Soft Tissue Sarcoma Research Articles

Response of Spontaneous Oral Tumors in Canine Cancer Patients Treated with Stereotactic Body Radiation Therapy (SBRT).

To describe outcome and toxicity for dogs with oral tumors, specifically oral malignant melanoma (OMM), squamous cell carcinoma (SCC), and soft tissue sarcoma (STS) after stereotactic body radiation therapy (SBRT). A single institution retrospective study was conducted. Outcomes were analyzed using Kaplan-Meier analysis and Cox proportional hazard analysis. Treatment responses at different time points were evaluated with Pearson's Chi-squared test to identify prognostic factors. Acute and late toxicities were recorded according to VRTOG criteria and were analyzed to identify risk factors. Adverse events other than acute and late toxicities were recorded. A total of 98 patients met the inclusion criteria (OMM n = 37; SCC n = 18; STS n = 43). The SBRT prescription was 1-6 fractions, with a total dose range of 12-40 Gy. Local progression-free survival (PFS) for OMM, SCC, and STS was 187, 253, and 161 days, respectively. Overall PFS was 152 days and median survival time (MST) was 270 days, with no statistical difference between tumor types. The presence of lymph node metastasis and the use of elective nodal irradiation (ENI) were associated with shorted PFS and MST. Severe acute toxicities to organs at risk affected 10/85 (11.8%) of patients. Osteoradionecrosis and oronasal fistula formation occurred in 23/81 (28.4%) of patients and was significantly associated with tumor type (SCC, P = 0.006). BRT can be offered as a treatment option for oral tumors in dogs. Toxicities were common and warrant risk factor considerations and adjustments to current SBRT protocols.

Survival prognostic factors and molecular aspects in extremity soft tissue sarcoma

Survival prognostic factors and molecular aspects in extremity soft tissue sarcoma

B7-H3 is widely expressed in soft tissue sarcomas

PurposeTargeted therapy development in soft tissue sarcoma (STS) has been burdened by the heterogeneity of this group of rare tumors. B7 homolog 3 protein (B7-H3) is a molecule in the same family as programmed death-ligand 1 (PD-L1). It has limited expression in noncancerous tissues and is overexpressed in many cancers, making it an attractive target for cancer therapy, and clinical trials targeting B7-H3 are actively underway. While available data demonstrate high expression levels of B7-H3 in individual sarcoma subtypes, its expression patterns across STS subtypes are not well described. The purpose of this study was to characterize the expression patterns of B7-H3 in STS.Patients and methodsThis retrospective analysis evaluated STS tumor specimens from patients with a variety of different subtypes. Specimens were evaluated by immunohistochemistry (IHC) for expression and staining pattern of B7-H3 both in tumors and in associated vasculature.ResultsSpecimens from 153 sarcoma patients included 15 different STS subtypes. B7-H3 was broadly expressed in 97% of samples (95% CI 0.93–0.99) and 69.2% demonstrated high levels of B7-H3 expression (95% CI 0.61–0.76). No significant association between B7-H3 positivity or expression level and prior treatment(s), tumor size, tumor grade, or patient age. B7-H3 positivity in vessels was found in 94.7% (145/153) of samples. In tumors that had been previously assessed for PD-L1 and PD-1, there was no correlation between B7-H3 positivity or expression and the positivity or expression level of PD-L1 or PD-1.ConclusionThese data show high levels of B7-H3 positivity across soft tissue sarcoma subtypes, suggesting its feasibility as a therapeutic target for future sarcoma treatments. Future clinical trials are needed to evaluate whether targeting B7-H3 can provide clinical benefit to help patients with sarcoma.

Outcome and survival analysis of pulmonary metastasectomy for primary sarcoma with pulmonary metastases.

Sarcomas are rare malignancies, accounting for approximately 1% of all cancers. Pulmonary metastases are the most preferential site for distant metastasis in malignant soft tissue sarcomas. Despite the lack of evidence from large randomized trials to support treatment guidelines, surgical resection of resectable metastatic tumors remains the current standard of care. This study aimed to explore the survival status of patients with soft tissue sarcoma after resection of pulmonary metastases. This study is a retrospective analysis of patients who mestastasectomy by means of lobar or sublobar resections at National Taiwan University Hospital and its branches. The statistical and investigation period was from February 2007 to December 2020. Among 110 samples during the investigation period, the overall 5-year survival rate was 62.9%, which was higher than the 15%-50.9% reported previously. A disease-free interval of more than 12 months and the occurrence of local recurrence of sarcoma at the time of resection of pulmonary metastases are associated with overall survival. Most of the samples were treated with minimally invasive surgery (VATS), and therefore, most patients had a shorter hospital stay and better postoperative recovery. For pulmonary metastatic sarcoma, pulmonary metastasectomy is a relatively safe treatment method with short hospital stay and short ICU stay. The results of this study suggest that VATS is preferred over thoracotomy, but further observations are needed to confirm these findings.

The efficacy and safety of anlotinib combined with chemotherapy in treatment of advanced soft tissue sarcoma

BackgroundTo evaluate the efficacy and safety of anlotinib combined with chemotherapy in the treatment of advanced soft tissue sarcoma (STS).MethodsA total of 14 patients with advanced STS consisting of 4 liposarcoma, 3 undifferentiated polymorphous sarcoma, 2 synovial sarcoma, 1 Extraosseous ewing sarcoma, 1 spindle cell sarcoma, 1 Sarcomatoid malignant mesothelioma, 1 hemangiosarcoma, and 1 fibrosarcoma, were treated with anlotinib plus chemotherapy. The anlotinib was combined with chemotherapy as the first-line treatment in 13 patients, and as second-line treatment in 1 patient. Chemotherapy regimens were based on anthracyclines and ifosfamide, and other drugs included paclitaxel, and so on. Efficacy and safety were evaluated every 2 treatment cycles.ResultsAccording to the stage of AJCC, 9 patients were stage III and 5 patients were stage IV. The average cycle of treatment is 3.86. Among the 14 patients, 2 cases had received surgical treatment after neoadjuvant chemothrapy, 5 cases had partial response (PR), 7 cases had stable disease (SD), and 2 cases had progressive disease (PD). The overall response rate (ORR) was 35.7% (5/14). Patients who had not underwent surgical treatment were with a disease control rate (DCR) of 83.3% (10/12). The median progression free survival (PFS) was 8.25 months. The common treatment-related adverse effects included bone marrow suppression, nausea, vomiting and hypertension. Three patients had severe adverse effect, which was febrile neutropenia. No treatment-related death was found.ConclusionsAnlotinib combined with chemotherapy in the treatment of STS is effective and tolerable, which is a promising strategy. It is worthy of further clinical research.

Real-world Referral Pattern of Unplanned Excision in Patients With Soft-tissue Sarcoma: A Multicenter Study Conducted by the Bone and Soft-tissue Tumor Study Group of the Japan Clinical Oncology Group.

Despite the well-publicized clinical outcomes after unplanned excision (UE) and re-excision (re-excision) in patients with soft-tissue sarcoma (STS), there is little information about the real-life referral patterns for UE, such as patient profile, details of procedures, and subsequent management after UE. We aimed to investigate the characteristics of patients with UE who were referred to sarcoma-specific centers. Between May 2022 and June 2023, we registered 97 patients who underwent UE and were referred to sarcoma-specific centers in Japan. We excluded those with well-differentiated liposarcomas and dermatofibrosarcoma protuberances. We investigated the details of UE and additional treatment after UE. There were 49 men and 48 women, with a mean age of 62 years. A broad range of surgeons performed UE; 36 plastic surgeons, 22 orthopedic surgeons, 17 general surgeons, 17 dermatologists, and 5 others. The mean tumor size was 4.1 cm. Local anesthesia was administered to 58 patients. Forty-five patients underwent UE without prior magnetic resonance imaging. Inappropriate transverse skin incisions were performed in 42 patients. Of the 97 patients, 82 underwent re-excision after UE. The mean time between UE and date of initial presentation at the referral hospital was 46 days. The mean interval between UE and re-excision was 96 days. Of the 82 patients, 59 underwent soft-tissue reconstruction after re-excision. A broad range of surgeons performed UE. Continuous education about STS should be considered for all surgeons. UE should be avoided because residual tumors are common, and reconstructive surgery may be necessary.

Patterns of expression of VEGFR2, PDGFRs and c-Kit in pediatric patients with high grade non-rhabdomyosarcoma soft tissue sarcoma.

Activated vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptors (PDGFRs) and c-Kit have been shown to be involved in the growth, invasion and metastasis of non-rhabdomyosarcoma soft tissue sarcoma tumor (NRSTS) with promising results for targeted therapy. Our aim was to assess the expression of these markers among different histological types and correlate with outcomes. This retrospective study included pediatric patients aged ≤ 18 years diagnosed with high-grade NRSTS who were treated at Children Cancer Hospital Egypt 57357 as per the COG NRSTS protocol (ARST0332). Expression of VEGFR2, PDGFRs (α and β) and c-Kit in tumor tissue was assessed by immunohistochemistry and correlated with clinical outcome. Of 113 patients, 96 were eligible for the analysis with a median age of 11 years. Overall, 32.3% demonstrated high expression of PDGFRα, 17.7% for PDGFRβ, 19.8% for VEGFR2 and 8.3% exhibited positive expression for c-kit on the tumor cells. Most cases of synovial sarcoma (45.8%) and 43.7% of patients with undifferentiated sarcoma exhibited high expression of PDGFRα while 41.6% of MPNST showed high expression to PDGFRβ. The 5-year overall survival (OS), event free survival and relapse free survival (RFS) for the whole cohort were 59%, 54% and 60% respectively. In univariate analyses, only PDGFRα had a negative prognostic impact on relapse free survival (RFS) (p=0.03). In multivariate analyses, VEGFR2 was found to have a negative prognostic impact for OS (p = 0.02). Our findings indicated that tyrosine kinase receptors are upregulated in NRSTS and exhibited a distinct expression pattern within various subgroups. High expression of VEGFR2 and PDGFRα significantly correlated with reduced survival and may guide targeted therapy approaches for this poor prognosis group of patients.

Accurate and Safe Tumor Targeting of Orally-administered Salmonella typhimurium A1-R Leads to Regression of an Aggressive Fibrosarcoma in Nude Mice.

Salmonella typhimurium A1-R has been shown to target and inhibit many types of cancers in mouse models without continuous infection of normal tissue. The objective of the present study was to determine the effective dose of orally-administered Salmonella typhimurium A1-R, expressing-green fluorescent protein (GFP), on an HT1080 human-fibrosarcoma nude-mouse model. The HT1080-human- fibrosarcoma nude-mouse models were randomized into the following three groups: G1: untreated control; G2: Oral Salmonella typhimurium A1-R (5×107 colony forming units [CFU]/body, twice a week, 2 weeks); G3: Oral Salmonella typhimurium A1-R (3.3×108 CFU/body, twice a week, 2 weeks). Each group comprised five mice. Body weight and tumor volume were measured twice a week. The number of colonies of Salmonella typhimurium A1-R-GFP in excised tumors and excised livers in groups G2 and G3 were determined on day 3, day 7 and 14 by growth on agar plates. Tukey-Kramer analysis was used to examine the relationships between variables. Statistically-significant results are defined as those with p≤0.05. Salmonella typhimurium A1-R was administered orally at a dose of 3.3×108 CFU, which successfully regressed the HT1080 tumor in nude mice. However, this effect was not observed at a lower dose of 5×107 CFU. After administering Salmonella typhimurium A1-R at 3.3×108 CFU, tumors and liver tissues were harvested, homogenized, and cultured on days 3, 7 and 14. Resulting GFP-expressing Salmonella typhimurium A1-R colonies were then counted. The number of GFP-bacterial colonies derived from excised tumors at intervals of 3, 7, and 14 days increased over time post-administration of oral GFP-Salmonella typhimurium. Conversely, the number of GFP-Salmonella typhimurium A1-R colonies that could be grown from excised livers decreased over time, following oral administration of GFP-Salmonella typhimurium. Additionally, the GFP-bacterial colonies grown from the excised tumors were significantly larger than those grown from the excised livers. The present study showed that an aggressive fibrosarcoma could be regressed by orally-administered Salmonella typhimurium A1-R which accurately targeted tumors without continuous growth in normal organs. The present results suggested the potential of orally-administered Salmonella typhimurium A1-R as a probiotic to treat aggressive soft-tissue sarcoma.

Left inguinal dedifferentiated liposarcoma and primary unclassified sarcoma of the left lung as synchronous multiple sarcomas: a case report

BackgroundPulmonary nodules in patients with soft tissue sarcomas are likely pulmonary metastases, whereas synchronous primary pulmonary sarcomas are rare. Without surgery, determining whether a solitary pulmonary nodule is a primary or metastatic nodule is difficult. Herein, we report a rare case of a primary pulmonary sarcoma that presented synchronously with a primary dedifferentiated liposarcoma.Case presentationA 77-year-old man presented to another hospital with left inguinal swelling and a suspected recurrent inguinal hernia. Computed tomography revealed a left inguinal mass and pure-solid nodule in the left lung and the patient was referred to our hospital for detailed examination and treatment. The inguinal mass was pathologically diagnosed as a dedifferentiated liposarcoma using needle biopsy, whereas bronchoscopic biopsy revealed histological findings suggestive of a sarcoma; however, the primary site could not be determined. Positron emission tomography–computed tomography revealed no high-accumulation lesions except for the two sarcomas. We decided to perform surgery on both sarcomas for diagnostic and curative purposes. The surgical specimens showed that the two sarcomas were different. Based on the immunohistochemical staining findings of MDM2, a left inguinal dedifferentiated liposarcoma and primary pulmonary unclassified sarcoma were diagnosed. The patient displayed no evidence of recurrence 1 year after surgery.ConclusionsWe encountered a rare case of synchronous multiple primary sarcomas, one presenting in the lung and the other in the soft tissue. Surgery was required to achieve a definitive diagnosis for the patient, who achieved disease-free survival at 1 year. This case suggests that proactive resection of pulmonary nodules in patients with soft tissue sarcomas may be feasible as a diagnostic treatment if complete resection is achieved.

Lymphoid Aggregates in Canine Cutaneous and Subcutaneous Sarcomas: Immunohistochemical and Gene Expression Evidence for Tertiary Lymphoid Structures.

Canine cutaneous/subcutaneous soft-tissue sarcomas (STS) are diversely derived mesenchymal neoplasms with a risk of recurrence and/or metastasis depending on the extent of surgical excision and histologic grade. Lymphoid aggregates (LAs) are often described in these tumours but not characterised. In humans, LA characterised as tertiary lymphoid structures (TLSs) improve the prognosis of many tumours, including sarcomas. We sought to determine if LA meeting a size criterion (> 700 cells) in canine sarcomas met the criteria of TLS and the overall prevalence of LA of any size. RNA expression in large LAs versus aggregate-adjacent sarcoma tissue (AAS) was measured in laser capture microdissected tissue and compared to curl-derived RNA from aggregate-free sarcomas and lymph nodes. CD3, CD20, MUM-1 and PNAd expressions were measured using immunohistochemistry. CD20 and CD3 mRNA were more highly expressed in LA versus AAS (13.8 fold, p = 0.0003 and 2.3 fold, p = 0.043). This was supported by the IHC findings. The large LAs were also enriched in chemokine RNA expression characteristic of TLS (CXCR5 5.8 fold, p < 00001, CCL19 3.68 fold, p = 0.0209, CCL21 6.87 fold, p = 0.0209 and CXCL13 2.68 fold, p = 0.0924). Plasma cells and high endothelial venules were identified in LA containing tumours but not in control tissue. Large LAs were present in 12% of tumours, and LA of any size in 30%. We conclude that large LAs in canine STS are consistent with TLS.

Integrated Care in Specialized Networks: Leveraging Early Referrals to Reduce Local Recurrence in Soft Tissue Sarcoma.

This study evaluated the impact of care pathways on the incidence of local recurrence (LR) in patients with soft tissue sarcomas (STS) and identified factors predictive of LR. It compared outcomes between patients managed entirely within a comprehensive care pathway (CCP) at the Swiss Sarcoma Network (SSN) and those who experienced fragmented care pathways (FCPs), where initial treatment occurred outside specialized centers. This prospective study utilized real-world-time data from the SSN-Sarconnector, capturing quality indicators through weekly Multidisciplinary Team/Sarcoma-Board (MDT/SB) meetings. The overall incidence of LR was 17.6% (n = 68/386), higher than rates typically reported in sarcoma center-based studies due to the inclusion of patients with prior inadequate management from real-world referrals. In a univariable logistic regression analysis, the FCP was significantly associated with higher LR rates, unplanned "whoops" resections (25.4%, n = 96), and positive surgical margins, emphasizing the detrimental impact of suboptimal initial management outside of specialized centers. Multivariable analysis confirmed that the FCP (aOR 2.7, 95% CI [1.41, 5.12], p = 0.003), tumor size (aOR 1.49, 95% CI [1.1, 2.02], p = 0.01), and biological behavior (aOR 5.84 95% CI [1.8, 18.86], p = 0.0003) are independent predictors of LR. Notably, patients referred to sarcoma centers after an initial FCP presented with inadequately managed disease, such as incomplete resections and unplanned surgeries, leading to increased complexity of subsequent treatments. These findings underscore the critical role of referral patterns on sarcoma center outcomes, highlighting the significant disparity in LR rates between institutions. The need for improved education and standardized early referral strategies at the spoke level is paramount to optimize patient outcomes and reduce the burden of LR. Enhanced spoke-level education and standardized referral protocols are critical to ensuring effective initial management and optimizing patient outcomes within specialized sarcoma networks like the SSN.

Intraoperative radiotherapy might not serve as a standard therapy for retroperitoneal liposarcoma: insights from a population-based propensity score-matched study.

Difficulty in achieving complete resection leads to a poor prognosis for retroperitoneal soft tissue sarcoma, hence emphasizing the significance of adjuvant treatment. The benefit of preoperative radiotherapy for retroperitoneal liposarcoma was initially demonstrated by the STRASS trial. However, the impact of intraoperative radiotherapy (IORT) on retroperitoneal liposarcoma remains unexplored. Patients with retroperitoneal liposarcoma were identified in the Surveillance, Epidemiology, and End Results (SEER) database, treated between 2000 and 2019. Subsequently, a 1:1 propensity score-matched (PSM) analysis was conducted based on variables identified from a multivariate analysis. T-tests were used to assess differences in normally distributed continuous variables, while the rank-sum test was applied to variables that did not follow a normal distribution. The chi-squared test was utilized to evaluate differences in categorical variables. Ultimately, survival analysis was performed using SPSS to evaluate patient prognosis. A total of 2129 patients with retroperitoneal liposarcoma were included in our study. Age, sex, histology, grading, chemotherapy, and tumor size as independent prognostic risk factors for these patients through multivariate Cox regression analysis. Subsequently, 66 patients were included in the survival analysis through PSM, with 33 patients receiving IORT. Finally, the survival analysis revealed that there was no difference in overall survival among patients with retroperitoneal liposarcoma, regardless of whether they received IORT or not (p= 0.711). As an exploratory study, our findings suggest that patients may not derive benefit from intraoperative radiotherapy. These observations are intended to lay the groundwork for future prospective clinical studies.

Anlotinib plus TQB2450, a PD-L1 Antibody, in Patients with Advanced Alveolar Soft Part Sarcoma: a single-arm, phase 2 trial.

Alveolar soft part sarcoma (ASPS) is an ultra-rare soft-tissue sarcoma with a high rate of metastasis and no established treatment. This study aimed to explore the efficacy and safety of anlotinib (a tyrosine-kinase inhibitor) and TQB2450 (a PD-L1 inhibitor) in ASPS patients. This single-arm, phase 2 study evaluated the efficacy of TQB2450, an anti-programmed death ligand 1 (PD-L1) agent, combined with anlotinib, a TKI, in adults with advanced ASPS. TQB2450 was given intravenously (1,200 mg) on day 1, and anlotinib (12 mg/day) was taken orally from day 1 to day 14 every 3 weeks. The primary endpoint was overall response rate, with secondary endpoints including duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Lymphocyte infiltration and tertiary lymphoid structure (TLS) were also analyzed as potential prognostic biomarkers. The study enrolled 29 patients, with 28 evaluable (one withdrew due to acute pancreatitis). An objective response was achieved in 82.1% of patients, including 4 complete and 19 partial responses. The median time to response was 2.8 months, and the DOR was not reached, with an estimated median PFS of 35.2 months. Grade 3-4 treatment-related adverse events occurred in 44.8% of patients, with no study-related deaths. Responders had a higher proportion of TLS area, density, and CD20-positive immune cells. The combination of anlotinib and TQB2450 is effective and tolerable in ASPS patients. TLS may serve as a prognostic biomarker, meriting further investigation.

The Critical Role of Stereotactic Body Radiation Therapy in Multimodal Treatment of Lung Metastasis from Bone and Soft Tissue Sarcomas.

Stereotactic body radiotherapy (SBRT) is increasingly used to treat lung metastasis (LM) in patients with soft tissue sarcoma (STS) and bone sarcoma (BS). This retrospective study evaluated the outcomes of patients with BS and STS treated with SBRT for LM between 2010 and 2023. We enrolled 102 patients (51 each with STS and BS), of whom 71 were males and 31 were females (median age, 40 years; range, 11-81 years). At diagnosis, 76 and 26 patients had localized and metastatic disease, respectively, with a median of 4 recurrences (range, 1-12). Before SBRT, 75 patients received chemotherapy and 52 underwent surgery for LM, with 276 nodules treated with SBRT (median dose, 48 Gy; range, 40-52). Local control of irradiated LM was 86% at 1 year and 78% at 2 years. By 31 December 2023 (median follow-up, 4.8 years), 60 patients had died and 42 survived (20 without ongoing disease). From the first LM relapse, the median overall survival (OS) was 4.8 years and the 5-year OS was 49% (95% confidence interval, 39-60%), with no difference between STS and BS; the median OS was 2.9 years and the 5-year OS was 36% after SBRT. Chemotherapy before SBRT was a negative prognostic factor by multivariate analysis. Long-term follow-up shows that SBRT as part of a multimodal treatment approach has reasonable survival rates in patients with LM due to sarcoma. Compared with historical results using only surgery and chemotherapy, SBRT has improved the 5-year OS.

Soft Tissue Sarcoma: Experience in a Tertiary Referral Center

Soft Tissue Sarcoma: Experience in a Tertiary Referral Center

Rare Head and Neck Cancers and Pathological Diagnosis Challenges: A Comprehensive Literature Review.

Head and neck cancers (HNCs) arise from anatomically adjacent sites and subsites, with varying etiological factors, diagnostic strategies, prognoses, and treatment approaches. While conventional squamous cell carcinoma (SCC) is the most common histology in the head and neck district, HNCs encompass a variety of rare histopathological entities, categorized into epithelial tumors such as salivary gland cancers, sinonasal tumors, neuroendocrine tumors, malignant odontogenic tumors, and SCC variants versus non-epithelial tumors including soft tissue sarcomas, mucosal melanomas, and hematological malignancies. Rare HNCs (R-HNCs) represent a diagnostic and clinical challenge, requiring histopathological expertise, the availability of peculiar molecular analysis, and the personalization of local and systemic treatments, all guided by a multidisciplinary tumor board. Here, we provide a comprehensive literature review on R-HNCs, emphasizing key histopathological and molecular characteristics that are crucial for guiding treatment decisions. An insight about the latest developments in systemic treatments is also reported.

A Rare Case Report of Malignant Peripheral Nerve Sheath Tumor in the Infratemporal Fossa.

Introduction: Malignant peripheral nerve sheath tumors (MPNSTs) are rare tumors that develop from peripheral nerve sheath cells and they account for approximately 5% to 10% of all soft-tissue sarcomas. MPNSTs in the head and neck region represent approximately 2% to 6% of all head and neck sarcomas and account for 12% to 19% of all MPNSTs, and the infratemporal fossa is a rare site for MPNSTs. MPNSTs originating from the trigeminal nerve are extremely rare. Case presentation: A 19-year-old female presented with a 6-month history of left-sided facial pain and paresthesia on the same side. On examination, there was left-sided facial paresthesia at the third trigeminal nerve (V3) areas; computed tomography scanning and magnetic resonance imaging showed an infratemporal lesion and surgical resection was done. Histological examination and the immunostaining finding showed high-grade MPNST. Conclusion: MPNSTs in the head and neck region may manifest with nonspecific symptoms. The diagnosis often requires a combination of clinical, pathological, and immunohistochemistry studies. Treatment involves total surgical resection with adjuvant radiotherapy.

Evaluation of a targeted anti-αvβ3 integrin near-infrared fluorescent dye for fluorescence-guided resection of naturally occurring soft tissue sarcomas in dogs.

Complete resection is a key prognostic factor for survival in patients with soft tissue sarcoma (STS), in humas and companion animals alike. Fluorescence-guided surgery could improve resection accuracy. As dogs are frequently affected by STS, they serve as a model to test an anti-αvβ3 integrin targeting near-infrared fluorescent (NIRF) dye (AngiostampTM800) for fluorescence-guided surgery in STS to evaluate its safety and feasibility in dogs, and if it translates into a clinically relevant benefit compared to the standard of care with regards to completeness of surgery and local recurrence. Furthermore, we aimed to correlate target expression and NIRF-signal intensity. Twenty dogs with STS were randomly allocated to either receive Angiostamp™ (NIRF group) or physiologic saline (control group) preoperatively. The researchers were blinded for treatment, and resections were adapted based on the NIRF-signal, if needed. Margin status was histologically determined at the 1 and 3cm margin. The tumor-to-background ratio was measured in native tissue biopsies and formalin-fixed tissue. The fluorescent area was compared to the corresponding tumor areas as confirmed by histology using the Dice coefficient. Target expression was quantified by immunohistochemistry and correlated to NIRF-signal ratios. A fluorescent signal was detected in all 10 tumors of the NIRF group, with a tumor-to-background ratioof 7.4 ± 5.8 in native biopsies and 13.5 ± 10.9 in formalin-fixed tissue. In the NIRF group, resection margins were adapted in 5/10 cases, leading to complete resection and preventing R1 in four of these cases. In the NIRF and control group 9/10 and 8/10 resections were R0, with one local recurrence in each group and one sarcoma-related death in the NIRF group. The NIRF-signal correlated with the histologically confirmed tumor area (Dice coefficient 0.75 ± 0.17). Target expression was higher in tumor compared to peritumoral tissue (p < 0.0003) and showed a moderate correlation with the NIRF-signal (r = 0.6516, p < 0.0001). Fluorescence-guided surgery using Angiostamp™ can pinpoint residual disease in the tumor bed and contributes to an improved resection accuracy in canine STS.

Results of an Integrated Phase I/II Prospective Clinical Trial (NEXIS) for Neoadjuvant Anti-PD-L1 (Durvalumab) and Anti-CTLA-4 (Tremelimumab) With Radiation for High-Risk Soft-Tissue Sarcoma of the Trunk and Extremities

Results of an Integrated Phase I/II Prospective Clinical Trial (NEXIS) for Neoadjuvant Anti-PD-L1 (Durvalumab) and Anti-CTLA-4 (Tremelimumab) With Radiation for High-Risk Soft-Tissue Sarcoma of the Trunk and Extremities

Peripheral immune profiling of soft tissue sarcoma: perspectives for disease monitoring.

Studying the tumor microenvironment and surrounding lymph nodes is the main focus of current immunological research on soft tissue sarcomas (STS). However, due to the restricted opportunity to examine tumor samples, alternative approaches are required to evaluate immune responses in non-surgical patients. Therefore, the purpose of this study was to evaluate the peripheral immune profile of STS patients, characterize patients accordingly and explore the impact of peripheral immunotypes on patient survival. Blood samples were collected from 55 STS patients and age-matched healthy donors (HD) controls. Deep immunophenotyping and gene expression analysis of whole blood was analyzed using multiparametric flow cytometry and real-time RT-qPCR, respectively. Using xMAP technology, proteomic analysis was also carried out on plasma samples. Unsupervised clustering analysis was used to classify patients based on their immune profiles to further analyze the impact of peripheral immunotypes on patient survival. Significant differences were found between STS patients and HD controls. It was found a contraction of B cells and CD4 T cells compartment, along with decreased expression levels of ICOSLG and CD40LG; a major contribution of suppressor factors, as increased frequency of M-MDSC and memory Tregs, increased expression levels of ARG1, and increased plasma levels of IL-10, soluble VISTA and soluble TIMD-4; and a compromised cytotoxic potential associated with NK and CD8 T cells, namely decreased frequency of CD56dim NK cells, and decreased levels of PRF1, GZMB, and KLRK1. In addition, the patients were classified into three peripheral immunotype groups: "immune-high," "immune-intermediate," and "immune-low." Furthermore, it was found a correlation between these immunotypes and patient survival. Patients classified as "immune-high" exhibited higher levels of immune-related factors linked to cytotoxic/effector activity and longer survival times, whereas patients classified as "immune-low" displayed higher levels of immune factors associated with immunosuppression and shorter survival times. In conclusion, it can be suggested that STS patients have a compromised systemic immunity, and the correlation between immunotypes and survival emphasizes the importance of studying peripheral blood samples in STS. Assessing the peripheral immune response holds promise as a useful method for monitoring and forecasting outcomes in STS.