International alliance sets bold research ambition to detect the (almost) undetectable

Cancer Research UK| October  2019 | International alliance sets bold research ambition to detect the (almost) undetectable

Developing radical new strategies and technologies to detect cancer at its earliest stage is the bold ambition of a new transatlantic research alliance, announced today by Cancer Research UK and partners.

Cancer Research UK is setting out a bold ambition to jump-start this under-explored field of research, collaborating with teams of scientists from across the UK and the US.

The International Alliance for Cancer Early Detection (ACED) is a partnership between Cancer Research UK, Canary Center at Stanford University, the University of Cambridge, the OHSU Knight Cancer InstituteUCL and the University of Manchester.

Scientists in the Alliance will work together at the forefront of technological innovation to translate research into realistic ways to improve cancer diagnosis, which can be implemented into health systems. Potential areas of research include: ​

  • Developing new improved imaging techniques and robotics, to detect early tumours and pre-cancerous lesions
  • Increasing understanding of how the environment surrounding a tumour influences cancer development
  • Developing less invasive and simpler detection techniques such as blood, breath and urine tests, which can monitor patients who are at a higher risk of certain cancers
  • Searching for early stress signals sent out from tumours or surrounding damaged tissue as a new indication of cancer
  • Looking for early signs of cancer in surrounding tissue and fluids to help diagnose hard to reach tumours
  • Harnessing the potential of artificial intelligence and big data to look for signs of cancer that are undetectable to humans.

As part of the Cancer Research UK’s early detection strategy, the charity will invest an essential cash injection of up to £40 million over the next five years into ACED. Stanford University and the OHSU Knight Cancer Institute will also significantly invest in the Alliance, taking the total potential contributions to more than £55 million (Source: Cancer Research UK).

Full details of the project are available from Cancer Research UK

See also:

BMJ New UK and US research alliance aims to detect cancer earlier and improve screening

Scientists discover new breakthrough in cancer hair loss treatment

University of Manchester| September 2019 |Scientists discover new breakthrough in cancer hair loss treatment

Scientists at the University of Manchester have discovered that damage in the hair follicle causing by taxanes cancer drugs which can cause permanent hair loss, can be prevented. Taxanes are very important anti-cancer drugs commonly used to treat, for example, patients with breast or lung carcinoma and particularly cause anxieties among breast cancer patients for the very distressing and sometimes long-lasting hair loss taxanes can induce. 

Source Purba et al 2019
Image source: Purba et al 2019

Lead author of the study Dr Talveen Purba explains:

Dr Purba emphasises: “A pivotal part of our study was to first get to grips with how exactly hair follicles responded to taxane chemotherapy, and we found that the specialised dividing cells at the base of the hair follicle that are critical for producing hair itself, and the stem cells from which they arise, are most vulnerable to taxanes. Therefore, we must protect these cells most from undesired chemotherapy effects – but so that the cancer does not profit from it.”

The team hope that their work will support the development of externally applicable medicines that will slow or briefly suspend cell division in the scalp hair follicles of patients undergoing chemotherapy to mitigate against chemotherapy-induced hair damage. This could complement and enhance the efficacy of existing preventive approaches i.e. scalp cooling devices (Source: University of Manchester)

The full new story is available from the University of Manchester

Full reference: Purba, T. S. et al 2019| CDK4/6 inhibition mitigates stem cell damage in a novel model for taxane‐induced alopecia| EMBO molecular medicine| https://doi.org/10.15252/emmm.201911031

Abstract

Taxanes are a leading cause of severe and often permanent chemotherapy‐induced alopecia. As the underlying pathobiology of taxane chemotherapy‐induced alopecia remains poorly understood, we investigated how paclitaxel and docetaxel damage human scalp hair follicles in a clinically relevant ex vivo organ culture model. Paclitaxel and docetaxel induced massive mitotic defects and apoptosis in transit amplifying hair matrix keratinocytes and within epithelial stem/progenitor cell‐rich outer root sheath compartments, including within Keratin 15+ cell populations, thus implicating direct damage to stem/progenitor cells as an explanation for the severity and permanence of taxane chemotherapy‐induced alopecia. Moreover, by administering the CDK4/6 inhibitor palbociclib, we show that transit amplifying and stem/progenitor cells can be protected from paclitaxel cytotoxicity through G1 arrest, without premature catagen induction and additional hair follicle damage. Thus, the current study elucidates the pathobiology of taxane chemotherapy‐induced alopecia, highlights the paramount importance of epithelial stem/progenitor cell‐protective therapy in taxane‐based oncotherapy, and provides preclinical proof‐of‐principle in a healthy human (mini‐) organ that G1 arrest therapy can limit taxane‐induced tissue damage.

 

The article can be read online or downloaded

 

 

 

 

UK cancer survival rates lag behind similar countries

Arnold, M. et al |2019| Progress in cancer control: survival, mortality and incidence in seven high-income countries 1995-2014 (the ICBP SURVMARK-2 project)| The Lancet | Doi:https://doi.org/10.1016/S1470-2045(19)30456-5

The Cancer Survival in High-Income Countries (SURVMARK-2), is a longitudinal, population-based study which aims to provide a comprehensive overview of cancer survival across seven high-income countries and a comparative assessment of corresponding incidence and mortality trends.

scienceblog.cancerresearchuk.org

Image source: scienceblog.cancerresearchuk.org

While the study’s evaluation indicated progress in four of the seven studied cancers. Cancer survival continues to increase across high-income countries; however, international disparities persist. The UK was behind Australia, New Zealand, Noway, Canada, Denmark and Norway. Some of the lowest rates of 1-year survival was observed for stomach, colon, rectal, and lung cancer in the UK (Source: Arnold, et al, 2019).

Summary

Background

Population-based cancer survival estimates provide valuable insights into the effectiveness of cancer services and can reflect the prospects of cure. As part of the second phase of the International Cancer Benchmarking Partnership (ICBP), the Cancer Survival in High-Income Countries (SURVMARK-2) project aims to provide a comprehensive overview of cancer survival across seven high-income countries and a comparative assessment of corresponding incidence and mortality trends.

 

Methods

In this longitudinal, population-based study, we collected patient-level data on 3·9 million patients with cancer from population-based cancer registries in 21 jurisdictions in seven countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway, and the UK) for seven sites of cancer (oesophagus, stomach, colon, rectum, pancreas, lung, and ovary) diagnosed between 1995 and 2014, and followed up until Dec 31, 2015. We calculated age-standardised net survival at 1 year and 5 years after diagnosis by site, age group, and period of diagnosis. We mapped changes in incidence and mortality to changes in survival to assess progress in cancer control.

 

Findings

In 19 eligible jurisdictions, 3 764 543 cases of cancer were eligible for inclusion in the study. In the 19 included jurisdictions, over 1995–2014, 1-year and 5-year net survival increased in each country across almost all cancer types, with, for example, 5-year rectal cancer survival increasing more than 13 percentage points in Denmark, Ireland, and the UK. For 2010–14, survival was generally higher in Australia, Canada, and Norway than in New Zealand, Denmark, Ireland, and the UK. Over the study period, larger survival improvements were observed for patients younger than 75 years at diagnosis than those aged 75 years and older, and notably for cancers with a poor prognosis (ie, oesophagus, stomach, pancreas, and lung). Progress in cancer control (ie, increased survival, decreased mortality and incidence) over the study period was evident for stomach, colon, lung (in males), and ovarian cancer.

 

Interpretation

The joint evaluation of trends in incidence, mortality, and survival indicated progress in four of the seven studied cancers. Cancer survival continues to increase across high-income countries; however, international disparities persist. While truly valid comparisons require differences in registration practice, classification, and coding to be minimal, stage of disease at diagnosis, timely access to effective treatment, and the extent of comorbidity are likely the main determinants of patient outcomes. Future studies are needed to assess the impact of these factors to further our understanding of international disparities in cancer survival.
The full article is available from The Lancet 
See also:

New blood test for prostate cancer is highly-accurate and avoids invasive biopsies

Queen Mary University | September 2019 | New blood test for prostate cancer is highly-accurate and avoids invasive biopsies

A blood test developed by experts at Queen Mary University marks a ‘paradigm shift’ in the way prostate cancer is diagnosed. 

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The new prostate cancer test detects early cancer cells, or circulating tumor cells (CTCs), that have left the original tumour and entered the bloodstream prior to spreading around the body. By measuring intact living cancer cells in the patient’s blood, rather than the PSA protein which may be present in the blood for reasons other than cancer, it potentially provides a more accurate test for prostate cancer.

The study tested the use of the CTC test in 98 pre-biopsy patients and 155 newly diagnosed prostate cancer patients enrolled at St Bartholomew’s Hospital in London.

The research team found that the presence of CTCs in pre-biopsy blood samples were indicative of the presence of aggressive prostate cancer, and efficiently and non-invasively predicted the later outcome of biopsy results.

When the CTC tests were used in combination with the current PSA test, it was able to predict the presence of aggressive prostate cancer in subsequent biopsies with over 90 per cent accuracy, better than any previously reported biomarkers.

Additionally, the number and type of CTCs present in the blood was also indicative of the aggressiveness of the cancer. Focusing on more aggressive prostate cancer may reduce over-treatment and unnecessary biopsies for benign and non-aggressive conditions.

(Source Queen Mary University) 

Full reference: Xu, L. | 2019|Non-invasive Detection of Clinically Significant Prostate Cancer Using Circulating Tumor Cells | Journal of Urology | https://doi.org/10.1097/JU.0000000000000475

Purpose:

PSA testing results in unnecessary biopsy and over-diagnosis with consequent over-treatment. Tissue biopsy is an invasive procedure, associated with significant morbidity. More accurate non- or minimum-invasive diagnostic approaches should be developed to avoid unnecessary prostate biopsy and over-diagnosis. We investigated the potential of using circulating tumor cell analysis in cancer diagnosis, particularly in predicting clinically significant prostate cancer in pre-biopsy patients.

Material and Methods:

We enrolled 155 treatment naïve prostate cancer patients and 98 pre-biopsy patients for circulating tumor cell numeration. RNA was extracted from circulating tumor cells from 184 patients for gene expression analysis. Kruskal-Wallis, Spearman’s rank, multivariate logistic regression and random forest were applied to assess the association of circulating tumor cells with aggressive prostate cancer.

Results:

In localized prostate cancer patients, 54% were scored as circulating tumor cell positive, which was associated with higher Gleason score ( p=0.0003), risk group ( p<0.0001) and clinically significant prostate cancer. In pre-biopsy group, positive circulating tumor cell score in combination with PSA predicted clinically significant prostate cancer with AUC=0.869. A 12-gene panel prognostic for clinically significant prostate cancer was also identified. Combining PSA level, circulating tumor cell-score and the 12-gene panel, AUC for clinically significant prostate cancer prediction was 0.927 and in cases with multi-parametric MRI data, adding these to multi-parametric MRI significantly increased the prediction accuracy.

Conclusions:

Circulating tumor cell analysis has the potential to significantly improve patient stratification by PSA and/or multi-parametric MRI for biopsy and treatment.

The Library can provide the full article to Rotherham NHS Staff, request here

 

See also:

Science Daily New blood test for prostate cancer is highly-accurate and avoids invasive biopsies

Cancer overtakes CVD to become leading cause of death in high income countries

Mahase, E.| 2019|  Cancer overtakes CVD to become leading cause of death in high income countries| 

Cancer is now responsible for twice as many deaths as cardiovascular disease (CVD) in high income countries, according to two new papers published in The Lancet.

The studies said that while CVD remains the leading cause of mortality among middle aged adults globally, accounting for 40% of all deaths, this is no longer the case in high income countries.

The researchers estimated that of 55 million deaths that occurred in the world in 2017, approximately 17.7 million were from CVD.

The findings come from the PURE study, a large prospective international cohort study that involves substantial data from a large number of middle, low, and high income countries.

Countries analysed in the two reports include: Argentina, Bangladesh, Brazil, Canada, Chile, China, Colombia, India, Iran, Malaysia, Pakistan, Palestine, Philippines, Poland, Saudi Arabia, South Africa, Sweden, Tanzania, Turkey, United Arab Emirates, and Zimbabwe (Source: BMJ).

The full story is available from the the BMJ 

These are the full-text journal articles featured in the The BMJ article:

Dagenais, G. R. | 2019| Variations in common diseases, hospital admissions, and deaths in middle-aged adults in 21 countries from five continents (PURE): a prospective cohort study | The Lancet | https://doi.org/10.1016/S0140-6736(19)32007-0

Summary

Background

To our knowledge, no previous study has prospectively documented the incidence of common diseases and related mortality in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) with standardised approaches. Such information is key to developing global and context-specific health strategies. In our analysis of the Prospective Urban Rural Epidemiology (PURE) study, we aimed to evaluate differences in the incidence of common diseases, related hospital admissions, and related mortality in a large contemporary cohort of adults from 21 HICs, MICs, and LICs across five continents by use of standardised approaches.

 

Methods

The PURE study is a prospective, population-based cohort study of individuals aged 35–70 years who have been enrolled from 21 countries across five continents. The key outcomes were the incidence of fatal and non-fatal cardiovascular diseases, cancers, injuries, respiratory diseases, and hospital admissions, and we calculated the age-standardised and sex-standardised incidence of these events per 1000 person-years.

 

Findings

This analysis assesses the incidence of events in 162 534 participants who were enrolled in the first two phases of the PURE core study, between Jan 6, 2005, and Dec 4, 2016, and who were assessed for a median of 9·5 years. During follow-up, 11 307 (7·0%) participants died, 9329 (5·7%) participants had cardiovascular disease, 5151 (3·2%) participants had a cancer, 4386 (2·7%) participants had injuries requiring hospital admission, 2911 (1·8%) participants had pneumonia, and 1830 (1·1%) participants had chronic obstructive pulmonary disease (COPD). Cardiovascular disease occurred more often in LICs (7·1 cases per 1000 person-years) and in MICs (6·8 cases per 1000 person-years) than in HICs (4·3 cases per 1000 person-years). However, incident cancers, injuries, COPD, and pneumonia were most common in HICs and least common in LICs. Overall mortality rates in LICs (13·3 deaths per 1000 person-years) were double those in MICs (6·9 deaths per 1000 person-years) and four times higher than in HICs (3·4 deaths per 1000 person-years). This pattern of the highest mortality in LICs and the lowest in HICs was observed for all causes of death except cancer, where mortality was similar across country income levels. Cardiovascular disease was the most common cause of deaths overall (40%) but accounted for only 23% of deaths in HICs ( vs 41% in MICs and 43% in LICs), despite more cardiovascular disease risk factors (as judged by INTERHEART risk scores) in HICs and the fewest such risk factors in LICs. The ratio of deaths from cardiovascular disease to those from cancer was 0·4 in HICs, 1·3 in MICs, and 3·0 in LICs, and four upper-MICs (Argentina, Chile, Turkey, and Poland) showed ratios similar to the HICs. Rates of first hospital admission and cardiovascular disease medication use were lowest in LICs and highest in HICs.

 

Interpretation

Among adults aged 35–70 years, cardiovascular disease is the major cause of mortality globally. However, in HICs and some upper-MICs, deaths from cancer are now more common than those from cardiovascular disease, indicating a transition in the predominant causes of deaths in middle-age. As cardiovascular disease decreases in many countries, mortality from cancer will probably become the leading cause of death. The high mortality in poorer countries is not related to risk factors, but it might be related to poorer access to health care.
Article available here

Yusuf, S. | 2019| Modifiable risk factors, cardiovascular disease, and mortality in 155 722 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study | The Lancet | DOI:https://doi.org/10.1016/S0140-6736(19)32008-2

Summary

Background

Global estimates of the effect of common modifiable risk factors on cardiovascular disease and mortality are largely based on data from separate studies, using different methodologies. The Prospective Urban Rural Epidemiology (PURE) study overcomes these limitations by using similar methods to prospectively measure the effect of modifiable risk factors on cardiovascular disease and mortality across 21 countries (spanning five continents) grouped by different economic levels.

 

Methods

In this multinational, prospective cohort study, we examined associations for 14 potentially modifiable risk factors with mortality and cardiovascular disease in 155 722 participants without a prior history of cardiovascular disease from 21 high-income, middle-income, or low-income countries (HICs, MICs, or LICs). The primary outcomes for this paper were composites of cardiovascular disease events (defined as cardiovascular death, myocardial infarction, stroke, and heart failure) and mortality. We describe the prevalence, hazard ratios (HRs), and population-attributable fractions (PAFs) for cardiovascular disease and mortality associated with a cluster of behavioural factors (ie, tobacco use, alcohol, diet, physical activity, and sodium intake), metabolic factors (ie, lipids, blood pressure, diabetes, obesity), socioeconomic and psychosocial factors (ie, education, symptoms of depression), grip strength, and household and ambient pollution. Associations between risk factors and the outcomes were established using multivariable Cox frailty models and using PAFs for the entire cohort, and also by countries grouped by income level. Associations are presented as HRs and PAFs with 95% CIs.

 

Findings

Between Jan 6, 2005, and Dec 4, 2016, 155 722 participants were enrolled and followed up for measurement of risk factors. 17 249 (11·1%) participants were from HICs, 102 680 (65·9%) were from MICs, and 35 793 (23·0%) from LICs. Approximately 70% of cardiovascular disease cases and deaths in the overall study population were attributed to modifiable risk factors. Metabolic factors were the predominant risk factors for cardiovascular disease (41·2% of the PAF), with hypertension being the largest (22·3% of the PAF). As a cluster, behavioural risk factors contributed most to deaths (26·3% of the PAF), although the single largest risk factor was a low education level (12·5% of the PAF). Ambient air pollution was associated with 13·9% of the PAF for cardiovascular disease, although different statistical methods were used for this analysis. In MICs and LICs, household air pollution, poor diet, low education, and low grip strength had stronger effects on cardiovascular disease or mortality than in HICs.

 

Interpretation

Most cardiovascular disease cases and deaths can be attributed to a small number of common, modifiable risk factors. While some factors have extensive global effects (eg, hypertension and education), others (eg, household air pollution and poor diet) vary by a country’s economic level. Health policies should focus on risk factors that have the greatest effects on averting cardiovascular disease and death globally, with additional emphasis on risk factors of greatest importance in specific groups of countries.
Full article available from The Lancet 

Oral antibiotic use and risk of colorectal cancer in the United Kingdom, 1989–2012: a matched case–control study

Zhang, J.Haines, C.Watson, A.J.M., et al | 2019| 
Oral antibiotic use and risk of colorectal cancer in the United Kingdom, 1989–2012: a matched case–control study | 

 

Researchers behind a population-based study of oral antibiotic exposure and risk   looked at the association between oral antibiotic use and (colorectal cancer) CRC risk have published their findings in the BMJ Journal Gut. 

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Abstract

Background Microbiome dysbiosis predisposes to colorectal cancer (CRC), but a population-based study of oral antibiotic exposure and risk patterns is lacking.

Objective To assess the association between oral antibiotic use and CRC risk.

Design A matched case–control study (incident CRC cases and up to five matched controls) was performed using the Clinical Practice Research Datalink from 1989 to 2012.

Results 28 980 CRC cases and 137 077 controls were identified. Oral antibiotic use was associated with CRC risk, but effects differed by anatomical location. Antibiotic use increased the risk of colon cancer in a dose-dependent fashion. The risk was observed after minimal use, and was greatest in the proximal colon and with antibiotics with anti-anaerobic activity. In contrast, an inverse association was detected between antibiotic use and rectal cancers, particularly with length of antibiotic exposure more than 60 days as compared with no antibiotic exposure. Penicillins, particularly ampicillin/amoxicillin increased the risk of colon cancer, whereas tetracyclines reduced the risk of rectal cancer. Significant interactions were detected between antibiotic use and tumour location. The antibiotic–cancer association was found for antibiotic exposure occurring more than 10 years before diagnosis.

Conclusion Oral antibiotic use is associated with an increased risk of colon cancer but a reduced risk of rectal cancer. This effect heterogeneity may suggest differences in gut microbiota and carcinogenesis mechanisms along the lower intestinal tract. (Source: Zhang et al, 2019)

The full article is available from BMJ Gut 

In the news:

OnMedica Oral antibiotic use linked to heightened bowel cancer risk

Leeds Research: A miniature robot that could check colons for early signs of disease

University of Leeds | July 2019| A miniature robot that could check colons for early signs of disease

An  academic at the University of Leeds is a senior author of a piece of research that demonstrates it is technically possible to guide a tiny robotic capsule inside the colon to take micro-ultrasound images. The capsule, known as Sonopill, has taken an international consortium of scientists and engineers a decade to develop. 

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It is hoped that the technology will one day mean patients will not need to undergo an endoscopic examination- as the Sonopill is capable of intelligent magnetic manipulation. Based on the principle that magnets can attract and repel one another, a series of magnets on a robotic arm that passes over the patient interacts with a magnet inside the capsule, gently manoeuvring it through the colon (Source: University of Leeds).

The full news story is available from the University of Leeds

Full reference:

Norton, J.C. et al. | 2019| Intelligent magnetic manipulation for gastrointestinal ultrasound | Science Robotics | Vol. 4|31| eaav7725
DOI: 10.1126/scirobotics.aav7725

Abstract

Diagnostic endoscopy in the gastrointestinal tract has remained largely unchanged for decades and is limited to the visualization of the tissue surface, the collection of biopsy samples for diagnoses, and minor interventions such as clipping or tissue removal. In this work, we present the autonomous servoing of a magnetic capsule robot for in situ, subsurface diagnostics of microanatomy. We investigated and showed the feasibility of closed-loop magnetic control using digitized microultrasound (μUS) feedback; this is crucial for obtaining robust imaging in an unknown and unconstrained environment. We demonstrated the functionality of an autonomous servoing algorithm that uses μUS feedback, both on benchtop trials and in vivo in a porcine model. We have validated this magnetic μUS servoing in instances of autonomous linear probe motion and were able to locate markers in an agar phantom with 1.0 ± 0.9 mm position accuracy using a fusion of robot localization and μUS image information. This work demonstrates the feasibility of closed-loop robotic μUS imaging in the bowel without the need for either a rigid physical link between the transducer and extracorporeal tools or complex manual manipulation.

Diagnostic endoscopy in the gastrointestinal tract has remained largely unchanged for decades and is limited to the visualization of the tissue surface, the collection of biopsy samples for diagnoses, and minor interventions such as clipping or tissue removal. In this work, we present the autonomous servoing of a magnetic capsule robot for in situ, subsurface diagnostics of microanatomy. We investigated and showed the feasibility of closed-loop magnetic control using digitized microultrasound (μUS) feedback; this is crucial for obtaining robust imaging in an unknown and unconstrained environment. We demonstrated the functionality of an autonomous servoing algorithm that uses μUS feedback, both on benchtop trials and in vivo in a porcine model. We have validated this magnetic μUS servoing in instances of autonomous linear probe motion and were able to locate markers in an agar phantom with 1.0 ± 0.9 mm position accuracy using a fusion of robot localization and μUS image information. This work demonstrates the feasibility of closed-loop robotic μUS imaging in the bowel without the need for either a rigid physical link between the transducer and extracorporeal tools or complex manual manipulation.

Rotherham NHS staff can request a copy of this article here