Literature Scan
Adolescent and Young Adult Cancer Survivors
Face Higher Risk of Second Cancers
People who were diagnosed with cancer as
adolescents or young adults (AYAs) have
an excess risk of developing a subsequent
primary neoplasm later in life, compared with
the general population, according to findings
from a large-scale study published in Lancet
Oncology. Among 16 types of cancer studied,
Hodgkin lymphoma (HL) appeared to be as-
sociated with the greatest risk of developing a
second cancer.
The authors, led by Chloe J. Bright, MD,
from the Centre for Childhood Cancer Survi-
vor Studies at the Institute of Applied Health
Research at the University of Birmingham in
the U.K., also observed that a small number
of specific cancers – including lung cancer
– accounted for most of the total excess num-
ber of secondary neoplasms.
“The prominence of lung cancer after
each of these AYA cancers indicates the need
for further work aimed at preventing and
reducing the burden of this cancer in future
survivors of AYA cancer,” the researchers
noted, adding that “[our study] provides an
evidence base to inform priorities for clinical
long-term follow-up.”
cervical, testicular, HL (separate categories
for male and female patients), melanoma,
central nervous system tumors, colorectal,
non-HL, thyroid, soft-tissue sarcoma, ovar-
ian, bladder, other female genital, leukemia,
and head and neck cancer.
Standardized incidence ratios (SIRs) were
calculated by comparing observed numbers
of neoplasms divided by expected numbers;
expected incidence was derived from the cor-
responding cancer rate among age- and sex-
matched controls in the general population.
Next, absolute excess risks (AERs) were cal-
culated as the excess number of subsequent
primary neoplasms beyond those expected
from the general population and reported as
neoplasms per 10,000 patient-years.
Median follow-up for each participant was
16.8 years (interquartile range = 10.5-25.2
years), and patients were followed for a total
of 2,631,326 person-years.
During this time, 12,321 subsequent
primary neoplasms were diagnosed in 11,565
survivors, most frequently among survivors
of breast cancer, cervical cancer, testicular
cancer, and HL ( TABLE ).
“The burden of the excess number of
neoplasms … accounted for by lung
cancer was substantial and apparent
across all AYA cancers investigated.”
—CHLOE J. BRIGHT, MD
To characterize the risks of developing
secondary cancers among this population, the
authors collected information from the Teen-
age and Young Adult Cancer Survivor Study,
a population-based cohort of 200,945 patients
living in England and Wales who were diag-
nosed with cancer between the ages of 15 and
39. Participants were followed from five years
after diagnosis until death, emigration, or
study end date (December 31, 2012).
In this analysis, researchers focused on
the risk of specific subsequent primary neo-
plasms after 16 types of AYA cancer: breast,
TABLE.
For patients with HL, the AER of any
subsequent primary neoplasm in women was
56 excess subsequent primary neoplasms per
10,000 person-years, corresponding to an SIR
of 3.1. In men, the AER was 30 per 10,000
person-years and the SIR was 2.6.
“The excess number of subsequent pri-
mary neoplasms observed increases with
increased period of follow-up from diagno-
sis after each AYA cancer investigated,” the
authors reported. At 30 years or longer after
diagnosis of HL, for example, the AER for any
subsequent primary neoplasm reached 168.6
per 10,000 person-years in women and 121.9
per 10,000 person-years in men.
In survivors of other AYA cancers, lung
cancer was the most commonly observed
subsequent cancer: The cumulative inci-
dence of lung neoplasms at 35 years after
the initial HL diagnosis was 3.8 percent for
women and 5.1 percent for men, compared
with expected incidences of 0.9 percent and
1.4 percent in the general population. Lung
cancer also accounted for 15.4 percent and
41.2 percent of the total number of excess
neoplasms in men and women with HL,
respectively.
Across the entire cohort of survivors, “the
burden of the excess number of neoplasms …
accounted for by lung cancer was substantial
and apparent across all AYA cancers investi-
gated,” they added. Smoking status contrib-
uted to this excess risk, but the authors also
noted that the risk of developing second can-
cers has been shown to be elevated in patients
who have been treated with radiation therapy
or chemotherapy.
“The evidence presented in our study,
along with previous literature on smoking in
cancer survivors, clearly suggests that clinical
follow-up of survivors of AYA cancer, par-
ticularly survivors of breast cancer, cervical
cancer, and HL, should focus on subsequent
lung cancer and provision of smoking cessa-
tion advice,” the authors commented.
The study’s implications are limited by its
reliance on data from a cancer registry that
did not contain detailed treatment informa-
tion. Also, these results might not be general-
izable to patients outside of the U.K. “We are
planning to conduct case-control studies with
detailed treatment dosimetry, questionnaires
for lifestyle and other relevant factors, and
saliva collection for genotypic factors,” the
authors noted.
The authors report no relevant conflicts of
interest. ●
REFERENCE
Bright CJ, Reulen RC, Winter DL, et al. Risk of subsequent primary neoplasms
in survivors of adolescent and young adult cancer (Teenage and Young Adult
Cancer Survivor Study): a population-based, cohort study. Lancet Oncol.
2019;20:531-45.
Risk of Any Subsequent Primary Neoplasm After AYA Cancers
Breast cancer
Total Number
of Subsequent
Primary Neoplasms Standardized Incidence Ratio
(95% CI) Absolute Excess Risk per
10,000 Person-Years
(95% CI) 35-Year Cumulative
Incidence, % (95% CI)
1,877 1.8 (1.7–1.8) 19.5 (17.4– 21.5) 11.9% (11.3–12.6)
Cervical cancer 1,675 1.3 (1.2–1.3) 10.2 (8.0–12.4) 15.8% (14.8–16.7)
Testicular cancer 1,435 1.8 (1.7–1.9) 18.9 (16.6–21.1) 20.2% (18.9–21.5)
3.1 (2.9–3.3) 29.9 (26.3–33.6) Hodgkin lymphoma, men 703
Hodgkin lymphoma, women 903
34
ASH Clinical News
2.6 (2.4–2.8)
16.5% (15.2–18.0)
May 2019