Wednesday December 9 2009
Childhood cancers tend to be rare but very aggressive
The risk of heart problems is more than five times greater in survivors of childhood cancer according to The Daily Telegraph. The newspaper said new research found that the risk was still high 30 years after they had beaten their cancer.
The research compared the rates of subsequent heart problems in adult survivors of childhood cancers to those seen in siblings that had not had cancer. While the overall risk of heart problems was still low in cancer survivors, it was found to be much higher than that of their siblings. The risk was found to be associated with the use of certain chemotherapy and radiotherapy treatments.
All the people in the study received their cancer treatments between 1970 and 1986, and it is likely that chemotherapy and radiotherapy regimens have altered since then. On this basis these results cannot be generalised to children being treated with cancer today. However, UK guidelines suggest that routine heart checks should be made every five years following childhood cancer. This research further emphasises the importance of these checks.
Where did the story come from?
This research was conducted by Dr Daniel Mulrooney and colleagues at the University of Minnesota Medical School. The study was funded by several US institutions including the National Cancer Institute, the National Institute of Health and the Children’s Cancer Research Fund Minneapolis. The study was published in the peer-review peer-reviewed British Medical Journal.
The Daily Telegraph and the BBC have generally reported the research well. The BBC has highlighted UK guidelines that suggest that cancer patients should be monitored every five years for heart problems, saying that US doctors feel that many patients in the US do not receive this follow-up. As this particular study did not assess the methods used to follow up survivors or how their heart problems were detected, the study cannot answer the question of how cancer survivors should be clinically monitored or assessed.
What kind of research was this?
This was a retrospective cohort study looking at whether survivors of childhood cancer had an increased risk of heart problems compared with their siblings. The researchers were exploring the theory that cancer treatments can increase the risk of later heart problems.
What did the research involve?
The research took data from the US Childhood Cancer Survivor Study, which collected data on adults who had been diagnosed with childhood cancer between 1970 and 1986. The data taken included measures of demographic characteristics, height, weight, lifestyle and medical conditions.
All participants were under 21 years old when their cancer diagnosis was made and had survived for at least five years after treatment. The types of cancer looked at by the study were Hodgkin’s and non-Hodgkin’s lymphomas, kidney cancer, bone cancer, neuroblastoma (a cancer of nerve cells) and soft tissue sarcoma (cancer of connective tissue). The participants’ medical records were examined to find out whether they had received chemotherapy and to estimate doses of radiation given.
Heart problems were recorded using two questionnaires, one from the Childhood Cancer Survivor Study in 1995-96 and a follow-up questionnaire in 2000-02. In total, 14,358 cancer survivors completed the first questionnaire. A random sample of survivors was asked to nominate their sibling closest in age to participate in the control group. In total, 3,899 control siblings took part in the study.
The study was large, but as it required participants to self-report their medical histories, this may have biased the outcomes.
The study had attempted to validate the self-reported incidence of heart problems through a doctor checking medical records, but the researchers could not obtain and assure the adequacy of records for all events. They, therefore, relied solely on self-reported details of heart problems.
What were the basic results?
The researchers found that the majority of individuals’ cancer treatment used a combination of chemotherapy and radiation therapy, either with or without surgery:
- 44.3% had received chemotherapy, radiation and surgery
- 11.7% had received chemotherapy and radiation
- 6.5% had received chemotherapy alone
- 0.3% had received radiation therapy alone
The types of heart problem reported were congestive heart failure (where the heart cannot pump sufficient blood around the body), heart attack, pericardial disease (inflammation of the heart) and problems with the valves of the heart.
The researchers found that the prevalence of a first report of any of these conditions was greater in the cancer survivors than in their siblings:
- heart failure was reported by 1.7% of cancer survivors and 0.2% of siblings
- heart attacks were reported by 0.7% of cancer survivors and 0.2% of siblings
- pericardial disease was reported by 1.3% of cancer survivors and 0.3% of siblings
- valve problems were reported by 1.6% of cancer survivors and 0.5% of siblings
Although the prevalence was low, the risk of having any of these heart problems was significantly greater in cancer survivors than in their siblings.
The researchers found that over a 30-year follow-up period the cumulative incidence of heart failure, pericardial disease and valve problems continued to increase in cancer survivors, although this was not measured in siblings. One quarter of cancer survivors reported more than one cardiac event and when the total incidence of heart problems was compared over the 30-year survey period, cancer survivors were approximately five to six times more likely to experience heart problems than the sibling group.
Within the cancer survivor group, patients who had received anthracycline (a particular chemotherapy drug) were more likely to have developed heart failure, pericardial disease and valve problems compared to those who had not. Patients who had received high-dose cardiac radiation were more likely to have developed heart problems than those patients who had received no radiation treatment.
How did the researchers interpret the results?
The researchers concluded that cardiac events, generally rare in young adults, were significantly more frequent in young survivors of cancer than in siblings. They say the relative risk of a survivor reporting cardiovascular disease was higher than in the sibling group across most diagnoses, and that this risk was significantly associated with specific therapeutic exposures, notably exposure to anthracyclines or high-dose cardiac radiation.
This well-conducted review, which has followed a large number of childhood cancer survivors over a long period of time, gives evidence for an association between being treated for childhood cancer and subsequently developing heart problems.
Although this was a large cohort study, there are a few limitations that need to be considered when interpreting the outcomes of this study, many of which were highlighted by the researchers themselves:
- The study relied on the self-reporting of diagnoses of heart problems as it was not possible for the researchers to have each participant’s report validated by a clinician. This could lead to some diagnoses being inaccurate.
- Although there was an increased risk of heart problems in cancer survivors, the actual incidence of problems during follow-up was relatively low.
- Although the researchers had found that certain chemotherapy treatments and radiation doses increased the likelihood of heart problems, over half of the cancer survivors included in their study had received a combination of treatments. Also, as all people in the study received their cancer treatments between 1970 and 1986, it is likely that chemotherapy and radiotherapy regimens have altered since then and, therefore, results cannot be generalised to children being treated for cancer today.
- It is difficult to conclude that any one cancer treatment definitely increased the risk of heart problems as it could have been the physiological effects of having the cancer itself that increased risk. It is also unclear whether any participants could have suffered from any heart problems at the time of their cancer diagnosis or prior to it.
- The study looked at the healthy controls’ overall risk of heart problems but not how this risk changed over time. This means the study cannot provide information about how long child cancer patients should be monitored to detect any heart problems.
- There are other risk factors for heart problems that have not been taken into account in the analyses, for example blood pressure, cholesterol or diabetes.
- The results cannot be generalised to people who are treated for other cancers or those who go on to develop cancers in adulthood.