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Looking for answers: the current status of neoadjuvant treatment in localized soft tissue sarcomas.

ABSTRACT: PURPOSE:Sarcomas are a rare and heterogeneous variant of cancer. The standard of care treatment involves surgical resection with radiation in high-risk patients. Despite appropriate treatment approximately 50 % of patients will suffer and die from recurrent disease. The purpose of this article is to review the current evidence concerning the use of neoadjuvant chemotherapy with or without radiation in soft tissue sarcomas. METHODS:An in-depth literature search was conducted using Ovid Medline and PubMed. RESULTS:The most active chemotherapeutic agents in sarcoma are anthracyclines and ifosfamide. Adjuvant chemotherapy trials show only minimal benefit. Neoadjuvant chemotherapy offers the potential advantage of reducing the extent of surgery, increasing the limb salvage rate, early exposure of micrometastatic disease to chemotherapy, and assessment of tumor response to chemotherapy. Some retrospective and phase II trials suggest a benefit to neoadjuvant chemotherapy. Unfortunately, no clearly positive phase III prospectively randomized trials exist for neoadjuvant therapy in soft tissue sarcomas. CONCLUSIONS:The current neoadjuvant chemotherapy trials that do exist are heterogeneous resulting in conflicting results. However, neoadjuvant chemotherapy with or without radiation can be considered in patients with high-risk disease in an attempt to improve long-term outcomes.

SUBMITTER: Nathenson MJ

PROVIDER: S-EPMC7577379 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Looking for answers: the current status of neoadjuvant treatment in localized soft tissue sarcomas.

Nathenson Michael J MJ Sausville Edward E

Cancer chemotherapy and pharmacology 20160520 5

<h4>Purpose</h4>Sarcomas are a rare and heterogeneous variant of cancer. The standard of care treatment involves surgical resection with radiation in high-risk patients. Despite appropriate treatment approximately 50 % of patients will suffer and die from recurrent disease. The purpose of this article is to review the current evidence concerning the use of neoadjuvant chemotherapy with or without radiation in soft tissue sarcomas.<h4>Methods</h4>An in-depth literature search was conducted using ...[more]

PMID: 27206640

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Project description:PurposeNumerous preclinical studies have demonstrated that angiogenesis inhibitors can increase the efficacy of radiotherapy (RT). We sought to examine the safety and efficacy of bevacizumab (BV) and RT in soft tissue sarcomas and explore biomarkers to help determine the treatment response.Methods and materialsPatients with ≥5 cm, intermediate- or high-grade soft tissue sarcomas at significant risk of local recurrence received neoadjuvant BV alone followed by BV plus RT before surgical resection. Correlative science studies included analysis of the serial blood and tumor samples and serial perfusion computed tomography scans.ResultsThe 20 patients had a median tumor size of 8.25 cm, with 13 extremity, 1 trunk, and 6 retroperitoneal/pelvis tumors. The neoadjuvant treatment was well tolerated, with only 4 patients having Grade 3 toxicities (hypertension, liver function test elevation). BV plus RT resulted in ≥80% pathologic necrosis in 9 (45%) of 20 tumors, more than double the historical rate seen with RT alone. Three patients had a complete pathologic response. The median microvessel density decreased 53% after BV alone (p <.05). After combination therapy, the median tumor cell proliferation decreased by 73%, apoptosis increased 10.4-fold, and the blood flow, blood volume, and permeability surface area decreased by 62-72% (p <.05). Analysis of gene expression microarrays of untreated tumors identified a 24-gene signature for treatment response. The microvessel density and circulating progenitor cells at baseline and the reduction in microvessel density and plasma soluble c-KIT with BV therapy also correlated with a good pathologic response (p <.05). After a median follow-up of 20 months, only 1 patient had developed local recurrence.ConclusionsThe results from the present exploratory study indicated that BV increases the efficacy of RT against soft tissue sarcomas and might reduce the incidence of local recurrence. Thus, this regimen warrants additional investigation. Gene expression profiles and other tissue and circulating biomarkers showed promising correlations with treatment response.

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Looking for answers: the current status of neoadjuvant treatment in localized soft tissue sarcomas.

Publications

Looking for answers: the current status of neoadjuvant treatment in localized soft tissue sarcomas.

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