Publications
246 results found
Gkika E, Brunner T, Abbasi-Senger N, et al., 2019, SBRT compared to sorafenib in locally advanced hepatocellular carcinoma: a propensity score analysis, 38th Annual Meeting of the European-Society-for-Radiotherapy-and-Oncology (ESTRO), Publisher: ELSEVIER IRELAND LTD, Pages: S423-S423, ISSN: 0167-8140
Hajiev S, Pinato DJ, Ramaswami R, et al., 2019, Sorafenib starting dose impacts on survival in the elderly population with hepatocellular cancer, International Liver Congress / 54th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL), Publisher: ELSEVIER, Pages: E621-E621, ISSN: 0168-8278
Evans J, Pinato D, Ward C, et al., 2019, Longitudinal monitoring of cell-free DNA predicts for transarterial chemo-embolization failure in hepatocellular carcinoma, International Liver Congress / 54th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL), Publisher: ELSEVIER, Pages: E362-E362, ISSN: 0168-8278
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Pinato DJ, Goldin RD, Mineo T, et al., 2019, Trans-arterial chemoembolization as a loco-regional inducer of immunogenic cell death in hepatocellular carcinoma, International Liver Congress / 54th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL), Publisher: ELSEVIER, Pages: E374-E375, ISSN: 0168-8278
Samani A, Pinato DJ, Bettinger D, et al., 2019, Sorafenib use in patients with HCC on a background of non-alcoholic fatty liver disease, International Liver Congress / 54th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL), Publisher: ELSEVIER, Pages: E621-E621, ISSN: 0168-8278
Pinato D, Brown MW, Trousil S, et al., 2019, Integrated analysis of multiple receptor tyrosine kinases identifies Axl as a therapeutic target and mediator of resistance to sorafenib in hepatocellular carcinoma., British Journal of Cancer, Vol: 120, Pages: 512-521, ISSN: 0007-0920
Background: Aberrant activation of Axl is implicated in the progression of HCC. We explored biologic significance and preclinical efficacy of Axl inhibition as a therapeutic strategy in sorafenib-naïve and resistant HCC.Methods: We evaluated Axl expression in sorafenib-naïve and resistant (SR) clones of epithelial (HuH7) and mesenchymal origin (SKHep-1) using antibody arrays and confirmed tissue expression. We tested the effect of Axl inhibition with RNA-interference and pharmacologically with R428 on a number of phenotypic assays. Results: Axl mRNA overexpression in cell lines (n=28) and RNA-seq tissue datasets (n=373) correlated with epithelial-to-mesenchymal transition (EMT). Axl was overexpressed in HCC compared to cirrhosis and normal liver. We confirmed sorafenib-resistance to be associated with EMT and enhanced motility in both HuH7-SR and SKHep-1-SR cells documenting a 4-fold increase in Axl phosphorylation as an adaptive feature of chronic sorafenib treatment in SKHep-1-SR cells. Axl inhibition reduced motility and enhanced sensitivity to sorafenib in SKHep-1SR cells. In patients treated with sorafenib (n=40) circulating Axl levels correlated with shorter survival.Conclusions: Suppression of Axl-dependent signaling influences the transformed phenotype in HCC cells and contributes to adaptive resistance to sorafenib, providing a pre-clinical rationale for the development of Axl inhibitors as a measure to overcome sorafenib resistance.
Black J, Atkinson S, Singh A, et al., 2019, The inflammation-based index can predict response and improve patient selection in NETs treated with PRRT: a pilot study, Journal of Clinical Endocrinology and Metabolism, Vol: 104, Pages: 285-292, ISSN: 0021-972X
BackgroundPeptide Receptor Radionuclide Therapy (PRRT) is an effective treatment for certain patients with metastatic neuroendocrine tumours (NETs). Tumour response is highly variable; no biomarker in clinical practice has been demonstrated to reliably predict outcome. The Inflammation-Based Index (IBI), derived from serum C-reactive protein and albumin levels, predicts survival and response to treatment in patients in a number of cancer types and was therefore explored in this setting.Materials and MethodsClinico-pathological data from patients undergoing PRRT for metastatic NETs were collected at baseline and during treatment. The primary endpoint was progression free survival (PFS) with a secondary endpoint of overall survival (OS). Cox regression analysis tested associations between baseline variables and their dynamic changes, and PFS and OS. Decision curve analysis (DCA) was used to determine the net benefit associated with a treatment strategy determined by the baseline IBI and non-response to PRRT.ResultsFifty-five patients were recruited. Baseline IBI >0 was associated with inferior PFS (HR 14.2 (95% CI 5.25-38.5), p<0.001) and OS (p<0.001). Multivariate analysis confirmed an independent association between IBI and PFS (p=0.001). DCA indicated a net clinical benefit at risk thresholds between 0.03 and 0.58.ConclusionBaseline IBI score and its dynamic change through treatment are associated with both PFS and OS. At a risk threshold equivalent to the currently accepted rate of non-response to therapy, implementation of this easily derived score could avoid a significant number of futile treatments. These findings should be validated in additional independent cohorts.
Evans J, Yang WM, Newsom-Davis T, et al., 2019, Peptide receptor radionuclide therapy for metastatic bronchopulmonary carcinoid tumours: a single ENETS Centre of Excellence experience, Publisher: ELSEVIER IRELAND LTD, Pages: S59-S59, ISSN: 0169-5002
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Sharma R, Sharma SK, Singh BK, et al., 2019, High degree of fluoroquinolone resistance among pulmonary tuberculosis patients in New Delhi, India., Indian J Med Res, Vol: 149, Pages: 62-66, ISSN: 0971-5916
BACKGROUND & OBJECTIVES: : The fluoroquinolones (FQs) group of antibiotics is the backbone drugs for the management of drug-resistant tuberculosis (TB). In routine clinical practice, drug susceptibility testing (DST) for FQs is not performed, and the patients are empirically treated. A limited information exists regarding FQs resistance among pulmonary TB cases. The present study was conducted to determine the FQs resistance among drug sensitive and drug-resistant pulmonary TB patients in a tertiary care centre in north India. METHODS: : A total of 1619 sputum/smear-positive specimens of pulmonary TB patients were subjected to DST for first-line drugs (FLDs) and second-line drugs. In addition, FQs DST was also performed using automated Mycobacterial Growth Indicator Tube-960 liquid culture technique. The immuno-chromatographic assay was performed to distinguish Mycobacterium tuberculosis complex (MTBC) from non-MTBC. RESULTS: : Mycobacterium tuberculosis (Mtb) was isolated in 1499 sputum specimens; 1099 culture specimens were sensitive to FLDs, 249 grew as multidrug-resistant (MDR) Mtb and the remaining 151 isolates revealed any drug resistance to FLDs. While FQs monoresistance among the FLD sensitive isolates was 3.1 per cent (35/1099), 27.3 per cent (68/249) among MDR Mtb isolates had additional FQs resistance. INTERPRETATION & CONCLUSIONS: : FQs resistance among drug sensitive and MDR Mtb isolates was high in Delhi, India. Based on these findings, it is recommended that the DST for FQs should be routinely performed to avoid further amplification of drug resistance.
Tan T, Shen L, Hajiev S, et al., 2018, Development and external international validation of a therapy-independent HCC survival prediction score from a cohort of 1270 patients, Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) / Liver Meeting, Publisher: Wiley, Pages: 551A-551A, ISSN: 0270-9139
Black JRM, Atkinson SR, Singh A, et al., 2018, Markers of the systemic inflammatory response can predict response and improve patient selection in Neuroendocrine Tumours treated with Peptide Radionuclide Receptor Therapy, 31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), Publisher: SPRINGER, Pages: S60-S60, ISSN: 1619-7070
Lavdas I, Rockall AG, Daulton E, et al., 2018, Histogram analysis of apparent diffusion coefficient from whole-body diffusion-weighted MRI to predict early response to chemotherapy in patients with metastatic colorectal cancer: preliminary results, Clinical Radiology, Vol: 73, Pages: 832.e9-832.e16, ISSN: 0009-9260
AimTo evaluate apparent diffusion coefficient (ADC) histogram analysis parameters, acquired from whole-body diffusion-weighted magnetic resonance imaging (DW-MRI), as very early predictors of response to chemotherapy in patients with metastatic colorectal cancer (mCRC).Materials and methodsThis was a single-institution prospective study, approved by the West Midlands-South Birmingham research ethics committee. All patients gave fully informed consent prior to imaging. Sixteen patients with histologically confirmed mCRC were enrolled to the study and 11 were successfully scanned with whole-body DW-MRI before (baseline) and 10.8±2.7 days after commencing chemotherapy (follow-up). Therapy response was assessed by RECIST 1.1. Mean ADC and histogram parameters (skewness, kurtosis, 25th, 50th, and 75th percentiles) were compared between progressors and non-progressors at baseline and follow-up. Receiver operating characteristics (ROC) analysis was performed for the statistically significant parameters. Data from metastases were also compared to normative tissue data acquired from healthy volunteers.ResultsThree patients had progressive disease (progressors) and eight had partial response/stable disease (non-progressors). Mean, 25th, 50th, and 75th percentiles were significantly lower for progressors at baseline (p=0.012, 0.012, 0.012 and 0.025 respectively) with areas under the ROC curves (AUC)=0.58, 0.50, 0.58 and 0.63, respectively. Skewness and kurtosis were significantly lower for non-progressors at follow-up (p=0.001 and 0.003 respectively) with AUC=0.67 and 0.79 respectively.ConclusionADC histogram analysis shows potential in discriminating progressive from non-progressive disease in patients with mCRC, who underwent whole-body DW-MRI. The technique can potentially be tested as a response assessment methodology in larger trials.
Howell J, Atkinson SR, Pinato DJ, et al., 2018, Identification of mutations in circulating cell-free tumor DNA as a prognostic biomarker in hepatocellular carcinoma, Publisher: WILEY, Pages: 29-29, ISSN: 0815-9319
Sharma SK, Mohan A, Singh AD, et al., 2018, Impact of nicotine replacement therapy as an adjunct to anti-tuberculosis treatment and behaviour change counselling in newly diagnosed pulmonary tuberculosis patients: an open-label, randomised controlled trial., Sci Rep, Vol: 8
We evaluated the impact of intensive smoking cessation activities as an adjunct to anti-tuberculosis treatment on patient-related treatment outcomes. In this open-label, randomised controlled trial, self-reporting smokers with pulmonary tuberculosis who initiated standard anti-tuberculosis treatment were randomised to either nicotine replacement therapy and behaviour change counselling (n = 400) or counselling alone (n = 400) provided at baseline and two follow-up visits. The primary outcomes were change in TBscore at 24-weeks and culture conversion at 8-weeks. Biochemical smoking quit rates defined as serum cotinine levels <10 ng/mL and/or exhaled carbon monoxide levels <6 ppm (47·8% vs 32·4%, p-value =< 0·001) and self-reported quit rates (69.3% vs 38·7%, p-value =< 0·001) were significantly higher in the intervention arm at 24-weeks. Though the TBscores at 24 weeks (95% CI) were lower in the intervention arm [2·07 (1·98, 2·17) versus 2.12 (2·02, 2·21)], the difference was not clinically meaningful. Patients in the control arm required treatment extension more often than intervention arm (6·4% vs 2·6%, p-value = 0·02). Combining nicotine replacement therapy with behaviour change counselling resulted in significantly higher quit rates and lower cotinine levels, however, impact on patient-related (TBscore) or microbiological outcomes (culture conversion) were not seen.
Pinato DJ, Pai M, Reccia I, et al., 2018, Preliminary qualification of a novel, hypoxic-based radiologic signature for trans-arterial chemoembolization in hepatocellular carcinoma., BMC Cancer, Vol: 18, ISSN: 1471-2407
BACKGROUND: Survival advantage following trans-arterial chemoembolization (TACE) is variable in patients with hepatocellular carcinoma (HCC). We combined pre-TACE radiologic features to derive a novel prognostic signature in HCC. METHODS: A multi-institutional dataset of 98 patients was generated from two retrospective cohorts from United Kingdom (65%) and Italy (36%). The prognostic impact of a number baseline imaging parameters was assessed and factors significant on univariate analysis were combined to create a novel radiologic signature on multivariable analyses predictive of overall survival (OS) following TACE. RESULTS: Median OS was 15.4 months. Tumour size > 7 cm (p < 0.001), intra-tumour necrosis (ITN) (p = 0.02) and arterial ectatic neovascularisation (AEN) (p = 0.03) emerged as individual prognostic factors together with radiologic response (p < 0.001) and elevated alpha-fetoprotein (AFP) (p = 0.01). Combination of tumour size > 7 cm, ITN and AEN identified patients with poor prognosis (p < 0.001). CONCLUSIONS: We identified a coherent signature based on commonly available imaging biomarkers likely to be reflective of differential patterns of relative hypoxia and neovascularisation. Large tumours displaying AEN and ITN are characterised by a shorter survival after TACE.
Pinato DJ, Mauri FA, Spina P, et al., 2018, Quantitative comparison of PD-L1 immunohistochemical assays in hepatocellular carcinoma: The Blueprint-HCC study, ASCO-SITC Clinical Immuno-Oncology Symposium, Publisher: American Society of Clinical Oncology, ISSN: 0732-183X
Chaubey J, Shrivastava D, Pawar S, et al., 2018, High degree of fluoroquinolone resistance among extrapulmonary tuberculosis patients at a tertiary care center in North India, International Conference of the American-Thoracic-Society, Publisher: WOLTERS KLUWER MEDKNOW PUBLICATIONS, Pages: 309-312, ISSN: 2212-5531
Pinato DJ, Sharma R, Citti C, et al., 2017, The albumin-bilirubin grade uncovers the prognostic relationship between hepatic reserve and immune dysfunction in HIV-associated hepatocellular carcinoma, Alimentary Pharmacology and Therapeutics, Vol: 47, Pages: 95-103, ISSN: 0269-2813
Background:Hepatocellular carcinoma (HCC) is a leading cause of liver-related mortality in people living with HIV, where co-infection with hepatotropic viruses accelerates the course of chronic liver disease.Aim:To evaluate whether the albumin-bilirubin (ALBI) grade, a more accurate marker of liver dysfunction in HCC, might identify patients with progressive liver dysfunction in the context of HIV/hepatitis co-infection.Methods:Using uni- and multi-variable analyses, we studied the albumin-bilirubin grade as a predictor of overall survival (OS) in a large, multi-center cohort of patients with HIV-associated HCC recruited from 44 centres in 9 countries within the Liver Cancer in HIV study group. Patients who underwent liver transplantation were excluded.Results:A total of 387 patients, predominantly HCV co-infected (78%) with balanced representation of all Barcelona Clinic Liver Cancer (BCLC) stages (A = 33%, B = 18%, C = 37%, D = 12%) were recruited. At HCC diagnosis, 84% had been on anti-retrovirals for a median duration of 8.8 years. The albumin-bilirubin grade identified significant differences in median survival of 97 months for grade 1 (95% CI 13-180 months), 17 months for grade 2 (95% CI 11-22 months) and 6 months for grade 3 (95% CI 4-9 months, P < .001). A more advanced albumin-bilirubin grade correlated with lower CD4 counts (464/373/288 cells/mm3 for grades 1/2/3) and higher HIV viraemia (3.337/8.701/61.845 copies/mL for grades 1/2/3, P < .001).Conclusions:In this large, multi-center retrospective study, the albumin-bilirubin grade highlights the interplay between liver reserve and immune dysfunction as prognostic determinants in HIV-associated HCC.
Sharma SK, Chaubey J, Singh BK, et al., 2017, Drug resistance patterns among extra-pulmonary tuberculosis cases in a tertiary care centre in North India., Int J Tuberc Lung Dis, Vol: 21, Pages: 1112-1117
BACKGROUND: xtra-pulmonary tuberculosis (EPTB) is a growing public health concern, and data on drug resistance are limited. MATERIAL AND METHODS: Specimens from 2468 clinically diagnosed EPTB patients received at the Intermediate Reference Laboratory (IRL) of a tertiary centre in India were subjected to Ziehl-Neelsen staining, Xpert® MTB/RIF testing, liquid culture and drug susceptibility testing (DST) using automated BACTEC MGIT™ 960™. Line-probe assay (LPA) was performed on all culture-positive isolates. Gene sequencing was performed on rifampicin-resistant/multidrug-resistant TB (RR/MDR-TB) and phenotypic/genotypic discrepant isolates. RESULTS: The culture positivity rate was 18.9% (483/2553). The sensitivity and specificity of Xpert in diagnosing EPTB were respectively 70.8% (95%CI 66.5-74.8) and 97.7% (95%CI 96.9-98.3), with liquid culture as the reference standard. Prevalence of RR/MDR-TB was 10.1% (49/483). Prevalence of pre-extensively drug-resistant TB (pre-XDR-TB) was 18.4% (09/49), whereas the prevalence of XDR-TB among MDR-TB patients was 2% (01/49). The sensitivity of genotypic DST for the detection of rifampicin resistance was 92.7% (95%CI 81.1-98.5) and specificity was 99.3% (95%CI 97.5-99.9), with 100% concordance between Xpert and LPA. CONCLUSION: The burden of drug resistance, including M/XDR-TB, among EPTB patients is high. Novel molecular tests can help in early diagnosis and treatment to prevent disease progression and amplification of resistance.
Kumar N, Khamri W, Sadiq F, et al., 2017, Circulating Natural Killer cells in Hepatocellular Carcinoma are hypofunctional with an exhausted phenotype, 68th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) / Liver Meeting, Publisher: WILEY, Pages: 355A-355A, ISSN: 0270-9139
Pinato DJ, Black J, Trousil S, et al., 2017, Programmed cell death ligands expression in phaeochromocytomas and paragangliomas: relationship with the hypoxic response, immune evasion and malignant behaviour., OncoImmunology, Vol: 6, ISSN: 2162-4011
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 diagnosed between 1983-2011 were stained for PD-L1 & 2, hypoxia inducible factor 1a (Hif-1a), Carbonic Anhydrase IX (CaIX), Vascular Endothelial Growth Factor-A (VEGF-A). We explored the biologic significance of PD ligands expression using gene set enrichment analysis (GSEA) on The Cancer Genome Atlas (TCGA) for PCC/PGL (n=184). 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. We found PD-L1 expression in 18% of PCC/PGL, which was independent of adverse pathological features including capsular (CI), vascular invasion (VI), necrosis (N) and expression of biomarkers of hypoxia. PD-L2 expression (16%) strongly correlated with CI, VI, N and malignant behaviour (p<0.05) and was associated with stronger Hif-1a and CaIX immunolabeling (p<0.01). PD-L2 was predictive of shorter survival (162 versus 309 months, HR 3.1 95%CI 1.1-9.2, p=0.02). GSEA on TGCA samples confirmed enrichment of transcripts involved in hypoxia and anti-cancer immunity.Conclusions: We report for the first time PD ligands expression in PCC/PGL with a distinctive prognostic, clinico-pathologic and immuno-biologic role. These findings support a potential therapeutic role for PD-1/PD-L1 targeted checkpoint inhibitors in these tumours.
Khan SA, McClements S, Reccia I, et al., 2017, The next generation of hepatocellular cancer experts: what do they think?, Hepatic Oncology, Vol: 3, Pages: 213-215, ISSN: 2045-0923
Sharma R, Wang WM, Evans J, et al., 2017, 68Ga-DOTATATE PET/CT to predict response to peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumours (NETs), ASCO, Publisher: American Society of Clinical Oncology, ISSN: 0732-183X
Pinato DJ, Black JM, Trousil S, et al., 2017, Programmed cell death ligands expression in pheochromocytomas (PCC) and paragangliomas (PGL): Relationship with the hypoxic response and malignant behaviour., Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: AMER SOC CLINICAL ONCOLOGY, ISSN: 0732-183X
Pinato DJ, Victor S, Spina P, et al., 2017, Intra-tumour heterogeneity in the regulation of immune-tolerogenic pathways in primary and metastatic hepatocellular carcinoma (HCC)., 53rd Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: AMER SOC CLINICAL ONCOLOGY, ISSN: 0732-183X
Citti C, Pinato D, Ventura-Cots M, et al., 2017, Liver transplantation for human immunodeficiency virus-Infected patients with hepatocellular carcinoma, International Liver Congress / 52nd Annual Meeting of the European-Association-for-the-Study-of-the-Liver, Publisher: Elsevier, Pages: S216-S216, ISSN: 0168-8278
Sharma R, 2017, Editorial: sorafenib toxicity, a biomarker of effect? Authors' reply, ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Vol: 45, Pages: 1470-1471, ISSN: 0269-2813
Pinato DJ, Howell J, Ramaswami R, et al., 2017, Review article: delivering precision oncology in intermediate-stage liver cancer, Alimentary Pharmacology and Therapeutics, Vol: 45, Pages: 1514-1523, ISSN: 0269-2813
BackgroundIntermediate-stage hepatocellular carcinoma (HCC), for which trans-arterial chemoembolization (TACE) constitutes the standard of care, is a patient subgroup with significant heterogeneity in clinical outcome. Sources of variation relate to differences in tumour burden, hepatic reserve, ethnicity and treatment modalities. Increasing research efforts have been dedicated to minimise the clinical diversity of this patient population and enhance optimal provision of treatment.AimTo comprehensively review the diverse prognostic models that have been proposed to refine the prognostic prediction of patients with HCC undergoing TACE.ResultsA number of prognostic algorithms (HAP, ART, ABCR score and many others) have shown potential to address the clinical heterogeneity characterising patients with intermediate-stage HCC and facilitate early identification of patients with poor prognostic features in whom alternative treatments or best supportive care might be more appropriate than TACE.ConclusionsWhile an improved characterisation of intermediate-stage HCC is a highly important clinical aim, current evidence suggests that novel prognostic algorithms in this patient population may offer potential benefits but non-negligible challenges in the provision of TACE. This review summarises the currently available evidence to facilitate the development of precision oncology in intermediate-stage HCC.
Pinato D, Pria AD, Aravind P, et al., 2017, HIV-associated hepatocellular carcinoma: validation of the albumin-bilirubin (ALBI) grade as a prognostic indicator in 387 patients, BHIVA, Publisher: WILEY, Pages: 39-39, ISSN: 1464-2662
Brodie BA, Marker SR, Romano A, et al., 2017, Non-invasive exhaled breath volatile organic compound analysis for the diagnosis of pancreatic cancer, Annual Meeting of the Society-of-Academic-and-Research-Surgery (SARS), Publisher: WILEY, Pages: 37-37, ISSN: 0007-1323
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