Predictors of acute chemotherapy‐associated toxicity in patients with Ewing sarcoma

Abstract

Background Ewing sarcoma (ES) is a malignant tumor of bone and soft tissue of children and young adults. Patients with ES are treated with intensive chemotherapy regimens. We describe predictors of acute chemotherapy-associated toxicity in this population. Procedure In this retrospective cohort study, records of ES patients treated at two academic medical centers between 1980 and 2010 were reviewed. Grade 3 and 4 non-hematologic chemotherapy-associated toxicities during frontline therapy were recorded for each patient, along with potential clinical and demographic predictors of toxicity. Bivariate analyses were performed using the Fisher exact test. Multivariate analysis was performed using logistic regression. Results The cohort included 142 patients with ES and toxicity data. In bivariate analyses, age <12 years at diagnosis, Latino ethnicity, low family income, and treatment on a clinical trial were associated with higher incidence of toxicity (p <0.01). Tumor size, site, stage, mode of local control, body mass index, overall chemotherapy exposure and dose-intensity were not associated with toxicity. In multivariate analysis, low income (odds ratio (OR) 4.97, 95% CI 1.9–13.1), clinical trial enrollment (OR 3.67, 95% CI 1.2–10.9), pelvic tumor site (OR 3.88, 95% CI 1.17–12.88), and age <12 years (OR 2.8, 95% CI 1.0–7.5) were independent predictors of toxicity. Conclusion ES patients who are younger, of Latino ethnicity, have pelvic tumors or low income have higher rates of toxicity that may require increased supportive care. Treatment on a clinical trial was also associated with higher rates of toxicity, though this finding may reflect better reporting in these patients.

Characterization of Localized Osteosarcoma of the Extremity in Children, Adolescents, and Young Adults From a Single Institution in South Texas

“…Moreover, our patients were very compliant and therefore received the recommended chemotherapy with no difference between preadolescents and older patients with regard to chemoreduction for toxicities. There is a recent report by Sharib et al18 that mentioned increased toxicity in young patients and in their Latino population with Ewing Sarcoma. We did not find an increase in toxicity in either of these groups within our cohort and thus could not use it as an explanation for the trend toward inferior outcome.…”

Comparative Toxicity by Sex Among Children Treated for Acute Lymphoblastic Leukemia: A Report From the Children's Oncology Group

“…Among adolescent/young adults with Ewing sarcoma, osteosarcoma, and Hodgkin lymphoma, Khamly and co‐workers found chemotherapy both more toxic (greater neutropenia and transfusion use) and more effective for female patients . In contrast, Sharib and co‐workers found no male/female differences in treatment‐related toxicities among Ewing sarcoma patients (n = 142). Some of the above studies suggest a positive relationship between toxicities and treatment outcome, a relationship that is intriguing considering the differences in toxicities found for males and females.…”

Clinical features and outcomes of infants with Ewing sarcoma under 12 months of age

“…It is not clear from the available registry data whether these early deaths are due to early disease progression or due to the toxicity of the intensive therapies used to treat this disease. At least one previous report found that younger age was associated with increased therapy‐associated toxicity, although young patients in that analysis included all patients <12 years of age . However, our finding that infants who did not receive surgery had significantly inferior outcomes suggests that difficulty attaining adequate local control may be partially responsible for these early failures.…”

“…At least one previous report found that younger age was associated with increased therapy-associated toxicity, although young patients in that analysis included all patients <12 years of age. [35] However, our finding that infants who did not receive surgery had significantly inferior outcomes suggests that difficulty attaining adequate local control may be partially responsible for these early failures. The observed trend indicating lower survival in patients not treated with radiation supports this hypothesis.…”