Reduction of Glucose Metabolic Activity Is More Accurate than Change in Size at Predicting Histopathologic Response to Neoadjuvant Therapy in High-Grade Soft-Tissue Sarcomas

10017 Background: Change in size by RECIST (Response Evaluation Criteria in Solid Tumors) has been the standard to assess response to therapy in non-GIST soft tissue sarcomas (STS). Although recent studies have demonstrated that Positron Emission Tomography with F18-fluorodeoxyglucose (FDG-PET) may be used to assess response, there has not been a direct comparison between these modalities. The aim of this study was to prospectively evaluate whether a change in quantitative FDG-PET or a change in size [computed tomography(CT)] was more accurate at predicting histopathologic response to neoadjuvant therapy in patients with high grade STS using a combined FDG-PET/CT scan. Methods: From 1/05 - 12/06 58 patients with resectable biopsy proven high grade STS scheduled to undergo neoadjuvant chemotherapy were prospectively enrolled in this study. Patients underwent FDG-PET/CT prior to and after neoadjuvant treatment (prior to surgery). Tumor FDG-uptake was quantified by standardized uptake values (SUV). Changes in tumor size were quantified according to RECIST. Following tumor resection, response was assessed histopathologically. Patients with = 10% viable tumor cells were classified as responders. To date, 36 patients have completed the study and are the subject of this analysis. Results: In histopathologic responders (n=10, 28%), reduction of tumor FDG-uptake was significantly greater (-64%) than in histopathologic non-responders (-37%), (p=0.005). Using a 50% decrease in tumor SUV as a threshold value resulted in a sensitivity of 90% and a specificity of 58% for assessment of histopathologic response (p=0.01). Response assessment per RECIST showed no significant correlation with histopathologic response (sensitivity 20%, specificity 89%, p=0.4). There was no correlation between changes in tumor size and histopathologic response (area under the ROC curve = 0.6, p=0.1). Conclusions: In patients with high grade STS, quantitative FDG-PET was significantly more accurate than size based criteria for assessment of histopathologic response to neoadjuvant therapy. FDG-PET should be considered as a modality to monitor treatment response is patients with high grade STS. No significant financial relationships to disclose.

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Tumor FDG-uptake after the initial cycle of chemotherapy and histopathologic response to neoadjuvant therapy in high-grade soft tissue sarcomas

Journal of Clinical Oncology ◽

10.1200/jco.2008.26.15_suppl.10528 ◽

2008 ◽

Vol 26 (15_suppl) ◽

pp. 10528-10528

Author(s):

M. R. Benz ◽

W. A. Weber ◽

M. S. Allen-Auerbach ◽

W. D. Tap ◽

D. Elashoff ◽

...

Keyword(s):

Soft Tissue ◽

Neoadjuvant Therapy ◽

Soft Tissue Sarcomas ◽

High Grade ◽

Fdg Uptake ◽

Histopathologic Response ◽

Initial Cycle

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Treatment-Induced Pathologic Necrosis: A Predictor of Local Recurrence and Survival in Patients Receiving Neoadjuvant Therapy for High-Grade Extremity Soft Tissue Sarcomas

Journal of Clinical Oncology ◽

10.1200/jco.2001.19.13.3203 ◽

2001 ◽

Vol 19 (13) ◽

pp. 3203-3209 ◽

Cited By ~ 218

Author(s):

Fritz C. Eilber ◽

Gerald Rosen ◽

Jeffery Eckardt ◽

Charles Forscher ◽

Scott D. Nelson ◽

...

Keyword(s):

Overall Survival ◽

Soft Tissue ◽

Local Recurrence ◽

Neoadjuvant Therapy ◽

Independent Predictor ◽

Survival Rates ◽

Soft Tissue Sarcomas ◽

High Grade ◽

Recurrence Rates ◽

Pathologic Assessment

PURPOSE: To determine whether treatment-induced pathologic necrosis correlates with local recurrence and overall survival in patients who receive neoadjuvant therapy for high-grade extremity soft tissue sarcomas. PATIENTS AND METHODS: Four hundred ninety-six patients with intermediate- to high-grade extremity soft tissue sarcomas received protocol neoadjuvant therapy. All patients underwent surgical resection after neoadjuvant therapy and had pathologic assessment of tumor necrosis in the resected specimens. RESULTS: The 5- and 10-year local recurrence rates for patients with ≥ 95% pathologic necrosis were significantly lower (6% and 11%, respectively) than the local recurrence rates for patients with less than 95% pathologic necrosis (17% and 23%, respectively). The 5- and 10-year survival rates for the patients with ≥ 95% pathologic necrosis were significantly higher (80% and 71%, respectively) than the survival rates for the patients with less than 95% pathologic necrosis (62% and 55%, respectively). Patients with less than 95% pathologic necrosis were 2.51 times more likely to develop a local recurrence and 1.86 times more likely to die of their disease as compared with patients with ≥ 95% pathologic necrosis. The percentage of patients who achieved ≥ 95% pathologic necrosis increased to 48% with the addition of ifosfamide as compared with 13% of the patients in all the other protocols combined. CONCLUSION: Treatment-induced pathologic necrosis is an independent predictor of both local recurrence and overall survival in patients who receive neoadjuvant therapy for high-grade extremity soft tissue sarcomas. A complete pathologic response (≥ 95% pathologic necrosis) correlated with a significantly lower rate of local recurrence and improved overall survival.

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Clinical Factors That Affect the Establishment of Soft Tissue Sarcoma Patient-Derived Orthotopic Xenografts: A University of California, Los Angeles, Sarcoma Program Prospective Clinical Trial

JCO Precision Oncology ◽

10.1200/po.17.00071 ◽

2017 ◽

pp. 1-13 ◽

Cited By ~ 3

Author(s):

Tara A. Russell ◽

Mark A. Eckardt ◽

Takashi Murakami ◽

Irmina A. Elliott ◽

Kei Kawaguchi ◽

...

Keyword(s):

Soft Tissue ◽

Los Angeles ◽

Neoadjuvant Therapy ◽

Neoadjuvant Treatment ◽

Soft Tissue Sarcomas ◽

Pathologic Response ◽

Response To Treatment ◽

High Grade ◽

Factors Associated ◽

Orthotopic Xenografts

Purpose Given the diverse and aggressive nature of soft tissue sarcomas (STSs), a need exists for more-precise therapy. Patient-derived orthotopic xenografts (PDOXs) provide a unique platform for personalized treatment. Thus, identification of patient and treatment factors that predict PDOX establishment is important. This study assessed the feasibility of incorporating PDOXs into the clinical setting and identifying factors associated with PDOX establishment. Patients and Methods From May 2015 to May 2016, 107 patients with biopsy-proven or potential STS were enrolled. Tumor samples were obtained intraoperatively and orthotopically implanted into nude mice in the corresponding anatomic location. PDOXs were considered established after engraftment and serial passage. Factors associated with establishment were analyzed by logistic regression and time to establishment by time-to-event analysis. Results Only high-grade tumors established (32 of 72 [44.4%]). The establishment rate (ER) varied by neoadjuvant therapy and treatment response, with the highest ER among untreated high-grade tumors (26 of 42 [61.9%]). Tumors exposed to radiation preoperatively did not establish (zero of 11 [0%]), and tumors exposed to neoadjuvant chemotherapy had a lower ER (31.9%) than untreated tumors. Only STSs with minimal pathologic response to neoadjuvant treatment (≤ 30%) established a PDOX (six of 18 [33.3%]). Median establishment time was 54 days, which varied by neoadjuvant therapy but was not statistically significant ( P = .180). Conclusion To our knowledge, in the largest STS PDOX study to date, we demonstrate a 62% ER among untreated high-grade tumors with a median establishment time of 54 days. Neoadjuvant therapy, particularly radiation, and pathologic response to treatment were associated with a reduced rate of PDOX establishment.

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18f-FDG-PET imaging as an early survival predictor in patients with high-grade soft tissue sarcomas undergoing neoadjuvant therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.10012 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 10012-10012

Author(s):

Ken Herrmann ◽

Matthias R. Benz ◽

Johannes Czernin ◽

Martin Auerbach ◽

William D. Tap ◽

...

Keyword(s):

Overall Survival ◽

Soft Tissue ◽

Neoadjuvant Therapy ◽

Pet Imaging ◽

Fdg Pet ◽

Survival Rates ◽

Soft Tissue Sarcomas ◽

Rank Test ◽

High Grade ◽

Initial Cycle

10012 Background: Neoadjuvant therapy is associated with considerable toxicity and limited survival benefits in patients with soft tissue sarcoma (STS). We prospectively evaluated whether 18F-FDG PET/CT (PET) imaging after the initial cycle and after end of neoadjuvant therapy could predict overall survival in these patients. Methods: 76 patients (primary STS: n=57; metastatic disease: n=19) with high grade STS were included in this study. PET was performed prior to (n=76), after one cycle (n=52) and after the end of neoadjuvant therapy (n=74). Overall survival was correlated with changes of SUVpeak, RECIST, histopathological response and other parameters predictive of STS survival. Results: One-, two- and five- year survival rates were 95±3.0%, 86±4.6% and 68±6.6% for primary STS. Corresponding one- and two- year survival rates for recurrent/metastatic STS were 77±10.0% and 47±12.1%. Optimal cut-off for early decreases in SUV peak were significant predictors of survival in log-rank test (p=0.027 and p=0.043). However, late decreases in SUV peak were only predictive in primary STS (SUV peak decrease 57%; p=0.035) but not in recurrent/metastatic STS (SUV peak decrease 52%; p=0.057). In primary STS, 7/15 early PET non-responders but only 4/24 early PET responders died during follow up (p=0.068). Conclusions: 18F-FDG-PET seems feasible to predict survival after the initial cycle of neoadjuvant chemotherapy in both patients with primary STS and recurrent/metastatic STS and can potentially serve as an intermediate endpoint biomarker in clinical research and patient care.

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18F-FDG-PET/CT Imaging as an Early Survival Predictor in Patients with Primary High-Grade Soft Tissue Sarcomas Undergoing Neoadjuvant Therapy

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-11-2139 ◽

2012 ◽

Vol 18 (7) ◽

pp. 2024-2031 ◽

Cited By ~ 52

Author(s):

Ken Herrmann ◽

Matthias R. Benz ◽

Johannes Czernin ◽

Martin S. Allen-Auerbach ◽

William D. Tap ◽

...

Keyword(s):

Soft Tissue ◽

Neoadjuvant Therapy ◽

Fdg Pet ◽

Soft Tissue Sarcomas ◽

Ct Imaging ◽

High Grade ◽

Pet Ct ◽

18F Fdg ◽

Fdg Pet Ct ◽

Survival Predictor

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Myxofibrosarcoma: clinical and prognostic value of MRI features

Current Medical Imaging Formerly Current Medical Imaging Reviews ◽

10.2174/1573405616999200729152135 ◽

2020 ◽

Vol 16 ◽

Cited By ~ 1

Author(s):

Paolo Spinnato ◽

Andrea Sambri ◽

Tomohiro Fujiwara ◽

Luca Ceccarelli ◽

Roberta Clinca ◽

...

Keyword(s):

Soft Tissue ◽

Local Recurrence ◽

Contrast Enhancement ◽

Imaging Modality ◽

Soft Tissue Sarcomas ◽

The Elderly ◽

High Rate ◽

Imaging Features ◽

High Grade ◽

Mri Features

: Myxofibrosarcoma is one of the most common soft tissue sarcomas in the elderly. It is characterized by an extremely high rate of local recurrence, higher than other soft tissue tumors, and a relatively low risk of distant metastases.Magnetic resonance imaging (MRI) is the imaging modality of choice for the assessment of myxofibrosarcoma and plays a key role in the preoperative setting of these patients.MRI features associated with high risk of local recurrence are: high myxoid matrix content (water-like appearance of the lesions), high grade of contrast enhancement, presence of an infiltrative pattern (“tail sign”). On the other hand, MRI features associated with worse sarcoma specific survival are: large size of the lesion, deep location, high grade of contrast enhancement. Recognizing the above-mentioned imaging features of myxofibrosarcoma may be helpful to stratify the risk for local recurrence and disease-specific survival. Moreover, the surgical planning should be adjusted according to the MRI features

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Functional and psychosocial effects of multimodality limb-sparing therapy in patients with soft tissue sarcomas.

Journal of Clinical Oncology ◽

10.1200/jco.1989.7.9.1217 ◽

1989 ◽

Vol 7 (9) ◽

pp. 1217-1228 ◽

Cited By ~ 28

Author(s):

A E Chang ◽

S M Steinberg ◽

M Culnane ◽

M H Lampert ◽

A J Reggia ◽

...

Keyword(s):

Radiation Therapy ◽

Soft Tissue ◽

Sexual Activity ◽

Standardized Test ◽

Soft Tissue Sarcomas ◽

High Grade ◽

Postoperative Radiation ◽

Limb Function ◽

Postoperative Radiation Therapy ◽

Global Quality Of Life

We have documented functional and psychosocial changes in patients with extremity soft tissue sarcomas who have undergone multimodality limb-sparing treatments. In 88 patients, parameters related to economic status, sexual activity, pain, limb function, and global quality of life (QOL) were recorded prior to surgery and every 6 months postoperatively. Changes from the preoperative assessment for every parameter were analyzed in each patient. Six months after surgery, there was a decrease in employment status, sexual activity, and in limb function in a significant number of patients. At 12 months, these decreases were still evident. Despite these changes, global QOL measured by a standardized test showed at least some improvement in a significant proportion of patients at 12 months. These findings highlight the difficulty in defining QOL. It could not be ascertained if radiation therapy and/or chemotherapy were causative factors in specific changes because of the small numbers of patients in each subgroup. However, among 60 patients with high-grade sarcomas, significant wound problems developed in 10 of 33 who received postoperative radiation therapy in combination with adjuvant doxorubicin and cyclophosphamide chemotherapy compared with one of 27 patients who received adjuvant chemotherapy alone (P = .016). Also, among high-grade sarcoma patients with 12-month follow-up, six of 19 patients who received radiation therapy and chemotherapy developed joint contractures compared with zero of 15 patients who received chemotherapy alone (P less than .04). The combination of postoperative radiation therapy and chemotherapy appeared to be associated with significantly more tissue-related injury in patients with high-grade sarcomas compared with chemotherapy alone.

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