Medical imaging & patient care

After the cure

While survival rates for childhood cancer have increased, many survivors are blighted by health problems later in life. According to a new study, these ‘late effects’ seem to be no better for more recently treated patients than for those who were treated in the 1970s. So what needs to be done to improve the situation? We speak to the study authors to find out.

When thinking about childhood cancer, the emphasis is usually on survival – treating the patient, guarding against remission, and eradicating the cancer for good. Of course, this is as it should be. In the United States, 15,700 children each year are diagnosed with cancer, and it is mostly thanks to recent advances in treatment that 88% of them now survive five years or more.

However, one major question is often overlooked, and that is what happens next. According to the children’s cancer charity CureSearch, three out of five survivors develop ‘late effects’ (i.e. problems related to cancer treatment that persist once the treatment is over). These can include hormonal or gastrointestinal problems, chronic pain, or even secondary cancers.

When you consider the sheer number of adult survivors (more than 420,000 in the United States[1]), it is clear that the longer-term prognosis ought not to be overlooked.

This was the thinking behind the Childhood Cancer Survivor Study (CCSS), which published its findings in November in the Annals of Internal Medicine. A retrospective cohort study, it looked at survivors of childhood cancer, more than five years removed from treatment, who were treated between 1970 and 1999.

“The study was designed to evaluate late outcomes among survivors of childhood cancer, with the goal of providing the foundation for interventions to prevent or remediate adverse health outcomes and also to guide current therapies to minimise late effects,” explains Dr Kirsten Ness, one of the lead investigators and a member of the St Jude Department of Epidemiology and Cancer Control, which co-ordinated the study.

Lingering effects

CCSS involved 14,566 adult patients, who had been treated for paediatric cancer in 27 institutions across the United States, alongside 4,000 siblings of survivors who served as a comparison group. As well as looking at overall health trends, the researchers wanted to see whether there were any differences between survivors treated in the 1970s, and those who had benefited from more contemporary therapies. Would the group treated in the 1990s be healthier overall?

Each participant filled in a questionnaire, which allowed the researchers to ascertain their overall health status. This covered functional impairment, limits to activity, mental health, pain, anxiety and overall wellbeing. The patients’ medical records were also analysed, with detailed diagnostic treatment information abstracted for reference.

Unfortunately, there was no clear upward trend – patients treated in the 1970s, 1980s and 1990s all reported similar long-term outcomes. This suggests that, despite improved survival rates, newer and better treatments had done little to counteract the lingering difficulties. In fact, survivors treated between 1990 and 1999 were more likely to report poor general health and anxiety.

Explanations and limitations

On the face of things, these findings may seem surprising, or even damning. However, Ness believes there may be several underlying factors, which don’t necessarily reflect badly on modern treatment protocols.

“Survivors treated in the 1990s include people who may not have survived if they been diagnosed and treated in the 1970s,” she points out. “For example, in the 1960s, five-year survival rates for acute lymphoblastic leukaemia were less than 10%, and have risen to higher than 90% today. The additional survivors include individuals who received intense therapy, and thus those who may have participation-limiting health outcomes like poor exercise tolerance and persistent pain.”

While several paediatric cancers were represented (such as Hodgkin lymphoma, non-Hodgkin lymphoma and neuroblastoma) the data set was largely driven by leukaemia and osteosarcoma. These cancers have seen a surge in survival rates, both in the short- and long-term. However, the very advances that have saved patients’ lives have also tended to compromise their health.

“For example, increased doses of neurotoxic agents, like vincristine, methotrexate, have helped improve survival rates, while reducing exposure to radiation,” explains Ness. “There’s also been a movement away from amputation for osteosarcoma survivors – the preferred practice is limb sparing, for cosmetic and functional reasons, which may result in increased reported pain.”

It is also possible, she contends, that more recent survivors have received more follow-up clinically. This may lead to worse perceived health outcomes, for the simple reason that the negative aspects of their health status have been more fully explored.

The findings should therefore be taken with certain caveats: firstly, that the data is subject to survival bias, and secondly that perceived health does not always correspond with the presence of chronic health conditions. Another potential limitation is that not everybody eligible for inclusion agreed to take part.

Room for improvement

This said, it is clear that work remains to be done in improving ‘late effects’. This may mean modifying current cancer treatments to reduce their neurotoxicity, or introducing new therapies and interventions for survivors. For those interested in developing new intervention strategies, the CCSS data is likely to prove an excellent starting point.

“Findings from this study indicate that current therapies, with the continued goal of 100% cure, may still result in poor perceived health outcomes, and more work is needed to address these toxicities in treatment,” says Ness. “For those who develop adverse outcomes, rehabilitation strategies that work in other populations with pain and mobility limitations may be effective and need to be tested.”

Already, several randomised intervention studies have been completed off the back of CCSS-based research. Having recruited a cohort of high-risk childhood cancer survivors, these studies looked into the benefits of breast cancer screening, cardiovascular screening, and stopping smoking. There are two others currently underway – one exploring sun protection for those at highest risk of radiation-associated skin cancer, and another aiming to reduce obesity in survivors of acute lymphoblastic leukaemia.

The Children’s Oncology Group has also prepared a resource for physicians, called ‘Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent and Young Adult Cancers’. This provides screening recommendations, and general advice on how doctors should deal with the likely health complications.

As Ness puts it: “Childhood cancer survivors are vulnerable to adverse outcomes in terms of perceived health – survivors should be monitored and referred to appropriate services to address their needs.”

The upshot is clear: while increased survivorship is undoubtedly a good thing, this should not be the only metric of how well a treatment works. The cure, in fact, should just be a starting point, rather than an end.

[1] https://clinicaltrials.gov/ct2/show/NCT02046811?term=NCT02046811&rank=1

This article appears in the February 2017 edition of Pharma Technology Focus

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s