bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcome evaluation of prophylactic internal iliac balloon occlusion in the management of patients with placenta accreta spectrum
Authors: Osman Asaad , Das Raj , Pinas Ana , Hartopp Richard , Livermore Deborah , Hawthorn Benjamin , Chun Joo-Young , Mailli Leto , Morgan Robert , Ratnam Lakshmi 
Published: July 2024

Abstract
Purpose
To evaluate outcomes and complications of prophylactic internal iliac balloon occlusion (PIIBO) in the management of patients with placenta accreta spectrum (PAS) at a large regional referral centre.

Materials and methods
A retrospective review of all PIIBO for PAS performed over a 12-year period (2010–2022). Information for analysis was gathered from the local RIS/PACS and clinical documentation. Collected data included patient demographics, indication for procedure, sheath insertion and removal time, total duration of balloon inflation and complications that occurred.

Results
106 patients underwent temporary internal iliac artery balloon occlusion within the 12-year period. All procedures utilised bilateral common femoral artery punctures, 6Fr sheath and 5Fr Le Maitre occlusion balloons. Catheters were successfully positioned and balloons inflated in obstetric theatre following caesarean delivery in 100% of the cases. The uterus was conserved in every case. There was no maternal mortality or foetal morbidity.
Twenty patients (18.9%) had some form of complication that required further intervention. Of these, 7(6.6%) had post-operative PPH, which was treated with uterine artery embolisation; and 13 (12.3%) had arterial thrombus which required aspiration thrombectomy. All procedures were technically successful with no long-term sequelae.

Conclusion
PIIBO plays an important part in reducing morbidity and mortality in patients with PAS. Clear pathways and multidisciplinary team working is critical in the management of these patients to ensure that any complications are dealt with promptly to avoid long-term sequelae.
Examining audiologist candidates' self-esteem and professional self-esteem
Authors: Koçyiğit Azize Arzu , Dizdar Handan Turan 
Published: July 2024

Abstract
Background
Self-esteem is an individual's perception of themselves. Professional self-esteem is defined as the individual's perception of worthiness regarding their preferred profession. The research aims to examine the relationship between the self-esteem and professional self-esteem of Audiology department students and raise awareness of this issue.

Material and Method
In our study, 532 students in the Audiology undergraduate department were included. Professional Self-Esteem and Self-Esteem questionnaires were delivered to the students online via Google Forms, using snowball sampling, in social media groups of the Audiology undergraduate students. Data were analyzed using Spearman correlation analysis, Mann Whitney U, and Kruskal Wallis Test. p < 0.05 was accepted as significance value.

Results
According to the results, it has been observed that there is a weak and significant positive correlation between the professional self-esteem of the audiologist candidates and their total self-esteem scores (p < 0.05). Self-esteem and professional self-esteem scores of those who chose the profession willingly were significantly higher than those who did not choose the profession willingly (p < 0.05). As the grade level increased, professional self-esteem decreased significantly (p < 0.05). There was no significant difference between the scores in both scales according to income, university type, and gender (p > 0.05).

Conclusion
As a result, it was observed that as the self-esteem of the audiologist candidates increased, their professional self-esteem increased. Also, as the class level increased, their professional self-esteem decreased.
Clinical outcomes in salivary adenoid cystic carcinoma.
Authors: Dalal Prarthana , Dermody Sarah , Brummel Collin , Brenner Chad , Casper Keith , Chinn Steven B. , Malloy Kelly M , Mierzwa Michelle Lynn , Heft Neal Molly , Prince Mark , Shah Jennifer Lobo , Shuman Andrew , Stucken Chaz , Spector Matthew , Worden Francis P. , Swiecicki Paul 
Published: July 2024

6102 Background: Adenoid cystic carcinoma (ACC) is a rare salivary gland malignancy with a paucity of clinical outcome data. As such, evidence supporting and informing current guidelines remains limited. Methods: Inclusion criteria stipulated adults with adenoid cystic carcinoma treated at the University of Michigan between 1988 and 2019 with complete records (n=102). Clinical variables including demographics, disease stage, and treatment modality were abstracted. Pathologic variables analyzed included tumor grade, perineural invasion, lymphovascular invasion, and surgical margin status. Multivariate analyses were performed with disease recurrence calculated with Kaplan-Meier methodology as the primary outcome. Results: Mean age at diagnosis was 59 years; stage I and II disease accounted for 35 (38%) patients. Initial treatment was most commonly surgery with adjuvant radiation (77%). Median follow-up was 3 years. Distant metastatic disease developed in 34 (33%) patients. Most common sites included lung (68%), bone (21%), and brain (21%). Median time to distant metastases was 46 months with median overall survival of 58 months. Patients with locoregional recurrence experienced median survival of 91 months. Multivariate analysis adjusted for grade, perineural invasion, and surgical margin status (Table). Grade 3 tumors with predominantly solid histologic pattern pose higher risk of recurrence compared to grade 1 tubular histologic patterns as a reference (HR 3.69, 95% CI 1.15-11.88, p=0.028). Conclusions: Survival among patients with adenoid cystic carcinoma after locoregional recurrence is significantly better compared to those experiencing distant metastasis. Furthermore, tumor grade is most predictive of recurrence. Additionally, distant metastases may emerge over the course of many years. These data from one of the largest retrospective databases to date may inform the development of disease-specific surveillance guidelines and novel salvage treatment paradigms. [Table: see text]
Unraveling the synergistic mechanisms of pyrotinib in combination with trastuzumab: Insights from the PHILA trial.
Authors: Liu Shuning , Lan Bo , Li Lixi , Qian Haili , Ma Fei 
Published: July 2024

e13015 Background: There are many options for the treatment of advanced HER2-positive breast cancer. The results of PHILA study suggest that pyrotinib, trastuzumab and docetaxel may be considered as a potential first line treatment for patients with untreated HER2-positive metastatic breast cancer. We aimed to investigate the synergistic mechanisms of pyrotinib plus trastuzumab and compare them to trastuzumab plus pertuzumab, providing further insights for the PHILA trial. Methods: The efficacy of combination treatments was detected by cell vitality assay, Western blot and immunohistochemistry. The relevant mechanism was examined by flow cytometry and co-immunoprecipitation. Cell-derived xenografts and TUBO tumor model were utilized to evaluate the anti-tumor activity of rational combinations. Next-generation sequencing of circulating tumor DNA from a cohort of 18 patients in the PHILA trial was performed to evaluate molecular alterations associated with clinical response. Results: We demonstrated that pyrotinib plus trastuzumab superiorly inhibited cell growth than trastuzumab plus pertuzumab in models of HER2-dependent breast cancer. In addition to inhibiting HER family phosphorylation, pyrotinib plus trastuzumab synergistically reduced membrane HER2 levels by inducing receptor ubiquitination and internalization via HSP90 dissociation, which resulted in a comprehensive blockade of HER signaling pathway. Moreover, TUBO tumor model was utilized to further confirm the synergistic effects of pyrotinib and anti-neu antibody on HER2 signaling cascade. In both treatment groups of PHILA study, patients with aberrant mutations in HER2 signaling cascade showed a significantly shorter median progression-free survival compared to individuals with wild-type pathway. Correspondingly, in models of HCC1954 breast cancer cell harboring PIK3CA H1047R mutation, we did not observe a synergy between pyrotinib and trastuzumab. Conclusions: Pyrotinib and trastuzumab synergistically achieve the comprehensive blockade of HER signaling pathway in HER2-dependent breast cancer. Patients with advanced HER2-positive breast cancer, who are addicted to HER2 signaling cascade, could be considered for pyrotinib in combination with trastuzumab and docetaxel as an alternative first line treatment.
Comparing the mutation profiles of primary HER2-positive breast cancers in patients with and without brain metastases.
Authors: Du Tian , Sun Peng , Chen Yuhong , Deng Rong , Tang Jun 
Published: July 2024

e13018 Background: Brain metastasis is a frequent and devastating event of HER2-positive breast cancer. Identifying the driver genes of brain metastasis is important for the prevention and treatment of brain metastasis. In this study, we compared the gene mutation profiles of primary breast cancers between patients with and without brain metastases, aiming to identify new candidate genes associated with brain metastases. Methods: HER2-positive and lymph node-positive early breast cancers of 21 patients who eventually developed brain metastases (BM group) and 27 patients without any metastasis (NM group) at a minimum 5-year follow-up were retrieved from the Sun Yat-sen University Cancer Center. Whole-exome sequencing was performed on primary breast cancers (FFPE) and matched normal breast tissues or peripheral blood. Mutect2 was used to detect somatic mutations, and Fisher’s exact test was used to identify genes mutated at different frequencies in the BM and NM groups. The mRNA expression changes of genes mutated at higher frequencies in the BM group were further analyzed in 16-pair matched HER2-positive primary breast cancers and brain metastases using the public dataset (1). Results: The BM and NM groups exhibited similar TP53 (33.3% vs. 55.6%, p=0.15) and PIK3CA (23.8% vs. 25.9%, p=1) mutation rates. The mutation rates of AP3B1 (38.1% vs. 3.7%), DHTKD1 (23.8% vs. 0), ERCC6L2 (38.1% vs. 7.4%), DNAH5 (33.3% vs. 3.7%), ZNF207 (33.3% vs. 7.4%), SPATA31E1 (19.0% vs. 0), FAM111B (19.0% vs. 0), ATG3 (19.0% vs. 0), CDK14 (19.0% vs. 0), TUT4 (19.0% vs. 0), CCNB3 (19.0% vs. 0), MGA (19.0% vs. 0), CLCA1 (28.6% vs. 3.7%), BBS7 (28.5% vs. 3.7%) and GABRG1 (38.1% vs. 11.1%) were significantly (p<0.05) higher in the BM group than in the NM group. Among these genes, CDK14 and TUT4 were significantly downregulated, and ZNF207 and FAM111B were significantly upregulated in brain metastases compared to their matched primary breast cancers. Conclusions: We identified several genes with higher mutation rates in primary breast cancer of patients who eventually developed brain metastases. These genes warrant further investigation in the development of brain metastases in HER2-positive breast cancer. 1. Cosgrove et al. NC 2022.
Association of low adherence to weekly cisplatin with outcomes in patients with head and neck cancer treated with chemoradiation.
Authors: Virk Jas , Gill Jasmin , Fekrmandi Fatemeh , Iovoli Austin , Farrugia Mark , Ma Sung Jun , Singh Anurag K. 
Published: July 2024

e18053 Background: The National Comprehensive Cancer Network (NCCN) guideline recommends consideration of weekly cisplatin as an alternative option for patients with head and neck cancer undergoing definitive chemoradiation. However, in a recent phase III trial (ConCERT), 20% of patients treated with weekly cisplatin could not receive a total of 200 mg/m2, and the association of low adherence to weekly cisplatin and cancer control outcomes remains unclear. To fill this knowledge gap, we performed an observational cohort study of patients with head and neck cancer undergoing definitive chemoradiation with weekly cisplatin. Methods: Our institutional database at the Roswell Park Comprehensive Cancer Center was queried for patients with non-metastatic head and neck cancer who underwent definitive chemoradiation with weekly cisplatin (40 mg/m2) between November 2007 and April 2023. Adherence to weekly cisplatin was defined as receiving at least 5 cycles with a total cumulative dose of 200 mg/m2. Survival outcomes were evaluated using Kaplan-Meier method, log-rank tests, Cox proportional hazard multivariable (MVA) analyses. Logistic MVA was performed to identify variables associated with low adherence to weekly cisplatin. Fine-Gray MVA was performed to analyze failure outcomes with death as a competing event. Results: Among 119 patients who met our criteria, 51 patients (42.9%) had low adherence to weekly cisplatin. Median follow up was 19.8 months (interquartile range 8.8-65.6). Low adherence to weekly cisplatin was associated with worse overall survival (adjusted hazards ratio [aHR] 2.94, 95% confidence interval [CI] 1.58-5.47, p<0.001) and progression-free survival (aHR 2.32, 95% CI 1.29-4.17, p=0.005). It was also associated with worse distant failure (aHR 4.55, 95% CI 1.19-17.3, p=0.03), but not locoregional failure (aHR 1.61, 95% CI 0.46-5.58, p=0.46). KPS <90 was the only variable associated with low adherence to weekly cisplatin (adjusted odds ratio [aOR] 2.67, 95% CI 1.10-6.65, p=0.03). Conclusions: Our study suggested that over 40% of patients underwent fewer than 5 weekly cisplatin cycles and that low adherence to weekly cisplatin was an independent, adverse prognostic factor for worse survival and distant failure outcomes. Those with reduced adherence to weekly cisplatin were more likely to have poor performance status. Further studies are warranted to improve the adherence to chemotherapy and outcomes.
Association of absolute neutrophil count with outcomes in patients with head and neck cancer treated with chemoradiation.
Authors: Gill Jasmin , Virk Jas , Fekrmandi Fatemeh , Iovoli Austin , Farrugia Mark , Ma Sung Jun , Singh Anurag K. 
Published: July 2024

e18055 Background: Systematic inflammation plays an integral role in tumor development and metastasis. High neutrophil counts, among various peripheral blood biomarkers, have been shown to be associated with worse survival outcomes in multiple cancer types. To evaluate the absolute neutrophil count (ANC) as a prognostic biomarker in head and neck cancer, we performed an observational cohort study of patients undergoing definitive chemoradiation. Methods: Our institutional database at the Roswell Park Comprehensive Cancer Center was queried for patients with non-metastatic head and neck cancer who underwent definitive chemoradiation between June 2007 and April 2023. ANC was analyzed as a continuous variable. Survival outcomes were assessed using Kaplan-Meier method, log-rank tests, Cox proportional hazard multivariable (MVA) analyses. Fine-Gray MVA was used to analyze failure outcomes with death as a competing event. To reduce selection bias, propensity score matching was performed using ANC as a dichotomous variable with its median value as a cutoff. Subgroup analyses were performed among p16-negative and p16-positive cohorts. Results: A total of 668 patients who met our criteria. Median follow up was 30.3 months (interquartile range 9.9-60.7). Elevated ANC as a continuous variable was associated with worse overall survival (OS; adjusted hazards ratio [aHR] 1.02, 95% confidence interval [CI] 1.01-1.04, p=0.003), progression free survival (PFS; aHR 1.03, 95% CI 1.01-1.04, p<0.001), and distant failure (DF; aHR 1.03, 95% CI 1.01-1.05, p=0.007), but not locoregional failure (LRF; aHR 1.02, 95% CI 1.00-1.05, p=0.10). Similar findings were noted among 278 matched pairs (OS: hazards ratio [HR] 1.66, 95% CI 1.23-2.26, p=0.001; PFS: HR 1.74, 95% CI 1.31-2.29, p<0.001; LRF: HR 1.66, 95% CI 0.98-2.80, p=0.06; DF: HR 1.64, 95% CI 1.03-2.60, p=0.04). On subgroup analysis, among 118 patients with p16-negative tumors, elevated ANC as a continuous variable was not associated with OS (aHR 1.00, 95% CI 0.90-1.11, p=0.97) and PFS (aHR 0.97, 95% CI 0.87-1.08, p=0.54). The number of LRF (n=21) and DF (n=17) were too few to analyze in this subgroup. However, among 344 patients with p16-positive tumors, high ANC was associated with worse OS (aHR 1.03, 95% CI 1.00-1.06, p=0.046), PFS (aHR 1.05, 95% CI 1.02-1.07, p<0.001), LRF (aHR 1.08, 95% CI 1.05-1.12, p<0.001), and DF (aHR 1.04, 95% CI 1.01-1.08, p=0.02). Conclusions: Our study suggested that elevated ANC was an independent, adverse prognostic factor for worse survival and distant metastasis outcomes. Similar findings were also observed among patients with p16-positive tumors, with high ANC also associated with worse locoregional failure. Further studies are warranted to tailor interventions based on such biomarkers.
Study on the efficacy and toxicity of pamiparib combined with tamoxifen in the treatment of patients with epithelial ovarian cancer with biochemical recurrence during first-line PARPi maintenance therapy.
Authors: Meng Yifan , Li Jundong , Wan Ting 
Published: July 2024

TPS5621 Background: A high proportion of ovarian cancer patients tend to have elevated CA-125 1-6 months before imaging recurrence. The time between biochemical recurrence (i.e., only elevated CA-125 without imaging finding or clinical symptoms) to imaging recurrence can be considered a "window period", and if the “window period” can be extended, it may convert platinum-resistant relapsed patients to platinum-sensitive patients, and ultimately improving patient outcomes. The timing of treatment for the biochemical recurrent patients has been controversial. Tamoxifen, an anti-estrogenic drug, is considered an effective option for these patients. Pamiparib (BGB-290) is an investigational small molecule inhibitor of PARP1 and PARP2. According to OReO study(NCT03106987), the "PARPi after PARPi" strategy is effective in recurrent ovarian cancer patients previously treated with a PARP inhibitor. Therefore, we aim to further explore the use of PARP inhibitors in maintenance therapy for patients with ovarian cancer. Methods: This study (NCT05669768) will evaluate the efficacy and toxicity of pamiparib and tamoxifen in ovarian cancer patients with biochemical recurrence during first-line PARPi maintenance therapy. The included ovarian cancer patients are required to achieve No Evidence of Disease (NED) or demonstrated a response following platinum-based chemotherapy, with normalized CA-125 levels. First-line maintenance treatment with a PARP inhibitor is mandatory, with a minimum interval of ≥6 months to biochemical recurrence. The trial design is interventional, employing a Simon two-stage design to estimate sample size. The primary outcome of the study is the CA-125 response rate, which was assessed according to the GCIG criteria.1 The secondary outcome was Time to First Subsequent Therapy (TFST). Patients undergo regular assessments for tumor markers and imaging throughout treatment. If persistent elevation of tumor markers or the detection of recurrent lesions or distant metastases is observed, the patient is promptly removed from the study group. Standardized antitumor therapy is then initiated based on the patient's condition. The total planned enrollment is 46 participants, utilizing a single-group assignment and an open-label design. 1 of planned 12 patients for the first stage of accrual have been enrolled. Reference: 1. Rustin GJ, Vergote I, Eisenhauer E, et al. Definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and CA 125 agreed by the Gynecological Cancer Intergroup (GCIG). Int J Gynecol Cancer. 2011;21(2):419-423. Clinical trial information: NCT05669768 .
A phase 2 study to evaluate efficacy and safety of PRGN-2009, a novel gorilla adenovirus-based immunotherapy, in combination with pembrolizumab versus pembrolizumab monotherapy in patients with recurrent or metastatic cervical cancer.
Authors: Tschernia Nicholas , Birrer Michael J. , Liao John B. , Lankford Amy , Disis Mary L. , Gulley James L. 
Published: July 2024

TPS5623 Background: The association between cervical cancer and human papillomavirus (HPV) is well understood, with nearly all cervical cancer known to be caused by high risk HPV infection. HPV16 and HPV18 are the most common high-risk HPV types and are responsible for about 70% of cervical cancer cases. Recurrent or metastatic cervical cancer is currently treated with pembrolizumab alone or in combination with chemotherapy, however t there remains a significant need for treatments for patients that recur or do not respond at all to pembrolizumab treatment. PRGN-2009 is a gorilla adenovirus-based immunotherapy targeting cancers caused by HPV16 or HPV18. PRGN-2009 includes a novel HPV antigen design to induce HPV16/18-specific T cell immune responses against cancer cells. The rationale for combining the PRGN-2009 with immune checkpoint inhibitor is based on preclinical and clinical data demonstrating that combination of cancer vaccines and immune checkpoint inhibitors can trigger intensified immunogenicity leading to increased antitumor efficacy compared to either treatment alone. PRGN-2009 has been characterized in both in vitroand in vivostudies to support the scientific rationale and the safety of PRGN-2009 has been demonstrated in evaluated in initial Phase 1/2 studies in patients with HPV+ malignancies. Methods: This is a randomized, Phase 2 study to evaluate efficacy and safety of PRGN-2009 in combination with pembrolizumab compared to pembrolizumab alone in patients with recurrent or metastatic cervical cancer. Key inclusion criteria include recurrent or metastatic cervical cancer (histologically or cytologically confirmed) resistant to pembrolizumab. Subjects will be randomized 1:1 to Cohort 1: Combination of PRGN-2009, 5 x 1011 PU (Day 0, Day 21 and Day 42, then q6w), plus pembrolizumab, 400mg q6w, or to Cohort 2: pembrolizumab alone (400 mg q6w). Subjects randomized to Cohort 2 (pembrolizumab monotherapy) and who have confirmed disease progression (per RECIST 1.1) after at least one cycle of pembrolizumab and have had no Grade ≥ 3 adverse events related to treatment will be offered the option to crossover to Cohort 1 (PRGN-2009 plus pembrolizumab). All subjects will be evaluated for safety and efficacy of PRGN-2009 in combination with pembrolizumab, and for biological correlative assays. The primary endpoint is objective response rate (ORR) following treatment with PRGN-2009 in combination with pembrolizumab or pembrolizumab monotherapy, and will be tested using Fleming’s two-stage design and the stopping boundaries for futility and efficacy applied. The study is currently recruiting patients with recurrent or metastatic cervical cancer (NCT06157151). Clinical trial information: NCT06157151 .