bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship of preoperative frailty with short- and long-term surgical outcomes among octogenarians with hepatocellular carcinoma: A multicenter comprehensive analysis.
Authors: Yang Yi-Fan , Zhang Ping , Wu Bo , Wang Si-Yuan , Guo Hong-Wei , Zheng Qi-Xuan , Chen Ting-Hao , Li Jie , Wang Xian-Ming , Liang Ying-Jian , Wang Hong , Wu Xiao-Chang , Gu Wei-Min , Zhou Ya-Hao , Zeng Yong-Yi , Wang Ming-Da , Chen Zhong , Shen Feng , Lv Guo-Yue , Yang Tian 
Published: July 2024

e16269 Background: Hepatocellular carcinoma (HCC) management in very elderly individuals, particularly those considering hepatectomy, demands a balanced evaluation of surgical safety and survival outcomes. This multicenter study aims to elucidate the influence of preoperative frailty, as determined by the Clinical Frailty Scale (CFS), on both short-term and long-term outcomes in octogenarians undergoing hepatectomy for HCC. Methods: We conducted a retrospective analysis of a cohort of octogenarians (≥ 80 years) who underwent hepatectomy for HCC from 2010 to 2022 across 16 hepatobiliary centers. Patients were categorized into frail and non-frail groups based on their preoperative CFS scores, with a CFS score of ≥ 5 indicating frailty. We primarily focused on overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival (CSS). Secondary endpoints included perioperative outcomes such as postoperative morbidity and mortality. Results: The study encompassed 240 octogenarians, with 105 (43.8%) classified as frail. Frail patients exhibited significantly higher postoperative 30-day morbidity (61.0% vs. 43.0%, P = 0.006) and mortality at both 30-day (5.8% vs. 0.7%, P = 0.045) and 90-day (6.7% vs. 1.5%, P = 0.044) intervals compared to their non-frail counterparts. Furthermore, 5-year OS, RFS, and CSS were markedly lower in frail patients (25.1%, 15.6%, and 43.7% respectively) as opposed to non-frail patients (51.4%, 36.2%, and 66.7%; all P < 0.001). Both univariable and multivariable analyses identified preoperative frailty as an independent risk factor for postoperative 30-day morbidity (OR: 2.060, 95% CI: 1.215-3.494, P = 0.007), as well as for OS (HR: 2.384, 1.682-3.380, P < 0.001), RFS (HR: 2.190, 1.588-3.019, P < 0.001), and CSS (HR: 2.203, 1.397-3.472, P = 0.001). Conclusions: Preoperative frailty emerges as a significant independent predictor of both short-term and long-term outcomes in octogenarians undergoing hepatectomy for HCC. Integrating frailty assessment into preoperative evaluations could substantially enhance patient selection and optimize perioperative management strategies.
Impact of adjuvant chemotherapy on outcomes after curative-intent surgery for biliary tract cancer: A 10-year retrospective single-center study.
Authors: Levy Rachel , Zhen Simon , Zhang Chenxin , Moon Jee-Young , Bteich Fernand , Kuang Chaoyuan 
Published: July 2024

e16273 Background: Surgical resection remains the mainstay of treatment for biliary tract cancers (BTCs). Although adjuvant capecitabine has been shown to reduce recurrence, the best adjuvant chemotherapy remains unclear and numerous practice differences exist. Methods: This study is a retrospective review of patients with BTCs who received curative-intent resection at one institution (Montefiore Medical Center) between 01/2014 and 04/2023. The primary outcome was relapse risk. Kaplan-Meier curves and Cox regression were used to analyze relapse-free and overall survival rates. Results: 146 patients met entry criteria. Median age was 72.2 years (IQR 62.4-77.9 months) and median follow-up time was 20 months (IQR 1-111 months). 35.6% of patients had gallbladder cancer and 64.4% cholangiocarcinoma. 57 patients (39%) relapsed and 30 patients (20.5%) died. 105 patients (71.9%) received adjuvant chemotherapy (41% single agent, 42.9% a double-agent regimen, and 16.2% triple-agent therapy). Examining individual factors (univariate analysis) revealed several linked to higher relapse risk. Patients with advanced cancer stages (III-IV vs I-II) had 2.1 times higher risk. Higher T stages also showed increased risk: 5.6 times greater for T2 and 6.7 times greater for T3 compared to T1. Additionally, positive lymph nodes (N+), elevated post-surgical CA19-9, and presence of lymphovascular or perineural invasion were all significantly associated with 1.88-2.78 times higher relapse risk. Surprisingly, receipt of adjuvant chemotherapy was associated with a higher relapse risk (HR 2.42, 95% CI 1.18, 4.95, p-value 0.015). The association between receipt of adjuvant chemotherapy and relapse remained significant (HR 2.41, 95% CI 1.09-5.35, p = 0.03), after adjusting for age, sex, residual CA19-9, and receipt of adjuvant radiation therapy. Higher overall stage (III-IV vs I-II) was identified as a significant predictor of poorer overall survival (OS) with a hazard ratio of 21.70 (2.94-27.70, p = 0.009). Node-positive disease (HR = 2.25, 1.05-4.80, p = 0.036) and relapse (HR = 3.61, 1.58-8.28, p = 0.002) were also independently associated with worse OS. Conclusions: Adjuvant chemotherapy is commonly given after curative-intent surgery for BTCs at our center. Numerous factors are associated with an increased risk of relapse. Receipt of adjuvant chemotherapy was associated with a higher relapse risk even after adjustment for multiple covariates; the reason for this association remains unclear. More studies are needed to better understand the role and best form of adjuvant chemotherapy in the treatment of BTCs.
Prognostic indicators of recurrence after surgical resection in non-pancreatic gastrointestinal neuroendocrine tumors.
Authors: Schonman Ian , Zahurak Marianna , Marvania Nirali , Urman Arielle Rose , Laheru Daniel A. , He Jin , Greer Jonathan , De Jesus-Acosta Ana 
Published: July 2024

e16287 Background: The incidence of gastrointestinal neuroendocrine tumors (GI-NETs) has continued to increase over the last two decades. In patients with locoregional disease, surgical resection of the primary tumor without additional therapies is considered standard of care. The frequency and risk factors associated with recurrence and survival in patients with non-pancreatic GI-NETs are poorly defined. We aimed to evaluate clinical and pathological factors associated with recurrence and survival in patients with resected non-pancreatic GI-NETs. Methods: We conducted a retrospective review of patients who presented to the Johns Hopkins Hospital between 2000-2019 with locoregional small bowel, colon, appendiceal, and rectal neuroendocrine tumors who underwent surgical resection with curative intent. We collected clinical and pathological data including tumor primary site, tumor differentiation, grade using Ki-67 labeling index (grade 1, 2, or 3), margin involvement, perineural or vascular invasion, time of recurrence, patterns of recurrence, and death. Patients with metastatic disease at the time of diagnosis and insufficient follow up were excluded. Results: A total of 133 patients met inclusion criteria. Most patients had tumors originating from the small bowel (n = 87, 66%), followed by the appendix (n = 19, 15%), rectum (n = 18, 14%), and colon (n = 7, 5%). With a median follow-up of 35 months, 23 patients (17%) had tumor progression after curative-intent surgery, with the liver (n = 13, 57%) as the most common site. In the majority of patients, tumors were well-differentiated (n = 118, 97%) and grade 1 (n = 78, 75%). Intermediate/high grade tumors (grade 2/3) occurred in 26 (25%) of patients. Median progression-free survival was 226 months (18.8 years). Age (greater than 60) and intermediate/high grade tumors (grade 2 or 3) were associated with worse overall survival HR = 5.5 (95% CI: 1.5, 19.6), p = 0.009, and HR = 3.3 (95% CI: 1.1, 10.2), p = 0.034, respectively. Tumor grade (2 or 3) and positive nodes were associated with worse progression-free survival HR = 4.5 (95% CI: 2.0, 10.1), p = 4e-04, and HR = 3.1 (95% CI: 1.4, 6.8), p = 0.009, respectively. Conclusions: A significant number of patients (17%) with non-pancreatic GI-NETs had tumor progression after curative-intent surgery. Risk factors for recurrence include intermediate/high-grade tumors and positive lymph nodes. Further studies are needed to evaluate the role of adjuvant therapy in patients at higher risk of recurrence following surgical resection for non-pancreatic GI-NETs.
PBP1510, a novel monoclonal antibody targeting pancreatic adenocarcinoma upregulated factor (PAUF): Phase 1/2a monotherapy and combination with gemcitabine in patients with advanced/metastatic pancreatic cancer.
Authors: Feliu Jaime , Ghanem Ismael , King Daniel , Park Yun-Yong , Kim Jamie , Pradhan Sumita , Ho Jessica , Loh Wei Qi , Mandakhalikar Kedar Diwakar 
Published: July 2024

e16296 Background: PAUF, a protein overexpressed in pancreatic cancer but not in non-cancerous tissues, plays a key role in cancer progression and metastasis. PBP1510 is a novel first-in-class humanized IgG1 monoclonal antibody that binds to and neutralizes PAUF with high specificity and affinity. PAUF-I (NCT05141149) is a first-in-human, multicenter, open-label study in patients with advanced/metastatic pancreatic cancer. Early Phase 1 results are presented here. Methods: Key eligibility criteria for Phase 1 include: locally advanced/metastatic pancreatic cancer; at least 1 previous line of chemotherapy; ECOG 0-1; and measurable disease by RECIST v1.1. A 3+3 dose escalation design is planned for 5 dose levels of intravenous PBP1510 (doses of 1, 3, 6, 10, and 15 mg/kg), either alone (monotherapy cohorts) or in combination with gemcitabine at a dose of 1000 mg/m2 (combination cohorts), in 28-day cycles. Tumor assessments are performed every 8 weeks from the first dose of PBP1510. Dose is escalated following a safety review committee meeting, if all patients in a cohort complete the dose-limiting toxicity (DLT) observation period (28 days from first dose) without any DLTs. Primary endpoints are safety parameters including treatment emergent adverse events (TEAEs) and laboratory findings. Results: As of January 2024, 6 patients (4 males, 2 females), aged 54-71 years, were enrolled. All patients had stage IV ductal adenocarcinoma and had received at least 2 prior lines of chemotherapy. Five patients received 2 cycles of PBP1510 each at 1 mg/kg or 3 mg/kg based on their cohort. One patient received 1 cycle of PBP1510 at 3 mg/kg. Seventeen TEAEs were assessed to be related to study treatment. The most frequently reported treatment-related TEAE was asthenia (n = 7). Most treatment-related TEAEs were NCI-CTCAE Grade 1 in severity (n = 14). Five serious TEAEs not related to study treatment were reported in 2 patients. There was 1 death reported due to disease progression. No patient discontinued treatment due to TEAEs. No clinically significant abnormalities in ECG, LVEF, and clinical laboratory assessments were reported during the DLT observation period. All patients in the first 2 monotherapy cohorts completed the DLT observation period without any DLTs. Conclusions: PBP1510 was well tolerated by all patients at 1 mg/kg or 3 mg/kg in the first 2 monotherapy cohorts. The next monotherapy (PBP1510, 6 mg/kg) and combination (PBP1510, 1 mg/kg; gemcitabine 1000 mg/m2) cohorts are open for recruitment. Clinical trial information: NCT05141149 .
Mutational analysis of cfDNA to identify predictive biomarkers in previously untreated patients with metastatic pancreatic cancer receiving the GSK-3 inhibitor elraglusib (9-ING-41) in combination with gemcitabine/nab-paclitaxel in the 1801 phase 2 study.
Authors: Ugolkov Andrey , Weiskittel Taylor , Koukol Austin , Kellinger Caroline , Li Hu , Mazar Andrew Paul 
Published: July 2024

e16306 Background: Glycogen Synthase Kinase-3beta has been well-credentialed as a therapeutic target in patients with advanced cancer including pancreatic cancer. Elraglusib (9-ING-41), a novel best-in-class GSK-3 inhibitor, is being developed in combination with gemcitabine/nab-paclitaxel (GnP) as first-line therapy for patients with metastatic pancreatic cancer (mPDAC). Using liquid biopsy samples from an ongoing randomized phase 2 trial (1801 Part 3B; NCT03678883), we examined whether gene mutations in cfDNA correlated with clinical outcomes in mPDAC patients treated with GnP or elraglusib/GnP. Methods: Pre-dose plasma samples were obtained from 37 (GnP arm) and 89 (elraglusib/GnP arm) mPDAC patients previously untreated for advanced disease. Mutational analysis of cfDNA extracted from plasma samples was performed by Tempus (Chicago, IL) using the xF+ platform. The Tempus xF+ assay is an NGS cfDNA liquid biopsy tumor profiling assay for identifying genomic alterations in 523 genes. Tempus xF+ reports were used for analysis of gene mutations. Results: In 126 pancreatic cancer patients, frequently mutated genes ( > 10%) consisted of KRAS (93/126, 74%), TP53 (79/126, 63%), CDKN2A (26/126, 21%), DNMT3A (25/126, 20%), NOTCH1/2 (25/126, 20%), and MLL3 (23/126, 18%). Gain-of-function mutations in KRAS, and loss-of-function mutations of TP53, and CDKN2A genes were associated with worse overall survival (OS) in patients treated with elraglusib/GnP (P < 0.05) but not in GnP-treated patients. Multivariate analysis of frequently mutated genes showed that patients with double (KRAS+TP53) and triple (KRAS+TP53+CDKN2A) mutations had significantly worse OS only in the elraglusib/GnP arm. The presence of DNMT3A, NOTCH1/2 or MLL3 gene mutations did not correlate with any clinical outcomes. Conclusions: Our preliminary analysis of gene mutations in liquid biopsy samples obtained from patients in the ongoing 1801 Part 3B phase 2 trial identified potential predictive biomarkers of clinical outcome in mPDAC patients treated with combination of elraglusib/GnP. Clinical trial information: NCT03678883 .
Longitudinal changes in triceps skinfold thickness and serum albumin during chemotherapy in patients with pancreatic cancer: Gender-based prognostic insights—A prospective cohort study.
Authors: Park Joo Kyung 
Published: July 2024

e16308 Background: Cachexia, characterized by distinct fat loss and poor nutritional status, is common in patients with pancreatic cancer. This study investigated the association between triceps skinfold thickness(TSF), indicative of body fat, and serum albumin levels, reflecting nutritional status, with overall survival(OS) in patients with pancreatic cancer. Methods: A prospective cohort of 353 patients with pancreatic cancer from April 2018 to June 2021 who received chemotherapy was queried. TSF(mm) and serum albumin(g/dL) were measured at baseline and every three weeks during follow-up. The optimal cutoffs for their six-month changes(six-month value minus initial value) were determined. We performed a landmark analysis of OS six months after the diagnosis of pancreatic cancer and assessed the factors influencing OS. Gender-specific survival analysis was conducted, culminating in the construction of nomograms for risk stratification. Results: Two hundred ninety-two patients survived over six months, with a median follow-up of 40.9 months. Changes in TSF, albumin, and protein levels over six months and initial albumin levels were independently associated with OS. Cancer stage, response to chemotherapy, and six-month serum CA 19-9 levels were also independent factors for OS. Gender-stratified analysis revealed gender-specific prognostic factors: TSF changes over six months£ 0 were associated with reduced OS (hazard ratio [HR], 1.84; 95% confidence interval [CI], 1.14–2.95) in men; initial albumin levels£ 3.5g/dl (HR, 5.73; 95% CI, 2.48–13.21) and albumin changes over six months£ -0.7g/dl (HR, 3.03; 95% CI, 1.51–6.07) were associated with reduced OS in women. Patients were categorized into low-, medium-, and high-risk groups for each gender based on nomogram scores, and increased risk levels were associated with elevated mortality risk. Conclusions: This was the first prospective cohort study to demonstrate that changes in TSF and albumin levels were associated with OS in pancreatic cancer patients undergoing chemotherapy in a gender-dependent manner.
Enhancing appendiceal cancer care: Towards evidence-based practice and continuous education for healthcare providers.
Authors: Wu Sulin , Nimer Jenna , Gujarathi Rushabh , Bansal Varun Vivek , Liao Chih-Yi , Amin Manik A. , Chin Janet , Moller Mecker , Merkow Ryan P , Eng Oliver S. , Polite Blase N. , Turaga Kiran , Shergill Ardaman 
Published: July 2024

e16377 Background: Appendiceal cancers (AC) are a set of rare and histologically diverse malignancies with distinct biological features and treatment implications. Despite surgical advances, there are gaps in the standardization of systemic therapies for AC. Hence, there is a pressing need to understand the current practice patterns amongst oncologists to facilitate unifying management strategies. Methods: A cross-sectional survey was distributed electronically among GI oncology specialists between April – October 2023 to map current practices in AC care. The survey contained 18 questions structured in three sections— participant demographics, treatment experiences, and management preferences for hypothetical cases. The analysis focused on response frequencies informing the need to develop targeted educational and research initiatives. Results: Most of the respondents (N = 104; response rate 22%), primarily from academic (86%) and urban settings (77%), manage up to 10 AC patients annually. Despite over five years of practice experience for 80% of respondents, high confidence in treating AC was modest (38%). The majority (83%) cited lack of guidelines and standardized treatments as a concern. The NCCN guidelines were commonly referred to, but only 13% were satisfied with AC education. For intermediate and high-grade AC, 63% and 53%, respectively, of respondents reported using perioperative chemotherapy with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. 40% opted for systemic therapy for low-grade neoplasms. 5FU/Capecitabine and oxaliplatin were the most common regimens of choice, whereas irinotecan, anti-VEGF, and anti-EGFR agents were used less frequently. Surveillance primarily involved serum CEA (91%) and CT scans (99%), with PET, MRI, and ctDNA used by 20-30% of the respondents. Free-text comments noted deficient evidence and educational needs to guide clinical practice. Conclusions: Our study is the first to describe physician attitudes and practice patterns in the management of AC. The survey highlights that even experienced providers feel underconfident when treating AC patients and supports the need for better evidence and data for systemic therapies. About 40% of the respondents noted offering chemotherapy to low grade neoplasms – a disease that is not thought to respond to systemic therapy, highlighting the need for education and clinical trials to guide evidence-based decision-making in this disease. In addition, multidisciplinary, multi-institutional efforts to unify treatment approaches and enhance patient outcomes are needed.
Improving outcomes in high-grade goblet cell adenocarcinomas: The interplay of complete cytoreduction, HIPEC and fibrosis.
Authors: Koukoutsidi Panagiota Chrysovalanto , Nugent Francis W. , Schnelldorfer Thomas , Sabo Jennifer L. , Goodman Martin D. 
Published: July 2024

e16379 Background: High-grade goblet cell adenocarcinomas (GCA), including signet-ring cell type (SRC) and poorly differentiated, behave more aggressively compared to typical GCA and are associated with poor prognosis. Due to GCA’s rarity, the treatment aligns with colon cancer guidelines, including surgery, chemotherapy and/or cytoreductive surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for peritoneal carcinomatosis (PC). In our case series, we assessed the outcome of patients with high grade GCA tumors and PC, who underwent either CRS with HIPEC or tumor debulking. Methods: A prospectively maintained database of patients treated at the Division of Surgical Oncology for Peritoneal Carcinomatosis (PC) from 2007 to 2022 was reviewed retrospectively. Patient selection was based on the primary tumor’s original pathology report and scheduling to undergo CRS/HIPEC for PC. We calculated median overall survival from the time of diagnosed peritoneal carcinomatosis, with focus on the attainment of complete cytoreduction (CC) and HIPEC administration. Results: 385 records were screened and 21 cases of GCA were identified. Thirteen (13) patients had a diagnosis of high-grade GCA with PC. Complete cytoreduction (CC0/CC1) with HIPEC was achieved in 7/13 patients, and 6/13 patients underwent tumor debulking. The median overall survival after diagnosing peritoneal carcinomatosis was 53 months for the patients who underwent CC/HIPEC and 20 months for the patients who received debulking. Of note, in the debulking group, 5/6 patients had a poorly differentiated GCA and exhibited intraoperatively tumor characteristics of infiltration, thickening and fibrosis, confirmed by the pathology report, which rendered CC unsuccessful. In contrast, within the CC/HIPEC group, pathology reported localized fibrosis as a chemotherapy response in only 2/7 patients, which did not impede the achievement of CC. Preoperative 5-FU based chemotherapy was administered to 4/7 patients in the CC/HIPEC group and to 5/6 patients in the debulking group. Conclusions: Our results demonstrate that CC with HIPEC may improve overall survival in patients with high grade GCA with PC. Notably, poorly differentiated GCA and the presence of fibrotic tissue, stemming from the tumor and/or preoperative chemotherapy, influences CC success. Considering the potential impact of fibrosis on surgical outcomes, pathological assessment of fibrosis preoperatively and/or use of fibrosis-specific biomarkers could guide cytoreduction strategies and treatment choices in patients diagnosed with high-grade GCA.