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  • 1
    Online Resource
    Online Resource
    Discussing POLST-facilitated hospice care enrollment in patients with terminal cancer
    Springer Science and Business Media LLC ; 2022
    In:  Supportive Care in Cancer Vol. 30, No. 9 ( 2022-09), p. 7431-7438
    Details
    In: Supportive Care in Cancer, Springer Science and Business Media LLC, Vol. 30, No. 9 ( 2022-09), p. 7431-7438
    Type of Medium: Online Resource
    ISSN: 0941-4355 , 1433-7339
    URL: Article
    DOI: 10.1007/s00520-022-07143-x
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1463166-0
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  • 2
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    Rhein augments ATRA-induced differentiation of acute promyelocytic leukemia cells
    Elsevier BV ; 2018
    In:  Phytomedicine Vol. 49 ( 2018-10), p. 66-74
    Details
    In: Phytomedicine, Elsevier BV, Vol. 49 ( 2018-10), p. 66-74
    Type of Medium: Online Resource
    ISSN: 0944-7113
    URL: Article
    DOI: 10.1016/j.phymed.2018.06.027
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
    detail.hit.zdb_id: 2040195-4
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  • 3
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    Efficacy and safety of liposomal irinotecan plus fluorouracil/leucovorin after progression on conventional irinotecan-containing chemotherapy for metastatic pancreatic adenocarcinoma.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 3_suppl ( 2021-01-20), p. 382-382
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 3_suppl ( 2021-01-20), p. 382-382
    Abstract: 382 Background: Liposomal irinotecan (nal-IRI) plus fluorouracil/leucovorin (5-FU/LV) has demonstrated its clinical benefit in patients with metastatic pancreatic adenocarcinoma (mPAC) who progressed on prior gemcitabine-based chemotherapy. However, its role in patients who previously treated with conventional irinotecan has not been investigated. We analyzed clinical outcomes of nal-IRI + 5-FU/LV in mPAC patients after progression on conventional irinotecan-containing chemotherapy. Methods: In this multicenter retrospective analysis, a total of 35 patients with mPAC who received nal-IRI + 5-FU/LV after progression on irinotecan-containing regimen, between January 2017 and March 2020, were included. The ratio of time-to-progression (TTP) with nal-IRI + 5-FU/LV to TTP with conventional irinotecan (TTPr) was correlated with duration and cumulative dose of prior conventional irinotecan. Results: The median age was 58 years (range, 35-73) and 16 patients (46%) were male. All patients received prior irinotecan as the component of FOLFIRINOX. The median duration of prior irinotecan was 4.6 months (range, 0.5-16.8) and median cumulative dose of prior irinotecan was 1230 mg (range, 150-4650). Objective response rate of nal-IRI + 5-FU/LV was 2.9% (1 partial response) and stable disease was achieved in 31.4% (n = 11). With median follow-up duration of 9.2 months [95% CI, 7.8-10.5], the median PFS and OS were 2.0 months [95% CI, 1.4-2.6] and 4.4 months [95% CI, 3.6-5.7], respectively. 6-month PFS rate was 16.3% and OS rate was 37.5%. The median TTPr was 0.41 (range 0.07-2.07) and this showed negative correlation between cumulative dose of prior irinotecan (R = -0.37, p = 0.041). There was a tendency for the negative correlation between TTPr and duration of prior irinotecan (R = -0.35, p = 0.062). Most common grade 3-4 toxicities were neutropenia (20%) and fatigue (8.6%). Conclusions: Nal-IRI + 5-FU/LV showed only modest efficacy for mPAC patients who progressed on conventional irinotecan-containing chemotherapy. Cumulative dose of prior conventional irinotecan may be correlated with the efficacy of nal-IRI + 5-FU/LV.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.3_suppl.382
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 4
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    The clinical feasibility of circulating tumor DNA alterations in patients with advanced hepatocellular carcinoma.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 4110-4110
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 4110-4110
    Abstract: 4110 Background: Need for individualized treatment based on tumor attributes is being reinforced with the rapid development of targeted therapies and immune checkpoint inhibitors for hepatocellular carcinoma (HCC). Lack of mandatory tissue biopsy for the diagnosis of HCC, continues to be a challenge for development of precision medicine for HCC compared to other solid tumors. Liquid biopsy enables comprehensive genomic profiling of circulating tumor DNA (ctDNA) shed from tumors into the circulation. This could compensate for the lack of tissue-based analysis in HCC providing a non-invasive and safer option for genomic profiling. This study aims to address the concordance between commercially available ctDNA and tissue genomic profiling in patients with advanced HCC and to assess the feasibility of liquid biopsy in the treatment of patients with HCC. Methods: Patients subjected to tissue-based next-generation sequencing (NGS) before systemic therapy for advanced HCC at CHA Bundang Medical Center from June 2020 to October 2022 and also had sufficient plasma samples available for ctDNA analysis were included. Oncomine Comprehensive Assay (OCA) ThermoFisher was used for tissue-based NGS and Guardant360 for ctDNA based NGS. For the concordance assessment for the same patient, paired samples of ctDNA and tumor tissue, we investigated the common targeted regions across both the panels. Results: Out of hundred thirty patients included in this study, 98% percent of ctDNA samples for these patients were successfully sequenced; ctDNA were detected in 88% of the samples. For the assessment of concordance between intra-patient ctDNA and tumor tissues, we investigated only clinically important (AMP/ASCO/CAP guidelines tier 1 or 2) variants. When we considered the variants detected in tissues as true positive, the concordance between the mutations detected from ctDNA and tissue samples indicated 68.9% sensitivity and 63.1% positive predictive value (PPV). In ctDNA, targetable alterations were detected in 16.9% of samples, such as ARID1A mutations (7.7%), PTEN mutations (6.9%), PIK3CA hotspot mutations (1.5%), RAS mutations (1.5%), and one RET fusion (0.8%). Regarding the concordance between ctDNA and tumor tissue, the sensitivity for mutation was high for RAS mutation (100.0%), PTEN mutations (100.0%), and ARID1A mutations (75.0%) but low for PIK3CA hotspot mutations (0.0%). One RET fusion was identified only in ctDNA. Conclusions: ctDNA-based genotyping demonstrated clinically acceptable concordance with tissue genomic profiling in patients with advanced HCC. Thus, liquid biopsy using ctDNA help address any challenges associated with the limited use of tissue-based genomic profiling in HCC. Investigation of time between blood and tissue collection and the impact it has on concordance is ongoing.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.4110
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 5
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    A phase II clinical trial to study the use of cabozantinib (cabo) in patients with hepatocellular carcinoma (HCC) post immunotherapy treatment.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 4_suppl ( 2023-02-01), p. 571-571
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 4_suppl ( 2023-02-01), p. 571-571
    Abstract: 571 Background: There has been a lack of prospective clinical trial data on subsequent treatment after immune checkpoint inhibitor (ICI)-based treatment in HCC. To address this question, we designed and completed a phase II multicentred study to evaluate the use of cabo in HCC after prior ICI-based treatment. Methods: This is an investigator-initiated clinical trial involving 3 academic centres in Hong Kong and Korea. Key eligibility criteria include confirmed diagnosis of HCC; refractoriness to prior ICI-based treatment; duration of prior ICI-based treatment ≥2 months; Child's A liver function; ECOG performance status 0-2; maximal 2 lines of therapy. All patients (pts) were started cabo at 60mg once daily to progressive disease or intolerable toxicity. The primary endpoint is progression-free survival (PFS). Other secondary endpoints including response rate (RR) according to the RECIST, overall survival (OS) and treatment-related adverse event (TRAE). Total sample size is 48 (one-sided alpha 0.05; power 80%). Results: Total 48 pts were recruited from Oct 2020 to May 2022. Data were frozen on 1 Aug 2022 for analyses. The median follow-up was 11.2m. Seven (14.9%) pts remained on treatment; 1pt was found to ineligible and excluded from the analysis. The median age is 61 (Range 36-83). Aetiology of HCC: HBV 34 (72.3%); HCV 2 (4.3%); alcoholic 8 (17%); Most pts have BCLC stage C (93.6%). All pts have Child’s A liver function. Total 39 (83%) pts receive ICI-based first-line therapy, and 19 (40.4%) pts have prior atezolizumab-bevacizumab (AB) treatment. The median PFS is 4.1m (95% CI 3.3-5.3). Regarding RR, PR and SD occurs in 3 (6.4%) and 36 (76.6%) pts, respectively. The median OS is 9.9m (95% CI 7.3-14.4) and the 1-year survival rate is 45.3%. Amongst the 19 pts receiving prior AB treatment, the median OS is 14.3m (95% CI: 5.5-14.4) with 1-year survival rate of 50.7%. For non-AB regimen, the median OS is 8.9m (95% CI 6.1-NR) with 1-year survival rate of 42.0%. Commonest G3-4 TRAE is thrombocytopenia (6%); hypertension (4%) and ALT elevation (4%).The median dose of cabo is 41.6mg per day (range: 24.3-60.0 mg). Conclusions: Post-ICI use of cabo is associated with a median PFS of 4.1m and median OS of 9.9m. AB-cabo sequence appears to have more favourable outcome than non-AB-cabo sequence. No new safety signals were observed. This clinical trial reports the first prospective post-ICI survival data on TKI. Clinical trial information: NCT04588051 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.4_suppl.571
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 6
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    Phase II trial of second-line regorafenib in patients with unresectable hepatocellular carcinoma after progression on first-line atezolizumab plus bevacizumab: REGONEXT trial.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 4_suppl ( 2023-02-01), p. TPS634-TPS634
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 4_suppl ( 2023-02-01), p. TPS634-TPS634
    Abstract: TPS634 Background: Atezolizumab-bevacizumab (Ate/Bev) has demonstrated efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) in the phase III trial, and is the new standard of care for first-line treatment of advanced HCC. However, the optimal sequence of therapy after failure of Ate/Bev is unknown. Regorafenib is an oral multikinase inhibitor that blocks the activity of protein kinases involved in angiogenesis, oncogenesis, metastasis, and tumour immunity. Although regorafenib showed survival benefit as subsequent treatment in patients with advanced HCC after progression on sorafenib, the efficacy and safety of regorafenib as subsequent therapy after Ate/Bev has not been investigated yet. Therefore, we designed a phase II trial investigating the efficacy and safety of regorafenib as second-line therapy in patients with advanced HCC who progressed on first-line Ate/Bev. Methods: This is a phase II, multicenter, single-arm study in patients with advanced HCC who had progression on first-line Ate/Bev. Additional key eligibility criteria include with Eastern Cooperative Oncology Group performance status 0–1, Child-Pugh score of 5 or 6, evaluable disease per RECIST v1.1, prior administration of at least 2 cycles of Ate/Bev, and adequate organ function. Key exclusion criteria include fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma, prior regorafenib treatment, clinically significant bleeding within 28 days of enrollment and untreated or symptomatic CNS or leptomeningeal metastasis. Eligible patients will receive oral regorafenib 160 mg daily for 3 weeks of every 4-week cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death. The primary endpoint is progression-free survival (PFS), and the secondary endpoints are overall survival, time to progression, overall response rate (ORR), disease control rate and safety. ORR and PFS is assessed per RECIST v 1.1. This study is ongoing and 18 of planned 40 patients have been enrolled. This study is prospectively registered at ClinicalTrials.gov, NCT5134532.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.4_suppl.TPS634
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 7
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    α‐FAtE : A new predictive score of response to atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma
    Wiley ; 2024
    In:  International Journal of Cancer Vol. 154, No. 6 ( 2024-03-15), p. 1043-1056
    Details
    In: International Journal of Cancer, Wiley, Vol. 154, No. 6 ( 2024-03-15), p. 1043-1056
    Abstract: Atezolizumab plus bevacizumab (AB) and lenvatinib can be alternatively used as first‐line systemic treatment of unresectable hepatocellular carcinoma (HCC). However, no direct comparison of the two regimens has been performed in randomized clinical trials, making the identification of baseline differential predictors of response of major relevance to tailor the best therapeutic option to each patient. Baseline clinical and laboratory characteristics of real‐world AB‐treated HCC patients were analyzed in uni‐ and multivariate analyses to find potential prognostic factors of overall survival (OS). Significant variables were incorporated in a composite score (α‐FAtE) and it was tested for specificity and sensitivity in receiver operating characteristic (ROC) curve and in multivariate analysis for OS. The score was applied in uni‐ and multivariate analyses for OS of a comparable lenvatinib‐treated HCC population. Finally, comparison between treatments was performed in patients with low and high α‐FAtE scores and predictivity estimated by interaction analysis. Time‐to‐progression (TTP) was a secondary endpoint. OS of AB‐treated HCC patients was statistically longer in those with α‐fetoprotein 〈 400 ng/mL (HR 0.62, p = .0407), alkaline phosphatase (ALP) 〈 125 IU/L (HR 0.52, p = .0189) and eosinophil count ≥70/μL (HR 0.46, p = .0013). The α‐FAtE score was generated by the sum of single points attributed to each variable among the above reported. In ROC curve analysis, superior sensitivity and specificity were achieved by the score compared to individual variables (AUC 0.794, p 〈 .02). Patients with high score had longer OS (HR 0.44, p = .0009) and TTP (HR 0.34, p 〈 .0001) compared to low score if treated with AB, but not with lenvatinib. Overall, AB was superior to lenvatinib in high score patients (HR 0.55, p = .0043) and inferior in low score ones (HR 1.75, p = .0227). At interaction test, low α‐FAtE score resulted as negative predictive factor of response to AB ( p = .0004). In conclusion, α‐FAtE is a novel prognostic and predictive score of response to first‐line AB for HCC patients that, if validated in prospective studies, could drive therapeutic choice between lenvatinib and AB.
    Type of Medium: Online Resource
    ISSN: 0020-7136 , 1097-0215
    URL: Issue
    URL: Article
    DOI: 10.1002/ijc.v154.6
    DOI: 10.1002/ijc.34799
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2024
    detail.hit.zdb_id: 218257-9
    detail.hit.zdb_id: 1474822-8
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  • 8
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    The c-Abl inhibitor, radotinib induces apoptosis in multiple myeloma cells via mitochondrial-dependent pathway
    Springer Science and Business Media LLC ; 2021
    In:  Scientific Reports Vol. 11, No. 1 ( 2021-06-24)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2021-06-24)
    Abstract: Multiple myeloma (MM) is a hematological cancer resulting from accumulated abnormal plasma cells. Unfortunately, MM remains an incurable disease, as relapse is very common. Therefore, there is urgent need to develop new treatment options for MM. Radotinib is a novel anti-cancer drug, currently approved in South Korea for the treatment of chronic myeloid leukemia patients. Its mechanism of action involves inhibition of the tyrosine kinase Bcr-Abl and the platelet-derived growth factor receptor. Generally, the mechanism of inhibition of non-receptor tyrosine kinase c-Abl has played an essential role in the inhibition of cancer progression. However, little is known regarding the effects of the c-Abl inhibitor, radotinib on MM cells. In this study, we analyzed the effect of radotinib on multiple myeloma cells. Interestingly, radotinib caused apoptosis in MM cells including RPMI-8226, MM.1S, and IM-9 cells, even in the absence of c-kit expression in 2 of these lines. Radotinib treatment significantly increased the number Annexin V-positive cells and decreased the mitochondrial membrane potential in MM cells. Additionally, we observed that cytochrome C was localized in the cytosol of radotinib-treated MM cells. Moreover, radotinib decreased the expression of Bcl-2 and Bcl-xL, and increased the expression of Bax and Bak in MM cells. Furthermore, radotinib promoted caspase pathway activation by inducing the expression and activity of caspase-3, -7, and -9. Expression of cleaved PARP-1 was also increased by radotinib treatment in various MM cells. In addition, radotinib significantly suppressed MM cell growth in a xenograft animal model using RPMI-8226 cells, and killed ex vivo myeloma cells from patients. In conclusion, radotinib may play an important role as a candidate agent or chemosensitizer for the treatment of MM.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-021-92651-9
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2615211-3
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  • 9
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    New Load Modulation Combiner Having a Capability of Back-Off Control for Doherty Power Amplifiers
    Institute of Electrical and Electronics Engineers (IEEE) ; 2023
    In:  IEEE Access Vol. 11 ( 2023), p. 11479-11488
    Details
    In: IEEE Access, Institute of Electrical and Electronics Engineers (IEEE), Vol. 11 ( 2023), p. 11479-11488
    Type of Medium: Online Resource
    ISSN: 2169-3536
    URL: Article
    DOI: 10.1109/ACCESS.2023.3240649
    Language: Unknown
    Publisher: Institute of Electrical and Electronics Engineers (IEEE)
    Publication Date: 2023
    detail.hit.zdb_id: 2687964-5
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  • 10
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    Regorafenib in patients with advanced Child‐Pugh B hepatocellular carcinoma: A multicentre retrospective study
    Wiley ; 2020
    In:  Liver International Vol. 40, No. 10 ( 2020-10), p. 2544-2552
    Details
    In: Liver International, Wiley, Vol. 40, No. 10 ( 2020-10), p. 2544-2552
    Abstract: Regorafenib is an approved agent in patients with advanced hepatocellular carcinoma (HCC) who progressed on sorafenib, but little is known about its clinical outcomes in Child‐Pugh B patients. We aimed to investigate the safety and effectiveness of regorafenib in Child‐Pugh B HCC patients. Methods This multicentre retrospective study included 59 patients with Child‐Pugh B HCC who received regorafenib. Comparative analyses were performed with an independent cohort of Child‐Pugh class A patients from the same registry (n = 440). Results The median age was 58 years (range, 19‐83). All patients had progression on prior sorafenib. Regorafenib was given as 2nd line, and 3rd‐4th line systemic therapy in 37 (62.7%) and 22 (37.3%) patients respectively. Compared to Child‐Pugh A cohort, grade 3‐4 AEs were more common in the Child‐Pugh B cohort (27.1% vs 14.1%, P  = .017). The median progression‐free survival (PFS) and overall survival (OS) were 1.8 and 4.6 months, respectively, and these were significantly poorer than the Child‐Pugh A cohort ( P  = .008 and P   〈  .001 respectively). Child‐Pugh B patients with albumin‐bilirubin (ALBI) grade 3 had a significantly higher frequency of increased bilirubin ( P  = .01 for any grade and P  = .01 for grade 3‐4) and showed significantly poorer OS ( P  = .021), compared to those with ALBI grade 1 or 2. Conclusion Regorafenib's poor clinical outcomes and increased frequency of severe adverse events lead us to discourage its use in the Child‐Pugh B population. In particular, regorafenib should not be used in Child‐Pugh B patients with ALBI grade 3.
    Type of Medium: Online Resource
    ISSN: 1478-3223 , 1478-3231
    URL: Issue
    URL: Article
    DOI: 10.1111/liv.v40.10
    DOI: 10.1111/liv.14573
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2124684-1
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