Response Assessment of NovoTTF-100A Versus Best Physician\u27s Choice Chemotherapy in Recurrent Glioblastoma

The NovoTTF-100A device emits frequency-tuned alternating electric fields that interfere with tumor cell mitosis. In phase III trial for recurrent glioblastomas, NovoTTF-100A was shown to have equivalent efficacy and less toxicity when compared to Best Physician\u27s Choice (BPC) chemotherapy. We analyzed the characteristics of responders and nonresponders in both cohorts to determine the characteristics of response and potential predictive factors. Tumor response and progression were determined by Macdonald criteria. Time to response, response duration, progression-free survival (PFS) ± Simon-Makuch correction, overall survival (OS), prognostic factors, and relative hazard rates were compared between responders and nonresponders. Median response duration was 7.3 versus 5.6 months for NovoTTF-100A and BPC chemotherapy, respectively (P = 0.0009). Five of 14 NovoTTF-100A responders but none of seven BPC responders had prior low-grade histology. Mean cumulative dexamethasone dose was 35.9 mg for responders versus 485.6 mg for nonresponders in the NovoTTF-100A cohort (P \u3c 0.0001). Hazard analysis showed delayed tumor progression in responders compared to nonresponders. Simon-Makuch-adjusted PFS was longer in responders than in nonresponders treated with NovoTTF-100A (P = 0.0007) or BPC chemotherapy (P = 0.0222). Median OS was longer for responders than nonresponders treated with NovoTTF-100A (P \u3c 0.0001) and BPC chemotherapy (P = 0.0235). Pearson analysis showed strong correlation between response and OS in NovoTTF-100A (P = 0.0002) but not in BPC cohort (P = 0.2900). Our results indicate that the response characteristics favor NovoTTF-100A and data on prior low-grade histology and dexamethasone suggest potential genetic and epigenetic determinants of NovoTTF-100A response

Treatment of central nervous system metastases: Parenchymal, epidural, and leptomeningeal

PURPOSE OF REVIEW: With prolonged survival from systemic therapies in the adjuvant and salvage setting, and because these agents cannot cross the intact blood-brain barrier, central nervous system metastases are becoming a therapeutic challenge in oncology. RECENT FINDINGS: Recent therapeutic achievements include an extended use of surgery and radiosurgery. Although each of these treatment modalities has its own indications, in patients eligible for both treatments the upfront comparison of these two techniques has not been performed yet. Systemic chemotherapies and biotherapies may be effective in the management of central nervous system metastases as they may act on both neurologic and extra-central nervous system lesions. In the treatment of epidural metastases, a surgical procedure providing immediate direct circumferential decompression of the spinal cord followed by local irradiation has been demonstrated in a prospective randomized trial. The management of leptomeningeal metastases remains controversial and of limited efficacy especially in chemoresistant tumours and still relies on the combination of chemotherapy (intrathecal and intravenous) and focal radiotherapy. SUMMARY: Aggressive treatments in patients with early diagnosis and in whom central nervous system metastases are the life-threatening location may provide a substantial increase in survival and favourably affect quality of life. © 2006 Lippincott Williams & Wilkins.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Chemobrain: is systemic chemotherapy neurotoxic?

The existence of chemobrain has become almost universally accepted, although many details of the concept are controversial. Data about the different types of cognitive impairment and their duration are not always consistent in the literature. We still do not know which cytotoxic agents are responsible, which characteristics make patients vulnerable, and which biologic mechanisms are involved.Journal ArticleReviewSCOPUS: re.jinfo:eu-repo/semantics/publishe

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

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Tumor treating fields

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Anaplastic glioma: current treatment and management

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Chemotherapy-Related Neurotoxicity

International audienceChemotherapy may have detrimental effects on either the central or peripheral nervous system. Central nervous system neurotoxicity resulting from chemotherapy manifests as a wide range of clinical syndromes including acute, subacute, and chronic encephalopathies, posterior reversible encephalopathy, acute cerebellar dysfunction, chronic cognitive impairment, myelopathy, meningitis, and neurovascular syndromes. These clinical entities vary by causative agent, degree of severity, evolution, and timing of occurrence. In the peripheral nervous system, chemotherapy-induced peripheral neuropathy (CIPN) and myopathy are the two main complications of chemotherapy. CIPN is the most common complication, and the majority manifest as a dose-dependent length-dependent sensory axonopathy. In severe cases of CIPN, the dose of chemotherapy is reduced, the administration delayed, or the treatment discontinued. Few treatments are available for CIPN and based on meta-analysis, duloxetine is the preferred symptomatic treatment. Myopathy due to corticosteroid use is the most frequent cause of muscle disorders in patients with cancer

Current Management of Adult Diffuse Infiltrative Low Grade Gliomas

International audienceDiffuse infiltrative low grade gliomas (LGG) account for approximately 15 % of all gliomas. The prognosis of LGG differs between high-risk and low-risk patients notwithstanding varying definitions of what constitutes a high-risk patient. Maximal safe resection optimally is the initial treatment. Surgery that achieves a large volume resection improves both progression-free and overall survival. Based on results of three randomized clinical trials (RCT), radiotherapy (RT) may be deferred in patients with low-risk LGG (defined as age 40 years or incomplete resection) by demonstrating a nearly twofold improvement in overall survival with the addition of PCV (procarbazine, CCNU, vincristine) chemotherapy following RT as compared to RT alone. Chemotherapy alone as a treatment of LGG may result in less toxicity than RT; however, this has only been prospectively studied once (EORTC 22033) in high-risk patients. A challenge remains to define when an aggressive treatment improves survival without impacting quality of life (QoL) or neurocognitive function and when an effective treatment can be delayed in order to preserve QoL without impacting survival. Current WHO histopathological classification is poorly predictive of outcome in patients with LGG. The integration of molecular biomarkers with histology will lead to an improved classification that more accurately reflects underlying tumor biology, prognosis, and hopefully best 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

Complications related to the use of an intraventricular access device for the treatment of leptomeningeal metastases from solid tumor: a single centre experience in 112 patients

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