Adjuvant therapy for extremity sarcomas

Abstract

Extremity soft tissue sarcomas (STS) represent a rare, heterogeneous malignancy. Surgery is the primary treatment for patients with no evidence of metastatic disease, and for small low-grade superficial tumors in which adequate margins can be obtained, it may be the only therapy indicated. For large, deep tumors or tumors that are close to important neurovascular structures or bone, the addition of radiotherapy to resection has improved local control and increased limb salvage without affecting overall survival. Adjuvant chemotherapy has been an issue of considerable debate. Because 50% of patients with high-risk tumors will develop metastatic disease, effective systemic treatment with chemotherapy is needed. Unfortunately, studies have shown minimal improvement in overall survival when chemotherapy is added to the local treatment of high-risk extremity STS. More recently, a few trials of neoadjuvant chemotherapy consisting of mesna, doxorubicin, ifosfamide, and dacarbazine and high-dose doxorubicin and ifosfamide have shown some early promising results, but at the price of increased toxicity. Targeted therapy has shown some of its best results with gastrointestinal stromal tumors, but so far there has been little success in treating extremity STS. At this time, high-dose adjuvant or neoadjuvant chemotherapy should be given in the setting of a clinical trial to patients with high-risk tumors who can tolerate a potentially toxic chemotherapeutic regimen. The goal of these trials should be to assess new combination therapies, possibly including targeted therapies, for the management of large high-grade, high-risk soft tissue sarcomas.

Adjuvant Therapy With Agonistic Antibodies to CD134 (OX40) Increases Local Control After Surgical or Radiation Therapy of Cancer in Mice

“…This relatively high local recurrence rate in sarcoma treated with surgery alone relates to the lack of distinct tumor margin, such that microscopic disease can be detected at large distances from the primary tumor mass 6. For this reason, multiple clinical trials have tested neoadjuvant or adjuvant chemotherapy and/or radiation therapy in patients with soft-tissue sarcoma 35. These additional cytotoxic therapies may have implications for tumor antigen specific immune responses, therefore careful consideration should be given to the combination of immunotherapy in these circumstances.…”

Multimodality treatment of locally advanced soft-tissue sarcomas of the extremities

“…10 For large, deep tumours where surgical margins are likely to be close in order to preserve important neurovascular structures and bone, the addition of radiotherapy to resection has improved local control and increased limb salvage but without affecting overall survival. 15 Intuitively, decreasing local failures and thus distant metastases would improve overall survival, but this has not yet been proven.…”

Skin and Subcutaneous Tumors

“…No clinical studies in the dog suggest whether neoadjuvant chemotherapy has any beneficial impact on patient outcome or surgical margins (Bray 2016;Elmslie et al 2008;Kuntz et al 1997;Rassnick 2003;Schlieman et al 2006).…”