Effect of beta blocker use in soft tissue sarcomas.

e23571 Background: Soft tissue sarcomas (STS) are a rare, heterogenous group of cancers that tend to have a poor prognosis and few effective treatment strategies. Beta blockers (BB), in particular non-selective BB such as propranolol, have been shown to have an antitumor effect in different malignancies, including breast, colon, and angiosarcomas. The underlying mechanism is unclear but it is thought to be related to the inhibition of beta receptors on malignant cells, which leads to decrease in tumor vascularity and hematogenous spread. In this retrospective analysis, we examined the effect of BB on the outcomes of STS at a tertiary referral center. Methods: Adult patients from 2000 through 2019 with a diagnosis of STS with adequate follow up were included, and were divided into 2 groups: patients on BB at any point during treatment and/or up to 6 months prior to diagnosis, and patients without BB. The patient and tumor data were extracted and analyzed. The primary outcome was overall survival (OS). Statistical methods included descriptive analysis, univariable and multivariable Cox proportional hazard regression analyses and Kaplan-Meier survival plots. Results: 448 patient charts were analyzed. Median age at diagnosis was 55 (range 18-89). 54% were male. 4.9% of patients were diagnosed with stage 4 disease. Histologies included: undifferentiated pleomorphic sarcoma 26.1%, leiomyosarcoma 10%, synovial sarcoma 9.2%, liposarcoma 7.8%, osteosarcoma 2.7%, Ewing sarcoma 2% and others 42.2%. 18.1% of patients were on BB during treatment, with metoprolol the most commonly used (59%). 96% of patients on BB had HTN and 44% had coronary artery disease. Patients on BB were less likely to receive adjuvant therapy (18% vs 26%). Patients on BB were more likely to have stage 4 disease at presentation (9.9% vs 3.8%). Multivariate analysis showed there was no significant difference in overall survival between patients on BB and those not on BB, HR 1.3 (CI 0.8-2.1, p = 0.24). Conclusions: There is no difference in overall survival in patients on beta blockers during treatment for STS after controlling for stage, comorbidities, smoking, and age. Further studies are needed to evaluate the effect of specific beta blocker drugs on soft tissue sarcoma outcomes.

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Extraskeletal Osteosarcoma: Analysis of Outcome of a Rare Neoplasm

Sarcoma ◽

10.1080/13577140020008084 ◽

2000 ◽

Vol 4 (3) ◽

pp. 119-123 ◽

Cited By ~ 44

Author(s):

Martin D. McCarter ◽

Jonathan J. Lewis ◽

Cristina R. Antonescu ◽

Murray F. Brennan

Keyword(s):

Soft Tissue ◽

Treatment Strategies ◽

Soft Tissue Sarcomas ◽

Individual Risk ◽

Disease Specific Survival ◽

Extraskeletal Osteosarcoma ◽

Comparable Group ◽

Prognostic Features ◽

Significant Difference ◽

Disease Specific

Purpose.Extraskeletal osteosarcoma represents an unusual soft-tissue sarcoma that historically is reported to carry an exceptionally poor prognosis.The objectives of this study were to use a prospectively gathered sarcoma database to test the prevailing clinical bias and more accurately describe the natural history, characterize the prognostic features, estimate survival and evaluate treatment strategies for this unusual sarcoma.Patients and methods.From a large database of nearly 4000 sarcomas at a single institution, 15 patients with pathologically confirmed extraskeletal osteosarcoma were analysed.Results and discussion.Extraskeletal osteosarcoma usually occurs as a large, deep, high-grade lesion in the lower extremity of older patients. Overall and disease-specific survival at 5 years was 50%, with a median follow-up of 35 months (range 3– 200 months). Use of adjuvant chemotherapy or radiation therapy did not appear to influence survival, but an effect may have been missed by the relatively low numbers in each group.When matched to a comparable group of patients with stage III extremity sarcomas, there was no significant difference in overall or disease-specific survival between groups. Treatment for extraskeletal osteosarcoma should follow established guidelines for treatment of soft-tissue sarcomas, with the decision regarding adjuvant therapy to be based on individual risk factors.

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Is local recurrence in bone and soft tissue sarcomas just a local recurrence or does it impact the overall survival, retrospective cohort from a sarcoma referral center

Journal of Surgical Oncology ◽

10.1002/jso.26663 ◽

2021 ◽

Author(s):

Obada Hasan ◽

Momin Nasir ◽

Muneeba Jessar ◽

Mustafa Hashimi ◽

Qiang An ◽

...

Keyword(s):

Overall Survival ◽

Soft Tissue ◽

Local Recurrence ◽

Retrospective Cohort ◽

Soft Tissue Sarcomas ◽

Referral Center ◽

It Impact

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Differences in clinical characteristics and tumor prognosis between primary and secondary conventional pelvic chondrosarcoma

BMC Cancer ◽

10.1186/s12885-020-07530-9 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Jie Zang ◽

Wei Guo ◽

Rongli Yang ◽

Xiaodong Tang ◽

Haijie Liang

Keyword(s):

Overall Survival ◽

Survival Rate ◽

Soft Tissue ◽

Clinical Characteristics ◽

Soft Tissue Mass ◽

Tumor Grade ◽

Overall Survival Rate ◽

Tissue Mass ◽

Significant Difference ◽

Initial Tumor

Abstract Background Chondrosarcoma (CS) most commonly involves the pelvis. This study aimed to analyze differences in clinical characteristics and prognostic factors between primary and secondary conventional pelvic CS, and provide reference for clinical diagnosis and treatment. Methods Eighty patients (54 primary cases and 26 secondary cases) with pelvic CS were included in this retrospective study. The tumor site, Enneking stage, soft tissue mass, margin, initial tumor grade, incidence of local recurrence and distant metastasis were evaluated. Kaplan-Meier method was used to calculate the overall survival rate. X2 test and log-rank test were used for univariate analysis, and Cox test was used in multivariate analysis. Results The average age of patients with secondary CS was significantly younger than that of patients with primary CS (P < 0.001). The soft tissue mass of patients with secondary CS was significantly larger than that of patients with primary CS (P = 0.002). There was a significant difference in initial tumor pathologic grade between the two groups (P = 0.002). No statistically significant difference was observed in the local recurrence rate between the two groups. The median recurrence time of patients with primary CS after the first treatment was significantly shorter than that of patients with secondary CS (P < 0.001). The overall survival rate of patients with secondary CS was much higher than that of patients with primary CS (P = 0.003). Cox regression analysis showed that the initial tumor grade was an independent factor in the overall survival rate of patients with CS. Conclusion There were significant differences in age, soft tissue mass, initial tumor grade, and overall survival rate between the two groups. The overall survival rate of pelvic CS was related to the initial tumor grade of CS.

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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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Soft Tissue Sarcoma – a Current Review of the Diagnostic and Treatment Strategies

Zeitschrift für Orthopädie und Unfallchirurgie ◽

10.1055/a-0820-6366 ◽

2019 ◽

Vol 157 (06) ◽

pp. 644-653 ◽

Cited By ~ 1

Author(s):

Sebastian Scheidt ◽

Cornelius Jacobs ◽

Sebastian Koob ◽

Kristian Welle ◽

Sebastian Walter ◽

...

Keyword(s):

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Treatment Algorithm ◽

Treatment Strategies ◽

Soft Tissue Sarcomas ◽

Current Evidence ◽

Delayed Treatment ◽

Current Review ◽

Soft Tissue Swelling ◽

A Current

AbstractSoft tissue sarcomas are a heterogeneous group of neoplasias that due to their often clinically silent appearance often remain undetected or experience delayed treatment. Especially soft tissue swelling is often misinterpreted by patients and doctors and trivialized or verified with an incorrect biopsy technique. The hereby evoked complications for the patients are serious and may be reduced by simply following the available guidelines. The treatment of soft tissue sarcomas requires a close interdisciplinary coordination between specialists in tumor orthopedics, oncology, radiology, pathology and radiotherapy. On the basis of a selective literature review, the following article points out the current evidence on the treatment and illustrates a treatment algorithm.

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Combination chemotherapy using adriamycin, DTIC, cyclophosphamide, and actinomycin D for advanced soft tissue sarcomas: a randomized comparative trial. A phase III, Southwest Oncology Group Study (7613).

Journal of Clinical Oncology ◽

10.1200/jco.1987.5.6.851 ◽

1987 ◽

Vol 5 (6) ◽

pp. 851-861 ◽

Cited By ~ 62

Author(s):

L H Baker ◽

J Frank ◽

G Fine ◽

S P Balcerzak ◽

R L Stephens ◽

...

Keyword(s):

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Actinomycin D ◽

Malignant Tumors ◽

Soft Tissue Sarcomas ◽

Comparative Trial ◽

Phase Iii ◽

Oncology Group ◽

Southwest Oncology Group ◽

Significant Difference

The term soft tissue sarcoma refers to a large variety of malignant tumors arising in extraskeletal connective tissues that connect, support, and surround discrete anatomic structures. All visceral organs also contain a connective stroma that can undergo malignant transformation. Because of the histological similarities of this group of tumors and their relative rarity, treatment prescriptions for patients that have disseminated disease are most often uniform. In this study, we asked the question whether adding a third drug (cyclophosphamide or actinomycin D) to Adriamycin (Adr [Adria Laboratories, Columbus, OH])-(3,3-dimethyl-1-triazeno)- imidazole-4-carboxamide (DTIC) would improve the response rate and/or survival. A unique feature of this cooperative group clinical trial was the mandatory pathology review of the histological material. All patients of the Southwest Oncology Group between June 1, 1976, and November 17, 1979, who had a biopsy-confirmed diagnosis of a soft tissue sarcoma with convincing clinical or biopsy-documented evidence of metastatic disease were eligible for the study. Patients were randomized to receive (1) Adr, 60 mg/m2 intravenously, day 1, and DTIC, 250 mg/m2 every 3 weeks (104 patients); (2) Adr and DTIC as in (1) and cyclophosphamide, 500 mg/m2, day 1 (112 patients); or (3) Adr and DTIC as in (1) and actinomycin D, 1.2 mg/m2, day 1, (119 patients). There was no statistically significant difference in response rates (33%, 34%, and 24%) (P = .25). Median durations of response were 31 weeks in the Adr-DTIC arm, 26 weeks in the cyclophosphamide-DTIC-Adr arm, and 23 weeks in the Adr-DTIC-Actinomycin D arm (P = .78). Median durations of survival were 37, 42, and 50 weeks, respectively. Again, no statistically significant differences were observed (P = .59). Toxicities from each of these treatment arms were formidable and were equivalent. Prognostic factor analysis showed a prognosis based on bone marrow reserve, sex, and pathology subtype favorable to patients.

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A randomized phase II study of durvalumab and tremelimumab compared to doxorubicin in patients with advanced or metastatic soft tissue sarcoma (MEDISARC, AIO-STS 0415).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.tps11075 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. TPS11075-TPS11075

Author(s):

Viktor Grünwald ◽

Sebastian Bauer ◽

Barbara Hermes ◽

Philipp Ivanyi ◽

Lars H Lindner ◽

...

Keyword(s):

Clinical Trial ◽

Overall Survival ◽

Soft Tissue ◽

Phase Ii ◽

Checkpoint Inhibitors ◽

Performance Status ◽

Soft Tissue Sarcomas ◽

Predictive Biomarkers ◽

Ecog Performance Status ◽

Curative Intent

TPS11075 Background: Soft tissue sarcomas (STS) are rare tumors and exhibit substantial histological diversity. Efficacious targeted 1st line treatment for advanced or metastatic STS is not available, and the standard therapy has been anthracycline-based for decades. This strategy shows poor efficacy, as demonstrated by a median Overall Survival (OS) of 12-20 months. Several STS subtypes, however, have been shown to express PD-L1, and immune checkpoint inhibitors (ICI) have demonstrated principle anti-tumor activity in pretreated STS. Our ongoing clinical trial tests the activity and safety of ICI combination therapy in the first-line setting. We hypothesize that the dual checkpoint blockade with Durvalumab (PD-L1) and Tremelimumab (CTLA-4) improves overall survival in STS when compared to the standard of care doxorubicin. Methods: MEDISARC is a multi-center phase II trial that is enrolling adult treatment-naïve patients with histologically confirmed STS of intermediate or high grade (FNCLCC grade 2 or 3) not amenable to surgery with curative intent and ECOG performance status 0-2. Chemosensitive histologic STS are eligible. 100 patients will be randomized 1:1, stratified by ECOG status (0 vs. 1/2). Patients in the experimental arm are treated with fixed doses of durvalumab (1.5 g Q4W) and tremelimumab (75 mg Q4W for 3 cycles, then Q12W) until Progressive Disease (PD) or for a maximum of 12 months. Doxorubicin treatment in the standard arm is at 75 mg/m2 Q3W and limited to 6 cycles. OS is the primary endpoint. Secondary endpoints include 2-year OS rate, PFS, ORR according to conventional and modified RECIST 1.1, safety and tolerability and health-related quality of life (EORTC QLQ-C30). OS analysis may be performed when the required number of events (E=70) has been observed. All randomized and treated subjects will be included in the efficacy and safety analysis. The accompanying translational research aims to identify prognostic and predictive biomarkers in blood and tumor tissue. Enrollment of patients started in April 2018 and is ongoing. As of February 2019, 32 patients have been enrolled. The study is sponsored by AIO-Studien-gGmbH, Berlin, Germany. Clinical trial information: 2016-004750-15.

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Skp2 Protein Expression in Soft Tissue Sarcomas

Journal of Clinical Oncology ◽

10.1200/jco.2003.05.112 ◽

2003 ◽

Vol 21 (4) ◽

pp. 722-727 ◽

Cited By ~ 33

Author(s):

Andre M. Oliveira ◽

Scott H. Okuno ◽

Antonio G. Nascimento ◽

Ricardo V. Lloyd

Keyword(s):

Overall Survival ◽

Soft Tissue ◽

Cox Regression ◽

Univariate Analysis ◽

Soft Tissue Sarcomas ◽

Inverse Correlation ◽

Ki 67 ◽

Female Ratio ◽

Skp2 Expression ◽

Disease Free

Background: p45 S phase kinase-associated protein-2 (p45skp2), a member of the F-box family of proteins, is an important component of the Skp1-Cullin-F-box protein (SCF) ubiquitin-ligase complex (SCFskp2). The latter has been implicated in the ubiquitination and degradation of p27kip1 (p27) and G1-S cell cycle progression. The expression and prognostic role of Skp2 in a large series of soft tissue sarcomas has not been previously investigated. Methods: Clinicopathologic features and immunohistochemical expression of Skp2, p27, and Ki-67 proteins were studied in 182 cases of soft tissue sarcomas (American Joint Committee on Cancer stages II and III). Survival analyses were performed using the Kaplan-Meier method and the Cox regression model. Results: The male to female ratio was 1.2:1, and the median age at the diagnosis was 53 years. The tumors were predominantly located in the lower extremities (n = 163; 90%) and had a median size of 9 cm. High Skp2 expression (≥ 10% of the cells) was identified in 68 tumors (37%), and was correlated with high grade histology (P = .002) and Ki-67 proliferative index (r = 0.44; P < .0001), but not with p27 expression (r = −0.02; P = .80). By univariate analysis, high Skp2 expression was associated with decreased metastasis-free, disease-free, and overall survival. In a multivariate model, high Skp2 expression was an independent predictor for decreased local recurrence-free, disease-free, and overall survival. Conclusion: These results indicate that Skp2 expression is associated with cell proliferation and a worse prognosis in soft tissue sarcomas. The lack of an inverse correlation between Skp2 and p27 suggests that additional molecular events associated with either Skp2 expression or p27 proteolysis may be operating in these tumors.

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