Intrathecal Catheter for Chemotherapy in Leptomeningeal Carcinomatosis From HER2-Negative Metastatic Breast Cancer.

PURPOSE: Most oncological treatments for leptomeningeal metastasis (LM) do not cross the blood-brain barrier (BBB). One therapeutic option is intrathecal (IT) chemotherapy. Both the brain-implanted Omaya reservoir and lumbar puncture (LP) are classic routes for IT chemotherapy delivery. An intrathecal catheter (IC) connected to a subcutaneous port is a recently developed option for the management of chemotherapy infusions. It is essential to evaluate the efficacy and safety of chemotherapy infusion using such device. METHODS: We conducted a retrospective monocentric study within Institut de cancerologie de l'Ouest at Angers, including all patients with advanced breast cancer (aBC) with LM implanted with an IT device for IT chemotherapy between January 2013 and May 2020. The primary endpoint was overall survival (OS) and secondary endpoints included surgical feasibility, patient safety, and progression-free survival (PFS). The catheter was inserted through an LP, the tip was positioned at the right level and connected to a subcutaneous port implanted under the skin of the anterior thoracic wall. IT chemotherapy is painless and easy for qualified nurses to administer on an outpatient basis. RESULTS: Thirty women underwent the implantation. No failures occurred during the procedure. A total of 77% of patients reported no complications after implantation. Only three complications required surgical treatment. The median number of IT chemotherapy courses per patient was 8 (range, 2-27). The tolerance profile for iterative IT chemotherapy was manageable in ambulatory care. With a median follow-up of 76.5 months (95% confidence interval [CI], 11.6-not available), the median OS was 158 days (95% CI, 87-235), and the median PFS was 116 days (95% CI, 58-174). CONCLUSION: Infusing chemotherapy using an implanted catheter is an efficient option for managing IT chemotherapy with a good tolerance profile. Patient-reported outcomes for the evaluation of IT chemotherapy toxicity are currently being developed.

Management of Recurrent Glioblastomas: What Can We Learn from the French Glioblastoma Biobank?

Safe maximal resection followed by radiotherapy plus concomitant and adjuvant temozolomide (TMZ) is universally accepted as the first-line treatment for glioblastoma (GB), but no standard of care has yet been defined for managing recurrent GB (rGB). We used the French GB biobank (FGB) to evaluate the second-line options currently used, with a view to defining the optimal approach and future directions in GB research. We retrospectively analyzed data for 338 patients with de novo isocitrate dehydrogenase (IDH)-wildtype GB recurring after TMZ chemoradiotherapy. Cox proportional hazards models and Kaplan-Meier analyses were used to investigate survival outcomes. Median overall survival after first surgery (OS1) was 19.8 months (95% CI: 18.5-22.0) and median OS after first progression (OS2) was 9.9 months (95% CI: 8.8-10.8). Two second-line options were noted for rGB patients in the FGB: supportive care and treatments, with systemic treatment being the treatment most frequently used. The supportive care option was independently associated with a shorter OS2 (p < 0.001). None of the systemic treatment regimens was unequivocally better than the others for rGB patients. An analysis of survival outcomes based on time to first recurrence (TFR) after chemoradiotherapy indicated that survival was best for patients with a long TFR (≥18 months; median OS1: 44.3 months (95% CI: 41.7-56.4) and median OS2: 13.0 months (95% CI: 11.2-17.7), but that such patients constituted only a small proportion of the total patient population (13.0%). This better survival appeared to be more strongly associated with response to first-line treatment than with response to second-line treatment, indicating that the recurring tumors were more aggressive and/or resistant than the initial tumors in these patients. In the face of high rates of treatment failure for GB, the establishment of well-designed large cohorts of primary and rGB samples, with the help of biobanks, such as the FGB, taking into account the TFR and survival outcomes of GB patients, is urgently required for solid comparative biological analyses to drive the discovery of novel prognostic and/or therapeutic clinical markers for GB.

Eye movement abnormalities in neurodegenerative langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare inflammatory myeloid neoplasm characterized by proliferation of tumor histiocytes that involves multiple organs including central nervous system. The physiopathologic process underlying degenerative neuro-LCH (i.e., DN-LCH) remains imperfectly settled. Since the main clinical features of DN-LCH are cerebellar ataxia and dysexecutive syndrome, eye movements might be disrupted and may help in disease diagnosis and monitoring. We retrospectively analyzed the medical records of twenty DN-LCH patients investigated using eye movement recording (EMR) in our hospital between 2015 and 2018. DN-LCH patients exhibited (i) abnormal gain in visually guided saccades including hypermetric saccades and excessive gain variability -45.0%-, (ii) increased mean antisaccade error rates -66.7%-, (iii) altered smooth pursuit -50.0%-, and (iv) excessive number of square wave jerks-25%- and gaze-evoked nystagmus. Our study suggests that DN-LCH patients present a peculiar pattern of eye movement impairments supporting cerebellar and prefrontal dysfunctions. As a non-invasive method, EMR could therefore be a useful tool for quantitative monitoring of DN-LCH patients. Further studies are warranted to support our findings.

A new glioblastoma cell trap for implantation after surgical resection.

Glioblastoma (GB) is a highly infiltrative tumor, recurring, in 90% of cases, within a few centimeters of the surgical resection cavity, even with adjuvant chemo/radiotherapy. Residual GB cells left in the margins or infiltrating the brain parenchyma shelter behind the extremely fragile and sensitive brain tissue and may favor recurrence. Tools for eliminating these cells without damaging the brain microenvironment are urgently required. We propose a strategy involving the implantation, into the tumor bed after resection, of a scaffold to concentrate and trap these cells, to facilitate their destruction by targeted therapies, such as stereotactic radiosurgery. We used bacterial cellulose (BC), an easily synthesized and modifiable random nanofibrous biomaterial, to make the trap. We showed that the structure of BC membranes was ideal for trapping tumor cells and that BC implants were biocompatible with brain parenchyma. We also demonstrated the visibility of BC on magnetic resonance imaging, making it possible to follow its fate in clinical situations and to define the target volume for stereotactic radiosurgery more precisely. Furthermore, BC membranes can be loaded with chemoattractants, which were released and attracted tumor cells in vitro. This is of particular interest for trapping GB cells infiltrating tissues within a few centimeters of the resection cavity. Our data suggest that BC membranes could be a scaffold of choice for implantation after surgical resection to trap residual GB cells. STATEMENT OF SIGNIFICANCE: Glioblastoma is a highly infiltrative tumor, recurring, in 90% of cases, within a few centimeters of the surgical resection cavity, even with adjuvant chemo/radiotherapy. Residual tumor cells left in the margins or infiltrating the brain parenchyma shelter behind the extremely fragile and sensitive brain tissue and contribute to the risk of recurrence. Finding tools to eliminate these cells without damaging the brain microenvironment is a real challenge. We propose a strategy involving the implantation, into the walls of the surgical resection cavity, of a scaffold to concentrate and trap the residual tumor cells, to facilitate their destruction by targeted therapies, such as stereotactic radiosurgery.