Chondrosarcomas are notorious for their resistance to conventional chemo- and radiotherapy, indicating there are no curative treatment possibilities for patients with inoperable or metastatic disease. We therefore explored the existence of molecular targets for systemic treatment of chondrosarcoma using kinome profiling. Peptide array was performed for 4 chondrosarcoma cell lines and 9 primary chondrosarcoma cultures. Acitivity of kinases was verified using immunoblot and active Src- and PDGFR signaling were further explored using
Diffuse-type Tenosynovial Giant-Cell Tumour (d-TGCT) of large joints is a rare, locally aggressive, soft tissue tumour affecting predominantly the knee. Previously classified as Pigmented Villonodular Synovitis (PVNS), this monoarticular disease arises from the synovial lining and is more common in younger adults. Given the diffuse and aggressive nature of this tumour, local control is often difficult and recurrence rates are high. Current literature is comprised primarily of small, and a few larger but heterogeneous, observational studies. Both arthroscopic and open synovectomy techniques, or combinations thereof, have been described for the treatment of d-TGCT of the knee. There is, however, no consensus on the best approach to minimize recurrence of d-TGCT of the knee. Some limited evidence would suggest that a staged, open anterior and posterior synovectomy might be of benefit in reducing recurrence. To our knowledge, no case series has specifically looked at the recurrence rate of d-TGCT of the knee following a staged, open, posterior and anterior approach. We hypothesized that this approach may provide better recurrence rates as suggested by larger more heterogeneous series. A retrospective review of the local pathology database was performed to identify all cases of d-TGCT or PVNS of the knee treated surgically at our institution over the past 15 years. All cases were treated by a single fellowship-trained orthopaedic oncology surgeon, using a consistent, staged, open, posterior and anterior approach for synovectomy. All cases were confirmed by histopathology and followed-up with regular repeat MRI to monitor for recurrence. Medical records of these patients were reviewed to extract demographic information, as well as outcomes data, specifically recurrence rate and complications. Any adjuvant treatments or subsequent surgical interventions were noted. Twenty-three patients with a minimum follow-up of two years were identified. Mean age was 36.3 at the time of treatment. There were 10 females and 13 males. Mean follow-up was seven and a half years. Fourteen of 23 (60.9%) had no previous treatment. Five of 23 had a previous arthroscopic synovectomy, one of 23 had a previous combined anterior arthroscopic and posterior open synovectomy, and three of 23 had a previous open synovectomy. Mean time between stages was 87 days (2.9 months). Seven of 23 (30.4%) patients had a recurrence. Of these, three of seven (42.9%) were treated with
Diffuse-type Tenosynovial Giant-Cell Tumour (d-TGCT) of large joints is a rare, locally aggressive, soft tissue tumour affecting predominantly the knee. Previously classified as Pigmented Villonodular Synovitis (PVNS), this monoarticular disease arises from the synovial lining and is more common in younger adults. Given the diffuse and aggressive nature of this tumour, local control is often difficult and recurrence rates are high. Current literature is comprised primarily of small, and a few larger but heterogeneous, observational studies. Both arthroscopic and open synovectomy techniques, or combinations thereof, have been described for the treatment of d-TGCT of the knee. There is, however, no consensus on the best approach to minimize recurrence of d-TGCT of the knee. Some limited evidence would suggest that a staged, open anterior and posterior synovectomy might be of benefit in reducing recurrence. To our knowledge, no case series has specifically looked at the recurrence rate of d-TGCT of the knee following a staged, open, posterior and anterior approach. We hypothesized that this approach may provide better recurrence rates as suggested by larger more heterogeneous series. A retrospective review of the local pathology database was performed to identify all cases of d-TGCT or PVNS of the knee treated surgically at our institution over the past 15 years. All cases were treated by a single fellowship-trained orthopaedic oncology surgeon, using a consistent, staged, open, posterior and anterior approach for synovectomy. All cases were confirmed by histopathology and followed-up with regular repeat MRI to monitor for recurrence. Medical records of these patients were reviewed to extract demographic information, as well as outcomes data, specifically recurrence rate and complications. Any adjuvant treatments or subsequent surgical interventions were noted. Twenty-three patients with a minimum follow-up of two years were identified. Mean age was 36.3 at the time of treatment. There were 10 females and 13 males. Mean follow-up was seven and a half years. Fourteen of 23 (60.9%) had no previous treatment. Five of 23 had a previous arthroscopic synovectomy, one of 23 had a previous combined anterior arthroscopic and posterior open synovectomy, and three of 23 had a previous open synovectomy. Mean time between stages was 87 days (2.9 months). Seven of 23 (30.4%) patients had a recurrence. Of these, three of seven (42.9%) were treated with
Soft tissue sarcomas (STS) include a spectrum of his-tologically and clinically different tumors. Patients are typically relatively young and the course of disease is characterized by early metastasis as well as limited response to chemotherapy. However, a few subtypes such as small round cell tumors (SRCTs) and rhabdomyosarcoma (except from pleomorphic), are considered chemotherapy-sensitive. In addition, reflecting successful translational research of recent years, gastrointestinal stromal tumor (GIST) and dermatofibrosarcoma protuberans have become model diseases for targeted oncological therapy. With a very limited number of active compounds at hand, treatment choices in metastatic STS with inkonsistent genomic alterations were easy to overview until only a few years ago. However, with novel therapeutic strategies such as the antiangiogenic approach and a multitude of novel compounds available both outside and within clinical studies, it may have become more difficult to keep track of currently available treatment options and their clinical safety and efficacy. Anthracyclines with or without ifosfamide are still considered standard of care in most STS-subtypes, especially in high-grade tumors. There is no evidence-based recommendation as to second-line treatment options. However, a number of established compounds, including dacarbazine/temozolomide, gemcitabine, taxanes, trofosfamide, DNA topoisomerase I inhibitors, DNA minor groove binders, and bendamustine, have shown activity. Recently, trabectedin, a DNA minor groove binder initially isolated from a sea sponge, has proven effective and received European approval for use in treatment-refractory STS. In addition, novel compounds such as bevacizumab, multityrosine kinase inhibitors, mTOR inhibitors,
Desmoid tumours are a rare fibroblastic proliferation of monoclonal origin, arising in deep soft-tissues. Histologically, they are characterized by locally aggressive behaviour and an inability to metastasize, and clinically by a heterogeneous and unpredictable course. Desmoid tumours can occur in any anatomical site, but commonly arise in the limbs. Despite their benign nature, they can be extremely disabling and sometimes life-threatening, causing severe pain and functional limitations. Their surgical management is complex and challenging, due to uncertainties surrounding the biological and clinical behaviour, rarity, and limited available literature. Resection has been the first-line approach for patients with a desmoid tumour but, during the last few decades, a shift towards a more conservative approach has occurred, with an initial ‘wait and see’ policy. Many medical and regional forms of treatment are also available for the management of this condition, and others have recently emerged with promising results. However, many areas of controversy remain, and further studies and global collaboration are needed to obtain prospective and randomized data, in order to develop an appropriate shared stepwise approach. Cite this article:
This article provides an overview of the role of genomics in sarcomas and describes how new methods of analysis and comparative screening have provided the potential to progress understanding and treatment of sarcoma. This article reviews genomic techniques, the evolution of the use of genomics in cancer, the current state of genomic analysis, and also provides an overview of the medical, social and economic implications of recent genomic advances.
