bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pancreatic cancer associated ascites: Risk factors, outcomes, and management.
Authors: Wang Justin Dejia , Hendifar Andrew Eugene 
Published: June 2023

e16305 Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with significant morbidity and mortality as most patients present with advanced disease. The development of ascites has been associated with poor outcomes and further characterization and contemporary management strategies are needed. Therefore, we performed a comprehensive analysis of PDAC patients with ascites, including clinical and biological data, to describe its incidence, associated clinical factors, and outcomes. Methods: Patients were prospectively consented and enrolled the Gastrointestinal Biobank (“GI-Bank”) at Cedars-Sinai Medical Center, which collected patient specimens, associated clinical data, and self-reported questionnaires. Data was consolidated using a standard software tool (Redcap). Statistical analysis was conducted using Excel and using Datatab.net software tools. Results: Of the 437 patients with PDAC, 182 (41.6%) developed ascites. Overall survival (OS) between ascites and non-ascites groups were significantly different by log-rank test (p = 0.001), and estimated median OS was 473 days (95% CI [407, 537]) in ascites patients versus 554 days [467, 678] in non-ascites patients. In Cox proportional hazards model analysis, ascites status, but not sex or race, was associated with decreased survival (HR 1.49, [1.18, 1.87]). Ascitic fluid data was obtained in 77 patients; 62 (80.5%) had SAAG > 1.1; 14(22.6%) of SAAG > 1.1 patients also had positive cytology. The estimated median OS from the diagnosis of ascites was 100 days [76, 128] and median time to puncture was 4 days. Estimated median time from first tap to death was 56 days [42, 95]. 90 (49.5%) were treated with diuretics and 41 (22.5%) were treated with PleurX catheter. Patients with ascites had a worse survival and were more likely to receive greater than one chemotherapy regimen. There was no relationship between ascites and receipt of surgery or radiation. Conclusions: The development of ascites in patients with pancreatic cancer is common and contributes to significant morbidity and mortality. The use of diuretics is lower than would be expected for patients with elevated SAAG. Prospective evaluation of management strategies is needed to improve this important clinical conundrum.
Characteristics of survivors with peritoneal mesothelioma.
Authors: Muminovic Meri , Samuels Shenae , Erskine Aja , Ferraro Pablo H. , Gannon Christopher J. , Llaguna Omar H. 
Published: June 2023

e16325 Background: Peritoneal mesothelioma (PM) is a rare, fatal malignancy. The aim of the study is to determine the clinical and sociodemographic characteristics associated with long-term survival (LTS). Methods: The 2004 - 2019 National Cancer Database was queried for patients with PM. LTS was defined as having survived at least 5 years following diagnosis. Univariate and multivariate logistic analyses were performed to identify characteristics associated with LTS. A nomogram predicting the likelihood of LTS was developed. Results: 3,636 patients were identified, of which, 18% experienced LTS. The median overall survival (OS) for the entire study population was 17.7 months. The median OS for the LTS cohort was 92 months and 11.7 months for non-long-term survivors (NLTS). In univariate analysis, LTS was more likely to occur in younger (< 50 years), healthy (Charlson-Deyo = 0), female and privately insured patients that traveled farther for care, were treated at an academic or very high-volume center, had epithelial histology, underwent radical surgery and received chemotherapy (p < 0.001). Interestingly, among those who were treated non-operatively, LTS was associated with a longer time-to-chemotherapy (LTS = 50 days, NLTS = 32 days, p < 0.001). Although not statistically significant, among those who received surgery, results suggest that LTS was more likely achieved in those who received hyperthermic intraperitoneal chemotherapy (HIPEC) (p = 0.086). Patients who underwent surgery plus HIPEC experienced the longest median OS (65.9 months) when compared those who underwent surgery plus systemic therapy (38 months) or surgery alone (9.6 months) (p < 0.001). Multivariate logistic regression analysis suggests that age, female gender, and surgical margins are independent predictors of LTS. Based on our nomogram, patients with favorable characteristics resulted in a total score of at least 19 and had an approximate 50% chance of LTS. Conclusions: Age, gender and surgical margins were found to be independent predictors of LTS. Additionally, our nomogram may help predict LTS among patients with PM.
Technical performance of cancer detection and TOO identification of PanSeer7, a targeted bisulfite sequencing assay for non-invasive multi-cancer detection.
Authors: Sun Jin , Su Ming-Yang , Xu Min-Jie , He Qi-Ye , Ma Jian-Hua , Su Zhi-Xi , Yang Xin-Rong , Liu Rui 
Published: June 2023

e16338 Background: Many cancers are symptoms free in early clinical stages, resulting in nearly half of cancer patients diagnosed in advanced-stages when therapeutic options are limited. Early cancer detection is key to improve clinical outcomes. We developed PanSeer7, a multi-cancer detection assay based on targeted bisulfite sequencing of circulating cell-free DNA (cfDNA) and evaluated its technical performances of reproducibility and sensitivity. Methods: The panel of PanSeer7 consists of 2447 markers which were either differentially methylated between healthy and cancer samples, or distinctively methylated in a specific cancer. We assessed PanSeer7’s reproducibility by using it to sequence technical replicates of cfDNA samples. For its limit of detection (LOD), we prepared samples mimicking cancer plasma DNA by diluting fragmented cancer cell line DNA, which represent 7 common cancer types, into GM12878 control at ratios of 1/10,000 to 1/100. We further tested PanSeer7’s ability to identify tissue of origin (TOO) by analyzing DNA samples from formalin-fixed paraffin-embedded (FFPE) tissues and healthy plasma. Results: We analyzed PanSeer7’s reproducibility by sequencing 40 replicates of synthetic healthy cfDNA samples on four independent batches and with different inputs (from 2ng to 20ng). Results show that at a minimum of 10ng input, PanSeer7 produced highly consistent methylation levels among replicates. As to cancer signal detection, we found that PanSeer7’s technical LOD was 1/10,000 for lung cancer cell line H1650, liver cancer line HepG2, gastric cancer line HGC27, esophageal cancer line KYSE150 and colorectal cancer line SW480; it was slightly lower as 5/10,000 for pancreatic cancer line PANC1 and breast cancer line MDA-MB-231. To evaluate PanSeer7’s accuracy of TOO identification, we sequenced 38 healthy plasma and 121 FFPE tissues (17 of liver cancer, 13 of pancreatic cancer, 21 of gastric cancer, 18 of esophageal cancer, 16 of colorectal cancer, 14 of lung cancer, and 22 of breast cancer). Clustering analysis showed that they were segregated according to their TOO based on methylation levels. We also generated 3500 sets of simulated data by mixing the reads of cancer tissue into those of healthy plasma at ratios of 1/10,000 to 1/100, and trained TOO-predicting models with train data sets. At a ratio of 5/10,000, the model predicted TOO of test data sets with an accuracy of over 95%. Conclusions: PanSeer7 required as low as 10ng input DNA for high reproducibility. Its technical LOD in detecting cancer signal was no lower than 5/10,000 for all 7 cancer cell lines tested, and has an in silico TOO detection LOD of 5/10,000. Thus, PanSeer7 had excellent performances in both cancer signal detection and TOO identification, showing promise to be clinically applied for non-invasive multi-cancer detection after future optimization and validation.
Risk factors, clinical characteristics, and treatment outcomes for hepatocellular carcinoma in Rwanda.
Authors: Uwimana Ange , Kubwayo Prince Alain , Dukundane Damas , Nkeshimana Menelas , Naveed Ammara , Gupta Neil , Seruyange Eric , Bosland Maarten C , Rubagumya Fidel 
Published: June 2023

e16339 Background: Hepatocellular carcinoma (HCC) is increasing worldwide with limited treatment options, a poor prognosis, and survival rates of less than 5 years. In Sub-Saharan Africa, over 46,000 new cases are reported every year, and HCC is commonly associated with alcohol consumption, viral hepatitis, especially Hepatitis B (HBV) and C (HCV), aflatoxin exposure, obesity, type II diabetes, and HIV infection. In Rwanda, often young people are diagnosed with HCC in the late stages of the disease, and treatment options are limited. Rwanda has made great achievements in the prevention and treatment of HBV and HCV. However, there is a lack of data on HCC in Rwanda and its associated risk factors. In this study, we report the prevalence of common risk factors, available treatment options, and treatment outcomes among patients with HCC in Rwanda. Methods: This was a retrospective study of patients aged 18 years of age and above diagnosed with HCC from 2016 to 2021 in three tertiary hospitals: University Teaching Hospital of Kigali, King Faisal Hospital, and Rwanda Military Hospitals. Data were abstracted from patients’ paper charts and electronic medical records and recorded in REDCap and analyzed in STATA. Results: Overall, 219 individuals were included in the study. 32.9% were female, the median age was 32 (26–54) years, and 48.4% came from the capital city of Kigali. Only 13.3% of patients had histo-pathological confirmation of HCC, while 86.7 % were diagnosed clinically with radiological images, alpha-fetoprotein, and other clinical findings. The most common risk factors were HCV and HBV infection with a prevalence of 27.4% and 20.1%, respectively. HIV infection and diabetes mellitus were present in 6.9% and 6.2% of patients, respectively. More than 80% of patients had had clinical or ultrasound evidence of cirrhosis, including ascites or hepatic encephalopathy and only 8.9% of patients received Sorafenib, and no patient had surgical resection, ablation, or liver transplant. Only 15.1% of patients received palliative care with opiate therapy. Among all patient diagnosed with HCC, 36% died within 3 months of diagnosis. Conclusions: In this retrospective study of the three largest treatment centers in Rwanda, the majority of HCC cases occurred at a young age with a high rate of mortality. HBV and HCV were the most frequent risk factors, and the majority of patients had clinical characteristics of decompensated liver failure. There is a clear lack of diagnostic tools, most glaringly pathologic diagnosis, and an extreme lack of treatment options. Increased awareness for HBV and HCV prevention and screening as well as further studies on etiology of HCC cases and management are needed.
The emerging use of immunotherapy as a treatment option in metastatic renal cell carcinoma: Real-world evidence from a single UK tertiary cancer centre.
Authors: Liu Justin KH , Irvine Andrew F. , Altarqane Mustafa , Arif Mariyam , Bansal Vikram , Boyle Anne , Campbell Fiona C , Elsayed Noha , Hafiz Mdehteshamul E. , Huda Ashraful , Soe Aye , Maraveyas Anthony , McGrane John , Muazzam Iqtedar A 
Published: June 2023

e16509 Background: The landscape of systemic anticancer therapy (SACT) options for the treatment of metastatic renal cell carcinoma (mRCC) has recently evolved following results from the CheckMate 214 trial in 2018 which demonstrated improved overall survival in patients with International mRCC Database Consortium (IMDC) intermediate- and poor-risk mRCC clear cell histological subtype receiving combination immunotherapy (Ipilimumab/Nivolumab) in the first-line setting compared to Sunitinib. This is in addition to other treatment options including: vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) (e.g. Sunitinib, Pazopanib, Tivozanib, Cabozantinib, etc.), combination immunotherapy/TKI (e.g. Avelumab/Axitinib), VEGF/mammalian target of Rapamycin (mTOR) inhibitors (e.g. Lenvatinib/Everolimus) and single-agent immunotherapy (e.g. Nivolumab) in both first- and second-line settings. Methods: An audit of SACT prescribing practices in mRCC between 2019-2022 in a single UK tertiary cancer centre (Castle Hill Hospital, Hull, UK) was conducted as part of a national collaboration multi-centre UK audit looking into the real-world landscape and treatment choices in mRCC. Information was derived from the Somerset Cancer Registry and a dataset containing 87 patients with a coded diagnosis of ‘malignant neoplasm of kidney, except renal pelvis (CX64X)’ and ‘secondary malignant neoplasm of kidney & renal pelvis (C790)’ was generated. Results: Of the 81 patients included in the final analysis, 65% (n = 53) were male and 81% (n = 66) had a clear cell histological subtype. The main sites of metastases were lung (n = 58) and lymph nodes (n = 45). Most of the patients (n = 72) received either one or two lines of SACT. Of those with clear cell mRCC, 74% (n = 51/69) were classed as having IMDC intermediate- or poor-risk features with almost half (n = 34/69) receiving combination Ipilimumab/Nivolumab. Comparing overall survival (OS) and progression-free survival (PFS) to the published Kaplan-Meier curves in the CheckMate 214 trial, no significant differences in OS (p = 0.6) and PFS (p = 0.13) were observed, although there was an overall trend towards improved PFS in the first 6 months (82.4% vs 63.3%) in our local dataset. Conclusions: The results of our real-world evaluation of prescribing practices in mRCC favoured the use of combination immunotherapy in the first-line setting for the treatment of IMDC intermediate- and poor-risk clear cell mRCC with similar outcomes to the published data in the CheckMate 214 trial. The overall trend towards improved PFS in the first 6 months in our local dataset highlights the importance of patient selection when using immunotherapy.
Salvage lenvatinib/everolimus (LE) combination therapy after immune checkpoint inhibitor (ICI) and VEGFR tyrosine kinase inhibitor (TKI) for metastatic renal cell carcinoma (mRCC).
Authors: Khorasanchi Adam , Kwok Christopher , Psutka Sarah P. , Hinkley Megan , Dason Shawn , Yang Yuanquan (Aaron) , Verschraegen Claire F. , Gross Evan , Orcutt Delaney , Yin Ming 
Published: June 2023

e16520 Background: The optimal treatment for mRCC patients (pts) who have progressed after both ICI and TKI remains uncertain. LE is frequently used as a salvage treatment due to different antitumor mechanisms, but efficacy and toxicity data in this setting are limited. Methods: We retrospectively reviewed charts from two academic centers for 71 adult mRCC pts who received LE after prior ICI and TKI exposure. Collected data included patient demographics, histology, International mRCC Database Consortium (IMDC) risk group, treatment history, and toxicity details using CTCAEv5. Outcomes were objective response rate (ORR) per RECIST 1.1, median time to treatment failure (mTTF), and toxicity. Descriptive statistics, Cox proportional hazards model and Kaplan-Meier method were utilized. Results: The median age was 64 (range: 31–84). Most pts had clear cell histology (84.5%) and had undergone nephrectomy (75%). IMDC risks were favorable (19.7%), intermediate (int) (66.2%), poor (11.3%), and unknown (2.8%). Pts received a median of 3 (range 1-10) prior therapy lines (L) and 42 pts had sequential ICI and TKI, while 29 received ICI/TKI combination therapy. Average ORR was 26.8%, but numerically better when given earlier (2L/3L vs. ≥4L: 28.6% vs. 22%). The mTTF was 5.5 months (m) (95% confidence interval [CI], 3.5–7.6 m), which was not significantly changed by sequential or combinational ICI/TKI treatment exposure. In multivariable Cox analyses, int/poor IMDC risk was associated with a significantly worse TTF compared to favorable risk (HR, 2.2, 95% CI, 1.1-4.1; mTTF: 4.5 vs 12.9 m), and so was ≥4L treatment compared to 2L/3L treatment (HR, 3.2, 95% CI, 1.3-7.6; mTTF: 4.5 vs. 6.6 m). In 57 pts with int/poor IMDC risk, ≥4L treatment was associated with a significantly worse TTF (HR, 2.3, 95% CI, 1.2-4.5; mTTF: 3.6 vs. 6.6 m), while prior nephrectomy was associated with a significantly better TTF (HR, 0.46, 95% CI, 0.22-0.97; mTTF: 5.4 vs. 3.1 m) compared to those without nephrectomy. Of the 71 pts, 64% had ≥ grade 3 adverse events, 60% had treatment interruption, 44.3% had dose reduction, and 21% stopped treatment due to intolerance. Conclusions: LE therapy is feasible but has modest efficacy following ICI/TKI treatment. Pts with favorable risk, prior nephrectomy or early salvage may have a better treatment response. These observations need to be confirmed in prospective studies.
Association between time to treatment initiation and survival in metastatic renal cell cancer: A population-based study of 5,193 cases from the California Cancer Registry (2010-2019).
Authors: Benjamin David Joseph , Shrestha Anshu , Fellman Dimitra , Rezazadeh Arash 
Published: June 2023

e16530 Background: The treatment of metastatic renal cell cancer (RCC) has changed since the approval of the first tyrosine kinase inhibitor (TKI) in 2005. Since then, combination therapy with immunotherapy and TKI is considered standard-of-care. Despite multiple drug approvals, it remains unclear whether patients should be initiated on treatment immediately (within 30 days) as opposed to delay treatment (after 30 days), and if time to initiating treatment correlates with survival. Methods: Adults aged 20 years and older with newly diagnosed metastatic RCC between 2010 and 2019 were identified through the California Cancer Registry (n = 5,193). Time to treatment was calculated as duration between date of diagnosis and date of treatment initiation, then categorized into: No treatment, treatment within 30 days, between 31-60 days, and > 60 days. Association between treatment timing and overall and cancer-specific survival were assessed using Cox proportional hazard model and Fine and Gray sub-distribution hazard model accounting for competing risk. Both models included patient and baseline clinical characteristics. Results: 47.6% (n = 2,470) of patients received treatment with 30 days of diagnosis, while 24.3% received treatment between days 31-60 from diagnosis and 14.1% started treatment at 61 days or after from the time of diagnosis. After adjusting for all covariates, patients who received treatment at 61 days or later were less likely to experience mortality from cancer (HR 0.76, 95% 0.69-0.84, p < 0.0001) compared to those who started treatment within 30 days. Patients who started treatment between days 31-60 from diagnosis were also less likely to experience mortality from cancer (HR 0.82, 95% CI 0.76-0.89, p < 0.001). There were no statistically significant associations between cancer-specific survival and variables such as sex, race/ethnicity, or neighborhood SES. Conclusions: Patients who started treatment within 30 days of diagnosis of metastatic kidney cancer experienced worse cancer-specific survival compared to those who started treatment between days 30-60 or after day 61 from time of diagnosis. The differences in survival may be a reflection of tumor biology and high- versus low-risk disease groups. Further research is warranted to identify which patients benefit from early versus delayed treatment initiation. [Table: see text]
A randomized, open-label, phase II study of high-dose interleukin 2 vs high-dose interleukin 2 plus entinostat in renal cell carcinoma.
Authors: Pili Roberto , Quinn David I. , Hauke Ralph J. , Kuzel Timothy , Han Yan , Adra Nabil , Logan Theodore F. 
Published: June 2023

e16540 Background: Immunosuppressive factors such as regulatory T cells (Tregs) limit the efficacy of immunotherapies such as high dose interleukin 2 (HD-IL2). We previously reported that the histone deacetylase (HDAC) inhibitor entinostat has antitumor effects in combination with HD-IL2 by decreasing Tregs function in a preclinical model of kidney cancer. Based on these preliminary data, we hypothesized that HDAC inhibition may enhance or resensitize patients (pts) with clear cell renal cell carcinoma (ccRCC) to HD-IL2. Our group has previously conducted a Phase II, single arm, clinical trial of entinostat in combination with HD-IL2 in ccRCC, which showed an objective response rate (ORR) of 37% and a median progression-free survival (mPFS) of 13.6 months as compared to historical data with single agent HD-IL2 of 20-25% and 4.2 months, respectively. Thus, we designed a multi-center, randomized, open label Phase II study with entinostat in combination with HD-IL2 in ccRCC patients. Methods: The primary objective was to estimate and compare PFS in pts randomized to receive either HD-IL2 plus entinostat (Arm 1) or HD-IL2 (Arm 2) and stratified by no prior therapies vs prior therapies. Due to unforeseen circumstances, enrollment halted after the first 10 patients. The treatment schedule was HD-IL2 600,000 units/kg administered IV every 8 hrs on Days 1-5 and Days 15-19 (maximum 28 doses) +/- entinostat 5 mg orally given every 2 weeks starting on Day-14, continuously. The study was originally designed to detect a 100% improvement of median PFS to 8.4 months in ARM 1. A one-sided stratified log-rank test with an overall sample size of 46 subjects (23 per group) achieves 80% power at a 0.10 significance level to detect a hazard ratio of 0.5 (median PFS of 4.2 months vs 8.4 months). Results: 10 pts (6 pts in Arm 1 and 4 pts in Arm 2) were enrolled. Among the 10 pts, only one had prior therapy (Arm 1). The most common treatment-related toxicities ( > 50%, any grade) were diarrhea, hypotension, nausea, hypomagnesemia, hypophosphatemia, pruritus, hypocalcemia and thrombocytopenia, hypophosphatemia, proteinuria, diarrhea, fatigue, and neutropenia. The most common ≥ grade 3 toxicities were hypotension (80%), hypophosphatemia (70%), and thrombocytopenia (60%). Two pts (33%: CI 4.3%-77.7%) achieved a partial response in Arm 1 and no pts in Arm 2. The median PFS was 12.4 months (CI 2.3-NE) in Arm 1 (13.3 months in pts with no prior therapies) and 2.8 months (CI 1.2-3.3) in Arm 2 (Logrank p-value 0.0167). We have collected blood samples to conduct several correlative studies including flow cytometry and gene expression analysis on peripheral blood mononuclear cells. Conclusions: The preliminary results from this study confirm that the combination of entinostat and HD-IL2 may be more active than HD-IL2 alone in pts with ccRCC. Clinical trial information: NCT03501381 .