Guideline sources The following summarized guidelines for the evaluation and management of chondrosarcoma are prepared by our editorial team based on guidelines from the European Reference Network on Genetic Tumour Risk Syndromes (GENTURIS/ERN PaedCan/EURACAN/ESMO 2021), the National Comprehensive Cancer Network (NCCN 2021), and the Spanish Group for Research on Sarcomas (GEIS 2017). 1 2 3 Calculator Calculator Calculator Eastern Cooperative Oncology G Karnofsky performance status s TNM class Guidelines https://web.pathway.md/diseases/recesWUDo2114dnji 1/6 6/29/23, 3:51 AM Chondrosarcoma Pathway 1. Diagnostic investigations History and physical examination: as per ESMO 2021 guidelines, elicit medical history and perform physical examination in the initial work-up of patients with suspected primary bone sarcoma. B Imaging for staging: Obtain radiological assessment in the initial work-up of patients with suspected primary bone sarcoma. B Obtain the following imaging modalities as clinically indicated for general staging to assess the extent of distant disease, to detect lung, bone and bone marrow metastases: chest CT bone scintigraphy whole body-MRI 18F-FDG positron emission tomography-CT/MRI. B 2. Diagnostic procedures Biopsy and pathology: perform biopsy in the initial work-op of patients with suspected primary bone sarcoma. B Show 2 more 3. Medical management Setting of care: manage patients with bone sarcomas at reference centers and/or within reference networks able to provide access to the full spectrum of care and age-specific expertise. B Chemotherapy: As per ESMO 2021 guidelines: Offer neoadjuvant/adjuvant chemotherapy combining anthracycline and alkylating agents in patients with localized mesenchymal chondrosarcomas. B Consider offering neoadjuvant/adjuvant chemotherapy in patients with localized differentiated chondrosarcomas. C As per NCCN 2021 guidelines, recognize that there are no known standard chemotherapy options available for patients with conventional chondrosarcomas (grades I-III). B Show 2 more As per GEIS 2017 guidelines: Avoid using adjuvant therapy in patients with conventional chondrosarcomas due to its low sensitivity to chemotherapy. D Consider offering adjuvant or neoadjuvant therapy, mainly with Ewing's sarcoma-like regimens, in patients with mesenchymal chondrosarcomas because these tumors are more https://web.pathway.md/diseases/recesWUDo2114dnji 2/6 6/29/23, 3:51 AM Chondrosarcoma Pathway chemotherapy-sensitive. C Management of metastatic disease: As per ESMO 2021 guidelines: Recognize that chemotherapy in patients with widely metastatic disease is of limited benefit, with higher responses seen in patients receiving combination anthracycline-based therapy and those with differentiated or mesenchymal chondrosarcomas. Consider offering trabectedin as an option in patients with mesenchymal chondrosarcoma. B Consider offering the following options in patients with oligometastatic, resectable lung disease, especially with conventional chondrosarcomas: surgery radiotherapy local ablation. C As per NCCN 2021 guidelines: Offer the following options in patients with oligometastatic chondrosarcoma: surgical excision of all sites if possible consider radiotherapy for unresectable sites consider enrollment in a clinical trial. B Offer the following options in patients with widespread disease: consider radiotherapy, surgery, and/or ablative therapies for symptomatic sites consider systemic therapy (sasatinib, pazopanib) consider enrollment in a clinical trial. B As per GEIS 2017 guidelines, recognize that patients with inoperable or metastatic high-grade chondrosarcomas have a poor prognosis because of resistance to conventional treatments, such as radiotherapy and chemotherapy. B Show 2 more Management of recurrent disease: As per ESMO 2021 guidelines, consider offering radiotherapy in patients with recurrent unresectable disease. C As per NCCN 2021 guidelines, perform wide excision, if resectable, B or offer radiotherapy, if unresectable, in patients with local recurrence of low-grade, intracompartmental, high-grade, clear cell or extracompartmental chondrosarcoma. B Show 2 more As per GEIS 2017 guidelines, perform surgical resection (local or pulmonary) as the first option in patients with recurrence. B Show 3 more 4. Therapeutic procedures Radiotherapy: https://web.pathway.md/diseases/recesWUDo2114dnji 3/6 6/29/23, 3:51 AM Chondrosarcoma Pathway As per ESMO 2021 guidelines: Consider offering radiotherapy in patients with primary unresectable disease, after incomplete surgery and for symptoms palliation. C Offer high-dose radiotherapy in patients with skull base chondrosarcomas. B As per NCCN 2021 guidelines: Consider offering radiotherapy in patients with low-grade or intracompartmental chondrosarcomas, if unresectable. C Consider offering radiotherapy in patients with high-grade (grade II, grade III), clear cell or extracompartmental chondrosarcomas, if borderline resectable or unresectable. C As per GEIS 2017 guidelines, avoid using adjuvant therapy in patients with conventional chondrosarcomas due to its low sensitivity to radiotherapy. D Show 2 more 5. Surgical interventions Wide-local excision: Perform surgical excision with wide margins in patients with high-grade chondrosarcomas and all chondrosarcomas of the pelvis or axial skeleton. B As per NCCN 2021 guidelines, perform wide excision, if resectable, in patients with low-grade, intracompartmental, high-grade (grade II, grade III), clear cell or extracompartmental chondrosarcomas. B As per GEIS 2017 guidelines, perform surgery as the mainstay of treatment in patients with chondrosarcomas, with an approach largely depending on the grade and anatomic location. B Intralesional excision: As per ESMO 2021 guidelines, consider performing curettage with or without local adjuvant therapy (such as phenol, cement and cryotherapy), with a high chance of success in patients with atypical cartilaginous tumors in the long bones of the limbs. C As per NCCN 2021 guidelines, perform intralesional excision with or without adjuvant therapy in patients with low-grade or intracompartmental chondrosarcomas. B As per GEIS 2017 guidelines, consider performing extensive intralesional resection combined with local adjuvant treatment (high-speed burr, phenolization or cryotherapy, lavage with a high- pressure pulsatile system, and packing the defect with cement or bone graft) in patients with low-grade intracompartmental chondrosarcomas of the extremities. B 6. Specific circumstances Patients with mesenchymal chondrosarcoma: treat patients with mesenchymal chondrosarcoma as Ewing's sarcoma. B https://web.pathway.md/diseases/recesWUDo2114dnji 4/6 6/29/23, 3:51 AM Chondrosarcoma Pathway 7. Patient education Genetic counseling: consider referring selected patients with chondrosarcoma for genetic consultation and testing based on family history with a genetic predisposition for bone sarcomas. C 8. Follow-up and surveillance Surveillance: As per ESMO 2021 guidelines, consider including the following in the follow-up of patients with high-grade bone sarcomas: physical examination cross-sectional imaging plain radiograph of the primary site CXR/chest CT. C Show 2 more As per NCCN 2021 guidelines: Include the following in the surveillance of patients with low-grade or intracompartmental chondrosarcomas: physical examination radiographs of primary site and/or cross-sectional imaging MRI or CT (both with contrast) as clinically indicated every 6-12 months for 2 years, then yearly as appropriate chest imaging as clinically indicated every 6-12 months for 2 years, then yearly as appropriate. B Include the following in the surveillance of patients with high-grade (grade II, grade III), clear cell or extracompartmental chondrosarcomas: physical examination radiographs of primary site and/or cross-sectional imaging MRI or CT (both with contrast) as clinically indicated chest imaging every 3-6 months, consider obtaining include CT, at least every 6 months for 5 years, then yearly for a minimum of 10 years reassessment of function at every follow-up visit. B Clinical findings Symptoms Past medical history Localized bone pain Bone metastasis Localized bone swelling Liver metastasis Lung metastasis https://web.pathway.md/diseases/recesWUDo2114dnji 5/6 6/29/23, 3:51 AM Chondrosarcoma Pathway Pathological fracture Lab findings Imaging findings Hyperglycemia serum ALP Endochondral ossification Endosteal scalloping Genetic testing Mottled bone lesion Idh1 gene mutation Osteolytic lesion Periosteal reaction Popcorn calcification Rings and arcs calcification Thi k d ti l b References 1. S J Strauss, A M Frezza, N Abecassis et al. Bone sarcomas: ESMO EURACAN GENTURIS ERN PaedCan Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2021 Dec;32 12 1520 1536. Open 2. Andr s Redondo, Silvia Bagu , Daniel Bernabeu et al. Malignant bone tumors (other than Ewing's): clinical practice guidelines for diagnosis, treatment and follow-up by Spanish Group for Research on Sarcomas GEIS . Cancer Chemother Pharmacol. 2017 Dec;80 6 1113 1131. Open 3. J Sybil Biermann, Angela Hirbe, Warren Chow et al. Bone Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. NCCN. 2021 Oct 8. Open https://web.pathway.md/diseases/recesWUDo2114dnji 6/6