Rhabdoid tumor predisposition syndrome: A historical review of treatments and outcomes for associated pediatric malignancies.

Rhabdoid tumor predisposition syndrome (RTPS) is a rare disorder associated with malignant rhabdoid tumor of the kidney (RTK), atypical teratoid rhabdoid tumor (ATRT), and/or other extracranial, extrarenal rhabdoid tumors (EERT), and these pediatric malignancies are difficult to treat. Presently, most of the information regarding clinical manifestations, treatment, and outcomes of rhabdoid tumors comes from large data registries and case series. Our current understanding of treatments for patients with rhabdoid tumors may inform how we approach patients with RTPS. In this manuscript, we review the genetic and clinical features of RTPS and, using known registry data and clinical reports, review associated tumor types ATRT, RTK, and EERT, closing with potential new approaches to treatment. We propose collaborative international efforts to study the use of SMARC (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin)-targeting agents, high-dose consolidative therapy, and age-based irradiation of disease sites in RTPS.

Marrow-ablative consolidation chemotherapy and molecular targeted therapy delivered in a risk-adapted manner for newly diagnosed children with choroid plexus carcinoma: A work in progress.

Choroid plexus carcinomas (CPC) are early childhood cancers characterized by loss of TP53 function and poor survival. We are analyzing data on TP53 status, survival, and second cancers from the largest cohort of CPC receiving chemotherapy followed by consolidation with marrow-ablative chemotherapy (HDCx). Additionally, we discuss the rationale for targeted therapies for CPC patients. Currently, 8 of the 13 with Li-Fraumeni Syndrome-associated CPC were treated and continued CPC-free, indicating that HDCx improves CPC-free survival in young children with TP53-mutated CPC. These data justify the inclusion of HDCx in the planned prospective international trial for children with TP53-mutated CPC.

Final report of the phase II NEXT/CNS-GCT-4 trial: GemPOx followed by marrow-ablative chemotherapy for recurrent intracranial germ cell tumors.

Background: Patients with relapsed intracranial germinoma can achieve durable remission with standard chemotherapy regimens and/or reirradiation; however, innovative therapies are required for patients with relapsed and/or refractory intracranial nongerminomatous germ cell tumors (NGGCTs) due to their poor prognosis. Improved outcomes have been reported using reinduction chemotherapy to achieve minimal residual disease, followed by marrow-ablative chemotherapy (HDCx) with autologous hematopoietic progenitor cell rescue (AuHPCR). We conducted a phase II trial evaluating the response and toxicity of a 3-drug combination developed for recurrent intracranial germ cell tumors consisting of gemcitabine, paclitaxel, and oxaliplatin (GemPOx). Methods: A total of 9 patients with confirmed relapsed or refractory intracranial GCT were enrolled after signing informed consent, and received at least 2 cycles of GemPOx, of which all but 1 had relapsed or refractory NGGCTs. One patient with progressive disease was found to have pathologically confirmed malignant transformation to pure embryonal rhabdomyosarcoma (without GCT elements), hence was ineligible and not included in the analysis. Patients who experienced sufficient responses proceeded to receive HDCx with AuHPCR. Treatment response was determined based on radiographic tumor assessments and tumor markers. Results: A total of 7 patients achieved sufficient response and proceeded with HDCx and AuHPCR, and 5 subsequently received additional radiotherapy. A total of 2 patients developed progressive disease while receiving GemPOx. Myelosuppression and transaminitis were the most common treatment-related adverse events. With a mean follow-up of 44 months, 4 patients (3 NGGCTs, 1 germinoma) are alive without evidence of disease. Conclusions: GemPOx demonstrates efficacy in facilitating stem cell mobilization, thus facilitating the feasibility of both HDCx and radiotherapy.

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.

O uso de eritropoetina em crianças com tumores cerebrais em tratamento intensivo com quimioterapia / Use of erythropoietin in children with brain tumors in intensive treatment with chemotherapy

Foram analisadas cinco crianças portadoras de tumores cerebrais malignos em vigencia de quimioterapia intensiva, com a finalidade de estudar a eficacia da eritropoetina recombinante humana (rHuEPO), em diminuir as necessidades de transfusöes de concentrados de hemacias. Duas crianças testemunhas de Jeova receberam rHuEPO. Nenhuma diferença foi observada nos requerimentos de concentrados de hemacias, comparando-se com o grupo de pacientes que näo receberam rHuEPO