Post-operative meningeal thickening seen on magnetic resonance imaging

Posterior fossa tumors are relatively common in children, and the meningeal dissemination of these tumors is well established in the literature. Although leptomeningeal dissemination is more common in high-grade tumors, even low-grade tumors can generate meningeal metastases. In this case report, we would like to discuss the importance of leptomeningeal dissemination assessment of posterior fossa tumors in children, in the preoperative period, through the entire neuroaxis magnetic resonance imaging (MRI). This is important since transient meningeal thickening is very common in the postoperative periods of neurosurgical patients, and can be found for up to 5 or 6 years after surgery, causing these patients to undergo prolonged follow-ups and repeated MRIs and lumbar punctures.

RONC-06. VOLUMETRIC-MODULATED ARC WHOLE-BRAIN RADIOTHERAPY FOR THE PREVENTION OF PERMANENT ALOPECIA IN PEDIATRIC PATIENTS

Permanent alopecia is a grave late complication of multi-drug chemotherapy (CTx) plus cranial irradiation, reducing both patient self-esteem and quality of life in pediatric patients. We started to use craniospinal irradiation (CSI) using the volumetric-modulated arc whole-brain radiotherapy (VMAT-WBRT) in order to prevent permanent alopecia. We treated 5 pediatric patients with CSI using VMAT-WBRT, and report the initial clinical outcome. Five consecutive patients (4–11 years old) who received CSI using VMAT-WBRT from June 2015 to November 2018 were included into this study. One patient with embryonic carcinoma received radiotherapy (RT) with concurrent CTx; four patients with medulloblastoma (two patients with standard risk, and two patients with high risk) received RT followed by CTx. The prescribed doses of CSI were 23.4–35.2 Gy in 13–22 fractions, respectively. Optimization for VMAT-WBRT was performed to reduce doses to the hair follicles with keeping the dose coverage to the planning target volume. Although all patients experienced temporary alopecia, their hair fully recovered over the whole scalp within 8 months after finishing RT. One patient had disease progression after 6 months after completing CTx; this patient who was diagnosed as Group 3 subtype had diffuse meningeal dissemination confirmed with contrast enhanced spinal MRI before RT. The other four patients had no evidence of recurrence. Although CSI with VMAT-WBRT might be one of considerable options, more cases are needed to verify the efficacy to prevent permanent alopecia for pediatric patients who receive multi-drug CTx and cranial irradiation.

P14.16 Complete sustaining radiological response of a multi-recurrent disseminated adult medulloblastoma after antiangiogenic metronomic combined pediatric regimen MEMMAT: a case report

BACKGROUND Even if medulloblastoma is considered as a curable disease, recurrent medulloblastoma has a poor prognosis, independently of therapy used. Medulloblastoma is very rare in adults, unlike children, and therapeutic strategies at recurrence are lacking. Nevertheless, adult teams sometimes use as “compassionate” chemotherapy some regimens published in children, such as the MEMMAT metronomic combination. However, this treatment, targeting both endothelial and proliferating tumor cells, has to date not been studied in the adult population. MATERIAL AND METHODS We present the case of a 40-year-old man, suffering from a right cerebellar SHH mutated medulloblastoma initially diagnosed and treated in 2014 by craniospinal radiotherapy associated with 4 cycles of carboplatine-VP16 following complete resection. Since April 2016, date of first relapse, numerous successive recurrences occurred, initially focal, treated by several surgeries (April and November 2016, January 2017), chemotherapy (rechallenge by carboplatine-VP16) then stereotactic radiotherapy. He then developed in October 2017 a new relapse in the posterior fossa, also associated with a meningeal dissemination on lumbar MRI. IK was 90%. He was then treated by TOTEM regimen (Temozolomide-Topotecan) followed by “Packer” regimen (Cisplatin-Belustine-Vincristin), without tumor control. However, because patient was non symptomatic with a KPS of 80%, we decided, according to the AJA French group, to propose what we presumed to be a “compassionate” chemotherapy, by metronomic pediatric regimen “MEMMAT”. For “supportive care” reasons, we decided not to realize the “Intrathecal part” of this regimen and administered to the patient intravenous bevacizumab (10 mg/kg d1-d14-d21), thalidomide (100 mg/d), celecoxib (300 mg bid), fenofibrate (160 mg/d) and etoposide (100 mg/d d1-21), alternating with cyclophosphamide (100 mg/d d22-42). RESULTS Clinical tolerance was very good, except grade 1 heel pain and fatigue; hematological toxicity was mild (transient grade 3 neutropenia, grade 4 lymphopenia); renal impairment, already present at the beginning, was increasing, and justified dose adjustment after 5 cycles and nephrologic explorations, ongoing. Radiological evaluation showed a complete radiological response with complete disappearance of enhancing lesions on first MRIs realized after 3 months (2 cycles); this response was confirmed after 6 months (4 cycles) and 9 months (6 cycles) on both cerebral and spinal MRI. Patient is now receiving the 7th cycle. CONCLUSION We report here the first case of a complete and sustaining response of an adult multi-recurrent metastatic medulloblastoma treated by a pediatric antiangiogenic metronomic regimen “MEMMAT”. This promising result incites to develop a dedicated prospective trial in adults in view to confirm the interest of this strategy.

IL10 and IL10:IL6 Ratio in CSF Is Useful at Diagnosis but Also in the Assessment of Therapeutic Response in Patients with Primary Central Nervous System Lymphoma (PCNSL)

Reliable biomarkers of primary central nervous system lymphoma (PCNSL) are needed to support the magnetic resonance imaging (MRI) findings especially when the cerebral biopsy cannot be performed for pathologic examination. Biomarkers are also needed to optimize the assessment of therapeutic response, which so far relies only on gadolinium uptake on MRI, although large discrepancies of outcomes are observed in patients in complete remission assessed by MRI criteria. The aim of the present study was to evaluate the diagnostic and prognostic values of the cerebrospinal fluid (CSF) concentrations of interleukin (IL)-10 and IL-6 and of the IL-10:IL-6 ratio in patients with diffuse large B-cell type (DLBCL) PCNSL, at time of diagnosis and after treatment. IL-10 and IL-6 levels were measured in 120 patients with DLBCL-PCNSL and 36 control patients with other brain tumor or inflammatory neurologic diseases, using the quantitative Cytometric Bead Array® technique (human IL-10 CBA kit and human IL-6 CBA kit; BD BiosciencesTM) on a FACSCanto II cytometer (BD BiosciencesTM) according to the manufacturer’s recommendations. Serial measures of cytokines were performed in 57 patients. The IL-10:IL-6 ratio distinguishes PCNSL from other neurological diseases. Using a cutoff level of 1.0, the sensitivity and specificity are 94% and 80% respectively. Meningeal dissemination defined by cytological examination and/or flow cytometry analysis, is significantly associated with a higher IL-10 concentration (417 pg/ml vs 22 pg/ml; p = 0.0024) and a higher IL-10:IL-6 ratio (32 vs 6 ; p = 0.0011). Previous treatment with corticosteroids significantly reduces the IL-10:IL-6 ratio (ratio=7.6 with corticosteroids vs 21.9 without corticosteroids; p= 0.02). With a median follow-up of 25 months, the pre-therapeutic concentration of IL-10 has no prognostic value on overall and progression free survivals. After treatment, the median concentration of IL-10 is significantly decreased in patients entering complete (CR) or partial response (PR) compared to non-responder patients (median = 35.9 pg/ml and 235.5 pg/ml respectively, p = 0.01). We demonstrate for the first time that among patients in CR or PR (as per MRI criteria), a persistent detectable IL-10 level in CSF (> 2,5 pg/ml) has an impact on the progression free survival (1 year PFS: 21.2 % vs 53.6%; p= 0,004) (figure 1). Our study shows that IL-10:IL-6 ratio can be used as a diagnostic biomarker for PCNSL of DLBCL type . Analysis will be done to determine the cut off values of IL10 and IL-10:IL-6 ratio in a predictive model of meningeal dissemination. We also provide evidence that IL-10 concentration may be useful to complete the assessment of therapeutic response in PCNSL. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.