Clinical outcome of central conventional chondrosarcoma
IV Department of Orthopaedics, University of Bologna, Istituto Ortopedico Rizzoli, Bologna, Italy. Journal of Surgical Oncology
(Impact Factor: 3.24).
12/2012; 106(8). DOI: 10.1002/jso.23173
INTRODUCTION: Aim of this study was to analyze (1) survival, local recurrence (LR), and metastasis rates between the three histological tumor grades; (2) whether type of treatment and tumor site influenced prognosis for each histologic grade. METHODS: We retrospectively studied 296 patients with central conventional chondrosarcomas (CS) (87 grade 1, 162 grade 2, and 47 grade 3). The femur was the most common site (91 cases), followed by the pelvis (82) and other less frequent sites. Type of surgery was related with histologic grade. Margins were wide in 222 cases, marginal in 23, and intralesional in 51 cases. RESULTS: At a mean of 7 years, 201 patients remained continuously NED, 33 were NED after treatment of relapse, 15 were AWD, 35 were died of disease, and 12 of other causes. Survival was 92% at 5 years and 84% at 10 years, significantly influenced by histological grading. In grade 3 CS, two factors influenced survival: type of surgery (resection vs. amputation, P = 0.051) and site (P = 0.039). The two significant factors lost their significance at multivariate analysis. CONCLUSION: Central conventional CS with low/intermediate grade has a good prognosis, while high-grade tumors have poor outcome. Tumor relapses are strictly related with histologic grade. J. Surg. Oncol © 2012 Wiley Periodicals, Inc.
Figures in this publication
Available from: Javier Vaquero
- "However, it is not easy to find homogenous samples that avoid mixing histological grades (with low grade cases often being included), as well as staging. These are the 2 prognostic factors with most extensive evidence.2,3,14,15,21,22,31,36,37In our cohort, survival between the first and second year decreased from nearly 80% to 54%, reaching 46% at the end of the follow-up period, thus reflecting a stability in the rate of overall survival after the second year. "
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The low incidence and histological heterogeneity of primary sarcomas located in the pelvis makes it difficult to find homogeneous cohorts.
To describe the life and functional prognosis depending on the histological type of sarcoma in a series of locally advanced high-grade pelvis located sarcomas treated by hemipelvectomy.
A descriptive epidemiological and functional study was conducted on 15 cases treated between 2006 and 2012. Survival analysis, functional assessment, and a comparative study by histological type were performed, comparing chondrosarcomas to other histological diagnoses.
The most frequent histological type was chondrosarcoma (46%), and the most frequent location was P2 (periacetabular) (73%). An internal hemipelvectomy was performed in 66% of cases, with a higher incidence (83%) in chondrosarcomas. Overall two-year survival was 54%, with higher survival in the chondrosarcoma group (67%) than in the other sarcomas (43%). Functional status depended on the type of intervention, with no differences in histological type or the performance of the reconstruction.
Discussion and conclusions:
Hemipelvectomy is a surgical procedure that is indicated for the treatment of locally advanced high grade pelvis located sarcomas, regardless of histological type. The incidence of limb preservation and overall survival is higher in chondrosarcomas compared to other sarcomas.
Available from: Judith Bovee
- "CS belong to a very diverse group of tumors having in common the production of cartilaginous matrix. Almost 90% of the CS are of the conventional subtype, but there are also the more rare subtypes with their own distinct histological and clinical features including clear cell, mesenchymal and dedifferentiated CS
. The prognosis for patients with CS is very diverse with a very good prognosis for atypical cartilaginous tumour/CS grade I which are slow growing and do not metastasize and a poor prognosis for grade III CS which have a high risk, up to 70%, for local recurrence and metastasis
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The majority of patients with chondrosarcoma of bone have an excellent overall survival after local therapy. However, in case of unresectable locally advanced or metastatic disease the outcome is poor and limited treatment options exist. Therefore we conducted a survey of clinical phase I or II trials and retrospective studies that described systemic therapy for chondrosarcoma patients.
Materials and methods
Using PubMed, clinicaltrials.gov, the Cochrane controlled trial register and American Society of Clinical Oncology (ASCO) abstracts a literature survey was conducted. From the identified items, data were collected by a systematic analysis. We limited our search to semi-recent studies published between 2000 and 2013 to include modern drugs, imaging techniques and disease evaluations.
A total of 31 studies were found which met the criteria: 9 phase I trials, 11 phase II and 8 retrospective studies. In these studies 855 chondrosarcoma patients were reported. The tested drugs were mostly non-cytotoxic, either alone or in combination with another non-cytotoxic agent or chemotherapy. Currently two phase I trials, one phase IB/II trial and three phase II trials are enrolling chondrosarcoma patients.
Because chondrosarcoma of bone is an orphan disease it is difficult to conduct clinical trials. The meagre outcome data for locally advanced or metastatic patients indicate that new treatment options are needed. For the phase I trials it is difficult to draw conclusions because of the low numbers of chondrosarcoma patients enrolled, and at different dose levels. Some phase II trials show promising results which support further research. Retrospective studies are encouraged as they could add to the limited data available. Efforts to increase the number of studies for this orphan disease are urgently needed.
Available from: Catherine Bauge
- "With the advent of systemic chemotherapy in the management of mesenchymal malignancies such as osteosarcoma and Ewing's sarcoma, there has been an increase in the long-term survival of patients. In contrast, chondrosarcomas continue to have a poor prognosis owing to the absence of an effective therapy –. Identifying new drugs that enables to reduce chondrosarcoma growth may improve survival of patients. Here, we identified, 3-Deazaneplanocin A (DZNep), a small molecule EZH2 inhibitor , , as a putative treatment of chondrosarcomas. "
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Growing evidences indicate that the histone methyltransferase EZH2 (enhancer of zeste homolog 2) may be an appropriate therapeutic target in some tumors. Indeed, a high expression of EZH2 is correlated with poor prognosis and metastasis in many cancers. In addition, 3-Deazaneplanocin A (DZNep), an S-adenosyl-L homocysteine hydrolase inhibitor which induces EZH2 protein depletion, leads to cell death in several cancers and tumors. The aim of this study was to determine whether an epigenetic therapy targeting EZH2 with DZNep may be also efficient to treat chondrosarcomas.
EZH2 expression was determined by immunohistochemistry and western-blot. Chondrosarcoma cell line CH2879 was cultured in the presence of DZNep, and its growth and survival were evaluated by counting adherent cells periodically. Apoptosis was assayed by cell cycle analysis, Apo2.7 expression using flow cytometry, and by PARP cleavage using western-blot. Cell migration was assessed by wound healing assay.
Chondrosarcomas (at least with high grade) highly express EZH2, at contrary to enchondromas or chondrocytes. In vitro, DZNep inhibits EZH2 protein expression, and subsequently reduces the trimethylation of lysine 27 on histone H3 (H3K27me3). Interestingly, DZNep induces cell death of chondrosarcoma cell lines by apoptosis, while it slightly reduces growth of normal chondrocytes. In addition, DZNep reduces cell migration.
These results indicate that an epigenetic therapy that pharmacologically targets EZH2 via DZNep may constitute a novel approach to treat chondrosarcomas.
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