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Sarcomas

Histologic Alterations from Neoadjuvant Chemotherapy in High-Grade Extremity Soft Tissue Sarcoma: Clinicopathological Correlation

Departments of ^aPathology, ^bOrthopedic Surgery, ^dInternal Medicine, and ^ePharmacology, University of Michigan, Ann Arbor, Michigan, USA; ^cDepartment of Pediatrics, Wayne State University, Detroit, Michigan, USA

Key Words. Sarcoma • Soft tissue neoplasms • Neoadjuvant therapy • Drug therapy • Pathology

Correspondence: David R. Lucas, M.D., 2G332 UH, Ann Arbor, Michigan 48109-0054, USA. Telephone: 734-936-6776; Fax: 734-763-4095; e-mail: drlucas{at}umich.edu

Disclosure: S.M.S. has performed contract work for the National Cancer Institute. L.H.B. is an advisory board member of Ascenta Therapeutics, Inc., The Hope Foundation, NCCN Guidelines Committee, and SARC (Sarcoma Alliance for Research through Collaboration), for which he receives no compensation. No other potential conflicts of interest were reported by the authors, planners, reviewers, or staff managers of this article.

Histologic response to chemotherapy is generally regarded as an independent prognostic variable in bone sarcomas, both osteosarcoma and Ewing's sarcoma. In soft tissue sarcomas, however, descriptions of histologic alterations from chemotherapy and correlative outcome studies are much more limited. Herein we report clinicopathological findings from a homogeneously treated group of 31 patients with tumor stage T2 grade 3 extremity soft tissue sarcomas treated with the same neoadjuvant chemotherapy followed by surgical excision, treated by the same medical oncologist and orthopedic surgeon. Histologic response to therapy was evaluated by multiple parameters using a semiquantitative grading system. Based upon the percentage of post-treatment viable tumor, tumors were arbitrarily categorized similarly to Huvos score as showing excellent (5% viability), moderate (6%–49% viability), or poor (50% viability) responses. Nineteen percent had excellent, 10% had moderate, and 71% had poor responses. These histologic response groups did not correlate with overall or event-free survival. For example, of the 22 patients showing a "poor" response, 13 were cured. Similarly, other histologic parameters, including percentages of necrosis, fibrosis/hyalinization, and cellular degeneration, did not correlate with outcome. Chemotherapy induces profound tissue alterations in soft tissue sarcomas. However, histologic alteration by itself may not be a reliable prognostic variable. Correlation of all data from clinical, imaging, and pathological observations by a multidisciplinary tumor board should have greater prognostic value than histology alone. Finally, although the histologic grading system used in this study could not be validated, the criteria we employed are simple and reproducible and take into account the major histologic patterns seen after therapy, and would be amenable for use in future studies.

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