bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimization and Local Cost-Effectiveness of Nasopharyngeal Carcinoma Screening Strategies in Southern China: Secondary Analysis of the Guangdong Randomized Trial
Authors: Miller Jacob A. , Liu Zhiwei , Pinsky Benjamin A. , Le Quynh-Thu , Li Tong , Yu Kelly J. , Hildesheim Allan , Cao Su-Mei 
Published: May 2024

Abstract

Background:
Screening with anti-Epstein–Barr virus (EBV) serology and endoscopy decreased nasopharyngeal carcinoma (NPC) mortality in Guangdong in a randomized trial. We conducted a secondary analysis of this trial using local incidence and cost data to optimize screening programs, hypothesizing that screening could be cost-effective in southern China.

Methods:
Screening costs and life-years after NPC diagnosis were obtained from the Guangdong trial’s intent-to-screen population (men and women aged 30–69). Seropositive subjects were rescreened annually for 5 years. Thereafter, we evaluated 12 screening strategies in Guangdong and Guangxi using a validated model. Strategies used combinations of serology, nasopharyngeal swab PCR (NP PCR), endoscopy, and MRI from trial subcohorts. Incidence data and costs were obtained from local cancer registries and the provincial healthcare system.

Results:
In the intent-to-screen population, screening with serology and endoscopy was cost-effective (¥42,366/life-year, 0.52 GDP per capita). Screening for 5 to 15 years between ages 35 and 59 years met a willingness-to-pay threshold of 1.5 GDP/quality-adjusted life-years in all modeled populations. Despite doubling costs, adding MRI could be cost-effective via improved sensitivity. NP PCR triage reduced endoscopy/MRI referrals by 37%. One-lifetime screen could reduce NPC mortality by approximately 20%.

Conclusions:
EBV–based serologic screening for NPC is likely to be cost-effective in southern China. Among seropositive subjects, the preferred strategies use endoscopy alone or selective endoscopy triaged by MRI with or without NP PCR. These data may aid the design of screening programs in this region.

Impact:
These findings support population-based screening in southern China by defining the target population, cost-effectiveness, and optimized screening approach.
Abstract ED04-02: Combination endocrine therapy following progression on first-line therapy
Authors: O'Regan R. 
Published: May 2024

Abstract
Assessing genomic status is critical to make treatment decisions in patients who have experienced disease progression following a CDK 4/6 inhibition with endocrine therapy. Three trials have evaluated CDK 4/6 inhibition with endocrine therapy through progression and show that switching CDK 4/6 inhibitor results in modest efficacy while continuing the same CDK 4/6 inhibitor is not effective. The optimal therapy for patients whose tumors have a PI3-kinase mutation is alpelisib and fulvestrant. Other PIK3-ca inhibitors have not shown efficacy to date. Everolimus with endocrine therapy is an effective second line approach. Emerging data demonstrate efficacy of AKT inhibition with endocrine therapy. Several other agents are in clinical development.
Citation Format: R. O'Regan. Combination endocrine therapy following progression on first-line therapy [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 ED04-02.
Abstract ED11-03: Approaches to radiation therapy for inflammatory breast cancer
Authors: Bellon J. 
Published: May 2024

Abstract
Inflammatory breasst cancer ((BC) is an uncommon and highly agressive form of breast cancer, with a predilection for both distant metastases and local regional recurrence. In this talk we will review challenges in radiation therapy planning and execution unique to IBC. These include staging studies and photographs to define the full extent of disease prior to systemic therapy, as well as current thoughts on dose and fractionation. We will also discuss pros and cons of local therapy in patients with metastatic disease, as well as ongoing research studying ways to optimize local regional control with concurrent systemic therapy and radiation.
Citation Format: J. Bellon. Approaches to radiation therapy for inflammatory 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 ED11-03.
Abstract PO1-04-13: CARDIAC-STAR: Prevalence of Cardiovascular Comorbidities in Hormone Receptor Positive Human Epidermal Growth Factor Negative metaStatic breasT cAnceR
Authors: Dent Susan , Guha Avirup , Moore Heather , McCaleb Rachael , Arias Irene , Stergiopoulos Stella , Li Benjamin , Makari Doris , Fradley Michael 
Published: May 2024

Abstract
BACKGROUND: Baseline cardiovascular (CV) comorbidities can impact treatment decisions for patients (pts) with metastatic breast cancer (mBC). There is limited data on the prevalence of CV comorbidities at the time of hormone receptor positive human epidermal growth factor negative (HR+/HER2-) mBC diagnosis. The primary objective of this study is to describe the prevalence of pre-existing CV comorbidities in women and men with newly diagnosed HR+/HER2- mBC. A secondary objective is to describe the first documented cancer treatment for patients with or without CV comorbidities. METHODS: Women and men ≥18 years of age with newly diagnosed HR+/HER2- mBC from 01/2016 to 12/2021 were included in this retrospective, observational study using the Merative™ Marketscan® Commercial and Medicare Databases which is nationally representative. Evidence of mBC was defined as having two or more claims containing one or more diagnosis code for BC at least 30 days apart and at least two secondary malignancy diagnosis codes. Previously published claims-based algorithms were used to identify the HR+/HER2- molecular subtype. The index date is defined as the date of first mBC diagnosis. Patients had a 1-year pre-index period for observation of CV comorbidities and a 6-month post-index period for first documented cancer treatmen RESULTS: We identified 5,452 pts with HR+/HER2- mBC, 99% of whom were female, with a median age of 58 years (yrs) (IQR 13), and 83% having a health plan from an employer; i.e., are still employed. At mBC diagnosis, 3,335 pts (61.2%) had at least one pre-existing CV comorbidity (see Table). The most reported CV comorbidities were hypertension (50.7%), hyperlipidemia (33.7%), and diabetes (19.2%). The median age of pts with or without a CV comorbidity was 61 and 52 yrs, respectively; 16.2% with CV comorbidities were ≥75 yrs. Additional data, including first documented treatment, will be presented at the meeting. CONCLUSIONS: The prevalence of CV comorbidities in pts with HR+/HER2- mBC is often underrecognized. In this analysis, more than half of pts had at least one CV comorbidity by mBC diagnosis. CV comorbidities may impact treatment decisions in the HR+/HER2- mBC population, particularly in older pts.
Table
Citation Format: Susan Dent, Avirup Guha, Heather Moore, Rachael McCaleb, Irene Arias, Stella Stergiopoulos, Benjamin Li, Doris Makari, Michael Fradley. CARDIAC-STAR: Prevalence of Cardiovascular Comorbidities in Hormone Receptor Positive Human Epidermal Growth Factor Negative metaStatic 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 PO1-04-13.
Abstract PO1-11-02: Reporting of Post-protocol Therapies in Metastatic Breast Cancer Registration Clinical Trials: A Systematic Review
Authors: Shachar Shlomit , Korzets Yasmin , Shepshelovich Daniel , Zlotchover Noa , Amir Eitan , Tibau Ariadna , Goldvaser Hadar 
Published: May 2024

Abstract
BACKGROUND As the treatment for metastatic breast cancer (MBC) often includes sequential lines of therapy, data on post-protocol treatment in clinical trials are valuable in the assessment of long-term outcome. The objective of this study was to assess the reported data on post-protocol therapy in clinical trials supporting US Food and Drug Administration (FDA) approval of drugs for MBC.
METHODS We identified all initial and subsequent published trials supporting FDA approved indications for MBC between 1/2000-2/2023.
Collected data included study design, patient characteristics and whether reporting on post-protocol therapy was available. Differences in study design and population between studies with and without data on post-protocol therapy were evaluated.
FINDINGS A total of 41 indications for MBC were identified. Supporting studies comprised 20,152 patients. Data were evaluated from 241 publications or abstracts. Reporting of post progression therapy was available for 21 (51%) indications. Of these, post-progression therapy data were often partial and the appropriateness of the therapy could not be evaluated. At the time of FDA approval, data on overall survival (OS) were reported only in 17 (41%) studies. Of these, in 8 studies OS was significantly improved, in 7 studies OS was not improved and 2 studies were single arm. Differences between studies with and without data on post progression therapy are presented in the Table. Studies with OS as their primary endpoints were associated with significantly higher reporting of post-protocol therapy, while studies with both OS and progression free survival (PFS) as their primary endpoint had low reporting rate. There were no other statistically significant differences. Reporting post-protocol therapy has not changed over time with reported data in 50% and 52% studies between 2000-2010 and 2011-2023, respectively.
CONCLUSIONS Data on post progression therapy in trials supporting FDA approval of drugs for MBC are available in fewer than half of indications. Reported data are often partial and may not include sequential therapies consistent with standard of care. As subsequent lines of therapy may have a crucial role in patients' outcome, post protocol reporting should be included in the regulatory submission and be made available publicly.
Differences between studies with and without data on post progression therapy
Citation Format: Shlomit Shachar, Yasmin Korzets, Daniel Shepshelovich, Noa Zlotchover, Eitan Amir, Ariadna Tibau, Hadar Goldvaser. Reporting of Post-protocol Therapies in Metastatic Breast Cancer Registration Clinical Trials: A Systematic Review [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 PO1-11-02.
Abstract PO1-12-07: Denosumab vs. Pamidronate in the Management of Osteolytic Bone Metastases Secondary to Breast Cancer, a Multi-Institutional Analysis
Authors: Bradley Megan , Nichols Mabry , Miles Brittany 
Published: May 2024

Abstract
Breast cancer is one of the most common cancers in women and is associated with poor outcomes due to the metastatic potential of high-grade tumors. One common site of breast cancer metastasis is to the bone, leading to serious adverse effects such as bone pain, bone fracture, and spinal cord compression. Denosumab, a monoclonal antibody against the receptor activator of nuclear factor kappa-b (RANK) ligand (RANKL), and Pamidronate, a bisphosphonate, are two pharmacologic agents offered for the treatment of these adverse complications. The goal of this study was to conduct a retrospective cohort analysis across multiple institutions to compare the efficacy of Denosumab vs. Pamidronate in the management of osteolytic bone metastases secondary to breast cancer by evaluating the risk of adverse events. TriNetX, an online network that provides access to anonymized medical records for more than 108 million patients in 72 large healthcare organizations, was used in this study. Two cohorts, consisting of 847 patients with a diagnosis of bone metastases and breast cancer, were created and subsequently matched for age, race, gender, and ethnicity. One cohort was given Denosumab while the other was given Pamidronate, and each cohort was excluded from receiving the other medication. The occurrence of pathologic fracture in each arm, spinal cord compression, and overall five-year survival rate was measured and analyzed. The results of this study showed that Denosumab had a statistically insignificant risk reduction in both pathological fracture (2.7% vs. 2.8%, p = 0.88) and spinal cord compression (2.6% vs. 2.7%, p = 0.88) and a statistically insignificant difference in the overall five-year survival rate (45.5% vs. 52.4%, p = 0.78) when compared to Pamidronate. As a result, additional factors such as financial cost, route of administration, dosing schedule, and potential adverse side effects should be discussed with each individual who requires pharmacological therapy for bone metastases secondary to breast cancer.
Citation Format: Megan Bradley, Mabry Nichols, Brittany Miles. Denosumab vs. Pamidronate in the Management of Osteolytic Bone Metastases Secondary to Breast Cancer, a Multi-Institutional Analysis [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 PO1-12-07.
Abstract PO1-13-06: Androgen Receptor Isoform V7 (AR-V7): A Promising Biomarker for Prognosticating Breast Cancer Aggressiveness
Authors: Srivastava Tryambak Pratap , Talukdar Joyeeta , Verma Rohit Kumar , Karmakar Subhradip 
Published: May 2024

Abstract
Androgen Receptor (AR) is an emerging endocrine therapy target in Breast Cancer (BrCa) with up to 80% expression in clinical cases. AR-V7 is a constitutively activated splice variant of AR having a truncated ligand-binding domain (LBD). This confers ligand-independent transcriptional activity to AR-V7 and makes it susceptible to nonsteroidal antiandrogens such as Bicalutamide or Enzalutamide which target the LBD of AR. Higher levels of AR-V7 in metastatic prostate cancer leads to therapeutic resistance and enhanced metastasis. We assessed AR-full length (AR-FL) and AR-V7 expression in BrCa cell lines of different molecular subtypes. This was extended for a clinical correlation of AR-FL and AR-V7 in validated treatment naïve BrCa patients undergoing surgical intervention at a tertiary care hospital in India. Transcriptomic and proteomic analysis was performed using qRT-PCR and Western Blotting. Immunocytochemistry and immunohistochemistry were used to examine protein expression and localisation in cells and tissues. AR-FL and AR-V7 were variably expressed in cell lines which got elevated with Dihydrotestosterone (DHT) treatment. Cell lines stimulated with Bicalutamide or Enzalutamide showed significant downregulation in AR-FL expression. From a cohort of 82 clinical cases, more than 50% originated from the urban setting, post-menopausal stage, and in the age groups of 61 to 70 years. ER, PR, HER2, and AR were positive in 65%, 55%, 24%, and 67% respectively. We were able to correlate aggressive clinical traits and higher pathological grades with increased expression of AR-V7 in the AR-positive BrCa fraction. This was consistent with the cell line-based preclinical research. This study affiliates AR-V7 as an important prognostic biomarker for predicting breast cancer aggressiveness. It can serve as a screening marker of poor clinical outcomes and aid in appropriate therapeutic intervention. These outcomes, however, seek extensive prospective validation.
Citation Format: Tryambak Pratap Srivastava, Joyeeta Talukdar, Rohit Kumar Verma, Subhradip Karmakar. Androgen Receptor Isoform V7 (AR-V7): A Promising Biomarker for Prognosticating Breast Cancer Aggressiveness [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 PO1-13-06.
Abstract PO1-16-09: Does T1c-2N0-1M0 triple negative breast cancer derive a benefit from neoadjuvant chemotherapy?
Authors: Zhang Jie , Yu Yushuai , Chen Weiwei , Fu Wenfen , Chen Ruiliang , Yi Jialu , Song Chuangui 
Published: May 2024

Abstract
Objective: Although neoadjuvant chemotherapy (NCT) is a standard approach for operable triple negative breast cancer (TNBC), the potential risks brought by it should also be noticed. Is the expanding indication of NCT to T1cN0M0 population appropriate? We conducted an investigation to compare the long-term survival of small tumor TNBC between NCT and adjuvant chemotherapy (ACT). Methods: For this propensity-matched analysis, we used data from SEER database. We enrolled 1183 cases with NCT and 2550 cases with ACT who are AJCC clinical T1c-T2 N0-N1, diagnosed with TNBC, from 2016 to 2017. The propensity score matching was utilized to minimize baseline characteristics bias. Based on the Cox proportional hazard regression model, we calculated hazard ratios (HR) with 95% confidence intervals (CIs). Results: Multivariate analysis in matched patients showed that NCT had no significant survival benefit compared with ACT in T1c-2N0-1M0 TNBC patients. Stratified analyses by T stage and N stage demonstrated NCT mainly presented a survival advantage in patients with N1 stage. Further investigation found that NCT didn’t improve BCSS (HR=0.472; 95% CI: 0.135-1.647; p=0.239) and OS (HR=0.392; 95% CI: 0.147-1.047; p=0.062) for patients with T1cN0M0 TNBC; however, for patients with T2N1M0 TNBC, it was associated with improved OS (HR=1.951; 95% CI: 1.003-3.797; p=0.049). Conclusion: In our study, we did not find any profit brought by NCT in the stage I and stage IIa cohorts, but even more unfavorable outcomes appeared in the T1cN0M0 cohort. Therefore, whether the candidates of NCT should be extended to T1cN0M0 still need to be cautious.
Treatment effect on breast cancer-specific survival (BCSS) and overall survival (OS) by subgroup.
Citation Format: Jie Zhang, Yushuai Yu, Weiwei Chen, Wenfen Fu, Ruiliang Chen, Jialu Yi, Chuangui Song. Does T1c-2N0-1M0 triple negative breast cancer derive a benefit from neoadjuvant chemotherapy? [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 PO1-16-09.
Abstract PO1-20-10: Wernicke Encephalopathy Syndrome in Metastatic Breast Cancer – A Diagnostic Dilemma or An Underdiagnosed Entity
Authors: Patel Archit , Roy Arya Mariam , Alberico Ronald , Gandhi Shipra 
Published: May 2024

Abstract
Wernicke encephalopathy (WE) is an acute medical syndrome that manifests as a clinical triad of encephalopathy, gait ataxia, and oculomotor dysfunction, requiring urgent treatment. Early recognition and treatment can prevent severe neurological morbidity and the chronic neurological consequence of WE, known as Korsakoff syndrome. Thiamine (vitamin B1) deficiency is the root cause of WE, which can occur due to several underlying conditions, including chronic alcoholism, hyperemesis of pregnancy, malnutrition, prolonged fasting, and malignancy. In cases of malignancy, WE is often undiagnosed or misdiagnosed because the presenting symptoms can be confused with several other complications of malignancy. We present the case of a 47-year-old woman with no significant medical history who was diagnosed with triple negative metastatic breast cancer and admitted to the hospital with confusion, memory loss, and progressive lower extremity weakness. During her breast cancer treatments, she experienced significant nausea and vomiting, leading to a prolonged state of nutritional imbalance. Patient underwent extensive infectious and neurological workup for encephalopathy including lumbar puncture which was negative for leptomeningeal disease or infection. MRI brain did not show any new metastatic lesions however revealed enhancement of mammillary bodies bilaterally. Mammillary body enhancement can be seen in WE but not always present on imaging. She was treated for WE with high dose of thiamine infusion for five days, resulting in an improvement of her neurological symptoms.
Diagnosing WE in cancer patients is challenging, as there are various factors to consider, such as cerebral metastasis, infection, chemotherapy treatment, and electrolyte imbalances, that can cause neurological symptoms. Cancer patients are at high risk for development of WE due to chemotherapy or whole brain radiation induced nausea and vomiting that can lead to chronic malnutrition. The typical triad of symptoms is not present in many cases and presenting symptoms can be nonspecific which makes the diagnosis challenging. As a result, WE is often underdiagnosed in such patients, making it essential to educate the physician community about this acute neurological manifestation that can be easily treated. A high index of suspicion is necessary for early recognition, and prompt treatment can prevent Korsakoff syndrome, thereby enhancing the overall quality of life of patients with malignancy.
Citation Format: Archit Patel, Arya Mariam Roy, Ronald Alberico, Shipra Gandhi. Wernicke Encephalopathy Syndrome in Metastatic Breast Cancer – A Diagnostic Dilemma or An Underdiagnosed Entity [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 PO1-20-10.
Abstract PO1-22-06: Pre-operative radiotherapy followed by mastectomy and breast reconstruction – a systematic review of oncological and reconstructive outcomes
Authors: Ho Ken , Ward Joseph , Ike Chiugo , Thiruchelvam Paul , Khan Aadil , Leff Daniel 
Published: May 2024

Abstract
Background Pre-operative radiotherapy (PRT) followed by mastectomy and autologous breast reconstruction for locally advanced breast cancer has the potential to reduce the deleterious impact of radiotherapy on the reconstructed breast and expedite treatment without impact on oncologic control. The PRADA feasibility study (Lancet Oncol 2022; 23: 682-90) has previously demonstrated the technique is technically feasible and safe in modern breast oncology practice, however, there is a clear necessity for longer term outcome data to precisely determine clinical efficacy. In order to understand and appraise this evidence gap, we performed a systematic review focused on oncologic and reconstructive outcomes of PRT followed by mastectomy and breast reconstruction. Methods A prospectively registered search (PROSPERO ID: CRD42023349524) of Medline (Ovid), EMBASE (Ovid), EMCARE (Ovid) and CINAHL (EBSCO) databases was performed in August 2022 for studies reporting NART prior to mastectomy and breast reconstruction. Oncological and aesthetic outcomes were extracted with risk of bias (ROBINS-I) and methodological quality assessed (STROBE checklist) for each study. Results Twenty one published articles (18 papers and 3 abstracts) were identified reporting the outcomes of 1,126 patients with median follow-up between 19.0-212.4 months. Seventeen studies were non randomised single-centre cohort studies (12 retrospective and 5 prospective). Patients received neoadjuvant chemotherapy in 18 studies. The majority of studies were of low methodological quality and at serious risk of bias. Rates of locoregional recurrence and overall survival ranged between 0-21.7% and 79.8%-98.3% respectively. Rates of flap loss or necrosis ranged from 0-12.0%. Rates of revisional procedures ranged between 0-35.3%. Patient-reported outcomes were reported in 8 studies and were mostly ‘good’ or ‘excellent’. Conclusion The published literature described a heterogeneity of outcome for patients undergoing NART prior to mastectomy and breast reconstruction. This reflects a large number of small retrospective single-centre cohort studies of low methodological quality at risk of bias. There is a clear need for a prospective randomised controlled trial appraising the outcomes of PRT in the context of autologous breast reconstruction.
Citation Format: Ken Ho, Joseph Ward, Chiugo Ike, Paul Thiruchelvam, Aadil Khan, Daniel Leff. Pre-operative radiotherapy followed by mastectomy and breast reconstruction – a systematic review of oncological and reconstructive outcomes [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 PO1-22-06.