Importance of optimizing duration of adjuvant immune checkpoint inhibitor therapy to treat postoperative hepatocellular carcinoma after conversion therapy: a case report
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PROVIDER: S-EPMC10641292 | biostudies-literature | 2023 Nov
REPOSITORIES: biostudies-literature
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Project description:Hepatocellular carcinoma (HCC) is the fifth most common cancer, and its incidence is rapidly increasing in North America and Western Europe as well as South-East Asia. Patients with advanced stage HCC have very poor outcomes; therefore, the discovery of new innovative approaches is urgently needed. Cancer immunotherapy has become a game-changer and revolutionized cancer treatment. A comprehensive understanding of tumor-immune interactions led to the development of immune checkpoint inhibitors (ICIs) as new therapeutic tools, which have been used with great success. Targeting immune checkpoint molecules such as programmed cell death-1 (PD-1) and cytotoxic T lymphocyte-associated protein-4 (CTLA-4) reinvigorates anti-tumor immunity by restoring exhausted T cells. Despite their effectiveness in several types of cancer, of the many immune suppressive mechanisms limit the efficacy of ICI monotherapy. Radiation therapy (RT) is an essential local treatment modality for a broad range of malignancies, and it is currently gaining extensive attention as a promising combination partner with ICIs because of its ability to trigger immunogenic cell death. The efficacy of combination approaches using RT and ICIs has been well documented in numerous preclinical and clinical studies on various types of cancers but not HCC. The application of ICIs has now expanded to HCC, and RT is recognized as a promising modality in HCC. This review will highlight the current roles of PD-1 and CTLA-4 therapies and their combination with RT in the treatment of cancers, including HCC. In addition, this review will discuss the future perspectives of the combination of ICIs and RT in HCC treatment.
| S-EPMC6543238 | biostudies-literature
Project description:Background and aimStandardized approach to postoperative adjuvant therapy for hepatocellular carcinoma (HCC) remains elusive. This study endeavors to examine the effects of postoperative PD-1 adjuvant therapy on the short-term and long-term prognosis of patients at a heightened risk of post-surgical recurrence.MethodsThe data of HCC patients who underwent hepatectomy at our center from June 2018 to March 2023 were collected from the hospital database. Propensity score matching (PSM) was employed to perform a 1:1 match between the postoperative anti-PD-1 antibody group and the postoperative non-anti-PD-1 antibody group. Kaplan-Meier method was utilized to compare the overall survival (OS) and recurrence-free survival (RFS) between the two groups. Cox regression analysis was conducted to identify the prognostic factors affecting patient outcomes. Subgroup analyses were performed for different high-risk factors.ResultsAmong the 446 patients included in the study, 122 patients received adjuvant therapy with postoperative anti-PD-1 antibodies. After PSM, the PD-1 group had postoperative 1-year, 2-year, 3-year, and 4-year OS rates of 93.1%, 86.8%, 78.2%, and 51.1%, respectively, while the non-PD-1 group had rates of 85.3%, 70.2%, 47.7%, and 30.0%. The PD-1 group had postoperative 1-year, 2-year, 3-year, and 4-year RFS rates of 81.7%, 77.0%, 52.3%, and 23.1%, respectively, whereas the non-PD-1 group had rates of 68.4%, 47.7%, and 25.8% in 1-year, 2-year, 3-year. A multifactorial Cox regression analysis revealed that postoperative PD-1 use was a prognostic protective factor associated with OS and RFS. Subgroup analysis results indicated that HCC patients with high recurrence risks significantly benefited from postoperative anti-PD-1 antibody treatment in terms of OS and RFS.ConclusionFor HCC patients with high-risk recurrence factors and undergoing hepatectomy, postoperative adjuvant therapy with anti-PD-1 antibodies can effectively improve their survival prognosis.
| S-EPMC10766105 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality in Taiwan. Some patients with HCC are diagnosed with macrovascular invasion (MVI), which is associated with a poorer prognosis. In Taiwan, sorafenib is the first-line therapy for patients with advanced HCC. However, the efficacy of adjuvant sorafenib therapy remains unclear for the subset of patients with HCC and MVI who are eligible for surgery. Therefore, we investigated the potential benefit of adjuvant sorafenib therapy for patients with HCC and MVI after surgery. Our study showed that the lack of improved PFS or OS of adjuvant sorafenib challenged the therapeutic benefit of postoperative sorafenib. Alcohol consumption and an α-fetoprotein level of ≥400 ng/mL were independent predictors of overall survival (OS); however, adjuvant sorafenib therapy was not a predictor of progression-free survival (PFS) or OS. In conclusion, our study indicated that adjuvant sorafenib therapy did not provide PFS or OS benefits in patients with HCC and MVI.
| S-EPMC10742418 | biostudies-literature
Project description: Not available
| S-EPMC10282663 | biostudies-literature
Project description:ObjectiveThe role of adjuvant therapy in small bowel adenocarcinoma (SBA), a rare malignancy with a poor prognosis, is controversial. The purpose of this article is to investigate the impact of adjuvant therapy on the survival of patients with SBA in a meta-analysis.MethodsWe performed a comprehensive search of PubMed, EMBASE and the Cochrane Library database between 2010 and 2017. Hazard ratios (HR) with 95% confidence intervals (95%CI) were used to assess the effect of adjuvant chemotherapy and/or radiation treatment after curative surgery in patients with SBA. Moreover, impact of age, sex, stage, differentiation, lymph node involvement, and margin status was also evaluated.ResultsWe included 15 studies to evaluate the effect of adjuvant therapy on the survival of patients with SBA. The pooled HR of overall survival (OS) involving 5986 patients showed that adjuvant therapy did not have a statistically significant effect on the survival of patients with SBA (pooled HR = 0.89, 95% CI = 0.73-1.09, p = 0.25). Further, 607 patients with duodenal adenocarcinoma (DA) had similar results (pooled HR = 0.96, 95% CI = 0.75-1.23, p = 0.77). Similarly, adjuvant treatment vs. non-adjuvant treatment in terms of disease-free survival (DFS) or relapse-free survival (RFS) showed the same results (pooled HR = 0.89, 95% CI = 0.64-1.23, p = 0.48). However, we found that adjuvant therapy resulted in favorable postoperative survival in Europe according to the subgroup analysis (pooled HR = 0.63, 95% CI = 0.5-0.8, p = 0.0002). In addition, the pooled HR shows that stage, differentiation, lymph node involvement, and margin status were related to the OS of patients with SBA.ConclusionPatients with SBA who received adjuvant therapy after surgery did not receive a significant survival benefit. Adjuvant therapy may be more useful in advanced cancer or metastatic patients.
| S-EPMC6086425 | biostudies-literature
Project description:Glioblastoma (GBM) is the most prevalent and aggressive adult primary cancer in the central nervous system. Therapeutic approaches for GBM treatment are under intense investigation, including the use of emerging immunotherapies. Here, we propose an alternative approach to treat GBM through reprogramming proliferative GBM cells into non-proliferative neurons. Retroviruses were used to target highly proliferative human GBM cells through overexpression of neural transcription factors. Immunostaining, electrophysiological recording, and bulk RNA-seq were performed to investigate the mechanisms underlying the neuronal conversion of human GBM cells. An in vivo intracranial xenograft mouse model was used to examine the neuronal conversion of human GBM cells. We report efficient neuronal conversion from human GBM cells by overexpressing single neural transcription factor Neurogenic differentiation 1 (NeuroD1), Neurogenin-2 (Neurog2), or Achaete-scute homolog 1 (Ascl1). Subtype characterization showed that the majority of Neurog2- and NeuroD1-converted neurons were glutamatergic, while Ascl1 favored GABAergic neuron generation. The GBM cell-converted neurons not only showed pan-neuronal markers but also exhibited neuron-specific electrophysiological activities. Transcriptome analyses revealed that neuronal genes were activated in glioma cells after overexpression of neural transcription factors, and different signaling pathways were activated by different neural transcription factors. Importantly, the neuronal conversion of GBM cells was accompanied by significant inhibition of GBM cell proliferation in both in vitro and in vivo models. These results suggest that GBM cells can be reprogrammed into different subtypes of neurons, leading to a potential alternative approach to treat brain tumors using in vivo cell conversion technology.
| S-EPMC8330525 | biostudies-literature
Project description: Not available
| S-EPMC10282679 | biostudies-literature
Project description:We previously described adoptive immunotherapy (AIT) with cytotoxic T lymphocytes (CTLs) stimulated by the mucin 1 (MUC1)-expressing human pancreatic cancer cell line YPK-1 (MUC1-CTLs) and demonstrated that MUC1-CTLs might prevent liver metastasis. In the present study, we combined gemcitabine (GEM) and AIT for the treatment of pancreatic cancer.A total of 43 patients who underwent radical pancreatectomy received treatment with MUC1-CTLs and GEM. After surgery, MUC1-CTLs were induced and administered intravenously 3 times, and GEM administered according to the standard regimen for 6 months. The patients whose relative dose intensity of GEM was 50% or more and who received 2 or more MUC1-CTL treatments were used as the adequate treatment group (n = 21).In the adequate treatment group, disease-free survival was 15.8 months, and overall survival was 24.7 months. Liver metastasis was found only in 7 patients (33%), and local recurrence occurred in 4 patients (19%). The independent prognostic factor of long-term disease-free survival on multivariate analysis was the average number of CTLs administered (P = 0.0133).The combination therapy with AIT and GEM prevented liver metastasis and local recurrence. Moreover, the disease free-survival was improved in patients who received sufficient CTLs.
| S-EPMC5555975 | biostudies-other
Project description:IntroductionXiaoyaosan (XYS), a traditional Chinese formula, not only has good antitumor effects but also attenuates distress, anorexia, and quality of life (QoL) by regulating neurology, the microbiota, immunology, and oxidative stress. This study aimed to assess the effect of XYS on QoL, psychological pressure, and spiritual well-being in breast cancer patients undergoing adjuvant chemotherapy.MethodsThis prospective cohort study enrolled 176 postoperative breast cancer patients who received adjuvant chemotherapy combined with (n = 81) or without (n = 95) XYS for comparison. The Quality-of-Life Questionnaire Core-30 (QLQ-C30), Hospital Anxiety and Depression Scale (HADS), University of California Los Angeles (UCLA-LS), and Functional Assessment of Chronic Illness Therapy-Spiritual Well-being (FACIT-Sp) scores were evaluated before adjuvant chemotherapy (T0) and after the first (T1), second (T2), third (T3), and fourth cycles (T4) of adjuvant chemotherapy.ResultsXYS improved the QLQ-C30 score at T2 (p = 0.043), T3 (p = 0.021), and T4 (p = 0.040) and the QLQ-C30 score at T4 (p = 0.027); moreover, XYS attenuated the QLQ-C30 score at T2 (p = 0.040), T3 (p = 0.023), and T4 (p = 0.027). Regarding distress, XYS reduced the HADS-anxiety score at T2 (p = 0.010), T3 (p = 0.025), and T4 (p = 0.019) and the HADS-defined anxiety score at T3 (p = 0.038). XYS also decreased the HADS-depression score at T2 (p = 0.016), T3 (p = 0.018), and T4 (p = 0.017) and the HADS-defined depression rate at T2 (p = 0.047), T3 (p = 0.012), and T4 (p = 0.013). In addition, XYS decreased the UCLA-LS at T2 (p = 0.023) but enhanced the FACIT-Sp at T2 (p = 0.029) and T4 (p = 0.026). Furthermore, after adjustment via propensity score matching, most of the significant findings remained.DiscussionThe addition of XYS to adjuvant chemotherapy improved QoL, psychological health, and spiritual well-being in breast cancer patients.
| S-EPMC11344260 | biostudies-literature
Project description: Not available
| S-EPMC7791205 | biostudies-literature