ORIGINAL ARTICLE – BONE AND SOFT TISSUE SARCOMAS
Radiographic and Histologic Response to Neoadjuvant
Radiotherapy in Patients With Soft Tissue Sarcoma
Robert J. Canter, MD1, Steve R. Martinez, MD, MAS1, Robert M. Tamurian, MD2, Maaya Wilton, MD3,
Chin-Shang Li, PhD4, Janice Ryu, MD5, Walter Mak, MD6, Wayne L. Monsky, MD, PhD6,
and Dariusz Borys, MD3
1Division of Surgical Oncology, University of California Davis Medical Center, Sacramento, CA;2Division of Orthopedic
Oncology, University of California Davis Medical Center, Sacramento, CA;3Department of Pathology and Laboratory
Medicine, University of California Davis Medical Center, Sacramento, CA;4Division of Biostatistics, Department of
Public Health Sciences, University of California Davis, Sacramento, CA;5Department of Radiation Oncology, University
of California Davis Medical Center, Sacramento, CA;6Department of Radiology, University of California Davis Medical
Center, Sacramento, CA
Background. Limited data exist regarding the radio-
graphic and histologic response of soft tissue sarcoma
(STS) to neoadjuvant radiotherapy (RT).
Methods. Between February 2000 and January 2009, a
total of 25 patients aged [16 years with intermediate- or
high-grade primary STS of all sites were treated with
neoadjuvant RT followed by definitive resection. Patients
receiving chemoradiotherapy were excluded. Cross-sec-
tional images obtained before and after RT as well as
pathologic specimens were reviewed for maximal change
in tumor diameter and percentage tumor necrosis, respec-
tively. Clinicopathologic variables were analyzed for their
association with pathologic and radiographic response.
Results. There were 18 extremity (72%) and 7 retroperi-
toneal (28%) tumors. Median maximal tumor size was
9 cm (range, 3.3–35 cm), and 88% were of high grade.
There were 21 R0 resections (84%) and 4 R1 resections
(16%). Radiographically, the median percentage change in
tumor diameter was 0% (range, -25 to ?86%). By
Response Evaluation Criteria in Solid Tumors (RECIST), 5
patients demonstrated progressive disease, 20 demon-
strated stable disease, and 0 demonstrated partial/complete
response. The median pathologic percentage tumor necro-
sis was 30% (range, 5–100%). Two tumors (8%)
demonstrated near-complete pathologic response (C95%
necrosis). Near-complete pathologic response was associ-
ated with favorable oncologic outcomes, although these
associations were not statistically significant.
Conclusions. Radiologic and near-complete pathologic
responses are rare events after preoperative RT for STS.
Near-complete pathologic response may be a potentially
meaningful surrogate marker for disease outcome and is
not predicted by RECIST response. Knowledge of these
historical response rates is important for the evaluation of
novel neoadjuvant therapies for patients with STS.
External-beam radiotherapy (RT) is an important com-
ponent of the multimodality treatment of patients with
localized soft tissue sarcoma (STS) and has contributed
substantially to both effective local disease control and
successful limb-sparing surgery.1Since the publication of
the landmark National Cancer Institute of Canada ran-
domized trial comparing preoperative to postoperative RT
for patients with extremity STS, preoperative RT for STS
has been widely accepted. Although oncologic outcomes
are essentially equivalent regardless of the timing of RT,
many clinicians favor preoperative RT because treatment
fields are well-defined and long-term, potentially irrevers-
ible, RT-related complications are fewer.2,3
Among patients with retroperitoneal sarcoma (RPS), data
examining the use of preoperative RT are predominantly
Presented in part at the Society of Surgical Oncology 62nd Annual
Cancer Symposium, Phoenix, AZ, March 4–8, 2009.
? The Author(s) 2010. This article is published with open access
First Received: 29 January 2010;
Published Online: 17 June 2010
R. J. Canter, MD
Ann Surg Oncol (2010) 17:2578–2584
21. Evilevitch V, Weber WA, Tap WD, et al. Reduction of glucose
metabolic activity is more accurate than change in size at pre-
dicting histopathologic response to neoadjuvant therapy in high-
grade soft-tissue sarcomas. Clin Cancer Res. 2008;14:715–20.
22. Eilber FC, Rosen G, Eckardt J, et al. Treatment-induced patho-
logic necrosis: a predictor of local recurrence and survival in
patients receiving neoadjuvant therapy for high-grade extremity
soft tissue sarcomas. J Clin Oncol. 2001;19:3203–9.
23. Macdermed DM, Miller LL, Peabody TD, et al. Primary tumor
necrosis predicts distant control in locally advanced soft-tissue
sarcomas after preoperative concurrent chemoradiotherapy. Int J
Radiat Oncol Biol Phys. 2010;76:1147–53.
2584 R. J. Canter et al.