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Purpose: The use of stereotactic body radiation therapy (SBRT) in pediatric patients has been underreported. We reviewed practice patterns, outcomes, and toxicity of SBRT in this population., Methods and Materials: In this multi-institutional study, 55 patients with 107 non-central nervous system lesions treated with SBRT between 2010 and 2016 were reviewed. Treatment response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and modified RECIST v1.1 criteria for soft-tissue and bone lesions, respectively. Patterns of local failure (LF) were assessed dosimetrically. The cumulative incidence of LF and toxicity were estimated accounting for the competing risk event of death. Predictors of LF were identified through joint frailty models for clustered competing risks., Results: The median (range) dose/fraction was 7 (4.5-25) Gy, the total (range) dose/site was 35 (12-45), and the median (range) number of fractions was 5 (1-9). The radiographic response rates of bone and soft-tissue lesions were 90.6% and 76.7%, respectively. Symptom improvement was observed for 62% of symptomatic sites. A total of 27 LFs were documented, with 14 in-field, 9 marginal, and 4 out-of-field LFs. The 1-year estimated cumulative LF rate, progression-free survival, and overall survival were 25.2% (95% confidence interval [CI], 17.2%-36.1%), 17.5% (95% CI, 9.0%-34.1%), and 61% (95% CI, 48.9%-76.1%), respectively. Lesion type (soft tissue vs bone) was the only significant predictor of LF on multivariable analysis (P = .04), with increased hazard for soft-tissue lesions. No acute or late toxicity of grade 4 or higher was observed; the estimated 1-year cumulative incidence of late toxicity of any grade was 7.5% (95% CI, 3.6%-12.1%)., Conclusions: The SBRT was well tolerated and resulted in radiographic response and symptom palliation in most pediatric patients with advanced disease. The 1-year cumulative LF rate of 25% will serve as a benchmark for further modifications to radiation therapy indications, parameters, and combination therapy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Pencil-beam scanning proton therapy is particularly sensitive to anatomic changes, which may affect the delivered dose distribution. This study examined whether offline adaptation using on-treatment magnetic resonance imaging (MRI) scan during proton therapy could improve plan quality for pediatric patients., Methods and Materials: Pediatric patients with at least 1 MRI scan in the treatment position (MRI tx ) during proton therapy between January 2017 and July 2019 were retrospectively reviewed. Patients underwent MRI and computed tomography simulation. Cases were planned with scenario-based optimization with 3 mm/3% positional/range uncertainty. Patients demonstrating anatomic change on MRI tx were recontoured. The original plans were applied to the anatomy-of-the-day for dose recalculation (delivered plans). Plans were subsequently reoptimized offline, using original beam angles and dose-volume constraints (adapted plans). Delivered plans were compared with adapted plans to detect significant changes in plan quality, defined as a ≥5% decrease in the clinical target volume (CTV) receiving 95% of the prescription dose (V95) or a ≥5% increase in the dose-volume parameter used as an organ-at-risk constraint., Results: Seventy-three pediatric patients were eligible, with 303 MRI scans (73 simulation and 230 MRI tx scans) available for analysis. The median MRI tx scans per patient was 3 (range, 1-7). Twenty patients (27%) showed anatomic change, with 11 (55%) demonstrating a significant change in delivered plan quality. Significant changes were noted on MRI tx from week 2 (n = 3) or week 3 (n = 8). Seven of these 11 patients (64%) had a significantly reduced CTV V95 (median decrease, 7.6%; range, 5%-16%). Four (36%) had a significantly increased dose to the brain stem, hippocampus, and/or optic apparatus. Eight had a suprasellar low-grade glioma or head and neck rhabdomyosarcoma., Conclusion: On-treatment MRI was useful in detecting anatomic changes during proton therapy. MRI-based offline adaptation improved plan quality for most patients with anatomic changes. Further studies should determine the clinical value of MRI-based adaptive therapy for pediatric patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Our purpose was to assess disease outcomes and late toxicities in pediatric patients with rhabdomyosarcoma treated with conformal photon radiation therapy (RT)., Methods and Materials: Sixty-eight patients (median age, 6.9 years) were treated with conformal photon RT to the primary site on a prospective clinical trial. Target volumes included a 1-cm expansion encompassing microscopic disease. Prescribed doses were 36 Gy to this target volume and 50.4 Gy to gross residual disease. Chemotherapy consisted of vincristine/dactinomycin (n = 6), vincristine/dactinomycin/cyclophosphamide (n = 37), or vincristine/dactinomycin/cyclophosphamide-based combinations (n = 25). Patients were evaluated with primary-site magnetic resonance imaging, whole-body [ 18 F]fluorodeoxyglucose positron emission tomography, and chest computed tomography for 5 years after treatment., Results: Five-year disease-free survival was 88% for low-risk (n = 8), 76% for intermediate-risk (n = 37), and 36% for high-risk (n = 23) patients (P ≤ .01 for low risk/intermediate risk vs high risk). The cumulative incidence of local failure (LF) at 5 years for the entire cohort was 10.4%. Tumor size at diagnosis was a significant predictor of LF (P < .01). Patients with head and neck primary tumors (n = 31) had a 35% cumulative incidence of cataracts; the risk correlated with lens dose (P = .0025). Jaw dysfunction was more severe when the pterygoid and masseter muscles received a mean dose of >20 Gy (P = .013). Orbital hypoplasia developed more frequently after a mean bony orbit dose of >30 Gy (P = .041). Late toxicity in patients with genitourinary tumors included microscopic hematuria (9 of 14), bladder-wall thickening (10 of 14), and vaginal stenosis (2 of 5)., Conclusions: Long-term LF rates were low, and higher rates correlated with larger tumors. Treatment-related toxicities resulting in measurable functional deficits were not infrequent, despite the conformal RT approach., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: This study aimed to report on the institutional outcomes after proton therapy for pelvic rhabdomyosarcoma (RMS)., Methods and Materials: Thirty-one children (≤21 years old) with group III pelvic RMS were enrolled on a prospective outcome study and treated between 2007 and 2018. Patients with vaginal/cervical RMS were excluded. The median age was 2.6 years. Twenty-four patients had embryonal RMS. At diagnosis, the median tumor volume was 185 cm 3 and the median maximum diameter was 9.4 cm. Seven patients had N1 disease. Nineteen and 12 patients received European Pediatric Soft Tissue Sarcoma Study Group- and Children's Oncology Group-based chemotherapy, respectively. Fourteen patients underwent resection of the primary tumor after induction chemotherapy, including 6 patients who had a total cystectomy. The median radiation dose was 50.4 Gy relative biological effectiveness., Results: With a median follow-up of 4.2 years, the 5-year local control, progression-free survival, and overall survival rates were 83%, 80%, and 84%, respectively. Patients <3 years old had better local control (100% vs 68%; P = .02), and patients with embryonal histology had better survival (96% vs 54%; P = .02). No other factors were significantly associated with disease control or survival. Specifically, no statistically significant difference was observed in local control, progression-free survival, or overall survival when comparing patients who underwent biopsy versus gross total resection (75% vs 93%, 68% vs 93%, 75% vs 93%, respectively). Excluding patients who underwent cystectomy, urinary toxicity was limited to 2 patients with nocturnal enuresis. Exploratory surgery to address a persistent mass or thickened bladder wall after radiation was the most common source of serious toxicity., Conclusions: This cohort of young children with large pelvic tumors treated with proton therapy demonstrates similar local control with less toxicity than historic reports. Functional bladder preservation is possible in most patients. Exploratory biopsy in the 18 months after radiation should be approached with caution., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To characterize respiration-induced abdominal organ motion in children receiving radiation treatment with a 4-dimensional (4D) magnetic resonance imaging (MRI) method., Methods and Materials: We analyzed free-breathing coronal 4D MRI datasets acquired from 35 patients (aged 1-20 years) with abdominal tumors. A deformable image registration of the 4D MRI datasets was performed to derive motion trajectories of selected anatomic landmarks, from which organ motions were quantified. The association between organ motion and patient characteristics was investigated and compared with previous studies. The relation between patient height and organ motion was further investigated to predict organ motion in prospective patients., Results: Organ motion and its individual variation were reduced in younger patients (eg, kidney peak-to-peak motion <5 mm for all but 1 patient aged ≤8 years), although special motion management may be warranted in some adolescents. The liver and spleen exhibited greater motion than did the kidneys, while intraorgan variation was present. The motions in the liver and kidneys agreed with those reported by the previous 4D computed tomography studies. Individual variations of organ motion in younger patients were due, in part, to changes in respiration rate, which ostensibly reflected the effect of anesthesia. The prediction of organ motion was limited by large individual variations, particularly for older patients., Conclusions: The 4D MRI acquisition method and motion analysis described in this study provide a nonionizing approach to understand age-associated organ motion, which aids in the planning of abdominal radiation therapy for pediatric patients. Use of 4D MRI facilitates monitoring of changes in target motion patterns during treatment courses and in various studies of the effect of organ motion on radiation treatment., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To determine the rate of local failure using focal conformal, limited margin radiation therapy (RT) and dose escalation for tumors ≥8 cm (greatest dimension at diagnosis) in children and young adults with Ewing sarcoma (EWS)., Methods and Materials: Eligible patients with EWS were treated on a phase 2 institutional trial of focal conformal, limited margin RT using conformal or intensity modulated techniques. The treatment volume incorporated a 1-cm constrained margin around the gross tumor. Unresected tumors, <8 cm at diagnosis, received a standard dose of 55.8 Gy and tumors ≥8 cm, an escalated dose to 64.8 Gy. Patients with microscopic residual disease after resection received adjuvant RT to 50.4 Gy. Adjuvant brachytherapy was permitted in selected patients., Results: Forty-five patients were enrolled: 26 with localized and 19 with metastatic disease. Median (range) age, tumor size, and follow-up were 13.0 years (2.9-24.7 years), 9.0 cm (2.4-17.0 cm), and 54.5 months (1.9-122.2 months), respectively. All patients received systemic chemotherapy. The median (range) RT dose for all patients was 56.1 Gy (45-65.5 Gy). Seventeen patients received adjuvant, 16 standard-dose, and 12 escalated-dose RT. Failures included 1 local, 10 distant, and 1 local/distant. The estimated 10-year cumulative incidence of local failure was 4.4% ± 3.1%, with no statistical difference seen between RT treatment groups and no local failures in the escalated-dose RT treatment group., Conclusions: Treatment with focal conformal, limited margin RT, including dose escalation for larger tumors, provides favorable local tumor control in EWS., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: Abdominal intensity-modulated radiation therapy and proton therapy require quantification of target and organ motion to optimize localization and treatment. Although addressed in adults, there is no available literature on this issue in pediatric patients. We assessed physiologic renal motion in pediatric patients., Methods and Materials: Twenty free-breathing pediatric patients at a median age of 8 years (range, 2-18 years) with intra-abdominal tumors underwent computed tomography simulation and four-dimensional computed tomography acquisition (slice thickness, 3 mm). Kidneys and diaphragms were contoured during eight phases of respiration to estimate center-of-mass motion. We quantified center of kidney mass mobility vectors in three dimensions: anteroposterior (AP), mediolateral (ML), and superoinferior (SI)., Results: Kidney motion decreases linearly with decreasing age and height. The 95% confidence interval for the averaged minima and maxima of renal motion in children younger than 9 years was 5-9 mm in the ML direction, 4-11 mm in the AP direction, and 12-25 mm in the SI dimension for both kidneys. In children older than 9 years, the same confidence interval reveals a widening range of motion that was 5-16 mm in the ML direction, 6-17 mm in the AP direction, and 21-52 mm in the SI direction. Although not statistically significant, renal motion correlated with diaphragm motion in older patients. The correlation between diaphragm motion and body mass index was borderline (r = 0.52, p = 0.0816) in younger patients., Conclusions: Renal motion is age and height dependent. Measuring diaphragmatic motion alone does not reliably quantify pediatric renal motion. Renal motion in young children ranges from 5 to 25 mm in orientation-specific directions. The vectors of motion range from 5 to 52 mm in older children. These preliminary data represent novel analyses of pediatric intra-abdominal organ motion., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To investigate the relationship between jaw function, patient and treatment variables, and radiation dosimetry of the mandibular muscles and joints in children and young adults receiving radiation for soft-tissue and bone sarcomas., Methods and Materials: Twenty-four pediatric and young adult patients with head-and-neck sarcomas were treated on an institutional review board-approved prospective study of focal radiation therapy for local tumor control. Serial jaw depression measurements were related to radiation dosimetry delivered to the medial and lateral pterygoid muscles, masseter muscles, and temporomandibular joints to generate mathematical models of jaw function., Results: Baseline jaw depression was only influenced by the degree of surgical resection. In the first 12 weeks from initiation of radiation, surgical procedures greater than a biopsy, administration of cyclophosphamide containing chemotherapy regimes, and large gross tumor volumes adversely affected jaw depression. Increasing dose to the pterygoid and masseter muscles above 40 Gy predicted loss of jaw function over the full course of follow-up., Conclusions: Clinical and treatment factors are related to initial and subsequent jaw dysfunction. Understanding these complex interactions and the affect of specific radiation doses may help reduce the risk for jaw dysfunction in future children and young adults undergoing radiation therapy for the management of soft-tissue and bone sarcomas., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To estimate radiation therapy planning margins based on inter- and intrafractional uncertainty for pediatric brain and head and neck tumor patients at different imaging frequencies., Methods: Pediatric patients with brain (n = 83) and head and neck (n = 17) tumors (median age = 7.2 years) were enrolled on an internal review board-approved localization protocol and stratified according to treatment position and use of anesthesia. Megavoltage cone-beam CT (CBCT) was performed before each treatment and after every other treatment. The pretreatment offsets were used to calculate the interfractional setup uncertainty (SU), and posttreatment offsets were used to calculate the intrafractional residual uncertainty (RU). The SU and RU are the patient-related components of the setup margin (SM), which is part of the planning target volume (PTV). SU data was used to simulate four intervention strategies using different imaging frequencies and thresholds., Results: The SM based on all patients treated on this study was 2.1 mm (SU = 0.9 mm, RU = 1.9 mm) and varied according to treatment position (supine = 1.8 mm, prone = 2.6 mm) and use of anesthesia (with = 1.7 mm, without = 2.5 mm) because of differences in the RU. The average SU for a 2-mm threshold based on no imaging, once per week imaging, initial five images, and daily imaging was 3.6, 2.1, 2.2, and 0.9 mm, respectively., Conclusion: On the basis of this study, the SM component of the PTV may be reduced to 2 mm for daily CBCT compared with 3.5 mm for weekly CBCT. Considering patients who undergo daily pretreatment CBCT, the SM is larger for those treated in the prone position or smaller for those treated under anesthesia because of differences in the RU., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To provide a radiation pneumonitis risk estimate and investigate the correlation of clinical and dosimetric factors in pediatric patients receiving chest irradiation., Methods and Materials: A total of 122 patients diagnosed with sarcoma or Hodgkin lymphoma who received radiotherapy to the chest were evaluated for symptomatic radiation pneumonitis (Common Toxicity Criteria Grade 1 with respiratory symptom or higher grade). Pneumonitis data were collected from either prospective toxicity screenings as part of a clinical trial or through chart review. Dosimetric parameters including V(10)-V(25), mean lung dose, binned lung dose, and tissue complication probability models were used, as well as clinical features to correlate with the development of pneumonitis., Results: The 1- and 2-year cumulative incidence of symptomatic radiation pneumonitis for all patients was 8.2% and 9.1%, respectively. Nine patients experienced symptomatic Grade 1 toxicity, and 2 experienced Grade 2. From univariate analysis, chemotherapy containing bleomycin (chi(2) test, p = 0.027) and V(24) (logistic regression, p = 0.019) were the clinical and dosimetric factors that resulted in statistically significant differences in the occurrence of pneumonitis. The probability of pneumonitis increased more dramatically with increasing V(24) in patients receiving bleomycin than in those who did not. Adult tissue complication models did not differentiate pediatric patients with radiation pneumonitis from those without., Conclusions: The incidence of symptomatic radiation pneumonitis in pediatric patients is low and its severity mild. Parameters frequently used in adult radiation oncology provide some guidance as to risk, but pediatric patients warrant their own specific models for risk assessment, incorporating dosimetry and clinical factors., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Purpose: There is renewed attention to primary site irradiation and local control for patients with high-risk neuroblastoma (NB). We conducted a retrospective review to identify factors that might predict for locoregional tumor control and its impact on overall survival., Methods and Materials: Between July 2000 through August 2006, a total of 44 pediatric patients with NB received radiation therapy (RT) with curative intent using computed tomography (CT)-based treatment planning. The median age was 3.4 years and the median cumulative dose was 23.4 Gy. Overall survival and locoregional tumor control were measured from the start of RT to the date of death or event as determined by CT/magnetic resonance imaging/meta-iodobenzylguanidine. The influence of age at irradiation, gender, race, cumulative radiation dose, International Neuroblastoma Staging System stage, treatment protocol and resection status was determined with respect to locoregional tumor control., Results: With a median follow-up of 34 months +/- 21 months, locoregional tumor progression was observed in 11 (25%) and was evenly divided between primary site and adjacent nodal/visceral site failure. The influence of locoregional control reached borderline statistical significance (p = 0.06). Age (p = 0.5), dose (p = 0.6), resection status (p = 0.7), and International Neuroblastoma Staging System stage (p = 0.08) did not influence overall survival., Conclusions: Overall survival in high-risk neuroblastoma is influenced by locoregional tumor control. Despite CT-based planning, progression in adjacent nodal/visceral sites appears to be common; this requires further investigation regarding target volume definitions, dose, and the effects of systemic therapy., (Copyright 2010 Elsevier Inc. All rights reserved.)

Purpose: To demonstrate the safety and efficacy of limited margin radiotherapy in the local control of pediatric and young adult patients with high-grade nonrhabdomyosarcoma soft tissue sarcoma (NRSTS)., Methods and Materials: Pediatric patients with high-grade NRSTS requiring radiation were treated on an institutional review board approved prospective institutional study of conformal/intensity-modulated/interstitial brachytherapy using a 2-cm anatomically constrained margin., Results: A total of 32 patients (median age, 15.3 years; range, 2-22 years) received adjuvant (27 patients) or definitive (5 patients) irradiation. With a median follow-up of 32 months, the 3-year cumulative incidence of local failure was 3.7% for patients undergoing irradiation after surgical resection. Four patients experienced local failure; the mean dose to the volume of recurrence was >or=97% of the prescribed dose., Conclusions: Delivery of limited margin radiotherapy using external beam or brachytherapy provides a high rate of local tumor control without marginal failure. Further follow-up is required to determine whether normal tissue effects are minimized using this approach., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Purpose: To estimate the effects of radiotherapy and clinical factors on vertebral growth in patients with medulloblastoma and supratentorial primitive neuroectodermal tumors treated with craniospinal irradiation (CSI) and chemotherapy., Methods and Materials: The height of eight individual or grouped vertebral bodies (C3, C3-C4, T4, T4-T5, C6-T3, T4-T7, L3, L1-L5) was measured before and after CSI (23.4 or 36-39.6 Gy) in 61 patients. Of the 61 patients, 40 were boys and 21 were girls (median age, 7 years; range, 3-13 years), treated between October 1996 and October 2003. Sagittal T(1)-weighted magnetic resonance images were used for the craniocaudal measurements. The measurements numbered 275 (median, 5/patient; range, 3-7). The median follow-up after CSI was 44.1 months (range, 13.8-74.9 months)., Results: Significant growth was observed in all measured vertebrae. Excluding C3-C4, the growth rate of the grouped vertebrae was affected by age, gender, and CSI dose (risk classification). The risk classification alone affected the growth rates of C3 (p = 0.002) and L3 (p = 0.02). Before CSI, the length of all vertebral bodies was an increasing function of age (p <0.0001). The C3 length before CSI was affected by gender and risk classification: C3 was longer for female (p = 0.07) and high-risk (p = 0.07) patients., Conclusion: All vertebrae grew significantly after CSI, with the vertebrae of the boys and younger patients growing at a rate greater than that of their counterparts. The effect of age was similar across all vertebrae, and gender had the greatest effect on the growth of the lower cervical and upper thoracic vertebrae. The effect of the risk classification was greatest in the lumbar spine by a factor of < or = 10.

Purpose: To describe and review the radiotherapy (RT) treatment planning and delivery techniques used for pediatric sarcoma patients at St. Jude Children's Research Hospital. The treatment characteristics serve as a baseline for future comparison with developing treatment modalities., Patients and Methods: Since January 2003, we have prospectively treated pediatric and young-adult patients with soft-tissue and bone sarcomas on an institutional Phase II protocol evaluating local control and RT-related treatment effects from external-beam RT (conformal or intensity-modulated RT; 83.4%), low-dose-rate brachytherapy (8.3%), or both (8.3%). Here we describe the treatment dosimetry and delivery parameters of the initial 72 patients (median, 11.6 years; range, 1.4-21.6 years)., Results: Cumulative doses from all RT modalities ranged from 41.4 to 70.2 Gy (median, 50.4 Gy). Median D(95) and V(95) of the planning target volume of external-beam RT plans were, respectively, 93.4% of the prescribed dose and 94.6% of the target volume for the primary phase and 97.8% and 99.2% for the cone-down/boost phase. The dose-volume histogram statistics for 27 critical organs varied greatly. The spinal cord in 13 of 36 patients received dose >45 Gy (up to 52 Gy in 1 cc) because of tumor proximity., Conclusions: Planning and delivery of complex multifield external beam RT is feasible in pediatric patients with sarcomas. Improvements on conformity and dose gradients are still desired in many cases with sensitive adjacent critical structures. Long-term follow-up will determine the risk of local failure and the benefit of normal tissue avoidance for this population.

Purpose: Limiting the neurocognitive sequelae of radiotherapy (RT) has been an objective in the treatment of medulloblastoma. Conformal RT to less than the entire posterior fossa (PF) after craniospinal irradiation might reduce neurocognitive sequelae and requires evaluation., Methods and Materials: Between October 1996 and August 2003, 86 patients, 3-21 years of age, with newly diagnosed, average-risk medulloblastoma were treated in a prospective, institutional review board-approved, multi-institution trial of risk-adapted RT and dose-intensive chemotherapy. RT began within 28 days of definitive surgery and consisted of craniospinal irradiation (23.4 Gy), conformal PF RT (36.0 Gy), and primary site RT (55.8 Gy). The planning target volume for the primary site included the postoperative tumor bed surrounded by an anatomically confined margin of 2 cm that was then expanded with a geometric margin of 0.3-0.5 cm. Chemotherapy was initiated 6 weeks after RT and included four cycles of high-dose cyclophosphamide, cisplatin, and vincristine., Results: At a median follow-up of 61.2 months (range, 5.2-115.0 months), the estimated 5-year event-free survival and cumulative incidence of PF failure rate was 83.0% +/- 5.3% and 4.9% +/- 2.4% (+/- standard error), respectively. The targeting guidelines used in this study resulted in a mean reduction of 13% in the volume of the PF receiving doses >55 Gy compared with conventionally planned RT. The reductions in the dose to the temporal lobes, cochleae, and hypothalamus were statistically significant., Conclusion: This prospective trial has demonstrated that irradiation of less than the entire PF after 23.4 Gy craniospinal irradiation for average-risk medulloblastoma results in disease control comparable to that after treatment of the entire PF.

Purpose: To estimate potential differences in volumetric bone growth in children with sarcoma treated with intensity-modulated (IMRT) and conformal (CRT) radiation therapy using an empiric dose-effect model., Methods and Materials: A random coefficient model was used to estimate potential volumetric bone growth of 36 pelvic bones (ischiopubis and ilium) from 11 patients 4 years after radiotherapy. The model incorporated patient age, pretreatment bone volume, integral dose >35 Gy, and time since completion of radiation therapy. Three dosimetry plans were entered into the model: the actual CRT/IMRT plan, a nontreated comparable IMRT/CRT plan, and an idealized plan in which dose was delivered only to the planning target volume. The results were compared with modeled normal bone growth., Results: The model predicted that by using the idealized, IMRT, and CRT approaches, patients would maintain 93%, 87%, and 84%, respectively (p = 0.06), of their expected normal growth. Patients older than 10 years would maintain 98% of normal growth, regardless of treatment method. Those younger than 10 years would maintain 87% (idealized), 76% (IMRT), or 70% (CRT) of their expected growth (p = 0.015). Post hoc testing (Tukey) revealed that the CRT and IMRT approaches differed significantly from the idealized one but not from each other., Conclusions: Dose-effect models facilitate the comparison of treatment methods and potential interventions. Although treatment methods do not alter the growth of flat bones in older pediatric patients, they may significantly impact bone growth in children younger than age 10 years, especially as we move toward techniques with high conformity and sharper dose gradient.

Purpose: To model the effects of external beam irradiation on the developing flat bones of pediatric patients undergoing radiation therapy (RT) for tumors involving the musculoskeletal system., Methods and Materials: Patients with image-guided RT plans including areas adjacent to facial or pelvic flat bones underwent retrospective contouring of nontumor involved flat bones ipsilateral and contralateral to the treatment side. Radiation dose-volume information and bone volume data (initial and the most recent follow-up) were analyzed in 15 paired flat bones from 10 patients (ages 1.0-17.0 years). The models to predict bone growth after completion of RT (v(post)) were based on initial bone volume (v(pre)), the patient's age, time to follow-up (t), and the dose-volume parameter (v(Int35+))., Results: We developed a dose effects model as follows: Log (v(post) / v(pre)) = beta(time)t + beta(age group)t + beta(dose)t v(Int35). The dose-volume parameter v(Int35) predicted significantly for alterations in growth in younger patients, but not for older patients. The predictability of the fitted model for relative change in bone growth improved in the younger age group with the addition of the dose-volume term v(Int35) (correlation coefficient of r = 0.5510 to r = 0.6760 with the addition v(Int35))., Conclusions: Our model accurately predicted flat bone growth and is notable for the inclusion of radiation dose-volume information, which is now available in the image-guided RT era. Further refinement of this model in a prospective patient population is underway.

Purpose: To assess the effect of radiation dose on local tumor control of the Ewing sarcoma family of tumors in 79 patients with localized disease treated at a single institution., Methods and Materials: Thirty-seven patients received vincristine, actinomycin D, cyclophosphamide, and doxorubicin, and 42 received vincristine, actinomycin D, and cyclophosphamide, with alternating cycles of ifosfamide and etoposide; all underwent definitive radiotherapy (median dose, 37.5 Gy) with either low-dose (<40 Gy) or standard dose (> or =40 Gy) radiation delivered according to the protocol. We calculated the cumulative incidence of local treatment failure, disease recurrence, and overall survival and analyzed the effect of known prognostic factors and radiation dose., Results: The cumulative incidence of local treatment failure at 10 years was 30.4% and that of disease recurrence was 40%. The overall survival rate was 64.5%. Patient age > or =14 years and tumor size > or =8 cm were adverse prognostic factors for local treatment failure; patient age > or =14 years was also associated with worse survival. Although the radiation dose alone did not predict for local treatment failure, the cumulative incidence of local failure at 10 years was 19% when tumors <8 cm were treated with <40 Gy, and no patient treated with standard doses (> or =40 Gy) developed local recurrence (p = 0.084)., Conclusion: Tumor size and patient age predict for local tumor control in patients with Ewing sarcoma family of tumors treated with systemic therapy and definitive radiotherapy. Patients treated with reduced-dose radiotherapy experienced unacceptably high rates of local recurrence.

Purpose: Central nervous system (CNS) irradiation can cause sensorineural hearing loss. The relationship between the dose to the cochlea and the development of hearing loss is unknown. Conformal radiation therapy (CRT) techniques facilitate accurate cochlear dosimetry. We modeled hearing threshold levels (HTL) after CRT in children with localized primary brain tumors (ependymoma, low- or high-grade astrocytoma, craniopharyngioma, or CNS germinoma) by using cochlear dose and clinical variables., Patients and Methods: We evaluated 72 children (median age, 9.5 years) with audiograms before and every 6 months after CRT (median follow-up, 16.6 months; range, 4.3-42.6 months). We used a mixed-effects model to predict change in hearing for each ear as a function of time, cochlear dose, and clinical variables., Results: Hearing was affected the greatest in patients with CSF shunts and pre-CRT ototoxic chemotherapy, enhanced by cochlear dose, and was more prominent on the right side. Hearing impairment after CRT alone occurred at low and intermediate frequencies in patients with shunts and supratentorial tumors when the cochlear dose exceeded 32 Gy. Patients with shunts and central supratentorial tumors developed intermediate-frequency hearing loss after CRT alone regardless of dose., Conclusions: Hearing loss during the first 4 years after CRT alone is uncommon, although patients with shunts and supratentorial tumors appear to be at increased risk for low- and intermediate-frequency effects. CSF shunting and increased cochlear dose enhance the effect of ototoxic chemotherapy. If possible, the average cochlear dose should be <32 Gy over a 6-week course of treatment until more specific dose data become available.

Purpose: The purpose of this study was to evaluate the possible effect of adjunctive involved field (IF) radiotherapy on long-term local control for patients with Ann Arbor Stage I-III diffuse large cell lymphoma (DLCL) who achieved a complete remission on a combined modality program which included cyclophosphamide, doxorubicin, vincristine, prednisone, and Bleomycin (CHOP-Bleo)., Methods and Materials: One hundred and ninety patients with Ann Arbor Stage I-III DLCL were treated with CHOP-Bleo and radiotherapy. Analyses were undertaken to determine (a) response to treatment according to stage, extent of maximum local disease, and irradiation dose either < 40 Gy or > or = 40 Gy and (b) relapse patterns., Results: A complete remission (CR) was achieved in 162 patients. Among patients who achieved a CR, local control was better for those who received tumor doses of > or = 40 Gy (97%) than for those who received < 40 Gy (83%) (p = 0.002.) Among those with extensive local disease, the corresponding control rates were 88% and 71%, respectively. A study of distant relapse patterns following a CR showed that the first relapse usually involved an extranodal site., Conclusion: Radiotherapy was an effective adjunctive treatment to CHOP-Bleo for patients with stage I-III DLCL who achieved a CR. Patterns of relapse suggested that total nodal irradiation (TNI) possibly could have benefited a small subset of patients.