bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors that impact aromatase inhibitor adherence in early-stage hormone receptor positive breast cancer.
Authors: Yang Angela , Baldwin Elena , Casasanta Nicole , Tiersten Amy , Kier Melanie Wain 
Published: July 2024

e12524 Background: Despite efficacy of aromatase inhibitors (AI) in improving survival for patients with hormone receptor positive (HR+) breast cancer, adherence to AI remains suboptimal. The aim of this study is to evaluate factors that may affect patient adherence to first-line AI. Methods: We retrospectively reviewed records of 195 female patients with HR+, HER2 negative early-stage breast cancer who were started on first-line adjuvant AI between 2011-2020 at our academic institution. We collected information on recurrence risk (defined by Oncotype score, with low risk ≤ 15, moderate risk 16-25, high risk ≥ 26), AI-related side effects, supportive therapy use for side effects, and socioeconomic demographics (i.e. income, insurance type, and race). We linked median family income with zip codes based on national census data and sorted them based on the Pew Research Center categorization. The primary end point was the rate of first-line AI adherence at 4 years. The Kruskal-Wallis rank sum test, Fisher’s exact test, and Pearson’s chi-squared test were used to compare AI adherence when varying patient profiles. Results: In our cohort, 50% (n=98) were adherent to first-line AI at 4 years, 9% (n=17) were still taking first-line AI but have not yet reached 4 years, and 41% (n=80) discontinued first-line AI early. Of those who discontinued first-line AI early, 68% (n=54) switched to an alternate endocrine treatment due to side effects, 4% (n=3) stopped all endocrine treatment, and 28% (n=23) were lost to follow up. AI-related side effects were common; 83% (n=162) reported AI-related side effects, yet only 27% of those patients received supportive therapy. Supportive therapy use was not significantly different when varying patients’ recurrence risk and socioeconomic demographics. In addition, adherence did not differ based on side effect frequency or supportive therapy use. The population’s Oncotypes included 36% (n=70) low risk, 36% (n=70) moderate risk and 12% (n=24) high risk; the remaining had no Oncotype sent. There was no significant difference in adherence among the risk groups. In evaluating demographics, the cohort’s median age was 62 and it included 9% Asian, 13% Black, 5% Hispanic, 54% White, and 19% Other/Unknown. The majority (62%) of patients were of middle income ($52,000-145,000), followed by 29% in upper and 9% in lower income. The minority (22%) of patients were on Medicaid. Those with a lower discontinuation rate were older (64 vs. 61, p=0.019), while there was no significant difference based on race, income, or insurance. Conclusions: Despite the small sample, it is reassuring that at our institution, long term adherence to first-line AI and supportive therapy use did not vary among socioeconomic demographics. However, a gap persists between the prevalence of AI-related side effects and usage of proven supportive treatments. Further study on strategies to enhance AI tolerance and adherence is needed.
Effects of a pilot 12-week exercise program on breast cancer survivors’ quality of life.
Authors: Imai Lauren , Baron Kirsten , Toyama Matthew , Pagano Ian , Yamada Paulette , Teranishi-Hashimoto Cheri , Fukui Jami Aya 
Published: July 2024

e12525 Background: Previous studies have demonstrated that breast cancer survivors commonly experience a decrease in quality of life including an increased risk of depression, insomnia, cancer-related fatigue, and negative body image. Several studies have shown that exercise interventions, such as yoga, Pilates, water aerobics, and strengthening exercises can improve survivors’ quality of life. We implemented a 12-week exercise program in breast cancer survivors and evaluated quality of life changes. Here we discuss our findings evaluating 13 quality of life questionnaires. Methods: We evaluated 46 participants who completed a baseline and post 12-week questionnaire assessment. All participants underwent an exercise program 3 times/week for 90 minutes/session. We calculated differences in baseline and post 12-week quality of life through 13 questionnaires: Functional Assessment of Cancer Therapy - General (FACT-G) Physical, Social/Family, Emotional, and Functional, Social Support, Insomnia Severity Index, Brief Fatigue Inventory, Patient Health Questionnaire, and Body Image after Breast Cancer (BIBCQ) Vulnerability Scale (VS), Body Stigma Scale (BSS), Limitations Scale (LS), Body Concerns Scale (BCS), Transparency Scale (TS), and Arm Concerns Scale (ACS) and assessed the intervention's efficacy by comparing the baseline and post 12-week scores using paired t-tests. Results: The difference between baseline and post 12-week quality of life are presented in the Table. 7/13 questionnaires showed statistical significance: FACT-G Physical and Functional, Insomnia Severity Index, Brief Fatigue Inventory, Patient Health Questionnaire, and BIBCQ LS and BCS. Conclusions: Our study showed improvement in metrics evaluated in breast cancer survivors who underwent the personalized exercise program. Specifically, body image was improved with exercise which further exemplifies the impact of lifestyle changes on quality of life measures and is an important adjunct to future cancer survivorship studies. Clinical trial information: NCT04013568 . [Table: see text]
Impact of comorbidity on surgical management of breast cancer in elderly patients.
Authors: Shivilov Evgenii , Anichkina Kristina , Arslanov Khalil , Kvetenadze Gurami , Zhukova Lyudmila 
Published: July 2024

e12596 Background: More than half of breast cancers are diagnosed above the age of 60 years, a quarter of which diagnosed with invasive breast cancer among those over 75 years of age. Treatment of breast cancer (BC) at this age remains a complex problem. Elderly patients often have various comorbidities that impose increased risks of complications with antitumor treatment. This leads to both excessive and insufficient treatment of BC. In patients over 75 years of age, an individual approach to treatment is recommended, taking into account their general health and life expectancy, the risk of death from breast cancer compared to other causes, as well as the advantages and disadvantages of treatment methods. Objective: To evaluate the influence of comorbidity on the risks of complications (early and delay) after surgical treatment in elderly and senile patients (pts). Methods: A retrospective analysis of the results of breast cancer treatment in 292 pts over 75 years of age, who underwent surgical treatment at the first stage in SBIH Moscow Clinical Scientific and Practical Center named after A.S. Loginov of DHM from 2016 to 2019. The initial stages of breast cancer (I and IIA) were diagnosed in 257 (88.0%) pts, 35 pts (12.0%) has IIB and IIIA clinical stages. Radical mastectomy was performed in 171 (58.6%) cases, breast-conserving surgery was performed in the remaining 121 (41.4%). Forty-six (15.8%) patients had diabetes mellitus, 121 (41.4%) had cardiovascular disease, 36 (12.3%) had heart rhythm disorders, 38 (13.0%) had chronic cerebral ischemia, and the risk of grade 3 and 4 cardiovascular complications was found in 251 (86.0%) cases. Results: In the early postoperative period severe complications occurred in 1 (1.7%) patient (acute coronary syndrome) leading to death. No local recurrences were detected. The overall 3-year survival rate was 86.3% and the recurrence-free survival rate was 89.7%. In 10 (3.4%) cases, death was due to progression of RRMS, 30 (10.3%) patients died from other causes (acute cardiovascular failure, stroke, COVID-19). Conclusions: Comorbid conditions in elderly patients after surgery did not affect the development of complications in the early postoperative period. Preliminary preoperative preparation of elderly patients (correction and selection of drug therapy for concomitant chronic diseases) reduces the risk of early postoperative complications.
Single institution analysis of glioblastoma multiforme (GBM) outcomes based on year of diagnosis: A 17 year review.
Authors: Mustafa Yazan Hani , Keogh Rachel J , Barry Simon , O'Reilly Seamus , Gleeson Jack , Bambury Richard Martin 
Published: July 2024

e14023 Background: GBM is the most common brain tumour in adults. The latest WHO classification excludes IDH mutated tumours, acknowledging their favourable prognosis. MGMT methylation is a prognostic biomarker and predicts level of benefit from Temozolomide. The standard of care management includes maximal surgical resection followed by radiotherapy with concurrent and adjuvant Temozolomide. This has remained largely unchanged for nearly 20 years. We analysed 17 years of newly diagnosed GBM cases attending Medical Oncology at our institution to assess outcome advancements. Methods: Demographic information, clinicopathological characteristics, surgery, radiotherapy and systemic anti-cancer treatment data were collected from the charts of patients diagnosed with GBM and seen by the Medical Oncology department at Cork University Hospital between 2005-2021. The study population was divided into 2 time periods: 2005-2016 and 2017-2021. Overall survival was recorded. Baseline characteristics was compared across time periods using the Chi-Square test. Univariate and multivariate analysis was performed to assess impact of different variables on overall survival. Results: The analysis comprised 306 patients, with 142 and 164 diagnosed between 2005-2016 and 2017-2021 respectively. Median age was 62 years (range 17-86) and patients were predominantly male (65%). Patients in the earlier time period were more likely to have ECOG performance status 0-1 (80% vs 65% p = 0.011) and were more likely to commence treatment on Stupp protocol (99% vs 80% p = <0.001). IDH and MGMT testing were less prevalent in the earlier time period. Median overall survival (mOS) for the entire cohort was 11.6 months. Univariate analysis revealed correlations between overall survival and time period of diagnosis, age >65, MGMT status, ECOG performance status, steroid use, surgery, re-resection, and completion of adjuvant chemoradiation protocols. The mOS was 12.3 months in the earlier time period and 10.4 months in the later time period (HR = 1.35 p = 0.012). Time period of diagnosis remained an independent prognostic factor for poor outcome on multivariate analysis. Notably, mOS during the COVID-19 pandemic (2020-2021) was 10.6 months, showing no difference from other time periods. Conclusions: Despite advances in our knowledge regarding the molecular biology of GBM, prognosis remains poor. Our institution’s 17 year survival data indicates no improvement over time emphasising the urgent need for new treatment strategies. Notably, the more recent time period had an increased number of frailer patients who were too unwell to commence any adjuvant treatment, possibly indicating a lower referral threshold which may have negatively impacted mOS in that cohort. Additionally, the absence of IDH status assessment in the earlier era means some IDH mutant patients were likely included, thereby inflating the mOS for that cohort.
Personalized neoantigen-pulsed autologous dendritic cells vaccine as an adjuvant treatment for patients with newly-diagnosed glioblastoma multiforme: A phase I trial.
Authors: Zhang Yang , Chi Xiaohan , Cheng Xudong , Zhang Yu , Zhang Kangna , Huang Na , Ji Nan 
Published: July 2024

e14025 Background: Glioblastoma Multiforme (GBM) is the most common and aggressive primary brain malignancy in adults. We herein report a phase I trial using personalized neoantigen-pulsed autologous dendritic cells (nDC) vaccine as an adjuvant treatment for patients with newly-diagnosed GBM. Methods: It is a single-center, single-arm phase I trial, enrolling patients aged 18-75 years old, with newly-diagnosed GBM and tumor resection extent ≥90%. Tumor specimens were sequenced for identification of personalized neoantigens. A total of 3-10 neoantigen peptides were loaded into DC to generate the nDC vaccine. The vaccine was administered subcutaneously for 5-6 doses at 1×10^7 cells following concomitant radiotherapy plus temozolomide. The primary objective is safety. Secondary objectives include survival outcomes and T cell immune response against the neoantigens. Results: As of Dec. 31, 2023, eleven patients completed at least one dose of vaccination and were included in the safety analysis; eight patients completed planned doses and were included in the efficacy analysis. All the patients reported Treatment-emergent adverse events (TEAEs). Most TEAEs were grade 1 or 2. One patient reported two grade 3 TEAEs: decreased white blood cell count and decreased lymphocyte count. Pyrexia was considered as treatment-related adverse event (TRAE) that was reported in two (18.2%) patients. No treatment-related deaths occurred. Among eight efficacy-assessable patients, seven (87.5%) patients kept progression-free for at least 5.4-27.3 months; one patient progressed at 10.2 months after surgery and achieved complete remission after receiving anti-PD1 plus bevacizumab therapy; compared to the baseline level, a median 15-fold (3 to 506-fold) increase of neoantigen-specific cytotoxic T cells was detected in their peripheral blood samples post-vaccination, indicating strong anti-tumor T cell responses elicited by the nDC vaccine. Conclusions: The nDC vaccine, combined with the standard treatments for GBM, was well tolerated. Initial results from this ongoing study have exhibited encouraging survival outcome of the nDC vaccine for patients with newly-diagnosed GBMs. Clinical trial information: NCT04968366 . [Table: see text]
Co-treatment of human GBM cell lines with imipridone ONC206 and tumor treating fields: Effect on on cell death and p-AKT.
Authors: Tajiknia Vida , El-Deiry Wafik S. , Schwermann Maximilian , MacDonald William J. , Stubbs Nolan 
Published: July 2024

e14033 Background: Glioblastoma (GBM) is the most common primary brain malignancy with dismal prognosis. Tumor Treating Fields (TTFields) therapy is available for the treatment of both newly diagnosed and recurrent glioblastoma and represents a new category of treatment modalities in oncologic therapy. Despite decades of study, few FDA approved modalities are available for GBM and provide limited survival improvements for patients. AKT functions as a key serine/threonine kinase in the RTK/PTEN/PI3K pathway, and extensive genomic analysis of GBM has revealed that this pathway is mutated in a significant majority of GBM cases. Activation of this pathway ultimately leads to the activation of AKT, and phospho-AKT levels are elevated in the majority of GBM tumor samples and cell lines. Studies have shown that increased p-AKT levels contribute to uncontrolled growth, resistance to apoptosis, and enhanced invasive capabilities of glioma cells, which are characteristics of tumor progression in GBM. AKT serves as a critical hub in this pathway, enabling the amplification of growth signals, thereby making the inhibition of AKT an appealing and promising therapeutic target for treating GBM. Imipridone ONC206 is under clinical development for treatment of pediatric and adult patients with primary brain tumors (NCT04732065 and NCT04541082). Here we show inhibition of p-AKT as well as upregulation of cleaved PARP following cotreatment of ONC206 and TTFields. Methods: We investigated the effect of ONC206 at IC50s plus TTFields in LN229, U138, U251 and T98G human GBM cell lines at different time points. Effect of treatment on cPARP, BCL-2, CHOP, caspase-10, and p-AKT were investigated using western blot. Results: Treatment with ONC206 at the IC50 in T98G cells with TTFields at 24h showed synergistic upregulation of cPARP as well as inhibition of BCL-2. At 96hour time point, inhibition of p-AKT was observed following all treatments (ONC206, TTFields, and co-application compared to control. In U251 cells, following treatment of ONC206 and TTFields, inhibition of BCL-2 was observed at 24h time point. Upregulation of CHOP and Casapse-10 at 96h time point was seen, as well as inhibition of p-AKT. Spheroid models showed structure disruption and growth arrest following combination treatment. At 72 h time point co treatment with ONC206 and TTFields resulted in synergistic upregulation of cleaved PARP. Conclusions: Here we showed cotreatment with TTFields and ONC206 results in inhibition of p-AKT, the key node in GBM growth pathway. This is the first report of cleaved PARP upregulation following TTFields and ONC206 in Human GBM cell line. Further studies to investigate the in vivo efficacy of TTField treatment in GBM with ONC206 are warranted. More studies are needed to understand the exact mechanism of synergy.
Exploring the diagnostic potential of cerebrospinal fluid (CSF) IL-10:IL-6 ratio in patients with primary central nervous system lymphoma (PCNSL).
Authors: Singh Sofia , Kapila Aastha Takkar , Prakash Gaurav , Lal Vivek , Gupta Vishali , Minz Ranjana Walker , Mahesh karthik Vinay 
Published: July 2024

e14041 Background: Primary Central Nervous System Lymphomas (PCNSL) present significant diagnostic challenges due to their aggressive nature. Current diagnostic methods include neuroimaging, CSF cytology, FDG-PET scans, and biopsies. Building upon the success of the IL-10:IL-6 ratio as a diagnostic biomarker in intraocular lymphoma, this study investigates its potential in PCNSL diagnosis. CSF IL-10:IL-6 ratio emerges as a promising, easily accessible biomarker for early PCNSL detection. Methods: Fifteen histopathologically confirmed PCNSL patients were compared with fifteen CNS inflammatory condition patients and ten patients with other CNS malignancies. Detailed clinical assessments were conducted, and IL-10:IL-6 levels were measured in serum and CSF using Flow cytometry. Results: The CSF IL-10:IL-6 Ratio was elevated (> 1) compared to serum levels in PCNSL patients in contrast to other control groups. The mean age ± SD of PCNSL patients was 55.47 ± 17.29, with a male-to-female ratio of 8:7. The mean (SD) for CSF IL-10:IL-6 ratio in PCNSL was 3.35 (3.88), while the mean (SD) for serum IL-10:IL-6 ratio was 0.438 (1.54). The statistical analysis revealed a significant difference (P = 0.0058 < 0.05). Conversely, comparing the CSF IL-10:IL-6 ratio with serum levels in controls with CNS inflammatory conditions and CNS malignancies showed no statistical significance (P > 0.05). Conclusions: Elevated CSF IL-10 and CSF IL-10/IL-6 ratios suggest their potential as early diagnostic markers for large B cell PCNSL. The IL-10:IL-6 ratio holds promise as a novel, easily accessible biomarker in readily available body fluids for PCNSL diagnosis.
Combined NF2/PTEN mutations as predictors of meningioma aggressiveness.
Authors: Gandhi Om H. , Ajmera Sonia , Tarbay Antonio Corral , Patel Saawan , Mannam Sneha Sai , Karsalia Ritesh , Jackson Christina 
Published: July 2024

e14044 Background: In meningiomas, loss of the NF2 tumor suppressor gene function leads to dysregulation of cell proliferation and tumor formation. PTEN, another tumor suppressor gene correlated with worse prognosis in tumors like gliomas, has also been reported in meningiomas, but the impact of its mutation alone or in conjunction with NF2 loss on outcomes in these tumors is unexplored. We aimed to evaluate whether dual NF2/PTEN mutations comprise a more aggressive meningioma phenotype compared to tumors with only NF2 mutations. Identifying this high-risk genetic profile could allow for preventative and individualized treatment of these aggressive meningiomas. Methods: We reviewed patients who underwent meningioma resection at our institution from January 2018 through October 2022. Demographic information, tumor characteristics, pre- and post-operative clinical characteristics, and outcomes were collected. Meningioma specimens were analyzed by immunohistochemistry for WHO grading and Ki67 proliferation index and by sequencing for genomic alterations. We performed multivariable logistic regression analyses to identify clinical outcomes associated with proliferation index and genetic mutations. Results: We identified NF2 mutations in 24 meningiomas and dual NF2/PTEN mutations in 7 meningiomas. Mutation rates did not significantly differ based on demographic factors including sex, age, race, socioeconomic status, or prior cranial radiation status (p>0.05). The majority of tumors with these mutations (93%) were in non-skull base regions (i.e. convexity, parafalcine). Tumors with both NF2 and PTEN mutations were more likely to be WHO grade III tumors than those with the NF2 mutation alone (29% versus 9%). Tumors with dual mutations had higher likelihood of having Ki67 proliferation indices ≥ 10% (OR 5.98, p<0.01). While higher Ki67 index was significantly associated with features of more aggressive tumors including higher WHO grade and recurrence rates, dual mutation in NF2 and PTEN is associated with higher rate of recurrence (OR 13.13, p<0.001) and mortality (OR 5.14, p<0.05) compared to NF2 irrespective of Ki67 index. Notably, patients with mutations in NF2 alone or both NF2/PTEN did not differ in preoperative Karnofsky performance score, Simpson resection grade, or presence of post operative residual tumor. Conclusions: Our results demonstrated that concomitant NF2 and PTEN mutations in meningiomas were associated with higher WHO grades, tumor proliferation indices, recurrence rates, and mortality rates. This finding suggests that NF2/PTEN mutated meningiomas represent a distinct subset of tumors that demonstrate a more aggressive clinical and histopathological phenotype that may require more aggressive treatment and closer surveillance. Further investigation is warranted to confirm the prognostic relevance of NF2/PTEN mutations in meningioma and elucidate their underlying molecular mechanisms.
Epigenetic silencing of LDHB to promote hepatocellular carcinoma by remodeling the tumor microenvironment.
Authors: Zhang Peng , Zhang Chengsheng 
Published: July 2024

e16220 Background: Hepatocellular carcinoma (HCC) is a deadly disease with limited therapeutic options. Low expression of the LDHB has been associated with poor prognosis of HCC patients, but the role and underlying mechanism remains unclear. Methods: The HCC dada from The Cancer Genome Atlas (TCGA) and GEO were obtained to analyze the LDHB expression and DNA methylation levels. Next, the correlation between LDHB and Hallmark gene sets was analyzed by GO and KEGG. RNA-seq, Western blotting, Immunohistochemistry, and Bisulfite DNA sequencing were performed to explore the relationship between DNA methylation and LDHB expression. CCK8 and colony formation assay were used to evaluate the effect of overexpression of LDHB on the proliferation of hepatocellular carcinoma cells in vitro. Finally, the role of LDHB in HCC tumor immunity was assessed in multiple mouse models in vivo. Results: Here, we found that down-regulation of LDHB was coupled with the promoter hypermethylation and knocking down the DNMT 3A restored LDHB expression levels in HCC cell lines. Bioinformatics analysis of the HCC cohort from The Cancer Genome Atlas revealed a significant positive correlation between LDHB expression and immune regulatory signaling pathways and immune cell infiltrations. Notably, HCC patients with high LDHB expression responded better to immune checkpoint inhibitors. Finally, we demonstrated that there was no difference in the tumor growth rate between the LDHB-expressing tumors and the control tumors in immunodeficient BALB/c nude mice. However, the LDHB-expressing tumors were significantly inhibited in immunocompetent C57BL/6 mice, suggesting that the host immune system was involved in the LDHB-medicated tumor suppression. Moreover, as compared with the LDHB+/+ mice, LDHB-/- mice showed promoted tumor growth in an NRAS/shp53 plasmid-induced primary liver tumor model. Conclusions: Overall, our findings indicate that DNMT3A-mediated epigenetic silencing of LDHB may contribute to HCC progression through remodeling the tumor immune microenvironment, and LDHB may become a potential prognostic biomarker and target for HCC immunotherapy.