NHS England: A record year for people receiving lifesaving NHS cancer checks

Almost three million people were referred for cancer checks over the last 12 months – the highest year on record – up by over a tenth on the 2.4 million people referred before the pandemic.

NHS cancer chiefs continue to urge people to come forward as the latest data shows that record numbers of people have received vital NHS cancer tests in the last year (March 2021 – February 2022).

Despite pressures on hospitals due to Covid-19, the number of people being treated for the disease remained higher than before the pandemic – with 315,000 starting treatment b compared to 313,000 before the pandemic.

In order to meet increasing demand for cancer checks, NHS services across the country are expanding their diagnostic capabilities through one stop shops for tests, mobile clinics and cancer symptom hotlines, ensuring people are diagnosed and treated as early as possible to give them a much better chance of beating the disease.

At The Rotherham NHS Foundation Trust, they have introduced telephone triage for certain cancer referrals so that patients can speak to doctors sooner, as well as increasing the use of ‘straight-to-test’ pathways for lower gastrointestinal patients to get diagnosed as early as possible, and expanding one-stop-shop slots for patients referred under a breast cancer pathway, so patients can get all their tests in one trip.

In Merseyside, a grandmother of three has become the first person in the region to receive life-changing hip replacement surgery and go home safely in the same day.

Liverpool University Hospitals NHS Foundation is now rolling out this brand-new day case procedure to more patients, helping to reduce waiting lists for orthopaedic treatments and allowing people to recover in the comfort of their own homes.

In Buckinghamshire, a new mobile cataract suite on the grounds of Stoke Mandeville Hospital enables the Trust to perform 80-100 additional cataract surgeries each week.

Staff in Mid Yorkshire Hospitals NHS Trust have used additional NHS England funding to make improvements to see and treat more people, including converting one large open plan room into three new rooms which means oral and maxillofacial patients can be seen, diagnosed and treated on the same day, cutting back the number of visits patients need to make to see specialists.

A new theatre for minor operations means 40 patients each week can be moved out of main theatres, enabling more complex inpatient operating such as hip and knee replacements, to take place in the main theatres at Pinderfields Hospital, while laminar flow systems in two theatres at the Trust will double the rate of orthopaedic operations available.

More than 30,000 people every month are being invited for lung cancer checks through NHS mobile trucks visiting at risk communities across the country, as part of the biggest programme to improve early lung cancer diagnosis in health service history.

News release available in full from NHS England

‘As a cancer survivor you’re expected to feel grateful’: Laura Fulcher’s campaign for better care

The Guardian | April 2022 | ‘As a cancer survivor you’re expected to feel grateful’: Laura Fulcher’s campaign for better care

News article in today’s (29 April 2022) Guardian explaiing former English teacher Laura Fulcher’s patient experience and life as a cancer survivor. Fulcher had agonising symptoms for 15 months before she was finally diagnosed with bowel cancer, then received little support after her treatment. So Fulcher set up a charity- Mission Remission- to help cancer survivors and to campaign for faster diagnoses.

Read Fulcher’s experience as a patient in The Guardian

Substitution mutational signatures in whole-genome–sequenced cancers in the UK population

Degasperi, A. et al (2022). Substitution mutational signatures in whole-genome–sequenced cancers in the UK population. Science. Vol 376. Issue 6591 • DOI: 10.1126/science.abl9283

Structured Abstract

Introduction

Mutational signatures—imprints of DNA damage and repair processes that have been operative during tumorigenesis—provide insights into environmental and endogenous causes of each patient’s cancer. Cancer genome sequencing studies permit exploration of mutational signatures. We investigated a very large number of whole-genome–sequenced cancers of many tumor types, substantially more than in previous efforts, to comprehensively reinforce our understanding of mutational signatures.

Rationale

We present mutational signature analyses of 12,222 whole-genome–sequenced cancers collected prospectively via the UK National Health Service (NHS) for the 100,000 Genomes Project. We identified single-base substitution (SBS) and double-base substitution (DBS) signatures independently in each organ. Exploiting this unusually large cohort, we developed a method to enhance discrimination of common mutational processes from rare, lower-frequency mutagenic processes. We validated our findings by independently performing analyses with data from two publicly available cohorts: 3001 primary cancers from the International Cancer Genome Consortium (ICGC) and 3417 metastatic cancers from the Hartwig Medical Foundation. We produced a set of reference signatures by comparing and contrasting the independently derived tissue-specific signatures and performing clustering analysis to unite mutational signatures from different tissues that could be due to similar processes. We included additional quality control measures such as dimensionality reduction of mixed signatures and gathered evidence that could help elucidate mechanisms and etiologies such as transcriptional and replication strand bias, associations with somatic drivers, and germline predisposition mutations. We also investigated additional mutation context and examined past clinical and treatment histories when possible, to explore potential etiologies.

Results

Each organ contained a limited number of common SBS signatures (typically between 5 and 10). The number of common signatures was independent of cohort size. By contrast, the number of rare signatures was dependent on sample size, as the likelihood of detecting a rare signature is a function of its population prevalence. The same biological process produced slightly different signatures in diverse tissues, reinforcing that mutational signatures are tissue specific.

Across organs, we clustered all tissue-specific signatures to ascertain mutational processes that were equivalent but occurring in different tissues (i.e., reference signatures). We obtained 82 high-confidence SBS reference signatures and 27 high-confidence DBS reference signatures. We compared these with previously reported mutational signatures, revealing 40 and 18 previously unidentified SBS and DBS signatures, respectively.

Because we are cognizant of increasing complexity in mutational signatures and want to enable general users, we developed an algorithm called Signature Fit Multi-Step (FitMS) that seeks signatures in new samples while taking advantage of our recent findings. In a first step, FitMS detects common, organ-specific signatures; in a second step, it determines whether an additional rare signature is also present.

Conclusion

Mutational signature analysis of 18,640 cancers, the largest cohort of whole-genome–sequenced samples to date, has required methodological advances, permitting knowledge expansion. We have identified many previously unreported signatures and established the concept of common and rare signatures. The FitMS algorithm has been designed to exploit these advances to aid users in accurately identifying mutational processes in new samples.

Substitution mutational signatures in whole-genome–sequenced cancers in the UK population [paper]

See also:

New insights on self-sampling for cervical cancer screening

Drysdale, H. et al. (2022). Self-sampling for cervical screening offered at the point of invitation: A cross-sectional study of preferences in England. Journal of Medical Screening. https://doi.org/10.1177/09691413221092246

A study funded by Cancer Research UK has published the results of its qualitative study which assessed intentions (motivational stage) to provide an upper estimate of how many women might select self-sampling over clinician screening if they were offered a choice. The research team also examined associations between demographic factors and past screening behaviours and preferences for self-sampling, as well as reasons for women’s choices.

Abstract

Objectives

This study assessed preferences for human papillomavirus (HPV) self-sampling if offered as an alternative to clinician-based screening at the point of invitation for cervical screening.

Setting and Methods

An online questionnaire was completed by screening-eligible women living in England (n equal to  3672). Logistic regressions explored associations between demographic characteristics and screening preferences, stratified by previous screening attendance. Reasons for preferences were also assessed.

Results

Half of participants (51.4 per cent) intended to choose self-sampling, 36.5 per cent preferred clinician screening, 10.5 per cent were unsure, and less than 2 per cent preferred no screening. More irregular and never attenders chose self-sampling, compared with regular attenders (71.1 per cent and 70.1 per cent vs. 41.0 per cent respectively). Among regular attenders, self-sampling was preferred more frequently by the highest occupational grade, older and lesbian, gay and bisexual women, and those with experience of blood self-tests. In the irregular attender group, older women and those with experience of blood self-tests were more likely to choose self-sampling. In ‘never attenders’, self-sampling was less popular in ethnic minority groups.

Conclusions

If offered a choice of screening, around half of women in England may choose self-sampling, but a substantial proportion would still opt for clinician screening. Screening providers will need to manage a high take-up of self-sampling if many regular attenders switch to self-sampling.

Cancer Research UK New insights on self-sampling for cervical cancer screening

Self-sampling for cervical screening offered at the point of invitation: A cross-sectional study of preferences in England [paper]

Substitution mutational signatures in whole-genome–sequenced cancers in the UK population

Nik-Zainal Abidin, S. (2022). Substitution mutational signatures in whole-genome–sequenced cancers in the UK population. American Association for the Advancement of Science.

Structured Abstract

Introduction

Mutational signatures—imprints of DNA damage and repair processes that have been operative during tumorigenesis—provide insights into environmental and endogenous causes of each patient’s cancer. Cancer genome sequencing studies permit exploration of mutational signatures. We investigated a very large number of whole-genome–sequenced cancers of many tumor types, substantially more than in previous efforts, to comprehensively reinforce our understanding of mutational signatures.

Rationale

We present mutational signature analyses of 12,222 whole-genome–sequenced cancers collected prospectively via the UK National Health Service (NHS) for the 100,000 Genomes Project. We identified single-base substitution (SBS) and double-base substitution (DBS) signatures independently in each organ. Exploiting this unusually large cohort, we developed a method to enhance discrimination of common mutational processes from rare, lower-frequency mutagenic processes. We validated our findings by independently performing analyses with data from two publicly available cohorts: 3001 primary cancers from the International Cancer Genome Consortium (ICGC) and 3417 metastatic cancers from the Hartwig Medical Foundation. We produced a set of reference signatures by comparing and contrasting the independently derived tissue-specific signatures and performing clustering analysis to unite mutational signatures from different tissues that could be due to similar processes. We included additional quality control measures such as dimensionality reduction of mixed signatures and gathered evidence that could help elucidate mechanisms and etiologies such as transcriptional and replication strand bias, associations with somatic drivers, and germline predisposition mutations. We also investigated additional mutation context and examined past clinical and treatment histories when possible, to explore potential etiologies.

Results

Each organ contained a limited number of common SBS signatures (typically between 5 and 10). The number of common signatures was independent of cohort size. By contrast, the number of rare signatures was dependent on sample size, as the likelihood of detecting a rare signature is a function of its population prevalence. The same biological process produced slightly different signatures in diverse tissues, reinforcing that mutational signatures are tissue specific.

Across organs, we clustered all tissue-specific signatures to ascertain mutational processes that were equivalent but occurring in different tissues (i.e., reference signatures). We obtained 82 high-confidence SBS reference signatures and 27 high-confidence DBS reference signatures. We compared these with previously reported mutational signatures, revealing 40 and 18 previously unidentified SBS and DBS signatures, respectively.

Because we are cognizant of increasing complexity in mutational signatures and want to enable general users, we developed an algorithm called Signature Fit Multi-Step (FitMS) that seeks signatures in new samples while taking advantage of our recent findings. In a first step, FitMS detects common, organ-specific signatures; in a second step, it determines whether an additional rare signature is also present.

Conclusion

Mutational signature analysis of 18,640 cancers, the largest cohort of whole-genome–sequenced samples to date, has required methodological advances, permitting knowledge expansion. We have identified many previously unreported signatures and established the concept of common and rare signatures. The FitMS algorithm has been designed to exploit these advances to aid users in accurately identifying mutational processes in new samples.

The full paper is available from Science

In the news:

Guardian ‘Like fingerprints at a crime scene’: study finds new clues about causes of cancer

Cancer alliance implements AI tool to help match patients with clinical trials

Digital Health | | February 2022 | Cancer alliance implements AI tool to help match patients with clinical trials

The NHS Somerset, Wiltshire, Avon and Gloucester (SWAG) Cancer Alliance has partnered up with Inspirata for a project which will see artificial intelligence (AI) being used to help match patients with relevant clinical trials. 

Inspirata’s Trial Navigator uses AI technology to speed up the process of identifying patients with relevant clinical trials and research studies with the aim of helping to improve patient outcomes and breakthroughs in cancer research.

The software uses oncology-specific natural language processing AI to eliminate common bottlenecks within the trial. It matches workflow by working with the trust’s existing information governance processes to search individual medical reports, notes and referral letters, drawing key information about their disease

Full details from Digital Health

Hundreds of people diagnosed with cancer early through life-saving NHS lung checks

NHS England | 19 April 2022 | Hundreds of people diagnosed with cancer early through life-saving NHS lung checks

Hundreds of people have been diagnosed with lung cancer earlier through NHS mobile trucks, as part of the biggest programme to improve early lung cancer diagnosis in health service history.

Today, NHS cancer chiefs are urging those most at risk of lung cancer to come forward as soon as they are invited for a life-saving health check, to help even more people benefit from early diagnosis.

The call comes as new figures show only a third (35 per cent) of patients go to their lung health check when invited by the NHS.

A further 20 NHS lung truck sites are due to go live shortly with the capacity to invite 750,000 more people at increased risk for a check, in efforts to catch thousands more cancers at an earlier stage.

So far, the 23 existing truck sites have issued up to 25,000 invitations every month.

Hundreds of people diagnosed with cancer early through life-saving NHS lung checks

In the news

Guardian NHS urges people to attend vital lung cancer check-ups in England

Over 700 people a year could benefit from a new potentially life-extending lung cancer drug which targets a specific genetic mutation

NICE | April 2022 | Over 700 people a year could benefit from a new potentially life-extending lung cancer drug which targets a specific genetic mutation

NICE has announced that a new treatment will be available for people with lung cancer. The innovative and potentially life-extending drug for treating people with a specific gene mutation of advanced non-small-cell lung cancer (NSCLC) has been recommended by NICE and will be available to patients from today (14 April 2022)

Full details are available from NICE

Further information about the project is available from NICE

Sheffield Research: Lung cancer drug could improve survival rates for bladder cancer patients undergoing chemotherapy

University of Sheffield | April 2022 | Lung cancer drug could improve survival rates for bladder cancer patients undergoing chemotherapy

Researchers found that adding nintedanib – a targeted cancer growth inhibitor currently used to treat non-small cell lung cancer – to chemotherapy, could significantly improve overall survival rate for bladder cancer patients.

• Phase two randomised placebo controlled trial (NEOBLADE) showed giving patients nintedanib, as well as chemotherapy before surgery or radiotherapy, significantly increased overall survival rates at one, two and five years
• Nintedanib belongs to a group of targeted therapy drugs known as cancer growth inhibitors which are already used to treat non-small cell lung cancer
• The inhibitor blocks different proteins from sending signals to the cancer cells to grow causing the cancer cells to die

UoS Lung cancer drug could improve survival rates for bladder cancer patients undergoing chemotherapy [news release]

Blood cancer treatments impair antibody response to COVID-19 vaccines, but T cell response remains intact #Covid19RftLks

UK Covid Vaccine Research Hub | April 2022 | Blood cancer treatments impair antibody response to COVID-19 vaccines, but T cell response remains intact

This new study, published in the journal Nature Cancer, looked at 457 people with various types of lymphoma, who received two or three doses of either the Pfizer or AstraZeneca vaccine. The researchers compared immune responses in people at different stages of treatment. For the purposes of the study, they defined being vaccinated ‘on treatment’ as having a first vaccine dose within 24 weeks of completing treatment or starting treatment within four weeks of a first vaccine dose.

More than half on treatment had no antibodies

The researchers found that just over half (52%) of people on treatment for their cancer had no antibody response at all after two doses. This increased to 60% for people on a specific treatment called anti-CD20 therapy, even if this treatment had been received up to 12 months prior to vaccination.

Anti-CD20 monoclonal antibodies are used to deplete B cells in illnesses which otherwise would cause a proliferation of these cells. They were initially developed to treat certain types of lymphoma, and have subsequently been tested and used in the treatment of other conditions including rheumatoid arthritis, lupus and MS.

All those in the study who were vaccinated more than 12 months after anti-CD20 completion had a detectable antibody response.

The researchers also looked at the impact of stem cell transplantation on vaccine responses. Stem cell transplants are an intensive form of treatment that replaces damaged or destroyed stem cells in bone marrow with healthy stem cells. This allows people to be treated with a higher dose of chemotherapy. 5 out of 19 participants who had received two doses of vaccine either three weeks before transplantation or within five months after transplantation, had a reduced antibody response compared to those vaccinated 12 months or more after transplantation.

Blood cancer treatments impair antibody response to COVID-19 vaccines, but T cell response remains intact

Further information available from Covid vaccine research