ORCID Profile
0000-0003-1943-7360
Current Organisations
University of Southampton
,
University Hospitals Bristol NHS Foundation Trust
,
University of Oxford
,
University of Bristol
,
Royal College of Physicians
,
Oxford Brookes University
,
National Institute for Health and Care Excellence
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Publications
A phase II study of mitomycin C and oral etoposide for advanced adenocarcinoma of the upper gastrointestinal tract
Publisher: Elsevier BV
Date: 03-1997
Phase II study of second-line therapy with DTIC, BCNU, cisplatin and tamoxifen (Dartmouth regimen) chemotherapy in patients with malignant melanoma previously treated with dacarbazine
Publisher: Springer Science and Business Media LLC
Date: 2000
Induction of thymidine phosphorylase as a pharmacodynamic end-point in patients with advanced carcinoma treated with 5-fluorouracil, folinic acid and interferon alpha
Publisher: Springer Science and Business Media LLC
Date: 07-2000
The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group
Publisher: Springer Science and Business Media LLC
Date: 12-2021
DOI: 10.1038/S41523-021-00346-1
Abstract: The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group , we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.
Evaluation of the alkaline comet assay and urinary 3-methyladenine excretion for monitoring DNA damage in melanoma patients treated with dacarbazine and tamoxifen
Publisher: Springer Science and Business Media LLC
Date: 12-01-2000
Abstract: To develop, using dacarbazine as a model, reliable techniques for measuring DNA damage and repair as pharmacodynamic endpoints for patients receiving chemotherapy. A group of 39 patients with malignant melanoma were treated with dacarbazine 1 g/m(2) i.v. every 21 days. Tamoxifen 20 mg daily was commenced 24 h after the first infusion and continued until 3 weeks after the last cycle of chemotherapy. DNA strand breaks formed during dacarbazine-induced DNA damage and repair were measured in in idual cells by the alkaline comet assay. DNA methyl adducts were quantified by measuring urinary 3-methyladenine (3-MeA) excretion using immunoaffinity ELISA. Venous blood was taken on cycles 1 and 2 for separation of peripheral blood lymphocytes (PBLs) for measurement of DNA strand breaks. Wide interpatient variation in PBL DNA strand breaks occurred following chemotherapy, with a peak at 4 h (median 26.6 h, interquartile range 14.75-40.5 h) and incomplete repair by 24 h. Similarly, there was a range of 3-MeA excretion with peak levels 4-10 h after chemotherapy (median 33 nmol/h, interquartile range 20.4-48.65 nmol/h). Peak 3-MeA excretion was positively correlated with DNA strand breaks at 4 h (Spearman's correlation coefficient, r=0.39, P=0.036) and 24 h (r=0.46, P=0.01). Drug-induced emesis correlated with PBL DNA strand breaks (Mann Whitney U-test, P=0.03) but not with peak 3-MeA excretion. DNA damage and repair following cytotoxic chemotherapy can be measured in vivo by the alkaline comet assay and by urinary 3-MeA excretion in patients receiving chemotherapy.
Aromatase inhibitors versus tamoxifen in premenopausal women with oestrogen receptor-positive early-stage breast cancer treated with ovarian suppression: a patient-level meta-analysis of 7030 women fr
Publisher: Elsevier BV
Date: 03-2022
Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials
Publisher: Elsevier BV
Date: 04-2019
Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials
Publisher: Springer Science and Business Media LLC
Date: 12-05-2020
DOI: 10.1038/S41523-020-0155-1
Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting.
Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer
Publisher: Springer Science and Business Media LLC
Date: 12-05-2020
DOI: 10.1038/S41523-020-0156-0
Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues scoring outside the tumor boundary tumors with minimal assessable stroma including lymphocytes associated with other structures and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at itfalls .
Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group
Publisher: Springer Science and Business Media LLC
Date: 12-05-2020
DOI: 10.1038/S41523-020-0154-2
Abstract: Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring.
A phase II study of bryostatin 1 in metastatic malignant melanoma
Publisher: Springer Science and Business Media LLC
Date: 11-1998
DOI: 10.1038/BJC.1998.680
Abstract: Bryostatin 1 is a protein kinase C partial agonist which has both antineoplastic and immune-stimulatory properties, including the induction of cytokine release and expansion of tumour-specific lymphocyte populations. In phase I studies, tumour responses have been observed in patients with malignant melanoma, lymphoma and ovarian carcinoma. The dose-limiting toxicity is myalgia. Sixteen patients (age 35-76 years, median 57 years) with malignant melanoma were treated. All had received prior chemotherapy. In each cycle of treatment, patients received bryostatin 25 degrees g m(-2) weekly for three courses followed by a rest week. The drug was given in PET diluent (10 microg bryostatin ml(-1) of 60% polyethylene glycol, 30% ethanol, 10% Tween 80) and infused in normal saline over 1 h. The principal toxicities were myalgia (grade 2, eight patients and grade 3, six patients) and grade 2 phlebitis (four patients), fatigue (three patients) and vomiting (one patient). Of 15 patients evaluable for tumour response, 14 developed progressive disease. One patient developed stable disease for 9 months after bryostatin treatment. In conclusion, single-agent bryostatin appears ineffective in the treatment of metastatic melanoma in patients previously treated with chemotherapy. It should, however, be investigated further in previously untreated patients.
Phase II study of the oxygen saturation curve left shifting agent BW12C in combination with the hypoxia activated drug mitomycin C in advanced colorectal cancer
Publisher: Springer Science and Business Media LLC
Date: 2000
A phase II study of the modulation of 5-fluorouracil and folinic acid with high-dose infusional hydroxyurea in metastatic colorectal carcinoma
Publisher: Elsevier BV
Date: 08-1999
Phase II study of RC-160 (vapreotide), an octapeptide analogue of somatostatin, in the treatment of metastatic breast cancer
Publisher: Springer Science and Business Media LLC
Date: 26-02-1999
Related Organisations
University Of Southampton
Location: United Kingdom of Great Britain and Northern Ireland
University Hospitals Bristol NHS Foundation Trust
Location: United Kingdom of Great Britain and Northern Ireland
University Of Oxford
Location: United Kingdom of Great Britain and Northern Ireland
University Of Bristol
Location: United Kingdom of Great Britain and Northern Ireland
Royal College Of Physicians
Location: United Kingdom of Great Britain and Northern Ireland
Oxford Brookes University
Location: United Kingdom of Great Britain and Northern Ireland
National Institute For Health And Care Excellence
Location: United Kingdom of Great Britain and Northern Ireland
Related Funding Activities
No related grants have been discovered for Jeremy Braybrooke.