Predictors of acute chemotherapy-associated toxicity in patients with Ewing sarcoma
ABSTRACT 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.
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.
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% confidence interval (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.
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.
SourceAvailable from: Christian Rothermundt[Show abstract] [Hide abstract]
ABSTRACT: Background To evaluate tolerability and maintenance of dose intensity of 2 weekly treatment with vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide, etoposide (VDC/IE) in patients with advanced small round cell sarcomas including Ewing family tumours (EFT), desmoplastic small round cell tumours (DSRCT) and undifferentiated high grade round cell sarcomas (UHGRCS). Methods Retrospective review of 16 patients treated at a single centre with VDC/IE. Dose received, treatment delay, toxicity and clinical outcome were recorded for each cycle up to a maximum of 14 cycles. Results A total 193 cycles of VDC/IE were administered to 10 patients with EFT, 4 with DSRCT and 2 with UHGRCS. Median age was 22 years with 75% over 18 years. Metastases were present in 14 patients. The mean duration of each cycle was 16.7 days. Febrile neutropenia occurred in 14 % of cycles, and grade 3/4 haematologic toxicity including anaemia and thrombocytopenia in 16 % and 11 % of cycles respectively. Seven patients had a dose reduction. Five patients discontinued VDC/IE early due to toxicity. Conclusions This schedule of VDC/IE is feasible in patients with EFT and DSRCT including adults and those with metastases. Its comparison with other standard regimens for these diseases is justified.09/2012; 2(1). DOI:10.1186/2045-3329-2-12
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ABSTRACT: Despite surgery, chemotherapy and radiotherapy treatments, the children, adolescents and young adults who are diagnosed with metastasized Ewing sarcoma face a dismal prognosis. Amyloid precursor-like protein 2 (APLP2) has recently been implicated in the survival of cancer cells and in our current study, APLP2's contribution to the survival of Ewing sarcoma cells was examined. APLP2 was readily detected in all Ewing sarcoma cell lines analyzed by western blotting, with the TC71 Ewing sarcoma cells expressing the lowest level of APLP2 among the lines. While irradiation induces apoptosis in TC71 Ewing sarcoma cells (as we determined by quantifying the proportion of cells in the sub-G 1 population), transfection of additional APLP2 into TC71 decreased irradiation-induced apoptosis. Consistent with these findings, in parallel studies, we noted that isolates of the TC71 cell line that survived co-culture with lymphokine-activated killer (LAK) cells (which kill by inducing apoptosis in target cells) displayed increased expression of APLP2, in addition to smaller sub-G 1 cell populations after irradiation. Together, these findings suggest that APLP2 lowers the sensitivity of Ewing sarcoma cells to radiotherapy-induced apoptosis and that APLP2 expression is increased in Ewing sarcoma cells able to survive exposure to cytotoxic immune cells.Cancer biology & therapy 06/2013; 14(8). DOI:10.4161/cbt.25183 · 3.63 Impact Factor
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ABSTRACT: Osteosarcoma is the most common bone malignancy in children, adolescents, and young adults. Most study cohorts have 10% to 15% Hispanic patients that encompass many different Hispanic backgrounds. This study characterizes the effect of mainly Mexican American ethnicity on the outcome of children, adolescents, and young adults with osteosarcoma. A retrospective analysis of demographics, tumor characteristics, response to treatment, and survival outcome of all localized osteosarcoma of the extremity patients below 30 years of age was performed. A Kaplan-Meier estimates with log-rank tests and Cox proportional hazard regression models were used. Fifty patients (median age, 15; range, 2 to 28 y) with localized high-grade osteosarcoma of the extremity were diagnosed between January 2000 and December 2010. The cohort was 70% Mexican Americans. With a median follow-up of 39 months (range, 5 to 142 mo), patients had a 5-year overall survival and event-free survival of 65% and 48%, respectively. We observed a significantly decreased 5-year event-free survival in patients diagnosed before age 12 relative to patients diagnosed between ages 12 and 29 (11% vs. 57%, P<0.001). We also found that tumor necrosis was not predictive of outcome in our patients. The preadolescent patients of predominately Mexican American ethnicity had an increased rate of relapse when compared with previous studies. Tumor necrosis is not directly predictive of outcome in this population.Journal of Pediatric Hematology/Oncology 01/2014; DOI:10.1097/MPH.0000000000000104 · 0.96 Impact Factor