bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrating pathomics and radiomics for predicting survival among patients with intrahepatic cholangiocarcinoma undergoing surgical resection.
Authors: Wan Mingyu , Shen Yifei , Xu Nong , Ruan Jian 
Published: July 2024

e16255 Background: Intrahepatic cholangiocarcinoma (ICC) is characterized by a high degree of malignancy and poor prognosis. Surgical resection remains the primary curative approach for this type of cancer. However, there is a lack of effective predictive tools for patients undergoing such treatments. Methods: In this study, we employed a random forest algorithm to develop our predictive model, which was rigorously validated through a ten-fold cross-validation method. The model leveraged the five most pertinent features extracted from the radiomics dataset to generate predictions. Subsequently, these predictive outcomes were utilized to discern and analyze the distinctions among features within the proteomics dataset to uncover the intricate associations between radiomic signatures and proteomic profiles. Results: In this study, a radiomics prognostic model based on MRI data (n = 150) was developed using a random forest algorithm, and validated using ten-fold cross-validation, achieving an AUC of 0.709. Subsequently, a similar approach was applied to construct a pathology-based model (n = 150), which resulted in an AUC of 0.815. The integration of proteomic and radiomic models reveals that the upregulation of VNN1 and the downregulation of SCGN are significantly associated with prognosis, suggesting a group of highly interactive proteins that may play key roles in the biological process under study. Conclusions: The integration of these omics models is beneficial for predicting the prognosis of ICC patients post-surgery.
First-line treatment patterns among patients with metastatic pancreatic ductal adenocarcinoma in the real-world setting.
Authors: Dennen Syvart , Harton Joanna , Cockrum Paul , Kim George P. , MacEwan Joanna P. 
Published: July 2024

e16320 Background: Treatment options for patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) have historically been limited. FOLFIRINOX (FFX) and gemcitabine + nab-paclitaxel (GnP) are both recommended first line (1L) treatments that have shown efficacy vs. gemcitabine monotherapy in clinical trials. More recently, small subgroups of pts have benefitted from regimens that include irinotecan liposome injection, targeted therapies, and checkpoint inhibitors (CPIs). To better understand treatment patterns in current practice, we examined the distribution of 1L therapies in a RW cohort of mPDAC pts diagnosed between 2015 and 2022. Methods: This retrospective observational study utilized the Ontada Clinical Data View: Pancreatic Cancer database. Adult pts diagnosed with mPDAC between November 2018 and November 2022 who initiated 1L treatment within 90 days of their diagnosis for metastatic disease were included in the study. Regimens were grouped into the following categories: FFX, GnP, gemcitabine monotherapy, FOLFOX, FOLFIRI, capecitabine/5-FU monotherapy, irinotecan liposome injection-containing regimens, CPI monotherapy, PARP inhibitors and other targeted therapy-containing regimens, no 1L, and other regimens (comprised of combinations of FFX and GnP components as well as other chemotherapeutic agents). Results: Of the 5,358 pts eligible for inclusion in the study, the majority received GnP (33%, 1,785 pts) or FFX (23%, 1,254 pts) in 1L. The next largest segment of pts did not receive 1L therapy (23%, 1,229 pts). Just 6% (345 pts) received gemcitabine monotherapy. The remaining 14% of pts received therapies other than the three primary 1L mPDAC treatments: 4% (207 pts) received FOLFOX, 2% (109 pts) received capecitabine/5-FU monotherapy, 2% (96 pts) received an irinotecan liposome injection-containing regimen, 0.7% (39 pts) received FOLFIRI, 0.5% (28 pts) received CPI monotherapy, and 0.5% (26 pts) received PARP inhibitors or other targeted therapies. 4% (240 pts) received various other chemotherapy combinations (comprised of combinations of FFX and GnP components and a small number of other chemotherapeutic agents, with ≤40 pts per combination). FFX pts were the youngest, with a mean age of 64yrs, compared to 70yrs for gemcitabine + nab-paclitaxel (p < .001). Gemcitabine monotherapy pts were the oldest (mean = 73yrs, p < .001 vs. GnP) and were more likely to have metastatic disease and an ECOG ≥2 (p < .001 vs. GnP). Conclusions: There are limited 1L treatment options for mPDAC. Since the and PRODIGE and MPACT trials, FFX, GnP, or gemcitabine monotherapy have been the primary recommended 1L treatments for most pts with mPDAC. While recent years have seen an increase in the availability of targeted and CPI therapies appropriate for small subgroups of mPDAC pts, in a RW sample, almost all pts received one of the three standard therapies.
Chemotherapy with or without surgery for locally advanced or borderline resectable pancreatic ductal adenocarcinoma: A retrospective multicenter international study.
Authors: Venerito Marino , Zhang Danmei , Becht Selina , Schütz Juliane , Steup ChristophDaniel , Bankstahl Ulli Simone , Habibzada Timorshah , Sadeghlar Farsaneh , De Scordilli Marco , Ongaro Elena , Krug Sebastian , Gonzalez-Carmona Maria A , Goetze Thorsten , Finkelmeier Fabian , Ettrich Thomas Jens , Cannizzaro Renato , Dorman Klara , Franck Caspar 
Published: July 2024

e16352 Background: Current clinical guidelines recommend surgery for patients with locally advanced (LA)/borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) who achieve disease control after induction therapy. However, the additional survival benefit of surgery in these patients is unknown. Methods: In this multicenter international retrospective cohort study, consecutive patients with BR/LA PDAC who achieved disease control after three to six months of induction therapy (combination chemotherapy or chemoradiotherapy) between January 2014 and July 2021 were retrospectively identified at 8 centers in Germany and Italy. Resectability status was determined by consensus in a multidisciplinary tumor board based on imaging findings, serum CA19-9, performance status and clinical response. Patient characteristics, progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox regression analysis was used to compare survival data. Results: A total of 138 patients who achieved disease control with induction therapy were analyzed. The median age at diagnosis was 66 years (range 45-82) and 43% of patients were female. 73 patients underwent surgery and 65 patients did not (median age 64 and 69 years, respectively, p = 0.02). Median OS was 20.0 months (95%CI 16.1-23.8) in the surgery group and 18.0 months (95%CI 13.6-22.4) in the nonsurgery group (hazard ratio for death, 0.90; 95%CI, 0.63 to 1.29, p = 0.57). Median PFS was 14.0 months (95%CI 8.9-19.1) in the surgery group and 15.0 months (95%CI 11.7-18.3) in the nonsurgery group (hazard ratio for disease progression, 1.04; 95%CI, 73 to 1,47, p = 0.83). The 2-year survival rates in the surgery and nonsurgery groups were 32.9% and 40.0%, respectively, with an overall odds ratio of 0.74 (95% CI: 0.37-1.47). Conclusions: In our multicenter international retrospective analysis, additional surgery did not confer a survival advantage to patients with BR/LA PDAC who achieved disease control with induction therapy.
Early prediction of pancreatic cancer through detection of methylated circulating DNA in blood.
Authors: Lin Ruo-Kai 
Published: July 2024

e16353 Background: Pancreatic cancer represents a significant oncological challenge, contributing markedly to cancer-associated mortalities. This is attributed to the asymptomatic nature of early-stage disease, its inherently aggressive phenotype, and a notably suboptimal response to existing systemic therapies. Hence, the formulation of efficacious early diagnostic modalities for pancreatic cancer amenable to surgical resection is imperative to augment patient prognoses and enhance survival outcomes. Methods: The Infinium MethylationEPIC v2.0 BeadChip platform facilitated the examination of methylation profiles within plasma samples, while the HumanMethylation450 BeadChip array was employed for analogous analyses in corresponding tissue specimens from Taiwanese pancreatic cancer cohorts, aiding in gene selection. Subsequent methylation status verification was conducted via quantitative Methylation-Specific PCR (qMSP) on both genomic DNA and circulating cell-free DNA samples. For external methylation confirmation within a Western demographic, data from The Cancer Genome Atlas (TCGA) Portal were utilized, with further validation conducted using plasma samples from U.S. pancreatic cancer patients. Total 105 plasma from pancreatic cancer patients and healthy subjects were analyzed to calculate the candidate the accuracy, sensitivity, specificity of biomarkers for predict the pancreatic cancer. Results: The test exhibited an accuracy of 90.4%, sensitivity of 92.3%, and specificity of 90.1% in the detection of pancreatic cancer. Detection levels increased from 0% in healthy individuals to 87.5% in Stage I and 100% in Stages II, III, and IV. The CA19-9 marker displayed limited specificity with a high rate of false positives. Moreover, the test dynamically evaluated tumor burden by monitoring circulating methylated ZFP30 and FBXL7 in the plasma of breast cancer patients post-treatment. Conclusions: The analysis of plasma for methylated ZFP30 and FBXL7 provides an innovative and accurate noninvasive method that outperforms the existing blood biomarker CA19-9 for the prediction and ongoing assessment of tumor burden following treatment in pancreatic cancer.
ctDNA for clinical decision support in pancreatic cancer.
Authors: ASCHERMAN BENJAMIN , Amini Neda , Koti Shruti , King Daniel 
Published: July 2024

e16354 Background: Circulating tumor DNA (ctDNA) is increasingly used to inform therapeutic decisions and its applicability to pancreatic cancer is emerging. We explore the adoption of ctDNA profiling in patients presenting to our pancreatic cancer clinic to help guide localized and metastatic pancreatic cancer treatment. Methods: This was an IRB-approved retrospective cohort study of Signatera ctDNA profiling among patients with pancreatic cancer at Northwell Health between October 2021 and September 2023. Patients received ctDNA testing at various treatment timepoints and were categorized according to clinical context: neoadjuvant, adjuvant, surveillance, radiographic relapse, and metastatic. Average ctDNA level and conversion rates were calculated for each group. Results: There were 203 tests completed among 59 patients representing the following clinical contexts: 36% metastatic disease, 27% in the adjuvant setting, 23% during surveillance, 7% prior to surgery, and 6% after relapse. 43 patients had ctDNA tests that were drawn but were cancelled or could not be performed due to inadequate tissue samples, of which 8 had at least one completed test and were included in final analysis. Of all 27 metastatic patients, 8 patients had tests that were never completed. 46% of all tests were positive, which ranged from 0.3 to 8089 MTM/mL, and averaged 196 MTM/mL. 51% of all patients had ctDNA results that remained positive, 34% remained negative, and 15% changed over time from either positive to negative or vice versa. Median ctDNA level was 0.1 MTM/mL or less for patients who were tested prior to surgery or during adjuvant treatment or surveillance and the median ranged from 0.0-67.1 for patients with metastatic disease or relapse. All ctDNA tests sent after radiographic relapse also tested positive. Conclusions: ctDNA testing was most commonly performed in patients with localized disease on adjuvant chemotherapy, and in those with metastatic disease at time of diagnosis, who also had the highest rates of positive tests by stage at diagnosis. Given all patients tested during relapse had positive tests, ctDNA may be an early predictor of disease progression in patients with negative tests on surveillance. When tissue is limited, such as in metastatic patients who are less likely to undergo surgery, production of the ctDNA assay may be hindered. A prospective, larger scale, and more longitudinal study would add greater power and clinical context.
Development of a multi-analyte blood test for the early detection of pancreatic ductal adenocarcinoma (PDAC) and performance compared to CA19-9.
Authors: Athanasiou Alcibiade , Kureshi Natasha , Palma Norma Alonzo , Schiess Ralph , King Thomas C. 
Published: July 2024

e16360 Background: Early detection of PDAC can improve survival but is hampered by the lack of recognizable symptoms in early disease. Imaging has been the mainstay for surveillance of high-risk individuals but has proven to be cumbersome and may lack sensitivity to detect small tumors. CA19-9 is the only available blood biomarker for PDAC, but it is neither sensitive nor specific enough for it to be recommended for high-risk surveillance. A sensitive and specific blood biomarker for PDAC could positively impact this situation. Methods: Serum samples from patients across multiple centers with stage I and II PDAC (n = 75) and matched controls at high risk for PDAC (genetic and familial) (n = 83) were assessed for more than 2,900 protein analytes using O-link multiplex technology and conventional immunoassays for selected protein candidates. Machine learning was used to combine the biomarker candidates to create 4-plex signatures discriminating PDAC and controls. Results: ROC (receiver operating characteristic) curve analysis of these revealed signatures with performance superior to CA19-9 and a previously commercially available assay, IMMRay PanCan-d (AUC of 0.97 and 0.94 vs. 0.87 for CA19-9 and 0.88 for IMMRay). A subset of these candidate biomarkers has now been transitioned to standardized ELISA assays which are being used to construct a final signature for clinical validation in an independent set of PDAC and high-risk control samples. Conclusions: A novel multi-analyte blood test utilizing newly-discovered PDAC biomarkers has the potential to improve early detection of PDAC in high-risk individuals.
Laparoscopic versus open pancreatoduodenectomy for periampullary tumors: An updated systematic review and meta-analysis.
Authors: Bittar Vinicius , Reis Pedro Cotta Abrahão , Almirón Giulia , Schramm Ana Júlia , Oliveira João Pedro , Cagnacci Renato , Camandaroba Marcos Pedro Guedes 
Published: July 2024

e16362 Background: Laparoscopic pancreatoduodenectomy (LPD) has emerged as an alternative to open technique in treating periampullary tumors, particularly pancreatic ductal adenocarcinoma (PDAC). However, the evidence regarding safety and efficacy of LPD compared to open pancreatoduodenectomy (OPD) remains unclear. Methods: According to PRISMA guidelines, we searched PubMed, Embase, and Cochrane Library in December 2023 for randomized controlled trials (RCTs) that directly compare LPD versus OPD in patients with periampullary tumors. Outcomes were stratified as intraoperative outcomes, postoperative complications, in-hospital and short-term, and prespecified subanalysis was performed in patients with PDAC. All statistical analysis was performed using R software version 4.3.1 with a random-effects model. Results: Five RCTs yielding 1,018 patients with periampullary tumors were included, of whom 511 (50.2%) were randomized to LPD group. The total follow-up time was 90 days. LPD was associated with a longer operation time (MD 66.75; 95% CI 26.59 to 106.92; p = 0.001; I2= 87%; Figure 1A), lower intraoperative blood loss (MD -124.05; 95% CI -178.56 to -69.53; p < 0.001; I2= 86%; Figure 1B), and shorter length of stay (MD -1.37; 95% IC -2.31 to -0.43; p = 0.004; I2= 14%; Figure 1C) as compared to OPD. In terms of 90-day mortality rates and number of lymph nodes yield, no significant differences were found between both groups. Subgroup analysis for PDAC consistently aligned with the overall results and provided relatively lower heterogeneity compared to the primary analysis. Conclusions: Our meta-analysis of RCTs suggests that LPD is an effective and safe alternative for patients with periampullary tumors, with lower intraoperative blood loss and shorter length of stay.
A phase I/II study of enzalutamide in combination with indomethacin in men with castration-resistant prostate cancer (CRPC).
Authors: Leibrandt Ryan , Ullah Ayman Teeham , Verma Rashmi , Gao Allen , Lara Primo N. , Pan Chong-xian , Parikh Mamta 
Published: July 2024

e17027 Background: Metastatic castration resistant prostate cancer (mCRPC) remains an incurable disease despite recent advances in therapy. In patients (pts) receiving the second-generation androgen receptor antagonist enzalutamide (enza), primary or adaptive resistance can occur due to upregulation of the steroidogenesis pathway, including aldo-keto reductase 1C3 (AKR1C3), which can also upregulate intratumoral androgen synthesis. Indomethacin, a non-steroidal anti-inflammatory drug and selective inhibitor of AKR1C3, demonstrates synergistic activity when combined with enza against enza-resistant CRPC in vitro and in vivo. We thus sought to study this combination in a clinical trial. Methods: This investigator-initiated Phase I/II trial enrolled pts with enza-naive mCRPC on androgen deprivation therapy. Prior abiraterone was allowed. Pts must have adequate organ function and ECOG performance status 0-2. In the phase I lead-in, a 3+3 dose de-escalation design was used to identify the recommended Phase II dose (RP2D) of indomethacin in combination with enza 160 mg oral (PO) once daily, after which a Phase II expansion proceeded. Pts continued treatment until disease progression or unacceptable toxicity. Co-primary endpoints were safety and PSA response, defined as 50% or more reduction from baseline. Secondary endpoints included overall response as determined by Prostate Cancer Working Group 2 criteria (PCWG2). Results: From 2017 - 2022, 26 pts were enrolled, with a median age of 71 (range 50-88), primarily white (n=16, 62%), median baseline PSA 19.45 (range 1.5-210), ECOG 1 (n=12, 46%), and most received prior abiraterone (n=24, 92%). In 6 pts enrolled to the phase I cohort, there were no grade 3 adverse events (AEs); RP2D of indomethacin was 50mg PO twice daily. All 26 pts were evaluable for safety and efficacy. Most common treatment-related AEs (n; %) were nausea (12; 46%), fatigue (11; 42%), diarrhea (8; 31%), hypertension (7; 27%), anorexia (6; 23%). Most common ≥ grade 3 treatment-related AEs were acute kidney injury (3; 12%), hypertension (3; 12%), and anemia (2; 8%). PSA response was observed in 8 pts (31%). By PCWG2, 14 pts (54%) experienced stable disease, while 10 pts (38%) had progressive disease. Conclusions: The combination of enza and indomethacin was safe, clinically feasible, and had clinical activity in pts with abiraterone-pretreated mCRPC. Further correlative studies are needed to identify pts who may benefit from AKR1C3 inhibition. Clinical trial information: NCT02935205 .
Clinical efficacy and safety analysis of immune checkpoint inhibitors combined with concurrent chemoradiotherapy for stage IIIC1-IVA cervical cancer: A prospective cohort study.
Authors: Ma YiMing , Zhang Mingchuan , Wu Hao , Chen Huimin , Wang Dandan , Xu Yuanyuan , Cheng Shuxia 
Published: July 2024

e17505 Background: Stage IIIC1 with larger/more short lymph node diameters and IIIC2-IVA cervical cancer patients had a particularly poor prognosis. Clinical practices have found that stage IIIC1-IVA patients diagnosed with pelvic lymph node short diameter ≥ 1.5cm/number of positive lymph nodes ≥ 3, or paraaortic lymph node metastasis, had a higher recurrence rate and lower overall survival rate. The overall survival rate is approximately 29% -52%. Sequential systemic chemotherapy after concurrent chemoradiotherapy (CCRT) can not improve survival in such patients. However, the current research results on the combination of CCRT with immune checkpoint inhibitors for cervical cancer are not ideal, which may be due to the lack of stratified analysis. This study compared the efficacy and safety of CCRT and combined use of immune checkpoint inhibitors (non sequential) for stage IIIC1-IVA cervical cancer through the cohort analysis, and analyzed the prognostic factors. Methods: Patients diagnosed with stage IIIC1-IVA cervical cancer who underwent concurrent chemoradiotherapy from October 2019 to October 2022 were enrolled. Patients were divided into the study group (35 cases) receiving Sintilimab concurrently with chemoradiotherapy and the control group (35 cases) receiving standard treatment. The primary endpoints were the assessment of one-year progression-free survival (PFS), objective response rate (ORR), and associated influencing factors. Secondary endpoints included treatment-related adverse events (TRAEs). Results: The one-year PFS rates were 88.6% in the study group and 62.9% in the control group, showing a significant difference (χ2=6.293, P=0.012). The median PFS was not reached. The ORR for tumor response was 74.30% in the study group, significantly higher than the 51.43% in the control group (P=0.048). Univariate analysis identified tumor maximum diameter (p = 0.01) and concurrent use of ICIs (p = 0.039) as prognostic factors for PFS. Multivariate Cox analysis also revealed tumor maximum diameter (p = 0.0121) and concurrent use of ICIs (p=0.049) as independent predictors of PFS. The most common TRAEs in both groups included leukopenia, decreased appetite, nausea/vomiting, and fatigue, with no significant differences in incidence (P>0.050). Grade ≥3 TRAEs were most frequently leukopenia (47.5%) and thrombocytopenia (17.1%) in the study group and leukopenia (51.4%) in the control group. All adverse reactions were alleviated after symptomatic treatment, dose reduction, or discontinuation, and no TRAE-related deaths occurred. Conclusions: In patients with stage IIIC1-IVA cervical cancer undergoing definitive concurrent chemoradiotherapy, the addition of ICIs may improve patient survival with manageable safety.