Development and Validation of Novel Nomograms for Predicting Specific Distant Metastatic Sites and Overall Survival of Patients With Soft Tissue Sarcoma

Purpose: The goal of this study is to construct nomograms to effectively predict the distant metastatic sites and overall survival (OS) of soft tissue sarcoma (STS) patients. Methods: STS case data between 2010 and 2015 for retrospective study were gathered from public databases. According to the chi-square and multivariate logistic regression analysis determined independent predictive factors of specific metastatic sites, the nomograms based on these factors were consturced. Subsequently, combined metastatic information a nomogram to predict 1-, 2-, and 3-year OS of STS patients was developed. The performance of models was validated by the area under the curve (AUC), calibration plots, and decision curve analyses (DCA). Results: A total of 7001 STS patients were included in this retrospective study, including 4901 cases in the training group and the remaining 2,100 patients in the validation group. Three nomograms were established to predict lung, liver and bone metastasis, and satisfactory results have been obtained by internal and external validation. The AUCs for predicting lung, liver, and bone metastases in the training cohort were 0.796, 0.799, and 0.766, respectively, and in the validation cohort were 0.807, 0.787, and 0.775, respectively, which means that the nomograms have good discrimination. The calibration curves showed that the models have high precision, and the DCA manifested that the nomograms have great clinical application prospects. Through univariate and multivariate COX regression analyses, 8 independent prognosis factors of age, grade, histological type, tumor size, surgery, chemotherapy, radiatiotherapy and lung metastasis were determined. A nomogram was then constructed to predict the 1-, 2-, and 3-years OS, which has a good performance in both internal and external validations. Conclusion: The nomograms for predicting specific metastatic sites and OS have good discrimination, accuracy and clinical applicability. The models could accurately predict the metastatic risk and survival information, and help clinical decision-making.

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Prognostic implications of tumor associated macrophages (TAMs) in soft tissue sarcoma.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e22548 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e22548-e22548 ◽

Cited By ~ 1

Author(s):

Shailaja KS Raj ◽

Mitra Kooshki ◽

Melissa Winters ◽

Greg B. Russell ◽

Lance D Miller ◽

...

Keyword(s):

Overall Survival ◽

Soft Tissue ◽

Neoadjuvant Chemotherapy ◽

Soft Tissue Sarcoma ◽

Immune Checkpoint ◽

Cox Regression ◽

Macrophage Infiltration ◽

Tumor Associated Macrophages ◽

Tumor Immunogenicity ◽

Mutation Data

e22548 Background: Clinical responses in patients with soft tissue sarcoma administered immune checkpoint inhibitors have been infrequent. Little is known regarding the immune microenvironment in soft tissue sarcoma that leads to a lack of effective responses with immune therapies. Whilst several studies have shown T cell infiltration in sarcomas, these tumors do not respond to immunotherapies. Macrophages are important regulators of immune responses in the tumor microenvironment. Studies in mouse models indicate that macrophages regulate immune checkpoint inhibitor response. With the overall goal of developing more effective combination immunotherapies for sarcoma, we examined tumor associated macrophages in patients with soft tissue sarcoma administered neoadjuvant chemotherapy. Interactions between macrophage infiltration, tumor immunogenicity and overall survival were also assessed using publicly available RNAseq and exome mutation data. Methods: Immunohistochemistry was performed on formalin fixed soft tissue sarcoma tissue. Tissues from 20 patients with soft tissue sarcoma pre and post neo-adjuvant chemotherapy were included. TAMs were detected by CD68; M2 subtype were detected by CD163. CD4, CD8, and CD25 T cells were also examined. The density of CD68+ TAMs, CD163+ TAMs and the ratio of CD163+ TAMs / CD68+ TAMs were calculated and their correlation with survival was also made. Publicly available RNAseq and exome mutation data were assembled from The Cancer Genome Atlas (TCGA) sarcoma cohort (n = 259). For each tumor, a relative measure of abundance of tumor-infiltrating macrophages was estimated using gene expression. Tumor mutational burden (TMB), expressed as the rate of non- synonymous mutations per megabase of sequenced DNA, was used as a measure of tumor immunogenicity. Interactions between macrophage infiltration, tumor immunogenicity and overall survival were assessed by Cox regression and Kaplan-Meier analysis. Categorical relationships involving clinical, immunologic, and genomic features of the tumor immune subclasses were compared. Results: Specific alteration in the density of CD68+ TAMs, CD163+ TAMs, and the CD163 / CD68 ratio were observed in patients with soft tissue sarcoma responding to neoadjuvant chemotherapy. Categorical relationships involving macrophage infiltration, TMB, and survival were also observed. Conclusions: These study support the targeting of tumor associated macrophages in patients with soft tissue sarcoma and suggest that changes in TAMs may be achievable using neoadjuvant chemotherapy.

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Non-surgical Treatments for Lung Metastases in Patients with soft Tissue Sarcoma: Stereotactic Body Radiation Therapy (SBRT) and Radiofrequency Ablation (RFA)

Current Medical Imaging Formerly Current Medical Imaging Reviews ◽

10.2174/1573405616999200819165709 ◽

2020 ◽

Vol 16 ◽

Author(s):

Cecilia Tetta ◽

Maria Carpenzano ◽

Areej Tawfiq J Algargoush ◽

Marwah Algargoosh ◽

Francesco Londero ◽

...

Keyword(s):

Overall Survival ◽

Radiation Therapy ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Stereotactic Body Radiation Therapy ◽

Lung Metastases ◽

Disease Free Interval ◽

Stereotactic Body Radiation ◽

Free Interval ◽

Disease Free

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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Prognostic Association between Common Laboratory Tests and Overall Survival in Elderly Men with De Novo Metastatic Castration Sensitive Prostate Cancer: A Population-Based Study in Canada

Cancers ◽

10.3390/cancers13112844 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2844

Author(s):

Christopher J. D. Wallis ◽

Bobby Shayegan ◽

Scott C. Morgan ◽

Robert J. Hamilton ◽

Ilias Cagiannos ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Clinical Decision Making ◽

Cox Regression ◽

De Novo ◽

Population Based ◽

Population Based Study ◽

Cox Regression Analysis ◽

Lymphocyte Ratio ◽

Laboratory Markers

De novo cases of metastatic prostate cancer (mCSPC) are associated with poorer prognosis. To assist in clinical decision-making, we aimed to determine the prognostic utility of commonly available laboratory-based markers with overall survival (OS). In a retrospective population-based study, a cohort of 3556 men aged ≥66 years diagnosed with de novo mCSPC between 2014 and 2019 was identified in Ontario (Canada) administrative database. OS was assessed by using the Kaplan–Meier method. Multivariate Cox regression analysis was performed to evaluate the association between laboratory markers and OS adjusting for patient and disease characteristics. Laboratory markers that were assessed include neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), albumin, hemoglobin, serum testosterone and PSA kinetics. Among the 3556 older men with de novo mCSPC, their median age was 77 years (IQR: 71–83). The median survival was 18 months (IQR: 10–31). In multivariate analysis, a statistically significant association with OS was observed with all the markers (NLR, PLR, albumin, hemoglobin, PSA decrease, reaching PSA nadir and a 50% PSA decline), except for testosterone levels. Our findings support the use of markers of systemic inflammation (NLR, PLR and albumin), hemoglobin and PSA metrics as prognostic indicators for OS in de novo mCSPC.

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Impact of sarcopenia in advanced and metastatic soft tissue sarcoma

International Journal of Clinical Oncology ◽

10.1007/s10147-021-01997-7 ◽

2021 ◽

Author(s):

Dennis Strassmann ◽

Bennet Hensen ◽

Viktor Grünwald ◽

Katharina Stange ◽

Hendrik Eggers ◽

...

Keyword(s):

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Cox Regression ◽

Therapy Response ◽

Prognostic Impact ◽

Patient Counseling ◽

Skeletal Muscle Index ◽

Prognostic Parameter ◽

Dismal Prognosis ◽

Metastatic Soft Tissue Sarcoma

Abstract Introduction Advanced or metastatic soft tissue sarcoma (a/mSTS) is associated with a dismal prognosis. Patient counseling on treatment aggressiveness is pivotal to avoid over- or undertreatment. Recently, evaluation of body composition markers like the skeletal muscle index (SMI) became focus of interest in a variety of cancers. This study focuses on the prognostic impact of SMI in a/mSTS, retrospectively. Methods 181 a/mSTS patients were identified, 89 were eligible due to prespecified criteria for SMI assessment. Baseline CT-Scans were analyzed using an institutional software solution. Sarcopenia defining cut-off values for the SMI were established by optimal fitting method. Primary end point was overall survival (OS) and secondary endpoints were progression free survival (PFS), disease control rate (DCR), overall response rate (ORR). Descriptive statistics as well as Kaplan Meier- and Cox regression analyses were administered. Results 28/89 a/mSTS patients showed sarcopenia. Sarcopenic patients were significantly older, generally tended to receive less multimodal therapies (62 vs. 57 years, P = 0.025; respectively median 2.5 vs. 4, P = 0.132) and showed a significantly lower median OS (4 months [95%CI 1.9–6.0] vs. 16 months [95%CI 8.8–23.2], Log-rank P = 0.002). Sarcopenia was identified as independent prognostic parameter of impaired OS (HR 2.40 [95%-CI 1.4–4.0], P < 0.001). Moreover, DCR of first palliative medical treatment was superior in non-sarcopenic patients (49.2% vs. 25%, P = 0.032). Conclusion This study identifies sarcopenia as a prognostic parameter in a/mSTS. Further on, the data suggest that sarcopenia shows a trend of being associated with first line therapy response. SMI is a promising prognostic parameter, which needs further validation.

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

Clinical Orthopaedics and Related Research ◽

10.1097/corr.0000000000002045 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Ian D. Hutchinson ◽

Ashar Ata ◽

Matthew R. DiCaprio

Keyword(s):

Overall Survival ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

End Results

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Retroperitoneal Soft-Tissue Sarcoma: Retrospective Study from a Cancer Hospital in Pakistan

Journal of Surgery and Research ◽

10.26502/jsr.10020110 ◽

2021 ◽

Vol 04 (01) ◽

Author(s):

Jibran Mohsin ◽

Aun Jamal ◽

Noor-ul Mubeen ◽

Aamir Ali Syed

Keyword(s):

Retrospective Study ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Cancer Hospital ◽

Retroperitoneal Soft Tissue Sarcoma

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Clinicopathological study of soft tissue sarcoma-retrospective study of tertiary cancer institute in eastern India

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20204907 ◽

2020 ◽

Vol 8 (11) ◽

pp. 4075

Author(s):

Kunhi Mohammed K. P. ◽

Snehasis Pradhan ◽

Supratim Bhattacharyya ◽

Prafulla Kumar Das ◽

Muhammed Navas N. K.

Keyword(s):

Retrospective Study ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Malignant Tumors ◽

Soft Tissue Sarcomas ◽

The Body ◽

Female Ratio ◽

Pleomorphic Sarcoma ◽

Frequent Variety ◽

Male To Female

Background: Soft tissue sarcomas are a rare and heterogeneous group of malignant tumors of mesenchymal origin that comprise less than 1 percent of all adult malignancies. Although they occur anywhere in the body, they involve most commonly in extremities, trunk, retroperitoneum and head and neck. The aim of the study was to analyze clinical and histopathological features of various soft tissue sarcomas.Methods: This was a retrospective study, conducted in tertiary cancer centre in Odisha during the period 2015 to 2018. We collected clinical parameters like age, sex, site of swelling, any associated pain and biopsy reports and these variables were correlated with final histopathology reports.Results: A total of 107 patients were included in the study, with male to female ratio of 2:1(71 and 36) and average age of 43.45 years. All of them presented with a swelling. The lower extremities were the most common sites i.e. 44.62%. Pleomorphic sarcoma was the most frequent histologic variety comprising 43% and less frequent variety were angiosarcoma, and myxoid sarcoma.Conclusions: Soft tissue sarcoma are predominant in males and middle aged population are frequently affected. Most common affected site is lower extremity and pleomorphic sarcoma is the prominent histologic type.

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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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