Pleomorphic xanthoastrocytoma: a brief review
Pleomorphic xanthoastrocytoma: a brief review
https://asa1cadmoremedia.blob.core.windows.net/asset-b82525b2-3d66-4001-8b7f-84690aec0b89/Dr Rimas Lukas V4.mp4
Segment:1 Pleomorphic xanthoastrocytoma: a brief review.
NARRATOR: In this publication perspective, Dr. Rimas Lukas of Northwestern University provides a summary of the paper Pleomorphic xanthcastrocytoma, a brief review, published recently in CNS Oncology. Pleomorphic xanthcastrocytoma, or PXA, is a rare primary CNS tumor. Recent advances in the molecular characterisation are helping to define subtypes of the tumor. The discovery of RAF mutations within a substantial percentage of PXA fosters a clearer understanding of the pathophysiology of these tumors, with clear prognostic and therapeutic implications.
NARRATOR: These findings are expected to provide insight into the spectrum of clinical behavior observed in PXA, ranging from cure with surgery to diffuse dissemination throughout the neuroaxis. Here, Dr. Lukas will discuss the clinical presentation, pathology, prognosis, and therapeutic management of PXA.
Segment:2 What is the clinical presentation of pleomorphic xanthoastrocytoma? .
DR. RIMAS LUKAS: On imaging studies, these tumors are typically robustly enhancing. There may be some heterogeneity within the pattern of enhancement, and cystic lesions can oftentimes be seen. Unlike the higher grade gliomas, these tumors are usually fairly well circumscribed. These tumors frequently present in the temporal lobe, so they can be anywhere within the neuroaxis. These lesions also have the potential for cerebral spinal fluid dissemination. While this is typically not an initial presentation, it's something that develops as disease progresses.
Segment:3 What is the pathology?.
DR. RIMAS LUKAS: With respect to the pathologic appearance, this was first described in 1973, and then the term pleomorphic xanthcastrocytoma was coined in 1979. It was in 1993 that it was incorporated the World Health Organization's CNS tumor classification system as a Grade 2 glial tumor.
DR. RIMAS LUKAS: With regards to the histology, these tumors are moderately cellular. There is variability within the tumor types that are seen. Some of them are spindle-shaped with elongated nuclei, and then there are others with large round cells that may have single, multiple, or multilobulated nuclei, sometimes described as bizarre multinucleated giant cells. On immunohistochemistry, they're positive for GFAP, as are other glial tumors.
DR. RIMAS LUKAS: A subset of these tumors have anaplasia, and are associated with a more aggressive natural history. What's exciting in the recent past is the demonstration of the presence of BRAF mutation within a large subset of these tumors. Out of all the glial tumors, these have the highest incidence of BRAF mutation, and we begin to now conceptualize them as BRAF wild type or BRAF mutated PXAs.
DR. RIMAS LUKAS:
Segment:4 What is the prognosis?.
DR. RIMAS LUKAS: Prognosis for these tumors is favorable overall, with some patients being cured of the disease with aggressive approaches. BRAF mutated tumors have a higher overall survival. Three year survival in the general population with PXAs is 80%, and five year survival is 75%. However, when the tumors are anaplastic histologically, this five year survival decreases to 57%.
Segment:5 What are the treatment options?.
DR. RIMAS LUKAS: With regards to therapeutic management, because these tumors are quite rare, there are no formal guidelines, nor are there any large scale trials that help guide the management. The initial approach involves surgical resection, ideally with a goal of gross total resection, which may at times be curative. In addition to that, radiation therapy is considered.
DR. RIMAS LUKAS: But again, because of the paucity of data, it's unclear whether this should be performed in the adjuvant setting or whether this should be remained in the setting of recurrent or progressive disease. Typically, doses up to 54 Gray are utilized in these tumors. Regarding systemic therapies, again, there is a paucity of data. A number of small, non-randomized studies have looked at a wide range of chemotherapeutic approaches, including temozolomide chemotherapy, which is used for glioblastoma and other high grade astrocytomas, and other older chemotherapeutic regimens.
DR. RIMAS LUKAS: Thus far, unfortunately, none of these have proven to be adequately successful. In the more recent past, the utilization of BRAF inhibition has shown value. The largest evaluation of this has been within the context of the VE-BASKET trial, which was recently published in The Journal of Clinical Oncology. In this study, a large number of patients with BRAF-mutated glial tumors were treated with a monotherapy of a BRAF inhibitor.
DR. RIMAS LUKAS: And this has shown that patients with PXA can have partial responses or stable disease. In clinical practice, this is oftentimes utilized either as a monotherapy or in conjunction with a MEK inhibitor. There are numerous case reports to help support this type of an approach.
Segment:6 What are your future perspectives?.
DR. RIMAS LUKAS: It is anticipated that the molecular neuropathology will play an increasingly important role in defined CNS tumors, including PXAs.
DR. RIMAS LUKAS: The presence of BRAF driver mutations in a subset of PXA may be a more unifying feature tying them both pathophysiologically, and in turn therapeutically, to other relatively low grade glial tumors. The value of these molecular features may supersede the identical histological features of BRAF mutated and BRAF wild type PXA, in the way clinicians and investigators conceptualize these tumors.
DR. RIMAS LUKAS: It is likely that while Level 1 evidence may be lacking, BRAF-pathway directed therapies will become standard treatments for BRAF-mutated PXA. The optimal future therapies for BRAF wild type PXA are less clear. While complete surgical resection and RT will continue to be the components of the standard of care for both PXA subtypes, novel therapeutics may be of interest for the less treatment-responsive BRAF wild type tumors.
DR. RIMAS LUKAS: [MUSIC PLAYING]