Filippo Spreafico

Scopus Publications

Challenges and Opportunities of a Multi-Institutional Treatment Guideline for Wilms Tumor in Low-Middle-Income Countries—A Report from the Asociación de Hemato-Oncología Pediátrica de Centro América (AHOPCA)
Patricia Valverde, Thelma Velasquez, Roberta Ortiz, Soad Linneth Fuentes‐Alabi, Armando Peña, José Fernando Gonzalez, Tito Luis Gutierrez, Luis Enrique Melendez, Enrique Tome, Magda Arreola,et al.
Wiley
ABSTRACTSince 2000, centers across Central America have shared treatment guidelines for Wilms tumor, using histology (anaplasia present or absent) and tumor stage to stratify patients into low‐, intermediate‐, and high‐risk groups. Weekly virtual tumor board meetings involving local and international experts were held to ensure consistent treatment assignments. We analyzed data from 367 children with unilateral tumors treated per these guidelines. Five‐year abandonment‐sensitive event‐free and overall survival estimates were: low risk 82% ± 3.8% and 86% ± 3.6%, intermediate risk 50% ± 3.4% and 60% ± 3.4%, and high risk 36% ± 7.6% and 45% ± 7.9%. Survival outcomes were suboptimal, primarily due to advanced disease in fragile children at presentation and abandonment of treatment.

Hallmark discoveries in the biology of non-Wilms tumour childhood kidney cancers
Daniela Perotti, Maureen J. O’Sullivan, Amy L. Walz, Jonathan Davick, Reem Al-Saadi, Daniel J. Benedetti, Jack Brzezinski, Sara Ciceri, Nicholas G. Cost, Jeffrey S. Dome,et al.
Springer Science and Business Media LLC

Long-term outcome of the Milano-hyperfractionated accelerated radiotherapy strategy for high-risk medulloblastoma, including the impact of molecular subtype
Maura Massimino, Francesco Barretta, Chiara Dossena, Simone Minasi, Francesca Romana Buttarelli, Veronica Biassoni, Matilde Oriani, Elisabetta Schiavello, Marica Ficorilli, Olga Nigro,et al.
Oxford University Press (OUP)
Abstract Background We applied the strategy for M+ medulloblastoma across all high-risk subgroups, including LC/A histology, TP53 mutations, and MYC/MYCN amplification. Methods Patients over 3 years old received, after surgery, staging and histo-biological analysis, sequential high-dose-methotrexate(HD-MTX), high-dose-etoposide(HD-VP16), high-dose-cyclophosphamide(HD-Cyclo), and high-dose-carboplatin(HD-Carbo). Hyperfractionated-accelerated-radiotherapy–craniospinal(HART-CSI), administered twice daily 1.3 Gy-fractions reached a total dose tailored to the patients’ age and pre-radiation response to chemotherapy(CT): 31.2 Gy if under 10-years-old and complete response(CR) or partial response(PR) obtained or absence of metastatic disease, 39 Gy in other/older patients. Boosts to posterior fossa/residual metastatic(M+) deposits were given up to a total dose of 60 Gy/9 Gy, respectively, but avoided if metastatic nodules were very big or patients were very young. Two courses of high-dose-thiotepa were delivered in case of not CR/PR after the pre-radiotherapy (RT) phase and in all M0 patients either—pre/post-HART. Subgrouping was performed where the tissue was available. Results Eighty-nine patients were enrolled, with a median age of 8.8 years, and a median follow-up of 136 months. Overall survival (OS) and event-free survival (EFS) at 5/15 years were 75.9/66.5% and 68.2/65.3%, respectively; 5/28 fatal events were not related to relapse(3 developed secondary malignancies). Sex, age less than 10 years, histological subtype, presence of MYC/MYCN amplification, reduction in CSI dose, omission of RT-boosts, implementation of myeloablative therapy, presence–absence of metastases did not impact prognosis.Patients progressing after pre-HART CT(14/89) and stable-disease(SD)+PD after HART(10/89) negatively affected outcome(P &lt; .001).Subgrouping in 66/89 patients’ samples demonstrated a significantly worse EFS for patients with Sonic Hedgehog(SHH)-tumors(#15, 2 with constitutional TP53-mutations) versus groups 3 and 4(15 and 29 patients, respectively, group3/4 in 7).Patients younger than 10 received lower CSI doses if stratified according to CT response. Conclusions This strategy, partly adopted in the ongoing SIOPE protocol, confirmed improved EFS and OS over previously reported outcomes in all high-risk categories; SHH tumors appeared the most aggressive.

Children and adolescent solid tumours and high-intensity end-of-life care: what can be done to reduce acute care admissions?
Marta Giorgia Podda, Elisabetta Schiavello, Carlo Alfredo Clerici, Roberto Luksch, Monica Terenziani, Andrea Ferrari, Michela Casanova, Filippo Spreafico, Cristina Meazza, Veronica Biassoni,et al.
BMJ
Despite improvements in survival, cancer remains the leading cause of non-accidental death in children and adolescents, who risk receiving high-intensity end-of-life (HI-EOL) care.ObjectiveTo analyse treatments for relapses (particularly in the last weeks of life), assess their impact on the EOL, identify patients most likely to receive HI-EOL care and examine whether palliative care services can contain the intensity of EOL care.MethodsThis retrospective study involved patients treated at the paediatric oncology unit of the Istituto Nazionale Tumori in Milan who died between 2018 and 2020. The primary outcome was HI-EOL care, defined as: ≥1 session of intravenous chemotherapy <14 days before death; ≥1 hospitalisation in intensive care in the last 30 days of life and ≥1 emergency room admission in the last 30 days of life.ResultsThe study concerned 68 patients, and 17 had HI-EOL care. Patients given specific in-hospital treatments in the last 14 days of their life more frequently died in hospital. Those given aggressive EOL care were less likely to die at home or in the hospice. Patients with central nervous system (CNS) tumours were more likely to have treatments requiring hospitalisation, and to receive HI-EOL care.ConclusionThese results underscore the importance of considering specific treatments at the EOL with caution. Treatments should be administered at home whenever possible.The early activation of palliative care, especially for fragile and complicated patients like those with CNS cancers, could help families cope with the many problems they face.

Outcome after treatment with axitinib in children, young adults, and adults with renal cell carcinoma: a narrative review
Julia Sprokkerieft, Justine N. van der Beek, Filippo Spreafico, Barbara Selle, Tanzina Chowdhury, Norbert Graf, Arnauld C. Verschuur, Rana Dandis, Axel Bex, James I. Geller,et al.
Elsevier BV

Foreign patients and multicultural challenges in pediatric oncology: The experience of the Istituto Nazionale dei Tumori in Milan
Martina Lombardi, Matteo Silva, Monica Giovanetti, Daniele Cabibbe, Roberto Luksch, Monica Terenziani, Michela Casanova, Filippo Spreafico, Cristina Meazza, Marta Podda,et al.
Wiley
AbstractThis paper describes the complexity of the clinical management of foreign minors suffering from cancer, through the clinical experience of an Italian referral center. The study includes 50 patients less than 18 years (22% of the patients admitted to the unit in 2023), 32 foreigners who were Italian resident and 18 who had come to Italy specifically to receive cancer treatment. Patients who migrate for healthcare reasons often arrive at the referral center with advanced disease or relapse. Numerous socio‐cultural issues were reported. To address them, specific strategies were implemented to ensure equal and high‐quality care for all patients, respecting their needs.

Widening the spectrum of players affected by genetic changes in Wilms tumor relapse
Sara Ciceri, Alessia Bertolotti, Annalisa Serra, Giovanna Gattuso, Luna Boschetti, Maria Capasso, Cecilia Cecchi, Stefania Sorrentino, Paola Quarello, Chiara Maura Ciniselli,et al.
Elsevier BV

Caring for children with cancer evacuated from Ukraine: The patients’ perception
Marcello Bolognese, Maura Massimino, Daniele Cabibbe, Marco Zecca, Marta Fornara, Mariangela Armiraglio, Roman Kyzima, Roberto Luksch, Monica Terenziani, Michela Casanova,et al.
Wiley
AbstractBackground and aimsSince the beginning of the war in Ukraine on February 24, 2022, many pediatric oncology centers welcomed evacuated patients. To better understanding the needs of patients and families arriving at two Lombardy hospitals in the period March to November 2022, an anonymous questionnaire investigated the families’ backgrounds, feelings, and impressions about hospitality and care.MethodsTwenty questions investigated how patients had reached Italy, from whom they had received help (logistically/financially); the emotions regarding their status as war refugees; the knowledge, expectations, and opinions about Italy and Italians; the quality of medical care received and the relationships with the healthcare staff; lastly, suggestions to improve assistance.ResultsThe questionnaires were completed by 19/32 patients/parents in November 2022 in two different pediatric‐oncology centers. Most families had reached Italy (58%) and received medical care (95%) with the help of charities and the Italian Public Health Care System. A significant majority (69%) expressed satisfaction with the assistance provided. The Italian population demonstrated remarkable warmth, for 95% exhibiting friendliness and for 58% generosity. An improvement in their stay could be linked with the positive outcome of their children's cancer (15%), achieving complete family reunification (15%), the cessation of the conflict (10%), and the overcoming of language barriers (10%).ConclusionsProviding care for children from another country, not only grappling with the trauma of fleeing their homeland but also battling cancer, is an immense undertaking. It demands a diverse range of efforts and resources to ensure a positive and fulfilling outcome for this experience.

General support of physical exercise programs in pediatric oncology but differences in perception by childhood cancer care professionals at European and North-African/Arab centers
Moatasem El-Ayadi, Kyra Druivenga, Thomas Perwein, Gunther Nussbaumer, Filippo Spreafico, Maura Massimino, Shady Fadel, Nisreen Amayiri, Nisrine Khoubila, Laila Hessissen,et al.
Elsevier BV

Diagnostic magnetic resonance imaging characteristics of congenital mesoblastic nephroma: a retrospective multi-center International Society of Pediatric Oncology-Renal Tumor Study Group (SIOP-RTSG) radiology panel study
Justine N. van der Beek, Jens-Peter Schenk, Carlo Morosi, Tom A. Watson, Ana Coma, Norbert Graf, Tanzina Chowdhury, Gema L. Ramírez-Villar, Filippo Spreafico, Nils Welter,et al.
Springer Science and Business Media LLC
Abstract Background Congenital mesoblastic nephroma is the most common solid renal tumor in neonates. Therefore, patients <3 months of age are advised to undergo upfront nephrectomy, whereas invasive procedures at diagnosis in patients ≥3 months of age are discouraged by the International Society of Pediatric Oncology-Renal Tumor Study Group (SIOP-RTSG). Nevertheless, discriminating congenital mesoblastic nephroma, especially from the more common Wilms tumor, solely based on imaging remains difficult. Recently, magnetic resonance imaging (MRI) has become the preferred modality. Studies focusing on MRI characteristics of congenital mesoblastic nephroma are limited. Objective This study aims to identify diagnostic MRI characteristics of congenital mesoblastic nephroma in the largest series of patients to date. Materials and methods In this retrospective multicenter study, five SIOP-RTSG national review radiologists identified 52 diagnostic MRIs of histologically proven congenital mesoblastic nephromas. MRI was performed following SIOP-RTSG protocols, while radiologists assessed their national cases using a validated case report form. Results Patients (24/52 classic, 11/52 cellular, and 15/52 mixed type congenital mesoblastic nephroma, 2/52 unknown) had a median age of 1 month (range 1 day–3 months). Classic type congenital mesoblastic nephroma appeared homogeneous with a lack of hemorrhage, necrosis and/or cysts, showing a concentric ring sign in 14 (58.3%) patients. Cellular and mixed type congenital mesoblastic nephroma appeared more heterogeneous and were larger (311.6 and 174.2 cm3, respectively, versus 41.0 cm3 for the classic type (P<0.001)). All cases were predominantly T2-weighted isointense and T1-weighted hypointense, and mean overall apparent diffusion coefficient values ranged from 1.05–1.10×10−3 mm2/s. Conclusion This retrospective international collaborative study showed classic type congenital mesoblastic nephroma predominantly presented as a homogeneous T2-weighted isointense mass with a typical concentric ring sign, whereas the cellular type appeared more heterogeneous. Future studies may use identified MRI characteristic of congenital mesoblastic nephroma for validation and for exploring the discriminative non-invasive value of MRI, especially from Wilms tumor. Graphical Abstract

Local treatment in initially unresected non-rhabdomyosarcoma soft-tissue sarcomas of children and adolescents: A retrospective single-center experience
Andrea Ferrari, Sabina Vennarini, Marco Fiore, Luca Bergamaschi, Stefano Chiaravalli, Carlo Morosi, Chiara Colombo, Emilia Pecori, Nadia Puma, Roberto Luksch,et al.
Wiley
AbstractBackgroundPediatric non‐rhabdomyosarcoma soft‐tissue sarcomas (NRSTS) are a heterogeneous group of aggressive tumors. Patients with locally advanced/initially unresected disease represent a subset of patients with unsatisfactory outcome: limited data are available on the best treatment approach, in particular regarding local therapy.MethodsThis retrospective analysis concerned 71 patients < 21 years old with nonmetastatic, initially unresected adult‐type NRSTS, treated at a referral center for pediatric sarcomas from 1990 to 2021. Patients were treated using a multimodal approach, based on the protocols adopted at the time of their diagnosis.ResultsThe series included a selected group of patients with unfavorable clinical characteristics, i.e., most cases had high‐grade and large tumors, arising from axial sites in 61% of cases. All patients received neoadjuvant chemotherapy, 58 (82%) had delayed surgery (R0 in 45 cases), and 50 (70%) had radiotherapy. Partial response to chemotherapy was observed in 46% of cases. With a median follow‐up of 152 months (range, 18–233), 5‐year event‐free survival (EFS) and overall survival (OS) were 39.9% and 56.5%, respectively. Survival was significantly better for patients who responded to chemotherapy, and those who had a delayed R0 resection. Local relapse at 5 years was 7.7% for patients who did not undergo delayed surgery.ConclusionsOur series underscores the unsatisfactory outcome of initially unresected NRSTS patients. Improving the outcome of this patient category requires therapeutic strategies able to combine novel effective systemic therapies with a better‐defined local treatment approach to offer patients the best chances to have R0 surgery.

Most appropriate surgical approach in children with Wilms tumour, risk of kidney disease, and related considerations
Filippo Spreafico, Davide Biasoni, and Giovanni Montini
Springer Science and Business Media LLC

Childhood cancer survivors: improving our practice today to reduce late, major surgical interventions tomorrow
Olga Nigro, Giovanna Gattuso, Giovanna Sironi, Marta Podda, Elisabetta Schiavello, Filippo Spreafico, and Monica Terenziani
AME Publishing Company
replacement or revision in CNS survivors, correction of spinal deformity subsequent to radiotherapy or laminectomy, many limb salvage procedures, prosthetic substitutions, complications of amputations, and surgical treatment of osteonecrosis

Bevacizumab-containing treatment for relapsed or refractory Wilms tumor
Sarah Al-Jilaihawi, Filippo Spreafico, Annelies Mavinkurve-Groothuis, Jarno Drost, Daniela Perotti, Christa Koenig, and Jesper Brok
Informa UK Limited
INTRODUCTION Angiogenesis is critical for tumor growth and metastasis. Bevacizumab is an antiangiogenic drug used to treat various adult and childhood solid tumors. Its potential efficacy in Wilms tumor (WT) with poor prognosis is not established. AREAS COVERED The response to bevacizumab-containing regimens in relapsed or refractory WT was reviewed in available literature. Searches were conducted using Pubmed, Scopus and ClinicalTrials.gov databases. Eight papers were identified, published between 2007 and 2020 including 6 treatment regimens, predominantly vincristine, irinotecan and bevacizumab (VIB) ± temozolomide (VITB). Among 16 evaluable patients, there were two complete responses, 7 partial responses, 5 patients achieved stable disease (SD) and two patients had progressive disease. Objective responses (OR) were observed in 56% of all cases. OR or SD was observed in 89% (8/9) patients who received VIB/VITB. Bevacizumab was generally well tolerated. Related toxicities included hypertension, proteinuria and delayed wound healing. EXPERT OPINION This review suggests potential effectiveness and good tolerability of bevacizumab in the setting of relapsed/refractory WT when used in combination with other drugs. Such combination therapies may serve as a bridging treatment option to other interventions and more personalized treatment options in the future, however focused trials are needed to obtain additional evidence.

Impact of a Regional Pediatric Hematology/Oncology Fellowship Program in Guatemala
Daniel C. Moreira, Claudia Garrido, Roy Rosado, Verónica Girón, Tomás Letona, Gerson Morales, Patricia Valverde, Thelma Velásquez, Jeanine Alfaro, Elizabeth Orellana,et al.
American Society of Clinical Oncology (ASCO)
PURPOSE This study aimed to describe and assess the regional experience of a pediatric hematology/oncology fellowship program based in Guatemala. METHODS The Unidad Nacional de Oncología Pediátrica (UNOP) in Guatemala City, Guatemala, is the only hospital in Central America dedicated exclusively to childhood and adolescent cancer. To address the regional need for specialists, a fellowship program in pediatric hematology/oncology was launched in 2003. The UNOP fellowship program comprises 3 years of training. Although the program is based at UNOP, it also includes rotations locally and internationally to enhance clinical exposure. The curriculum is based on international standards to cover clinical expertise, research, professionalism, communication, and health advocacy. Trainees are selected according to country or facility-level need for pediatric hematologists/oncologists, with a plan for them to be hired immediately after completing their training. RESULTS Forty physicians from 10 countries in Latin America have completed training. In addition, there are currently 13 fellows from five countries in training. Of the graduates, 39 (98%) are now practicing in pediatric hematology/oncology in Latin America. Moreover, many of them have leadership positions within their institutions and participate in research, advocacy, and policy making. Graduates from the UNOP program contribute to institutions by providing care for an increasing number of patients with pediatric cancer. The UNOP program is the first pediatric hematology/oncology fellowship program in the world to be accredited by Accreditation Council for Graduate Medical Education-International, an international body accrediting clinical training programs. CONCLUSION The UNOP program has trained specialists to increase the available care for children with cancer in Latin America. This regional approach to specialist training can maximize resources and serve as a model for other programs and regions.

A Gradual Transition Toward Anaplasia in Wilms Tumor Through Tolerance to Genetic Damage
Kaname Uno, Bahar Rastegar, Caroline Jansson, Geoffroy Durand, Anders Valind, Subhayan Chattopadhyay, Alessia Bertolotti, Sara Ciceri, Filippo Spreafico, Paola Collini,et al.
Elsevier BV

Targeted therapies in children with renal cell carcinoma (RCC): An International Society of Pediatric Oncology—Renal Tumor Study Group (SIOP-RTSG)-related retrospective descriptive study
Julia Sprokkerieft, Justine N. van der Beek, Filippo Spreafico, Barbara Selle, Estelle Thebaud, Tanzina Chowdhury, Jesper Brok, Gábor Ottóffy, Xiaofei Sun, Gema L. Ramírez Villar,et al.
Wiley
AbstractIntroductionIntroduction: Renal cell carcinoma (RCC) is a very rare pediatric renal tumor. Robust evidence to guide treatment is lacking and knowledge on targeted therapies and immunotherapy is mainly based on adult studies. Currently, the International Society of Pediatric Oncology–Renal Tumor Study Group (SIOP‐RTSG) 2016 UMBRELLA protocol recommends sunitinib for metastatic or unresectable RCC.MethodsThis retrospective study describes the effects of tyrosine kinase inhibitors (TKI), anti‐programmed cell death 1 (PD‐(L)1) monoclonal antibodies, and immunotherapeutic regimens in advanced‐stage and relapsed pediatric RCC.ResultsOf the 31 identified patients (0–18 years) with histologically proven RCC, 3/31 presented with TNM stage I/II, 8/31 with TNM stage III, and 20/31 with TNM stage IV at diagnosis. The majority were diagnosed with translocation type RCC (MiT‐RCC) (21/31) and the remaining patients mainly presented with papillary or clear‐cell RCC. Treatment in a neoadjuvant or adjuvant setting, or upon relapse or progression, included mono‐ or combination therapy with a large variety of drugs, illustrating center specific choices in most patients. Sunitinib was often administered as first choice and predominantly resulted in stable disease (53%). Other frequently used drugs included axitinib, cabozantinib, sorafenib, and nivolumab; however, no treatment seemed more promising than sunitinib. Overall, 15/31 patients died of disease, 12/31 are alive with active disease, and only four patients had a complete response. The sample size and heterogeneity of this cohort only allowed descriptive statistical analysis.ConclusionThis study provides an overview of a unique series of clinical and treatment characteristics of pediatric patients with RCC treated with targeted therapies.

Diagnostic MRI characteristics of pediatric clear cell sarcoma of the kidney and rhabdoid tumor of the kidney: A retrospective multi-center SIOP-RTSG Radiology panel study
Justine N. van der Beek, Jens-Peter Schenk, Tom A. Watson, Ana Coma, Carlo Morosi, Norbert Graf, Tanzina Chowdhury, Gema L. Ramírez-Villar, Filippo Spreafico, Kristina Dzhuma,et al.
Elsevier BV

End-of-Life transfusion support at hospice and pediatric oncology unit: Bridging the gap between benefits and therapeutic alliance
Olga Nigro, Marta G Podda, Federico Pellegatta, Elisabetta Schiavello, Carlo A Clerici, Igor Catalano, Giovanna Visconti, Marco Albarini, Roberto Luksch, Monica Terenziani,et al.
SAGE Publications
Objectives: Although transfusion support is commonly used in oncological palliative care, there is still a paucity of literature. We examined the transfusion support provided in the terminal stage of the disease and compared the approach at a pediatric oncology unit and a pediatric hospice. Case description This case series analyzed patients treated at the Fondazione IRCCS Istituto Nazionale dei Tumori di Milano (INT)’s pediatric oncology unit who died between January 2018 and April 2022. We compared these with those who died at the VIDAS hospice and analyzed the number of complete blood counts taken in a patient’s last 14 days of life, and the number of transfusions performed in the same period. We analyzed 44 patients (22 in pediatric oncology unit; 22 in hospice) in total. Twenty-eight complete blood counts were performed (7/22 patients at the hospice; 21/22 patients at the pediatric oncology unit). Nine patients were given transfusions, three at the hospice, six at our pediatric oncology unit (24 transfusions in total): 20 transfusions at the pediatric oncology unit, four at the hospice. In total 17/44 patients were given active therapies in the last 14 days of life: 13 at the pediatric oncology unit, four at the pediatric hospice. Ongoing cancer treatments did not correlate with a greater likelihood of receiving a transfusion (p=0.91). Conclusions: The hospice’s approach was more conservative than the pediatric oncology one. In the in-hospital setting, the need for a transfusion cannot always be decided on by a combination of numerical values and parameters alone. The family’s emotional-relational response must be considered too.

Treating secondary malignant neoplasms: A burden of childhood cancer survivors
Marta G Podda, Cristina Meazza, Giovanna Gattuso, Giovanna Sironi, Olga Nigro, Luca Bergamaschi, Veronica Biassoni, Michela Casanova, Stefano Chiaravalli, Andrea Ferrari,et al.
SAGE Publications
Each year approximately 35,000 children and adolescents are diagnosed with cancer in Europe. Five-year survival rates have improved and now reach 80% in most European countries, thanks to a combination of chemotherapy, radiotherapy, and surgery. To date, there are more than 44,000 Italians still living several years after being diagnosed with cancer in developmental age. The risk of premature morbidity and mortality for cancer survivors is well known and documented. Approximately 60% of survivors of cancer in childhood and adolescence have at least one chronic health condition in later life, and more than one in four develop severe or life-threatening disorders. Among the various long-term iatrogenic sequelae of cancer treatments, the most worrisome are second malignant neoplasms. We reported on our mono-institutional experiences of screening and treating secondary breast cancer, secondary thyroid cancer and secondary osteosarcoma. Recommendations on the surveillance needed for cancer survivors because of the risk of late effects of their disease or its treatment suggest that discussing the potential problems early on can be crucial to a patient’s future health. These considerations and our consolidated experience strengthen our conviction that survivors of cancer in childhood and adolescence who develop second malignant neoplasms should be treated at highly-specialized centers. Multidisciplinary care requires close communications and high levels of up-to-date professional expertise. This challenging area of health care is also changing rapidly because cancer survivorship is a work in progress, but we cannot wait for definitive conclusions on many aspects because this will take decades, especially for pediatric patients.

Impact of the COVID-19 pandemic on paediatric renal tumour presentation and management, a SIOP renal tumour study group study
Prakriti Roy, Sophie E. van Peer, Rana Dandis, Catriona Duncan, Joaquim Caetano de Aguirre‐Neto, Arnauld Verschuur, Beatriz de Camargo, Henrike E. Karim‐Kos, Luna Boschetti, Filippo Spreafico,et al.
Wiley
AbstractBackgroundThe COVID‐19 pandemic had global catastrophic effects on the management of non‐communicable diseases including paediatric cancers. Restrictions during the start of 2020 complicated timely referrals of patients to specialized centres. We aimed to evaluate the pandemic’s impact on the number of new diagnoses, disease characteristics and management delay for paediatric renal tumour patients included in the SIOP‐RTSG‐UMBRELLA study, as compared with data from a historical SIOP‐RTSG trial (2005–2009).MethodsThe number of intensive care admissions, population mobility rates and national lockdown periods/restrictions were used as proxies of the pandemic’s severity and impact on societies. Clinical and tumour data were extracted from the SIOP‐RTSG‐UMBRELLA study and from historical SIOP‐RTSG trials.ResultsDuring the first lockdown in Europe, the number of newly diagnosed patients decreased following restrictions and population immobilisation. Additionally, there was a higher proportion of advanced disease (37% vs. 17% before and after COVID‐9, p < 0.001) and larger median tumour volume (559 cm3 vs. 328 and 434 cm3 before and after, p < 0.0001). Also in Brazil, the proportion of advanced disease was higher during the national decrease in mobilisation and start of restrictions (50% and 24% vs. 11% and 18% before and after, p < 0.01). Tumour volume in Brazil was also higher during the first months of COVID‐19 (599 cm3 vs. 459 and 514 cm3), although not significant (p = 0.17). We did not observe any delays in referral time nor in time to start treatment, even though COVID‐19 restrictions may have caused children to reach care later.ConclusionThe COVID‐19 pandemic briefly changed the tumour characteristics of children presenting with renal tumours. The longer‐term impact on clinical outcomes will be kept under review.

Advances in the clinical management of high-risk Wilms tumors
Michael V. Ortiz, Christa Koenig, Amy E. Armstrong, Jesper Brok, Beatriz de Camargo, Annelies M. C. Mavinkurve‐Groothuis, Thelma B. Velasquez Herrera, Rajkumar Venkatramani, Andrew D. Woods, Jeffrey S. Dome,et al.
Wiley
AbstractOutcomes are excellent for the majority of patients with Wilms tumors (WT). However, there remain WT subgroups for which the survival rate is approximately 50% or lower. Acknowledging that the composition of this high‐risk group has changed over time reflecting improvements in therapy, we introduce the authors’ view of the historical and current approach to the classification and treatment of high‐risk WT. For this review, we consider high‐risk WT to include patients with newly diagnosed metastatic blastemal‐type or diffuse anaplastic histology, those who relapse after having been initially treated with three or more different chemotherapeutics, or those who relapse more than once. In certain low‐ or low middle‐income settings, socio‐economic factors expand the definition of what constitutes a high‐risk WT. As conventional therapies are inadequate to cure the majority of high‐risk WT patients, advancement of laboratory and early‐phase clinical investigations to identify active agents is urgently needed.

Should we reduce routine surveillance imaging in pediatric germ cell tumors?
Monica Terenziani, Francesco Barretta, Giovanna Gattuso, Gianni Bisogno, Massimo Conte, Alessandro Crocoli, Maria Debora De Pasquale, Davide Biasoni, Filippo Spreafico, and Paolo D'Angelo
Wiley
This paper retrospectively investigated the site and the detection method of relapses in children and adolescents with malignant germ cell tumors enrolled in the TCGM‐AIEOP‐2004 Study and subsequently developed a relapse, in order to evaluate a possible reduction in radiological exposure during follow‐up. Including all malignant cases, serum tumor markers identified a relapse in more than 70% and, according to the selection criteria published by Children Oncology Group in 2018, in more than 90% of cases. These results confirm the importance of serum tumor markers as a relapse detection method, with possible reduction of radiology exams in specific subgroups.

Molecular Signature of Biological Aggressiveness in Clear Cell Sarcoma of the Kidney (CCSK)
Michele Fiore, Alberto Taddia, Valentina Indio, Salvatore Nicola Bertuccio, Daria Messelodi, Salvatore Serravalle, Jessica Bandini, Filippo Spreafico, Daniela Perotti, Paola Collini,et al.
MDPI AG
Clear cell sarcoma of the kidney (CCSK) is a rare pediatric renal tumor with a worse prognosis than Wilms’ tumor. Although recently, BCOR internal tandem duplication (ITD) has been found as a driver mutation in more than 80% of cases, a deep molecular characterization of this tumor is still lacking, as well as its correlation with the clinical course. The aim of this study was to investigate the differential molecular signature between metastatic and localized BCOR-ITD-positive CCSK at diagnosis. Whole-exome sequencing (WES) and whole-transcriptome sequencing (WTS) were performed on six localized and three metastatic BCOR-ITD-positive CCSKs, confirming that this tumor carries a low mutational burden. No significant recurrences of somatic or germline mutations other than BCOR-ITD were identified among the evaluated samples. Supervised analysis of gene expression data showed enrichment of hundreds of genes, with a significant overrepresentation of the MAPK signaling pathway in metastatic cases (p < 0.0001). Within the molecular signature of metastatic CCSK, five genes were highly and significantly over-expressed: FGF3, VEGFA, SPP1, ADM, and JUND. The role of FGF3 in the acquisition of a more aggressive phenotype was investigated in a cell model system obtained by introducing the ITD into the last exon of BCOR by Crispr/Cas9 gene editing of the HEK-293 cell line. Treatment with FGF3 of BCOR-ITD HEK-293 cell line induced a significant increase in cell migration versus both untreated and scramble cell clone. The identification of over-expressed genes in metastatic CCSKs, with a particular focus on FGF3, could offer new prognostic and therapeutic targets in more aggressive cases.

Filippo Spreafico

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Scopus Publications