Clival chordomas: A pathological, surgical, and radiotherapeutic review

Fernández-Miranda, Juan C.; Gardner, Paul A.; Snyderman, Carl H.; Devaney, Kenneth O.; Mendenhall, William M.; Suárez, Carlos; Rinaldo, Alessandra; Ferlito, Alfio

doi:10.1002/hed.23415

Cited by 122 publications

(100 citation statements)

References 80 publications

(87 reference statements)

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“…In view of the benefit of minimally invasive surgery to the quality of life of patients with skull base tumors, we believe that endoscopic techniques should be considered appropriate for patients with clival chordoma. 4,30…”

Section: Discussionmentioning

confidence: 99%

Treatment and Outcome of Patients with Skull Base Chordoma: A Meta-analysis

et al. 2014

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Objective Chordoma is a locally aggressive tumor. The aim of this study was to assess the efficacy of different surgical approaches and adjuvant radiation modalities used to treat these patients. Design Meta-analysis. Main Outcome Measures Overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS). Results The 5-year OS and PFS rates of the whole cohort (n = 467) were 86% and 65.7%, respectively. The 5-year DSS for patients who underwent open surgery and endoscopic surgery was 45% and 49%, respectively (p = 0.8); PFS was 94% and 79%, respectively (p = 0.11). The 5-year OS of patients treated with surgery followed by adjuvant radiotherapy was 90% compared with 70% of those treated by surgery alone (p = 0.24). Patients undergoing partial resection without adjuvant radiotherapy had a 5-year OS of 41% and a DSS of 45%, significantly lower than in the total-resection group (p = 0.0002 and p = 0.01, respectively). The complication rates were similar in the open and endoscopic groups. Conclusions Patients undergoing total resection have the best outcome; adjuvant radiation therapy improves the survival of patients undergoing partial resection. In view of the advantages of minimally invasive techniques, endoscopic surgery appears an appropriate surgical approach for this disease.

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Section: Discussionmentioning

confidence: 99%

Treatment and Outcome of Patients with Skull Base Chordoma: A Meta-analysis

et al. 2014

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“…The majority of these tumors occur in either the base of the skull (35%) or in the sacrum (50%), and these are typically managed with surgery and/or radiation[2]–[10]. Their clinical behavior is marked by slow growth and a predilection to recur despite surgical resection.…”

Section: Introductionmentioning

confidence: 99%

Genotyping Cancer-Associated Genes in Chordoma Identifies Mutations in Oncogenes and Areas of Chromosomal Loss Involving CDKN2A, PTEN, and SMARCB1

et al. 2014

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The molecular mechanisms underlying chordoma pathogenesis are unknown. We therefore sought to identify novel mutations to better understand chordoma biology and to potentially identify therapeutic targets. Given the relatively high costs of whole genome sequencing, we performed a focused genetic analysis using matrix-assisted laser desorption/ionization-time of flight mass spectrometer (Sequenom iPLEX genotyping). We tested 865 hotspot mutations in 111 oncogenes and selected tumor suppressor genes (OncoMap v. 3.0) of 45 human chordoma tumor samples. Of the analyzed samples, seven were identified with at least one mutation. Six of these were from fresh frozen samples, and one was from a paraffin embedded sample. These observations were validated using an independent platform using homogeneous mass extend MALDI-TOF (Sequenom hME Genotyping). These genetic alterations include: ALK (A877S), CTNNB1 (T41A), NRAS (Q61R), PIK3CA (E545K), PTEN (R130), CDKN2A (R58*), and SMARCB1 (R40*). This study reports on the largest comprehensive mutational analysis of chordomas performed to date. To focus on mutations that have the greatest chance of clinical relevance, we tested only oncogenes and tumor suppressor genes that have been previously implicated in the tumorigenesis of more common malignancies. We identified rare genetic changes that may have functional significance to the underlying biology and potential therapeutics for chordomas. Mutations in CDKN2A and PTEN occurred in areas of chromosomal copy loss. When this data is paired with the studies showing 18 of 21 chordoma samples displaying copy loss at the locus for CDKN2A, 17 of 21 chordoma samples displaying copy loss at PTEN, and 3 of 4 chordoma samples displaying deletion at the SMARCB1 locus, we can infer that a loss of heterozygosity at these three loci may play a significant role in chordoma pathogenesis.

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“…The inherent proximity of neurovascular structures such as the spinal cord make disease-free resection margins difficult to achieve; recurrence is 100% within 2 years with either inadequate margins or subtotal resection, or radiation therapy alone 4 10. Presurgical radiotherapy may be used to de-bulk disease 11 12. PBT often has a larger role in clival disease control, as high-dose radiation can be delivered precisely to the target area—with reduced damage to surrounding neurovascular tissue—compared to traditional photon radiation 7 9.…”

Section: Discussionmentioning

confidence: 99%

Fifty-four-month survival in a 3-year-old child presenting with an aggressive metastatic dedifferentiated clival chordoma

Kearns¹,

Kearns

2016

BMJ Case Reports

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Dedifferentiated chordoma is a rare, aggressive, chemoresistant and radioresistant malignancy arising from notochord remnants that can occur anywhere along the spine. Incidence in patients under 20 years of age is 1 per 250 million. We report a case of dedifferentiated clival chordoma presenting in a 3-year-old boy with pulmonary metastasis, which responded unusually well to chemotherapy, achieving complete metastatic clearance and debulking of the primary tumour. Proton beam therapy achieved further tumour control, with excellent quality of life for multiple years. On disease relapse, an atypical lateral transcondylar surgical approach achieved complete macroscopic clearance but there was cutaneous seeding. This, and continued primary site activity, failed to be controlled with targeted therapy, traditional chemotherapy and photon radiation, resulting in gradual neurological decline and death. Intensive management resulted in above-average survival despite diagnosis late in the disease course, which may be of value directing investigation into optimal management.

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Clival chordomas: A pathological, surgical, and radiotherapeutic review

Cited by 122 publications

References 80 publications

Treatment and Outcome of Patients with Skull Base Chordoma: A Meta-analysis

Treatment and Outcome of Patients with Skull Base Chordoma: A Meta-analysis

Genotyping Cancer-Associated Genes in Chordoma Identifies Mutations in Oncogenes and Areas of Chromosomal Loss Involving CDKN2A, PTEN, and SMARCB1

Fifty-four-month survival in a 3-year-old child presenting with an aggressive metastatic dedifferentiated clival chordoma

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