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21st December 2022
Cannabidiol (CBD) oil given to patients with advanced cancer receiving palliative care provided no additional benefit to that care according to the findings of a randomised trial by Australian researchers.
Although there have been several advances in medical care, a proportion of patients with advanced cancer still experience substantial symptom distress. The use of palliative care seeks to improve both symptom control and quality of life but despite this, some symptoms can be difficult to control, necessitating more effective medications. Both cannabis and cannabinoid drugs containing cannabidiol, are widely used to treat disease or alleviate symptoms. However, a 2015 meta-analysis concluded that whilst there was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity, there was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy. In a feasibility study, Australian researchers examined the use of global symptom burden measures to assess the response to medicinal cannabis with both cannabidiol and tetrahydrocannabinol. They concluded that doses of both cannabidiol and tetrahydrocannabinol were generally well tolerated and that the outcome measure of total symptom distress was promising as a measure of overall symptom benefit.
Based on the these early and promising findings, the same group undertook a randomised trial to determine whether cannabidiol oil could improve symptom distress in patients with advanced cancer receiving palliative care. They included adult participants with advanced cancer and symptom distress which was measured using the Edmonton Symptom Assessment Scale [ESAS]. Participants received titrated CBD oil 100 mg/mL, 0.5 mL once daily to 2 mL three times a day, or matched placebo for 28 days. The ESAS scale is designed to rate the intensity of nine common symptoms experienced by cancer patients, including pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, well-being and shortness of breath. For the trial participants, the inclusion criterion was an ESAS score greater than or equal to 10/90. The primary outcome was set as the total ESAS symptom distress score (TSDS) at day 14, with a response defined as a decrease greater than or equal to, 6 at day 14.
Cannabidiol oil and symptom distress
A total of 58 patients receiving CBD and 63 placebo, reached the primary analysis point (i.e., day 14) and the median dose of participant-selected CBD was 400 mg per day.
The unadjusted change in TSDS from baseline -6.2 for the placebo group and -3.0 for those receiving CBD and this difference was non-significant (p = 0.24). Equally, there was no significant difference in proportion of responders (placebo = 58.7% and CBD = 44.8% p = 0.13).
In fact, during the study, all components of the ESAS improved (that is, reduced) over time with no difference between the placebo and CBD arms. In addition, there was no detectable effect of CBD on quality of life, depression, or anxiety. Overall, most participants reported feeling better (53% CBD vs 65% placebo) or much better (70% CBD and 64% placebo) by day 14.
The authors concluded that CBD oil did not add value to the reduction in symptom distress provided by specialist palliative care alone.
Citation
Hardy J et al. Phase IIb Randomized, Placebo-Controlled, Dose-Escalating, Double-Blind Study of Cannabidiol Oil for the Relief of Symptoms in Advanced Cancer (MedCan1-CBD). J Clin Oncol 2022
12th May 2022
Cancer patients with COVID-19 have been found to be at a greater risk of hospitalisation and 30-day all-cause mortality compared to those without the disease according to the results of a study by a US team from Texas.
The presence of cancer has become a recognised factor that is associated with a higher risk for severe outcomes in those infected with COVID-19 and which is largely due to the presence of a compromised immune system. During the early course of the pandemic, studies observed that a higher proportion of cancer patients infected with COVID-19 were both hospitalised and subsequently died, compared to those without the disease. In contrast, however, other studies have suggested that cancer and non-cancer patients have comparable COVID-19 outcomes after adjusting for age, sex, and comorbidity. Furthermore, the impact of factors such as cancer treatments, different cancer types on COVID-19 related outcomes has been less well studied. For the present study, the US researchers examined the association between cancer-specific characteristics and COVID-19 outcomes. They turned to the Optum de-identified COVID-19 electronic health record, which is derived from over 700 hospitals and 7000 clinics across the USA. Using these data, the researchers examined the outcome of those with a laboratory confirmed COVID-19 and a recorded cancer diagnosis. The primary objective was to determine the effect of cancer on COVID-19 outcomes including 30-day all-cause mortality, hospitalisation, intensive care unit (ICU) admission and ventilator use. These outcomes were also analysed by the nature and type of cancer in comparison to patients without cancer. The authors the explored if there were any other specific factors in those with cancer which impacted on COVID-19 outcomes.
Cancer patient with COVID-19 and related outcomes
A total of 271,639 patients with confirmed COVID-19 of whom 18,460, with a mean age of 66 years (45.3% male) had a cancer diagnosis were analysed. Among those with cancer, 8034 patients had a history of cancer for longer than 12 months and 10,426 had a more recent diagnosis, i.e., within 1 year before COVID-19.
30-day all-cause mortality was more than three times higher among those with cancer (6.8% vs 1.9%) compared to non-cancer patients. After adjustment for age, sex, ethnicity and risk factors, the presence of cancer was associated with a 7% higher risk of death (relative risk, RR = 1.07, 95% CI 1.01 – 1.14, p = 0.028) compared to those without the disease. Similarly, there was a 4% higher risk of hospitalisation (RR = 1.04, 95% CI 1.01 – 1.07, p = 0.006). When comparing the duration of cancer, those with a recent diagnosis had both a significant (p < 0.001) increased risk of mortality (RR = 1.17) and hospitalisation (RR = 1.10) although this risk was non-significant for those who had cancer for much longer.
There was also an increased mortality risk for those with recent metastatic (RR = 2.09), solid tumour (RR = 1.12) and haematological (RR = 1.48) cancers compared with those without the disease. Individual cancers with a significantly elevated risk were leukaemia (RR = 1.58), liver (RR = 2.46), lung (RR = 1.85) and pancreatic (RR = 1.94).
When exploring the factors related to COVID-19 mortality in those with recent cancer, both chemotherapy (RR = 1.37) and radiotherapy (RR = 1.83) within 3-months before COVID-19, were significantly associated with a higher risk of death as was increasing age (i.e., > 75 years) (RR = 6.69). In addition, the only significant co-morbidities were cardiovascular disease (RR = 1.72), diabetes (RR = 1.39) and renal disease (RR = 1.51).
Citation
Kim Y et al. Characterizing cancer and COVID-19 outcomes using electronic health records PLoS One 2022
28th January 2022
Heart failure (HF) patients have a higher risk of cancer and cancer-related mortality compared to matched-controls according to research by a team from the Cardiovascular Disease Unit, Genoa, Italy.
There is emerging evidence that the incidence of cancer is higher among those with cardiovascular disease and heart failure and this latter group frequently die from cancer. In fact, research has uncovered the increased risk of cancer among HF patients, persists beyond the first year after their HF diagnosis and that their prognosis is worse compared to non-heart failure patients with cancer. Despite this purported association, other work among 28,341 Physicians’ Health Study participants, has shown that HF is not associated with an increased risk of cancer among male physicians. It has also been suggested that while heart failure patients did have a slightly increased risk of various cancer subtypes, these increased risks were largely drive by comorbidities.
Given this potential uncertainty over the HF-cancer association, the Italian team attempted to provide greater clarity by undertaking a retrospective cohort study of healthcare records in Puglia, a region of southern Italy. They included patients aged 50 years and older, diagnosed with heart failure but without a history of cancer in the three years prior to their inclusion in the analysis. The team included a control group without HF who were matched on age and sex. The primary outcomes of the study were cancer incidence as well as mortality. In an effort to examine whether HF severity influenced the study outcomes, the researchers also explored patients use of doses in excess of 80 mg/day of furosemide and equivalents for longer than 30 days in the year before the index date.
Heart failure patients and cancer
A total of 104,020 HF patients with a mean age of 76 years were matched to an equal number of control patients. The researchers identified a total of 12,036 new diagnoses of cancer in HF patients and 7,045 in controls after a median follow-up period of 5 years. This gave an incidence cancer rate of 21.36 per 1000 person-years among those with HF and 12.42 in the control arm (Hazard ratio, HR = 1.76, 95% CI 1.71 – 1.81).
The cancer mortality rate was also higher among HF patients compared with controls (HR = 4.11, 95% CI 3.86 – 4.38). This difference was also seen among HF patients aged less than 70 years (HR = 1.66, 95% CI 1.58 – 1.75) and in those over 80 years of age (HR = 2.07).
High dose loop diuretics also showed an important effect with a higher cancer incidence (HR = 1.11, 95% CI 1.03 – 1.21) and cancer-related mortality (HR = 1.35).
The authors concluded that HF patients had both a higher incidence of cancer and cancer mortality than matched controls and speculated that given that the risk was elevated among those with high dose loop diuretics, it was possible that the overall cancer risks were potentially higher in those with decompensated, i.e., more severe HF.
Citation
Bertero E et al. Cancer Incidence and Mortality According to Pre-Existing Heart Failure in a Community-Based Cohort JACC CardioOncology 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
25th October 2021
Physical inactivity could be the cause of 46,356 cancer cases across the US based on an analysis by researchers from the Department of Surveillance and Health Equity Science, Atlanta, US, on behalf of the American Cancer Society. The importance of undertaking physical activity as a means of reducing the risk of cancer, was highlighted in a 2019 systematic review which found strong evidence for an association between the highest versus lowest physical activity levels and reduced risks of bladder, breast, colon, endometrial, oesophageal adenocarcinoma, renal and gastric cancers. The review also identified how greater amounts of physical activity reduced cancer-specific mortality in those with breast, colorectal, or prostate cancer, with relative risk reductions of between 40 and 50 percent.
But how the risk of cancer due to physical inactivity vary across different states in the US was the question posed in the study by the American Cancer Society. The researchers estimated the proportion of cancer cases attributable to physical inactivity overall and for seven types of cancer (oesophagus, stomach, colon, breast in women, corpus uteri, kidney and bladder). The researchers drew on data from the Behavioural Risk Factor Surveillance System (BRFSS), which collects state-level estimates of various health-related behaviours including information on physical activity. The information on physical activity was drawn from surveys conducted between 2003 and 2006 across a wide age range and the number of incident cancer cases in 2013 – 2016, were obtained from the US Cancer Statistics database, to allow for a lag time between exposure prevalence and the occurrence of cancer.
The levels of physical activity were categorised in terms of metabolic equivalent task (MET) hours/week. A MET is the amount of energy an average adult expends sitting at rest. With the US physical activity guidelines recommending that adults engage in 2.5 to 5 hours/week of moderate intensity activity, this equates to at least 7.5 – 15 MET hours/week. For the purposes of their analysis, the researchers defined optimal physical activity as > 5 hours/week or > 15 MET-hours/week. The team also calculated the population attributable fraction (PAF) which can be used to quantify how a risk factor contributes to the outcome of interest compared, in this case, physical inactivity and cancer.
Findings
When optimal physical activity was defined as > 15 MET-hours/week, the overall PAF for both sexes was 3% (95% CI 2.9 – 3%). This amounted to 46,356 incident cancer cases in adults aged > 30 years, that could be attributed to physical inactivity. The overall PAF was higher in women than men (4.1% vs 1.8%), with the result that 32,089 incident cancer cases in women and 14,277 cases in men were attributable physical inactivity.
With respect to the individual cancers, stomach cancer had the highest PAF (16.9%), followed by corpus uteri (11.9%), kidney (11%), colon (9.3%), oesophagus (8.1%), breast (6.5%) and bladder (3.9%). In addition, PAF values varied across the US for the different cancer. For example, the PAF for stomach cancer was 14% in Montana and 21.1% in Kentucky.
The researchers concluded that physical inactivity was a potentially avoidable cause of a large number of cancers and that promoting physical activity could prevent many cases.
Citation
Minihan AK et al. Proportion of Cancer Cases Attributable to Physical Inactivity by US State, 2013-2016. Med Sci Sports Exerc 2021
18th January 2021
The risk-benefit ratio for the use of aspirin in older adults is still unclear though some secondary analyses of randomised trials have indicated that aspirin can reduce the incidence and mortality due to colorectal cancer. Given this uncertainty, a team from the Division of Cancer Prevention, National Cancer Institute, Maryland, US, decided to focus their investigation on a post hoc analysis of older individuals in the prostate, lung, colorectal and ovarian cancer screening trial (PLCO).
PLCO was a large trial to determine the effects of screening on cancer-related mortality and secondary endpoints in people aged 55 to 74 years of age. The researchers limited their analysis to individuals at least 65 years of age after enrolment and whose baseline questionnaire contained information on aspirin use. Individuals who had a history of any of the cancers studied were excluded. The use of aspirin was then categorised as either less than or more than three-times/week. The aim of the study was to evaluate whether use of aspirin had an impact on the incidence and survival from bladder, breast, oesophageal, gastric, pancreatic and uterine cancers among individuals 65 years of age and older. The original PLCO data collection was completed in 2009 after 13 years of follow-up but for the current study, data collection continued until 2014, among individuals who consented to further follow-up or 2009 in those unwilling to be followed.
Findings
The eligible study population included 139,896 individuals with a mean age at baseline of 66.4 years (51.4% female). A total of 32,580 incident cancers were recorded during the follow-up period. The use of aspirin at least three times per week not associated with the incident risk of any of the included cancers. However, the researchers did find that after adjustment for co-morbidities, aspirin use (i.e., at least three times per week) was associated with a significantly increased survival compared to no use of the drug for bladder (hazard ratio, HR = 0.67, 95% CI 0.51–0.88, p = 0.003) and breast cancer (HR = 0.75, 95% CI 0.59–0.96, p = 0.02) only. In addition, any use of aspirin was also associated with a reduced risk of death from both bladder (HR = 0.75, 95% CI 0.58 – 0.98) and breast cancer (HR = 0.79, 95% CI 0.63–0.99) but again, not for any of the other cancers.
Unfortunately, the authors were unable to account for their findings and concluded that further work is needed to consider the relative benefits and harms associated with longterm use of aspirin.
Citation
Loomans-Kropps HA, Pinksky P, Umar A. Evaluation of aspirin use with cancer incidence and survival among older adults in the prostate, lung, colorectal, and ovarian cancer screening trial. JAMA Netw Open 2021
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