OBJECTIVE: To investigate the value of multi-parametric MRI-based radiomics for preoperative prediction of lung metastases from soft tissue sarcoma (STS).
METHODS: In total, 122 patients with clinicopathologically confirmed STS who underwent pretreatment T1-weighted contrast-enhanced (T1-CE) and T2-weighted fat-suppressed (T2FS) MRI scans were enrolled between Jul. 2017 and Mar. 2021. Radiomics signatures were established by calculating and selecting radiomics features from the two sequences. Clinical independent predictors were evaluated by statistical analysis. The radiomics nomogram was constructed from margin and radiomics features by multivariable logistic regression. Finally, the study used receiver operating characteristic (ROC) and calibration curves to evaluate performance of radiomics models. Decision curve analyses (DCA) were performed to evaluate clinical usefulness of the models.
RESULTS: The margin was considered as an independent predictor (p < 0.05). A total of 4 MRI features were selected and used to develop the radiomics signature. By incorporating the margin and radiomics signature, the developed nomogram showed the best prediction performance in the training (AUCs, margin vs. radiomics signature vs. nomogram, 0.609 vs. 0.909 vs. 0.910) and validation (AUCs, margin vs. radiomics signature vs. nomogram, 0.666 vs. 0.841 vs. 0.894) cohorts. DCA indicated potential usefulness of the nomogram model.
CONCLUSIONS: This feasibility study evaluated predictive values of multi-parametric MRI for the prediction of lung metastasis, and proposed a nomogram model to potentially facilitate the individualized treatment decision-making for STSs.

BACKGROUND: Risk prediction models (RPM) can help soft-tissue sarcoma(STS) patients and clinicians make informed treatment decisions by providing them with estimates of (disease-free) survival for different treatment options. However, it is unknown how RPMs are used in the clinical encounter to support decision-making. This study aimed to understand how a PERsonalised SARcoma Care (PERSARC) RPM is used to support treatment decisions and which barriers and facilitators influence its use in daily clinical practice.
METHODS: A convergent mixed-methods design is used to understand how PERSARC is integrated in the clinical encounter in three Dutch sarcoma centers. Data were collected using qualitative interviews with STS patients (n = 15) and clinicians (n = 8), quantitative surveys (n = 50) and audiotaped consultations (n = 30). Qualitative data were analyzed using thematic analysis and integrated with quantitative data through merging guided by the SEIPS model.
RESULTS: PERSARC was generally used to support clinicians\' proposed treatment plan and not to help patients weigh available treatment options. Use of PERSARC in decision-making was hampered by clinician\'s doubts about whether there were multiple viable treatment options,the accuracy of risk estimates, and time constraints. On the other hand, use of PERSARC facilitated clinicians to estimate and communicate the expected benefit of adjuvant therapy to patients.
CONCLUSIONS: PERSARC was not used to support informed treatment decision-making in STS patients. Integrating RPMs into clinical consultations requires acknowledgement of their benefits in facilitating clinicians\' estimation of the expected benefit of adjuvant therapies and information provision to patients, while also considering concerns regarding RPM quality and treatment options\' viability.

We describe a case of a leiomyosarcoma of the thigh, the resection of all the anterior muscular compartment, and the reanimation of knee extension, using a latissimus dorsi (LD) free flap and tendon transfer. Surgical technique and postoperative care management are described. Functional results, neuropathic pain, and range of motion (ROM) were assessed at 3 months and 12 months after discharge. A complete excision (R0) was carried out and rapid wound healing was obtained despite developing a seroma infection. The patient was able to walk without technical support nor limping at 3 months post-surgery. The patient was still in remission at 12 months follow-up, with Medical Research Council (MRC) scale assessed at 4/5 and ROM rated at 5-105°. In case of total quadriceps resection, knee extension reconstruction can be obtained with tendon transfers and reinnervated free muscular flaps. Combining these techniques could be a good strategy for rapid recovery, with optimal scarring and tissue coverage.

BACKGROUND: No previous reports have characterized national profiles of soft-tissue sarcoma overall. We examined the nationwide statistics for soft-tissue sarcoma in Japan using data from the population-based National Cancer Registry.
METHODS: We identified 23 522 soft-tissue-sarcoma patients who were entered in the National Cancer Registry during 2016-19 using International Classification of Diseases-Oncology, Third Edition codes for cancer topography and morphology. We extracted data on patient demographics, tumor details (reason for diagnosis, tumor location, histology, extent of disease), hospital volume/type, treatment, and prognosis for each patient.
RESULTS: Soft-tissue sarcoma showed a slight male preponderance. Approximately 5500-6000 new cases were diagnosed as soft-tissue sarcoma per year, with the age-adjusted incidence of soft-tissue sarcoma being 3.22/100000/year. The age distribution showed a single peak in the 70-79 age range, and sex-stratified data showed it was higher in men. The most common histologic subtype was liposarcoma. The most frequent tumor locations were the soft tissue and skin, followed by the retroperitoneum. Extent of disease was categorized as: \"localized\" (31.3%), \"regional\" (38.9%), or \"distant\" (10.5%). We found significant associations between overall survival and sex, age, tumor location, facility type, hospital volume, reason for diagnosis, extent of disease, and surgical treatment.
CONCLUSIONS: This is the first study to outline the epidemiology, clinical features, treatment, prognosis, and significant factors affecting prognosis of soft-tissue sarcoma in Japan using the National Cancer Registry. Documenting our data regarding elderly patients\' outcomes is essential so other countries showing similar population-aging trends can learn from our experiences.
METHODS: Prognostic studies, Level III.

OBJECTIVE: 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.
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).
CONCLUSIONS: Preoperative and postoperative PLR ratio can be used as a cost-effective prognostic marker for oncologic outcomes in patients with STS who undergo surgery.

Background: Clear cell sarcoma (CCS) is an extremely rare form of sarcoma representing less than 1% of all soft-tissue sarcomas. It has morphological, structural, and immunohistochemical similarities to malignant melanoma, affecting young adults and equally affecting both sexes, and is usually located in the tendinous sheaths and aponeuroses of the limbs. Gastrointestinal localization is exceptional, with less than 100 cases reported thus far. The gene fusion of activating transcription factor 1 (ATF1) and the Ewing sarcoma breakpoint region 1 (EWSR1) are pathognomonic for clear cell sarcoma, representing the key to the diagnosis. CCS is an extremely aggressive tumor, with >30% having distant or lymphatic metastasis at the time of diagnostic, and it has a high recurrence rate of over 80% in the first year after diagnosis and a high tendency for metastatic dissemination. Given the rarity of this tumor, there is no standardized treatment. Early diagnosis and radical surgery are essential in the treatment of CCS both for the primary tumor and for recurrence or metastasis. Chemo-radiotherapy has very little effect and is rarely indicated, and the role of targeted therapies is still under investigation. Case presentation: We present an extremely rare case of intestinal CSS in a 44-year-old Caucasian female. The patient, asymptomatic, first presented for a routine checkup and was diagnosed with mild iron-deficiency anemia. Given her family history of multiple digestive cancers, additional investigations were requested (gastroscopy, colonoscopy, tumoral markers and imaging) and the results were all within normal limits. In the subsequent period, the patient experienced mild diffuse recurrent abdominal pain, which occurred every 2-3 months. Two years later, the patient presented with symptoms of intestinal obstruction and underwent an emergency laparotomy followed by segmental enterectomy and regional lymphadenectomy for stenotic tumor of the jejunum. Histology, immunohistochemistry, and genetic testing established the diagnosis of CCS. No adjuvant therapy was indicated. Initially, no signs of recurrence or metastasis were detected, but after 30 and 46 months, respectively, from the primary treatment, the patient developed liver metastasis and pericolic peritoneal implants treated by atypical hepatic resections and right hemicolectomy. The patient remains under observation.

OBJECTIVE: Almost half of all patients with soft-tissue sarcoma are over 65 years of age, and the proportion of older patients is increasing. Despite this, they have been underrepresented in clinical trials and only limited data are available to guide treatment decisions. The aim of this study was to investigate treatment patterns and outcomes in older patients with soft-tissue sarcoma.
METHODS: Patients over 50 years old treated for advanced soft-tissue sarcoma at the Helsinki University Hospital between January 2000 and July 2020 were included. Data on patient and tumor characteristics, treatment, and survival were retrospectively collected. A total of 152 patients were included: 14.5% (n=22) were over 75 years old, 34.2% (n=52) were 65-74 and 51.3% (n=78) were 50-64 years old.
RESULTS: The outcomes of the oldest group differed from those of younger patients; they were more likely to receive single-agent treatment as first-line therapy (90.9% vs. 28.8% and 24.4%, p<0.001) and had the lowest relative dose-intensity (70% vs. 88% and 95%, p<0.05). They experienced grade three to four hematological adverse events less frequently (38.1%, 56.9% and 72.7%, respectively, p=0.031), and received fewer lines of treatment (median of 1, 2 and 2, respectively, p=0.01). In patients aged ≥75 years, there was no association between further lines of therapy and improved survival. Compared to the youngest group, the oldest patients had a greater risk of dying (hazard ratio=1.7, 95% confidence interval=1.0-2.8, p=0.041) and their median overall survival was only 7.4 months, compared to 14.3 and 12.9 months in the two younger groups.
CONCLUSIONS: These findings suggest that older patients tolerate chemotherapy when treatment is tailored to their needs but may not benefit as much as younger patients.

Background: Nowadays, limb-sparing procedures are the gold standard in the treatment of soft-tissue sarcomas of the limbs. Wide tumor resection with appropriate oncological margins, reconstruction, and stabilization of the involved bone and joint and restoration of the soft tissue lost are essential in order to obtain good clinical and functional outcomes. Tumor excision and soft-tissue reconstruction performed in one-step surgery is chosen by many centers as the preferred approach; however, according to our experience in some selected patients, two-step surgery performed using a dermal regeneration template first and then a margin revision, taking into account the definitive results of the anatomopathological exam conducted over the surgical specimen from the previous surgery, associated with definitive reconstruction surgery over a healthy bed of granulated tissue, showed many potential benefits. Methods: A retrospective observational study was conducted on thirteen patients who underwent a two-step reconstruction procedure using dermal substitution after soft-tissue sarcoma excision. Results: Clinically, the enrolled patients achieved excellent contour and cosmesis of their surgical wounds, with a mean VSS value of 3.07. During the follow-up period, no local recurrences were observed in any patient. Conclusions: Two-step surgery represents the most suitable solution to allow surgical radicality with minimal recurrency and adequate soft-tissue reconstruction, avoiding the possibility of wasting autologous tissue. Our patients generally embraced this approach and the management that followed.

HMGA1 is a structural epigenetic chromatin factor that has been associated with tumor progression and drug resistance. Here, we reported the prognostic/predictive value of HMGA1 for trabectedin in advanced soft-tissue sarcoma (STS) and the effect of inhibiting HMGA1 or the mTOR downstream pathway in trabectedin activity. The prognostic/predictive value of HMGA1 expression was assessed in a cohort of 301 STS patients at mRNA (n = 133) and protein level (n = 272), by HTG EdgeSeq transcriptomics and immunohistochemistry, respectively. The effect of HMGA1 silencing on trabectedin activity and gene expression profiling was measured in leiomyosarcoma cells. The effect of combining mTOR inhibitors with trabectedin was assessed on cell viability in vitro studies, whereas in vivo studies tested the activity of this combination. HMGA1 mRNA and protein expression were significantly associated with worse progression-free survival of trabectedin and worse overall survival in STS. HMGA1 silencing sensitized leiomyosarcoma cells for trabectedin treatment, reducing the spheroid area and increasing cell death. The downregulation of HGMA1 significantly decreased the enrichment of some specific gene sets, including the PI3K/AKT/mTOR pathway. The inhibition of mTOR, sensitized leiomyosarcoma cultures for trabectedin treatment, increasing cell death. In in vivo studies, the combination of rapamycin with trabectedin downregulated HMGA1 expression and stabilized tumor growth of 3-methylcholantrene-induced sarcoma-like models. HMGA1 is an adverse prognostic factor for trabectedin treatment in advanced STS. HMGA1 silencing increases trabectedin efficacy, in part by modulating the mTOR signaling pathway. Trabectedin plus mTOR inhibitors are active in preclinical models of sarcoma, downregulating HMGA1 expression levels and stabilizing tumor growth.

Desmoplastic small round cell tumor (DSRCT) is a rare multifocal peritoneal sarcoma, typically found in adolescent and young adult males. Symptoms are nonspecific and vary depending on tumor involvement. Diagnosis is primarily histopathological, although imaging results can assist in the diagnostic process. Although not pathognomonic, certain radiologic findings can help narrow down potential diagnoses and sometimes suggest the condition, as seen in our cases. Treatment options are not well-established or effective, and despite employing various therapeutic approaches, the prognosis remains poor. We present two cases of boys aged 11 and 10 with a final diagnosis of DSRCT, emphasizing the imaging findings.