Preoperative and Postoperative Platelet-Lymphocyte Ratio Is a Prognostic Marker for Patients With Soft Tissue Sarcoma Treated With Curative Resection.

BACKGROUND/AIM: Systemic inflammation has been implicated in the development and progression of cancer. Inflammatory markers have been identified as prognostic indicators in numerous malignancies. This study explored the prognostic relevance of the initial and postoperative neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) on relapse-free survival (RFS) and overall survival (OS) in patients with soft-tissue sarcoma (STS) who underwent curative resection. PATIENTS AND METHODS: We included 89 patients with STS who underwent extensive and radical resection at the Kyungpook National University Chilgok Hospital between 2004 and 2018. Kaplan-Meier curves for RFS and OS were calculated using multivariate Cox proportional models. RESULTS: A total of 67 (75.3%) patients demonstrated a high initial NLR (≥4.1) and 65 (75.3%) showed a high initial PLR (≥231). In the univariate and multivariate analyses, an elevated initial PLR ratio was significantly associated with a decreased RFS (p=0.017) and OS (p=0.003). Patients with a high PLR (PLR >231) had a median RFS of 24 months, whereas those with a low PLR (PLR ≤231) had a median RFS of 96 months. The median OS was 50 and 298 months for the high PLR and low PLR groups, respectively. Furthermore, a high postoperative PLR ratio was associated with a decreased RFS (p=0.001) and OS (p=0.038). CONCLUSION: Preoperative and postoperative PLR ratio can be used as a cost-effective prognostic marker for oncologic outcomes in patients with STS who undergo surgery.

Investigating surface proteins and antibody combinations for detecting circulating tumor cells of various sarcomas.

Circulating tumor cells (CTCs) have gathered attention as a biomarker for carcinomas. However, CTCs in sarcomas have received little attention. In this work, we investigated cell surface proteins and antibody combinations for immunofluorescence detection of sarcoma CTCs. A microfluidic device that combines filtration and immunoaffinity using gangliosides 2 and cell surface vimentin (CSV) antibodies was employed to capture CTCs. For CTC detection, antibodies against cytokeratins 7 and 8 (CK), pan-cytokeratin (panCK), or a combination of panCK and CSV were used. Thirty-nine blood samples were collected from 21 patients of various sarcoma subtypes. In the independent samples study, samples were subjected to one of three antibody combination choices. Significant difference in CTC enumeration was found between CK and panCK + CSV, and between panCK and panCK + CSV. Upon stratification of CK+ samples, those of metastatic disease had a higher CTC number than those of localized disease. In the paired samples study involving cytokeratin-positive sarcoma subtypes, using panCK antibody detected more CTCs than CK. Similarly, for osteosarcoma, using panCK + CSV combination resulted in a higher CTC count than panCK. This study emphasized deliberate selection of cell surface proteins for sarcoma CTC detection and subtype stratification for studying cancers as heterogeneous as sarcomas.

Predicting Trabectedin Efficacy in Soft Tissue Sarcoma: Inflammatory Biomarker Analysis.

BACKGROUND/AIM: Trabectedin is used as a treatment for advanced-stage soft tissue sarcomas (STSs), particularly liposarcoma and leiomyosarcoma. Aside from its direct effect on tumor cells, trabectedin can affect the immune system in the tumor microenvironment. This study aimed to evaluate whether inflammatory biomarkers predict trabectedin efficacy in STSs. PATIENTS AND METHODS: We retrospectively reviewed the clinical features and outcomes of patients with STS treated with trabectedin at our institution between 2016 and 2020. The neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation response index (SIRI=neutrophil × monocyte/lymphocyte) were calculated based on the blood samples obtained prior to trabectedin treatment initiation. Analyses of overall survival (OS) and progression-free survival (PFS) were performed according to various factors. RESULTS: Of the 101 patients identified, 54 had L-sarcoma (leiomyosarcoma: 30; liposarcoma: 24), and 47 had other types of STSs. Elevated SIRI, NLR, PLR, LMR, and C-reactive protein (CRP) were associated with worse PFS (p<0.001, p=0.008, p=0.027, p=0.013, and p<0.001, respectively) according to the results of the univariate analysis. Multivariate analysis showed that elevated SIRI, other histology, and CRP were associated with poor PFS (p=0.007, p=0.008, and p=0.029, respectively). In addition, the multivariate analysis of OS showed that SIRI was an independent prognostic factor (hazard ratio=2.16, p=0.006). CONCLUSION: Pretreatment SIRI can be considered a biomarker for the prognostic prediction of patients with STS treated with trabectedin.

Neutrophil-to-lymphocyte ratio for the prediction of soft tissue sarcomas response to pre-operative radiation therapy.

PURPOSE/OBJECTIVE: This study aims to assess the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in soft tissue sarcomas (STS) treated with pre-operative hypofractionated radiotherapy (HFRT). MATERIALS/METHODS: This retrospective analysis included patients treated with pre-operative HFRT of 30 Gy in 5 fractions between 2016 and 2023. Clinical, demographic, and complete blood count (CBC) data were collected. NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. Only patients with CBCs conducted within 6 months after radiotherapy were included. Cox proportional-hazard regression models were used to assess the impact of NLR and different variables on outcomes. Kaplan Meier were used to illustrate survival curves. A p-value < 0.05 was considered significant, and 95 % confidence intervals (CI) were employed. RESULTS: A total of 40 patients received HFRT and had CBCs within 6 months after radiotherapy. There were 17 (42.5 %) females and 23 (57.5 %) males with a mean age of 66 years. The mean largest tumor size dimension was 7.1 cm, and the mean NLR post-RT was 5.3. The most frequent histological subtypes were myxofibrosarcoma (17.5 %), pleomorphic spindle cell sarcoma (10 %), leiomyosarcoma (7.5 %), and myxoid liposarcoma (5 %). The median follow-up period was 15.4 months. From all patients, 14 patients had disease progression, 12 metastatic disease and 3 died of disease. Multivariable Cox proportional-hazards regression analysis displayed that a higher post-RT NLR was associated with worse disease-free survival (DFS) (HR: 1.303 [1.098-1.548], p = 0.003), and distant metastasis-free survival (DMFS) (HR: 1.38 [1.115-1.710], p = 0.003). Moreover, post-NLR ≥ 4 as a single variable was associated with worse DFS, DMFS, but not worse local recurrence or overall survival. CONCLUSION: This study is the first to evaluate NLR as a prognostic biomarker in STS patients treated with pre-operative radiotherapy. A higher NLR after pre-operative radiotherapy was associated with increased disease progression.

Serum Concentration of Thymidine Kinase 1 (TK1) as a Tumor Marker in Soft Tissue Sarcomas.

BACKGROUND/AIM: The aim of this prospective study was to determine whether serum Thymidine kinase -1 (TK1) could serve as a tumor marker in soft tissue sarcomas (STS). PATIENTS AND METHODS: A total of 48 patients diagnosed with localized STS were included. None had received preoperative oncological treatment. Samples were collected before and after surgery and TK1 levels measured with the AroCell TK210 ELISA. RESULTS: Mean preoperative TK1 was 0.32 µg/l, range=0.11-1.47, and 18 cases (38%) had values above the reference limit (0.41 µg/l). Mean postoperative TK1 was 0.35 µg/l (0.06-0.86). In patients with preoperative values above the reference limit, TK1 decreased significantly after surgery (n=13, p=0.001). We found no association between increased preoperative TK1 and age, sex, tumor size, grade, and the presence of vascular invasion or necrosis. CONCLUSION: TK1 has limited use as a tumor marker in localized STS.

Does the modified Glasgow Prognostic Score aid in the management of patients undergoing surgery for a soft-tissue sarcoma? : an international multicentre study.

AIMS: The modified Glasgow Prognostic Score (mGPS) uses preoperative CRP and albumin to calculate a score from 0 to 2 (2 being associated with poor outcomes). mGPS is validated in multiple carcinomas. To date, its use in soft-tissue sarcoma (STS) is limited, with only small cohorts reporting that increased mGPS scores correlates with decreased survival in STS patients. METHODS: This retrospective multicentre cohort study identified 493 STS patients using clinical databases from six collaborating hospitals in three countries. Centres performed a retrospective data collection for patient demographics, preoperative blood results (CRP and albumin levels and neutrophil, leucocyte, and platelets counts), and oncological outcomes (disease-free survival, local, or metastatic recurrence) with a minimum of two years' follow-up. RESULTS: We found that increased mGPS, tumour size, grade, neutrophil/lymphocyte ratio, and disease recurrence were associated with reduced survival. Importantly, mGPS was the best at stratifying prognosis and could be used in conjunction with tumour grade to sub-stratify patient survival. CONCLUSION: This study demonstrated that prognosis of localized STS strongly correlates with mGPS, as an increasing score is associated with a poorer outcome. We note that 203 patients (41%) with an STS have evidence of systemic inflammation. We recommend the mGPS and other biochemical blood indicators be introduced into the routine diagnostic assessment in STS patients to stratify patient prognosis. Its use will support clinical decision-making, especially when morbid treatment options such as amputation are being considered. Cite this article: Bone Joint J 2022;104-B(1):168-176.

Is early change in systemic inflammatory markers associated with treatment response in patients who received pazopanib?

PURPOSE: To demonstrate whether early changes in systemic inflammatory markers are related with pazopanib treatment response in soft tissue sarcoma and renal cell carcinoma. METHODS: Forty-one patients with metastatic clear cell renal carcinoma (mRCC) (n=22) and advanced stage soft tissue sarcoma (STS) (n=19) were assessed. Systemic inflammatory markers such as neutrophils, lymphocytes, c-reactive protein (CRP), mean platelet volume (MPV), lactate dehydrogenase (LDH) and neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) at both baseline and 1-month of pazopanib treatment were obtained and their relation with the first radiological response about 3-months later after pazopanib treatment was evaluated. RESULTS: Disease control rate (DCR) at the first initial radiological evaluation was 58.5 % for all, it was 77.3% for the RCC group and 36.8% in the STS group. Serum neutrophil, NLR and CRP levels were significantly decreased from baseline in RCC patients who had DCR with pazopanib treatment. Also, serum CRP levels after pazopanib treatment was significantly lower in RCC patients who had DCR (+) rather than those who progressed. CONCLUSIONS: Early decline in serum CRP, neutrophil and NLR levels in RCC patients who received pazopanib at the first month was significantly associated with disease control, assuming a predictive role for the first radiological assessment. However, there was no significant association between change in serum inflammatory marker levels and disease control in STS patients.

Liquid Biopsy: A New Translational Diagnostic and Monitoring Tool for Musculoskeletal Tumors.

Soft tissue and bone sarcomas represent a group of aggressive neoplasms often accompanied by dismal patient prognosis, especially when distant metastases are present. Moreover, effective treatment can pose a challenge, as recurrences are frequent and almost half of patients present with advanced disease. Researchers have unveiled the molecular abnormalities implicated in sarcomas' carcinogenesis, paving the way for novel treatment strategies based on each individual tumor's characteristics. Therefore, the development of new techniques aiding in early disease detection and tumor molecular profiling is imperative. Liquid biopsy refers to the sampling and analysis of patients' fluids, such as blood, to identify tumor biomarkers, through a variety of methods, including qRT-PCR, qPCR, droplet digital PCR, magnetic microbeads and digital PCR. Assessment of circulating tumor cells (CTCs), circulating free DNA (ctDNA), micro RNAs (miRs), long non-coding RNAs (lncRNAs), exosomes and exosome-associated proteins can yield a plethora of information on tumor molecular signature, histologic type and disease stage. In addition, the minimal invasiveness of the procedure renders possible its wide application in the clinical setting, and, therefore, the early detection of the presence of tumors. In this review of the literature, we gathered information on biomarkers assessed through liquid biopsy in soft tissue and bone sarcoma patients and we present the information they can yield for each individual tumor type.

Lysosome purinergic receptor P2X4 regulates neoangiogenesis induced by microvesicles from sarcoma patients.

The tumor microenvironment modulates cancer growth. Extracellular vesicles (EVs) have been identified as key mediators of intercellular communication, but their role in tumor growth is largely unexplored. Here, we demonstrate that EVs from sarcoma patients promote neoangiogenesis via a purinergic X receptor 4 (P2XR4) -dependent mechanism in vitro and in vivo. Using a proteomic approach, we analyzed the protein content of plasma EVs and identified critical activated pathways in human umbilical vein endothelial cells (HUVECs) and human progenitor hematopoietic cells (CD34+). We then showed that vessel formation was due to rapid mitochondrial activation, intracellular Ca2+ mobilization, increased extracellular ATP, and trafficking of the lysosomal P2XR4 to the cell membrane, which is required for cell motility and formation of stable branching vascular networks. Cell membrane translocation of P2XR4 was induced by proteins and chemokines contained in EVs (e.g. Del-1 and SDF-1). Del-1 was found expressed in many EVs from sarcoma tumors and several tumor types. P2XR4 blockade reduced EVs-induced vessels in angioreactors, as well as intratumor vascularization in mouse xenografts. Together, these findings identify P2XR4 as a key mediator of EVs-induced tumor angiogenesis via a signaling mediated by mitochondria-lysosome-sensing response in endothelial cells, and indicate a novel target for therapeutic interventions.

Prognostic Value of Pretreated Blood Inflammatory Markers in Patients with Bone Sarcoma: A Meta-Analysis.

METHOD: We conducted a detailed literature search in Medline and Embase databases and collected relevant publications written in English before April 2020. Overall survival (OS) and disease-free survival (DFS) were the primary and secondary outcomes, respectively. Basic features of patients, hazard ratios (HRs), and 95% confidence intervals (CI) were retrieved to assess the correlation between pretreated blood inflammatory markers and patients with bone sarcoma. This meta-analysis used Stata 12.0. RESULTS: A total of 10 studies containing 1845 cases were included for analysis. Nine of them evaluated the neutrophil lymphocyte ratio (NLR), 7 the platelet lymphocyte ratio (PLR), and 4 the lymphocyte monocyte ratio (LMR). Pooled results revealed that higher pretreatment NLR was associated with poorer OS (HR = 1.76, 95% CI: 1.29-2.41, and P < 0.001) and DFS (HR = 1.77, 95% CI: 1.09-2.88, and P = 0.021). In contrast, a lower LMR was related to worse OS (HR = 0.73, 95% CI: 0.57-0.92, and P = 0.009), but not DFS (HR = 0.68, 95% CI: 0.41-1.11, and P > 0.05). Combined results did not show a significant predictive effect of PLR on the clinical outcomes of patients with bone sarcoma (OS : HR = 1.32, 95% CI: 0.99-1.75, and P > 0.05; DFS: HR = 1.12, 95% CI: 0.87-1.44, P > 0.05). CONCLUSION: NLR and LMR might be promising predictive biomarkers for patients with bone sarcoma and could be used to stratify patients and provide personalized therapeutic strategies.

Evaluation of Absolute Lymphocyte Count at Diagnosis and Mortality Among Patients With Localized Bone or Soft Tissue Sarcoma.

Importance: Host-related immune factors have been implicated in the development and progression of diverse malignant neoplasms. Identifying associations between immunologic laboratory parameters and overall survival may inform novel prognostic biomarkers and mechanisms of antitumor immunity in localized bone and soft tissue sarcoma. Objective: To assess whether lymphopenia at diagnosis is associated with overall survival among patients with localized bone and soft tissue sarcoma. Design, Setting, and Participants: This retrospective cohort study analyzed patients from the Stanford Cancer Institute with localized bone and soft tissue sarcoma between September 1, 1998, and November 1, 2018. Patients were included if laboratory values were available within 60 days of diagnosis and, if applicable, prior to the initiation of chemotherapy and/or radiotherapy. Statistical analysis was performed from January 1, 2019, to November 1, 2020. Exposures: Absolute lymphocyte count within 60 days of diagnosis and antimicrobial exposure, defined by the number of antimicrobial agent prescriptions and the cumulative duration of antimicrobial administration within 60 days of diagnosis. Main Outcomes and Measures: The association between minimum absolute lymphocyte count at diagnosis and 5-year overall survival probability was characterized with the Kaplan-Meier method and multivariate Cox proportional hazards regression models. Multivariable logistic regressions were fitted to evaluate whether patients with lymphopenia were at greater risk of increased antimicrobial exposure. Results: Among 634 patients, the median age at diagnosis was 53.7 years (interquartile range, 37.5-66.8 years), and 290 patients (45.7%) were women, with a 5-year survival probability of 67.9%. There was a significant inverse association between lymphopenia at diagnosis and overall survival (hazard ratio [HR], 1.82; 95% CI, 1.39-1.40), resulting in a 13.5% 5-year survival probability difference compared with patients who did not have lymphopenia at diagnosis (60.2% vs 73.7% for those who never had lymphopenia). In addition, poorer survival was observed with higher-grade lymphopenia (grades 3 and 4: HR, 2.44; 95% CI, 1.68-3.55; grades 1 and 2: HR, 1.60; 95% CI, 1.18-2.18). In an exploratory analysis, patients with increased antibiotic exposure were more likely to have lymphopenia (odds ratio, 1.96; 95% CI, 1.26-3.07 for total number of antimicrobial agents; odds ratio, 1.70; 95% CI, 1.10-2.57 for antimicrobial duration) than antimicrobial-naive patients. Conclusions and Relevance: This study suggests that an abnormally low absolute lymphocyte count at diagnosis is associated with higher mortality among patients with localized bone and soft tissue sarcoma; therefore, lymphopenia may serve as a reliable prognostic biomarker. Potential mechanisms associated with host immunity and overall survival include a suppressed antitumor response and increased infectious complications, which merit future investigation.

Tumour markers with clinically controlled cut-offs for suspected cancer.

BACKGROUND: Due to insufficient scientific evidence, panels of tumour markers (TMs) are currently not recommended for use in suspected cancer. However, recent well-designed studies have revealed a potential clinical value in lung cancer. We analysed the diagnostic accuracy of a panel of 11 circulating TMs with clinically controlled thresholds in the differentiation of cancer from nonmalignant diseases. METHODS: We prospectively recruited 4776 consecutive patients presenting with focal or nonspecific symptoms suggestive of cancer who underwent testing for 11 serum TMs before diagnosis was known. The study abided by 2015 STARD guidelines. Tumour markers included, among others, carbohydrate antigen 19-9, carcinoembryonic antigen, alpha-fetoprotein, squamous cell carcinoma-associated antigen, prostate-specific antigen (males), neuron-specific enolase, progastrin-releasing peptide and carbohydrate antigen 125. Thresholds were adjusted for the presence of kidney failure, liver disease, effusions and dermatological disorders. Results showing ≥1 TMs with concentrations above threshold were considered positive. RESULTS: Benign diseases were diagnosed in 3281 (68.7%) patients and cancer in 1495 (31.3%), with epithelial cancers in 1214 (77% at stage IV). When applying criteria for controlled thresholds, overall specificity was 98%. Overall sensitivity of the panel in epithelial cancers was 72.2%, positive predictive value 93% and negative predictive value 90.5%. The area under the receiver operating characteristic curve was 0.920 (95% confidence interval, 0.902-0.924). CONCLUSIONS: By using clinically controlled cut-offs, the combined panel demonstrated an excellent ability to discriminate epithelial cancers from nonmalignant diseases. However, its use in clinical practice would need formal validation through a multicentre controlled trial assessing a panel-guided strategy vs. standard diagnosis.

Pre-treatment Neutrophil-to-Lymphocyte Ratio Predicts Efficacy of Eribulin for Soft-tissue Sarcoma.

BACKGROUND: Eribulin is widely used for the treatment of breast cancer and soft-tissue sarcoma (STS). Previous studies identified the pre-treatment absolute lymphocyte count, baseline neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein concentration as potential prognostic markers in patients with breast cancer treated with eribulin. However, prognostic factors for eribulin treatment in patients with STS have not been identified. PATIENTS AND METHODS: This was a retrospective analysis of data collected prospectively from 53 patients who were treated with eribulin for recurrent or metastatic STS between March 2016 and August 2019. Univariate and multivariate analyses were performed to determine the predictive factors of durable clinical benefit, progression-free survival, and overall survival. RESULTS: L-Sarcoma histology [hazard ratio (HR)=28.20, 95% confidence intervaI (CI)=1.67-476.00; p=0.021] and pre-treatment NLR <3.0 (HR=9.96, 95% CI=1.28-77.7; p=0.028) were independent factors predictive of durable clinical benefit. In addition, pre-treatment NLR <3.0 (HR=0.34, 95% CI=0.16-0.74; p=0.0059) and male sex (HR=0.23, 95% CI=0.10-0.52; p<0.001) were independent factors predictive of better progression-free survival. CONCLUSION: This retrospective study found that baseline NLR predicts the efficacy of eribulin for STS.

Specificity of the lactate dehydrogenase isoenzyme index as a preoperative screen for uterine sarcoma before myomectomy.

OBJECTIVE: To evaluate the applicability of the Uterine mass Magna Graecia (UMG) risk index (elevation defined by a lactate dehydrogenase isoenzyme index >29) in women undergoing surgery for benign fibroids and to determine whether other factors were associated with an elevated index. An elevated UMG index has been reported to be associated with an increased risk of uterine sarcoma in Italian women. DESIGN: Retrospective cohort study. SETTING: University fibroid center. PATIENTS: All women presenting from July 1, 2013, through June 30, 2019, with fibroids who had lactate dehydrogenase isoenzymes collected and surgery performed. INTERVENTIONS: Calculation of UMG index. MAIN OUTCOME MEASURE: Applicability of UMG index. RESULTS: Of 272 patients initially identified, 179 met inclusion criteria, 163 with UMG index ≤29 and 16 with UMG index >29. There were no cases of uterine sarcoma. Race, age, and presence of endometriosis, adenomyosis, or degenerating fibroids were not predictors of elevated UMG index. Body mass index (BMI) was positively associated with elevated UMG index. Specificity of UMG index to exclude uterine sarcoma was 91.1% (163/179) and higher in non-obese (BMI<30; 95.1%) than obese women (85.5%). CONCLUSION: A previously reported UMG index cutoff of 29 had a specificity of 91.1% (higher with normal BMI and lower when obese) in our patient population. Although lower than previously reported, the index could be a useful initial method of preoperative screening of women with symptomatic fibroids. Higher BMI appears to be associated with elevated UMG indices, increasing the false-positive rate in obese women.

Potential contrasting effects of platelets on the migration and invasion of sarcomas versus carcinomas.

The ability of platelets to promote carcinoma and melanoma progression has been thoroughly studied and occurs in numerous ways. In contrast, the effect of platelets on sarcomas, tumors arising from mesenchymal cells, has received very little attention. This study was undertaken to simultaneously compare the effects of platelets on murine and human sarcomas and carcinomas. In contrast to their effect on carcinomas, platelets inhibited the invasion of some murine- and all human sarcomas tested in vitro. Further invasion studies with TGFß treatment only partially recapitulated the results seen with whole platelets. In a spontaneous tumor growth and lung metastasis model, platelets promoted 4T1 mammary carcinoma metastasis but not MCA-1 fibrosarcoma metastasis. Gene expression analysis of the platelet-promoted MDA-MB-231 breast carcinoma, and the platelet-inhibited HT1080 fibrosarcoma cell lines revealed that exposure of MDA-MB-231 to platelets, resulted in upregulation of oncogenes and EMT-associated genes whereas in HT1080 a tumor-suppressor gene was significantly upregulated. Thus, this study has revealed a potential diametrically opposing effect of platelets on mesenchymal and epithelial cancers, a finding that warrants further investigation.

The free amino acid profiles and metabolic biomarkers of predicting the chemotherapeutic response in advanced sarcoma patients.

PURPOSE: Metabolomics is an emerging field in cancer research. Plasma free amino acid profiles (PFAAs) have shown different features in various cancers, but the characteristic in advanced sarcoma remains unclear. We aimed to uncover the specific PFAAs in advanced sarcoma and to find the relationship between the altering of PFAAs and response to chemotherapy. PATIENTS AND METHODS: We analyzed the differences in PFAAs between 23 sarcoma patients and 30 healthy subjects basing on liquid chromatography-tandem mass spectrometry (LC-MS/MS). Then, we compared the dynamics of PFAAs after chemotherapy between improvement group and deterioration group. RESULTS: We identified seven biological differential amino acids and four pathways which were perturbed in the sarcoma patients compared with healthy subjects. After one cycle chemotherapy, the levels of γ-aminobutyric acid (GABA) and carnosine (Car) decreased significantly in the improvement group but not in deterioration group. The levels of α-aminobutyric acid (Abu) increased significantly in the deterioration group but not in the improvement group. CONCLUSION: Our study suggests the potential specific PFAAs in sarcoma patients. The unusual amino acids and metabolic pathways may provide ideas for clinical drugs targeting therapy. Three amino acids including Car, GABA and Abu may be metabolic biomarkers playing a role in dynamic monitoring of the therapeutic effect.

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

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.

Multidisciplinary Oncovascular Surgery is Safe and Effective in the Treatment of Intra-abdominal and Retroperitoneal Sarcomas: A Retrospective Single Centre Cohort Study and a Comprehensive Literature Review.

OBJECTIVE: Radical excision of retroperitoneal or intra-abdominal soft tissue sarcomas may necessitate vessel resection and reconstruction. The aim of this study was to assess surgical results of retroperitoneal or intra-abdominal sarcomas involving major blood vessels. METHODS: This was a retrospective single centre cohort study and a comprehensive review of literature. Patients with retroperitoneal or intra-abdominal sarcomas treated by the oncovascular team in Helsinki University Hospital from 2010 to 2018 were reviewed for vascular and oncological outcomes. A comprehensive literature review of vascular reconstructions in patients with retroperitoneal sarcoma was performed. RESULTS: Vascular reconstruction was performed in 17 patients, 11 of whom required arterial reconstructions. Sixteen of the operations were sarcoma resections; the post-operative diagnosis for one patient was thrombosis instead of the presumed recurrent leiomyosarcoma. Early graft thrombosis occurred in two venous and one arterial reconstruction. Late thrombosis was detected in three (18%). The median follow up was 27 (range 0-82) months. Of the patients with sarcoma resections 5 (31%) died of sarcoma and further 4 (25%) developed local recurrence or new distant metastases. The comprehensive review of literature identified 37 articles with 110 patients, 89 of whom had inferior vena cava reconstruction only. Eight arterial reconstructions were described. Late graft thrombosis occurred in 14%. The follow up was 0-181 months, during which 57% remained disease free and 7% died of sarcoma. CONCLUSION: Vascular reconstructions enable radical resection of retroperitoneal and intra-abdominal sarcomas in patients with advanced disease. The complex operations are associated with an acceptable rate of serious peri-operative complications and symptomatic thrombosis of the repaired vessel is rare. However, further studies are needed to assess the performance of the vascular reconstructions in the long term.

A novel serum miRNA-pair classifier for diagnosis of sarcoma.

Soft tissue sarcomas (STS) is a set of rare malignant tumor originated from mesoderm. For the prognosis of sarcoma, early diagnosis is important, however, currently no mature and non-invasive method for diagnosis exists. MicroRNAs (miRNAs) are a class of noncoding RNAs and their expression varies greatly, especially during tumor activity. The purpose of this study was to construct a predictive model for the diagnosis of sarcomas based on the relative expression level of miRNA in serum. miRNA array expression data of 677 samples including 402 malignant sarcoma samples and 275 healthy samples was used to construct the prediction model. Based on 6 gene pairs, random generalized linear model (RGLM) was constructed, with an accuracy of 100% in the internal test dataset and of 74.3% in the merged external dataset in prediction whether a serum sample was obtained from a sarcoma patient, with a specificity of 100% in the internal test dataset and 90.5% in the external dataset. In conclusion, our serum miRNA-pair classifier has the potential to be used for the screening of sarcoma with high accuracy and specificity.