Long-term follow-up of a cohort of childhood survivors of Hodgkin lymphoma (HL) has identified subgroups at highest risk of breast, lung, colorectal, and thyroid cancers, according to researchers, who noted that the findings may help refine guidelines for individual cancer screening.
With a median follow-up of 26.6 years in 1,136 patients who were age 17 or younger at the time of diagnosis, the latest update for the Late Effects Study Group (LESG) cohort shows that the overall risk of solid subsequent malignant neoplasms is 14 times higher in HL survivors compared with the general population.
By age 50, the cumulative incidences of breast, lung, colorectal, and thyroid cancers in patient subgroups at highest risk were 45.3%, 4.2%, 9.5%, and 17.3%, respectively, Smita Bhatia, MD, MPH, of the University of Alabama at Birmingham, and colleagues, reported online in Cancer.
“These findings support the need for continued surveillance of patients with HL, regardless of the era in which they were treated,” the team wrote.
A total of 196 tumors were diagnosed in 162 HL survivors, and 40 years after diagnosis of HL the cumulative incidence of any subsequent solid malignant neoplasm was 26.4%, the study showed.
Women diagnosed between the ages of 10 and 16 and treated with chest radiotherapy had the highest risk of breast cancer, while men treated with chest radiotherapy before the age of 10 had the highest risk of lung cancer. HL survivors who received abdominal/pelvic radiotherapy and high-dose alkylating agents in childhood had the highest risk of colorectal cancer. Women treated with neck radiotherapy before the age of 10 had the highest risk of thyroid cancer.
The median latency between the diagnoses of HL and breast cancer was 25 years, and the shortest interval was 10 years, the study showed. In addition, the incidence of breast cancer started to increase at age 25 and remained elevated until at least age 50.
“Taken together, these findings provide additional evidence for initiating surveillance at either 8 years after the diagnosis of HL or at age 25, whichever occurs later,” the researchers said.
Although screening strategies for childhood cancer survivors have been developed through the Children’s Oncology Group, this report provides evidence that could be used to develop screening strategies for individual survivors, Bhatia told MedPage Today.
“Childhood Hodgkin lymphoma survivors continue to be at high risk for subsequent solid tumors well into their 50s and there is no evidence for a decline in this risk,” she said. “Clinicians should be aware of this elevated risk and should follow the recommendations for screening and early detection.”
Bhatia noted that the LESG was established in 1979 as a multinational cohort of children ages 16 and younger who were diagnosed with HL and other cancers between 1955 and 1979. In 1994, the cohort was expanded to include 1,380 patients at 15 institutions and the follow-up was extended to 11 years. In 2001, the median follow-up was extended to 17 years.
The current report, now with 25 years of follow-up, showed that in 42 women who developed breast cancer, the median age at HL diagnosis was 13. The cumulative incidence of breast cancer was 20.1% after 40 years, with a median age of 37 at diagnosis. When compared with the general population, patients with HL had a 25.8-fold increased risk of developing breast cancer.
In 11 HL survivors who developed lung cancer a median of 28 years after HL diagnosis, 10 were male and all had been treated with chest radiotherapy. Compared with the general population, male HL survivors had a 26.7-fold increased risk of lung cancer, whereas female survivors had a 3.3-fold increased risk. And 40 years after HL diagnosis, the cumulative incidence of lung cancer was 2.2%, and by the age of 50, it was 2.3%.
In the 15 patients who developed colorectal cancer a median of 25 years after HL diagnosis, the cumulative incidence at 40 years was 2.7%. Compared with the general population, HL survivors had a 16.2-fold increased risk of developing colorectal cancer.
Thyroid cancer developed in 30 patients at a median age of 34.5. HL survivors had a 27.7-fold increased risk of developing thyroid cancer compared with the general population. “Approximately 93% of thyroid cancers developed in the radiotherapy field, thereby precluding evaluation of radiotherapy as a risk factor,” the investigators noted.
Limitations of the study, Bhatia and colleagues said, included a failure to capture non-therapeutic exposures such as tobacco, alcohol, and diet, or to collect information on patients’ surveillance history. In addition, even though patients more recently treated for HL may receive lower radiation doses and volumes, the researchers pointed out that the Childhood Cancer Survivor Study recently reported that patients with HL treated in the 1990s were at an increased risk of developing a solid subsequent malignant neoplasm.
Bhatia and co-authors reported having no conflicts of interest.