CORR Insights®: Is Metformin Use Associated With Prolonged Overall Survival In Patients with Soft Tissue Sarcoma? A Surveillance, Epidemiology, and End Results-Medicare Study

Background: Radio-frequency ablation (RFA) and Stereotactic Body Radiation Therapy (SBRT) are two emerging therapies for lung metastases. Introduction: We performed a literature review to evaluate outcomes and complications of these procedures in patients with lung metastases from soft tissue sarcoma (STS). Method: After selection, seven studies were included for each treatment encompassing a total of 424 patients: 218 in the SBRT group and 206 in the RFA group. Results: The mean age ranged from 47.9 to 64 years in the SBRT group and from 48 to 62.7 years in the RFA group. The most common histologic subtype was, in both groups, leiomyosarcoma. : In the SBRT group, median overall survival ranged from 25.2 to 69 months and median disease-free interval from 8.4 to 45 months. Two out of seven studies reported G3 and one G3 toxicity, respectively. In RFA patients, overall survival ranged from 15 to 50 months. The most frequent complication was pneumothorax. : Local control showed high percentage for both procedures. Conclusion: SBRT is recommended in patients unsuitable to surgery, in synchronous bilateral pulmonary metastases, in case of deep lesions and in patients receiving high-risk systemic therapies. RFA is indicated in case of a long disease-free interval, in oligometastatic disease, when only the lung is involved, in small size lesions far from large vessels. : Further large randomized studies are necessary to establish whether these treatments may also represent a reliable alternative to surgery.

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

Current Oncology ◽

10.3390/curroncol28010078 ◽

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.

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Identification of Aneuploid Circulating Tumor Cells in Soft-Tissue Sarcoma Patients: A Pilot Study

Oncology ◽

10.1159/000509326 ◽

2020 ◽

Vol 98 (12) ◽

pp. 893-896

Author(s):

Andrea Napolitano ◽

Alessandro Minelli ◽

Daniele Santini ◽

Giuseppe Tonini ◽

Bruno Vincenzi

Keyword(s):

Overall Survival ◽

Pilot Study ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Tumor Cells ◽

In Silico ◽

The Cancer Genome Atlas ◽

Cancer Genome Atlas ◽

First Time ◽

Genome Atlas

Background: Circulating tumor cells (CTCs) have been identified and shown to have prognostic and predictive roles in several types of carcinoma. More recently, aneuploid CTCs have become subject of a growing interest, as aneuploidy is considered a hallmark of cancer often associated with poor prognosis. Here, we aimed to identify for the first time aneuploid CTCs in soft-tissue sarcoma (STS) patients and show supportive in silico evidence on the prognostic role of aneuploidy in mesenchymal cancers. Methods: In our pilot study, we collected blood from 4 metastatic STS patients and 4 age- and sex-matched healthy controls. After sample processing, cells were cyto-centrifuged onto glass slides and FISH was performed using 5 probes. The in silico analysis was performed using data from The Cancer Genome Atlas cohort of STS patients, using the validated Aneuploidy Score. We divided the patients in two populations (aneuploidy-high, Ane-Hi, and aneuploidy-low, Ane-Lo) using the median value of the Aneuploidy Score as a cutoff. Kaplan-Meier curves associated with log-rank test were used to compare progression-free and overall survival between groups. GraphPad Prism 8.0 (La Jolla, CA, USA) was used for statistical analyses. Results: Aneuploid CTCs were identified in all 4 STS patients and in none of the controls, with a median value of 4 (range 3–6) per 7 mL of blood. Ane-Hi patients showed a significantly worse progression-free and overall survival compared to Ane-Lo patients. The same trend was maintained when analyzing the data based on the different histologies. Conclusions: We identified for the first time aneuploid CTCs in STS patients using fluorescence in situ hybridization in a surface marker-independent way. We also showed that the Aneuploidy Score has a prognostic value both in terms of progression-free survival and overall survival in STS patients using The Cancer Genome Atlas data, regardless of the histology.

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Complement and coagulation cascades pathway correlates with chemosensitivity and overall survival in patients with soft tissue sarcoma

European Journal of Pharmacology ◽

10.1016/j.ejphar.2020.173121 ◽

2020 ◽

Vol 879 ◽

pp. 173121 ◽

Cited By ~ 1

Author(s):

Jing Zhang ◽

Maoshan Chen ◽

Yuanyuan Zhao ◽

Huihua Xiong ◽

Tal Sneh ◽

...

Keyword(s):

Overall Survival ◽

Soft Tissue ◽

Soft Tissue Sarcoma

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ASO Author Reflections: Does a Nonsystematic Regarding Excision Approach After Complete Unplanned Excision of a Soft Tissue Sarcoma Impact Amputation Rate, Metastatic Risk, or Overall Survival?

Annals of Surgical Oncology ◽

10.1245/s10434-019-07919-2 ◽

2019 ◽

Vol 26 (S3) ◽

pp. 768-769 ◽

Cited By ~ 1

Author(s):

Gauthier Decanter ◽

Sylvie Bonvalot

Keyword(s):

Overall Survival ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Amputation Rate ◽

Unplanned Excision ◽

Metastatic Risk

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Indeterminate Pulmonary Nodules at Diagnosis in Rhabdomyosarcoma: Are They Clinically Significant? A Report From the European Paediatric Soft Tissue Sarcoma Study Group

Journal of Clinical Oncology ◽

10.1200/jco.18.01535 ◽

2019 ◽

Vol 37 (9) ◽

pp. 723-730 ◽

Cited By ~ 5

Author(s):

Bas Vaarwerk ◽

Gianni Bisogno ◽

Kieran McHugh ◽

Hervé J. Brisse ◽

Carlo Morosi ◽

...

Keyword(s):

Computed Tomography ◽

Overall Survival ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Pulmonary Nodules ◽

Study Group ◽

Event Free Survival ◽

Free Survival ◽

Chest Computed Tomography ◽

Computed Tomography Scans

Purpose To evaluate the clinical significance of indeterminate pulmonary nodules at diagnosis (defined as ≤ 4 pulmonary nodules < 5 mm or 1 nodule measuring ≥ 5 and < 10 mm) in patients with pediatric rhabdomyosarcoma (RMS). Patients and Methods We selected patients with supposed nonmetastatic RMS treated in large pediatric oncology centers in the United Kingdom, France, Italy, and the Netherlands, who were enrolled in the European Soft Tissue Sarcoma Study Group (E pSSG) RMS 2005 study. Patients included in the current study received a diagnosis between September 2005 and December 2013, and had chest computed tomography scans available for review that were done at time of diagnosis. Local radiologists were asked to review the chest computed tomography scans for the presence of pulmonary nodules and to record their findings on a standardized case report form. In the E pSSG RMS 2005 Study, patients with indeterminate pulmonary nodules were treated identically to patients without pulmonary nodules, enabling us to compare event-free survival and overall survival between groups by log-rank test. Results In total, 316 patients were included; 67 patients (21.2%) had indeterminate pulmonary nodules on imaging and 249 patients (78.8%) had no pulmonary nodules evident at diagnosis. Median follow-up for survivors (n = 258) was 75.1 months; respective 5-year event-free survival and overall survival rates (95% CI) were 77.0% (64.8% to 85.5%) and 82.0% (69.7% to 89.6%) for patients with indeterminate nodules and 73.2% (67.1% to 78.3%) and 80.8% (75.1% to 85.3%) for patients without nodules at diagnosis ( P = .68 and .76, respectively). Conclusion Our study demonstrated that indeterminate pulmonary nodules at diagnosis do not affect outcome in patients with otherwise localized RMS. There is no need to biopsy or upstage patients with RMS who have indeterminate pulmonary nodules at diagnosis.

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Doxorubicin-Based Chemotherapy for the Palliative Treatment of Adult Patients with Locally Advanced or Metastatic Soft-Tissue Sarcoma: A Meta-Analysis and Clinical Practice Guideline

Sarcoma ◽

10.1080/13577140020008066 ◽

2000 ◽

Vol 4 (3) ◽

pp. 103-112 ◽

Cited By ~ 69

Author(s):

Vivien H. C. Bramwell ◽

Dale Anderson ◽

Manya L. Charette

Keyword(s):

Overall Survival ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Adverse Effects ◽

Combination Therapy ◽

Meta Analysis ◽

Single Agent ◽

Locally Advanced ◽

Metastatic Soft Tissue Sarcoma ◽

Single Agent Chemotherapy

Purpose.To make recommendations for the use of doxorubicin-based chemotherapy in patients with soft-tissue sarcoma.Patients.The recommendations apply to patients with symptomatic unresectable locally advanced or metastatic soft-tissue sarcoma who are candidates for palliative chemotherapy.Methods.A systematic review of the published literature was combined with a consensus process around the interpretation of the evidence in the context of conventional practice to develop an evidence-based practice guideline.Results.Eight randomized trials comparing doxorubicin-based combination versus doxorubicin single-agent chemotherapy were reviewed. Response rates and overall survival were evaluated using pooled statistical analysis.The pooled response data in 2281 patients showed a slight trend favouring the combination therapy, although this did not reach statistical significance (odds ratio (OR), 0.79; 95% confidence interval (CI), 0.60–1.05;p=0.10). Survival data could only be abstracted from six studies involving 2097 patients, and showed no significant advantage for combination therapy (OR, 0.84; 95% CI, 0.67–1.06;p=0.13). Data on adverse effects could not be combined in a meta-analysis; however nausea, vomiting and myelosuppression were consistently more severe with combination chemotherapy than with single-agent chemotherapy.Discussion.Single-agent doxorubicin is an appropriate first-line chemotherapy option for advanced or metastatic soft-tissue sarcoma. Some doxorubicin-based combination chemotherapy regimens, given in conventional doses, produce only marginal increases in response rates, at the expense of increased adverse effects, and with no improvements in overall survival. Future randomized clinical trials should compare new regimens, whose activity has been established in single-arm studies, with single-agent doxorubicin, and include quality of life as an outcome measure.

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

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e21503 ◽

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.

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