A multidisciplinary team approach to skull base chordomas.
ABSTRACT A multidisciplinary team devised a protocol for long-term care of patients with skull base chordomas. In this study they describe their approach.
Forty-two patients presented between 1986 and 1998 and were treated by maximum surgical cytoreduction and photon radiation therapy. Tumor volume-doubling time determined on the basis of magnetic resonance imaging, immunostaining, and cell proliferation (Ki67 labeling index [LI]) studies indicated growth rates of individual chordomas. The best outlook was associated with the greatest extent of tumor removal achieved during the first operation. There were no deaths associated with patients who underwent first-time surgery, but there was a 7.1% mortality rate associated with those who underwent subsequent operations. Cerebrospinal fluid leaks, additional cranial nerve palsies, and pharyngeal wound problems were the most difficult management problems encountered after second and subsequent surgeries. The time interval between operations was usually between 2 years and 3 years after the first surgery; very few patients required a second surgery, with a quiescent period in excess of 5 years. Life-table 5- and 10-year survival rates were 77% and 69%, respectively.
The authors believe that this series of skull base chordomas provides new insights into the management of these lesions, particularly with regard to techniques that increase survival times and studies that aid in formulating prognoses.
[show abstract] [hide abstract]
ABSTRACT: Clival chordomas have traditionally been removed using a variety of anterior and lateral skull base approaches. Herein, we evaluate the outcomes of patients who underwent an extended endonasal transsphenoidal removal of a clival chordoma. All consecutive patients with a clival chordoma treated using an endonasal microscope approach were identified. In 8 cases, frameless surgical navigation was used, and in 4 cases, endoscopic assistance was used. Patients treated with prior radiotherapy were excluded. Over 5 years, 18 procedures were performed on 14 patients (7 females; mean age, 47 years). Patients were followed from 3 to 58 months (median, 20 months). Mean tumor diameter was 32 +/- 17 mm; 7 (50%) patients had intradural extension. Postoperative MRIs after the initial operation showed gross total, near-total (>90%), and subtotal resection in 43%, 43%, and 14% of patients, respectively. Use of the endoscope was associated with gross total or near-total tumor removal in 4 of 4 cases. Tumor regrowth occurred in 2 (14%) cases 10 and 12 months after the initial surgery and before radiotherapy. Two patients had multiple operations, in one as a planned staged operation, and in the other, 3 additional debulkings were performed despite an initial gross total removal. Nine patients, all with CS invasion, had subsequent stereotactic radiation. Of 10 patients with cranial neuropathy, 80% improved or resolved including 75% and 67% of sixth and fifth CN palsies, respectively. Complications included one each of adrenal insufficiency and chemical meningitis. There were no CSF leaks or new neurological deficits. In this small series with relatively short follow-up, endonasal microscopic removal of clival chordomas proved safe and elfective with gross total or near-total removal in 86% of patients and improvement of cranial neuropathy in 80% of patients. Endoscopy for aiding tumor removal and assessing completeness of resection, as well as surgical navigation, are recommended for all cases.Surgical Neurology 05/2008; 69(4):331-8. · 1.67 Impact Factor
[show abstract] [hide abstract]
ABSTRACT: Chordoma is a rare mesenchymal tumour of complex biology for which only histologic and immunohistochemical criteria have been defined, but no biomarkers predicting the clinical outcome and response to treatment have yet been recognised. We herein review the interdisciplinary information achieved by epidemiologists, neurosurgeons and basic scientists on chordoma, usually a sporadic tumour, which also includes a small fraction of familial cases. Main focus is on the current knowledge of the genetic alterations which might pinpoint candidate genes and molecular mechanisms shared by sporadic and familiar chordomas. Due to the scarcity of the investigated tumour specimens and the multiple chromosome abnormalities found in tumours with aberrant karyotypes, conventional cytogenetics and Fluorescence In Situ Hybridization failed to detect recurrent chordoma-specific chromosomal rearrangements. Genome-wide approaches such as Comparative Genomic Hybridization (CGH) are yet at an initial stage of application and should be implemented using BAC arrays either genome-wide or targeting selected genomic regions, disclosed by Loss of Heterozygosity (LOH) studies. An LOH region was shown by a systematic study on a consistent number of chordomas to encompass 1p36, a genomic interval where a candidate gene was suggested to reside. Despite the rarity of multiplex families with chordoma impaired linkage studies, a chordoma locus could be mapped to chromosome 7q33 by positive lod score in three independent families. The role in chordomagenesis of the Tuberous Sclerosis Complex (TSC) genes has been proved, but the extent of involvement of TSC1 and TSC2 oncosuppressors in chordoma remains to be assessed. In spite of the scarce knowledge on the genetics and molecular biology of chordoma, recent initiation of clinical trials using molecular-targeted therapy, should validate new molecular targets and predict the efficacy of a given therapy. Comparative genetic and biomolecular studies should enhance the molecular taxonomy of chordoma which might have a prognostic significance and better orient the therapeutic options.Hereditary Cancer in Clinical Practice 01/2005; 3(1):29-41. · 1.68 Impact Factor
Article: Brachyury, a crucial regulator of notochordal development, is a novel biomarker for chordomas.[show abstract] [hide abstract]
ABSTRACT: Chordomas are malignant tumours that occur along the spine and are thought to derive from notochordal remnants. There is significant morphological variability between and within chordomas, with some showing prominent areas of chondroid differentiation. Our microarray data from a broad range of connective tissue neoplasms indicate that, at the transcriptional level, chordomas resemble cartilaginous neoplasms. Here we show that chordomas express many genes known to be involved in cartilage development, but they also uniquely express genes distinguishing them from chondroid neoplasms. The brachyury transcription factor, known to be involved in notochordal development, is only expressed by chordomas. Using a polyclonal antibody, we show that brachyury is expressed in the embryonic notochord and in all 53 chordomas analysed, labelling both chondroid and chordoid areas of these tumours. In contrast, the protein was not detected in over 300 neoplasms, including 163 chondroid tumours. Brachyury was not detected in the nucleus pulposus, arguing against the hypothesis that this tissue derives directly from the notochord. These data provide compelling evidence that chordomas derive from notochord and demonstrate that brachyury is a specific marker for the notochord and notochord-derived tumours.The Journal of Pathology 07/2006; 209(2):157-65. · 6.32 Impact Factor