A Retrospective Evaluation of Ototoxicity Monitoring in a Cohort of Pediatric Patients With Solid Tumors, Treated in the Dutch National Cancer Center.

Introduction: Ototoxicity is an adverse effect of childhood cancer treatment with a negative impact on speech-language development and quality of life. This study aimed to retrospectively assess ototoxicity monitoring in a national cohort of pediatric patients with solid tumors, examining the frequency and determinants associated with hearing loss (HL).

Methods: This retrospective cohort study included 305 patients treated between 2015 and 2020 at the Princess Máxima Center.

Predictive gene expression profile for adjuvant taxane benefit in breast cancer in the MATADOR trial.

The primary objective of the prospective, randomized, multicenter, phase 3 biomarker Microarray Analysis in breast cancer to Taylor Adjuvant Drugs Or Regimens trial (MATADOR: ISRCTN61893718) is to generate a gene expression profile that can predict benefit from either docetaxel, doxorubicin, and cyclophosphamide (TAC) or dose-dense scheduled doxorubicin and cyclophosphamide (ddAC). Patients with a pT1-3, pN0-3 tumor were randomized 1:1 between ddAC and TAC. The primary endpoint was a gene profile-treatment interaction for recurrence-free survival (RFS).

Characteristics and outcome of synchronous bilateral Wilms tumour in the SIOP WT 2001 Study: Report from the SIOP Renal Tumour Study Group (SIOP-RTSG).

Background: Among patients with nephroblastoma, those with bilateral disease are a unique population where maximising tumour control must be balanced with preserving renal parenchyma.

Methods: The SIOP 2001 protocol recommended surgery after neoadjuvant cycle(s) of Dactinomycin and Vincristine (AV) with response-adapted intensification, if needed. Adjuvant treatment was given based on the lesion with the worst histology.

The PedAL/EuPAL Project: A Global Initiative to Address the Unmet Medical Needs of Pediatric Patients with Relapsed or Refractory Acute Myeloid Leukemia.

The prognosis of children with acute myeloid leukemia (AML) has improved incrementally over the last few decades. However, at relapse, overall survival (OS) is approximately 40-50% and is even lower for patients with chemo-refractory disease. Effective and less toxic therapies are urgently needed for these children.

Omission of adjuvant chemotherapy in patients with completely necrotic Wilms tumor stage I and radiotherapy in stage III: The 30-year SIOP-RTSG experience.

Background: Completely necrotic Wilms tumor (CN-WT) following preoperative chemotherapy has been regarded as low-risk WT since the International Society of Paediatric Oncology (SIOP) 93-01 study, and patients have been treated with reduced postoperative therapy. The aim of the study was to evaluate whether the omission of adjuvant chemotherapy in patients with localized CN-WT stage I and radiotherapy in stage III was safe.

Patients And Methods: The retrospective observational study of outcomes of patients diagnosed with localized CN-WT on central pathology review and treated according to the SIOP 93-01 and SIOP-WT-2001 protocols (1993-2022).

Bosutinib in Resistant and Intolerant Pediatric Patients With Chronic Phase Chronic Myeloid Leukemia: Results From the Phase I Part of Study ITCC054/COG AAML1921.

Purpose: Bosutinib is approved for adults with chronic myeloid leukemia (CML): 400 mg once daily in newly diagnosed (ND); 500 mg once daily in resistant/intolerant (R/I) patients. Bosutinib has a different tolerability profile than other tyrosine kinase inhibitors (TKIs) and potentially less impact on growth (preclinical data). The primary objective of this first-in-child trial was to determine the recommended phase II dose (RP2D) for pediatric R/I and ND patients.

Azacitidine (Vidaza) in Pediatric Patients with Relapsed Advanced MDS and JMML: Results of a Phase I/II Study by the ITCC Consortium and the EWOG-MDS Group (Study ITCC-015).

Background: Advanced myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukemia (JMML) are rare hematological malignancies in children. A second allograft is recommended if a relapse occurs after hematopoietic stem cell transplantation, but the outcome is poor.

Objective: We conducted a phase I/II multicenter study to evaluate the safety, pharmacokinetics, and activity of azacitidine in children with relapsed MDS/JMML prior to the second hematopoietic stem cell transplantation.

Impact of the COVID-19 pandemic on paediatric renal tumour presentation and management, a SIOP renal tumour study group study.

Background: The 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).

A joint international consensus statement for measuring quality of survival for patients with childhood cancer.

The aim of treating childhood cancer remains to cure all. As survival rates improve, long-term health outcomes increasingly define quality of care. The International Childhood Cancer Outcome Project developed a set of core outcomes for most types of childhood cancers involving relevant international stakeholders (survivors; pediatric oncologists; other medical, nursing or paramedical care providers; and psychosocial or neurocognitive care providers) to allow outcome-based evaluation of childhood cancer care.

Pediatric renal tumor epidemiology: Global perspectives, progress, and challenges.

Pediatric renal tumors account for 3%-11% of childhood cancers, the most common of which is Wilms tumor or nephroblastoma. Epidemiology plays a key role in cancer prevention and control by describing the distribution of cancer and discovering risk factors for cancer. Large pediatric research consortium trials have led to a clearer understanding of pediatric renal tumors, identification of risk factors, and development of more risk-adapted therapies.

Radiologic versus Segmentation Measurements to Quantify Wilms Tumor Volume on MRI in Pediatric Patients.

Wilms tumor is a common pediatric solid tumor. To evaluate tumor response to chemotherapy and decide whether nephron-sparing surgery is possible, tumor volume measurements based on magnetic resonance imaging (MRI) are important. Currently, radiological volume measurements are based on measuring tumor dimensions in three directions.

MEK inhibition causes BIM stabilization and increased sensitivity to BCL-2 family member inhibitors in RAS-MAPK-mutated neuroblastoma.

Introduction: Mutations affecting the RAS-MAPK pathway occur frequently in relapsed neuroblastoma tumors and are associated with response to MEK inhibition . However, these inhibitors alone do not lead to tumor regression , indicating the need for combination therapy.

Methods And Results: high-throughput combination screening, we identified that the MEK inhibitor trametinib can be combined with BCL-2 family member inhibitors, to efficiently inhibit growth of neuroblastoma cell lines with RAS-MAPK mutations.

Cognitive and Behavioral Development of 9-Year-Old Children After Maternal Cancer During Pregnancy: A Prospective Multicenter Cohort Study.

JCO This multicenter cohort study reports on the long-term effects of prenatal exposure to maternal cancer and its treatment on cognitive and behavioral outcomes in 9-year-old children. In total, 151 children (mean age, 9.3 years; range, 7.

Patterns of Hearing Loss in Irradiated Survivors of Head and Neck Rhabdomyosarcoma.

Purpose: The frequency and patterns of HL in a HNRMS survivor cohort were investigated. A dose-effect relationship between the dose to the cochlea and HL was explored.

Methods: Dutch survivors treated for HNRMS between 1993 and 2017 with no relapse and at least two years after the end of treatment were eligible for inclusion.

Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma.

Background: Immune checkpoint inhibitors and targeted therapies have dramatically improved outcomes in patients with advanced melanoma, but approximately half these patients will not have a durable benefit. Phase 1-2 trials of adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) have shown promising responses, but data from phase 3 trials are lacking to determine the role of TILs in treating advanced melanoma.

Methods: In this phase 3, multicenter, open-label trial, we randomly assigned patients with unresectable stage IIIC or IV melanoma in a 1:1 ratio to receive TIL or anti-cytotoxic T-lymphocyte antigen 4 therapy (ipilimumab at 3 mg per kilogram of body weight).

Incidence and survival of paediatric renal tumours in the Netherlands between 1990 and 2014.

Background: This population-based study is the first to provide a detailed analysis of trends in incidence and survival of children and adolescents diagnosed with renal malignancies in the Netherlands.

Methods: Data on all renal malignancies diagnosed in paediatric patients (0-18 years) between 1990 and 2014 [N = 648, 92% Wilms tumour (WT)] were extracted from the Netherlands Cancer Registry. Five-year overall survival (OS) was estimated using the actuarial method.

Ten-year follow-up of the observational RASTER study, prospective evaluation of the 70-gene signature in ER-positive, HER2-negative, node-negative, early breast cancer.

Introduction: Prognostic gene expression signatures can be used in combination with classical clinicopathological factors to guide adjuvant chemotherapy decisions in ER-positive, HER2-negative breast cancer. However, long-term outcome data after introduction of genomic testing in the treatment decision-making process are limited.

Methods: In the prospective RASTER study, the tumours of 427 patients with cTanyN0M0 breast cancer were tested to assess the 70-gene signature (MammaPrint).

Limiting systemic endocrine overtreatment in postmenopausal breast cancer patients with an ultralow classification of the 70-gene signature.

Purpose: Guidelines recommend endocrine treatment for estrogen receptor-positive (ER+) breast cancers for up to 10 years. Earlier data suggest that the 70-gene signature (MammaPrint) has potential to select patients that have an excellent survival without chemotherapy and limited or no tamoxifen treatment. The aim was to validate the 70-gene signature ultralow-risk classification for endocrine therapy decision making.