DEPUY SYNTHES SKULL BASE SURGERY AWARD DEPUY SYNTHES SKULL BASE SURGERY AWARD
Skull Base Chondrosarcoma Radiosurgery: A Literature Review Hideyuki Kano, MD, PhD* Aditya Iyer, MD‡ L. Dade Lunsford, MD* *Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania; ‡Department of Neurosurgery, Stanford University, Stanford, California Correspondence: Hideyuki Kano, MD, PhD, Research Assistant Professor of Neurological Surgery, University of Pittsburgh, Suite B-400, UPMC Presbyterian, 200 Lothrop St, Pittsburgh, PA 15213. E-mail: [email protected] Copyright © 2014 by the Congress of Neurological Surgeons.
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hondrosarcomas are relatively slow growing and locally invasive tumors that usually do not metastasize until very late in the natural history.1 Chondrosarcomas are the third most common primary malignancy of bone after myelomas and osteosarcomas.2 Primary intracranial chondrosarcomas are rare, with a reported incidence of approximately 0.15% of tumors of the skull base.3-5 Cranial chondrosarcomas originate from primitive mesenchymal cells within the cartilaginous matrix of the skull base.6 The imaging features and clinical presentations of patients harboring either chordomas or chondrosarcomas are similar. Whereas chordomas have a tendency to cause brainstem compression because they arise from the clivus, chondrosarcomas tend to affect the lower cranial nerves, because they frequently originate from the occipitotemporal bone synchondrosis.7 The most common presenting symptom of chondrosarcoma is diplopia, secondary to an abducens nerve palsy.8 The ability to distinguish chondrosarcomas from chordomas by imaging alone is often difficult but important, because the prognosis is generally considered better for chondrosarcomas.9,10
SURGICAL RESECTION FOR CHONDROSARCOMAS Maximal safe microsurgical resection is considered the first-line management for intracranial chondrosarcomas11,12 in order to confirm the histological analysis and pursue the first-line option of maximal safe resection. Chondrosarcomas are rarely completely resectable, and additional management options must be considered for residual tumors. Since the development of microsurgical techniques and new skull base strategies, the ability to obtain a gross total resection has improved.12,13 Korten et al14 reviewed a series of patients with intracranial chondrosarcomas in the Netherlands. They found that surgery alone was associated with a 53% local recurrence rate and the mean time to recurrence was 32 months. Wanebo et al15 reported 23 patients who underwent a total of
CLINICAL NEUROSURGERY
43 surgical resections of skull base chondrosarcomas. The 5- and 10-year overall survival rates were 93% at 5 years and 71% at 10 years. Ten patients underwent adjuvant radiation therapy. Crockard et al16 reported a 93% 5-year survival rate for 17 patients who underwent surgery alone. Bloch et al17 found a recurrence rate of 44% in patients who underwent surgical resection alone, compared with 9% in patients who had surgery followed by radiation therapy. A review of the literature described 560 patients with intracranial chondrosarcomas, which were associated with a 5-year mortality of 11.5% and a poor median survival of 24 months. There was also no association between the rate of recurrence and the histological grade of the tumor.17
PROTON-BASED AND PHOTON-BASED RADIATION THERAPY FOR CHONDROSARCOMAS In 1999, the Harvard Cyclotron Laboratory at Massachusetts General Hospital (Cambridge, Massachusetts) reported 229 patients with chondrosarcomas who underwent a combination of mixed fractionated proton/photon radiation. Delivered doses ranged from 66 to 83 Cobalt Gray Equivalent, a radiation dose reported by adding the theoretical increased relative biological effectiveness value of 4 daily sessions of protons to 1 day of photon radiation. The 5- and 10-year actuarial progression-free survival rates were 97% and 92% for chondrosarcomas, at a median follow-up time of 41 months.3,10,18 Depending on the skull base location, dose plans must carefully assess the entrance dose in structures such as the temporal lobe. Proton radiation therapy is typically fractionated over multiple treatments. For patients who have undergone initial resection, the target volume during fractionated radiation therapy techniques likely includes the tumor bed as well as any residual tumor identified by postoperative magnetic resonance imaging (MRI). Fractionation is performed to reduce toxicity risks to adjacent
VOLUME 61 | NUMBER 1 | AUGUST 2014 | 155
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KANO ET AL
central nervous system structures. Advances in photon-based radiation therapy (RT) such as intensity-modulated RT have enabled improved dose conformality to a defined target volume and increased sparing of adjacent normal tissue. Combs et al19 reported that current high-precision RT series that treated patients to a dose ranging from 66 to 76 Gy report a 5-year progression-free survival and survival of 100% without cranial nerve deficit or brainstem damage. The 5-year control rate after proton therapy for chondrosarcoma is also in the range of 85% to 95%, albeit with some toxicity such as brainstem and temporal lobe necrosis.20-22
STEREOTACTIC RADIOSURGERY FOR CHONDROSARCOMAS Stereotactic radiosurgery (SRS) has been used as a minimally invasive primary, adjuvant, or salvage option for a relatively few patients with chondrosarcomas, primarily those with smaller tumor volumes (Table).23-27 Relatively few data exist to define the use of SRS in the multimodality management of chondrosarcoma. The tumor margin after surgical resection is often unclear on MRI because of bone destruction and surrounding tissue infiltration. In such cases, the coregistration of MRI and computed tomography (CT) images during dose planning are useful. Residual tumors after surgical resection are often divided into multiple separate volumes. Therefore, target selection must be carefully crafted in order to avoid delayed out-of-field tumor recurrence. SRS has been shown to result in less toxicity to surrounding structures and fewer complications than fractionated RT in the management of chondrosarcomas. Krishnan et al27 reported 25 patients with chordomas and 4 patients with chondrosarcomas who were treated by SRS. All 4 patients with chondrosarcomas had tumor control at 5 years. No prognostic factors were identified in these early studies. Hasegawa et al24 reported 30 patients with chordomas and 7 patients with chondrosarcomas who underwent SRS. The actuarial 5-year progression-free survival rate in patients with low-grade chondrosarcomas was 80%. A tumor volume of less than 20 mL significantly improved progression-free survival. Koga et al26 reported 4 patients who had surgical resection followed by SRS (median follow-up of 99 months; range, 45-145). One patient who received a tumor margin dose of 12 Gy developed a tumor
recurrence 100 months after SRS. Three of 4 patients (margin doses: 15, 16, and 20 Gy) had no change in tumor volume during follow-up. In most studies, the outcomes after SRS include both chordomas and chondrosarcomas. Iyer et al25 studied 22 patients who underwent Gamma Knife SRS for residual or recurrent intracranial chondrosarcomas. The overall patient survival after SRS was 95%, 70%, and 56% at 1, 5 and 10 years, respectively. Factors associated with longer survival after SRS included a shorter interval (,6 months) between diagnosis and SRS, age greater than 40 years, and either a single or no prior resection. Treated tumor control rates were 91% at 1 year, 72% at 5 years, and 54% at 10 years. Factors associated with longer progression-free survival after SRS included patient age greater than 40 years and no prior RT. Jiang et al28 reported 16 intracranial and spinal chondrosarcoma patients who underwent Cyberknife SRS with a median follow-up of 33 months. The mean tumor volume was 35.1 mL. The margin dose varied from 22 Gy with a single fraction to 30 Gy with 5 fractions. The overall patient survival was 81% at 1 year, 67% at 3 years, and 55% at 5 years. The tumor control was 80% in primary, 50% in recurrent, and 0% in metastatic tumor. Adverse radiation effects were seen in 1 patient.
SKULL BASE CHONDROSARCOMA RADIOSURGERY: REPORT OF THE NORTH AMERICAN GAMMA KNIFE CONSORTIUM Seven participating centers of the North American Gamma Knife Consortium identified 46 patients who underwent Gamma knife SRS for skull base chondrosarcomas. Thirty-six patients had prior surgical resections and 6 had prior fractionated RT. The median target volume was 7.8 mL (0.9-41 mL) and the median margin dose was 15 Gy (10.5-20 Gy). At a median follow-up of 66 months after SRS, 8 patients were dead. The overall survival after SRS was 89% at 3 years, 86% at 5 years, and 76% at 10 years. The overall survival after SRS in patients without prior RT (n = 41) was 94% at 3 years, 91% at 5 years, and 80% at 10 years (Figure). In the group of patients without prior RT, larger tumor volume (continuous data) was significantly associated with worse overall survival (P = .049; hazard ratio, 1.07; 95% confidence interval, 1.00–1.14). In the group of patients without prior RT, the 5-year
TABLE. Studies and Patient Characteristics in Published Series of Chondrosarcoma Treated With Stereotactic Radiosurgerya
a
Reference
N
Radiation
Tumor Volume, mL
Median Margin Dose, Gy
% Survival
% Local Control
Median Follow-up, mo
Krishnan et al27 Hasegawa et al24 Koga et al26 Iyer et al25 Jiang et al28
4 7 4 22 16
GK GK GK GK 6 RT CK
14.4 19.7 NA 8.0 35.1
15 14 15.6 15 22 (1 fraction) to 30 (5 fractions)
NA 5 y: 90; 10 y: 53 NA 5 y: 70; 10 y: 56 5 yr: 55
5 y: 100 5 y: 76; 10 y: 67 5 y: 100 5 y: 72; 10 y: 54 5 yr: 41
58 59 65 60 33
GK, gamma knife; RT, fractionated radiation therapy; CK, cyber knife; NA, not available.
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SKULL BASE CHONDROSARCOMA RADIOSURGERY
FIGURE. Kaplan-Meier estimate of overall survival and recurrence-free survival curve after the SRS in chondrosarcoma patients without prior fractionated radiation therapy. SRS, stereotactic radiosurgery; cum, cumulative.
overall survival was 100% when the tumor volume was ,5 mL compared with 84% for patients whose tumor volumes were $5 mL (P = .049). Local tumor progression occurred in 10 patients. The progression-free survival after SRS was 88% at 3 years, 85% at 5 years, and 70% at 10 years. Prior RT was significantly associated with a shorter progression-free survival (PFS). The PFS in patients without prior RT was 92% at 3 years, 88% at 5 years, and 81% at 10 years (Figure). In patients without prior RT, larger tumor volume (continuous: P = .035; hazard ratio, 1.074; 95% confidence interval, 1.005–1.147; $5 mL: P = .043) was significantly associated with shorter PFS. The PFS in patients without prior RT and with tumor volume ,5 mL was 100% at 10 years, while the PFS in patients without prior RT and with tumor volume $5 mL was 87% at 3 years, 81% at 5 years, and 69% at 10 years. The PFS in patients with residual tumor and no prior RT (n = 33) was 94% at 3 years, 90% at 5 years, and 82% at 10 years after SRS. The PFS in patients with recurrent tumor and no prior RT (n = 8) was 86% at 3, 5, and 10 years after SRS. Recurrent tumors were not associated with PFS (P = .977). Eight patients required a salvage surgical resection, and 3 patients (7%) developed adverse radiation effects. Twenty-two (56%) of 39 patients who had cranial nerve deficits before SRS improved. Clinical improvement after SRS was noted in patients with abducens paralysis (61%), oculomotor paralysis (50%), lower cranial dysfunction (50%), optic neuropathy (43%), facial
CLINICAL NEUROSURGERY
neuropathy (38%), trochlear paralysis (33%), trigeminal neuropathy (15%), and hearing loss (10%).
CONCLUSION The ability to achieve tumor growth control of chondrosarcomas is likely to be enhanced by earlier recognition and the application of multimodal treatment in appropriate patients. Maximal safe resection should be the primary initial management of chondrosarcomas. Gamma Knife radiosurgery is an effective therapeutic option as an adjuvant treatment following resection in selected patients with chondrosarcomas. Patients with smaller volume residual tumors not previously treated by RT do best. Disclosure Dr Lunsford is a consultant and stockholder for AB Elekta. The other authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.
REFERENCES 1. Gay E, Sekhar LN, Rubinstein E, et al. Chordomas and chondrosarcomas of the cranial base: results and follow-up of 60 patients. Neurosurgery. 1995;36(5):887896; discussion 896-887. 2. Murphey MD, Walker EA, Wilson AJ, Kransdorf MJ, Temple HT, Gannon FH. From the archives of the AFIP: imaging of primary chondrosarcoma: radiologicpathologic correlation. Radiographics. 2003;23(5):1245-1278.
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KANO ET AL
3. Nguyen QN, Chang EL. Emerging role of proton beam radiation therapy for chordoma and chondrosarcoma of the skull base. Curr Oncol Rep. 2008;10(4): 338-343. 4. Bourgouin PM, Tampieri D, Robitaille Y, et al. Low-grade myxoid chondrosarcoma of the base of the skull: CT, MR, and histopathology. J Comput Assist Tomogr. 1992;16(2):268-273. 5. Cianfriglia FPA, Occhipinti E. Intracranial malignant cartilaginous tumors. Report of two cases and review of the literature. Acta Neurochir. 1978;45(1-2):163-175. 6. Heffelfinger MJ, Dahlin DC, MacCarty CS, Beabout JW. Chordomas and cartilaginous tumors at the skull base. Cancer. 1973;32(2):410-420. 7. Volpe NJ, Liebsch NJ, Munzenrider JE, Lessell S. Neuro-ophthalmologic findings in chordoma and chondrosarcoma of the skull base. Am J Ophthalmol. 1993;115 (1):97-104. 8. Bloch OG, Jian BJ, Yang I, et al. Cranial chondrosarcoma and recurrence. Skull Base. 2010;20(3):149-156. 9. Goel A. Chordoma and chondrosarcoma: relationship to the internal carotid artery. Acta Neurochir (Wien). 1995;133(1-2):30-35. 10. Munzenrider JE, Liebsch NJ. Proton therapy for tumors of the skull base. Strahlenther Onkol. 1999;175(suppl 2):57-63. 11. Lanzino G, Dumont AS, Lopes MB, Laws ER Jr. Skull base chordomas: overview of disease, management options, and outcome. Neurosurg Focus. 2001;10(3):E12. 12. Sekhar LN, Pranatartiharan R, Chanda A, Wright DC. Chordomas and chondrosarcomas of the skull base: results and complications of surgical management. Neurosurg Focus. 2001;10(3):E2. 13. Sen CN, Sekhar LN. The subtemporal and preauricular infratemporal approach to intradural structures ventral to the brain stem. J Neurosurg. 1990;73(3):345-354. 14. Korten AG, ter Berg HJ, Spincemaille GH, van der Laan RT, Van de Wel AM. Intracranial chondrosarcoma: review of the literature and report of 15 cases. J Neurol Neurosurg Psychiatry. 1998;65(1):88-92. 15. Wanebo JE, Bristol RE, Porter RR, Coons SW, Spetzler RF. Management of cranial base chondrosarcomas. Neurosurgery. 2006;58(2):249-255; discussion 249-255. 16. Crockard HA, Cheeseman A, Steel T, et al. A multidisciplinary team approach to skull base chondrosarcomas. J Neurosurg. 2001;95(2):184-189. 17. Bloch OG, Jian BJ, Yang I, et al. A systematic review of intracranial chondrosarcoma and survival. J Clin Neurosci. 2009;16(12):1547-1551. 18. Hug EB. Review of skull base chordomas: prognostic factors and long-term results of proton-beam radiotherapy. Neurosurg Focus. 2001;10(3):E11.
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19. Combs SE, Laperriere N, Brada M. Clinical controversies: proton radiation therapy for brain and skull base tumors. Semin Radiat Oncol. 2013;23(2): 120-126. 20. Ares C, Hug EB, Lomax AJ, et al. Effectiveness and safety of spot scanning proton radiation therapy for chordomas and chondrosarcomas of the skull base: first longterm report. Int J Radiat Oncol Biol Phys. 2009;75(4):1111-1118. 21. Santoni R, Liebsch N, Finkelstein DM, et al. Temporal lobe (TL) damage following surgery and high-dose photon and proton irradiation in 96 patients affected by chordomas and chondrosarcomas of the base of the skull. Int J Radiat Oncol Biol Phys. 1998;41(1):59-68. 22. Weber DC, Rutz HP, Pedroni ES, et al. Results of spot-scanning proton radiation therapy for chordoma and chondrosarcoma of the skull base: the Paul Scherrer Institut experience. Int J Radiat Oncol Biol Phys. 2005;63(2): 401-409. 23. Cho YH, Kim JH, Khang SK, Lee JK, Kim CJ. Chordomas and chondrosarcomas of the skull base: comparative analysis of clinical results in 30 patients. Neurosurg Rev. 2008;31(1):35-43; discussion 43. 24. Hasegawa T, Ishii D, Kida Y, Yoshimoto M, Koike J, Iizuka H. Gamma Knife surgery for skull base chordomas and chondrosarcomas. J Neurosurg. 2007;107(4): 752-757. 25. Iyer A, Kano H, Kondziolka D, et al. Stereotactic radiosurgery for intracranial chondrosarcoma. J Neurooncol. 2012;108(3):535-542. 26. Koga T, Shin M, Saito N. Treatment with high marginal dose is mandatory to achieve long-term control of skull base chordomas and chondrosarcomas by means of stereotactic radiosurgery. J Neurooncol. 2010;98(2):233-238. 27. Krishnan S, Foote RL, Brown PD, Pollock BE, Link MJ, Garces YI. Radiosurgery for cranial base chordomas and chondrosarcomas. Neurosurgery. 2005;56(4): 777-784; discussion 777-784. 28. Jiang B, Veeravagu A, Feroze AH, et al. CyberKnife radiosurgery for the management of skull base and spinal chondrosarcomas. J Neuro-oncology. 2013; 114(2):209-218.
Acknowledgments This study was presented and awarded the Synthes Skull Base Surgery Award at the 2013 Annual Meeting of the Congress of Neurological Surgeons, San Francisco.
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Skull Base Chondrosarcoma Radiosurgery: A Literature Review Hideyuki Kano, MD, PhD* Aditya Iyer, MD‡ L. Dade Lunsford, MD* *Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania; ‡Department of Neurosurgery, Stanford University, Stanford, California Correspondence: Hideyuki Kano, MD, PhD, Research Assistant Professor of Neurological Surgery, University of Pittsburgh, Suite B-400, UPMC Presbyterian, 200 Lothrop St, Pittsburgh, PA 15213. E-mail: [email protected] Copyright © 2014 by the Congress of Neurological Surgeons.
C
hondrosarcomas are relatively slow growing and locally invasive tumors that usually do not metastasize until very late in the natural history.1 Chondrosarcomas are the third most common primary malignancy of bone after myelomas and osteosarcomas.2 Primary intracranial chondrosarcomas are rare, with a reported incidence of approximately 0.15% of tumors of the skull base.3-5 Cranial chondrosarcomas originate from primitive mesenchymal cells within the cartilaginous matrix of the skull base.6 The imaging features and clinical presentations of patients harboring either chordomas or chondrosarcomas are similar. Whereas chordomas have a tendency to cause brainstem compression because they arise from the clivus, chondrosarcomas tend to affect the lower cranial nerves, because they frequently originate from the occipitotemporal bone synchondrosis.7 The most common presenting symptom of chondrosarcoma is diplopia, secondary to an abducens nerve palsy.8 The ability to distinguish chondrosarcomas from chordomas by imaging alone is often difficult but important, because the prognosis is generally considered better for chondrosarcomas.9,10
SURGICAL RESECTION FOR CHONDROSARCOMAS Maximal safe microsurgical resection is considered the first-line management for intracranial chondrosarcomas11,12 in order to confirm the histological analysis and pursue the first-line option of maximal safe resection. Chondrosarcomas are rarely completely resectable, and additional management options must be considered for residual tumors. Since the development of microsurgical techniques and new skull base strategies, the ability to obtain a gross total resection has improved.12,13 Korten et al14 reviewed a series of patients with intracranial chondrosarcomas in the Netherlands. They found that surgery alone was associated with a 53% local recurrence rate and the mean time to recurrence was 32 months. Wanebo et al15 reported 23 patients who underwent a total of
CLINICAL NEUROSURGERY
43 surgical resections of skull base chondrosarcomas. The 5- and 10-year overall survival rates were 93% at 5 years and 71% at 10 years. Ten patients underwent adjuvant radiation therapy. Crockard et al16 reported a 93% 5-year survival rate for 17 patients who underwent surgery alone. Bloch et al17 found a recurrence rate of 44% in patients who underwent surgical resection alone, compared with 9% in patients who had surgery followed by radiation therapy. A review of the literature described 560 patients with intracranial chondrosarcomas, which were associated with a 5-year mortality of 11.5% and a poor median survival of 24 months. There was also no association between the rate of recurrence and the histological grade of the tumor.17
PROTON-BASED AND PHOTON-BASED RADIATION THERAPY FOR CHONDROSARCOMAS In 1999, the Harvard Cyclotron Laboratory at Massachusetts General Hospital (Cambridge, Massachusetts) reported 229 patients with chondrosarcomas who underwent a combination of mixed fractionated proton/photon radiation. Delivered doses ranged from 66 to 83 Cobalt Gray Equivalent, a radiation dose reported by adding the theoretical increased relative biological effectiveness value of 4 daily sessions of protons to 1 day of photon radiation. The 5- and 10-year actuarial progression-free survival rates were 97% and 92% for chondrosarcomas, at a median follow-up time of 41 months.3,10,18 Depending on the skull base location, dose plans must carefully assess the entrance dose in structures such as the temporal lobe. Proton radiation therapy is typically fractionated over multiple treatments. For patients who have undergone initial resection, the target volume during fractionated radiation therapy techniques likely includes the tumor bed as well as any residual tumor identified by postoperative magnetic resonance imaging (MRI). Fractionation is performed to reduce toxicity risks to adjacent
VOLUME 61 | NUMBER 1 | AUGUST 2014 | 155
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KANO ET AL
central nervous system structures. Advances in photon-based radiation therapy (RT) such as intensity-modulated RT have enabled improved dose conformality to a defined target volume and increased sparing of adjacent normal tissue. Combs et al19 reported that current high-precision RT series that treated patients to a dose ranging from 66 to 76 Gy report a 5-year progression-free survival and survival of 100% without cranial nerve deficit or brainstem damage. The 5-year control rate after proton therapy for chondrosarcoma is also in the range of 85% to 95%, albeit with some toxicity such as brainstem and temporal lobe necrosis.20-22
STEREOTACTIC RADIOSURGERY FOR CHONDROSARCOMAS Stereotactic radiosurgery (SRS) has been used as a minimally invasive primary, adjuvant, or salvage option for a relatively few patients with chondrosarcomas, primarily those with smaller tumor volumes (Table).23-27 Relatively few data exist to define the use of SRS in the multimodality management of chondrosarcoma. The tumor margin after surgical resection is often unclear on MRI because of bone destruction and surrounding tissue infiltration. In such cases, the coregistration of MRI and computed tomography (CT) images during dose planning are useful. Residual tumors after surgical resection are often divided into multiple separate volumes. Therefore, target selection must be carefully crafted in order to avoid delayed out-of-field tumor recurrence. SRS has been shown to result in less toxicity to surrounding structures and fewer complications than fractionated RT in the management of chondrosarcomas. Krishnan et al27 reported 25 patients with chordomas and 4 patients with chondrosarcomas who were treated by SRS. All 4 patients with chondrosarcomas had tumor control at 5 years. No prognostic factors were identified in these early studies. Hasegawa et al24 reported 30 patients with chordomas and 7 patients with chondrosarcomas who underwent SRS. The actuarial 5-year progression-free survival rate in patients with low-grade chondrosarcomas was 80%. A tumor volume of less than 20 mL significantly improved progression-free survival. Koga et al26 reported 4 patients who had surgical resection followed by SRS (median follow-up of 99 months; range, 45-145). One patient who received a tumor margin dose of 12 Gy developed a tumor
recurrence 100 months after SRS. Three of 4 patients (margin doses: 15, 16, and 20 Gy) had no change in tumor volume during follow-up. In most studies, the outcomes after SRS include both chordomas and chondrosarcomas. Iyer et al25 studied 22 patients who underwent Gamma Knife SRS for residual or recurrent intracranial chondrosarcomas. The overall patient survival after SRS was 95%, 70%, and 56% at 1, 5 and 10 years, respectively. Factors associated with longer survival after SRS included a shorter interval (,6 months) between diagnosis and SRS, age greater than 40 years, and either a single or no prior resection. Treated tumor control rates were 91% at 1 year, 72% at 5 years, and 54% at 10 years. Factors associated with longer progression-free survival after SRS included patient age greater than 40 years and no prior RT. Jiang et al28 reported 16 intracranial and spinal chondrosarcoma patients who underwent Cyberknife SRS with a median follow-up of 33 months. The mean tumor volume was 35.1 mL. The margin dose varied from 22 Gy with a single fraction to 30 Gy with 5 fractions. The overall patient survival was 81% at 1 year, 67% at 3 years, and 55% at 5 years. The tumor control was 80% in primary, 50% in recurrent, and 0% in metastatic tumor. Adverse radiation effects were seen in 1 patient.
SKULL BASE CHONDROSARCOMA RADIOSURGERY: REPORT OF THE NORTH AMERICAN GAMMA KNIFE CONSORTIUM Seven participating centers of the North American Gamma Knife Consortium identified 46 patients who underwent Gamma knife SRS for skull base chondrosarcomas. Thirty-six patients had prior surgical resections and 6 had prior fractionated RT. The median target volume was 7.8 mL (0.9-41 mL) and the median margin dose was 15 Gy (10.5-20 Gy). At a median follow-up of 66 months after SRS, 8 patients were dead. The overall survival after SRS was 89% at 3 years, 86% at 5 years, and 76% at 10 years. The overall survival after SRS in patients without prior RT (n = 41) was 94% at 3 years, 91% at 5 years, and 80% at 10 years (Figure). In the group of patients without prior RT, larger tumor volume (continuous data) was significantly associated with worse overall survival (P = .049; hazard ratio, 1.07; 95% confidence interval, 1.00–1.14). In the group of patients without prior RT, the 5-year
TABLE. Studies and Patient Characteristics in Published Series of Chondrosarcoma Treated With Stereotactic Radiosurgerya
a
Reference
N
Radiation
Tumor Volume, mL
Median Margin Dose, Gy
% Survival
% Local Control
Median Follow-up, mo
Krishnan et al27 Hasegawa et al24 Koga et al26 Iyer et al25 Jiang et al28
4 7 4 22 16
GK GK GK GK 6 RT CK
14.4 19.7 NA 8.0 35.1
15 14 15.6 15 22 (1 fraction) to 30 (5 fractions)
NA 5 y: 90; 10 y: 53 NA 5 y: 70; 10 y: 56 5 yr: 55
5 y: 100 5 y: 76; 10 y: 67 5 y: 100 5 y: 72; 10 y: 54 5 yr: 41
58 59 65 60 33
GK, gamma knife; RT, fractionated radiation therapy; CK, cyber knife; NA, not available.
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SKULL BASE CHONDROSARCOMA RADIOSURGERY
FIGURE. Kaplan-Meier estimate of overall survival and recurrence-free survival curve after the SRS in chondrosarcoma patients without prior fractionated radiation therapy. SRS, stereotactic radiosurgery; cum, cumulative.
overall survival was 100% when the tumor volume was ,5 mL compared with 84% for patients whose tumor volumes were $5 mL (P = .049). Local tumor progression occurred in 10 patients. The progression-free survival after SRS was 88% at 3 years, 85% at 5 years, and 70% at 10 years. Prior RT was significantly associated with a shorter progression-free survival (PFS). The PFS in patients without prior RT was 92% at 3 years, 88% at 5 years, and 81% at 10 years (Figure). In patients without prior RT, larger tumor volume (continuous: P = .035; hazard ratio, 1.074; 95% confidence interval, 1.005–1.147; $5 mL: P = .043) was significantly associated with shorter PFS. The PFS in patients without prior RT and with tumor volume ,5 mL was 100% at 10 years, while the PFS in patients without prior RT and with tumor volume $5 mL was 87% at 3 years, 81% at 5 years, and 69% at 10 years. The PFS in patients with residual tumor and no prior RT (n = 33) was 94% at 3 years, 90% at 5 years, and 82% at 10 years after SRS. The PFS in patients with recurrent tumor and no prior RT (n = 8) was 86% at 3, 5, and 10 years after SRS. Recurrent tumors were not associated with PFS (P = .977). Eight patients required a salvage surgical resection, and 3 patients (7%) developed adverse radiation effects. Twenty-two (56%) of 39 patients who had cranial nerve deficits before SRS improved. Clinical improvement after SRS was noted in patients with abducens paralysis (61%), oculomotor paralysis (50%), lower cranial dysfunction (50%), optic neuropathy (43%), facial
CLINICAL NEUROSURGERY
neuropathy (38%), trochlear paralysis (33%), trigeminal neuropathy (15%), and hearing loss (10%).
CONCLUSION The ability to achieve tumor growth control of chondrosarcomas is likely to be enhanced by earlier recognition and the application of multimodal treatment in appropriate patients. Maximal safe resection should be the primary initial management of chondrosarcomas. Gamma Knife radiosurgery is an effective therapeutic option as an adjuvant treatment following resection in selected patients with chondrosarcomas. Patients with smaller volume residual tumors not previously treated by RT do best. Disclosure Dr Lunsford is a consultant and stockholder for AB Elekta. The other authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.
REFERENCES 1. Gay E, Sekhar LN, Rubinstein E, et al. Chordomas and chondrosarcomas of the cranial base: results and follow-up of 60 patients. Neurosurgery. 1995;36(5):887896; discussion 896-887. 2. Murphey MD, Walker EA, Wilson AJ, Kransdorf MJ, Temple HT, Gannon FH. From the archives of the AFIP: imaging of primary chondrosarcoma: radiologicpathologic correlation. Radiographics. 2003;23(5):1245-1278.
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KANO ET AL
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Acknowledgments This study was presented and awarded the Synthes Skull Base Surgery Award at the 2013 Annual Meeting of the Congress of Neurological Surgeons, San Francisco.
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