late-effects

People diagnosed between 15 and 39 get different cancers from children and from older adults, and for years their survival improved more slowly than either. Since 2000 that has changed: five-year survival gains for this group have paralleled those of childhood cancers. The obstacles that remain are trial enrolment, access and insurance, and support that fits the age.

A child treated during the years in which bone is laid down may never reach the peak bone mass they would have had, which is a different problem from an adult losing bone already built. Thirty per cent of adult survivors of childhood leukaemia had low bone density, most strongly associated with growth hormone deficiency and smoking, both treatable.

Four problems that turn up years later and are easy to miss because each belongs to a different specialty: bone that thins or, less often, dies at the hip; cataract, which is common after total body irradiation and is fixed by an operation; kidney function that drifts down; and lungs that stiffen rather than obstruct. Each has a cheap test.

A girl who had radiotherapy to the chest carries a risk of breast cancer by age 50 of about 30 per cent. It is not only about dose: a low dose to the whole lung gave a higher standardised incidence than a high dose to a smaller field, because volume matters. Surveillance is recommended from early adulthood, decades before ordinary screening starts.

Britain's own survivor cohort, built on national registration rather than on hospital volunteers, which is why it can follow people for half a century and count deaths that nobody reported. Its central finding is that what kills survivors changes with time: recurrence early, second cancers and heart disease late.

Cancer in the years when education and first jobs happen costs more than the time taken. In the largest cohort, 23 per cent of childhood cancer survivors had used special education services against 8 per cent of siblings, and survivors of several cancers were less likely to finish high school. The important finding is that where the educational support was given, the gap closed.

Male survivors were about half as likely as their brothers to father a child, and the causes are specific: testicular radiotherapy above 7.5 gray, and high cumulative cyclophosphamide, ifosfamide, procarbazine or cisplatin. A young man with none of those was no less likely than his brother. Sperm banking works; tissue banking before puberty has produced no births.

Most female survivors treated with chemotherapy and no radiotherapy to the pelvis or brain can become pregnant: the large cohort that asked found chemotherapy-specific effects were few. The exceptions are busulfan, high-dose lomustine, pelvic and cranial radiotherapy and transplant conditioning. Before puberty, freezing ovarian tissue is the only option.

Transplant conditioning, and total body irradiation in particular, usually ends natural fertility and in children slows growth. The decisions that preserve the most are made before conditioning starts. A randomised trial in children with leukaemia tested replacing the radiation with chemotherapy and found the radiation worked better.

The clearest evidence that treatment ages people is not a laboratory marker, it is what happens to survivors decades later. In the St Jude Lifetime Cohort, one in eight women who had cancer as a child met the clinical definition of frailty at a mean age of 33, a rate usually seen after 65. Frailty predicted new chronic conditions and death.

Radiotherapy that reaches the pituitary stops the growth hormone signal, and radiotherapy to the spine stops the spine growing. In a Dutch cohort of 573 survivors, 8.9 per cent ended up more than two standard deviations below mean adult height, the largest losses after total body irradiation and craniospinal radiotherapy. Replacement restores some height.

Hearing loss in a child still learning to speak and read costs more than the same loss in an adult. In the St Jude Lifetime Cohort, severe hearing impairment affected 34.9 per cent of platinum-treated survivors and 38.3 per cent of those irradiated at the cochlea, against 8.8 per cent of unexposed survivors, and tracked deficits in reasoning, fluency and mathematics.

Transplant conditioning can leave the thyroid underactive, the ovaries or testes not working, and the handling of sugar and fat altered in a way that raises heart risk years later. Much of this is treatable with ordinary medicine, and the familiar things about weight, exercise and smoking matter more here than usual, not less.

Young people often say their cancer took a long time to diagnose, and the research agrees that time to diagnosis varies widely by tumour type and age. What the research does not support is a single number: a systematic review found the studies used different definitions and skewed data that could not be combined, so no meta-analysis was possible.

The figures, with the cohort and the age attached, because they are misquoted more than any others. On self-report at a mean age of 26, 62.3 per cent of survivors had a chronic condition. On clinical testing, the cumulative prevalence of any chronic condition by age 45 was 95.5 per cent, and by age 50 a survivor had 17.1 conditions against 9.2 in matched controls.

Most immune side effects of checkpoint inhibitors settle. The hormone glands are the exception: a pituitary, thyroid, adrenal or insulin-making gland destroyed by the immune system does not grow back, and the replacement treatment that follows is usually for life. In the follow-up cohorts 83 per cent of hormone problems were still present three months after the drug stopped.

Three countries wrote three different sets of follow-up rules for the same survivors, and the rules disagreed about who to screen, how and how often. Since 2010 this group has been settling those disagreements one organ at a time, in public, with the evidence graded and the disagreement named.

Every unit of red cells carries iron the body cannot excrete, and someone who has been through leukaemia treatment may have had dozens. It settles in the liver and sometimes the heart. A blood test finds it and an MRI confirms it, and it can be removed either by a chelating drug or by taking blood off once the marrow is working again.

A Cochrane review of 61 studies found reported rates of kidney damage after childhood cancer treatment ranging from nought to 84 per cent, which is a statement about the literature rather than about kidneys. On systematic clinical testing of one large cohort, kidney dysfunction was present in 5 per cent, among the least common of the organ problems measured.

Five-year survivors still die earlier than their peers, but much less than they did. Fifteen-year mortality among American five-year survivors fell from 12.4 per cent for children treated in the early 1970s to 6.0 per cent for those treated in the 1990s, and the fall tracks the radiotherapy and anthracycline that were taken out of the protocols.

There are now around half a million people alive worldwide who have had a blood or marrow transplant. Most of them have at least one lasting health problem from it, and many have several. The list is long and reads heavily, but almost every item on it is either preventable or detectable early, which is the reason to know what is on it rather than to avoid knowing.

Britain sorts survivors into three levels of follow-up by how intensive their treatment was: a postal or telephone review at one end, a specialist late-effects clinic at the other. A Scottish cohort applied the levels retrospectively and found they worked: late effects affected 11.6 per cent of level one survivors and 65.2 per cent of level three.

The commonest pattern after cranial radiotherapy in a young child is not forgetting what was learned but learning more slowly than other children, so the gap widens with every year at school. In 44 children treated for medulloblastoma the measured loss was 2.55 IQ points a year, and raw scores were still rising: they were gaining skills, just more slowly than the test expected for their age.

Europe's answer to the American cohorts: thirteen data providers in twelve countries pooled their records to build what its own authors call the largest cohort of children with cancer to date, 83,333 five-year survivors, so that second cancers and heart disease could be counted on a continent that keeps its data in national pieces.

What treatment took, and whether it comes back: hair, hearing, fertility, bone, muscle, nerves, memory, heart, skin and sexual function. Recovery begins during treatment, not after it.

People who have had a donor transplant develop new, unrelated cancers about twice as often as people of the same age, and by fifteen years about three times as often. Radiation in the conditioning matters most for those irradiated young, and chronic GvHD raises squamous cancers of skin and mouth. Both point at lifelong screening.

The largest late risk a childhood cancer survivor carries. Thirty years after diagnosis, 20.5 per cent of survivors treated in the 1970s and early 1980s had developed a subsequent neoplasm. The fifteen-year risk of a second malignancy has since fallen from 2.1 to 1.3 per cent across treatment decades, and the fall tracks the radiotherapy taken out.

A second cancer is a brand new cancer, not the first one coming back. Most are found by the ordinary routes, and some have a screening programme attached, which is the part worth asking about by name. The risk comes from three things that add together: the treatment, the thing that caused the first cancer and has not gone away, and simply having lived longer.

England built specialist units for 13 to 24 year olds and then evaluated them nationally, which almost no health system does. The results were mixed enough that young people were asked to interpret them, and they pointed out that three years of follow-up was too short and that the study had defined specialist care by how many admissions a person had rather than how long they spent there.

The study that brought survivors back to a hospital and tested them, rather than asking them what was wrong. It found that most of what it found had not been diagnosed: by age 45, on clinical testing, 95.5 per cent of survivors had a chronic health condition and 80.5 per cent had a serious, disabling or life-threatening one.

If you are alive and free of disease two years after a donor transplant, around nine in ten are alive five years later and 85 per cent at ten years. The death rate among transplant survivors stays higher than in people of the same age who never had one, for many years. The two things that matter most are age and chronic graft-versus-host disease.

Treatment given while the teeth are forming can stop them forming. In the largest survey, survivors were three times more likely than siblings to report small teeth, three times more likely to report abnormal roots and nearly ten times more likely to report a dry mouth, and the risk was concentrated in children treated with alkylating drugs before the age of five.

The most widely used rulebook in childhood cancer survivorship, and the one that made follow-up exposure-based rather than diagnosis-based: what you were given decides what you are screened for. It comes with Health Links, plain-language sheets written for the survivor rather than the doctor, and it is free to download.

For several treatments there is a published number above which lasting damage becomes much likelier: the total anthracycline dose and heart failure, the total cisplatin dose and hearing, the radiation dose to the parotid gland and dry mouth. Twenty-three thresholds are listed with their sources, because the total you have had is a question your team can answer.

This is where survivorship care is lost. Of 8,522 adult survivors asked, 88.8 per cent had seen a doctor in the previous two years but only 17.8 per cent had received care that addressed their cancer history with risk advice or screening. Among those who should have had an echocardiogram, 28.2 per cent had; among those due a mammogram, 40.8 per cent had.

Heart damage from childhood treatment appears quietly and decades later. When 1,853 adult survivors were examined rather than asked, 7.4 per cent had cardiomyopathy and 28 per cent had valve disease, and most of it was new at that visit: nearly all of them had no symptoms. High blood pressure multiplied the risk of heart failure nineteenfold, which makes it the most treatable thing on the page.

Radiotherapy near the base of the brain damages the gland that runs growth, puberty, the thyroid and the stress response, in that order of sensitivity. In 748 survivors treated with cranial radiotherapy, 46.5 per cent had growth hormone deficiency, 10.8 per cent sex hormone deficiency, 7.5 per cent thyroid deficiency and 4 per cent adrenal deficiency, and most of it had not been treated.

For each treatment and each lasting effect, whether recovery is usual, partial or unlikely, how long it takes and in what proportion of people, with the source for every answer. The grid is mostly empty, because for most pairs nobody has published a recovery figure, and the page says how empty it is rather than hiding it.

Four different things get called the same thing in conversation and in the news, and the difference changes what the news means. A second cancer is a new disease with its own stage and its own chance of cure. A recurrence is the first one back. A metastasis is the first one somewhere else. Field cancerisation is a whole area of tissue that was already changed before any of them.