Choroid Plexus Carcinomas With TP53 Germline Mutations: Management and Outcome

BackgroundChoroid plexus carcinomas (CPCs) are rare pediatric tumors commonly associated with Li-Fraumeni syndrome (LFS), which involves a germline mutation of the tumor suppressor gene TP53.Materials and MethodsWe retrospectively analyzed the corresponding information of 12 cases, including the effects of surgery and radiotherapy and TP53 germline mutations, to analyse the management strategies. Kaplan-Meier curves and the log-rank test were used to evaluate the progression-free survival (PFS).ResultsTwelve CPC patients were included, of which TP53 germline mutations were found in eight cases. All patients underwent surgical resection, and six patients received radiotherapy following with operation after initial diagnosis, one patient received radiotherapy following relapse. It was significantly different (P=0.012 and 0.028) that patients with TP53 germline mutation receiving the gross total resection (GTR) without radiotherapy showed survival advantages. Without TP53 germline mutations also showed survival advantages, but there is no statistical significance (P=0.063)ConclusionsThese findings provide evidence for the therapeutic strategy that radiotherapy should not be considered for patients with TP53 germline mutations.

Choroid plexus carcinoma in children

Choroid plexus carcinomas (CPCs) are rare pediatric tumors with a generally poor prognosis. Currently there is no definite optimal treatment strategy for this neoplasm. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. This study included patients with a verified diagnosis of CPC at the age 0 to 18 years in the period from 01.01.2009 to 31.12.2019. A total of 32 patients were registered. The median age was 2.65 years; 93.5% of CPCs were localized in the lateral ventricles. Initial metastases were found in 21.8% of cases; 5-year event-free survival (EFS) in children with metastases was lower than in those who did not have metastases 29 ± 17% and 49 ± 12%. In our cohort, gross total resection (GTR) was performed in 65.6% of patients. The five-year EFS in patients with complete CPC removal was higher than in patients who underwent subtotal and partial resection (63 ± 13%, 12 ± 11%, and 0%, respectively). In addition, overall survival (OS) was slightly higher in those who underwent GTR compared with subtotal and partial resection (74 ± 12%, 67 ± 16%, and 0%, respectively). Of the 32 children with CPCs, 15 children received programm chemotherapy, 17 non-programm chemotherapy, 5-year EFS in patients who received programm and non-programm chemotherapy was 79 ± 11% and 0%, respectively (p = 0.0006), 5-year OS in patients who received programm and non-programm chemotherapy was 93 ± 7% and 36 ± 14% (p = 0.0054).

NURS-01. INTRACEREBROVENTRICULAR DRUG ADMINISTRATION FOR TREATMENT OF PEDIATRIC BRAIN TUMORS

Intrathecal (IT) chemotherapy, given via lumbar puncture (LP) or an intracerebroventricular (ICV) device has become a safe and effective way to deliver chemotherapy into the cerebrospinal fluid (CSF) space. The blood brain barrier makes treating tumors with CSF dissemination difficult with systemic chemotherapy alone. IT chemotherapy is often necessary for tumors which disseminate into the CSF space including embryonal tumors and choroid plexus carcinomas. It is also used for relapsed or recurrent tumors. Giving IT chemotherapy via an ICV device instead of via an LP can be preferable as it requires no deep sedation and allows for more uniform drug distribution. Drugs given IT include methotrexate, cytarabine, hydrocortisone, etoposide, and topotecan. ICV devices can be placed in patients with adequate CSF flow and a flow study can be done if needed to confirm. Accessing the ICV device for administration of chemotherapy is typically done by a physician or nurse practitioner using sterile technique. Our institution has had success using music therapy and child life specialists for assistance with coping during the procedure as patients are awake. The procedure has few complications the most common being infection usually with skin flora. It can also cause nausea and headache. There are few long term risks.

RARE-52. RB1 GENE DELETIONS ARE THE NOVEL MECHANISM OF CHOROID PLEXUS TUMORS (CPT) ONCOGENESIS

BACKGROUND CPTs are known to be rare TP53-dependent neoplasms, while major molecular alterations underlying tumor progression, especially in TP53-wild type cases, are still unclear. METHODS 18 primary CPT, including 16 choroid plexus carcinomas (CPC) and two atypical choroid plexus papillomas (CPP), were evaluated for copy number status of 87 major oncogenes and tumor suppressor genes by nCounter Cancer CNV assay by Nanostring and TP53 and RB1 by MLPA. Germline TP53 nucleotide substitutions were analyzed by Sanger sequencing. RESULTS Pathogenic germline TP53 variants were present in 4 cases confirming Li-Fraumeni syndrome (LFS). Two patients have somatic TP53 substitutions. Only one patient with LFS harbored somatic TP53 deletion. In 7 patients, heterozygous deletions of RB1 involving from 3 exons to the whole coding sequence detected by MLPA were discovered. All these findings were validated by nCounter CNV assay. Additionally, four patients have WT1 deletions, two patients – BRCA2, and in 1 case - NF1, concomitant with RB1 deletions in 3 cases. Interestingly, in one patient who faced a progression of CPP to CPC germline, RB1 deletion was detected, and in both subsequent tumors, the length of the deleted region progressively increased. Notably, that RB1 deletions are mostly mutually exclusive to TP53 substitutions. 3 of 4 patients with RB1 deletions having follow-up period >1 year faced with tumor-related adverse events. CONCLUSIONS Somatic or uncommon germline RB1 heterozygous deletions have been unraveled as a novel mechanism of aggressive CPT and could be implemented in prognosis definition schemes.

Choroid Plexus Tumors

This chapter presents the case of an 11-month-old male with a history of macrocephaly, anorexia, and right upper extremity tremors. His family history was significant for a father with anaplastic astrocytoma. Physical exam was notable for left asymmetric macrocephaly and a full/tense fontanelle. The chapter reviews the differential diagnoses for macrocephaly. Imaging, including magnetic resonance spectroscopy, revealed a highly vascular intraventricular mass with some areas of likely necrosis, suggesting choroid plexus carcinoma. The authors review the preoperative planning and surgical management of this case, including potential complications and their management. Finally, choroid plexus carcinomas are reviewed in light of evidence-based medicine and clinical outcomes.

Neoadjuvant chemotherapy reduces blood loss during the resection of pediatric choroid plexus carcinomas

OBJECT Choroid plexus carcinomas (CPCs) are rare brain tumors originating from the ventricular choroid plexus. They account for 2%–4% of all pediatric brain tumors and are most frequently seen in very young children. This pediatric proclivity, in combination with a marked vascularity, renders an aggressive resection a difficult and often dangerous endeavor. Blood losses of several total blood volumes in small children are not uncommon, sometimes forcing the neurosurgeon to abort the procedure, often leaving residual tumor. Great extent of tumor resection is an accepted beneficial factor for overall survival. Therefore, a second resection usually follows the administration of adjuvant chemotherapy. Second-look surgery appears to be associated with markedly decreased blood loss. Histological examination of specimens obtained at a second intervention shows decreased vascularity and fibrotic changes in tumor tissue. At the Hospital for Sick Children in Toronto, this empirical finding led to the strategy of neoadjuvant chemotherapy to minimize blood loss and maximize cytoreduction. The authors undertook this study to assess the potentially beneficial effect of neoadjuvant chemotherapy on blood loss during surgery for CPCs. METHODS In this retrospective cohort review, the demographic, clinical, and treatment parameters of 22 consecutive patients diagnosed with CPC are presented. All underwent surgical treatment at the Hospital for Sick Children from 1982 to 2013. Special attention was given to the impact of neoadjuvant chemotherapy on extent of resection and intraoperative blood loss. Extent of resection was calculated based on perioperative neuroimaging, and amount of blood loss was estimated based on transfusion parameters and perioperative changes in hematocrit. RESULTS Ten patients did not receive neoadjuvant chemotherapy, and 12 were treated with 2–5 cycles of ICE (ifosfamide, carboplatin, etoposide) chemotherapy in a neoadjuvant fashion. The 22 patients included in the study underwent a total of 37 tumor resection surgeries. In all of the cases in which neoadjuvant chemotherapy was used, at least a near-total resection (> 95% of tumor volume) was achieved. Patients who underwent gross-total resection had prolonged overall survival. Of the 37 resections, 18 were performed after chemotherapy. Mean blood loss in the neoadjuvant chemotherapy group was 22% of total estimated blood volume as opposed to 96% in patients without preoperative chemotherapy. CONCLUSIONS In children with CPC, the administration of neoadjuvant chemotherapy decreases intraoperative blood loss and increases extent of resection with a significant positive effect on overall survival.