PD-1 inhibitors plus anti-angiogenic therapy with or without intensity-modulated radiotherapy for advanced hepatocellular carcinoma: A propensity score matching study

Su, Ke; Guo, Lu; Ma, Wenqiong; Wang, Jing; Xie, Yunchuan; Rao, Mingyue; Zhang, Jianwen; Li, Xueting; Wen, Lianbin; Li, Bo; Yang, Xiaoli; Song, Yanqiong; Huang, Weihong; Chi, Hao; Gu, Tao; Xu, Ke; Liu, Yanlin; Chen, Jiali; Wu, Zhenying; Jiang, Yi; Li, Han; Zeng, Hao; Wang, Pan; Feng, Xunjie; Chen, Siyu; Yang, Binbin; Jin, Hongping; He, Kun; Han, Yunwei

doi:10.3389/fimmu.2022.972503

Cited by 36 publications

(34 citation statements)

References 27 publications

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“… 4 , 5 , 31 Furthermore, our previous research discovered that programmed death 1 (PD-1) inhibitors combined with anti-angiogenic therapy and intensity-modulated radiotherapy can extend the OS of advanced HCC patients to 20.1 months. 32 Moreover, selective internal radiotherapy (SIRT) extended the OS of advanced HCC patients to 8.8 months. 33 Zhang et al found that the mOS of inoperable HCC patients receiving TACE-lenvatinib was 30.5 months.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Lactate Dehydrogenase and Alkaline Phosphatase as Predictive Biomarkers in the Prognosis of Hepatocellular Carcinoma and Development of a New Nomogram

Su¹,

Huang²,

Li³

et al. 2023

JHC

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Background Tumor proliferation is frequently accompanied by aberrant enzyme production. We aim to investigate the potential predictive value of both plasma alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in patients with HCC and to develop a nomogram to assess the prognosis of HCC. Methods The trial involved 2327 patients between May 2015 and March 2022. Within 7 days of enrollment, the levels of ALP and LDH were measured, and their association with survival was assessed. And we had developed and validated a new nomogram based on ALD and ALP. Results Using X-tile software, the optimal cut-off values were determined to be ALP = 172 U/L and LDH = 241 U/L. The high ALP (≥ 172), LDH (≥ 241), and ALP/LDH (≥ 0.91) groups had lower median overall survival (mOS) than low ALP (< 172), LDH (< 241), and ALP/LDH (< 0.91) groups (all p < 0.001). In addition, elevated ALP and LDH levels are independent negative prognostic indicators. Moreover, we established that the area under the curve (AUC) values of the predicted 1-, 2-, and 3-year survival rates of receiver operating characteristic curve (ROC) based on the nomogram were 0.79, 0.77, and 0.74, respectively. In addition, the calibration curves and decision curve analyses (DCA) demonstrated that this model possessed strong predictive capability. Conclusion ALP, LDH and ALP/LDH can be employed as biomarkers for predicting the prognosis of HCC. Furthermore, the nomograph based on ALH and ALP demonstrates good HCC prediction performance. For HCC patients with high ALH or ALP or ALP/LDH, close surveillance program and adjuvant therapy should be considered.

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Section: Discussionmentioning

confidence: 99%

Evaluation of Lactate Dehydrogenase and Alkaline Phosphatase as Predictive Biomarkers in the Prognosis of Hepatocellular Carcinoma and Development of a New Nomogram

Su¹,

Huang²,

Li³

et al. 2023

JHC

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“…Immunotherapy can greatly activate the autoimmunity of HCC patients but the therapeutic performance in clinical trials remain unsatisfactory till now ( Chen et al, 2022 ). For example, the objective response rate of HCC was still low in the patient received combination therapy of PD-1/PD-L1 inhibitors and targeted drugs ( Su et al, 2022b ). In this work, we analyzed the tumor microenvironment and found that the prognosis-related gene DAPK1 was correlated with several immune cells, immunostimulators and targeting drugs.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel prognostic biomarkers in the TF-enhancer-target regulatory network in hepatocellular carcinoma and immune infiltration analysis

Yan

Shao

et al. 2023

Front. Genet.

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Background: Hepatocellular carcinoma (HCC) remains notorious for its high malignancy, poor prognosis and high mortality. The exploration of novel therapeutic agents for HCC has remained challenging due to its complex aetiology. Therefore, it is necessary to elucidate the pathogenesis and mechanism of HCC for clinical intervention.Methods: We collected data from several public data portals and systematically analysed the association between transcription factors (TFs), eRNA-associated enhancers and downstream targets. We next filtered the prognostic genes and established a novel prognosis-related nomogram model. Moreover, we explored the potential mechanisms of the identified prognostic genes. The expression level was validated by several ways.Results: We first constructed a significant TF-enhancer-target regulatory network and identified DAPK1 as a coregulatory differentially expressed prognosis-related gene. We combined common clinicopathological factors and built a prognostic nomogram model for HCC. We found that our regulatory network was correlated with the processes of synthesizing various substances. Moreover, we explored the role of DAPK1 in HCC and found that it was associated with immune cell infiltration and DNA methylation. Several immunostimulators and targeting drugs could be promising immune therapy targets. The tumor immune microenvironment was analyzed. Finally, the lower DAPK1 expression in HCC was validated via the GEO database, UALCAN cohort, and qRT-PCR.Conclusion: In conclusion, we established a significant TF-enhancer-target regulatory network and identified downregulated DAPK1 as an important prognostic and diagnostic gene in HCC. Its potential biological functions and mechanisms were annotated using bioinformatics tools.

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“…After eliminating duplicates (n = 257), titles and abstracts were browsed and filtered. The full text of the remaining 42 studies was screened, and 10 articles [13][14][15][16][17][18][19][20][21][22] were finally included according to the inclusion criteria. The literature review and identification processes are shown in Figure 1.…”

Section: Study Selectionmentioning

confidence: 99%

“…Nine included studies [13,[15][16][17][18][19][20][21][22] reported ORR and DCR as clinical outcomes. The pooled ORR after PD1/ PDL1 inhibitors combined with RT and anti-angiogenic agents (RIT) was 59% (95% CI: 48-70%, P = .00), whereas the pooled DCR was 92% (95% CI: 81-103%, P = .00) (Figs.…”

Section: Tumor Responsementioning

confidence: 99%

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Efficacy and safety of PD1/PDL1 inhibitors combined with radiotherapy and anti-angiogenic therapy for solid tumors: A systematic review and meta-analysis

Xian

Zhong

et al. 2023

Medicine

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Background: The triple combination of programmed cell death 1 (PD1)/programmed cell death ligand 1 (PDL1) inhibitors, radiotherapy (RT), and anti-angiogenesis agents has been widely used in the treatment of solid tumors and has shown positive efficacy. We conducted a meta-analysis to evaluate the efficacy and safety of PD1/PDL1 inhibitors combined with anti-angiogenic agents and RT for the treatment of solid cancers.Methods: A systematic search of PubMed, Embase, Cochrane Library, and Web of Science databases was conducted from inception to October 31, 2022. Studies involving patients with solid cancers who received PD1/PDL1 inhibitors combined with RT and anti-angiogenic agents treatment that reported overall response rate, complete remission rate, disease control rate, and adverse events (AEs) were included. A random-effects or fixed-effects model was used for the pooled rates, and 95% confidence intervals (CIs) were determined for all outcomes. The quality of the included literature was assessed using the methodological index for nonrandomized studies critical appraisal checklist. Egger test was used to assess the publication bias in the included studies.Results: Ten studies (4 nonrandomized controlled trials and 6 single-arm trials), including 365 patients, were identified and included in the meta-analysis. The pooled overall response rate after treatment with PD1/PDL1 inhibitors combined with RT and anti-angiogenic agents was 59% (95% CI: 48-70%), whereas the disease control rate and complete remission rate were 92% (95% CI: 81-103%) and 48% (95% CI: 35-61%), respectively. Moreover, the meta-analysis showed that compared with tripleregimen, monotherapy or dual-combination treatment did not improve overall survival (hazard ratio = 0.499, 95% CI: 0.399-0.734) and progression-free survival (hazard ratio = 0.522, 95% CI: 0.352-0.774). The pooled rate of grade 3 to 4 AEs was 26.9% (95% CI: 7.8%-45.9), and the common AEs to triple therapy included leukopenia (25%), thrombocytopenia (23.8%), fatigue (23.2%), gastrointestinal discomfort (22%), increased alanine aminotransferase (22%), and neutropenia (21.4%). Conclusion:In the treatment of solid tumors, PD1/PDL1 inhibitors combined with RT and anti-angiogenic drugs achieved a positive response and better survival benefits than monotherapy or dual therapy. In addition, combination therapy is tolerable and safe.Registration: PROSPERO ID: CRD42022371433.Abbreviations: AEs = adverse events, CI = confidence interval, CRR = complete remission rate, DCR = disease control rate, HCC = hepatocellular carcinoma, HRs = hazard ratios, NPC = nasopharyngeal carcinoma, NSCLC = non-small-cell lung cancer, ORR = overall response rate, OS = overall survival, PD1 = programmed cell death 1, PD-L1 = programmed cell death ligand 1, PFS = progression-free survival, RCC = renal cell cancer, RIT = PD1/PDL1 inhibitors combined with RT and anti-angiogenic agents, RITC = RIT plus chemotherapy, RT = radiotherapy.

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PD-1 inhibitors plus anti-angiogenic therapy with or without intensity-modulated radiotherapy for advanced hepatocellular carcinoma: A propensity score matching study

Cited by 36 publications

References 27 publications

Evaluation of Lactate Dehydrogenase and Alkaline Phosphatase as Predictive Biomarkers in the Prognosis of Hepatocellular Carcinoma and Development of a New Nomogram

Evaluation of Lactate Dehydrogenase and Alkaline Phosphatase as Predictive Biomarkers in the Prognosis of Hepatocellular Carcinoma and Development of a New Nomogram

Identification of novel prognostic biomarkers in the TF-enhancer-target regulatory network in hepatocellular carcinoma and immune infiltration analysis

Efficacy and safety of PD1/PDL1 inhibitors combined with radiotherapy and anti-angiogenic therapy for solid tumors: A systematic review and meta-analysis

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