A clinical case of sacrum and coccyx chordoma having a massive intrapelvic component (surgical treatment with a brief review of the literature)

Abstract

BACKGROUND: Chordoma is a rare malignant tumor that develops from the remnants of the notochord and is located in the axial skeleton in the absolute majority of cases. It is most often localized in the sacrum, coccyx and pelvis, and is characterized by an initially asymptomatic long-time course, making early diagnosis difficult. Radical surgical treatment is the leading factor allowing to prolong the recurrence-free and overall survival of patients with chordoma, but it is often difficult due to complex anatomical localization of the tumor, as well as delayed medical treatment, frequently accompanied with the subsequent development of neurological complications, while in elderly patients with high comorbidity it is not always feasible.

CLINICAL CASE DESCRIPTION: We present a clinical case of radical surgical treatment of a patient with a S4-5 vertebral and coccyx chordoma showing a massive intrapelvic component. Clinical manifestations of the disease in the form of pain syndrome and pelvic organ dysfunction developed only when the tumor reached a larger size, forming a massive intrapelvic component up to 20 cm in size. The examination, including computer and magnetic resonance tomography, trepan biopsy with pathomorphologic examination, allowed to establish the diagnosis. Taking into account the size and localization of the tumor, the multidisciplinary team performed radical surgical intervention including sacral resection at the S3 level, coccygectomy with tumor removal. Morphological study of the removed tumor confirmed the diagnosis. In the early postoperative period, the wound healed by primary tension, the development of pelvic organs dysfunction was noted, which partially regressed by discharge. The article presents a brief review of the current problems of diagnosis and treatment of patients with chordoma.

CONCLUSION: Diagnosis and treatment of sacral chordoma is one of the most difficult problems of orthopedic oncology. A full preoperative examination and a multidisciplinary approach in this case made it possible to perform radical surgical intervention, reduce the risks of tumor progression, intra- and postoperative complications, and preserve the patient’s quality of life as much as possible.

Keywords

chordoma / bone tumors / tumors of the sacrum / surgical resection

References

[1] Barber SM, Sadrameli SS, Lee JJ, Fridley JS, Teh BS, Oyelese AA, Telfeian AE, Gokaslan ZL. Chordoma — Current Understanding and Modern Treatment Paradigms. J Clin Med. 2021;10(5):1054. doi: 10.3390/jcm10051054

[2] Barber S.M., Sadrameli S.S., Lee J.J., Fridley J.S., Teh B.S., Oyelese A.A., Telfeian A.E., Gokaslan Z.L. Chordoma — Current Understanding and Modern Treatment Paradigms // J Clin Med. 2021. Vol. 10, № 5. Р. 1054. doi: 10.3390/jcm10051054

[3] Corallo D, Trapani V, Bonaldo P. The notochord: structure and functions. Cell Mol Life Sci. 2015;72(16):2989–3008. doi: 10.1007/s00018-015-1897-z

[4] Corallo D., Trapani V., Bonaldo P. The notochord: structure and functions // Cell Mol Life Sci. 2015. Vol. 72, № 16. Р. 2989–3008. doi: 10.1007/s00018-015-1897-z

[5] Evans S, Khan Z, Jeys L, Grimer R. Extra-axial chordomas. Ann R Coll Surg Engl. 2016;98(5):324–8. doi: 10.1308/rcsann.2016.0138

[6] Evans S., Khan Z., Jeys L., Grimer R. Extra-axial chordomas // Ann R Coll Surg Engl. 2016. Vol. 98, № 5. Р. 324–8. doi: 10.1308/rcsann.2016.0138

[7] Dahlin DC, Unni KK. Bone Tumors. General aspects and Data on 8,542 Cases. 4th ed. Springfield, Illinois; 1986. P. 379–390.

[8] Dahlin D.C., Unni K.K. Bone Tumors. General aspects and Data on 8,542 Cases. 4th ed. Springfield, Illinois, 1986. P. 379–390.

[9] Czerniak B. Dorfman and Czerniak’s Bone Tumors. 2nd ed. Elsevier; 2015. P. 1179–1216.

[10] Czerniak B. Dorfman and Czerniak’s Bone Tumors. 2nd ed. Elsevier, 2015. P. 1179–1216.

[11] McMaster ML, Goldstein AM, Bromley CM, Ishibe N, Parry DM. Chordoma: incidence and survival patterns in the United States, 1973–1995. Cancer Causes Control. 2001;12(1):1–11. doi: 10.1023/a:1008947301735

[12] McMaster M.L., Goldstein A.M., Bromley C.M., Ishibe N., Parry D.M. Chordoma: incidence and survival patterns in the United States, 1973–1995 // Cancer Causes Control. 2001. Vol. 12, № 1. Р. 1–11. doi: 10.1023/a:1008947301735

[13] Pan Y, Lu L, Chen J, Zhong Y, Dai Z. Analysis of prognostic factors for survival in patients with primary spinal chordoma using the SEER Registry from 1973 to 2014. J Orthop Surg Res. 2018;13(1):76. doi: 10.1186/s13018-018-0784-3

[14] Pan Y., Lu L., Chen J., Zhong Y., Dai Z. Analysis of prognostic factors for survival in patients with primary spinal chordoma using the SEER Registry from 1973 to 2014 // J Orthop Surg Res. 2018. Vol. 13, № 1. Р. 76. doi: 10.1186/s13018-018-0784-3

[15] Dial BL, Kerr DL, Lazarides AL, Catanzano AA, Green CL, Risoli T Jr, Blazer DG, Goodwin RC, Brigman BE, Eward WC, Larrier NA, Kirsch DG, Mendoza-Lattes SA. The Role of Radiotherapy for Chordoma Patients Managed With Surgery: Analysis of the National Cancer Database. Spine (Phila Pa 1976). 2020;45(12):E742–E751. doi: 10.1097/BRS.0000000000003406

[16] Dial B.L., Kerr D.L., Lazarides A.L., Catanzano A.A., Green C.L., Risoli T. Jr, Blazer D.G., Goodwin R.C., Brigman B.E., Eward W.C., Larrier N.A., Kirsch D.G., Mendoza-Lattes S.A. The Role of Radiotherapy for Chordoma Patients Managed With Surgery: Analysis of the National Cancer Database // Spine (Phila Pa 1976). 2020. Vol. 45, № 12. Р. E742–E751. doi: 10.1097/BRS.0000000000003406

[17] Parry DM, McMaster ML, Liebsch NJ, Patronas NJ, Quezado MM, Zametkin D, Yang XR, Goldstein AM. Clinical findings in families with chordoma with and without T gene duplications and in patients with sporadic chordoma reported to the Surveillance, Epidemiology, and End Results program. J Neurosurg. 2020;134(5):1399–1408. doi: 10.3171/2020.4.JNS193505

[18] Parry D.M., McMaster M.L., Liebsch N.J., Patronas N.J., Quezado M.M., Zametkin D., Yang X.R., Goldstein A.M. Clinical findings in families with chordoma with and without T gene duplications and in patients with sporadic chordoma reported to the Surveillance, Epidemiology, and End Results program // J Neurosurg. 2020. Vol. 134, № 5. Р. 1399–1408. doi: 10.3171/2020.4.JNS193505

[19] Burdygin VN, Morozov AK, Belyaeva AA. Primary sacral tumors in adults: diagnostic problems. N.N. Priorov Journal of Traumatology and Orthopedics. 1998;5(1):3–12. (In Russ). doi: 10.17816/vto104020

[20] Бурдыгин В.Н., Морозов А.К., Беляева А.А. Первичные опухоли крестца у взрослых: проблемы диагностики // Вестник травматологии и ортопедии им. Н.Н. Приорова. 1998. Т. 5, № 1. С. 3–12. doi: 10.17816/vto104020

[21] Stacchiotti S, Casali PG, Lo Vullo S, Mariani L, Palassini E, Mercuri M, Alberghini M, Pilotti S, Zanella L, Gronchi A, Picci P. Chordoma of the mobile spine and sacrum: a retrospective analysis of a series of patients surgically treated at two referral centers. Ann Surg Oncol. 2010;17(1):211–9. doi: 10.1245/s10434-009-0740-x

[22] Stacchiotti S., Casali P.G., Lo Vullo S., Mariani L., Palassini E., Mercuri M., Alberghini M., Pilotti S., Zanella L., Gronchi A., Picci P. Chordoma of the mobile spine and sacrum: a retrospective analysis of a series of patients surgically treated at two referral centers // Ann Surg Oncol. 2010. Vol. 17, № 1. Р. 211–9. doi: 10.1245/s10434-009-0740-x

[23] Varga PP, Szövérfi Z, Fisher CG, Boriani S, Gokaslan ZL, Dekutoski MB, Chou D, Quraishi NA, Reynolds JJ, Luzzati A, Williams R, Fehlings MG, Germscheid NM, Lazary A, Rhines LD. Surgical treatment of sacral chordoma: prognostic variables for local recurrence and overall survival. Eur Spine J. 2015;24(5):1092–101. doi: 10.1007/s00586-014-3728-6

[24] Varga P.P., Szövérfi Z., Fisher C.G., Boriani S., Gokaslan Z.L., Dekutoski M.B., Chou D., Quraishi N.A., Reynolds J.J., Luzzati A., Williams R., Fehlings M.G., Germscheid N.M., Lazary A., Rhines L.D. Surgical treatment of sacral chordoma: prognostic variables for local recurrence and overall survival // Eur Spine J. 2015. Vol. 24. № 5. Р. 1092–101. doi: 10.1007/s00586-014-3728-6

[25] Bergh P, Kindblom LG, Gunterberg B, Remotti F, Ryd W, Meis-Kindblom JM. Prognostic factors in chordoma of the sacrum and mobile spine: a study of 39 patients. Cancer. 2000;88(9):2122–34. doi: 10.1002/(sici)1097-0142(20000501)88:9<2122::aid-cncr19>3.0.co;2-1

[26] Bergh P., Kindblom L.G., Gunterberg B., Remotti F., Ryd W., Meis-Kindblom J.M. Prognostic factors in chordoma of the sacrum and mobile spine: a study of 39 patients // Cancer. 2000. Vol. 88, № 9. Р. 2122–34. doi: 10.1002/(sici)1097-0142(20000501)88:9<2122::aid-cncr19>3.0.co;2-1

[27] Ruggieri P, Angelini A, Ussia G, Montalti M, Mercuri M. Surgical margins and local control in resection of sacral chordomas. Clin Orthop Relat Res. 2010;468(11):2939–47. doi: 10.1007/s11999-010-1472-8

[28] Ruggieri P., Angelini A., Ussia G., Montalti M., Mercuri M. Surgical margins and local control in resection of sacral chordomas // Clin Orthop Relat Res. 2010. Vol. 468, № 11. Р. 2939–47. doi: 10.1007/s11999-010-1472-8

[29] Wang J, Li D, Yang R, Tang X, Yan T, Guo W. Epidemiological characteristics of 1385 primary sacral tumors in one institution in China. World J Surg Oncol. 2020;18(1):297. doi: 10.1186/s12957-020-02045-w

[30] Wang J., Li D., Yang R., Tang X., Yan T., Guo W. Epidemiological characteristics of 1385 primary sacral tumors in one institution in China // World J Surg Oncol. 2020. Vol. 18, № 1. Р. 297. doi: 10.1186/s12957-020-02045-w

[31] Keykhosravi E, Rezaee H, Tavallaii A, Tavassoli A, Maftouh M, Aminzadeh B. A Giant Sacrococcygeal Chordoma: A Case Report. Brain Tumor Res Treat. 2022;10(1):29–33. doi: 10.14791/btrt.2022.10.e12

[32] Keykhosravi E., Rezaee H., Tavallaii A., Tavassoli A., Maftouh M., Aminzadeh B. A Giant Sacrococcygeal Chordoma: A Case Report // Brain Tumor Res Treat. 2022. Vol. 10, № 1. Р. 29–33. doi: 10.14791/btrt.2022.10.e12

[33] Phang ZH, Saw XY, Nor NFBM, Ahmad ZB, Ibrahim SB. Rare case of neglected large sacral Chordoma in a young female treated by wide En bloc resection and Sacrectomy. BMC Cancer. 2018;18(1):1112. doi: 10.1186/s12885-018-5012-3

[34] Phang Z.H., Saw X.Y., Nor N.F.B.M., Ahmad Z.B., Ibrahim S.B. Rare case of neglected large sacral Chordoma in a young female treated by wide En bloc resection and Sacrectomy // BMC Cancer. 2018. Vol. 18, № 1. Р. 1112. doi: 10.1186/s12885-018-5012-3

[35] Park M, Park I, Hong CK, Kim SH, Cha YJ. Differences in stromal component of chordoma are associated with contrast enhancement in MRI and differential gene expression in RNA sequencing. Sci Rep. 2022;12(1):16504. doi: 10.1038/s41598-022-20787-3

[36] Park M., Park I., Hong C.K., Kim S.H., Cha Y.J. Differences in stromal component of chordoma are associated with contrast enhancement in MRI and differential gene expression in RNA sequencing // Sci Rep. 2022. Vol. 12, № 1. Р. 16504. doi: 10.1038/s41598-022-20787-3

[37] Soft Tissue and Bone Tumours. WHO Classification of Tumours. 5th ed. Vol. 3. WHO Classification of Tumours Editorial Board. 2020. P. 451–457. Available from: https://publications.iarc.fr/588

[38] Soft Tissue and Bone Tumours. WHO Classification of Tumours. 5th ed. Vol. 3. WHO Classification of Tumours Editorial Board. 2020. P. 451–457. Режим доступа: https://publications.iarc.fr/588

[39] Schajowicz F. Tumors and Tumorlike Lesions of Bone: Pathology, Radiology, and Treatment. 2nd ed. Springer–Verlag; 1994. P. 459–468.

[40] Schajowicz F. Tumors and Tumorlike Lesions of Bone: Pathology, Radiology, and Treatment. 2nd ed. Springer–Verlag, 1994. P. 459–468.

[41] Shih AR, Cote GM, Chebib I, Choy E, DeLaney T, Deshpande V, Hornicek FJ, Miao R, Schwab JH, Nielsen GP, Chen YL. Clinicopathologic characteristics of poorly differentiated chordoma. Mod Pathol. 2018;31(8):1237–1245. doi: 10.1038/s41379-018-0002-1

[42] Shih A.R., Cote G.M., Chebib I., Choy E., DeLaney T., Deshpande V., Hornicek F.J., Miao R., Schwab J.H., Nielsen G.P., Chen Y.L. Clinicopathologic characteristics of poorly differentiated chordoma // Mod Pathol. 2018. Vol. 31, № 8. Р. 1237–1245. doi: 10.1038/s41379-018-0002-1

[43] Hung YP, Diaz-Perez JA, Cote GM, Wejde J, Schwab JH, Nardi V, Chebib IA, Deshpande V, Selig MK, Bredella MA, Rosenberg AE, Nielsen GP. Dedifferentiated Chordoma: Clinicopathologic and Molecular Characteristics With Integrative Analysis. Am J Surg Pathol. 2020;44(9):1213–1223. doi: 10.1097/PAS.0000000000001501

[44] Hung Y.P., Diaz-Perez J.A., Cote G.M., Wejde J., Schwab J.H., Nardi V., Chebib I.A., Deshpande V., Selig M.K., Bredella M.A., Rosenberg A.E., Nielsen G.P. Dedifferentiated Chordoma: Clinicopathologic and Molecular Characteristics With Integrative Analysis // Am J Surg Pathol. 2020. Vol. 44, № 9. Р. 1213–1223. doi: 10.1097/PAS.0000000000001501

[45] Tauziéde-Espariat A, Bresson D, Polivka M, Bouazza S, Labrousse F, Aronica E, Pretet JL, Projetti F, Herman P, Salle H, Monnien F, Valmary-Degano S, Laquerrière A, Pocard M, Chaigneau L, Isambert N, Aubriot-Lorton MH, Feuvret L, George B, Froelich S, Adle-Biassette H. Prognostic and Therapeutic Markers in Chordomas: A Study of 287 Tumors. J Neuropathol Exp Neurol. 2016;75(2):111–20. doi: 10.1093/jnen/nlv010

[46] Tauziéde-Espariat A., Bresson D., Polivka M., Bouazza S., Labrousse F., Aronica E., Pretet J.L., Projetti F., Herman P., Salle H., Monnien F., Valmary-Degano S., Laquerrière A., Pocard M., Chaigneau L., Isambert N., Aubriot-Lorton M.H., Feuvret L., George B., Froelich S., Adle-Biassette H. Prognostic and Therapeutic Markers in Chordomas: A Study of 287 Tumors // J Neuropathol Exp Neurol. 2016. Vol. 75, № 2. Р. 111–20. doi: 10.1093/jnen/nlv010

[47] Bai J, Shi J, Li C, Wang S, Zhang T, Hua X, Zhu B, Koka H, Wu HH, Song L, Wang D, Wang M, Zhou W, Ballew BJ, Zhu B, Hicks B, Mirabello L, Parry DM, Zhai Y, Li M, Du J, Wang J, Zhang S, Liu Q, Zhao P, Gui S, Goldstein AM, Zhang Y, Yang XR. Whole genome sequencing of skull-base chordoma reveals genomic alterations associated with recurrence and chordoma-specific survival. Nat Commun. 2021;12(1):757. doi: 10.1038/s41467-021-21026-5

[48] Bai J., Shi J., Li C., Wang S., Zhang T., Hua X., Zhu B., Koka H., Wu H.H., Song L., Wang D., Wang M., Zhou W., Ballew B.J., Zhu B., Hicks B., Mirabello L., Parry D.M., Zhai Y., Li M., Du J., Wang J., Zhang S., Liu Q., Zhao P., Gui S., Goldstein A.M., Zhang Y., Yang X.R. Whole genome sequencing of skull-base chordoma reveals genomic alterations associated with recurrence and chordoma-specific survival // Nat Commun. 2021. Vol. 12, № 1. Р. 757. doi: 10.1038/s41467-021-21026-5

[49] Nachwalter RN, Rothrock RJ, Katsoulakis E, Gounder MM, Boland PJ, Bilsky MH, Laufer I, Schmitt AM, Yamada Y, Higginson DS. Treatment of dedifferentiated chordoma: a retrospective study from a large volume cancer center. J Neurooncol. 2019;144(2):369–376. doi: 10.1007/s11060-019-03239-3

[50] Nachwalter R.N., Rothrock R.J., Katsoulakis E., Gounder M.M., Boland P.J., Bilsky M.H., Laufer I., Schmitt A.M., Yamada Y., Higginson D.S. Treatment of dedifferentiated chordoma: a retrospective study from a large volume cancer center // J Neurooncol. 2019. Vol. 144, № 2. Р. 369–376. doi: 10.1007/s11060-019-03239-3

[51] Yeter HG, Kosemehmetoglu K, Soylemezoglu F. Poorly differentiated chordoma: review of 53 cases. APMIS. 2019;127(9):607–615. doi: 10.1111/apm.12978

[52] Yeter H.G., Kosemehmetoglu K., Soylemezoglu F. Poorly differentiated chordoma: review of 53 cases // APMIS. 2019. Vol. 127, № 9. Р. 607–615. doi: 10.1111/apm.12978

[53] Varga PP, Szövérfi Z, Lazary A. Surgical treatment of primary malignant tumors of the sacrum. Neurol Res. 2014;36(6):577–87. doi: 10.1179/1743132814Y.0000000366

[54] Varga P.P., Szövérfi Z., Lazary A. Surgical treatment of primary malignant tumors of the sacrum // Neurol Res. 2014. Vol. 36, № 6. Р. 577–87. doi: 10.1179/1743132814Y.0000000366

[55] Fourney DR, Rhines LD, Hentschel SJ, Skibber JM, Wolinsky JP, Weber KL, Suki D, Gallia GL, Garonzik I, Gokaslan ZL. En bloc resection of primary sacral tumors: classification of surgical approaches and outcome. J Neurosurg Spine. 2005;3(2):111–22. doi: 10.3171/spi.2005.3.2.0111

[56] Fourney D.R., Rhines L.D., Hentschel S.J., Skibber J.M., Wolinsky J.P., Weber K.L., Suki D., Gallia G.L., Garonzik I., Gokaslan Z.L. En bloc resection of primary sacral tumors: classification of surgical approaches and outcome // J Neurosurg Spine. 2005. Vol. 3, № 2. Р. 111–22. doi: 10.3171/spi.2005.3.2.0111

[57] Musaev ERo. Modern approaches to surgical treatment of patients with pelvic bone tumors [dissertation]: 14.00.14. Moscow; 2008. 46 р. Available from: https://medical-diss.com/medicina/sovremennye-podhody-k-hirurgicheskomu-lecheniyu-bolnyh-opuholyami-kostey-taza (In Russ).

[58] Мусаев Э.Р.о. Современные подходы к хирургическому лечению больных с опухолями костей таза: автореферат дис. … доктора медицинских наук: 14.00.14. Москва, 2008. 46 с. Режим доступа: https://medical-diss.com/medicina/sovremennye-podhody-k-hirurgicheskomu-lecheniyu-bolnyh-opuholyami-kostey-taza

[59] Ailon T, Torabi R, Fisher CG, Rhines LD, Clarke MJ, Bettegowda C, Boriani S, Yamada YJ, Kawahara N, Varga PP, Shin JH, Saghal A, Gokaslan ZL. Management of Locally Recurrent Chordoma of the Mobile Spine and Sacrum: A Systematic Review. Spine (Phila Pa 1976). 2016;41(Suppl 20):S193–S198. doi: 10.1097/BRS.0000000000001812

[60] Ailon T., Torabi R., Fisher C.G., Rhines L.D., Clarke M.J., Bettegowda C., Boriani S., Yamada Y.J., Kawahara N., Varga P.P., Shin J.H., Saghal A., Gokaslan Z.L. Management of Locally Recurrent Chordoma of the Mobile Spine and Sacrum: A Systematic Review // Spine (Phila Pa 1976). 2016. Vol. 41 (Suppl 20). Р. S193–S198. doi: 10.1097/BRS.0000000000001812

[61] Zoccali C, Skoch J, Patel AS, Walter CM, Maykowski P, Baaj AA. Residual neurological function after sacral root resection during en-bloc sacrectomy: a systematic review. Eur Spine J. 2016;25(12):3925–3931. doi: 10.1007/s00586-016-4450-3

[62] Zoccali C., Skoch J., Patel A.S., Walter C.M., Maykowski P., Baaj A.A. Residual neurological function after sacral root resection during en-bloc sacrectomy: a systematic review // Eur Spine J. 2016. Vol. 25, № 12. Р. 3925–3931. doi: 10.1007/s00586-016-4450-3

[63] Cheng EY, Ozerdemoglu RA, Transfeldt EE, Thompson RC Jr. Lumbosacral chordoma. Prognostic factors and treatment. Spine (Phila Pa 1976). 1999;24(16):1639–45. doi: 10.1097/00007632-199908150-00004

[64] Cheng E.Y., Ozerdemoglu R.A., Transfeldt E.E., Thompson R.C. Jr. Lumbosacral chordoma. Prognostic factors and treatment // Spine (Phila Pa 1976). 1999. Vol. 24, № 16. Р. 1639–45. doi: 10.1097/00007632-199908150-00004

[65] Demizu Y, Jin D, Sulaiman NS, Nagano F, Terashima K, Tokumaru S, Akagi T, Fujii O, Daimon T, Sasaki R, Fuwa N, Okimoto T. Particle Therapy Using Protons or Carbon Ions for Unresectable or Incompletely Resected Bone and Soft Tissue Sarcomas of the Pelvis. Int J Radiat Oncol Biol Phys. 2017;98(2):367–374. doi: 10.1016/j.ijrobp.2017.02.030

[66] Demizu Y., Jin D., Sulaiman N.S., Nagano F., Terashima K., Tokumaru S., Akagi T., Fujii O., Daimon T., Sasaki R., Fuwa N., Okimoto T. Particle Therapy Using Protons or Carbon Ions for Unresectable or Incompletely Resected Bone and Soft Tissue Sarcomas of the Pelvis // Int J Radiat Oncol Biol Phys. 2017. Vol. 98, № 2. Р. 367–374. doi: 10.1016/j.ijrobp.2017.02.030

[67] Jin CJ, Berry-Candelario J, Reiner AS, Laufer I, Higginson DS, Schmitt AM, Lis E, Barzilai O, Boland P, Yamada Y, Bilsky MH. Long-term outcomes of high-dose single-fraction radiosurgery for chordomas of the spine and sacrum. J Neurosurg Spine. 2019:1–10. doi: 10.3171/2019.7.SPINE19515

[68] Jin C.J., Berry-Candelario J., Reiner A.S., Laufer I., Higginson D.S., Schmitt A.M., Lis E., Barzilai O., Boland P., Yamada Y., Bilsky M.H. Long-term outcomes of high-dose single-fraction radiosurgery for chordomas of the spine and sacrum // J Neurosurg Spine. 2019. Р. 1–10. doi: 10.3171/2019.7.SPINE19515

[69] Ozair MZ, Shah PP, Mathios D, Lim M, Moss NS. New Prospects for Molecular Targets for Chordomas. Neurosurg Clin N Am. 2020;31(2):289–300. doi: 10.1016/j.nec.2019.11.004

[70] Ozair M.Z., Shah P.P., Mathios D., Lim M., Moss N.S. New Prospects for Molecular Targets for Chordomas // Neurosurg Clin N Am. 2020. Vol. 31, № 2. Р. 289–300. doi: 10.1016/j.nec.2019.11.004

[71] Akinduro OO, Suarez-Meade P, Garcia D, Brown DA, Sarabia-Estrada R, Attia S, Gokaslan ZL, Quiñones-Hinojosa A. Targeted Therapy for Chordoma: Key Molecular Signaling Pathways and the Role of Multimodal Therapy. Target Oncol. 2021;16(3):325–337. doi: 10.1007/s11523-021-00814-5

[72] Akinduro O.O., Suarez-Meade P., Garcia D., Brown D.A., Sarabia-Estrada R., Attia S., Gokaslan Z.L., Quiñones-Hinojosa A. Targeted Therapy for Chordoma: Key Molecular Signaling Pathways and the Role of Multimodal Therapy // Target Oncol. 2021. Vol. 16, № 3. Р. 325–337. doi: 10.1007/s11523-021-00814-5

[73] Yang X, Li P, Kang Zh, Li W. Targeted therapy, immunotherapy, and chemotherapy for chordoma. Curr Med. 2023;2(3). doi: 10.1007/s44194-022-00017-8

[74] Yang X., Li P., Kang Zh., Li W. Targeted therapy, immunotherapy, and chemotherapy for chordoma // Curr Med. 2023. Vol. 2, № 3. doi: 10.1007/s44194-022-00017-8

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