Publications
302 results found
Domingo-Sabugo C, Willis-Owen SAG, Mandal A, et al., 2021, Distinct pancreatic and neuronal Lung Carcinoid molecular subtypes revealed by integrative omic analysis
<jats:title>Summary</jats:title><jats:p>Lung Carcinoids (L-CDs) are uncommon low-grade neuroendocrine tumours that are only recently becoming characterised at the molecular level. Notably data on the molecular events that precipitate altered gene expression programmes are very limited. Here we have identified two discrete L-CD subtypes from transcriptomic and whole-genome DNA methylation data, and comprehensively defined their molecular profiles using Whole-Exome Sequencing (WES) and Single Nucleotide Polymorphism (SNP) genotyping. Subtype (Group) 1 features upregulation of neuronal markers (L-CD-NeU) and is characterised by focal spindle cell morphology, peripheral location (71%), high mutational load (<jats:italic>P</jats:italic>=3.4×10<jats:sup>−4</jats:sup>), recurrent copy number alterations and is enriched for Atypical Lung Carcinoids. Group 2 (L-CD-PanC) are centrally located and feature upregulation of pancreatic and metabolic pathway genes concordant with promoter hypomethylation of beta cell and genes related to insulin secretion (<jats:italic>P</jats:italic><1×10<jats:sup>−6</jats:sup>). L-CD-NeU tumours harbour mutations in chromatin remodelling and in SWI/SNF complex members, while L-CD-PanC tumours show aflatoxin mutational signatures and significant DNA methylation loss genome-wide, particularly enriched in repetitive elements (<jats:italic>P</jats:italic><2.2 × 10<jats:sup>−16</jats:sup>). Our findings provide novel insights into the distinct mechanisms of epigenetic dysregulation in these lung malignancies, potentially opening new avenues for biomarker selection and treatment in L-CD patients.</jats:p>
Willis-Owen S, Domingo Sabugo C, Starren E, et al., 2021, Y disruption, autosomal hypomethylation and poor male lung cancer survival, Scientific Reports, Vol: 11, ISSN: 2045-2322
Lung cancer is the most frequent cause of cancer death worldwide. It affects more men than women, and men generally have worse survival outcomes. We compared gene co-expression networks in affected and unaffected lung tissue from 126 consecutive patients with Stage IA–IV lung cancer undergoing surgery with curative intent. We observed marked degradation of a sex-associated transcription network in tumour tissue. This disturbance, detected in 27.7% of male tumours in the discovery dataset and 27.3% of male tumours in a further 123-sample replication dataset, was coincident with partial losses of the Y chromosome and extensive autosomal DNA hypomethylation. Central to this network was the epigenetic modifier and regulator of sexually dimorphic gene expression, KDM5D. After accounting for prognostic and epidemiological covariates including stage and histology, male patients with tumour KDM5D deficiency showed a significantly increased risk of death (Hazard Ratio [HR] 3.80, 95% CI 1.40–10.3, P = 0.009). KDM5D deficiency was confirmed as a negative prognostic indicator in a further 1100 male lung tumours (HR 1.67, 95% CI 1.4–2.0, P = 1.2 × 10–10). Our findings identify tumour deficiency of KDM5D as a prognostic marker and credible mechanism underlying sex disparity in lung cancer.
Baudin E, Caplin M, Garcia-Carbonero R, et al., 2021, Lung and thymic carcinoids: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, ANNALS OF ONCOLOGY, Vol: 32, Pages: 439-451, ISSN: 0923-7534
- Author Web Link
- Cite
- Citations: 76
Zhang YZ, Brambilla C, Molyneaux PL, et al., 2020, Atypical mesothelial proliferation (amp) of the pleura: multidisciplinary approach, prognostic stratification and proposal of minimally invasive malignant pleural mesothelioma, Publisher: SPRINGER, Pages: S24-S25, ISSN: 0945-6317
Domingo-Sabugo C, Starren E, Mandal A, et al., 2020, Distinct Landscapes of Genomic Alterations between Lung Carcinoids and Non-Small Cell Lung Cancers, Publisher: SPRINGERNATURE, Pages: 528-528, ISSN: 1018-4813
Wright J, Lim E, Rice A, et al., 2020, Pulmonary carcinoid tumours with elevated proliferation rates - should there be a grade 3 subgroup of neuroendocrine tumours (NET)?, Publisher: SPRINGER, Pages: S127-S127, ISSN: 0945-6317
Lim E, 2020, What Is the Optimum Lymph Node Management in Patients Undergoing Surgery for Lung Cancer?, JOURNAL OF THORACIC ONCOLOGY, Vol: 15, Pages: 1565-1566, ISSN: 1556-0864
Bartlett EC, Kemp S, Ridge CA, et al., 2020, Baseline Results of the West London lung cancer screening pilot study - Impact of mobile scanners and dual risk model utilisation, LUNG CANCER, Vol: 148, Pages: 12-19, ISSN: 0169-5002
- Author Web Link
- Cite
- Citations: 25
Zhang YZ, Brambilla C, Molyneaux PL, et al., 2020, Presence of pleomorphic features but not growth patterns improves prognostic stratification of epithelioid malignant pleural mesothelioma by 2-tier nuclear grade, Histopathology, Vol: 77, Pages: 423-436, ISSN: 0309-0167
AIMS: Nuclear grade has been recently validated as a powerful prognostic tool in epithelioid malignant pleural mesothelioma (E-MPM). In other studies histological parameters including pleomorphic features and growth patterns were also shown to exert prognostic impact. The primary aims of our study are (1) externally validate the prognostic role of pleomorphic features in E-MPM and (2) investigate if evaluating growth pattern in addition to 2-tier nuclear grade improves prognostication. METHODS AND RESULTS: 614 consecutive cases of E-MPM from our institution over a period of 15 years were retrospectively reviewed, of which 51 showed pleomorphic features. E-MPM with pleomorphic features showed significantly worse overall survival compared those without (5.4 months vs 14.7 months). Tumours with predominantly micropapillary pattern showed the worst survival (6.2 months) followed by solid (10.5 months), microcystic (15.3 months), discohesive (16.1 months), trabecular (17.6 months) and tubulo-papillary (18.6 months). Sub-classification of growth patterns into high grade (solid, micropapillary) and low grade (all others) led to good separation of overall survival (10.5 months vs. 18.0 months) but did not predict survival independent of 2-tier nuclear grade. A composite score comprised of growth pattern and 2-tier nuclear grade did not improve prognostication compared with nuclear grade alone. Intra-tumoural heterogeneity in growth patterns is ubiquitous. CONCLUSIONS: Our findings support the incorporation of E-MPM with pleomorphic features in the epithelioid subtype as a highly aggressive variant distinct from 2-tier nuclear grade. E-MPM demonstrates extensive heterogeneity in growth pattern but its evaluation does not offer additional prognostic utility to 2-tier nuclear grade.
Lim E, Darlison L, Edwards J, et al., 2020, Mesothelioma and Radical Surgery 2 (MARS 2): protocol for a multicentre randomised trial comparing (extended) pleurectomy decortication versus no (extended) pleurectomy decortication for patients with malignant pleural mesothelioma., BMJ Open, Vol: 10, Pages: 1-9, ISSN: 2044-6055
INTRODUCTION: Mesothelioma remains a lethal cancer. To date, systemic therapy with pemetrexed and a platinum drug remains the only licensed standard of care. As the median survival for patients with mesothelioma is 12.1 months, surgery is an important consideration to improve survival and/or quality of life. Currently, only two surgical trials have been performed which found that neither extensive (extra-pleural pneumonectomy) or limited (partial pleurectomy) surgery improved survival (although there was some evidence of improved quality of life). Therefore, clinicians are now looking to evaluate pleurectomy decortication, the only radical treatment option left. METHODS AND ANALYSIS: The MARS 2 study is a UK multicentre open parallel group randomised controlled trial comparing the effectiveness and cost-effectiveness of surgery-(extended) pleurectomy decortication-versus no surgery for the treatment of pleural mesothelioma. The study will test the hypothesis that surgery and chemotherapy is superior to chemotherapy alone with respect to overall survival. Secondary outcomes include health-related quality of life, progression-free survival, measures of safety (adverse events) and resource use to 2 years. The QuinteT Recruitment Intervention is integrated into the trial to optimise recruitment. ETHICS AND DISSEMINATION: Research ethics approval was granted by London - Camberwell St. Giles Research Ethics Committee (reference 13/LO/1481) on 7 November 2013. We will submit the results for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBERS: ISRCTN-ISRCTN44351742 and ClinicalTrials.gov-NCT02040272.
Chang W-C, Zhang YZ, Lim E, et al., 2020, Prognostic Impact of Histopathologic Features in Pulmonary Invasive Mucinous Adenocarcinomas Proposal for a Pathologic Grading System, AMERICAN JOURNAL OF CLINICAL PATHOLOGY, Vol: 154, Pages: 88-102, ISSN: 0002-9173
- Author Web Link
- Cite
- Citations: 6
Edwards JG, Chansky K, Van Schil P, et al., 2020, The IASLC Lung Cancer Staging Project: Analysis of Resection Margin Status and Proposals for Residual Tumor Descriptors for Non-Small Cell Lung Cancer, JOURNAL OF THEORETICAL BIOLOGY, Vol: 492, Pages: 344-359, ISSN: 0022-5193
Lim E, Sousa I, Shah PL, et al., 2020, Lung Volume Reduction Surgery: Reinterpreted With Longitudinal Data Analyses Methodology, ANNALS OF THORACIC SURGERY, Vol: 109, Pages: 1496-+, ISSN: 0003-4975
- Author Web Link
- Cite
- Citations: 9
Leung M, Freidin MB, Freydina D, et al., 2020, Blood-based circulating tumor DNA mutations as a diagnostic and prognostic biomarker for lung cancer, CANCER, Vol: 126, Pages: 1804-1809, ISSN: 0008-543X
- Author Web Link
- Cite
- Citations: 8
Zhang YZ, Brambilla C, Molyneaux PL, et al., 2020, Utility of nuclear grading system in epithelioid malignant pleural mesothelioma in biopsy-heavy setting, The American Journal of Surgical Pathology, Vol: 44, Pages: 347-356, ISSN: 0147-5185
Nuclear grading systems for epithelioid malignant pleural mesothelioma (MPM) have been proposed but it remains uncertain if they could be applied in a biopsy-heavy setting. Using the proposed system, we conducted an independent, external validation study using 563 consecutive cases of epithelioid MPM diagnosed at our institution between 2003 and 2017, of which 87% of patients underwent biopsies only. The median number of sites sampled was 1, with a median maximum tissue dimension of 17 mm (biopsy) and 150 mm (resection). The median overall survival (OS) was 14.7 months. The frequencies of grade I, II, and III tumors were 31% (132/563), 52% (292/563), and 17% (94/563). Grade I tumors were associated with the most favorable median OS (24.7 mo) followed by grades II (12.7 mo) and III (7.2 mo). The 2-tier nuclear grade separated tumors into low grade (19.3 mo) and high grade (8.9 mo). In multivariate analysis, 3-tier nuclear grade, 2-tier nuclear grade, and mitosis-necrosis score predicted OS independent of age, procedural type, solid-predominant growth pattern, necrosis, and atypical mitosis (all P<0.001 except 2-tier nuclear grade, P=0.001). In the scenario of a single- site biopsy with tissue dimension ≤10 mm, none but age (P=0.002) were independently predictive. Our data also suggested sampling 3 sites or a maximum tissue dimension of at least 20 mm from a single site is optimal for nuclear grade assessment. In conclusion our study confirmed the utility of nuclear grade in epithelioid MPM using a biopsy-heavy cohort provided the tissue sample met minimum dimensional criteria.
Zang R, Shi J-F, Lerut TE, et al., 2020, Ten-Year Trends of Clinicopathologic Features and Surgical Treatment of Lung Cancer in China, ANNALS OF THORACIC SURGERY, Vol: 109, Pages: 389-395, ISSN: 0003-4975
- Author Web Link
- Cite
- Citations: 16
Lim E, Begum S, Batchelor T, et al., 2019, OPTIMUM DIAGNOSTIC PATHWAY AND PATHOLOGIC CONFIRMATION RATE OF EARLY STAGE LUNG CANCER: RESULTS FROM VIOLET, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A15-A15, ISSN: 0040-6376
Zhang YZ, Brambilla C, Molyneaux PL, et al., 2019, IMPACT OF NUMBER OF SAMPLING SITES AND SPECIMEN DIMENSION ON THE PERFORMANCE OF NUCLEAR GRADE AND GROWTH PATTERNS IN PREDICTING SURVIVAL IN EPITHELIOID MALIGNANT PLEURAL MESOTHELIOMA: A SINGLE INSTITUTION REVIEW OF 614 CASES, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A31-A32, ISSN: 0040-6376
Mandal A, Nastase A, Lu SK, et al., 2019, Analysis of Immune Phenotype Composition in Malignant Pleural Mesothelioma (MPM) Using Bulk RNA Sequencing, Publisher: ELSEVIER SCIENCE INC, Pages: S345-S346, ISSN: 1556-0864
De Sousa P, Mansour F, Barbosa M, et al., 2019, An Audit on IASLC Compliance of Lymph Nodes Dissection and Impact on Survival After Surgery for Non-Small Cell Lung Cancer, Publisher: ELSEVIER SCIENCE INC, Pages: S550-S550, ISSN: 1556-0864
De Sousa P, Gallina F, Tamburrini A, et al., 2019, Neutrophil to Lymphocyte Ratio Is an Independent Prognostic Predictor in Thymoma, Publisher: ELSEVIER SCIENCE INC, Pages: S332-S332, ISSN: 1556-0864
Domingo-Sabugo C, Starren E, Mandal A, et al., 2019, Comprehensive Molecular Profiling and Comparison of Common and Rarer Subtypes of Lung Cancer, Publisher: ELSEVIER SCIENCE INC, Pages: S686-S686, ISSN: 1556-0864
Lim E, Batchelor T, Shackcloth M, et al., 2019, Study protocol for VIdeo assisted thoracoscopic lobectomy versus conventional Open LobEcTomy for lung cancer, a UK multicentre randomised controlled trial with an internal pilot (the VIOLET study), BMJ OPEN, Vol: 9, ISSN: 2044-6055
- Author Web Link
- Cite
- Citations: 40
Lim E, Batchelor T, Dunning J, et al., 2019, In Hospital Clinical Efficacy, Safety and Oncologic Outcomes from VIOLET: A UK Multi-Centre RCT of VATS Versus Open Lobectomy for Lung Cancer, Publisher: ELSEVIER SCIENCE INC, Pages: S6-S6, ISSN: 1556-0864
- Author Web Link
- Cite
- Citations: 11
Zhang YZ, Brambilla C, Rice A, et al., 2019, Growth Patterns in Epithelioid Malignant Pleural Mesothelioma: A Clinicopathological Review of 614 Cases Over 15 Years, Publisher: ELSEVIER SCIENCE INC, Pages: S295-S296, ISSN: 1556-0864
Zhang YZ, Brambilla C, Rice A, et al., 2019, WDPM-Like but Not Cribriform as Secondary Growth Patterns Modify Survival in Epithelioid Malignant Pleural Mesothelioma, Publisher: ELSEVIER SCIENCE INC, Pages: S480-S481, ISSN: 1556-0864
Nastase A, Mandal A, Lu SK, et al., 2019, Low Number of Mutations and Frequent Co-Deletions of CDKN2A and IFN Type I Characterize Malignant Pleural Mesothelioma, Publisher: ELSEVIER SCIENCE INC, Pages: S345-S345, ISSN: 1556-0864
- Author Web Link
- Cite
- Citations: 1
Rosenthal R, Cadieux EL, Salgado R, et al., 2019, Neoantigen-directed immune escape in lung cancer evolution, NATURE, Vol: 567, Pages: 479-+, ISSN: 0028-0836
- Author Web Link
- Cite
- Citations: 483
Filosso PL, Guerrera F, Falco NR, et al., 2019, Anatomical resections are superior to wedge resections for overall survival in patients with Stage 1 typical carcinoids., Eur J Cardiothorac Surg, Vol: 55, Pages: 273-279
OBJECTIVES: Typical carcinoids (TCs) are rare, slow-growing neoplasms, usually characterized by satisfactory surgical outcomes. Due to the rarity of TCs, international guidelines for the management of particular clinical presentations currently do not exist. In particular, non-anatomical resections (wedges) are sometimes advocated for Stage 1 TCs because of their indolent behaviour. The aim of this paper was to evaluate the most effective type of surgery for Stage 1 TCs, using the European Society of Thoracic Surgeons retrospective database of the Neuroendocrine Tumors of the Lung Working Group. METHODS: We analysed the effect of surgical procedure on the survival of patients with Stage 1 TCs. Overall survival (OS) was calculated from the date of intervention. The cumulative incidence of cause-specific death (tumour- and non-tumour-related) was also estimated. The impact of the surgical procedure (i.e. lobectomy vs segmentectomy vs wedge resection) on survival was investigated using the Cox model with shared frailty (for OS, accounting for the within-centre correlation) and the Fine and Gray model (for cause-specific mortality) using the approach based on the multinomial propensity score. Effects were estimated including in the model the logit-transformed propensity scores of segmentectomy and wedge resection as covariates. RESULTS: A total of 876 patients with Stage 1 TCs (569 women, 65%) were included in this study. The median age was 60 years (interquartile range 47-69). At the last follow-up, 66 patients had died: The 5-year OS rate was 94.3% [95% confidence interval (CI) 92.2-95.9]. The 5-year cumulative incidences of tumour- and non-tumour-related deaths were 2.4% (95% CI 1.4-3.9) and 3.9% (95% CI 2.5-5.6%), respectively. The analysis performed using the multinomial propensity score approach confirmed the significantly worse survival of patients treated with a wedge resection compared to those treated with a lobectomy (hazard ratio 2.01, 95% CI 1.09-3.6
Baudin E, Hayes A, Scoazec J-Y, et al., 2019, Unmet medical needs in pulmonary neuroendocrine (carcinoid) neoplasms, Neuroendocrinology, Vol: 108, Pages: 7-17, ISSN: 0028-3835
Pulmonary carcinoids (PCs) display the common features of all well-differentiated neuroendocrine neoplasms (NEN) and are classified as low- and intermediate-grade malignant tumours (i.e. typical (TC) and atypical carcinoid (AC), respectively). There is a paucity of randomised studies dedicated to advanced PCs and management principles are drawn from the larger gastroenteropancreatic (GEP) NEN experience. There is growing evidence that NEN anatomic subgroups have different biology and different responses to treatment and, therefore, should be investigated as separate entities in clinical trials. In this review, we discuss the existing evidence and limitations of tumour classification, diagnostics and staging, prognostication and treatment in the setting of PC with focus on unmet medical needs and directions for the future.
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.