Acute Myeloid Leukemia (AML) patients have a wide array of cytogenetic and molecular aberrations which can influence response to therapy. Monosomy7 (Mono7) is a rare subset within pediatric AML (prevalence of 4-5%), that is highly associated with poor outcomes. Fusions involving the ALK gene (14.3%) were exclusively identified within this high-risk cohort while absent across all other AML. Given the dismal outcomes of Mono7, we evaluated the use of crizotinib, an FDA-approved tyrosine kinase inhibitor, used to treat patients with ALK fusions. Our findings suggest that crizotinib may serve as a novel therapy for these patients.

The PHO workforce landscape has been evolving over the past decades, with concern for waning interest in the subspecialty. In this study, we aimed to evaluate perceptions of the PHO workforce (both fellows and faculty), the experience of seeking an initial faculty position, and its impact on fellow stress and anxiety. An anonymous survey consisting of demographics, job search experiences including barriers and helpful tools, and emotional health impacts such as stress and anxiety was developed and distributed to all PHO fellowship programs. Seventy-nine fellows and 83 faculty responded. Faculty were less likely than fellows to perceive that fellows are struggling to find jobs ( P=0.0198). However, faculty were more likely than fellows to perceive that fellows are either “extremely stressed” or “stressed” due to job search ( P=0.0003). By June 2021, 30 of 44 (68%) candidates had been offered a position, and 80% of those had accepted. There were no significant associations between fellow stress level and job offering, proximity to their ideal goals, or change in career type. Common barriers to the job search included geographic constraints and partner employment. Respondents identified centralized job listings, formal training on career development strategies, introduction to various career paths, and more transparency about the job search as needed interventions. The perception of difficulty and stress regarding the job search is endorsed by most, identifying a need for more interventions to improve the job search experience. These data also highlight unmet mentorship and educational needs among PHO fellows in preparing for the job search.

Sickle cell disease is the most prevalent inherited blood disorder in the world, with significant morbidity and mortality. Patients often have recurrent painful vaso-occlusive episodes, and the American Society of Hematology gives a conditional recommendation for the use of regional anesthesia for acute sickle cell pain management. This scoping review summarizes the current evidence and identifies gaps for future research. Our screening process is outlined, and articles that mentioned the use of regional anesthesia for acute sickle cell crises were included. We present and interpret our results and highlight opportunities for future investigation.

Acute Lymphoblastic Leukemia of the Central Nervous System Presenting with Rapid Weight GainConnor P. Hall1 and Alan D. Friedman11Division of Pediatric Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USACorrespondence: Alan D. Friedman, MDJohns Hopkins UniversityCRB I, Rm. 253 1650 Orleans St. Baltimore, Maryland 21231 Phone: 410-955-2095; Fax: 410-955-8897 Email: [email protected] Count: 863Number of Figures: 1Running Title: Rapid Weight Gain in ALLKey Words: acute lymphoblastic leukemia/ relapse/ weight gain/ central nervous systemAbbreviations:

We conducted a cross-sectional study using a questionnaire to explore the late effects in survivors of juvenile myelomonocytic leukemia (JMML). The attending pediatric hematologist oncologists completed the questionnaires. All survivors (N=30) had undergone allogeneic hematopoietic stem cell transplantation. Approximately 83% survivors showed more than one late effect. The identified late effects included endocrine, dental, skin, ophthalmologic, musculoskeletal, pulmonary, neurocognitive, and cardiovascular dysfunction. The prevalence of short stature and cardiovascular and kidney dysfunction was significantly elevated among survivors aged ≥18 years. Therefore, a multidisciplinary follow-up system for survivors of JMML is crucial.

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 manuscript describes relevant imaging modalities and presents consensus-based recommendations for imaging at diagnosis and follow up.

The most common pediatric extragonadal pelvic cancers include germ cell tumors, sacrococcygeal teratomas, and rhabdomyosarcomas (arising from the urinary bladder, prostate, paratesticular tissues, vagina, uterus, and perineum). This manuscript describes the radiological and nuclear medicine features of these entities and provides consensus-based recommendations for the assessment at diagnosis, during and after treatment.

Purpose: Pediatric patients with medulloblastoma in LMICs are most treated with 3D conformal photon craniospinal irradiation (CSI), a time-consuming, complex treatment to plan, especially in resource-constrained settings. Therefore, we developed and tested a 3D conformal CSI autoplanning tool for varying patient lengths. Methods and Materials: Autocontours were generated with a deep learning model trained:tested (80:20 ratio) on 143 pediatric medulloblastoma CT scans (patient ages, 2-19 years, median=7 years). Using the verified autocontours, the autoplanning tool generated 2 lateral brain fields matched to a single spine field, an extended single spine field, or 2 matched spine fields. Additional spine sub-fields were added to optimize the corresponding dose distribution. Feathering was implemented (yielding 9-12 fields) to give a composite plan. Each planning approach was tested on 6 patients (ages, 3-10 years). A pediatric radiation oncologist assessed clinical acceptability of each autoplan. Results: The autocontoured structures’ average Dice similarity coefficient ranged from 0.65-0.98. The average V95 for the brain/spinal canal for single, extended, and multi-field spine configurations was 99.9±0.06%/99.9±0.10%, 99.9±0.07%/99.4±0.30%, and 99.9±0.06%/99.4±0.40%, respectively. The average maximum dose across all field configurations to the brainstem, eyes (L/R), lenses (L/R) and spinal cord were 23.7±0.08 Gy, 24.1±0.28 Gy, 13.3±5.27 Gy, 25.5±0.34 Gy, respectively (prescription=23.4 Gy/13 fractions). Of the 18 plans tested, all were scored as clinically acceptable as-is or clinically acceptable with minor, time-efficient edits preferred or required. No plans were scored as clinically unacceptable. Conclusion: The autoplanning tool successfully generated pediatric CSI plans for varying patient lengths in 3.50 ± 0.4 minutes on average, indicating potential for an efficient planning aid in resource-constrained settings.

Pediatric thyroid cancer is rare in children, however incidence is increasing. Papillary thyroid cancer and follicular thyroid cancer are the most common subtypes, comprising about 90% and 10% of cases respectively. This manuscript provides consensus imaging recommendations for evaluation of pediatric patients with thyroid cancer at diagnosis and during follow-up.

Introduction: The InPOG-HL-15-01, a multi-centric prospective study used a risk-stratified and response-based approach with a doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) backbone to treat children with newly diagnosed Hodgkin Lymphoma (HL) and reduce the use of radiation therapy (RT). Children/adolescents with bulky disease or inadequate response at early response assessment (ERA) after 2 cycles of chemotherapy were assigned to receive RT. For ERA, positron emission tomography computed tomography (PET-CT) was recommended but not mandatory in view of limited access. This study aimed to compare the impact of using contrast enhanced computed tomography (CECT) vs PET-CT on treatment decisions and outcomes. Methodology: 396 patients were enrolled and 382 had an ERA at the assigned time point. Results: At ERA, satisfactory response was documented in 277/382 (72.5%) participants and this was significantly higher in PET-CT (151/186, 81.2%) as compared to CECT (126/196, 64.3%) respectively (p value<0.001). Amongst the 203 patients with non-bulky disease (wherein the indication for RT was entirely dependent on ERA), 96/114 (84.2%) and 61/89 (68.5%) patients achieved a satisfactory response according to the PET-CT and CECT (p value=0.008) respectively and hence a lesser proportion of patients in the PET-CT arm received RT. Despite a lower usage of RT the 5 year overall survival (OS) of both groups- ERA based on CECT (91.8%) vs PET-CT (94.1%) was comparable (p value=0.391) and so was the 5 year event free survival (EFS) (86.7 vs 85.5%, p value=0.724). Conclusion: Use of PET-CT as the modality for ERA is more likely to indicate a satisfactory response as compared to CECT and thereby decreases the need for RT in response-based treatment algorithm for HL afflicted children. The reduction in the application of RT did not impact the overall outcome and plausibly would lower the risk of delayed toxic effects.

Title: BRAFMutation in Neuroblastoma: A Rare FindingAuthors: Sara C Hutchins1, Sara R Ferguson1, Geling Li2, Elizabeth A Beierle3*, Elizabeth Alva1

Sickle cell disease (SCD) requires coordinated, specialized medical care for optimal outcomes. There are no United States (US) guidelines that define a pediatric comprehensive SCD program. We report a modified Delphi consensus-seeking process to determine essential, optimal, and suggested elements of a comprehensive pediatric SCD center. Nineteen pediatric SCD specialists participated from the US. Consensus was predefined as 2/3 agreement on each element’s categorization. Twenty-six elements were considered essential (required for guideline-based SCD care), ten were optimal (recommended but not required), and five were suggested. This work lays the foundation for a formal recognition process of pediatric comprehensive SCD centers.

Background: Desmoid tumor (DT) is rare and challenging, often affects head neck (HN) region in children, and its appropriate treatments are under discussed. This study aimed to retrospectively evaluate long-term effectiveness and safety of 125I seed brachytherapy for pediatric DT in HN. Procedure: Seven pediatric patients with median age of 3 years old suffered from DT in HN treated with 125I brachytherapy from January 2008 to June 2018 were included. Among which, 5 underwent sole brachytherapy and the others combined with surgery under a prescription doses ranging from 10 000 cGy to 12 000 cGy. The rate of local control (LC), complete response (CR) and partial response (PR) were calculated after evaluation by radiological and pathological means. The radiation-associated toxicities were also evaluated Results: The LC rate was 7/7 during the follow-up time ranging from 43 to 135 months and with a mean of 57 months. No recurrent lesion was found in the patients receiving surgery combined with brachytherapy. In patients treated with sole brachytherapy, the radiological PR rate and CR rate were 4/5 and 1/5, respectively. In those reaching radiological PR, 3/4 were pathological CR. Slight acute radiation-associated toxicities were observed in all patients, and no late or severe acute toxicity was observed. Conclusion: 125I brachytherapy is effective and safe in the management of pediatric DT in HN as sole modality or combined with surgery in long term.

–Title:Pediatric Colon Cancer - When Enemies Band Together.

Local therapies replaced systemic chemotherapy for ocular preservation in retinoblastoma. In middle income countries, these techniques pose specific challenges mostly related to more advanced disease at diagnosis. The Grupo de America Latina de Oncologia Pediatrica (GALOP developed a consensus document for the management of conservative therapy for retinoblastoma. Intra-arterial chemotherapy (OAC) is the preferred therapy, except those with less advanced disease or age younger than 6 months. OAC allowed for the elimination of the use of external beam radiotherapy in our setting. Intravitreal chemotherapy is the preferred treatment for vitreous seeding. Enucleation is the treatment of choice for advanced eyes.

Background: Irinotecan and temozolmide achieve objective responses in patients with Ewing sarcoma which recurrences after initial therapy. Optional dose schedules have not been defined. Procedure: We reviewed published series of patients treated with irinotecan and temozolomide for Ewing sarcoma which recurred after initial therapy. We compared objective response rates for patients who received 5 day irinotecan treatment schedules to response rates for patients who achieved 10 day irinotecan treatment schedules. Results: Among 94 patients treated with a 10 day irinotecan schedule there were 48 objective responses (51%). Among 218 patients treated with a 5 day irinotecan schedule there were 65 responses (30%). Conclusion: When we use irinotecan to treat Ewing sarcoma we should administer 10 days of treatment.

Background and Objective: Immune thrombocytopenia (ITP) is an autoimmune-mediated hemorrhagic disease. Anti-glycoprotein autoantibodies play a key role in the pathophysiology of ITP, but the relationship between platelet-specific antibodies and bleeding severity is unclear. This study aimed to analyze the relationship between anti-glycoprotein autoantibodies and bleeding severity in children with newly diagnosed ITP and platelet count <10×109/L. Method: This was a single-center prospective observational study that analyzed children with newly diagnosed ITP and platelet count <10×109/L between June 2018 and September 2021 at our hospital. The children were classified into the mild and severe groups based on the bleeding scores. The type and titer of anti-glycoprotein autoantibodies were detected using an ELISA kit (PAKAUTO). We analyzed the relationship between bleeding severity and anti-glycoprotein autoantibodies. Results: A total of 86 cases were enrolled, including 42 in the mild group and 44 in the severe group. Patients with anti-GPIIb/IIIa or anti-GPIb/IX antibodies suffered more severe bleeding than patients without them (c2=7.303, p=0.007; c2=3.875, p=0.049), but there was no significant difference between patients with or without anti-GPIa/IIa antibody (c2=0.745, p=0.388). When antibodies were analyzed together, patients with three antibodies suffered more severe bleeding than those without three antibodies (c2=5.053, p=0.025). Patients with higher antibody titer in the eluent, but not in the plasma, suffered more severe bleeding in all three antibodies (Z=-2.389, p=0.017; Z=-2.108, p=0.035; Z=-2.557, p=0.011). Conclusion: Anti-glycoprotein autoantibodies led to more severe bleeding in children under 18 years of age without drug treatment with newly diagnosed ITP and platelet count <10×109/L.

A document by Seema Biswas. Click on the document to view its contents.