Background: Postoperative hypocalcemia is a frequent complication after thyroid surgery. Hypoparathyroidism may develop as transient (TtHP), with normalization within six months from surgery, or permanent (PtHP) if the patient requires replacement therapy. The present study analyzes rates and factors associated with the development of TtHP or PtHP following thyroid surgery in a pediatric population. Procedure: A retrospective multicenter study analyzing 363 patients was carried out. We recorded gender, age, tumor size, type of surgery, lymph node dissection, histology. Calcium levels were acquired daily for 72 hours after discharge. Subsequent sample collection was customized on the patient’s hypocalcemia severity. Results: We analyzed 363 patients aged ≤18 years (mean age 14.2 years) who underwent thyroid surgery clustered into age groups (≤15 or >15). Patients mean follow-up was 5.8 years (1-11yrs). At histology 310 (85%) were papillary carcinoma, 32 (9%) were follicular carcinoma, 6 (2%) presented diffuse sclerosing variant of papillary thyroid carcinoma whilst 15 (4%) had familial medullary carcinoma. TtHP developed in 36 (9,9%), PtHP in 20 (5.5%) cases. TtHP was more frequent in younger patients (p=0,009). Both PtHP and TtHP were increased in case of larger tumors (≥2 cm) (p=0,001). All TtHP and PtHP were in TT group. PtHP rate was increased if lymph node dissection was carried out (p<0.001). Conclusions: The risk of hypoparathyroidism is related to younger age, tumor size, TT and lymph node dissection therefore surgeons should tailor surgery as much as possible to avert such complication.

Background The International Soft Tissue Sarcoma Consortium (INSTRuCT) was founded as an international collaboration between different pediatric soft tissue sarcoma cooperative groups (COG, EpSSG, CWS). Besides other tasks, a major goal of the INSTRuCT is to develop consensus expert opinions for best clinical treatment. This consensus paper for patients with rhabdomyosarcoma of the female genital tract (FGU-RMS) provides treatment recommendations for local treatment, long term follow up and fertility preservation. Methods Review of the current literature was combined with recommendations of the treatment protocols of the appropriate clinical trials. Additionally, opinions of international FGU-RMS experts were incorporated into recommendations. Results The prognosis of FGU-RMS is favorable with an excellent response to chemotherapy. Initial complete surgical resection is not indicated, but diagnosis should be established properly. In patients with tumors localized at the vagina or cervix demonstrating incomplete response after induction chemotherapy, local radiotherapy (brachytherapy) should be carried out. In patients with persistent tumors at the corpus uteri, hysterectomy should be performed. Fertility preservation should be considered in all patients. Conclusion For the first time, an international consensus for the treatment of FGU-RMS patients could be achieved, which will help to harmonize the treatment in different study groups.

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.

Sickle cell disease (SCD) is a hematologic disorder defined by presence of sickle-shaped red blood cells that can occlude blood vessels and cause tissue ischemia and pain. Treating SCD pain adequately and safely is difficult given today’s opioid climate. Buprenorphine-naloxone is described in adult literature where it typically requires withdrawal of full-agonist opioids and inpatient hospitalization. Here we present two adolescents with SCD who successfully weaned off large doses of full-agonist opioids by using micro-dose induction of buprenorphine-naloxone in clinic. Ambulatory micro-dose induction may remove hurdles that otherwise would discourage patients from trying this regimen while still controlling pain safely.

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.

Objectives. Neuroblastoma is the most common extracranial tumour in children, and prognosis for refractory and relapsed disease is still poor. Early Phase clinical trials play a pivotal role in the development of novel drugs. Ensuring adequate recruitment is crucial. The primary aim was to determine the rate of participation trials for children with refractory/relapsed neuroblastoma in two of the largest Drug Development European institutions. Methods. Data from patients diagnosed with refractory/relapsed neuroblastoma between January 2012 and December 2018 at the two institutions were collected and analysed. Results. Overall, 48 patients were included. A total of 31 (65%) refractory/relapsed cases were enrolled in early Phase trials. The main reasons for not participating in clinical trials included: not fulfilling eligibility criteria prior to consent (12/17, 70%) and screening failure (2/17, 12%). Median time on trial was 4.3 months (range 0.6-13.4). Most common cause for trial discontinuation was disease progression (67.7%). Median overall survival was longer in refractory (28 months, 95% CI, 20.9-40.2) than in relapsed patients (14 months, 95% CI, 8.1-20.1)) [p=0,034]. Conclusions. Although two thirds of children with refractory/relapsed neuroblastoma were enrolled in early Phase trials, recruitment rates can still be improved. The main cause for not participating on trials was not fulfilling eligibility criteria prior to consent, mainly due to performance status and short life expectancy. This study highlights the hurdles to access to innovative therapies for children with relapsed/refractory neuroblastomas and identifies key areas of development to improve recruitment to early phase trials.

Background Based on previous reports of disparities in financial burden following cancer, this study aims to characterize mechanisms of disparities experienced by caregivers of children with cancer, including the impact of work flexibility and social support. Methods Cross-sectional survey (in English or Spanish) of caregivers of children with cancer that assessed household material hardship (HMH), financial toxicity and income change. Results Of 156 caregivers surveyed, 32% were Hispanic and 32% were low income. Hispanic caregivers were more likely to report HMH and financial toxicity compared to non-Hispanic White and Asian (HMH 57% v. 21% v. 19%, p<0.001; financial toxicity 73% v. 52% v. 53%, p=0.07). Low and middle income caregivers were more likely to experience HMH and financial toxicity compared to high income (HMH: 68% low v. 38% middle v 8.7% high, p<0.001; financial toxicity: 81% v. 68% v. 44%, p<0.001). All income categories demonstrated significant increases in HMH one year after diagnosis. Seventeen percent reported >40% income loss, more of whom were low income than high income (27% v. 12%, p=0.20). Work flexibility and social support were associated with income and financial toxicity. Conclusion HMH, financial toxicity, and income loss are prevalent after a child’s cancer diagnosis, suggesting that screening should be incorporated into routine care. This financial burden disproportionately affects low income and Hispanic caregivers. Further research is underway to understand how safety net services are utilized by families, how best to support families with HMH, and how the financial burden of cancer has been impacted by COVID-19.

Background: MYCN amplification represents a powerful prognostic factor in neuroblastoma (NB) and may occasionally account for intratumoral heterogeneity. Radiomics is an emerging field of advanced image analysis that aims to extract a large number of quantitative features from standard radiological images, providing valuable clinical information Procedure: In this retrospective study, we aimed to create a radiogenomics model by correlating computed tomography (CT) radiomics analysis with MYCN status and overall survival (OS). NB lesions were segmented on pre-therapy CT scans and radiomics features subsequently extracted using a dedicated library. Dimensionality reduction/features selection approaches were then used for features procession and logistic regression models have been developed for the considered outcome. Results: Seventy-eight patients were included in this study, 24 presented MYCN amplification. In total, 232 radiomics features were extracted. Eight features were selected through Boruta algorithm and 2 features were lastly chosen through Pearson correlation analysis: mean of voxel intensity histogram (p=0.0082) and zone size non-uniformity (p=0.038). Five-times repeated 3-fold cross-validation logistic regression models yielded an Area Under the Curve (AUC) value of 0.879 on the training and 0.865 on the testing set for MYCN. No statistical significant difference has been observed comparing radiomics predicted and actual OS data. Conclusions: CT based radiomics is able to predict MYCN amplification status and OS in NB, paving the way to the in depth analysis of imaging based biomarkers that could enhance outcomes prediction.

Population-based data on survival from childhood cancers in sub-Saharan Africa is sparse. We report data for nine childhood cancers in the population of Kampala Uganda. Survival for eight out of nine cancers was below the WHO’s global target of 60% (the exception was Hodgkin lymphoma (86% at 3 years)). There was significant (p<0.05) decline in survival between 1 and 3 years for Wilms tumour and Kaposi sarcoma (30% and 34% at 3-years respectively). Survival from Burkitt lymphoma, Wilms tumour and Kaposi sarcoma has not changed since 2005.

LETTER TO THE EDITOR

Background: Primary and secondary malignant tumors of the spine are relatively uncommon in the pediatric population but are associated with high morbidity and significantly decreased quality of life due to pain. Local management of these tumors is often challenging due to the importance of maintaining vertebral mechanical integrity as well as the spinal growth potential. Typically, surgery and/or radiation therapy have been used in the primary management of these tumors. However, treatment options become more limited when there is relapse or refractory disease, with re-resection or additional radiotherapy often not being viable therapies. The purpose of this study was to assess the feasibility of percutaneous vertebroplasty as a palliative treatment for intractable pain secondary to malignant tumors affecting the spine. Procedure: A retrospective review of all cases of vertebroplasty performed at a single institution between 2003 and 2020. Results: A total of 11 vertebral levels were treated in 3 children with relapsed cancers (two with alveolar rhabdomyosarcoma, and one with Wilms tumor). All three had clinical benefit with sustained significant improvement in their pain. Conclusions: Vertebroplasty is a currently underutilized modality that might provide excellent pain palliation in cases of relapsed cancer in the spine. Future prospective studies of its use in pediatric oncology are needed.

The care of patients with vascular anomalies is quickly becoming a complex field requiring high quality, coordinated multidisciplinary care. In this article, we review the history of multidisciplinary care in this field, discuss the benefits of this model of care, and outline some of the essential components and structure of a successful vascular anomalies team. We provide an overview of two example programs and a roadmap for other centers to develop their own multidisciplinary vascular anomalies teams.

Background While racial disparities in the clinical outcomes of hematopoietic stem cell transplant (HSCT) patients have been explored, racial disparities in quality of life (QoL) during the readjustment phase after transplant has yet to be investigated in pediatric patients. The objective of this study was to examine the role of patient race in QoL at least two years after pediatric HSCT. Procedure We conducted a retrospective chart review of patients under 21 years of age at diagnosis that received an allogeneic transplant at our institution between January 2007 and December 2017. Patient QoL was assessed using the PedsQL TM 4.0 at least two years post-transplant. Patient demographic, treatment, and transplant outcome data were obtained for subsequent analysis, where patient race was categorized as either Black, White, Hispanic, or Native American. Results Data were collected on 86 pediatric patients who underwent HSCT. Forty patients (46.5%) were non-Hispanic White, 29 (33.7%) Hispanic, 10 (11.6%) Black, and 7 (8.1%) Native American. Where preliminary analyses indicated a difference in QoL by patient race, there were no significant differences in physical, emotional, social, and school functioning by patient race after adjusting for transplant characteristics (age at transplant, sex, diagnosis, donor type and conditioning regimen) and determinants of socioeconomic status (insurance type, estimated household income). Conclusions Pediatric patients had comparable QoL, regardless of race, at a median of three years after HSCT in our study cohort.

The covid-19 pandemic has forced citizens worldwide to rely on social distancing measures as the main tools to prevent the rapid spreading of the virus (1). In pediatric oncology, there were important initial concerns for immunocompromised patients who were considered to be at higher risk of developing severe form of the disease (2,3). Consequently, potential challenges (2) have been identified and advice given by the principal child cancer organizations (3). Although more experience from countries that have been facing the pandemic are being published, results are inconsistent so far ranging from reassuring in Milano (4), Madrid (5) or New York (6) to worrying in France where 4 out of 33 Covid-19 positive patients required intensive care and 1 death at last follow up (7).Over the last weeks, despite the pandemic we were able to maintain “normal“ care for pediatric cancer patients in our institution, including high-dose chemotherapy followed by peripheral stem cells transplantations, or recruitment in early phase clinical trials. Only follow-up visits have been re-scheduled or switched to remote consultations. After almost 2 months of lock-down and still ongoing social distancing measures, an unexpected challenge has emerged. Inddeed, during that period, as usual we had to break bad news: for diagnosis, for relapse or palliative care. Initially, when breaking bad news, I had the feeling something was going wrong, or at least was not going as usual. Was I doing something wrong? Was stress induced by a high level of anxiety due to the lack of specific information on the real risk for adolescents/children with cancer both among the medical team and or parents affecting the “breaking bad news” process?Why didn’t I take that teenagers in my arms after disclosing her a metastatic relapse and she looked in such a distress?Social distancing!Masks to start with. They are of course a barrier to saliva droplets potentially containing covid-19, but most importantly they are also a barrier to adequately transmit and discriminate emotions just relying on eyes expression, looks…beyond tears. Silent communication with long looks without words can sometimes be enough and better that long talks but do parents and children feel the same when half of the face is covered. I asked about it to one of my patients and he answered“I think can read your eyes” . By increasing the physical space between people to avoid virus spreading, but here again, for physicians and some parents/patients, holding hands, holding shoulders, hugging are important non-verbal elements of communications and help showing compassion.We might break social distancing to break bad news, but if not pre-agreed by the patient or its parents, is it acceptable? Couldn’t it be perceived as an additional threat, contribute to alter intuitive communication which is characterized by broad, shared goals and mutual respect?Breaking bad news while trying to maintain social distancing is an unexpected new challenge associated with Covid-19. We will very likely learn to better communicate, read & share our respective emotions even with masks and physical distancing and sometimes allow ourselves exceptions to social distancing. Meanwhile, this impact shall be further evaluated among all stakeholders: patients, their parents, and physicians and adapted strategies to better cope with it developed.

Background Outcomes of Ewing sarcoma (ES) in low and middle income countries lags behind the rest of the world owing to multiple tumoral, logistical and socio-economic factors. The data of outcomes and toxicity in these countries is sparse, especially in the adolescent and adult (AA) population and merits exploration Procedure This was a retrospective analysis of prospectively collected data of non-metastatic AA-ES patients, who received standard institutional combination chemotherapy regimen (EFT-2001) along with surgery or definitive radiotherapy. Various cohorts were analyzed for treatment-related toxicities, event- free survival (EFS) and overall survival (OS). Results There were 235 patients (primary safety cohort, PSC) with median age of 23 years. One hundred and ninety six were treatment naïve (primary efficacy cohort, PEC) and of these 119 had surgery. In PEC, at a median follow up of 36.4 months, estimated 5 year EFS and OS were 60.9% (95% CI 53.1% - 69.9%) and 84.5% (95% CI 77.7% - 91.9%), respectively. Of these, 158 complying with intended treatment, had an estimated 5 year EFS of 63.1% (95% CI 54.8%-72.6%). In multivariate analysis, good prognostic factors included longer symptom duration, ≥ 99% necrosis and treatment completion. Among PSC, grade 3-4 toxicities were febrile-neutropenia (50.6%), anemia (55.3%), peripheral neuropathy (15.7%), with 3 (1.3%) chemo-toxic deaths. Conclusions The outcomes of AA non-metastatic ES patients treated with EFT-2001 regimen were comparable to those reported by others, with acceptable toxicity and can be considered as standard-of-care, especially in LMICs.

Introduction: The risk of relapse in retinoblastoma is currently determined by the presence of high-risk histopathologic factors in the enucleated eye. However, the probability of developing metastatic disease is heterogeneous among these patients. Evaluating a biological marker to identify high-risk patients could be useful in clinical setting. This study aims to evaluate whether the expression of TFF1, a surrogate for subtype 2 retinoblastoma, is a prognostic marker for relapse and death. Methods: This multicenter cohort study included 273 patients, 48 of whom had extraocular disease. Immunohistochemical staining were performed for CRX, ARR3, TFF1 and Ki67. Tumors were classified as histological subtype 1 (HS1) if they had low or no expression of TFF1 (quick score (QS) ≤ 50) and as histological subtype 2 (HS2) if they expressed TFF1 diffusely (QS > 50). We studied the association between HS classification and outcome. Results: Of 273 patients, 35.9% were classified as HS1, 59.3% as HS2 and 4.8% were not evaluable. In multivariate analysis, patients with HS2 tumors had a higher probability of relapse and death than those with HS1 ( P < 0.0001 and P = 0.00020, respectively). We identified a higher-risk subgroup among HS2 tumors, presenting non-mutually exclusive expression of ARR3 and TFF1 and had an increased risk of relapse and death compared to tumors that displayed mutually exclusive expression ( P = 0.012 and P = 0.027, respectively). Conclusions: Expression of TFF1, especially when it is not-mutually exclusive with ARR3, is an independent prognostic marker of poor outcome in retinoblastoma.

Background: Pediatric palliative care (PPC) for oncology patients improves quality of life and the likelihood of goal-concordant care. However, barriers to involvement exist. Objectives: We aimed to increase days between PPC consult and death for patients with refractory cancer from a baseline median of 13.5 days to ≥30 days between March 2019 and March 2020. Methods: Outcome measure was days from PPC consult to death; process measure was days from diagnosis to PPC consult. The project team surveyed oncologists to identify barriers. Plan-Do-Study-Act cycles included establishing target diagnoses, offering education, standardizing documentation, and sending reminders. Results: The 24-month baseline period included 30 patients that died and 25 newly diagnosed patients. The yearlong intervention period included 6 patients that died and 16 newly diagnosed patients. Interventions improved outcome and process measures. Targeted patients receiving PPC ≥ 30 days prior to death increased from 43% to 100%; median days from consult to death increased from 13.5 to 159.5. Targeted patients receiving PPC within 30 days of diagnosis increased from 28% to 63%; median days from diagnosis to consult decreased from 221.5 to 14. Of those without PPC consult within 30 days after diagnosis, 17% had template documentation of the rationale. Conclusion: Interventions utilized met the global aim, outcome and process measures. Use of QI methodology empowered providers to involve PPC. Poor template use was a barrier to identifying further drivers. Future directions for this project relate to expanding the target list, creating long-term sustainability, formalizing standards, and surveying patients and families.

Background. Adolescents/young adults (AYAs) with acute lymphoblastic leukemia (ALL) are more likely to have chemotherapy-related complications than children. In addition, several reports have shown that infections account for most of the therapy-related mortality during cancer treatment in AYAs. Thus, we hypothesized that chemotherapy-induced myelosuppression is more severe in AYAs than in children, and the state of neutropenia was compared between children and AYAs using the D-index, a numerical value calculated from the duration and depth of neutropenia. Procedure. This study retrospectively analyzed 95 patients newly diagnosed with ALL at our institution between 2007 and 2019. Of these, 81 were children (< 15 years old) and 14 were AYAs (≥ 15 years old). The D-index and duration of neutropenia during induction chemotherapy for ALL were compared between children and AYAs. Results. The median D-index of children was significantly higher than that of AYAs (8,187 vs. 6,446, respectively, P = 0.017). Moreover, the median duration of neutropenia was also significantly longer in children than in AYAs (24.0 days vs. 11.5 days, respectively, P = 0.007). Conclusion. Contrary to our expectations, myelosuppressive toxicity during induction chemotherapy for ALL was more severe in children than in AYAs.