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Higher AML, MDS risk linked to solid tumor chemotherapy

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Young patients face highest relative risk

Possibly the most clinical relevant finding of the study by Lindsay M. Morton, PhD, and her colleagues is that patients who received chemotherapy for solid tumor treatment at a younger age were at the highest relative risk for tMDS/AML.

The incidence of tMDS/AML was highest among patients treated with chemotherapy for bone, soft-tissue, and testicular cancers, where the median age of onset is often by 30 years, and the mean onset occurs before age 50.

The researchers also noted an increased risk for tMDS/AML associated with prolonged survival from primary tumors.

Going forward, research should consider those patients at highest risk for tMDS/AML and risk-assessment models for these therapy-related myeloid neoplasms should take into account the clonal evolution of subclinical mutations into overt disease.

The study findings point to the unanswered question of how best to perform risk assessment of chemotherapy in solid tumors. That risk stratification could include the probability of the specific chemotherapy agent initiating disease, the benefit of tumor regression from chemotherapy, and the potential consequences of tumor progression if chemotherapy is not administered.

Shyam A. Patel, MD, PhD, is with the department of medicine at Stanford (Calif.) University. Dr. Patel reported having no financial disclosures. These comments are adapted from his accompanying editorial (JAMA Oncol. 2018 Dec 20. doi: 10.1001/jamaoncol.2018.5617 ).



There is an increased risk for therapy-related myelodysplastic syndrome or acute myeloid leukemia (tMDS/AML) following chemotherapy for the majority of solid tumor types, according to an analysis of cancer registry data.

These findings suggest a substantial expansion in the patients at risk for tMDS/AML because, in the past, excess risks were established only after chemotherapy for cancers of the lung, ovary, breast, soft tissue, testis, and brain or central nervous system,” Lindsay M. Morton, PhD, of the National Institutes of Health, and her colleagues wrote in JAMA Oncology.

The researchers retrospectively analyzed data from 1,619 patients with tMDS/AML who were diagnosed with an initial primary solid tumor from 2000 to 2013. Data came from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program and Medicare claims.

Study participants were given initial chemotherapy and lived for at least 1 year after treatment. Subsequently, Dr. Morton and her colleagues linked patient database records with Medicare insurance claim information to confirm the accuracy of chemotherapy data.

“Because registry data [does] not include treatment details, we used an alternative database to provide descriptive information on population-based patterns of chemotherapeutic drug use,” the researchers wrote in JAMA Oncology.

After statistical analysis, the researchers found that the risk of developing tMDS/AML was significantly elevated following chemotherapy administration for 22 of 23 solid tumor types, excluding colon cancer. They reported a 1.5-fold to more than 10-fold increased relative risk for tMDS/AML in those patients who received chemotherapy for those 22 solid cancer types, compared with the general population.

The relative risks were highest after chemotherapy for bone, soft-tissue, and testis cancers.

The researchers found that the absolute risk of developing tMDS/AML was low. Excess absolute risks ranged from 1.4 to greater than 15 cases per 10,000 person-years, compared with the general population, in those 22 solid cancer types. The greatest absolute risks were for peritoneum, small-cell lung, bone, soft-tissue, and fallopian tube cancers.

“For patients treated with chemotherapy at the present time, approximately three-quarters of tMDS/AML cases expected to occur within the next 5 years will be attributable to chemotherapy,” they added.

The researchers acknowledged a key limitation of the study was the limited data on dosing and patient-specific chemotherapy. As a result, Dr. Morton and her colleagues called for a cautious interpretation of the magnitude of the risk.

The study was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, and the California Department of Public Health. The authors reported having no conflicts of interest.

SOURCE: Morton LM et al. JAMA Oncol. 2018 Dec 20. doi: 10.1001/jamaoncol.2018.5625.

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