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Significant progress has been made in radiation protection for children during the last 10 years. This includes increased awareness of the need for radiation protection for pediatric patients with international partnerships through the Alliance for Radiation Safety in Pediatric Imaging. This paper identifies five areas of significant progress in radiation safety for children: the growth of the Alliance; the development of an adult radiation protection campaign Image Wisely™; increased collaboration with government agencies, societies and the vendor community; the development of national guidelines in pediatric nuclear medicine, and the development of a size-based patient dose correction factor by the American Association of Physicists in Medicine, Task Group 204. However, many challenges remain. These include the need for continued education and change of practice at adult-focused hospitals where many pediatric CT exams are performed; the need for increased emphasis on appropriateness of pediatric imaging and outcomes research to validate the performance of CT studies, and the advancement of the work of the first pediatric national dose registry to determine the "state of the practice" with the final goal of establishing ranges of optimal CT technique for specific scan indications when imaging children with CT.

Pediatric patients might be as much as 10 times more radiosensitive than adults. Thus, adherence to the principle of "As low as reasonably achievable" (ALARA) represents a practice mandate that minimizes ionizing radiation exposure while optimizing imaging results. This symposium is the third multidisciplinary program that focused on the ALARA principle in pediatric imaging and addressed issues associated with pediatric fluoroscopy and interventional imaging techniques.

Background: Indications for and delivery of adjuvant therapies for pediatric nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) have been derived largely from adult studies; therefore, significant concern remains regarding radiation exposure to normal tissue. The authors report long-term treatment outcomes and toxicities for pediatric and young adult patients with high-grade NRSTS who were treated on a prospective trial using limited-margin radiotherapy.Methods: Sixty-two patients (ages 3-22 years) with predominantly high-grade NRSTS requiring radiation were treated on a phase 2 institutional study of conformal external-beam radiotherapy and/or brachytherapy using a 1.5-cm to 2-cm anatomically constrained margin. The estimated cumulative incidence of local failure, Gray's method estimated cumulative incidence of local failure, Kaplan-Meier method estimated survival, competing-risk regression model determined predictors of disease outcome, and toxicity was reported according to CTCAE v2.0.Results: At a median follow-up of 5.1 years (range, 0.2-10.9 years), 9 patients had experienced local failure. The 5-year overall cumulative incidence of local failure was 14.8% (95% confidence interval [CI], 7.2%-25%), and all but 1 local failure occurred outside the highest-dose irradiation volume. The 5-year Kaplan-Meier estimates for event-free and overall survival were 49.3% (95% CI, 36.3%-61.1%) and 67.9% (95% CI, 54.2%-78.3%), respectively. Multivariable analysis indicated that younger age was the only independent predictor of local recurrence (P = .004). The 5-year cumulative incidence of grade 3 or 4 late toxicity was 15% (95% CI, 7.2%-25.3%).Conclusions: The delivery of limited-margin radiotherapy using conformal external-beam radiotherapy or brachytherapy provides a high rate of local tumor control without an increase in marginal failures and with acceptable treatment-related morbidity. Cancer 2017;123:4419-29. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: It is unclear whether routine pelvic imaging is needed in patients with Wilms tumor. Thus, the primary objective of the current study was to examine the role of routine pelvic computed tomography (CT) in a cohort of pediatric patients with Wilms tumor. METHODS: With institutional review board approval, the authors retrospectively identified 110 patients who had Wilms tumor diagnosed between January 1999 and December 2009 with surveillance imaging that continued through March 2011. The authors estimated overall survival (OS), event-free survival (EFS), and dosimetry from dose length product (DLP) conversion to the effective dose (ED) for every CT in a subgroup of 80 patients who had CT studies obtained using contemporary scanners (2002-2011). Metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters were placed within organs of anthropomorphic phantoms to directly calculate the truncal ED. EDDLP was correlated with EDMOSFET to calculate potential pelvic dose savings. RESULTS: Eighty patients underwent 605 CT examinations that contained DLP information, including 352 CT scans of the chest, abdomen, and pelvis; 123 CT scans of the chest and abdomen; 102 CT scans of the chest only; 18 CT scans of the abdomen and pelvis; 9 CT scans of the abdomen only; and 1 CT that was limited to the pelvis. The respective 5-year OS and EFS estimates were 92.8% ± 3% and 2.6% ± 4.3%. Sixteen of 110 patients (15%) developed a relapse a median of 11.3 months (range, 5.0 months to 7.3 years) after diagnosis, and 4 patients died of disease recurrence. Three patients developed pelvic relapses, all 3 of which were symptomatic. The estimated ED savings from sex-neutral CT surveillance performed at a 120-kilovolt peak without pelvic imaging was calculated as 30.5% for the average patient aged 1 year, 30.4% for the average patient aged 5 years, 39.4% for the average patient aged 10 years, and 44.9% for the average patient aged 15 years. CONCLUSIONS: Omitting pelvic CT from the routine, off-therapy follow-up of patients with Wilms tumor saved an average 30% to 45% of the ED without compromising disease detection. Cancer 2013. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Skeletal bone accretion occurs throughout childhood. The integrity of this process can influence future adult bone health and the risk of osteoporosis. Although surveillance of children who are at risk of poor bone accretion is important, the most appropriate method to monitor childhood bone health has not been established. Previous investigators have proposed using bone age (BA) rather than chronological age (CA) when interpreting bone mineral density (BMD) values in children. To investigate the value of BA assessment for BMD measurement in a cohort of children at risk of poor accretion. A cohort of 163 children with brain tumors who completed both a BMD assessment (quantitative computed tomography, QCT) and who had a BA within a 6-month interval were identified. The difference in BMD Z-scores determined by CA and BA was determined. The impact of salient clinical features was assessed. No significant difference between CA and BA Z-scores was detected in the overall cohort ( P = 0.056). However, the scores in 18 children (all boys between the ages of 11 years and 15 years) were statistically determined to be outliers from the values in the rest of the cohort. Interpretation of BMD with BA measurement might be appropriate and affect treatment decisions in peripubertal males. [ABSTRACT FROM AUTHOR]

In parallel with the expansion of PET imaging to pediatric patients has been the technological development of merging state-of-the-art cross-sectional anatomic information (CT) with functional imaging (PET) into a single modality: PET-CT. Attending to the clinical, scheduling, and medical needs that are unique to imaging children and adolescents can be a challenge, particularly when instituting a single new modality. When that modality bridges two unique, previously independent methods-often previously located in two separate departmental divisions-the details and logistics required to set up a smoothly functioning process can be particularly difficult. This paper focuses on our experience in implementing PET-CT in a tertiary pediatric referral center. [ABSTRACT FROM AUTHOR]

The application of PET imaging to pediatric radiation oncology allows new approaches to targeting and selection of radiation dose based not only on the size of a tumor, but also on its metabolic activity. In order to integrate PET into treatment planning for radiation oncology, logistical issues regarding patient setup, image fusion, and target selection must be addressed. Through prospective study, the role of PET in pediatric malignancies will be established for diagnosis, treatment, and surveillance. To explore the potential role of PET and its incorporation into treatment planning in pediatric radiation oncology, an example case of pediatric Hodgkin's disease is discussed. [ABSTRACT FROM AUTHOR]

Advances in diagnostic imaging technology, especially functional imaging modalities like positron emission tomography (PET), have significantly influenced the staging and treatment approaches used for pediatric Hodgkin’s lymphoma. Today, the majority of children and adolescents diagnosed with Hodgkin’s lymphoma will be cured following treatment with non-cross-resistant combination chemotherapy alone or in combination with low-dose, involved-field radiation. This success produced a greater appreciation of long-term complications related to radiation, chemotherapy, and surgical staging that prompted significant changes in staging and treatment protocols for children and adolescents with Hodgkin’s lymphoma. Contemporary treatment for pediatric Hodgkin’s lymphoma uses a risk-adapted approach that reduces the number of combination chemotherapy cycles and radiation treatment fields and doses for patients with localized favorable disease presentation. Advances in diagnostic imaging technology have played a critical role in the development of these risk-adapted treatment regimens. The introduction of computed tomography (CT) provided an accurate and non-invasive modality to define nodal involvement below the diaphragm that motivated the change from surgical to clinical staging. The introduction of functional imaging modalities, like positron emission tomography (PET) scanning, provided the means to correlate tumor activity with anatomic features generated by CT and modify treatment based on tumor response. For centers with access to this modality, PET imaging plays an important role in staging, evaluating tumor response, planning radiation treatment fields, and monitoring after completion of therapy for pediatric Hodgkin’s lymphoma. This trend will likely increase in the future as a result of PET’s superior sensitivity in correlating sites of tumor activity compared to other available functional imaging modalities. Ongoing prospective studies of PET in pediatric patients will increase understanding about the optimal use of this modality in children with cancer and define the characteristics of FDG-avid nonmalignant conditions that may be problematic in the interpretation of tumor activity. [ABSTRACT FROM AUTHOR]

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. 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. 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. The combination of talazoparib and irinotecan with/without temozolomide is feasible and active in Ewing sarcoma, and further investigation is warranted. • Talazoparib with irinotecan and temozolomide is tolerated in paediatric patients. • There was no drug-drug interaction between talazoparib and irinotecan. • UGT1A1 status was significantly associated with a course 1 dose-limiting toxicity. • Schlafen family member 11 positivity was associated with best response to therapy. • This regimen had clinical benefit in patients with Ewing sarcoma. [ABSTRACT FROM AUTHOR]

Purpose: To determine the effects of 15 Gy on bone growth as a function of time and age by comparing clavicle length before and after asymmetric mantle irradiation in pediatric patients.Methods and materials: We measured the lengths of both clavicles from radiographs made before and after radiotherapy (median follow-up, 39.6 months), in 15 children (median age, 13.3 years) with early-stage Hodgkin''s disease treated with combined modality therapy. The intercepts and slopes of regression lines for individual patients were used to form an estimating regression curve for the population.Results: The irradiated volume, patient age, and time elapsed after treatment influenced the measured growth. Fully irradiated clavicles grew 1.3 ± 0.3 cm, significantly less (0.5 cm; p = 0.007) than did the partially irradiated clavicles. The difference between partially and fully irradiated clavicle lengths was statistically significant, regardless of age. Also, the growth rate of partially and fully irradiated clavicles was significantly different between younger (mean age, 9.9 years) and older (mean age, 16.4 years) patients (p = 0.036).Conclusion: Clavicle growth is vulnerable to radiation doses as low as 15 Gy, and patient age at the time of irradiation influences the growth rate. [Copyright &y& Elsevier]