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Press Releases

Take a look at a selection of our recent media coverage:

Neoadjuvant chemotherapy improves 2 year survival in operable colon cancer

14th February 2023

Neoadjuvant chemotherapy provided 6 weeks prior to colon cancer surgery reduces residual or recurrent disease within the following 2 years

The provision of neoadjuvant chemotherapy (NAC) for patients with operable colon cancer lead to histopathologic down-staging and better 2-year disease control according to the findings of study by Swedish and UK researchers.

Colorectal cancer is the 3rd most common cancer globally with 1.9 million new cases in 2020 and 935,173 deaths. The use of neoadjuvant chemotherapy has been shown to be of value at reducing tumour size and stage in patients with other operable cancers such as gastric and lower oesophageal adenocarcinomas but this approach has not been explored in the treatment of patients with colon cancer, possibly due to risk that treatment toxicities may compromise patient’s fitness for subsequent surgery.

However, despite the potential concerns, in the current study, researchers randomised patients 2:1 with radiologically staged T3-4, NO-2, MO colon cancer to either 6 weeks of preoperative oxaliplatin-fluoropyrimidine therapy followed by 18 weeks of postoperative adjuvant therapy (the intervention group) or postoperative chemotherapy only and which served as the control arm. They set the primary outcome as residual or recurrent disease within 2 years of randomisation, defined as no resection or macroscopic incomplete resection, that is, residual tumour or metastases following surgery. For the secondary outcomes, the team looked at several measures including surgical morbidity, histopathologic stage and cause-specific mortality.

Neoadjuvant chemotherapy and cancer surgery outcomes\

A total of 686 patients assigned to NAC and 351 control patients were included in the analysis.

The primary outcome occurred significantly less frequently in those assigned to NAC (rate ratio, RR = 0.72, 95% CI 0.54 – 0.98, p = 0.037). Moreover, there was also a reduction, albeit non-significant, in colon-cancer specific mortality (RR = 0.74, 95% CI 0.52 – 1.05, p = 0.095).

In addition, the researchers observed substantial reductions in T stage (21% vs 31%, NAC vs control, p < 0.001) and a higher proportion of NAC patients had histopathologically complete resections (94% vs 89%, p < 0.001).

Based on these findings, the authors concluded that NAC should be considered as a treatment option for patients with locally advanced colon cancer.

Citation
Morton D et al. Preoperative Chemotherapy for Operable Colon Cancer: Mature Results of an International Randomized Controlled Trial. J Clin Oncol 2023

Neoadjuvant therapy produces almost complete response in dMMR colon cancer

29th September 2022

Neoadjuvant therapy before surgery in patients with DNA mismatch repair deficient (dMMR) colon cancer gave rise to a huge pathologic response

Neoadjuvant therapy (NAT) prior to surgery in patients with DNA mismatch repair deficient (dMMR) colon cancer gave rise to a major pathologic response of 95% according to the findings by Dutch researchers presented at the recent European Society of Medical Oncology Congress.

The World Health Organisation estimated that in 20202, there were 1.93 million cases of colorectal cancers and which gave rise to 916 000 deaths. Moreover, defective DNA mismatch repair (dMMR) occurs in approximately 15% of sporadic colorectal cancers and evidence indicates that patients with dMMR colon cancers do not benefit from treatment with adjuvant 5-fluorouracil chemotherapy. In the Nivolumab, Ipilimumab and COX2-inhibition in Early Stage Colon Cancer: an Unbiased Approach for Signals of Sensitivity (NICHE) trial, patients with stage 1-3 adenocarcinoma of the colon and with no signs of distant metastases, were treated with short-term immunotherapy (nivolumab and ipilimumab) and COX2-inhibitors prior to surgical resection of the tumour. The results showed that a pathological response was observed in 20/20 dMMR tumours, with 19 major pathological responses (i.e., ≤10% residual viable tumour, RVT) and 12 pathological complete responses.

Based on these findings, researchers instigated NICHE-2 in which patients with non-metastatic dMMR colon cancer received NAT with 3 mg/kg of nivolumab plus 1 mg/kg of ipilimumab in the first cycle, then only nivolumab in the second cycle 2 weeks later, followed by surgery within 6 weeks of enrolling on the trial. They set the primary end points as 3-year disease-free survival (DFS) and safety with secondary end points including major pathological response (MPR) and complete response. For the purposes of the study, a pathologic response (PR) was defined as ≤ 50% residual viable tumour (RVT) and MPR as ≤ 10% RVT.

Neoadjuvant therapy treatment outcomes

A total of 112 patients with a median age of 60 years (58% female) were enrolled. For 107 patients included in the efficacy analysis, baseline radiologic assessment revealed 89% to be at stage III, 77% high-risk stage III and 64% T4 tumours. The median time between the first dose of neoadjuvant therapy and surgery was 5 weeks.

A pathologic response was observed in 106/107 (99%) patients with 95% achieving a MPR and a complete response was observed in 67% of patients with 4% achieving a partial response. After a median follow-up of 13 months none of the patients had disease recurrence. 

Grade 3-4 immune-related adverse events were observed in 3% of patients and only 3 experienced delay in surgery, meeting the safety primary endpoint.

The authors concluded by stating that ‘the first survival data suggest a strong potential for neoadjuvant immunotherapy to become standard of care and allow further exploration of organ-sparing approaches.’

Citation
Chalabi M et al. Neoadjuvant immune checkpoint inhibition in locally advanced MMR-deficient colon cancer: The NICHE-2 study LBA7

Overall uptake of CT colonography screening low but higher among ethnic minorities

6th May 2022

The nationwide use of CT colonography is low but appears to be higher among individuals from an ethnic background compared with their White counterparts, according to the results of a cross-sectional survey by researchers in the US.

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

Study provides insight into how aerobic exercise might reduce colon cancer cell proliferation

13th April 2022

Aerobic exercise induces interleukin-6 and suppresses a marker of DNA damage, offering insight as to how it could reduce the risk of colon cancer

Aerobic exercise increases expression of interleukin-6 (IL-6) and suppresses the level of γ-H2AX, a marker for DNA damage, in a colon cancer cell line, providing a possible explanation as to how exercise reduces the risk of colon cancer. This was the conclusion of a study by a team from the School of Biomedical, Nutritional and Sport Sciences, Newcastle University, Newcastle upon Tyne, UK.

In 2020, globally, colon cancer was responsible for over 1.9 million cases and 0.9 million deaths. Moreover, there is evidence that physical activity reduces cancer risk and in 2018, the American physical activity guidelines advisory committee concluded that there is now strong evidence that physical activity lowers the risk of seven types of cancer (namely colon, breast, kidney, endometrium, bladder, and stomach cancer, and oesophageal adenocarcinoma) although this evidence is derived from epidemiological studies.

Aerobic exercise is a form of physical activity and an accumulating body of evidence suggests that the incubation of cancer cells with post-exercise serum can have powerful effects on key hallmarks of cancer cell behaviour in vitro. I

n fact, a 2020 systematic review concluded that the transient serological responses to acute exercises reduce cancer cell growth, although many questions remain regarding the underlying mechanistic pathways and potential effect modifiers.

Nevertheless, while the evidence suggests a beneficial effect on cancer risk, in order to achieve a better understanding of how aerobic exercise affects the biological processes involved in cancer, requires comparison with a control group.

For the present study, the UK team recruited men with lifestyle risk factors for colon cancer e.g., older than 50 years of age, with a body mass index (BMI) > than 25 or a waist circumference > 94 cm and who did not engage in > 30 minutes of moderate physical activity at least 3 days/week over the previous 3 months.

The same participants served as their own control and undertook aerobic activity (6 x 5 minutes of cycling) and a control intervention (60 minutes of a quiet rested sitting), which was separated by a period of 2 to 7 days.

The team used LoVo cells, which served as a model of colon cancer and the primary outcome of the study was the mean difference in LoVo cell proliferation between exercise and control conditions. A total of 7 cytokines were quantified including interleukins (IL-) 6, 8 and 10 as well as markers of DNA damage such as γ-H2AX, were assessed.

Aerobic exercise and LoVo cell response

A total of 16 men with a mean age of 60 years and mean BMI of 29.9 were included in the study.

After stimulation of the LoVo cells with post-exercise serum, there was a decrease in cell proliferation compared to pre-exercise serum (-4.2%, 95% CI -6.8 to -1.5%, p = 0.006). In contrast, during the control period, there was a post-control increase in cell proliferation compared to pre-control serum (5.4%, 95% CI 2.2 to 8.6%, p = 0.003).

After adjustment for pre-values, the authors calculated that exercise-conditioned serum reduced cell proliferation compared to control by 5.7% (95% CI -8.8 to -2.6%, p = 0.002).

Turning to changes in biological markers, the researchers found that exercise reduced levels of γ-H2AX by 24% (p = 0.029) which reflected a decrease in DNA damage. In addition, the acute bout of aerobic exercise only significantly increased expression of one marker, IL-6, by 24.6% (p = 0.002).

The authors concluded the increased IL-6 expression may help explain the observed benefits of aerobic exercise in epidemiological studies and could account for why exercise helps to reduce colon cancer risk.

Citation
Orange ST et al. Acute aerobic exercise‐conditioned serum reduces colon cancer cell proliferation in vitro through interleukin‐6‐induced regulation of DNA damage Int J Cancer 2022

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