bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adjuvant donafenib for patients with hepatocellular carcinoma at high risk of recurrence following radical resection: A multi-center, retrospective study in China.
Authors: Zhang ShenYu , Yang Guibing , Song Ruipeng , Wang Wei , Meng Fanzheng , Yin Dalong , Wang Jiabei , Zhang Shugeng , Cai Wei , Liu Yao , Wang Jizhou , Luo Dayong , Liu Lianxin 
Published: June 2024

e15129 Background: The implementation of adjuvant therapy in reducing tumor recurrence of hepatocellular carcinoma (HCC) is an essential approach for extending the prognosis of patients. The exploration of treatment strategies that are both efficacious and secure remains a prominent area of research in recent years. Donafenib is a novel, oral, small-molecule, multikinase inhibitor, and has demonstrated promising efficacy and safety profiles in preclinical and clinical studies. However, there is currently a lack of reported data on the adjuvant donafenib for HCC following radical resection (R0). The present study aimed to explore the efficacy and safety of adjuvant donafenib for HCC patients at high risk of recurrence following R0. Methods: This retrospective study analyzed 196 patients who underwent R0 for HCC between April 2021 and October 2022. All patients exhibited at least one of the following high risk recurrence factors:① single lesion > 5 cm or multiple lesions of any size; ② microvascular invasion (MVI); and ③ satellite nodules. Among these patients, 49 received donafenib, while 147 (control group) did not. In the donafenib group, donafenib was administered at a dose of 100 or 200 mg bid until tumor recurrence and serious adverse events (AEs). The 1-year and 2-year recurrence-free survival (RFS) rates and overall survival (OS) rates were compared between the two groups, as well as the incidence of adverse events (AEs) in the donafenib group. Inverse probability of treatment weighting (IPTW) was used. Results: The patient population consisted of 167 males and 29 females, with a median age of 59 (range 30-83). All patients exhibited a high risk of recurrence (number of tumors single/multiple, 167/29; tumor size within 5.0/above 5.0 cm, 78/118; MVI yes/no, 140/56; satellite nodules yes/no, 39/157). The median follow-up was 21.8 (range 3.8-32.0) months. Before IPTW, the donafenib group exhibited significantly higher 1-year and 2-year RFS rates compared to the control group (83.7%, 68.0% vs 66.7%, 47,6%, p = 0.023), while no significant difference in 1-year and 2-year OS rates (97.8%, 93.9% vs 91.8%, 80.6%, p = 0.120). After IPTW, the 1-year, 2-year RFS rates and OS rates were more favorable for the donafenib group compared to the control group (86.6%, 72.5% vs 64.8%, 45.0%, P = 0.004; 97.9%, 95.6% vs 89.5%, 77.9%, P = 0.043, respectively). In the donafenib group, AEs occurred in 44 patients, including 39 with grade 1 or 2 AEs and 5 with grade 3 AEs. The most common AEs included hand-foot skin reaction, decreased platelet count, and diarrhea. Conclusions: Adjuvant donafenib may improve RFS of HCC patients at high risk of recurrence following R0, while exhibiting favorable safety. This finding deserves further exploration.
Multicenter study evaluating the utility of AI-aided HER2 scoring in the clinically relevant categories.
Authors: Krishnamurthy Savitri , Canas Marques Rita , Borkowski Piotr , Cates Justin , Shearon Elisabeth , MacGrogan Gaetan , Ding Qingqing , Chandra Pranil , Morphew Emilie , Yassin Rawia , Sweeney Keith , Sun Hongxia , Riben Michael , Wheeler Darren , Globerson Yuval , Ziv Raz , Etoz Sevde , Grinwald Maya , Vecsler Manuela 
Published: June 2024

e15150 Background: The availability of multiple therapeutic options for breast cancer patients with varying levels of protein expression necessitates precise and standardized HER2 scoring. This study explored the clinical utility of AI-aided HER2 scoring of whole-slide digital images by pathologists in breast core needle biopsies and excisions. Methods: The study included patients (n=764) with multiple subtypes of invasive breast cancer from 3 US reference laboratories and 1 academic medical center. The non-interventional two-arm multi-reader study retrospectively compared manual digital vs. AI-aided HER2 scoring of 8 pathologists. The fully automated HER2 AI solution detects the invasive tumor area and then classifies the tumor cells based on staining pattern based and the 2023 ASCO/CAP guidelines to output slide-level HER2 score. Both study arms were compared to reference ground truth (GT) established by the consensus of two breast subspecialists, ground truthers (GTer), who reviewed the slides digitally. One site recorded the time taken for HER2 scoring of both arms to determine the efficacy of the HER2 AI solution. Results: The initial interobserver agreement among expert GT pathologists for each HER2 score, 0, 1+, 2+, 3+, were 83%, 63.8%, 46%, and 92.6, respectively. At the clinically meaningful cut-offs, the reader pathologists’ performance improved with the AI support. At the 0 vs. 1+/2+/3+ and 0/1+ vs 2+/3+ clinical cutoffs, the readers' accuracy was 86.3% vs 88.6% and 93.7%, 93.8% with and without AI support, respectively. The AI use contributed to approximately 12%-time savings for the readers at the medical center. The AI solution demonstrated high accuracy for HER2 scoring, with 89.2% agreement with GT for 0 vs 1+/2+/3+ scores and 93.1% for 0/1+ vs 2+/3+ cutoff. The results will be updated in the final submission with the additional site data. The reader feedback survey regarding the solution’s usability will also be presented. Conclusions: The pathologists demonstrated improvements in consistency, evidenced by inter-reader agreement and accuracy with the aid of the AI. The AI solution can improve efficiency toward accurate HER2 scoring. [Table: see text]
The clinical utility of the 90-gene expression assay on diagnosis and management in patients with cancer of unknown or unclear primary.
Authors: Qi Peng , Sun Yifeng , Xu Qinghua , Wang Qifeng , Zhou Xiaoyan 
Published: June 2024

e15172 Background: The diagnosis and management of patients with cancer of unknown or unclear primary present significant clinical hurdles, often culminating in unfavorable outcomes. A randomized phase III trial (CUP001) has demonstrated that site-specific treatment guided by the 90-gene-expression assay (Canhelp-Origin Assay) resulted in more therapy options, and significantly improved progression-free survival compared with empirical chemotherapy in patients with cancer of unknown primary. This study evaluated the clinical utility of the 90-gene expression assay in the diagnosis and management of patients with cancer of unknown or unclear primary. Methods: Patients who underwent the 90-gene expression assay at Fudan University Shanghai Cancer Center (FUSCC) between February 2023 and December 2023 were enrolled in the study. Data collection encompassed patient demographics, clinical characteristics, and pathological features. Results: Patient enrollment began in February 2023 and closed in December 2023 after enrolling 303 patients with 51 inpatient cases and 244 pathological consultation cases (from 144 sites). Among them, 295 patients met all inclusion criteria, yielding an overall success rate of 97.4% (295/303). Tumor cells were enriched by either macrodissection (N = 257) or microdissection (N = 38), with median highest similarity scores of 57.5 and 67.1, respectively. Using a positive cutoff value of the highest similarity score ≥45.3, the positivity rates for macrodissection and microdissection were 66.5% (171/257) and 81.6% (31/38), respectively. Of the enrolled patients, 177 (60%) were male, and 118 (40%) were female, with a median age of 63 years (range: 25 to 85 years). Predictive results encompassed 21 tumor types, with the most common being gastroesophageal cancer (N = 40, 13.6%), lung cancer (N = 37, 12.5%), breast cancer (N = 36, 12.2%), head and neck squamous cell carcinoma (N = 29, 9.8%), and ovarian cancer (N = 28, 9.5%). Of 166 samples with an assigned grade, 89.8% were poorly differentiated or undifferentiated, 6.0% were moderately differentiated, and 4.2% were well differentiated. The consistency of prediction results and clinicopathological results will be further evaluated after follow-up. Conclusions: This study demonstrates that the 90-gene expression assay has diagnostic implications for patients with cancer of unknown or unclear primary. This affirms its clinical utility as a standard diagnostic approach in the diagnosis and management of these patients, facilitating the formulation of more precise treatment strategies and ultimately enhancing prognosis.
Evaluation of biomarkers of response in patients with breast cancer with BRCA 1/2 pathogenic variants treated with PARP inhibitors.
Authors: Akkoc Mustafayev Fatma Nihan , Gutierrez Angelica M. , Munsell Mark F. , Chen Junjie , Schlacher Katharina , Tainer John A. , Albarracin Constance T. , Arun Banu 
Published: June 2024

e15188 Background: Several prospective studies highlight the pivotal role of PARP inhibitors (PARPi) in treating BRCA-associated breast cancers (BC), demonstrating a significant overall response rate (ORR) of up to 60% in advanced BC patients with BRCA 1/2 germline pathogenic variants (PV). Despite their clinical efficacy, the factors predicting PARPi response, the mechanisms of resistance to PARPi, and the clinical strategies to overcome these challenges are still unknown. The aim of this study is to establish tissue microarrays (TMA) from primary breast tumor tissue from BC patients with BRCA1/2 PVs who were treated with PARPi and identify biomarkers of PARPi resistance. Methods: Stage 4 BC patients with BRCA 1/2 PVs who presented to the University of Texas MD Anderson Cancer Center Breast Medical Oncology clinics and were treated with PARPi between 2008-2023 were identified using our database. Available patient tissue samples were obtained from institutional tumor banks. TMA from breast tumor tissue created and evaluated by our collabrating pathologists for expression of biomarkers:Wee-1, MRE, BP1,and c-Myc. Clinical and tumor characteristics analyzed included:Age at diagnosis, treatment details, tumor characteristics including histological type, hormonal receptor status, Her-2/Neu status, grade, Ki-67 and clinical outcome. Descriptive statistics, the Fisher exact test, and the log rank test were used to report patient characteristics and outcomes. Here we report on initial TMA construct and biomarker analysis. Results: So far TMA from 12 patients treated with PARPi were succesfully constructed. Patient characteristics include: Median age of 36.5 years (29-57). Nine (75%) and 3 (25%) patients had BRCA1 and BRCA2 mutations, respectively. All patients had invasive ductal carcinoma and 9 (75%) had triple negative BC. Most patient (75%) had high nuclear grade BC and median Ki-67 was 75 (15-90). In 11 evaluable patients, the ORR was 72.7%. The median OS was 383.6 months (95% CI 62.5-383.6) and median PFS was 31.5 months (95% CI 10.8-NE). No significant difference in biomarker expression was observed between PARPi-responders and non-responders (Table1). Conclusions: This report presents unique data on novel predictive biomarkers of response and evaluates the evidence for potential biomarkers. Further analysis on a larger TMA cohort is ongoing. [Table: see text]
Synergistic cytotoxicity of histone deacetylase, poly-ADP ribose polymerase inhibitors and decitabine in breast and ovarian cancer cells: Therapeutic implications.
Authors: Tsimberidou Apostolia Maria , Valdez Benigno C. , Yuan Bin , Baysal Mehmet A. , Chakraborty Abhijit , Andersson Borje S. 
Published: June 2024

e15193 Background: Innovative strategies are needed for breast and ovarian cancer. We explored the synergistic cytotoxicity of histone deacetylase inhibitors (HDACi), poly(ADP-ribose) polymerase inhibitors (PARPi), and decitabine (DAC, D) in breast and ovarian cancer cells. The drugs affect epigenetic regulation and DNA repair, making them promising anticancer therapies. Methods: Breast (MDAMB231 and MCF-7) and ovarian (HEY-T30 and SKOV-3) cells were exposed to HDACi (panobinostat, Pano, P; vorinostat; Vori, V), PARPi (talazoparib, TLZ, T; olaparib, Ola, O) and DAC. Synergism was assessed by MTT and clonogenic assays. Changes in DNA damage response/repair markers were assessed with Western blotting. Results: The combinations of HDACi, PARPi, and DAC had synergistic effects in all cell lines, evidenced by combination index <1. Clonogenic assay confirmed sensitivity of all cell lines to the 3-drug combinations (Pano, TLZ, DAC; Pano, Ola, DAC; Vori, TLZ, DAC; Vori, Ola, DAC). Cell proliferation was inhibited by 50% - 70%, and Annexin V positivity was 51% - 58% in all cells exposed to the combinations. Western blots showed inhibited protein PARylation, cleaved caspase 3 and PARP1 (suggestive of apoptosis), and down-regulated c-MYC. The 3-drug combinations induced more DNA damage (increased phosphorylation of ƔH2AX) than the individual drugs, impaired DNA repair (decreased ATM, BRCA1, ATRX proteins; Artemis), and altered gene expression (reduced NuRD complex subunits). DNA damage caused by HDACis and DAC may confer increased cellular dependence on protein PARylation, increasing sensitivity to combined HDACi, PARPi, and DAC. The P values comparing the inhibitory effects of each drug combination with that of individual drugs (MTT assay) are shown in Table ( P ≤ .05, statistically significant). Conclusions: The results support exploring HDACi, PARPi, and DAC combinations to overcome drug resistance and improve patient outcomes, and carefully designed clinical trials are warranted in breast and ovarian cancer. [Table: see text]
Development of HLB3-002 (recombinant human PH20 stand-alone) and its applicability as an anticancer diffusion agent.
Authors: Kim Heeyoun , Byun Juyoung 
Published: June 2024

e15195 Background: HLB3-002 is a standalone of Halozyme's rHuPH20 (Original) and has the same amino acid sequence. HLB3-002 is being developed as a drug diffusion agent that decomposes subcutaneous hyaluronan, allowing substances such as anticancer drugs to be administered subcutaneously. This study was conducted to compare the in vivo efficacy and PK of original and HLB3-002 to confirm equivalence and thereby prove its applicability as a drug diffusion agent. Methods: In the in vivo efficacy test, Trypan blue was mixed with each original and HLB3-002 and administered subcutaneously to confirm diffusion and reconstruction equivalence in the nude mouse. The PK test was conducted using Rituximab, prepared in the same formulation as Rituximab SC by adding HLB3-002. A single dose was administered subcutaneously to the nape of the rat, and 12 points were collected for 28 days. The PK samples were measured by ELISA. When the Cmax and AUClast ratios of Rituximab between 2 groups were within 80.00 to 125.00%, they were evaluated as biologically equivalent. Results: As a result of efficacy test, the diffusion area of HLB3-002 was 104.7% compared to the original, which was confirmed to have an equivalent diffusion efficacy. In the skin reconstruction test, it was confirmed that both original and HLB3-002 rebuilt the skin layer to a similar to the negative control after 48 hours. As a result of the PK, Compared to Rituximab SC, the Cmax of Rituximab+HLB3-002 was similar at 98.53% and AUClast at 95.50%. Conclusions: Through an in vivo efficacy and PK test, we confirmed an equivalent drug diffusion effect, confirming that HLB3-002 applicability as an anticancer drug diffusion agent.[Table: see text]
A rapid assessment tool for systemic treatment outcomes in colorectal cancer with deep bidirectional transformers.
Authors: Kim Hyunwook , Yuh Taeho , Choi Jeong Eun , Baek Eunsil , Kim Han Sang , Beom Seung-Hoon , Ahn Joong Bae , Shin Sang Joon 
Published: June 2024

e15567 Background: Retrospective investigations involving cancer treatment encounter the challenge of manually reviewing voluminous imaging reports to identify the best responses and the timing of disease progression. Here, we employed natural language processing, specifically deep bidirectional transformers, to automate the extraction of treatment response data. Methods: Data were sourced from the Yonsei Cancer Data Library database, focusing on patients with stage II-IV colorectal cancer at the Yonsei Cancer Center from Jan 1, 2010, to Dec 31, 2020. Imaging reports from 6,574 patients were gathered, amounting to 97,119 CT readings. Among these, 9,000 CT reports corresponding to 2,859 patients were randomly subjected to multilabel manual labeling by four radiology experts, based on the RECIST version 1.1 classification (CR/NED, PR, SD, PD). The pretrained BERT-base-uncased model was employed and fine-tuned for the downstream tasks of multilabel classification. 6,765 reports were used for training, while the remaining 1,000 reports were divided equally between the validation and test sets. Additionally, an algorithm for integrating and extracting treatment response data was also implemented. Clinical data were meticulously collected for 47 patients with stage IV early-onset colorectal cancer (EOCRC) receiving palliative first-line chemotherapy. The primary objective was to evaluate the model’s accuracy in predicting the timing of disease progression events within a ±30-day window. Secondary objectives focused on the model’s ability to identify the best response and its timing within a ±45-day window. Results: The evaluation of the classification accuracy across 1,000 individual CT reports, categorized as CR/NED (319), PR (86), SD (272), and PD (298), revealed accuracy with an AUROC of 0.956 and an F1 score of 0.823. All EOCRC patients were initially diagnosed with stage IV disease, and 45 out of 47 (95.7%) underwent metastasectomy either before initiating chemotherapy or during the first-line chemotherapy treatment. In clinical evaluation, the model demonstrated 72.3% (95% Confidence Interval [CI], 59.5-85.1) accuracy in predicting the day of disease progression within a ±30-day window. It achieved 55.3% (95% CI, 41.1-69.5) accuracy in predicting the best response category and its timing within ±45-days. Notably, the model was more accurate in predicting CR/NED at 72% compared to SD and PR, which had accuracy of 27.3% and 15.4%, respectively. Conclusions: Our model demonstrated high performance in classifying CT reports, which is expected to provide rapid insights into patient progress and improve clinical decision-making. However, the complexity involved in integrating and extracting data result in slight constraints in performance. This emphasizes the need for further research into multimodal large language models that can integrate a wider variety of clinical data.
Rethinking rectal cancer management through COVID: Real word evidence in a public hospital in the south of Brazil.
Authors: Fabra Lucas Fernando , Nassif Pereira Lima Marta , Pereira Rodrigo Perez , Azevedo Sergio Jobim , Tarta Claudio , Stanham Valentina De Souza , Ley Laura Lessa Gaudie , Hütten Debora Oliveira 
Published: June 2024

e15620 Background: Treatment of locally advanced rectal cancer is based on a combination of radiotherapy and chemotherapy, either as adjuvant, neoadjuvant or total strategies. Short course radiotherapy followed by neoadjuvant chemotherapy, as described in the RAPIDO trial, was chosen by our Oncology, Radiotherapy and Coloproctological tumor board at Hospital de Clínicas de Porto Alegre during the COVID19 pandemic as a measure to reduce hospital visits and thus the possibility of transmission and infection by the SARS-COV-2 virus. Methods: We performed an observational analysis, including all patients treated with short course radiotherapy for locally advanced rectal cancer, at the Hospital de Clínicas de Porto Alegre in the period between January 2020 and March 2023. Metastatic patients were included, either treated with curative or palliative intent. Demographic characteristics, clinical staging, timing of chemotherapy, radiotherapy and surgery were analyzed. Clinical response was evaluated through sigmoidoscopy and clinical rectal exam. Patients with complete clinical response were offered the watch and wait strategy or surgery, after careful discussion of the possible benefits and risks. Results: Ninety-six patients were submitted to short course radiotherapy in the period described. Seven (7) patients were excluded; 89 patients were included in the final analysis. Fifty-five percent were male; mean age was 62 ±12.5 years; 52.8% were ECOG 1 at the diagnosis. Median CEA value at diagnosis was 7 ng/mL (CI 95%:4.4 - 9.8). Sixty-four percent were stage III, 31.4% stage IV, 3.3% stage II. Ninety-eight percent completed the programmed radiotherapy treatment. Only two patients received less than 25Gy. Forty-nine percent of patients completed the whole planned chemotherapy treatment; 15.7% were treated with palliative intent chemotherapy and 5.6% couldn’t receive chemotherapy for other reasons. Clinical response data were available in 62 patients: the main reason for unavailable clinical response was metastatic disease. Disease control was achieved in 98.4% of the cases, with only 1 patient having progressive disease during treatment (1.6%). The overall clinical response rate was 72.6%, 25.8% had stable disease and 24.2% complete clinical response. Fifteen of the 16 patients that presented with complete clinical response opted into a watch and wait strategy, achieving a 1-year disease free survival of 86.6%. Conclusions: Adopting the RAPIDO approach had a positive outcome in our advanced rectal cancer population. Short course radiotherapy followed by chemotherapy achieved excellent rates of disease control. Almost 25% of the non-metastatic patients undergoing RAPIDO treatment achieved complete clinical response opting into a watch and wait program.
An economic analysis of low-energy contact x-ray brachytherapy for treatment of rectal cancer.
Authors: Sun Myint Arthur , Bennett Hayley , Rao Christopher , Batten Leona , Hasler Elise , Jarrom David , Prettyjohns Matthew , Barrington Craig 
Published: June 2024

e15622 Background: Health Technology Wales sought to evaluate the clinical and cost-effectiveness of contact x-ray brachytherapy (CXB) in conjunction with external-beam radiotherapy (EBRT), compared to EBRT alone for early-stage (T2–3b, N0–1, M0) rectal cancer in a surgically fit population. Methods: An economic analysis was performed using a decision analytical, state transition model. Analysis was performed from a third-party payer perspective over a life-time horizon. The model was populated using data from the Organ Preservation in Early Rectal Adenocarcinoma (OPERA) trial. Results: . CXB was estimated to provide 0.2 quality-adjusted life years (QALYs) per patient at an additional cost of $1118 per person. CXB was cost-effective compared with external beam boost at a cost of $5623 per QALY gained. These findings did not change in deterministic sensitivity analysis and CXB was cost-effective in over 90% of probabilistic sensitivity analyses. Conclusions: CXB is likely to be cost-effective with a high degree of certainty in this patient population.