not-yet-known not-yet-known not-yet-known unknown Background: Timely diagnosis is critical in pediatric oncology to optimize treatment outcomes. Diagnostic delays may impact tumor extension and prognosis, necessitating analysis of diagnostic intervals across different neoplasms. Methods: We analyzed data from 749 pediatric patients diagnosed with rhabdomyosarcoma between 1996 and 2016. Diagnostic interval (DI) was defined as days from symptom onset to diagnosis, and treatment interval (TI) from symptom onset to treatment initiation. Factors influencing DI and TI were collected, including patient age, histology, tumor characteristics, and protocol of treatment. Survival outcomes were assessed using Kaplan-Meier analysis. Results: Median DI was 32 days, decreasing insignificantly from 1996-2004 to 2005-2016. Longer DI was associated with metastatic disease (p=0.0021). The proportion of patients diagnosed within one month increased over time, but remained lower for metastatic cases. Median TI was 48 days, unchanged over time. Longer TI correlated with larger tumors (p<0.0001). Adolescents had prolonged DI (>2 months) more frequently. The quantile regression models showed that on univariate analysis DI was associated with age at diagnosis, unfavourable histology and metastatic diaeses, but not confirmed in multivariate Five-year event-free survival (EFS) and overall survival (OS) were 59.7% and 69.3%, respectively. Conclusions: This study evaluated the role of timely diagnosis and treatment initiation in pediatric patients with rhabdomyosarcoma . Our data highlights that DI and TI are crucial in adolescents and often longer in metastatic patients. Future efforts should focus on streamlining access to diagnostic facilities and improving processes to ensure timely interventions, especially for patients presenting with more advanced disease.

In the era of big data, young patients are overwhelmed by artificial intelligence-based tools, such as chatbots. Five clinical experts were asked to evaluate the performance of four of the most currently used chatbots at providing information on a rare cancer affecting young people, such as rhabdomyosarcoma. In general, despite their high performance at giving general information about the disease, these chatbots were considered by the experts inappropriate at providing suggestion on cancer treatments and specialized centers, also lacking of "sensitivity". Efforts are envisioned by the pediatric oncology community to improve the quality of data used to train these tools.

Background and Aims. Since the war in Ukraine which began on February 2022, many pediatric oncology centers have welcomed patients from Ukraine. To understand the needs of patients and families arriving at our hospital, an anonymous questionnaire investigated the families’ backgrounds, feelings and impressions about hospitality and care. Methods Twenty items investigated how patients had reached Italy, from whom they received help (logistically/economically); emotions regarding their statusas war refugees; knowledge, expectations, and opinions about Italy and Italians; the quality of medical care received and relationships with the healthcare staff; suggestions to improve assistance. Results Questionnaires were completed by 19/32 patient/parents in the time interval May-November 2022 in two different pediatric-oncology centers in the north of Italy. Most families had reached Italy (58%) and received medical care (95%) thanks to the help of Charities and the Italian Public Health Care System. Many of them (69%) declared themselves to be satisfied by the assistance. The Italian population appeared friendly (95%) and generous (58%). The improvement of their stay correlated with the positive outcome of their children (15%), the presence of the whole family (15%), the end of the war (10%), and the overcoming of language barriers (10%) Conclusions. Taking care of children from a different country suffering the traumatic experience of fleeing their country in addition to the equally traumatic condition of cancer disease, is a huge task. Our questionnaire aimed at obtaining a better understanding of families’ conditions, not at bridging the relational gap due to different culture and experiences.

During SARS-CoV-2 pandemic, oncologists manage patients at higher risk of having a severe course of this infection. This raises new questions about their correct management, as well as the difficulty of distinguishing tumor/treatments complications from those related to Coronavirus disease 2019 (COVID-19). We report a case of an 11 year-old boy undergoing treatment for T cell lymphoblastic lymphoma who experienced a prolonged SARS-CoV-2 infection. Oncological therapy was continued without significant changes compared to the initially planned treatment. No relevant complications occurred. COVID-19 convalescent plasma (CP) was administered, resulting in a positive antibody titer after 24 days.

Background To assess the outcomes of pediatric patients with Undifferentiated Embryonal Sarcoma of the Liver (UESL) and treatment including at least surgery and systemic chemotherapy. Methods This study included patients aged up to 21 years with a pathological diagnosis of UESL prospectively enrolled from 1995 to 2016 in three european trials focusing on the effects of surgical margins, preoperative chemotherapy, use of radiotherapy (RT) and chemotherapy. Results Out of 65 patients with a median age at diagnosis of 8.7 years (0.6-20.8), 15 had T2 tumors, and 1 had lymph node spread, 14 were Intergroup Rhabdomyosarcoma Study (IRS) I, 9 IRSII, 38 IRSIII, and 4 IRSIV. Twenty-eight upfront surgeries resulted in 5 operative spillages and 11 infiltrated surgical margins, whereas 37 delayed surgeries resulted in no spillages (P= 0.0119) and 3 infiltrated margins (P=0.0238). All patients received chemotherapy, including anthracyclines in 47. Radiotherapy was administered in 15 patients. With a median follow-up of 78.6 months, 5 year overall and event free survivals (EFS) were 90.1% (95%CI 79.2-95.5) and 89.1% (95%CI 78.4-94.6), respectively. Two out 4 local relapses had previous infiltrated margins and 2 out of 3 patients with metastatic relapses received reduced doses of alkylating agents. Infiltrated margins (P=0.1607), T2 stage (P=0.3870), use of RT (P= 0.8731), and anthracycline-based chemotherapy (P= 0.1181) were not correlated with EFS. Conclusions Neoadjuvant chemotherapy for pediatric patients with UESL increases the probability of complete surgical resection. The role of anthracyclines and radiotherapy for localized disease remains unclear. The use of alkylating agents is recommended.

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.

Pancreatoblastoma (PBL) is a rare malignant epithelial neoplasm affecting typically young children. Signs related to advanced upper-abdominal tumor accompanied by elevated serum α-fetoprotein levels in a young child suggest PBL, however histopathological examination is required for diagnosis. The mainstay of treatment is a complete surgical resection. Inoperable and/or metastatic PBL may become amenable to complete, delayed surgery after neo-adjuvant chemotherapy. This manuscript presents the internationally consensus recommendations for the diagnosis and treatment of children with PBL, established by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) within the EU-funded PARTNER (Paediatric Rare Tumors Network – European Registry) project.

As part of the European Union-funded project designated PARTN-ER, the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) is continuously developing consensus recommendations in order to harmonize standard care for very rare solid tumors of children and adolescents. This paper presents the internationally recognized recommendations for the diagnosis and treatment of sex cord stromal tumors (SCST). The clinical approach to sex cord stromal tumors of the testis (TSCST) and ovary (OSCST) depends on histological differentiation and tumor stage. Virtually all TSCSTs present as localized non-metastatic tumors, with excellent prognosis after complete resection. In contrast, the prognosis of OSCSTs may be adversely affected by tumor spillage during surgery or presence of metastases. In these cases, cisplatin-based chemotherapy is recommended. Of note, some SCSTs may develop in the context of tumor predisposition syndromes e.g. DICER-1, so that specific follow-up is indicated. SCSTs should be diagnosed and treated according to standardized recommendations that include reference pathology, genetic testing for tumor predisposition syndromes in selected cases, and stratified adjuvant chemotherapy in patients with unfavorable risk profile. To ensure high quality of diagnosis and therapy, patients should be enrolled into prospective registries.

BACKGROUND: Irinotecan is a drug active against pediatric sarcomas with a toxicity profile that theoretically allows for its association with more myelotoxic drugs. We examined the feasibility of a dose-density strategy integrating irinotecan in standard chemotherapy regimens for patients with high-risk sarcomas. METHODS: Between November 2013 and January 2020, 23 patients < 21 years old with metastatic (11 children) or recurrent (12 children) sarcomas were treated with 9 IrIVA/IrVAC cycles. All newly-diagnosed patients received IrIVA (ifosfamide 3g/m2 on days 1 and 2, vincristine 1.5 mg/m2 on day 1, actinomycin D 1.5 mg/m2 on day 1, irinotecan 20 mg/m2 for 5 consecutive days starting on day 8). Two relapsed patients received IrIVA and 10 IrVAC (cyclophosphamide 1.5 g/m2 on day 1 instead of ifosfamide). Feasibility was assessed in terms of toxicity and time to complete the treatment. RESULTS: 17 rhabdomyosarcomas, 4 Ewing sarcomas, 2 desmoplastic round cell tumors received a total of 181 cycles (range 2-10). Grade 4 neutropenia occurred in 62.4% of the cycles. 13 patients had febrile neutropenia. Diarrhea occurred in 14 cycles. The median time to complete the treatment was 195 days (range 170-231), 83.4% of cycles were administered on time or with a delay <1 week. With a median follow-up of 2.6 years (range 0.2-5.0), 12 patients are alive, 9 complete remissions, 3 with the disease. Conclusions: A dose density strategy combining irinotecan with standard chemotherapy is feasible. This approach will be investigated in the next trial coordinated by the European pediatric Soft tissue sarcoma Study Group.

Introduction. Mutations of the APC (adenomatous polyposis coli) gene correlate mainly with familial adenomatous polyposis (FAP), but can occasionally be pathogenic for medulloblastoma (MBL) WNT subtype as well, the course of which has only recently been described. Methods. We retrospectively retrieved all patients with documented germline APC mutations and a centrally-reviewed diagnosis of MBL to examine the outcome of their MBL, late effects of its treatment, and further oncological events. Results. Between 2007-2016 we diagnosed and treated 6 patients, all with a pathogenic APC variant mutation, who all had MBL, classic histotype. None had metastatic disease. All patients were in complete remission a median 65 months after treatment with craniospinal irradiation at 23.4 Gy, plus a boost on the posterior fossa/tumor bed up to 54 Gy, followed by cisplatin/carboplatin, lomustine and vincristine for a maximum of 8 courses. Five of 6 diagnostic revised MRI were suggestive of the WNT molecular subgroup typical aspects. Four of 6 patients had a positive family history of FAP, while gastrointestinal symptoms prompted its identification in the other 2 cases. Four patients had developed other tumors (desmoid, MELTUMP, melanoma, pancreatoblastoma, thyroid Tir3) from 5 to 7 years after MBL. Discussion. Our data confirm a good prognosis for patients with MBL associated with FAP. Patients’ secondary tumors may or may not be related to their syndrome or treatment, but warrant adequate attention when planning shared guidelines for these patients.

Background: Children and adolescents with cancer are at risk of a poor health-related quality of life. Exercise interventions to enhance movement may be a valid strategy for managing some symptoms, including fatigue. Methods: Forty-four consecutive patients (20 females; aged 5-21 years old, median 15.5 years), without any contraindications significantly limiting their movements were invited to join an in-hospital 6-week supervised exercise program, and asked afterwards to complete the PedsQL-4.0 quality of life Generic Core Scales and the PedsQL Multidimensional Fatigue Scale. The program consisted of personalized workout sessions of aerobic, resistance and flexibility exercises. The results obtained on the scales were compared between patients who engaged in the exercise program (GYM group, n=21) and those who did not (No-GYM, n=23), with the aim of examining the different dimensions of health-related quality of life (physical, emotional, cognitive, social) and fatigue (general, sleep/rest, cognitive) comparing the two groups. Results: For 43 of 44 patients, being diagnosed with cancer initially prompted a drop-out from previous physical exercise or sports routines despite no contraindications to their continuation. After 6 weeks, the scores for patients in the GYM group showed a statistically significant better perceived emotional functioning, and a possible indication of improved social functioning compared with the No-GYM group. Conclusion: These findings suggest that to exercise improves the satisfaction of children and adolescents with cancer with their physical, mental and social functioning. It is worth further investigating the value of systematically including exercise workouts in their routine cancer practices.

We analyzed the nationwide hospital discharge records of adolescent inpatients in Italy to map where adolescents with melanoma are treated and identify expert centers. We identified 137 hospitals pointing out a dispersion of these patients that must be addressed to ensure to all adolescents with melanoma adequate treatment and enrolment in clinical studies.