ASCO Studies Point to Risks Associated with Treating Childhood Cancers


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Risks associated with being a young cancer survivor were emphasized by two studies highlighted in press briefings at the 2012 ASCO Annual Meeting.

Investigators from the Children’s Oncology Group (COG) reported that adolescents and young adults  treated for high-risk B-precursor acute lymphoblastic leukemia (ALL) had worse outcomes than younger children treated for the disease.1 A second study showed an increase in breast cancer among women who received low levels of radiation to the chest as children.2

More Events, Worse Survival among Adolescents and Young Adults

The phase III AALL0232 study tested four treatment regimens for high-risk ALL, and those outcomes were reported last year.3 This year, the investigators reported on event-free survival and overall survival of adolescent and young adult patients (aged 16 to 30) compared to younger patients (aged 1 to 15).

Historical data suggest that adolescent and young adult patients with high-risk ALL have inferior outcomes, but a direct comparison by age group, in a large enough trial, has not been available until now, said Eric Larsen, MD, of the Maine Children’s Cancer Program and Study Chair of the COG.

The study included 501 adolescent and young adult patients, which made up 20% of the overall trial enrollment of 2,574 subjects. The 5-year event-free survival rate was 68% in the adolescent and young adult patients compared to 80.9% in the younger patients (P < .0001), while the overall survival rate was 79.8% vs 88.4%, respectively (P < .0001). Relapses occurred in 21.3% vs 13.4%, respectively (P = .0018), mostly because the adolescents and young adults had more relapses in the bone marrow, Dr. Larsen reported.

There was no significant difference in induction mortality between adolescent and young adult (2.4%) and younger patients (1.8%). However, postinduction remission deaths at 5 years were significantly higher among adolescents and young adults (5.5% vs 2.1%; P < .0001).

Dr. Larsen said the findings might be due to differences in disease biology as well as patient-related factors. “Evolving data show that older patients with ALL are more likely to have unfavorable molecular characteristics in the leukemia cells. Also, perhaps they don’t tolerate chemotherapy as well and are given reduced doses. It’s also true that treatment protocols may differ for older patients; they are not as intensive,” he noted.

“Finally, there are complex social factors that may explain some of the difference, such as compliance with oral chemotherapy, which we are learning is less with older patients,” he added. “There is good evidence that poor compliance correlates with greater relapse.”

As a result of this study, the COG is considering options to enhance leukemia control and also reduce the toxicity of treatment for adolescents and young adults.

Childhood Radiation Increases Breast Cancer Risk

The risk of developing breast cancer after receiving radiotherapy to the chest as a child are as high as those for BRCA1 and BRCA2 mutation carriers, according to review of 1,268 cancer survivors participating in the Childhood Cancer Survivor Study (CCSS) and 4,570 female first-degree relatives of participants in the Women’s Environmental Cancer and Radiation Epidemiology (WECARE) Study. CCSS is a large North American cohort study of long-term childhood cancer survivors. WECARE enrolled patients with breast cancer who had survived at least 1 year after diagnosis.

Among the childhood cancer survivors, breast cancer was diagnosed by age 50 in 24% overall and in 30% of Hodgkin lymphoma survivors. In comparison, among first-degree relatives of WECARE Study probands, the cumulative incidence by age 50 among BRCA1 and BRCA2 mutation carriers was 31% and 10%, respectively. In contrast to these two high-risk populations, the expected cumulative incidence in the general U.S. population is 4%.

“Surprisingly, women treated with radiotherapy to the chest for Hodgkin lymphomas have a risk of breast cancer that is remarkably similar to BRCA1 mutation carriers,” said Chaya S. Moskowitz, PhD, a biostatistician at Memorial Sloan-Kettering Cancer Center, New York.

Radiotherapy dose mattered, but not completely. By age 40, women treated with ≥ 20 Gy had a 12% risk, while those receiving 10 to 19 Gy had a 7% risk. “Both groups need to be followed closely,” said Dr. Moskowitz.

She acknowledged that radiation doses are lower now, but the findings point to a need for caution and vigilance. “The goal is to maximize cure rates while minimizing future health problems,” she said. “For women treated with 20 Gy or more of chest radiotherapy, the COG recommends breast cancer surveillance with annual mammograms and breast MRI starting at age 25, or 8 years after the radiation, whichever is last.”

Approximately 50,000 American women received > 20 Gy as children, and another 7,000 to 9,000 were treated with lower doses, the investigators estimated.

Nicholas Vogelzang, MD, of the Comprehensive Cancer Centers of Nevada, who chairs ASCO’s Cancer Communications Committee, commented, “These are striking data and warrant our careful attention, not only to improve follow-up but to improve mammographic screening of these women. We have an obligation to those many thousands of young women treated years ago, and hopefully this will increase awareness.” ■

Disclosure: Drs. Larsen, Moskowitz, and Vogelzang reported no potential conflicts of interest.

References

1. Larsen E, Raetz EA, Winick NJ, et al: Outcome in adolescent and young adult patients compared with patients treated for high-risk B precursor acute lymphoblastic leukemia: A report from the Children’s Oncology Group study AALL0232. 2012 ASCO Annual Meeting. Abstract CRA9508. Presented June 2, 2012.

2. Moskowitz CS, Chou JF, Wolden SL, et al: New insights into the risk of breast cancer in childhood cancer survivors treated with chest radiation: A report from the Childhood Cancer Survivor Study and the Women’s Environmental Cancer and Radiation Epidemiology Study. 2012 ASCO Annual Meeting. Abstract CRA9513. Presented June 4, 2012.

3. Larsen EC, Salzer WL, Devidas M, et al: Comparison of high-dose methotrexate with Capizzi methotrexate plus asparaginase in children and young adults with high-risk acute lymphoblastic leukemia: A report from the Children’s Oncology Group Study AALL0232. 2011 ASCO Annual Meeting. Abstract 3. Presented June 5, 2011.


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