Search

Purpose: Myxopapillary ependymoma (MPE) is a rare, typically slow-growing subtype of spinal ependymomas. There are no standard guidelines for radiotherapy and long-term outcomes after radiation, particularly patterns of relapse, for pediatric and young adult (YA) patients with MPE remain under-characterized., Methods and Materials: This is an Institutional Review Board-approved multi-institutional retrospective cohort study of 60 pediatric and YA patients diagnosed with MPE and received radiotherapy between 2000-2020. Clinical and treatment characteristics, and long-term outcomes were recorded. Site(s) of progression was compared to radiation fields. Survival outcomes were analyzed using Kaplan-Meier method. Cumulative incidence of local in-field progression (CILP) after initial radiotherapy was analyzed using Gray's method with out-of-field-only progression as a competing risk. Univariate analyses were performed using Cox proportional hazard's model., Results: The median age at radiation was 14.8 years (range: 7.1-26.5). At time of radiotherapy, 45 (75.0%) and 35 (58.3%) patients had gross residual and multifocal disease, respectively. Forty-eight (80.0%), seven (11.7%) and five (8.3%) patients received involved field radiotherapy, craniospinal irradiation, and whole spine radiation, respectively. Median follow-up from end of radiotherapy was 6.2 years (range: 0.6-21.0). Five-year overall survival, progression-free survival, and CILP were 100%, 60.8% and 4.1%, respectively. Both local recurrences were at sites of gross residual disease. Of the eighteen out-of-field first recurrences after radiotherapy, all were superior to the initial treatment field and nine had intracranial relapse. On univariate analyses, distant-only recurrence before radiation (HR: 4.00, 95% CI: 1.54-10.43, p = 0.005) was significantly associated with shorter time to progression., Conclusions: While the risk of recurrence within the radiation field is low, pediatric and YA patients with high-risk MPE remain at risk for recurrences in the spine above the radiation field and intracranially after radiotherapy. Future prospective studies are needed to investigate the appropriate radiation field and dose based on the extent of metastases., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: It is of great interest to physicians and patients/patients' families to be able to predict the amount of growth decrement after craniospinal irradiation (CSI). Little data exist on the effect of proton CSI. Our aim was to determine the effect of proton CSI on vertebral body (VB) growth retardation, and to identify factors associated with growth delay., Methods and Materials: We performed a retrospective outcome data analysis of 80 patients <16 years old with central nervous system tumors who received proton radiation therapy (PRT) at the Massachusetts General Hospital between 2002 and 2010 with available spinal magnetic resonance imaging. Forty-eight patients received CSI, and 32 patients with brain tumors who received focal cranial irradiation served as controls. VB height was measured midline using sagittal T1-weighted contrast or noncontrast enhanced magnetic resonance imaging of the spine. Measurements were repeated at multiple levels (C3, C3-C4, T4, T4-T5, C3-T6, T4-T7, L3, L1-L5) on available scans for the duration of follow-up. Data were fitted using a mixed-effects multivariable regression model, including follow-up time, CSI dose, age at CSI, and pretreatment VB percentile as parameters., Results: Median follow-up was 69.6 months for patients treated with proton CSI and 52.9 months for the control group. There was a significant association of CSI dose, follow-up time, age at treatment, and pretreatment VB percentile with VB growth retardation. Growth retardation was shown to be independent of gender or growth hormone deficiency., Conclusions: Although the current practice of PRT CSI delivery allows for sparing of the organs anterior to the spine, the vertebral column receives radiation therapy because of its close proximity to the targeted spinal canal. In growing children, the whole VB has generally been included so that growth impairment is even across the VB. We present a quantitative model predicting the growth retardation of patients treated with PRT CSI based on age at treatment, CSI dose, follow-up time, and pretreatment growth percentile., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Few studies report outcomes in children treated with radiation for nonmyxopapillary ependymoma of the spinal cord, and little evidence exists to inform decisions regarding target volume and prescription dose. Moreover, virtually no mature outcome data exist on proton therapy for this tumor. We describe our combined institutional experience treating pediatric classical/anaplastic ependymoma of the spinal cord with proton therapy., Methods and Materials: Between 2008 and 2019, 14 pediatric patients with nonmetastatic nonmyxopapillary grade II (n = 6) and grade III (n = 8) spinal ependymoma received proton therapy. The median age at radiation was 14 years (range, 1.5-18 years). Five tumors arose within the cervical cord, 3 within the thoracic cord, and 6 within the lumbosacral cord. Before radiation therapy, 3 patients underwent subtotal resection, and 11 underwent gross-total or near total resection. Two patients received chemotherapy. For radiation, the clinical target volume received 50.4 Gy (n = 8), 52.2 (n = 1), or 54 Gy (n = 5), with the latter receiving a boost to the gross tumor volume after the initial 50.4 Gy, modified to respect spinal cord tolerance., Results: With a median follow-up of 6.3 years (range, 1.5-14.8 years), no tumors progressed. Although most patients experienced neurologic sequela after surgery, only 1 developed additional neurologic deficits after radiation: An 18-year-old male who received 54 Gy after gross total resection of a lumbosacral tumor developed grade 2 erectile dysfunction. There were 2 cases of musculoskeletal toxicity attributable to surgery and radiation. At analysis, no patient had developed cardiac, pulmonary, or other visceral organ complications or a second malignancy., Conclusion: Radiation to a total dose of 50 to 54 Gy can be safely delivered and plays a beneficial role in the multidisciplinary management of children with nonmyxopapillary spinal cord ependymoma. Proton therapy may reduce late radiation effects and is not associated with unexpected spinal cord toxicity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Radiation therapy (RT) is used for pediatric craniopharyngioma in the definitive, adjuvant, or salvage settings. Proton RT may be useful owing to tumor proximity to eloquent anatomy. We report clinical outcomes for a large cohort treated with proton therapy., Methods: We conducted a retrospective review of pediatric patients (≤21 years) treated with surgery and proton therapy for craniopharyngioma between August 2002 and October 2018. Clinical characteristics, treatment course, and outcomes were recorded. Acute toxicity was graded using Common Terminology Criteria for Adverse Events, version 5.0. Late toxicity was assessed using neuroendocrine, neuro-ophthalmologic, and neuropsychological testing., Results: Among 77 patients, median age at diagnosis was 8.6 years (range, 1.3-20); median age at radiation was 9.6 years (range, 2.3-20.5). Most common presenting symptoms were headache (58%), visual impairment (55%), and endocrinopathy (40%). Patients underwent a median of 2 surgical interventions (range, 1-7) before protons. At initial surgery, 18% had gross total resection, 60% had subtotal resection, and 22% had biopsy/cyst decompression. Median RT dose was 52.2 Gy (relative biologic effectiveness). Common acute toxicities were headache (29%), fatigue (35%), and nausea/vomiting (12%). Only 4% developed any acute grade 3 toxicity. Nine patients experienced cyst growth requiring replanning or surgical decompression. At a median of 4.8 years from RT (range, 0.8-15.6), there were 6 local failures and 3 deaths, 2 related to disease progression. Effect of tumor and treatment contributed to late toxicity including Moyamoya syndrome (13%), visual impairment (40%), and endocrine deficiency requiring hormone replacement (94%). Subclinical decline in functional independence and adaptive skills in everyday life was detected at follow-up., Conclusions: Surgery and proton therapy results in excellent disease control for pediatric craniopharyngioma. Severe acute toxicity is rare. Late toxicities from tumor, surgery, and radiation remain prevalent. Endocrine and ophthalmology follow-up is necessary, and neuropsychological testing may identify patients at risk for treatment-related cognitive and adaptive functioning changes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Decreased peripheral lymphocyte counts are associated with survival after radiation therapy (RT) in several solid tumors, although they appear late during or after the radiation course and often correlate with other clinical factors. Here we investigate if absolute lymphocyte counts (ALCs) are independently associated with recurrence in pediatric medulloblastoma early during RT., Methods and Materials: We assessed 202 patients with medulloblastoma treated between 2000 and 2016 and analyzed ALC throughout therapy, focusing on both early markers (ALC during week 1 - ALC wk1 ; grade 3+ Lymphopenia during week 2 - Lymphopenia wk2 ) and late markers (ALC nadir). Uni- and multivariable regressions were used to assess association of clinical and treatment variables with ALC and of ALC with recurrence., Results: Thirty-six recurrences were observed, with a median time to recurrence of 1.6 years (range, 0.2-10.3) and 7.1 years median follow-up. ALC during RT was associated with induction chemotherapy (P < .001), concurrent carboplatin (P = .009), age (P = .01), and high-risk status (P = .05). On univariable analysis, high-risk disease (hazard ratio = 2.0 [1.06-3.9]; P = .03) and M stage≥1 (hazard ratio = 2.2 [1.1-4.4]) were associated with recurrence risk, as was lower ALC early during RT (ALC wk1 , hazard ratio = 0.28 [0.12-0.65]; P = .003; Lymphopenia wk2 , hazard ratio = 2.27 [1.1-4.6]; P = .02). Neither baseline ALC nor nadir correlated with outcome. These associations persisted when excluding carboplatin and pre-RT chemotherapy patients, and in the multivariable analysis accounting for confounders lymphocyte counts remained significant (ALC wk1 , hazard-ratio = 0.23 [0.09-0.57]; P = .002; Lymphopenia wk2 , hazard-ratio = 2.3 [1.1-4.8]; P = .03)., Conclusions: ALC during weeks 1 and 2 of RT was associated with recurrence, and low ALC is an independent prognostic factor in medulloblastoma. Strategies to mitigate the risk of radiation-induced lymphopenia should be considered., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To report the long-term efficacy and toxicity of proton therapy for pediatric ependymoma., Methods and Materials: Between 2000 and 2019, 386 children with nonmetastatic grade 2/3 intracranial ependymoma received proton therapy at 1 of 2 academic institutions. Median age at treatment was 3.8 years (range, 0.7-21.3); 56% were male. Most (72%) tumors were in the posterior fossa and classified as World Health Organization grade 3 (65%). Eighty-five percent had a gross total or near total tumor resection before radiation therapy; 30% received chemotherapy. Median radiation dose was 55.8 Gy relative biologic effectiveness (RBE) (range, 50.4-59.4)., Results: Median follow-up was 5.0 years (range, 0.4-16.7). The 7-year local control, progression-free survival, and overall survival rates were 77.0% (95% confidence interval [CI], 71.9%-81.5%), 63.8% (95% CI, 58.0%-68.8%), and 82.2% (95% CI, 77.2%-86.3%), respectively. Subtotal resection was associated with inferior local control (59% vs 80%; P < .005), progression-free survival (48% vs 66%; P < .001), and overall survival (70% vs 84%; P < .05). Male sex was associated with inferior progression-free (60% vs 69%; P < .05) and overall survival (76% vs 89%; P < .05). Posterior fossa tumor site was also associated with inferior progression-free (59% vs 74%; P < .05) and overall survival (79% vs 89%; P < .01). Twenty-one patients (5.4%) required hearing aids; of these, 13 received cisplatin, including the 3 with bilateral hearing loss. Forty-five patients (11.7%) required hormone replacement, typically growth hormone (38/45). The cumulative incidence of grade 2+ brain stem toxicity was 4% and occurred more often in patients who received >54 GyRBE. Two patients (0.5%) died of brain stem necrosis. The second-malignancy rate was 0.8%., Conclusion: Proton therapy offers disease control commensurate with modern photon therapy without unexpected toxicity. The high rate of long-term survival justifies efforts to reduce radiation exposure in this young population. Independent of radiation modality, this large series confirms extent of resection as the most important modifiable factor for survival., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Radiation therapy is integral in treatment of pediatric brain tumors, but it is associated with negative long-term sequelae. Proton beam radiation therapy (PRT), which enables better focusing of radiation on tumors, may entail fewer sequelae. This prospective study examined cognitive and adaptive functioning in children and young adults treated with PRT., Methods and Materials: A total of 155 patients were assessed using age-appropriate measures for cognitive and adaptive functioning at start of or during PRT (baseline) and at follow-up. Mean age at baseline was 8.9 years; mean follow-up interval was 3.6 years. Diagnoses included medulloblastoma, craniopharyngioma, ependymoma, glial tumors, germ cell tumors, and others. The sample was divided by age at baseline (<6 years [N = 57, or 37%] and ≥6 years [N = 98, or 63%]) and by PRT field (craniospinal irradiation [CSI; 39%] and focal irradiation [61%])., Results: Scores for mean intelligence quotient (IQ) and adaptive functioning skills were in the average range at baseline and follow-up. Overall, mean IQ scores declined from 105.4 to 102.5 (P = .005); however, only the younger CSI group showed significant decline. Patients receiving CSI, regardless of age, appeared particularly vulnerable in IQ, processing speed, and working memory. Adaptive skills were stable across the 4 age-by-treatment field groups., Conclusions: At a mean of 3.6 years after PRT, IQ declined slightly for the group, largely because of significant IQ decline in younger patients treated with CSI. No significant change was seen in patients <6 years treated with focal PRT or in older patients. Adaptive skills remained stable across age and treatment type., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: While cranial irradiation is often essential to attain a cure for pediatric brain tumors, it is associated with adverse neurocognitive outcomes, primarily manifested as declines in full-scale IQ (FSIQ). This decline results primarily from a decline in processing speed, a component of FSIQ. However, estimated IQ (EIQ) is frequently used in research and clinical settings but does not incorporate processing speed. We hypothesized that EIQ systematically underestimates neurocognitive sequelae in irradiated pediatric brain tumor survivors., Methods and Materials: We treated 185 pediatric brain tumor patients with proton radiation therapy. All patients had at least 1 neuropsychological evaluation at baseline and/or 1 or more follow-up evaluations with sufficient data to calculate both FSIQ and EIQ. The Wechsler Intelligence Scales were used to calculate FSIQ and EIQ for each patient, and mixed linear models were used to assess disparities between FSIQ and EIQ., Results: At baseline, EIQ was 2.2 points (95% confidence interval 1.2-3.2 points) higher on average than FSIQ (P < .001). The median follow-up period was 26 months. The disparity between EIQ and FSIQ persisted and worsened over time (P = .012), with FSIQ losing on average 0.4 points/year (95% confidence interval 0.01-0.8 points/year) relative to EIQ. The disparity at baseline varied with sex and age., Conclusions: EIQ systematically underestimates the neurocognitive sequelae of children treated with cranial radiation therapy. FSIQ is much more likely than EIQ to identify neurocognitive deficits, allowing for appropriate interventions, as well as academic services and accommodations. Thus, EIQ should have a very limited role in both clinical and research settings for this population., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Proton radiation therapy is commonly used in young children with brain tumors for its potential to reduce late effects. However, some proton series report higher rates of brainstem injury (0%-16%) than most photon series (2.2%-8.6%). We report the incidence of brainstem injury and a risk factor analysis in pediatric patients with posterior fossa primary tumors treated with proton radiation therapy at our institution., Methods and Materials: The study included 216 consecutive patients treated between 2000 and 2015. Dosimetry was available for all but 4 patients. Grade 2 to 5 late brainstem toxicity was assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0., Results: The histologies include medulloblastoma (n=154, 71.3%), ependymoma (n=56, 25.9%), and atypical teratoid rhabdoid tumor (n=6, 2.8%). The median age at irradiation was 6.6 years (range, 0.5-23.1 years); median dose, 54 gray relative biological effectiveness (Gy RBE) (range, 46.8-59.4 Gy RBE); and median follow-up period, 4.2 years (range, 0.1-15.3 years) among 198 survivors. Of the patients, 83.3% received chemotherapy; 70.4% achieved gross total resection. The crude rate of injury was 2.3% in all patients, 1.9% in those with medulloblastoma, 3.6% in those with ependymoma, and 0% in those with atypical teratoid rhabdoid tumor. The 5-year cumulative incidence of injury was 2.0% (95% confidence interval, 0.7%-4.8%). The median brainstem dose (minimum dose received by 50% of brainstem) in the whole cohort was 53.6 Gy RBE (range, 16.5-56.8 Gy RBE); maximum point dose within the brainstem (D max ), 55.2 Gy RBE (range, 48.4-60.5 Gy RBE); and mean dose, 50.4 Gy RBE (range, 21.1-56.7 Gy RBE). In the 5 patients with injury, the median minimum dose received by 50% of the brainstem was 54.6 Gy RBE (range, 50.2-55.1 Gy RBE); D max , 56.2 Gy RBE (range, 55.0-57.1 Gy RBE); mean dose, 51.3 Gy RBE (range, 45.4-54.4 Gy RBE); and median volume of the brainstem receiving ≥55 Gy RBE (V 55 ), 27.4% (range, 0%-59.4%). Of the 5 patients with injury, 4 had a brainstem D max in the highest quartile (≥55.8 Gy RBE, P = .016) and a V 55 in the highest tertile (>6.0%) of the cohort distribution (P = .047). Of the 5 patients with injury, 3 were aged >6 years (age range, 4.1-22.8 years), and 4 of 5 patients received chemotherapy and achieved gross total resection., Conclusions: The incidence of injury in pediatric patients with posterior fossa tumors is consistent with previous reports in the photon setting. Our data suggest that when D max and V 55 are kept <55.8 Gy RBE and ≤6.0%, respectively, the 5-year rate of radiation brainstem injury would be <2%., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: At present, proton craniospinal irradiation (CSI) for growing children is delivered to the whole vertebral body (WVB) to avoid asymmetric growth. We aimed to demonstrate the feasibility and potential clinical benefit of delivering vertebral body sparing (VBS) versus WVB CSI with passively scattered (PS) and intensity modulated proton therapy (IMPT) in growing children treated for medulloblastoma., Methods and Materials: Five plans were generated for medulloblastoma patients, who had been previously treated with CSI PS proton radiation therapy: (1) single posteroanterior (PA) PS field covering the WVB (PS-PA-WVB); (2) single PA PS field that included only the thecal sac in the target volume (PS-PA-VBS); (3) single PA IMPT field covering the WVB (IMPT-PA-WVB); (4) single PA IMPT field, target volume including thecal sac only (IMPT-PA-VBS); and (5) 2 posterior-oblique (-35°, +35°) IMPT fields, with the target volume including the thecal sac only (IMPT2F-VBS). For all cases, 23.4 Gy (relative biologic effectiveness [RBE]) was prescribed to 95% of the spinal canal. The dose, linear energy transfer, and variable-RBE-weighted dose distributions were calculated for all plans using the tool for particle simulation, version 2, Monte Carlo system., Results: IMPT VBS techniques efficiently spared the anterior vertebral bodies (AVBs), even when accounting for potential higher variable RBE predicted by linear energy transfer distributions. Assuming an RBE of 1.1, the V10 Gy(RBE) decreased from 100% for the WVB techniques to 59.5% to 76.8% for the cervical, 29.9% to 34.6% for the thoracic, and 20.6% to 25.1% for the lumbar AVBs, and the V20 Gy(RBE) decreased from 99.0% to 17.8% to 20.0% for the cervical, 7.2% to 7.6% for the thoracic, and 4.0% to 4.6% for the lumbar AVBs when IMPT VBS techniques were applied. The corresponding percentages for the PS VBS technique were higher., Conclusions: Advanced proton techniques can sufficiently reduce the dose to the vertebral body and allow for vertebral column growth for children with central nervous system tumors requiring CSI. This was true even when considering variable RBE values. A clinical trial is planned for VBS to the thoracic and lumbosacral spine in growing children., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Central nervous system (CNS) injury is a rare complication of radiation therapy for pediatric brain tumors, but its incidence with proton radiation therapy (PRT) is less well defined. Increased linear energy transfer (LET) and relative biological effectiveness (RBE) at the distal end of proton beams may influence this risk. We report the incidence of CNS injury in medulloblastoma patients treated with PRT and investigate correlations with LET and RBE values., Methods and Materials: We reviewed 111 consecutive patients treated with PRT for medulloblastoma between 2002 and 2011 and selected patients with clinical symptoms of CNS injury. Magnetic resonance imaging (MRI) findings for all patients were contoured on original planning scans (treatment change areas [TCA]). Dose and LET distributions were calculated for the treated plans using Monte Carlo system. RBE values were estimated based on LET-based published models., Results: At a median follow-up of 4.2 years, the 5-year cumulative incidence of CNS injury was 3.6% for any grade and 2.7% for grade 3+. Three of 4 symptomatic patients were treated with a whole posterior fossa boost. Eight of 10 defined TCAs had higher LET values than the target but statistically nonsignificant differences in RBE values (P=.12)., Conclusions: Central nervous system and brainstem injury incidence for PRT in this series is similar to that reported for photon radiation therapy. The risk of CNS injury was higher for whole posterior fossa boost than for involved field. Although no clear correlation with RBE values was found, numbers were small and additional investigation is warranted to better determine the relationship between injury and LET., (Published by Elsevier Inc.)

Purpose: The purpose of this study was to compare long-term disease control and overall survival between children treated with proton and photon radiation therapy (RT) for standard-risk medulloblastoma., Methods and Materials: This multi-institution cohort study includes 88 children treated with chemotherapy and proton (n=45) or photon (n=43) RT between 2000 and 2009. Overall survival (OS), recurrence-free survival (RFS), and patterns of failure were compared between the 2 cohorts., Results: Median (range) age was 6 years old at diagnosis (3-21 years) for proton patients versus 8 years (3-19 years) for photon patients (P=.011). Cohorts were similar with respect to sex, histology, extent of surgical resection, craniospinal irradiation (CSI) RT dose, total RT dose, whether the RT boost was delivered to the posterior fossa (PF) or tumor bed (TB), time from surgery to RT start, or total duration of RT. RT consisted of a median (range) CSI dose of 23.4 Gy (18-27 Gy) and a boost of 30.6 Gy (27-37.8 Gy). Median follow-up time is 6.2 years (95% confidence interval [CI]: 5.1-6.6 years) for proton patients versus 7.0 years (95% CI: 5.8-8.9 years) for photon patients. There was no significant difference in RFS or OS between patients treated with proton versus photon RT; 6-year RFS was 78.8% versus 76.5% (P=.948) and 6-year OS was 82.0% versus 87.6%, respectively (P=.285). On multivariate analysis, there was a trend for longer RFS with females (P=.058) and higher CSI dose (P=.096) and for longer OS with females (P=.093). Patterns of failure were similar between the 2 cohorts (P=.908)., Conclusions: Disease control with proton and photon radiation therapy appears equivalent for standard risk medulloblastoma., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To report, from a longitudinal study, cognitive outcome in pediatric patients treated with proton radiation therapy (PRT) for central nervous system (CNS) tumors., Methods and Materials: Sixty patients receiving PRT for medulloblastoma (38.3%), gliomas (18.3%), craniopharyngioma (15.0%), ependymoma (11.7%), and other CNS tumors (16.7%) were administered age-appropriate measures of cognitive abilities at or near PRT initiation (baseline) and afterward (follow-up). Patients were aged ≥ 6 years at baseline to ensure consistency in neurocognitive measures., Results: Mean age was 12.3 years at baseline; mean follow-up interval was 2.5 years. Treatment included prior surgical resection (76.7%) and chemotherapy (61.7%). Proton radiation therapy included craniospinal irradiation (46.7%) and partial brain radiation (53.3%). At baseline, mean Wechsler Full Scale IQ was 104.6; means of all 4 Index scores were also in the average range. At follow-up, no significant change was observed in mean Wechsler Full Scale IQ, Verbal Comprehension, Perceptual Reasoning/Organization, or Working Memory. However, Processing Speed scores declined significantly (mean 5.2 points), with a significantly greater decline for subjects aged <12 years at baseline and those with the highest baseline scores. Cognitive outcome was not significantly related to gender, extent of radiation, radiation dose, tumor location, histology, socioeconomic status, chemotherapy, or history of surgical resection., Conclusions: Early cognitive outcomes after PRT for pediatric CNS tumors are encouraging, compared with published outcomes from photon radiation therapy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Local control remains a challenge in pediatric parameningeal rhabdomyosarcoma (PM-RMS), and survival after local failure (LF) is poor. Identifying patients with a high risk of LF is of great interest to clinicians. In this study, we examined whether tumor response to induction chemotherapy (CT) could predict LF in embryonal PM-RMS., Methods: We identified 24 patients with embryonal PM-RMS, age 2 to 18 years, with complete magnetic resonance imaging and gross residual disease after surgical resection. All patients received proton radiation therapy (RT), median dose 50.4 GyRBE (50.4-55.8 GyRBE). Tumor size was measured before initial CT and before RT., Results: With a median follow-up time of 4.1 years for survivors, LF was seen in 9 patients (37.5%). The median time from the initiation of CT to the start of RT was 4.8 weeks. Patients with LF had a similar initial (pre-CT) tumor volume compared with patients with local controlled (LC) (54 cm(3) vs 43 cm(3), P=.9) but a greater median volume before RT (pre-RT) (40 cm(3) vs 7 cm(3), P=.009) and a smaller median relative percent volume reduction (RPVR) in tumor size (0.4% vs 78%, P<.001). Older age (P=.05), larger pre-RT tumor volume (P=.03), and smaller RPVR (P=.003) were significantly associated with actuarial LF on univariate Cox analysis., Conclusions: Poor response to induction CT appears to be associated with an increased risk of LF in pediatric embryonal PM-RMS., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To investigate long-term disease and toxicity outcomes for pediatric retinoblastoma patients treated with proton radiation therapy (PRT)., Methods and Materials: This is a retrospective analysis of 49 retinoblastoma patients (60 eyes) treated with PRT between 1986 and 2012., Results: The majority (84%) of patients had bilateral disease, and nearly half (45%) had received prior chemotherapy. At a median follow-up of 8 years (range, 1-24 years), no patients died of retinoblastoma or developed metastatic disease. The post-PRT enucleation rate was low (18%), especially in patients with early-stage disease (11% for patients with International Classification for Intraocular Retinoblastoma [ICIR] stage A-B disease vs 23% for patients with ICIR stage C-D disease). Post-PRT ophthalmologic follow-up was available for 61% of the preserved eyes (30 of 49): 14 of 30 eyes (47%) had 20/40 visual acuity or better, 7 of 30 (23%) had moderate visual acuity (20/40-20/600), and 9 of 30 (30%) had little or no useful vision (worse than 20/600). Twelve of 60 treated eyes (20%) experienced a post-PRT event requiring intervention, with cataracts the most common (4 eyes). No patients developed an in-field second malignancy., Conclusions: Long-term follow-up of retinoblastoma patients treated with PRT demonstrates that PRT can achieve high local control rates, even in advanced cases, and many patients retain useful vision in the treated eye. Treatment-related ocular side effects were uncommon, and no radiation-associated malignancies were observed., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose/objective(s): Primary low-grade gliomas are common brain tumors of childhood, many of which require radiation therapy (RT) as definitive treatment. Increased conformality of RT could decrease the incidence and severity of late effects. We report our experience with 32 pediatric patients treated with proton RT., Methods and Materials: Thirty-two pediatric patients with low-grade gliomas of the brain or spinal cord were treated with proton RT from 1995 to 2007. Sixteen patients received at least 1 regimen of chemotherapy before definitive RT. The median radiation dose was 52.2 GyRBE (48.6-54 GyRBE)., Results: The median age at treatment was 11.0 years (range, 2.7-21.5 years), with a median follow-up time of 7.6 years (range, 3.2-18.2 years). The 6-year and 8-year rates of progression-free survival were 89.7% and 82.8%, respectively, with an 8-year overall survival of 100%. For the subset of patients who received serial neurocognitive testing, there were no significant declines in Full-Scale Intelligence Quotient (P=.80), with a median neurocognitive testing interval of 4.5 years (range, 1.2-8.1 years) from baseline to follow-up, but subgroup analysis indicated some significant decline in neurocognitive outcomes for young children (<7 years) and those with significant dose to the left temporal lobe/hippocampus. The incidence of endocrinopathy correlated with a mean dose of ≥40 GyRBE to the hypothalamus, pituitary, or optic chiasm. Stabilization or improvement of visual acuity was achieved in 83.3% of patients at risk for radiation-induced injury to the optic pathways., Conclusions: This report of late effects in children with low-grade gliomas after proton RT is encouraging. Proton RT appears to be associated with good clinical outcome, especially when the tumor location allows for increased sparing of the left temporal lobe, hippocampus, and hypothalamic-pituitary axis., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: The pattern of failure in medulloblastoma patients treated with proton radiation therapy is unknown. For this increasingly used modality, it is important to ensure that outcomes are comparable to those in modern photon series. It has been suggested this pattern may differ from photons because of variations in linear energy transfer (LET) and relative biological effectiveness (RBE). In addition, the use of matching fields for delivery of craniospinal irradiation (CSI) may influence patterns of relapse. Here we report the patterns of failure after the use of protons, compare it to that in the available photon literature, and determine the LET and RBE values in areas of recurrence., Methods and Materials: Retrospective review of patients with medulloblastoma treated with proton radiation therapy at Massachusetts General Hospital (MGH) between 2002 and 2011. We documented the locations of first relapse. Discrete failures were contoured on the original planning computed tomography scan. Monte Carlo calculation methods were used to estimate the proton LET distribution. Models were used to estimate RBE values based on the LET distributions., Results: A total of 109 patients were followed for a median of 38.8 months (range, 1.4-119.2 months). Of the patients, 16 experienced relapse. Relapse involved the supratentorial compartment (n=8), spinal compartment (n=11), and posterior fossa (n=5). Eleven failures were isolated to a single compartment; 6 failures in the spine, 4 failures in the supratentorium, and 1 failure in the posterior fossa. The remaining patients had multiple sites of disease. One isolated spinal failure occurred at the spinal junction of 2 fields. None of the 70 patients treated with an involved-field-only boost failed in the posterior fossa outside of the tumor bed. We found no correlation between Monte Carlo-calculated LET distribution and regions of recurrence., Conclusions: The most common site of failure in patients treated with protons for medulloblastoma was outside of the posterior fossa. The most common site for isolated local failure was the spine. We recommend consideration of spinal imaging in follow-up and careful attention to dose distribution in the spinal junction regions. Development of techniques that do not require field matching may be of benefit. We did not identify a direct correlation between lower LET values and recurrence in medulloblastoma patients treated with proton therapy. Patterns of failure do not appear to differ from those in patients treated with photon therapy., (Published by Elsevier Inc.)

Purpose: To report the early outcomes for very young children with medulloblastoma or supratentorial primitive neuroectodermal tumor (SPNET) treated with upfront chemotherapy followed by 3-dimensional proton radiation therapy (3D-CPT)., Methods and Materials: All patients aged <60 months with medulloblastoma or SPNET treated with chemotherapy before 3D-CPT from 2002 to 2010 at our institution were included. All patients underwent maximal surgical resection, chemotherapy, and adjuvant 3D-CPT with either craniospinal irradiation followed by involved-field radiation therapy or involved-field radiation therapy alone., Results: Fifteen patients (median age at diagnosis, 35 months) were treated with high-dose chemotherapy and 3D-CPT. Twelve of 15 patients had medulloblastoma; 3 of 15 patients had SPNET. Median time from surgery to initiation of radiation was 219 days. Median craniospinal irradiation dose was 21.6 Gy (relative biologic effectiveness); median boost dose was 54.0 Gy (relative biologic effectiveness). At a median of 39 months from completion of radiation, 1 of 15 was deceased after a local failure, 1 of 15 had died from a non-disease-related cause, and the remaining 13 of 15 patients were alive without evidence of disease recurrence. Ototoxicity and endocrinopathies were the most common long-term toxicities, with 2 of 15 children requiring hearing aids and 3 of 15 requiring exogenous hormones., Conclusions: Proton radiation after chemotherapy resulted in good disease outcomes for a small cohort of very young patients with medulloblastoma and SPNET. Longer follow-up and larger numbers of patients are needed to assess long-term outcomes and late toxicity., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: Proton radiation, when compared with photon radiation, allows delivery of increased radiation dose to the tumor while decreasing dose to adjacent critical structures. Given the recent expansion of proton facilities in the United States, the long-term sequelae of proton therapy should be carefully assessed. The objective of this study was to compare the incidence of second cancers in patients treated with proton radiation with a population-based cohort of matched patients treated with photon radiation., Methods and Materials: We performed a retrospective cohort study of 558 patients treated with proton radiation from 1973 to 2001 at the Harvard Cyclotron in Cambridge, MA and 558 matched patients treated with photon therapy in the Surveillance, Epidemiology, and End Results (SEER) Program cancer registry. Patients were matched by age at radiation treatment, sex, year of treatment, cancer histology, and site. The main outcome measure was the incidence of second malignancies after radiation., Results: We matched 558 proton patients with 558 photon patients from the Surveillance, Epidemiology, and End Results registry. The median duration of follow-up was 6.7 years (interquartile range, 7.4) and 6.0 years (interquartile range, 9.3) in the proton and photon cohorts, respectively. The median age at treatment was 59 years in each cohort. Second malignancies occurred in 29 proton patients (5.2%) and 42 photon patients (7.5%). After we adjusted for sex, age at treatment, primary site, and year of diagnosis, proton therapy was not associated with an increased risk of second malignancy (adjusted hazard ratio, 0.52 [95% confidence interval, 0.32-0.85]; P=.009)., Conclusions: The use of proton radiation therapy was not associated with a significantly increased risk of secondary malignancies compared with photon therapy. Longer follow-up of these patients is needed to determine if there is a significant decrease in second malignancies. Given the limitations of the study, these results should be viewed as hypothesis generating., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: Atypical teratoid/rhabdoid tumor (AT/RT) is an uncommon and aggressive tumor that often affects infants. Irradiation improves survival but has traditionally been avoided in patients under the age of 3 due to the increasing risk of neurocognitive side effects. We report the first cohort of AT/RT patients treated with proton therapy., Methods and Materials: All patients with AT/RT treated at Massachusetts General Hospital (MGH) Frances H. Burr Proton Beam Therapy Benter between July 2004 and November 2011 were included in this study. All patients were treated with 3-dimensional conformal proton therapy (3D-CPT)., Results: Ten consecutive patients of a median 2.3 years of age and with a median follow-up of 27.3 months (range, 11.3-99.4 months) were identified. Two patients suffered distant relapse; 1 patient was successfully treated with involved field irradiation and chemotherapy, while the second patient died of disease. At last follow-up, 9 patients were alive without evidence of disease. Proton radiation demonstrated increasing sparing of the cerebrum, temporal lobe, cochlea, and hypothalamus., Conclusions: Initial clinical outcomes with proton therapy are favorable. The advantages of proton therapy are particularly suited to the treatment of AT/RT, a tumor that often requires irradiation treatment at an age when avoiding irradiation to healthy tissues is most desirable., (Copyright © 2013. Published by Elsevier Inc.)

Purpose: Proton radiotherapy (PT) has been prescribed similarly to photon radiotherapy to achieve comparable disease control rates at comparable doses. The chief advantage of protons in this setting is to reduce acute and late toxicities by decreasing the amount of normal tissue irradiated. We report the preliminary clinical outcomes including late effects on our pediatric Ewing's sarcoma patients treated with PT at the Francis H. Burr Proton Therapy Center at Massachusetts General Hospital (Boston, MA)., Methods and Materials: This was a retrospective review of the medical records of 30 children with Ewing's sarcoma who were treated with PT between April 2003 and April 2009., Results: A total of 14 male and 16 female patients with tumors in several anatomic sites were treated with PT at a median age of 10 years. The median dose was 54 Gy (relative biological effectiveness) with a median follow-up of 38.4 months. The 3-year actuarial rates of event-free survival, local control, and overall survival were 60%, 86%, and 89%, respectively. PT was acutely well tolerated, with mostly mild-to-moderate skin reactions. At the time of writing, the only serious late effects have been four hematologic malignancies, which are known risks of topoisomerase and anthracyline exposure., Conclusions: Proton radiotherapy was well tolerated, with few adverse events. Longer follow-up is needed to more fully assess tumor control and late effects, but the preliminary results are encouraging., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To report the clinical outcome and late side effect profile of proton radiotherapy in the treatment of children with parameningeal rhabdomyosarcoma (PM-RMS)., Methods and Materials: Seventeen consecutive children with PM-RMS were treated with proton radiotherapy at Massachusetts General Hospital between 1996 and 2005. We reviewed the medical records of all patients and asked referring physicians to report specific side effects of interest., Results: Median patient age at diagnosis was 3.4 years (range, 0.4-17.6). Embryonal (n = 11), alveolar (n = 4), and undifferentiated (n = 2) histologies were represented. Ten patients (59%) had intracranial extension. Median prescribed dose was 50.4 cobalt gray equivalents (GyRBE) (range, 50.4-56.0 GyRBE) delivered in 1.8-2.0-GyRBE daily fractions. Median follow-up was 5.0 years for survivors. The 5-year failure-free survival estimate was 59% (95% confidence interval, 33-79%), and overall survival estimate was 64% (95% confidence interval, 37-82%). Among the 7 patients who failed, sites of first recurrence were local only (n = 2), regional only (n = 2), distant only (n = 2), and local and distant (n = 1). Late effects related to proton radiotherapy in the 10 recurrence-free patients (median follow-up, 5 years) include failure to maintain height velocity (n = 3), endocrinopathies (n = 2), mild facial hypoplasia (n = 7), failure of permanent tooth eruption (n = 3), dental caries (n = 5), and chronic nasal/sinus congestion (n = 2)., Conclusions: Proton radiotherapy for patients with PM-RMS yields tumor control and survival comparable to that in historical controls with similar poor prognostic factors. Furthermore, rates of late effects from proton radiotherapy compare favorably to published reports of photon-treated cohorts., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: In this study, we report the clinical outcomes of 7 children with bladder/prostate rhabdomyosarcoma (RMS) treated with proton radiation and compare proton treatment plans with matched intensity-modulated radiation therapy (IMRT) plans, with an emphasis on dose savings to reproductive and skeletal structures., Methods and Materials: Follow-up consisted of scheduled clinic appointments at our institution or direct communication with the treating physicians for referred patients. Each proton radiotherapy plan used for treatment was directly compared to an IMRT plan generated for the study. Clinical target volumes and normal tissue volumes were held constant to facilitate dosimetric comparisons. Each plan was optimized for target coverage and normal tissue sparing., Results: Seven male patients were treated with proton radiotherapy for bladder/prostate RMS at the Massachusetts General Hospital between 2002 and 2008. Median age at treatment was 30 months (11-70 months). Median follow-up was 27 months (10-90 months). Four patients underwent a gross total resection prior to radiation, and all patients received concurrent chemotherapy. Radiation doses ranged from 36 cobalt Gray equivalent (CGE) to 50.4 CGE. Five of 7 patients were without evidence of disease and with intact bladders at study completion. Target volume dosimetry was equivalent between the two modalities for all 7 patients. Proton radiotherapy led to a significant decrease in mean organ dose to the bladder (25.1 CGE vs. 33.2 Gy; p=0.03), testes (0.0 CGE vs. 0.6 Gy; p=0.016), femoral heads (1.6 CGE vs. 10.6 Gy; p=0.016), growth plates (21.7 CGE vs. 32.4 Gy; p=0.016), and pelvic bones (8.8 CGE vs. 13.5 Gy; p=0.016) compared to IMRT., Conclusions: This study provides evidence of significant dose savings to normal structures with proton radiotherapy compared to IMRT and is well tolerated in this patient population. The long-term impact of these reduced doses can be tested in future studies incorporating extended follow-up, objective outcome measures, and quality-of-life analyses., (Copyright © 2011. Published by Elsevier Inc.)

Purpose: To report early clinical outcomes for children with central nervous system (CNS) germ cell tumors treated with protons; to compare dose distributions for intensity-modulated photon radiotherapy (IMRT), three-dimensional conformal proton radiation (3D-CPT), and intensity-modulated proton therapy with pencil beam scanning (IMPT) for whole-ventricular irradiation with and without an involved-field boost., Methods and Materials: All children with CNS germinoma or nongerminomatous germ cell tumor who received treatment at the Massachusetts General Hospital between 1998 and 2007 were included in this study. The IMRT, 3D-CPT, and IMPT plans were generated and compared for a representative case., Results: Twenty-two patients were treated with 3D-CPT. At a median follow-up of 28 months, there were no CNS recurrences; 1 patient had a recurrence outside the CNS. Local control, progression-free survival, and overall survival rates were 100%, 95%, and 100%, respectively. Comparable tumor volume coverage was achieved with IMRT, 3D-CPT, and IMPT. Substantial normal tissue sparing was seen with any form of proton therapy as compared with IMRT. The use of IMPT may yield additional sparing of the brain and temporal lobes., Conclusions: Preliminary disease control with proton therapy compares favorably to the literature. Dosimetric comparisons demonstrate the advantage of proton radiation over IMRT for whole-ventricle radiation. Superior dose distributions were accomplished with fewer beam angles utilizing 3D-CPT and scanned protons. Intensity-modulated proton therapy with pencil beam scanning may improve dose distribution as compared with 3D-CPT for this treatment., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: We compared tumor and normal tissue dosimetry of proton radiation therapy with intensity-modulated radiation therapy (IMRT) for pediatric parameningeal rhabdomyosarcomas (PRMS)., Methods and Materials: To quantify dosimetric differences between contemporary proton and photon treatment for pediatric PRMS, proton beam plans were compared with IMRT plans. Ten patients treated with proton radiation therapy at Massachusetts General Hospital had IMRT plans generated. To facilitate dosimetric comparisons, clinical target volumes and normal tissue volumes were held constant. Plans were optimized for target volume coverage and normal tissue sparing., Results: Proton and IMRT plans provided acceptable and comparable target volume coverage, with at least 99% of the CTV receiving 95% of the prescribed dose in all cases. Improved dose conformality provided by proton therapy resulted in significant sparing of all examined normal tissues except for ipsilateral cochlea and mastoid; ipsilateral parotid gland sparing was of borderline statistical significance (p = 0.05). More profound sparing of contralateral structures by protons resulted in greater dose asymmetry between ipsilateral and contralateral retina, optic nerves, cochlea, and mastoids; dose asymmetry between ipsilateral and contralateral parotids was of borderline statistical significance (p = 0.05)., Conclusions: For pediatric PRMS, superior normal tissue sparing is achieved with proton radiation therapy compared with IMRT. Because of enhanced conformality, proton plans also demonstrate greater normal tissue dose distribution asymmetry. Longitudinal studies assessing the impact of proton radiotherapy and IMRT on normal tissue function and growth symmetry are necessary to define the clinical consequences of these differences.

Purpose: Craniopharyngiomas are benign, slow-growing tumors that frequently contain a cystic component. Even with gross total resection, the cyst can reform and cause symptoms. Fluctuations in cyst volume during radiotherapy (RT) can affect treatment planning and delivery. The aim of this study was to report our experience with cyst enlargement during conformal proton RT for children with craniopharyngioma and to make recommendations regarding mid-treatment surveillance., Methods and Materials: Between January 2001 and August 2007, 24 children (aged

Purpose: To evaluate the risk of breast cancer (BC) and the contributing risk factors in women after supradiaphragmatic irradiation (SDI) for Hodgkin's lymphoma (HL)., Subjects and Methods: Medical records of 248 women 60 years of age or less who received SDI for stage I/II HL between 1964 and 2001 at Massachusetts General Hospital were retrospectively reviewed., Results: The median age at SDI was 26 years (range, 5.7-59.3). The median follow-up was 15.2 years (range, 0.1-41.3). In 36 patients, BC developed (bilaterally in 11 patients) at a median interval of 18.4 years (range, 4.3-33.8) after SDI. Based on data from the National Cancer Institute Surveillance, Epidemiology, and End Results program, the standardized morbidity ratio (SMR) for the first BC after SDI was 9.78 (95% confidence interval [CI], 4.64-18.11, p < 0.0001). The SMR of patients who received radiation before age of 30 years was 19.05 (95% CI, 12.33-28.13) compared with 4.64 (95% CI, 2.31-8.30) for patients aged 30 years or more at the time of treatment (p < 0.00003). Risk for BC was significantly higher 15 years or more after SDI compared with the risk during the first 15 years (p = 0.0026). None of HL characteristics or treatment details was associated with higher risk of BC after adjusting for age and calendar time., Conclusions: Age at irradiation and time since therapy appear to be the only significant risk factors for development of BC after treatment of HL. The risk is significantly higher 15 years or more after radiation and for women treated before age 30 years. Long-term surveillance strategies are indicated for women at risk.

Purpose: To report preliminary clinical outcomes for pediatric patients treated with proton beam radiation for intracranial ependymoma and compare the dose distributions of intensity-modulated radiation therapy with photons (IMRT), three-dimensional conformal proton radiation, and intensity-modulated proton radiation therapy (IMPT) for representative patients., Methods and Materials: All children with intracranial ependymoma confined to the supratentorial or infratentorial brain treated at the Francis H. Burr Proton Facility and Harvard Cyclotron between November 2000 and March 2006 were included in this study. Seventeen patients were treated with protons. Proton, IMRT, and IMPT plans were generated with similar clinical constraints for representative infratentorial and supratentorial ependymoma cases. Tumor and normal tissue dose-volume histograms were calculated and compared., Results: At a median follow-up of 26 months from the start date of radiation therapy, local control, progression-free survival, and overall survival rates were 86%, 80%, and 89%, respectively. Subtotal resection was significantly associated with decreased local control (p = 0.016). Similar tumor volume coverage was achieved with IMPT, proton therapy, and IMRT. Substantial normal tissue sparing was seen with proton therapy compared with IMRT. Use of IMPT will allow for additional sparing of some critical structures., Conclusions: Preliminary disease control with proton therapy compares favorably with the literature. Dosimetric comparisons show the advantage of proton radiation compared with IMRT in the treatment of ependymoma. Further sparing of normal structures appears possible with IMPT. Superior dose distributions were accomplished with fewer beam angles with the use of protons and IMPT.

Purpose: To evaluate the effect of angle modification of cranial field proton beam therapy on the radiation dose delivered to the lens during craniospinal irradiation (CSI)., Methods and Materials: Thirty-nine patients with central nervous system tumors who received CSI with a posterior fossa boost were analyzed for the radiation dose to the lens. Thirteen patients received cranial field treatment using standard opposed-lateral proton beams, and 26 patients received treatment with angled posterior-oblique proton beams. The lens dose in a test case also was evaluated by comparing conventional X-rays with the two proton beam planning methods by using a CMS/Xio three-dimensional planning system., Results: Substantial lens dose sparing was realized with the angling of the cranial proton beams 15 degrees -20 degrees to the posterior. In the 39 treated patients who were analyzed (median age, 7 years), average dose delivered to the lens was decreased by approximately 50% by angling of the proton beams, with the average maximum dose decreasing from 74% to 40% of the prescribed dose (p < 0.0001). Significant lens sparing was seen in patients 10 years and younger (median age, 6 years; p < 0.0001), whereas an insignificant decrease was seen in older patients (median age, 16 years; p = 0.14). With the opposed-lateral technique (median age, 6 years), the lens dose increased significantly with decreasing age (p = 0.002), whereas there was no effect of age on lens dose in the angled beam-treated group (median age, 8.5 years; p = 0.73)., Conclusion: The present study clearly shows an advantage in sparing of the lens dose by angling the beams used during proton beam CSI. This effect is most pronounced in patients 10 years and younger because of anatomic effects of sinus development.

Purpose: Children with medulloblastoma undergo surgery, radiotherapy, and chemotherapy. After treatment, these children have numerous structural abnormalities. Using high-resolution magnetic resonance imaging, we measured the thickness of the cerebral cortex in a group of medulloblastoma patients and a group of normally developing children., Methods and Materials: We obtained magnetic resonance imaging scans and measured the cortical thickness in 9 children after treatment of medulloblastoma. The measurements from these children were compared with the measurements from age- and gender-matched normally developing children previously scanned. For additional comparison, the pattern of thickness change was compared with the cortical thickness maps from a larger group of 65 normally developing children., Results: In the left hemisphere, relatively thinner cortex was found in the perirolandic region and the parieto-occipital lobe. In the right hemisphere, relatively thinner cortex was found in the parietal lobe, posterior superior temporal gyrus, and lateral temporal lobe. These regions of cortical thinning overlapped with the regions of cortex that undergo normal age-related thinning., Conclusion: The spatial distribution of cortical thinning suggested that the areas of cortex that are undergoing development are more sensitive to the effects of treatment of medulloblastoma. Such quantitative methods may improve our understanding of the biologic effects that treatment has on the cerebral development and their neuropsychological implications.

Purpose: Fatty replacement of bone marrow resulting from radiation therapy can be seen on T1-weighted magnetic resonance (MR) images. We evaluated the radiographic appearance of the vertebral bodies in children treated with proton craniospinal irradiation (CSI) to illustrate the distal edge effect of proton radiotherapy., Methods and Materials: The study cohort consisted of 13 adolescents aged 12-18 years who received CSI with proton radiotherapy at Massachusetts General Hospital. Ten of these patients had reached maximal or near-maximal growth. Proton beam radiation for these 10 patients was delivered to the thecal sac and exiting nerve roots only, whereas the remaining 3 patients had a target volume that included the thecal sac, exiting nerve roots, and entire vertebral bodies. Median CSI dose was 27 [range, 23.4-36] cobalt gray equivalent (CGE) given in 1.8-CGE fractions. Magnetic resonance images of the spine were obtained after completion of radiotherapy., Results: Magnetic resonance images of patients who received proton radiotherapy to the thecal sac only demonstrate a sharp demarcation of hyperintense T1-weighted signal in the posterior aspects of the vertebral bodies, consistent with radiation-associated fatty marrow replacement. Magnetic resonance images of the patients prescribed proton radiotherapy to the entire vertebral column had corresponding hyperintense T1-weighted signal involving the entire vertebral bodies., Conclusion: The sharp delineation of radiation-associated fatty marrow replacement in the vertebral bodies demonstrates the rapid decrease in energy at the edge of the proton beam. This provides evidence for a sharp fall-off in radiation dose and supports the premise that proton radiotherapy spares normal tissues unnecessary irradiation.

Purpose: To evaluate the potential influence of radiotherapy quality on survival in high-risk pediatric medulloblastoma patients., Methods and Materials: Trial 9031 of the Pediatric Oncology Group (POG) aimed to study the relative benefit of cisplatin and etoposide randomization of high-risk patients with medulloblastoma to preradiotherapy vs. postradiotherapy treatment. Two-hundred and ten patients were treated according to protocol guidelines and were eligible for the present analysis. Treatment volume (whole brain, spine, posterior fossa, and primary tumor bed) and dose prescription deviations were assessed for each patient. An analysis of first site of failure was undertaken. Event-free and overall survival rates were calculated. A log-rank test was used to determine the significance of potential survival differences between patients with and without major deviations in the radiotherapy procedure., Results: Of 160 patients who were fully evaluable for all treatment quality parameters, 91 (57%) had 1 or more major deviations in their treatment schedule. Major deviations by treatment site were brain (26%), spinal (7%), posterior fossa (40%), and primary tumor bed (17%). Major treatment volume or total dose deviations did not significantly influence overall and event-free survival., Conclusions: Despite major treatment deviations in more than half of fully evaluable patients, underdosage or treatment volume misses were not associated with a worse event-free or overall survival.

Purpose: To evaluate the efficacy of stereotactic radiotherapy (SRT) for small, localized, pediatric brain tumors and to determine the patterns of failure., Methods and Materials: A total of 81 patients were enrolled in an institutional review board-approved prospective Dana-Farber Cancer Institute protocol between 1992 and 1998. Of the 81 patients, 50 had low-grade astrocytoma, 23 had residual or recurrent craniopharyngioma, 4 had posterior fossa ependymoma, and 4 had other histologic types. All patients underwent biopsy for diagnosis, with the exception of patients with neurofibromatosis and radiographic evidence of an optic system tumor. The neurocognitive outcome for all patients was also an endpoint of the study and will be reported separately. This report focused on the patients with low-grade gliomas only. Of the 50 patients, 26 were males and 24 females; the median age was 9 years (range, 2-26 years). The indications for treatment of patients with low-grade gliomas were progression during or after chemotherapy or progression after surgery alone. SRT was delivered using a dedicated 6-MV linear accelerator. Immobilization was accomplished with a removable head-frame. CT and MRI fusion was used for treatment planning. The target volume generally included the preoperative tumor plus a 2-mm margin for the planning target volume. The median collimator size was 47.25 mm (range, 30-60 mm). Three to nine arcs were used to deliver a mean total dose of 52.2 Gy in 1.8-Gy daily fractions., Results: With a median follow-up of 6.9 years (range, 0.9-10.2 years), the progression-free survival rate was 82.5% at 5 years and 65% at 8 years. The overall survival was 97.8% at 5 years and 82% at 8 years. Six patients had local progression. Two of the patients with local progression had pathologic progression to anaplastic astrocytoma 3 and 7 years after initial SRT. Five patients, all with optic system/hypothalamic primary tumors, developed central nervous system dissemination 1.0-7.4 years after SRT. One patient developed a presumed radiation-induced primitive neuroectodermal tumor 6 years after initial treatment. Six patients died, three of dissemination, two of progression to higher grade tumors, and one of a secondary radiation-induced tumor. All 6 cases of local progression were within the primary tumor bed at the time of progression and had received the full prescription dose. No marginal failures occurred., Conclusion: Stereotactic radiotherapy provides excellent local control for children with small, localized low-grade glial tumors. Marginal failures have not been observed, supporting the use of limited margins to minimize late sequelae using stereotactic immobilization and planning techniques.

Purpose: To study the optimization of proton beam arrangements for various intraocular tumor locations; and to correlate isodose distributions with various target and nontarget structures., Methods and Materials: We considered posterior-central, nasal, and temporal tumor locations, with straight, intrarotated, or extrarotated eye positions. Doses of 46 cobalt grey equivalent (CGE) to gross tumor volume (GTV) and 40 CGE to clinical target volume (CTV) (2 CGE per fraction) were assumed. Using three-dimensional planning, we compared isodose distributions for lateral, anterolateral oblique, and anteromedial oblique beams and dose-volume histograms of CTVs, GTVs, lens, lacrimal gland, bony orbit, and soft tissues., Results: All beam arrangements fully covered GTVs and CTVs with optimal lens sparing. Only 15% of orbital bone received doses > or =20 CGE with a lateral beam, with 20-26 CGE delivered to two of three growth centers. The anterolateral oblique approach with an intrarotated eye resulted in additional reduction of bony volume and exposure of only one growth center. No appreciable dose was delivered to the contralateral eye, brain tissue, or pituitary gland., Conclusions: Proton therapy achieved homogeneous target coverage with true lens sparing. Doses to orbit structures, including bony growth centers, were minimized with different beam arrangements and eye positions. Proton therapy could reduce the risks of second malignancy and cosmetic and functional sequelae.

Purpose: To develop a dose-response relationship for the occurrence of permanent alopecia after cranial irradiation and to analyze potential confounding variables that may contribute to this unwanted and often unavoidable complication of treatment., Methods and Materials: Twenty-six patients were enrolled in this study. Three reviewers independently assessed 61 scalp regions and assigned a score for the degree of alopecia in each region using a 4-point scale. Patient and treatment data were collected using a patient questionnaire and outpatient medical chart review. The hair follicle dose was calculated for each scalp region and correlated with the alopecia score for that region. A dose-response relationship was established using the data from these correlations., Results: Permanent alopecia correlated significantly with the follicle dose only (p < 0.001). A personal history of alopecia and the use of chemotherapy correlated with permanent alopecia with borderline statistical significance (p = 0.059 and p = 0.068, respectively). Patient age, family history of baldness, gender, tobacco use, diabetes, and beam energy did not correlate with alopecia., Conclusion: We report the first human dose-response relationship describing the effect of the follicle dose on the subsequent development of permanent scalp alopecia after cranial irradiation. This information will assist the radiation oncologist, physicist, and dosimetrist in designing a treatment plan that might minimize the risk of this untoward side effect of cranial irradiation.

Purpose: To analyze the sites of relapse, relapse-free survival, and overall survival in children with Group III rhabdomyosarcoma treated with or without radiotherapy (RT)., Methods and Materials: The outcomes of 48 children with Group III rhabdomyosarcoma treated between 1980 and 1997 were evaluated. The median overall survival follow-up was 7.3 years. Of the 48 patients, 65% had embryonal histology. Local treatment after induction chemotherapy included complete surgical resection (CSR) alone in 9 (19%), CSR plus RT in 13 (27%), partial resection or rebiopsy plus RT in 10 (21%), and RT alone in 15 patients (31%). One child developed distant disease before completing local therapy., Results: Of the 48 patients, 12 developed relapse at local (n = 3), regional (n = 4), or distant (n = 5) sites. All 9 patients treated with CSR after induction chemotherapy had embryonal/botryoid histology. Only 1 of these 9 patients developed relapse. No statistically significant difference was found in overall survival (p = 0.95) or relapse-free survival (p = 0.67) between patients treated with or without RT. The Kaplan-Meier estimate of 5-year overall survival and relapse-free survival was 76% +/- 7% and 74% +/- 7%, respectively. Significant predictors of relapse-free survival on univariate analysis included CSR (p = 0.03), nodal positivity (p = 0.001), and embryonal histology (p = 0.0003). On multivariate analysis, embryonal histology was the most significant predictor of relapse-free (p = 0.001) and overall (p = 0.01) survival., Conclusion: The overall survival for children with Group III rhabdomyosarcoma in this series was favorable. Embryonal/botryoid histology was the most significant predictor of both overall and relapse-free survival. We found that for a selected subgroup of children with embryonal histology, induction chemotherapy followed by complete surgical resection alone may be adequate local therapy.

Purpose: To compare treatment plans from standard photon therapy to intensity modulated X-rays (IMRT) and protons for craniospinal axis irradiation and posterior fossa boost in a patient with medulloblastoma., Methods: Proton planning was accomplished using an in-house 3D planning system. IMRT plans were developed using the KonRad treatment planning system with 6-MV photons., Results: Substantial normal-tissue dose sparing was realized with IMRT and proton treatment of the posterior fossa and spinal column. For example, the dose to 90% of the cochlea was reduced from 101.2% of the prescribed posterior fossa boost dose from conventional X-rays to 33.4% and 2.4% from IMRT and protons, respectively. Dose to 50% of the heart volume was reduced from 72.2% for conventional X-rays to 29.5% for IMRT and 0.5% for protons. Long-term toxicity with emphasis on hearing and endocrine and cardiac function should be substantially improved secondary to nontarget tissue sparing achieved with protons., Conclusion: The present study clearly demonstrates the advantage of conformal radiation methods for the treatment of posterior fossa and spinal column in children with medulloblastoma, when compared to conventional X-rays. Of the two conformal treatment methods evaluated, protons were found to be superior to IMRT.

Purpose: To evaluate the clinical behavior and treatment outcome of ocular adnexal lymphomas classified by the World Health Organization system, with emphasis on marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT)., Materials and Methods: The clinicopathologic materials from 98 consecutive patients treated for ocular adnexal lymphoma were reviewed. Fourteen patients had prior lymphoma and 84 patients had primary disease (75% Stage I, 6% Stage III, and 19% Stage IV). Radiation (photons/electrons) was administered to 102 eyes to a median dose of 30.6 Gy. The mean follow-up was 82 months., Results: The most common subtypes among the primary patients were MALT (57%) and follicular (18%) lymphoma. The 5-year actuarial local control rate in 102 irradiated eyes was 98%. Among the low-grade lymphomas, the 5-year local control rate correlated with the radiation dose in the MALT lymphoma subgroup (n = 53): 81% for <30 Gy and 100% for > or =30 Gy (p <0.01). For the non-MALT low-grade lymphomas such as follicular lymphoma (n = 30), the local control rate was 100% regardless of dose. For 39 Stage I MALT lymphoma patients treated with radiation alone, the distant relapse-free survival rate was 75% at 5 years and 45% at 10 years. Distant relapses were generally isolated and successfully salvaged by local therapy. The overall survival for this subgroup was 81% at 10 years, with no deaths from lymphoma., Conclusions: Dose-response data suggest that the optimal radiation dose for MALT lymphoma of the ocular adnexa is 30.6-32.4 Gy in 1.8-Gy fractions and follicular lymphoma is adequately controlled with doses in the mid-20 Gy range. The substantial risk of distant relapse in Stage I ocular adnexal MALT lymphoma underscores the importance of long-term follow-up for this disease and the need for additional comparative studies of MALT lymphoma of different anatomic sites.

Purpose: To determine the toxicity and maximum tolerated dose of etanidazole administered concurrently with hyperfractionated radiation therapy (HRT) for children with brainstem glioma., Methods and Materials: Eighteen patients with brainstem glioma were treated with etanidazole and HRT on a dose escalation protocol (Phase I trial) between 1990 and 1996. All patients had MRI confirmation of diffuse pontine glioma and signs/symptoms of cranial nerve deficit, ataxia, or long tract signs of <6 months' duration. Cervicomedullary tumors were excluded. Patients (median age: 8.5 years; 11 males, 7 females) received HRT to the tumor volume plus a 2-cm margin with parallel-opposed 6-15-MV photons. The total dose was 66 Gy in 44 fractions (1.5 Gy b.i.d., with at least 6 h between fractions) for the first 3 patients and 63 Gy in 42 fractions for the subsequent 15 patients. Etanidazole was administered as a rapid i.v. infusion 30 min before the morning fraction of HRT. Planned doses of etanidazole were 1.8 g/m(2) x 17 doses (30.6 g/m(2)) at Step 1 to a maximum of 2.4 g/m(2) x 21 doses (50.4 g/m(2)) at Step 8. Dose escalation was planned with 3 patients at each of the 8 levels., Results: Three patients were treated at each dose level except Level 2, on which only 1 patient was treated. The highest dose level achieved was Level 7, which delivered a total etanidazole dose of 46.2 g/m(2). Two patients were treated at this level, and both patients experienced Grade 3 toxicity in the form of a diffuse cutaneous rash. Three patients received a lower dose of 42 g/m(2) (dose Level 6) without significant toxicity, and this represents the maximum tolerated dose (MTD). There were 23 cases of Grade 1 toxicity (10 vomiting, 5 peripheral neuropathy, 2 rash, 2 constipation, 1 weight loss, 3 others), 11 cases of Grade 2 toxicity (4 vomiting, 2 skin erythema, 2 constipation, 1 arthralgia, 1 urinary retention, 1 hematologic), and 4 Grade 3 toxicities (2 rash, 1 vomiting, 1 skin desquamation). Grade 2 or 3 peripheral neuropathy was not seen at any dose level. The median survival from the start of treatment was 8.5 months (range: 3-58 months)., Conclusion: The MTD of etanidazole in children receiving HRT for brainstem glioma is 42 g/m(2), with cutaneous rash as the dose-limiting toxicity. This is in contrast to the adult experience, which demonstrates a 24% lower MTD of 34 g/m(2) limited by peripheral neuropathy.

Purpose: Intracranial germ cell tumors are rare, radiosensitive tumors seen most commonly in the second and third decades of life. Radiotherapy alone has been the primary treatment modality for germinomas, and is used with chemotherapy for nongerminomatous tumors. Stereotactic radiotherapy techniques minimize the volume of surrounding normal tissue irradiated and, hence, the late radiation morbidity. This study reports our experience with stereotactic radiotherapy in this group of tumors., Methods and Materials: Between December 1992 and December 1998, 18 patients with intracranial germ cell tumors were treated with stereotactic radiotherapy. A total of 23 histologically proven tumors were treated. Thirteen patients had a histologic diagnosis of germinoma, and 5 patients had germinoma with nongerminomatous elements. Of those patients with a histologic diagnosis of germinoma, 5 had multiple midline tumors. The median age of the patients was 12.9 years (range, 5.6-17.5 years)., Results: A boost using stereotactic radiotherapy was delivered to 19 tumors following whole-brain radiation in 8 cases and craniospinal radiation in 11 cases. Three tumors were treated with stereotactic radiotherapy to the tumor volume alone following chemotherapy, and 1 tumor received a boost using stereotactic radiosurgery following craniospinal radiation. A median dose of 2520 cGy (range, 1500-3600) cGy was given to the whole brain, and a median dose of 2160 (range, 2100-2600) cGy was given to the spinal field. The median boost dose to the tumor was 2600 (range, 2160-3600) cGy, given by stereotactic radiotherapy delivered to the 95% isodose line. At a median follow-up time of 40 (range, 12-73) months, no local or marginal recurrences were reported in patients with germinoma. Two patients with nongerminomatous tumors have relapsed. One had elevation of tumor markers only at 37 months following treatment, and the other had persistent disease following chemotherapy and radiation therapy. Eight patients documented pituitary-hypothalamic dysfunction; in 7 (87.5%) of these patients, the dysfunction was present before commencing radiotherapy. Four patients (22%) developed newly diagnosed diabetes insipidus following surgery. Three patients (17%) received antidepressant medication at follow-up., Conclusion: Our series shows that stereotactic radiotherapy is achievable and well tolerated in this group of patients. Longer follow-up is required to fully assess the impact on long-term toxicity. Psychologic assessment of mood and affect should be performed as part of routine follow-up in this group of adolescent children.

Objective: To describe the outcome of pediatric brain tumor patients following stereotactic radiosurgery (SRS), and factors associated with progression-free survival., Methods: We reviewed the outcome of 90 children treated with SRS for recurrent (n = 62) or residual (n = 28) brain tumors over a 10-year period. Median follow-up from SRS was 24 months for all patients and 55.5 months for the 34 patients currently alive., Results: The median progression-free survival (PFS) for all patients was 13 months. Median PFS according to tumor histology was medulloblastoma = 11 months, ependymoma = 8.5 months, glioblastoma and anaplastic astrocytoma = 12 months. Median PFS in patients treated to a single lesion was 15.4 months. No patient undergoing SRS to more than 1 lesion survived disease free beyond 2 years. After adjusting for histology and other clinical factors, SRS for tumor recurrence (RR = 2.49) and the presence of > 1 lesion (RR = 2.3) were associated with a significantly increased rate of progression (p < 0.05). Three-year actuarial local control (LC) was as follows: medulloblastoma = 57%, ependymoma = 29%, anaplastic astrocytoma/glioblastoma = 60%, other histologies = 56%. Nineteen patients with radionecrosis and progressive neurologic symptoms underwent reoperation after an interval of 0.6-62 months following SRS. Pathology revealed necrosis with no evidence of tumor in 9 of these cases., Conclusion: SRS can be given safely to selected children with brain tumors. SRS appears to reduce the proportion of first failures occurring locally and is associated with better outcome when given as a part of initial management. Some patients with unresectable relapsed disease can be salvaged with SRS. SRS to multiple lesions does not appear to be curative. Serious neurologic symptoms requiring reoperation is infrequently caused by radionecrosis alone.

Purpose: Patients with relapsed acute myelogenous leukemia (AML), who are not eligible for bone marrow transplantation, have a poor prognosis when treated with chemotherapy alone. Total body irradiation (TBI) is an effective modality against AML when used in doses of 1000-1400 cGy with hematopoietic stem cell support. We undertook a phase I study of TBI with granulocyte-colony-stimulating factor (G-CSF) support, without stem cell support in patients with AML either in relapse or second or subsequent remission., Methods and Materials: Patients with relapsed AML, or AML in second or subsequent remission were treated in a phase I study of TBI followed by G-CSF. The first dose level was 200 cGy. After the initial cohort of patients it was clear that patients with overt leukemia did not benefit from this treatment, and subsequent patients were required to be in remission at the time of TBI., Results: Eleven patients were treated, 4 in overt relapse, and 7 in remission. 200 cGy was used in all, and dose escalation was not possible due to prolonged thrombocytopenia in all patients but one. Neutrophil recovery was adequate in those patients who remained in remission after TBI. Patients with overt leukemia had transient reduction in blast counts, but rapid recurrence of their leukemia. Patients treated in remission had short remissions, with the exception of one patient who is in remission 32 months after treatment., Conclusion: There is some antileukemic effect of TBI even at 200 cGy, though this dose appears to be too low to help a significant number of patients. If TBI is to be escalated without stem cell support, then a thrombopoietic agent will need to be used.

Purpose: In children with chiasmal gliomas, radiation therapy can arrest progressive visual and neurologic impairment. We examined the radiographic response and clinical outcomes after irradiation., Methods and Materials: Forty-two children (median age at diagnosis, 6.6 years) with chiasmal gliomas were managed as follows: 11 asymptomatic patients with neurofibromatosis-1 (NF-1) were observed only; 2 patients, less than 3 years old, underwent surgery and chemotherapy to delay irradiation; and 29 patients with progressive disease received radiation with or without prior surgery or chemotherapy. Time to radiographic response, long-term tumor control and late sequelae were reviewed for the 29 irradiated patients., Results: The probability of at least 50% radiographic response at 24 months after irradiation was 18.1% and increased to 38.2% by 48 months and 45.9% by 60 months. By actuarial analysis, the median time for such radiographic response was 62 months. For the 29 irradiated patients, the 10-year freedom from progression and overall survival rates were 100% and 89%, respectively (median follow-up for surviving patients, 108 months). Stabilization or improvement in vision occurred in 81% of 26 evaluable irradiated patients., Conclusions: Notable radiographic response may be observed years after irradiation. Radiation therapy provides excellent long-term tumor control and vision preservation or improvement in the majority of patients with progressive chiasmal gliomas.

Purpose: To examine the presentation, management, and outcome of patients with extensive intrathoracic involvement in early-stage Hodgkin's disease., Patients and Methods: One hundred seventy-two patients with clinical Stage IA-IIB Hodgkin's disease and extensive intrathoracic involvement were studied. Extensive intrathoracic disease was defined as either large mediastinal adenopathy (LMA, defined as the width of the mass greater than one-third the maximum thoracic diameter, n = 154) or as extensive (> 10 cm) cephalocaudad intrathoracic disease that did not fulfill formal chest radiograph criteria for LMA (n = 18). Patients were divided into three groups based on staging and extent of treatment. Forty-seven patients were treated with radiation alone after a laparotomy (RT-lap), 47 patients received combined modality therapy after laparotomy (CMT-lap), and 78 patients were treated with combined modality therapy without staging laparotomy (CMT-no lap). MOPP was used in 82% of the CMT patients. Low-dose whole-cardiac RT was used in nearly 50% of patients treated either with RT or CMT., Results: The 10-year actuarial freedom from relapse rates were 54% with RT alone and 88% with CMT (p = 0.001); overall survival rates were 84 and 89%, respectively (p = NS). The median time to relapse was only 17 months. Over 80% of relapses occurred within the first 3 years. The most common site of relapse in all patients was the mediastinum. Relapses below the diaphragm were rare, even in CMT patients who did not receive abdominal radiation treatment. The principal acute morbidity was symptomatic pneumonitis, which occurred in 29% of patients receiving any part of their chemotherapy after RT, compared to 13% if all the chemotherapy was given before RT and 11% if RT alone was administered. There was a low late risk of myocardial infarction (3%) in the two groups with the longest follow up (RT-lap, CMT-lap), but a higher risk of second malignancy in the CMT-lap group (21%) compared with the RT-lap group (2%)., Conclusion: Extensive intrathoracic involvement is a distinctive presentation of early-stage HD that has a high relapse risk if treated with RT alone. The introduction of CMT has been associated with improvements in freedom from relapse. The low rate of peripheral relapse with CMT suggests that reductions in field size may be achievable. The use of low-dose whole-heart RT with modern techniques is not associated with a high risk of late cardiac complications and should be used in patients who present with extensive pericardial disease or cardiophrenic lymphadenopathy. The high rate of second malignancy in the CMT group with the longest follow-up suggests that careful long-term surveillance for such patients is warranted.

Purpose: To determine the optimal dose and treatment outcome of patients treated with radiation for intracranial germinoma., Methods and Materials: Between 1975 and 1995, 40 patients with the diagnosis of intracranial germinoma were treated with radiation (RT) to the central nervous system. All patients received whole-brain (WB) RT (median dose: 32.4 Gy, range: 15-44.37 Gy) and a boost to the tumor volume (median total tumor volume dose: 52 Gy, range: 45-59.5 Gy). Thirty patients received RT to the spine (median dose: 26 Gy, range: 18.75-37.5 Gy). Four patients were treated with cisplatin-based chemotherapy and WB RT with a boost to the tumor volume (dose range: 51-54 Gy). A low-dose RT only group was defined as < or = 25.5 Gy to the WB (9 patients); < 50 Gy to the primary site (14 patients); and < 22 Gy to the spine (9 patients). Seventeen tumors were biopsy-proven germinoma, and 17 patients presented with multiple midline germinomas (MMG). Among 26 patients who had tumor markers measured, 27% had elevation of beta-human chorionic gonadotropin and by definition, no patient had an elevation of AFP. Twenty-four percent of 26 patients who had spine imaging or cerebral spinal fluid cytology had evidence of tumor seeding at diagnosis. The male to female ratio was 1.9:1. Median age at diagnosis was 14 years for male patients and 9.5 years for female patients (p = 0.02), (overall age ranges: 0.5-31 years). Median follow-up was 62 months (range: 3-226 months). Late effects of 29 patients with follow-up of > or = 20 months and adequate documentation in their medical records were analyzed., Results: The 5-year actuarial rate of disease-free survival (DFS) and overall survival (OS) for biopsy-proven germinomas and presumed germinomas was 97%. No patient died of germinoma. There were no local failures regardless of the dose of RT, elevation of HCG tumor marker, or CSF dissemination at presentation. At presentation 22 patients had evidence of at least one endocrine abnormality. At follow-up there were no new patients diagnosed with an endocrine abnormality; however, 13 out of 22 patients had an increase in the number of endocrine deficiencies requiring hormone replacement. At presentation, 14 patients showed evidence of growth retardation. At follow-up there were no new cases of growth failure in the remaining patients., Conclusions: Germinomas are highly curable with RT alone. Lower doses of RT to the craniospinal axis without chemotherapy appear to produce equally effective DFS and OS as do higher doses of RT or combination chemotherapy and RT. Craniospinal RT may be indicated for patients with MMG or patients with evidence of spinal seeding. Long-term effects of growth retardation, and other endocrine deficiencies appear to be correlated with disease at presentation rather than solely with treatment.

Purpose: The patient population treated with fractionated stereotactic radiotherapy (SRT) is significantly different than that treated with stereotactic radiosurgery (SRS). Generally, lesions treated with SRT are larger, less spherical, and located within critical regions of the central nervous system; hence, they offer new challenges to the treatment planner. Here a simple, cost effective, beam shaping system has been evaluated relative to both circular collimators and an ideal dynamically conforming system for effectiveness in providing conformal therapy for these lesions., Methods and Materials: We have modeled a simple system for conformal arc therapy using four independent jaws. The jaw positions and collimator angle are changed between arcs but held fixed for the duration of each arc. Eleven previously treated SRT cases have been replanned using this system. The rectangular jaw plans were then compared to the original treatment plans which used circular collimators. The plans were evaluated with respect to tissue sparing at 100%, 80%, 50%, and 20% of the prescription dose. A plan was also done for each tumor in which the beam aperture was continuously conformed to the beams eye view projection of the tumor. This was used as an ideal standard for conformal therapy in the absence of fluence modulation., Results: For tumors with a maximum extent of over 3.5 cm the rectangular jaw plans reduced the mean volume of healthy tissue involved at the prescription dose by 57% relative to the circular collimator plans. The ideal conformal plans offered no significant further improvement at the prescription dose. The relative advantage of the rectangular jaw plans decreased at lower isodoses so that at 20% of the prescription dose tissue involvement for the rectangular jaw plans was equivalent to that for the circular collimator plans. At these isodoses the ideal conformal plans gave substantially better tissue sparing., Conclusion: A simple and economical field shaping device has been shown to provide all of the beam shaping advantage of a hypothetical ideal dynamically conforming system at the prescription level. This system may be immediately implemented in the clinic. It offers a substantial advantage over the currently used circular collimators in the high dose region with equivalent performance in the low dose region.

Purpose: The purpose of this project was to review the brachytherapy experience in the pediatric population at the Joint Center for Radiation Therapy (JCRT) with respect to efficacy and morbidity., Methods and Materials: Treatment outcome was reviewed for 18 children between the ages of 6 months and 23 years who received 19 implants between 1982 and 1992 at JCRT. Fourteen children received permanent Iodine-125 seed implants placed in the operative tumor bed at the time of resection. Two children received sterotactically placed afterloaded high-activity I-125 seed brain implants, and one child received a high-activity I-125 brain implant followed by a permanent I-125 seed brain implants 3 years later. One girl received a temporary Iridium-192 volume implant for a vulvar rhabdomyosarcoma. Among the 15 permanent I-125 implants, the cases included five primary brain tumors, one metastatic brain tumor, six sarcomas, and one each of the following: suprarenal neuroblastoma, hepatoblastoma, and adenocarcinoma of the pancreas. All patients underwent surgery and most patients (15 out of 18) received external beam radiotherapy to a field that included the implant., Results: The median follow-up from the time of diagnosis for patients who remain alive is 55 months (range 24 to 119 months), and the median follow-up from the time of implant is 46 months (15 to 60 months). Disease was controlled in the area of the implant in 13 of 17 evaluable cases. Two patients experienced treatment-related morbidity; one patient developed severe desquamation related to an "adriamycin recall reaction," and one patient died of postoperative complications., Conclusion: Despite the heterogeneous mix of cases, the use of brachytherapy in this pediatric population resulted in several cases of long-term disease control, and the overall morbidity was very low. Therefore, in properly selected pediatric cases, brachytherapy appears to be an efficacious adjunct to multimodality cancer management.