Recommendations For Therapy Research Articles

High Levels of Statin non‐acceptance shown to persists

Heart disease is the leading cause of death worldwide and statin therapy has consistently shown in multiple landmark studies to reduce cardiovascular events and death. Despite the strength of evidence of its benefits, clinicians face many patients who are reluctant to start statin therapy. A new study published in the JAMA Network Open, by investigators from Brigham and Women's Hospital has conducted the first population-based study on patients’ non-acceptance of statin therapy recommendations. The study focused on high-risk patients who either had coronary artery or vascular disease, diabetes, high cholesterol levels, or previous history of stroke. All of these patients were recommended statins by their physicians, by virtue of their high cardiovascular risk in order to reduce their risk of heart attack and stroke and reduce cholesterol levels. The retrospective study included more than 24,000 patients who were seen at Mass General Brigham between Jan. 1, 2000, and Dec. 31, 2018. The study found that in patients at high risk of developing cardiovascular disease, more than 20 percent of patients refused to take statin medications. Interestingly, they observed that women were more likely than men to refuse statin therapy, by about 20%, and 50 percent more likely than men to never accept the recommendation. The study also showed that all patients who refused statin therapy developed higher LDL cholesterol levels. Unfortunately, no data is available yet on whether nonacceptance of statin therapy wold adversely affect cardiovascular event rate such as heart attacks, strokes, and death. The study highlight the importance of targeting patients who decline statins by providing further education, understanding the reasons behind non-acceptance and devise strategies to further reduce patients cardiovascular disease risk.

MP10-14 TIKTOK AS AN EDUCATION TOOL FOR KIDNEY STONE PREVENTION

You have accessJournal of UrologyCME1 Apr 2023MP10-14 TIKTOK AS AN EDUCATION TOOL FOR KIDNEY STONE PREVENTION Bassel Salka, Firas Almsaddi, Hamza Kaakarli, Malik Aljamal, Sazid Hasan, Lauren Nesi, and Kenneth Lim Bassel SalkaBassel Salka More articles by this author , Firas AlmsaddiFiras Almsaddi More articles by this author , Hamza KaakarliHamza Kaakarli More articles by this author , Malik AljamalMalik Aljamal More articles by this author , Sazid HasanSazid Hasan More articles by this author , Lauren NesiLauren Nesi More articles by this author , and Kenneth LimKenneth Lim More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003225.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The incidence of kidney stones in the United States continues to increase. TikTok, a social media application with over one billion users worldwide, has emerged as an online center for medical knowledge sharing by physicians and non-physicians alike through short informational videos. Little is known regarding the quality of medical advice provided in these videos. The purpose of this study was to evaluate the reach and quality of kidney stone prevention information on TikTok. METHODS: We conducted a cross-sectional analysis of renal stone prevention content on TikTok utilizing the search term #kidneystoneprevention to assess all the videos appearing on October 10th, 2022. Only videos in English, related to the topic, and with >1000 views were included. Videos were analyzed for views, uploader profession, and stone prevention recommendations. Videos were assessed utilizing DISCERN, a questionnaire used to appraise the quality of consumer health information (max score of 80 per video). The one-way analysis of variance (ANOVA) was used to determine statistical significance groups. RESULTS: Out of a total of 131 videos, 87 fit the inclusion criteria, resulting in a total of 8.75 million views. An average DISCERN score of 27.0 was observed. Only 8 videos were published by physicians, of which the average DISCERN score of 35.3 was significantly greater than an average score of 26.2 for non-physicians (p<0.05). The most common recommendation was increased fluid intake (38.0%) followed by monitoring calcium levels (9.02%) and decreasing oxalate rich foods (9.2%). The most common nutritional supplementation was lemon water (8.0%). Table 1 displays the proportion of videos that match particular American Urologic Association (AUA) diet therapy recommendations. No pharmalogic therapies were addressed in any videos. CONCLUSIONS: Kidney stone prevention content on TikTok has a wide reach with millions of consumers. The majority of videos fail to match AUA recommendations regarding diet therapies for stone prevention. Further research is needed to understand the extent of kidney stone prevention misinformation on social media and how it contributes to patient outcomes. Increased engagement in TikTok by urologists and health organizations may improve public education. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e119 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Bassel Salka More articles by this author Firas Almsaddi More articles by this author Hamza Kaakarli More articles by this author Malik Aljamal More articles by this author Sazid Hasan More articles by this author Lauren Nesi More articles by this author Kenneth Lim More articles by this author Expand All Advertisement PDF downloadLoading ...

Relevance of tumor boards for the inclusion of patients in oncological clinical trials.

Major national and international oncological societies generally recommend treating a significant proportion of oncological patients in clinical trials to improve therapy strategies for cancer patients. At cancer centers, the recommendation about the appropriate therapy for the individual tumor patient is usually made in interdisciplinary case discussions in multidisciplinary tumor boards (MDT). In this study, we examined the impact of MDTs for the inclusion of patients in therapy trials. A prospective, explorative study of the Comprehensive Cancer Center Munich (CCCM) was conducted at both university hospitals in 2019. In the first phase, various MDTs' case discussions about oncological situations and their decisions regarding possible therapy trials were recorded in a structured manner. In the second phase, the actual inclusion rates of patients in therapy trials and reasons for non-inclusion were examined. Finally, the data of the respective university hospitals were anonymized, pooled and analyzed. A total of 1797 case discussions were reviewed. Therapy recommendations were made in 1527 case presentations. 38 (2.5%) of 1527 patients were already included in a therapy trial at the time of case presentation. The MDTs recommended inclusion of an additional 107 cases (7%), for a therapy trial. Of these patients, 41 were finally enrolled in a therapy trial which resulted in a total recruitment rate of 5.2%. Despite MDTs' recommendations, 66 patients were not included in a therapy trial. The main reason for non-inclusion was insufficient inclusion or existing exclusion criteria (n = 18, 28%). In 48% of all cases (n = 31), the reason for non-inclusion could not be determined. The potential of MDTs as an instrument for the inclusion of patients in therapy trials is high. To increase the enrollment of patients in oncological therapy trials, structural measures such as the central use of trial administration and MTB software in addition to standardized tumor board discussions must be established to ensure a seamless flow of information about actual recruiting trials and the current status of trial participation of patients.

Low intensity exercise training in patients with amyotrophic lateral sclerosis – factors influencing eligibility and compliance to the clinical trial

ABSTRACT Background To date, there are no evidence-based recommendations for physical therapy in amyotrophic lateral sclerosis (ALS). The reason is a low number of related clinical trials (CTs), restricted sample sizes and a high dropout rate. It may influence the profile of the participants, while the final results might not translate to the general ALS population. Objective To analyze factors affecting the ALS patients’ enrollment and retention to the study, and to describe a profile of participants as compared to the eligible group. Methods A total of 104 ALS patients were offered participation in a CT of low-intensity exercises at home. Forty-six patients were recruited. Demographic and clinical data (El Escorial criteria, site of onset, diagnosis delay, disease duration, amyotrophic lateral sclerosis functional rating scale – revised [ALSFRS-R], Medical Research Council [MRC], hand-held dynamometry) were analyzed every 3 months. Results Male gender, younger age and a higher ALSFRS predicted enrollment, while male gender, higher ALSFRS-R and MRC predicted retention in the study. A long commute to the study site and a fast disease progression were the main reasons influencing both enrollment and retention. Despite a high dropout rate, study participants were representative for the general ALS population. Conclusion The above demographic, clinical and logistic factors need to be considered when designing studies in ALS population.

Value of the clinical pharmacist interventions in the application of the American College of Cardiology (ACC/AHA) 2018 guideline for cholesterol management.

The study aims to examine the extent to which the updated ACC/AHA management of blood cholesterol guideline (2018) is implemented in practice and to assess the value of the clinical pharmacist interventions in improving physicians' adherence the guidelines recommendations. We utilized in this study an interventional before-after design. The study was conducted on 272 adult patients who visited the study site internal medicine clinics and were candidates for statin therapy based on the 2018 ACC/AHA guidelines for cholesterol management. Adherence to guideline recommendations was measured before and after clinical pharmacists' interventions by calculating the percentage of patients receiving statin therapy as per guideline recommendation, the type and intensity (moderate or high intensity) of statin therapy used, and the need for additional non-statin therapy. Adherence with guideline recommendations was significantly improved from 60.3% to 92.6% (X2 = 79.1, p = 0.0001) after clinical pharmacist interventions. Among patients who were on statin therapy, the percentage of those who were on proper statin intensity increased significantly from 47.6% to 94.4% (X2 = 72.5, p = 0.0001). The combination of statins with non-statin therapies such as ezetimibe and PCSK9 inhibitors increased from 8.5% to 30.6% (X2 = 95, p<0.0001) and from 0.0% to 1.6% (X2 = 6, p = 0.014), respectively. The use of other lipid-lowering agents was diminished from 14.6% to 3.2% (X2 = 19.2, p<0.0001). Collaboration between physicians and clinical pharmacists is a crucial strategy to improve patients' treatment and hence, achieve better health outcomes among patients suffering from dyslipidemia.

Cardiovascular Disease Risk Estimation for Transgender and Gender-Diverse Patients: Cross-Sectional Analysis of Baseline Data From the LITE Plus Cohort Study

Approximately 2% of the U.S. population identifies as transgender, and transgender people experience disproportionate rates of cardiovascular disease mortality. However, widely used cardiovascular disease risk estimators have not been validated in this population. This study sought to determine the impact on statin therapy recommendations using 3 different approaches to operationalizing sex in the American Health Association/American College of Cardiology Pooled Cohort Equation Risk Estimator. This is a cross-sectional analysis of baseline clinical data from LITE Plus, a prospective cohort study of Black and/or Latina transgender women with HIV. Data were collected from October 2020 to June 2022 and used to calculate Pooled Cohort Equation scores. The 102 participants had a mean age of 43 years. A total of 88% were Black, and 18% were Latina. A total of 79% were taking gender-affirming hormones. The average Pooled Cohort Equation risk score was 6% when sex assigned at birth was used and statins would be recommended for the 31% with Pooled Cohort Equation >7.5%. The average risk score was 4%, and 18% met the criteria for statin initiation when current gender was used; the mean risk score was 5%, and 22% met the criteria for statin initiation when current hormone therapy was used. Average Pooled Cohort Equation risk scores vary substantially depending on the approach to operationalizing the sex variable, suggesting that widely used cardiovascular risk estimators may be unreliable predictors of cardiovascular disease risk in transgender populations. Collection of sex, gender, and hormone use in longitudinal studies of cardiovascular health is needed to address this important limitation of current risk estimators.

Does Stage Migration Occur as a Consequence of Omitting Completion Lymph Node Dissection for Melanoma?

Completion lymph node dissection (CLND) is no longer recommended routinely in the treatment of melanoma. CLND omission may understage patients for whom the distinction between stage IIIA and IIIB-C could alter adjuvant therapy recommendations. The aim of this study is to determine if stage migration has occurred with the declining use of CLND. Patients with clinically node-negative ≥T1b cutaneous melanoma were identified from the National Cancer Database (NCDB) from 2012 to 2018. CLND utilization and changes in AJCC staging were analyzed. Patients undergoing sentinel lymph node biopsy (SLNB) alone were compared with those undergoing SLNB + CLND. Overall, 68,933 patients met inclusion criteria and 60,536 underwent SLNB, of which 9031 (14.9%) were tumor positive. CLND was performed in 3776 (41.8%). Patients undergoing CLND were younger (58 versus 62 years, p < 0.0001) and more likely male (61.5% versus 57.9%, p = 0.0005). Patients were more likely to have an N classification >N1a if they received SLNB + CLND (36.8%) versus SLNB alone (19.3%), p < 0.0001. This translated to a small difference in stage IIIA patients between groups (SLNB alone 34.0%, SLNB + CLND 31.8%, p < 0.0001). Of the patients with T1b/T2a tumors who would be upstaged from IIIA to IIIC with identification of additional positive nodes, IIIC incidence was only slightly higher after SLNB + CLND compared with SLNB alone (4.4% versus 1.1%, p < 0.0001). CLND utilization dramatically decreased from 59% in 2012 to 12.6% in 2018, p < 0.0001. However, the incidence of stage IIIA disease for all patients remained stable over the 7-year study period. While the utilization of CLND after positive SLNB has declined dramatically in the last 7 years, stage migration that may affect adjuvant therapy decisions has not occurred to a clinically meaningful degree.

Emergencies in movement disorders

Movement disorders can be defined as the abnormality of the speed and form of body movements. Although movement disorders often occur chronically, they can sometimes develop acutely or sub-acutely, and some can be fatal if not diagnosed and treated early. Here, emergencies in movement disorders are discussed under two main headings as emergencies related to hyperkinetic movement disorders and emergencies related to hypokinetic movement disorders. This review draws attention to the importance of that accurate diagnosis and early treatment can be life-saving in emergencies in movement disorders. It also provides recommendations for diagnosis and therapy.

Physical therapy and occupational therapy management of a person with bilateral transradial amputations: a case report

Objective This longitudinal case study describes the physical and occupational therapy interventions and recommendations for treatment of a person with bilateral transradial amputations during subacute rehabilitation, as there are currently few recommendations. Materials and methods A 53-year-old female with subacute bilateral transradial amputations received inpatient rehabilitation. Impairments include decreased balance, global weakness, and need for assistance with ADLs and transfers. Physical therapy, occupational therapy, nursing, a peer mentor, and a prosthetist collaborated. Interventions included task-specific and generalized strengthening, standing balance re-education, assistive device prescription, education using body-powered prostheses, home adaption recommendations, and activities of daily living practice. Results Patient progressed to independent functional mobility but required assist for activities of daily living and stairs negotiation due to limited caregiver support and poor prosthetic dexterity. She discharged to a skilled nursing facility. Conclusion Rehabilitation of a person with bilateral transradial amputations requires clinicians experienced with prostheses; excellent interdisciplinary coordination; early discernment of the available social support system; task-specific strengthening and coordination exercises to prepare the patient for prostheses; significant task-practice with prostheses; and a working knowledge of home modifications and adaptive equipment. This article describes recommendations, successful interventions, and lessons learned for future therapists when rehabilitating someone with bilateral transradial amputations. IMPLICATIONS FOR REHABILITATION Bilateral transradial amputations (BTAs) are a life-altering, but rare condition, meaning that literature surrounding this population is sparse and that guidelines for rehabilitation are unclear. This article provides recommendations so that clinicians can be better informed when treating BTA patients in the subacute phase and more quickly progress patients toward functional independence and discharge to the community.

Preclinical patient-derived modeling of castration-resistant prostate cancer facilitates individualized assessment of homologous recombination repair deficient disease.

The use of mutation analysis of homologous recombination repair (HRR) genes to estimate PARP-inhibition response may miss a larger proportion of responding patients. Here, we provide preclinical models for castration-resistant prostate cancer (CRPC) that can be used to functionally predict HRR defects. In vitro, CRPC LNCaP sublines revealed an HRR defect and enhanced sensitivity to olaparib and cisplatin due to impaired RAD51 expression and recruitment. Ex vivo-induced castration-resistant tumor slice cultures or tumor slice cultures derived directly from CRPC patients showed increased olaparib- or cisplatin-associated enhancement of residual radiation-induced γH2AX/53BP1 foci. We established patient-derived tumor organoids (PDOs) from CRPC patients. These PDOs are morphologically similar to their primary tumors and genetically clustered with prostate cancer but not with normal prostate or other tumor entities. Using these PDOs, we functionally confirmed the enhanced sensitivity of CRPC patients to olaparib and cisplatin. Moreover, olaparib but not cisplatin significantly decreased the migration rate in CRPC cells. Collectively, we present robust patient-derived preclinical models for CRPC that recapitulate the features of their primary tumors and enable individualized drug screening, allowing translation of treatment sensitivities into tailored clinical therapy recommendations.

Real-world performance analysis of a novel computational method in the precision oncology of pediatric tumors.

The utility of routine extensive molecular profiling of pediatric tumors is a matter of debate due to the high number of genetic alterations of unknown significance or low evidence and the lack of standardized and personalized decision support methods. Digital drug assignment (DDA) is a novel computational method to prioritize treatment options by aggregating numerous evidence-based associations between multiple drivers, targets, and targeted agents. DDA has been validated to improve personalized treatment decisions based on the outcome data of adult patients treated in the SHIVA01 clinical trial. The aim of this study was to evaluate the utility of DDA in pediatric oncology. Between 2017 and 2020, 103 high-risk pediatric cancer patients (< 21years) were involved in our precision oncology program, and samples from 100 patients were eligible for further analysis. Tissue or blood samples were analyzed by whole-exome (WES) or targeted panel sequencing and other molecular diagnostic modalities and processed by a software system using the DDA algorithm for therapeutic decision support. Finally, a molecular tumor board (MTB) evaluated the results to provide therapy recommendations. Of the 100 cases with comprehensive molecular diagnostic data, 88 yielded WES and 12 panel sequencing results. DDA identified matching off-label targeted treatment options (actionability) in 72/100 cases (72%), while 57/100 (57%) showed potential drug resistance. Actionability reached 88% (29/33) by 2020 due to the continuous updates of the evidence database. MTB approved the clinical use of a DDA-top-listed treatment in 56 of 72 actionable cases (78%). The approved therapies had significantly higher aggregated evidence levels (AELs) than dismissed therapies. Filtering of WES results for targeted panels missed important mutations affecting therapy selection. DDA is a promising approach to overcome challenges associated with the interpretation of extensive molecular profiling in the routine care of high-risk pediatric cancers. Knowledgebase updates enable automatic interpretation of a continuously expanding gene set, a "virtual" panel, filtered out from genome-wide analysis to always maximize the performance of precision treatment planning.

Medical Therapy After CABG: the Known Knowns, the Known Unknowns, and the Unknown Unknowns.

Medical therapies play a central role in secondary prevention after surgical revascularization. While coronary artery bypass grafting is the most definitive treatment for ischemic heart disease, progression of atherosclerotic disease in native coronary arteries and bypass grafts result in recurrent adverse ischemic events. The aim of this review is to summarize the recent evidence regarding current therapies in secondary prevention of adverse cardiovascular outcomes after CABG and review the existing recommendations as they pertain to the CABG subpopulations. There are many pharmacologic interventions recommended for secondary prevention in patients after coronary artery bypass grafting. Most of these recommendations are based on secondary outcomes from trials which include but did not focus on surgical patients as a cohort. Even those designed with CABG in mind lack the technical and demographic scope to provide universal recommendations for all CABG patients. Recommendations for medical therapy after surgical revascularization are chiefly based on large-scale randomized controlled trials and meta-analyses. Much of what is known about medical management after surgical revascularization results from trials comparing surgical to non-surgical approaches and important characteristics of the operative patients are omitted. These omissions create a group of patients who are relatively heterogenous making solid recommendations elusive. While advances in pharmacologic therapies are clearly adding to the armamentarium of options for secondary prevention, knowing what patients benefit most from each therapeutic option remains challenging and a personalized approach is still required.

Antitachycardic Therapy of ICD in Patients with Multiple Morphologies of Monomorphous Ventricular Tachycardia Refractory to Therapy

The article presents a description of a clinical case of a patient with structural myocardial pathology (postinfarction cardiosclerosis) with recurrent paroxysmal sustained monomorphic ventricular tachycardia (VT) refractory to the nominal recommended ICD (implantable cardioverter defibrillator) settings; as well as discusses the shortcomings of existing standard algorithms for antitachycardia pacing (ATP) of implantable cardioverter defibrillators and potential ways to increase its efficiency. The refractoriness of recurrent paroxysms of ventricular tachycardia to ATP therapy increases the risk of repeated ICD shocks.&#x0D; Despite the existence of universal recommendations for ICD programming and ATP therapy, there is a need in clinical practice for individualized ATP programming in patients refractory to nominal settings. Increasing the number of ATP series and changing algorithms enables to increase the efficiency of ATP up to 8089%. Refractoriness to standard ATP settings may be also overcome by using alternative ATP pacing algorithms (Ramp, Burst-plus, or Ramp-plus instead of Burst), changing the pacing interval, ATP sequence duration, pacing type, and even adding 12 extra stimuli, as well as using data from the previous intracardiac electrophysiological heart test.&#x0D; The presented clinical case of a patient with postinfarction cardiosclerosis and paroxysmal stable monomorphic VT (SM-VT) of several morphologies demonstrates that the arrhythmogenic substrate after myocardial infarction changes for a long time without new stenoses in large coronary arteries and without new episodes of acute coronary syndrome, as well as generates several different morphologies of VT from one scar (with different heart rates) and the effect on hemodynamics. The efficiency of early ATP pacing may differ for VT of various morphologies, which makes it reasonable to use alternative pacing algorithms (in addition to the standard Burst sequences recommended by the 2019 Consensus on ICD programming) and testing possible ATP algorithms during ablation of monomorphic VT, including during preventive VT ablation before ICD implantation.

Prediction of Relevant Training Control Parameters at Individual Anaerobic Threshold without Blood Lactate Measurement

Active exercise therapy plays an essential role in tackling the global burden of obesity. Optimizing recommendations in individual training therapy requires that the essential parameters heart rate HR(IAT) and work load (W/kg(IAT) at individual anaerobic threshold (IAT) are known. Performance diagnostics with blood lactate is one of the most established methods for these kinds of diagnostics, yet it is also time consuming and expensive. To establish a regression model which allows HR(IAT) and (W/kg(IAT) to be predicted without measuring blood lactate, a total of 1234 performance protocols with blood lactate in cycle ergometry were analyzed. Multiple linear regression analyses were performed to predict the essential parameters (HR(IAT)) (W/kg(IAT)) by using routine parameters for ergometry without blood lactate. HR(IAT) can be predicted with an RMSE of 8.77 bpm (p < 0.001), R2 = 0.799 (|R| = 0.798) without performing blood lactate diagnostics during cycle ergometry. In addition, it is possible to predict W/kg(IAT) with an RMSE (root mean square error) of 0.241 W/kg (p < 0.001), R2 = 0.897 (|R| = 0.897). It is possible to predict essential parameters for training management without measuring blood lactate. This model can easily be used in preventive medicine and results in an inexpensive yet better training management of the general population, which is essential for public health.

Avoidant/Restrictive Food Intake Disorder (ARFID)

This publication addresses the characteristics, health and nutrition implications, and medical nutrition therapy recommendations for Avoidant/Restrictive Food Intake Disorder (ARFID). Written by Lily Tucciarone, Sara Murphy, and Wendy J. Dahl, and published by the UF/IFAS Food Science and Human Nutrition Department, December 2022.

ESC-Leitlinie 2022: Management ventrikulärer Arrhythmien in der klinischen Praxis

The recently published guideline of the European Society of Cardiology for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death updates the guideline from 2015. Overall, the current guideline is characterised by a great practical relevance: Illustrative algorithms, e.g., for diagnostic evaluation, and tables make the guideline a user-friendly reference book. In the diagnostic evaluation and risk stratification of sudden cardiac death, cardiac magnetic resonance imaging and genetic testing are significantly upgraded. In long-term management, the optimal treatment of the underlying disease is essential, and recommendations for heart failure therapy are adapted to current international guidelines. Catheter ablation is upgraded especially for patients with ischaemic cardiomyopathy and recurrent ventricular tachycardia, as well as in the management of symptomatic idiopathic ventricular arrhythmias. Criteria for primary prophylactic defibrillator therapy remain controversial. In the context of dilated cardiomyopathy, imaging, genetic testing, and clinical factors are given special weight in addition to left ventricular function. Additionally, revised diagnostic criteria for a large number of primary electrical diseases are provided.

Anticoagulation Regimens in Pregnancy.

This article explores current recommendations for anticoagulation therapy in pregnancy, including antepartum, intrapartum, and postpartum guidelines. The authors review various screening strategies used to assess whether a patient is an appropriate candidate for anticoagulation during pregnancy and the postpartum period. The article includes dosing regimens, optimal surveillance, and medication reversal. The authors also address the challenges of transitioning between low-molecular-weight heparin and unfractionated heparin. Finally, there is a discussion of intrapartum anticoagulation management, especially as it relates to the administration of regional anesthesia, and the indications for and timing of thromboprophylaxis following delivery.

Abstract P4-02-17: Impact of low hormone receptor expression on neoadjuvant chemotherapy response and patterns of care in early-stage HER2-negative breast cancer: a US National Cancer Database analysis

Abstract Background: Hormone receptor (HR) low (1-10%) HER2-negative breast cancer (BC) is emerging as a distinct subtype with similarities in clinical outcomes to triple-negative BC. However, there is a lack of consensus on treatment recommendations for chemo-immunotherapy and endocrine therapy in this subset. Here, we present results from a US National Cancer Database (NCDB) analyses of patients with HER2-negative BC evaluating response to neoadjuvant chemotherapy (NAC) and patterns of care by HR expression. Methods: Patients with stage I-III HER2-negative BC diagnosed in 2018 were identified in NCDB, a nationwide oncology outcomes database in the US. Quantitative HR expression was unavailable prior to 2018. Data were categorized into four groups by estrogen receptor (ER) and progesterone receptor (PR) expression: ER&amp;lt; 1% &amp; PR&amp;lt; 1% (HR-Neg), ER 1-10% and/or PR 1-10% (HR-Low), ER &amp;gt;11-30% and/or PR&amp;gt;11-30% (HR-Int), ER&amp;gt; 30% and/or PR &amp;gt; 30% (HR-High). Those with undocumented HR status (3%) or without curative intent surgery (5%) were excluded. The primary outcome was pathologic complete response (pCR) by HR expression in those undergoing neoadjuvant chemotherapy. Key secondary objectives included assessment of clinicopathologic characteristics and practice patterns. The categorical variables were compared between the four groups using a Chi-square test. Age was compared using a Kruskal-Wallis test. Results: Out of 104,205 incident cases, 2541 (2.4%) were HR-Low and 1241 (1.2%) were HR-Int. Significant differences were found between HR groups with higher grade, clinical stage, and Ki-67 in HR-Low vs. HR-Int or HR-High groups (Table 1). Patients with HR-Low and HR-Int BC were more likely to receive chemotherapy than HR-High (74%, 70% vs. 20%; p &amp;lt; 0.001) and the use of adjuvant endocrine therapy correlated with HR expression. Only half of patients in the HR-Low group received any endocrine therapy compared to higher rates in the HR-Int and HR-High groups (52% vs. 74%, 92%; p&amp;lt; 0.001). pCR rates in those receiving neoadjuvant chemotherapy were significantly different by HR status, with higher pCR rates in HR-Low vs. HR-High groups (p&amp;lt; 0.001) (Table 2). NAC utilization significantly differed between groups. A higher proportion of patients with HR-Low BC received NAC than other HR-positive groups (p &amp;lt; 0.001). Additionally, there was an increased use of NAC in patients with HR-Low BC treated at academic vs. community cancer centers (p&amp;lt; 0.001). Conclusions: This is one of the largest real-world analyses comparing key differences in biology and practice patterns of HR-Low, HER2-negative BC. Consistent with prior studies, we report HR-Low BC to be a rare and distinct subtype with higher pCR rates compared to HR-High BC. Practice patterns show wide variability in utilization of neoadjuvant chemotherapy and endocrine therapy for these patients. Future studies should address this disparity and enhance representation of patients with HR-Low BC in clinical trials to improve long-term outcomes. Table 1: Patient demographics Table 2: Neoadjuvant chemotherapy response amongst differing HR expression levels Citation Format: Dionisia Quiroga, Michael Grimm, Julie Stephens, Kai Johnson, Nicole Williams, Preeti K. Sudheendra, Mathew A. Cherian, Daniel Stover, Ashley C. Pariser, Margaret Gatti-Mays, Robert Wesolowski, Jose G. Bazan, Sasha Beyer, Ko Un Park, Bridget Oppong, Bhuvaneswari Ramaswamy, Julia White, Sachin R. Jhawar, Sagar Sardesai. Impact of low hormone receptor expression on neoadjuvant chemotherapy response and patterns of care in early-stage HER2-negative breast cancer: a US National Cancer Database analysis [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 P4-02-17.

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.

Abstract P5-03-15: Application of 21-gene Breast Recurrence Score® assay to evaluate prognosis and benefit of adjuvant chemotherapy in BRCA1 and BRCA2 pathogenic variant carriers with early stage, estrogen receptor positive breast cancer

Abstract Background: Minimal data exists for the utilization of the Oncotype Dx® assay specifically in breast cancers associated with BRCA1/2 pathogenic variants (PVs). It is unknown whether estrogen receptor positive (ER+) breast cancer associated with an inherited BRCA1 or BRCA2 (BRCA1/2) PV is more aggressive than disease seen in patients who do not carry an inherited PV, and whether there are differences between BRCA1 and BRCA2. In prostate cancer patients with inherited cancer predisposition due to a BRCA2 PV, more aggressive cancers are observed, which influences first-line treatment. Limited data exists for the optimal management of early stage ER+ breast cancer in BRCA1/2 PV carriers. Comparing Recurrence Score® (RS) results in ER+ breast cancer patients with an inherited BRCA1/2 PV (cases) versus matched patients who test negative for a PV in BRCA1/2 (controls) may inform whether biologically more aggressive breast cancer is seen in BRCA1/2 carriers and optimal treatment approaches. Methods: A retrospective case control study was performed to compare RS results in women with breast cancer with an inherited BRCA1/2 PV versus patients who tested negative for an inherited BRCA1/2 PV. Female breast cancer patients seen between 2005-2020 at NorthShore University Health System with ER+Her2- early stage invasive breast cancer with 0-3 lymph nodes who completed genetic testing for BRCA1/2 were eligible for enrollment. BRCA1/2 cases were defined as individuals with an inherited PV in BRCA1/2 and controls were negative for BRCA1/2 or other known breast cancer risk gene PVs tested. Subjects were excluded if they had neoadjuvant therapy (hormonal or cytotoxic chemotherapy). Eligible cases were matched to control patients by age, grade, and stage. The Recurrence Score result was obtained by chart review; if not previously evaluated, Oncotype Dx assay was performed by Exact Sciences. Statistical analysis of the primary outcome used the paired t-test to determine mean difference in RS results between BRCA1/2 PV carriers and patients negative for a PV in BRCA1/2 using a 1:1 matched pairs design. Results: A total of 46 matched cases and controls were analyzed. Median age was 50 with a range of 28-74. Of the cases, 18 had a BRCA1 PV and 28 had a BRCA2 PV. Cases and controls were well matched for age (&amp;gt; 50 and ≤ 50); race, grade, stage, and progesterone receptor status. As expected, a higher number of BRCA1/2 carriers were treated with mastectomy while more of the controls received breast-conserving surgery. Chemotherapy was utilized more frequently in the cases (67.4%) versus the controls (54.4%). The average RS result was higher in the cases (27) than the controls (21.3) by a mean difference of 5.7 (p = 0.0195). Using Oncotype Dx cutoffs of low &amp;lt; 18, intermediate 18-30 and high ≥ 31, a statistically significant difference in RS result was noted in the cases versus controls. For cases in the highest risk group (Oncotype Dx ≥ 31), only 20% of their matches also had a score in the highest risk group while 35% had a score in the lowest risk group. Subgroup analysis showed that the cases had the largest difference in RS result from their controls in premenopausal women (age ≤ 50), BRCA1 carriers, and the node negative population. Conclusion We present one of the largest data sets available to date of a well-matched cohort of cases and controls which shows that BRCA1/2 PV carriers are more likely to have a higher Recurrence Score result than their matched controls when matched for age, grade, and stage. These findings suggest ER+ breast cancer in BRCA1/2 PV carriers is biologically more aggressive. Further investigation is warranted to evaluate how this important finding impacts adjuvant therapy recommendations for BRCA1/2 PV carriers. Citation Format: Poornima Saha, Ashley Aller, Amanda Deliere, Peter Hulick, Katharine Yao, Kristine Kuchta, Megan Sullivan, Allison DePersia. Application of 21-gene Breast Recurrence Score® assay to evaluate prognosis and benefit of adjuvant chemotherapy in BRCA1 and BRCA2 pathogenic variant carriers with early stage, estrogen receptor positive breast cancer [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 P5-03-15.