bluuebunny/crossref_metadata_2025 huggingface dataset:
Adjuvant therapy with donafenib plus anti–PD-1 antibody for patients (pts) with hepatocellular carcinoma (HCC) at high risk of recurrence after resection (PATH study).
Authors: Chen Yiwen , Shen Yan , Zhang Min , Wu Jian , Gao Shunliang , Que Risheng , Yu Jun , Tang Xiaofeng , Bai Xueli , Liang Tingbo
Published: July 2024

e16228

Background: There is no universally accepted standard treatment option or strategy for post-surgery adjuvant therapy for HCC. Among BCLC A/B patients with MVI, adjuvant TACE provided a 1-year recurrence-free survival rate (RFSR) of around 60-70%. We conducted a pilot study to explore the utility of donafenib combined with anti-PD-1 antibody as adjuvant therapy for pts with high risks of recurrence. Methods: It was planned to enroll 30 HCC pts who had undergone radical surgery and with at least one of the following risk factors: a) Presence of microvascular invasion (MVI); b) Presence of satellite nodule(s); c) > 3 tumor nodules; d) Portal vein tumor thrombus. Pts with invasion of main portal venous were excluded. Donafenib plus anti-PD-1 antibody was initiated at 4 to 8 weeks after resection and continued for up to six months. No other adjuvant therapies were allowed before enrollment and during the study, except for anti-virus treatment. The primary endpoint was the cumulative 1-year RFSR. The secondary endpoints included recurrence-free survival (RFS), overall survival, and safety. Results: From June 2020 to November 2023, a total of 30 pts were recruited. 27 pts were included in efficacy analysis. The mean and median follow-up time was 347.9 days and 179.5 days. The mean and median time from surgery to enrollment was 42.5 days and 42.0 days. MVI was the most common risk factor (Table). Majority of the pts had only one risk factor. Relapse occurred in two pts (7.4%) and RFS was very immature. The RFSR at one year was 89.7% (90% CI, 70.6%-96.7%) in all the evaluable pts, and slightly higher in pts with M1 or only one risk factor (92.9% [90% CI, 68.1%-98.6%] and 93.3% [90% CI, 69.9%-98.7%], respectively). No deaths were observed. In 30 pts who had received at least one dose, the incidence of grade 3 treatment-related adverse events (TRAEs) was 40.0% (12/30). No grade 4 or 5 TRAEs were reported. The grade 3 TRAEs occurred in ≥2 pts were palmar-plantar erythrodysesthesia syndrome (13.3%), rash (13.3%), alanine aminotransferase increased (10.0%), and aspartate aminotransferase increased (6.7%). Conclusions: These results showed that a regimen of 6 months of adjuvant therapy with donafenib plus anti-PD-1 antibody may be efficient to reduce recurrence for BCLC A/B pts at high risk of recurrence, particularly those with ≤2 risk factors. No new safety issues were noticed. Clinical trial information: NCT04418401 . [Table: see text]
Temporal dynamics and prognostic significance of cancer free status in patients with intermediate stage hepatocellular carcinoma: A multicenter cohort study.
Authors: Shen Lujun , Li Chen , Fan Wei-Jun
Published: July 2024

e16236

Background: A proportion of patients with intermediate stage hepatocellular carcinoma (HCC) can achieve cancer free status (CFS) during treatment, the prognostic value of CFS across the period of dynamic surveillance and treatment remained unknown. Methods: This longitudinal cohort study examined data from the electronic medical record system of four hospitals in China between January 1, 2007 to May 31, 2019. The data from Sun Yat-sen University Cancer Center served as the derivation cohort and other centers as testing cohort. The time-series data were converted into data of time slices, with an interval of three months. Image CFS is defined as patients with no evidence of disease based on imaging exams after treatment and Image-Bio CFS is defined as achievement of Image CFS, together with normal AFP level. Based on the dynamic changes of disease during treatment, patients at specific time slice were classified into either “Arrive”, “Maintain”, or “Not reached” CFS subgroups. The correlations between CFS subgroups and overall survival (OS) were determined by Cox regression. Results: A total of 945 (42.2%) and 741 (33.1%) patients in derivation cohort reached Image CFS and Image-Bio CFS during treatment, respectively. The corresponding rates for Image CFS and Image-Bio CFS in testing cohort were 155 (37.4%) and 130 (31.4%), respectively. Maintaining Image CFS or Image-Bio CFS, rather than just arrive Image CFS or Image-Bio CFS, had stable predictive value for improved OS across different time slices. The merged Hazard ratio of Maintain Image-Bio CFS was 0.23 (95%CI, 0.20-0.25, P < 0.001). The patients achieved Image-Bio CFS could be further classified into three subgroups with differential prognosis based on duration of CFS (≤ 4.5months; 4.5-18.0 months; > 18.0 months). Maintaining Image-Bio CFS for more than 18.0 months predicted long term survival (5-year OS: 91.2% in derivation cohort, 94.7% in testing cohort). Conclusions: Maintaining CFS, rather than just arrive CFS, is a key marker of favorable survival during dynamic management of intermediate stage HCC. A duration of Image-Biochemical CFS for more than eighteen months predicts long-term survival.
Machine learning identification of hypoxia-related genes and prognostic risk-scoring model for effective survival stratification in hepatocellular carcinoma.
Authors: Mohan Huang , Chan Wing Chi
Published: July 2024

e16261

Background: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality globally, where treatment and prognostic assessment have important implications in clinical practice. Hypoxia, as a common feature within solid tumors, can directly change the tumor microenvironment, which affects the efficacy of cancer treatment and prognosis. In this study, we constructed and validated a hypoxia-based prognostic model using bioinformatics and machine learning. Methods: Two public datasets, GSE14520 and GSE41666, were collected from the Gene Expression Omnibus: (1) HCC tumor tissues compared to adjacent normal tissues (N = 214) and (2) HepG2 cells under normoxic and hypoxic conditions (N = 6). Differential expression analysis was performed to identify HCC characteristic genes and hypoxia-related genes, including their common genes (HCC-Hypoxia Overlap genes, HHOs). Using RNA-seq data of HCC patients (N = 367) from the TCGA Liver Cancer (LIHC) database, univariate Cox regression models were identified, and the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm selected hypoxia-characteristic genes for the multivariate survival model. A hypoxia-related risk score was calculated based on the model of these characteristic genes and dichotomized cases into high-risk (HR) and low-risk (LR) groups. The model was validated using liver cancer cases (N = 232) from the International Cancer Genome Consortium database (ICGC-LIRI-JP). Results: Through differential expression analysis of the two datasets, we identified 52 HHOs. Univariate Cox analysis of these HHOs indicated that 21 genes were significantly associated with HCC patient survival. Through LASSO regression analysis, a total of 9 characteristic genes, including CENPA, KIF20A, DLGAP5, HMMR, UPB1, AFM, CABYR, PHLDA2, and N4BP2L1 were ultimately retained in the survival model. Based on these 9 genes, TCGA-LIHC samples were classified into HR and LR groups, and Kaplan-Meier (KM) analysis revealed significant differences in survival outcomes (p < 0.032). Risk scoring of the ICGC-LIRI-JP validation set classified samples into HR and LR. KM analysis showed that the survival times of patients in the HR group were significantly shorter than those in the LR group (p < 0.0001). Receiver Operating Characteristic Analysis analysis of the survival model showed area under the curve values of 0.815, 0.774, and 0.771 at 1, 2, and 3 years, respectively, demonstrating high performance in risk stratification. Conclusions: This study established a prognostic risk-scoring model based on 9 characteristic genes associated with hypoxia. This model can effectively stratify risks among HCC patients and demonstrate excellent performance in predicting survival. These findings may offer new biomarkers and therapeutic targets for the personalized treatment of HCC.
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.
Portal vein thrombosis in gastrointestinal cancers: Insights into prevalence and prognosis—A nationwide inpatient analysis 2018-2020.
Authors: Ginjupalli Manasa , Hotwani Priya , Jayakumar Jayalekshmi , Gaddam Mrunanjali , Iqbal Rabia , Vachhani Bhavyakumar , Sanghvi Ankushi , Sharma Anuj , Nanavaty Dhairya , Kumar Vikash , Clement Jincy
Published: July 2024

e16382

Background: The relation between cancer and thrombotic events has been well established over the past decade. Cancer is a prothrombotic state and thrombosis is the second most common cause of death in cancer. While portal vein thrombosis (PVT) has been extensively studied in individuals with Hepatocellular Carcinoma (HCC), its significance in other Gastrointestinal (GI) cancers is often overlooked. This study aims to investigate the prevalence and prognostic impact of PVT across various GI cancers. Methods: A retrospective analysis was performed on the National Inpatient Sample database (2018-2020) and the ICD-10 codes to identify the patients > 18 years old with primary diagnosis of GI cancers (pancreatic, HCC, gastric, small intestinal[SI], colorectal). Prevalence of PVT in individual GI cancers and effect of PVT on mortality, length of stay and Hospital cost utilization was studied. Multivariable regression analyses were performed adjusting for demographics, hospital-level characteristics, and relevant comorbidities. These included Age, Sex, Race, obesity, Smoking, Hypertension, Diabetes, CKD, liver disease, CHF, CAD, Hypothyroidism. Results: Our study analyzed data from 2,313,888 individuals with GI cancers, Including HCC, Gastric cancer, SI cancer, colorectal and pancreatic cancer, The incidence of PVT varied across cancer types, with 12.9% in pancreatic cancer, 0.74% in HCC, 0.99% in gastric cancer, 0.47% in colorectal cancer, and 3.6% in pancreatic cancer. Multivariate regression analysis, adjusting for confounders, revealed a significant association between PVT and increased mortality in various GI cancers. Specifically, the odds ratio (OR) for mortality in pancreatic cancer was 1.31 (p < 0.001), in HCC was 1.39 (p < 0.001), in gastric cancer was 1.88 (p < 0.001), and in colorectal cancer was 2.10 (p < 0.001). However, the incidence of mortality in SI cancer did not yield a significant result OR 1.42 [p- value 0.369] [Table 1]. Additionally, Our findings revealed an increase in length of stay and total healthcare resource utilization across all GI cancers for individuals with PVT compared to without PVT. Conclusions: There is a statistically significant effect of symptomatic and asymptomatic PVT on mortality in various other GI cancers in addition to HCC, which has been established and studied widely. Further prospective studies are needed to study the effect of diagnosing PVT earlier in the disease to predict mortality and other major complications in GI cancers.[Table: see text]
Real world data of leuprorelin castration efficacy in patients with prostate cancer: A comprehensive assessment of 1,744 tests.
Authors: Lages Dr. Paulo Sergio , Zulli Guilherme Augusto , Bergerot Paulo Gustavo , Barbosa Michelle , Carcano Flavio Mavignier , Lages Luciana , Azevedo Anita Chavez , Vargas Pivato de Almeida Daniel
Published: July 2024

e17000

Background: Androgen deprivation therapy (ADT) has been standing the cornerstone of systemic prostate cancer (PCa) treatment, since Huggins’ findings.Gonadotropin-releasing hormone (GnRH) agonists or antagonists has been used broadly as ADT. However, the majority of studies has focused on Gosserelin, leading to a lack of dedicated investigations into the efficacy of leuprorelin, despite its large use on practice. In this real-world study, we thoroughly analyzed data of testosterone tests in order to comprehensively assess the leuprorelin castration efficacy on the PCa management. Methods: We gathered data from patients diagnosed with PCa who were undergoing treatment with leuprorelin alone or in combination with a novel hormonal agent (NHA) in a single cancer center. The tests spanned a nine-year period from 2014 to 2023 and we assessed the testosterone levels in baseline and after leuprorelin administration, as well as their distribution according to clinicopathologic variables. Results: A total of 1,754 test reports were retrieved from 240 individual pts. The median baseline testosterone level was 317 ng/mL (range: 37-1,136) prior to leuprorelin initiation and the distribution across Gleason grades was: 20 pts had grade 1, 30 pts had grade 2, 61 pts had grade 3, 51 pts had grade 4, and 40 pts had grade 5. Testosterone levels < 50 ng/mL were achieved in 1,730 tests (98.7%) and testosterone levels < 20 ng/mL were found in 1,485 tests (84.7%). A total of 80 pts received combined treatment with leuprorelin + NHA, of which the majority received abiraterone/prednisone (n=52; 65%) or apalutamide (n=11; 13.8%). Following ADT discontinuation, 91 pts presented testosterone levels ≥ 50 ng/mL after a median interval of 258.5 days (range:82-710). Conclusions: In this comprehensive real world database analysis, leuprorelin is able to achieve suitable testosterone suppression levels in nearly the whole study population, such as are seen in others GnRH agonists pivotal trials. Deeper and maintained testosterone suppression levels is predictive of longer time to castration-resistant PCa and real life use of leuprorelin seems to meet this need.
The demographics of Sertoli cell carcinoma: A National Cancer Database analysis.
Authors: Tade Yanick , Silberstein Peter T. , Heise Craig , Hsia Beau
Published: July 2024

e17012

Background: Sertoli cell tumors (SCTs) are an extremely rare and lethal diagnosis responsible for roughly 1% of all testicular and ovarian carcinomas. No uniform treatment regimen with sufficient results has been established. Current combination of retroperitoneal lymph node dissection, chemotherapy, and radiation therapy provides the best known outcome. Analyzing trends in diagnosis may provide valuable information about its epidemiology. The National Cancer Database (NCDB) was analyzed to establish the demographic factors in diagnosed patients. Methods: A retrospective cohort study from 2004 to 2020 was conducted using the NCDB. 159 patients were found with a histologically confirmed diagnosis of SCTs (ICD-8640-3). Race, gender, Hispanic origin, type of treatment facility, insurance coverage, and distance from patient residence to treatment facility were analyzed via descriptive statistics, and trends in incidence were interpreted using regression analysis. Results: The number of patients diagnosed with SCTs has remained relatively consistent since 2004 (R^2 = 0.07), with approximately 9 diagnoses per year. Of the 159 patients found, the average age of diagnosis was 44.6 years (SD = 19.1, range = 2 – 89 years). A majority of patients were male (67%), while the remaining third were female (33%). Most of the patients were White (73%). Patient Hispanic status could not be reliably determined due to limited data. More patients were in the top income quartile (31%) than the second (24%), third (18%), or fourth (14%) quartiles, with 13% having unknown income status. Most patients were privately insured (59%), followed by coverage under Medicare/Medicaid (28%). More patients lived in metropolitan counties with a population of 250,000 or more (76%) compared to less-populated urban or rural regions (24%). The majority received treatment at comprehensive community cancer programs or academic/research programs (43%). Patients traveled an average of 30.2 miles (SD = 64.0, range = 0.5 – 474.9) to reach the treatment facility. Conclusions: SCTs remains a rare diagnosis. This study pursues a significant gap in existing knowledge on patient characteristics that may present with SCTs. Most patients were White, privately insured, in the top income quartile, and lived in metropolitan areas. This novel study may contribute data towards understanding the relationship between patient socioeconomic status and access to diagnosis. Further research is required to uncover the role of socioeconomic status in SCTs.
Real-world clinical outcomes and economic burden of early discontinuation of taxane therapy among patients with metastatic castration-resistant prostate cancer.
Authors: Patel Jeetvan , Nguyen Jennifer , Bollu Vamsi , Kang Barinder , Sawhney Amrita , Byrne Clare , Tang Jackson , Gorritz Magdaliz , Chen Chi-Chang , Shore Neal D.
Published: July 2024

e17043

Background: Despite comprising an important part of the treatment paradigm for metastatic castration-resistant prostate cancer (mCRPC) for over a decade, real-world use of taxanes is hindered by adverse events (AEs). AEs may lead to early treatment discontinuation, which may adversely affect outcomes. The two goals of this study were to determine the proportion of mCRPC patients who discontinue taxanes early (defining the early discontinuation threshold relative to efficacy results associated with androgen receptor pathway inhibitors [ARPIs]) and to evaluate the impact of early discontinuation on clinical outcomes, AEs, and healthcare costs. Methods: This was a retrospective, observational study of adult men with mCRPC treated with an ARPI as their first-line (1L) therapy and who initiated second-line (2L) therapy with another ARPI or a taxane. The Flatiron Health electronic health record database (07/01/2012–06/30/2020) was used to estimate Kaplan-Meier overall survival (OS) curves for the taxane cohort by the number of cycles received; these were compared with patients who received ARPI at 2L. Cox regression modeling and median PFS and OS values were used to identify the number of taxane cycles needed to achieve comparable OS to ARPI. The number of taxane cycles with similar OS outcomes to ARPI was then considered the threshold for early discontinuation. In addition, the IQVIA PharMetrics Plus claims database (01/01/2013–08/31/2021) was used to estimate taxane-related AEs (based on product information) and associated healthcare costs among patients who did and did not discontinue taxanes early. Results: From Flatiron, 473 2L ARPI patients and 214 2L taxane patients were included. Similar clinical characteristics – e.g., prostate-specific antigen level, ECOG performance status, and Gleason score – were observed between the two cohorts. Overall, 2L ARPI was associated with longer median OS (15.4 vs. 13.6 months) than 2L taxane. The number of taxane cycles needed to reach comparable OS to ARPI was determined to be 8. Patients receiving >8 cycles (n=48; 22%) compared to those receiving ≤8 cycles (n=166; 78%) had longer median OS (18.4 vs. 11.9 months, respectively) and PFS (9.0 vs. 4.3 months, respectively). From PharMetrics, 158 2L taxane patients were included. Patients receiving >8 cycles (n=20; 13%) were more likely to experience an AE (95% vs. 88%) than those receiving ≤8 cycles (n=138; 87%) but had lower mean AE-related total healthcare costs per patient per month ($3,429 vs. $6,334). Conclusions: These results suggest that mCRPC patients need to receive >8 cycles of taxane at 2L to receive more clinical benefit than 2L ARPI. However, the vast majority of patients in the study discontinued taxane early, resulting in shorter survival outcomes compared to ARPI.
Charlson’s comorbidity and remission outcomes in women diagnosed with epithelial ovarian cancer.
Authors: Cannavale Kimberly L. , Mukherjee Amrita , Xu Lanfang , Gilfillan Alec , Szamreta Elizabeth A. , Monberg Matthew , Hodeib Melissa , Chao Chun
Published: July 2024

e17562

Background: Several prior studies have examined the role of comorbidity on overall survival in ovarian cancer (OC) patients and reported an association between comorbidity and inferior overall survival. However, it is unclear if the inferior survival was solely due to the excess mortality from the comorbidities, or that the comorbidities can impact OC treatment outcomes. Our objective was to determine whether pre-existing Charlson comorbidity index (CCI) was associated with lower likelihood of achieving complete remission. Methods: This retrospective cohort study included patients diagnosed with OC of epithelial subtype between 01/01/2017-06/30/2021 at a large integrated healthcare delivery system in the United States. OC patients were identified from the healthcare system’s cancer registry or via chart review of those with the ICD-10 diagnosis code. Patient’s CCI was determined based on data from the 12-month window prior to OC diagnosis. Patients’ remission outcomes, including complete remission and clinical remission (complete + partial remission) were ascertained via chart review, considering physician’s assessment, CA125 value and imaging evidence. Data on potential confounders (pandemic period, age, race/ethnicity, FIGO stage, prior length of membership, and time to treatment) were obtained from the healthcare system’s electronic medical records. Bivariate and multivariable modified Poisson regressions adjusting for potential confounders were used to evaluate the associations between CCI and achieving complete remission or clinical remission by end of therapy. Results: A total of 799 patients diagnosed with OC were included in our study. Overall, the cohort was racially/ethnically diverse with 46.2% White, 33.8% Hispanic, 12.4% Asian, and 7.6% Black patients. In the crude analysis, those with CCI score=1 and CCI≥2 had lower likelihood of achieving complete remission, compared with those with CCI=0 (no Charlson comorbidity) [RR= 0.84 (0.76-0.93) and RR=0.72 (0.64-0.81), respectively]. In the multivariable analysis, those with CCI=1 and CCI≥2 continued to have lower likelihood of achieving complete remission, compared with those with CCI= 0 [RR= 0.84 (0.77-0.92) and RR=0.81 (0.72-0.91), respectively]. Similar findings were observed for clinical remission, although the associations were attenuated: RR= 0.95 (0.89-1.01) for CCI=1 and RR=0.92 (0.86-1.00) for CCI≥2 vs. CCI=0. Conclusions: Having Charlson comorbidity was associated with lower likelihood of achieving complete remission in OC patients. This finding suggest that pre-existing comorbidities may contribute to inferior survival via, at least in part, adversely affecting the likelihood of achieving complete remission. The potential mechanisms underlying this association should be further studied to inform patient management.
Development and validation of an efficacy assessment platform utilizing patient-derived xenograft (PDX) models in ovarian cancer research.
Authors: Kim Min Kyu , Shin Hayeon , Kim Jae Hoon , Jun Anna , Kim Jue Young , Ryu Ji-Won , Chung Dawn
Published: July 2024

e17564

Background: Ovarian cancer predominantly undergoes treatment through surgical and chemotherapeutic interventions. However, with an increasing rate of recurrence, there's a need for systemic chemotherapy. A paradigm shift towards personalized treatment is crucial with concerns escalating about chemotherapy resistance post PARP inhibitor treatment. This paper emphasizes the significance of preclinical drug evaluation platforms using Patient-Derived Xenograft (PDX) models, which resonate with the genuine characteristics of ovarian cancer tissues. Methods: The 112 epithelial ovarian patients' tumors sectioned to approximately 3 mm2 were subcutaneously transplanted into at least two female 5-week-old BALB/c nude mice. The xenograft tumors engrafted into mice from patient-derived tumors were defined as P1. After that, xenograft tumors serially engrafted into the following mice were termed P2 to P3. We collected and banked small pieces of tumor tissue from each passage of PDX tissue for performing Whole Exome Sequencing (WES) sequencing and RNA Sequencing. Results: We established 54 epithelial ovarian cancer PDX models that are stably growing. They show a ratio of 70.37% Serous, 11.11% clear cell, and 3.7% endometriod. The stage is 14.81% I/II, 61.11% III/IV, and 24.07% Recurrent. BRCA status consists of 59.26% wild type, 9.26% BRCA 1 mutation, 5.56% BRCA 2 mutation, and 11.11% BRAC VUS. We have obtained a variety of ovarian cancer PDX models and confirmed retained the histological characteristics of patients by H&E staining. We validated the similarity of genomic information in patients and PDX models via WES and RNA sequencing. Conclusions: We have a stable and growing PDX model that accurately reflects the actual tissue characteristics of ovarian cancer. In the future, we plan to characterize drug response further and build new models resistant to existing anti-cancer drugs. Based on these, we will validate the efficacy of new drugs and suggest strategies to overcome cancer resistance.