tbuckley/cabot-search huggingface dataset:
Association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and risk of endometrial cancer among US adults: A population-based study.
Authors: Penglin Liu, Wenzhi Kong, Jinwei Miao
Journal: Journal of Clinical Oncology (2024)

123 Background: Endometrial cancer, as one of the metabolic-related malignancies, is becoming a significant public health concern worldwide. The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) has emerged as a comprehensive biomarker of various lipid-related metabolic disorders. However, the association of NHHR with endometrial cancer risk remains unclear to date. Therefore, we conducted this nationwide cross-sectional study to investigate the association of NHHR with the risk of endometrial cancer among US adults. Methods: Data were obtained from the National Health and Nutrition Examination Survey (1999–2018). Female participants who provided complete data on the NHHR and endometrial cancer were enrolled. The association of the NHHR with endometrial cancer was assessed by multivariate logistic regression analyses, adjusted by multiple potential confounders. Meanwhile, sensitivity analyses and subgroup analyses were conducted. Results: A total of 25,411 eligible participants were enrolled, including 214 (0.8%) women with endometrial cancer. The fully-adjusted multivariate logistic model showed a significantly positive association of NHHR with the endometrial cancer risk (odds ratio [OR] 1.15, 95% confidence interval [CI]: 1.05–1.25; P=0.003). Comparing the highest to the lowest quartile of NHHR, the fully-adjusted OR was 1.52 (95% CI: 1.02–2.28, P for trend=0.017). In subgroup analyses, the significantly positive association between NHHR and the risk of endometrial cancer was also found in non-obese women (OR 1.18, 95% CI: 1.04–1.35, P=0.012), women without diabetes (OR 1.15, 95% CI: 1.02–1.30, P=0.027), women with hypertension (OR 1.15, 95% CI: 1.03–1.28, P=0.012), women who use oral contraceptives (OR 1.16, 95% CI: 1.04–1.30, P=0.009) and in parous women(OR 1.15, 95% CI: 1.05–1.27, P=0.003). Additionally, in the sensitivity analysis by excluding participants with NHHR below 5% or above 95% in total cohort, the positive association of NHHR with endometrial cancer risk remained significant (OR 1.21, 95% CI: 1.03–1.42, P=0.018). Conclusions: This population-based study found that a higher NHHR correlated with an increased risk of endometrial cancer among the US population. Our findings suggested that NHHR might be a promising tool for the risk assessment of endometrial cancer. Prospective studies are necessary to further verify these findings. [Table: see text]
Challenges of liquid panel in genomic profiling of esophageal squamous cell carcinoma (ESCC): Insights from an analysis of over 1000 cases.
Authors: Ryuichi Morita, Takeshi Ishikawa, Junichiro Itani, Daiki Sone, Naoto Iwai, Toshifumi Doi, Masahiro Iwasaku, Ken Inoue, Osamu Dohi, Naohisa Yoshida, Kazuhiko Uchiyama, Tomohisa Takagi, Hideyuki Konishi, Go Horiguchi, Koichi Takayama, Yoshito Itoh
Journal: Journal of Clinical Oncology (2024)

86 Background: Genomic analysis of ctDNA from cancer patients can allow identification of actionable alterations of tumor without an invasive biopsy. ctDNA analysis has been reported to be superior for global summary of tumor heterogeneity and a short turnaround time compared to tissue analysis,however, there are potential issues including the detection sensitivity, threshold to determine TMB-H, and clonal hematopoiesis of indeterminate potential (CHIP). In order to elucidate the impact of ctDNA analysis on personalized cancer treatment, we decided to examine the genetic landscape and clinical outcomes of ESCC cohort registered in the C-CAT database. Methods: We retrospectively analyzed data from 1059 cases of ESCC registered in the C-CAT from June 2019 to February 2024. Clinical characteristics, TMB status, pathological gene variants, and time to treatment failure (TTF) of first-line treatment were examined. Results: The panels applied to eligible patients consisted of 925 tumor tissue panels (87.3%) and 134 liquid panels (12.7%). Pathological gene mutations were detected in 924 cases (99.8%) in tissue panels and 133 cases (99.2%) in liquid panels. The top 10 detected genes were TP53 (93.4%), CDKN2A (57.8%), CDKN2B (45.5%), CCND1 (43.9%), FGF19 (41.0%), PIK3CA (29.0%), NFE2L2 (28.3%), BCL6 (16.5%), NOTCH1 (13.5%), and KMT2D (12.2%). The detection rate for these genes excluding NOTCH1 and KMT2D were significantly higher in tissue panels than in liquid panels (P≤0.01). The median TMB was 5.00 Muts/Mb for both. In first-line treatment, the TTF for immune checkpoint inhibitors (ICIs) and chemotherapy was significantly longer in TMB-H (≧10 Muts/Mb) compared to TMB-L (3.1M vs. 1.9M, P&lt;0.01) in patients evaluated by tissue panels, but it was not proven in patients evaluated by liquid panels (P=0.38). Furthermore, the results suggest that patients with CDKN2A, CCND1, and FGF19 variants benefit more by adding ICIs to chemotherapy than patients without these variants and while the opposite was true for BCL6 and NOTCH1 and KMT2D. Conclusions: In this ESCC cohort, detection rates in the liquid panels were generally lower than in the tissue panels, suggesting that sufficient ctDNA could not be obtained in many cases. The appropriate patient selection for the liquid panels and the timing of blood collection should be discussed. Furthermore, the ideal threshold for determining TMB-H in the liquid panels needs to be further investigated.
Safety, tolerability, and immunogenicity of WGc-043 in subjects with EBV-positive cancers: Results from an investigator-initiated trial.
Authors: Xingchen Peng, Xuan He, Weiwei Zhang, Hai Huang, Xue Li, Jie Chen, Yuquan Wei, Xiangrong Song
Journal: Journal of Clinical Oncology (2024)

139 Background: The Epstein-Barr virus (EBV) persists and spreads after infection in humans, leading to the occurrence and metastasis of a variety of cancers, posing great challenges in the treatment of cancer.. Conventional cancer therapies tend to have limited success and significant side effects. Therefore, there is an urgent need to develop more safe and efficient treatments such as innovative mRNA vaccines, which provide a new approach to cancer immunotherapy. WGc-043, an mRNA vaccine targeting EBV-positive tumor associated antigens, was evaluated for safety, tolerability, and immunogenicity in a prospective, single-center, investigator-initiated study. Methods: The study included 12 patients aged ≥18 with EBV-positive recurrent or metastatic nasopharyngeal carcinoma. Eligibility criteria included at least one measurable lesion, ECOG performance status 0-1, expected survival greater than three months, and no autoimmune disease. Participants were divided into three dose cohorts (25 μg, 50 μg, 100 μg) and received five administrations followed by optional continued monthly treatment of WGc-043 by intramuscular injection. The study assessed safety by adverse event monitoring, immune response based on the peripheral blood and tumor tissue sample analysis and efficacy according to imaging guidelines and irRECIST version 1.1. Results: The study results demonstrated that WGc-043 had a favorable safety profile with only grade 1 or 2 adverse events and fever (4/12) reported as the most common adverse event. Notably, two patients achieved partial response (PR) and five patients had stable disease (SD), highlighting the potential clinical efficacy of WGc-043. In addition, most (91.7%) subjects showed a significant reduction in plasma EBV DNA levels after administration. Immunogenicity analysis using IFN-γ ELISpot showed that 8 (66.7%) of the 12 enrolled patients developed strong specific immune responses against EBV-associated antigens, indicating that WGc-043 is a potent immunotherapy. Conclusions: This exploratory study underscores the safety and potential efficacy of WGc-043 as an mRNA vaccine for EBV-associated cancers, demonstrating its ability to induce specific immune responses and achieve substantial disease control in a challenging patient population, although further studies in larger clinical trials are needed. These results not only support the advancement of WGc-043 as a candidate for immunotherapy in EBV-positive cancers, but also highlight the translational potential of mRNA vaccine technology in the oncology landscape. Clinical trial information: NCT05714748 . [Table: see text]
The candidate novel markers PIV and PILE score to predict survival outcomes and therapeutic response in patients with primary central nervous system lymphoma.
Authors: Ling Duan, Wenbin Li, Feng Chen
Journal: Journal of Clinical Oncology (2024)

24 Background: Recent studies highlighted the predictive value of easily measurable blood-based biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR), the monocyte-to-lymphocyte ratio (MLR), the platelet-to-lymphocyte ratio (PLR), and the systemic immune-inflammation index (SII). Recently, a novel comprehensive marker that represents the pan-immune-inflammation value (PIV) has been proposed as a more reliable predictor of clinical outcomes. We aimed to investigate the prognostic significance of PIV and PILE score (a score based on PIV, lactate dehydrogenase (LDH), and Eastern Cooperative Oncology Group Performance Status (ECOG PS)), in patients with PCNSL. Methods: A total of 109 patients were enrolled. PIV was calculated as follows: (neutrophil count × platelet count × monocyte count)/lymphocyte count. The PILE score was calculated with the sum of individual values (for PIV &lt; median = 0, ≥ median = 1; for LDH ≤ upper limit of normal (ULN) = 0, &gt; ULN = 1; for ECOG PS &lt; 2 = 0, ≥ 2 = 1). The Kaplan–Meier method and Cox hazards regression models were used for survival analyses. The relationship between PIV, PILE, and therapeutic response was examined. Results: Pretreatment high PIV was confirmed to be an independent significant factor for overall survival (OS) in univariate (HR 3.990, 95%CI 1.778-8.954, p &lt; 0.001) and multivariate (HR 3.047, 95%CI 1.175-7.897, p = 0.022) analyses. Baseline PIV was also associated with worse progression-free survival (PFS). Regarding OS, PIV showed a better predictive performance than other widely used systemic inflammation parameters. Significantly shorter OS and PFS were observed in the high PILE group (median OS: 25.60, 95% CI 15.60-NR vs. NR months, 95% CI 26.10-NR, p = 0.008; median PFS: 26.13, 95% CI 23.30-NR vs. 7.13 months, 95% CI 4.87-NR, p &lt; 0.001). High PILE was associated with primary resistance to therapy (high PILE group: 21/42 patients, 50.00%; low PILE group: 5/45 patients, 11.11%; p &lt; 0.001). A significantly lower response rate to initial treatment was found in patients in the high PILE group (23/42, 54.76%) as compared to patients in the low PILE group (7/45, 15.56%; p &lt; 0.001). PILE was independently associated with therapeutic response to initial treatment (OR 0.17, 95% CI 0.05–0.46; p &lt; 0.001). Conclusions: High PIV and high PILE were correlated with worse clinical outcomes in PCNSL patients, indicating that PIV and PILE might be a powerful predictor of prognosis and a potential predictive indicator for treatment response in PCNSL.
Effect of statin use on long-term survival after diagnosis of colorectal cancer: Emulating hypothetical target trials using a nationwide real-world database.
Authors: Hyeong-taek Woo, Aesun Shin
Journal: Journal of Clinical Oncology (2024)

82 Background: Observational studies suggest that statin use after colorectal cancer (CRC) diagnosis is associated with improved survival. However, potential bias due to misalignment of time zero in observational studies may distort associations and therefore requires validation using robust epidemiological methods. We aimed to emulate a hypothetical randomized trial—a target trial—for estimating per-protocol effects of statin initiation in patients with incident colorectal cancer on long-term survival. Methods: To emulate a target trial using real-world data, we extracted information from 103,005 patients diagnosed with CRC between 2005 and 2015 from the Korean National Health Insurance (KNHI) database, encompassing health records for the entire Korean population. We excluded individuals who had been prescribed statins for at least 180 days before the CRC diagnosis or those with missing or incomplete demographic information. We set a 180-day grace period and compared the group that initiated statin treatment within 180 days after the CRC diagnosis with the non-statin group using the “clone-censor-weight” method. Patients' demographic and socioeconomic information, along with colorectal cancer treatment, were included as baseline covariates. Additionally, the Charlson Comorbidity Index (CCI) score was included both as a baseline covariate and as a time-varying covariate. Hazard ratios (HRs) for all-cause mortality and CRC-specific mortality within 60 months of baseline were calculated using pooled logistic regression models. Results: Among the 103,005 patients diagnosed with CRC, 88,516 were finally analyzed after the exclusion process. A total of 2,071 (2.3%) individuals initiated statin treatment during the grace period and 86,445 (97.7%) patients did not. Statin initiators, compared with statin noninitiators tended to be older (mean age: 65.7 vs. 62.6) and had a higher CCI score at baseline (mean CCI score: 1.38 vs.1.26). Individuals who initiated statin treatment did not reduce the hazard of all-cause mortality (The adjusted HR 1.01, 95% CI 0.98-1.04) and CRC-specific mortality (The adjusted HR 1.01, 95% CI 0.97-1.04). Conclusions: The results of the analysis after removing potential biases showed that statin was not related to improving survival in CRC patients. The study results conflict with those of previous observational studies but are consistent with the findings of other recently conducted target trial emulations.
Prognostic and immunological significance of tertiary lymphoid structures in nasopharyngeal carcinoma.
Authors: Daofeng Huang, Xu Liu, Hui Li, Zi-Qi Zheng, Juan Du, Jun Ma
Journal: Journal of Clinical Oncology (2024)

220 Background: Tertiary lymphoid structures (TLSs) are ectopic lymphoid tissues found in non-lymphoid organs, characterized by the presence of CD20 + B cell follicles adjacent to a T cell zone. Their presence has been associated with improved survival in various tumor types. However, the role of TLSs in nasopharyngeal carcinoma (NPC) remains unclear. In this study, we investigated the prognostic and immunological significance of TLSs in NPC patients. Methods: The investigation involved a discovery cohort (n = 145) comprising NPC patients diagnosed at Sun Yat-sen University Cancer Center between July 2010 and December 2016, with pretreatment primary tumor samples collected. An independent validation cohort included 150 NPC patients with gene expression profiles, among whom Hematoxylin &amp; Eosin (H&amp;E)-stained slides were available for 95 patients. The primary endpoint of this study is overall survival, defined as the duration of time from diagnosis until death from any cause. The presence of TLSs was assessed on H&amp;E and CD20-stained slides. Analyses of tumor-infiltrating immune cell subsets, differentially expressed genes, and BCR/TCR clonotypes were performed to explore the association between TLSs and the anti-tumor immune response. A molecular definition of TLSs was proposed and assessed for its prognostic value across multiple cohorts. Results: The presence of TLSs was independently associated with a favorable overall survival (hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.07-0.94; log-rank p = 0.04), surpassing the significance of B cell density in multivariate analysis (HR, 0.83; 95% CI, 0.38-1.79, log-rank p = 0.63). These findings were corroborated in the independent validation cohort. TLSs positively correlated with multiple immune-related pathways and a higher proportion of functionally mature immune cells. Notably, the counts of BCR and TCR clonotypes showed a significant positive correlation with the TLSs score. We proposed a TLSs gene signature and demonstrated its prognostic relevance across multiple cohorts, including patients treated with immune checkpoint blockade. Conclusions: TLSs exhibit heightened immune activity and indicate improved survival outcomes in NPC patients. A TLSs gene signature was proposed and demonstrated its prognostic relevance across multiple cohorts, indicating potential guidance for treatment decisions in cancer.
Patient reported outcome measures at a large district general hospital post-mastectomy and implant based reconstruction.
Authors: Danny Fraser
Journal: Journal of Clinical Oncology (2024)

11 Background: Breast reconstruction surgery for cancer can be a debilitating and life changing experience for patients, with complex affects on physical and mental health throughout the rehabilitation journey. We conduct a study on a cohort of patients undergoing this procedure, with focus on patient reported outcome measures. Methods: We reviewed all patients who underwent breast reconstruction surgery at our hospital from 2017 to 20223. Demographic, diagnosis, pre- and post-operative adjuvant treatment, and implant characteristics were collected. Psychosocial well being, physical wellbeing, satisfaction with breasts scales of the BREAST-Q were used. Independent t-test was conducted to find differences between PROMs for each group, and linear regression of age and implant size on each score. Results: 69 patients were contacted and 39 PROMS collected. The average age of patients was 57.6 years old. 40% were previous or current smokers and 40.8% had BMI&gt;30. 29 had pre-pectoral placement and 40 sub-pectoral. 17 had smooth implants and 52 textured. The average size of implant was 330mm. Immediate reconstruction was associated with a lower psychosocial score (66.0vs86.9, p=0.02) compared to multi-stage implants. Sub pectoral placement was associated with a higher (75.7vs61.9 p=0.046) psychosocial score than pre pectoral placement. Textured surface was associated with lower physical score than smooth surface (34.7vs50.2 P=0.046). On linear regression, age was positively associated (p=0.007) with psychosocial score. Conclusions: These findings underscore the importance of personalized approaches in surgery, considering implant type, placement technique, and patient age. Surgeons should prioritize patient preferences and needs to optimize post-surgical satisfaction and well-being.
Association of vitamin D deficiency with liver cirrhosis and hepatocellular carcinoma risk: A retrospective cohort study from the TriNetX US collaborative networks.
Authors: Yuan-Tsung Tseng, Chun-Hsiang Wang
Journal: Journal of Clinical Oncology (2024)

77 Background: Emerging evidence highlights the critical role of vitamin D in liver health, especially concerning the risk of liver cirrhosis and hepatocellular carcinoma (HCC). This investigation aims to explore the association between vitamin D deficiency and the prevalence of these liver diseases, contrasting outcomes between individuals with deficient and normal vitamin D levels. Methods: This cohort study utilized the US Collaborative Network within the TrinetX database, encompassing 63 medical institutions. It enrolled participants aged 20 years and older from 2011 to 2023. Vitamin D status was determined through serum 25-hydroxyvitamin D levels, categorizing deficiency as 20-30 ng/mL and normal levels as 30-80 ng/mL. Employing 1:1 propensity score matching, the study controlled for 32 characteristics, such as demographic information, health conditions, and medication use, to ensure equitable group comparisons. Additionally, a 1-year washout period was established. The primary aim was to assess the incidence of liver cirrhosis and HCC over a decade. Results: Analyzing data from over 1.86 million participants, the study ensured a balanced comparison across all variables. Participants had an average age of 50.6 years, with 66% identifying as white and 9% as black. Notably, vitamin D deficiency was significantly associated with an increased risk of liver cirrhosis (HR 1.16 [CI 1.11-1.21]) and HCC (HR 1.25 [CI 1.15-1.36]). Kaplan-Meier cumulative risk analysis further confirmed these elevated risks for both liver conditions in individuals with vitamin D deficiency compared to those with sufficient levels. Conclusions: This study confirms a significant association between vitamin D deficiency and a higher risk of liver cirrhosis and HCC, underscoring the importance of vitamin D in maintaining liver health. The findings support the potential of vitamin D level management as a preventive strategy against liver diseases. The implications of this research necessitate further exploration into the efficacy of vitamin D supplementation for liver disease prevention.
Impact of EOB-MRI on the outcome of patients with pancreatic cancer in real-world settings.
Authors: Atsushi Oba, Tomoyuki Taguchi, Naoto Fujikawa, Suguru Okami, Takashi Tsuji, Alexander Michel, Yuki Kado, Satoshi Goshima
Journal: Journal of Clinical Oncology (2024)

88 Background: Contrast-enhanced computed tomography (CE-CT) is a commonly used imaging modality for the preoperative detection of local extension and distant metastasis in patients (pts) with pancreatic cancer (PaC). There have been cases where surgical treatment was deemed unsuitable due to unexpected distant metastases discovered during surgery, which had not been detected by CE-CT. While studies have reported gadoxetate disodium-enhanced MRI (EOB-MRI) improves the detection of liver metastases, it is not clear whether adding EOB-MRI to CE-CT provides clinical benefits, e.g. improved outcomes through the early access to appropriate treatments by avoiding unnecessary surgery (open-close surgery) in pts with PaC. This study aimed to assess the effectiveness of adding EOB-MRI before surgical or non-surgical treatment on overall survival (OS) in pts with PaC in real world settings. Methods: This was a retrospective cohort study using a nationwide hospital-claims database in Japan. Pts aged ≥18 years diagnosed with PaC with a record of surgery, radiotherapy, or chemotherapy, who had an imaging modality were identified between January 1, 2011 to October 31, 2021. Pts were grouped into EOB-MRI and no EOB-MRI groups, and further grouped into surgery, no surgery and open-close laparotomy. OS was compared between propensity-score matched EOB-MRI and no EOB-MRI groups using the Cox regression model. Results: 39,624 pts were included in the study, of them, 4,477 (11.3%) underwent EOB-MRI prior to the initial treatment. 2,061 (46.0%) pts in EOB-MRI group underwent surgery, 2,346 (52.4%) had no surgery and 70 (1.6%) had open-close laparotomy. In 35,147 (88.7%) pts in no EOB-MRI group, 13,182 (37.5%) underwent surgery, 21,506 (61.2%) had no surgery, and 459 (1.3%) had open-close laparotomy. The OS results in subgroups are shown in the Table. Conclusions: In real-world settings, EOB-MRI performed prior to the initial treatment was associated with significantly higher OS than those without EOB-MRI in pts who did not undergo surgery, but there was no difference in OS in pts who underwent surgery. These results suggest that the early detection of micro hepatic metastases through EOB-MRI and multidisciplinary treatment that enables EOB-MRI may contribute to improved outcomes in pts with PaC. Clinical trial information: NCT06106568 . [Table: see text]