Postoperative Radiation Therapy in Patients with Extracranial Chondrosarcoma: A Joint Study of the French Sarcoma Group and Rare Cancer Network

Terlizzi, Mario; Péchoux, C. Le; Salas, Sébastien; Rapeaud, E.; Lerouge, D.; Sunyach, Marie Pierre; Vogin, Guillaume; Sole, C.V.; Zilli, Thomas; Lutsyk, Myroslav; Mampuya, Ange; Attal, Justine; Karahissarlian, V.; Bari, Berardino De; Özşahin, Mahmut; Baumard, Florian; Krengli, Marco; Gomez‐Brouchet, Anne; Sargos, P.; Rochcongar, Goulven; Bazille, Céline; Roth, Vincent; Salleron, Julia; Thariat, Juliette

doi:10.1016/j.ijrobp.2020.03.041

Cited by 7 publications

(2 citation statements)

References 33 publications

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“…In patients with chondrosarcoma with unfavorable initial characteristics, a high grade and incomplete resection, postoperative radiotherapy is an expedient option; it reduces the risk of local recurrence and improves 5-year disease-free survival from 64.2 to 71.8% (22). Chondrosarcomas exhibit variable response to irradiation, possibly due to their strong genetic heterogeneity, which is also evident in different chondrosarcoma cell lines (23,24).…”

Section: Discussionmentioning

confidence: 99%

Effects of a combined therapy of bortezomib and ionizing radiation on chondrosarcoma three-dimensional spheroid cultures

et al. 2021

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Chondrosarcomas represent a heterogeneous group of primary bone cancers that are characterized by hyaline cartilaginous neoplastic tissue and are predominantly resistant to radiation and chemotherapy. However, adjuvant radiotherapy is often recommended in inoperable cases or after incomplete resections. To improve the efficiency of treatment, the present study tested a combination therapy with ionizing radiation (IR) and the proteasome inhibitor bortezomib. Using a three-dimensional (3D) spheroid model, 0-20 Gy of IR was applied to chondrosarcoma cells and healthy human chondrocytes. Following combined treatment with IR and bortezomib, the cell cycle distribution, apoptotic induction, the survivin pathway, autophagy and DNA damage were evaluated. Both cell types exhibited a slight decrease in viability following increasing doses of IR; the chondrosarcoma cells demonstrated a significant dose-dependent increase in the expression levels of the DNA damage marker histone H2AX phosphorylation at serine 139 (γH2AX). The combination treatment with bortezomib significantly decreased the cell viability after 48 h compared with that in irradiated cells. High-dose IR induced a G 2 /M phase arrest, which was accompanied by a decrease in the number of cells at the G 1 and S phase. Co-treatment with bortezomib changed the distribution of the cell cycle phases. The mRNA expression levels of the proapoptotic genes Bcl-2-associated X protein (Bax) and Bak were significantly increased by bortezomib treatment and combination therapy with IR. In addition, the combination therapy resulted in a synergistic decrease of the expression levels of survivin and its corresponding downstream pathway molecules, including heat shock protein 90, X-linked inhibitor of apoptosis protein, smad 2 and smad 3. Comparative analyses of γH2AX at 1 and 24 h post-IR revealed efficient DNA repair in human chondrosarcoma cells. Therefore, additional bortezomib treatment may only temporarily improve the radiation sensitivity of chondrosarcoma cells. However, the inhibition of the survivin pathway by the combined treatment with IR and bortezomib, observed in the present study, revealed a novel aspect in the tumor biology of chondrosarcoma 3D spheroid cultures and may represent a potential target for therapy.

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Section: Discussionmentioning

confidence: 99%

Effects of a combined therapy of bortezomib and ionizing radiation on chondrosarcoma three-dimensional spheroid cultures

et al. 2021

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“…Additionally, research published in the past year has suggested that tumor grade has a significant impact on radiation responsiveness in chondrosarcoma. 68 To better appreciate the relative influence of charged-particle therapies on LC and OS, it will be necessary to incorporate these factors. Last, from a practical standpoint, proton treatment is offered in relatively few centers in the US, which may limit the feasibility of this treatment for patients from some geographic regions.…”

Section: Study Limitationsmentioning

confidence: 99%

Systematic review of charged-particle therapy for chordomas and sarcomas of the mobile spine and sacrum

Pennington

Ehresman

Elsamadicy

et al. 2021

Neurosurgical Focus

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OBJECTIVE Long-term local control in patients with primary chordoma and sarcoma of the spine and sacrum is increasingly reliant upon en bloc resection with negative margins. At many institutions, adjuvant radiation is recommended; definitive radiation is also recommended for the treatment of unresectable tumors. Because of the high off-target radiation toxicities associated with conventional radiotherapy, there has been growing interest in the use of proton and heavy-ion therapies. The aim of this study was to systematically review the literature regarding these therapies. METHODS The PubMed, OVID, Embase, and Web of Science databases were queried for articles describing the use of proton, combined proton/photon, or heavy-ion therapies for adjuvant or definitive radiotherapy in patients with primary sarcoma or chordoma of the mobile spine and sacrum. A qualitative synthesis of the results was performed, focusing on overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), and disease-specific survival (DSS); local control; and postradiation toxicities. RESULTS Of 595 unique articles, 64 underwent full-text screening and 38 were included in the final synthesis. All studies were level III or IV evidence with a high risk of bias; there was also significant overlap in the reported populations, with six centers accounting for roughly three-fourths of all reports. Five-year therapy outcomes were as follows: proton-only therapies, OS 67%–82%, PFS 31%–57%, and DFS 52%–62%; metastases occurred in 17%–18% and acute toxicities in 3%–100% of cases; combined proton/photon therapy, local control 62%–85%, OS 78%–87%, PFS 90%, and DFS 61%–72%; metastases occurred in 12%–14% and acute toxicities in 84%–100% of cases; and carbon ion therapy, local control 53%–100%, OS 52%–86%, PFS (only reported for 3 years) 48%–76%, and DFS 50%–53%; metastases occurred in 2%–39% and acute toxicities in 26%–48%. There were no studies directly comparing outcomes between photon and charged-particle therapies or comparing outcomes between radiation and surgical groups. CONCLUSIONS The current evidence for charged-particle therapies in the management of sarcomas of the spine and sacrum is limited. Preliminary evidence suggests that with these therapies local control and OS at 5 years are comparable among various charged-particle options and may be similar between those treated with definitive charged-particle therapy and historical surgical cohorts. Further research directly comparing charged-particle and photon-based therapies is necessary.

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Radiation Therapy in Chondrosarcoma

Ayestaran

Palma

2023

Radiation Oncology

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Postoperative Radiation Therapy in Patients with Extracranial Chondrosarcoma: A Joint Study of the French Sarcoma Group and Rare Cancer Network

Cited by 7 publications

References 33 publications

Effects of a combined therapy of bortezomib and ionizing radiation on chondrosarcoma three-dimensional spheroid cultures

Effects of a combined therapy of bortezomib and ionizing radiation on chondrosarcoma three-dimensional spheroid cultures

Systematic review of charged-particle therapy for chordomas and sarcomas of the mobile spine and sacrum

Radiation Therapy in Chondrosarcoma

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