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Risk of Local Recurrence Varies Across Sarcoma Histotypes With Adjuvant/Neoadjuvant Therapy

Virginia Powers, PhD
Published Online: 10:09 PM, Thu November 10, 2016
Adjuvant chemotherapy was found to decrease the rates of local recurrence in some subtypes of extremity soft tissue sarcoma; however, the use of adjuvant/neoadjuvant therapy did not impact overall survival, according to findings from a large analysis presented at the Connective Tissue Oncology Society (CTOS) conference in Lisbon, Portugal. 

In general, use of adjuvant chemotherapy and radiotherapy was found to vary among the international institutions studied, suggesting a standard approach does not exist. Dario Callegaro MD, Department of Clinical Epidemiology and Trial Organisation, Istituto Nazionale dei Tumori, Milan, Italy, presented findings on behalf of colleagues at the 4 participating centers providing the data that were compared in this analysis: The Istituto Nazionale dei Tumori, Milan, Italy, the Institut Curie, in Paris, France, the Mount Sinai Hospital, Toronto, Canada, and the Royal Marsden Hospital NHS Foundation Trust, London, UK. The analysis included data from 1452 patients in the Italian institution, 420 patients in the French cohort, 1436 patients in the Canadian cohort, and 444 patients in the UK cohort. The median follow-up durations were 86, 75, 85, and 54 months, respectively.
 
The study included data from adult patients (aged 18 years and older) with primary, extremity soft tissue sarcomas who underwent surgery at any of the institutions over a 9-year period beginning in 1994. Patients with pediatric sarcomas, or desmoids, and patients receiving R2 resections were excluded from the study.
 
The study sought to explore the outcome of resected primary extremity soft tissue sarcomas by institution, and tumor characteristics to evaluate the role of adjuvant radiotherapy and chemotherapy in different sarcoma histologies.
 
The use of adjuvant/neoadjuvant radiotherapy and chemotherapy was found to differ among the institutions; radiotherapy was administered to 50% of patients in the Italian cohort, 68% of the French, 82% of the Canadian, and to 48% of patients in the UK cohort, whereas chemotherapy was given to 2%, 2%, 52%, and 26% of patients in the respective country institutions.

“The quality of surgery was similar between the institutions; however, the use of radiotherapy and chemotherapy for subtypes of extremity soft-tissue sarcomas varied broadly,” Callegaro said.

The investigators developed a logistic model to evaluate the propensity to perform radiotherapy and chemotherapy in subtypes of sarcomas. These propensities were found to differ between subtypes, with the propensities to perform radiotherapy highest in synovial sarcoma followed by myxoid liposarcoma and undifferentiated pleomorphic sarcoma (UPS). The odd ratios (OR) for administering radiotherapy were 3.41, 2.47, and 2.41, respectively.
 
Patients with synovial sarcoma also were more likely to receive adjunct chemotherapy followed by vascular sarcoma, OR 15.0, and 4.29, respectively.
 
The 10-year crude cumulative incidence (CCI) of local recurrence across the institutions was 1.9% in the Italian cohort, 8.6% French cohort, 5.1% Canadian cohort, and 9.5% in the UK cohort (P < .0001).
 
Patient characteristics that emerged as predictors of local recurrence were tumor grade, histological subtype, surgical margins, and the administration of adjuvant/neoadjuvant radiotherapy.
 
The investigators found a higher risk of local recurrence was associated with a lesser use of adjuvant/neoadjuvant radiotherapy across all histology subtypes, that was most pronounced in myxoid liposarcoma, myxofibrosarcoma, and vascular sarcoma.
 
The tumor size, grade, and histological subtype were found to be significant predictors for distant metastasis.

“Chemotherapy administration varied widely among different referral centers,” said Callegaro. “The use of chemotherapy in vascular sarcoma, myxofibrosarcoma, myxoid liposarcoma and undifferentiated pleomorphic liposarcoma was associated with a trend in less distant metastasis and better overall survival; however, this is a heterogeneous population, with a metastatic risk averaging 30%. Hence, it is not the ideal setting to analyse the role of chemotherapy in soft tissue sarcoma.”

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