Primary chondrosarcoma of bone: a clinicopathological and oncological outcome analysis

INTRODUCTION

Chondrosarcoma, although relatively uncommon, constitutes a significant percentage of primary malignant osseous tumors. Following osteosarcoma, it is the second most common primary solid tumor of bone. Chondrosarcoma primarily affect adults with incidence rising with increasing age.¹ Survival rate of patients with chondrosarcoma is higher than that of osteosarcoma and Ewing’s sarcoma with 5-year survival rate between 72-75% and 10 year survival rate of 69%.^2-4 The standard treatment for chondrosarcoma is surgical excision with adequate margins. This can be because chondrosarcomas are resistant to both chemotherapy and radiotherapy due to poor vascularity, high extracellular matrix and low percentage of dividing cells.⁵ This study aims to analyse the demographic, clinical, pathological, and survival characteristics of chondrosarcoma cases at a tertiary care institute.

CASE SERIES

We report 20 cases of chondrosarcoma in the last 9 years with mean age of 45.2 years. Age at diagnosis ranged from 26 to 65 years. Out of 20 cases, 14 were male and 6 were female as shown in Table 1 and 2.

The 60% of cases were in extremities with lower extremity being most common, 30% in chest wall and 10% involving the pelvis. High grade tumor was more common constituting 60% of cases and low grade tumors 40% of cases. The most common pathological subtype of chondrosarcoma was conventional type (70%) and mesenchymal type (30%). The X-ray of local part was taken for all cases and majority showed features of lytic lesion with calcifications, cortical thickening and wide zone of transition. High grade lesions had permeative pattern, minimal or no calcifications, cortical breach on the X-ray.

*DFS-disease free survival, **OS-overall survival.

All 20 cases had undergone surgery according to the site of tumor namely hemipelvectomy for pelvic tumors (2 cases), bone resection with custom made prosthesis reconstruction for extremity tumors (12), wide local excision of chest wall tumors (7 cases), unilateral hip disarticulation (1case) and below knee amputation for ankle tumor (1 case). After complete surgical resection (R0 resection), none of the patients received adjuvant radiotherapy or chemotherapy.

Out of 20 patients, 3 patients developed lung metastasis during follow-up with average disease-free interval of 3 years and all 3 had high grade chondrosarcomas. All three were given palliative chemotherapy and all 3 died due to progressive disease. One patient who had chondrosarcoma of proximal femur and underwent hip disarticulation developed local recurrence after a disease-free period of 5 years for which hemipelvectomy was done. The 5-year disease-free survival is 85%, and 5-year overall survival is 85%.

DISCUSSION

Chondrosarcoma is the 2^nd most common primary osseous tumor behind osteosarcomas and makes up about 25% of total prevalence of bone tumors.⁶ Chondrosarcoma occurs predominantly in patients aged 50-70 years.^7,8 In our study, 50% cases were in patients aged <45 years and 50 % in patients >45 years. The most common location of involvement chondrosarcoma includes bones of axial skeleton (pelvis, scapula, sternum, ribs) followed by proximal humerus.⁹ In our study, 55% of tumors were found in lower limbs followed by chest wall (35%).

Most common subtype of chondrosarcoma in our study was conventional type. Primary or conventional chondrosarcoma arise in normal bone and is distinguished from rarer secondary tumors which occur in pre-existing enchondromas or osteochondroma.⁹ Conventional chondrosarcomas account for 85-95% of chondrosarcomas and is subdivided into central, peripheral and periosteal. Non-conventional variants include clear cell, mesenchymal, dedifferentiated chondrosarcomas.¹⁰ There are very limited treatment options for chondrosarcoma. Typically, chondrosarcomas are insensitive to chemotherapy and radiotherapy.¹¹ All the patients in our study had non metastatic disease at initial presentation and had undergone upfront surgery and none of them required adjuvant chemotherapy and radiation due complete resection. Zhan Wang et.al reported that surgical treatment of primary tumors would increase survival of metastatic chondrosarcomas.¹²

The most common site of distant metastasis in chondrosarcomas is the lung. Out of 20 patients, 3 of them developed lung metastasis during follow up period and received palliative chemotherapy but survived less than a year. All three had high grade chondrosarcoma (2 were conventional type and 1 was mesenchymal type). Conventional chondrosarcoma does not respond to chemotherapy.¹³ Additionally chemotherapy was not associated with improved survival.^14,15

Among the three most common primary sarcomas of the bone, chondrosarcoma has been shown to have the highest 5-year survival rate.³ The 5-year survival of grade I chondrosarcomas is 83%. In our study the 5 year- disease free survival is 85% and overall survival 85%. The 5-year survival of grade II and III chondrosarcomas is of 53%.¹⁶ The higher survival rate in high grade tumors in our case series is probably due to complete surgical resection with adequate negative margins.

CONCLUSION

This study has shown a variable incidence of chondrosarcoma in terms of age and tumor location. The continued role of surgical intervention over the years as the mainstay of treatment for both appendiceal and axial chondrosarcomas has been demonstrated in this study. Long -term survival of patients with chondrosarcoma depends on completeness of surgical resection which has been illustrated in our study. Also, survival rates vary significantly based on grade and metastases. Appropriate preoperative surgical planning enables completeness of surgical resection and good oncological outcomes.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: Not required

REFERENCES

1. 1. Hartley AL, Blair V, Harris M, Birch JM, Banerjee SS, Freemont AJ, et al. Sarcomas in north west England: II. Incidence. Br J Cancer. 1991;64(6):1145-50.
2. 2. Andreou D, Ruppin S, Fehlberg S, Pink D, Werner M, Tunn PU. Survival and prognostic factors in chondrosarcoma: results in 115 patients with long-term follow-up. Acta Orthop. 2011;82(6):749-55.
3. 3. Damron TA, Ward WG, Stewart A. Osteosarcoma, chondrosarcoma, and Ewing’s sarcoma: National Cancer Data Base Report. Clin Orthop Related Res. 2007;459:40-7.
4. 4. Wang Z, Chen G, Chen X, Huang X, Liu M, Pan W, et al. Predictors of the survival of patients with chondrosarcoma of bone and metastatic disease at diagnosis. J Cancer. 2019;10(11):2457-63.
5. 5. Gelderblom H, Hogendoorn PC, Dijkstra SD, van Rijswijk CS, Krol AD, Taminiau AH, et al. The clinical approach towards chondrosarcoma. Oncologist. 2008;13(3):320-9.
6. 6. Andreou D, Ruppin S, Fehlberg S, Pink D, Werner M, Tunn PU. Survival and prognostic factors in chondrosarcoma: results in 115 patients with long-term follow-up. Acta Orthop. 2011;82(6):749-55.
7. 7. Nakagawa M, Nakatani F, Matsunaga H, Seki T, Endo M, Ogawara Y, et al. Selective inhibition of mutant IDH1 by DS-1001b ameliorates aberrant histone modifications and impairs tumor activity in chondrosarcoma. Oncogene. 2019;38(42):6835-49.
8. 8. Heymann MF, Schiavone K, Heymann D. Bone sarcomas in the immunotherapy era. Br J Pharmacol. 2021;178(9):1955-72.
9. 9. Thorkildsen J, Taksdal I, Bjerkehagen B, Haugland HK, Børge Johannesen T, Viset T, et al. Chondrosarcoma in Norway 1990-2013; an epidemiological and prognostic observational study of a complete national cohort. Acta Oncol. 2019;58(3):273-82.
10. 10. Nazeri E, Gouran Savadkoohi M, Majidzadeh-A K, Esmaeili R. Chondrosarcoma: An overview of clinical behavior, molecular mechanisms mediated drug resistance and potential therapeutic targets. Crit Rev Oncol Hematol. 2018;131:102-9.
11. 11. Lohberger B, Glaenzer D, Eck N, Steinecker-Frohnwieser B, Leithner A, Rinner B, et al. Effects of a combined therapy of bortezomib and ionizing radiation on chondrosarcoma three-dimensional spheroid cultures. Oncol Lett. 2021;21(6):428.
12. 12. Wang Z, Chen G, Chen X, Huang X, Liu M, Pan W, et al. Predictors of the survival of patients with chondrosarcoma of bone and metastatic disease at diagnosis. J Cancer. 2019;10(11):2457-63.
13. 13. Weinschenk RC, Wang WL, Lewis VO. Chondrosarcoma. J Am Acad Orthop Surg. 2021;29(13):553-62.
14. 14. Wu X, Wang Y, Sun W, Tan M. Prognostic factors and a nomogram predicting overall survival in patients with limb chondrosarcomas: a population-based study. BioMed Res Int. 2021;4510423.
15. 15. Cranmer LD, Chau B, Mantilla JG, Loggers ET, Pollack SM, Kim TS, et al. Is chemotherapy associated with improved overall survival in patients with dedifferentiated chondrosarcoma? A SEER database analysis. Clin Orthop Relat Res. 2022;480(4):748-58.
16. 16. Gelderblom H, Hogendoorn PC, Dijkstra SD, van Rijswijk CS, Krol AD, Taminiau AH, et al. The clinical approach towards chondrosarcoma. Oncologist. 2008;13(3):320-9.