Shelly Sharma

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. Radiotherapy (RT) sequencing, chemotherapy, dose, timing, and volume administered after resection were also evaluated. RESULTS Thirty-one patients at a median age of 2.3 years at diagnosis (range, 0.45-16.87 years) were enrolled into protocols that included risk- and age-stratified RT. Craniospinal irradiation with focal tumor bed boost (median dose, 54 Gy) was administered to 18 patients. Gross total resection was achieved in 16. Ten patients presented with metastases at diagnosis. RT was delayed more than 3 months in 20 patients and between 1 and 3 months in 4; 7 patients received immediate postoperative irradiation preceding high-dose alkylator-based chemotherapy. At a median follow-up of 48 months, the cumulative incidence of local treatment failure was 37.5% ± 9%; progression-free survival was 33.2% ± 10%; and OS was 53.5% ± 10%. Children receiving delayed RT (≥1 month postoperatively) were more likely to experience local failure (hazard ratio [HR] 1.23, p = 0.007); the development of distant metastases before RT increased the risk of progression (HR 3.49, p = 0.006); and any evidence of disease progressionbefore RT decreased OS (HR 20.78, p = 0.004). Disease progression occurred in 52% (11/21) of children with initially localized tumors who underwent gross total resection, and the progression rate increased proportionally with increasing delay from surgery to RT. CONCLUSIONS Delayed RT is associated with a higher rate of local and metastatic disease progression in children with AT/RT. Current treatment regimens for pediatric patients with AT/RT are distinctly age stratified; novel protocols investigating RT volumes and sequencing are needed.

Effect of Cerebellum Radiation Dosimetry on Cognitive Outcomes in Children With Infratentorial Ependymoma

PURPOSE Cognitive decline is a recognized effect of radiation therapy (RT) in children treated for brain tumors. The importance of the cerebellum and its contribution to cognition have been recognized; however, the effect of RT on cerebellum-linked neurocognitive deficits has yet to be explored. METHODS AND MATERIALS Seventy-six children (39 males) at a median 3.3 years of age (range, 1-17 years old) were irradiated for infratentorial ependymoma from 1997 to 2008. The total prescribed dose was 54 to 59.4 Gy administered to the postoperative tumor bed with 5- or 10-mm clinical target volume margin. Age-appropriate cognitive and academic testing was performed prior to the start of RT and was then repeated at 6 months and annually throughout 5 years. The anterior and posterior cerebellum and other normal brain volumes were contoured on postcontrast, T1-weighted postoperative magnetic resonance images registered to treatment planning computed tomography images. Mean doses were calculated and used with time after RT and other clinical covariates to model their effect on neurocognitive test scores. RESULTS Considering only the statistically significant rates in longitudinal changes for test scores and models that included mean dose, there was a correlation between mean infratentorial dose and intelligence quotient (IQ; -0.190 patients/Gy/year; P=.001), math (-0.164 patients/Gy/year; P=.010), reading (-0.137 patients/Gy/year; P=.011), and spelling scores (-0.147 patients/Gy/year; P=.012), where Gy was measured as the difference between the mean dose received by an individual patient and the mean dose received by the patient group. There was a correlation between mean anterior cerebellum dose and IQ scores (-0.116 patients/Gy/year; P=.042) and mean posterior cerebellum dose and IQ (-0.150 patients/Gy/year; P=.002), math (-0.120 patients/Gy/year; P=.023), reading (-0.111 patients/Gy/year; P=.012), and spelling (-0.117 patients/Gy/year; P=.015) scores. CONCLUSIONS Sparing portions of the cerebellum should be considered in RT planning for children with infratentorial ependymoma because of the potential impact of radiation dose on cognitive function.

Prevalence of osteonecrosis and associated risk factors in children before allogeneic BMT.

Osteonecrosis (ON) is a debilitating long-term complication of allogeneic BMT (allo-BMT), but may begin before allo-BMT in some children because of their primary disease treatment. Therefore, to estimate the prevalence and associated risk factors for ON before allo-BMT, we conducted a retrospective analysis of magnetic resonance (MR) studies of 118 children who underwent first allo-BMT at our institution between December 2000 and September 2007. Of the 118 consecutive patients, 107 (90.7%) underwent prospective MR studies irrespective of symptoms (69 males; median age at allo-BMT 12.9 years), and 11 underwent MR studies for symptoms. Among the 107 who had prospective imaging, 23 (21.5%) had ON; nearly 50% had at least 30% epiphyseal involvement. Knees were more frequently involved than were hips; severity of ON was greater in hips. ON prevalence before allo-BMT was 23.72% when all 118 patients were included in the denominator. Risk factor analysis, limited to MR studies performed irrespective of symptoms, revealed female gender (P=0.049) and age ⩾10 years at the time of MR study (P=0.03) as significant risk factors, and primary diagnosis of lymphoid malignancies and aplastic anemia trended toward significance. ON before allo-BMT is a common occurrence in children.

Osteonecrosis in children after allogeneic hematopoietic cell transplantation: study of prevalence, risk factors and longitudinal changes using MR imaging

Osteonecrosis after hematopoietic SCT (HCT) has seldom been addressed in pediatric populations. At our institution, since January 2002, children undergoing allogeneic HCT (alloHCT) receive yearly follow-up magnetic resonance imaging (MR) of hips and knees. To estimate the prevalence, longitudinal changes and associated risk factors for osteonecrosis after alloHCT, we reviewed MRs for children who underwent single alloHCT during the study period. We analyzed 149 of 344 patients who had post-HCT MR imaging performed (84 males; median age 11 years (range, 0.5–21years)), median follow-up time was 32.6 months (range, 2.8–97.2 months). In all, 44 (29.5%) developed osteonecrosis of hips and/or knees; of those, 20 (45%) had at least 30% epiphyseal involvement. In 23 (52%), osteonecrosis lesions were identified in the first and in 43 (98%) by the third yearly scan. Knees were more frequently involved than hips; severity of osteonecrosis was greater in hips. Those who had pre-alloHCT osteonecrosis, two patients’ hips and six patients’ knees resolved completely; three patients’ osteonecrosis lesions regressed after alloHCT. On risk factor analysis, age at time of alloHCT (P=0.051) and osteonecrosis identified by MRs before alloHCT (P=0.001) were the primary risk factors. This analysis shows that preventive strategies for osteonecrosis in this population should focus on measures to minimize risk factors before alloHCT.

Abdominal aortic calcification in young adult survivors of childhood acute lymphoblastic leukemia: Results from the St. Jude Lifetime Cohort study†

Abdominal aortic calcification (AAC), metabolic syndrome, and low bone mineral density (BMD) are risk factors for atherosclerotic disease and cardiovascular morbidity. We evaluated AAC in 662 adult survivors of childhood ALL (median age 31 years). AAC was present in 10% of subjects, metabolic syndrome in 36%, and low BMD in 29%. The adjusted odds ratio (OR) for AAC among women with metabolic syndrome was 2.3 (95% CL = 1.0, 4.3). The adjusted OR for AAC in men with low BMD was 3.1 (95% CL = 1.3, 7.3). A substantial proportion of adult survivors of childhood ALL have AAC and/or metabolic syndrome, suggestive of early atherosclerotic disease. Pediatr Blood Cancer 2012; 59: 1307–1309.

TU‐C‐303A‐07: Pediatric Organ Motion Evaluated by Respiratory‐Correlated CT with a Pressure‐Sensitive Abdominal Belt

Purpose: We present the first report of pediatric thoracic and abdominal organ motion extent measured using respiratory‐correlated CT with an abdominal sensor belt. The knowledge is essential for defining internal target volumes and planning organ at risk volumes. It is also critical for safe employment of treatment techniques producing high dose gradient such as IMRT and intensity‐modulated proton therapy.Methods and Materials: Seventeen pediatric patients have undergone radiotherapy simulation including a respiratory‐correlated 4D CT scan in supine position for evaluation of target and internal organ motion. A pressure‐sensitive belt was wrapped around the abdomen just below the diaphragm. The pressure change was used as a respiratory surrogate. Each respiration cycle was divided into eight phases. Liver, left and right kidneys, and the representative 3rd, 7th, and 11th rib pairs were contoured on each of the eight CT datasets. Results: The center‐of‐mass displacements of kidneys in the lateral and anterior/posterior directions due to respiration were small (0–2mm). The superior/inferior displacement was larger (0.6–4.6mm). Younger pediatric patients tend to have smaller kidney motion than their older counterparts. Diaphragm motion (4–10mm) was larger than kidney motion. The magnitude of diaphragm motion did not predict the magnitude of kidney motion. The rib motion ranged from 0.5 to 2mm maximum displacement in the lateral direction and 2 to 4mm in the anterior/posterior and superior/inferior directions. The 11th pair of ribs had smaller respiratory motion than the 3rd and the 7th pair. Conclusion: Pediatric internal organ motion was smaller compared to adult data reported in the literature. Conventional large planning margin of 5–10mm may be reduced for tumors neighboring these organs such as neuroblastoma or chest wall sarcoma if treated with 3D conformal technique and verified with on‐treatment imaging. Whether motion management is required for proton beam scanning in children needs further investigation.