Agreement between serum estimates of glomerular filtration rate (GFR) and a reference standard of radioisotopic GFR in children with cancer.

BACKGROUND: Accurate assessment of renal function is important in the care of children with cancer because renal function has implications for anti-tumor medication dosing and eligibility for clinical trials. OBJECTIVE: To characterize agreement between serum estimates of glomerular filtration rate (GFR) and a reference standard of radioisotopic GFR in a large pediatric oncology cohort. MATERIALS AND METHODS: We conducted a retrospective cross-sectional study of children who had both radioisotopic GFR (99mTc-diethylenetriaminepentaacetic acid, or 99mTc-DTPA) and serum labs (creatinine, cystatin C) obtained <7 days apart between January 2017 and August 2019. We calculated estimated GFR from serum labs using published equations and calculated agreement using intraclass correlation coefficient (ICC) and Bland-Altman analysis with univariate regression to define predictors of agreement. RESULTS: We included 272 pairs of data. Mean patient age was (mean ± standard deviation) 7.8±5.7 years. Mean radioisotopic GFR was 112±33 mL/min/1.73 m2. Absolute agreement between radioisotopic GFR and serum estimates was only fair (ICC=0.46-0.58) with a mean difference of -26.6 to +0.12 mL/min/1.73 m2. For radioisotopic GFR measurements <60 mL/min/1.73 m2, mean differences were greater, with serum estimates overestimating GFR by a mean of 21.5-39.6 mL/min/1.73 m2. In multivariable modeling, significant predictors of agreement included age, height, acute kidney injury and tumor type. Sensitivity of serum estimates was 14-29% for a GFR <60 mL/min/1.73 m2. CONCLUSION: Agreement between radioisotopic GFR and serum estimates of GFR is only fair and serum estimates of GFR have poor sensitivity for clinically relevant GFR <60 mL/min/1.73 m2. Radioisotopic measurement of GFR likely remains necessary to assess renal function in pediatric oncology patients with decreased renal function.

A study of axitinib, a VEGF receptor tyrosine kinase inhibitor, in children and adolescents with recurrent or refractory solid tumors: A Children's Oncology Group phase 1 and pilot consortium trial (ADVL1315).

BACKGROUND: Axitinib is an oral small molecule that inhibits receptor tyrosine kinases vascular endothelial growth factor receptors 1 to 3. A phase 1 and pharmacokinetic (PK) trial evaluating axitinib was conducted in children with refractory solid tumors. METHODS: Axitinib was administered orally twice daily in continuous 28-day cycles. Dose levels (2.4 mg/m2 /dose and 3.2 mg/m2 /dose) were evaluated using a rolling 6 design. Serial PKs (cycle 1, days 1 and 8) and exploratory biomarkers were analyzed. RESULTS: A total of 19 patients were enrolled; 1 patient was ineligible due to inadequate time having elapsed from prior therapy. The median age of the patients was 13.5 years (range, 5-17 years). Two of 5 patients who were treated at dose level 2 experienced dose-limiting toxicities (palmar-plantar erythryodysesthesia syndrome in 1 patient and intratumoral hemorrhage in 1 patient). Frequent (>20%) grade 1 to 2 toxicities during cycle 1 included anemia, anorexia, fatigue, diarrhea, nausea, and hypertension. Nonhematological toxicities of grade ≥3 in subsequent cycles included hypertension and elevated serum lipase. PK analysis demonstrated variability in axitinib exposure, the median time to peak plasma concentration was 2 hours, and the half-life ranged from 0.7 to 5.2 hours. Exposure and dose were not found to be significantly associated with hypertension. Five patients achieved stable disease for ≤6 cycles as their best response, including patients with malignant peripheral nerve sheath tumor (1 patient), Ewing sarcoma (1 patient), hepatocellular carcinoma (1 patient), and osteosarcoma (2 patients). One patient with alveolar soft part sarcoma achieved a partial response. Kidney injury biomarkers were found to be elevated at baseline; no trends were identified. CONCLUSIONS: In children with refractory solid tumors, the maximum tolerated and recommended dose of axitinib appears to be 2.4 mg/m2 /dose, which provides PK exposures similar to those of adults.

The use of neoadjuvant larotrectinib in the management of children with locally advanced TRK fusion sarcomas.

BACKGROUND: The highly selective oral tropomyosin receptor kinase (TRK) inhibitor larotrectinib has demonstrated significant activity in adult and pediatric TRK fusion cancers. In the current study, the authors describe the clinical course of children with locally advanced TRK fusion sarcoma who were treated preoperatively with larotrectinib and underwent subsequent surgical resection. METHODS: A total of 24 children were treated on a pediatric phase 1 trial of larotrectinib (ClinicalTrials.gov identifier NCT02637687). Five children who had a documented TRK fusion sarcoma and underwent surgical resection were included in the current analysis. Tumor response (Response Evaluation Criteria In Solid Tumors [RECIST] version 1.1) and surgical outcomes were collected prospectively. RESULTS: A total of 5 patients (median age, 2 years; range, 0.4-12 years) had locally advanced infantile fibrosarcoma (3 patients) or soft-tissue sarcoma (2 patients). Four patients had disease that was refractory to standard therapy. All 5 patients achieved a partial response to larotrectinib by version 1.1 of RECIST and underwent surgical resection after a median of 6 cycles (range, 4-9 cycles) of treatment. Surgical resections were R0 (negative resection margins with no tumor at the inked resection margin) in 3 patients, R1 (microscopic residual tumor at the resection margin) in 1 patient, and R2 (macroscopic residual tumor at the resection margin) in 1 patient. Three patients achieved complete (2 patients) or near-complete (>98% treatment effect; 1 patient) pathologic responses. These patients remained in follow-up and were no longer receiving larotrectinib for a minimum of 7 to 15 months postoperatively. Two patients had viable tumor at the time of surgical resection and positive resection margins and continued to receive adjuvant larotrectinib. No patients experienced postoperative complications or wound healing issues. CONCLUSIONS: Children with locally advanced TRK fusion sarcomas may proceed to surgical resection after treatment with the selective TRK inhibitor larotrectinib, thereby sparing them the potentially significant morbidity noted with current approaches. These results support the evaluation of larotrectinib as presurgical therapy in children with newly diagnosed TRK fusion sarcomas.

Pazopanib therapy for desmoid tumors in adolescent and young adult patients.

BACKGROUND: Desmoid tumors/aggressive fibromatosis (DT/AF) lack a reliably effective medical therapy. Surgical resection may be morbid and does not preclude recurrence. Radiation may carry severe late effects, particularly detrimental in young patients. At our institution, we recently observed promising results with pazopanib therapy for DT/AF in adolescent and young adult (AYA) patients. PROCEDURE: Retrospective single-institution chart review. RESULTS: Six DT/AF patients of 3-21 years with previously treated DT/AF received pazopanib; 31 DT/AF patients received established therapies only. In both groups, median age at diagnosis was 16 years, female patients comprised 50%, and most common DT/AF site was extremity. Established therapies showed few objective responses and most patients therefore received multiple therapies. Surgical resection had a 68% recurrence rate. Of eight patients who received vinblastine/methotrexate, only one had a partial response (PR) by RECIST 1.1 and five had stable disease (SD); 62.5% required additional therapy. Of seven patients who received sulindac/tamoxifen, none showed objective improvement. In contrast, pazopanib demonstrated best responses by RECIST of PR in two of seven and SD in six of seven tumors. A PR of 66% was observed in a patient who had failed multiple prior therapies. The mesenteric DT/AF also showed PR. Maximum volumetric decrease by T2-weighted magnetic resonance imaging (MRI) was 97%. Dramatically increased fibrosis was seen on T2-weighted MRI. Patients reported pain relief and improvement in function within 1 month. Except for one case of edema, all other toxicities responded to dose reduction without sacrificing objective treatment response. CONCLUSION: Pazopanib provides a promising, well-tolerated therapy for DT/AF in the AYA population and warrants further study.

Detection of lymph node metastases in pediatric and adolescent/young adult sarcoma: Sentinel lymph node biopsy versus fludeoxyglucose positron emission tomography imaging-A prospective trial.

BACKGROUND: Lymph node metastases are an important cause of treatment failure for pediatric and adolescent/young adult (AYA) sarcoma patients. Nodal sampling is recommended for certain sarcoma subtypes that have a predilection for lymphatic spread. Sentinel lymph node biopsy (SLNB) may improve the diagnostic yield of nodal sampling, particularly when single-photon emission computed tomography/computed tomography (SPECT-CT) is used to facilitate anatomic localization. Functional imaging with positron emission tomography/computed tomography (PET-CT) is increasingly used for sarcoma staging and is a less invasive alternative to SLNB. To assess the utility of these 2 staging methods, this study prospectively compared SLNB plus SPECT-CT with PET-CT for the identification of nodal metastases in pediatric and AYA patients. METHODS: Twenty-eight pediatric and AYA sarcoma patients underwent SLNB with SPECT-CT. The histological findings of the excised lymph nodes were then correlated with preoperative PET-CT imaging. RESULTS: A median of 2.4 sentinel nodes were sampled per patient. No wound infections or chronic lymphedema occurred. SLNB identified tumors in 7 of the 28 patients (25%), including 3 patients who had normal PET-CT imaging of the nodal basin. In contrast, PET-CT demonstrated hypermetabolic regional nodes in 14 patients, and this resulted in a positive predictive value of only 29%. The sensitivity and specificity of PET-CT for detecting histologically confirmed nodal metastases were only 57% and 52%, respectively. CONCLUSIONS: SLNB can safely guide the rational selection of nodes for biopsy in pediatric and AYA sarcoma patients and can identify therapy-changing nodal disease not appreciated with PET-CT. Cancer 2017;155-160. © 2016 American Cancer Society.

Severe cytokine release syndrome in a patient receiving PD-1-directed therapy.

Cytokine release syndrome (CRS) is a phenomenon of immune hyperactivation described in the setting of cellular and bispecific T-cell engaging immunotherapy. Checkpoint blockade using anti-programmed cell death 1 (anti-PD-1) inhibitors is an approach to antitumor immune system stimulation. A 29-year-old female with alveolar soft part sarcoma developed severe CRS after treatment with anti-PD-1 therapy. CRS was characterized by high fevers, encephalopathy, hypotension, hypoxia, hepatic dysfunction, and evidence of coagulopathy, and resolved after infusion of the interleukin-6 inhibitor tocilizumab and corticosteroids.

Optimizing the interval between G-CSF therapy and F-18 FDG PET imaging in children and young adults receiving chemotherapy for sarcoma.

BACKGROUND: Granulocyte colony-stimulating factors (G-CSF) speed recovery from chemotherapy-induced myelosuppression but the marrow stimulation they cause can interfere with interpretation of F-18 fluorodeoxyglucose positron emission tomography (F-18 FDG PET) exams. OBJECTIVE: To assess the frequency of interfering G-CSF-induced bone marrow activity on FDG PET imaging in children and young adults with Ewing sarcoma and rhabdomyosarcoma and to define an interval between G-CSF administration and FDG PET imaging that limits marrow interference. MATERIALS AND METHODS: Blinded, retrospective review of FDG PET exams performed in patients treated with long-acting G-CSF as part of their chemotherapeutic regimen. Exams were subjectively scored by two reviewers (R1 and R2) who assessed the level of marrow uptake of FDG and measured standardized uptake values in the marrow, liver, spleen and blood pool. FDG PET findings were correlated with time since G-CSF administration and with blood cell counts. RESULTS: Thirty-eight FDG PET exams performed in 17 patients were reviewed with 47.4% (18/38) of exams having marrow uptake of FDG sufficient to interfere with image interpretation. Primary predictors of marrow uptake of FDG were patient age (P=0.0037) and time since G-CSF exposure (P=0.0028 for subjective marrow uptake of FDG, P=0.008 [R1] and P=0.004 [R2] for measured maximum standardized uptake value (SUVmax)). The median interval between G-CSF administration and PET imaging in cases with marrow activity considered normal or not likely to interfere was 19.5 days (range: 7-55 days). CONCLUSION: In pediatric and young adult patients with Ewing sarcoma and rhabdomyosarcoma, an interval of 20 days between administration of the long-acting form of G-CSF and FDG PET imaging should limit interference by stimulated marrow.

Histogram Analysis of Apparent Diffusion Coefficient Maps Provides Genotypic and Pretreatment Phenotypic Information in Pediatric and Young Adult Rhabdomyosarcoma.

INTRODUCTION: We evaluate the role of apparent diffusion coefficient (ADC) histogram metrics in stratifying pediatric and young adult rhabdomyosarcomas. METHODS: We retrospectively evaluated baseline diffusion-weighted imaging (DWI) from 38 patients with rhabdomyosarcomas (Not otherwise specified: 2; Embryonal: 21; Spindle Cell: 2; Alveolar: 13, mean ± std dev age: 8.1 ± 7.76 years). The diffusion images were obtained on a wide range of 1.5 T and 3 T scanners at multiple sites. FOXO1 fusion status was available for 35 patients, nine of whom harbored the fusion. 13 patients were TNM stage 1, eight had stage 2 disease, nine were stage 3, and eight had stage 4 disease. 23 patients belonged to Clinical Group III and seven to Group IV, while two and five were CG I and II, respectively. Nine patients were classified as low risk, while 21 and five were classified as intermediate and high risk respectively. Histogram parameters of the apparent diffusion coefficient (ADC) map from the entire tumor were obtained based on manual tumor contouring. A two-tailed Mann-Whitney U test was used for all two-group, and the Kruskal-Wallis's test was used for multiple-group comparisons. Bootstrapped receiver operating characteristic (ROC) curves and areas under the curve (AUC) were generated for the statistically significant histogram parameters to differentiate genotypic and phenotypic parameters. RESULTS: Alveolar rhabdomyosarcomas had a statistically significant lower 10th Percentile (586.54 ± 164.52, mean ± std dev, values are in ×10-6mm2/s) than embryonal rhabdomyosarcomas (966.51 ± 481.33) with an AUC of 0.85 (95%CI. 0.73-0.95) for differentiating the two. The 10th percentile was also significantly different between FOXO1 fusion-positive (553.87 ± 187.64) and negative (898.07 ± 449.38) rhabdomyosarcomas with an AUC of 0.83 (95% CI 0.71-0.94). Alveolar rhabdomyosarcomas also had statistically significant lower Mean, Median, and Root Mean Squared ADC histogram values than embryonal rhabdomyosarcomas. Four, five, and seven of the 18 histogram parameters evaluated demonstrated a statistically significant increase with higher TNM stage, clinical group, assignment, and pretreatment risk stratification, respectively. For example, Entropy had an AUC of 0.8 (95% CI. 0.67-0.92) for differentiating TNM stage 1 from ≥ stage 2 and 0.9 (95% CI. 0.8-0.98) for differentiating low from intermediate or high-risk stratification. CONCLUSION: Our findings demonstrate the potential of ADC histogram metrics to predict clinically relevant variables for rhabdomyosarcoma, including FOXO1 fusion status, histopathology, Clinical Group, TNM staging, and risk stratification.

Immunohistochemical assessment and clinical, histopathologic, and molecular correlates of membranous somatostatin type-2A receptor expression in high-risk pediatric central nervous system tumors.

Introduction: 177Lu-DOTATATE, a radionuclide therapy that binds somatostatin type-2A receptors (SST2A), has demonstrated efficacy in neuroendocrine tumors and evidence of central nervous system (CNS) penetration, supporting potential expansion within pediatric neuro-oncology. Understanding the prevalence of SST2A expression across pediatric CNS tumors is essential to identify patients who may benefit from somatostatin receptor-targeted therapy and to further elucidate the oncogenic role of SST2A. Methods: SST2A immunohistochemistry (IHC) was performed on tumor specimens and interpreted by an experienced pathologist (blinded), utilizing semi-quantitative scoring of membranous expression within viable tumor. Immunoreactive cell percentage was visually scored as 0 (none), 1 (<10%), 2 (10-50%), 3 (51-80%), or 4 (>80%). Staining intensity was scored as 0 (none), 1 (weak), 2 (moderate), or 3 (strong). Combined scores for each specimen were calculated by multiplying percent immunoreactivity and staining intensity values (Range: 0-12). Results: A total of 120 tumor samples from 114 patients were analyzed. Significant differences in SST2A IHC scores were observed across histopathologic diagnoses, with consistently high scores in medulloblastoma (mean ± SD: 7.5 ± 3.6 [n=38]) and meningioma (5.7 ± 3.4 [n=15]), compared to minimal or absent expression in ATRT (0.3 ± 0.6 [n=3]), ETMR (1.0 ± 0 [n=3]), ependymoma (grades I-III; 0.2 ± 0.7 [n=27]), and high-grade glioma (grades III-IV; 0.4 ± 0.7 [n=23]). Pineoblastoma (3.8 ± 1.5 [n=4]) and other embryonal tumors (2.0 ± 4.0 [n=7]) exhibited intermediate, variable expression. Among medulloblastomas, SST2A IHC scores were higher in non-SHH (8.5 ± 3.1) than SHH (5.0 ± 3.3) molecular subgroups (p=0.033). In a subset of paired primary and recurrent specimens from four patients, SST2A IHC scores remained largely unchanged. Discussion: High membranous SST2A expression was demonstrated in medulloblastoma, meningioma, and some rarer embryonal tumors with potential diagnostic, biologic, and therapeutic implications. Somatostatin receptor-targeted therapy such as 177Lu-DOTATATE deserves further investigation in these highly SST2A-expressing pediatric CNS tumors.

Immuno-transcriptomic profiling of extracranial pediatric solid malignancies.

We perform an immunogenomics analysis utilizing whole-transcriptome sequencing of 657 pediatric extracranial solid cancer samples representing 14 diagnoses, and additionally utilize transcriptomes of 131 pediatric cancer cell lines and 147 normal tissue samples for comparison. We describe patterns of infiltrating immune cells, T cell receptor (TCR) clonal expansion, and translationally relevant immune checkpoints. We find that tumor-infiltrating lymphocytes and TCR counts vary widely across cancer types and within each diagnosis, and notably are significantly predictive of survival in osteosarcoma patients. We identify potential cancer-specific immunotherapeutic targets for adoptive cell therapies including cell-surface proteins, tumor germline antigens, and lineage-specific transcription factors. Using an orthogonal immunopeptidomics approach, we find several potential immunotherapeutic targets in osteosarcoma and Ewing sarcoma and validated PRAME as a bona fide multi-pediatric cancer target. Importantly, this work provides a critical framework for immune targeting of extracranial solid tumors using parallel immuno-transcriptomic and -peptidomic approaches.

Common Secondary Genomic Variants Associated With Advanced Epithelioid Hemangioendothelioma.

Importance: Epithelioid hemangioendothelioma (EHE) is a rare, malignant vascular sarcoma characterized in most cases by a WWTR1-CAMTA1 fusion. The clinical course of EHE exhibits a dual nature. The condition is often indolent but can rapidly grow and metastasize unpredictably. No biomarkers to date are available to predict this phenotype. The hypothesis of this study was that better defining the genomic landscape of EHE using next-generation sequencing could offer additional therapies and insight into clinical outcomes. Objective: To characterize secondary EHE genomic alterations and their association with clinical outcomes. Design, Setting, and Participants: Multicenter, cross-sectional, retrospective study of next-generation sequencing results collected from participants diagnosed with EHE. Data were abstracted between May 1, 2013, and May 31, 2019. This analysis was conducted from January through June 2019. Summary genomic data were provided by commercial genomic testing companies. Main Outcomes and Measures: Presence or absence of secondary pathogenic genomic variants and their association with disease stage and clinical features. Results: A total of 49 participants with EHE were assessed for the presence or absence of secondary genomic variants. Of these, 32 (65.3%) were female; the mean (SD) age at diagnosis was 49.9 (18.3) years (range, 11-81 years). In all, 46 participants (93.9%) had confirmed WWTR1-CAMTA1 fusion; 26 participants (57.1%) exhibited a pathogenic genomic variant secondary to the WWTR1-CAMTA1 fusion; and 9 participants (18.4%) exhibited potentially targetable genomic variants. Commonly altered genes included CDKN2A/B, RB1, APC, and FANCA. Participants older than 45 years at diagnosis had an increased prevalence of secondary genomic variants that was not statistically significant (65.6% vs 38.5%; difference, 27.1%; 95% CI, -3.5% to 58.0%; P = .16) and were more likely to have a clinically targetable variant (28.1% vs 0%; difference, 28.1%; 95% CI, 11.2%-40.2%; P = .03). In 14 participants with clinical data available, those with stage III/IV EHE were more likely to exhibit a secondary pathogenic genomic variant (80% vs 0%; difference, 80%; 95% CI, 55.2%-100%; P = .006). Participants with stage III/IV EHE were diagnosed at an older age (mean [SD] age, 54.6 [14.1] years vs 31.7 [16.0] years; P = .05) and had elevated WWTR1-CAMTA1 fusion expression that was not statistically significant (mean [SD] expression, 677 [706] copies vs 231 [213] copies; P = .20). Conclusions and Relevance: Although EHE exhibits few secondary genomic variants, presence of key secondary variants may be prognostic for aggressive EHE. Further research is needed to confirm this finding and determine whether more intensive upfront treatment is necessary for these patients.

Undifferentiated myxoid lipoblastoma with PLAG1-HAS2 fusion in an infant; morphologically mimicking primitive myxoid mesenchymal tumor of infancy (PMMTI)--diagnostic importance of cytogenetic and molecular testing and literature review.

Lipoblastoma is a benign myxoid neoplasm arising in young children that typically demonstrates adipose differentiation. It is often morphologically indistinguishable from primitive myxoid mesenchymal tumor of infancy (PMMTI), which is characterized by a well-circumscribed myxoid mass with a proliferation of primitive mesenchymal cells with mild cytologic atypia. PMMTI occurs in the first year of life and is known to have locally aggressive behavior. No specific genetic rearrangements have been reported to date. In contrast, the presence of PLAG1 (Pleomorphic Adenoma Gene 1) rearrangement is diagnostic for lipoblastoma. We hereby demonstrate the combined application of multiple approaches to tackle the diagnostic challenges of a rapidly growing neck tumor in a 3-month-old female. An incisional tumor biopsy had features of an undifferentiated, myxoid mesenchymal neoplasm mimicking PMMTI. However, tumor cells showed diffuse nuclear expression by immunohistochemical (IHC) stain. Conventional cytogenetic and fluorescence in situ hybridization (FISH) analyses as well as next generation sequencing (NGS) demonstrated evidence of PLAG1 rearrangement, confirming the diagnosis of lipoblastoma. This experience warrants that undifferentiated myxoid lipoblastoma can mimic PMMTI, and the combination of cytogenetic and molecular approaches is essential to distinguish these two myxoid neoplasms. Literature on lipoblastomas with relevant molecular and cytogenetic findings is summarized. Our case is the first lipoblastoma diagnosed with a PLAG1 fusion defined by NGS technology.

Chylothorax in Henoch-Schonlein purpura: a case report and review of the literature.

Henoch-Schonlein purpura (HSP) is the most common acute vasculitis in the pediatric population, with an incidence of 10-14 per 100,000. The classic presentation of this disorder includes erythematous papules followed by palpable purpura in the lower extremities, trunk, and face, arthralgia or arthritis, abdominal pain, gastrointestinal bleeding, and nephritis. While renal abnormalities in HSP are common, the classic pulmonary manifestations, such as hemorrhage and pneumonitis, are thought to be infrequent. Subclinical pulmonary manifestations, including diffusion defects and radiographic anomalies, seem to be quite frequent in patients with HSP but are not commonly reported. Other respiratory manifestations include pleural effusion and chylothorax, but these are rarely mentioned in the literature. Chylothorax was only reported once in an adult patient with HSP in whom the mechanism of formation was demonstrated to be secondary to transdiaphragmatic passage of chylous fluid from the peritoneal cavity. Here we describe an 8-year-old girl with HSP, nephrotic syndrome, and chylothorax, and we report the results of a review of the literature regarding respiratory complications in HSP. The present case is the first pediatric patient reported with HSP and chylothorax. The therapeutic measures utilized were effective in resolving her edema, ascites, and chylothorax, and we advocate the use of these measures as first-line therapy in future patients with similar complications from HSP.

Minimizing nuclear medicine technologist radiation exposure during 131I-MIBG therapy.

131I-metaiodobenzylguanidine is a norepinephrine analog that concentrates in adrenergic tissue and has been shown to be an effective radiotherapeutic agent used to treat tumors of neural crest origin, particularly neuroblastoma, a sympathetic nervous system malignancy of children. The purpose of this study was to determine the radiation dose received by nuclear medicine technologists while preparing and administering 131I-metaiodobenzylguanidine therapy dosages, and if any changes could be implemented that would reduce a technologist's dose. The study involves the collection of total whole body doses received by technologists during the treatment of six patients. Patient dosages ranged from 9.25 to 31.1 GBq, with radiation exposures to the nuclear medicine technologists averaging 0.024 µSv per MBq administered to the patient. Subsequently, the doses received by the technologists were analyzed with respect to specific process steps performed during 131I-metaiodobenzylguanidine therapy including package receipt, dosage preparation, and dosage administration. Results show that the largest contribution to the technologist's whole body radiation dose (>83%) is received during the dosage administration process step. After additional shielding was installed for use during the dosage administration process step, technologists' doses decreased 80%.