tbuckley/cabot-search huggingface dataset:
Efficacy and safety of transarterial therapy combined with donafenib plus immune checkpoint inhibitors for unresectable hepatocellular carcinoma: A multicenter retrospective study.
Authors: Changzhen Shang, Jinyi Zhong, Xuan Luo, Bo Zhang, Huanwei Chen, Fengjie Wang, Xiaofeng Jiang, Liangqi Cao, Shun-Li Shen, Yajin Chen
Journal: Journal of Clinical Oncology (2024)

e16133 Background: Based on the different anti-malignant mechanisms of tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs) and transarterial therapy, several studies have demonstrated the potential of combining these three treatments to improve outcomes in patients with unresectable hepatocellular carcinoma (uHCC). This study aimed to evaluate the efficacy and safety of transarterial therapy plus donafenib and ICIs for uHCC patients in a real-world setting. Methods: This multicenter retrospective study included patients with uHCC who had received at least one cycle of transarterial therapy (hepatic arterial infusion chemotherapy, HAIC, or transarterial chemoembolization, TACE) and donafenib and ICIs (anti-PD-1 available in China) at five cancer centers. Other key inclusion criteria were: (1) no prior systemic treatment; (2) at least one follow-up image data. The primary endpoint was progression-free survival (PFS) according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Secondary endpoints included overall survival (OS), objective response rate (ORR) and toxicity. Results: Of the 61 eligible patients enrolled, 56 (91.8%) were men, 54 (88.5%) had HBV infection, 26 (42.6%) had AFP level &gt; 400 ng/mL, 38 (62.3%) were at BCLC stage C, 32 (52.5%) had macrovascular invasion, 14 (23.0%) had extrahepatic metastasis, 47 (77.0%) had multiple tumors and the median maximum tumor size was 86.0 mm (IQR, 61.5–122.6). Four kinds of ICIs were employed, including tislelizumab (n = 29), camrelizumab (n = 21), sintilimab (n = 9), toripalimab (n = 2). Up to the date of November 24, 2023, the median follow-up time was 13.0 months. The median PFS was 12.7 months (95%CI, 8.4–NA), with a 1-year PFS rate of 52.7% (95%CI, 37.9%–73.1%). The median OS was not reached, and 1-year OS rate was 88.4% (95%CI, 79.9%–97.8%). The ORR according to mRECIST was 70.5%. Twelve (19.7%) patients had received conversion resection, and the median conversion time was 3.1 months (95%CI, 2.37–NA). Overall, 51 (83.6%) patients experienced at least one treatment-related adverse events (TRAEs), 22 (36.1%) had grade 3 or 4 AEs, and no patients died due to AEs. The most common AEs greater than 15% were hand-foot skin reaction (47.5%), liver dysfunction (27.9%), decreased platelet count (19.7%) and hypoalbuminemia (16.4%). Conclusions: This retrospective real-world study showed that transarterial therapy combined with donafenib plus ICIs in the treatment of uHCC patients was well tolerated and comparable clinical efficacy to other triple therapies. This combination strategy may be an appropriate treatment option for uHCC patients.
Efficacy and safety of donafenib combined with anti-PD-1 antibodies for initially unresectable hepatocellular carcinoma (HCC): A retrospective real-world study.
Authors: Sulai Liu, Shuyi Zhou, Yinghui Song, Jianming Liu, Chao Guo, Pingzhou Yang, Ou Li, Weimin Yi, Chuang Peng
Journal: Journal of Clinical Oncology (2024)

e16131 Background: Given its clear efficacy and high safety demonstrated in the phase 3 ZGDH3 study, donafenib has been recommended by the Chinese guidelines for the first-line treatment of unresectable hepatocellular carcinoma (uHCC). Recently, combination therapies have shown favorable results. However, the clinical experience of donafenib combined with anti-PD-1 therapy for uHCC has not yet been investigated. Thus, we aimed to investigate the efficacy and safety of donafenib combined with anti-PD-1 antibody in the treatment of uHCC. Methods: A single-center, retrospective study was performed based on the medical records of consecutive patients diagnosed with HCC who were not suitable for curative surgery at Hunan Provincial People's Hospital from July 2021 to September 2023. Patient with ≥18 years, no prior systemic therapy, having at least one measurable lesion (per mRECIST) were enrolled. Patients were treated with donafenib and anti-PD-1 antibodies until disease progression or unacceptable toxicity, local treatment such as TACE, HAIC or ablation were allowed. The primary endpoint was progression-free survival (PFS) by mRecist criteria, and secondary endpoints included overall survival (OS), objective response rate (ORR) and disease control rate (DCR) by mRecist criteria, and safety. The last follow-up time was December 15, 2023. Results: In total, 48 patients were enrolled: 87.5% males, median age 59.5 years (range, 32.0-78.0), 95.8% ECOG of 0, 68.8% HBV positive, 14.6% BCLC stage B, 75.0% BCLC stage C, 47.9% baseline AFP≥400 ng/mL, 70.8% with macrovascular invasion. Among them, 9 patients (18.8%) received donafenib combined with anti-PD-1 antibody as first-line treatment, 37 (77.1%) with concurrent TACE(n = 25) or HAIC(n = 6) or both as treatment(n = 6), 2 (4.2%) received ablation treatment. At the time of data cut-off, the median follow-up time was 10.0 months (95% CI, 6.37-12.2). Considering efficacy, 9 pts (18.7%) achieved complete response, 20 (41.7%) achieved partial response, 17 (35.4%) had stable disease, and 2(4.2%) had progressive disease. The ORR and DCR were 60.4% and 95.8% by mRecist, respectively. Median progression-free survival was 15.8 months (95% CI, 8.9-NA). Median overall survival was not reached, 12-month OS rate were 90.7% (95% CI:73.7%-96.9%). In terms of safety, 44 pts (91.7%) had TRAEs. The incidence of ≥grade 3 TRAEs was 33.3% (16/48). Common TRAEs included elevated AST(45.8%), hand-foot syndrome (39.6%), decreased platelet count(35.4%),elevated ALT(31.2%), rash (25.0%) and decreased white blood cell count (14.6%). Grade 3/4 TRAEs included elevated AST(10.4%), elevated ALT(8.3%), rash(8.3%) and hand-foot syndrome (8.3%). No grade 5 TRAEs were observed. Conclusions: Donafenib combined with anti-PD-1 antibodies shows promising efficacy and manageable toxicity in patients with initially uHCC.
Infections in patients with mantle cell lymphoma
Authors: Kossi D. Abalo, Sara Ekberg, Therese M. L. Andersson, Simon Pahnke, Alexandra Albertsson‐Lindblad, Karin E. Smedby, Mats Jerkeman, Ingrid Glimelius
Journal: HemaSphere (2024)

Abstract Advancements in treatments have significantly improved the prognosis for mantle cell lymphoma (MCL), and there is a growing population of survivors with an increased susceptibility to infections. We assessed the incidence of infections by clinical characteristics and treatment both before and after MCL diagnosis in Sweden. Patients with a diagnosis of MCL ≥ 18 years between 2007 and 2019 were included, along with up to 10 matched comparators. Infectious disease diagnosis and anti‐infective drug dispensation were identified by the National Patient and the Prescribed Drug Registers, respectively. Patients and comparators were followed from the diagnosis/matching date until death, emigration, or June 30, 2020. Overall, 1559 patients and 15,571 comparators were followed for a median duration of 2.9 and 5 years, respectively. The infection rate among patients was twofold higher, RRadj = 2.14 (2.01–2.27), contrasted to the comparator group. There was a notable rise in infection rates already 4 years before MCL diagnosis, which reached a fourfold increase in the first year after diagnosis and persisted significantly increased for an additional 8 years. Among patients, 69% ( n = 1080) experienced at least one infection during the first year of follow‐up. Influenza, pneumonia, other bacterial infections, urinary tract infections, and acute upper respiratory infections were the most frequent. Notably, MCL remained to be the primary leading cause of death among patients (57%, n = 467/817). Infections as the main cause of death were rare (2.6%, n = 21). Our study highlights the importance of thoroughly assessing infectious morbidity when appraising new treatments. Further investigations are warranted to explore strategies for reducing infectious disease burden.
Predictive value of positive lymph node ratio in patients with locally advanced gastric remnant cancer.
Authors: Meng Zhuo, Ting Han, Xiaolin Lin, Xiuying Xiao
Journal: Journal of Clinical Oncology (2024)

e16119 Background: Traditional lymph node stage (N stage) has limitations in advanced gastric remnant cancer (GRC)patients; therefore, establishing a new predictive stage is necessary.To explore the predictive value of positive lymph node ratio (LNR) according to clinicopathological characteristics and prognosis of locally advanced GRC. Methods: Seventy-four patients who underwent radical gastrectomy and lymphadenectomy for locally advanced GRC were retrospectively reviewed. The relationship between LNR and clinicopathological characteristics was analyzed. The survival analysis was performed using Kaplan–Meier survival curves and Cox regression model. Results: Number of metastatic LNs, tumor diameter, depth of tumor invasion, Borrmann type, serum tumor biomarkers, and tumor–node–metastasis (TNM) stage were correlated with LNR stage and N stage. Univariate analysis revealed that the factors affecting survival included tumor diameter, anemia, serum tumor biomarkers, vascular or neural invasion, combined resection, LNR stage, N stage, and TNM stage (all P &lt; 0.05). The median survival time for those with LNR0, LNR1, LNR2 and LNR3 stage were 61, 31, 23 and 17 mo, respectively, and the differences were significant ( P = 0.000). Anemia, tumor biomarkers and LNR stage were independent prognostic factors for survival in multivariable analysis (all P &lt; 0.05). Conclusions: The new LNR stage is uniquely based on number of metastatic LNs, with significant prognostic value for locally advanced GRC, and could better differentiate overall survival, compared with N stage.
Whole exome sequencing analysis of intratumoral heterogeneity, tumor neoantigen burden and human leukocyte antigen loss of heterozygosity in HCC.
Authors: Wenting Liao, Yue Xiao, Wei Guo
Journal: Journal of Clinical Oncology (2024)

e16003 Background: Hepatocellular Carcinoma (HCC) patients has a high postoperative recurrence within 2 years and a low 5-year survival rate. However, molecular mechanisms for early recurrence are poorly understood. Immune checkpoint blockades (ICBs) show clinical benefits in HCC, with the immune microenvironment influencing ICBs therapeutic effects. Exploring the relationship between intratumoral heterogeneity (ITH), tumor neoantigen burden (TNB), and human leukocyte antigen loss of heterozygosity (HLA LOH) can deepen our understanding of the immune evasion mechanisms. Methods: In this study, whole exome sequencing (WES) was employed to analyze tumor specimens and matched peripheral blood controls derived from a cohort of 235 HCC patients. PD-L1 expression levels were assessed in the samples using immunohistochemistry. NetMHCpan was applied to predict neoantigen and quantified the peptide affinity of MHC-I genes measured by IC50. Neoantigen-MHC affinity was categorized as strong (IC50≤50nM), weak (50nM &lt; IC50≤500nM), and negative (IC50 &gt; 500nM). TNB was defined by the number of high affinity neoantigens per megabase in WES. Analysis of LOH was performed on HLA-I class genes and categorized as strong positive, weak positive, and negative groups. We used PyClone to conduct ITH analysis to assess the distribution of multiple subclones within a tumor. The average Cancer Cell Fraction (CCF) for each somatic mutation cluster was calculated, and these clusters were classified into major clones and subclones. Results: In 235 HCC samples, median TMB and TNB were 2.48 Muts/Mb and 0.30 Neos/Mb. Only 6.81% exhibited TMB-H (TMB≥10 Muts/Mb). TMB and TNB are significantly positively correlated (p &lt; 0.0001). HLA LOH occurred in 19.57% HCC patients, with high LOH samples having more high-affinity neoantigens (mean TNB 1.65 Neos/Mb). ITH analysis showed that 83.83% samples harbored subclonal clusters. HCC samples were divided into high (ITH≥0.908) and low (ITH &lt; 0.908) groups according to the median ITH of 0.908. High ITH group had higher TNB (median 0.43 vs 0.20 Neos/Mb) , more HLA LOH (9.24% vs 5.17% strong positive LOH). The high ITH groups exhibited a lower percentage of samples with elevated PD-L1 expression (14.29% vs 25.86%). The Combined Positive Score (CPS) revealed a significant difference between the groups (Fisher's test p = 0.03). Conclusions: In HCC, the high ITH group exhibited a higher proportion of HLA LOH compared to the low ITH group. Moreover, a decreased proportion of PD-L1 positive samples was observed in the high ITH group, suggesting that high ITH may be a key factor influencing treatment failure in immunotherapy. ITH analysis demonstrated a potential multi-subclonal origin of recurrent tumor cells, which is associated with immune escape, tumor malignancy,as well as the development of resistance.
Neoadjuvant chemoradiotherapy (nCRT) combined with sequential tislelizumab for resectable esophageal squamous cell carcinoma (ESCC): Preliminary results of a single-arm, open-label phase Ib trial (CRIS).
Authors: Youhua Jiang, Guoqin Qiu, Jianqiang Li, Jiangfeng Wang, Changchun Wang, Jie Wu, Lei Cheng, Yuanda Zheng, Rongwei Ruan, Ge Song, Xuemei Ye
Journal: Journal of Clinical Oncology (2024)

e16116 Background: Neoajuvant chemoradiation is the standard treatment for resectable locally advanced esophageal squamous cell carcinoma (ESCC). Immune checkpoint inhibitors (ICIs) have shown a survival benefit for advanced ESCC and showed promising efficacy in neoadjuvant treatment for several cancers. This study aimed to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) combined with sequential tislelizumab followed by surgery for resectable ESCC. Methods: This is a single-arm, phase Ib study. Eligibility criteria include histologically confirmed ESCC and clinical T3-4aN0M0 or T2-4aN+M0 (AJCC/UICC 8 th ). Patients received neoadjuvant radiotherapy (41.4Gy in 23 fractions) with concurrent chemotherapy (paclitaxel, 50 mg/m2, carboplatin area under the curve of 2mg/mL/min, QW*5). Then followed by two cycles of tislelizumab (200mg, Q3W). The primary endpoint was the pathological complete response (pCR) rate and safety. Results: From Feb 2022 to Jan 2024, 35 patients had been enrolled, of whom the median age was (65.5 (95%CI, 59-67), including 31 (88.6%) males. 12 patients were still undergoing chemoradiotherapy and 2 patients did not receive immunotherapy due to pneumonia and myocarditis after chemoradiotherapy. 16 patients completed all 2 cycles tislelizumab preoperatively and 5 patients completed 1 cycle tislelizumab because of AEs. Two patients refused surgery after achieved complete clinical response under radiology and were still alive, the other 19 patients underwent resection. The R0 resection rate was 94.7% (18/19). The pCR rate was 63.2% (12/19) and the MPR rate was 78.9% (15/19). During neoadjuvant treatment, 8 patients had a grade 3 or worse adverse event including leukopenia (33.3%, 7/21, Grade 3), esophagitis (4.8%, 1/21, Grade 3) and anemia (4.8%, 1/20, Grade 4). One patient developed grade 4 postoperative complication (5.3%, 1/19, pneumonia) and died within 90 days of surgery due to COVID-19. Grade 1-2 postoperative complications occurred in 21.1% (4/19) patients, including anastomotic fistula (21.1%, 4/19), chylothorax (5.3%, 1/19) and pneumonia (10.5%, 2/19). Conclusions: Preliminary results showed that neoadjuvant chemoradiotherapy (nCRT) combined with sequential tislelizumab showed promising outcomes and well tolerated for resectable ESCC patients. Further larger prospective studies are needed to confirm such findings.
LncRNA EGOT and tumorigenesis via Hedgehog pathway in gastric cancer.
Authors: Wenlong Ji, Zhaolong Yang, Kun Zhao, Jifeng Feng, Xia He, Guoren Zhou, Wei Peng
Journal: Journal of Clinical Oncology (2024)

e16130 Background: Gastric cancer (GC) is one of the mostly terminal malignancies with poor prognosis. Long noncoding RNA EGOT (EGOT) acts as a crucial regulator in the breast cancer. However, the function of EGOT in GC remains unknown. Methods: This work was to explore the clinical value and biological significance of EGOT in GC. EGOT levels in GC tissue and cell were analyzed by qRT–PCR. After knockdown of EGOT, GC cell growth and cycle progression were detected. Results: The expression of EGOTwas observably elevated in GC. Upregulation of EGOT was related with lymphatic metastasis and TNM stage. In addition, knockdown of EGOT by siRNA could significantly inhibit GC cell proliferation and arrest cycle progression in G1 phase. Moreover, EGOT mediated cyclin D1 expression in GC cells which was regulated by Hedgehog pathway. Further, loss of EGOT downregulated Hedgehog signaling pathway in GC cells. Conclusions: EGOT functions as an oncogene in GC, and may be useful as a conceivable diagnostic and prognostic biomarker for GC tumorigenesis.
Trends and disparities in the incidence and mortality of stomach cancer in the United States.
Authors: Temitope Ajibawo
Journal: Journal of Clinical Oncology (2024)

e16102 Background: Stomach cancer is the fifth most common cancer worldwide and has one of the lowest survival rates across all malignancies. There is a constant need to define current stomach cancer incidence and incidence-based mortality (IBM) rates among different population groups for improved clinical practice. We aimed to investigate the trends of stomach cancer incidence and IBM by population characteristics of age groups, gender and ethnic groups. Methods: Data obtained from the National Cancer Institute’s Surveillance, Epidemiology, and End results (SEER) Registry 12 were obtained to determine the incidence and IBM rate of stomach incidence from 1992 to 2020. Joinpoint Regression Analysis program was used to calculate the annual percent change (APC) for trend analysis. Results: A total of 82,810 stomach cancer patients were identified from the dataset. Most of the patients were males; N = 49,909(60.27%) and Non-Hispanic Whites, N = 40,894 (49.38%). The overall incidence rate was 8.00 (95% Confidence Interval [CI]: 7.95 to 8.06) and the overall IBM rate was 6.44 (95%CI: 6.39 to 6.49). The incidence rate of stomach cancer decreased significantly by 1.28 % per year from 1992 to 2020; however the degree of decline from 1992 to 2017, APC (-1.18, 95% CI: -1.27 to -1.04, p &lt; .001) was lower compared to between 2017 and 2020, APC (-3.42, 95% CI: -6.08 to -1.69, p = 0.01). Conversely, IBM rate increased significantly from 1992 to 1994, APC (36.59, 95% CI: 22.51 to 52.29, p &lt; .001) followed by a significant decrease from 1994 to 2020, APC (-1.29, 95%CI: -1.43 to -1.15, p &lt; .001).Incidence rates reduced significantly from 1992 to 2020 for all gender, ethnic and age groups except among the Non-Hispanic Asian Indian or Alaska Native (NHAIAN) population with APC (-0.67, 95 CI% -1.93 to 0.61, p = 0.29) and &lt; 60 years age group with APC (0.03, 95 CI % : 0.18 to 0.25, p = 0.76). Significant decline in IBM rate was observed from 2000 to 2020 across all gender, ethnicities and age groups except among the NHAIAN, APC (-0.21, 95 CI%: -1.26 to 0.84, p = 0.68) and the &lt; 60 years age group, APC (0.16, 95 CI%: -0.33 to -0.65, p = 0.52). Conclusions: Stomach cancer incidence and IBM rates have decreased significantly over the last 20 years except in NHAIAN and &lt; 60 years age populations. These findings suggest the need for further research focused efforts in these potentially high-risk groups.
Neoadjuvant serplulimab in combination with concurrent chemoradiotherapy for locally advanced, resectable esophagogastric junction adenocarcinoma.
Authors: Yuping Ge, Lin Zhao, Weiming Kang, Junfang Yan, Xiang Wang, Ningning Li, Xin Ye, Yan You, Xin Gao
Journal: Journal of Clinical Oncology (2024)

e16103 Background: Surgery combined with perioperative therapy was recommended as standard treatment for patients with locally advanced esophagogastric junction (EGJ) adenocarcinoma, but the survival rate was still poor. Immunotherapy has shown antitumor activity and an acceptable safety profile in advanced EGJ cancer. The aim of this study was to evaluate the efficacy and safety of neoadjuvant Serplulimab combined with concurrent chemoradiotherapy in previously untreated locally advanced resectable EGJ adenocarcinoma. Methods: Eligible patients with resectable EGJ(Siewert Type II and Type III, Siewert classification 2000)adenocarcinoma stage cT3-4 or N+ were enrolled. Patients received neoadjuvant Serplulimab (300mg on day 1) plus SOX(oxaliplatin at 130mg/㎡on day 1; TS1 40-60mg two times per day on D1-D14, Q3W) in first cycle, followed by Serplulimab (300mg on day 1) combined with concurrent chemoradiotherapy (Reduced SOX regimen: oxaliplatin at 100mg/㎡on day 1, TS1 40-60mg two times per day on D1-D14, Q3W; Radiotherapy dose:45Gy in 25f) in second and third cycle. The patient finished the preoperative treatment and rested for 6-8 weeks for surgery. The primary endpoint was pathological complete response (pCR) rate. Secondary endpoints were major pathological response(MPR) rate, R0 resection rate, objective response rate(ORR), disease-free survival(DFS), overall survival(OS), and toxicity. Results: From March 8, 2023 to January 31,2024,15 patients were enrolled. Nine patients completed neoadjuvant therapy. Eight of these patients underwent radical surgical resection. One out of nine achieved a confirmed pathological complete response (pCR) after three cycles of neoadjuvant treatment. Additionally, two out of nine patients achieved major pathological response(MPR). So, the pCR rate was 11.1%, and the MPR rate was 22.2%. The Tumor and Lymph Nodes downstaging rates are 62.5% and 87.5%, respectively. The median DFS and OS were not reached. In terms of safety, fifteen patients who received at least one cycle of neoadjuvant therapy were included. The most common treatment-related adverse events(TRAE) across all grades were nausea/vomiting(6/15), anorexia(5/15), thrombocytopenia(4/15), and fatigue(4/15). Four patients (26.7%) had grade≥3 adverse events during preoperative therapy, with thrombocytopenia(3/15) and hepatic veno-occlusive disease(1/15). Immune-related adverse reactions(irAE) included myositis(1/15) and rash(1/15), both were grade 1. No grade 4 or higher TRAEs were observed. Conclusions: Initial benefits were demonstrated when using Serplulimab with concurrent chemoradiotherapy for the treatment of locally advanced, resectable EGJ adenocarcinoma patients. The efficacy and safety of Serplulimab with chemoradiotherapy will be further investigated in this trial later. Clinical trial information: NCT05918419 .