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  • 1
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    Artificial intelligence-based pathology as a biomarker of sensitivity to atezolizumab–bevacizumab in patients with hepatocellular carcinoma: a multicentre retrospective study
    Elsevier BV ; 2023
    In:  The Lancet Oncology Vol. 24, No. 12 ( 2023-12), p. 1411-1422
    Details
    In: The Lancet Oncology, Elsevier BV, Vol. 24, No. 12 ( 2023-12), p. 1411-1422
    Type of Medium: Online Resource
    ISSN: 1470-2045
    URL: Article
    DOI: 10.1016/S1470-2045(23)00468-0
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2049730-1
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  • 2
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    Outcomes of immune checkpoint inhibitor-mediated colitis: Multicenter cohort study.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. 2643-2643
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 2643-2643
    Abstract: 2643 Background: Immune checkpoint inhibitor (ICI)-mediated colitis (IMC) is a common and serious adverse event. Although small series have described the clinical presentation of IMC, large multicenter series that integrate clinical, endoscopic, and histologic findings are lacking. Methods: We retrospectively assessed patients who received ICI and had endoscopically confirmed IMC from 2010 to 2019. IMC was graded based on the CTCAE version 5.0 criteria. Multivariate logistic regression analyses were conducted to assess factors associated with recurrence of IMC symptoms and long duration of corticosteroids use ( 〉 70 days). Results: 675 patients were included. 387 patients were males (57%). Median age was 63 years. Melanoma was the most common cancer type (327; 48%). Most (365; 54%) patients received CTLA-4 inhibitor ICI, as monotherapy or in combination with PD-(L)1. Median time from ICI therapy to IMC was 62 days. IMC was grade 2 in 335 (50%) patients, Grade 3 in 181 (27%), and grade 4 in 16 (3%). 155 (23%) patients had mucosal ulceration on endoscopy, 91 of them had severe features (deep, large, or multiple ulcers); 336 (50%) patients had non-ulcerative inflammation. The rest had normal endoscopic findings with histologic inflammation. Most patients were admitted to the hospital for management of IMC (405; 60%) and 16 (3%) needed ICU-level of care. Treatment included corticosteroids in 577 (85%) patients (median duration 52 days), TNF inhibitor in 245 (36%), and vedolizumab in 90 (13%). 202 (32%) patients had recurrent IMC after resolution of symptoms. On multivariate logistic regression, factors associated with IMC recurrence and long ( 〉 70 days) duration of corticosteroid therapy were grade of IMC ( p = 0.049), treatment with infliximab or vedolizumab ( p = 0.044), presence of mucosal ulceration ( p = 0.034 ), or features of active histologic inflammation ( p = 0.076). Of note, patients with mucosal ulceration received infliximab or vedolizumab more frequently ( p 〈 0.001). For patients with grade 2 IMC, mucosal inflammation on endoscopy and delay in performing endoscopy with time from IMC onset to endoscopy more than a month were associated with IMC recurrence and longer duration of corticosteroid use ( p = 0.029 and p 〈 0.001, respectively). 16 (3%) patients had colonic perforation, 7 of them underwent surgical resection. No IMC-related death occurred. Conclusions: IMC is a clinically significant adverse event that can lead to premature termination of ICI therapy with high rates of hospital admission. Rarely, it results in colonic perforation requiring surgical intervention and ICU admission. Our data suggest that there is a utility of endoscopic and histologic evaluation in the prediction of worse outcomes from IMC. This finding is particularly important for grade 2 IMC as current guidelines do not recommend endoscopic evaluation for this group.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.2643
    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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  • 3
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    Programmed cell death ligands expression in pheochromocytomas (PCC) and paragangliomas (PGL): Relationship with the hypoxic response and malignant behaviour.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. 11597-11597
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 11597-11597
    Abstract: 11597 Background: The hypoxic response underlies the pathogenesis and malignant behaviour of PCC/PGL. Regulation of PD-1 receptor-ligand signalling, a therapeutically actionable driver of the anti-tumour immune response, is a hypoxic-driven trait across malignancies. We evaluated the prognostic role of PD ligands in association with biomarkers of hypoxia and angiogenesis in patients with PCC/PGL. Methods: Tissue microarrays sections including consecutive cases of PCC/PGL diagnosed between 1983-2011 were stained for PD-L1 & 2, Ki-67, hypoxia inducible factor 1a (Hif-1a), Carbonic Anhydrase IX (CaIX), Vascular Endothelial Growth Factor-A (VEGF-A). Candidate biomarkers were assessed for correlation with clinical variables including overall survival. Results: In total, 100 patients, 10% malignant, 64% PCC, 29% familial with a median tumour size of 4.7 cm (range 1-14) were included. Median follow-up was 4.7 years. PD-L1 expression was observed in 18% of cases and was independent of adverse pathological features including capsular (CI), vascular invasion (VI), necrosis (N) and expression of biomarkers of hypoxia. We observed a trend towards association with malignancy (p = 0.08). PD-L2 expression was found in 16% of tumors. PD-L2 overexpression strongly correlated with CI, VI, N (p 〈 0.01) and malignant behaviour (p = 0.009) and was associated with stronger Hif-1a and CaIX immunolabeling (p 〈 0.01). PD-L2 but not PD-L1 expression was predictive of shorter survival (162 versus 309 months, HR 3.1 95%CI 1.1-9.2, Log-rank p = 0.03). Gene set enrichment analysis on the TGCA PCC/PGL RNA-seq dataset (n = 184) revealed a positive correlation between PD-L2 and a number of transcripts involved in angiogenesis and immunity including Interleukin-6 (Pearson R = 0.57) and CD-8a (R = 0.56). Conclusions: We report for the first time PD-1 ligands expression in PCC/PGL with a distinctive prognostic and clinicopathologic role. These findings support a potential therapeutic role for PD-1/PD-L1 targeted checkpoint inhibitors in these tumors.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.11597
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
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  • 4
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    Intra-tumoral heterogeneity in the expression of programmed-death (PD) ligands in isogeneic primary and metastatic lung cancer (LC): Implications for immunotherapy.
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 15_suppl ( 2016-05-20), p. 11601-11601
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. 11601-11601
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2016.34.15_suppl.11601
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
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  • 5
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    Post-registration experience of nivolumab (nivo) therapy in patients with advanced hepatocellular carcinoma (HCC): An international study.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e16677-e16677
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e16677-e16677
    Abstract: e16677 Background: Nivo is FDA-approved in sorafenib-experienced, advanced HCC. Post-registration data to portray treatment in a real-world setting is lacking. Methods: We describe safety and efficacy of nivo in patients (pts) from 8 centres (USA n = 181, Asia n = 47, Europe n = 5), documenting overall (OS), progression-free survival (PFS), overall response (ORR) and disease control rates (DCR) (RECIST). Results: We analysed 233 pts, mostly cirrhotic (n = 176, 75%) due to hepatitis C (n = 95, 54.0%) with Barcelona Clinic Stage (BCLC) C HCC (n = 178, 76.4%), Child-Pugh class (CP) A (n = 158, 67.8%) or B (n = 75, 32.2%), and AFP 〉 400 IU/mL (n = 132, 56.7%). Nivo was given as first (1L, n = 85, 36.5%), second line (2L, n = 130, 55.8%) or 〉 2L (n = 18, 7.7%), after local (n = 191, 82%) and systemic therapy (n = 148, 63.5%), mostly sorafenib (n = 142, 60.9%). Median duration of nivo was 6.0 months (mo, interquartile range [IQR] 2.6-11.9) and stopped due to progression (n = 109, 46.8%) or toxicity (n = 8, 3.4%). After median follow up of 7 mo (IQR 3.0-12.3), ORR was 22.4% and DCR was 52.1%. Best responses (n = 219, 94%) included complete and partial responses in 18 (7.7%) and 31 (13.3%) pts respectively, stable disease in 65 (27.9%) and progressive disease in 105 (45.1%), not dissimilar by CP (p = 0.26). Median OS was 12.2 mo (95%CI 8.4-16.0) and predicted by CP (CPA 16.3 mo 95%CI 11.7-20.8; CPB 7.3 mo 95%CI 4.2-10.4; hazard ratio [HR] 1.9, p = 0.01), nivo line (1L 16.3 mo 95%CI 8.0-24.5; 〉 1L 10.4 mo 95%CI 7.4-13.5; HR 0.68, p = 0.05), and PVT (PVT- 13.8 mo 95%CI 11.7-16.0; PVT+ 10.4 mo 95%CI 7.8-13.0; HR 1.8, p = 0.015) but not cirrhosis, AFP, BCLC or steroid use (p 〉 0.05). Median PFS was 10.1 mo (95%CI 6.1-14.2), predicted by BCLC (A-B 19.0 mo 95%CI 7.1-30.8; C 8.2 mo 95%CI 4.9-11.4; HR 2.8, p = 0.002) and line (1L 18.2 mo 95%CI 10.4-25.9; 〉 1L 8.2 mo 95% CI 6.2-10.2; HR 0.60, p = 0.021), but not cirrhosis, AFP, or steroid use (p 〉 0.05). 26 pts (11.2%) suffered 〉 = Grade 2 toxicities, most commonly fatigue (n = 29, 24.7%). Conclusions: Real-world use of nivo in advanced HCC across line of therapy suggests reproducible clinical efficacy and safety compared to prospective trials.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e16677
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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  • 6
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    A pharmacokinetic (PK) pharmacodynamic (PD) driven first-in-human study of the oral class I PI3K inhibitor CH5132799, in patients with advanced solid tumors.
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. 3022-3022
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 3022-3022
    Abstract: 3022 Background: The phosphatidylinositol 3-kinase (PI3K) pathway is a promising target in cancer. CH5132799 is a novel PI3K inhibitor, selectively inhibiting class I PI3Ks (α, β, δ and γ) with no inhibition of class II and III or mTOR, and with potent antitumor activity in preclinical studies (Tanaka et al, Clin Cancer Res; 17; 3272-81, 2011) . First-in-human study objectives were determination of maximum tolerated dose (MTD), safety/tolerability, PK/PD and clinical activity (RECIST). Methods: A 3+3 dose escalation design was used. The initial dosing schedule of CH5132799(schedule A) was once a day (QD). Due to a relatively short half-life, a twice a day (BID) schedule (schedule B) was introduced. PK profiles were studied over 72 hours. PD analyses included quantification of various phosphoproteins in platelet rich plasma (PRP). Tumor assessments were performed at baseline and cycle 3 day 1 (C3D1) and FDG-PET scans at baseline, C1D8 and C3D1. Results: 29 patients (pts) with a variety of solid tumors have been treated (A 23 pts, B 6 pts, the most common tumors were breast, oesophageal, colorectal and ovarian). The starting doses were 2 mg (A) and 48 mg (B). The current doses being explored are 96 mg (A) and 72 mg (B). The most frequently reported drug-related AEs were Grade 1/2 diarrhea, nausea, fatigue, anorexia and anemia. 1 DLT (Grade 3 elevated LFT) was observed in a hepatocellular carcinoma pt at 48 mg BID. MTD has not yet been determined. The preliminary mean ±SD C max and AUC at 96 mg QD were 202±129 ng/ml and 1407±935 ng·hr/ml respectively, which is consistent with an efficacious exposure based on preclinical models. Some patients achieved the expected exposure at over 32 mg. From single dose of 48mg there was a reduction of phosphorylation of AKT in PRP after treatment, consistent with pathway modulation. A patient with clear cell ovarian cancer and a PIK3CA mutation treated at 48 mg BID showed 〉 50% decrease in SUV on a PET scan at C1D8 and a 75% decrease in CA-125 at C2D1. 5 pts exhibited SD ( 〉 8 weeks). Conclusions: CH5132799 is well tolerated either QD ≤96 mg or BID ≤48 mg. Dose-escalation continues and updated safety/efficacy/PK/PD data will be presented.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.15_suppl.3022
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 7
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    Quantitative comparison of PD-L1 immuno-histochemical assays in hepatocellular carcinoma: The Blueprint-HCC study.
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 5_suppl ( 2018-02-10), p. 91-91
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 5_suppl ( 2018-02-10), p. 91-91
    Abstract: 91 Background: Programmed cell death ligand 1 (PD-L1) expression by immunohistochemistry (IHC) enriches for responses to PD-1/PD-L1 inhibitors, however its role as a predictive biomarker in hepatocellular carcinoma (HCC) is inconclusive, with no consensus on any particular assay. We evaluated the performance of 4 different PD-L1 detection assays previously published in landmark clinical studies. Methods: PD-L1 IHC was performed on 4 serial sections from tissue microarray (TMA) blocks containing 100 archival cases of HCC that included tumour and surrounding non-tumorous tissue. Antibody clones E1LN3, 28-8, 22c3, SP263 were compared on the basis of percentage and intensity of staining in malignant cells (M) to generate an H-score (range 0-300). Immune cells infiltrating (ICI) and at the periphery, in non-tumorous tissue (ICP) were scored on a 4-tier system (0-3). Results: Patients were 76% males, 20% HCV-positive, 64% cirrhotic with a median age of 67 years. Median tumour size was 4 cm, 70% of patients had T1-T2 tumours and 48% were of grade 2. The proportion of PD-L1 positive cases according to M-ICI-ICP pattern was 2-6-2% for E1LN3, 10-18-19% for 28-8, 9-22-18% for 22c3 and 5-14-13% for SP263. Pairwise comparison of M H-scores revealed heterogeneity across antibodies, with highest concordance between E1L3N/SP263 (R2 = 0.95), E1L3N/22c3 (R2 = 0.65), 22c3/SP263 (R2 = 0.66) and increasing discordance for 28-8/22c3 (R2 = 0.44), E1L3N/28-8 (R2 = 0.29), and 28-8/SP263 (R2 = 0.26). Detection of PD-L1-positive immune infiltrates using a semi-quantitative scoring system revealed significantly different scores in pairwise non-parametric comparisons of ICI (p 〈 0.05) but not ICP (p 〉 0.05 for chi-square test). Conclusions: In the Blueprint-HCC study we demonstrated that quantification of PD-L1 protein levels in tumour cells, intra-tumoural and peri-tumoural infiltrate is characterised by inter-assay discordance in HCC. This has profound implications in the clinical development of predictive correlates of efficacy to immunotherapy in HCC. Sources of such discordance should be explored.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2018.36.5_suppl.91
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
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  • 8
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    Influence of antibiotic therapy (ATB) on oncological outcomes of metastatic non-small cell lung cancer (mNSCLC) patients treated with chemo-immunotherapy (CIT).
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 3080-3080
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 3080-3080
    Abstract: 3080 Background: ATB exposure is proven to worsen response and survival in immunotherapy recipients. However, its influence on outcomes from CIT is currently undefined. Methods: We conducted a retrospective, multi-centre observational study including 77 mNSCLC patients who received pembrolizumab, pemetrexed and carboplatin CIT as first-line therapy for mNSCLC, between December 1, 2018 and January 1, 2020 in 3 academic referral centres in Europe and in the United States. We documented ATB exposure in the 30 days prior to CIT commencement (pATB) or concurrently (cATB) until CIT cessation. Outcome measures included overall (OS) and progression-free survival (PFS) calculated from commencement of CIT, and overall response rates (ORR) defined by Response Evaluation Criteria in Solid Tumors (v1.1). Results: We enrolled 77 patients, 41 of whom were female (n = 53%) with adenocarcinoma (n = 73, 95%), performance status (PS) 0-1 (n = 69, 90%) PD-L1 Tumour Proportion Score 〈 50 (n = 57, 74%). Median OS was 16.4 months (95%CI 8.4-24.4), median PFS was 6.7 months (95%CI 5.7-7.6). ORR was 48% including 1 complete (1%) and 36 partial responses (47%). Eleven patients (14%) received pATB, with penicillin/cephalosporins (p/c, n = 7, 63%) for 〈 7 days (n = 10, 90%). Thirty-five patients (45%) received cATB with p/c (n = 11, 40%) for 〈 7 days (n = 28, 80%). Most common indication for ATB was peri-procedure prophylaxis in pATB (n = 7, 63%) and suspected febrile neutropenia in cATB (n = 14, 40%). pATB (p = 0.004) but not cATB (p = 0.85) predicted for worse OS (19.6 vs 6.5 months, Hazard Ratio [HR] 2.9 95%CI 1.3-6.3). Neither pATB nor cATB predicted for PFS or ORR (p 〉 0.05). Multivariable analyses confirmed pATB (HR 2.3 95%CI 1.1-5.5, p = 0.05) to predict for OS independent of PD-L1 status, PS and cATB. pATB+/- groups were balanced with regards to age, gender, PS nor PD-L1 status (p 〉 0.05). Conclusions: Whilst cATB does not compromise outcome from CIT, this study reproduces the detrimental effects observed for pATB exposure in immunotherapy recipients. Mechanistic verification of the immune-biologic foundations underlying this association is urgently warranted.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.3080
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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  • 9
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    Intra-tumour heterogeneity in the regulation of immune-tolerogenic pathways in primary and metastatic hepatocellular carcinoma (HCC).
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. e14614-e14614
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e14614-e14614
    Abstract: e14614 Background: Anti-PD-1/PD-L1 checkpoint inhibitors have shown preliminary evidence of activity in HCC. PD-L1 status is a putative predictor of response, however PD ligands expression can be heterogeneous across sampled sites, with implications in the development of immunotherapy. Methods: We constructed a tissue microarray from 77 patients: 56 with surgically resected and 21 with intermediate/advanced HCC in whom 20 matching metastases were also available. Tumour and surrounding cirrhosis were analysed for PD-L1 and PD-L2 expression by immunohistochemistry. FFPE-extracted RNA was analyzed on the NanoString nCounter system using 12 paired primary/metastatic HCC cores from 6 patients, with validation in a subset of further 24 specimens. Results: Surgically resected cases were Child A (51/56, 91%), BCLC A (45/56, 80%). In resected tumour cores 11/56 (20%) were PD-L1 and 18/56 (32%) were PD-L2 positive. Surrounding cirrhotic liver revealed PD-L1 in the lymphocytic infiltrate in 8/56 samples (14%), whilst PD-L2 expression was found in the cirrhotic background in 29/56 cases (52%). PD-L2 expression in cirrhotic (p = 0.03) but not in tumour cores (p = 0.13) correlated with more advanced BCLC stage. In patients with intermediate-advanced HCC (n = 21), the prevalence of tumour PD-Ls expression was 40% (8/21) for both markers. Concordance between PD-L1 positive primary and metastases was 33% and 85% in PD-L1 negative tumours. In contrast, there was universal concordance between in PD-L2 expression between primary and metastatic HCC (p 〈 0.001). Targeted transcriptomic profiling revealed a subset of 40 genes involved in innate and adaptive immunity to be differentially regulated across primary and metastatic disease. Conclusions: Intra-tumour heterogeneity in the expression of PD-L1 is common in HCC, whilst PD-L2 is homogeneously distributed in primary and metastatic deposits. Unsupervised transcriptomic profiling confirms differential activation of innate and adaptive immune-related pathways in the metastatic dissemination of liver cancer. This has profound implications in the clinical development of immune response biomarkers in HCC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.e14614
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
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  • 10
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    Patterns and outcomes of subsequent therapy after immune checkpoint inhibitor discontinuation in HCC
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Hepatology Communications Vol. 6, No. 7 ( 2022-07), p. 1776-1785
    Details
    In: Hepatology Communications, Ovid Technologies (Wolters Kluwer Health), Vol. 6, No. 7 ( 2022-07), p. 1776-1785
    Abstract: The availability of immune checkpoint inhibitors (ICIs) for the management of advanced hepatocellular cancer (HCC) has changed the treatment paradigm. There are emerging questions regarding the efficacy of subsequent anticancer therapies. The primary aim of this retrospective, multicenter study was to examine the types of anticancer treatment received after ICIs and to assess the impact on post‐ICI survival. We established an international consortium of 11 tertiary‐care referral centers located in the USA (n = 249), Europe (n = 74), and Asia (n = 97), and described patterns of care following ICI therapy. The impact of subsequent therapy on overall survival (OS) was estimated using the Kaplan–Meier method and presented with a 95% confidence interval (CI). A total of 420 patients were treated with ICIs for advanced HCC after one line of systemic therapy (n = 371, 88.8%): 31 (8.8%) had died, 152 (36.2%) received best supportive care (BSC) following ICIs, and 163 patients (38.8%) received subsequent anticancer therapy. Tyrosine kinase inhibitors (TKIs, n = 132, 80.9%), in particular sorafenib (n = 49, 30.0%), were the most common post‐ICI therapy followed by external beam radiotherapy (n = 28, 17.2%), further immunotherapy (n = 21, 12.9%), locoregional therapy (n = 23, 14.1%), chemotherapy (n = 9, 5.5%), and surgery (n = 6, 3.6%). Receipt of post‐ICI therapy was associated with longer median OS compared with those who had received BSC (12.1 vs. 3.3 months; hazard ratio [HR]: 0.4 (95% CI: 2.7–5.0). No difference in OS was noted in those patients who received TKI before ICIs compared with those who received ICIs followed by TKI. Conclusion: Post‐ICI therapy is associated with OS in excess of 12 months, suggesting a role for therapeutic sequencing. OS from TKI therapy was similar to that reported in registration studies, suggesting preserved efficacy following ICIs.
    Type of Medium: Online Resource
    ISSN: 2471-254X , 2471-254X
    URL: Article
    DOI: 10.1002/hep4.1927
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2881134-3
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