Percent Necrosis in Extremity Soft Tissue Sarcoma After Preoperative Radiation Alone Versus Preoperative Radiation and Chemotherapy
Reviewer: Eric Shinohara MD, MSCI
Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 1, 2007
Presenter: Karl Haglund MD, PhD Presenter's Affiliation: Massachusetts General Hospital Type of Session: Scientific
Prior studies have found that treatment related necrosis is a prognostic marker in bone sarcomas.
Retrospective studies of soft tissue sarcomas from UCLA suggested that in soft tissue sarcomas of the extremities, necrosis is associated with outcome.
The present study investigates whether there was a difference in the extent of necrosis between patients treated with preoperative radiation alone versus those treated with radiation and chemotherapy. They also examined whether differences in necrosis could be correlated with patient outcomes.
Materials and Methods
This is a retrospective study of patients 357 patients treated from January 1974 to October of 2006.
All patients were 18 years old or older and were treated with preoperative radiation alone or chemoradiation for non-metastatic soft tissue sarcoma of the extremity.
Data on necrosis was available for 196 patients, 108 in the radiation alone group and 88 in the chemoradiation group.
Radiation dose was 42-52 Gy in both the radiation alone arm and the chemoradiation arm.
The majority of patients treated with chemotherapy received mesna, doxorubicin, ifosfamide, and dacarbazine (MAID).
Data from the two groups regarding percent necrosis, local control, disease free survival and overall survival were collected and compared.
Median follow up was 54.4 months for this study
There was no significant difference in the distribution of age, sex, or histology (liposarcoma and malignant fibrous histiocytoma) between the radiation and chemoradiation groups.
There were a larger proportion of patients with larger tumors in the chemoradiation group.
Radiation Alone versus Chemoradiation:
5 year overall survival: 76% versus 70.4% (p=NS)
5 year disease free survival: 59.8% versus 58% (p=NS)
5 year local control: 86.2% versus 92.2% (p=0.05)
Mean percent necrosis: 51.5% versus 77.6% (p=0.0001)
Mean percent necrosis (MPN):
When MPN was examined as a continuous variable for the entire cohort of patients there was no association between outcome and MPN.
They then broke MPN into various groups such as quarters and thirds and determined that a MPN of greater than 30% predicted for worse local control for the entire cohort.
A univariate analysis demonstrated that margin status and tumor size were both significantly associated with local control. MPN was found to be of borderline significance (p=0.06).
When the radiation alone group was examined separately MPN had no predictive value for local control, disease free survival or overall survival. The same results were also seen on multivariate analysis.
When the chemoradiation arm was examined separately MPN was predictive of local control (p=0.016) on univariate analysis. However, MPN was not predictive of disease free survival or overall survival on univariate analysis. On multivariate analysis gross margin status (p=0.03) and necrosis (p=0.04) were found to be predictive of local control.
Necrosis can be used to predict local control in patients with soft tissue sarcomas treated with preoperative chemoradiation. However, necrosis had no predictive value in patients treated with preoperative radiation alone. Necrosis had no predictive value regarding overall survival.
In patients who have less than 30% necrosis after preoperative chemoradiation, it may be appropriate to consider further adjuvant systemic treatment or a radiation boost.
Currently they are reviewing more patients’ pathology to increase the number of patients in the study.
The follow study presents some intriguing results regarding the use of necrosis as a predictor of outcome in patients treated with preoperative chemoradiation. However, conclusions based on this study are limited as it is retrospective and without randomization there may be potential hidden biases. Furthermore, histological evaluation of the tumors may have changed from 1974 to 2006 when the study was conducted which may limit the reproducibility of necrosis quantification. It is also not possible to determine what the baseline level of necrosis was prior to treatment and what influence this could have on outcome. Given these limitations it is difficult to apply necrosis as any sort of predictor of outcome into current clinical practice without more data. It may prove to be a useful surrogate marker for local control but further data are needed.
However, this study may be helpful in determining the baseline levels of necrosis that occurs with current chemotherapy and radiation. This could then serve as a reference for necrosis and when additional agents are added the effects on necrosis can be determined.
Partially funded by an unrestricted educational grant from Bristol-Myers Squibb.
Sep 22, 2011 - Tumor necrosis factor-α and melphalan-based isolated limb perfusion therapy has a limb salvage rate of 81 percent in patients with locally advanced extremity soft tissue sarcomas who would have otherwise undergone amputation, according to a study published online Sept. 19 in the Journal of Clinical Oncology.