Liquid Crystal Monomer: A Potential PPARγ Antagonist.

Liquid crystal monomers (LCMs) are a large family of artificial ingredients that have been widely used in global liquid crystal display (LCD) industries. As a major constituent in LCDs as well as the end products of e-waste dismantling, LCMs are of growing research interest with regard to their environmental occurrences and biochemical consequences. Many studies have analyzed LCMs in multiple environmental matrices, yet limited research has investigated the toxic effects upon exposure to them. In this study, we combined in silico simulation and in vitro assay validation along with omics integration analysis to achieve a comprehensive toxicity elucidation as well as a systematic mechanism interpretation of LCMs for the first time. Briefly, the high-throughput virtual screen and reporter gene assay revealed that peroxisome proliferator-activated receptor gamma (PPARγ) was significantly antagonized by certain LCMs. Besides, LCMs induced global metabolome and transcriptome dysregulation in HK2 cells. Notably, fatty acid ß-oxidation was conspicuously dysregulated, which might be mediated through multiple pathways (IL-17, TNF, and NF-kB), whereas the activation of AMPK and ligand-dependent PPARγ antagonism may play particularly important parts. This study illustrated LCMs as a potential PPARγ antagonist and explored their toxicological mode of action on the trans-omics level, which provided an insightful overview in future chemical risk assessment.

Long-term complications and reconstruction failures in previously radiated breast cancer patients receiving salvage mastectomy with autologous reconstruction or tissue expander/implant-based reconstruction.

Salvage mastectomy (SM) is the standard of care for patients with local recurrence (LR) after breast conservation therapy (BCT), often with immediate reconstruction. Complications of reconstruction are a concern for these patients, and long-term data are limited. We sought to compare rates of complications requiring re-operation (CRR) and reconstruction failure (RF) between autologous reconstruction (AR) and tissue expander/implant reconstruction (TE/I). Patients with locally recurrent breast cancer after BCT, treated with SM and immediate AR or TE/I between 2000 and 2008, were identified. CRR was defined as unplanned return to operating room for wound infection, dehiscence, necrosis (including flap, skin, or fat), hematoma, or hernia (for AR) and extrusion, leak, or capsular contracture (for TE/I). RF was defined as conversion to another reconstruction technique or to flat chest wall. This study included 103 patients with 107 reconstructions. Median follow-up was 6.6 years. CRR and RF were significantly higher with TE/I (n = 34) compared to AR (n = 73) at 5 years (50.9% vs 25.5%; P = 0.02) and (42.1% vs 5.8%; P < 0.001). On univariate analysis (UVA), TE/I (HR = 2.14; P = 0.02) and diabetes (HR = 5.10; P = 0.007) were significant predictors for CRR. On UVA, TE/I (HR = 7.30; P < 0.001) and older age at reconstruction (HR = 1.03; P = 0.003) were significant predictors for RF. In this population of previously irradiated patients, TE/I was associated with significantly higher CRR and RF. Complications continue to occur up to 10 years after TE/I. AR should be considered in appropriately selected patients, though TE/I may remain a reasonable option in patients without high-risk factors for surgical complications.

Kidney organoid models reveal cilium-autophagy metabolic axis as a therapeutic target for PKD both in vitro and in vivo.

Human pluripotent stem cell-derived kidney organoids offer unprecedented opportunities for studying polycystic kidney disease (PKD), which still has no effective cure. Here, we developed both in vitro and in vivo organoid models of PKD that manifested tubular injury and aberrant upregulation of renin-angiotensin aldosterone system. Single-cell analysis revealed that a myriad of metabolic changes occurred during cystogenesis, including defective autophagy. Experimental activation of autophagy via ATG5 overexpression or primary cilia ablation significantly inhibited cystogenesis in PKD kidney organoids. Employing the organoid xenograft model of PKD, which spontaneously developed tubular cysts, we demonstrate that minoxidil, a potent autophagy activator and an FDA-approved drug, effectively attenuated cyst formation in vivo. This in vivo organoid model of PKD will enhance our capability to discover novel disease mechanisms and validate candidate drugs for clinical translation.

PET/CT for staging and follow-up of pediatric nasopharyngeal carcinoma.

PURPOSE: While FDG PET/CT for the evaluation of nasopharyngeal carcinoma (NPC) in adult patients has documented advantages and disadvantages compared with conventional imaging, to our knowledge, no studies of FDG PET/CT for the evaluation of NPC in pediatric patients have been performed. In this investigation, we studied the utility of FDG PET/CT in children with NPC. METHODS: The study group comprised 18 children with biopsy-proven NPC who underwent FDG PET/CT and MRI (total 38 pairs of images). All baseline and follow-up FDG PET/CT and MRI studies were independently reviewed for restaging of disease. RESULTS: The concordance between FDG PET/CT and MRI in T, N, and overall staging was 29%, 64%, and 43%, respectively. Compared with MRI, FDG PET/CT yielded lower T and overall staging and showed less cervical and retropharyngeal lymphadenopathy. The concordance between follow-up FDG PET/CT and MRI was 79% overall and 100% 9 months after therapy. In patients who achieved complete remission, FDG PET/CT showed disease clearance 3-6 months earlier than MRI. There were no false-positive or false-negative FDG PET/CT scans during follow-up. CONCLUSION: FDG PET/CT may underestimate tumor extent and regional lymphadenopathy compared with MRI at the time of diagnosis, but it helps to detect metastases and clarify ambiguous findings. FDG PET/CT is sensitive and specific for follow-up and enables earlier determination of disease remission. FDG PET/CT is a valuable imaging modality for the evaluation and monitoring of NPC in pediatric patients.

Decompartmentalisation as a simple color manipulation of plant-based marbling meat alternatives.

Recent efforts for cell-based meat cuts focus on engineering edible scaffolds, with visual cues which are key to enhancing consumer acceptance, receiving less attention Here, we employed artificial intelligence (AI)-based screening of potential plant materials and discovered that jackfruit (Artocarpus heterophyllus) has the natural structures to recapitulate marbling visuals of meat cuts. Plant tissue compositions are exploited for its differential polyphenol adsorption to produce complex marbling patterns. A one-step colour control method by varying oxidation and incubation conditions of polyphenols was developed to produce permanent meat-like colours resembling chicken, pork, and beef. The scaffold exhibits a meat-like browning behaviour when cooked and is shown to support high-density porcine myoblasts culture without masking the marbled appearance. Surveys with 78 volunteers found that marbled jackfruit scaffolds improved consumer perception of cell-based meat by ∼8%. Our approach of combining AI, tissue engineering, and sensory science unlocks the possibility of creating a range of novel cell-based meat cuts with consumer focus.

Metastasectomy versus radiation of secondary sites in stage IV breast cancer: Analysis from a national cancer registry.

PURPOSE: Locoregional therapy at primary or secondary sites in breast cancer may be associated with improved survival as compared to systemic therapy alone. We explored the sociodemographic and clinicopathologic factors associated with the use of radiation versus surgical resection of metastatic sites (metastasectomy) in patients with de novo stage IV breast cancer, followed by the associated overall survival. METHODS: We sampled the National Cancer Database for patients with de novo stage IV breast cancer, (2010-2017) and described cohort's characteristics using univariate analyses. We identified 5 subgroups based on malignant site involvement: 1. Bone only, 2. Brain only, 3. Liver only, 4. Lung only, and 5. Metastasis involving >1 site. Kaplan-Meier modeling with log-rank testing and multivariate Cox Regression analysis were used to explore differences in overall survival between those that received radiation at secondary sites and those that underwent metastasectomy. RESULTS: N = 22,749patients were included in this analysis. Radiation (81.2%) was used more commonly than metastasectomy (28.8%). Metastasectomy was associated with better median overall survival across all 5 cohorts (p < .001), with the survival benefit being the most pronounced with lung only (OS: 56.9 months; HR 0.8, 95% CI 0.7-0.9, p = .032), or liver only (OS: 41.6 months; HR: 0.9; 95% CI: 0.7-1.1, p < .001) metastasis. CONCLUSION: Metastasectomy in patients with de novo stage IV breast cancer may be associated with improved overall survival as compared to radiation of secondary lesions, particularly in those with only liver or lung involvement. Prospective randomized controlled trials investigating surgical resection of metastatic sites in patients with breast cancer are warranted.

Effect of Propranolol on 18F-Fluorodeoxyglucose Uptake in Brown Adipose Tissue in Children and Young Adults with Neoplastic Diseases.

PURPOSE: To evaluate the effectiveness of propranolol at mitigating FDG uptake in brown adipose tissue (BAT) of pediatric patients with known or suspected malignancies. METHODS: PET/CT scans of 3 cohorts of patients treated from 2005 to 2017 were scored for the presence of FDG uptake by BAT at 7 sites: right or left neck/supraclavicular area, right or left axilla, mediastinum, posterior thorax, and abdomen/pelvis. Uptake was scored as follows: 0, none; 1, mild uptake < liver; 2, moderate uptake = liver; and 3, intense uptake > liver. Group 1 consisted of 323 patients (630 scans) who had no specific preparation to mitigate FDG uptake by BAT. Group 2 consisted of 345 patients (705 scans) who underwent only warming in an uptake room with a fixed temperature at 24 °C. Group 3 consisted of 622 patients (1457 scans) who underwent warming. In group 3, patients 8 years and older, 471 patients (1114 scans), were also pre-medicated with oral propranolol 60 min before injection of FDG. Generalized estimation equation, using the logit link method, was used to model the relationship between the incidence of BAT score > 0, in any site, as a function of age, sex, seasonal effect, and body surface area (BSA). RESULTS: In patients aged 8 years or older, the incidence of BAT uptake was 35-44 % and declined to 15 % with propranolol. BAT was most frequent in the neck (26 %), axilla (18 %), posterior thorax (18 %), mediastinum (14 %), and abdomen/pelvis (8 %); BAT was less common in warm months (p = 0.001). No substantial benefit was shown with pre-injection warming alone. No significant effect was found for age, sex, or BSA separately. When BAT uptake was present, it was usually intense. CONCLUSION: Propranolol preparation minimizes FDG uptake by BAT and should be considered routine for pediatric FDG PET/CT cancer-related protocols in children, adolescents, and young adults.

Analyzing the role of adjuvant or salvage radiotherapy for spinal myxopapillary ependymomas.

OBJECTIVE: The authors sought to describe the long-term recurrence patterns, prognostic factors, and effect of adjuvant or salvage radiotherapy (RT) on treatment outcomes for patients with spinal myxopapillary ependymoma (MPE). METHODS: The authors reviewed a tertiary institution IRB-approved database and collected data regarding patient, tumor, and treatment characteristics for all patients treated consecutively from 1974 to 2015 for histologically confirmed spinal MPE. Key outcomes included relapse-free survival (RFS), postrecurrence RFS, failure patterns, and influence of timing of RT on recurrence patterns. Cox proportional hazards regression and Kaplan-Meier analyses were utilized. RESULTS: Of the 59 patients included in the study, the median age at initial surgery was 34 years (range 12-74 years), 30 patients (51%) were female, and the most common presenting symptom was pain (n = 52, 88%). Extent of resection at diagnosis was gross-total resection (GTR) in 39 patients (66%), subtotal resection (STR) in 15 (25%), and unknown in 5 patients (9%). After surgery, 10 patients (17%) underwent adjuvant RT (5/39 GTR [13%] and 5/15 STR [33%] patients). Median follow-up was 6.2 years (range 0.1-35.3 years). Overall, 20 patients (34%) experienced recurrence (local, n = 15; distant, n = 5). The median RFS was 11.2 years (95% CI 77 to not reached), and the 5- and 10-year RFS rates were 72.3% (95% CI 59.4-86.3) and 54.0% (95% CI, 36.4-71.6), respectively.STR was associated with a higher risk of recurrence (HR 6.45, 95% CI 2.15-19.23, p < 0.001) than GTR, and the median RFS after GTR was 17.2 years versus 5.5 years after STR. Adjuvant RT was not associated with improved RFS, regardless of whether it was delivered after GTR or STR. Of the 20 patients with recurrence, 12 (60%) underwent salvage treatment with surgery alone (GTR, n = 6), 4 (20%) with RT alone, and 4 (20%) with surgery and RT. Compared to salvage surgery alone, salvage RT, with or without surgery, was associated with a significantly longer postrecurrence RFS (median 9.5 years vs 1.6 years; log-rank, p = 0.006). CONCLUSIONS: At initial diagnosis of spinal MPE, GTR is key to long-term RFS, with no benefit to immediate adjuvant RT observed in this series. RT at the time of recurrence, however, is associated with a significantly longer time to second disease recurrence. Surveillance imaging of the entire neuraxis remains crucial, as distant failure is not uncommon in this patient population.

Long-Term Outcomes After Autologous or Tissue Expander/Implant-Based Breast Reconstruction and Postmastectomy Radiation for Breast Cancer.

PURPOSE: The toxicity profile of breast reconstruction with postmastectomy radiation therapy (PMRT) varies by technique and timing, and long-term data are limited. We compared rates of complications requiring reoperation (CRR) and reconstruction failure (RF) between immediate autologous reconstruction (I-AR), immediate tissue expander/implant reconstruction (I-TE/I), delayed autologous reconstruction (D-AR), and delayed tissue expander/implant reconstruction (D-TE/I) in patients receiving PMRT. METHODS AND MATERIALS: Patients who received autologous reconstruction (AR) or tissue expander/implant reconstruction (TE/I) and PMRT between 2000 to 2008 were included. Reconstruction was immediate if performed on the same day as mastectomy followed by PMRT (I-AR or I-TE/I) or delayed if after PMRT (D-AR and D-TE/I). CRR was defined as an unplanned return to the operating room for infection, dehiscence, necrosis, hematoma, or hernia (with AR) and extrusion, leak, or contracture (with TE/I). RF was defined as unplanned conversion to another reconstruction technique or to flat chest wall. Cumulative incidence of CRR and RF was calculated using Kaplan-Meier and compared using the log-rank test. Logistic regression was used to identify variables associated with CRR and RF. RESULTS: Two hundred four patients were included. Median follow-up was 8 years. There were 127 AR cases (63%) and 77 TE/I cases (38%). At 5 years, CRR was 18%, 38%, 34%, and 70% (P = .010) and RF was 4%, 22%, 7%, and 56% (P < .0001) for I-AR, I-TE/I, D-AR, and D-TE/I, respectively. On multivariate analysis, TE/I (hazard ratio [HR] 2.0; P = .011), body mass index ≥30 (HR 3.9; P = .002), and smoking (HR 2.7; P = .001) were significant predictors for CRR, and TE/I (HR 6.6; P < .0001), diabetes (HR 4.1; P = .044), and hypertension (HR 3.5; P = .005) were significant for RF. When excluding RF because of infection, the rate of RF was not significantly different among the 4 groups (P = .23). CONCLUSIONS: With PMRT, TE/I reconstruction in the immediate and delayed setting is associated with higher CRR and RF compared with AR. Patient factors should guide selection of technique. Efforts to reduce rates of RF with TE/I should focus on minimizing risks for infection.

Pain flare after stereotactic radiosurgery for spine metastases.

PURPOSE: Understanding of pain flare (PF) following spine stereotactic radiosurgery (sSRS) is lacking. This study sought to determine the incidence and risk factors associated with PF following single fraction sSRS. MATERIALS/METHODS: An IRB-approved database was compiled to include patients who underwent sSRS. Patient and disease characteristics as well as treatment and dosimetric details were collected retrospectively. Pain relief post-sSRS was prospectively collected using the Brief Pain Inventory (BPI). These factors were correlated to the development of PF (defined as an increase in pain within 7 days of treatment which resolved with steroids). Survival was calculated using Kaplan-Meier analysis and logistic regression was utilized to evaluate the association between the clinical and treatment factors and occurrence of PF. RESULTS: A total of 348 patients with 507 treatments were included. Median age and prescription dose were 59 years and 15 Gy (range: 7-18), respectively, and 62% of patients were male. Renal cell carcinoma (24%), lung cancer (14%), and breast cancer (11%) were the most common histologies, and 74% had epidural disease and 43% had thecal sac compression. The most common location of metastases was in the cervical/thoracic spine (59%), followed by lumbar spine (32%), and sacral spine (9%). Most common reason for treatment was pain (73%), followed by pain and neurological deficit (13%), asymptomatic disease (10%), and neurologic deficit only (3%). Median time to pain relief was 1.8 months. Median overall survival, time to radiographic failure, and time to pain progression were 13.6 months, 26.5 months, and 56.6 months, respectively. Only 14.4% of treatments resulted in the development of PF. Univariate analysis showed that higher Karnofsky performance score (KPS) (OR=1.03, p=0.03), female gender (OR=1.80, p=0.02), higher prescription dose (OR=1.30, p=0.008), and tumor location of cervical/thoracic spine vs lumbar spine (OR=1.81, p=0.047) were predictors for the development of PF. On multivariate analysis, higher consult KPS (OR=1.03, p=0.04), female gender (OR=1.93, p=0.01), higher prescription dose (OR=1.27, p=0.02), and tumor location of cervical/thoracic spine vs lumbar spine (OR=1.81, p=0.05) remained predictors of PF. No other dosimetric parameters were associated with the development of PF. CONCLUSION: PF is an infrequent complication of sSRS. Predictors for the development of PF include higher consult KPS, female gender, higher prescription dose, and cervical/thoracic tumor location. Dose to the spinal cord was not a predictor of PF. Since a minority (14.4%) of treatments result in PF, we do not routinely utilize prophylactic steroid treatment; however, prophylactic steroids may be considered in female patients with cervical/thoracic metastases receiving higher dose sSRS.

Posttreatment Prostate-Specific Antigen 6 Months After Radiation With Androgen Deprivation Therapy Predicts for Distant Metastasis-Free Survival and Prostate Cancer-Specific Mortality.

OBJECTIVES/BACKGROUND: To determine whether a 6-month posttreatment prostate-specific antigen (PSA) value in patients with prostate cancer (PCa) treated with concurrent androgen deprivation therapy (ADT) and external beam radiation therapy (EBRT) serves as an early predictor for biochemical relapse free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific mortality (PCSM). METHODS: A retrospective review of intermediate-risk and high-risk PCa patients treated with EBRT and concurrent ADT at a single institution between 1996 and 2012. All patients received high-dose radiation with either 78 Gy in 39 fractions or 70 Gy in 28 fractions. Kaplan-Meier analysis was used to estimate bRFS and DMFS, and cumulative incidence was used to estimate PCSM. RESULTS: 532 patients were identified. The median follow-up time was 7.5 years (range, 1-16.25 years). The median initial PSA (iPSA) was 13.0 ng/mL (range, 0.37-255 ng/mL), and the median duration of ADT was 6 months (range, 1-78 months). The median PSA 6 months after EBRT was 0.1 ng/mL (range, 0-19 ng/mL), and 310 patients (58.3%) had a 6-month PSA ≤0.1 ng/mL. Multivariable analysis (MVA) demonstrated that a 6-month post-EBRT PSA of >0.1 ng/mL was an independent predictor of worse bRFS (hazard ratio [HR] = 2.518; P<.0001), DMFS (HR=3.743; P<.0001), and PCSM (HR=5.435; P<.0001). On MVA, a Gleason score of 8 to 10 also correlated with worse DMFS and PCSM (P<.05). The duration of ADT (1-6 vs >6 months) was not predictive of any clinical endpoint. CONCLUSIONS: A 6-month posttreatment PSA >0.1 ng/mL in intermediate-risk and high-risk PCa patients treated with concurrent high-dose EBRT and ADT is associated with worse bRFS, DMFS, and PCSM. The duration of ADT was not predictive of any clinical endpoint. A 6-month PSA after definitive EBRT and ADT helps identify patients at higher risk of disease progression and may serve as a predictive tool to select patients for early salvage therapy on future clinical trials.

Long-term outcomes and role of chemotherapy in adults with newly diagnosed medulloblastoma.

OBJECTIVE: To assess the survival and role of adjuvant chemotherapy in adult medulloblastoma. METHODS: We reviewed outcomes of 66 patients (aged 18 y or more; median age, 33 y) with medulloblastoma. Forty-four (67%) patients had M0 disease, 9 had M1-M4, and 13 had MX. Thirty-one patients each for whom risk stratification was available were classified as high risk or standard risk. Fifty-six patients had histologic results: classic histology was the most common (n=46 [84%]), followed by desmoplastic (n=9), and large cell/anaplastic (n=1). Overall survival (OS) and progression-free survival (PFS) were estimated with Kaplan-Meier curves and log-rank tests. Cox regression analysis was used to compare recurrences. RESULTS: Median follow-up was 6.7 years. The estimated 5-year OS and PFS were 74% and 59%, respectively. High-risk versus standard-risk classification was associated with worse OS (61% vs. 86%; P=0.03) and recurrence (hazard ratio, 2.56; P=0.05) and a trend for worse PFS (49% vs. 69%; P=0.13). Gross total resection was associated with improved OS (P=0.03) and a trend toward improved PFS (P=0.09). No chemotherapy benefit could be demonstrated for the group as a whole. For high-risk patients with classic histology (n=25), chemotherapy was associated with a trend for improvement in 5-year PFS from 36% to 71% (P=0.10) and in 5-year OS from 49% to 100% (P=0.08). CONCLUSIONS: In adult patients with medulloblastoma, the extent of resection and risk classification predicts the outcome. These results suggest a chemotherapy benefit for high-risk patients with classic histology.

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

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

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

PURPOSE: Investigate the effect of tumor change and setup uncertainties on target coverage for pediatric craniopharyngioma during RT. METHODS AND MATERIALS: Fifteen pediatric patients with craniopharyngioma (mean 5.1 years) were included in this study. MRI was performed before and a median of six times during RT to monitor changes in the tumor volume. IMRT plans were created and compared to the CRT plan used for treatment. The role of adaptive therapy based on GTV changes was investigated. Dosimetric effects of interfraction and intrafraction motion were examined. RESULTS: The mean of the maximal change in the GTV was 28.5% [-20.7% to 82.0%]. For the standard margin IMRT plans, the mean D(95) of the base plan on the base target was 53.6 Gy [53.1-54.1]. The mean D(95) of the base plans on the adaptive targets was 52.1 Gy [47.9-54.1]. The D(95) for the adaptive plan on the adaptive target was 53.8 Gy [53.4-54.3]. A linear regression equation of y=-0.12x , r(2)=0.70, was found for the percent change in D(95) of the PTV (y) vs. the percent change in the GTV (x). Inter and intrafraction motion did not affect the target coverage for standard and reduced margin plans. CONCLUSIONS: The GTV of pediatric craniopharyngioma patients change size during therapy and adaptive planning is critical for conformal plans; therefore early and regular surveillance imaging is required.

Dosimetric effect of setup motion and target volume margin reduction in pediatric ependymoma.

PURPOSE: Quantify the dosimetric effect of inter- and intrafractional motion on intensity-modulated radiation therapy (IMRT) and three-dimensional (3D) planning via changes in the generalized equivalent uniform dose (gEUD), predicted tumor control probability (TCP) and normal tissue complication probability (NTCP) for pediatric ependymoma. METHODS AND MATERIALS: Twenty patients treated between 1998 and 2002 with a 3D plan (CTV = 1 cm, PTV = 5 mm) were selected. Two IMRT plans were created for the 1 cm CTV (PTV = 5 mm and PTV = 0 mm), and a third IMRT plan for a 5 mm CTV (PTV = 0 mm). Direct simulation with inter- and intrafractional motion was performed for 3D and IMRT plans based on daily pre and post-treatment cone beam CT information obtained from 20 well-matched patients (age, supine/prone, use of GA) on a localization protocol. Calculated TCP, NTCP, Conformity Index (CI), and predictive IQ were compared. RESULTS: IMRT improved the calculated TCP by 2.8+/-2.8 vs. 3D (p<0.001). Inter- and intrafractional motion results in a TCP loss of 0.4+/-0.7 (p=0.02) and 0.0+/-0.1 (p=0.14) for the IMRT plan with PTV = 0 mm. Mean NTCP for 3D and IMRT with PTV = 5 mm, PTV = 0 mm, and CTV = 5 mm for the cochlea was: 66.6, 29.4, 8.7. Mean NTCP change due to motion was <5%. CI was 0.70+/-0.06 for IMRT and 0.5+/-0.10 for 3D. Predictive IQ was 10.0+/-10.3 points higher for IMRT vs. 3D. CONCLUSIONS: IMRT improves calculated TCP vs. 3D. Daily localization can allow for a safe reduction in the PTV margin, while maintaining target coverage; reducing the CTV margin can further reduce NTCP and may reduce future side-effects.