Intracranial non-germinomatous germ cell tumors in children and adolescents: how can the experience from an uppermiddle-income country contribute to the worldwide effort to improve outcomes?

Background: Non-germinomatous germ cell tumors (NGGCT) accounts for one third of intracranial GCT. While the germinoma group have an excellent overall survival, the standard of practice for children with NGGCT is still under evaluation. Aims: Describe the results of the of the Brazilian consortium protocol. Methods: Since 2013, 15 patients with a diagnosis of NGGCT by histopathology and/or serum/cerebrospinal fluid (CSF) tumor markers, ßHCG >200mlU/ml and/or positive alpha-fetoprotein were treated with neoadjuvant chemotherapy with carboplatin, cyclophosphamide and etoposide followed by ventricular radiotherapy (RTV) of 18Gy with boost (32Gy) to the primary site. Metastatic patients underwent craniospinal irradiation (CSI) and "slow responders" to the four initial cycles of CT, to autologous stem cell transplantation (ASCT) followed by CSI. Results: Mean age, 13.1 years. Thirteen males. Primary sites: pineal (n=12), suprasellar (n=2) and bifocal (n=1). Four patients were metastatic at diagnosis. Eight patients had CSF and/or serum alpha-fetoprotein levels > 1,000ng/ml. Tumor responses after chemotherapy demonstrated complete in six cases and partial in seven, with "second-look" surgery being performed in five cases, and two patients presenting viable lesions being referred to ASCT. The main toxicity observed was hematological grades 3/4. Two patients with metastatic disease, one with Down Syndrome and AFP > 1,000ng/ml and the other with choriocarcinoma and pulmonary metastases, developed progressive disease resulting in death, as well as two other patients without evidence of disease, due to endocrinological disorders. Event-free and overall survival at 2 and 5 years were 80% and 72.7%, respectively, with a mean follow-up of 48 months (range, 7-107). Conclusions: Despite the small number of patients, in our series, treatment with six cycles of chemotherapy and RTV with focal boost for localized disease (n=11) and ACST for identified slow responders (n=2) seem to be effective strategies contributing to the overall effort to improve outcomes of this group of patients.

Invasive fungal infections in pediatric patients with central nervous system tumors: novel insights for prophylactic treatments?

Background and aims: Invasive fungal disease (IFD) poses significant morbidity and mortality risks, especially in pediatric patients with neoplastic diseases. However, there is a notable lack of data concerning patients with central nervous system (CNS) tumors. Considering vulnerability factors to infections such as neutropenia, corticosteroids, chemotherapy, surgical interventions, and others, this study aims to evaluate the incidence of IFD in pediatric patients with CNS tumors and determine appropriate indications for prophylactic measures. This is a single-center, retrospective study conducted between 2011 and 2022 at the Pediatric Institute of Oncology (IOP-GRAACC-UNIFESP). Results: A total of 38 cases of IFD were diagnosed in 818 children with CNS malignancies (4,6%). The mean age was 3.5 years (0.4-28y), with 22 (57.9%) male patients. Embryonal tumors (18/38, 47.3%) were the most prevalent CNS tumors, followed by low-grade gliomas (13/38, 34.2%). All episodes met the EORTC IFD criteria, and 36/38 (94.7%) were proven. Invasive yeast infections (33/36, 91.6%), predominantly Candida (30/33, 90.9%), were the most common diagnosis. In total, 25 patients (25/38, 65.8%) were receiving chemotherapy, with 13 of them having embryonal tumors. A total of 11 infants were in the Head Start scheme, resulting in a high prevalence of IFD in these group of patients (11/58, 18.9%). In total, 13 (13/38, 34.2%) patients underwent neurosurgery, mostly ventricular-peritoneal shunts revisions (10/13, 76.9%). Nine (9/38, 23.7%) were with prolonged use of corticosteroids, eight of them associated with neurosurgery. Conclusion: Routine systemic antifungal prophylaxis based solely on diagnosis is not recommended for low-risk cases. Evaluating patient- and treatment-specific risk factors is crucial in infants undergoing high-dose chemotherapy with expected neutropenia and in patients requiring prolonged corticosteroid therapy alongside neurosurgical procedures.

Outcome of Children and Adolescents With Primary Intracranial Germinoma Treated With Chemotherapy and Reduced Dose-Field Irradiation: A Prospective Brazilian Experience.

PURPOSE: This prospective Brazilian single-arm trial was conducted to determine response to chemotherapy and survival after response-based radiotherapy in children with intracranial germinomas, in the setting of a multi-institutional study in a middle-income country (MIC) with significant disparity of subspecialty care. PATIENTS AND METHODS: Since 2013, 58 patients with histologic and/or serum and CSF tumor marker evaluations of primary intracranial germ cell tumors were diagnosed; 43 were germinoma with HCGß levels ≤200 mIU/mL and five between 100 and 200 mIU/mL. The treatment plan consisted of four cycles of carboplatin and etoposide followed by 18 Gy whole-ventricular field irradiation (WVFI) and primary site(s) boost up to 30 Gy; 24 Gy craniospinal was prescribed for disseminated disease. RESULTS: Mean age 13.2 years (range, 4.7-25.5 years); 29 were males. Diagnosis was made by tumor markers (n = 6), surgery (n = 25), or both (n = 10). Two bifocal cases with negative tumor markers were treated as germinoma. Primary tumor location was pineal (n = 18), suprasellar (n = 14), bifocal (n = 10), and basal ganglia/thalamus (n = 1). Fourteen had ventricular/spinal spread documented by imaging studies. Second-look surgery occurred in three patients after chemotherapy. Thirty-five patients achieved complete responses after chemotherapy, and eight showed residual teratoma/scar. Toxicity was mostly grade 3/4 neutropenia/thrombocytopenia during chemotherapy. At a median follow-up of 44.5 months, overall and event-free survivals were 100%. CONCLUSION: The treatment is tolerable, and WVFI dose reduction to 18 Gy preserves efficacy; we have demonstrated the feasibility of successfully conducting a prospective multicenter trial in a large MIC despite resource disparity.

Reduction in the cerebrospinal fluid protein level after bevacizumab treatment in patients with optic pathway low-grade gliomas.

Optic pathway gliomas (OPG) can cause elevated cerebrospinal fluid (CSF) protein concentrations. We report on two patients with suprasellar low-grade gliomas and high CSF protein levels (590 and 551 mg/dl) that precluded shunt implantation. After two and three doses of bevacizumab, respectively, the levels dropped dramatically to 191 and 178 mg/dl, respectively. Bevacizumab treatment was associated with a decrease in CSF protein level, allowing successful shunt placement. Our results are consistent with the pharmacological mechanism of bevacizumab, which decreases protein leakage from blood vessels to the ventricles.

A importância do diagnóstico precoce em oncologia pediátrica - Tumor de Wilms: relato de caso / The importance of early diagnosis in pediatric oncology – Wilms’ tumor: a case report

Introdução: O câncer representa a primeira causa de morte por doença entre crianças de 1 a 19 anos. Os tumores renais são responsáveis por 5% a 10% destas neoplasias. A apresentação clínica inicial mais frequente é a presença de massa abdominal assintomática. Hipertensão arterial, dores abdominais, hematúria macroscópica, anorexia e associação com anormalidades congênitas podem ocorrer. Este caso objetiva chamar a atenção para o diagnóstico diferencial das massas abdominais e ratifi car a importância do exame clínico no diagnóstico precoce. Descrição de Caso: Menina, 11 meses, natural e procedente de Canoas. Consultava regularmente na UBS com médico generalista e nas emergências. Há dois meses, mãe levou menina à UBS por dores abdominais e irritabilidade. Foi liberada com sintomáticos. Dias após, percebeu massa abdominal e procurou a emergência. Após exame clínico, fez-se ecografia abdominal que evidenciou massa renal unilateral. A paciente foi encaminhada ao nosso serviço. Chegou nutrida, descorada, irritada, com massa palpável em hipocôndrio esquerdo, estendendo-se até fossa ilíaca e ultrapassando a linha média. Realizou TC abdome: massa renal de 9,2x 8,9 cm, sugestiva de tumor de Wilms. Fez quimioterapia por 4 semanas e nefrectomia à esquerda. Anatomopatológico confirmou tumor de Wilms localizado. Conclusões: Estima-se que cerca de 70% das crianças com câncer possam ser curadas se diagnosticadas precocemente e tratadas em centros especializados. Com a descrição deste caso, chamamos a atenção para a importância do exame clínico e a valorização das queixas do paciente e de seus familiares, bem como para investigação das massas abdominais.

Background: Cancer is the leading cause of death by disease among children 1-19 years of age. Renal tumors account for 5-10% of these neoplasms. The most frequent initial clinical presentation is the presence of asymptomatic abdominal mass. High blood pressure, abdominal pain, macroscopic hematuria, anorexia and association with congenital abnormalities may occur. This case aims to draw attention to the differential diagnosis of abdominal masses and ratify the importance of clinical examination in early diagnosis. Description of case: Girl 11 months, born and living in Canoas. She consulted regularly with general practitioner and emergencies at the BHU. Two months ago, mother took the girl to BHU complaining of abdominal pain and irritability. She was released with symptomatic medications. A few days later, an abdominal mass was perceived and the patient was brought to the emergency. After clinical examination, abdominal ultrasonography showed unilateral renal mass. The patient was referred to our service. She was nourished, discolored, irritated, with a palpable mass in the left hypochondrium, extending to the iliac fossa and surpassing the midline. Abdominal CT showed renal mass 9,2 x 8.9 cm suggestive of Wilms' tumor. She was submitted to chemotherapy for 4 weeks and left nephrectomy. Pathology confi rmed localized Wilms’ tumor. Conclusions: It is estimated that about 70% of children with cancer can be cured if diagnosed early and treated in specialized centers. With the description of this case, we draw attention to the importance of clinical examination and appreciation of the patient's and their families’ complaints, as well as to the investigation of abdominal masses.