tbuckley/cabot-search huggingface dataset:
Spatiotemporal single-cell analysis decodes cellular dynamics underlying different responses to immunotherapy in colorectal cancer
Authors: Yuqing Chen, Dongfang Wang, Yingjie Li, Lu Qi, Wen Si, Yufei Bo, Xueyan Chen, Zhaochen Ye, Hongtao Fan, Baolin Liu, Chang Liu, Li Zhang, Xiaoyan Zhang, Zhongwu Li, Linna Zhu, Aiwen Wu, Zemin Zhang
Journal: Cancer Cell (2024)

Expanding the efficacy of immune checkpoint blockade (ICB) in colorectal cancer (CRC) presses for a comprehensive understanding of treatment responsiveness. Here, we analyze multiple sequential single-cell samples from 22 patients undergoing PD-1 blockade to map the evolution of local and systemic immunity of CRC patients. In tumors, we identify coordinated cellular programs exhibiting distinct response associations. Specifically, exhausted T (Tex) or tumor-reactive-like CD8+ T (Ttr-like) cells are closely related to treatment efficacy, and Tex cells show correlated proportion changes with multiple other tumor-enriched cell types following PD-1 blockade. In addition, we reveal the less-exhausted phenotype of blood-associated Ttr-like cells in tumors and find that their higher abundance suggests better treatment outcomes. Finally, a higher major histocompatibility complex (MHC) II-related signature in circulating CD8+ T cells at baseline is linked to superior responses. Our study provides insights into the spatiotemporal cellular dynamics following neoadjuvant PD-1 blockade in CRC.
Lenvatinib (Lenv) plus tislelizumab (Tis) combined with or without transarterial chemoembolization (TACE) in first-line treatment of unresectable hepatocellular carcinoma (uHCC): A prospective, non-randomized, open-label, phase II cohort study.
Authors: Nan Zhang, Jiongyuan Li, Mingjian Piao, Chengjie Li, Ziyu Xun, Longhao Zhang, Yanyu Wang, Kai Liu, Shanshan Wang, Hanping Wang, Hai-Tao Zhao
Journal: Journal of Clinical Oncology (2024)

e16169 Background: The synergistic potential of programmed death protein-1 inhibitors and tyrosine kinase inhibitors in treating uHCC has been established. TACE, a cornerstone in uHCC therapy, primes the tumor microenvironment for immunotherapy by releasing neoantigens and inducing ischemia. This study explores the efficacy and safety of Lenv plus Tis, combined with or without TACE, in a first-line setting. Methods: This phase II study enrolled patients (pts) with pathologically and/or radiologically diagnosed uHCC eligible for embolization, with at least one measurable lesion, Child-Pugh class A/B, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Pts received Tis (200mg every 3 weeks) and Lenv (oral dose adjusted by weight: 8mg for &lt;60kg and 12mg for ≥60kg) with or without conventional TACE, as determined by the treating physician. The primary endpoint was the objective response rate (ORR), with secondary endpoints including overall survival (OS), progression-free survival (PFS), and disease control rate (DCR). Results: By the data cutoff on January 27, 2024, 37 pts were enrolled: 12 received Lenv+Tis (cohort 1), and 25 received Lenv+Tis+TACE (cohort 2). Median follow-up time was 10.66 months. The ORR was 33.3% in cohort 1 and 68.0% in cohort 2, with DCRs of 100% and 96%, respectively (mRECIST). Median OS was 10.85 months (95% CI, 4.76-16.95) for cohort 1 and 13.61 months (95%CI, NE-NE) for cohort 2. Median PFS was 10.85 months (95% CI, NE-NE) for cohort 1, and 11.86 months (95% CI, 6.49-16.73) for cohort 2. Grade 3-4 treatment-emergent adverse events (teAE) occurred in 50% of cohort 1 and 68% of cohort 2. No fatal adverse event was reported. The most common grade 3-4 teAE (incidence &gt;10%) were anaemia (17%) in cohort 1, and decreased platelet count (16%), hypertension (16%), rash (16%), fatigue (12%), elevated ALT (12%) in cohort 2. Conclusions: Both Lenv+Tis and Lenv+Tis+TACE showed promising efficacy and manageable safety in the first-line treatment of uHCC. More pts were recruiting to further prove these results. Clinical trial information: NCT05842317 . [Table: see text]
The efficacy and safety of donafenib combined with transcatheter arterial chemoembolization and anti-PD-1 antibodies as first-line therapy for hepatocellular carcinoma: A retrospective study.
Authors: Danjun Song, Weiyuan Hao, Fei Cao, Jun Luo, Liwen Guo, Zhewei Zhang, Jiaping Zheng
Journal: Journal of Clinical Oncology (2024)

e16178 Background: In Phase III study (ZGDH3), donafenib showed the survival benefit and better safety compared with sorafenib as the first-line treatment for uHCC. Recently, combination therapies have shown favorable results in patients with HCC. Some studies have shown that molecular targeted drugs combined with anti-PD1 antibodies and TACE exhibit improved anti-tumor efficacy compared with monotherapy. This study aimed to evaluate the efficacy and safety of the combination therapy of donafenib,anti-PD-1 antibodies and TACE as first-line treatments for HCC patients in the real world. Methods: This single-center retrospective study involved patients with histopathologically/cytologically or clinically confirmed HCC at Zhejiang Cancer Hospital between July 2021 and June 2023. Eligible patients were treated with donafenib (100 mg po bid) combined with TACE and anti-PD-1 antibodies until the point of disease progression, death, or intolerable toxicity. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) datas of patients were collected and analyzed according to the mRECIST, and the incidence of adverse events (AEs) was evaluated using CTCAE 5.0. Results: There were 34 patients in this study (Table). The median age was 64 years (IQR: 57, 69) at the data cut-off in January 2024, with 94.1% of the population being male and 82.4% having HBV infection. Of these patients, 5(14.7%) were classed as BCLC stage A, 11(32.3%) were classed as BCLC stage B, and 18 (52.9%) were BCLC stage C. The median PFS was 7.9 months (95%CI, 5.6–NA), and median OS was not reached, respectively, the 12-month PFS and OS rates were 46.9% (95%CI: 16.8%-72.5%) and 96.9% (95%CI: 79.8%-99.6%). The ORR and DCR for all patients were 73.5% and 97.1%, respectively, based on both mRECIST (CR 3 [8.8%], PR 22 [64.7%], SD 8 [23.5%]). The surgical conversion rate was 26.5%. Treatment-related adverse events (TRAE) of any grade were observed by 18 patients (52.9%), of which 4 patients (11.8%) had grade 3 TRAE. No grade 4 or 5 TRAE was observed. Conclusions: The study indicated that donafenib combined with TACE and anti PD-1 antibodies exhibited encouraging efficacy and favorable safety profile in patients with HCC. [Table: see text]
The safety of atezolizumab plus bevacizumab (atezo/bev) treatment in Chinese patients (pts) with hepatocellular carcinoma (HCC) with active hepatitis B virus (HBV) infection: Results from the TALENTop study.
Authors: Xiao-Dong Zhu, Hui-Chuan Sun, Feng Shen, Xueli Bai, Minshan Chen, Zhiyong Huang, Tianqiang Song, Yongyi Zeng, Ming Kuang, Bangde Xiang, Lianxin Liu, Deyu Li, Tianfu Wen, Yongjun Chen, Tao Peng, Xiangcheng Li, Jian Zhou, Jia Fan
Journal: Journal of Clinical Oncology (2024)

e16168 Background: HCC pts with active HBV infection were excluded from most clinical trials involving immune checkpoint inhibitors because of safety concerns. We are aiming to evaluate the treatment safety of atezo/bev treatment in the TALENTop study (NCT04649489) which enrolled a large number of pts with active HBV infection. Methods: The TALENTop study is to clarify whether liver resection may provide additional benefits in Chinese HCC pts with macrovascular invasion who responded to conversion therapy with atezo/bev. After two versions of protocol modification, pts with active HBV infection were allowed. This study is ongoing, and the primary analysis is expected later. The current analysis is to evaluate treatment safety in pts with active HBV infection in the induction phase when pts received 3 cycles of atezo/bev and 1 cycle of atezo monotherapy. We compared the adverse events (AEs) between pts with active (baseline serum HBV-DNA ≥500 IU/mL) or inactive HBV infection (HBV-DNA &lt; 500 IU/mL). All pts with detectable HBV-DNA or positive hepatitis B surface antigen received oral antiviral therapy throughout the study. Results: From Apr 2021 to Sep 2023, 296 pts were enrolled and completed induction phase therapy of atezo/bev. 274 pts (92.6%) had HBV-related HCC, and 133 pts (44.9%) had active HBV infection. The baseline characteristics were mainly balanced between groups, except pts with active HBV infection were younger (52 vs 56 years, P = 0.024), had larger tumor size (the diameter of target lesion 88.3 vs 78.1 mm, P = 0.007), and had higher album-bilirubin score (-2.62 vs -2.80, P &lt; 0.001). In the induction phase, the AEs of any grade were higher in pts with active HBV infection (88.0% vs 73.6%, P = 0.002). However, the grade ≥3 AEs (20.3% vs 17.8%, P = 0.584), grade ≥3 treatment-related AEs (12.0% vs 12.3%, P = 0.950) and serious AEs (15.0% vs 13.5%, P = 0.706) were comparable between pts with active and inactive HBV infection. Additionally, the incidence of liver-related AEs was also comparable, including increased AST (17.3% vs 16.0%), increased ALT (17.3% vs 14.7%), and increased bilirubin (10.5% vs 12.9%). AEs leading to treatment withdrawal were also comparable (6.0% vs 6.1%, P = 0.966). In pts with active HBV infection, 20.8% remained serum HBV-DNA ≥500 IU/mL at the end of cycle 4. Conclusions: Active HBV infection did not compromise the safety of atezo/bev therapy. These findings could support that, with concurrent use of oral antiviral therapy, pts with active HBV infection should be not excluded from clinical trials or delayed for immunotherapy. Clinical trial information: NCT04649489 .
Changing treatment patterns for hepatocellular carcinoma: A SEER-Medicare study.
Authors: Franklin Iheanacho, Angela Tramontano, Thomas Adam Abrams, Christopher Manz
Journal: Journal of Clinical Oncology (2024)

e16166 Background: Sorafenib was the first systemic therapy approved in 2005 for hepatocellular carcinoma (HCC), then 9 new therapies were approved between 2017-2022. No studies have evaluated treatment patterns of systemic therapy since these therapies became available. Methods: This retrospective cohort study used SEER-Medicare data to identify patients with a new diagnosis of HCC between 2014-2019 and associated comorbidity and treatment claims through 2020. Patients had continuous coverage with Medicare Parts A/B/D from 3 months before diagnosis to the earlier of 3 years, death or censoring. We excluded deaths reported by death certificate or autopsy. We used claims to identify receipt of local therapies (ablation, transplant, resection, transarterial bland/chemo/radioembolization, external/stereotactic radiation, brachytherapy) and all FDA-approved systemic therapies for HCC. We described cohort characteristics, treatment patterns, and overall survival (OS) and used Chi-squared statistics to compare treatment patterns and OS for patients diagnosed between 2014-17 vs 2018-19. Results: 11,799 patients were included (69.2% male, 76.9% White, median age: 71 years, 36.2% NAFLD, 44.1% Hepatitis C, 10.6% Hepatitis B, 28.1% alcoholic liver disease). Within one year of diagnosis, 76.3% of all patients received any local or systemic treatment, which did not change over time (2014-17: 76.1%, 2018-19: 76.6%, p=0.60). Receipt of local therapy within 1 year was unchanged (2014-17: 73%, 2018-19: 73.2%, p=0.77) and there were no clinically significant changes in treatment rates for specific local therapies. Receipt of systemic therapy in the first year decreased slightly (2014-17: 16.97%, 2018-19: 15.2%, p=0.012). First line systemic treatment changed drastically: 83.7% of patients diagnosed in 2014-17 received first-line sorafenib vs only 40.1% of those diagnosed 2018-19 (Table). Median overall survival for patients receiving no treatment, systemic therapies first or local therapies first was 1.9, 11 and 16.3 months, respectively. Among patients receiving systemic therapy first, survival from initiation of first line treatment increased from 9.1 to 11.2 months for patients diagnosed in 2014-17 vs 2018-19 (p= &lt;.0001). Conclusions: While overall local and systemic treatment rates have not changed substantially, more recent patients with HCC are more likely to receive first-line novel therapies over first-line sorafenib and associated survival has modestly increased. [Table: see text]
Efficacy and safety of TACE combined with ablation and regorafenib for unresectable hepatocellular carcinoma: A real-world study.
Authors: YiQi Xiong, WenFeng Gao, Jiang Long, CaiXia Hu, ChunWang Yuan, Yu Sun, QinSheng Shi, Bin Sun, YingHua Zhang, XiongWei Cui, MeiJun Hao, Jianjun Li, Yonghong Zhang
Journal: Journal of Clinical Oncology (2024)

e16170 Background: The purpose of our study was to determine the efficacy and safety of transarterial chemoembolization (TACE) combined with regorafenib as second-line therapy in patients with unresectable hepatocellular carcinoma (HCC). Methods: Patients with HCC at Barcelona Clinic Liver Cancer (BCLC) stage B or C who received the combined treatment of TACE, ablation, and regorafenib or regorafenib plus anti-PD-1 immune checkpoint inhibitors (ICIs) in Youan hospital between April 2020 to June 2023 were reviewed. The primary end-point was progression-free survival (PFS). Overall survival (OS), objective response rate (ORR), disease control rate (DCR), and toxicity were the secondary endpoints. Results: A total of 73 patients were enrolled in our study, including 63 (86.3%) males and 10 (13.7%) females. 16 (21.9%) patients had portal vein tumor thrombosis (PVTT) and 33 (45.2%) patients had extrahepatic metastasis. There were 53 (72.6%) patients with multiple tumor numbers and 23 (31.5%) patients with large tumors (≥30mm). All patients received TACE combined with regorafenib, while 37 (50.7%) patients plus ICIs and 36 (49.3%) patients not plus with ICIs. Besides, the majority of patients (N=61, 83.6%) in our cohort received ablation. The patients with AFP&gt;400U/L were 22 (20.1%). The average follow-up of the cohort was 24.6 months. The median PFS was 7.06 months (95%CI: 4.77-9.36 months) and the median OS was 23.47 months (9.79-37.15 months). Treatment response is shown in Table 2. According to mRECIST criteria, the ORR was 58.9% and the DCR was 91.8%, respectively. No adverse effects (AEs) were reported in the 11 patients in the study. The most common any-grade treatment-related AEs were hand-foot syndrome (21.9%), diarrhea (23.28%), and hypertension (21.9%). Grade≥3 treatment-related AE occurred in 12.3% of the patients. The most common grade 3 treatment-related AE was hypertension (5.48%). Conclusions: TACE combined with ablation and regorafenib is an effective, safe, and promising second-line treatment option for patients with unresectable HCC after progression from first-line therapy. [Table: see text]
Efficacy and safety of regorafenib and/or immune checkpoint inhibitors as a second-line therapy for advanced hepatocellular carcinoma: A real-world study from a single center.
Authors: Songtao Liu, Xueying Huang, Jingjing Chen, Qiaoxin Wei, Mei Liu
Journal: Journal of Clinical Oncology (2024)

e16165 Background: This study aimed to assess the efficacy and safety of regorafenib and/or immune checkpoint inhibitors (ICIs) as a second-line treatment in patients with pretreated hepatocellular carcinoma (HCC). Methods: Patients diagnosed with advanced HCC who had received regorafenib treatment in our hospital from January 2020 to November 2023 were reviewed. Overall survival (OS) was the primary endpoint. Progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and toxicity were the secondary end points. Results: Forty-five patients were included with a median age of 61 (31-83) years. Thirty-two patients (71.1%) were in Barcelona Clinic Liver Cancer (BCLC) stage C. Twenty-three patients (51.1%) had extrahepatic metastasis. ICIs were applied to 30 patients (66.7%) at the use of regorafenib. Local treatments were applied to 17 patients (37.8%). The median OS was 14.5 (11.3, 26.4) months in all patients. Regorafenib plus ICIs had a longer survival than regorafenib alone (20.5 [11.6, NA] vs 11.3 [3.0, 13.9] months, P = 0.019). Local treatment had no obvious effect. The median PFS was 6.8 (4.5, 11.7) months in all patients. The median PFS was 9.7 (4.6, 14.5) months in regorafenib plus ICIs that was longer than regorafenib alone with 3.0 (2.0, 8.0) months. Local treatment only showed a trend of prolongation (11.8 [2.5, 22.6] vs 4.7 [3.5, 9.7] months, P = 0.059). The 1-year OS and PFS were 43.2% and 20.0%, respectively. ORR and DCR was 29.0% and 71.0% according to mRECIST criteria, respectively. The most common any-grade treatment-related adverse events (TRAEs) were rash/itching (41.3%), hand-foot syndrome (19.6%), and anorexia (13.0%). Grade≥3 TRAEs occurred in 8.9% (4/45) of the patients and hypertension (4.4%) had the highest proportion. Conclusions: Regorafenib plus ICIs therapy is an effective promising regimen regardless of first-line treatments in advanced HCC. Combined with local treatment only showed a trend of PFS, further prospective research is needed.
Plasma growth hormone as a prognostic biomarker to durvalumab and tremelimumab in patients with advanced hepatocellular carcinoma.
Authors: Shadi Chamseddine, Michael Brian LaPelusa, Lianchun Xiao, Yehia I. Abugabal, Sunyoung S. Lee, Zishuo Ian Hu, Zishuo Ian Hu, Rikita Hatia, Manal Hassan, James C. Yao, Dan G. Duda, Saumil Datar, Hesham M. Amin, Ahmed Omar Kaseb
Journal: Journal of Clinical Oncology (2024)

e16161 Background: In this study, we explored the potential of plasma growth hormone (GH) as a prognostic biomarker in patients with advanced HCC treated with durvalumab plus tremelimumab (D+T). Methods: In this study, we included 24 patients with advanced HCC who received D+T at MD Anderson Cancer Center between 2022 and 2023. Plasma GH levels were measured from prospectively collected blood samples from 16 of the 24 patients and were correlated with progression-free survival (PFS) and overall survival (OS). The cutoff for normal GH levels in women and men was defined as ≤3.7 μg/L and ≤0.9 μg/L, respectively. The Kaplan-Meier method was employed to compute the median OS and PFS, while the Log-rank test was applied to compare the survival outcomes between the GH-high and GH-low groups. Results: Twenty-four patients were included in this analysis, four female and twenty male, with a median age of 66.5 years. Of these 24 patients, 16 had GH levels available for analysis. At the time of the analysis, the 6-month OS rate was 100% among GH-low patients (6 patients) and 30% among GH-high patients (10 patients). OS was significantly longer in GH-low patients (not evaluable) compared to GH-high patients (3.94 months) (p = 0.030). PFS was also significantly longer in GH-low patients (not evaluable) compared to the GH-high patients (1.87 months) (p = 0.036). Conclusions: Plasma GH is a prognostic biomarker in patients with advanced HCC treated with D+T. Given the relatively small patient cohort size, this finding should be further validated in larger randomized clinical trials in advanced HCC patients.
Des-gamma-carboxy prothrombin (DCP) as a prognostic biomarker in patients with advanced hepatocellular carcinoma treated with atezolizumab/bevacizumab.
Authors: Elizabeth Conner, Jeremy Chang, Adam Burgoyne
Journal: Journal of Clinical Oncology (2024)

e16167 Background: Causes of variable disease response to first-line treatment with atezolizumab plus bevacizumab in patients with advanced hepatocellular carcinoma (HCC) remain unclear. Identifying tumor markers that predict treatment response and provide prognostic information may help clinicians optimize treatment strategies and patient outcomes. The role of des-gamma-carboxy prothrombin (DCP) is not well established in Hepatitis B Virus non-endemic areas. This study aimed to investigate DCP as a predictive biomarker of treatment response as well as explore prognostic implications of DCP in patients with advanced HCC. Methods: This single-center retrospective analysis evaluated DCP and radiographic response in patients with advanced HCC who received atezolizumab/bevacizumab in the first-line setting. DCP was measured at the time of best response, determined by radiographic evaluation, and compared to day one of atezolizumab/bevacizumab initiation. Elevated DCP was defined as &gt; = 7.5 ng/mL. DCP response was defined as a decrease of &gt; = 50% at response assessment compared with baseline. Comparisons of treatment effects were performed using two-tailed Fisher Exact Probability Test. Overall survival (OS) was defined as the interval between the first treatment and either the date of death or the last follow-up visit. OS was analyzed using the Kaplan–Meier method and compared between groups using the log-rank test. Results: A total of 53 patients with advanced HCC treated with atezolizumab/bevacizumab were included. Radiographic treatment responses were complete response 3.8%, partial response 22.6%, stable disease 52.8% and progression of disease 20.8%, respectively. On day one of treatment 70% of patients had an elevated DCP. Patients with DCP response had ORR of 69% (odds ratio, 15.75; 95% CI, 3.50 – 70.9; p = 0.0002) and disease control rate of 100% (p = 0.047). Conversely, patients with &gt; = 50% increase in DCP at response evaluation compared to day one of treatment had ORR of 4.5% and no response rate of 95% (p = 0.0035). Furthermore, patients who had &gt; = 50% increase in DCP had median OS of 15.4 months compared to patients without &gt; = 50% increase in DCP who had median OS of 28.4 months (HR = 2.48; 95% CI, 1.035 – 5.93; p = 0.042). There was no difference in ORR, or OS, between patients who had elevated DCP on day one of treatment and those who did not. Conclusions: DCP response correlates with objective radiographic response in patients with advanced HCC treated with atezolizumab plus bevacizumab in the first-line setting. DCP increase of &gt; = 50% correlates with decreased median OS and may serve as a negative prognostic biomarker in such patients.