Use of ultrasound in diagnosing postoperative small-bowel intussusception in pediatric surgical oncology patients: a single-center retrospective review.

BACKGROUND: Postoperative intussusception can be a complication of abdominal surgery and often poses a diagnostic dilemma. OBJECTIVE: The purpose of this study was to evaluate the utility of ultrasonography in the diagnosis of intussusception in children who had recently undergone resection of a primary solid tumor. MATERIALS AND METHODS: We performed a retrospective review of all pediatric surgical oncology patients undergoing laparotomy for excision of an abdominal tumor at our institution from 1995 to 2015. We reviewed those with documented postoperative intussusception. In addition we searched the radiology database for all ultrasound examinations requested to rule out postoperative intussusception during our study interval. We analyzed demographics, primary diagnosis, surgical procedure, presentation, diagnostic investigations and definitive treatment. RESULTS: At our institution 852 laparotomies for abdominal tumor resection were performed during the study period, resulting in 10 postoperative intussusceptions (1.2% of cases), of which half were following neuroblastoma resection and the other half following nephrectomy for Wilms tumor. Postoperative intussusception was suspected if the patient had increasing nasogastric output, abdominal distension or feeding intolerance. Ultrasound was used to diagnose intussusception in 9/10 cases, on postoperative day 6 (standard deviation [SD] 5.6 days) on average, with a sensitivity of 89% (8/9; one false negative; 95% confidence interval [CI] 0.52, 1.00) and a specificity of 100% (no false positives; 95% CI 0.96, 1.00). CONCLUSION: Ultrasound was highly accurate in diagnosing postoperative intussusception in children who underwent resection of retroperitoneal tumors.

The role of FDG-PET/CT in the evaluation of residual disease in paediatric non-Hodgkin lymphoma.

(18) F-labelled-fluorodeoxyglucose positron emission tomography (FDG-PET) findings are challenging to interpret for residual disease versus complete response in paediatric patients with non-Hodgkin lymphoma (NHL). A biopsy is often warranted to confirm the presence or absence of viable tumour if there is clinical or radiographic evidence of residual disease. In this study, we compared conventional imaging and FDG-PET/computerized tomography (CT) findings with biopsy results in 18 children with NHL. Our goal was to provide additional data to establish more reliable criteria for response evaluation. Residual disease was suspected after conventional imaging alone in eight patients, after FDG-PET/CT alone in three and after both modalities in seven patients. Biopsy confirmed the presence of viable tumour in two patients. Two additional patients experienced progressive disease or relapse. The sensitivity and negative predictive value of FDG-PET/CT using the London criteria to indicate residual tumour detectable by biopsy were 100%, but specificity was low (60%), as was the positive predictive value (25%). Thus, in this study, a negative FDG-PET/CT finding was a good indicator of complete remission. However, because false-positive FDG-PET/CT findings are common, biopsy and close monitoring are required for accurate determination of residual disease in individual patients.

Phase I expansion cohort to evaluate the combination of bevacizumab, sorafenib and low-dose cyclophosphamide in children and young adults with refractory or recurrent solid tumours.

BACKGROUND: Angiogenesis is critical for tumour growth and metastasis. Dual inhibition of vascular endothelial growth factors and platelet-derived growth factor receptors suppresses angiogenesis. This expansion cohort of a phase I study targeted angiogenesis with sorafenib, bevacizumab and low-dose cyclophosphamide in children and young adults with recurrent solid tumours. METHODS: An expansion cohort including patients with refractory or recurrent solid tumours was enrolled and received bevacizumab (15 mg/kg IV, day 1), sorafenib (90 mg/m2 po twice daily, days 1-21) and low-dose cyclophosphamide (50 mg/m2 po daily, days 1-21). Each course was 21 days. Toxicities were assessed using Common Terminology Criteria for Adverse Events, v3.0, and responses were evaluated by Response Evaluation Criteria in Solid Tumors criteria. Serial bevacizumab pharmacokinetic (PK) studies were performed during course 1. RESULTS: Twenty-four patients (15 males; median age 14.5 yrs; range 1-22 yr) received a median of 6 courses (range 1-18). Twelve patients had a bone or soft tissue sarcoma. The most common grade III/IV non-haematologic toxicities were hypertension (N = 4), hand/foot rash (N = 3) and elevated lipase (N = 3). The most common grade III/IV haematologic toxicities were neutropenia (N = 7) and lymphopenia (N = 17). Three patients (2 synovial sarcoma, 1 rhabdoid tumour) achieved a partial response and 18 had stable disease. The progression-free survival at 3 and 6 months were 78.1% (95% confidence interval [CI] 60.6-95.6%) and 54% (95% CI 30.2-78.2%), respectively. Bevacizumab PKs in 15 patients was similar to published adult PK results. CONCLUSIONS: Intravenous bevacizumab combined with oral sorafenib and low-dose cyclophosphamide was tolerated and demonstrated promising activity in a subset of childhood solid tumours.

A phase I trial of talazoparib and irinotecan with and without temozolomide in children and young adults with recurrent or refractory solid malignancies.

BACKGROUND: Talazoparib combined with irinotecan and temozolomide demonstrated efficacy in a murine Ewing sarcoma model. Based on these data, we conducted a phase I trial of talazoparib and irinotecan with/without temozolomide in paediatric patients with recurrent/refractory solid malignancies. PATIENTS AND METHODS: Cohorts of 3-6 patients with recurrent/refractory solid malignancies received escalating doses of oral talazoparib and intravenous irinotecan (arm A) and oral talazoparib, oral temozolomide and intravenous irinotecan (arm B) in a 3 + 3 design. Talazoparib was administered on days 1-6, and intravenous irinotecan and oral temozolomide were administered on days 2-6, of a 21-day course. Serum for talazoparib and irinotecan pharmacokinetics was obtained during course 1. UGT1A1 polymorphism and Schlafen family member 11 (SLFN11) immunohistochemical staining were performed. RESULTS: Forty-one patients (20 males; median age, 14.6 years; 24 with recurrent disease) were evaluable for dose escalation. Twenty-nine and 12 patients were treated on arm A and arm B, respectively, for a total of 208 courses. The most common diagnosis was Ewing sarcoma (53%). The most common ≥grade III haematologic toxicities in arms A and B included neutropenia (78% and 31%, respectively) and thrombocytopenia (42% and 31%, respectively). In arms A and B, febrile neutropenia (24% and 14%, respectively) and diarrhoea (21% and 7%, respectively) were the most common ≥grade III non-hematologic toxicities. Six patients (Ewing sarcoma [5 patients] and synovial sarcoma [1 patient]) had a response (1 with a complete response, 5 with a partial response). The objective response rates were 10.3% (arm A) and 25% (arm B). Pharmacokinetic testing demonstrated no evidence of drug-drug interaction between talazoparib and irinotecan. UGT1A1 was not related to response. SLFN11 positivity was associated with best response to therapy. CONCLUSIONS: The combination of talazoparib and irinotecan with/without temozolomide is feasible and active in Ewing sarcoma, and further investigation is warranted.

Bone and [18F]fluorodeoxyglucose positron-emission tomography/computed tomography scanning for the assessment of osseous involvement in Hodgkin lymphoma in children and young adults.

To compare FDG PET/CT and bone scans for the management of young patients with Hodgkin lymphoma (HL). Eighteen patients, aged 7-24 years, with HL received bone and PET scans within 2 weeks--11 at diagnosis and 7 at known or suspected relapse (37 scan pairs). In six patients (nine scan pairs) both studies were positive. In four patients (five scan pairs), PET showed involvement not evident on bone scan. In four patients (four scan pairs), one of the studies was equivocal and the other negative. In one patient, bone scan showed abnormal uptake in a benign lesion. In nine patients (19 scan pairs), both studies were negative. All osseous metastases identified on bone scan were present on PET. Many additional sites of bony involvement were identified on PET. The bone scan may be safely eliminated.