Proportion Of Tests Research Articles

Open-label, randomized, multicenter, phase 3, ELAINE 3 study of the efficacy and safety of lasofoxifene plus abemaciclib for treating ER+/HER2-, locally advanced or metastatic breast cancer with an ESR1 mutation.

TPS1127 Background: Patients with estrogen receptor-positive (ER+) metastatic breast cancer (mBC) may develop resistance to endocrine therapy (ET), particularly following treatment with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), potentially driven by a mutation in the ERa-coding gene, ESR1. Lasofoxifene (LAS), an oral, next-generation ET and ER breast antagonist, was evaluated in two phase 2 studies of women with ER+/HER2- mBC and an ESR1 mutation who had disease progression on previous ET and CDK4/6i. The ELAINE 1 trial showed numerically greater progression-free survival (PFS, median ~6 vs 4 mos; P=0.138), objective response rate (ORR, 13% vs 3%; P=0.124), and clinical benefit rate (CBR, 37% vs 22%; P=0.117) with LAS monotherapy versus the ER degrader fulvestrant (fulv), with a favorable safety profile (1). The single-arm, ELAINE 2 trial demonstrated that LAS plus abemaciclib (Abema) was well tolerated with a median PFS of ~13 mos, ORR of 56%, and CBR of 66% (2). Based on these data, the phase 3, registrational, ELAINE 3 trial was initiated. Methods: ELAINE 3 (NCT05696626) is an open-label, phase 3, multicenter study evaluating the efficacy, safety, and tolerability of LAS plus Abema versus fulv plus Abema. Key inclusion criteria are pre- and postmenopausal women and men aged ≥18 yrs; ER+/HER2-, locally advanced and/or mBC (measurable and/or non-measurable disease); ≥1 acquired ESR1 mutation; progression on an aromatase inhibitor plus palbociclib or ribociclib as their first hormonal treatment for advanced/mBC; and ≤1 line of chemotherapy in the advanced/metastatic setting. Patients will be randomized 1:1 to receive LAS 5 mg/day plus Abema 150 mg BID, or fulv 500 mg IM on days 1, 15, and 29, then once monthly plus Abema 150 mg BID. Treatment will continue until progression, death, unacceptable toxicity, or withdrawal from the study. The primary endpoint is PFS; key secondary endpoints are ORR, overall survival, CBR, duration of response, and time to response. Time to cytotoxic chemotherapy, quality of life, and safety will also be evaluated. Blood samples for circulating tumor DNA (ctDNA) will be collected for genomic analyses at screening, at weeks 4 and 8 and every 8 weeks thereafter, and at the final visit. Outcomes with LAS/Abema and fulv/Abema will be compared using a stratified Cox proportional hazards model and stratified logrank test. Expected PFS is ≥10.3 mos for LAS/Abema and 7 mos for fulv/Abema (PFS hazard ratio of 0.68 at final analysis). The target sample size is 400, to achieve 90% power with a one-sided type I error rate of 0.025 after 285 PFS events. Full recruitment is expected to occur over 18 mos at approximately 125 global sites. 1. Goetz MP, et al. Ann Oncol. 2023;34:1141-1151. 2. Damodaran S, et al. Ann Oncol. 2023;34:1131-1140. Clinical trial information: NCT05696626 .

Trends in the use of immunotherapy to treat soft tissue sarcoma

BackgroundThe role of immune-oncology (IO) therapy in soft tissue sarcoma (STS) is underexplored. This study characterized IO use in STS. MethodsThis is a retrospective analysis of patients with a soft tissue mass in the National Cancer Database, 2011–2021. Patients were categorized by IO receipt status. Groupwise testing and proportional trend tests were performed with Chi-squared tests. Multivariate logistic regression was performed to assess factors associated with IO receipt. ResultsOf the 103,092 patients with STS, 1935 (1.9 ​%) received or were recommended IO therapy. IO use increased 10-fold (0.24 ​%–2.5 ​% from 2011 to 2021; p ​< ​0.0001). Patients had higher odds of receiving IO when having higher grade tumors and metastatic disease, and when treated at an academic research center (all p ​< ​0.001). ConclusionsIO use in STS is low but increasing and primarily used in the metastatic setting. Future studies should identify biomarkers of IO response and facilitators for treatment receipt.

Factors associated with surgical intervention in Native American patients with hepatocellular carcinoma.

e16279 Background: Hepatocellular carcinoma (HCC) is the prevailing type of primary liver cancer, exhibited at a higher frequency in individuals afflicted by chronic liver conditions. Past literature has demonstrated the impact certain socioeconomic factors have on the prognosis of HCC. Native American patients often face late-stage cancer diagnoses and have the lowest survival rates among racial and ethnic groups. While surgery offers potential for cure, factors related to surgical interventions in liver cancer for Native American patients remain largely unexplored. Through the NCDB, this study analyzed factors associated with surgical intervention and survival trends in Native American patients with HCC. Methods: The National Cancer Database (NCDB) was used to identify Native American patients diagnosed with Hepatocellular Carcinoma from 2004 to 2019 using the histology code 8170 and race code 03 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, and Cox Proportional Hazards tests were performed. Data was analyzed using SPSS version 27, and statistical significance was set at α = 0.05. Results: Of 1193 Native American patients included in this sample, 172 (14.4%) patients received surgical treatment for HCC, while 1021 (85.6%) patients did not receive surgical treatment for HCC. Native American patients who received surgery for HCC experienced a greater mean overall survival (90 months) when compared to the mean overall survival (24 months) in HCC Native American patients who did not receive surgical treatments (p &lt; 0.001). When controlling for age, year of diagnosis, stage, grade, facility type and income status, receiving surgery showed an independent decrease in hazard (HR = 0.245; p &lt; 0.05). HCC Native American patients who received surgery were more likely to be treated an at academic facility, have stage I disease, and have less aggressive tumors (grade) (p &lt; 0.05). Native American patients who did not receive surgery were more likely to be older (62 vs 60 years old), have larger tumors, and have brain, bone, lung, and liver metastases (p &lt; 0.05). No associations of surgical versus non-surgical treatment were seen in Charlson-Deyo score, urban or rural residence, and primary payor at diagnosis. Conclusions: Native American patients with HCC who received surgical intervention experienced improved overall survival compared to non-surgical treatment groups. Native American patients undergoing surgical intervention more often received care at academic or private institutions and had lower stages of HCC. These results follow previous trends, where cancer patients receiving adequate surgical intervention generally survive longer. Further research is needed to examine other treatment differences among Native American patients and how these findings compare across other disadvantaged groups.

Unveiling inequities in representation: Racial disparities in supportive care breast cancer clinical trial enrollment.

1605 Background: Supportive care is an integral part of breast cancer survivorship care. However, not much is known if there is adequate representation of racial minorities in supportive care breast cancer (BC) clinical trials (CTs). Methods: We conducted a systematic review of supportive care CTs for patients with BC using Covidence. A search of clinicaltrials.gov identified 2695 CTs, of which 173 met inclusion criteria. The SEER database was used as a racial distribution data reference for patients with BC. One-sample proportion tests were performed to assess adequacy in racial representation among supportive care CTs and by intervention type. Results: Of 173 supportive care CTs, 133 (77%) trials reported race-specific data. Characteristics of supportive care CTs based on intervention type and race are shown (Table). Although no statistically significant differences in frequencies of Black participants in supportive BC CTs overall were observed compared to the US population (11% vs 12%, p= 0.40), they were underrepresented in symptom management CTs specifically (8% vs 12%, p= 0.004). When stratified based on diet/physical activity CTs, Black participants were overrepresented in the study population (18% vs 11%, p= &lt;0.001). Asian participants were underrepresented in the overall study population compared to the US population (5% vs 7%, p= 0.01). However, within psycho-oncology CTs, there was an overrepresentation of Asian participants in the study population (21% vs 7%, p = &lt;0.001). No significant differences in enrollment frequencies of Black and Asian participants were found in cognitive health, complementary and alternative medicine, education/communication, and sexual health interventional CTs. Conclusions: Our findings highlight inadequate representation of Asian participants in supportive care BC CTs and Black participants in symptom management CTs. This study is limited in that ethnicity was not included in this analysis. Strategies are needed to promote recruitment of diverse individuals in these settings so that we can more accurately generalize findings from supportive care BC CTs. [Table: see text]

Contextualizing post day-one childhood immunization in-take drop-off rate in Nigeria: An assessment of working mothers in Ibadan

Background Contextualizing childhood immunization in the context of working mothers can boost coverage and completion. This study examines how informal working mothers perceive post-day-one routine immunization, and vaccines not covered under the National Program on Immunization (NPI), immunization schedules, timing, and duration. Methods The study was conducted in Ibadan, Nigeria and involved 1,044 quantitative and 73 qualitative samples of working nursing mothers. A mixed methods approach was used, including a semi-structured questionnaire to gather immunization experiences. Data were analyzed using descriptive statistics, chi-square test for proportions, and t-test for means (p&lt;0.05), while qualitative data were subjected to content analysis. Results The average age of mothers participating in this study was 31.39 years. The mean age of mothers at their first childbirth within the study group was 24.12 years. A significant majority of these mothers (95%) are married. Around three-quarters of women in this population ensured immediate immunization for their infants after birth, but less than a third achieved the complete age-specific vaccination series due to livelihood related causes, long waiting time spent in conventional immunization clinic. Around 40% of interviewed mothers vaccinated their children up to the third DPT dose, and just over 30% achieved full vaccination. Many informal working mothers, have concerning practice of adding 'supplements' to their children's immunization, driven by a lack of sufficient information about the vaccines. Some mothers also seemed unaware of these specialized vaccines. Conclusions Promoting complete immunization requires more than just raising awareness about childhood vaccinations but close and quick immunization service delivery is required. It is crucial for mothers to possess comprehensive knowledge about the mechanics and operation of immunization. Achieving this understanding could involve translating vaccine names and functions into indigenous terms, enhancing clarity and comprehension. Furthermore, a firm grasp of the immunization schedule significantly contributes to successful immunization completion.

How Can Malaysian Courts Consistently Perform Meaningful Constitutional Rights Review? Lessons from Past Cases and the Way Forward

Abstract In the past, Malaysian courts performing constitutional rights review played a merely clerical role, applying a test that was trivially easy for legislation to pass. Then a more rigorous proportionality test took root. However, the Federal Court in the 2020 case of Letitia Bosman whittled the test down again, and the courts once more played a minimal role in checking state action. The reasons for this cannot be explained merely by diversity in judicial philosophy or political contextual factors. Rather, the near-demise of proportionality (and, with it, robust constitutional review) was made possible by a lack of a clear sense of the doctrinal foundations of proportionality (and, indeed, of constitutional rights review generally), and the relative roles of the courts and the legislature therein. As a result, there is a risk that the courts’ important role in safeguarding constitutional rights has been minimised to near vanishing point. This article aims, through an analysis of the case law and its foundations, to explain how this came to be, and hence highlight important issues which Malaysian constitutional law must grapple with if meaningful rights review is to take place.

Dirbtinio intelekto taikymo įmonių vidaus tyrimuose teisinės ribos ir baudžiamieji procesiniai padariniai

The paper addressed the following questions: how can AI be applied in corporate internal investigations and what are the legal limits for its use? In case of effective application, how can it affect the admissibility and valuation of the information collected from these procedures in an eventual criminal lawsuit? It was demonstrated that, with the expectation of increasing the effectiveness and efficiency of compliance programs, AI has been used in real-time – and often predictive – supervision of employees, as well as in carrying out internal investigations, through, for example, lie detection systems. However, due to the limitations and risks of this technology, its employment must comply with legal parameters and restrictions. Therefore, three categories of restrictions were analyzed: with respect to (i) legal requirements for data processing, we noted that the processing of data to be used as input in those systems must find legal support in one of the hypotheses provided for in Articles 6 and 9(2) of the GDPR. Furthermore, the fundamental principles that substantiate the test of proportionality between the intended purpose and the intervention to be carried out, provided for in Article 5, must be observed. Regarding (ii) possible prohibitions on the use of AI systems in the context of internal investigations, we observed that the use of technologies to control and supervise the work environment must take into account the requirements of legality, shall not affect areas in which employees’ expectations of privacy must prevail, and, lastly, must observe a second test of proportionality, aimed at assessing whether the technology in question is adequate and necessary to achieve the purpose intended with it and whether the rights possibly affected by it should not prevail. About the (iii) limits to the admissibility and valuation of elements of information from internal investigations, we concluded that their admission in criminal proceedings will depend on a new judgment of legality and proportionality. In addition, they may be admitted when presented by the company, in its defence, or by Public Prosecution, provided that a third test of proportionality is observed and that these elements of information are not considered sufficient to substantiate the conviction of any defendant, therefore having probative value similar to elements from state investigation acts.

Kiedy cnota staje się maską tyranii, czyli jeszcze kilka uwag o rozstrzygnięciu Trybunału Konstytucyjnego w sprawie K 1/20

In its judgment of 22.10.2020 (K 1/20), the Constitutional Court ruled out the possibility of aborting a pregnancy due to the occurrence of a so-called embryopathological premise. It deprived women of the possibility to make an autonomous decision in the case of severe and irreversible disability or incurable disease of the fetus. The paper analyses the Court’s errors in, inter alia, establishing the constitutional status of the nasciturus, conducting the dignity argument or the proportionality test. The authoress shows that the judgment is political and ideological in nature and that the Court refers to the judgment in Case K 26/96 in a selective and manipulative manner. The text to some extent polemics with the theses of P. Łącki and B. Wróblewski presented in the paper on Niekonstytucyjność tzw. aborcji eugenicznej (embriopatologicznej). Schemat argumentacji Trybunału Konstytucyjnego w sprawie K 1/20 (Unconstitutionality of the so-called eugenic (embryopathological) abortion. The pattern of argumentation of the Constitutional Tribunal in Case K 1/20), which came out in the previous issue of the “Przegląd Konstytucyjny” quarterly.

The maintenance of mexican traditional medicine practices among mexicans in southern Arizona

Mexicans in the United States have been reported to maintain practices of Mexican traditional medicine at comparably higher rates than most other populations, including other Latino sub-groups. In this cross-sectional study, we examined the pre- and post-migration traditional medicine practices of first-generation immigrants from Mexico living in southern Arizona. Our objective was to assess how migration affected Mexican immigrants' ethnomedical practices and to better understand the mechanisms and motivating factors for the post-migration maintenance of practice. We designed a survey instrument based off prior qualitative data on traditional medicine practices and translated it into Spanish. The survey measured the rates and frequency of six domains of lay healing practices: herbal medicine, healing foods, self-medication with over-the-counter medicine, and three types of specialty healers (curandero/a, and sobador/a, or partero/a), and asked questions about knowledge sources, reasons for maintaining practice post-migration, and to what extent participants believed the remedies were effective. The research team fielded the telephone-based survey from April 2022 to February 2023 to 300 first-generation adult Mexican immigrants residing in southern Arizona. A series of proportions tests were conducted to examine differences in reliance on lay healing pre- and post-migration as well as to assess differences between women's and men's lay practices. The data indicate a general, but moderated decline in lay medical practices post-migration, with the usage of expert healers declining at much higher rates than the three self-care domains. Women tend to use herbal medicine and healing foods at higher rates than men post-migration. This cross-sectional quantitative study confirms prior research indicating that traditional medicine practices are heavily relied upon by Mexican origin people both pre- and post-migration. These findings suggest that public health messaging and medical providers should better address and harness Mexican immigrants' lay medical practices in order to optimize health in this population.

Epidemiological Features of Hepatitis C in China From 2015 to 2021: Insights From National Surveillance Data.

The COVID-19 pandemic overwhelmed national health care systems, not least in the context of hepatitis elimination. This study investigates the effects of the pandemic response on the incidence rate, mortality rate, and case fatality rate (CFR) for hepatitis C virus (HCV) cases in China. We extracted the number of hepatitis C cases and HCV-related deaths by month and year for 2015 to 2021 in China and applied two proportional tests to analyze changes in the average yearly incidence rates, mortality rates, and CFRs for 2015 to 2020. We used the autoregressive integrated moving average model to predict these three rates for 2020 based on 2015 to 2019 HCV data. The incidence of hepatitis C decreased by 7.11% and 1.42% (P < .001) in 2020 and 2021, respectively, compared with 2015 to 2019, while it increased by 6.13% (P < .001) in 2021 relative to 2020. The monthly observed incidence in 2020 was significantly lower (-26.07%) than predicted. Meanwhile, no differences in mortality rate or CFR were observed between 2021, 2020, and 2015 to 2019. Our findings suggested that nonpharmaceutical interventions and behavioral changes to mitigate COVID-19 could have reduced hepatitis C incidence and accelerated China's implementation of a plan to eliminate HCV infection.

Geographic Proximity of Medical Students to PM&R Residency Programs Is Associated With Increased Match Rates Into PM&R.

Despite the growing popularity of physical medicine and rehabilitation as a specialty among medical students, meaningful experiences and mentorship can be challenging to obtain and may significantly vary depending on opportunities available to interact with physiatrists. This study explores the association between the geographic proximity of physical medicine and rehabilitation residency programs to medical schools and the match rate of medical students into physical medicine and rehabilitation from 2019 to 2021. Data on US medical schools, graduates, and physical medicine and rehabilitation residency programs were collected from publicly available sources, and a sample of 1193 physical medicine and rehabilitation residents from US medical schools was analyzed using a one-sample proportion test. The proportion of physical medicine and rehabilitation residents originating from medical schools with physical medicine and rehabilitation residency programs in the same metropolitan area was significantly greater than the corresponding proportion of expected residents based on medical school graduates, even when controlling for medical school affiliations with physical medicine and rehabilitation residency programs. These findings suggest that exposure and opportunities provided by physical medicine and rehabilitation residency programs may influence nearby medical students and that expanding residency programs into geographic regions without existing physical medicine and rehabilitation programs may foster interest and promote growth in the field of physiatry.

Numerical simulations and testing of notched composite plates under envelope loadings: Validation with the safe life domain method

The certification of aircraft structures specifies various loads, possibly combined, to be considered to demonstrate its strength. In general, structural testing up to static failure is performed using proportional loading. In this study, the effects of loading with combinations of tension-shear-pressure are studied on large notched composite specimens. The VERTEX test rig is used. The Safe Life Domain method is proposed to validate whole domains of loading combination by means of a single envelope test. Envelope validation tests are implemented on tension-shear loadings with and without pressure, based on numerical predictions of the specimen failure and of the bench behaviour. Buckling mode variability and its impact on failure is considered, to show possible path-dependency of failure and thus highlight an ignored complexity of structure failure. Therefore, the numerous proportional tests needed for compliance demonstration can be reduced thanks to a few envelope tests instead.

Frequency of Hypocalcemia and Hypomagnesemia in Autistic Spectrum Disordered Children of Bangladesh

Background: Autistic spectrum disorder (ASD) in children is commonly associated with mitochondrial dysfunction and mineral deficiency. Studies have highlighted links between Ca2+ and Mg2+ deficiency and neuronal excitability, along with connections between iron deficiency and behavioral abnormalities in individuals with ASD. Objective: This study was aimed to assess the frequency of hypocalcemia and hypomagnesemia in autistic spectrum-disordered children of Bangladesh. Methods: This cross-sectional study was conducted in the Department of Physiology, Bangabandhu Sheikh Mujib Medical University, Dhaka from March 2014 to January 2015. The study included 100 randomly selected male children, with 50 in a healthy control group (Group A) and 50 diagnosed with autistic spectrum disorder (Group B). Children with ASD were selected from the Parents Forum (DOHS, Mohakhali), while the control group was chosen from schools with typically developing children. Fasting serum levels of various components along with calcium and magnesium were measured, and statistical analysis was conducted using independent sample 't' tests and proportion (Z) tests, with a significance level set at p-value ˂0.05. Results: In this study, out of 50 autistic spectrum disorder cases, the frequencies of hypocalcemia and hypomagnesemia were 74% and 52%, respectively. A comparison with the control group revealed significantly higher frequencies of both hypomagnesemia and hypocalcemia in the ASD group, with p-values &lt;0.001. Conclusions: Among most children with autism spectrum disorder in Bangladesh, hypocalcemia and hypomagnesemia are prevalent. These prevalences are significantly higher than those observed in healthy children. J Rang Med Col. March 2024; Vol. 9, No. 1: 55-58

Vitamin D and it’s Association with FokI VDR Polymorphism in Patients with Asthma-COPD Overlap

Background: Asthma-COPD overlap is a new phenotype in respiratory ailments. It has been shown that this group of patients might possess vitamin D3 deficiency. The association of vitamin D receptor (VDR) gene polymorphism with serum vitamin D status in ACO patients has not been investigated yet. Objective: To assess the association of VDR gene polymorphism (FokI) with serum vitamin D status in patients with Asthma-COPD overlap. Methods: This cross-sectional study was carried out in the Department of Physiology of Bangabandhu Sheikh Mujib Medical University, Dhaka, from January 2018 to July 2018 on 23 (twenty-three) patients (aged ≥40 years) with ACO. For comparison, 24 (twenty-four) apparently healthy age, smoking duration and BMI matched subjects were selected. For all participants single nucleotide polymorphism of VDR gene FokI (rs10735810) was done by DNA extraction, polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Vitamin D3 was measured by using automated analyzer: ARCHITECT Plus ci4100. The results were expressed as mean with standard error (mean±SEM) and frequency distribution. The data were statistically analyzed by Graphpad prism (Version 7) using independent sample ‘t’ test, two sample proportion test, Fisher exact test and ANOVA test. In the interpretation of results, ≤0.05 level of probability (p) was accepted as significant. Results: The mean±SEM of serum 25(OH)D were 16.37±0.78 and 18.46±1.01 ng/ml in control and study groups, respectively. The frequency distribution of FokI genotype was 86.95% (FF), 8.69% (Ff), 4.35% (ff) and 91.66% (FF), 4.17% (Ff), 4.17% (ff) in ACO patients and healthy subjects, respectively. When FoKI VDR SNP was analyzed with serum vitamin D status in patients with ACO, statistically no association was seen. Conclusions: FokI VDR SNP is not associated with serum vitamin D status in patients with ACO. J Rang Med Col. March 2024; Vol. 9, No. 1: 22-27

Abstract PO4-25-03: Comprehensive immune profiling reveals factors associated with neoadjuvant chemotherapy response in triple negative breast cancer

Abstract Background: KEYNOTE-522 has resulted in FDA approval of the immune checkpoint blocker pembrolizumab with neoadjuvant chemotherapy for patients with high-risk triple negative breast cancer (TNBC), given the remarkable improvement in pCR rate to 65% along with improvement in event free survival, while with chemotherapy alone, the pCR rate is 40-50%. Unfortunately, use of pembrolizumab is associated with several immune related adverse events (irAE), some of which can be life-threatening and debilitating, including cardiomyositis, encephalitis, and adrenal insufficiency, among others. Hence, there is an unmet need to identify biomarkers in the tumor microenvironment which could predict patients who may attain pCR with chemotherapy alone and be spared the side effects from the added PD-1 inhibition. Methods: Comprehensive immune profiling, including PD-L1 IHC and the expression of 395 immune genes by RNA-seq, was performed on 1:2 matched FFPE tumor samples from 23 stage 1-3 TNBC patients (2 stage 1, 6 stage 2, 15 stage 3). All patients were female with an average age of 48 years (range: 25-79 years). 14 patients were treated with neoadjuvant chemotherapy alone (NAC) and 9 were treated with neoadjuvant chemotherapy combined with the checkpoint inhibitor pembrolizumab (NAC+I). mRNA expression signatures of tumor inflammation (TIGS, weak/moderate/strong), cell proliferation (CP, poor/moderate/high), and cancer testis antigen expression burden (CTAB) were determined by RNA-sequencing. Statistical comparisons of quantitative biomarkers between groups were calculated using the Wilcoxon Rank-Sum test, overrepresentation analysis of categorical variables between groups was calculated by proportions test, and survival differences were quantified by Cox proportional hazards analysis. Pathological responses were documented as pathological complete response (pCR) vs. non-pCR. Results: Across the entire cohort, patients with a BMI &amp;lt; 30 had significantly higher PD-L1 expression (assessed by RNA) than those with a BMI ³ 30 [p=0.047]. While not a statistically significant association, the NAC+I group tended to have a higher pCR rate compared to the NAC group [44.4% vs. 28.6%, p=0.66]. Across the entire cohort, tumors with high CTA expression, designated as CTAB high, had a higher pCR rate than CTAB low tumors [54.5% vs 16.7%, p=0.089]. No significant difference in pCR rate between TIGS or CP groups was detected for the NAC group, but in the NAC+I group, highly proliferative tumors had a lower pCR rate than moderately proliferative tumors [0% vs. 80%, p=0.048]. The pCR and non-pCR groups for each treatment type also exhibited distinct gene expression profiles. Among the NAC group, underexpression of FOXP3 and overexpression of MAPK14 and CD44 were associated with pCR [p≤0.031], while underexpression of IFNB1, MAPK14, and CD44 was associated with non-pCR [p≤0.029]. Among the NAC+I group, overexpression of CXCR4, TNFR and CCL20 was associated with non-pCR [p≤0.046]. Interestingly, SDHA was significantly overexpressed in the non-pCR subset of patients in the NAC group and significantly underexpressed in the non-pCR subset of patients in the NAC+I group [p≤0.031]. Conclusions: The development of biomarkers of treatment response is essential to the integration of immunotherapy with chemotherapy as a combined cancer treatment. Our study profiled the immune context of both NAC and NAC+I and identified several key microenvironmental differences underlying divergent treatment response in both groups. A comprehensive understanding of these factors could potentially predict pCR to chemotherapy alone, enabling the avoidance of the unnecessary treatment of these tumors with immunotherapy. Citation Format: Robert Seager, Heidi Ko, Sarabjot Pabla, Maria-Fernanda Senosain, Pawel Kalinski, Erik Van Roey, Shuang Gao, Kyle Strickland, Rebecca Previs, Mary Nesline, Stephanie Hastings, Shengle Zhang, Jeffrey Conroy, Taylor Jensen, Marcia Eisenberg, Brian Caveney, Eric Severson, Shakti Ramkissoon, Shipra Gandhi. Comprehensive immune profiling reveals factors associated with neoadjuvant chemotherapy response in triple negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-25-03.

Abstract PO4-19-03: FES-PET/MRI for Tailored treatment of luminal A and lobular breast cancer: a prospective cohort study

Abstract Background: Breast cancer (BC) staging is essential to planning the most appropriate treatment pathway. Currently, BC management has become more tailored to the tumor’s and patient’s characteristics. However, BC imaging shows varying performance according to tumor subtypes. In particular, routine imaging may pose some challenges when evaluating luminal A BC (LumA) and lobular BC (Lob). LumA, due to low grade and proliferation index (&amp;lt; 20%) shows lower sensitivity on axillary US, reduced MRI enhancement, and low FDG-avidity on PET. Similarly, Lob, due to its peculiar single-cell growth pattern, exhibits inferior sensitivity on axillary MRI and FDG-avidity. LumA and Lob account for &amp;gt;50% of all BCs. Despite their favourable prognosis, metastases and recurrences still occur; this translates into a higher absolute number of events than in other subtypes. As a result, a concrete risk of disease underestimation and under-treatment exists. Two ongoing studies on FDG-PET/MRI imaging in our institution have already demonstrated that its sensitivity also decreases in LumA and Lob. Based on these premises, our hypothesis states that by combining the advantages of hybrid PET/MRI with the high accuracy of 16α -18F-fluoro-17-beta-estradiol(FES), a radiolabeled form of estrogen binding to functionally active ER, we could obtain a reliable, non-invasive, operator-independent, one-stage imaging method for staging LumA and ER-positive Lob. Trial design: This is a prospective cohort study where patients with LumA and ER-positive Lob will be enrolled in four cohorts undergoing: A) primary surgery; B) induction endocrine therapy; C) neoadjuvant chemotherapy, and D) systemic therapy for metastatic disease. FES PET/MRI examinations will be performed at baseline for local and systemic staging in all cohorts and a second exam after systemic therapy in cohorts C-D. Correlations between the FES PET/MRI parameters and pathology, gene expression, and FDG PET parameters, when available, will be investigated. Study aims will evaluate: 1) the performance of the FES PET/MRI in axillary staging compared with axillary surgery; 2) potential correlations between changes in FES uptake and changes in proliferation index after three weeks of endocrine therapy (ET); 3) the performance of the FES PET/MRI in systemic staging of patients undergoing systemic therapy in comparison with standard imaging; 4) biological determinants of tumor heterogeneity on pathological, imaging, and genomic levels. Statistics: The primary analysis in cohort A will test the sensitivity of the FES PET/MRI in detecting macrometastatic axillary nodes. Assuming that the probability that a patient has positive nodes is 33%, 119 patients (10% drop-out included) will provide 80% power to reject the null hypothesis about sensitivity at a 5% significance level if the true sensitivity is at least 50%. Results from the FES PET/MRI will be also compared with standard imaging in terms of sensitivity and number of lesions detected using the Mc-Nemar test for paired proportions and the Wilcoxon signed-rank test for paired data. The primary analysis in Cohort B will test the association between the FES-SUV change from pre-ET to post-ET and the Ki-67 change from core biopsy to post-ET in ER positive BC patients with a Ki-67 &amp;gt;10%. The association between these changes will be measured by the Pearson correlation index ρ. Α total of 52 patients (10% drop-out included) from Cohort B will provide 80% power to reject the null hypothesis about ρ at a 5% significance level if the true ρ is at least 0.4. No formal sample size was calculated for cohort C and D: results will be considered descriptive in nature, informing sample size considerations for future trials. We intent to recruit 20 and 30 patients, respectively. Accrual has not started yet. Project funded by AIRC (Associazione Italiana Ricerca sul Cancro) Next Gen Clinician Scientist ID 28378 Contact: Dr. Rosa Di Micco, dimicco.rosa@hsr.it Citation Format: Rosa Di Micco, Carla Canevari, Francesca Gallivanone, Nicole Rotmensz, Veronica Zuber, Sara Baleri, Giovanni Cisternino, Mario Rampa, Stefania Zambelli, Giulia Viale, Patrizia Zucchinelli, Manuela Morgante, Paola Scifo, Elena Venturini, Paola Magnani, Isabella Sassi, Vincenzo Bagnardi, Pietro Panizza, Giampaolo Bianchini, Arturo Chiti, Oreste Davide Gentilini. FES-PET/MRI for Tailored treatment of luminal A and lobular breast cancer: a prospective cohort study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-19-03.

Abstract PO1-18-12: Trial in progress: Open-label, randomized, multicenter, phase 3, ELAINE 3 study of the efficacy and safety of lasofoxifene plus abemaciclib for treating locally advanced or ER+/HER2- metastatic breast cancer with an ESR1 mutation

Abstract Background: Patients with estrogen receptor-positive (ER+) metastatic breast cancer (BC) may develop resistance to endocrine therapy (ET), particularly following treatment with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), potentially driven by a mutation in the ERa-coding gene, ESR1. Lasofoxifene, an oral, next-generation ET and ER breast antagonist, had potent activity in mBC xenograft models expressing ESR1 mutations, either as a single agent or combined with a CDK4/6i. Subsequently, two phase 2 studies evaluated lasofoxifene in women with ER+/HER2- metastatic BC and an ESR1 mutation who had disease progression on previous ET and CDK4/6i. The ELAINE 1 trial showed numerically greater progression-free survival (PFS, median ~6 vs 4 months; P=0.138), objective response rate (ORR, 13% vs 3%; P=0.124), and clinical benefit rate (CBR, 37% vs 22%; P=0.117) with lasofoxifene monotherapy versus the ER degrader fulvestrant, with a favorable safety profile (Goetz MP, et al. Ann Oncol. 2022;33:S1387). The single-arm, ELAINE 2 trial demonstrated that lasofoxifene combined with abemaciclib was well tolerated with a median PFS of ~13 months, ORR of 56%, and CBR of 66% (Damodaran S, et al. J Clin Oncol. 2023;41:suppl 16; abstr 1057). Based on these data, the phase 3, registrational, ELAINE 3 trial was initiated. Methods: ELAINE 3 (NCT05696626) is an open-label, phase 3, multicenter study evaluating the efficacy, safety, and tolerability of lasofoxifene plus abemaciclib versus fulvestrant plus abemaciclib. Key inclusion criteria are pre- and postmenopausal women and men aged ≥18 years; ER+/HER2-, locally advanced and/or metastatic BC (measurable and/or non-measurable disease); ≥1 acquired ESR1 mutation; progression on an aromatase inhibitor plus palbociclib or ribociclib as their first hormonal treatment for advanced/metastatic BC; and ≤1 line of chemotherapy in the advanced/metastatic setting. Patients will be randomized 1:1 to receive lasofoxifene 5 mg/day plus abemaciclib 150 mg BID, or fulvestrant 500 mg IM on days 1, 15, and 29, then 4 weekly plus abemaciclib 150 mg BID. Treatment will continue until progression, death, unacceptable toxicity, or withdrawal from the study. The primary endpoint is PFS; key secondary endpoints are ORR, overall survival, CBR, duration of response, and time to response. Time to cytotoxic chemotherapy, quality of life, and safety will also be evaluated. Blood samples for circulating tumor DNA (ctDNA) will be collected at screening, at weeks 4 and 8 and every 8 weeks thereafter, and at the final visit for genomic analyses. Outcomes with lasofoxifene/abemaciclib and fulvestrant/abemaciclib will be compared using a stratified Cox proportional hazards model and stratified logrank test. Expected PFS is ≥10.3 months for lasofoxifene/abemaciclib and 7 months for fulvestrant/abemaciclib (PFS hazard ratio of 0.68 at final analysis). The target sample size is 400, to achieve 90% power with a one-sided type I error rate of 0.025 after 285 PFS events. Full recruitment is expected to occur over 18 months at 125 global sites. Citation Format: Matthew Goetz, Seth Wander, Thomas Bachelot, Gerald Batist, Javier Cortés, Massimo Cristofanilli, Giuseppe Curigliano, Alexandre de Nonneville, Einav Nili-Gal Yam, Komal Jhaveri, Cynthia Ma, Heather Parsons, Hope Rugo, Sarah Sammons, Daniel Stover, Chris Twelves, Aditya Bardia, Paul V. Plourde, David J Portman, Senthil Damodaran. Trial in progress: Open-label, randomized, multicenter, phase 3, ELAINE 3 study of the efficacy and safety of lasofoxifene plus abemaciclib for treating locally advanced or ER+/HER2- metastatic breast cancer with an ESR1 mutation [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-18-12.

Abstract PO5-06-09: Metastatic triple negative breast cancer has distinct tumor immune landscape

Abstract Background: Triple negative breast cancer (TNBC) is considered the most immunogenic breast cancer subtype due to higher levels of tumor infiltrating immune cells (TILS), elevated tumor mutational burden and PD-L1 expression, providing a rationale for immunotherapy. Here we aimed to investigate the differences in the immune microenvironment of primary vs. metastatic sites in TNBC vs. non-TNBC and their impact on survival. Methods: Comprehensive immune profiling, including PD-L1 IHC and the expression of 395 immune genes, was performed on 147 real-world FFPE breast cancer samples (32 primary, 115 metastatic). 37 samples were, by definition, triple negative for ER, PR, and HER2 overexpression. PD-L1 (CPS positive ≥1% and CPS positive ≥10%) was determined using immunohistochemistry (22C3). mRNA expression signatures of tumor inflammation (TIGS, weak/moderate/strong) and cell proliferation (CP, poor/moderate/high) were determined by RNA-sequencing. Demographic and clinicopathologic variables were collected. Statistical comparisons of biomarkers between groups were calculated using the Wilcoxon Rank-Sum test for continuous variables and the proportions test for categorical variables (p≤0.05 for significance). Survival differences were quantified by Cox proportional hazards analysis (p≤0.05 for significance). Results: Triple negative status was associated with current use of alcohol [p=0.03]. Black patients were also more likely to have TNBC, constituting 24% of TNBC patients while only making up 14% of the total cohort [p=0.04]. Conversely, white patients were less likely to have TNBC, constituting 73% of TNBC patients while making up 84% of the total cohort [p=0.04]. Comparing TNBC and non-TNBC cases, TNBC cases were observed to have significantly higher TIGS [p=0.014] and PD-L1 expression [p=4.4 × 10−7]. Additionally, TNBC cases trended towards exhibiting greater cell proliferation [p=0.069]. These differences were found to be driven primarily by metastatic tumors, among which TNBC tumors showed significantly higher TIGS [p=0.015], cell proliferation [p=0.021], and PD-L1 expression [p=2.9 × 10−7] than non-TNBC tumors, while none of these significant associations were observed among primary tumors. Triple negative status was significantly associated with PD-L1 expression (assessed by IHC), with a majority of PD-L1 positive cases determined to be triple negative [70% of CPS≥1% cases, p=5 × 10-5; 59% of CPS≥10% cases, p=6 × 10−4]. Several immune-related genes and immune checkpoint molecules were over-expressed in triple negative breast cancer, including CD8, GZMB, PRF1, CCL5, IFNG, TIGIT and CXCL10. A number of genes were also significantly overexpressed in metastatic tumors: KRT5 [p=0.02], TFRC [p=0.04], ABCF1 [p=0.04], FCRLA [p=0.05], LAMP3 [p=0.05], and underexpressed in metastatic tumors: ENTPD1 [p=0.05], IGSF6 [p=0.03], and ITGA1 [p=0.03]. Conclusions: Our comprehensive biomarker analyses showed that metastatic TNBC has a more inflamed tumor microenvironment and higher checkpoint target expression compared to non-TNBC. Further analysis of immune expression by site-specific metastases and correlation with immunotherapy outcomes is warranted to guide clinicians in selection of the ideal metastatic site to biopsy for therapeutic decision making. However, in a collective TNBC context, these data support the use of immunotherapy in metastatic TNBC. Citation Format: Robert Seager, Heidi Ko, Sarabjot Pabla, Maria-Fernanda Senosain, Erik Van Roey, Shuang Gao, Kyle Strickland, Rebecca Previs, Mary Nesline, Stephanie Hastings, Shengle Zhang, Jeffrey Conroy, Taylor Jensen, Marcia Eisenberg, Brian Caveney, Eric Severson, Shakti Ramkissoon, Shipra Gandhi. Metastatic triple negative breast cancer has distinct tumor immune landscape [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-06-09.

Determining the Optimal Length of Clinical Education Experiences: Surveying Doctor of Physical Therapy Academic and Clinical Faculty.

There is wide variability in the length of full-time clinical education experiences (CEEs) among Doctor of Physical Therapy (DPT) programs. We investigated academic and clinical faculty perspectives on the optimal length and level of agreement on the length, timing, and offering of full-time CEEs. A survey assessing perspectives on the optimal length and level of agreement for the length, timing, and offering of full-time CEEs was completed by 100 academic and 240 clinical faculty. Differences between academic and clinical faculty responses on the optimal length and level of agreement were assessed with a 2-sample test of proportions and 2-sample t -test. Participants believed that the length of full-time CEEs (in weeks) should be single CEE 10.6 (SD 2.3); first CEE 7.8 (SD 2.1); terminal CEE 12.5 (SD 5.4); integrated CEE 9.6 (SD 1.9); and total CEEs 37.2 (SD 6.9). There were significant differences (MD = -3.0; 95% confidence interval [CI] -4.6 to -1.6) between academic and clinical faculty perspectives for the total length of CEEs. No significant differences between academic and clinical faculty perspectives for the length of single, first, terminal, or integrated CEEs. There were significant differences between academic and clinical faculty perspectives for the optimal length of inpatient (MD = 1.1; 95% CI 0.6-1.6) and specialty (MD = 0.8; 95% CI 0.2-1.3) settings. There were significant differences between academic and clinical faculty level of agreement for 8 of 15 items. There was consistency between academic and clinical faculty regarding the perceived optimal length of full-time CEEs. Academic and clinical faculty perspectives for the optimal length of terminal full-time CEEs (12.5 weeks) were different than those for the national average (21.8 weeks) length of terminal full-time CEEs. Our study provides evidence to support DPT programs' clinical education curriculum decisions regarding the length of full-time CEEs to optimize students learning and maturation.

Quantitative Time-of-Flight Head Magnetic Resonance Angiography of Cerebrovascular Disease.

Standard Cartesian time-of-flight (TOF) head magnetic resonance angiography (MRA) is routinely used to evaluate the intracranial arteries, but does not provide quantitative hemodynamic information that is useful for patient risk stratification as well as for monitoring treatment and tracking changes in blood flow over time. Quantitative TOF (qTOF) MRA represents a new and efficient method for simultaneous evaluating the intracranial arteries and quantifying blood flow velocity, but it has not yet been evaluated in patients with cerebrovascular disease. To evaluate qTOF for simultaneously evaluating the intracranial arteries and quantifying intracranial blood flow velocity in patients with cerebrovascular disease, without the need for a phase contrast (PC) scan. Prospective. Twenty-four patients (18 female, 6 male) with cerebrovascular disease. Head MRA at 3 T using gradient-echo 3D qTOF, standard Cartesian TOF, and PC protocols. Three independent readers assessed arterial image quality using a 4-point scale (1: non-diagnostic, 4: excellent) and artifact presence. Total and component flow velocities obtained with qTOF and PC were measured. Wilcoxon signed-rank tests, Gwet's AC2, intraclass correlation coefficients (ICC) for absolute agreement, Bland-Altman analyses, tests of equal proportions. P values <0.05 were considered statistically significant. Averaged across readers and compared to standard Cartesian TOF, qTOF significantly improved overall arterial image quality (3.8 ± 0.2 vs. 3.6 ± 0.5), image quality at locations of pathology (3.7 ± 0.5 vs. 3.4 ± 0.7), and increased the proportion of evaluations rated without artifacts (63.9% [46/72] vs. 37.5% [27/72]). qTOF significantly agreed with PC for total flow velocity (ICC = 0.71) and component flow velocity (ICC = 0.89). qTOF angiography of the head matched or improved upon the image quality of standard Cartesian TOF, reduced image artifacts, and provided quantitative hemodynamic data, without the need for a PC scan. 2 TECHNICAL EFFICACY: Stage 2.