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27th September 2024
The idea of cancer vaccines is not new, but Dr Victoria Kunene, consultant medical oncologist at Queen Elizabeth Hospital Birmingham, UK, is leading the charge in their latest iteration: personalised preventative and therapeutic mRNA vaccines against colorectal cancer. With an introduction from Helena Beer, Dr Kunene shares first-hand insights into the clinical trial, the NHS Cancer Vaccine Launch Pad initiative and their potential for revolutionising patient care.
Ask Dr Victoria Kunene why she wanted to specialise in oncology and her answer won’t be too dissimilar to the one she gave 15 years ago interviewing as a registrar: it’s the opportunity to help a unique patient group navigate an extremely challenging period in their lives and, where possible, give them extra time to spend with loved ones and achieve their goals.
‘Just being part of that journey and helping someone through a difficult time is humbling,’ she says. ‘It’s not easy, but it’s satisfying. You feel like you have positively contributed at a crucial time.’
While Dr Kunene’s drive, empathy and ambition have remained constant during her career, one thing that’s changed during the intervening years is the means by which she is able to help due to a ‘constant stream of new information and new treatments’ coming through the clinical development pipeline.
‘Treatment has advanced since my oncology registrar years – we’ve made some progress,’ she confirms. ‘Everyone would probably blow their trumpet about their own field, but [oncology is] the one field whereby science meets clinical practice so completely.’
As a senior house officer (SHO), it was gastroenterology that sparked Dr Kunene’s interest and it was this, as well as working with ‘a brilliant team’ at Wansbeck General Hospital in Northumberland, UK, that steered her to specialising in gastrointestinal (GI) cancers.
‘Through my SHO training, I found myself drawn to cancer patients and, because I didn’t want to lose the GI aspect [of my training], this was my default,’ she says. ‘I found that I enjoyed GI oncology more than all the other tumour sites, so getting a job fitting with what I liked was the aim.’
Taking up a consultant medical oncologist post at Queen Elizabeth Hospital Birmingham (QEHB) in 2012, Dr Kunene now specialises in upper and lower GI cancers, and cancers of unknown primary. She has taken the lead on multiple clinical trials as principal investigator to continue satisfying her passion for marrying science and clinical practice.
On 31 May 2024, Dr Kunene led a team to administer the very first personalised vaccine against colorectal cancer in England as part of the pioneering NHS Cancer Vaccine Launch Pad (CVLP) initiative.
The overarching aim of this is to speed up access to messenger ribonucleic acid (mRNA) personalised cancer vaccine clinical trials for people who have been diagnosed with cancer to support treatment alongside chemotherapy, as well as prevention.
Speaking at the time of the CVLP launch, NHS chief executive Amanda Pritchard said: ‘Thanks to advances in care and treatment, cancer survival is at an all-time high in this country, but these vaccine trials could one day offer us a way of vaccinating people against their own cancer to help save more lives.’
Working to achieve this ambition is something that Dr Kunene is proud to be a part of, especially as it has the potential for allowing her to offer patients that all-important extra time.
When I started as a registrar 15 years ago, we only used chemotherapy but there were clinical trials in the background where we investigated targeted therapies like trastuzumab (brand name Herceptin) for upper GI cancers. I remember recruiting patients into the ToGA trial and now to see trastuzumab as part of standard of care for HER2-positive upper GI cancers is great.
Of course, we’ve also had the advent of immune checkpoint inhibitors. These immunotherapies are now part of standard of care with or without chemotherapy for patients who have PD-L1 positive or microsatellite-high tumours.
Another treatment combination is chemotherapy with zolbetuximab – an antibody directed against claudin 18.6. Although the QEHB didn’t take part in the related study, our neighbouring hospital of University Hospital Coventry and Warwickshire did, and the results are positive. Zolbetuximab received Medicines and Healthcare products Regulatory Agency approval in August and is currently undergoing review by the National Institute for Health and Care Excellence.
In lower GI cancers, we regularly conduct tests for RAS and BRAF mutations, mismatch repair proteins, NTRK gene fusions and HER2 amplifications. This allows us to utilise appropriate antibodies such as anti-epidermal growth factor inhibitors, immunotherapy, trastuzumab and larotrectinib to positively impact clinical outcomes.
Other drugs like bevacizumab and aflibercept, which are vascular endothelial receptor inhibitors, do not require genomic or immunohistochemistry testing. In suitable cases, these are administered in combination with chemotherapy.
Interestingly, we also see advocacy for old drugs like aspirin, which could improve outcomes in certain groups of patients. Over the years, various study groups have reported improved survival with the use of aspirin and other non-steroidal anti-inflammatories. Thus, it’s not only about new drug discoveries but leveraging current technology to optimise the use of old drugs.
We have witnessed the advancement of radiotherapy with new techniques like stereotactic body radiotherapy, which enables clinicians to deliver high doses of radiotherapy with precision and reduced toxicity. Surgeons are performing more intricate procedures, leading to longer survival for patients due to the increased use of combinations of treatment methods.
We are currently in the era of stratified medicine, where genomic sequencing, circulating tumour DNA, prognostic scoring systems and predictive artificial intelligence models are being optimised so they can be incorporated into routine care to improve survival and reduce treatment toxicity.
The idea of cancer vaccines is not new, but previous studies were not very successful, especially in metastatic settings. Following the Covid-19 pandemic, we have seen increased research into personalised mRNA anticancer vaccines and, so far, early phase studies have shown promising results.
Of course, there are other types of vaccines available such as DNA-based vaccines, peptide-based vaccines and dendritic cell vaccines, which are also being investigated in various tumour groups.
The study that we’re doing is in high-risk, stage two and stage three colon cancers. In these patients, especially the stage three cancers, 20-30% will experience cancer recurrence despite receiving post operative chemotherapy.
For a very long time, we relied on CT scan staging to decide which patients would benefit from chemotherapy, however this method is not reliable.
In the last five to 10 years, there’s been more work in the area of circulating tumour DNA and minimal residual disease in solid cancers. Haematology has always been at the forefront of this, and they have always considered minimal residual disease in their treatments.
We know from recent literature – even just observational studies – that patients who have detectible circulating tumour DNA after the removal of their cancer are at a high risk of cancer reoccurrence. Therefore, this study concentrates on this group of patients.
We offer the patients participation in the study when they attend for consideration of post-operative chemotherapy. If they agree to have both the chemotherapy and the clinical trial, we do screening blood tests for circulating tumour DNA at least four weeks post-surgery, but no later than 10 weeks, as treatment must start within 10 weeks of surgery and not a day later.
Blood tests take a few weeks to become available, so patients continue with their standard post-operative chemotherapy, which could be for three or six months. The results could be either positive or negative for circulating tumour DNA and sometimes the test fails. This is screening phase one.
Screening phase two is for patients who test positive for circulating tumour DNA. If they are happy to continue the study, they will sign a second consent form to allow the study team to manufacture a bespoke vaccine by sequencing the tumour and identifying appropriate neoantigens. A minimum of five and up to 20 neoantigens are required to successfully manufacture the vaccine. These neoantigens are interrogated through a computer algorithm to assess if they can elicit the desired anticancer immune response.
If the neoantigens meet the requirement, the vaccine is then manufactured and can only be given to that particular patient.
What we’re trying to do with the vaccine is re-educate the immune system by generating specific T-cells against the cancer, thus giving the person a fighting chance. Vaccines are normally preventative – we vaccinate against measles, TB, rubella – but these vaccines are not just preventative, they are also therapeutic. If the cancer resurfaces, the immune system should be able to recognise it and get rid of it.
This phase involves blood tests and CT scans at the end of chemotherapy. If the blood results are satisfactory, there is no evidence of cancer recurrence and the vaccine has been successfully manufactured, the patient can be randomised.
Half of the patients will receive the vaccine, and the other half will be observed, which is the standard of care. If a patient is randomised into the vaccine arm, they will receive treatment once a week for the first six weeks, once every two weeks for a month and then every four to six weeks for up to 15 doses over the course of a year.
The vaccine made for the patients who don’t receive it will be destroyed and the ‘blueprint’ used to create the vaccine will not be used for other participants.
Patients who are randomised to standard of care are likely to be disappointed. We warn our patients that they might not get the vaccine. However, we highlight the benefit of receiving much closer monitoring [within the clinical trial] than the usual standard of care protocol.
We conduct blood tests and CT scans more frequently than usual, which increases the chances of detecting cancer recurrence earlier and taking prompt action. We also emphasise that the product is still being studied so we cannot predict the outcome.
The CVLP is a collaboration between NHS England and companies delivering this cancer vaccine technology. The aim is to be able to allow patients across the country to access these vaccine trials. Oxford was the first site to open the CVLP and we received their first patient.
QEHB is one of the vaccine delivery study centres. I also work at Walsall Manor Hospital, a district general hospital, with the CVLP. We [the Walsall team] approach suitable patients based on histology staging. If they agree, we will see them at the QEHB for the circulating tumour DNA screening blood test after signing the consent form. Then, they start chemotherapy at Walsall Manor Hospital, and we inform them of their results as soon as they become available. If they are deemed suitable for the study, they will undergo screening phases two and three if they are still happy to proceed.
One or two hospitals around Birmingham are not part of the CVLP and they also refer patients. Therefore, patients can still access the studies even if their hospitals don’t have the CVLP. We also get a lot of enquiries from colleagues around the country and we can steer them in the right direction.
My colleague Dr Shivan Sivakumar is conducting a vaccine study for pancreatic cancer and I am pleased that QEHB is the first hospital in Europe to have opened the trial. We also have melanoma and lung cancer vaccine studies in our centre run by Dr Lalit Pallan and Professor Gary Middleton, respectively. It would be great to see these studies incorporated into the CVLP. Other hospitals around the country are conducting similar studies in various tumour sites. CVLP is about improving access and delivering the studies to patients with the aim of improving patient outcomes.
When patients hear about CVLP and start to understand the science behind the personalised vaccine, the uptake is relatively high. People want to improve their chances of survival as much as possible, but they also want to take part for the benefit of others. Most of them say: ‘I just want to contribute to the future’.
All these patients have shown a lot of selflessness, saying, ‘even if it doesn’t help me, if it helps somebody else, I’ll be happy to take part in it’. And that’s amazing.
I know there’s a lot of criticism of the NHS and that things could be better in certain areas. I agree. However, some aspects of NHS are beyond the ability of one person or Trust to deliver and we need that coordinated effort to provide something as big as this.
The United Kingdom is doing very well and recruiting faster than other countries. We are really proud of what we are doing. We should build on this model to deliver other research that will only benefit patients.
Dr Victoria Kunene, consultant medical oncologist at Queen Elizabeth Hospital Birmingham, UK, was speaking to pharmacist and medical writer Steve Titmarsh.
20th October 2023
The potential for detection of colorectal cancer based on an analysis of the variability in a patient‘s gut microbiome has been highlighted in a study presented at United European Gastroenterology (UEG) Week.
The findings come from the Dutch microbiome project, which is a large-scale studying involving 8,208 participants. Researchers analysed the gut microbiome of those who developed pre-cancerous colorectal lesions before faecal sampling between 2000 and 2015, in addition to those who developed such lesions following sampling between 2015 and 2022.
They then compared the results with samples taken from individuals with a normal colonoscopy, as well as exploring the range of bacterial species present and their function within the gut by reconstructing their genomes from metagenomic data.
The team identified that when compared to those who had a normal colonoscopy, individuals who developed colonic lesions after faecal sampling displayed a greater diversity in their gut microbiome. In addition, the composition and function of the microbes differed in those with pre-existing or future lesions based on the type of lesion.
In terms of the specific organisms, researchers identified that those from the family of Lachnospiraceae and the genera Roseburia and Eubacterium were linked with the future development of lesions.
Significant variation in the gut microbiome of individuals who developed pre-cancerous colorectal lesions offers another potential avenue to explore to enhance the detection and prevention of colorectal cancer.
Commenting on the findings, study lead, Dr Ranko Gacesa, postdoctoral researcher at the University Medical Center Groningen in the Netherlands, said: ‘While we didn’t investigate mechanisms in this study, it is known from previous research that some of the bacterial species identified may have properties that could contribute to the development of colorectal lesions.
‘A bacterium called Bacteroides fragilis, for example, is known to produce a toxin that can lead to chronic low-grade inflammation in the gut. Prolonged inflammation is believed to be potentially genotoxic and carcinogenic, meaning it may cause genetic damage and promote cancer.’
In a discussion of the potential implications of the study findings, Dr Gacesa added: ‘The connection between the gut microbiome and pre-cancerous lesions has been underexplored, leaving uncertainty about whether gut bacteria can predict the future onset of colorectal cancer.
‘Our findings suggest that the microbiome could act as a valuable tool to improve existing tests, advancing early detection methods for pre-cancerous lesions and colorectal cancer.’
According to the World Health Organization, colorectal cancer is the third most common cancer and there were nearly two million cases and almost one million deaths in 2020, with a spike in diagnoses of the cancer at an advanced stage during the pandemic.
In addition, an increasing number of studies reveal how the progression of colorectal cancer is related to gut microbiome composition. In fact, the published literature related to the development of colorectal cancer has demonstrated that many bacteria affect tumour development and growth. It is also clear that gut microbiome can modulate the efficacy of conventional chemotherapy, through regulating cytotoxicity by participating in the metabolic process of anti-cancer drugs.
20th December 2022
Widespread state medical marijuana legalisation in the US is associated with a lower rate of opioid dispensing and pain-related hospital events among some adults receiving treatment for newly diagnosed cancer according to an analysis by US researchers.
Pain is an extremely common cancer symptom with a 2022 meta-analysis of 12 studies (10 with breast cancer and 2 lung cancer) patients, finding a pooled pain prevalence rate of 40%. Although paracetamol and non-steroidal anti-inflammatory drugs are universally accepted as part of the treatment of cancer pain at any stage of the WHO analgesic ladder, strong opioids are the mainstay of analgesic therapy in treating moderate to severe cancer-related pain. Nevertheless, with tightened regulations leading to a decrease in opioid prescribing across the United States, evidence points to a decline in opioid use among end-of-life care in those with cancer although there has been a rise in pain-related emergency department visits, suggesting that end of life cancer pain management may be worsening. Although medical marijuana has been studied and found to be efficacious for relief of pain in patients with advanced cancer pain not fully relieved by strong opioids, a 2016 review suggested that while marijuana may have the potential for refractory cancer pain, much of the data are based on animal data, small trials, or are outdated.
With the potential to help patients with cancer pain, in the current study, US researchers set out to assess the associations between medical marijuana legalisation and opioid-related and pain-related outcomes for adult patients receiving cancer treatment. The team used data from national commercial claims between 2012 to 2017. The researchers assessed several measures including the proportion of patients having 1 or more days of opioids and 1 or more pain-related emergency department visits or hospital events, during the 6 months after a new cancer diagnosis.
Medical marijuana and opiate use
A total of 38,189 patients with newly diagnosed breast cancer, 12,816 with colorectal cancer (55.4% male) and 7,190 (51.1% female) with lung cancer were included in the analysis.
Medical marijuana legalisation was associated with a reduction in the rate of 1 or more opioid days from 90.1% to 84.4% (difference = 5.6, 95% CI 2.2 – 9.0, p = 0.01) among breast cancer patients. For colorectal cancer patients, there was also a reduction, this time from 89.4% to 84.4% (difference = 4.9, 95% CI 0.5 – 9.4, p = 0.03). Finally, opioid use reduced from 31.5% to 22.1% (difference = 9.4, 95% CI 0.8 – 17.9, p = 0.03) among patients with lung cancer with recent opioids.
Medical marijuana legalisation was also associated with a reduction in the rate of 1 or more pain-related hospital events from 19.3% to 13.0% (difference = 6.3, 95% CI 0.70 – 12.0, p = 0.03) among patients with lung cancer with recent opioids. However, the difference for the other two forms of cancer was not significant.
The authors concluded that medical marijuana legalisation was associated with a lower rate of opioid dispensing and pain-related hospital events among some adults receiving treatment for newly diagnosed cancer.
Citation
Bao Y et al. Medical Marijuana Legalization and Opioid- and Pain-Related Outcomes Among Patients Newly Diagnosed With Cancer Receiving Anticancer Treatment. JAMA Oncol 2022
19th December 2022
The COVID-19 pandemic period was associated with a higher level of advanced colorectal cancer diagnoses compared to pre-pandemic levels.
Italian researchers have found that the COVID-19 pandemic was associated with the diagnosis of more advanced stage colorectal cancer in comparison to pre-pandemic levels.
The World Health Organization describes how globally, colorectal cancer is the third most common cancer with nearly two million cases and almost one million deaths in 2020.
Nevertheless, despite screening programs being widely available, emerging data from, for example, the US, clearly shows how after the national lockdowns imposed because of COVID-19, while stool testing increased by 7%, there was a 16% decrease in colonoscopy between 2018 and 2020.
Consequently, there have been concerns that the pandemic together with a reluctance of patients to seek medical attention, could be associated with a risk of more advanced colorectal cancer at diagnosis.
Moreover, one modelling study estimated 1,176,942 to 2,014,164 fewer colorectal cancer screenings, 8,346 to 12,894 fewer colorectal cancer diagnoses and 6,113 to 9,301 fewer early-stage colorectal cancer diagnoses between 2020 and 2023.
Nevertheless, there has been a lack of real-world evidence on the actual level of advanced colorectal diagnoses because of COVID-19.
In the present study, the Italian team set out to determine if the pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer.
The team undertook a retrospective, multicentre cohort study of all adult patients who underwent surgery for colorectal cancer from 1 March 2020, to 31 December 2021 (pandemic period) in comparison to 1 January 2018, to 29 February 2020 (the pre-pandemic period).
They considered any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections.
The primary outcome was advanced stage of colorectal cancer at diagnosis whereas secondary outcomes included distant metastasis and T4 stage.
A total of 17,938 patients with a mean age of 70.6 years (55.8% male) underwent surgery for colorectal cancer, 43.5% of whom had surgery during the pandemic period.
The proportion of patients with stage 1 disease was significantly lower during the pandemic period compared to the pre-pandemic phase (20.7% vs 23.3%, p < 0.001). In addition, there was a significantly higher proportion of stage 4 disease during the pandemic (15% vs 13.9%, p = 0.03).
Using regression analysis, the pandemic period was found to be significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio, OR = 1.07, 95% CI 1.01 – 1.13, p = 0.03), an aggressive biology (OR = 1.32, p < 0.01) and stenotic lesions (OR = 1.15, p = 0.03).
The authors concluded that the COVID-19 pandemic was significantly associated with a risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer. They added that these results may indicate a potential reduced survival for these patients.
Citation
Rottoli M et al. Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy. JAMA Netw Open 2022.
8th August 2022
Resistant starch does not reduce colorectal cancer (CRC) among patients with Lynch syndrome (LS) but does significantly lower the risk of developing non-colorectal LS cancers, according to the findings of a randomised, placebo-controlled trial by an international research team.
Lynch syndrome is characterised by an increased risk for the development of colorectal cancer, endometrial cancer and various other cancers because of a mutation in one of several mismatch repair genes. In effect, LS can be described as a hereditary cancer syndrome and is estimated that 1 in every 300 people may be carriers of an alteration in a gene associated with it.
Another option to help reduce the risk of CRC is through greater intake of dietary fibre. In 1972, Burkitt suggested that dietary fibre has a role in the prevention of certain large-bowel and other diseases which have become prevalent in Western countries.
Despite this belief which has subsequently popularised the importance of fibre for the prevention of colorectal cancer, a 2005 meta-analysis concluded that while dietary fibre intake is inversely associated with risk of colorectal cancer in age-adjusted analyses, after adjusting for other dietary risk factors, the association became non-significant.
In the present study, researchers recruited patients with LS as part of the CAPP2 study in which participants were randomised to receive aspirin and/or resistant starch and followed for several years with the primary hypothesis being that both interventions might prevent colorectal cancer.
The researchers focused on CAPP2 participants randomly assigned to resistant starch, which was given as a 30g daily supplement or matching placebo. The primary outcome was the development of colorectal cancers after 2 years whereas secondary outcomes focused on non-colorectal LS cancers which included those affecting the stomach/duodenum, urinary, ovarian and bile duct pancreas. In addition, non-LS cancer incidence, such as bladder, bone, breast, lung and many others, were also examined.
Resistant starch and cancer outcomes
A total of 918 participants with a mean age of 45 years (56.3% female) were included in the analysis, 463 of whom were randomised to resistant starch and followed for a mean of 25 months.
A total of 52 and 53 participants developed colorectal cancer in the resistant starch and placebo groups, which was not significantly different (incidence rate ratio, IRR = 0.85, 95% CI 0.58 – 1.25, p = 0.41). However, more patients in the placebo group developed non-colorectal LS cancers (27 vs 53) and this difference was significant (IRR = 0.52, 95% CI 0.32 – 0.84, p = 0.0075). Despite this reduction, there was no difference between the two groups for non-LS cancers (IRR = 0.88, 95% CI 0.56 – 1.40, p = 0.60).
The authors discussed that while resistant starch did not reduce colorectal cancer, there was a significant effect against non-colorectal LS cancers and concluded that this should be investigated further.
Citation
Mathers JC et al. Cancer Prevention with Resistant Starch in Lynch Syndrome Patients in the CAPP2-Randomized Placebo Controlled Trial: Planned 10-Year Follow-up Cancer Prev Res (Phila) 2022
11th July 2022
Cancer screening for breast, colorectal and cervical cancers was significantly reduced during the period of the pandemic compared to pre-pandemic levels according to the results of a systematic review by a group of Italian and US researchers.
According to GLOBOCAN in 2020 there were an estimated 19.3 million new cancer cases and almost 10.0 million cancer deaths and that cancer screening has contributed to a decrease in both cancer morbidity and mortality. As a result, any reduction in screening could potentially lead to a surge in cases. In fact, modelling studies have already indicated a possibly large increase in cases due to the pandemic.
Moreover, in a UK-based modelling study, the authors estimated that as a consequence of the pandemic, there would be a 7·9-9·6% increase in the number of deaths due to breast cancer up to year 5 after diagnosis and for colorectal cancer a 15·3 – 16·6% increase in additional deaths.
However, because of differences in the start date and duration of lockdown measures across the world, for the present study, the researchers wanted to examine how this variation impacted on screening. They focused on breast, colorectal and cervical cancer screening since the beginning of the pandemic and made a comparison with pre-pandemic levels.
The team searched all the major databases for observational studies and articles that reported data from cancer registries and which compared the level of screening tests performed before and during the pandemic and in different areas of the world.
Cancer screening reductions during the pandemic
A total of 39 articles were identified and included in the analysis with 21 related to breast, 22 colorectal and 11 for cervical cancers.
For the period between January and October 2020, there was an overall 46.7% (95% CI -55.5% to -37.8%) decrease in breast cancer screening in comparison the pre-pandemic level.
For colorectal cancer, the overall reduction was 44.9% (95% CI -53.8% to -36.1%) and this included a 52.5% reduction in colonoscopy, a 37.8% decrease in faecal occult blood testing and a 37.8% decrease in immuno-chemical testing.
With cervical cancer, the overall reduction was -51.8% (95% CI -64.7% to -38.9%).
Commenting on their findings, the authors noted that these reductions in screening occurred across the world but that there were some obvious differences. For example, Europe saw the largest reduction in mammography compared to North America. although the decrease for both colorectal and cervical cancer screening was similar in both areas.
The authors suggested that the most likely explanation for the reduced screening was the ‘stay at home’ order introduced during the early stages of the pandemic.
They concluded that there was a large reduction in cancer screening as a consequence of the COVID-19 pandemic and which could be associated with an increased number of deaths and called for further work to investigate the relationship between cancer diagnosis and treatment during the pandemic.
Citation
Teglia F et al. Global Association of COVID-19 Pandemic Measures With Cancer Screening: A Systematic Review and Meta-analysis JAMA Oncol 2022
9th June 2022
The use of screening endoscopy in women before the age of 50 is associated with a 55% lower risk of being diagnosed with colorectal cancer (CRC) at age 55. This was the conclusion of a prospective cohort study of US women.
Although incidence rates among those of screening age have decreased, data from the US shows that among individuals under 50 years of age, the incidence rate has increased by approximately 2% between 2011 and 2016.
According to the American Cancer Society, screening for CRC is associated with a significant reduction in CRC incidence and CRC-related mortality and have recommended that adults aged 45 years and older with an average risk of CRC should undergo regular screening.
Furthermore, long-term follow studies suggest that screening endoscopy is associated with a reduced colorectal-cancer mortality. Nevertheless, there are limited data on the value of screening endoscopy in younger patients.
For the present study, the US researchers used data in the Nurses’ Health Study II, primarily because participants in this prospective registry were aged 26 to 45 at enrolment and this therefore provided an opportunity to examine any potential associations between the age of screening endoscopy and the development of CRC.
Using 1991 as the baseline because this was the first year when questions about screening endoscopy were included, participants were asked in subsequent questionnaires if they had undergone sigmoidoscopy or colonoscopy in the past two years and the reason for this screening.
The primary endpoint was overall CRC incidence although the researchers included the incidence of younger-onset CRC (diagnosed before age 55) and CRC mortality as secondary outcomes.
Screening endoscopy and development of colorectal cancer
A total of 111,801 women with a median of 36 years at enrolment were included in the analysis and followed for 26 years, during which time 519 incident cases of CRC were documented. Compared to women who underwent screening endoscopy age 50 or later, those who underwent a screen before 45 years of age were more likely to have a family history of CRC.
When compared to women who did not undergo screening endoscopy, the adjusted hazard ratios (HRs) for any CRC were 0.37 (95% CI 0.26 – 0.53) for women aged under 45 years, 0.43 (95% CI 0.29 – 0.62) for those 45 to 49 years of age and 0.46 (95% CI 0.30 – 0.69) for those 55 years and older. Hence there was a significantly lower risk of incident CRC when screening was started before the age of 45.
The authors calculated that the absolute reduction in the estimated cumulative incidence of CRC up to age 60 was 72 per 100,00 people if screening endoscopy was started between the ages of 45 to 49 compared to being performed between the ages of 50 to 54.
The risk of being diagnosed with CRC at age 55 was 55% lower if screening was started before the age of 45 (HR = 0.45, 95% CI 0.29 – 0.70) and equally lower (HR = 0.43) when started between the ages of 45 and 49.
The authors concluded that earlier screening endoscopy (before 50 years of age) was associated with a significantly lower risk of both CRC and a diagnosis before age 55.
Citation
Ma W et al. Age at Initiation of Lower Gastrointestinal Endoscopy and Colorectal Cancer Risk Among US Women JAMA Oncol 2022
6th May 2022
Globally, cancer of the colon and rectum (colorectal cancer) was diagnosed in 1.93 million people in 2020 and responsible for 916,000 deaths. Moreover, screening colonoscopy has been shown to be associated with a substantial decreased mortality risk.
CT colonography (CTC) is a minimally invasive test that uses CT scans to check the colon and rectum. In a 2008 study, the authors concluded that CTC screening identified 90% of subjects with adenomas or cancers measuring 10 mm or more in diameter and that the results augmented published data on the role of CTC in screening patients with an average risk of colorectal cancer. However, to date, there is limited information on the sociodemographic factors that might influence uptake of CTC.
For the present investigation, the researchers turned to the National Health Interview Survey (NHIS), which is a nationally representative cross-sectional survey and used data collected in 2019.
Included participants were aged 50 to 75 years of age and with no recorded history of colorectal cancer. In the NHIS survey, individuals were asked about whether or not they ever had a CTC and if they responded positively, when the scan had been performed.
The researchers collected additional information on age, gender, ethnicity and employment status. They employed multiple variable logistic regression to evaluate predictors of CTC use.
Predictors of CTC utilisation
A total of 13,709 individuals with a mean age of 61.4 years (52.7% female) were included in the analysis, of whom, 70.3% were White, 10.4% Black and 12.1% Hispanic.
In total, only 1.4% of participants reported having previously undergone CTC and, of these, 39.9% had the procedure within the last 12 months.
When analysing the association between CTC use and ethnicity, Hispanic individuals were more than twice as likely to undergo CTC compared with White participants (OR = 2.67, 95% CI 1.66 – 4.29, p < 0.001). There was also a similarly higher use among Black individuals (OR = 2.47, 95% CI 1.60 – 3.82, p < 0.001) than White participants.
Among the other sociodemographic factors examined, only participants who reported that they worked in the last week were significantly less likely to have a CTC (OR = 0.61, 95% CI 0.40 – 0.94, p = 0.024).
One limitation recognised by the authors was how the study data were collected in 2019 prior to the COVID-19 pandemic and therefore they were unable to assess any potential impact on CTC uptake. They concluded that strategies improving access to CTC services could mitigate the observed racial disparities.
Citation
O’Connor B et al. Predictors of CT Colonography Use: Results From the 2019 National Health Interview Cross-Sectional Survey J Am Coll Radiol 2022
19th January 2022
The presence of neoplasia or precancerous lesions, have been identified after colorectal screening in patients aged 45 to 49 years of age, highlighting the need for lowering the age of such screening for average risk individuals. This was the finding from an examination of real-world outpatient colonoscopy data by a team from the Dr. Henry D. Janowitz Division of Gastroenterology, New York, US.
Colorectal cancer is a malignant tumour that forms in the tissues of the colon and is often grouped together with rectal cancer, due to the fact that these cancers share common features. During 2020 in Europe, colorectal cancer became the second most common cancer and the second highest cause of cancer death, accounting for 12.7% of all new cancer diagnoses and 12.4% of cancer deaths.
Moreover, the importance of screening has been highlighted in a study which observed that the largest decreases in colorectal cancer mortality were seen in countries with long-standing screening programmes.
The incidence of early-onset colorectal cancer (i.e., cases in those aged under 50 years of age) has seen a world-wide increase, especially in high-income countries although the reasons behind this increase are uncertain.
In addition, data suggests that the incidence of deaths due to early-onset colorectal cancer are also rising, had that these had increased by 1.3% annually between 2008 and 2017, in those aged younger than 50 years. Despite this, most screening programmes in Europe begin at 50 years of age.
But could there be an advantage from earlier screening and could this help identify those with neoplasia? This was the aim of the present study and the US team analysed data from a large and nationally representative set of outpatient colonoscopies to identify colorectal neoplasia among patients aged 18 to 54 years of age.
They undertook a retrospective analysis of colonoscopy data and compared a ‘young onset group (defined as aged 18 to 49) with those aged 50 to 54 years.
Findings
A total of 562,559 colonoscopy procedures were included in the analysis, 145,998 of which were undertaken in those aged 18 to 44 years and 79,934 in those aged 45 to49 years.
Among individuals aged 45 to 49, approximately 32% had any form of neoplasia, 7.5% had advanced premalignant lesions and 0.58% had colorectal cancer with a neoplasia present in 26.6% of those aged 40 to 44 years.
Discussing their findings, the authors stated that in a representative sample of patients under 50 years of age, the prevalence of any neoplasia among those aged 45 to 49 were almost as high as in those in the 50 to 54 year olds. They concluded that lowering the screening age to 45 will likely enable the detection of important pathology more frequently.
Citation
Trivedi PD et al. Prevalence and Predictors of Young-Onset Colorectal Neoplasia: Insights from a Nationally Representative Colonoscopy Registry Gastroenterology 2022.
4th January 2022
Dietary supplements (DS) are used by 40% of adult patients diagnosed with either breast, prostate or colorectal cancer according to research by a team from the Department of Behavioural Science and Health, University College London, UK.
Survival from cancer appears to be increasing, with a 2018 global surveillance study finding that survival trends are generally increasing, even for some of the more lethal cancers.
While evidence supporting various strategies aimed at reducing cancer risk in those living with and beyond cancer is rather limited, a 2018 report by the World Cancer Research fund and the American Institute for Cancer research, is clear in its view that ‘high-dose dietary supplements are not recommended for cancer prevention’, encouraging individuals to meet their nutritional needs through diet alone.
Nevertheless, some data shows that cancer survivors tend to report a higher usage of DS than those with the disease.
For the current study, the authors sought to gain a better understanding the range of and reasons for, use of DS among survivors of breast, prostate and colorectal cancer. They undertook a cross-sectional survey using data from the Advancing Survival Cancer Outcomes Trial (ASCOT) and asked respondents with each of the three cancers their thoughts about lifestyle and cancer, use of specific foods, e.g. fruits, vegetables, meat and high calorie foods together with information on the use of DS and any other non-prescribed treatments such as herbal extracts.
Respondents were asked to express their views (using a Likert scale) on the perceived importance of supplements as an approach to prevent cancer reoccurrence.
Findings
A total of 1049 participants with mean age of 64.4 years (62.1% female) provided usable data for analysis. Breast cancer was the most common (54.4%) among respondents, followed by prostate (25.2%) and colorectal (20.4%). In addition, the majority were of white ethnicity (94%) and 68% had either no (34.9%) or at least one co-morbidity.
In total, 40% of respondents reported DS use, of whom, 32% believed that these supplements were important for a reduction in cancer recurrence. The most commonly used form of supplements were fish oils (13.1%), followed by calcium and vitamin D (9.1%) and multivitamin and minerals (8.2%).
Using regression analysis, the only factors significantly associated with DS use were meeting the requirements for fruit and vegetable intake (odds ratio, OR = 1.36, 95% CI 1.02 – 1.82, p = 0.039), a belief in the importance of supplements to prevent cancer recurrence (OR = 3.13, 95% CI 2.35 – 4.18, p < 0.001) and the absence of obesity (OR = 0.58, 95% CI 0.38 – 0.87, p = 0.010).
The authors concluded that DS use among cancer survivors was common and influenced by patient’s beliefs about recurrence. They added that further work was required to better understand the reasons for such beliefs and how best to provide appropriate supplement advice to those living with a cancer diagnosis.
Citation
Conway RE et al. Dietary supplement use by individuals living with and beyond breast, prostate, and colorectal cancer: A cross‐sectional survey Cancer 2021.
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