Survivors of adolescent and young adult lymphoma, leukemia face elevated risk for subsequent cancers

ATLANTA — Survivors of adolescent and young adult hematologic cancers demonstrated increased risk for subsequent malignant neoplasms compared with controls, according to study results presented at ASH Annual Meeting and Exposition.

Solid tumor subsequent malignant neoplasms (SMN) accounted for much of the risk. In addition, researchers observed what they called “a steep increase” in incidence of solid tumors among these survivors more than 15 years after completion of cancer therapy.

“Certain patient and treatment characteristics appear to be important modifiers of risk,” Saro H. Armenian, DO, MPH, of the department of population sciences at City of Hope, said during his presentation. “In addition, survival after solid SMN ... was significantly worse when compared [with] survival after de novo cancer.”

Advances in treatment and supportive care have contributed to a dramatic increase in cancer survivorship. There are 16 million cancer survivors in the United States. More than 1 million of them are survivors of hematologic cancers, and that number is projected to exceed 1.4 million by 2024.

Cancer survivors are at increased risk for SMN. However, limited data exist about the magnitude of SMN risk among survivors of adolescent and young adult hematologic cancers, as well as the factors that contribute to that risk and patient outcomes after SMN onset.

Armenian and colleagues conducted a retrospective cohort study to determine the incidence of and risk factors for SMN — excluding nonmelanoma skin cancer — among 2-year survivors of adolescent- and young adult-onset hematologic malignancy compared with individuals who had no cancer history. The analysis accounted for competing risks.

The study population included 1,315 cancer survivors diagnosed with a first cancer between 1990 and 2012. All survivors had been diagnosed between ages 15 and 39 years with non-Hodgkin lymphoma, Hodgkin lymphoma or acute leukemia, and they underwent treatment at Kaiser Permanente Southern California, an integrated managed care organization. They all survived at least 2 years after treatment discontinuation and had no SMN prior to the index date.

Researchers matched survivors 1:13 with 17,020 controls who had no history of cancer.

The two cohorts were well balanced with regard to median age (28 years for both), sex (51.6% male for each group), and race/ethnicity.

Follow-up continued from index date to SMN diagnosis, death or the end of 2014, whichever came first. Median follow-up was 8.9 years, equating to 11,675 person-years.

During that time, 71 survivors developed an SMN. The majority (72%) were solid SMNs, the most common of which were breast cancer (14%) and gastrointestinal cancers (13%). The remaining SMNs were nonsolid, which comprised Hodgkin or non-Hodgkin lymphoma, myeloma or acute leukemia.

Results showed a significantly higher SMN incidence among cancer survivors than controls (17.8% vs. 4.5%; P < .01). Risk increased sharply after 15 years, driven largely by solid SMNs.

Median time from index date to diagnosis was 9.6 years (range, 0.3-21.1) for solid SMN and 5.9 years (range, 0.4-18.6) for nonsolid SMN.

Female survivors demonstrated nearly a twofold risk for solid SMNs compared with males, and radiation exposure also was associated with a near-doubling of risk for solid SMNs.

Results of an analysis restricted to patients treated between 2000 and 2014, no type of chemotherapy exposure was associated with increased risk for SMN. However, Armenian acknowledged the limitation of follow-up time limited to 2 to 15 years.

Among all cancer survivors analyzed, those who developed an SMN demonstrated a significantly increased risk for all-cause mortality (HR = 11.3; 95% CI, 6.9-18.7).

Five-year OS was 86% for controls who developed a de novo cancer after the index date, compared with 65% for cancer survivors who developed solid SMNs (P = .02). The difference in 5-year OS between controls who developed a de novo cancer after the index date and survivors who developed nonsolid SMNs did not reach statistical significance (80% vs. 73%).

“We have additional analyses that are ongoing, which include extending the follow-up to further quantify the relationship between treatment and SMN risk, focusing on cumulative chemotherapy exposure and radiation dose, and to understand if and how traditional risk factors such as lifestyle factors, obesity and environmental exposure modify risk,” Armenian said.

“And in a certain subset of individuals, we want to look at genetic predisposition for SMN, which could have implications for testing, counseling and screening, with the ultimate goal of developing a personalized screening and surveillance regimen.” – by Mark Leiser

Reference:

Chao C, et al. Abstract 902. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2017; Atlanta.

Disclosure: The researchers report no relevant financial disclosures.