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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.
This is the single clearest demonstration in oncology that reducing the intensity of a curative treatment can be measured decades later in lives.
The Childhood Cancer Survivor Study followed 34,033 people who survived at least five years after a childhood cancer treated between 1970 and 1999, median follow-up 21 years. Of 3,958 deaths, 1,618 (41 per cent) were attributable to health-related causes: 746 from subsequent neoplasms, 241 cardiac, 137 pulmonary and 494 other. Fifteen-year all-cause mortality fell from 12.4 per cent for diagnoses in the early 1970s to 6.0 per cent in the 1990s, and health-related mortality from 3.5 to 2.1 per cent, with falls in death from subsequent neoplasm, cardiac and pulmonary causes. The exposures fell alongside: cranial radiotherapy for acute lymphoblastic leukaemia was given to 85 per cent of children in the 1970s, 51 per cent in the 1980s and 19 per cent in the 1990s; abdominal radiotherapy for Wilms tumour to 78, 53 and 43 per cent; chest radiotherapy for Hodgkin lymphoma to 87, 79 and 61 per cent; and anthracycline exposure fell too. Reduction in exposure was associated with reduced late mortality among survivors of acute lymphoblastic leukaemia and Wilms tumour.
The British population-based cohort shows the same thing from a different direction and adds the long tail. Among 17,981 five-year survivors diagnosed 1940 to 1991 and followed to 2006, there were 3,049 deaths, a standardised mortality ratio of 10.7 (95 per cent confidence interval 10.3 to 11.1), still threefold higher than expected 45 years from diagnosis. What changes is the cause. The absolute excess from recurrence fell from 97 extra deaths per 10,000 person-years at 5 to 14 years to 8 beyond 45 years; the excess from second primary cancers rose from 8 to 58 and from circulatory causes from 2 to 29 over the same intervals. Beyond 45 years, recurrence accounted for 7 per cent of the excess deaths and second cancers plus circulatory disease for 77 per cent.
The 2016 extension to 34,489 survivors diagnosed 1940 to 2006 found 4,475 deaths, 9.1 times expected (8.9 to 9.4), 64.2 excess deaths per 10,000 person-years (62.1 to 66.3), and that those treated in 1990 to 2006 experienced 30 per cent of the excess deaths of those treated before 1970. Among survivors aged 60 or more, excess deaths from circulatory causes exceeded those from second cancers, which is why cardiovascular risk management belongs in survivorship care and not only cancer screening.
What comes back, and when: nothing here reverses, but the trend is the argument for every de-escalation trial running now. A child treated today carries a materially smaller late risk than the cohorts measure, and the honest way to say that to a parent is to name the exposure that was removed.
Late mortality in survivors is dominated by two mechanisms with long latencies: radiation carcinogenesis, which produces second cancers at a rate rising with dose and with time since exposure, and radiation and anthracycline injury to the heart and vessels, which becomes clinically apparent when ordinary cardiovascular ageing removes the reserve. Both scale with the dose given, so reducing the dose reduces the hazard decades later.
Query for this technology: (TITLE:"Late deaths after childhood cancer, what causes them, and the proof that gentler treatment worked" OR ABSTRACT:"Late deaths after childhood cancer, what causes them, and the proof that gentler treatment worked") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Late deaths after childhood cancer, what causes them, and the proof that gentler treatment worked, not a curated reading list.
Shares Second cancers after childhood cancer: the risk by treatment, and why it is falling, Childhood Cancer Survivor Study (CCSS), Wilms tumour (nephroblastoma), Radiotherapy and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares British Childhood Cancer Survivor Study (BCCSS), Wilms tumour (nephroblastoma), Medulloblastoma, Childhood cancers (all types) and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares How much illness childhood cancer survivors carry, and at what age, Childhood Cancer Survivor Study (CCSS), Radiotherapy, Medulloblastoma and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares How much illness childhood cancer survivors carry, and at what age, Childhood Cancer Survivor Study (CCSS), Radiotherapy, Medulloblastoma and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares The heart after anthracyclines and chest radiotherapy in childhood, Second cancers after childhood cancer: the risk by treatment, and why it is falling, How much illness childhood cancer survivors carry, and at what age, Childhood Cancer Survivor Study (CCSS) and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares How much illness childhood cancer survivors carry, and at what age, Childhood Cancer Survivor Study (CCSS), Medulloblastoma, Childhood cancers (all types) and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares How much illness childhood cancer survivors carry, and at what age, Childhood Cancer Survivor Study (CCSS), Radiotherapy, Medulloblastoma and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares The heart after anthracyclines and chest radiotherapy in childhood, How much illness childhood cancer survivors carry, and at what age, Wilms tumour (nephroblastoma), Radiotherapy and the tags rejuvenation, survivorship, paediatric, late-effects.