tbuckley/cabot-search huggingface dataset:
Impact of bowel ischemia on mortality in gastrointestinal malignancies: A nationwide analysis.
Authors: Natchaya Polpichai, Sakditad Saowapa, Phuuwadith Wattanachayakul, Aunchalee Jaroenlapnopparat, Monzer Abdalla, Chawin Lopimpisuth, Ekaphop Sirachainan
Journal: Journal of Clinical Oncology (2024)

e16370 Background: Bowel ischemia, characterized by reduced blood supply to the gastrointestinal (GI) tract, critically influences the pathogenesis and outcomes of GI malignancies through complex interactions involving vascular compromise, tumor biology, and systemic consequences. Despite this, the link between bowel ischemia and increased mortality in GI cancers remains unknown. This study aims to evaluate the impact of bowel ischemia on in-hospital mortality in GI cancer patients in the United States. Methods: This retrospective analysis utilized the 2016-2020 National Inpatient Survey (NIS) database. Adults aged 18 and above with esophageal, gastric, colon, cholangiocarcinoma, hepatocellular carcinoma, and pancreatic cancers were identified using the International Classification of Disease-10 (ICD-10) code. The cohort was stratified into patients with and without bowel ischemia. Hospital mortality was analyzed using STATA 18, adjusting for age, gender, race, insurance, Charlson’s index, baseline hospital characteristics, and comorbidities. Multivariate logistic regression analysis was performed, with all P values ≤ 0.05 considered statistically significant. Results: Among 2,133,465 adults with GI malignancies, 3,240 were hospitalized with bowel ischemia. Patients with bowel ischemia were older (mean age 68.10 vs. 67.07 years, P = 0.033), predominantly from the Southern region (33.49%, P = 0.019), and urban and teaching hospitals (76.83%; P = 0.006). Bowel ischemia was most associated with Pancreatic cancer (37.35%), Colon cancer (35.49%), and Hepatocellular carcinoma (11.57%). Within the cohort of patients with bowel ischemia, gastric cancer patients had the highest mortality rates of 45.83%. After adjusting for potential confounders, patients with gastric, esophageal, colon, and pancreatic cancers had significantly higher odds of in-hospital mortality of 11.90, 6.45, 4.14, 4.08, and 2.71, respectively. Conclusions: This study reveals an association between outcomes in hospitalized GI cancer patients and bowel ischemia, leading to increased mortality despite adjusting for potential confounders. Bowel ischemia significantly heightens the mortality risk in GI cancers through impaired nutrient and oxygen delivery, enhanced tumor aggressiveness, systemic inflammation, immune suppression, and compromised treatment efficacy. Understanding the intricate interplay between vascular compromise and cancer biology is crucial to improving patient care and outcomes in the face of these challenging malignancies.
Prognostic indicators of recurrence after surgical resection in non-pancreatic gastrointestinal neuroendocrine tumors.
Authors: Ian Schonman, Marianna Zahurak, Nirali Marvania, Arielle Rose Urman, Daniel A. Laheru, Jin He, Jonathan Greer, Ana De Jesus-Acosta
Journal: Journal of Clinical Oncology (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.
An analysis of the evidence underpinning the surgical treatment of hepatocellular carcinoma.
Authors: Imad Radi, Samantha Zhan-Moodie, Luke Scanlan, Viktoriya Sapkalova, Nerella Resheek, Mehul Mehra, Steven Colquhoun, Danny Yakoub
Journal: Journal of Clinical Oncology (2024)

e16278 Background: The American Association for the Study of Liver Diseases (AASLD) and National Comprehensive Cancer Network (NCCN) guidelines on Hepatocellular Carcinoma (HCC) surgery are based on evidence from many different systematic reviews (SRs) and meta-analyses (MAs). Quality of these studies needs to be standardized. Methods: SRs and MAs cited in AASLD and NCCN HCC (2023) surgery guidelines were collated by two independent reviewers. An independent third reviewer acted as tie-breaker when necessary. The standardized assessment tools, the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and Assessing the Methodological Quality of Systematic Reviews (AMSTAR) were used to evaluate the quality of these studies. Quality of studies was determined based on adherence to items of the checklist. The PRISMA and AMSTAR checklists consist of 41 and 16 items, respectively. Results: Overall, 13 studies were identified, 9 from AASLD guidelines and 4 from the NCCN. Studies were published between 2007 and 2023, with 38% being published in the last 5 years. Studies had an average of 23,829 patients. Many of the studies (71%) reported use of the PRISMA checklist, but no studies cited the AMSTAR checklist. Studies had an average adherence of 68% to the PRISMA checklist, with a median of 76% (range 17-88%). 23% of studies adhered to less than half of the PRISMA checklist. Looking at the AMSTAR checklist, studies had an average adherence of 51%, with a median of 56% (range 4-72%). 31% of studies adhered to less than half the AMSTAR checklist. Adherence was lowest in items involving availability and accessibility of protocols, assessing risk of bias, and transparency of protocols. Additionally, no papers reported funding sources of their reviewed articles. Conclusions: There is significant room for improvement in MAs and SRs about HCC surgical management. Many quoted studies needed more rigorous methodology and quality control for conducting and reporting. It is important to fully investigate and communicate the biases present in MAs and SRs to readers. PRISMA and AMSTAR checklists can be used when reviewing and selecting evidence for future guideline development to offer the most complete and transparent understanding of data presented.
Clinical and molecular mechanisms for predicting the efficacy of immunotherapy for hepatocellular carcinoma based on gut microbiome.
Authors: Wenwen Zhu, Ningning Zhang, Yuexi Yu, Yiming Huo, Wei Lu
Journal: Journal of Clinical Oncology (2024)

e16222 Background: Hepatocellular carcinoma (HCC) is an aggressive malignant tumor, ranking as the fifth most common cancer and the third leading cause of cancer-related deaths globally, posing a significant global health issue. Increasing evidence suggests that the gut microbiome and their metabolites play a crucial role in the development and therapeutic processes of cancer. Immune checkpoint inhibitors (ICIs) have recently become a treatment option for unresectable advanced HCC. To further guide the selection of immunotherapy for clinical HCC patients, it is necessary to further elucidate the prediction of immunotherapy efficacy for HCC based on the microbiome. Methods: The study enrolled 26 unresectable advanced HCC patients and collected baseline clinical laboratory data. We administered ICIs therapy to HCC patients every three weeks. After 6 months of treatment, patients were divided the responsive group (R group) and the non-responsive group (NR group) based on imaging evaluation according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Prior to the application of anti-tumor treatment, fecal samples were collected from the patients for 16S rRNA microbiome sequencing analysis. Immunofluorescence was used to detect the expression of PD-L1 in tumor tissue, and immunohistochemistry was used to assess changes in lymphocyte subsets CD3+T cells, CD4+T cells, CD8+T cells and Treg cells, as well as the expression of TNF-α, γ-IFN, and GZMB. Additionally, the peripheral blood lymphocyte subsets CD3+T cells, CD4+T cells and CD8+T cells were analyzed by flow cytometry. Results: In our study, R group showed higher taxa richness and more gene counts than those of NR group. Comparing with NR group, the relative abundance of Firmicutes were significantly increased, whereas Proteobacteria and Bacteroidota were significantly decreased in R group at phylum level (all P &lt; 0.05). Our study showed that R group had high level of lymphocyte subsets CD3+T cells and CD8+T cells and low level of CD4+T cells and Treg cells compared to NR group (all P &lt; 0.05). And the expressions of PD-L1, TNF-α,γ-IFN and GZMB were upregulated in R group(all P &lt; 0.05). Conclusions: These findings suggested that the characteristics of gut-microbial diversity and composition at the early treatment period of ICIs therapy in HCC may have distinct implications on drug efficacy and disease prognosis. ICIs therapy reshaped HCC tumor microenvironment in parallel with regulating the gut microbiome and lymphocyte subsets immunity.
WDR4 as a potential indicator of clinical prognosis and immunotherapy in hepatocellular carcinoma.
Authors: Chi Lin, Juan Wang, Long Ouyang, Huaxin Duan, Shasha Fan
Journal: Journal of Clinical Oncology (2024)

e16275 Background: Immunotherapy has garnered increasing attention in hepatocellular carcinoma (HCC) treatment. However, there remains a pressing need for effective immunological predictive biomarkers. In our previous study, utilizing data extracted from The Cancer Genome Atlas (TCGA) database, we identified a positive correlation between WDR4 expression levels in hepatocellular carcinoma and various clinical parameters, encompassing Stage, T-stage, pathological grade, AFP level, and vascular invasion. Additionally, higher WDR4 expression was linked to poorer prognosis. Leveraging The TIMER and GEPIA databases, we further elucidated a significant association between WDR4 expression levels and the extent of immune cell infiltration, particularly macrophages, B lymphocytes, and myeloid suppressor cells, in hepatocellular carcinoma. These findings propose the potential utility of WDR4 as a biomarker for immune infiltration in hepatocellular carcinoma. As noted in the trial NCT03867084, which hypothesized that adjuvant pembrolizumab might surpass placebo efficacy, there still exists a gap in identifying the specific population benefiting from adjuvant immunotherapy. Methods: Clinical and pathological data from patients who underwent single-agent immunotherapy for HCC were additionally collected from Hunan Provincial People's Hospital between January 1, 2019, and January 31, 2024. These patients participated in the clinical trial (NCT03867084) with informed consent. The relationship between WDR4 expression levels, clinical pathological data, and patient prognosis was assessed using the Kruskal-Wallis test and Kaplan-Meier survival curve analysis. Results: WDR4 displayed significant upregulation in HCC tissues compared to para-carcinoma tissues (P &lt; 0.001) and exhibited robust diagnostic potential. WDR4 expression showed significant associations with various immune cells, including macrophages (r = 0.278, P &lt; 0.001). Kaplan-Meier survival analysis indicated that patients with high WDR4 expression had shorter postoperative progression-free survival in the context of immunotherapy. Data from 37 patients who underwent postoperative single-agent immunotherapy for hepatocellular carcinoma (NCT03867084) revealed a significant correlation between WDR4 expression levels and Disease-Free Survival (DFS), with notable statistical significance (Log-rank P &lt; 0.001). Conclusions: WDR4 demonstrates elevated expression levels within HCC tissues and is associated with immune infiltration, establishing it as a prognostic biomarker in HCC. Furthermore, the positive correlation observed between WDR4 and CD68 as well as PD-L1 underscores its potential as a guiding factor in immunotherapeutic approaches for HCC.
Quality of life (QoL) benefits following <sup>177</sup>Lu-DOTATATE therapy in patients (pts) with <sup>68</sup>Ga-DOTATATE PET positive primary site agnostic neuroendocrine tumors (NET).
Authors: Rebecca KS Wong, Sten Myrehaug, Rosalyn A. Juergens, David Laidley, Shereen Ezzat, Jean-Mathieu Beauregard, Oren Hannun Levine, Patrick Veit-Haibach, Ur Metser, Brandon Driscoll, Andrea Shessel, Ivan Yeung, Aruz Mesci, Julia Publicover, Edward Sun, Katherine Lajkosz
Journal: Journal of Clinical Oncology (2024)

e16291 Background: The QoL experience during the 1st year of follow up for 68 Ga-DOTATATE PET positive primary site agnostic pts with progressive metastatic NET enrolled in a prospective single arm clinical trial of 177 Lu-DOTATATE therapy (OZM 067) is described here. Methods: Pts with progressive NET, Ki67 Index &lt; 30%, adequate organ function &amp; ECOG £2 were eligible. Only pts demonstrating positive disease (Krenning score 3-4) on 68 Ga-DOTATATE PET were eligible to proceed to 177 Lu-DOTATATE therapy (4 cycles at 8- to 12- week intervals. Primary outcome was progression free survival (PFS) at 12 mths. QoL (EORTC QLQ 30 and GINET21) at baseline, 6, 12, 18, 24, 30 months were recorded. Summary scores at time point of interest, and their change from baseline were estimated using a mixed model repeated measure, with baseline assessment included in the model as covariate. Data were normalized with a range of 0-100. A positive change score for Global Summary Status, Functioning Domains, and a negative change score for Symptom Scales and Items represent improvement. A ≥5 point change score is used as a threshold for Minimal Clinically Important Difference (MCID). Results: 195 pts were enrolled. 13 pts were 68 Ga-DOTATATE PET negative while 5 pts withdrew consent. 177 pts received at least one dose of 177 Lu-DOTATATE. All pts enrolled were eligible for a minimum of 12 mths follow up at time of data lock. The primary site was GEPNET in 143 (81%) and non GEPNET in 34 (19%). At 12 mths, the median follow-up was 33 (range 3-71) mths. PFS and OS were 81 (95% CI: 75-86)% and 92 (87-95)% respectively. QoL data at the following timepoints baseline, 6 &amp; 12 (±2) mths were available in 174,128 &amp; 111 pts respectively. The top three symptoms captured in EORTC QLQ 30 was Fatigue (32.5 SD 23.8) , Insomnia (26.7 SD 28.1) and Diarrhea (22.1 SD 29.4). At 12 mths, an improvement in mean score of ≥MCID in Global Health status (GHS) (+5.4), Role Fc Scale (+7,1), Social Fc Scale (+8.7) and multiple symptoms (Fatigue, Pain, Appetite, Constipation, Diarrhea, Financial Difficulties), Sexual fc, Social, Body image (Table 1) were captured. Conclusions: Patients with primary site agnostic 68 Ga-DOTATATE PET positive NET experienced improvement in multiple quality of life domains including multiple symptoms post 177 Lu-DOTATATE at 12 mths. Sexual fc and body image had the largest improvement. Clinical trial information: NCT02743741 . [Table: see text]
The efficacy and safety study of thymosin α1 combined with PD-1 antibodies as adjuvant therapy in patients with hepatocellular carcinoma with high-risk recurrence factors after radical resection.
Authors: Zhu RongHua, Huang Zhiyong
Journal: Journal of Clinical Oncology (2024)

e16226 Background: Anti-PD-1 immunotherapy has revolutionized unresectable hepatocellular carcinoma (HCC) treatment. The efficacy of postoperative adjuvant therapy (PAT) using anti-PD-1 in treating HCC is currently the subject of extensive research. This study explored the efficacy and safety of anti-PD-1 antibodies combined with thymosin alpha-1 (Tα1) for patients with HCC and high-risk recurrent factors (HRRFs) post-hepatectomy. Methods: Data from 273 patients with HCC and HRRFs who underwent hepatectomy at Tongji Hospital (January 2019 to July 2022) were prospectively collected. Patients were nonrandomly divided into Tα1+ anti-PD-1 antibodies (65, 23.8%), anti-PD-1 antibodies (84, 30.8%), and control (no adjuvant therapy, 124, 45.4%) groups based on finances and willingness. After propensity score matching (PSM), recurrence-free survival (RFS) and overall survival (OS) were compared. Cox regression analysis identified the RFS- and OS-related prognostic factors, followed by subgroup analysis. Results: After PSM, 65 patients were matched. The anti-PD-1 antibodies + Tα1 group exhibited longer RFS than the anti-PD-1 antibodies (P = 0.014) and control (P &lt; 0.0001) groups. The anti-PD-1 antibodies group had longer RFS than the control group (P &lt; 0.0001). The anti-PD-1 antibodies + Tα1 (P = 0.00049) and anti-PD-1 antibodies groups (P = 0.0041) demonstrated longer OS than the control group. The 1- and 2-year RFS rates in the Tα1 + anti-PD-1 antibodies, anti-PD-1 antibodies, and control groups were 98.4%, 86.2%, and 49.2% (P &lt; 0.001), and 80.2%, 65.8%, and 24.6% (P &lt; 0.001), respectively. The corresponding 1-, 2-, and 3-year OS rates were 100.0%, 100.0%, and 84.6% (P &lt; 0.001), 98.0%, 91.4%, and 69.0% (P &lt; 0.001), and 91.3%, 86.8%, and 57.4% (P &lt; 0.001), respectively. Multivariable analyses suggested that the Tα1 + anti-PD-1 antibodies treatment improved the RFS and OS more than the non-anti-PD-1 antibodies + Tα1 treatment (hazard ratio (HR): 0.174, 95% confidence intervals (CI): 0.089–0.340, P &lt; 0.001 and HR: 0.240, 95% CI: 0.084–0.683, P = 0.008, respectively). Subgroup analysis demonstrated significant RFS and OS benefits for patients with HCC and vascular invasion treated with Tα1 + anti-PD-1 antibodies. Grade 1 and 2 toxicities included rash/pruritus (21.5%), diarrhea (18.5%), and reactive cutaneous capillary endothelial proliferation (RCCEP)(15.4%). Grade 3 toxicities included RCCEP (1.5%), diarrhea (1.5%), rash/pruritus (0.8%), edema (0.8%), hepatitis (0.8%), nausea/vomiting (0.8%), and hypothyroidism (0.8%). No grade 4/5 toxicities or severe adverse events were detected. Conclusions: Combining anti-PD-1 antibodies with Tα1 as adjuvant therapy is safe, improving postoperative prognosis in patients with HCC and HRRFs after hepatectomy, proving more effective than anti-PD-1 antibodies alone.
Yolk sac tumor of the liver: Presentation, diagnosis, and treatment review.
Authors: Awais Paracha, Brittany Kwait, Amanda Lee, Anthony Papale, Michael Attanasi, Fahad Hussain, Umar Durrani, Veena S. John
Journal: Journal of Clinical Oncology (2024)

e16371 Background: Yolk Sac Tumor of the Liver (YSTL) is an extremely rare extragonadal germ cell tumor with gonadal origin and histology which presents in the liver. While uncommon, this tumor is often misdiagnosed due to the similarities between YSTL, HCC, and Hepatoblastoma (HB). As this cancer can present with serious mortality, our review aimed to evaluate clinical findings, diagnostic workup, and treatments in patients with YSTL. Methods: We performed a literature search in PubMed from 1950 to October 2023 using filters English language and full text with keywords “Yolk sac tumor of the liver”, “Endodermal Sinus tumor of liver”, “Hepatic Yolk sac tumor”, and “Hepatic Endodermal sinus tumor”. We also conducted a combined search query with all these search terms and “primary”. Patients were included in the study if they had primary YSTL and no other malignancy. Results: Our results looked at 19 patients ranging from 15 months to 64 years with median age being 27 years, including 13 female (68%) and 6 male (32%) patients, percentages reflect the total number of patients. The key presenting symptom in adults was abdominal pain (55%), while the key presenting symptom in children was abdominal distention (63%). All patients in the study had a diagnostic workup that included imaging and pathology. Imaging included CT Abdomen (68%) and MRI (37%), in 58% of patients a solitary mass was seen on imaging, while in 42% of patients multiple hepatic masses were seen. Histology workup mainly noted Shiller Duval Bodies(SDBs)(76%). Molecular Markers included AFP(42%), Alpha-1 anti-trypsin(A1AT)(26%), SALL4(21%), Pancytokeratin(PK)(11%), and Placental-like alkaline phosphatase(PALP)(11%). Treatment included chemotherapy(58%), surgery(47%), transplant(11%), and trans-arterial chemoembolization(5%). Out of the 11 patients who were treated with chemotherapy, 91% received the bleomycin, etoposide, and cisplatin (BEP) regimen. The remaining 9 % of patients received a regimen of cisplatin, adriamycin, and pepleomycin. Conclusions: YSTL is a unique tumor presenting in patients of all ages, tending to present vaguely often with abdominal pain or distension. Diagnostic workup often includes abdominal imaging (MRI and CT Abdomen) and pathology with a focus on SDBs on histologic examination and stains like AFP, A1AT, SALL4, etc. Treatment often focuses on surgery and chemotherapy, notably BEP. Though both HCC and HB traditionally present as a multifocal liver mass on imaging along with positive staining for AFP and PK, our study helps differentiate this tumor from others by emphasizing the importance of SDBs in diagnosis and highlighting new molecular markers to help make the diagnosis easier.