bluuebunny/crossref_metadata_2025_split huggingface dataset:
Awareness, Knowledge, and Current Practice of Breast Cancer Among Surgeons in Jordan
Authors: Al-Balas Mahmoud , Al-Balas Hamzeh , Al-Amer Zain , Ashour Laith , Obiedat Mufleh 
Published: June 2024

PURPOSE Breast cancer (BC) is the most prevalent cancer in Jordan. De-escalation in treatment reflects a paradigm shift in BC treatment. More tailored strategies and the adoption of a multidisciplinary approach are essential to apply recent changes in management. In the era of breast surgery fellowship, adopting well-structured training is essential to apply recent therapeutic guidelines and meet patients' expectations. METHODS A cross-sectional study using a customized, self-reported questionnaire was used. Data collection occurred anonymously using a link via WhatsApp in the period between February 2023 and April 2023. RESULTS A total of 89 surgeons were involved in this study, and only 14 (15.7%) completed a subspecialty in breast surgery. About 58.4% considered the age of 40 years as the starting point for screening, and 84.3% reported that mammogram screening is associated with improved BC survival. Only 10.1% and 28.1% acknowledged the applicability of both tomosynthesis and breast magnetic resonance imaging in screening, respectively. A significant difference in the mean knowledge score about BC is observed between general surgeon and those with subspecialty. Varying levels of awareness concerning different risk factors and their correlation with the likelihood of BC occurrence observed. Although 56.2% of participants could offer breast conserving surgery and consider it oncological safe, only 48.3% defined it correctly. Of the participants, 61.8% and 76.4% stated that sentinel lymph node biopsy can be safely applied in clinically negative or suspicious axillary nodes, respectively, with <50% of surgeon performing it in their practice. CONCLUSION More efforts are required to enhance the knowledge and practice of surgeons in the field of breast surgery. Adopting national guidelines can facilitate the acceptance and improvement of current practices among surgeons in Jordan.
Long-term outcomes of ablation versus surgery in patients with colorectal lung oligometastasis: A retrospective cohort study.
Authors: Zhang Tian-Qi , Cao Yu-Zhe , Zheng Xin , Fan Wei-Jun , Wu Pei-Hong , Huang Jin-Hua 
Published: June 2024

3581 Background: Lung is the common metastatic site of colorectal carcinoma. Treatment of colorectal lung oligometastasis (CLOM) by surgical and ablative procedures has been proved to prolong survival and palliate symptoms. We aimed to analyze the long-term outcomes of patients with CLOM treated with surgery or ablation. Methods: From January 2012 to October 2018, patients diagnosed with CLOM that underwent surgery or ablation at the Sun Yat-sen University Cancer Center were retrospectively analyzed. Results: The study included 96 patients with 134 lesions, including 25 females (26.0%) and 71 males (74.0%). All the patients had received the primary colorectal lesion resection before treatment of metastasis. There were 41 patients with 75 lesions receiving ablation and 55 patients with 59 lesions receiving surgery. The median follow-up time was 58.3 months (IQR: 38.6-73.7). The median overall survivals (mOS), 3- and 5-year survival rates between the two groups showed no significant difference (Ablation vs. Surgery, mOS: 73.3 months vs 70.4 months, P=0.64; 3-year survival rate: 82.6% vs. 79.8%; 5-year survival rate: 59.9% vs. 58.7%. The median progression-free survivals (mPFS) were 12.1 months in the ablation group and 11.5 months in the surgery group (P=0.48), respectively. Local rates of recurrence per lesion were 26.7% and 22.0% (P=0.68). And the pulmonary mPFS were 14.5 months vs. 14.1 months (P=0.95). Conclusions: Our retrospective cohort data showed that there was no significant difference between surgery and ablation in long-term survival benefit to CLOM patients. [Table: see text]
Long-term survival comparison of adjuvant FLOT versus XELOX chemotherapy for locally advanced gastric cancer in a large real-world cohort.
Authors: Jiao Zuoyi , Gan Shiying , Long Bo , Zhou Huinian , Yu Zyuaun , Mao Jie 
Published: June 2024

4080 Background: Recent Attraction-5 study has shown that logically advanced gastric cancer (LAGC) patients can't benefit from postoperative immunochemotherapy. The preferred adjuvant regimen for LAGC remains two-drug based chemotherapy as XELOX protocol, though three-drug based adjuvant FLOT regimen has not been well studied yet. This studyaimsto explore 10-year survival advantages of adjuvant FLOT versus XELOX regimen for LAGC. Methods: We retrospectively collected and analyzed data from 248 LAGC patients mainly composed of pathological T (pT) 3-4 stage, who received at least 4 cycles of FLOT or XELOX adjuvant chemotherapy at Lanzhou University Second Hospital from 2013 to 2018. To eliminate interference of confounding factors, we conducted a propensity score matching (PSM). The median follow-up time for all patients was 90.90 months. Results: After PSM, the median overall survival (OS) was 44.80 months in FLOT group and 34.87 months in XELOX group, with 5-year OS rate of 41.4% versus 25.3% and 10-year OS rate of 31.9% versus 11.8%. Subgroup analysis showed that patients with ECOG performance status 0 or pT3-4 stage attained significant survival benefits from adjuvant FLOT regimen. Grade 3-4 treatment-related adverse events occurred in 57.9% patients of FLOT group and 33.6% patients of XELOX group, while most of them were manageable. Conclusions: This study demonstrates that adjuvant FLOT regimen exhibits significantly long-term survival advantages for LAGC patients with good performance status and late disease stage compared with XELOX regimen, facilitating adjuvant FLOT regimen as a prospectively alternative option for LAGC.
Cabozantinib plus atezolizumab in patients with advanced and progressive neuroendocrine neoplasms (NENs): A prospective multi-cohort basket phase II trial (CABATEN / GETNE-T1914).
Authors: Hernando Jorge , Molina-Cerrillo Javier , Grande Enrique , Benavent Viñuales Marta , Garcia-Carbonero Rocio , Teule Alex , Custodio Ana , Jimenez-Fonseca Paula , Hierro Cinta , López López Carlos , Sevilla Isabel , Llanos Marta , Carmona-Bayonas Alberto , Alonso Vicente , Gallego Javier , Gallego Jiménez Inmaculada , Orta Alberto , Franco Fernando , García-Álvarez Alejandro , Capdevila Jaume 
Published: June 2024

4128 Background: Early results with immune-checkpoint inhibitors (ICI) in NENs when used as single agents achieve limited response rates. Angiogenesis plays a key role in development and progression of NENs and synergism has been observed when antiangiogenics are combined with ICI in other tumors, whereas. We aimed to assess the efficacy and safety of cabozantinib (Cabo) plus atezolizumab (Atezo) in advanced and progressive NENs. Methods: CABATEN was a single-arm basket study using Atezo 1200 mg every 3 weeks plus Cabo 40 mg/day until progression or unacceptable toxicity in 6 NENs independent cohorts. We here focus in: well-differentiated lung neuroendocrine tumors (LungNET), pheochromocytoma paraganglioma (PPGL), well-differentiated gastroenteropancreatic (GEPNET) and grade 3 extrapulmonary neuroendocrine carcinomas (G3 EP-NEN). Primary endpoint was Overall Response Rate (ORR) by RECIST 1.1. The study had a Simon-II design. Here we present a subgroup analysis of efficacy for NENs (n=55), and for Cabo reduction using a relative dose intensity (RDI)<81% threshold and 3-month interval by Landmark analysis. Baseline characteristics were analyzed in subgroups with prolonged disease stability (PFS>12m or >15m) Results: Median (95%CI) age was 60 (56.0, 63.0) years and 62% were male. Cabo and Atezo treatment were administered for a median of 8.7m (95%CI: 6.2-11.9) and 9.0m (95%CI: 6.8-13.5) and interrupted due to AE’s in 80.0% and 40.0% of pts respectively. Cabo was reduced to 20 mg/day in 58,2% of patients. The 12-m PFS was 50% (95%CI: 29.6-84.4) RDI<81% vs 55.6% (95%CI: 39.7-77.9) RDI≥81% (p=0.9), 12-m OS was 86.7% (CI 95%: 71.1-100) RDI<81% vs 84.7% (CI 95%: 72.0-99.7) RDI≥81% (p=0.6), Cox. LungNET, PPGL, GEPNET and G3 EP-NEN presented a median PFS (m, 95% CI) of 8.4 [7.7-NR], 8.4 [5.7-NR], 13 [11.2-NR] and 2.7 [2.6-NR] respectively. PFS>12m subgroup had a trend towards better ECOG. PFS>15m GEP-NET presented a non-significant trend towards a lower Ki67 index and less previous treatment (no chemotherapy). ORR were 15.4% (95%CI:1.9-45.5) in PPGL and 16.7% (95%CI:4.7-37.4) in GEP-NET. LungNETs and G3 EP-NEN had no responses. Duration of response (DoR) were 12.2m (5.5-19.0) and 15.8m (10.6 - 20.2) in PPGL and GEP-NET cohorts, respectively. Conclusions: Cabo and Atezo showed limited activity but achieved prolonged disease control in a small group of patients with PPGL and GEPNET but not in LungNET and G3 EP-NEN, regardless of RDI of Cabo. Clinical trial information: 2019-002279-32.
Treatment landscape, outcome and quality of life in patients with pancreatic cancer: IKF642/PARAGON study.
Authors: Goetze Thorsten , Liersch Ruediger , Scheuer Lars , Göhler Thomas , Kaiser Ulrich , Denzlinger Claudio , Pink Daniel , Wierecky Jan , Klagges Jorge , Pauligk Claudia , Zäpf Bianca , Hofheinz Ralf-Dieter , Al-Batran Salah-Eddin 
Published: June 2024

4155 Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with a 5-year relative survival rate of only 13% for all stages combined (1). All treatment options available to date are options that can prolong survival and/or alleviate symptoms, but rarely cure. Therefore, it seems important to obtain more real-world data covering the entire clinical life cycle of PDAC patients, including quality of life (QoL) for all therapies used. Methods: Since November 2019 until October 2021 the multicenter, prospective, PARAGON study (NCT04119362) included patients (pts) diagnosed with PDAC planned for or recently started with neoadjuvant, adjuvant or 1st line therapy. Pts were followed during the entire course of their disease and all treatment lines for efficacy and QoL. Follow up ended June 2023. 46 German study sites participated at the study. Analysis included data on demography, comorbidities, treatments, and efficacy as well QoL (EORTC QLQ-C30). Results: PARAGON enrolled 468 PDAC pts, comprising 52% male, median age of 69 years [31- 90] with ECOG 0 to 1 in 76% at baseline. Six percent of all pts started in a neoadjuvant setting (FFX, 50%; NP-G, 38%), 32% in the adjuvant setting (FFX, 52%; gemcitabine, 28%; NP-G, 4%), and 76% in the first-line setting (NP-G, 44%; FFX, 36%; gemcitabine, 13%). 37% of all pts received 2nd line therapy with NP-G (39,5%), NalIRI-5FU (12%) and gemcitabine (6%). 14% of all pts started a 3rd line therapy and 4% a 4th line therapy. The median overall survival (mOS) in the adjuvant-therapy setting was 30 months, median progression free survival (mPFS) 16 months. mOS in the 1st line therapy was 10.0 months, mPFS 5.6 months. mOS in 2nd line was 7.7 months, mPFS 3.0 months. Differences can be described, among others, for mOS in 1st line FFX with 12.7 months, in NP-G with 10.7 months and in the Gemcitabine subgroup with 8.3 months. QoL data is available for all pts at baseline and throughout the further course of therapy. Results according to treatment line will be presented in detail at the meeting. Conclusions: PARAGON is the largest study on QoL and treatment landscape in PDAC so far. Data allow broad insight in real-world efficacy and QoL in the different treatment lines, regimens, and subgroups of pts. 1. American Cancer Society. Cancer Facts & Figures 2024. Atlanta: American Cancer Society; 2024. Clinical trial information: NCT04119362 .
Comparative effectiveness of NALIRIFOX vs. FOLFIRINOX in pancreatic cancer.
Authors: Jiao Xiayu , Barzi Afsaneh 
Published: June 2024

4160 Background: Metastatic pancreatic cancer is associated with limited survival, poor quality of life, and limited treatment options. FOLFIRINOX and gemcitabine/nab-paclitaxel (GNP) are associated with survival gain compared to gemcitabine and NALIRIFOX is associated with survival improvement compared to GNP. NALIRIFOX and FOLFIRINOX are not directly compared to each other. We conducted an analysis of oncologic benefits and costs of NALIRIFOX vs. FOLFIRINOX. Methods: A cost-effectiveness model was developed using partitioned survival analysis with three health states: progression-free, progression, and death. Data on overall survival and progression-free survival were derived from PRODIGE and NAPOLI-3 published data to reconstruct the states in the model. The time horizon of the model was set to 36 months. Costs included treatment costs and adverse event management as well as supportive care cost. We used Veteran Affair’s data for unit cost of each agent. To calculate the cost of treatment we assumed the average body surface area to be 1.79. Five adverse events (AEs) were included in the cost analysis: neutropenia, febrile neutropenia, anemia, diarrhea, and thrombocytopenia. We used the utility of 0.80 during PFS and 0.73 during progression for assessment of Quality Adjusted Life Year (QALY). The benefits and costs of treatment was calculated and used to estimate the incremental cost-effectiveness ratio (ICER) of NALIRIFOX compared with FOLFIRINOX. Results: The calculated PFS for FOLFIRINOX was 6.8 months and for NALIRIFOX was 8.9 months. Compared to FOLFIRINOX, NALIRIFOX was associated with an improvement in life year gain (11.97 months vs. 10.95 months). The monthly acquisition cost for NALIRIFOX was $13,610 and for FOLFIRINOX $5,501. Based on the probabilities of selected AEs, the monthly cost of AE management for NALIRIFOX was $5,589 and for FOLFIRINOX was $ 15,511. QALY for NALIRIFOX was 10.23 and for FOLFIRINOX was 9.59 months. The incremental cost effectiveness ratio for NALIRIFOX vs. FOLFIRINOX was $1,368,937. Conclusions: In this modeling analysis, NALIRIFOX is associated with improvement in PFS and QALY. The analysis highlights the importance of AE management for improving quality of life and cost in the recipients of FOLFIRINOX. The economic value for use of NALIRIFOX is very high and outside of any conventional boundary of acceptable value threshold for treatment.
KRAS mutations allelic frequency dynamics using plasma extracellular vesicles: Association with survival outcomes in localized pancreatic adenocarcinoma.
Authors: Chopra Asmita , He Hongzhang , Milosevic Jadranka , Tirukkovalur Nikhil , El Asmar Rudy , Nassour Ibrahim , Nunns Geoffrey , Chen Mingxi , Chen Jiaqi , Jiang Siyu , Singhi Aatur D. , Saeed Anwaar , Zhang Janie Yue , Lee Kenneth K. , Zureikat Amer H. , Jiang Si-Yang , Paniccia Alessandro 
Published: June 2024

4167 Background: Pancreatic ductal adenocarcinoma (PDAC) lacks an effective and consistent biomarker to emulate treatment response and predict survival. Extracellular vesicles (EV) carrying tumor-specific mutations are disease-specific biomarkers that hold promise to address this unmet need. Methods: Informed by tumor profiling, plasma from 44 PDAC patients with confirmed KRAS mutations, treated with neoadjuvant therapy (NAT) and definitive surgery between 2019 and 2021, was analyzed. Samples were collected at diagnosis, day of surgery, and 1-month post-surgery. A lipid nanoprobe technique was used for EV isolation and droplet digital PCR was used for detection of tumor-specific KRAS mutations. Patients were categorized based on the temporal change in KRAS mutation allelic frequencies (MAF) into ND (no detection at any time point), ID (increasing MAF detection), or DD (decreasing MAF detection). Optimal CA19-9 response was defined as >50% reduction from baseline and normalization (<37 U/mL) before surgery. Survival associations were evaluated using Kaplan-Meier analysis and log-rank tests. The median follow-up was 36.1 months. Results: Among the cohort (mean age 66.5±8.2 years, 36% females), 29 (65.9%) patients had ND, 7 (15.9%) had ID and 8 (18.2%) had DD of KRAS MAF. No significant differences were noted in demographic or clinical variables (p > 0.05). Stages III, II, and I PDAC had detectable mutant KRAS in 50%, 30%, and 21% cases, respectively. The ND group exhibited significantly longer restricted mean disease-free survival (rmDFS) [31.2 months (95% CI: 24.1–38.3)] compared to DD [27.8 months (95% CI: 12.4–43.1)] and ID [9.8 months (95% CI: 0.1–19.7)] (p=0.010). The ND group also showed a superior rmOS [40.3 months (95% CI: 34.2–46.4)] outperforming DD [35.7 months (95% CI: 22.1–49.2)] and ID [17.7 months (95% CI: 6.4–28.9] (p = 0.012). Eleven patients (25%) exhibited optimal CA19-9 response. Patients in ND cohort with optimal CA19-9 response (n=6; 20%) had the longest DFS and OS (median DFS and OS not reached), outperforming all other subgroups (p<0.001). Conversely, patients in ID group had the lowest rmDFS (5.1 months 95%CI 2.4-7.8), irrespective of CA19-9 response (p<0.001). Conclusions: Detection and temporal increase of EV-KRAS MAF are significant indicators of reduced DFS and OS in PDAC patients. These findings highlight the potential of dynamic EV-KRAS profiling as a prognostic biomarker and underscore the need for expansive validation studies.
Predicting real-world overall survival for post-operative pancreatic ductal adenocarcinoma: An ASCO CancerLinQ Discovery analysis.
Authors: Ahmed Kaleem Sohail , Issaka Sheriff M , Marcinak Clayton Thomas , Zafar Syed Nabeel 
Published: June 2024

4169 Background: Pancreatic ductal adenocarcinoma (PDAC) is the second leading cause of cancer-related deaths in the US. There is a need to improve risk-stratification of patients to facilitate treatment decisions. Novel datasets such as the American Society of Clinical Oncology (ASCO)’s CancerLinQ Discovery (CLQD) combined with machine learning (ML) methods provide an opportunity to generate new insights from “real-world data” (RWD) to study patient outcomes. The objective of this study was to develop an ML model using RWD to predict 1-year survival (1YS) for patients undergoing pancreatectomy for PDAC. Methods: Using the CLQD database, we identified patients diagnosed with PDAC who had undergone surgical resection between July 1998 and May 2021. Patients with complete data on procedure and tumor characteristics were included. Patients lost to follow-up within 12 months of surgery were excluded. We trained a multivariable Logistic Regression (LR) for baseline comparison. Gradient Boosting Classifier (GBC) and Random Forest (RF) models were then trained on demographic and clinico-pathologic data, with and without pre-operative laboratory (lab) data. GBC-1 and RF-1 were trained only on demographic and clinico-pathologic data (n=1440). GBC-2 and RF-2 were trained on a subset of patients who had non-missing lab data (n=669). We performed a one-way ANOVA to compare the area-under-the-curve (AUC) scores for each GBC and RF model to the corresponding LR. Results: Of the 1440 patients analyzed, 44.7% were male, 53.6% were White, and the mean age was 69.7 ± 10.9 years. Majority had a T3-stage tumor (53.7%) and 70.3% received either neoadjuvant, adjuvant, delayed and/or recurrent chemotherapy. Unadjusted median OS was 16.5 months [95% CI: 15.1-17.6], and 1YS was 60.8% [95% CI: 58.2-63.3]. GBC and RF models were able to outperform the baseline LRs (Table 1). RF-2 and LR-2 performed the best (AUC: 0.83 each) with lab data, followed by RF-1 (AUC: 0.81) without lab data. Factors that were most predictive of survival were: receipt of chemotherapy, tumor size, pre-operative BMI, age, and pre-operative neutrophil count, serum cholesterol, and serum CA-19-9 levels. Conclusions: In this study, we show that ML models using clinicopathologic, demographic, and laboratory data provide more accurate prediction of 1 year survival than prior strategies. Such models can be used to identify patients at high risk for poor outcomes following pancreatectomy and alternative treatments may be offered. [Table: see text]
Molecular insights into oxaliplatin-induced peripheral neuropathy in colorectal cancer: Unraveling a potential signature.
Authors: Modekurty Suneeta , Iglesia Michael , Pedersen Katrina Sophia , Salvador Carolina , Haroutounian Simon , Lim Kian-Huat , Trikalinos Nikolaos , Suresh Rama , Aranha Olivia , Grierson Patrick , Tan Benjamin R. , Khushman Moh'd M. 
Published: June 2024

e15506 Background: Oxaliplatin (OXA) is a platinum chemotherapy utilized for treating patients with colorectal cancer (CRC). OXA-induced peripheral neuropathy (OXAIPN) stands as the primary non-hematological dose-limiting toxicity. Despite its clinical significance, there exists no reliable molecular predictive biomarker of OXAIPN in current clinical practice. In this study, we delved into the molecular signature associated with OXAIPN in CRC. Methods: OXAIPN-related genes were curated through an extensive literature review. Utilizing publicly available bulk transcriptomic data from the Illumina HiSeq 2500 platform, encompassing tumor and adjacent normal tissues from 18 individuals with CRC, we identified differentially expressed genes (DEGs). Furthermore, single-cell RNA sequencing (scRNA-seq) data from 10X genomics, including normal and tumor tissues from 3 CRC patients, underwent analysis using Seurat and sctype R packages to unveil DEGs associated with cancer cells. Functional and pathway enrichment analysis was performed using the Genecodis4 web-based tool. To validate the inhibition of a curated list of neuropathy-associated genes, RNA-seq data from CRC cell lines (HCT116 and DLD1) treated with Oxaliplatin were processed, and DEGs were determined. Results: A total of 1367 OXAIPN-related genes were identified. Bulk transcriptomic data analysis revealed 715 DEGs, while scRNA-seq analysis uncovered 2,854 DEGs. Noteworthy, upregulated genes from scRNA-seq analysis, including LGALS4, SPINK4, TFF3, REG4, and REG1A, were associated with tumor proliferation through epithelial-mesenchymal transitions, oxidative stress, dysregulated immune system, and inflammation. In CRC cell lines (HCT116 and DLD1), the administration of oxaliplatin resulted in the downregulation of proteins involved in axon excitability (NGF, SOD1, ROBO1, CNTNAP2, and KCNMB1), normal sensory neuron function (SOX10, APOE, SST, S1PR1, and KCND3), voltage-gated sodium (SCNN1B, SCNN1G, SCNN1A, SCN1B, and SCN2B), calcium (CACNA2D2, CACNA1A, CACNA1C, CACNA1E, and CACNA1F), and potassium channels (KCND3, KCNMB1, KCNMA1, KCNJ2, and KCNN4). Conclusions: A molecular signature associated with OXAIPN was identified in patients with CRC and validated in CRC cell lines (HCT116 and DLD1). Further studies to reproduce and evaluate its potential in predicting OXAIPN in CRC patients in the clinic are warranted.