bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pilot trial of personalized neoantigen pulsed autologous dendritic cell vaccine as adjuvant treatment in hepatocellular carcinoma.
Authors: Wu Qiuji , Li Qiu 
Published: July 2024

e16264 Background: The primary treatment for hepatocellular carcinoma (HCC) is radical surgery. However, HCC has a high propensity to recur postoperatively and no standard adjuvant therapies have been approved. This Phase I trial aims to evaluate the safety and efficacy of an adjuvant personalized neoantigen pulsed autologous dendritic cell vaccine (Neo-DCVac-02) in patients with HCC. Methods: Eligible patients had histologically confirmed high-risk HCC after radical surgery. After obtaining the necessary baseline biopsy specimens and PBMCs of appropriate quality for DNA and RNA sequencing, neoantigen prediction, screening and synthesis were performed. Subsequently, leukapheresis was performed and DCs were isolated and cultured. DCs were then pulsed with neoantigen peptides to produce Neo-DCVac-02. On day 0, patients were treated with cyclophosphamide at a dose of 250 mg/m2. The prepared Neo-DCVac-02 vaccine was administered subcutaneously to the axillary and inguinal regions bilaterally on day 1, followed by daily administration of GM-CSF at a dose of 0.075 mg for 5 days (days 2-6). The primary objectives of this study were to assess feasibility and safety/tolerability. Secondary objectives included evaluation of immune responses (via vaccine response: IFNγ ELISpot), relapse-free survival (RFS) and overall survival (OS). Results: A total of 32 patients provided informed consent to initiate the process of personalized neoantigen discovery, of which 26 (81%) met the requirements for successful product selection for clinical manufacturing. Feasibility was demonstrated with 13 patients receiving Neo-DCVac-02. 13 patients did not receive the neoantigen vaccine (7 due to progressive disease, 6 due to withdrawal of informed consent because of COVID-19). The treatment was well tolerated with no grade 2+ treatment-related adverse events (TRAEs). The most common Grade 1 TRAEs were injection site reactions (75%), rash (16.7%), fatigue (8.3%), neutropenia (8.3%), and headache (8.3%). Five of 13 evaluable patients showed increased antigen-specific T-cell activity and more than 50% of the neoantigen peptides in Neo-DCVac-02, and sustained cellular responses were observed up to one year. Increases in T-cell activation/co-stimulation seen after treatment with Neo-DCVac-02, as demonstrated by flow cytometric analysis, suggest immune priming. At a median follow-up of 29.7 months, median RFS was not reached, with 1- and 2-year RFS of 84.6% and 60%, respectively, and all patients are alive. Patients with a strong immune response had a longer median relapse-free survival (not reached) compared to patients with a weak immune response (17.6 months, P = 0.003). Conclusions: These data demonstrate that Neo-DCVac-02 is safe, well tolerated and capable of inducing durable antigen-specific lymphocyte immune responses that may correlate with delayed HCC recurrence. Clinical trial information: NCT04147078 .
Bi-institutional spline curve analysis of lymph node mapping in gallbladder cancer operated over 12 years: Impact of location and number of lymph nodal stations.
Authors: Patkar Shraddha , Bhargava Prabhat Ghanshyam , Ostwal Vikas S. , Ramaswamy Anant , Patel Swapnil , Goel Mahesh 
Published: July 2024

e16274 Background: Current staging system for gallbladder cancers (GBC) takes into account only the number of metastatic lymph nodes without addressing their location. The current study evaluates the prognostic impact of lymph node mapping (number and location) in node positive GBCs. Methods: Prospectively maintained operative database of GBC patients with positive lymph nodes were analysed from two tertiary cancer care centers in a retrospective cohort study design between April 2010 till March 2022. Nodal burden was assessed including both, the number of metastatic nodes and the lymph node station. Impact of lymph node ratio (LNR) and log odds of positive lymph nodes (LODDS) was evaluated using regression and spline curve analysis. Results: Amongst 1312 operated GBC patients, 272 patients with node positive disease were included. The median nodal yield was 8. The median LNR and LODDS was 0.222 and -0.48 respectively. The 5-year DFS and OS for patients with only cystic node metastases was 52.3% and 50.8% respectively (median: not reached), as compared to 24.6% and 35.2% for involvement of regional nodal stations beyond cystic nodes. Higher LODDS was associated with inferior DFS and OS when compared to the LNR. On multivariate analysis, multi-station involvement was the only factor associated with inferior DFS (p < 0.001) and OS (p = 0.007). Conclusions: Station wise pathological assessment of lymph nodal involvement could potentially provide superior prognostic information, in addition to number of involved nodes. Involvement of cystic lymph node alone has relatively superior prognosis as compared to multi-station involvement.
WDR4 as a potential indicator of clinical prognosis and immunotherapy in hepatocellular carcinoma.
Authors: Lin Chi , Wang Juan , Ouyang Long , Duan Huaxin , Fan Shasha 
Published: July 2024

e16275 Background: Immunotherapy has garnered increasing attention in hepatocellular carcinoma (HCC) treatment. However, there remains a pressing need for effective immunological predictive biomarkers. In our previous study, utilizing data extracted from The Cancer Genome Atlas (TCGA) database, we identified a positive correlation between WDR4 expression levels in hepatocellular carcinoma and various clinical parameters, encompassing Stage, T-stage, pathological grade, AFP level, and vascular invasion. Additionally, higher WDR4 expression was linked to poorer prognosis. Leveraging The TIMER and GEPIA databases, we further elucidated a significant association between WDR4 expression levels and the extent of immune cell infiltration, particularly macrophages, B lymphocytes, and myeloid suppressor cells, in hepatocellular carcinoma. These findings propose the potential utility of WDR4 as a biomarker for immune infiltration in hepatocellular carcinoma. As noted in the trial NCT03867084, which hypothesized that adjuvant pembrolizumab might surpass placebo efficacy, there still exists a gap in identifying the specific population benefiting from adjuvant immunotherapy. Methods: Clinical and pathological data from patients who underwent single-agent immunotherapy for HCC were additionally collected from Hunan Provincial People's Hospital between January 1, 2019, and January 31, 2024. These patients participated in the clinical trial (NCT03867084) with informed consent. The relationship between WDR4 expression levels, clinical pathological data, and patient prognosis was assessed using the Kruskal-Wallis test and Kaplan-Meier survival curve analysis. Results: WDR4 displayed significant upregulation in HCC tissues compared to para-carcinoma tissues (P < 0.001) and exhibited robust diagnostic potential. WDR4 expression showed significant associations with various immune cells, including macrophages (r = 0.278, P < 0.001). Kaplan-Meier survival analysis indicated that patients with high WDR4 expression had shorter postoperative progression-free survival in the context of immunotherapy. Data from 37 patients who underwent postoperative single-agent immunotherapy for hepatocellular carcinoma (NCT03867084) revealed a significant correlation between WDR4 expression levels and Disease-Free Survival (DFS), with notable statistical significance (Log-rank P < 0.001). Conclusions: WDR4 demonstrates elevated expression levels within HCC tissues and is associated with immune infiltration, establishing it as a prognostic biomarker in HCC. Furthermore, the positive correlation observed between WDR4 and CD68 as well as PD-L1 underscores its potential as a guiding factor in immunotherapeutic approaches for HCC.
Anatomical and demographic prognosticators of pancreatic cancer.
Authors: Desai Krishna , Pereira Kristal , Prabhakaran Sivaguha Yadunath , Ali Hassan , Thar Yu Yu , Choi Eugene , Thirumaran Rajesh 
Published: July 2024

e16310 Background: Pancreatic cancer is known to have one of the poorest median of survival (mOS) of all cancers. It is now the third leading cause of cancer-related mortality after lung & colorectal cancer. With the current trends, understanding & knowing prognosticators can aid in determining outcomes of pancreatic cancer. Methods: The data was collected from Surveillance, Epidemiology and End Result database Research Plus Data, 17 Registries, Nov 2022 Sub (2000-2020). We extracted pancreatic cancer cases based on primary site encoding for head, body & tail of pancreas, Islets of Langerhans (IoL), other specified parts & overlapping lesion of pancreas, pancreas, NOS (no other specific). The analysis was further completed by comparing survival using the Log-rank test (GraphPad Prism). Results: A total of 221,304 cases were extracted between 2000-2020. The median age of diagnosis was 71 years. 50.54% were males, & 49.45% were females. The incidence rates are shown below. Whites (69.99%) were commonly affected, followed by Blacks (11.05%), Hispanics (10.79%), Asians & Pacific islanders (7.41%), Alaskan natives & American-Indians (0.57%). A distribution in anatomy was notable for head of the pancreas (46.00%), followed by tail (13.20%), body (11.34%), pancreatic duct (0.49%), IoL (0.10%). A survival curves were compared on different variables. Gender showed no statistical difference. mOS for patients diagnosed >70 years was 3 months & <70 years was 8 months (p value <0.0001, CI 0.3716 to 0.3784, HR 1.731). mOS for calculated for Whites (5), Blacks (4), Asian & Pacific islanders (6), Alaskan natives & American-Indians (4), & hispanics (5) (p value <0.0001). mOS based on involved parts of pancreas were compared for: head (6), body (6), tail (5), pancreatic duct (8), IoL (59) (p <0.0001). Conclusions: Median age of diagnosis was in 71, with a slight male predilection. Overall incidence rate is trending up. It is significantly higher for males, & is significantly lower for females than that of the general population. Whites are most commonly affected, & Alaskan natives & American natives are rarely affected. Survival is significantly greater if diagnosed <70 years. Most common site involved is the head of pancreas, & the least is IoL. mOS is ~10 times greater for IoL, but it's an endocrine pancreatic cancer which is treated differently. From the exocrine pancreas, survival is the best for pancreatic duct cancer, & the worst for pancreatic duct. If anatomic & demographic prognosticators are combined with molecular, radiologic factors, it can be beneficial in predicting the outcomes of this cancer with poor prognosis. [Table: see text]
PD-1 blockade plus chemotherapy followed by concurrent SBRT with SIB as preoperative therapy for patients with potentially resectable pancreatic cancer: A single-arm phase 2 study.
Authors: Du Juan , Ni Jiayao , Sun Yi , Sha Hui-zi , Tong Fan , Mao Liang , Kong Weiwei , Shen Shanshan , Gu Qing , Wang Lei , Qiu Yudong , Liu Baorui 
Published: July 2024

e16312 Background: Pancreatic cancer has 10% low rate of early diagnosis and resection due to its insidious onset and poor prognosis. We aimed to assess the safety and efficacy of a new mode of preoperative therapy for patients with Potentially Resectable Pancreatic Cancer. Methods: This is a single arm clinical trial (NCT05634564). Gemcitabine (1000 mg/m2) and nabpaclitaxel (125 mg/m2; AG) were administered to patients with LAPC or BRPC on days 1 and 8, along with tislelizumab (200 mg) on day 1 intravenously (IV) every three weeks. Concurrently, the patients underwent stereotactic body radiotherapy (SBRT) with simultaneous integrated boost (SIB)during the third cycle of treatment. Surgical intervention was reassessed after four cycles of treatment. Objective response rate (ORR) was the primary endpoint and Disease control rate (DCR), R0 resection rate, median overall survival (mOS), median progression free survival (mPFS) rate, time to progression (TTP) and safety were analyzed as secondary endpoints. Results: Between May 2020 and April 2023, 62 patients with LAPC or BRPC were enrolled. Until the last follow-up time (January 30, 2024) ,56 of them included in the intention-to-treat (ITT) analysis who completed at least three cycles of tislelizumab plus AG and underwent concurrent radiotherapy. The median age in intention-to-treat analysis was 65 years. 25 patients had a best response of partial response, the ORR was 44.6%, DCR was 100%. Thirty-one patients met the criteria for surgical resection after treatment, 9 of whom refused surgery and continued conservative treatment. 22 patients underwent resection, and the R0 resection rate was 95.45%. Two of the 22 resected patients achieved pathologic complete response (pCR) and five patients achieved major pathological response (MPR). The pathologic complete response rate was 9.10% and significant pathological response rate was 31.82%. The TTP was 19.38 months (95% CI: 12.8%-27.9%), and the mOS was 21.32 months (95% CI:15.9%-NR). The 12-months PFS rate and 12-months OS rate were 59.9% (95% CI:45.2%-71.8%) and 74.4% (95% CI:59.9%-84.3%), respectively. Grade 5 adverse events were not observed. The most common grade 3-4 hematological and non-hematological toxicities were leukopenia (17.9%), neutropenia (16.1%), anemia (8.9%), thrombocytopenia (7.1%), rash: dermatitis (7.1%), Peripheral neuropathy (3.6%). Conclusions: Anti-PD-1 inhibitor tislelizumab plus AG chemotherapy followed by concurrent SBRT with SIB significantly prolonged mPFS rate, as well as R0 resection rate of surgical patients, and also improved the major pathological response rate. Clinical trial information: NCT05634564 .
Tislelizumab with anlotinib and chemotherapy for second-line treatment of pancreatic ductal adenocarcinoma: A pilot study early result.
Authors: Dong Xuyuan , Wu Yinying , Fan Yangwei , Shi Yu , Wang Meichen , Dong Danfeng , Li Enxiao 
Published: July 2024

e16316 Background: Advanced pancreatic ductal adenocarcinoma is a malignant tumor with poor prognosis. At present, chemotherapy is still the standard treatment, however the efficacy is unsatisfied. The lack of second-line treatment options for pancreatic cancer results in progression-free survival often lasting less than 3 months. For pancreatic cancer is an immune desert type of tumor, immunotherapy has not brought breakthrough therapeutic regimen compared to the remarkable data in other tumors.There is still insufficient therapeutic evidence treated with PD1 antibody in pancreatic cancer. Anlotinib is a tyrosine kinase inhibitor (TKI) with anti-tumor effects. It has been shown the combination of PD1 and multi-target tyrosine kinase inhibitors can increase immunotherapy efficacy. The purpose of this study is to evaluate the efficacy and tolerability of Tislelizumab combined with Anlotinib, as well as chemotherapy (the choice of the investigator) in second-line treatment of patients with pancreatic ductal adenocarcinoma. Methods: In this single arm, phase II, prospective exploratory study, it was planned to recruit 30 adult patients with treated pancreatic ductal adenocarcinoma who have never received any PD (L) 1 and TKI. Eligible patients received Tislelizumab (iv, 200mg, Q3W), Anlotinib (PO, 10mg, QD), and chemotherapy (determined by the researchers) till disease progression or death. The primary endpoint was median progression-free survival (mPFS), the secondary endpoints were objective response rate (ORR), median overall survival(mOS), disease control rate (DCR), and treatment safety profile. Results: 14 eligible patients were recruited till Jan 2024, 12 patients with PFS records were included. Median follow-up time was 208 days (104 days-504 days). mPFS was 106 days, OS is not reached, BOR (best of response) was stable disease. The 3-months DCR rate was 58.3%, 6-months DCR rate was 25%. One patient was observed to have a 20% tumor shrinkage after two cycles of treatment and is still being followed up. The most common treatment-related adverse events(TRAEs) was neutropenia with level ≤grade 3, observed in 8/14 patients. The immune-related adverse event of concern was hypothyroidism(grade 1/2), which occurred in two patients. Two patients experienced grade 4 obstructive jaundice caused by the progression of the disease. Conclusions: The second-line combination regimen of Tislelizumab with Anlotinib based on chemotherapy demonstrated survival improvement trend and no new safety signals identified in pancreatic cancer. These data suggest Tislelizumab + Anlotinib+Chemo may be a promising novel treatment option for patients with pancreatic cancer. Clinical trial information: NCT05681390 .
Unfavourable carcinoma of unknown primary (CUP) with gastrointestinal profile: A retrospective study.
Authors: Guidi Lorenzo , Valenza Carmine , Battaiotto Elena , Boscolo Bielo Luca , Crimini Edoardo , Belli Carmen , Gervaso Lorenzo , Cella Chiara Alessandra , Ciardiello Davide , Venetis Konstantinos , Bottiglieri Luca , Ghioni Mariacristina , Guerini Rocco Elena , Fazio Nicola , Zampino Maria Giulia , Curigliano Giuseppe 
Published: July 2024

e16374 Background: According to European Society of Medical Oncology (ESMO) guidelines, CUP are classified in favorable and unfavorable subsets. Favorable CUPs (20% of pts) have clinical aspects and either pathology highly suggestive for specific site of origin or with amenable metastases for localized treatment with curative intent; they are treated with site-specific chemotherapy (CT). All other CUPs (80%) are defined unfavorable and are treated with empiric CT regimens. There is no data about the best CT regimen for unfavourable CUPs with GI profile, i.e., those CUPs that do not meet the criteria of favourable colon-like CUP (CK7-/CK20+/CDX2+) but have a morphological/immunohistochemical profile suggestive for the digestive system. Methods: We conducted a single-center retrospective study to describe outcomes and prognostic factors of pts with unfavourable CUPs with GI profile, referred to our center from Jan 2000 to Aug 2023, who received at least one cycle of first-line CT. The definition of GI profile was: a) negativity for GATA-3, PAX-8 and TTF-1 and b) CK7+/CK20-/anyCDX2 or CK7-/CK20+/CDX2- or CK7-/CK20-/CDX2+, or c) presence of an abundant mucinous component and/or a signet ring cell component. The primary endpoint was the progression free survival (PFS) of first line chemotherapy for advanced disease. Results: 43 pts were included (characteristics in table). After a median follow-up of 43.9 months, 33 deaths were registered and the mOS was 12.6 months (95% CI, 8.7-16.5). Forty PFS events were registered and the mPFS was 6.1 months (95% CI, 3.5-8.9). At univariate analysis, male pts (p=0.034), peritoneal metastases (p=0.0282), residual tumor after surgery (p=0.002), suspected biliopancreatic origin (p=0.033), PS ECOG > 1 (p<0.001) and CDX2- status (p=0.025) were associated with shorter PFS. No CT regimen was superior in terms of PFS at both univariate (p=0.282) and multivariable analysis after adjusting for peritoneal metastases, suspected origin, gender and baseline ECOG PS. Conclusions: Although limited by the small sample size, this study showed that all CT regimens were comparable in terms of PFS among patients with unfavorable CUP with gastrointestinal profile. Keywords (3/10): cancer of unknown primary; peritoneal metastases; chemotherapy. [Table: see text]
FOLFOX as a therapeutic option in patients with hepatic failure due to liver metastasis of gastrointestinal (GI) system malignancies: A case series.
Authors: Başkurt Kadriye , Sütcüoğlu Osman , Mizrak Kaya Dilsa 
Published: July 2024

e16378 Background: The treatment options for patients with hepatic metastasis presenting with liver dysfunction, particularly those experiencing severe hyperbilirubinemia, are limited. The oxaliplatin and fluorouracil/folinic acid regimen, known as FOLFOX, stands out as a viable option based on its pharmacokinetics. However, clinical data regarding the specific dosage and tolerability of this regimen are limited, and clear recommendations are not currently available. Patients and Methods: Patients who presented with severe hyperbilirubinemia immediately after the diagnosis of GI adeno cancer, and who were not eligible for drainage options, were prospectively observed in our clinic in Turkey throughout the year 2023. Severe hyperbilirubinemia was defined as a bilirubin level > 5mg/dL. The FOLFOX regimen was administered every two weeks, and the fluorouracil dose was initially reduced by 50% for the first two cycles. Subsequently, the dose was increased to the total amount if no toxicity occurred. Results: Six cases of GI cancer patients meeting the criteria were identified. Subsequent laboratory data for these six patients were collected after initiating the FOLFOX regimen. All six patients underwent the FOLFOX regimen with dose reduction for the first two cycles. Following the first cycle of chemotherapy, bilirubin levels dropped and normalized (Table 1), leading to an improvement in the patients' clinical condition. Conclusions: While our series is limited by a small number of patients, treatment with FOLFOX has proven to be feasible and may yield significant benefits in patients with severe liver dysfunction caused by GI cancer, especially when no further drainage options are available. [Table: see text]
Relugolix prescribing practices and clinical experiences at an urban academic center.
Authors: Fernandez Turizo Maria Jose , Stevens Julia , Xu Guiyu Jessie , Yankama Tuyen , Garnick Marc B. , Lichtenstein Morgan R. L. , Fein Daniel E.C. 
Published: July 2024

e17008 Background: Relugolix is a novel oral GnRH antagonist that is now an alternative option for patients with prostate cancer (PC) who require androgen deprivation therapy (ADT). The potential benefits of relugolix include rapid testosterone decline and recovery, oral administration, and a possible cardiovascular (CV) benefit compared to traditional GnRH agonists. This study examines real-world data on relugolix prescribing practices and clinical experiences at a large, urban academic center. Methods: We conducted a retrospective, single-center cohort study of patients with PC prescribed relugolix from March 2021 through December 2023 at Beth Israel Deaconess Medical Center. We collected patient-related and clinical factors including demographics, comorbidities, CV risk factors, treatment history, reasons for relugolix prescription over GnRH agonists, medication compliance, adverse effects, and treatment outcomes. Descriptive statistics were used to characterize the cohort. Results: Among 267 patients who received a relugolix prescription, median age was 70 years old, 186 patients (69.6%) were Non-Hispanic White, 37 (13.9%) Non-Hispanic Black, 13 (4.9%) Asian, and 6 (2.2%) Hispanic of any race. Across all patients, 228 (85.3%) initiated relugolix with a median therapy duration of 181 days (range: 10 - 807). At the time of prescription, 88 patients (32.9%) were prescribed concurrent androgen receptor signal inhibitors (ARSI) and 186 (69.6%) had localized disease. Median CV risk factors per patient was 2 (range 0 - 7), and 4 patients (1.5%) developed major adverse CV events (MACE), including acute heart failure decompensation, sick sinus syndrome, ventricular tachycardia, and death during treatment. Among physician prescribers, the most common reasons for prescribing relugolix included concern for CV risk (90 prescriptions, 33.3%) and patient preference for oral administration (55 prescriptions, 20.4%). Forty-nine patients (18.3%) were switched from a GnRH agonist, mainly due to physician concern for CV risk (13, 4.9%) or patient preference (17, 6.4%). Conclusions: We describe real-world use of relugolix for PC in a large, diverse single center cohort. The most frequent reasons for choosing relugolix over a GnRH agonist were physician concern for CV risk and patient preference for a tablet over injection. Investigations of treatment initiation and adherence in relation to insurance coverage, adverse effects, and socioeconomic factors require further investigation.