scholarly journals Treatment of advanced, metastatic soft tissue sarcoma: latest evidence and clinical considerations

2017 ◽  
Vol 9 (8) ◽  
pp. 533-550 ◽  
Author(s):  
Gino K. In ◽  
James S. Hu ◽  
William W. Tseng
Keyword(s):  
Overall Survival ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Alkylating Agents ◽  
Treatment Options ◽  
Cytotoxic Agents ◽  
High Grade ◽  
Metastatic Setting ◽  
Line Setting ◽  
New Treatments

Soft tissue sarcoma (STS) is a biologically heterogeneous malignancy with over 50 subtypes. Historically, there have been few systemic treatment options for this relatively rare disease. Traditional cytotoxic agents, such as anthracyclines, alkylating agents, and taxanes have limited clinical benefit beyond the first-line setting; across all high-grade STS subtypes, median overall survival remains approximately 12–18 months for advanced metastatic disease. The development of targeted therapies has led to recent US Food and Drug Administration approval of four new treatments for high-grade STS in the advanced metastatic setting. Among these, olaratumab is most notable for its improvement in overall survival for patients with anthracycline-naïve disease. Further progress in STS management will rely on novel trial design, subtype-specific therapies and validation of biomarkers to tailor therapy. Immunotherapy has shown promise as a new, but yet undiscovered frontier in the management of STS.

scholarly journals Gemcitabine-Containing Chemotherapy for the Treatment of Metastatic Myxofibrosarcoma Refractory to Doxorubicin: A Case Series

2021 ◽  
Vol 28 (1) ◽  
pp. 813-817
Author(s):  
Arielle Elkrief ◽  
Suzanne Kazandjian ◽  
Thierry Alcindor
Keyword(s):  
Overall Survival ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Objective Response ◽  
Case Series ◽  
Progression Free Survival ◽  
Distant Metastases ◽  
First Line ◽  
Pleomorphic Sarcoma ◽  
Line Setting

Background: Myxofibrosarcoma is a type of soft-tissue sarcoma that is associated with high rates of local recurrence and distant metastases. The first-line treatment for metastatic soft-tissue sarcoma has conventionally been doxorubicin-based. Recent evidence suggests that myxofibrosarcoma may be molecularly similar to undifferentiated pleomorphic sarcoma (UPS), which is particularly sensitive to gemcitabine-based therapy. The goal of this study was to evaluate the activity of gemcitabine-containing regimens for the treatment of metastatic myxofibrosarcoma refractory to doxorubicin. Material and Methods: We retrospectively evaluated seven consecutive cases of metastatic myxofibrosarcoma at our institution treated with gemcitabine-based therapy in the second-line setting, after progression on doxorubicin. Baseline clinical and baseline characteristics were collected. Primary endpoints were objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: After progression on first-line doxorubicin, a partial, or complete radiological response was observed in four of seven patients who received gemcitabine-based chemotherapy. With a median follow-up of 14 months, median progression-free and overall survival were 8.5 months and 11.4 months, respectively. Conclusions: Gemcitabine-based chemotherapy was associated with encouraging response rates in this cohort, similar to those seen in UPS. Both entities could be studied together for novel gemcitabine-based regimens.

Efficacy and safety of administration of gemcitabine and docetaxel with radiation therapy in patients with high-grade soft tissue sarcoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e21503-e21503
Author(s):  
G. G. Raval ◽  
R. Govindarajan
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Adjuvant Chemotherapy ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Tumor Necrosis ◽  
Outpatient Basis ◽  
High Grade ◽  
Time Of Surgery ◽  
Neo Adjuvant Chemotherapy

e21503 Background: Neo-adjuvant therapy of soft tissue sarcoma is not standardized. Anthracyclines (A) improve disease free and overall survival in high grade extremity soft tissue sarcomas measuring more than 5 cm. A and ifosfamide (I) therapy require inpatient administration and is associated with significant toxicities when administered in combination with RT. G in combination with D has been shown to prolong progression free and overall survival in patients with advanced or metastatic STS after progression on A and I, and in patients unable to receive the combination. The safety of administration of G with radiation is not known. We evaluated the safety of neo-adjuvant G and D in combination with RT in patients with STS. Methods: Retrospective analysis of subjects with high grade STS treated with RT and neo-adjuvant chemotherapy with G and D was conducted. G 600mg/m2 was administered on days 1 and 8 along with D 75 mg/m2 on day 8 for a total of 3 cycles. 2200 cGY RT was administered in 11 daily fractions between cycles 1 and 2 and between cycles 2 and 3. 72 hour gap was given between RT and chemotherapy. Chemotherapy was administered on outpatient basis. Efficacy was evaluated by the extent of tumor necrosis at the time of surgery. Safety was evaluated by the presence of complications following chemotherapy. Results: GD + R was administered to 12 patients in the neo-adjuvant setting. 11 of them were evaluable for response. 10 of the 11 patients had evidence of tumor necrosis at the time of surgery. 1 patient had poor response. 3 of 11 patients had neutropenia complicating neo-adjuvant chemotherapy. 4 patients required hospital admission post chemotherapy. 3 for neutopenic fever, and 1 for fever, chills and pneumonia without neutropenia. Conclusions: Gemcitabine and taxotere combination with radiation therapy can be administered safely on outpatient basis with minimal toxicity. Further safety and efficacy evaluation of this therapy will need to be confirmed in a prospective phase II study. No significant financial relationships to disclose.

Adjuvant Therapy for Soft Tissue Sarcoma

2005 ◽  
Vol 3 (2) ◽  
pp. 207-213 ◽  
Author(s):  
Scott M. Schuetze ◽  
Michael E. Ray
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
High Risk ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Survival Rates ◽  
Wide Resection ◽  
High Grade ◽  
Postoperative Radiation Therapy ◽  
Increased Risk

Wide surgical excision is the backbone of therapy for localized soft tissue sarcoma and often produces excellent results. Patients with a marginal resection of disease and high-grade or large tumors are at an increased risk of recurrence. Radiation therapy (external beam or brachytherapy) has been shown to reduce the risk of local recurrence of disease and should be offered to patients with large (>5 cm) or high-grade sarcomas, especially if a wide resection cannot be performed. Use of preoperative versus postoperative radiation therapy should be planned, in consultation with a radiation oncologist and a surgical oncologist, before resection of the sarcoma if possible. Chemotherapy using an anthracycline- and ifosfamide-based regimen may improve disease-free and overall survival rates. Chemotherapy appears to be most beneficial for patients with very large (≥10 cm), high-grade sarcomas of the extremity who are at a high risk of experiencing distant recurrence of disease. The effect of adjuvant chemotherapy on overall survival remains controversial. Research is greatly needed to identify the patients who are most likely to benefit from conventional chemotherapy, improve the treatment of retroperitoneal sarcomas, and identify novel agents that may impact the natural history of high-risk soft tissue sarcoma.

scholarly journals Dynamic prediction of overall survival for patients with high-grade extremity soft tissue sarcoma

2018 ◽  
Vol 27 (4) ◽  
pp. 695-701 ◽  
Author(s):  
A.J. Rueten-Budde ◽  
V.M. van Praag ◽  
M.A.J. van de Sande ◽  
M. Fiocco ◽  
Lee M. Jeys ◽  
...  
Keyword(s):  
Overall Survival ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
High Grade ◽  
Dynamic Prediction ◽  
Extremity Soft Tissue Sarcoma

Does the addition of chemotherapy to neoadjuvant radiotherapy impact survival in high-risk extremity and trunk soft tissue sarcoma?

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11054-11054
Author(s):  
Mudit Chowdhary ◽  
Akansha Chowdhary ◽  
Neilayan Sen ◽  
Nicholas George Zaorsky ◽  
Kirtesh R. Patel ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Tumor Size ◽  
Primary Site ◽  
High Grade ◽  
Neoadjuvant Radiotherapy ◽  
Cancer Data ◽  
The Impact

11054 Background: Large, high-grade extremity/trunk (ET) non-rhabdomyosarcoma soft-tissue sarcoma (STS) is at high risk for distant recurrence and death. The integration of chemotherapy (C) to standard of care neoadjuvant radiotherapy (RT) remains controversial, even for these patients. This study examines the impact of adding C to neoadjuvant RT on overall survival (OS) in high risk ET-STS. Methods: The National Cancer Data Base (NCDB) was queried for patients ≥18 years with high risk (≥5 cm + high grade) non-rhabdomyosarcoma ET-STS (WHO histology) who received neoadjuvant RT and limb sparing surgery from 2006-2014. Patients were next stratified based upon receipt of C (RT and CRT cohorts). Overall survival (OS) for RT vs CRT cohorts was analyzed using the Kaplan-Meier (KM) method, log-rank test, and Cox proportional hazards models. Propensity score-matched analysis (PSM) was employed to account for potential treatment selection bias between cohorts. Results: A total of 848 (71.1%) and 344 (28.9%) patients received RT and CRT, respectively. Patient cohorts were well-balanced except for the CRT cohort having higher rates of treatment in the West (22.1% vs 10.6%) & Midwest (28.3% vs 22.7%), Charlson-Deyo [CD] score 0 vs ≥1 (85.5% vs 79.4%), younger age (≤50) (45.9% vs 21.7%), synovial sarcoma histology (18.9% vs 3.2%), earlier year of diagnosis (2006-2010) (39.5% vs 32.3%), and positive lymphovascular invasion (2.0 vs 1.51%), (p < 0.05 each). The KM 5-year OS was significantly higher in the CRT vs RT cohort: 69.2% vs 58.1% on univariate (p < 0.0001) and multivariate analysis (Hazard Ratio [HR]: 0.66; 95% Confidence Interval [CI]: 0.52-0.85; p = 0.001) even after adjusting for age, race, income, CD score, histology, tumor size, tumor grade, and primary site (lower extremity; upper extremity; trunk). PSM identified evenly matched cohorts of 300 patients each with respect to age, income, CD score, histology, grade, tumor size, and primary site. The addition of neoadjuvant C remained prognostic for OS on PSM (HR: 0.74 [0.56-0.99], p = 0.042). Conclusions: The addition of C to neoadjuvant RT was associated with improved OS in patients with high risk non-rhabdomyosarcoma ET-STS in the NCDB. These hypothesis generating results support prospective evaluation.

Patients with an increased time to treatment initiation have a poorer overall survival after definitive surgery for localized high-grade soft-tissue sarcoma in the extremity or trunk

2021 ◽  
Vol 103-B (6) ◽  
pp. 1142-1149 ◽  
Author(s):  
Koichi Ogura ◽  
Tomohiro Fujiwara ◽  
John H. Healey
Keyword(s):  
Overall Survival ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Treatment Initiation ◽  
Private Insurance ◽  
Hazard Ratio ◽  
High Grade ◽  
Time To Treatment ◽  
Definitive Surgery ◽  
Time To Treatment Initiation

Aims Time to treatment initiation (TTI) is generally defined as the time from the histological diagnosis of malignancy to the initiation of first definitive treatment. There is no consensus on the impact of TTI on the overall survival in patients with a soft-tissue sarcoma. The purpose of this study was to determine if an increased TTI is associated with overall survival in patients with a soft-tissue sarcoma, and to identify the factors associated with a prolonged TTI. Methods We identified 23,786 patients from the National Cancer Database who had undergone definitive surgery between 2004 and 2015 for a localized high-grade soft-tissue sarcoma of the limbs or trunk. A Cox proportional hazards model was used to examine the relationship between a number of factors and overall survival. We calculated the incidence rate ratio (IRR) using negative binomial regression models to identify the factors that affected TTI. Results Patients in whom the time to treatment initiation was prolonged had poorer overall survival than those with a TTI of 0 to 30 days. These were: 31 to 60 days (hazard ratio (HR) 1.08, p = 0.011); 61 to 90 days (HR 1.11, p = 0.044); and 91 days (HR 1.22; p = 0.003). The restricted cubic spline showed that the hazard ratio increased substantially with a TTI longer than 50 days. Non-academic centres (vs academic centres; IRR ranging from 0.64 to 0.86; p < 0.001) had a shorter TTI. Those insured by Medicaid (vs private insurance; IRR 1.34), were uninsured (vs private insurance; IRR 1.17), or underwent a transition in care (IRR 1.62) had a longer TTI. Conclusion A time to treatment initiation of more than 30 days after diagnosis was independently associated with poorer survival. The hazard ratio showed linear increase, especially if the TTI was more than 50 days. We recommend starting treatment within 30 days of diagnosis to achieve the highest likelihood of cure for localized high-grade soft-tissue sarcomas in the limbs and trunk, even when a patient needs to be referred to a specialist centre. Cite this article: Bone Joint J 2021;103-B(6):1142–1149.

Prognosis and surgical outcome of soft tissue sarcoma with malignant fungating wounds

2020 ◽  
Vol 51 (1) ◽  
pp. 78-84
Author(s):  
Koichi Okajima ◽  
Hiroshi Kobayashi ◽  
Tomotake Okuma ◽  
Sho Arai ◽  
Liuzhe Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Soft Tissue ◽  
Local Recurrence ◽  
Soft Tissue Sarcoma ◽  
Limb Salvage ◽  
Salvage Surgery ◽  
Wound Complications ◽  
Limb Salvage Surgery ◽  
High Grade ◽  
Surgical Wound

Abstract Objective Malignant fungating wounds are ulcerating tumors that infiltrate the overlying skin. Little evidence exists regarding the prognosis or treatment of malignant fungating wound in soft tissue sarcoma. This study aimed to reveal the prognosis and outcome of surgical treatment of malignant fungating wound in soft tissue sarcoma. Methods We retrospectively reviewed 26 patients with malignant fungating wound in high-grade soft tissue sarcoma between 2005 and 2018. The patients’ characteristics, treatments, surgical wound complications, local recurrences and prognoses were analyzed. Overall survival was analyzed using the Kaplan–Meier method and compared with that of the control cohort, consisting of 236 consecutive patients with non-malignant fungating wound high-grade soft tissue sarcoma treated during the same period. Results Among the 26 patients, undifferentiated pleomorphic sarcoma was the most common subtype. Twenty-three patients, including 20 (87%) and 3 (13%), underwent limb-salvage surgery and amputation, respectively. Among the 20 patients who underwent limb-salvage surgery, 4 (20%) had surgical wound complications, which required additional surgical procedures. Excluding the patients who underwent palliative surgery, local recurrence occurred in 2 patients (11%). The 5-year overall survival rate for all high-grade malignant fungating wound and non-malignant fungating wound patients was 26.0 and 67.3% (P &lt; 0.0001), respectively. Conclusions Malignant fungating wounds in soft tissue sarcoma were significantly associated with a poor prognosis; however, the incidence of surgical complications and local recurrence after limb-salvage surgery was comparable to that of general soft tissue sarcoma cases. Limb-salvage surgery should be considered, if possible, to preserve the patient’s quality of life because of the dismal prognosis of patients with malignant fungating wound in soft tissue sarcoma.

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