Faculty Bibliography

BACKGROUND: Patients with Ewing sarcoma require local primary tumor control with surgery, radiation, or both. The optimal choice of local control for overall and local disease control remains unclear. METHODS: Patients with localized Ewing sarcoma of bone who were treated on 3 consecutive protocols with standard-dose, 5-drug chemotherapy every 3 weeks were included (n=465). Propensity scores were used to control for differences between local control groups by constructing multivariate models to assess the impact of local control type on clinical endpoints (event-free survival [EFS], overall survival, local failure, and distant failure) independent of differences in their propensity to receive each local control type. RESULTS: Patients who underwent surgery were younger (P=.02) and had more appendicular tumors (P<.001). Compared with surgery, radiation had higher unadjusted risks of any event (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.18-2.44), death (HR, 1.84; 95% CI, 1.18-2.85), and local failure (HR, 2.57; 95% CI, 1.37-4.83). On multivariate analysis, compared with surgery, radiation had a higher risk of local failure (HR, 2.41; 95% CI, 1.24-4.68), although there were no significant differences in EFS (HR, 1.42; 95% CI, 0.94-2.14), overall survival (HR, 1.37; 95% CI, 0.83-2.26), or distant failure (HR, 1.13; 95% CI, 0.70-1.84) between local control groups. CONCLUSIONS: In this large group of similarly treated patients, choice of the mode of local control was not related significantly to EFS, overall survival, or distant failure, although the risk of local failure was greater for radiation compared with surgery. These data support surgical resection when appropriate, whereas radiotherapy remains a reasonable alternative in selected patients. Cancer 2014. (c) 2014 American Cancer Society.

Purpose. To associate baseline patient characteristics and relapse across consecutive COG studies. Methods. We analyzed risk factors for LESFT patients in three randomized COG trials. We evaluated age at enrollment, primary site, gender, tumor size, and treatment (as randomized). We estimated event-free survival (EFS, Kaplan-Meier) and compared risk across groups (log-rank test). Characteristics were assessed by proportional hazards regression with the characteristic of interest as the only component. Confidence intervals (CI) for RR were derived. Factors related to outcome at level 0.05 were included in a multivariate regression model. Results. Between 12/1988 and 8/2005, 1444 patients were enrolled and data current to 2001, 2004, or 2008 were used. Patients were with a median age of 12 years (0-45), 55% male and 88% Caucasian. The 5-year EFS was 68.3% +/- 1.3%. In univariate analysis age, treatment, and tumor location were identified for inclusion in the multivariate model, and all remained significant (p < 0.01). Since tumor size was not collected in the last study, the other two were reanalyzed. This model identified age, treatment, tumor location, and tumor size as significant predictors. Conclusion. Age > 18 years, pelvic tumor, size > 8 cms, and chemotherapy without ifosfamide/etoposide significantly predict worse outcome. AEWS0031 is NCT00006734, INT0091 and INT0054 designed before 1993 (unregistered).

BACKGROUND: Cisplatinum (CP) is associated with acute kidney injury. The aim of this study was to define the spectrum of CP-induced nephrotoxicity in current practice. CASE-DIAGNOSIS/TREATMENT: A single-center, retrospective chart review was performed on children who received CP for treatment of a malignancy at the Hassenfeld Children's Center for Blood and Cancer Disorders of NYU Langone Medical Center between 2005 and 2012. Patients were considered to have nephrotoxicity if they had: (1) a decrease in estimated glomerular filtration rate (eGFR) of >/=30 % or (2) a decline in serum magnesium of >/=0.2 meq/L or (3) a decline in serum potassium of >/=0.2 meq/L. Thirty-two patients (mean age 8.0 +/- 7.0 years) were included in this review, of whom 21 had a brain tumor (BT) and 11 had an osteosarcoma (OS); 31 (97 %) of the patients had a disturbance in renal function. The mean reduction in eGFR, serum magnesium and potassium was 37 +/- 17, 30 +/- 16 and 25 +/- 14 %, respectively. The decline in eGFR, hypomagnesemia and hypokalemia was persistent in 38, 60 and 40 % of cases, respectively, through the short-term follow-up period. No patients required dialysis. CONCLUSIONS: Nearly all patients receiving CP in current care experience modest glomerular and tubular injury. The abnormalities persist in 40-60 % of cases during the short-term recovery period after CP treatment.

Sialoblastoma is a rare salivary neoplasm which presents either congenitally or during early infancy. It was originally considered a benign neoplasm, however a number of reported cases have documented locoregional recurrence and distant metastases. Currently, there is no consensus on the appropriate treatment for this neoplasm. We report on long term follow-up of a patient with metastatic sialoblastoma, and a brief discussion of the possible treatment modalities currently being considered.

Phenomenologic analysis of initial consults provided during the first year of a new Pediatric Advanced Care Team (PACT) program provides essential understanding of the experience and inform program direction and future clinical research. Parents bring to the consult a desire to remain experts in their children's lives yet experience vulnerability as they seek assistance in making critical decisions often under conditions of disquieting uncertainty. Dynamic communication efforts involving the referring providers, PACT team members, and family are a key influence in facilitating consults' stated goals and in establishing the integrated palliative paradigm in a tertiary care environment. Validation was provided for a new research infrastructure that will function concurrently with the PACT clinical program in this rapidly evolving field

PURPOSE: The Ewing sarcoma family of tumors (ESFT) is a group of malignant tumors of soft tissue and bone sharing a chromosomal translocation affecting the EWS locus. The Intergroup INT-0091 demonstrated the superiority of a regimen of vincristine, cyclophosphamide, doxorubicin (VDC), and dactinomycin alternating with ifosfamide and etoposide (IE) over VDC for patients with nonmetastatic ESFT of bone. The goal of this study was to determine whether a dose-intensified regimen of VDC alternating with IE would further improve the outcome for patients with nonmetastatic ESFT of bone or soft tissue. METHODS: Patients with previously untreated, nonmetastatic ESFT of bone or soft tissue were eligible. They were randomly assigned to receive standard doses of VDC/IE over 48 weeks or a dose-intensified regimen of VDC/IE over 30 weeks. RESULTS: Four hundred seventy-eight patients met eligibility requirements: 231 patients received the standard regimen; 247 patients received the intensified regimen. The 5-year event-free survival (EFS) and overall survival rates for all eligible patients were 71.1% (95% CI, 67.7% to 75.0%) and 78.6% (95% CI, 74.6% to 82.1%), respectively. There was no significant difference (P = .57) in EFS between patients treated with the standard (5-year EFS, 72.1%; 95% CI, 65.8% to 77.5%) or intensified regimen (5-year EFS, 70.1%; 63.9% to 75%). Patients with soft tissue tumors accounted for 20% of the study population; there was no difference in outcome between patients with soft tissue and bone primary sites. CONCLUSION: Dose escalation of alkylating agents as tested in this trial did not improve the outcome for patients with nonmetastatic ESFT of bone or soft tissue

BACKGROUND: The prognosis for patients with recurrent Ewing sarcoma (EWS) is very poor with 5-year survival of 13%. METHODS: To evaluate prognostic factors for these patients we studied patients initially treated on the multi-institutional study INT0091. RESULTS: Two hundred sixty-two patients experienced disease recurrence. The median time to first recurrence was 1.3 years (0-7.4 years), 1.4 years (0-7.4 years) for patients with initially localized disease and 1 year (0-6 years) for patients with initially metastatic disease. Time to first recurrence from date of initial diagnosis was a predictor of post-recurrence survival (P < 0.0001). Twenty-one percent of patients, with recurrent or progressive disease >or=2 years from initial diagnosis, had an estimated 5-year survival of 30% (vs. 7% estimated 5-year survival with an earlier recurrence). No statistical difference was detected between patients whose disease recurred <1 year and between 1 and 2 years from initial diagnosis. A stepwise relative risk model and backwards stepwise regression was used to explore factors significantly associated with risk for post-recurrence death. Significant risk factors for death after recurrence included recurrence at combined local and distant sites, elevated LDH at initial diagnosis and initial recurrence less than 2 years after diagnosis. Isolated pulmonary recurrence was not predictive of survival after recurrence. CONCLUSION: Patients with a longer disease control interval represent the subset of patients most likely to survive following recurrence of EWS. All patients with recurrence would benefit from collaborative trials to investigate new therapeutic options

PURPOSE: To determine the efficacy and safety of using vinblastine (Vbl) and methotrexate (Mtx) in children with desmoid-type fibromatosis that is recurrent or not amenable to treatment with radiation or surgery. PATIENTS AND METHODS: A phase II study was conducted within the Pediatric Oncology Group. Patients were treated using Vbl (5 mg/m2/dose) and Mtx (30 mg/m2/dose), both administered by intravenous injection weekly for 26 weeks and every other week for an additional 26 weeks. Response was assessed by bidimensional measurements of tumor on axial imaging (magnetic resonance imaging or computed tomography). RESULTS: Over 35 months, 28 patients were enrolled; 27 were eligible, and 26 were assessable for response. A measurable response was documented in eight patients (31%), and 10 patients had stable disease documented as the best response to treatment. Eighteen patients had disease progression at a median time of 9.1 months. Eight patients remain free of disease progression at a median of 43.4 months from study entry. Nine patients reported no to moderate toxicity. Neutropenia was the most common toxicity (n = 22) and the most common grade 4 toxicity (n = 5). Anemia, nausea, vomiting, and elevations in hepatic transaminases were also common and were reversible with interruption of chemotherapy. CONCLUSION: Vbl and Mtx are well tolerated in children with desmoid-type fibromatosis. Furthermore, this combination can promote tumor regression or block tumor growth in most children