Publications by authors named "Nicos Fotiadis"

29 Publications

  • Page 1 of 1

Diagnostic Accuracy and Safety of Coaxial System in Oncology Patients Treated in a Specialist Cancer Center With Prospective Validation Within Clinical Trial Data.

Front Oncol 2020 4;10:1634. Epub 2020 Sep 4.

Cancer Research UK Cancer Imaging Centre, Division of Radiotherapy and Imaging, The Institute of Cancer Research and Royal Marsden Hospital, London, United Kingdom.

Background: Image-guided tissue biopsies are critically important in the diagnosis and management of cancer patients. High-yield samples are also vital for biomarker and resistance mechanism discovery through molecular/genomic analyses.

Patients And Methods: All consecutive patients who underwent plugged image-guided biopsy at Royal Marsden from June 2013 until September 2016 were included in the analysis. In the next step, a second cohort of patients prospectively treated within two clinical trials (PROSPECT-C and PROSPECT-R) were assessed for the DNA yield from biopsies assessed for complex genomic analysis.

Results: A total of 522 plugged core biopsies were performed in 457 patients [men, 52%; median age, 63 years (range, 17-93)]. Histological diagnosis was achieved in 501 of 522 (96%) performed biopsies. Age, gender, modality, metastatic site, and seniority of the interventionist were not found to be significant factors associated with odds of failure on a logistic regression. Seventeen (3.3%) were admitted due to biopsy-related complications; nine, three, two, one, one, and one were admitted for grade I/II pain control, sepsis, vasovagal syncope, thrombosis, hematuria, and deranged liver functions, respectively; two patients with right upper quadrant pain after liver biopsy were found to have radiologically confirmed subcapsular hematoma requiring conservative treatment. One patient (0.2%) developed grade III hemorrhage following biopsy of a gastric gastrointestinal stromal tumor (GIST). Overall molecular analysis was successful in 89% (197/222 biopsies). Prospective validation in 62 biopsies gave success rates of 92.06 and 79.03% for DNA extraction of >1 μm and tmour content of >20%, respectively.

Conclusion: The probability of diagnostic success for complex molecular analysis is increased with plugged large coaxial needle biopsy technique, which also minimizes complications and reduces hospital stay. High-yield DNA acquisition allows genomic molecular characterization for personalized medicine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.01634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500492PMC
September 2020

Comparison of a coaxial versus non-coaxial liver biopsy technique in an oncological setting: diagnostic yield, complications and seeding risk.

Eur Radiol 2020 Dec 14;30(12):6702-6708. Epub 2020 Jul 14.

Department of Radiology, The Royal Marsden NHS Foundation Trust, Downs Rd, Sutton, London, SW2 5PT, UK.

Objectives: Percutaneous liver biopsy (PLB) poses specific challenges in oncological patients such as bleeding and tumour seeding. This study's aim was to compare a coaxial (C-PLB) and non-coaxial (NC-PLB) biopsy technique in terms of diagnostic yield, safety and seeding risk of image-guided PLB techniques in an oncological setting.

Methods: Local research committee approval was obtained for this single-site retrospective study. Patients who underwent a PLB between November 2011 and December 2017 were consecutively included. Medical records were reviewed to determine diagnostic yield and complications. Follow-up imaging was re-reviewed for seeding, defined as visible tumour deposits along the PLB track. Mann-Whitney U and chi-squared tests were performed to investigate differences between biopsy techniques in sample number, complications and seeding rate.

Results: In total, 741 patients (62 ± 13 years, 378 women) underwent 932 PLB (C-PLB 72.9% (679/932); NC-PLB 27.1% (253/932)). More tissue cores (p < 0.001) were obtained with C-PLB (median 4 cores; range 1-12) compared with NC-PLB (2 cores; range 1-4) and diagnostic yield was similar for both techniques (C-PLB 92.6% (629/679); NC-PLB 92.5% (234/253); p = 0.940). Complication rate (9.3%; 87/932) using C-PLB (8.2% (56/679)) was lower compared with NC-PLB (12.3% (31/253); p = 0.024). Major complications were uncommon (C-PLB 2.7% (18/679); NC-PLB 2.8% (7/253)); bleeding developed in 1.2% (11/932; C-PLB 1.2% (8/679); NC-PLB 1.2% (3/253)). Seeding was a rare event, occurring significantly less in C-PLB cases (C-PLB 1.3% (7/544); NC-PLB 3.1% (6/197); p = 0.021).

Conclusions: C-PLB allows for high diagnostic tissue yield with a lower complication and seeding rate than a NC-PLB and should be the preferred method in an oncological setting.

Key Points: • A coaxial percutaneous liver biopsy achieves a significant higher number of cores and fewer complications than a non-coaxial biopsy technique. • The risk of tumour seeding is very low and is significantly lower using the coaxial biopsy technique. • In this study, a larger number of cores (median = 4) could be safely acquired using the coaxial technique, providing sufficient material for advanced molecular analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-020-07038-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599171PMC
December 2020

Revolutions in treatment options in gastrointestinal stromal tumours (GISTs): the latest updates

Curr Treat Options Oncol 2020 05 27;21(7):55. Epub 2020 May 27.

Sarcoma Unit, The Royal Marsden Hospital (NHS Foundation Trust) and Institute of Cancer Research, Fulham Road, London, SW3 6JJ, UK.

Opinion Statement: The treatment of advanced GIST is rapidly evolving with the development of novel molecular compounds such as avapritinib and ripretinib, but also promising results have been achieved with cabozantinib in a phase II trial. The availability of over five lines of treatment for patients with advanced GIST is likely to completely shift the current second-line and third-line treatment options, and will also potentially enable a personalised approach to treatment. Imatinib will most likely remain as the first-line treatment of choice for the vast majority of GIST patients. However, for GIST patients with tumours harbouring a D842V mutation in PDGFRA exon 18, avapritinib has shown efficacy and will become first-line therapy for this molecular subgroup. For second- and third-line treatment, results are awaited of a number of clinical trials. However, second-line and further treatment could potentially be tailored depending on secondary mutations found in imatinib-resistant GISTs. As secondary resistance to TKIs remains the biggest challenge in the treatment of GIST and despite negative results with alternating regimens in phase II, combination treatments should be further evaluated to tackle this issue. Moreover, the favourable safety profiles observed with avapritinib and ripretinib suggest that combination treatments are feasible, for instance, combining two TKIs or a TKI with drugs targeting downstream signalling pathways, such as PI3K inhibitors or MEK inhibitors. Finally, in line with further personalisation of treatment in GIST, a multidisciplinary approach is essential, and local treatment options, such as RFA, resection in case of unifocal progression, and radiotherapy, should be considered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11864-020-00754-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253383PMC
May 2020

Molecular and immunological features of a prolonged exceptional responder with malignant pleural mesothelioma treated initially and rechallenged with pembrolizumab.

J Immunother Cancer 2020 03;8(1)

Drug Development Unit, Royal Marsden Hospital/ Institute of Cancer Research, Sutton, UK.

Background: This case represents an exceptional response to pembrolizumab in a patient with epithelioid mesothelioma with a further response on rechallenge.

Case Presentation: A 77-year-old woman with advanced epithelioid mesothelioma extensively pretreated with chemotherapy demonstrated a prolonged response of 45 months to 52 cycles of pembrolizumab. On rechallenge with pembrolizumab, further disease stability was achieved. Serial biopsies and analysis by immunohistochemistry and immunofluorescence demonstrated marked immune infiltration and documented the emergency of markers of immune exhaustion. Whole exome sequencing demonstrated a reduction in tumor mutational burden consistent with subclone elimination by immune checkpoint inhibitor (CPI) therapy. The relapse biopsy had missense mutation in BTN2A1.

Conclusion: This case supports rechallenge of programme death receptor 1 inhibitor in cases of previous CPI sensitivity and gives molecular insights.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jitc-2020-000713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069263PMC
March 2020

Oncological Outcome After Diagnostic Biopsies in Gastrointestinal Stromal Tumors: A Retrospective Cohort Study.

Ann Surg 2019 Dec 10. Epub 2019 Dec 10.

Sarcoma Unit, Department of Surgical Oncology, Royal Marsden Hospital and Institute of Cancer Research, London, UK.

Objective: To analyze whether the route of preoperative biopsy influences oncological outcome in GIST patients.

Summary Of Background Data: Preoperative biopsies are widely used for diagnosing GIST. Little is known about the risk of tumor seeding after different routes of biopsy.

Methods: Patients who underwent resection of a primary GIST between 1996 and 2014 were identified from 2 databases from 2 tertiary referral centers. Survival data were obtained using the Kaplan-Meier method. Possible confounders were identified using Cox regression analysis. The primary endpoint was local recurrence free survival (RFS) and the secondary endpoint was DSS.

Results: A total of 228 patients were included, with a median age of 62 years (range 17-86) and a median follow-up time of 53 months (range 1-204). From these patients, 42 patients did not have a biopsy (18%), 70 underwent a transcutaneous biopsy (31%), and 116 a transluminal biopsy (51%). A total of 42 patients (19.0%) had a local and/or distant recurrence. From the 70 patients with a transcutaneous biopsy, only 1 patient developed a needle tract recurrence (1.4%). Local RFS and DSS were both significantly shorter in the transcutaneous biopsy group on univariate analysis compared to the other groups; however, in multivariate analysis the route of biopsy did not influence local RFS (P = 0.128) or DSS (P = 0.096).

Conclusions: Transluminal or transcutaneous biopsies for diagnosing GIST do not significantly alter the risk of local recurrent disease or DSS in multivariate Cox regressions. The risk of needle tract seeding after transcutaneous biopsy was low.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000003744DOI Listing
December 2019

The Role of Local Therapy in Multi-focal Epithelioid Haemangioendothelioma.

Anticancer Res 2019 Sep;39(9):4891-4896

Sarcoma Unit, Royal Marsden Hospital, Fulham, London, U.K.

Background/aim: Epithelioid haemangioendothelioma (EHE) is a rare tumor with a wide spectrum of clinical behavior. There is no consensus on the role of local therapy in symptomatic, multi-focal disease.

Patients And Methods: A retrospective review of patients presenting to the Royal Marsden Hospital between January 2000 and December 2017 was conducted.

Results: Fifty-three patients with EHE were identified, of which 18 patients (34.0%) received local therapy, and 11 patients (20.8%) underwent active surveillance. A variety of local treatment modalities were used with few toxicities, and local recurrence was managed with other local treatments or systemic therapy. Distal disease progression was infrequent (n=4, 7.5%). Patients who developed pleural effusion (n=5, 9.4%) had poor outcome irrespective of treatment.

Conclusion: Local therapy has a role in a selected patient group managed in a multidisciplinary setting, including patients with indolent disease, and patients with a solitary area of progression/symptomatic disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21873/anticanres.13675DOI Listing
September 2019

CEA expression heterogeneity and plasticity confer resistance to the CEA-targeting bispecific immunotherapy antibody cibisatamab (CEA-TCB) in patient-derived colorectal cancer organoids.

J Immunother Cancer 2019 04 15;7(1):101. Epub 2019 Apr 15.

Translational Oncogenomics Laboratory, Centre for Evolution and Cancer, The Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK.

Background: The T cell bispecific antibody cibisatamab (CEA-TCB) binds Carcino-Embryonic Antigen (CEA) on cancer cells and CD3 on T cells, which triggers T cell killing of cancer cell lines expressing moderate to high levels of CEA at the cell surface. Patient derived colorectal cancer organoids (PDOs) may more accurately represent patient tumors than established cell lines which potentially enables more detailed insights into mechanisms of cibisatamab resistance and sensitivity.

Methods: We established PDOs from multidrug-resistant metastatic CRCs. CEA expression of PDOs was determined by FACS and sensitivity to cibisatamab immunotherapy was assessed by co-culture of PDOs and allogeneic CD8 T cells.

Results: PDOs could be categorized into 3 groups based on CEA cell-surface expression: CEA (n = 3), CEA (n = 1) and CEA PDOs (n = 4), that stably maintained populations of CEA and CEA cells, which has not previously been described in CRC cell lines. CEA PDOs were sensitive whereas CEA PDOs showed resistance to cibisatamab. PDOs with mixed expression showed low sensitivity to cibisatamab, suggesting that CEA cells maintain cancer cell growth. Culture of FACS-sorted CEA and CEA cells from PDOs with mixed CEA expression demonstrated high plasticity of CEA expression, contributing to resistance acquisition through CEA antigen loss. RNA-sequencing revealed increased WNT/β-catenin pathway activity in CEA cells. Cell surface CEA expression was up-regulated by inhibitors of the WNT/β-catenin pathway.

Conclusions: Based on these preclinical findings, heterogeneity and plasticity of CEA expression appear to confer low cibisatamab sensitivity in PDOs, supporting further clinical evaluation of their predictive effect in CRC. Pharmacological inhibition of the WNT/β-catenin pathway may be a rational combination to sensitize CRCs to cibisatamab. Our novel PDO and T cell co-culture immunotherapy models enable pre-clinical discovery of candidate biomarkers and combination therapies that may inform and accelerate the development of immuno-oncology agents in the clinic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40425-019-0575-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463631PMC
April 2019

miR-31-3p Expression and Benefit from Anti-EGFR Inhibitors in Metastatic Colorectal Cancer Patients Enrolled in the Prospective Phase II PROSPECT-C Trial.

Clin Cancer Res 2019 07 5;25(13):3830-3838. Epub 2019 Apr 5.

Department of Medicine, The Royal Marsden NHS Trust, London and Sutton, United Kingdom.

Purpose: Anti-EGFR mAbs are effective in the treatment of metastatic colorectal cancer (mCRC) patients. status and tumor location (sidedness) are predictive markers of patients' response to anti-EGFR mAbs. Recently, low miR-31-3p expression levels have been correlated with clinical benefit from the anti-EGFR mAb cetuximab. Here, we aimed to validate the predictive power of miR-31-3p in a prospective cohort of chemorefractory mCRC patients treated with single-agent anti-EGFR mAbs.

Experimental Design: miR-31-3p was tested by hybridization (ISH) in 91 pretreatment core biopsies from metastatic deposits of 45 patients with mCRC. Sequential tissue biopsies obtained before treatment, at the time of partial response, and at disease progression were tested to monitor changes in miR-31-3p expression overtreatment. miR-31-3p expression, sidedness, and status in pretreatment cell-free DNA were combined in multivariable regression models to assess the predictive value of each variable alone or in combination.

Results: Patients with low miR-31-3p expression in pretreatment biopsies showed better overall response rate, as well as better progression-free survival and overall survival, compared to those with high miR-31-3p expression. The prognostic effect of miR-31-3p was independent from age, gender, and sidedness. No significant changes in the expression of miR-31-3p were observed when sequential tissue biopsies were tested in long-term or poor responders to anti-EGFR mAbs. miR-31-3p scores were similar when pretreatment biopsies were compared with treatment-naïve archival tissues (often primary colorectal cancer).

Conclusions: Our study validates the role of miR-31-3p as potential predictive biomarker of selection for anti-EGFR mAbs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-18-3769DOI Listing
July 2019

Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal.

Cell 2018 04 12;173(3):595-610.e11. Epub 2018 Apr 12.

Department of Scientific Computing, the Francis Crick Institute, London NW1 1AT, UK.

The evolutionary features of clear-cell renal cell carcinoma (ccRCC) have not been systematically studied to date. We analyzed 1,206 primary tumor regions from 101 patients recruited into the multi-center prospective study, TRACERx Renal. We observe up to 30 driver events per tumor and show that subclonal diversification is associated with known prognostic parameters. By resolving the patterns of driver event ordering, co-occurrence, and mutual exclusivity at clone level, we show the deterministic nature of clonal evolution. ccRCC can be grouped into seven evolutionary subtypes, ranging from tumors characterized by early fixation of multiple mutational and copy number drivers and rapid metastases to highly branched tumors with >10 subclonal drivers and extensive parallel evolution associated with attenuated progression. We identify genetic diversity and chromosomal complexity as determinants of patient outcome. Our insights reconcile the variable clinical behavior of ccRCC and suggest evolutionary potential as a biomarker for both intervention and surveillance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2018.03.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938372PMC
April 2018

Timing the Landmark Events in the Evolution of Clear Cell Renal Cell Cancer: TRACERx Renal.

Cell 2018 04 12;173(3):611-623.e17. Epub 2018 Apr 12.

Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.

Clear cell renal cell carcinoma (ccRCC) is characterized by near-universal loss of the short arm of chromosome 3, deleting several tumor suppressor genes. We analyzed whole genomes from 95 biopsies across 33 patients with clear cell renal cell carcinoma. We find hotspots of point mutations in the 5' UTR of TERT, targeting a MYC-MAX-MAD1 repressor associated with telomere lengthening. The most common structural abnormality generates simultaneous 3p loss and 5q gain (36% patients), typically through chromothripsis. This event occurs in childhood or adolescence, generally as the initiating event that precedes emergence of the tumor's most recent common ancestor by years to decades. Similar genomic changes drive inherited ccRCC. Modeling differences in age incidence between inherited and sporadic cancers suggests that the number of cells with 3p loss capable of initiating sporadic tumors is no more than a few hundred. Early development of ccRCC follows well-defined evolutionary trajectories, offering opportunity for early intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2018.02.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5927631PMC
April 2018

Patient-derived organoids model treatment response of metastatic gastrointestinal cancers.

Science 2018 02;359(6378):920-926

Division of Molecular Pathology, The Institute of Cancer Research, London, UK.

Patient-derived organoids (PDOs) have recently emerged as robust preclinical models; however, their potential to predict clinical outcomes in patients has remained unclear. We report on a living biobank of PDOs from metastatic, heavily pretreated colorectal and gastroesophageal cancer patients recruited in phase 1/2 clinical trials. Phenotypic and genotypic profiling of PDOs showed a high degree of similarity to the original patient tumors. Molecular profiling of tumor organoids was matched to drug-screening results, suggesting that PDOs could complement existing approaches in defining cancer vulnerabilities and improving treatment responses. We compared responses to anticancer agents ex vivo in organoids and PDO-based orthotopic mouse tumor xenograft models with the responses of the patients in clinical trials. Our data suggest that PDOs can recapitulate patient responses in the clinic and could be implemented in personalized medicine programs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.aao2774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6112415PMC
February 2018

MIR21 Drives Resistance to Heat Shock Protein 90 Inhibition in Cholangiocarcinoma.

Gastroenterology 2018 03 4;154(4):1066-1079.e5. Epub 2017 Nov 4.

The Royal Marsden NHS Trust, London and Surrey, UK.

Background & Aims: Cholangiocarcinomas (CCA) are resistant to chemotherapy, so new therapeutic agents are needed. We performed a screen to identify small-molecule compounds that are active against CCAs. Levels of microRNA 21 (MIR21 or miRNA21) are increased in CCAs. We investigated whether miRNA21 mediates resistance of CCA cells and organoids to HSP90 inhibitors.

Methods: We performed a high-throughput screen of 484 small-molecule compounds to identify those that reduced viability of 6 human CCA cell lines. We tested the effects of HSP90 inhibitors on cells with disruption of the MIR21 gene, cells incubated with MIR21 inhibitors, and stable cell lines with inducible expression of MIR21. We obtained CCA biopsies from patients, cultured them as organoids (patient-derived organoids). We assessed their architecture, mutation and gene expression patterns, response to compounds in culture, and when grown as subcutaneous xenograft tumors in mice.

Results: Cells with IDH1 and PBRM1 mutations had the highest level of sensitivity to histone deacetylase inhibitors. HSP90 inhibitors were effective in all cell lines, irrespective of mutations. Sensitivity of cells to HSP90 inhibitors correlated inversely with baseline level of MIR21. Disruption of MIR21 increased cell sensitivity to HSP90 inhibitors. CCA cells that expressed transgenic MIR21 were more resistant to HSP90 inhibitors than cells transfected with control vectors; inactivation of MIR21 in these cells restored sensitivity to these agents. MIR21 was shown to target the DnaJ heat shock protein family (Hsp40) member B5 (DNAJB5). Transgenic expression of DNAJB5 in CCA cells that overexpressed MIR21 re-sensitized them to HSP90 inhibitors. Sensitivity of patient-derived organoids to HSP90 inhibitors, in culture and when grown as xenograft tumors in mice, depended on expression of miRNA21.

Conclusions: miRNA21 appears to mediate resistance of CCA cells to HSP90 inhibitors by reducing levels of DNAJB5. HSP90 inhibitors might be developed for the treatment of CCA and miRNA21 might be a marker of sensitivity to these agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2017.10.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863695PMC
March 2018

Molecular Adequacy of Image-Guided Rebiopsies for Molecular Retesting in Advanced Non-Small Cell Lung Cancer: A Single-Center Experience.

J Thorac Oncol 2018 01 6;13(1):63-72. Epub 2017 Oct 6.

Royal Marsden Hospital, London, United Kingdom. Electronic address:

Introduction: In the era of biomarker-driven systemic therapy for advanced NSCLC, the role of routine repeated biopsies for decision making outside EGFR-mutant disease remains unproven. We report our center's experience of safety and adequacy for molecular retesting of tumor material obtained from image-guided lung rebiopsies in NSCLC.

Methods: We performed a retrospective case note analysis of patients undergoing image-guided lung rebiopsies at a single cancer center between 2011 and 2014. The primary objective was to determine the pathological success rate. Secondary and exploratory objectives were to determine technical success rate, histological concordance, molecular adequacy, genotypes identified, and complication rate.

Results: In all, 103 patients underwent transthoracic image-guided procedures. A total of 66 rebiopsies in NSCLC were identified and analyzed. The pathological success rate was 87.1%. A high histological discordance rate was observed (12 of 52 evaluable cases [23.1%]). Pretest molecular adequacy as determined by the lung pathologist was 78.8% (52 of 66). Of 52 adequate samples 51 were sent for molecular analysis, with a total of 209 genes analyzed (including EGFR, ALK receptor tyrosine kinase gene [ALK], KRAS, BRAF, dicoidin domain receptor tyrosine kinase 2 gene [DDR2], NRAS, ROS1, and rearranged during transfection proto-oncogene gene [RET]). The rate of postgenotyping molecular adequacy was 87.1% (182 of 209). Overall, 20 new potentially actionable mutations were identified, with 13 of 66 patients (19.7%) starting to receive new targeted treatment as a result. Overall, rebiopsies informed clinical decision making in 63.6% of cases. The rates of complications were 15% for pneumothorax, 3% for pneumothorax requiring chest drain, and 8% for hemoptysis.

Conclusions: We have validated the pathological and molecular adequacy rates of rebiopsies and demonstrated clinical utility in routine decision making.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtho.2017.09.1958DOI Listing
January 2018

Lack of response to nivolumab in a patient with EGFR-mutant non-small cell lung cancer adenocarcinoma sub-type transformed to small cell lung cancer.

Lung Cancer 2017 09 11;111:65-68. Epub 2017 Jul 11.

Lung Unit, Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, United Kingdom; National Heart and Lung Institute, Imperial College London, Cale Street, London, SW3 6LY, United Kingdom. Electronic address:

Small cell transformation is a rare but well recognised mechanism of acquired resistance to EGFR-TKI therapy in EGFR-mutated NSCLC, but optimal drug therapy thereof is unknown. Nivolumab has demonstrated activity in relapsed de novo small cell lung cancer in early phase trials. Here, we report a case of transformed EGFR-mutant SCLC treated with nivolumab with no benefit.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lungcan.2017.07.012DOI Listing
September 2017

Functional imaging and circulating biomarkers of response to regorafenib in treatment-refractory metastatic colorectal cancer patients in a prospective phase II study.

Gut 2018 08 8;67(8):1484-1492. Epub 2017 Aug 8.

Department of Medicine, The Royal Marsden NHS Trust, London and Sutton, UK.

Objective: Regorafenib demonstrated efficacy in patients with metastatic colorectal cancer (mCRC). Lack of predictive biomarkers, potential toxicities and cost-effectiveness concerns highlight the unmet need for better patient selection.

Design: Patients with mutant mCRC with biopsiable metastases were enrolled in this phase II trial. Dynamic contrast-enhanced (DCE) MRI was acquired pretreatment and at day 15 post-treatment. Median values of volume transfer constant (K), enhancing fraction (EF) and their product KEF (summarised median values of K× EF) were generated. Circulating tumour (ct) DNA was collected monthly until progressive disease and tested for clonal mutations by digital-droplet PCR. Tumour vasculature (CD-31) was scored by immunohistochemistry on 70 sequential tissue biopsies.

Results: Twenty-seven patients with paired DCE-MRI scans were analysed. Median KEF decrease was 58.2%. Of the 23 patients with outcome data, >70% drop in KEF (6/23) was associated with higher disease control rate (p=0.048) measured by RECIST V. 1.1 at 2 months, improved progression-free survival (PFS) (HR 0.16 (95% CI 0.04 to 0.72), p=0.02), 4-month PFS (66.7% vs 23.5%) and overall survival (OS) (HR 0.08 (95% CI 0.01 to 0.63), p=0.02). KEF drop correlated with CD-31 reduction in sequential tissue biopsies (p=0.04). mutant clones decay in ctDNA after 8 weeks of treatment was associated with better PFS (HR 0.21 (95% CI 0.06 to 0.71), p=0.01) and OS (HR 0.28 (95% CI 0.07-1.04), p=0.06).

Conclusions: Combining DCE-MRI and ctDNA predicts duration of anti-angiogenic response to regorafenib and may improve patient management with potential health/economic implications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/gutjnl-2017-314178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204951PMC
August 2018

Small-for-Size Liver Syndrome: a Case Series with a Proposal for Management Based on Portal Flow Modulation.

J Gastrointest Cancer 2015 Jun;46(2):185-9

Hepatopancreatobiliary Division, Academic Department of Surgery, The Royal Marsden Hospital, 233 Fulham Road, London, SW3 6JJ, UK,

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12029-015-9701-8DOI Listing
June 2015

Hemophilic arthropathy: a review of imaging and staging.

Semin Ultrasound CT MR 2013 Dec;34(6):516-24

Radiology Department, Chelsea and Westminster NHS Foundation Trust, London, UK. Electronic address:

Hemophilic arthropathy (HA) contributes the greatest morbidity and cost in the hemophilic population. Imaging plays a crucial role in accurately monitoring the disease process in all phases and evaluating treatment. It has been shown that prophylactic factor VIII replacement therapy, if given early in life, can prevent or delay the progression of HA and reduce the frequency of hemarthroses. This review evaluates the role of the different imaging modalities used in the staging of HA. It is noteworthy that a new refined consensus magnetic resonance imaging scale for assessment of HA has recently been published which together with introduction of semiquantitative scoring systems in ultrasound will help to provide a more tailored approach to the management of HA in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.sult.2013.05.007DOI Listing
December 2013

Endovascular repair of symptomatic hemodialysis access graft pseudoaneurysms.

J Vasc Access 2014 Jan-Feb;15(1):5-11. Epub 2013 Aug 9.

Interventional Radiology Department, The Royal London Hospital, London - UK.

Aim: Repeated needle punctures of arteriovenous hemodialysis grafts can lead to the development of pseudoaneurysms. As they enlarge, graft pseudoaneurysms are associated with significant morbidity and require treatment. We present our single-center experience using stent grafts in selected patients to exclude symptomatic hemodialysis graft pseudoaneurysms.

Materials And Methods: Between March 2007 and December 2010, 11 consecutive patients (7 men and 4 women, mean age 57 years) underwent percutaneous endovascular repair of symptomatic hemodialysis access graft pseudoaneurysms. Indications for treatment were rapidly enlarging pseudoaneurysm in 5 patients, high venous pressures, limb edema and pseudoaneurysm in 3, skin breakdown over the pseudoaneurysm site in 2 and acute rupture and bleeding in 1 patient. No patient was lost to follow-up.

Results: Technical success across the 11 patients was 90.9%. The patient who presented with rupture required ligation of the access due to continuous bleeding after stent graft insertion. Balloon angioplasty of a separate hemodynamically significant stenosis at the time of stent graft insertion was performed in 7 of 11 (63.6%) patients. The primary access patency rates were 72.7% (95% CI of 0.390-0.939) at 3 months and 36.4% (95% CI 0.109-0.692) at 6 months. Secondary access patency rates were 72.7% at 6 months (95% CI 0.233-0.832). There were no procedure-related complications. Mean follow-up was 9 months (range 2-29 months).

Conclusions: Endovascular treatment of symptomatic hemodialysis graft pseudoaneurysms is safe and effective with similar patency rates to surgical approaches. Importantly, this approach allows aggressive management of associated access circuit stenoses at the same time and avoids interval tunneled dialysis line insertion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5301/jva.5000161DOI Listing
December 2014

A telltale heart: an unusual chest radiograph in a trauma patient. Cardiac torsion.

CJEM 2012 Sep;14(5):315-6, 314

Department of Trauma and Orthopaedics, The Whittington Hospital, London, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2310/8000.2012.110749aDOI Listing
September 2012

Cephalic arch stenosis in autogenous haemodialysis fistulas: treatment with the viabahn stent-graft.

Cardiovasc Intervent Radiol 2013 Feb 27;36(1):133-9. Epub 2012 Jun 27.

Radiology Department, The Royal London Hospital, London, UK.

Purpose: Cephalic arch stenosis (CAS) is an important and common cause of dysfunction in autogenous haemodialysis fistulas that requires multiple reinterventions and aggressive surveillance. We evaluated the safety and efficacy of the Viabahn stent-graft for the management of CAS.

Methods: Between April 2005 and October 2011, 11 consecutive patients [four men and seven women (mean age 56.7 years)] with CAS and dysfunctional fistulas were treated with insertion of 11 Viabahn stent-grafts. Six stent-grafts were inserted due to residual stenosis after angioplasty and five for fistuloplasty-induced rupture. No patient was lost to follow-up.

Results: The technical and clinical success rate was 100 %. Primary access patency rates were 81.8 % [95 % confidence interval (CI) 0.482-0.977] at 6 months and 72.7 % (95 % CI 0.390-0.939) at 12 months. Secondary access patency rates were 90.9 % at 6 months (95 % CI 0.587-0.997). There were no procedure-related complications. Mean follow-up was 543.8 days (range 156-2,282).

Conclusion: The use of the Viabahn stent-graft in the management of CAS is technically feasible and, in this small series, showed patency rates that compare favorably with historical data of angioplasty and bare stents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00270-012-0433-xDOI Listing
February 2013

A pictorial review of traumatic pericardial injuries.

Insights Imaging 2012 Aug 15;3(4):307-11. Epub 2012 May 15.

The Royal London Hospital, Barts and the London NHS Trust, Whitechapel Road, Whitechapel, London, E1 1BB, UK.

Background: Thoracic injuries are the third most common injuries in trauma patients with cardiac injuries amongst the most lethal. Imaging is essential in diagnosis and triage of patients with pericardial injuries, and this review aims to highlight the spectrum of imaging findings of pericardial trauma. Focussed assessment with sonography for trauma (FAST) is the preferred initial examination, being rapid and accurate. Sensitivity of FAST for pericardial fluid detection is high with reported sensitivities of 97-100%. Plain chest radiography has low sensitivity for pericardial injuries but is useful in the evaluation of associated injuries. Computed tomography (CT) is the modality of choice for stable patients and can accurately diagnose traumatic pathology of the pericardium being especially useful in identification of cardiac herniation. The spectrum of CT findings includes pericardial fluid collections, focal pericardial defects and pneumopericardium.

Methods: A selection of cases of pericardial trauma encountered at a level one trauma centre is presented. Operative findings were correlated with the FAST scan, plain radiography and computed tomography imaging.

Conclusion: The imaging findings of pericardial trauma with various imaging modalities (ultrasound, plain radiography and computed tomography) are presented in order to aid interpretation during the acute trauma setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13244-012-0177-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481075PMC
August 2012

Perforation and abscess formation after radiological placement of a retrievable plastic biliary stent.

J Med Case Rep 2011 Mar 14;5:103. Epub 2011 Mar 14.

Department of Diagnostic Imaging, Barts and The London NHS Trust, The Royal London Hospital, London, E1 1BB, UK.

Introduction: Retrievable plastic biliary stents are usually inserted endoscopically. When endoscopic placement fails, radiological percutaneous transhepatic placement is indicated. We report the occurrence of a case of delayed duodenal perforation with abscess formation after radiological placement of a plastic stent. To the best of our knowledge, this is the first report of this complication after radiological stenting.

Case Presentation: A 58-year-old Caucasian man had a mass 30 mm in size in the head of the pancreas and obstructive jaundice. He was referred for radiological insertion of plastic biliary stents after a failed endoscopic attempt. The procedure was uneventful, and the patient was discharged. Two weeks after the procedure, the patient presented with an acute abdomen and signs of sepsis. Computed tomography revealed erosion of the posterior duodenal wall from the plastic stent, and a large retroperitoneal abscess. The abscess was drained under computed tomography guidance, and the migrated stent was removed percutaneously with a snare under fluoroscopic guidance. Our patient had an uneventful recovery and was discharged after a week.

Conclusion: Late retroperitoneal duodenal perforation is a very rare but severe complication of biliary stenting with plastic stents. Gastroenterologists, surgeons and radiologists should all be aware of its existence, clinical presentation and management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1752-1947-5-103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068103PMC
March 2011

Direct erosion and prolapse of esophageal stents into the tracheobronchial tree leading to life-threatening airway compromise.

J Vasc Interv Radiol 2009 Nov;20(11):1491-5

Department of Interventional Radiology, Guy's and St. Thomas' Hospital, SE1 7EH, London, England.

Covered or uncovered self-expanding metal stents are currently used for the palliative treatment of neoplastic esophageal obstructions or compressions and malignant esophageal leaks or fistulas. This small series, from three different European hospitals, highlights the unusual but significant complication of esophageal stent perforation followed by erosion and prolapse of the endoprosthesis into the tracheobronchial tree causing acute airway compromise or aspiration. Possible causal mechanisms and means of treatment are discussed to raise physician awareness of this life-threatening complication.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvir.2009.07.039DOI Listing
November 2009

Endoscopic management of intraductal papillary mucinous tumors fistulating into the common bile duct.

Gastrointest Endosc 2007 Nov;66(5):1060-2

Department of Gastroenterology, Derriford Hospital, Plymouth, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gie.2007.03.1061DOI Listing
November 2007

Modern trends in interventional radiology.

Br Med Bull 2007 30;81-82:167-82. Epub 2007 Apr 30.

Interventional Radiology Department, Guys' and St Thomas' Hospital, London, UK.

Objective: To review the current applications of Interventional Radiology (IR), outline newer technologies and techniques and emphasize the role of Interventional Radiologists as clinical practitioners.

Background: IR is a clinical modality that makes use of imaging guidance for the performance of minimally invasive treatment. The development of new imaging technologies and interventional devices has greatly increased the number of medical conditions that may now be treated by IR.

Summary: Promising new treatments in cancer therapy, the treatment of fibroids, venous access and spine interventions as well as advances in non-invasive vascular imaging, pharmacological therapies and peripheral arterial and venous interventions are providing exciting opportunities for IR, attracting significant patient interest and promising tremendous public benefit.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/bmb/ldm006DOI Listing
December 2007

Combined percutaneous radiofrequency ablation and ethanol injection of renal tumours: midterm results.

Eur Urol 2007 Sep 28;52(3):777-84. Epub 2007 Mar 28.

Department of Interventional Radiology, Guy's and St Thomas' Hospital, London, UK.

Objectives: To evaluate the safety and efficacy of combined percutaneous, image-guided, radiofrequency (RF) ablation and ethanol injection of renal tumours, and to present our midterm results.

Methods: Since February 2002, 27 consecutive patients (22 men, 5 women; age range: 39-84 yr; mean: 69) with 28 renal tumours (mean diameter: 2.87cm) were treated with combined percutaneous RF and ethanol ablation, and were prospectively evaluated. Twenty-five patients were considered nonsurgical candidates because of comorbid conditions (16 patients) or had previous nephrectomy (9 patients), and 2 had refused surgery. Thirty-three ablation sessions were performed, with computed tomography (26 sessions), ultrasound (6), or combined magnetic resonance imaging/fluoroscopic guidance in 1. Absolute ethanol (0.5-3ml; mean: 1.7) was injected into the tumour immediately before treatment with radiofrequency. Mean follow-up period was 18.6 mo (range: 3-56).

Results: Twenty-seven of the 28 tumours were completely ablated with either one (21 tumours) or two treatment sessions (6 tumours). One patient with residual disease refused further treatment. Only three minor complications, including a subcapsular haematoma and two patients with loin pain, occurred; all three patients were treated conservatively. None of the complications was related to the ethanol injection. During the follow-up period, no evidence of local recurrence or metastatic disease was seen. Creatinine levels have not changed significantly in any of the patients following ablation.

Conclusions: Combined use of percutaneous RF and ethanol ablation is a safe and effective alternative treatment for selective patients with renal tumours.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eururo.2007.03.063DOI Listing
September 2007
-->