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Background: Cerebral vessel diameter changes objectively and automatically derived from longitudinal magnetic resonance angiography (MRA) facilitate quantification of vessel changes and further modeling.Purpose: To characterize longitudinal changes in intracranial vessel diameter using time-of-flight (TOF) MRA.Study Type: Retrospective longitudinal study.Subject Population: IN all, 112 pediatric patients, aged 9.96 ± 4.59 years, with craniopharyngioma from 2006-2011 scanned annually.Field Strength/sequence: 1.5T and 3T TOF MRA.Statistical Tests: Chi-square and Wilcoxon-Mann-Whitney tests.Assessment: Manual measurements using interventional angiography was established as a reference standard for diameter measurements. Constant and linear quantile regression with absolute difference, percentage difference, and relative difference was used for outlier detection.Results: Major vessels surrounding the circle of Willis were successfully segmented except for posterior communicating arteries, mostly due to disease-related hypoplasia. Diameter measurements were calculated at 1-mm segments with a median computed vessel diameter of 1.25 mm. Diameter distortion due to registration was within 0.04 mm for 99% of vessel segments. Outlier detection using quantile regression detected less than 4.34% as being outliers. Outliers were more frequent in smaller vessels and proximity to bifurcations (P < 0.001).Data Conclusion: Using the proposed method, objective changes in vessel diameter can be acquired noninvasively from routine longitudinal imaging. High-throughput analyses of imaging-derived vascular trees combined with clinical and treatment parameters will allow rigorous modeling of vessel diameter changes.Level Of Evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1063-1074. [ABSTRACT FROM AUTHOR]

Cyclophosphamide dosing has previously been implicated as a risk factor for local failure in rhabdomyosarcoma. Casey et al report on findings from ARST0531 that provide ancillary support for this hypothesis. [ABSTRACT FROM AUTHOR]

Purpose: We sought to investigate the pattern of treatment failure with respect to anatomic extent, radiation dose, and criteria for failure according to the Response Assessment in Neuro-Oncology (RANO). We evaluated the corresponding prognostic significance of these factors in patients with pediatric high-grade glioma (pHGG).Methods and Materials: Fifty-six patients with pHGG were enrolled in an institutional phase 1 to 2 prospective trial that included maximal safe resection and radiation therapy with concurrent and adjuvant erlotinib. The radiation therapy dose administered was 54 to 59.4 Gy at 1.8 Gy/d. Tumor progression was defined according to clinical symptoms and imaging features and was classified in relation to the original extent of the tumor, radiation prescription target volume coverage, and RANO criteria (RANOc).Results: With a median follow-up period of 90 months (range, 70-124 months), progression occurred in 48 patients (85.7%) while 8 (14.3%) were without progression. Central failure represented 42.6% of the total cohort, while in-field, marginal, and distant failures occurred in 7.4%, 9.3%, and 22.2%, respectively. Patients with biopsy or subtotal resection had increased rates of central failure and represented 14.81% and 16.67% of the total cohort, respectively. Tumor progression was classified as local, local plus distant, or distant. Among patients with local failure as a component of failure, 5 were considered to have marginal failure. Patients with frontal, temporal, and parietal disease had the highest rates of multifocal failure. A comparison between responses defined by RANOc demonstrated varied time to death (TTD) from progression.Conclusions: Pediatric high-grade glioma was shown to have high rates of central failure, particularly in cases with limited resection. Patients with central failure had a trend toward more prolonged TTD from failure relative to other failure patterns. The low marginal failure rates seen in this group suggest that less conservative radiation target margins may be possible. TTD from failure varied according to RANO type, suggesting that adult RANOc require modification before being applied to pHGG. [ABSTRACT FROM AUTHOR]

Background: Local control for patients with Ewing sarcoma (EWS) who present with large tumors are suboptimal when treated with standard radiation therapy (RT) doses of 54-55.8 Gy. The purpose of this study is to determine local control and toxicity of dose-escalated RT for tumors ≥8 cm (greatest diameter at diagnosis) in pediatric and young adult patients with EWS., Methods: Eligible patients ≤30 years old with newly diagnosed EWS ≥8 cm treated with definitive conformal or intensity modulated photon, or proton radiation therapy techniques were included. All patients in the study received dose-escalated RT doses. Outcomes included overall survival (OS), event-free survival (EFS), local failure rates, and toxicity., Results: Thirty-two patients were included, 20 patients presented with metastatic disease and 12 patients with localized disease. The median RT dose was 64.8 Gy (range, 59.4-69.4 Gy) with variability of doses to protect normal surrounding tissues. All patients received systemic chemotherapy. The 5-year OS and EFS for the cohort was 64.2% and 42%, respectively. The 5-year cumulative incidence of local failure was 6.6%. There were two combined local and distant failures with no isolated local failures. Twenty-nine patients experienced short term toxicity, 90% of those being radiation dermatitis. Twenty-seven patients experienced long-term toxicity, with only one experiencing grade 4 toxicity, a secondary malignancy after therapy., Conclusion: This study demonstrates that definitive RT for pediatric and young adult patients with EWS ≥8 cm provides high rates of local control, while maintaining a tolerable toxicity profile., (© 2024 American Cancer Society.)

Data commons have proven to be an indispensable avenue for advancing pediatric cancer research by serving as unified information technology platforms that, when coupled with data standards, facilitate data sharing. The Pediatric Cancer Data Commons, the flagship project of Data for the Common Good (D4CG), collaborates with disease-based consortia to facilitate development of clinical data standards, harmonization and pooling of clinical data from disparate sources, establishment of governance structure, and sharing of clinical data. In the interest of international collaboration, researchers developed the Hodgkin Lymphoma Data Collaboration and forged a relationship with the Pediatric Cancer Data Commons to establish a data commons for pediatric Hodgkin lymphoma. Herein, we describe the progress made in the formation of Hodgkin Lymphoma Data Collaboration and foundational goals to advance pediatric Hodgkin lymphoma research., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: To leverage baseline global longitudinal strain (GLS) and N-terminal-pro-B-type natriuretic peptide (NT-proBNP) to identify childhood cancer survivors with a normal left ventricular ejection fraction (LVEF) at highest risk of future treatment-related cardiomyopathy., Methods: St Jude Lifetime Cohort participants ≥5 years from diagnosis, at increased risk for cardiomyopathy per the International Guideline Harmonization Group (IGHG), with an LVEF ≥50% on baseline echocardiography (n = 1,483) underwent measurement of GLS (n = 1,483) and NT-proBNP (n = 1,052; 71%). Multivariable Cox regression models estimated hazard ratios (HRs) and 95% CIs for postbaseline cardiomyopathy (modified Common Terminology Criteria for Adverse Events ≥grade 2) incidence in association with echocardiogram-based GLS (≥-18) and/or NT-proBNP (>age-sex-specific 97.5th percentiles). Prediction performance was assessed using AUC in models with and without GLS and NT-proBNP and compared using DeLong's test for IGHG moderate- and high-risk individuals treated with anthracyclines., Results: Among survivors (median age, 37.6; range, 10.2-70.4 years), 162 (11.1%) developed ≥grade 2 cardiomyopathy 5.1 (0.7-10.0) years from baseline assessment. The 5-year cumulative incidence of cardiomyopathy for survivors with and without abnormal GLS was, respectively, 7.3% (95% CI, 4.7 to 9.9) versus 4.4% (95% CI, 3.0 to 5.7) and abnormal NT-proBNP was 9.9% (95% CI, 5.8 to 14.1) versus 4.7% (95% CI, 3.2 to 6.2). Among survivors with a normal LVEF, abnormal baseline GLS and NT-proBNP identified anthracycline-exposed, IGHG-defined moderate-/high-risk survivors at a four-fold increased hazard of postbaseline cardiomyopathy (HR, 4.39 [95% CI, 2.46 to 7.83]; P < .001), increasing to a HR of 14.16 (95% CI, 6.45 to 31.08; P < .001) among survivors who received ≥250 mg/m 2 of anthracyclines. Six years after baseline, AUCs for individual risk prediction were 0.70 for models with and 0.63 for models without GLS and NT-proBNP ( P = .022)., Conclusion: GLS and NT-proBNP should be considered for improved identification of survivors at high risk for future cardiomyopathy.

Background: Pleuropulmonary blastoma (PPB) is the most common primary lung neoplasm of infancy and early childhood. Given the rarity of PPB, the role of positron emission tomography (PET) and bone scintigraphy (bone scans) in diagnostic evaluation and surveillance has not been documented to date. Available PET and bone scan data are presented in this study., Procedures: Patients with PPB enrolled in the International PPB/DICER1 Registry and available PET imaging and/or bone scan reports were retrospectively abstracted., Results: On retrospective analysis, 133 patients with type II and III (advanced) PPB were identified with available report(s) (PET scan only = 34, bone scan only = 83, and both bone scan and PET = 16). All advanced primary PPB (n = 11) and recurrent (n = 8) tumors prior to treatment presented with 18 F-fluorodeoxyglucose (FDG)-avid lesions, with median maximum standardized uptake values of 7.4 and 6.7, respectively. False positive FDG uptake in the thorax was noted during surveillance (specificity: 59%). Bone metastases were FDG-avid prior to treatment. Central nervous system metastases were not discernable on PET imaging. Sensitivity and specificity of bone scans for metastatic bone disease were 89% and 92%, respectively. Bone scans had a negative predictive value of 99%, although positive predictive value was 53%. Four patients with distant bone metastases had concordant true positive bone scan and PET., Conclusion: Primary, recurrent, and/or extracranial metastatic PPB presents with an FDG-avid lesion on PET imaging. Additional prospective studies are needed to fully assess the utility of nuclear medicine imaging in surveillance for patients with advanced PPB., (© 2023 Wiley Periodicals LLC.)

(1) Background: The most significant cause of an unacceptable deviation from the planned dose during respiratory motion is the interplay effect. We examined the correlation between the magnitude of splenic motion and its impact on plan quality for total lymphoid irradiation (TLI); (2) Methods: Static and 4D CT images from ten patients were used for interplay effect simulations. Patients' original plans were optimized based on the average CT extracted from the 4D CT and planned with two posterior beams using scenario-based optimization (±3 mm of setup and ±3% of range uncertainty) and gradient matching at the level of mid-spleen. Dynamically accumulated 4D doses (interplay effect dose) were calculated based on the time-dependent delivery sequence of radiation fluence across all phases of the 4D CT. Dose volume parameters for each simulated treatment delivery were evaluated for plan quality; (3) Results: Peak-to-peak splenic motion (≤12 mm) was measured from the 4D CT of ten patients. Interplay effect simulations revealed that the ITV coverage of the spleen remained within the protocol tolerance for splenic motion, ≤8 mm. The D100% coverage for ITV spleen decreased from 95.0% (nominal plan) to 89.3% with 10 mm and 87.2% with 12 mm of splenic motion; (4) Conclusions: 4D plan evaluation and robust optimization may overcome problems associated with respiratory motion in proton TLI treatments. Patient-specific respiratory motion evaluations are essential to confirming adequate dosimetric coverage when proton therapy is utilized.

Purpose: Pleuropulmonary blastoma (PPB) is the most common primary lung neoplasm of infancy and early childhood. Type II and type III PPB have historically been associated with a poor prognosis., Methods: Patients with known or suspected PPB were enrolled in the International PPB/ DICER1 Registry. Medical records were abstracted with follow-up ascertained annually. All PPB diagnoses were confirmed by central pathology review. Beginning in 2007, the IVADo regimen (ifosfamide, vincristine, actinomycin-D, and doxorubicin) was recommended as a potential treatment regimen for children with type II and type III PPB. This regimen was compared with a historical control cohort., Results: From 1987 to 2021, 314 children with centrally confirmed type II and type III PPB who received upfront chemotherapy were enrolled; 132 children (75 with type II and 57 with type III) received IVADo chemotherapy. Adjusted analyses suggest improved overall survival for children treated with IVADo in comparison with historical controls with an estimated hazard ratio of 0.65 (95% CI, 0.39 to 1.08). Compared with localized disease, distant metastasis at diagnosis was associated with worse PPB event-free survival and overall survival with hazard ratio of 4.23 (95% CI, 2.42 to 7.38) and 4.69 (95% CI, 2.50 to 8.80), respectively., Conclusion: The use of IVADo in children with type II and type III PPB resulted in similar-to-improved outcomes compared with historical controls. Inferior outcomes with metastatic disease suggest the need for novel therapies. This large cohort of uniformly treated children with advanced PPB serves as a benchmark for future multicenter therapeutic studies for this rare pediatric tumor.

Purpose: Challenges in proton therapy include identifying patients most likely to benefit; ensuring consistent, high-quality plans as its adoption becomes more widespread; and recognizing biological uncertainties that may be related to increased relative biologic effectiveness driven by linear energy transfer (LET). Knowledge-based planning (KBP) is a domain that may help to address all three., Methods: Artificial neural networks were trained using 117 unique treatment plans and associated dose and dose-weighted LET (LET D ) distributions. The data set was split into training (n = 82), validation (n = 17), and test (n = 18) sets. Model performance was evaluated on the test set using dose- and LET D -volume metrics in the clinical target volume (CTV) and nearby organs at risk and Dice similarity coefficients (DSC) comparing predicted and planned isodose lines at 50%, 75%, and 95% of the prescription dose., Results: Dose-volume metrics significantly differed (α = 0.05) between predicted and planned dose distributions in only one dose-volume metric, D 2% to the CTV. The maximum observed root mean square (RMS) difference between corresponding metrics was 4.3 Gy RBE (8% of prescription) for D 1cc to optic chiasm. DSC were 0.90, 0.93, and 0.88 for the 50%, 75%, and 95% isodose lines, respectively. LET D -volume metrics significantly differed in all but one metric, L 0.1cc of the brainstem. The maximum observed difference in RMS differences for LET D metrics was 1.0 keV/μm for L 0.1cc to brainstem., Conclusions: We have devised the first three-dimensional dose and LET D -prediction model for cranial proton radiation therapy has been developed. Dose accuracy compared favorably with that of previously published models in other treatment sites. The agreement in LET D supports future investigations with biological doses in mind to enable the full potential of KBP in proton therapy., (© 2022 American Association of Physicists in Medicine.)

Purpose: Image-defined risk factors (IDRFs) are associated with surgical risks in neuroblastoma. We sought to evaluate the impact of neoadjuvant therapy on IDRFs and associated ability to achieve gross total resection (GTR) of locoregional disease in patients with high-risk neuroblastoma., Methods: We retrospectively reviewed charts of patients treated on four consecutive high-risk neuroblastoma protocols over a 20-year period at a single institution. The number of IDRFs at diagnosis and just prior to surgery, and the percent decrease of tumor volume from just prior to surgery to the end of induction were determined., Results: Eighty-eight patients were included. There were 438 IDRFs (average 5.0 ± 3.1 per patient) at diagnosis and 198 (average 2.3 ± 1.9 per patient) after neoadjuvant chemotherapy (p < 0.01). A reduction in IDRFs was seen in 81.8% of patients with average decrease of 2.9 ± 2.5 per patient. The average percent reduction in tumor volume was 89.8 ± 18.9% and correlated with the number of IDRFs present after chemotherapy (p < 0.01). Three or fewer IDRFs prior to surgery was associated with the highest odds ratio for > 90% GTR at 9.33 [95% confidence interval 3.14-31.5]., Conclusion: Neoadjuvant chemotherapy reduced the number of IDRFs in the majority of patients with high-risk neuroblastoma. The number of IDRFs present after neoadjuvant therapy correlated with the extent of resection., (© 2021. Society of Surgical Oncology.)

Background: Central nervous system (CNS) germinomas are treatment-sensitive tumors with excellent survival outcomes. Current treatment strategies combine chemotherapy with radiotherapy (RT) in order to reduce the field and dose of RT. Germinomas originating in the basal ganglia/thalamus (BGTGs) have proven challenging to treat given their rarity and poorly defined imaging characteristics. Craniospinal (CSI), whole brain (WBI), whole ventricle (WVI), and focal RT have all been utilized; however, the best treatment strategy remains unclear., Methods: Retrospective multi-institutional analysis has been conducted across 18 institutions in four countries., Results: For 43 cases of nonmetastatic BGTGs, the 5- and 10-year event-free survivals (EFS) were 85.8% and 81.0%, respectively, while the 5- and 10-year overall survivals (OS) were 100% and 95.5%, respectively (one patient fatality from unrelated cause). Median RT doses were as follows: CSI: 2250 cGy/cGy(RBE) (1980-2400); WBI: 2340 cGy/cGy(RBE) (1800-3000); WVI: 2340 cGy/cGy(RBE) (1800-2550); focal: 3600 cGy (3060-5400). Thirty-eight patients (90.5%) received chemotherapy. There was no statistically significant difference in the EFS based on initial field extent (p = .84). Nevertheless, no relapses were reported in patients who received CSI or WBI. Chemotherapy alone had significantly inferior EFS compared to combined therapy (p = .0092), but patients were salvageable with RT., Conclusion: Patients with BGTGs have excellent outcomes and RT proved to be an integral component of the treatment plan. This group of patients should be included in future prospective clinical trials and the best RT field should be investigated further., (© 2021 Wiley Periodicals LLC.)

Radiation-induced high-grade gliomas (RIGs) are an incurable late complication of cranial radiation therapy. We performed DNA methylation profiling, RNA-seq, and DNA sequencing on 32 RIG tumors and an in vitro drug screen in two RIG cell lines. We report that based on DNA methylation, RIGs cluster primarily with the pediatric receptor tyrosine kinase I high-grade glioma subtype. Common copy-number alterations include Chromosome (Ch.) 1p loss/1q gain, and Ch. 13q and Ch. 14q loss; focal alterations include PDGFRA and CDK4 gain and CDKN2A and BCOR loss. Transcriptomically, RIGs comprise a stem-like subgroup with lesser mutation burden and Ch. 1p loss and a pro-inflammatory subgroup with greater mutation burden and depleted DNA repair gene expression. Chromothripsis in several RIG samples is associated with extrachromosomal circular DNA-mediated amplification of PDGFRA and CDK4. Drug screening suggests microtubule inhibitors/stabilizers, DNA-damaging agents, MEK inhibition, and, in the inflammatory subgroup, proteasome inhibitors, as potentially effective therapies., (© 2021. The Author(s).)

Purpose: Early identification of childhood cancer survivors at high risk for treatment-related cardiomyopathy may improve outcomes by enabling intervention before development of heart failure. We implemented artificial intelligence (AI) methods using the Children's Oncology Group guideline-recommended baseline ECG to predict cardiomyopathy., Material and Methods: Seven AI and signal processing methods were applied to 10-second 12-lead ECGs obtained on 1,217 adult survivors of childhood cancer prospectively followed in the St Jude Lifetime Cohort (SJLIFE) study. Clinical and echocardiographic assessment of cardiac function was performed at initial and follow-up SJLIFE visits. Cardiomyopathy was defined as an ejection fraction < 50% or an absolute drop from baseline ≥ 10%. Genetic algorithm was used for feature selection, and extreme gradient boosting was applied to predict cardiomyopathy during the follow-up period. Model performance was evaluated by five-fold stratified cross-validation., Results: The median age at baseline SJLIFE evaluation was 31.7 years (range 18.4-66.4), and the time between baseline and follow-up evaluations was 5.2 years (0.5-9.5). Two thirds (67.1%) of patients were exposed to chest radiation, and 76.6% to anthracycline chemotherapy. One hundred seventeen (9.6%) patients developed cardiomyopathy during follow-up. In the model based solely on ECG features, the cross-validation area under the curve (AUC) was 0.87 (95% CI, 0.83 to 0.90), whereas the model based on clinical features had an AUC of 0.69 (95% CI, 0.64 to 0.74). In the model based on ECG and clinical features, the cross-validation AUC was 0.89 (95% CI, 0.86 to 0.91), with a sensitivity of 78% and a specificity of 81%., Conclusion: AI using ECG data may assist in the identification of childhood cancer survivors at increased risk for developing future cardiomyopathy., Competing Interests: Rebecca M. HowellResearch Funding: MD Anderson Cancer Center John L. JefferiesHonoraria: Genzyme, Amicus Therapeutics, Pfizer, Abbott Diagnostics, Stealth Biotherapeutics, Novartis, ChiesiConsulting or Advisory Role: Abbott Diagnostics, Amicus Therapeutics, Chiesi, Medtronic, CHF Solutions, Stealth Biotherapeutics, Pfizer, NovartisSpeakers' Bureau: Genzyme, PfizerResearch Funding: Medtronic, Myokardia, Sanofi, Innolife, Novartis, Lilly, CHF Solutions, RegeneronTravel, Accommodations, Expenses: Genzyme, Abbott Diagnostics, Amicus Therapeutics, Novartis, Medtronic, Chiesi, PQBypass Deo Kumar SrivastavaConsulting or Advisory Role: GENERAL DYNAMICS Information Technology Peer Review and Science Management Melissa M. HudsonConsulting or Advisory Role: Oncology Research Information Exchange Network, Princess Máxima CenterNo other potential conflicts of interest were reported.

Brain tumors are the most common solid tumors of childhood, and the genetic drivers and optimal therapeutic strategies for many of the different subtypes remain unknown. Here, we identify that bithalamic gliomas harbor frequent mutations in the EGFR oncogene, only rare histone H3 mutation (in contrast to their unilateral counterparts), and a distinct genome-wide DNA methylation profile compared to all other glioma subtypes studied to date. These EGFR mutations are either small in-frame insertions within exon 20 (intracellular tyrosine kinase domain) or missense mutations within exon 7 (extracellular ligand-binding domain) that occur in the absence of accompanying gene amplification. We find these EGFR mutations are oncogenic in primary astrocyte models and confer sensitivity to specific tyrosine kinase inhibitors dependent on location within the kinase domain or extracellular domain. We initiated treatment with targeted kinase inhibitors in four children whose tumors harbor EGFR mutations with encouraging results. This study identifies a promising genomically-tailored therapeutic strategy for bithalamic gliomas, a lethal and genetically distinct brain tumor of childhood.

Background: Desmoplastic small round cell tumor (DSRCT) is a rare intra-abdominal soft tissue sarcoma affecting adolescents and young adults. Cytoreduction, hyperthermic intraperitoneal chemotherapy (CRS/HIPEC), and adjuvant radiotherapy may improve local control. We review our experience with patients who undergo CRS/HIPEC and adjuvant radiotherapy for DSRCT., Methods: A retrospective review was performed for patients with DSRCT from 2013 to 2017 who underwent CRS/HIPEC. Clinicopathologic, operative, and outcome data were reviewed., Results: Ten CRS/HIPEC procedures were performed for nine patients (7 males, 6 Caucasian, median age 19 years (range 10-24)). Four patients presented with extra-abdominal disease; five had liver involvement. The median peritoneal cancer index was 16 (range 5-20). All received neoadjuvant chemotherapy. CCR 0/1 resection was possible in nine patients. Major complications occurred in four with no operative mortalities. All received adjuvant chemotherapy, seven received radiation therapy, and three received stem-cell transplant. All but one patient recurred after treatment. The median recurrence-free and overall survival (OS) were 12 and 45 months (95% confidence interval 35.1-54.9) respectively, with a 3-year OS of 55%. Long-term parenteral nutrition was required in eight for a median of 261 days (range 37-997). Clinically significant long-term complications requiring further surgery included gastroparesis (N = 1), small bowel obstruction (N = 3) and hemorrhagic cystitis (N = 2)., Conclusions: Multimodal therapy for DSRCT consisting of multiagent neoadjuvant chemotherapy, CRS/HIPEC, adjuvant chemotherapy, and radiation therapy is associated with potential cumulative toxicity. Recurrence after resection is common. Prolonged parenteral nutrition may be necessary, and late gastrointestinal and genitourinary complications may require additional treatment.

Background and Purpose: The role of perfusion imaging in the management of pediatric high grade glioma is unclear. We evaluated the ability of dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) to determine grade, evaluate post-treatment response and predict treatment failure., Material and Methods: In this study 22 patients with high-grade glioma underwent biopsy and were treated with concurrent and sequential radiotherapy and erlotinib as part of a phase I/II clinical trial (NCT00124657). Preradiotherapy, immediate postradiotherapy, 6‑month and treatment failure DSC MR images were reviewed, registered, and processed for the ratio of cerebral blood flow (CBF) and cerebral blood volume (CBV). Processed, derived perfusion, and T1-weighted images (T1WI), T2WI, and fluid attenuation inversion recovery (FLAIR) MRI sequences were used for segmentation and extraction of tumor perfusion parameters at all time points. Patient, tumor, treatment, and outcome data were summarized and related to perfusion data., Results: Regional CBF in tumors increased from diagnosis to postradiotherapy, while they decreased to levels below those at diagnosis from postradiotherapy to 6‑month follow-up. At 6 months, the median regional CBF was higher in tumors that progressed (median 1.16) than in those that did not (median, 0.95; P < 0.05). Patients with regional CBF ratios above 1.4 at diagnosis had shorter survival times than did those with regional CBF ratios below 1.4 (P = 0.77). Tumors with a regional CBV above 1.15 at the postradiotherapy (1-3 months) follow-up scan were associated with an earlier time to death than that of tumors with a regional CBV below 1.15 (P < 0.05)., Conclusion: Posttreatment perfusion characteristics are prognostic and may help predict survival. Overall, perfusion MRI is useful for managing pediatric high-grade glioma and should be incorporated into future clinical trials.

Pediatric patients with parameningeal rhabdomyosarcoma and high-risk features are recommended to receive radiotherapy at initiation of protocol therapy due to concerns about the increased risk of local and leptomeningeal failure from treatment delay. We report our early experience on a multi-institutional prospective trial incorporating delayed primary site radiation and reduced dose cyclophosphamide in all patients with parameningeal tumors. We observed an excessive number of locoregional treatment failures following this approach and have subsequently amended our trial to move radiation therapy upfront for those patients with high-risk features. We suggest that investigators should be vigilant for treatment failure given our early prospective experience with delayed radiotherapy and reduced dose cyclophosphamide.

Identification of FDGavid- neoplasms may be obscured by high-uptake normal tissues, thus limiting inferences about the natural history of disease. We introduce a FDG-PET radiomics tissue classifier for differentiating FDGavid- normal tissues from tumor. Thirty-three scans from 15 patients with Hodgkin lymphoma and 68 scans from 23 patients with Ewing sarcoma treated on two prospective clinical trials were retrospectively analyzed. Disease volumes were manually segmented on FDG-PET and CT scans. Brain, heart, kidneys and bladder and tumor volumes were automatically segmented on PET images. Standard-uptake-value (SUV) derived shape and first order radiomics features were computed to build a random forest classifier. Manually segmented volumes were compared to automatically segmented tumor volumes. Classifier accuracy for normal tissues was 90%. Classifier performance was varied across normal tissue types (brain, left kidney and bladder, hear and right kidney were 100%, 96%, 97%, 83% and 87% respectively). Automatically segmented tumor volumes showed high concordance with the manually segmented tumor volumes (R 2  = 0.97). Inclusion of texture-based radiomics features minimally contributed to classifier performance. Accurate normal tissue segmentation and classification facilitates accurate identification of FDGavid tissues and classification of those tissues as either tumor or normal tissue.

The population of adult survivors of childhood cancer continues to grow as survival rates improve. Although it is well established that these survivors experience various complications and comorbidities related to their malignancy and treatment, this risk is modified by many factors that are not directly linked to their cancer history. Research evaluating the influence of patient-specific demographic and genetic factors, premorbid and comorbid conditions, health behaviors, and aging has identified additional risk factors that influence cancer treatment-related toxicity and possible targets for intervention in this population. Furthermore, although current long-term follow-up guidelines comprehensively address specific therapy-related risks and provide screening recommendations, the risk profile of the population continues to evolve with ongoing modification of treatment strategies and the emergence of novel therapeutics. To address the multifactorial modifiers of cancer treatment-related health risk and evolving treatment approaches, a patient-centered and risk-adapted approach to care that often requires a multidisciplinary team approach, including medical and behavioral providers, is necessary for this population. CA Cancer J Clin 2018;68:133-152. © 2018 American Cancer Society., (© 2018 American Cancer Society.)