Management Of Chordomas Research Articles

The biological basis for modern treatment of chordoma

Chordomas are rare malignant tumors arising in bone of the spheno-occiput, sacrum, and vertebral column which can cause neurological deficit. Current management of chordoma involves safe resection followed by radiation therapy. However, surgical resection is often subtotal and chordoma often recurs despite optimal therapy. Despite years of effort, effective adjuvant therapy for denovo, recurrent and metastatic chordoma are absent and 5-year survival is at best 65%. While no chemotherapeutic agent has been demonstrated to be effective against chordoma in vivo, a greater understanding of the genetics and molecular biology of chordoma is opening up avenues of investigation towards the rational development of targeted therapies. Although enthusiasm for the use of already established or new investigational agents will increase with greater understanding of chordoma biology, laboratory studies of these agents are important prior to incorporation into clinical human trials. The authors review the current state of knowledge regarding chordoma and offer insight into potential new therapies for this rare and challenging tumor.

Current Management of Chordoma

Chordomas are relatively rare, slowly growing primary tumors of bone that arise from embryonic remnants of the notochord. These neoplasms typically occur in the axial skeleton mainly in the skull base (about 35%) and sacral region (about 50%) and have an overall peak distribution in patients aged 55-65 years. Chordomas are divided into conventional (the most common type), chondroid, and dedifferentiated types. Aggressive initial therapy, based on radical-maximal surgery followed by post-operative irradiation, improves overall outcome. Patients who relapse locally have a poor prognosis but both radiation and surgery can be used as salvage therapy. Radiation therapy alone may also be used in order to treat some patients with advanced, inoperable lesions or local recurrence. Proton beam irradiation has been reported as a very active form of irradiation for its peculiar physical properties. Chordomas are reported as tumors non sensitive to chemotherapy, even though anecdotal reports have been shown some sensitivity to molecularly targeted therapies.

Challenges of Local Recurrence and Cure in Low Grade Malignant Tumors of the Spine

Systematic review and ambispective multicenter cohort study. 1. To compare the effects of wide/marginal (en bloc) resection with intralesional resection on local recurrence and survival for chordomas and chondrosarcomas of the spine. 2. To determine the influence of radiation therapy in the management of chordomas and chondrosarcomas. Chordomas and chondrosarcomas of the spine are prone to local recurrence and death despite being low-grade malignant tumors. No study to date has enough numbers or adequate scientific rigor to determine the influence of resection or radiation therapy on outcome. A systematic review was performed to evaluate the 2 objectives. In addition an ambispective multicenter cohort analysis of chordomas and chondrosarcomas was performed. The GRADE system of analysis integrating the results of the systematic review, the multicenter cohort study and the expert opinion of the Spine Oncology Study Group (SOSG) was used to arrive at treatment recommendations. A total of 63 articles were included in the systematic reviews. Evidence was low quality. En bloc resection appeared to improve both local recurrence and disease free survival in Chordoma and Chondrosarcoma. Radiation therapy had a positive impact on the management of Chordoma and Chondrosarcoma with predictably low side effects. The cohort analysis showed significantly decreased local recurrence for Chordoma (P < 0.0001) and Chondrosarcoma (P < 0.0001) with en bloc resection, and significantly decreased death for both Chordoma (P = 0.0001) and Chondrosarcoma (P = 0.0015) with en bloc resection. When wide or marginal margins (en bloc) are achieved in surgical resection of chordomas and chondrosarcomas of the spine there is a decrease in local recurrence and mortality. Therefore, en bloc resection should be undertaken for the treatment of chordomas and chondrosarcomas of the spine. Strong Recommendation, Moderate Quality Evidence.Radiation therapy of at least 60 to 65 Gy equivalents is indicated as an adjuvant treatment for chordoma and chondrosarcoma of the spine when there has been incomplete resection or an intralesional margin. Weak Recommendation, Low Quality Evidence.

High-dose Radiotherapy in the Management of Chordoma and Chondrosarcoma of the Skull Base and Cervical Spine: Part 1 — Clinical Outcomes

Aims Patients with chordoma and chondrosarcoma in the skull base present a complex multidisciplinary problem. These tumours are rare and occur in difficult anatomical regions. We reviewed the local control and survival of patients treated in our centre. Materials and methods Between 1996 and 2005, 12 adult cases of chordoma (nine) and chondrosarcoma (three) in the skull base or cervical spine were treated in our centre. The median follow-up is currently 38 months. One patient was treated with palliative intent. In 10 cases the prescription dose was 65 Gy in 39 fractions. The target volumes were measured, and the target maximum and minimum doses and the equivalent uniform dose (EUD) for the phase I plans were recorded. Results Local control was achieved in 11 of 12 cases. One chordoma patient failed locally, and one other died of metastatic disease despite local control. The 3- and 5-year cause-specific survival for the series was 88 and 75%, respectively. The mean phase I planning target volume (PTV) was 120.4 cm 3. The median minimum dose in the phase I PTV was 81.0%. The median EUD (expressed as a percentage of the prescribed dose) for the phase I PTV, calculated using a value for the exponent a of −15, was 98.3%. The phase I EUD was below 80% in two of the 12 cases. Conclusions Our results confirm a need for aggressive local surgery and high-dose radiotherapy, and endorse multidisciplinary working. Although charged particle therapy is accepted as providing optimal treatment plans, in eight of our patients travel abroad would not have been feasible. This series provides encouraging results for carefully planned photon conformal radiotherapy, carried out in close collaboration with a specialist surgical team.

Surgical management of chordomas of the cervical spine

Chordomas of the cervical spine are rare tumors. Although en bloc resection has proven to be the ideal procedure in other areas, there is controversy regarding this approach in the cervical spine. The goal in this study was to determine whether piecemeal tumor resection was efficient in the management of chordomas that arise in this location. The authors retrospectively reviewed all 74 cases of chordoma treated by their group. Seven patients with isolated cervical chordomas who were treated between October 1992 and January 2006 were identified. There were four male and three female patients, whose ages ranged from 6 to 61 years (mean 34.4 years). Follow-up duration ranged from 7 to 169 months (median 23 months). All cases were managed using a retrocarotid approach with mobilization of the vertebral artery. When the tumor could not be completely resected via the initial anterior approach, a subsequent posterior resection was performed. Tumor resection was intralesional in all cases, and gross-total tumor resection was achieved in six cases. One patient required a second resection 4 months later. In all cases, a posterior stabilization procedure was performed. Five patients underwent anterior fusion (three with fibular allograft and two with iliac crest), whereas two underwent occipitocervical fusion. In two patients with dedifferentiated chordoma metastasis developed, and one of them died 7 months later. The other patient with metastasis died suddenly at home 26 months postsurgery, presumably from aspiration. At the time of this submission, there were no signs of recurrence in five patients. The authors believe that, in most cases, en bloc resection of cervical chordoma is not feasible. This is due to the tendency of chordomas to involve multiple compartments at the time of diagnosis. In the authors' experience, intralesional radical resection remains an effective surgical approach to this disease entity.

The Role of Radiosurgery and Stereotaxis in the Management of Chordoma and Chondrosarcoma of the Cranial Base

Summary: Fourteen patients (8 women, 6 men) with chordoma and 2 patients (men) with chondrosarcoma were treated in our department in the Hospital Na Homolce during last 10 years. In one patient chordoma was diagnosed by stereotactic biopsy; 13 patients with chordoma underwent gamma knife radiosurgery; 1 case was treated with fractionated radiosurgery. Ten patients underwent partial resection before the stereotactic radiosurgery; 2 patients were reoperated. Because of his hydrocephalus, 1 patient underwent a ventriculoperitoneal shunt. The minimal dose to the margin was 12 to 27.5 Gy, with a median of 20 Gy. We have evaluated the effect of radiosurgical treatment with a follow-up median of 45 months (5 to 94 mos) in 11 surviving patients with chordoma. Three patients with follow-up less than 1 year are still in stable clinical condition; in 2 patients the imaging control in an interval 1 to 3 years after the radiosurgery showed that their tumor was stationary without a growing progression; and in 4 patients the tumor volume decreased to 38% on average in an interval 36 to 83 months after the radiosurgery. In 2 patients it was necessary to supplement the gamma knife radiosurgery by additional treatment. Despite reirradiation of his newly developed tumor, in 1 patient we have detected continuing growth progression 58 months from the first radiation; in the other patient we had detected a recurrence of her tumor 11 months after radiosurgery, which was successfully resolved by an open operation. In the group of patients that underwent radiosurgery for their chordoma, 2 patients died, the first without a connection to her irradiated tumor. The other patient died 94 months after the first radiosurgery with continuing growth progression of her tumor despite reirradiation of a newly growing tumor and repeated operations. In both patients with chondrosarcoma the stereotactic radiosurgery followed the stereotactic biopsy. In the first patient we detected continuing growth progression of his tumor 21 months after radiosurgery (marginal dose, 15 Gy); in the second patient, after the staged radiosurgery (marginal dose, 12 and 16 Gy) the tumor remains stationary without a growing progression even 85 months after the first radiosurgery.

Surgical Management of Chordomas and Chondrosarcomas

Surgical Management of Chordomas and Chondrosarcomas

High Dose Photon Radiotherapy in the Management of Chordoma and Chondrosarcoma of the Skull Base and Cervical Spine

Introduction: Patients with chordoma and chrondrosarcoma in the skull base present a complex multidisciplinary problem. These tumours are rare, occur in difficult anatomical regions and have a reputation for being relatively resistant to radiotherapy.

The Role of Radiosurgery and Stereotaxis in the Management of Chordoma and Chondrosarcoma of the Cranial Base

The Role of Radiosurgery and Stereotaxis in the Management of Chordoma and Chondrosarcoma of the Cranial Base

Surgical Management of Chordomas and Chondrosarcomas

Surgical Management of Chordomas and Chondrosarcomas

En bloc marginal excision of a multilevel cervical chordoma

The purpose of this case report is to demonstrate that an en bloc resection with negative surgical margins can be successfully achieved in a case of a seemingly unresectable C-2 chordoma if appropriate preoperative staging and planning are performed. The management of chordomas is controversial and challenging because of their location and often large size at presentation. Because chordomas are malignant and will aggressively recur locally if intralesional resection is conducted, wide or true en bloc resection is generally recommended. The literature indicates, however, that surgeons are reluctant to perform wide or even marginal resections because of the lesion's complex surrounding anatomy and the risk of significant neurological compromise when a tumor abuts the dura mater or neural tissues. In this report the authors outline the successful en bloc resection of a large C1-3 chordoma and discuss the importance of preoperative staging and planning.

Commentary

The authors present eight patients who underwent surgical treatment for petroclival region chordomas. Their approach to these complex patients incorporates many aspects critical to the treatment of chordomas: maximal surgical resection, use of a variety of skull base approaches tailored to the location of tumor, extensive resection of bone surrounding the soft tissue tumor component, and adjunctive radiation therapy. The authors used stereotactic radiosurgery (SRS) to treat residual and recurrent tumors. We prefer the use of proton beam therapy, which has the longest treatment record and highest success rate associated with the treatment of chordomas. SRS is more readily accessible than proton beam therapy, which would make treatment with this modality advantageous. However, a large series of patients treated with SRS would be required to ascertain the role of this modality in the management of chordomas.

Clival Chordomas: Management and Follow-Up Results in a Series of 29 Consecutive Patients

Introduction: The management of chordomas involving the cranial base remains controversial. Because of their critical location, invasive nature, and aggressive recurrence, clival chordomas are challenging tumors to treat. Both radical surgical removal and high-dose radiation therapy, particularly proton beam therapy, reportedly are effective in tumor control and improve survival rates.

Surgical approaches and strategies for skull base chordomas

The management of chordomas involving the skull base continues to present a number of treatment-related problems. Recently, both radical resection and charged-particle irradiation or stereotactic radiosurgery have reportedly been found effective for tumor control and for promoting a better quality of life in patients. In this article the authors analyzed the outcomes in 17 patients with skull base chordomas who were surgically treated at Kobe University Hospital between 1972 and 2000. Preoperative radiological examinations included magnetic resonance imaging, computerized tomography, angiography, and balloon occlusion test of the internal carotid artery. Among the various surgical approaches used to remove the tumor were the frontoorbitozygomatic, transmaxillary, transcondylar, transsphenoidal, and the transbasal. Total removal was achieved in two (12%), near-total removal in three (18%), subtotal removal in nine (52%), and partial removal in three patients (18%). Since 1990, chordomas have been radically resected via various skull base approaches; the combined total or near-total removal rate has been 80% in this period. Radical removal of the tumors has not led to an increased risk. At the final follow-up review (mean 59.5 month), 75% of the patients were still alive, and 25% had died of chordoma recurrence. The overall recurrence-free survival rate was 82% at 3 years and 51% at 5 years. The 5-year recurrence-free survival rate in the five patients who underwent the operation during the past decade was 77% (mean follow up of 5.2 years). In two patients with recurrent tumors who underwent radiosurgery, no evidence of tumor regrowth was demonstrated at 3 years posttreatment. The authors suggest that for the treatment of skull base chordomas radical resection is a key factor for longer survival and improved quality of life. Patients with sufficiently small tumors, which show a favorable configuration and location, can be suitable candidates for stereotactic radiosurgery.

Management of chordomas and chondrosarcomas of the skull base

Management of chordomas and chondrosarcomas of the skull base

Chordomas and Chondrosarcomas of the Cranial Base

The management of chordomas and chondrosarcomas involving the cranial base remains controversial. The options for therapy include biopsy, partial resection, radical resection, and various forms of radiotherapy. In this article, we analyze the outcome of 60 patients with cranial base chordoma or chondrosarcoma treated with extensive surgical resection between 1984 and 1993. Forty-six patients had chordomas, and 14 had low-grade chondrosarcomas; 50% of these patients had been treated previously. Preoperative studies included computed tomography, magnetic resonance imaging, cerebral angiography, and balloon occlusion test of the internal carotid artery, as indicated. Magnetic resonance imaging was performed on all patients during follow-up. The surgical approaches used for tumor resection were predominantly the following: subtemporal, transzygomatic, transcavernous, and transpetrous apex; subtemporal and infratemporal; extended frontal; and extreme lateral transcondylar. Staged operations with a combination of approaches were used when necessary (52% of cases) to remove a tumor more completely. Statistical analysis was done by the chi 2 test and correlation matrix. Sixty-seven percent of the patients had total or near-total resection. Twenty percent of the patients received postoperative radiotherapy. Eleven patients died during the postoperative follow-up period, nine with chordomas and two with chondrosarcomas. Three patients died because of systemic complications within 3 months after surgery, five died because of tumor recurrence, one died from unrelated causes, and two died from late complications of radiotherapy. The recurrence-free survival rate for all tumors was 80% at 3 years and 76% at 5 years. Chondrosarcomas had a better prognosis than chordomas (recurrence-free survival rates, 90% at 5 years and 65% at 5 years, respectively; P = 0.09). Patients who had undergone previous surgery had a greater risk of recurrence (5-year recurrence-free survival rate, 64%) than did patients who had not undergone previous surgery (5-year recurrence-free survival rate, 93%; P < 0.05). Patients with total or near-total resection had a better 5-year recurrence-free survival rate (84%) than did patients with partial or subtotal resection (64%) (P < 0.05). Postoperative leakage of cerebrospinal fluid was the most frequent complication (30% of patients) and was found to increase the risk of permanent disability. Patients who had undergone previous radiotherapy had a greater risk of death in the postoperative period (within 3 months of their operations) and during follow-up. However, total or near-total resection did not increase the rate of postoperative disability.(ABSTRACT TRUNCATED AT 400 WORDS)

The Role of Radiosurgery in the Management of Chordoma and Chondrosarcoma of the Cranial Base

Abstract Despite conventional multimodality treatment (surgery and fractionated radiation therapy), recurrence and clinical progression of cranial base chordomas and chondrosarcomas are common. The malignant behavior of these tumors is a result of their critical location, locally aggressive nature, and high recurrence rate. To explore the role of radiosurgery in the treatment of these skull base neoplasms, we assessed its use in four patients with chordoma and two with chondrosarcoma. In five of the patients, radiosurgery was used as adjuvant therapy for residual or recurrent tumors after surgical debulking, and in one patient with a chordoma, it was the primary treatment. No patient received fractionated external beam radiotherapy. All tumors were less than 30 mm in diameter and were treated with 20 Gy to the tumor margin. Skull base computed tomography and magnetic resonance images were essential to define the anatomic relationships between tumor and adjacent basal structures. During follow-up (mean, 22 mo; range, 8-36 mo), we found no progression of the treated tumor volume in any patient. Neurological deficits before treatment improved in three patients; the other three patients remained in stable neurological condition. Serial follow-up imaging studies demonstrated that two patients showed reduction in tumor size and four patients had no tumor growth. In one patient, a metastatic parietal lobe chondrosarcoma developed and was treated by microsurgery. Another patient showed tumor progression outside of the radiosurgical trcatment volume. Our results attest to the value of stereotactic radiosurgery as an adjuvant or primary treatment for selected patients with chordoma or chondrosarcoma and demonstrate its potential advantages over standard fractionated irradiation. Analysis of the long-term clinical and imaging effects after radiosurgery is warranted. (Neurosurgery 29:38-46, 1991)

The role of radiosurgery in the management of chordoma and chondrosarcoma of the cranial base

Despite conventional multimodality treatment (surgery and fractionated radiation therapy), recurrence and clinical progression of cranial base chordomas and chondrosarcomas are common. The malignant behavior of these tumors is a result of their critical location, locally aggressive nature, and high recurrence rate. To explore the role of radiosurgery in the treatment of these skull base neoplasms, we assessed its use in four patients with chordoma and two with chondrosarcoma. In five of the patients, radiosurgery was used as adjuvant therapy for residual or recurrent tumors after surgical debulking, and in one patient with a chordoma, it was the primary treatment. No patient received fractionated external beam radiotherapy. All tumors were less than 30 mm in diameter and were treated with 20 Gy to the tumor margin. Skull base computed tomography and magnetic resonance images were essential to define the anatomic relationships between tumor and adjacent basal structures. During follow-up (mean, 22 mo; range, 8-36 mo), we found no progression of the treated tumor volume in any patient. Neurological deficits before treatment improved in three patients; the other three patients remained in stable neurological condition. Serial follow-up imaging studies demonstrated that two patients showed reduction in tumor size and four patients had no tumor growth. In one patient, a metastatic parietal lobe chondrosarcoma developed and was treated by microsurgery. Another patient showed tumor progression outside of the radiosurgical treatment volume. Our results attest to the value of stereotactic radiosurgery as an adjuvant or primary treatment for selected patients with chordoma or chondrosarcoma and demonstrate its potential advantages over standard fractionated irradiation. Analysis of the long-term clinical and imaging effects after radiosurgery is warranted.

Radiation in the management of chordomas: Treatment response weighed against risks of spinal cord injury

Radiation in the management of chordomas: Treatment response weighed against risks of spinal cord injury

Chordoma: brief review of the literature and report of a case with widespread metastases.

The natural course and management of chordoma are reviewed. A report of an unusual case of widespread metastatic chordoma is reported. Radiation therapy, though primarily palliative in nature, is of value.