Allan Hackshaw
As seen in:
Nature,
Human Reproduction Update,
Memory Studies,
MDPI,
The BMJ,
Cell Press,
The Lancet,
Lung Cancer
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Articles by Allan Hackshaw
Strategic roadmap for delivery of clinical trials in rare childhood central nervous system (CNS) tumours: a multi-stakeholder consensus
Abstract Rare paediatric central nervous system (CNS) tumours comprise a biologically-heterogeneous group of low-incidence diseases that present significant challenges to both therapeutic development and clinical research, limiting the availability of high-quality evidence to guide clinical care.
The effect of cigar, cigarillo and pipe smoking on lung cancer risk and screening eligibility
Abstract Smokers are eligible for lung cancer screening using low dose CT (LDCT) if they have a sufficiently high risk of lung cancer. In England, for example, people are eligible if their estimated risk using either of two validated models (PLCOm2012 and Liverpool Lung Project) exceeds a certain threshold. Risk is often estimated using only cigarette consumption (duration and number per day), yet many smokers also use other cancer-causing tobacco products.
UK National Screening Committee position statement on surrogate outcomes in cancer screening trials
Principles for appropriate use of surrogate outcomes in cancer screening Until better methods are available that account for the nuanced context of screening and go beyond simple correlations, we lack reliable tools to judge whether potential surrogates can truly replace mortality as the main outcome in screening trials.
Combined ctDNA and serum PSA for dynamic monitoring of metastatic prostate cancer starting first-line treatment: a prospective national cohort study
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Abstract The prognosis of newly diagnosed metastatic prostate cancer is highly variable. The primary objective of the PARADIGM prospective cohort study was to evaluate predictors of survival in blood collected at the start of each of the first six treatment cycles from 114 patients with high-volume metastatic prostate cancer (biologically male) who were starting androgen deprivation therapy in combination with docetaxel or an androgen receptor pathway inhibitor.
By Anuradha Jayaram, Alison Reid, Francesco Orlando, Leila Zakka, Miriam Gonçalves, Constantine Alifrangis, Rob Jones Verified, Sarah H. Needleman, Diletta Bianchini, Anna Wingate, Kenrick Ng, Mark Linch, Ursula McGovern, John Staffurth, Simon J Crabb, Alison Birtle, Osvaldas Vainauskas, Gianmarco Leone, Allan Hackshaw, Andre Romualdo Lopes, André D. Lopes, Daniel Wetterskog, Francesca Demichelis, Gerhardt Attard, Memuna Rashid, Suparna Thakali, Jacqueline O’Dwyer, Elias Pintus, Susannah Brock, Millenn Chiwewe
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Nature
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Thymic health and immunotherapy outcomes in patients with cancer
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Abstract Although immunotherapy has revolutionized cancer treatment, many patients still experience limited benefit, highlighting the urgent need for improved biomarkers1. Although immunotherapy is founded on unleashing T cells2, most existing biomarkers remain tumour-centric and mainly overlook host immune competence. The thymus is a key immune organ that is crucial for T cell maturation, and we hypothesized that thymic functionality is associated with immunotherapy outcomes3.
By Simon Bernatz, Vasco Prudente, Suraj Pai, Asbjørn K. Attermann, Alessandro Di Federico, Andrew Rowan Verified, Selvaraju Veeriah, Lars Dyrskjøt, Leonard Nürnberg, Joao V Alessi, Patrick A. Ott, Elad Sharon, Allan Hackshaw, Nicholas McGranahan, Christopher Abbosh, Raymond Mak, Danielle S Bitterman, Mark Awad, Biagio Ricciuti, Charles Swanton, Mariam Jamal-Hanjani, Nicolai J. Birkbak, Hugo J. W. L. Aerts
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Nature
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AI for breast cancer screening
Whether support from artificial intelligence (AI) models improves breast screening is a topic of research in national cancer screening programmes and clinical oncology. Three studies now show that AI tools can assist radiologists with evaluating mammograms, substantially reducing workloads and possibly improving screening performance.
Retraction Note: Antibodies against endogenous retroviruses promote lung cancer immunotherapy - Nature
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The authors have retracted this article. An investigation by The Francis Crick institute found concerns regarding some of the data presented in the figures, specifically: 1. The A549 cell binding data in Fig. 5c are manipulated and could not be reproduced. 2. The antibody-dependent cellular cytotoxicity (ADCC) experiments shown in Fig. 5d and 5e may contain manipulated data. 3. The integrity of the source data for the B cell and antibody quantitation in Fig. 3c and Extended Data Fig.
By Jorge Almagro, Oriol Pich, Takahiro Karasaki, Roberto Salgado, George Young, Miriam Molina-Arcas, Jan Attig, Sophia Ward, Alexander Frankell, Maise Al Bakir, Mark Hill, Daniel Cook, Nicolai J. Birkbak, Axel Behrens, Sanjay Popat, Allan Hackshaw, TRACERx consortium, Kevin Litchfield, Nicholas McGranahan, Se-Hoon Lee, Samra Turajlic, Charles Swanton, Julian Downward
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Nature
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Clone copy number diversity is linked to survival in lung cancer - Nature
Abstract Both single nucleotide variants (SNVs) and somatic copy number alterations (SCNAs) accumulate in cancer cells during tumour development, fuelling clonal evolution. However, accurate estimation of clone-specific copy numbers from bulk DNA-sequencing data is challenging.
Ultrasensitive ctDNA detection for preoperative disease stratification in early-stage lung adenocarcinoma - Nature Medicine
Abstract Circulating tumor DNA (ctDNA) detection can predict clinical risk in early-stage tumors. However, clinical applications are constrained by the sensitivity of clinically validated ctDNA detection approaches. NeXT Personal is a whole-genome-based, tumor-informed platform that has been analytically validated for ultrasensitive ctDNA detection at 1–3 ppm of ctDNA with 99.9% specificity.
Prospective validation of ORACLE, a clonal expression biomarker associated with survival of patients with lung adenocarcinoma - Nature Cancer
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Abstract Human tumors are diverse in their natural history and response to treatment, which in part results from genetic and transcriptomic heterogeneity. In clinical practice, single-site needle biopsies are used to sample this diversity, but cancer biomarkers may be confounded by spatiogenomic heterogeneity within individual tumors.
By Dhruva Biswas, Yun-Hsin Liu, Javier Herrero, Yin Chao Wu, David Moore, Takahiro Karasaki, Kristiana Grigoriadis, Wei-Ting Lu, Cristina Naceur-Lombardelli, Sophia Ward, Alexander Frankell, Mark Hill, Emma Colliver, Sophie de Carné Trécesson, Philip East, Amanda Lindberg, Jerome Nicod, Julian Downward, Zoltán Szállási, TRACERx consortium, Allan Hackshaw, Mariam Jamal-Hanjani, Nnennaya Kanu, Nicolai J. Birkbak
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Nature
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Long term efficacy of first-line afatinib and the clinical utility of ctDNA monitoring in patients with suspected or confirmed EGFR mutant non-small cell lung cancer who were unsuitable for chemotherapy | British Journal of Cancer
Abstract Here we present long-term outcomes of first line afatinib in comorbid patients with suspected or confirmed EGFR mutant NSCLC otherwise considered unsuitable for chemotherapy, and the clinical utility of serial ctDNA monitoring. TIMELY (NCT01415011) was a multicentre, single arm, phase II trial conducted in the UK. Patients aged ≥18 were treated with daily oral afatinib (40 mg) until disease progression or unacceptable toxicity.
Author Correction: The evolution of lung cancer and impact of subclonal selection in TRACERx - Nature
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Correction to: Nature https://doi.org/10.1038/s41586-023-05783-5 Published online 12 April 2023 In the version of the article initially published, the symbols for death (x) and censored (>) were swapped in the graphs in Fig. 1. The figure has now been corrected in the HTML and PDF versions of the article.
By Alexander Frankell, Michelle Dietzen, Maise Al Bakir, Takahiro Karasaki, Sophia Ward, Emma Colliver, Ariana Huebner, Abigail Bunkum, Mark Hill, Kristiana Grigoriadis, David Moore, Oriol Pich, Daniel Cook, Mihaela Angelova, Carlos Martinez-Ruiz, Christopher Abbosh, John Le Quesne, Dhruva Biswas, Sonya Hessey, Claudia Lee, Jerome Nicod, Gary Middleton, Javier Herrero, Sergio A Quezada, Peter Van Loo, Nicolai J. Birkbak, Allan Hackshaw, Simone Zaccaria, TRACERx consortium, Mariam Jamal-Hanjani, Nicholas McGranahan
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Nature
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The artificial intelligence-based model ANORAK improves histopathological grading of lung adenocarcinoma - Nature Cancer
Abstract The introduction of the International Association for the Study of Lung Cancer grading system has furthered interest in histopathological grading for risk stratification in lung adenocarcinoma. Complex morphology and high intratumoral heterogeneity present challenges to pathologists, prompting the development of artificial intelligence (AI) methods.
Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA - Nature
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Abstract Circulating tumour DNA (ctDNA) can be used to detect and profile residual tumour cells persisting after curative intent therapy1. The study of large patient cohorts incorporating longitudinal plasma sampling and extended follow-up is required to determine the role of ctDNA as a phylogenetic biomarker of relapse in early-stage non-small-cell lung cancer (NSCLC).
By Christopher Abbosh, Alexander Frankell, Sophia Ward, Kristiana Grigoriadis, Dhruva Biswas, Takahiro Karasaki, Carlos Martinez-Ruiz, Maise Al Bakir, Oriol Pich, Ariana Huebner, David Moore, Nicolas Carey, Daniel Cook, Roderik M. Kortlever, Gerard Evan, Allan Hackshaw, Jacqui Shaw, Mariam Jamal-Hanjani, TRACERx consortium, Nicolai J. Birkbak, Nicholas McGranahan, Nadia Godin-Heymann
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Nature
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Antibodies against endogenous retroviruses promote lung cancer immunotherapy - Nature
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Abstract B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS)1,2. Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive1,2.
By Jorge Almagro, Oriol Pich, Takahiro Karasaki, Roberto Salgado, George Young, Miriam Molina-Arcas, Jan Attig, Sophia Ward, Alexander Frankell, Maise Al Bakir, Mark Hill, Daniel Cook, Nicolai J. Birkbak, Axel Behrens, Sanjay Popat, Allan Hackshaw, TRACERx consortium, Kevin Litchfield, Nicholas McGranahan, Se-Hoon Lee, Samra Turajlic, Charles Swanton, Julian Downward
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Nature
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Body composition and lung cancer-associated cachexia in TRACERx - Nature Medicine
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Abstract Cancer-associated cachexia (CAC) is a major contributor to morbidity and mortality in individuals with non-small cell lung cancer. Key features of CAC include alterations in body composition and body weight. Here, we explore the association between body composition and body weight with survival and delineate potential biological processes and mediators that contribute to the development of CAC.
By Othman Al-Sawaf, Takahiro Karasaki, Alexander Frankell, Carlos Martinez-Ruiz, Ariana Huebner, Maise Al Bakir, Sophia Ward, Roberto Salgado, Christopher P. Bridge, David C. Christiani, Raymond Mak, Paul Welsh Verified, Ying Liu, Norbert Perrimon, Allan Hackshaw, Stephen O’Rahilly, Nicolai J. Birkbak, TRACERx consortium, Mariam Jamal-Hanjani
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Nature
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Genomic–transcriptomic evolution in lung cancer and metastasis - Nature
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Abstract Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy1. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study2,3.
By Carlos Martinez-Ruiz, Mark Hill, Jonas Demeulemeester, Kerstin Thol, Sophia Ward, Oriol Pich, Takahiro Karasaki, David Moore, Roberto Salgado, Emma Colliver, Michelle Dietzen, Ariana Huebner, Maise Al Bakir, Miljana Tanić, James Clements, Daniel Cook, Alexander Frankell, Philip East, Nicolai J. Birkbak, Allan Hackshaw, Stephan Beck, Peter Van Loo, Mariam Jamal-Hanjani, TRACERx consortium, Charles Swanton, Elizabeth Larose Cadieux, Ali M. Al-Rashed
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Nature
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Evolutionary characterization of lung adenocarcinoma morphology in TRACERx - Nature Medicine
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Abstract Lung adenocarcinomas (LUADs) display a broad histological spectrum from low-grade lepidic tumors through to mid-grade acinar and papillary and high-grade solid, cribriform and micropapillary tumors. How morphology reflects tumor evolution and disease progression is poorly understood.
By Takahiro Karasaki, David Moore, Sophia Ward, Maise Al Bakir, Kristiana Grigoriadis, Ariana Huebner, Mark Hill, Alexander Frankell, Christopher Abbosh, Michelle Dietzen, Oriol Pich, Carlos Martinez-Ruiz, Dhruva Biswas, Claudia Lee, Emma Colliver, Sonya Hessey, Simone Zaccaria, Nicolai J. Birkbak, Jonas Demeulemeester, Peter Van Loo, Prasad S. Adusumilli, Waseem Cheema, Francisco Sanchez-Vega, David Jones, Allan Hackshaw, Roberto Salgado, John Le Quesne, TRACERx consortium, Nicholas McGranahan, Charles Swanton
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Nature
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The evolution of non-small cell lung cancer metastases in TRACERx - Nature
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Abstract Metastatic disease is responsible for the majority of cancer-related deaths1. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours.
By Maise Al Bakir, Ariana Huebner, Carlos Martinez-Ruiz, Oriol Pich, David Moore, Sophia Ward, Michelle Dietzen, Emma Colliver, Alexander Frankell, Takahiro Karasaki, Christopher Abbosh, Mark Hill, Daniel Cook, Roberto Salgado, Gary Middleton, Neal Navani, Sam M. Janes, Sergio A Quezada, Peter Van Loo, Allan Hackshaw, Nicolai J. Birkbak, Simone Zaccaria, TRACERx consortium, Mariam Jamal-Hanjani, Nicholas McGranahan, Kristiana Grigoriadis, Joanne Laycock, Sonya Hessey, Abigail Bunkum
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Nature
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Lung adenocarcinoma promotion by air pollutants - Nature
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Abstract A complete understanding of how exposure to environmental substances promotes cancer formation is lacking. More than 70 years ago, tumorigenesis was proposed to occur in a two-step process: an initiating step that induces mutations in healthy cells, followed by a promoter step that triggers cancer development1.
By Claudia Lee, David Moore, Oriol Pich, Bjorn Bakker, Takahiro Karasaki, Ai Nagano, Carlos Martinez-Ruiz, Ryan Huff, Alejandro Suárez-Bonnet, Simon L. Priestnall, Fiona E. McRonald, Meng-Hung Lin, Maise Al Bakir, Mark Hill, Anthony George, Christopher Abbosh, Se-Hoon Lee, Nicholas McGranahan, Peter D Sasieni, Richard S. Houlston, Philip Awadalla, Eva Grönroos, Julian Downward, Tyler Jacks, Ilaria Malanchi, Allan Hackshaw, Kevin Litchfield, TRACERx consortium, James DeGregori, Mariam Jamal-Hanjani
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Nature
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Modern cancer trials still lack information about QoL impacts on patients
Statistics from Altmetric.com Request Permissions If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways. Drug delivery Medical oncology The majority of the initial seminal cancer treatment trials during the 1970s and later on focused on clinical efficacy and clinician-assessed harms.
An Approach to Solving the Complex Clinicogenomic Data Landscape in Precision Oncology: Learnings From the Design of WAYFIND-R, a Global Precision Oncology Registry | JCO Precision Oncology
Challenge and Learning No. 4: Data Sharing and Privacy and Use of Technology To facilitate data exploration and advance the field of precision oncology, WAYFIND-R will incorporate computerized systems at three levels: (1) a local, site-level data capture system; (2) an online research platform to access the global patient-level data set; and (3) a dashboard showing aggregated data from patients with solid tumors across the globe (Fig 3). Data entered manually will be collected on the EDC system.
A local human Vδ1 T cell population is associated with survival in nonsmall-cell lung cancer - Nature Cancer
Abstract Murine tissues harbor signature γδ T cell compartments with profound yet differential impacts on carcinogenesis. Conversely, human tissue-resident γδ cells are less well defined. In the present study, we show that human lung tissues harbor a resident Vδ1 γδ T cell population. Moreover, we demonstrate that Vδ1 T cells with resident memory and effector memory phenotypes were enriched in lung tumors compared with nontumor lung tissues.
Intermittent PI3Kδ inhibition sustains anti-tumour immunity and curbs irAEs - Nature
Abstract Phosphoinositide 3-kinase δ (PI3Kδ) has a key role in lymphocytes, and inhibitors that target this PI3K have been approved for treatment of B cell malignancies1,2,3. Although studies in mouse models of solid tumours have demonstrated that PI3Kδ inhibitors (PI3Kδi) can induce anti-tumour immunity4,5, its effect on solid tumours in humans remains unclear.
New genomic technologies for multi-cancer early detection: Rethinking the scope of cancer screening
Cancers other than breast, colorectal, cervical, and lung do not have guideline-recommended screening. New multi-cancer early detection (MCED) tests—using a single blood sample—have been developed based on circulating cell-free DNA (cfDNA) or other analytes.
An efficient randomised trial design for multi-cancer screening blood tests: nested enhanced mortality outcomes of screening trial
Screening aims to detect cancer at an early, curable stage, and is currently recommended for breast, lung, colorectal, and cervical cancers in some countries. Prostate cancer screening might be considered for some men. Individual screening programmes for most other cancer types are unlikely to be worthwhile, mainly because each of these cancers has relatively low incidence and mortality. To read this article in full you will need to make a payment Subscribe to The Lancet Oncology References 1.
Including a general practice endorsement letter with the testing kit in the Bowel Cancer Screening Programme: Results of a cluster randomised trial
Article Information Article first published online: February 27, 2021 Amanda J Cross1, Jonathan Myles2, Paul Greliak1, Allan Hackshaw3, Stephen Halloran4, 5, Sally C Benton4, 6, Caroline Addison7, Caroline Chapman8, Natasha Djedovic9, Stephen Smith10, Christian von Wagner11, Stephen W Duffy2*, Rosalind Raine11* 1Department of Surgery and Cancer, Imperial College London, London, UK 2Wolfson Institute for Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary...
Reply to Comment(s) on “Nationwide randomised trial evaluating elective neck dissection for early stage oral cancer (SEND study) with meta-analysis and concurrent real-world cohort”
References 1. Dhar, H., Vaish, R. & D’Cruz, A. Comment on “Nationwide randomised trial evaluating elective neck dissection for early stage oral cancer (SEND study) with meta-analysis and concurrent real-world cohort.” Br. J. Cancer https://doi.org/10.1038/s41416-020-0981-9 2. Hutchison, I. L., Ridout, F., Cheung, S. M. Y., Shah, N., Hardee, P., Surwald, C. et al.
Fatigue, quality of life and physical fitness following an exercise intervention in multiple myeloma survivors (MASCOT): an exploratory randomised Phase 2 trial utilising a modified Zelen design
Abstract Background Exercise may improve fatigue in multiple myeloma survivors, but trial evidence is limited, and exercise may be perceived as risky in this older patient group with osteolytic bone destruction. Methods In this Phase 2 Zelen trial, multiple myeloma survivors who had completed treatment at least 6 weeks ago, or were on maintenance only, were enrolled in a cohort study and randomly assigned to usual care or a 6-month exercise programme of tailored aerobic and resistance training.
Thyroid cancer recurrence in the HiLo trial - Authors' reply
1 Dehbi HM Mallick U Wadsley J Newbold K Harmer C Hackshaw A Recurrence after low-dose radioiodine ablation and recombinant human thyroid-stimulating hormone for differentiated thyroid cancer (HiLo): long-term results of an open-label, non-inferiority randomised controlled trial. Lancet Diabetes Endocrinol. 2019; 7: 44-51 We stated in the Discussion that HiLo was not powered for non-inferiority for cancer recurrence.
A phase I study of nintedanib combined with cisplatin/gemcitabine as first-line therapy for advanced squamous non-small cell lung cancer (LUME-Lung 3)
Publication HistoryPublished online: March 09, 2018Accepted: March 8, 2018; Received in revised form: March 2, 2018; Received: August 16, 2017;
Low cigarette consumption and risk of coronary heart disease and stroke: meta-analysis of 141 cohort studies in 55 study reports
Discussion We have shown that a large proportion of the risk of coronary heart disease and stroke comes from smoking only a few cigarettes. This has important consequences for smokers who believe that light smoking carries little or no harm. Our estimates for people who smoke one or five cigarettes per day represent light smoking, given that the daily habits of such smokers typically vary between one and five cigarettes per day.
Life expectancy difference and life expectancy ratio: two measures of treatment effects in randomised trials with non-proportional hazards
The hazard ratio (HR) is the most common measure of treatment effect in clinical trials that use time-to-event outcomes such as survival. When survival curves cross over or separate only after a considerable time, the proportional hazards assumption of the Cox model is violated, and HR can be misleading. We present two measures of treatment effects for situations where the HR changes over time: the life expectancy difference (LED) and life expectancy ratio (LER).
Maternal smoking in pregnancy and birth defects: a systematic review based on 173 687 malformed cases and 11.7 million controls
BACKGROUND There is uncertainty over whether maternal smoking is associated with birth defects. We conducted the first ever comprehensive systematic review to establish which specific malformations are associated with smoking. METHODS Observational studies published 1959–2010 were identified (Medline), and included if they reported the odds ratio (OR) for having a non-chromosomal birth defect among women who smoked during pregnancy compared with non-smokers.
Down's syndrome screening with nuchal translucency
Get full text access Log in, subscribe or purchase for full access. References 1. Nicolaides, KH ∙ Sebire, NJ ∙ Snijders, RJM ∙ et al. Down's syndrome screening in the UK Lancet. 1996; 347:906-907 2. Macintosh, McM ∙ Wald, NJ ∙ Chard, T ∙ et al. Correction: the selective miscarriage of Down's syndrome for 10 weeks of pregnancy Br J Obstet Gynaecol. 1995; 102:798-801 3. Hyett, JA ∙ Sebire, NJ ∙ Snijders, RJM ∙ et al.
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