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A radiation-induced cancer appears in or at the edge of the treated area, usually more than ten years later, and the risk rises with the dose the organ received and falls with the age at which the person was treated. Which organs sat in the field is therefore the question that decides everything that follows, and it is answerable from the radiotherapy record.
What is done about it. Two things, one at the time and one afterwards. At the time: smaller fields, the modern techniques that cut dose to nearby organs, and omitting radiotherapy where an equally good option exists. Afterwards: knowing which organs were in the field, because that is what decides whether a screening programme applies. The radiotherapy department keeps the plan; a late-effects clinic or a general practitioner can request it.
The three variables, and how each behaves. Dose to the organ drives the risk, and the relationship is graded rather than threshold-like: in the SEER analysis of 647,672 five-year survivors, relative risk "was highest for organs that typically received greater than 5 Gy". Age at exposure runs the other way: the same analysis found that risk "decreased with increasing age at diagnosis". Time since treatment runs upwards: risk "increased with time since diagnosis", which is the opposite of the leukaemia pattern, where risk falls away after about ten years.
The absolute size of it in adults. Across those fifteen cancer sites, the estimated excess was 3,266 second solid cancers (95% CI 2,862 to 3,670), 8 per cent (7 to 9) of all second solid cancers in people who had radiotherapy, and five excess cancers per 1,000 people treated by fifteen years after diagnosis.
Breast cancer radiotherapy, as the worked example. A meta-analysis of 13 cohort studies covering 762,468 women found that five or more years after a breast cancer diagnosis, radiotherapy was associated with second non-breast cancer at a relative risk of 1.12 (95% CI 1.06 to 1.19), lung 1.39 (1.28 to 1.51), oesophagus 1.53 (1.01 to 2.31) and sarcoma 2.53 (1.74 to 3.70), with no significant association for thyroid. Fifteen or more years out the lung figure rose to 1.66 (1.36 to 2.01) and the oesophageal one to 2.17 (1.11 to 4.25). The same authors' later meta-analysis of 22 population-based studies compared 245,575 irradiated and 277,164 unirradiated women against general-population rates: the standardised incidence ratio for second non-breast cancer was 1.23 (1.12 to 1.36) in irradiated women and 1.08 (1.03 to 1.13) in unirradiated ones, and in irradiated women the incidence of lung, oesophageal, thyroid and connective-tissue cancers rose over time, peaking at ten to fifteen years. At fifteen years or more the summary estimates were 1.91 for lung, 2.71 for oesophagus and 3.15 for thyroid, and 6.54 for sarcoma at ten years or more. Unirradiated women had no raised risk of lung or oesophageal cancer at any point.
Pelvic radiotherapy, as the second worked example. A meta-analysis of 21 observational studies of radiotherapy for prostate cancer found raised risks, against men not irradiated, of bladder cancer (adjusted hazard ratio 1.67, 1.55 to 1.80), colorectum (1.79, 1.34 to 2.38) and rectum (1.79, 1.34 to 2.38), and no significant excess of haematological (1.64, 0.90 to 2.99) or lung cancer (1.45, 0.70 to 3.01). Across the included studies the highest reported absolute rates were 3.8 per cent for bladder, 4.2 per cent for colorectal and 1.2 per cent for rectal cancer, and the lowest were 0.1, 0.3 and 0.3 per cent, a spread the authors attribute to differing follow-up and study quality. The modality mattered: external beam radiotherapy was consistently associated with raised odds and brachytherapy was not.
The proof that it is the field and not the person. In a SEER cohort of 30,552 men treated with radiotherapy and 55,263 with surgery alone for prostate cancer between 1973 and 1994, all surviving at least five years, 1,437 colorectal cancers developed: 267 at definitely irradiated sites, 686 at potentially irradiated sites and 484 at non-irradiated sites. Radiation was associated with cancer in the irradiated rectum (adjusted hazard ratio 1.7, 1.4 to 2.2) and had no effect on the rest of the colon. A risk confined to the tissue that was irradiated, and absent from identical tissue a few centimetres away in the same person, is the cleanest evidence in this field that the radiation is the cause.
What the older cohorts cannot tell you. Every long cohort describes fields that are no longer used. Mantle fields, whole-pelvis fields and two-dimensional planning delivered much larger volumes at higher dose than modern conformal or intensity-modulated plans. Whether the smaller fields of the last twenty years have lowered the forty-year second cancer rate is not known, because nobody treated with them has yet been followed for forty years, and saying otherwise would be a guess.
Showing the technology this term belongs to: IMRT / IGRT (modern external beam).
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