Assessment of viable cells as a predictor of response in soft tissue sarcomas treated with neoadjuvant therapy.

e21507 Background: Soft Tissue Sarcomas (STS) are an uncommon neoplasm with many histological subtypes with different behaviors, response to treatments and developments. The treatment of these tumors is using surgery, radiotherapy or chemotherapy. The pathological response using degree of tumor necrosis has been implicated in survival rates. However comes to assessing the degree of tumor necrosis in the surgical specimens as response parameter could be confuse because the high-grade sarcomas exhibit a high rate of necrosis even without any treatment. Methods: 31 patients with STS of high grade located in extremities treated with neoadjuvant doxorubicin and ifosfamide were observed prospectively since January 2005 to June 2011. For evaluation of surgical specimens post neoadjuvant chemotherapy, a slice of the specimen in with lower gross of necrosis was represented and after mapped evaluating grade of necrosis, fibrosis and percentage of viable cells. Results: Six patients had ≤5% of viable cells, eight had ≤10% and 12 with 30% or less in the sample. Overall survival (OS) was 100%, 100% and 91% with Disease free survival (DFS) were 100%, 85.7% and 82.5%, respectively. No patient had ≥95% necrosis in the surgical specimens considering that a large part of the tissue had fibrosis in patients with few viable cells, which do not correlate with survival. Conclusions: The viable cell count in the sample is feasible, and relates well with survival. We consider this the ideal method for response evaluation in SPM instead of counting necrosis. In combination with the literature data we suggest cutoff points of 5%, 10% and 30%.

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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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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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Nuclear SMAD4 as a predictor of survival in patientes with extremity soft tissue sarcomas submitted to neoadjuvant chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.10586 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 10586-10586

Author(s):

Isabela Werneck Cunha ◽

Ranyell Spencer Sobreira Batista ◽

Paulo Roberto Stevanato ◽

Samuel Aguiar ◽

Ademar Lopes ◽

...

Keyword(s):

Soft Tissue ◽

Neoadjuvant Chemotherapy ◽

Locally Advanced ◽

Neoadjuvant Treatment ◽

Soft Tissue Sarcomas ◽

Disease Free Survival ◽

Chemotherapy Response ◽

Surgical Specimen ◽

Viable Cells ◽

Low Expression

10586 Background: Neoadjuvant chemotherapy for locally advanced soft tissue sarcomas, although not standard, represents a promising option for resectable tumours. The discovery of biological predictors of chemotherapy response highlights the possibility to develop individualised therapeutic approaches in selected group of patients or predict survival also. The SMAD4 protein, a member of TGFβ superfamily has a role in progression and tumor metastasis and may be involved sarcomas recurrence. Methods: 30 patients with soft tissue sarcomas (STS) of high-grade located in extremities treated with neoadjuvant doxorubicin and ifosfamide chemotherapy were observed prospectively since January 2005 to June 2011. All patients were submitted to radiation therapy adjuvant. Surgical specimens after neoadjuvant treatment were evaluated of SMAD4 nuclear expression by immuno-histochemistry and percentage of viable cells Results: The median follow-up time was 42 months. The overall survival (OS) was 91.7% in patients with low expression SMAD4 nuclear protein associated with ≤10% of viable cells (n=12) in the surgical specimen and 68.9% in the remaining patients. Likewise, the disease free survival (DSF) was 91.7% versus 38.6% (p 0.01) respectively. Conclusions: The combination of nuclear SMAD4 low expression and 10% or less of viable cells in the surgical specimen was statistically significant in better DFS in patients with locally advanced extremity STS treated with neoajuvant chemotherapy with benefit in OS.

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Adjuvant Treatment of High-risk Adult Soft Tissue Sarcomas: A Survey by the Italian Sarcoma Group

Tumori Journal ◽

10.1177/030089160609200202 ◽

2006 ◽

Vol 92 (2) ◽

pp. 92-97 ◽

Cited By ~ 5

Author(s):

Sergio Frustaci ◽

Massimiliano Berretta ◽

Alessandro Comandone ◽

Ettore Bidoli ◽

Antonino De Paoli ◽

...

Keyword(s):

Overall Survival ◽

High Risk ◽

Soft Tissue ◽

Survival Rates ◽

Soft Tissue Sarcomas ◽

Disease Free Survival ◽

Free Survival ◽

Disease Free ◽

Overall Survival Rates

Aims and Background After the first adjuvant study on adult soft tissue sarcomas was concluded, the participating institutions continued to select and treat patients according to that protocol. The aim of this study was to test the protocol reproducibility when applied as a standard practice. Methods A call for retrospective data was launched in June 1999 (self-referral of consecutive unregistered patients); thereafter, a prospective follow-up was performed. The treatment regimen consisted of epirubicin (60 mg/m2 days 1 and 2), ifosfamide (3 g/m2/die for 3 days) and equimolar doses of 6-mercapto-ethansulfonate (MESNA), with 300 μg G-CSF administered subcutaneously from day +8 until recovery, every 3 weeks for a total of 5 cycles. Results From November 1996 to June 1999, 55 high-risk, adult patients were treated. The average median dose intensity was 89% of the planned program. Grade 3-4 toxicities were leukopenia (49%), thrombocytopenia (14%), transfusion requiring anemia in 7 patients (16%), and alopecia in all patients (100%). After a median follow-up of 70 months, 23 patients (41.8%) relapsed and 19 died. Median disease-free, local disease-free and overall survival rates have not yet been reached. The disease-free survival rates at 2 and 4 years were 73% and 57%, respectively; the corresponding overall survival rates were 91% and 70%, respectively. Conclusions The feasibility and reproducibility of the original protocol were confirmed, since disease-specific overall survival and disease-free survival rates at the same period of observation and with the same prolonged follow-up did not differ.

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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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LONG-TERM RESULTS OF EXTREMITY SOFT TISSUE SARCOMAS LIMB-SPARING SURGERY AND RADIOTHERAPY

Acta Ortopédica Brasileira ◽

10.1590/1413-785220192704217574 ◽

2019 ◽

Vol 27 (4) ◽

pp. 207-211

Author(s):

Özlem Yetmen Dogan ◽

Didem Çolpan Oksuz ◽

Banu Atalar ◽

Fazilet Oner Dincbas

Keyword(s):

Prognostic Factors ◽

Soft Tissue ◽

Postoperative Radiotherapy ◽

Survival Rates ◽

Soft Tissue Sarcomas ◽

Disease Free Survival ◽

Long Term Results ◽

Level Of Evidence ◽

Actuarial Survival

ABSTRACT Objective: To assess the prognostic factors and results of limb sparing surgery and postoperative radiotherapy (PORT) in patients with non-metastatic soft tissue sarcomas (STS) of the extremities. Methods: Between 1980-2007, 114 extremity-located STS treated with PORT were analyzed retrospectively. Tumors were mostly localized in the lower extremities (71,9%). The median radiotherapy (RT) dose was 60.9 Gy. Chemotherapy was administered to 37.7% of the patients. Tumor sizes were between 3-26 cm (median 7 cm). The three most frequent histological types included undifferentiated pleomorphic sarcoma (26.3%), liposarcoma (25.4%), and synovial sarcoma (13.2%). The median follow-up for all patients was 60 months, and 81 months for survivors. Results: The 5- and 10-year local control (LC) rates were 77% and 70.4%, respectively; actuarial survival rates for 5 and 10 years were 71.8% and 69.1%, respectively. Increasing the dose above 60 Gy for all patients and the patients with positive margins demonstrated a clear benefit on 5-year LC (p=0.03 and p=0.04, respectively). Based on multivariate analysis, the addition of chemotherapy and RT dose were independent prognostic factors for LC. A recurrent presentation significantly affects the disease-free survival. Conclusions: PORT for STS of the extremities provides good long-term disease control with acceptable toxicity in a multidisciplinary approach. Level of evidence III, Retrospective study.

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LOCAL RECURRENCES AFTER THE TREATMENT OF SOFT TISSUE MALIGNANT FIBROUS HISTIOCYTOMA (UNCLASSIFIEDPLEOMORPHIC SARCOMA) OF THE LIMBS

Wiadomości Lekarskie ◽

10.36740/wlek201908120 ◽

2019 ◽

Vol 72 (8) ◽

pp. 1523-1526

Author(s):

Oleksandr O. Lytvynenko ◽

Volodymyr F. Konovalenko ◽

Anton Yu. Ryzhov

Keyword(s):

Soft Tissue ◽

Malignant Fibrous Histiocytoma ◽

Fibrous Histiocytoma ◽

Survival Rates ◽

Soft Tissue Sarcomas ◽

Primary Treatment ◽

Radical Excision ◽

Local Recurrences ◽

Results Of Treatment

Introduction: The treatment of patients with malignant fibrous histiocytoma as well as other soft tissue sarcomas is not sufficiently effective up to date, and has largely changed and reflects the alterations, occurred in oncology as a whole. The number of amputation decreased over the last 10-15 years. Some researchers associate the improvement of treatment outcomes with the development of combined and complex methods. The aim of the study is an improvement of the results of treatment of patients with soft tissue malignant histiocytoma on the basis of determination of factors, influencing local recurrence development. Materials and methods: The basis of our study was a comprehensive analysis of examination and treatment results of 130 patients with MFH of the soft tissue of limbs, of them in 84 patients (64.6%) the recurrences developed. The group included 45 (53.6%) males and 39 (46.4%) females. The major part of patients – 82.1% (60 patients) were older than 40 years. Results and conclusions: The number of recurrences after the treatment in general surgical facilities is 86.9%, whereas in the patients after the treatment in the specialized oncological facilities this figure is twice lower (40%). The characteristic of the medical facility where the patient receives his/her primary treatment largely affects the development of local recurrences, patients’ quality of life and overall survival rates. The surgical method remains the leading modality in the treatment of MFH of ST. Wide and radical excision of tumors in the specialized oncological facilities allows achieving better survival outcomes of the patients.

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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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