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Expanded use of solid tumor chemotherapy drives excess risk for certain blood cancers
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Rates of therapy-related myelodysplastic syndrome and acute myeloid leukemia have risen significantly in the modern era following chemotherapy for nearly all solid tumor cancer types, according to results of a population-based cohort study published in JAMA Oncology.
The rate increase coincides with the expanded use of known leukemogenic agents.
“The 21st century has seen substantial changes in the agents and clinical approaches to cancer chemotherapy, with corresponding improvements in prognosis for many cancers,” Lindsay M. Morton, PhD, senior investigator in the division of cancer epidemiology and genetics at NCI, and colleagues wrote. “However, the longer-term balance of benefits and risks of new treatment approaches often are not well understood because clinical trials for many cancers lack sufficient sample size and long-term patient follow-up.”
Morton and colleagues used the SEER database to analyze 1,619 cases (mean age of patients, 64.3 years; 70.9% women) of therapy- related myelodysplastic syndrome (MDS) and AML among 700,612 adults who were diagnosed with first primary solid cancer, received chemotherapy and survived 1 year or longer.
Results showed that the risks for therapy-related MDS/AML were significantly elevated after chemotherapy for 22 of 23 types of solid cancers, with the risk persisting for 5 years or longer for 15 of these cancer types. The only solid cancer that did not have an elevated risk was colon cancer (standardized incidence ratio = 1.1; 95% CI, 0.9-1.3).
Relative risks for therapy-related MDS/AML were highest in bone (SIR = 39; 95% CI, 21.4-65.5), soft tissue (SIR = 10.4; 95% CI, 6.4-15.9) and testis (SIR = 12.3; 95% CI, 7.6-18.8) cancers.
SIRs also appeared 5- to 9-fold greater following chemotherapy for peritoneum, small cell lung, ovary, fallopian tube, and brain or central nervous system cancers.
SIRs appeared significantly higher among patients who received initial chemoradiotherapy compared with chemotherapy alone for stomach (SIR = 3.3; 95% CI, 2.1-4.9 vs. SIR = 1.5; 95% CI, 0.6-3.4), non-small cell lung (SIR = 4.4; 95% CI, 3.6-5.2 vs. SIR = 2.5; 95% CI, 1.9-3.2), and female breast cancers (SIR = 4.3; 95% CI, 3.9-4.7 vs. SIR = 3.1; 95% CI, 2.7-3.5).
SIRs for therapy-related MDS/AML were consistently highest for younger patients at first primary cancer diagnosis. However, researchers also observed significantly high rates among patients aged 65 years or older.
SIRs were also higher among patients with female breast, uterine corpus, ovary, testis and bladder cancers after receiving chemotherapy for regional or distant vs. localized stage disease.
Excess absolute risk (EAR) increased with patient age and was highest — defined as more than 10 cases per 10,000 human years — following chemotherapy for peritoneum, small cell lung, bone, soft tissue and fallopian tube cancers.
OS following diagnosis of therapy-related MDS/AML was poor, with 78.4% (n = 1,270) of the patients dying (median OS, 7 months).
Comparing these data with U.S. cancer statistics data, Morton and colleagues calculated that about 360,000 adults aged 20 years or older will have received initial chemotherapy for one of these 23 solid cancers in 2018 and will survive at least 1 year. Of them, researchers estimated that 714 will be diagnosed with therapy-related MDS/AML within 5 years, 521 cases of which can be directly linked to chemotherapy.
Limitations to this study included the lack of data on chemotherapy agents and doses and on follow-up therapy.
“Treatment risk and benefit assessments should balance therapy-related MDS/AML risks and other chemotherapy-related adverse effects against potential gains in survival, particularly for patients with a favorable prognosis,” Morton and colleagues wrote. “Continued efforts to develop effective and less toxic chemotherapeutic approaches are needed.”
The most intriguing study finding was that young people are at highest risk for therapy-related MDS/AML, Shyam A. Patel, MD, PhD, postdoctoral medical fellow at Stanford Cancer Institute, wrote in an accompanying editorial.
Patel added that there could be multiple reasons why patients with colon cancer do not appear to be at an increased risk for therapy-related MDS/AML, such as the specific chemotherapy used, or because people diagnosed with the diseases tend to be older.
“The findings by Morton [and colleagues] beg the question of how best to perform risk assessment of chemotherapy administration for solid tumors,” Patel wrote. “Because patients who receive chemotherapy for solid tumors are expected to live longer, the incidence of treatment-related myeloid neoplasms is likely to increase, pending further availability of non-DNA-damaging agents such as targeted therapy.”– by John DeRosier
Disclosures : The NIH and NCI funded this study. Morton reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures. Patel reports no relevant financial disclosures.
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