-Assisted Serial Analysis of Clinical Cancer Genomics Data Identifies Changing Treatment Recommendations and Therapeutic Targets.

Given the pace of predictive biomarker and targeted therapy development, it is unknown whether repeat annotation of the same next-generation sequencing data can identify additional clinically actionable targets that could be therapeutically leveraged. In this study, we sought to determine the predictive yield of serial reanalysis of clinical tumor sequencing data. Using artificial intelligence (AI)-assisted variant annotation, we retrospectively reanalyzed sequencing data from 2,219 patients with cancer from a single academic medical center at 3-month intervals totaling 9 months in 2020. The yield of serial reanalysis was assessed by the proportion of patients with improved strength of therapeutic recommendations. A total of 1,775 patients (80%) had ≥1 potentially clinically actionable mutation at baseline, including 243 (11%) patients who had an alteration targeted by an FDA-approved drug for their cancer type. By month 9, the latter increased to 458 (21%) patients mainly due to a single pan-cancer agent directed against tumors with high tumor mutation burden. Within this timeframe, 67 new therapies became available and 45 were no longer available. Variant pathogenicity classifications also changed leading to changes in treatment recommendations for 124 patients (6%). Serial reannotation of tumor sequencing data improved the strength of treatment recommendations (based on level of evidence) in a mixed cancer cohort and showed substantial changes in available therapies and variant classifications. These results suggest a role for repeat analysis of tumor sequencing data in clinical practice, which can be streamlined with AI support.

Abstract OT1-09-02: The PREDICT Registry: A prospective registry to evaluate the effect of a predictive assay on treatment decisions in patients with DCIS following breast conserving therapy

Abstract Background. The benefits of adjuvant radiation therapy (RT) in patients with ductal carcinoma in situ (DCIS) treated with breast conserving surgery (BCS) remains controversial. Although there is level-I evidence supporting the role of RT in reducing the risk of local recurrence, the absolute benefit is variable. Current guidelines generally recommend RT for all patients having BCS, but it is important to develop prognostic and predictive tools to better assess risk and understand the impact such a tool would have on treatment decisions. The DCISionRT Test(PreludeDx, Laguna Hills, CA) is a biologic signature that provides a validated score for assessing 10-year risk of recurrence and RT benefit using individual tumor biology as assessed by clinical and pathologic biomarkers. Methods. This is a prospective cohort study for patients diagnosed with DCIS of the breast. Treating physicians complete a treatment recommendation survey before and after receiving DCISionRT test results. Test results, treatment recommendations, patient preferences and clinico-pathologic features are stored in a de-identified registry for participating institutions from a variety of geographic regions across the US. The study will also collect 5- and 10-year recurrence and survival data. The study includes females over age 25 who are candidates for BCS and eligible for RT and/or systemic treatment with sufficient tissue to generate test results. Subjects must not have been previously treated for DCIS or have previous or current invasive or micro-invasive breast cancer. The primary endpoints are changes in treatment recommendations for surgical, radiation and hormonal therapy. Secondary endpoints are identification of key drivers for treatment recommendations, including age, size, grade, necrosis, hormone receptor status and other clinico-pathologic factors. Changes in treatment recommendations will be assessed using McNemar's test with an alpha level of 0.05. Differences in recurrence-free and overall survival will be evaluated by Kaplan-Meier survival analysis using the log-rank test and/or the Cox Proportional Hazards model. A planned early interim analysis based on the first 200 patients has been recently completed and reported. Results. As of July 9, 2021, 1,986 patients have been accrued from 64 institutions. Ten additional institutions are currently in the process of joining the study. We are planning to enroll up to 2,500 patients from up to 100 institutions. Citation Format: Steven C Shivers, Pat W Whitworth, Rakesh Patel, Troy Bremer, Charles E Cox. The PREDICT Registry: A prospective registry to evaluate the effect of a predictive assay on treatment decisions in patients with DCIS following breast conserving therapy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-09-02.

Abstract OT1-11-01: The PREDICT registry Australia: A prospective registry study to evaluate the clinical utility of the DCISionRT test on treatment decisions in patients with DCIS following breast conserving surgery

Abstract Background: The benefit of adjuvant radiation therapy (RT) for women with ductal carcinoma in situ (DCIS) treated with breast conserving surgery (BCS) remains controversial. Since there is level-I evidence supporting the role of RT in reducing the risk of local recurrence, current guidelines generally recommend adjuvant RT for all women having BCS. However, the absolute benefit of RT is variable in women with DCIS and so it is important to develop prognostic and predictive tools to better assess risk and RT benefit. The DCISionRT Test (PreludeDx, Laguna Hills, CA) is a biologic signature that provides a validated score (DS) for assessing 10-year risk of recurrence and RT benefit using individual tumor biology, as assessed by clinical and pathologic biomarkers. The primary objective of the PREDICT registries is to understand the decision impact such a tool would have on treatment decisions. Prospective Clinical Trial Design: This is a multicenter, prospective, non-interventional (observational) cohort study for women diagnosed with DCIS of the breast. After diagnosis of DCIS, sites will send the most representative tissue block or sections mounted on charged slides to PreludeDx for DCISionRT testing. Treating physicians complete a treatment recommendation survey before and after receiving DCISionRT test results. Test results, treatment recommendations, patient preferences and clinicopathologic features will be stored in a de-identified registry for participating institutions from a variety of geographic regions across Australia. Women will then be followed for up to 10 years with completion of a follow-up form. The study has been approved by the North Shore Local Health District Human Research Ethics Committee, St Leonards, NSW, Australia. Universal Trial Number (UTN): U1111-1266-0439; ANZCTR: ACTRN12621000695808; ClinicalTrials.gov: NCT04916808. Eligibility Criteria: The study includes females age 26 or older who are candidates for BCS and eligible for RT and/or systemic treatment. Subjects must not have been previously treated for DCIS or have previous or current invasive or micro-invasive breast cancer. Specific Aims: The primary endpoints are changes in treatment recommendations for surgical, radiation and hormonal therapy. Secondary endpoints are identification of key drivers for treatment recommendations, including age, size, grade, necrosis, hormone receptor status and patient preference. Statistical Methods: Changes in pre- and post-DCISionRT treatment recommendations will be analyzed using McNemar's test (alpha level = 0.05). Multivariate logistic regression will be used to determine odds ratios of clinicopathologic factors leading to pre- and post-test treatment recommendations. Pre-test covariates include patient age, tumor size, palpability, margin status, hormone receptor status, nuclear grade, tumor necrosis, family history of breast cancer, race, ethnicity and patient preference, as well as physician specialty (surgeons vs. radiation oncologists) and post-test covariates will also include the DCISionRT Decision Score (DS). Differences in recurrence-free and overall survival will be assessed by Kaplan-Meier survival analysis using the log-rank test and/or the Cox Proportional Hazards model. Statistical analyses will be carried out using R (https://www.r-project.org) or SAS. An early interim analysis based on the first 200 enrolled patients is planned. Present and Planned Accrual: We are planning to enroll up to 1,500 women from up to 100 sites across Australia. A similar registry in the US has enrolled 1,985 women from 64 sites towards a goal of 2,500. Citation Format: Yvonne Zissiadis, G Bruce Mann, Steven C Shivers, Troy Bremer. The PREDICT registry Australia: A prospective registry study to evaluate the clinical utility of the DCISionRT test on treatment decisions in patients with DCIS following breast conserving surgery [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-11-01.

STANDARDS OF MEDICAL CARE “INVASIVE CANDIDIASIS IN NEWBORNS”

Candida infection (candidiasis) is an important clinical problem in newborns who need treatment in modern intensive care units. Organ and/or systemic infections caused by these fungi are called invasive candidiasis (IC). Newborns are especially vulnerable to IC, and their incidence is 3-5 times higher than the corresponding rates in children or adults. Invasive fungal infections caused by Candida are the third most common late-onset infection in infants born with a birth weight &lt;1500 g. IC in newborns is associated with approximately 20% mortality, and about half of survivors have serious long- term neurological damage. In recent years, new data have been obtained on the diagnosis, prevention and treatment of IC in newborns, which has determined a change in treatment recommendations. Accordingly, the need arose to ensure the compliance of our clinical practice with modern evidence-based approaches. Early diagnosis of candidiasis and prompt treatment with effective antifungal agents such as fluconazole, amphotericin B, and micafungin, when indicated, are critical to improving outcomes.

Impact of the EndoPredict genomic assay on treatment decisions for oestrogen receptor-positive early breast cancer patients: benefits of physician selective testing.

Genomic tests improve accuracy of risk prediction for early breast cancers but these are expensive. This study evaluated the clinical utility of EndoPredict®, in terms of impact on adjuvant therapy recommendations and identification of parameters to guide selective application. Patients with ER-positive, HER2-negative, and early-stage invasive breast cancer were tested with EndoPredict®. Two cohorts were recruited: one consecutively and another at clinical team discretion. Systemic treatment recommendations were recorded before and after EndoPredict® results were revealed to the multidisciplinary team. 233 patients were recruited across five sites: 123 consecutive and 110 at clinical team discretion. In the consecutive cohort 50.6% (62/123) cases were classified high risk of recurrence by EndoPredict®, compared with 62.7% (69/110) in the selective cohort. A change in treatment recommendation was significantly more likely (p < 0.0001) in the selective cohort (43/110, 39.1%) compared to the consecutive group (11/123, 8.9%). The strongest driver of selective recruitment was intermediate grade histology, whilst logistic regression modelling demonstrated that nodal status (p < 0.001), proliferative rate (p = 0.001), and progesterone receptor positivity (p < 0.001) were the strongest discriminators of risk. Whilst molecular risk can be predicted by traditional variables in a high proportion of cases, EndoPredict® had a greater impact on treatment decisions in those cases selected for testing at team discretion. This is indicative of the robust ability of the clinical team to identify cases most likely to benefit from testing, underscoring the value of genomic tests in the oncologists' tool kit.