Faculty Bibliography

Purpose/Objective(s): To identify potential clinical prognostic factors associated with a higher risk of local recurrence in localized pelvic Ewing Sarcoma (ES) patients treated with radiation therapy. Materials/Methods: Data for 101 patients treated with definitive radiotherapy (RT) or both surgery and radiation (S+RT) on INT-0091, INT-0154, and AEWS0031 were analyzed. Radiation and imaging data was reviewed at IROC QARC. Imaging data for patients who did not receive radiation was not available, so surgery only patients were excluded. Tumor size was classified as = 8 cm in maximum dimension and = 200 mL volumetrically. Pelvic subsites were categorized as sacrum, iliac/buttock, or ischiopubic-acetabulum. Five-year cumulative incidence of local failure was defined as standard.
Result(s): The most common primary pelvic subsite was sacrum, 44.6%. Median tumor size at diagnosis was 9.7 cm (range: 2.4-16.0 cm) in maximum dimension and 215.9 mL (range: 3.7-1400.0 mL) volumetrically. RT was utilized in 68% of patients and S+RT in 32%. There was no statistically significant difference in local therapy modality employed based on tumor subsite or size. The five-year cumulative incidence of local failure for the entire cohort was 19.0% (95% CI, 12.7-28.5%). RT was associated with a higher incidence of local failure at 25.0% compared to 6.3% for S+RT (p=0.046). There was no difference in local failure outcomes by tumor size = 8 cm in maximum dimension or = 200 mL volumetrically. A higher incidence of local failure was seen with each additional 100 mL of tumor at diagnosis for all patients (p=0.04) and for RT only patients (p=0.005). Tumors originating in the ischiopubic-acetabular region were associated with the highest local failure incidence of 37.5%, compared to 20.0% for iliac-buttock and 11.4% for sacrum (p=0.02). Ischiopubic-acetabulum tumors treated with RT alone had the highest local failure rate in the cohort (50.0%, p=0.06). Multivariable analysis demonstrated RT alone (HR 5.1, p=0.04), tumor subsite (particularly ischiopubic-acetabulum tumors, HR 4.6, p=0.02), and increasing volume per 100 mL (HR 1.2, p=0.01) were associated with a higher incidence of local recurrence.
Conclusion(s): Patients with pelvic ES selected for S+RT had lower rates of local failure compared to patients selected for definitive RT. Tumors involving the ischiopubic-acetabular region and increasing tumor volume at diagnosis likely correlate with inferior local tumor control outcomes, especially for RT only patients, indicating local therapy intensification may be warranted for this cohort. Tumor characteristics did not correlate with choice of local therapy modality suggesting an opportunity to develop best local therapy practices guidelines for future studies based on tumor features.
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BACKGROUND: The neutropenic diet (ND) is prescribed to avoid introduction of bacteria into a host's gastrointestinal tract and reduce infection. Due to a lack of evidence to support the ND, there continues to be debate among pediatric oncologists regarding its usefulness. This prospective randomized controlled trial evaluated the difference in neutropenic infection rates in pediatric oncology patients randomized to Food and Drug Administration approved food safety guidelines (FSGs) versus the ND plus FSGs during one cycle of chemotherapy. PROCEDURE: Pediatric patients receiving cancer treatment with myelosuppressive chemotherapy were eligible. Neutropenic infection was the primary outcome and defined as (i) fever with neutropenia or (ii) hospital admission and treatment for clinical infection and neutropenia. The rate of neutropenic infection was compared with Student's t-test for independent samples. Documented infections were identified by comprehensive chart review and compared between groups using a chi2 test. RESULTS: One hundred fifty patients were randomly assigned to FSGs (n = 73) or ND + FSGs (n = 77). The most common diagnoses were acute lymphoblastic leukemia (32%) and sarcoma (32%). There was no significant difference between the groups in the percentage of patients who developed neutropenic infection: FSGs 33% versus ND + FSGs 35% (P = 0.78). Patients randomized to ND + FSGs reported that following the diet required more effort than those on FSGs alone. CONCLUSION: The ND offers no benefit over FSGs in the prevention of infection in pediatric oncology patients undergoing myelosuppressive chemotherapy and adherence requires more effort for patients and families. Institutions caring for children with cancer should consider replacing ND guidelines with FSGs.

Introduction Mucosal damage secondary to cancer therapy occurs in 30% of patients receiving standard chemotherapy and 80% of patients receiving high dose chemotherapy. Mucositis is painful, interferes with nutrition, hydration, and often causes delay or reduction in chemotherapy. 20%of CLABSIs at NYU Langone Health (NYULH) in 2015 were secondary to mucosal translocation Objectives The goal of the NYULH Interprofessional Mucositis Workgroup is to decrease the incidence of mucositis in adult and pediatric oncology patients. Methods An interprofessional team of inpatient and outpatient, adult and pediatric medical providers, dentists, nurse practitioners, nurses, pharmacists, and IT collaborated to develop a standardized NYULH mucositis guideline for prevention and treatment. Results An evidenced-based standardized guideline for mucositis prevention and treatment across adult and pediatric inpatient and outpatient was developed. Conclusions This project suggests that interprofessional collaboration is an effective strategy for development and implementation of a standardized guideline for both pediatric and adult inpatients and outpatients

PURPOSE: To identify clinical and treatment variables associated with a higher risk of local failure in Ewing sarcoma patients treated on recent Children's Oncology Group protocols. METHODS AND MATERIALS: Data for 956 patients treated with ifosfamide and etoposide-based chemotherapy on INT-0091, INT-0154, and AEWS0031 were analyzed. Local treatment modalities were defined as surgery, definitive radiation therapy (RT), or surgery plus radiation (S+RT). Five-year cumulative incidence of local failure was determined. RESULTS: The local failure rate for the entire cohort was 7.3%, with a 3.9% rate for surgery, 15.3% for RT (P<.01), and 6.6% for S+RT (P=.12). The local failure incidence was 5.4% for extremity tumors, 13.2% for pelvis tumors (P<.01), 5.3% for axial non-spine tumors (P=.90), 9.1% for extraskeletal tumors (P=.08), and 3.6% for spine tumors (P=.49). The incidence of local failure was 14.8% for extremity tumors and 22.4% for pelvis tumors treated with RT, compared with 3.7% for extremity tumors and 3.9% for pelvis tumors treated with surgery (P/=18 years versus 6.7% in patients aged <18 years (P=.02). Age >/=18 years (hazard ratio 1.9, P=.04) and treatment with RT (hazard ratio 2.40, P<.01) remained independent prognostic factors for higher local failure incidence on multivariate analysis. Tumor size (/= 8 cm) was available in 40% of patients and did not correlate with local failure incidence. CONCLUSIONS: Local tumor control is excellent and similar between surgery and RT for axial non-spine, spine, and extraskeletal tumors. Age >/=18 years and use of RT, primarily for pelvis and extremity tumors, are associated with the highest risk of local failure. Further efforts should focus on improving outcomes for these patients.

BACKGROUND: The choice of a local control (LC) modality for Ewing sarcoma (EWS) of the femur is controversial. This study aimed to determine the effect of LC modality on tumor LC and patient outcomes. METHODS: The study reviewed the treatment and outcomes for 115 patients who had EWS of the femur treated with similar chemotherapy in three cooperative group trials. Patient outcomes were analyzed according to the LC modality using the log-rank test and the cumulative incidence of local or distant failure using competing risks regression. RESULTS: The median age of the patients was 13 years. The most common tumor location was the proximal femur followed by the mid femur. For 55 patients with available data, the tumor was larger than 8 cm in 29 patients and 8 cm or smaller in 26 patients. For 84 patients (73 %), surgery only was performed, whereas 17 patients (15 %) had surgery plus radiation, and 14 patients (12 %) had radiation only. The 5-year event-free survival (EFS) rate was 65 % (95 % confidence interval [CI], 55-73 %), and the 5-year overall survival (OS) rate was 70 % (95 % CI, 61-78 %). Patient outcomes did not differ significantly according to tumor location within the femur (proximal, mid or distal) or tumor size (<8 vs >/=8 cm). The findings showed no statistically significant differences in EFS, OS, cumulative incidence of local failure, or cumulative incidence of distant failure according to LC modality (surgery, surgery plus radiation, or radiation). CONCLUSIONS: The LC modality did not significantly affect disease outcome for EWS of the femur. Further study of treatment complications and functional outcome may help to define the optimal LC modality.

BACKGROUND: The prognostic significance of having extraskeletal (EES) versus skeletal Ewing sarcoma (ES) in the setting of modern chemotherapy protocols is unknown. The purpose of this study was to compare the clinical characteristics, biologic features, and outcomes for patients with EES and skeletal ES. METHODS: Patients had localized ES and were treated on two consecutive protocols using five-drug chemotherapy (INT-0154 and AEWS0031). Patients were analyzed based on having an extraskeletal (n = 213) or skeletal (n = 826) site of tumor origin. Event-free survival (EFS) was estimated using the Kaplan-Meier method, compared using the log-rank test, and modeled using Cox multivariate regression. RESULTS: Patients with extraskeletal ES (EES) were more likely to have axial tumors (72% vs. 55%; P < 0.001), less likely to have tumors >8 cm (9% vs. 17%; P < 0.01), and less likely to be white (81% vs. 87%; P < 0.001) compared to patients with skeletal ES. There was no difference in key genomic features (type of EWSR1 translocation, TP53 mutation, CDKN2A mutation/loss) between groups. After controlling for age, race, and primary site, EES was associated with superior EFS (hazard ratio = 0.69; 95% confidence interval: 0.50-0.95; P = 0.02). Among patients with EES, age >/=18, nonwhite race, and elevated baseline erythrocyte sedimentation rate were independently associated with inferior EFS. CONCLUSION: Clinical characteristics, but not key tumor genomic features, differ between EES and skeletal ES. Extraskeletal origin is a favorable prognostic factor, independent of age, race, and primary site.

Osteosarcoma (OS) and the Ewing sarcoma family of tumors (ESFT) are the most common malignant bone tumors in children and adolescents. While significant improvements in survival have been seen in other pediatric malignancies the treatment and prognosis for pediatric bone tumors has remained unchanged for the past 3 decades. This review and update of pediatric malignant bone tumors will provide a general overview of osteosarcoma and the Ewing sarcoma family of tumors, discuss bone tumor genomics, current challenges, and emerging drug targets.

BACKGROUND: Although multiple prognostic variables have been proposed for Ewing sarcoma (EWS), little work has been done to further categorize these variables into prognostic groups for risk classification. PROCEDURE: We derived initial prognostic groups from 2,124 patients with EWS in the SEER database. We constructed a multivariable recursive partitioning model of overall survival using the following covariates: age; stage; race/ethnicity; sex; axial primary; pelvic primary; and bone or soft tissue primary. Based on this model, we identified risk groups and estimated 5-year overall survival for each group using Kaplan-Meier methods. We then applied these groups to 1,680 patients enrolled on COG clinical trials. RESULTS: A multivariable model identified five prognostic groups with significantly different overall survival: (i) localized, age <18 years, non-pelvic primary; (ii) localized, age <18, pelvic primary or localized, age >/=18, white, non-Hispanic; (iii) localized, age >/=18, all races/ethnicities other than white, non-Hispanic; (iv) metastatic, age <18; and (v) metastatic, age >/=18. These five groups were applied to the COG dataset and showed significantly different overall and event-free survival based upon this classification system (P < 0.0001). A sub-analysis of COG patients treated with ifosfamide and etoposide as a component of therapy evaluated these findings in patients receiving contemporary therapy. CONCLUSIONS: Recursive partitioning analysis yields discrete prognostic groups in EWS that provide valuable information for patients and clinicians in determining an individual patient's risk of death. These groups may enable future clinical trials to adjust EWS treatment according to individualized risk. Pediatr Blood Cancer (c) 2015 Wiley Periodicals, Inc.