Sophie Taillibert

A retrospective case series of 103 consecutive patients with leptomeningeal metastasis and breast cancer

Approximately 2–5xa0% of patients with breast cancer (BC) develop leptomeningeal metastasis (LM). 103 consecutive patients with BC were diagnosed with LM and initially treated with intra-CSF liposomal cytarabine from 2007 to 2011 at a single institution. Correlations were determined with respect to patient characteristics and BC subtype with regard to overall survival (OS). At LM diagnosis, 61xa0% of patients had a 0–2 performance status (PS), the remaining 39xa0% were severely neurologically impaired. Regardless of PS, all patients received intra-cerebrospinal fluid (CSF) liposomal cytarabine as first-line treatment. Systemic treatment and radiotherapy were also given in 58 and 17xa0% of patients respectively as clinically appropriate. Second- (intra-CSF thiotepa) and third-line (intra-CSF methotrexate) treatment was administered in 24 and 6 patients respectively. Median OS was 3.8xa0months (range 1xa0day–2.8xa0years). In multivariate analysis, an initial combined treatment, a second-line treatment with intra-CSF thiotepa, an initial clinical response, and a non-‘ER/PR/HER2 negative’ BC were significantly associated with a better OS. Median OS in this heterogeneous retrospective case series was similar to that of previously observed BC patients treated with intra-CSF methotrexate suggesting intra-CSF liposomal cytarabine is a reasonable first choice therapy of BC-related LM.

The future of high-grade glioma: Where we are and where are we going.

High-grade glioma (HGG) are optimally treated with maximum safe surgery, followed by radiotherapy (RT) and/or systemic chemotherapy (CT). Recently, the treatment of newly diagnosed anaplastic glioma (AG) has changed, particularly in patients with 1p19q codeleted tumors. Results of trials currenlty ongoing are likely to determine the best standard of care for patients with noncodeleted AG tumors. Trials in AG illustrate the importance of molecular characterization, which are germane to both prognosis and treatment. In contrast, efforts to improve the current standard of care of newly diagnosed glioblastoma (GB) with, for example, the addition of bevacizumab (BEV), have been largely disappointing and furthermore molecular characterization has not changed therapy except in elderly patients. Novel approaches, such as vaccine-based immunotherapy, for newly diagnosed GB are currently being pursued in multiple clinical trials. Recurrent disease, an event inevitable in nearly all patients with HGG, continues to be a challenge. Both recurrent GB and AG are managed in similar manner and when feasible re-resection is often suggested notwithstanding limited data to suggest benefit from repeat surgery. Occassional patients may be candidates for re-irradiation but again there is a paucity of data to commend this therapy and only a minority of selected patients are eligible for this approach. Consequently systemic therapy continues to be the most often utilized treatment in recurrent HGG. Choice of therapy, however, varies and revolves around re-challenge with temozolomide (TMZ), use of a nitrosourea (most often lomustine; CCNU) or BEV, the most frequently used angiogenic inhibitor. Nevertheless, no clear standard recommendation regarding the prefered agent or combination of agents is avaliable. Prognosis after progression of a HGG remains poor, with an unmet need to improve therapy.

Prolonged Response and Restoration of Functional Independence with Bevacizumab plus Vinorelbine as Third-Line Treatment for Breast Cancer-Related Leptomeningeal Metastases

Background: Survival of patients with leptomeningeal metastases (LM) and impaired functional status is limited to several months, and rarely does neurological function improve with treatment. Case Report: A 34-year-old female with hormone-negative and HER2-positive metastatic breast cancer was diagnosed with bulky radiographic LM 45 months after initial diagnosis. She was treated with intra-CSF trastuzumab followed by intra-CSF liposomal cytarabine; however, the cancer progressed 8 months after the diagnosis of LM. At the time of the third LM progression, the patient presented with a cauda equina syndrome and cerebellar impairment resulting in an inability to walk. She was treated with CNS-directed radiotherapy (lumbosacral and cerebellar) and bevacizumab plus vinorelbine. Rapid functional improvement occurred, and the patient regained the ability to walk and independently manage her daily activities. Twelve months later, she presented with rapid progression of the LM resulting in death within several weeks. Conclusion: In radiographically defined bulky LM, the combination of systemic therapy and CNS-directed radiotherapy likely is more active than intra-CSF therapy only. In lieu of the rapid and significant improvement in neurological function combined with the prolonged response, bevacizumab alone or in combination with chemotherapy and CNS-directed radiotherapy may be considered in select patients with radiographically bulky breast cancer-related LM.

Oxaliplatin plus irinotecan and FU-FOL combination and pharmacokinetic analysis in advanced colorectal cancer patients

This phase I-II trial was designed to assess the effect of irinotecan on oxaliplatin pharmacokinetics and to determine the MDT of both drugs when administered in combination. Treatment was repeated every 2 weeks. Pharmacokinetic studies were performed on cycle 1 and 2 to assess the best sequence and detect any interaction between the two drugs. Thirty-four patients with advanced colorectal cancer were enrolled; 28 of them (82%) had liver involvement. The main toxicities were neutropenia and delayed diarrhea; 5 patients (14%) experienced febrile neutropenia. Dose-limiting toxicity was experienced at levels 1/2/3/4/5 by 4/10, 1/6, 3/6, 3/8, and 3/4 patients, respectively. Fifteen patients responded (2 CR; 13 PR) for an ORR of 44%. No pharmacokinetic interactions between irinotecan and oxaliplatin were detected. The recommended dose for future phase II trials is oxaliplatin 85 mg/m2 and irinotecan 180 mg/m2 on day 1 combined with 5FU/leucovorin according to the de Gramont regimen at days 2 and 3. Twenty-nine percent of patients underwent secondary hepatectomy with curative intent, and two of them are long-term disease-free survivors. It would appear that the dose and schedule defined by this trial could be proposed as front-line therapy for advanced colorectal carcinoma to establish rapid disease control and to permit patients to proceed to surgery.

Systemic therapy for recurrent meningioma

ABSTRACT Introduction: Meningioma comprise 20-30% of all primary brain tumors. Notwithstanding surgery and radiotherapy, a subset of patients will manifest recurrent meningioma. Systemic therapy is recommended only when further surgery and radiotherapy are not possible. No prospective study with a high level of evidence is available to inform as to recommendations regarding systemic therapy. Areas covered: We aim to summarize systemic therapies for recurrent meningioma. Expert commentary: Hydroxurea, temozolomide, irinotecan, the combination of cyclophosphamide/adriamycine/vincristine, interferon-alpha, somatostatin analogs, mifepristone, megestrol acetate, imatinib, erlotinib and gefitinib are considered as having limited efficacy. Potential activity of VEGF (vascular endothelial growth factor) inhibitors such as sunitinib, valatinib, and bevacizumab is suggested in small non-controlled studies and requires validation in randomized trials. The identification of new prognostic markers such as TERT promoter mutations and potential new therapeutic targets, such as KLF4, AKT1, TRAF7, and SMO mutations hopefully facilitate this endeavor.

Salvage intracerebrospinal fluid thiotepa in breast cancer-related leptomeningeal metastases: a retrospective case series.

There is currently a paucity of data on salvage intracerebrospinal fluid (intra-CSF) chemotherapy in leptomeningeal metastases (LM). This report is a single-institution experience with salvage treatment in patients with breast cancer (BC) and LM. This retrospective cohort describes 24 consecutive patients with BC selected for a second-line of treatment for LM. The first line of LM treatment consisted of intra-CSF liposomal cytarabine in all patients combined with systemic therapy in 18 cases and radiotherapy in four cases. Second-line (salvage) treatment utilized intra-CSF thiotepa in all and systemic chemotherapy in nine patients. No patient received CNS-directed radiotherapy. The median Eastern Cooperative Oncology Group performance status at initiation of intra-CSF thiotepa treatment was 3 (range 1–4). The median progression-free survival and median survival following intra-CSF thiotepa was 3.1 months (range 3 days–2 years) and 4.0 months (range 6 days–2.5 years), respectively. The median overall survival from LM diagnosis was 9.5 months (range 1.3 months–2.7 years). No grade 3 or higher toxicity was observed. Recognizing the limits of a retrospective study, intra-CSF thiotepa has an acceptable toxicity profile and appears to be a reasonable option for selected BC patients.

Soins de support, cognition, qualité de vie et métastases cérébrales

Brain metastases impact on the survival of the patients, but on their quality of life as well. The objective of the management of these patients is then double. Currently, due to medical advances, survivals tend to improve, especially for some tumor subtypes. During the course of the disease, different neurological signs and symptoms can be observed according to the location, the number and the volume of the metastase(s). Patients and caregivers are especially worried about the loss of autonomy and cognitive impairments. A permanent dialogue, during the course of the disease, is mandatory, in order to adapt the management to the objectives determined by the patients and the medical team. These objectives may vary according to the objective response rates of the disease to anticancer therapies, according to the impact of the disease and its management in daily living. Anticancer therapies and supportive care must be appreciated according to their impact on the survival, on the preservation of the functional independence and the quality of life of the patient, on their abilities to preserve the neurological status and delay the apparition of new neurological signs and symptoms, and their adverse events. Supportive care, cognition and quality of life should be regularly evaluated and adapted according to the objectives of the management of brain metastases patients. Different approaches are described in this paper.