bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of recreational and medical cannabis products in Veterans and their interactions with cancer directed pharmacological treatment.
Authors: Todorova Tsvetelina V , John Elizabeth , Sareen Srishti , Tandra Vaishnavi , Davis Jessica Daune Rich , DiLoreto Nicholas A , Weir Alva Bowen 
Published: July 2024

3089 Background: There is proliferation of literature about the medical uses of cannabis products in patients with malignancies. However, research is lacking as to how cannabis use is affecting the efficacy and toxicity of anti-neoplastic regimens It is known that cannabis is metabolized by the cytochrome p450 pathway, the same as many anti-neoplastic agents and thus there are concerns for potential interactions. Methods: We report an observational study to identify cannabis users in veterans receiving anti-neoplastic therapy in the Memphis VA health system, and to then analyzed for potential interactions between cannabis product and the antineoplastic agent/s they were receiving. Data was collected via voluntary surveys. We then reviewed their charts, recorded the anti- neoplastic medications they were receiving, and evaluated for potential interactions with cannabis, based on a literature review of potential interactions. Results: In this study, 132 veterans agreed to participate. 50 of them acknowledged recent use of cannabis products within the last 90 days. Thus, the prevalence of cannabis use amongst those who participated is 37.87%. Demographically, 10% of the cannabis users were female, and 90% were male, with the majority aged 60-65 (range 46-85). Predominantly, patients inhaled cannabis once daily (38%) as opposed to using a different formulation. The patients who admitted cannabis use were primarily on chemotherapy (42%), while 38% were on immunotherapy, 24% were on targeted therapy and 20% were on endocrine therapy. Some were on multiple drugs. Based on this data and a literature search for interactions, we found that a significant number of the patients in our Veteran’s oncology clinic have a potential increase in toxicity or decreased efficacy from their ant-neoplastic therapy due to CYP interactions with cannabis use. Conclusions: In this exploratory study, we discovered a notable prevalence of patients concurrently using cannabis products while on anti-neoplastic treatment. Given that many anti-neoplastic agents undergo metabolism via the CYP450 pathway, our data suggest that a moderate number of patients in our clinic risk less than optimal outcomes due to concurrent cannabis and anti-neoplastic therapy. To delve deeper, we intend to conduct a follow-up study, focusing on specific adverse effects, hospitalizations, and the subsequent need for 2nd and 3rd line treatments in patients using cannabis. A much larger multi-institutional study should be considered to provide statistically relevant data on true outcomes. [Table: see text]
A phase 2 study of de-escalation in resectable, locally advanced cutaneous squamous cell carcinoma (cSCC) with the use of neoadjuvant pembrolizumab: De-Squamate.
Authors: Ladwa Rahul , Lee Jenny HJ , Porceddu Sandro V , McGrath Margaret Louise , Cooper Caroline , Liu Howard , Gupta Ruta , Cuscaden Claire , Nottage Michelle K. , Clark Jonathan , Le Dieu , Pauley Marketa , Gonzalez-Cruz Jazmina , Frazer Ian , Hughes Brett Gordon Maxwell , Panizza Benedict J 
Published: July 2024

9514 Background: Neoadjuvant anti-Programmed Death therapy has shown a 64% complete or major pathological response rate in patients (pts) with resected stage II-IV(M0) cSCC. The De-Squamate study (NCT05025813) evaluated the feasibility of a risk adapted surgical de-escalation approach guided by clinical, radiological and pathological response in resectable cSCC pts of all sites receiving neoadjuvant pembrolizumab. Methods: This multi-centre, open-labelled, non-randomised, single-arm phase 2 study evaluated the response of neoadjuvant Pembrolizumab for 4 cycles administered IV 200mg Q3W in immunocompetent pts with Stage II-IV (M0) resectable cSCC. Pts underwent CT/MRI and 18F-FDG-PET imaging at baseline and following completion of neoadjuvant pembrolizumab. In those with a complete metabolic response, mapping biopsies of target site(s) were performed and if negative for residual SCC (clinical complete response [CCR]), surgery and post operative radiation therapy (PORT) were omitted. Patients with clinical or radiological residual disease/ positive mapping biopsy underwent surgical resection. PORT was de-escalated if there was a pathological complete response (PCR - no residual tumour cells) or major pathological response (MPR - less than or equal to 10% viable tumour cells). Pts proceeded to 13 cycles of maintenance Pembrolizumab. The primary endpoint was the combined rate of PCR, MPR and CCR following neoadjuvant Pembrolizumab and secondary endpoint includes treatment de-escalation and safety. Results: All 27 patients were enrolled and received a minimum of 2 cycles of neoadjuvant Pembrolizumab. The primary endpoint was observed in 17 patients (63%, 95% CI: 42-80), comprised of PCR (15%), MPR (0%) and CCR (48%). De-escalation of both surgery and PORT was achieved in 48% and a further 15% avoided PORT alone. With a minimum follow up of 6 months, no pts with PCR/MPR/CCR recurred. Investigator assessed treatment-related adverse events ≥ grade 3 was seen in 2 patients (7%). Conclusions: Pembrolizumab led to a high rate of PCR and CCR in resectable cSCC. The de-squamate study design effectively selected pts for surgical and PORT de-escalation and demonstrated a sustained response in this cohort. Clinical trial information: NCT05025813 .
Prediction of CCL2 in breast cancer based on enhanced MRI radiomics model with integrated bioinformatics analysis and machine learning.
Authors: Fu Chen , Chen Qiuchen 
Published: July 2024

e12509 Background: Breast cancer is the most common malignant tumor in women. According to the 2023 Cancer Statistics Report, breast cancer has surpassed lung cancer to become the most common malignant tumor. Its incidence and mortality both rank first among female malignant tumors. This study proposes non-invasive prediction of CCL2 mRNA expression in breast cancer tissue through enhanced MRI radiomics, while integrating bioinformatics analysis to explore the underlying molecular mechanisms and their association with the immune microenvironment. Methods: Excluding criteria were applied to select primary solid tumor samples with RNA-seq data (n = 840) from the TCGA-BRCA database. Enhanced MRI imaging data (n = 98) intersecting with the TCGA-BRCA data were obtained from TCIA-BRCA. The imaging data were randomly divided into training (n = 70) and testing sets (n = 28) in a 7:3 ratio. A feature subset was selected, and a model was constructed using the support vector machine (SVM) algorithm in the training set. The predictive performance of the model was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and the Hosmer-Lemeshow goodness-of-fit test. The calibration of the radiomics prediction model was assessed using the Brier score, and the clinical utility of the radiomics prediction model was demonstrated by drawing decision curves (DCA). External validation of the model was performed using a validation set. The radiomics score (RS) was calculated using the LR radiomics model and categorized as a binary variable (Low/High RS). Subsequently, KEGG pathway, immune-related genes, and gene mutation analysis were conducted based on the CCL2 high and low expression levels. Results: A total of 1810 radiomic features were obtained with ICC values ≥ 0.75. Subsequently, the mRMR (Maximum relevance, minimum redundancy) method, and the optimal 7 feature subsets were further identified using the RFE (Recursive feature elimination) algorithm. The SVM model demonstrated favorable predictive performance, with an AUC value of 0.822 for the training set and 0.779 for the validation set, as indicated by the ROC curve. Calibration curve and Hosmer-Lemeshow goodness-of-fit test revealed good consistency between the radiomic predictive model for the probability of high gene expression and the actual values (P > 0.05). Additionally, the decision curve analysis (DCA) demonstrated high clinical utility of the model. The TNF-α signaling pathway was found to influence the occurrence and development of breast cancer. Furthermore, the degree of Plasma Cell infiltration was observed to be highest in breast cancer. Conclusions: The CCL2 model constructed using a combination of machine learning and radiomic features, can non-invasively predict the prognosis of breast cancer treatment and exhibits good generalizability.
Efficacy of a combined diet and exercise intervention in patients with breast cancer undergoing chemotherapy: A meta-analysis of randomized controlled trials.
Authors: Roca Mora Maria Meritxell , Marin Cunha Luisa , Kozhokar Mikhaylovskaya Angelina , Afzal Farhan , Godoi Amanda 
Published: July 2024

e12517 Background: Breast cancer treatment presents challenging side effects that may compromise patients’ health and quality of life (QoL). While exercise programmes have been shown to improve survival, the impact of combined exercise and dietary interventions compared to usual practices alongside chemotherapy remains controversial. Methods: PubMed, Embase, Cochrane Central, and ClinicalTrials.gov were systematically searched up to October 2023. We included randomized controlled trials (RCTs) involving adult breast cancer patients undergoing chemotherapy and comparing combined diet and exercise interventions with usual care. Outcomes of interest included weight change, relative dose intensity (RDI), and Functional Assessment of Cancer Therapy-General scale (FACT-G) score for QoL. Statistical analysis was performed using Review Manager 5.4.1 and RStudio version 4.1.2. The protocol was registered on PROSPERO (ID: CRD42023463543). Results: Seven RCTs with 960 patients undergoing breast cancer therapy were included, of whom 506 (53%) were assigned to combined exercise and dietary interventions. Participants had a mean BMI of 26.6 kg/m2, and approximately 52% were postmenopausal. Combined exercise and dietary interventions resulted in significant reductions in weight loss (MD -1.06 kg, 95% CI -1.68 to -0.44; p<0.01), BMI (MD -0.44; 95% CI -1.76 to -0.13; p<0.01), body fat (MD -2.12%; 95% CI -3.99 to -0.26; p=0.03), and FACT-G (MD -3.40; 95% CI -6.25 to -0.55; p=0.02) compared to usual care. No significant differences were observed in waist circumference (p=0.05), RDI (p=0.23), or fatigue levels (p=0.98) between groups. Conclusions: In this meta-analysis of randomized trials, combined exercise and dietary interventions improved weight management in breast cancer patients undergoing chemotherapy but did not significantly impact chemotherapy completion, fatigue levels, and worsened FACT-G score (QoL). Findings can help to further holistic cancer care, taking into account both physical and psychosocial dimensions of patient health.
Clinical outcomes and prognostic factors in epithelial-myoepithelial carcinoma (EMC) of the breast.
Authors: Joshi Utsav , Budhathoki Pravash , Gaire Suman , Niu Chengu , Neupane Niraj , Agrawal Vishakha , Soliman Hatem Hussein 
Published: July 2024

e12529 Background: EMC is a biphasic neoplasm of the breast and comprises of malignant components derived from both luminal epithelium and myoepithelium. Most of the published data on EMC consists of individual case reports, and hence survival outcomes and prognosis are not clearly defined to guide evidence‐based management. We aimed to evaluate the clinical characteristics, survival outcomes, and prognostic factors in patients with EMC. Methods: All women with a histologic diagnosis of EMC irrespective of age and stage at diagnosis till 2018 in the National Cancer Database (NCDB) were included (N=111). Overall survival (OS) was assessed utilizing the Kaplan–Meier method and compared among groups using the log-rank test. Results: The median age at diagnosis was 67 years, and 101 (88.6%) were greater than 50 years of age. Most women were white (84.7%), non-Hispanic (91.9%), had a Charleston-Deyo score of 0-1 (95.5%), and treated at an academic or comprehensive community cancer programs (70.2%). Ten percent of patients were ER+/Her2-, 29.7% were ER-/Her2-, 0.9% were Her2+, 5.4% were ER+/Her2 unknown, 24% were ER-/Her2 unknown, and 29.7% had no data on ER status. Almost one-third of the women had poorly differentiated or undifferentiated tumors. Of the patients with available data, 46.7% had tumor ≤2 cm and more than 97% had no lymph node involvement or metastases. Most underwent surgical resection- radical mastectomy (16.2%), total mastectomy (18.9%), and partial mastectomy (56.8%). Chemotherapy and radiation were utilized in 35.2% and 40.6% of the women, respectively. At a median follow up of 67.6 months, the 3-year and 5-year OS was 81.6% and 74.3% respectively. The 5-year OS was 82.7%, 76.5%, and 50% for tumor ≤2 cm, 2-5 cm, and >5 cm respectively (p=0.009). Details on 5-year OS based on chemotherapy, radiation, and tumor size are shown in the table below. Among women who underwent lumpectomy (N=35), the 5-year OS for those who received adjuvant radiation vs surgery alone was 81.9% vs 76% (p=0.4). Conclusions: EMC demonstrates distinctive clinicopathologic features and receptor status. Administration of chemotherapy or radiation was associated with improved OS in tumors >5 cm, although small sample size and lack of recurrence data may limit this conclusion. Further studies using larger cohorts are needed to demonstrate objective efficacy of systemic treatment in lymph node positive and metastatic EMC. [Table: see text]
Risk factors for positive margin in breast conservation surgery for localized breast cancer.
Authors: Ferrick James P , Zubair Hina , Salvi Sumeet , Davis Elaine A , Welch Christine A , Kamran Amir Shahzad 
Published: July 2024

e12539 Background: Breast cancer is an evolving global concern due to its increasingly high morbidity and mortality rates. This is, in part, due to health care disparities in breast cancer patients that have been a problem for screening, diagnosis, and treatment. Breast-conservation surgery (BCS) is defined as the removal of breast tumor tissue surrounded by a margin of normal tissue and includes lumpectomy, partial mastectomy, wide excision, and segmental mastectomy. Negative margins post-BCS are necessary to avoid any breast cancer recurrence. A negative margin is defined as no gross or microscopic disease, also known as no tumor on ink. Positive margins are associated with patients who may have to undergo re-excisions with larger margins or total mastectomy, exposing patients to greater morbidity and delaying the start of adjuvant therapy. Methods: This was a retrospective cohort study designed to examine factors associated with positive margins (PM) in breast cancer patients undergoing breast-conserving surgery. The Charleston Area Medical Center cancer registry was queried from 2009-2022 for females diagnosed with invasive breast cancer who had surgery for localized disease (TxN0M0), excluding those with previous malignancies. Data were analyzed with SAS 9.4 using student’s t-test for continuous variables, Chi-square or Fisher’s exact for categorical variables, and multivariate analysis to identify factors predictive of positive margins. Results: In total, 1133 female patients with mean age of 64±11 met inclusion criteria. The positive margin group (PMG) made up 10.2% of the population while the negative margin group (NMG) was 89.8%. The PMG had significantly (p < .0001) larger tumors than the NMG, 19.7±12 and 13.8±9, respectively. Multifocal tumors made up 18% of the PMG compared to 4.4% of the NMG (p < .0001). Invasive lobular carcinoma made up 20% of the PMG compared to 7.2% of the NMG (p = .003). Recurrence was significantly (p = .030) higher in the PMG compared to the NMG, 7.4% and 3.2%, respectively; however, 5-year survival showed no difference. Regression modeling showed that multifocal tumors were 4.4 times (95% CI: 2.4-8; p < .0001) more likely to be associated with PM, lobular carcinoma was 2.8 times (95% CI: 1.6-4.8; p = .0003) more likely to be associated with PM, and stage II patients were 2.4 times (95% CI: 1.5-3.7; p = .0002) more likely to have PM. Conclusions: Univariately, tumor size, multifocality, lobular carcinoma, stage II, and local/distant recurrence were all associated with positive margins. This finding was re-demonstrated with respect to multifocality, lobular carcinoma, and stage II following multivariate analysis. The results of this study may help to guide surgeons and oncologists in the management of localized, invasive breast cancer, especially in emphasizing the importance of timely follow-up in patients at higher risk and in the education of patients regarding their care.
Intraoperative ultrasound guided wire (IOUS-wire) localization biopsy with frozen section versus preoperative fine needle aspiration cytology (FNAC) for the evaluation of clinically positive nodes in patients with early breast cancer in China real-world clinical practice.
Authors: Song Xue , Chen Qianjun , He Jiafa , Xu Rui , Tan Shijun , Dai Yan , Ye Lingling , Lin Xiaojie 
Published: July 2024

e12600 Background: Appropriate biopsy procedure for clinically positive (suspicious) lymph nodes (LN) plays a key role in accurate axillary staging of early breast cancer. Fine needle aspiration (FNA) is a recommended method for clinically suspicious nodes in the National Comprehensive Cancer Network (NCCN) guidelines. However, the false negative rate (FNR) of FNA remains too high. Therefore, it is valuable to explore an alternative and appropriate procedure in clinical practice. We conducted a retrospective review to compare the feasibility and diagnostic efficiency of using a novel procedure, the intraoperative ultrasound guided wire (IOUS-wire) localization biopsy with frozen section, to FNA for assessment of clinically positive nodes in patients with early breast cancer. Methods: Data on consecutive primary breast cancer patients with documented axillary ultrasound results who had clinically positive lymph nodes (cN1) between January 2015 and September 2023 either utilization of IOUS-wire localization or ultrasonography-guided fine-needle aspiration cytology (US-FNAC) for clinically positive lymph nodes were retrospectively analyzed. Sentinel lymph node biopsy (SLNB) was performed in patients with negative histopathological or cytological results. The false negative rate (FNR) of histopathology between two groups was calculated. Results: Eligible patients (n=198) referred to axillary biopsy by IOUS-wire localization biopsy(n=100) and US-FNAC(n=98) in this study. The FNR of clinically positive lymph nodes biopsy was 12.8 percent in the IOUS-wire localization group and 87.5 percent in the US-FNAC group.IOUS-wire failed in 5 patients. Among the remaining 32 successful identifications, 26 were IOUS-wire-node positive by intraoperative frozen section. 42 patients with additional lymph node metastases were found in FNAC-LN-negative patients by SLNB. The accuracy rate was respectively 95% and 57.1%. No significant difference was observed in complications and median number of SLNs harvested (5.3 versus 5.5; P=0.631) between the groups. Sufficient tissue samples can be obtained for intraoperative frozen pathology so the FNR is potentially reduced. In addition, the interval of waiting time for pathological results is reduced. Conclusions: Intraoperative US-guided wire localization biopsy is a feasible and alternative procedure compared to preoperative FNA for clinically node-positive patients with early breast cancer. This novel method is suitable for China's national conditions and should be further pursued as a potential biopsy method for evaluation of axillary node status in clinical practice.
Current trends in lung cancer brain metastases trials.
Authors: Petrosyan Edgar , Fares Jawad , Fernandez Luis G. , Oyon Daniel E. , Gibson William S. , Sonabend Adam M. , Lesniak Maciej S. 
Published: July 2024

e14006 Background: Brain metastases are the predominant central nervous system malignancy, primarily originating from lung cancer. In the era of precision medicine, enhanced control of extracranial disease is increasing the incidence of brain metastases, underscoring their status as a growing unmet need in modern Neurooncology. Methods: On December 12, 2023, we searched ClinicalTrials.gov for interventional and therapeutic clinical trials focusing on lung cancer brain metastases (LCBM). We gathered information on trial characteristics, including phase, study design, primary and secondary endpoints, status, enrollment criteria, size, duration, and results. Subsequently, the collected data was subjected to systematic analysis. Results: Among 198 identified trials, the majority were in early phases: 12% in phase I, 6% in phase I/II, and 60% in phase II. Only 27% of trials in phase II & II/III were randomized, with 92% lacking blinding. Trials were concentrated in North America (36%) and Asia/Africa/Australia (33%), predominantly targeting non-small cell lung cancer (NSCLC) (82%). Patients with leptomeningeal metastases were included in only about 10.5% of the trials. Out of 44 completed trials, only 21 resulted in published original articles. Termination occurred in 38 trials, primarily due to insufficient participant enrollment. Tyrosine kinase inhibitors emerged as promising treatments for brain parenchymal and leptomeningeal NSCLC metastases. Conclusions: This study highlights critical deficiencies in LCBM trials, ranging from inadequate trial numbers and recruitment difficulties to the overwhelming focus on NSCLC trials, insufficient randomization and blinding, and a marked scarcity of trials involving patients with leptomeningeal metastases. Addressing these issues is pivotal for advancing the understanding and treatment of LCBM.