53 Neoadjuvant chemotherapy and radiotherapy for large soft tissue sarcomas

20006 Background: Patients with high grade soft tissue sarcomas are treated with neoadjuvant chemotherapy. Sarcomas have biological features that may predict for poor outcome. Some of these features are tumor proliferation rate, level of tumor hypoxia, and upregulation of tumor drug resistance mechanisms. Methods: We have a group of specific PET imaging agents to quantify the level of activity of these tumor processes. Patients with soft tissue sarcomas receive [C-11]Thymidine (TdR) to assess cellular proliferation, [O-15] Water to quantify tumor blood flow and to serve as the input function for quantification of the other tracers, [C-11]Verapamil to assess drug resistance mechanism activity, and [F-18]Fluoromisonidazole) FMISO to quantify changes in tumor hypoxic volume in response to treatment. These studies are performed in a single PET imaging session prior to neoadjuvant chemotherapy, after the second of four cycles of therapy and in the week prior to resection. Results: An example of this complex study result, is demonstrated by a recent patient with a high grade soft tissue sarcoma. The tumor showed increased TdR uptake, a moderate hypoxic volume, and [C-11] verapamil uptake prior to initiation of neoadjuvant adriamycin based chemotherapy. After 2 cycles of therapy, there was a significant decrease in the maximum level and volume of TdR uptake and a large reduction in tumor hypoxic volume. Conclusions: These data would imply a high risk soft tissue sarcoma due the presence of increased cellular proliferation, a significant hypoxic volume and the absence of p-glycoprotein activity determined by the presence of [C-11]Verapamil uptake. However, early response is also suggested by the findings above. Patient outcome will be assessed and correlated with these tumor parameters to further understand what tumor biological risk factors can be quantified non-invasively and repeated throughout the clinical course in soft tissue sarcoma patients. Supported by NIH NCI PO1 42045–18 and S10 RR017229–01 [Table: see text] No significant financial relationships to disclose.

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Adjuvant and neoadjuvant chemotherapy (NAC) with ifosfamide (IFO) and doxorubicin hydrochloride (ADM) for high-grade soft tissue sarcomas (STS) in the extremities: Japan Clinical Oncology Group study JCOG030404.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.10078 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. 10078-10078

Author(s):

K. Tanaka ◽

J. Mizusawa ◽

H. Fukuda ◽

N. Araki ◽

H. Chuuman ◽

...

Keyword(s):

Soft Tissue ◽

Neoadjuvant Chemotherapy ◽

Clinical Oncology ◽

Soft Tissue Sarcomas ◽

High Grade ◽

Doxorubicin Hydrochloride ◽

Oncology Group ◽

Japan Clinical Oncology Group ◽

Oncology Group Study

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Predictive role of topoisomerase IIα, gp170, Bcl-2, tumor burden, and histology in neoadjuvant chemotherapy for soft tissue sarcomas of the extremities.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.10086 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. 10086-10086

Author(s):

A. Comandone ◽

P. Porrino ◽

E. Berardengo ◽

A. Linari ◽

A. Boglione ◽

...

Keyword(s):

Soft Tissue ◽

Neoadjuvant Chemotherapy ◽

Soft Tissue Sarcomas ◽

Tumor Burden ◽

Topoisomerase Iiα ◽

Predictive Role

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Neoadjuvant chemotherapy for adult soft tissue sarcomas: A phase II trial.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.10069 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 10069-10069

Author(s):

Samuel Aguiar ◽

Fabio Oliveira Ferreira ◽

Ranyell Spencer Sobreira Batista ◽

Alexsander Kurowa Bressan ◽

Celso Lopes Mello ◽

...

Keyword(s):

Soft Tissue ◽

Neoadjuvant Chemotherapy ◽

Phase Ii ◽

Soft Tissue Sarcomas ◽

Pathological Response ◽

Amputation Rate ◽

Wound Complications ◽

Complication Rates ◽

Preoperative Radiation ◽

Chemotherapeutic Regimen

10069 Background: Treatment of soft tissue sarcomas (STS) is characterized by high rates of local control, but poor overall survival because of distant relapses and high rates of wound complications, when preoperative radiation is used. The objective of this study was to test the effectiveness of a protocol with neoadjuvant chemotherapy for STS. Methods: A phase II single-arm prospective trial was carried out. Only adult patients with high grade extremity lesions and tumors deep and larger than 5 cm were included. A total of four cycles of chemotherapy was administered pre-operatively. The chemotherapeutic regimen was: ifosfamide – total of 9.0 g/m2 per cycle, infused in 2 hours from Day 1 to Day 5 (1.8 mg/m2/day). Half of the equivalent dose of mesna was infused 15 min pre-ifosfamide and 4 hours post-ifosfamide. Doxorubicin – total of 60mg/m2 per cycle, was infused in bolus on Day 1. Filgrastima 300 mcg, SC, was administered after the last dose of chemotherapy for 5 days. Radiation was given after surgery. Toxicity was classified by the NIH Toxicity Criteria and response was determined by the RECIST criteria. The others endpoints were the amputation and the wound-related complication rates. Results: Between January, 2005 and May, 2011, 42 patients were included. 21(50%) patients have completed the 4 cycles. Nineteen patients (45.2%) have grade 3 or 4 toxicity, and one (2.3%) death related to treatment had occurred. Between severe complications, febrile neutropenia was the most frequent. By using the RECIST criteria, we observed 10(24.5%) cases of progression, 24(58.5%) cases of stable disease, and 7(17%) partial responses. No complete clinical or radiological response was observed. In the pathological analysis of the surgical specimens, 4(9.7%) cases showed no residual disease (complete pathological response), and a total of 6 (14.6%) showed ≤ 5% of viable residual cells. The amputation rate was 4.8% (2 cases) and complications related to the wound were observed in 9 patients (21.9%). Conclusions: The protocol showed a good rate of objective and pathological response, low rate of complications related to the operative wound, and maintained an acceptable amputation rate. On the other hand, we observed high rate of progression, by RECIST criteria.

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