Publications
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Popat S, Ramagopalan SV, Ray J, et al., 2022, Assessment of tumour-agnostic therapies in basket trials, LANCET ONCOLOGY, Vol: 23, Pages: E7-E7, ISSN: 1470-2045
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- Citations: 2
Peters S, Pujol J-L, Dafni U, et al., 2022, Consolidation nivolumab and ipilimumab versus observation in limited-disease small-cell lung cancer after chemo-radiotherapy - results from the randomised phase II ETOP/IFCT 4-12 STIMULI trial, ANNALS OF ONCOLOGY, Vol: 33, Pages: 67-79, ISSN: 0923-7534
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- Citations: 30
Castagnoli F, Doran S, Lunn J, et al., 2022, Splenic volume as a predictor of treatment response in patients with non-small cell lung cancer receiving immunotherapy., PLoS One, Vol: 17
INTRODUCTION: The spleen is a lymphoid organ and we hypothesize that clinical benefit to immunotherapy may present with an increase in splenic volume during treatment. The purpose of this study was to investigate whether changes in splenic volume could be observed in those showing clinical benefit versus those not showing clinical benefit to pembrolizumab treatment in non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: In this study, 70 patients with locally advanced or metastatic NSCLC treated with pembrolizumab; and who underwent baseline CT scan within 2 weeks before treatment and follow-up CT within 3 months after commencing immunotherapy were retrospectively evaluated. The splenic volume on each CT was segmented manually by outlining the splenic contour on every image and the total volume summated. We compared the splenic volume in those achieving a clinical benefit and those not achieving clinical benefit, using non-parametric Wilcoxon signed-rank test. Clinical benefit was defined as stable disease or partial response lasting for greater than 24 weeks. A p-value of <0.05 was considered statistically significant. RESULTS: There were 23 responders and 47 non-responders based on iRECIST criteria and 35 patients with clinical benefit and 35 without clinical benefit. There was no significant difference in the median pre-treatment volume (175 vs 187 cm3, p = 0.34), post-treatment volume (168 vs 167 cm3, p = 0.39) or change in splenic volume (-0.002 vs 0.0002 cm3, p = 0.97) between the two groups. No significant differences were also found between the splenic volume of patients with partial response, stable disease or progressive disease (p>0.017). Moreover, there was no statistically significant difference between progression-free survival and time to disease progression when the splenic volume was categorized as smaller or larger than the median pre-treatment or post-treatment volume (p>0.05). CONCLUSION: No significant differences were ob
Miura S, Jung HA, Lee SY, et al., 2022, Sequential Afatinib and Osimertinib in Asian Patients with<i> EGFR</i> Mutation-Positive Non-Small Cell Lung Cancer and Acquired T790M: Combined Analysis of Two Global Non-Interventional Studies, ONCOTARGETS AND THERAPY, Vol: 15, Pages: 873-882, ISSN: 1178-6930
Eastwood M, Marc ST, Gao X, et al., 2022, Malignant Mesothelioma Subtyping of Tissue Images via Sampling Driven Multiple Instance Prediction, 20th International Conference on Artificial Intelligence in Medicine (AIME), Publisher: SPRINGER INTERNATIONAL PUBLISHING AG, Pages: 263-272, ISSN: 0302-9743
Fendler A, Shepherd STC, Au L, et al., 2021, Immune responses following third COVID-19 vaccination are reduced in patients with hematological malignancies compared to patients with solid cancer., Cancer Cell, ISSN: 1535-6108
Curcean S, Cheng L, Picchia S, et al., 2021, Early Response to Chemotherapy in Malignant Pleural Mesothelioma Evaluated Using Diffusion-Weighted Magnetic Resonance Imaging: Initial Observations., JTO Clin Res Rep, Vol: 2
INTRODUCTION: We compared the magnetic resonance imaging total tumor volume (TTV) and median apparent diffusion coefficient (ADC) of malignant pleural mesothelioma (MPM) before and at 4 weeks after chemotherapy, to evaluate whether these are potential early markers of treatment response. METHODS: Diffusion-weighted magnetic resonance imaging was performed in 23 patients with MPM before and after 4 weeks of chemotherapy. The TTV was measured by semiautomatic segmentation (GrowCut) and transferred onto ADC maps to record the median ADC. Test-retest repeatability of TTV and ADC was evaluated in eight patients. TTV and median ADC changes were compared between responders and nonresponders, defined using modified Response Evaluation Criteria In Solid Tumors on computed tomography (CT) at 12 weeks after treatment. TTV and median ADC were also correlated with CT size measurement and disease survival. RESULTS: The test-retest 95% limits of agreement for TTV were -13.9% to 16.2% and for median ADC -1.2% to 3.3%. A significant increase in median ADC in responders was observed at 4 weeks after treatment (p = 0.02). Correlation was found between CT tumor size change at 12 weeks and median ADC changes at 4 weeks post-treatment (r = -0.560, p = 0.006). An increase in median ADC greater than 5.1% at 4 weeks has 100% sensitivity and 90% specificity for responders (area under the curve = 0.933, p < 0.001). There was also moderate correlation between median tumor ADC at baseline and overall survival (r = 0.45, p = 0.03). CONCLUSIONS: Diffusion-weighted magnetic resonance imaging measurements of TTV and median ADC in MPM have good measurement repeatability. Increase in ADC at 4 weeks post-treatment has the potential to be an early response biomarker.
Girard N, Popat S, Shoshkova S, et al., 2021, IMreal Cohort 2: First interim analysis of patient (pt) characteristics and safety data in pts with locally advanced or metastatic NSCLC (aNSCLC) receiving atezolizumab (atezo) under real-world conditions, ESMO Immuno-Oncology Congres, Publisher: ELSEVIER, Pages: S1418-S1419, ISSN: 0923-7534
Camidge DR, Kim HR, Ahn M-J, et al., 2021, Brigatinib Versus Crizotinib in ALK Inhibitor-Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial, JOURNAL OF THORACIC ONCOLOGY, Vol: 16, Pages: 2091-2108, ISSN: 1556-0864
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- Citations: 104
Popat S, Jung HA, Lee SY, et al., 2021, Sequential afatinib and osimertinib in patients with <i>EGFR</i> mutation-positive NSCLC and acquired T790M: A global non-interventional study (UpSwinG), LUNG CANCER, Vol: 162, Pages: 9-15, ISSN: 0169-5002
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- Citations: 12
Au L, Hatipoglu E, de Massy MR, et al., 2021, Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma, CANCER CELL, Vol: 39, Pages: 1497-+, ISSN: 1535-6108
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- Citations: 85
Dziadziuszko R, Ahn MJ, Kelly K, et al., 2021, SKYSCRAPER-03: A Phase III, Open-Label, Randomized Study of Atezolizumab Plus Tiragolumab Compared With Durvalumab in Patients With Locally Advanced, Unresectable, Stage III NSCLC Who Have Not Progressed After Platinum-Based Concurrent Chemoradiation, Publisher: ELSEVIER SCIENCE INC, Pages: E420-E421, ISSN: 0360-3016
Popat S, Welsh L, 2021, Brain metastases in solid tumours: new guidelines for a new era, ANNALS OF ONCOLOGY, Vol: 32, Pages: 1322-1324, ISSN: 0923-7534
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- Citations: 2
Hindocha S, Campbell D, Ahmed M, et al., 2021, Immune checkpoint inhibitor and radiotherapy-related pneumonitis: an informatics approach to determine real-world incidence, severity, management & resource implications, Frontiers in Medicine, Vol: 8, Pages: 1-10, ISSN: 2296-858X
Pneumonitis is a well-described, potentially life-threatening adverse effect of immune checkpoint inhibitors (ICI) and thoracic radiotherapy. It can require additional investigations, treatment, and interruption of cancer therapy. It is important for clinicians to have an awareness of its incidence and severity, however real-world data are lacking and do not always correlate with findings from clinical trials. Similarly, there is a dearth of information on cost impact of symptomatic pneumonitis. Informatics approaches are increasingly being applied to healthcare data for their ability to identify specific patient cohorts efficiently, at scale. We developed a Structured Query Language (SQL)-based informatics algorithm which we applied to CT report text to identify cases of ICI and radiotherapy pneumonitis between 1/1/2015 and 31/12/2020. Further data on severity, investigations, medical management were also acquired from the electronic health record. We identified 248 cases of pneumonitis attributable to ICI and/or radiotherapy, of which 139 were symptomatic with CTCAE severity grade 2 or more. The grade ≥2 ICI pneumonitis incidence in our cohort is 5.43%, greater than the all-grade 1.3–2.7% incidence reported in the literature. Time to onset of ICI pneumonitis was also longer in our cohort (mean 4.5 months, range 4 days-21 months), compared to the median 2.7 months (range 9 days−19.2 months) described in the literature. The estimated average healthcare cost of symptomatic pneumonitis is £3932.33 per patient. In this study we use an informatics approach to present new real-world data on the incidence, severity, management, and resource burden of ICI and radiotherapy pneumonitis. To our knowledge, this is the first study to look at real-world incidence and healthcare resource utilisation at the per-patient level in a UK cancer hospital. Improved management of pneumonitis may facilitate prompt continuation of cancer therapy, and improved outcomes f
Cui W, Popat S, 2021, Pleural mesothelioma (PM)-The status of systemic therapy, CANCER TREATMENT REVIEWS, Vol: 100, ISSN: 0305-7372
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- Citations: 3
Nicholson AG, Moreira AL, Mino-Kenudson M, et al., 2021, Grading in Lung Adenocarcinoma: Another New Normal, JOURNAL OF THORACIC ONCOLOGY, Vol: 16, Pages: 1601-1604, ISSN: 1556-0864
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- Citations: 4
Popat S, Jung HA, Lee SY, et al., 2021, Sequential Afatinib and Osimertinib in Patients With Advanced <i>EGFR</i>m plus NSCLC and Acquired T790M: The Real-World UpSwinG study, Publisher: ELSEVIER SCIENCE INC, Pages: S1120-S1121, ISSN: 1556-0864
Miura S, Hsia T, Hung J, et al., 2021, A Real-World Cohort Study of EGFR TKIs in Patients with NSCLC with Uncommon <i>EGFR</i> mutations (UpSwinG), Publisher: ELSEVIER SCIENCE INC, Pages: S1115-S1116, ISSN: 1556-0864
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- Citations: 1
Garcia Campelo MR, Zhou C, Ramalingam S, et al., 2021, Mobocertinib (TAK-788) in EGFR Exon 20 Insertion+ Metastatic NSCLC: Patient-Reported Outcomes From EXCLAIM Extension Cohort, Publisher: ELSEVIER SCIENCE INC, Pages: S960-S961, ISSN: 1556-0864
Smeltzer M, Bunn B, Choi YS, et al., 2021, The Global Impact of COVID-19 on Telehealth and Care for Persons With Thoracic Cancers, Publisher: ELSEVIER SCIENCE INC, Pages: S879-S879, ISSN: 1556-0864
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- Citations: 1
Popat S, 2021, Charting a New Path: Defining Better Endpoints in Immune Therapy Trials in Lung Cancer, Publisher: ELSEVIER SCIENCE INC, Pages: S840-S840, ISSN: 1556-0864
Nastase A, Mandal A, Lu SK, et al., 2021, Integrated genomics point to immune vulnerabilities in pleural mesothelioma, Scientific Reports, Vol: 11, ISSN: 2045-2322
Pleural mesothelioma is an aggressive malignancy with limited effective therapies. In order to identify therapeutic targets, we integrated SNP genotyping, sequencing and transcriptomics from tumours and low-passage patient-derived cells. Previously unrecognised deletions of SUFU locus (10q24.32), observed in 21% of 118 tumours, resulted in disordered expression of transcripts from Hedgehog pathways and the T-cell synapse including VISTA. Co-deletion of Interferon Type I genes and CDKN2A was present in half of tumours and was a predictor of poor survival. We also found previously unrecognised deletions in RB1 in 26% of cases and show sub-micromolar responses to downstream PLK1, CHEK1 and Aurora Kinase inhibitors in primary mesothelioma cells. Defects in Hippo pathways that included RASSF7 amplification and NF2 or LATS1/2 mutations were present in 50% of tumours and were accompanied by micromolar responses to the YAP1 inhibitor Verteporfin. Our results suggest new therapeutic avenues in mesothelioma and indicate targets and biomarkers for immunotherapy.
Lindsay CR, Shaw EC, Moore DA, et al., 2021, Large cell neuroendocrine lung carcinoma: consensus statement from The British Thoracic Oncology Group and the Association of Pulmonary Pathologists, British Journal of Cancer, Vol: 125, Pages: 1210-1216, ISSN: 0007-0920
Over the past 10 years, lung cancer clinical and translational research has been characterised by exponential progress, exemplified by the introduction of molecularly targeted therapies, immunotherapy and chemo-immunotherapy combinations to stage III and IV non-small cell lung cancer. Along with squamous and small cell lung cancers, large cell neuroendocrine carcinoma (LCNEC) now represents an area of unmet need, particularly hampered by the lack of an encompassing pathological definition that can facilitate real-world and clinical trial progress. The steps we have proposed in this article represent an iterative and rational path forward towards clinical breakthroughs that can be modelled on success in other lung cancer pathologies.
Begum P, Goldin RD, Possamai LA, et al., 2021, Severe immune checkpoint inhibitor hepatitis in KRAS G12C-mutant NSCLC potentially triggered by sotorasib: case report, JTO Clinical and Research Reports, Vol: 2, ISSN: 2666-3643
Sotorasib is a first-in-class small molecule that irreversibly inhibits KRAS G12C, locking it in an inactive state, inhibiting oncogenic signaling, and inducing a proinflammatory microenvironment. Here, we report the first case of life-threatening hepatitis in a patient with NSCLC shortly after commencing sotorasib, in which biopsy result was consistent with checkpoint inhibitor (CPI) immune-related adverse event, implicating sotorasib as being able to trigger CPI immune hepatitis. Given the large proportion of patients potentially treatable with sequential sotorasib after CPI, coupled with limited trial data, sotorasib-triggered CPI immune-related hepatitis should be considered in patients with sotorasib hepatotoxicity.
Tomasik B, Bienkowski M, Braun M, et al., 2021, Effectiveness and safety of immunotherapy in NSCLC patients with ECOG PS score ≥2-Systematic review and meta-analysis, LUNG CANCER, Vol: 158, Pages: 97-106, ISSN: 0169-5002
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- Citations: 22
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>
Popat S, Liu G, Lu S, et al., 2021, Brigatinib vs Alectinib in Crizotinib-Resistant Advanced Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer (ALTA-3), FUTURE ONCOLOGY, Vol: 17, Pages: 4237-4247, ISSN: 1479-6694
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- Citations: 6
Popat S, Brustugun OT, Cadranel J, et al., 2021, Real-world treatment outcomes with brigatinib in patients with pretreated ALK plus metastatic non-small cell lung cancer, LUNG CANCER, Vol: 157, Pages: 9-16, ISSN: 0169-5002
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- Citations: 8
Miura S, Hsia T-C, Hung J-Y, et al., 2021, UpSwinG: real-world, non-interventional cohort study on TKI activity in patients (pts) with EGFR mutation-positive (EGFRm plus ) NSCLC with uncommon mutations., Annual Meeting of the American-Association-for-Cancer-Research (AACR), Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
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- Citations: 1
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.
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