Redesigning radiotherapy quality assurance: opportunities to develop an efficient, evidence-based system to support clinical trials--report of the National Cancer Institute Work Group on Radiotherapy Quality Assurance.

Purpose: In the context of national calls for reorganizing cancer clinical trials, the National Cancer Institute sponsored a 2-day workshop to examine challenges and opportunities for optimizing radiotherapy quality assurance (QA) in clinical trial design.

Methods And Materials: Participants reviewed the current processes of clinical trial QA and noted the QA challenges presented by advanced technologies. The lessons learned from the radiotherapy QA programs of recent trials were discussed in detail.

Carboplatin-associated ototoxicity in children with retinoblastoma.

Purpose: Carboplatin-induced ototoxicity remains poorly defined but is of potential great consequence in children with retinoblastoma. We retrospectively assessed the incidence of ototoxicity and its risk factors in children with retinoblastoma who were treated with carboplatin.

Patients And Methods: We reviewed the audiologic test results of 60 patients with retinoblastoma who received front-line treatment with systemic carboplatin and vincristine according to the St Jude RET-3 protocol (n = 23) or best clinical management (n = 37).

Effects of irradiation on brain vasculature using an in situ tumor model.

Purpose: Damage to normal tissue is a limiting factor in clinical radiotherapy (RT). We tested the hypothesis that the presence of tumor alters the response of normal tissues to irradiation using a rat in situ brain tumor model.

Methods And Materials: Intravital microscopy was used with a rat cranial window to assess the in situ effect of rat C6 glioma on peritumoral tissue with and without RT.

Dependence of intrafraction motion on fraction duration for pediatric patients with brain tumors.

The purpose of this study was to quantify the intrafraction motion of pediatric patients with brain tumors during radiation therapy and investigate any correlation between motion, use of general anesthesia, and daily treatment duration. 100 pediatric patients with a mean age of 8.5 years (range: 1.

Growth hormone secretion after conformal radiation therapy in pediatric patients with localized brain tumors.

Purpose: Growth hormone deficiency (GHD) after radiation therapy negatively affects growth and development and quality of life in children with brain tumors.

Patients And Materials: Between 1997 and 2008, 192 pediatric patients with localized primary brain tumors (ependymoma, n = 88; low-grade glioma, n = 51; craniopharyngioma, n = 28; high-grade glioma, n = 23; and other tumor types, n = 2) underwent provocative testing of GH secretion by using the secretogogues arginine and L-dopa before and after (6, 12, 36, and 60 months) conformal radiation therapy (CRT). A total of 664 arginine/l-dopa test procedures were performed.

Excessive daytime sleepiness and sleep-disordered breathing disturbances in survivors of childhood central nervous system tumors.

Background: Improvements in treatment and management for pediatric central nervous system (CNS) tumors have increased survival rates, allowing clinicians to focus on long-term sequelae, including sleep disorders. The objective of this study was to describe a series of CNS tumor survivors who had sleep evaluations that included polysomnography (PSG) with attention to sleep disorder in relation to the tumor site.

Procedure: We report on 31 patients who had retrievable reports including an overnight PSG; 17 also underwent multiple sleep latency tests (MSLT) to characterize their sleepiness.

Dosimetric consequences of rotational errors in radiation therapy of pediatric brain tumor patients.

Purpose: To quantify the rotational offsets and estimate the dose effect of rotation on the target volume and normal tissues in children with brain tumor.

Methods: Twenty-one pediatric patients with brain tumors were included in this study. Cone-beam CT was performed before each treatment and at the end of every other treatment.

Brain tumor therapy-induced changes in normal-appearing brainstem measured with longitudinal diffusion tensor imaging.

Purpose: To characterize therapy-induced changes in normal-appearing brainstems of childhood brain tumor patients by serial diffusion tensor imaging (DTI).

Methods And Materials: We analyzed 109 DTI studies from 20 brain tumor patients, aged 4 to 23 years, with normal-appearing brainstems included in the treatment fields. Those with medulloblastomas, supratentorial primitive neuroectodermal tumors, and atypical teratoid rhabdoid tumors (n = 10) received postoperative craniospinal irradiation (23.

Post-operative radiation improves survival in children younger than 3 years with intracranial ependymoma.

Concerns regarding long-term toxicities have led to the avoidance of post-operative radiation (PORT) in young children with intracranial ependymoma. We investigated the association between post-operative radiation therapy and overall survival (OS) in children younger than 3 years and compared their survival to other age groups. The study sample from the SEER database included 804 patients with intracranial ependymoma, grades 2-3, and diagnosed between 1988 and 2005.

Novel assessment of renal motion in children as measured via four-dimensional computed tomography.

Objectives: Abdominal intensity-modulated radiation therapy and proton therapy require quantification of target and organ motion to optimize localization and treatment. Although addressed in adults, there is no available literature on this issue in pediatric patients. We assessed physiologic renal motion in pediatric patients.

Sequencing of local therapy affects the pattern of treatment failure and survival in children with atypical teratoid rhabdoid tumors of the central nervous system.

Purpose: To assess the pattern of treatment failure associated with current therapeutic paradigms for childhood atypical teratoid rhabdoid tumors (AT/RT).

Methods And Materials: Pediatric patients with AT/RT of the central nervous system treated at our institution between 1987 and 2007 were retrospectively evaluated. Overall survival (OS), progression-free survival, and cumulative incidence of local failure were correlated with age, sex, tumor location, extent of disease, and extent of surgical resection.

Role of adaptive radiation therapy for pediatric patients with diffuse pontine glioma.

We investigate the role of adaptive radiation therapy in pediatric patients with diffuse pontine glioma and the impact of steroid-related weight gain on treatment parameters utilizing cone-beam CT. Fifteen patients with diffuse pontine glioma were treated with three-dimensional conformal radiation therapy and enrolled on a daily localization protocol. The median age was 6 years (range: 2-13 years).

Intensity-modulated arc therapy for pediatric posterior fossa tumors.

Purpose: To compare intensity-modulated arc therapy (IMAT) to noncoplanar intensity-modulated radiation therapy (IMRT) in the treatment of pediatric posterior fossa tumors.

Methods And Materials: Nine pediatric patients with posterior fossa tumors, mean age 9 years (range, 6-15 years), treated using IMRT were chosen for this comparative planning study because of their tumor location. Each patient's treatment was replanned to receive 54 Gy to the planning target volume (PTV) using five different methods: eight-field noncoplanar IMRT, single coplanar IMAT, double coplanar IMAT, single noncoplanar IMAT, and double noncoplanar IMAT.

On the benefits and risks of proton therapy in pediatric craniopharyngioma.

Purpose: Craniopharyngioma is a pediatric brain tumor whose volume is prone to change during radiation therapy. We compared photon- and proton-based irradiation methods to determine the effect of tumor volume change on target coverage and normal tissue irradiation in these patients.

Methods And Materials: For this retrospective study, we acquired imaging and treatment-planning data from 14 children with craniopharyngioma (mean age, 5.

Health status in long-term survivors of pediatric craniopharyngiomas.

Craniopharyngiomas are the third most common pediatric brain tumor and most common pediatric suprasellar tumor. Contemporary treatment of craniopharyngiomas uses limited surgery and radiation in an effort to minimize morbidity, but the long-term health status of patients treated in this fashion has not been well described. The purpose of this study was to analyze the health status of long-term survivors of pediatric craniopharyngioma treated primarily with radiation and conservative surgical resection.

Survival and long-term health and cognitive outcomes after low-grade glioma.

Long-term morbidity for children with low-grade glioma (LGG) requires exposure-specific characterization. Overall survival (OS) and progression-free survival (PFS) were estimated for 361 children diagnosed with LGG between 1985 and 2007 at a single institution. Five-year survivors (n = 240) received risk-based clinical assessment.

Jaw dysfunction related to pterygoid and masseter muscle dosimetry after radiation therapy in children and young adults with head-and-neck sarcomas.

Purpose: To investigate the relationship between jaw function, patient and treatment variables, and radiation dosimetry of the mandibular muscles and joints in children and young adults receiving radiation for soft-tissue and bone sarcomas.

Methods And Materials: Twenty-four pediatric and young adult patients with head-and-neck sarcomas were treated on an institutional review board-approved prospective study of focal radiation therapy for local tumor control. Serial jaw depression measurements were related to radiation dosimetry delivered to the medial and lateral pterygoid muscles, masseter muscles, and temporomandibular joints to generate mathematical models of jaw function.

Daily image-guided localization for neuroblastoma.

The purpose was to quantify the setup margin for pediatric patients with neuro-blastoma using cone beam CT imaging (CBCT) and ultrasound localization. Ten patients, with a median age of 4.3 years (1.

Dosimetric effect of target expansion and setup uncertainty during radiation therapy in pediatric craniopharyngioma.

Purpose: Investigate the effect of tumor change and setup uncertainties on target coverage for pediatric craniopharyngioma during RT.

Methods And Materials: Fifteen pediatric patients with craniopharyngioma (mean 5.1 years) were included in this study.

Phase I study of vandetanib during and after radiotherapy in children with diffuse intrinsic pontine glioma.

Purpose: To evaluate the safety, maximum-tolerated dose, pharmacokinetics, and pharmacodynamics of vandetanib, an oral vascular endothelial growth factor receptor 2 (VEGFR2) and epidermal growth factor receptor inhibitor, administered once daily during and after radiotherapy in children with newly diagnosed diffuse intrinsic pontine glioma.

Patients And Methods: Radiotherapy was administered as 1.8-Gy fractions (total cumulative dose of 54 Gy).

Region-specific radiotherapy and neuropsychological outcomes in adult survivors of childhood CNS malignancies.

Childhood cancer survivors exposed to CNS irradiation are at increased risk for neurocognitive deficits; however, limited data exist linking outcomes with region-specific exposure to CNS irradiation. We report associations between region-specific radiation dose and self-reported neurocognitive and health-related quality of life (HRQOL) outcomes in 818 adult survivors of childhood central nervous system (CNS) malignancies from the Childhood Cancer Survivor Study. Survivors were compared with a sibling group and national normative samples to calculate standardized scores.

Dysembryoplastic neuroepithelial tumors and cognitive outcome: cure at a price?

Background: Dysembryoplastic neuroepithelial tumors (DNETs) are benign glioneuronal tumors that occur in children. These tumors are characterized by seizures, lack of neurologic deficits, and a seemingly benign course after resection.

Methods: A retrospective review was conducted of data relating to 11 children diagnosed with DNETs between January 1988 and December 2007 at St.

Cross-species genomics matches driver mutations and cell compartments to model ependymoma.

Understanding the biology that underlies histologically similar but molecularly distinct subgroups of cancer has proven difficult because their defining genetic alterations are often numerous, and the cellular origins of most cancers remain unknown. We sought to decipher this heterogeneity by integrating matched genetic alterations and candidate cells of origin to generate accurate disease models. First, we identified subgroups of human ependymoma, a form of neural tumour that arises throughout the central nervous system (CNS).

Inter- and intrafractional positional uncertainties in pediatric radiotherapy patients with brain and head and neck tumors.

Purpose: To estimate radiation therapy planning margins based on inter- and intrafractional uncertainty for pediatric brain and head and neck tumor patients at different imaging frequencies.

Methods: Pediatric patients with brain (n = 83) and head and neck (n = 17) tumors (median age = 7.2 years) were enrolled on an internal review board-approved localization protocol and stratified according to treatment position and use of anesthesia.

Radiation therapy for pediatric craniopharyngioma.

Object: The treatment of craniopharyngioma is highly controversial. Continued advances in limited surgery and radiation therapy have maintained excellent local disease control while minimizing treatment-related sequelae. Further analyses of outcomes are necessary to characterize the long-term effects of radiation therapy.