Revisiting the Role of Radiation Therapy in Chondrosarcoma: A National Cancer Database Study

Abstract

Background Although chondrosarcomas (CS) are mostly considered radioresistant, advancements in radiotherapy have brought attention to its use in these patients. Using the largest registry of primary bone tumors, the National Cancer Database (NCDB), we sought to better characterize the current use of radiotherapy in CS patients and identify any potential survival benefit with higher radiation doses and advanced radiation therapies. Methods We retrospectively analyzed CS patients in the NCDB from 2004 to 2015 who underwent radiotherapy. The Kaplan–Meier method with statistical comparisons was used to identify which individual variables related to dosage and delivery modality were associated with improved 5-year survival rates. Multivariate proportional hazards analyses were performed to determine independent predictors of survival. Results Of 5,427 patients with a histologic diagnosis of chondrosarcoma, 680 received a form of radiation therapy (13%). The multivariate proportional hazards analysis controlling for various patient, tumor, and treatment variables, including RT dose and modality, demonstrated that while overall radiation therapy (RT) was not associated with improved survival (HR 0.96, 95% CI 0.76–1.20), when examining just the patient cohort with positive surgical margins, RT trended towards improved survival (HR 0.81, 95% CI 0.58–1.13). When comparing advanced and conventional RT modalities, advanced RT was associated with significantly decreased mortality (HR 0.55, 95% CI 0.38–0.80). However, advanced modality and high-dose RT both trended only toward improved survival compared to patients who did not receive any RT (HR 0.74, 95% CI 0.52–1.06 and HR 0.93, 95% CI 0.71–1.21, respectively). Conclusions Despite the suggested radioresistance of CS, modern radiotherapies may present a treatment option for certain patients. Our results support a role for high-dose, advanced radiation therapies in selected high-risk CS patients with tumors in surgically challenging locations or unplanned positive margins. While there is an associated survival rate benefit, further, prospective studies are needed for validation.

Selection of Effective Therapies Using Three-Dimensional in vitro Modeling of Chondrosarcoma

“…In two retrospective studies: Advanced modality radiation treatment and higher dose treatment associated with improved survival in positive margin patient cohort (n = ?/680) † (Catanzano et al, 2019). For patients who had locally advanced disease without metastases, radiotherapy was associated with a survival benefit (n = 45) (Van Maldegem et al, 2014).…”

“…Advanced radiotherapy modalities may be able to overcome the observed resistance, because radio resistance has been linked to the total radiation dose applied, and modern techniques enable the safe application of a higher total dose. Current clinical data indeed show that the use of advanced radiation modalities, such as intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), stereotactic radiosurgery (SRS) and especially particle therapy (radiotherapy with protons or carbon ions) result in a trend toward improved survival with higher radiation doses applied for patients with positive margins after resection (Weber et al, 2016;Catanzano et al, 2019). Therefore, the 3D chondrosarcoma spheroid model provides an excellent model to further investigate the use of these modalities for chondrosarcoma.…”

Targeting cancer stem cells by disulfiram and copper sensitizes radioresistant chondrosarcoma to radiation

“…Chondrosarcoma (CS) is the second most common primary bone tumor in adults [ 1 , 2 ] and characteristically produces cartilage matrix from neoplastic tissue devoid of osteoid. Radiotherapy (RT) is standard care for cases of incompletely resected or inoperable tumors [ 3 , 4 ]. However, RT for such tumors is not associated with improved survival, and only patients receiving both high-dose and advanced RT had improved survival compared to patients who did not receive RT [ 4 ].…”

“…Radiotherapy (RT) is standard care for cases of incompletely resected or inoperable tumors [ 3 , 4 ]. However, RT for such tumors is not associated with improved survival, and only patients receiving both high-dose and advanced RT had improved survival compared to patients who did not receive RT [ 4 ].…”

Estado actual del condrosarcoma en un centro de referencia

“…De nuestra serie, 28 pacientes (32.9%) recibieron tratamiento con radioterapia, la indicación fue en aquellos tumores en esqueleto axial irresecables o en las recurrencias en esqueleto axial irresecables. 17 Nuestro estudio tiene limitaciones que se relacionan directamente con el carácter retrospectivo y con una gran cantidad de variables; sin embargo, presenta una serie de casos que nos da un panorama global de la enfermedad y por qué no, intentar desarrollar futuras investigaciones. Las diferentes características del CS limitan el tratamiento y condicionan un pronóstico.…”