Pediatric Leukemia Roadmaps Are a Guide for Positive Metastatic Bone Sarcoma Trials.

ALL cures require many MRD therapies. This strategy should drive experiments and trials in metastatic bone sarcomas.

Universal germline genetic testing in patients with hematologic malignancies using DNA isolated from nail clippings.

Not available.

Molecular Imaging with PET-CT and PET-MRI in Pediatric Musculoskeletal Diseases.

Molecular imaging has emerged as an integral part of oncologic imaging. Given the physiologic changes that precede anatomic changes, molecular imaging can enable early detection of disease and monitoring of response. [18F] Fluorodeoxyglucose (FDG) Positron emission tomography (PET) is the predominant molecular imaging modality used in oncologic assessment and can be performed using PET/CT or PET/MR. In pediatric patients, PET/MRI imaging is generally preferred due to low radiation exposure and PET/MRI is particularly advantageous for imaging musculoskeletal (MSK) diseases, as MRI provides superior characterization of tissue changes as compared to CT. In this article, we provide an overview of the typical role of PET CT/MRI in assessment of some common pediatric malignancies and benign MSK diseases with case examples. We also discuss the relative advantages of PET/MRI compared to PET/CT, and review published data with a primary focus on the use of PET/MR.

Osteopetrorickets: two contradictory patterns-one unifying diagnosis.

A 5-month-old infant with bone findings on x-ray presented an apparent contradiction including findings of both diffusely dense bones and rickets in the context of a history and laboratory investigation that suggested leukemia. Next generation gene panel sequencing revealed a TCIRG1 mutation which is consistent with autosomal recessive osteopetrosis. The paradoxical x-ray findings underscore a recently elucidated mechanism for the pathogenesis of a TCIRG mutation. This case highlights the importance of recognizing this radiographic, seeming contradictory, association in the context of a confusing clinical presentation. Failure to recognize this pattern promptly may lead to a delay in diagnosis, thus potentially permanent organ failure.

Free-breathing high isotropic resolution quantitative susceptibility mapping (QSM) of liver using 3D multi-echo UTE cones acquisition and respiratory motion-resolved image reconstruction.

PURPOSE: To enable free-breathing and high isotropic resolution liver quantitative susceptibility mapping (QSM) using 3D multi-echo UTE cones acquisition and respiratory motion-resolved image reconstruction. METHODS: Using 3D multi-echo UTE cones MRI, a respiratory motion was estimated from the k-space center of the imaging data. After sorting the k-space data with estimated motion, respiratory motion state-resolved reconstruction was performed for multi-echo data followed by nonlinear least-squares fitting for proton density fat fraction (PDFF), R 2 * $$ {\mathrm{R}}_2^{\ast } $$ , and fat-corrected B0 field maps. PDFF and B0 field maps were subsequently used for QSM reconstruction. The proposed method was compared with motion-averaged (gridding) reconstruction and conventional 3D multi-echo Cartesian MRI in moving gadolinium phantom and in vivo studies. Region of interest (ROI)-based linear regression analysis was performed on these methods to investigate correlations between gadolinium concentration and QSM in the phantom study and between R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and QSM in in vivo study. RESULTS: Cones with motion-resolved reconstruction showed sharper image quality compared to motion-averaged reconstruction with a substantial reduction of motion artifacts in both moving phantom and in vivo studies. For ROI-based linear regression analysis of the phantom study, susceptibility values from cones with motion-resolved reconstruction ( QSM ppm $$ {\mathrm{QSM}}_{\mathrm{ppm}} $$ = 0.31 × gadolinium mM + $$ \times {\mathrm{gadolinium}}_{\mathrm{mM}}+ $$ 0.05, R 2 $$ {R}^2 $$ = 0.999) and Cartesian without motion ( QSM ppm $$ {\mathrm{QSM}}_{\mathrm{ppm}} $$ = 0.32 × gadolinium mM + $$ \times {\mathrm{gadolinium}}_{\mathrm{mM}}+ $$ 0.04, R 2 $$ {R}^2 $$ = 1.000) showed linear relationships with gadolinium concentrations and showed good agreement with each other. For in vivo, motion-resolved reconstruction showed higher goodness of fit ( QSM ppm $$ {\mathrm{QSM}}_{\mathrm{ppm}} $$ = 0.00261 × R 2 s - 1 * - $$ \times {\mathrm{R}}_{2_{{\mathrm{s}}^{-1}}}^{\ast }- $$ 0.524, R 2 $$ {R}^2 $$ = 0.977) compared to motion-averaged reconstruction ( QSM ppm $$ {\mathrm{QSM}}_{\mathrm{ppm}} $$ = 0.0021 × R 2 s - 1 * - $$ \times {\mathrm{R}}_{2_{{\mathrm{s}}^{-1}}}^{\ast }- $$ 0.572, R 2 $$ {R}^2 $$ = 0.723) in ROI-based linear regression analysis between R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and QSM. CONCLUSION: Feasibility of free-breathing liver QSM was demonstrated with motion-resolved 3D multi-echo UTE cones MRI, achieving high isotropic resolution currently unachievable in conventional Cartesian MRI.

Slipped capital femoral epiphyses: A major on-target adverse event associated with FGFR tyrosine kinase inhibitors in pediatric patients.

Fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitors (TKIs) are increasingly being used off label in pediatrics. Long-term safety data are limited, and serious toxicities unique to pediatrics may emerge. In a retrospective analysis of patients less than 18 years of age with recurrent/refractory FGFR altered gliomas treated with FGFR TKIs at MSKCC (n = 7), we observed slipped capital femoral epiphyses in three of seven patients along with increased linear growth velocity. Clinicians should closely monitor bone health and have a low index of suspicion for serious orthopedic complications including slipped capital femoral epiphyses and inform patients of related risks as part of consent when treating with FGFR TKIs.

Imaging of pediatric pancreas tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper.

Primary pancreatic tumors in children are rare with an overall age-adjusted incidence of 0.018 new cases per 100,000 pediatric patients. The most prevalent histologic type is the solid pseudopapillary neoplasm, followed by pancreatoblastoma. This paper describes relevant imaging modalities and presents consensus-based recommendations for imaging at diagnosis and follow-up.

Imaging of pediatric adrenal tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper.

Adrenal tumors other than neuroblastoma are uncommon in children. The most frequently encountered are adrenocortical carcinoma and pheochromocytoma. This paper offers consensus recommendations for imaging of pediatric patients with a known or suspected primary adrenal malignancy other than neuroblastoma at diagnosis and during follow-up.

Imaging of pediatric ovarian tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper.

Ovarian tumors in children are uncommon. Like those arising in the adult population, they may be broadly divided into germ cell, sex cord, and surface epithelium subtypes; however, germ cell tumors comprise the majority of lesions in children, whereas tumors of surface epithelial origin predominate in adults. Diagnostic workup, including the use of imaging, requires an approach that often differs from that required in an adult. This paper offers consensus recommendations for imaging of pediatric patients with a known or suspected primary ovarian malignancy at diagnosis and during follow-up.

Imaging of pediatric testicular tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper.

Primary intratesticular tumors are uncommon in children, but incidence and risk of malignancy both sharply increase during adolescence. Ultrasound is the mainstay for imaging the primary lesion, and cross-sectional modalities are often required for evaluation of regional or distant disease. However, variations to this approach are dictated by additional clinical and imaging nuances. This paper offers consensus recommendations for imaging of pediatric patients with a known or suspected primary testicular malignancy at diagnosis and during follow-up.

Lumps and bumps: What not to miss.

The evaluation of pediatric patients with subcutaneous nodules remains a diagnostic challenge. Pediatric dermatologists are regularly confronted with patients who have a nonspecific nodule. Though most masses that require evaluation are ultimately benign, the possibility of a more aggressive process, including borderline or malignant neoplasms, underscores the pivotal role of the pediatric dermatologist in recognizing these lesions. The aim of this review is to provide an overview of lumps and bumps that are important to recognize to prevent delay in diagnosis or treatment of a serious underlying condition. Clinical clues that may lead the pediatric dermatologist to have a higher index of suspicion for more aggressive lesions are reviewed. Suggestions for evaluation and workup, as well as tips for the difficult to discern lesion, are proposed.

Clinical and imaging experience with COVID-19 in nonvaccinated children with cancer.

Children with COVID-19 fare much better than adults but less is known about children with both COVID-19 and a cancer diagnosis in terms of clinical outcome and imaging. We describe our experience with a cohort of children with COVID-19 and cancer who have undergone medical imaging. We reviewed imaging and recorded clinical data and separated this group into two subgroups - hematologic and solid malignancies. Our observational data show that 1)children with hematologic malignancies may be at higher risk for complications, including death than, those with solid tumors, 2) that pulmonary imaging in the former group more often shows abnormalities and 3) that presence of pulmonary imaging abnormalities may portend an unfavorable outcome.

Emergency room imaging in pediatric patients with cancer: analysis of the spectrum and frequency of imaging modalities and findings in a tertiary cancer center and their relationship with survival.

BACKGROUND: To assess the spectrum and frequency of modalities used for emergency room (ER) imaging and their findings in pediatric cancer patients and assess their relationship with survival. METHODS: Consecutive pediatric cancer patients that underwent imaging during an ER visit at our tertiary cancer center over a 5-year period were retrospectively analyzed. Imaging findings were considered positive when they were relevant to the ER presenting complaint. Imaging positivity was correlated with inpatient admission. Overall survival (OS) was assessed with Kaplan-Meier curves and uni- and multi-variate Cox proportional hazards model was used to identify significant factors associated with OS. RESULTS: Two hundred sixty-one patients (135 males and 126 females; median age 11 years [interquartile range 5-16 years] with 348 visits and a total of 406 imaging studies were included. Common chief complaints were related to the chest (100 [28.7 %]) and fever (99 [28.4 %]). ER imaging was positive in 207 visits (59.5 %), commonly revealing increased metastases (50 [14.4 %]), pneumonia (47 [13.5 %]), and other lung problems (12 [2.9 %]). Positive ER imaging was associated with inpatient admission (69.3 % [133/192] vs. 40.4 % [63/156], p < 0.01). Multivariate survival analysis showed that positive ER imaging (hazard ratio [HR] = 2.35 [95% CI 1.44-3.83, p < 0.01), admission (HR = 1.86 [95% CI 1.17-3.00], p < 0.01), number of ER visits (HR = 3.08 [95% CI 1.62-5.83], p < 0.01 for ≥ 3 visits) were associated with poorer survival. CONCLUSIONS: Imaging was able to delineate the cause for ER visits in children with cancer in over half of the cases. Positive ER imaging was associated with admission and worse survival.

Is IV contrast necessary for MRI follow-up in children with abdominal neuroblastoma?

PURPOSE: The safety of multiple doses of gadolinium-based MRI IV contrast has recently been called in to question. While the long-term safety is being investigated, here, we seek to determine if there is added value to the use of IV contrast for improving detection of tumoral recurrences in children with a history of abdominal neuroblastoma. METHODS: This is a retrospective review of children who underwent abdominal MRI with gadolinium contrast. One radiologist reviewer determined presence or absence of tumor, both before and after administration of IV contrast material and documented level of confidence when a finding was encountered. Change in reader confidence after the use of contrast was measured and fraction of missed lesions on pre-contrast was calculated. Liver and spleen lesions were documented separately. RESULTS: 453 MRI scans in 110 unique patients were reviewed. 65 patients were documented to have a total of 125 lesions, excluding liver, spleen and bones. There were 23 instances of contrast altering the radiologist's confidence and one lesion was missed without the use of contrast. Among liver and spleen, several hepatic lesions were seen only after contrast, but all were benign lesions. CONCLUSION: In selected patients who are undergoing MRI for neuroblastoma, it may be reasonable to forgo the use of IV contrast.

Patient-adapted organ absorbed dose and effective dose estimates in pediatric 18F-FDG positron emission tomography/computed tomography studies.

BACKGROUND: Organ absorbed doses and effective doses can be used to compare radiation exposure among medical imaging procedures, compare alternative imaging options, and guide dose optimization efforts. Individual dose estimates are important for relatively radiosensitive patient populations such as children and for radiosensitive organs such as the eye lens. Software-based dose calculation methods conveniently calculate organ dose using patient-adjusted and examination-specific inputs. METHODS: Organ absorbed doses and effective doses were calculated for 429 pediatric 18F-FDG PET-CT patients. Patient-adjusted and scan-specific information was extracted from the electronic medical record and scanner dose-monitoring software. The VirtualDose and OLINDA/EXM (version 2.0) programs, respectively, were used to calculate the CT and the radiopharmaceutical organ absorbed doses and effective doses. Patients were grouped according to age at the time of the scan as follows: less than 1 year old, 1 to 5 years old, 6 to 10 years old, 11 to 15 years old, and 16 to 17 years old. RESULTS: The mean (+/- standard deviation, range) total PET plus CT effective dose was 14.5 (1.9, 11.2-22.3) mSv. The mean (+/- standard deviation, range) PET effective dose was 8.1 (1.2, 5.7-16.5) mSv. The mean (+/- standard deviation, range) CT effective dose was 6.4 (1.8, 2.9-14.7) mSv. The five organs with highest PET dose were: Urinary bladder, heart, liver, lungs, and brain. The five organs with highest CT dose were: Thymus, thyroid, kidneys, eye lens, and gonads. CONCLUSIONS: Organ and effective dose for both the CT and PET components can be estimated with actual patient and scan data using commercial software. Doses calculated using software generally agree with those calculated using dose conversion factors, although some organ doses were found to be appreciably different. Software-based dose calculation methods allow patient-adjusted dose factors. The effort to gather the needed patient data is justified by the resulting value of the characterization of patient-adjusted dosimetry.

Off-the-shelf EBV-specific T cell immunotherapy for rituximab-refractory EBV-associated lymphoma following transplantation.

BACKGROUNDAdoptive transfer of donor-derived EBV-specific cytotoxic T-lymphocytes (EBV-CTLs) can eradicate EBV-associated lymphomas (EBV-PTLD) after transplantation of hematopoietic cell (HCT) or solid organ (SOT) but is unavailable for most patients.METHODSWe developed a third-party, allogeneic, off-the-shelf bank of 330 GMP-grade EBV-CTL lines from specifically consented healthy HCT donors. We treated 46 recipients of HCT (n = 33) or SOT (n = 13) with established EBV-PTLD, who had failed rituximab therapy, with third-party EBV-CTLs. Treatment cycles consisted of 3 weekly infusions of EBV-CTLs and 3 weeks of observation.RESULTSEBV-CTLs did not induce significant toxicities. One patient developed grade I skin graft-versus-host disease. Complete remission (CR) or sustained partial remission (PR) was achieved in 68% of HCT recipients and 54% of SOT recipients. For patients who achieved CR/PR or stable disease after cycle 1, one year overall survival was 88.9% and 81.8%, respectively. In addition, 3 of 5 recipients with POD after a first cycle who received EBV-CTLs from a different donor achieved CR or durable PR (60%) and survived longer than 1 year. Maximal responses were achieved after a median of 2 cycles.CONCLUSIONThird-party EBV-CTLs of defined HLA restriction provide safe, immediately accessible treatment for EBV-PTLD. Secondary treatment with EBV-CTLs restricted by a different HLA allele (switch therapy) can also induce remissions if initial EBV-CTLs are ineffective. These results suggest a promising potential therapy for patients with rituximab-refractory EBV-associated lymphoma after transplantation.TRIAL REGISTRATIONPhase II protocols (NCT01498484 and NCT00002663) were approved by the Institutional Review Board at Memorial Sloan Kettering Cancer Center, the FDA, and the National Marrow Donor Program.FUNDINGThis work was supported by NIH grants CA23766 and R21CA162002, the Aubrey Fund, the Claire Tow Foundation, the Major Family Foundation, the Max Cure Foundation, the Richard "Rick" J. Eisemann Pediatric Research Fund, the Banbury Foundation, the Edith Robertson Foundation, and the Larry Smead Foundation. Atara Biotherapeutics licensed the bank of third-party EBV-CTLs from Memorial Sloan Kettering Cancer Center in June 2015.

Proportion and Clinical Relevance of Intraspinal Air in Patients With Pneumomediastinum.

OBJECTIVE: The purposes of this study were to determine the incidence of pneumorrhachis among patients with pneumomediastinum, determine whether its proportion correlates with the extent of pneumomediastinum, and ascertain its clinical relevance. MATERIALS AND METHODS: The radiologic database was searched for CT reports between January 2009 and September 2013 containing the term "pneumomediastinum" or "mediastinal air." Scans were examined for pneumomediastinum, pneumorrhachis, pneumothorax, sternotomy, and distribution of pneumomediastinum. The age and sex of the patient and probable cause of the abnormality were recorded. Cases that might have had another cause were excluded. RESULTS: The search yielded 422 CT scans. Among these, 242 instances of pneumomediastinum in 241 patients were found. Fifteen of these patients had pneumorrhachis. One was excluded because of recent traumatic spinal penetration. There was no significant difference in age or sex between patients with and those without pneumorrhachis. After application of the exclusion criteria, there were 14 cases of pneumorrhachis, yielding a proportion of 5.8%. Pneumorrhachis was observed more frequently in cases of the most severe grade (grade C) of pneumomediastinum; however, that relationship was not statistically significant (11 cases [8.2%]; p = 0.304). Pneumorrhachis was found significantly more frequently in patients with distribution of air in all three mediastinal compartments (13 cases, 16.2%, p < 0.001). Pneumorrhachis was overrepresented among subjects with spontaneous compared with those with secondary pneumomediastinum, although the trend did not reach statistical significance. CONCLUSION: Pneumorrhachis was present in 5.8% of patients. It is significantly more common in patients with the broadest distributions of mediastinal air and nonsignificantly more common in association with spontaneous as opposed to secondary pneumomediastinum. Pneumorrhachis in patients with pneumomediastinum is a generally benign, self-resolving condition.

Preprocedural Ultrasound for Infant Lumbar Puncture: A Randomized Clinical Trial.

BACKGROUND: Our purpose was to determine the potential effect of preprocedural ultrasound (US) to increase lumbar puncture (LP) success compared with standard palpation method. Further, we assessed feasibility of and clinician satisfaction with a standardized US protocol. METHODS: This prospective, two-arm, parallel-group randomized trial was conducted in a single-center pediatric emergency department. We compared preprocedural US versus palpation method on success with infant LPs. Infants less than 3 months of age requiring LP were enrolled. Sixteen pediatric emergency medicine physicians with varied US experience were trained to conduct the USs to mark interspace locations. Primary outcome was successful LP, defined as obtaining a cerebrospinal fluid (CSF) sample on first attempt with < 1,000 red blood cells per high-powered field (clear CSF). Secondary outcomes included clear CSF on any attempt, any CSF on the first attempt, traumatic LP proportion, and LP attempt frequency. Feasibility was assessed by comparing provider number attempting the LP and procedure duration. Clinician satisfaction and sonographer perceptions of US acceptability and impact were assessed. RESULTS: Eighty-one patients consented and 80 were analyzed (99%): 40 per group. No statistical difference was seen for the primary outcome (p > 0.05) between intervention and control groups (difference 3%; 95% confidence interval = -19% to 24%). There were no statistical differences between intervention and controls groups for secondary outcomes including the rate of traumatic LPs, number of attempts, and the duration of LP procedure. Most sonographers (84%) strongly agreed or agreed that the US protocol was technically easy to perform, well tolerated by the patient (94%), well accepted by the family (100%), and well accepted by the LP procedural clinicians (99%). In the US group, the majority of clinicians who performed the LPs (68.4%) noted that the preprocedural US influenced their behavior, most commonly helping with overall visualization at the selected interspace (28.9%) or prompting a change in interspace (26.3% higher, 5.3% lower). Seventy-seven percent agreed or strongly agreed that they would like to use the technique again for their next LP. The mean US duration was 4.6 minutes. CONCLUSIONS: Preprocedural US by did not improve the rates of first-attempt success when compared with palpation method. Our results suggest that US is feasible and well accepted, with a perceptible impact on care.

Patient-specific organ and effective dose estimates in pediatric oncology computed tomography.

PURPOSE: Estimate organ and effective doses from computed tomography scans of pediatric oncologic patients using patient-specific information. MATERIALS AND METHODS: With IRB approval patient-specific scan parameters and patient size obtained from DICOM images and vendor-provided dose monitoring application were obtained for a cross-sectional study of 1250 pediatric patients from 0 through 20 y-olds who underwent head, chest, abdomen-pelvis, or chest-abdomen-pelvis CT scans. Patients were categorized by age. Organ doses and effective doses were estimated using VirtualDose™ CT based on patient-specific information, tube current modulation (TCM), and age-specific realistic phantoms. CTDIvol, DLP, and dose results were compared with those reported in the literature. RESULTS: CTDIvol and DLP varied widely as patient size varied. The 75th percentiles of CTDIvol and DLP were no greater than in the literature with the exception of head scans of 16-20 y-olds and of abdomen-pelvis scans of larger patients. Eye lens dose from a head scan was up to 69 mGy. Mean organ doses agreed with other studies at maximal difference of 38% for chest and 41% for abdomen-pelvis scans. Mean effective dose was generally higher for older patients. The highest effective doses were estimated for the 16-20 y-olds as: head 3.3 mSv, chest 4.1 mSv, abdomen-pelvis 10.0 mSv, chest-abdomen-pelvis 14.0 mSv. CONCLUSION: Patient-specific organ and effective doses have been estimated for pediatric oncologic patients from <1 through 20 y-olds. The effect of TCM was successfully accounted for in the estimates. Output parameters varied with patient size. CTDIvol and DLP results are useful for future protocol optimization.