Outcome In Soft Tissue Sarcoma Patients Research Articles

Diabetes mellitus is independently associated with adverse clinical outcome in soft tissue sarcoma patients

Diabetes mellitus (DM) and hyperglycemia are known predictors of adverse outcome in different tumor entities. The present study investigated the effect of DM and pre-surgery blood glucose levels on cancer specific survival (CSS), overall survival (OS), and disease-free survival (DFS) in non-metastatic soft tissue sarcoma (STS) patients. A total of 475 STS patients who underwent curative resection were included in this retrospective study. CSS, DFS, and OS were assessed using Kaplan–Meier curves. The association between pre-existing DM as well as mean pre-surgery blood glucose levels and all 3 survival endpoints was analyzed using Cox-hazard proportional (for OS and DFS) and competing risk regression models (for CSS). In unadjusted analysis, DM was significantly associated with adverse CSS (sub-hazard ratio [SHR]: 2.14, 95% confidence interval [CI] 1.18–3.90, p = 0.013) and OS (hazard ratio [HR]: 2.05, 95% CI 1.28–3.28) and remained significant after adjusting for established prognostic factors (CSS: adjusted SHR 2.33, 95% CI 1.21–4.49, p = 0.012; OS: adjusted HR 1.96, 95% CI 1.17–3.28, p = 0.010), respectively. There was no significant association of DM with DFS (p = 0.149). The mean pre-surgery glucose levels were not significantly associated with inferior outcome (CSS: p = 0.510, OS: p = 0.382 and DFS: p = 0.786). This study shows, that DM represents a negative prognostic factor for clinical outcome in STS patients after curative resection.

The pretreatment erythrocyte sedimentation rate predicts survival outcomes after surgery and adjuvant radiotherapy for extremity soft tissue sarcoma.

BackgroundSystemic inflammation plays a critical role in cancer progression and oncologic outcomes in cancer patients. We investigated whether preoperative inflammatory biomarkers, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and neutrophil to lymphocyte ratio (NLR), could be surrogate biomarkers for predicting overall survival (OS) in soft tissue sarcoma (STS) patients treated with surgery and postoperative radiotherapy.MethodsA series of 99 patients who presented with localized extremity STS were retrospectively reviewed. The preoperative CRP levels, ESR, and NLR were evaluated for associations with OS, disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS). Cutoff values for CRP, ESR, and NLR were derived from receiver-operating characteristic curve analysis.ResultsElevated CRP (> 0.14 mg/dL), ESR (> 15 mm/h), and NLR (> 1.95) levels were seen in 33, 44, and 45 patients, respectively. Of these three inflammatory biomarkers, elevated CRP and ESR were associated with a poorer OS (CRP: P = 0.050; ESR: P = 0.001), DFS (CRP: P = 0.023; ESR: P = 0.003), and DMFS (CRP: P = 0.015; ESR: P = 0.001). By multivariate analysis, an elevated ESR was found to be an independent prognostic factor for OS (HR 3.580, P = 0.025) and DMFS (HR 3.850, P = 0.036) after adjustment for other established prognostic factors.ConclusionsThe preoperative ESR level is a simple and useful surrogate biomarker for predicting survival outcomes in STS patients and might improve the identification of high-risk patients of tumor relapse in clinical practice.

Serum C-reactive Protein and Neutrophil/Lymphocyte Ratio After Neoadjuvant Radiotherapy in Soft Tissue Sarcoma.

The predictive value of serum C-reactive protein (CRP) and neutrophil/lymphocyte (N/L) ratio in soft tissue sarcoma (STS) patients receiving neoadjuvant radiotherapy (RT) has not been analyzed. From 2007 to 2015, we identified 98 STS patients from a prospective database. Using multivariate analysis, we analyzed CRP and N/L ratios as predictors of overall survival (OS). Mean age of patients was 59 years, 46% were female, and 55% of tumors were located at the extremity. A total of 15 histologies were represented. Fifty percent received preoperative RT. Except for extremity location, characteristics were similar between the preoperative RT and upfront surgery cohorts, including baseline CRP levels and N/L ratios. Multivariate analysis of upfront surgery revealed histological grade, tumor size, and baseline N/L ratio to be predictors of OS, while for preoperative RT, baseline CRP and N/L ratio were not predictive. Baseline CRP and N/L ratio did not predict poor clinical outcome in STS patients receiving neoadjuvant RT.

Uric acid levels in blood are associated with clinical outcome in soft-tissue sarcoma patients

Recent evidence indicates toward a role of uric acid (UA) as a potential antioxidant. Elevated UA levels were shown to be associated with better survival in various malignancies. The aim of the present study was to evaluate the prognostic relevance of pre-operative UA levels on cancer-specific survival (CSS) in soft-tissue sarcoma (STS) patients who underwent curative surgical resection. Three hundred and fifty-seven patients with STS were included in the study. Pre-operative serum UA level was measured using an enzymatic colorimetric assay. The effect of UA levels on CSS was analyzed using Kaplan-Meier curves. To further evaluate the prognostic impact of UA levels, univariate and multivariate Cox proportional models were calculated. Among the 357 STS patients, cancer-related deaths occurred in 20 (24.7%) of 81 patients with a serum UA level <279.6 µmol/L and in 36 (13%) of 276 patients with a UA level ≥279.6 µmol/L. In univariate analysis, elevated UA levels were significantly associated with increased CSS in STS patients [hazard ratio (HR) 0.44, 95% confidence interval (CI) 0.26-0.77, p=0.004]. Furthermore, elevated UA levels remain a significant factor for better CCS in multivariate analysis (HR 0.42, 95% CI 0.23-0.75, p=0.003). Our study is the first one to demonstrate that higher UA levels are associated with positive clinical outcome in STS patients. UA levels are a simple and cost-effective test for the assessment of the prognosis of STS patients.

Pre-treatment anemia is a poor prognostic factor in soft tissue sarcoma patients.

BackgroundAnemia refers to low hemoglobin (Hb) levels, represents a common symptom and complication in cancer patients and was reported to negatively influence survival in patients with various malignancies. In the present study, we aimed to explore the prognostic impact of pre-operative Hb levels on clinical outcome in a large cohort of soft tissue sarcoma (STS) patients after curative surgery.MethodsRetrospective data from 367 STS patients, which were operated between 1998 and 2013, were included in the study. Cut-off levels for anemia were defined as Hb<13 g/dl in males and Hb<12 g/dl in females according to the current WHO guidelines. The impact of pre-operative Hb levels on cancer-specific survival (CSS) and overall survival (OS) was assessed using Kaplan-Meier curves. Additionally, Hb levels were compared for the prognostic influence on CSS and OS applying univariate and multivariate Cox proportional models.ResultsHb level was associated with established prognostic factors, including age, tumor grade, size and depth (p<0.05). Kaplan-Meier curves showed that low Hb levels were significantly associated with decreased CSS and OS in STS patients (p<0.001 for both endpoints, log-rank test). In multivariate analysis, we found an independent association between low Hb levels and poor CSS and OS (HR = 0.46, Cl 95% = 0.25–0.85, p = 0.012; HR = 0.34, Cl 95% = 0.23–0.51, p<0.001).ConclusionThe present data underline a negative prognostic impact of low pre-operative Hb levels on clinical outcome in STS patients. Thus, Hb levels may provide an additional and cost-effective tool to discriminate between STS patients that are at high risk of mortality.

Trabectedin-Related Liver Toxicity in Soft Tissue Sarcoma Patients: Always a Good Reason to Discontinue the Treatment?

ABSTRACT Aim: A transient increase in liver enzymes is a well described side effect developed by almost 40% of soft tissue sarcoma (STS) patients treated with trabectedin, often leading to treatment delays or discontinuation. We retrospectively analysed the correlation between trabectedin-related liver toxicity and treatment outcome. Methods: Data from a total of 113 patients receiving trabectedin administered at the dose of 1.5 mg/m2 iv 24 hours in 3 reference centers were evaluated. This exploratory analysis was performed to assess the impact of liver toxicity (grade 3-4 AST and ALT increases) on the trabectedin efficacy and outcome in STS patients. All the patients included had metastatic disease or locally advanced inoperable and received at least one previous line of treatment containing anthracycline. All patients received standard steroids premedication. Results: Median age was 57 years (range: 27-79 ys) and male/female ratio was 71/42. STS histologies were: liposarcoma 32 cases, leiomiosarcoma 27, pleomorphic sarcoma 17, synovial sarcoma 13, 24 other histologies. For 45 patients a G3-4 ALT increase in the first two cycles was reported while for 68 was not. Calculations show that hazard ratios for PFS and OS are not statistically significant (HR=1.124; p=0.734 and HR=0.104; p=0.850, respectively). Furthermore, the analysis was repeated dividing the population between patients with G3-4 ALT elevation during treatment vs. patients without such elevation. Again, hazard ratios for PFS and OS are not statistically significant (HR=0.791; p=0.309 and HR=0.930; p=0.810930, respectively). Finally, the analyses was repeated, splitting the population in patients with peak>15 ULN vs. patients with peak Conclusions: Liver toxicity is a common event during treatment with trabectedin and does not affect outcome. These results should discourage the premature discontinuation of the drug due to the increase in liver enzymes. Disclosure: All authors have declared no conflicts of interest.

Trabectedin-related liver toxicity in soft tissue sarcoma patients: Always a good reason to discontinue the treatment?

10572 Background: A transient increase in liver enzymes is a well described side effect developed by almost 40% of soft tissue sarcoma (STS) patients treated with trabectedin, often leading to treatment delays or discontinuation. We retrospectively analysed the correlation between trabectedin-related liver toxicity and treatment outcome. Methods: Data from a total of 113 patients receiving trabectedin administered at the dose of 1.5 mg/m2iv 24 hours in 3 reference centers were evaluated. This exploratory analysis was performed to assess the impact of liver toxicity (grade 3-4 AST and ALT increases) on the trabectedin efficacy and outcome in STS patients. All the patients included had metastatic disease or locally advanced inoperable and received at least one previous line of treatment containing anthracycline. All patients received standard steroids premedication. Results: Median age was 57 years (range: 27-79 ys) and male/female ratio was 71/42. STS histologies were: liposarcoma 32 cases, leiomeiosarcoma...

The lymphocyte/monocyte ratio predicts poor clinical outcome and improves the predictive accuracy in patients with soft tissue sarcomas

Increasing evidence indicates the involvement of inflammation and coagulation in cancer progression and metastases. Inflammatory biomarkers hold great promise for improving the predictive ability of existing prognostic tools in cancer patients. In the present study, we investigated several inflammatory indices with regard to their prognostic relevance for predicting clinical outcome in soft tissue sarcoma (STS) patients. Three hundred and forty STS patients were divided into a training set (n = 170) and a validation set (n = 170). Besides well-established clinico-pathological prognostic factors, we evaluated the prognostic value of the neutrophil/lymphocyte (N/L) ratio, the lymphocyte/monocyte (L/M) ratio and the platelet/lymphocyte (P/L) ratio using Kaplan-Meier curves and univariate as well as multivariate Cox regression models. Additionally, we developed a nomogram by supplementing the L/M ratio to the well-established Kattan nomogram and evaluated the predictive accuracy of this novel nomogram by applying calibration and Harrell's concordance index (c-index). In multivariate analysis, a low L/M ratio was significantly associated with decreased CSS and DFS (HR = 0.41, 95% CI = 0.18-0.97, p = 0.043; HR = 0.39, 95% CI = 0.16-0.91, p = 0.031, respectively) in the training set. Using the validation set for confirmation, we found also in multivariate analysis an independent value for CSS (HR = 0.33, 95% CI = 0.12-0.90, p = 0.03) and for DFS (HR = 0.36, 95% CI = 0.16-0.79, p = 0.01). The estimated c-index was 0.74 using the original Kattan nomogram and 0.78 when the L/M ratio was added. Our study reports for the first time that the pre-operative L/M ratio represents a novel independent prognostic factor for prediction the clinical outcome in STS patients. This easily determinable biomarker might be helpful in improved individual risk assessment.

Common gene variants in RAD51, XRCC2 and XPD are not associated with clinical outcome in soft-tissue sarcoma patients

BackgroundDNA repair mechanisms play a major role in cancer risk and progression. Germline variants in DNA repair genes may result in altered gene function and/or activity, thereby causing inter-individual differences in a patient's tumor recurrence capacity. In genes of the DNA repair pathway the gene variants RAD51 rs1801320 G>C, XRCC2 rs3218536 G>A and XPD rs13181 A>C have been previously related to genetic predisposition and prognosis of various cancer entities. In this study we investigated the association between these polymorphisms and time to recurrence (TTR) and overall survival (OS) in soft-tissue sarcoma (STS) patients after curative surgery. MethodsTwo hundred sixty STS patients were included in this retrospective study. Germline DNA was genotyped by 5′-exonuclease (TaqMan) technology. Kaplan Meier curves and multivariate Cox proportional models were calculated for TTR and OS. ResultsA statistically significant association was observed between tumor grade and adjuvant radiotherapy and TTR and between tumor grade and OS. No association was found between RAD51 rs1801320 G>C, XRCC2 rs3218536 G>A and XPD rs13181 A>C and TTR and OS in univariate and multivariate analysis. ConclusionOur results underline a prognostic effect of tumor grade and adjuvant radiotherapy in STS patients but indicate no association between RAD51 rs1801320 G>C, XRCC2 rs3218536 G>A and XPD rs13181 A>C and clinical outcome in STS patients after curative surgery.

Outcome of soft-tissue sarcoma patients who were alive and event-free more than five years after initial treatment

We evaluated the risk of late relapse and further outcome in patients with soft-tissue sarcomas who were alive and event-free more than five years after initial treatment. From our database we identified 1912 patients with these pathologies treated between 1980 and 2006. Of these 1912 patients, 603 were alive and event-free more than five years after initial treatment and we retrospectively reviewed them. The mean age of this group was 48 years (4 to 94) and 340 were men. The mean follow-up was 106 months (60 to 336). Of the original cohort, 582 (97%) were alive at final follow-up. The disease-specific survival was 96.4% (95% confidence interval (CI) 94.4 to 98.3) at ten years and 92.9% (95% CI 89 to 96.8) at 15 years. The rate of late relapse was 6.3% (38 of 603). The ten- and 15-year event-free rates were 93.2% (95% CI 90.8 to 95.7) and 86.1% (95% CI 80.2 to 92.1), respectively. Multivariate analysis showed that tumour size and tumour grade remained independent predictors of events. In spite of further treatment, 19 of the 38 patients died of sarcoma. The three- and five-year survival rates after the late relapse were 56.2% (95% CI 39.5 to 73.3) and 43.2% (95% CI 24.7 to 61.7), respectively, with a median survival time of 46 months. Patients with soft-tissue sarcoma, especially if large, require long-term follow-up, especially as they have moderate potential to have their disease controlled.

Elevated preoperative neutrophil/lymphocyte ratio is associated with poor prognosis in soft-tissue sarcoma patients

Background:Recent data indicate that tumour microenvironment, which is influenced by inflammatory cells, has a crucial role in cancer progression and clinical outcome of patients. In the present study, we investigated the prognostic relevance of preoperative neutrophil/lymphocyte (N/L) ratio on time to tumour recurrence (TTR) and overall survival (OS) in soft-tissue sarcoma (STS) patients who underwent curative surgical resection.Methods:In all, 260 STS patients were included in this retrospective study. Kaplan–Meier curves and multivariate Cox proportional models were calculated for TTR and OS.Results:In univariate analysis, elevated N/L ratio was significantly associated with decreased TTR (hazard ratio (HR), 2.32; 95% confidence interval (CI), 1.30–4.14; P=0.005) and remained significant in the multivariate analysis (HR, 1.98; 95%CI, 1.05–3.71; P=0.035). Patients with elevated N/L ratio showed a median TTR of 77.9 months. In contrast, patients with low N/L ratio had a median TTR of 99.1 months. Regarding OS, elevated N/L ratio was also significantly associated with decreased survival in univariate analysis (HR, 2.90; 95%CI, 1.82–4.61; P=0.001) and remained significant in multivariate analysis (HR, 1.88; 95%CI, 1.14–3.12; P=0.014).Conclusion:In conclusion, our findings suggest that an elevated preoperative N/L ratio predicts poor clinical outcome in STS patients and may serve as a cost-effective and broadly available independent prognostic biomarker.

Evaluation of newer prognostic markers for adult soft tissue sarcomas.

In addition to tumor size, grade, location, and the presence of metastases, other factors may be useful in prognostication for adults with soft tissue sarcoma (STS). This study examines the relationship of MDR-1 mRNA, p-glycoprotein (P-gp), Ki-67 expression, and DNA content expression to clinical outcome in adults with STS. Snap-frozen STS specimens from 65 patients were analyzed and compared with clinical outcomes. Immunohistochemistry was performed for the Ki-67 antigen and P-gp. DNA content was determined using the Feulgen reaction and quantitated using image analysis. MDR-1 mRNA expression was determined using a reverse-transcriptase polymerase chain reaction (RT-PCR)-based assay. P-glycoprotein expression was found by immunohistochemistry in 48% of cases with 5-year overall (54% v 14%, P = .07) and disease-free survival rates (32% v 18%, P = .039) higher in high-grade tumors that did not express P-gp. MDR-1 mRNA was detected in 51% of cases and no patient with high levels of MDR-1 mRNA expression was a long-term survivor. Patients with diploid tumors had significantly better survival than those with nondiploid tumors (51% v 31%, P = .03). High levels of Ki-67 were associated with poorer overall survival (46% v 31%, P = .04). On multivariate analysis, American Joint Committee on Cancer (AJCC) staging, DNA content, Ki-67, and P-gp staining were significant prognostic factors for 5-year overall and disease-free survival. P-gp expression, high-level Ki-67 expression, and nondiploid DNA content are independent prognostic indicators that correlate with poor outcomes in STS patients. However, MDR-1 mRNA was not found to be predictive of survival. These newer markers are useful additions to AJCC staging for prognostication for patients with STS. Such markers may be useful in selecting high-risk STS patients who could benefit from systemic adjuvant therapy.