Aberrant positivity for BCOR immunohistochemistry in merkel cell carcinoma - a potential diagnostic pitfall.

BACKRGOUND: Merkel cell carcinoma (MCC) is a rare, aggressive primary cutaneous neuroendocrine carcinoma, frequently associated with clonal Merkel cell polyomavirus integration. MCC can pose significant diagnostic challenges due to its diverse clinical presentation and its broad histological differential diagnosis. Histologically, MCC presents as a small-round-blue cell neoplasm, where the differential diagnosis includes basal cell carcinoma, melanoma, hematologic malignancies, round cell sarcoma and metastatic small cell carcinoma of any site. We here report strong aberrant immunoreactivity for BCOR in MCC, a marker commonly used to identify round cell sarcomas and other neoplasms with BCOR alterations. METHODS: Based on strong BCOR expression in three index cases of MCC, clinically mistaken as sarcoma, a retrospective analysis of three patient cohorts, comprising 31 MCC, 19 small cell lung carcinoma (SCLC) and 5 cases of neoplasms with molecularly confirmed BCOR alteration was conducted. Immunohistochemical staining intensity and localization for BCOR was semi-quantitatively analyzed. RESULTS: Three cases, clinically and radiologically mimicking a sarcoma were analyzed in our soft tissue and bone pathology service. Histologically, the cases showed sheets of a small round blue cell neoplasm. A broad panel of immunohistochemistry was used for lineage classification. Positivity for synaptophysin, CK20 and Merkel cell polyoma virus large T-antigen lead to the diagnosis of a MCC. Interestingly, all cases showed strong positive nuclear staining for BCOR, which was included for the initial work-up with the clinical differential of a round cell sarcoma. We analyzed a larger retrospective MCC cohort and found aberrant weak to strong BCOR positivity (nuclear and/or cytoplasmic) in up to 90% of the cases. As a positive control, we compared the expression to a small group of BCOR-altered neoplasms. Furthermore, we investigated a cohort of SCLC as another neuroendocrine neoplasm and found in all cases a diffuse moderate to strong BCOR positivity. CONCLUSIONS: This study demonstrates that neuroendocrine neoplasms, such as MCC and SCLC can express strong aberrant BCOR. This might represent a diagnostic challenge or pitfall, in particular when MCC is clinically mistaken as a soft tissue or a bone sarcoma.

A multicenter, randomized, non-comparative, phase II study of nivolumab ± ipilimumab for patients with metastatic sarcoma (Alliance A091401): expansion cohorts and correlative analyses.

BACKGROUND: In this open-label, randomized, non-comparative, multicenter phase II study (Alliance A091401) we report on three expansion cohorts treated with nivolumab (N) with and without ipilimumab (N+I) and provide a multi-omic correlative analysis of actionable biomarkers. METHODS: Patients were randomized (non-comparative) to receive either N or N+I. The primary endpoint was a 6-month confirmed response rate (CRR) defined by Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included treatment-related adverse events (TRAEs), progression-free survival, and overall survival. Multi-omic correlative analyses were conducted using samples from both the primary and expansion cohorts. RESULTS: A total of 66 patients were evaluated for the primary endpoint with disease including gastrointestinal stromal tumor (GIST, n=18), undifferentiated pleomorphic sarcoma (UPS, n=24), and dedifferentiated liposarcoma (DDLPS, n=24). Neither N nor N+I achieved a complete or partial response in the GIST expansion cohort. In DDLPS and UPS, the primary response endpoint of CRR was met with N+I (both 16.6%, 2/12) but not with N alone (both 8.3%, 1/12). In the GIST cohort, TRAE was higher with N+I treatment, halting enrollment as required per protocol. In a correlative analysis of patients for the expansion cohort and the original cohort (n=86), traditional biomarkers of immunotherapy response were not correlated with response in any histological subtype. Markers of genomic instability including the presence of gene fusions and increased subclonal mutations correlated with improved clinical outcomes. CONCLUSIONS: This expansion cohort reaffirms the outcomes of A091401. There remains a pressing need to determine the role of and predictive biomarkers for immunotherapy in sarcoma. TRIAL REGISTRATION NUMBER: NCT02500797.

Radiomics of multi-parametric MRI for the prediction of lung metastasis in soft-tissue sarcoma: a feasibility study.

PURPOSE: 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.

New strategies in soft tissue sarcoma treatment.

Soft tissue sarcomas (STS) have long been a formidable challenge in oncology, partly because of their rarity and diversity, which complicates large-scale studies and slows the advent of new treatments. Traditionally anchored by anthracycline-based chemotherapy, the landscape of STS treatment hasn't shifted dramatically in the past twenty years. However, recent strides in research are starting to paint a more hopeful picture. Leveraging advanced molecular profiling, researchers are now tailoring treatments to the unique genetic makeup of tumors, with targeted therapies showing promise. Innovations such as NTRK inhibitors for NTRK-rearranged sarcomas and gamma-secretase inhibitors for desmoid tumors are changing clinical practices. The rise of immunotherapy, including novel agents like LAG-3 inhibitors and bifunctional proteins that target both TGF-ß and PD-L1, offers new avenues for treatment, particularly when combined with traditional therapies like chemotherapy. Meanwhile, the approval of epigenetic treatments for specific sarcoma subtypes heralds a new wave of strategy based on histological specificity, which could lead to more personalized and effective care. While challenges remain, the field of STS treatment is evolving, driven by a deeper understanding of the disease's biological underpinnings and a commitment to innovative research approaches.

Understanding how a personalized risk prediction tool (VALUE-PERSARC) supports informed treatment decisions of soft-tissue sarcomas patients in daily clinical practice - A mixed methods study.

INTRODUCTION: 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. CONCLUSION: 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.

Toxicity Profile of eBAT, a Bispecific Ligand-Targeted Toxin Directed to EGFR and uPAR, in Mice and a Clinical Dog Model.

EGFR-targeted therapies are efficacious, but toxicity is common and can be severe. Urokinase type plasminogen activator receptor (uPAR)-targeted drugs are only emerging, so neither their efficacy nor toxicity is fully established. Recombinant eBAT was created by combining cytokines EGF and uPA on the same single-chain molecule with truncated Pseudomonas toxin. Its purpose was to simultaneously target tumors and their vasculature in the tumor microenvironment. In prior studies on mice and dogs, the drug proved efficacious. Here, we report the safety of eBAT in normal wildtype, uPAR knockout, and immunoreplete and immunodeficient tumor-bearing mice, as well as in dogs with spontaneous sarcoma that more closely mirror human cancer onset. In immunocompetent mice, tumor-bearing mice, uPAR knockout mice, and mice receiving species-optimized eBAT, toxicities were mild and self-limiting. Likewise, in dogs with life-threatening sarcoma given dosages found to be biologically active, eBAT was well tolerated. In mice receiving higher doses, eBAT was associated with dose-dependent evidence of liver injury, including portal biliary hyperplasia, oval cell proliferation, lymphoplasmacytic inflammation, periportal hepatocellular microvesicular change, hemorrhage, necrosis, and apoptosis. The results support continuing the clinical development of eBAT as a therapeutic agent for individuals with sarcoma and other cancers.

Large Nodular Fasciitis of the Shoulder Presenting as Soft Tissue Sarcoma: A Case Report.

CASE: This case report describes a patient who presented with clinical and radiographic features of a soft tissue sarcoma of the shoulder. Despite having a painless and relatively large mass, a biopsy and resection revealed nodular fasciitis (NF). CONCLUSION: This is an unusual case of a painless 10 cm mass that histopathologically was diagnosed as NF in the upper extremity with proximity to the axillary nerve and posterior humeral circumflex vessels. The USP6 rearrangement was helpful in confirming the diagnosis. Careful clinical, radiographic, and pathologic correlation is necessary in diagnosing these relatively rare tumors. In cases where there are discordant findings, molecular markers can be very helpful.

Evaluation of magnetic resonance thermometry performance during MR-guided hyperthermia treatment of soft-tissue sarcomas in the lower extremities and pelvis.

INTRODUCTION: This study evaluated the performance of magnetic resonance thermometry (MRT) during deep-regional hyperthermia (HT) in pelvic and lower-extremity soft-tissue sarcomas. MATERIALS AND METHODS: 17 pelvic (45 treatments) and 16 lower-extremity (42 treatments) patients underwent standard regional HT and chemotherapy. Pairs of double-echo gradient-echo scans were acquired during the MR protocol 1.4 s apart. For each pair, precision was quantified using phase data from both echoes ('dual-echo') or only one ('single-echo') in- or excluding body fat pixels in the field drift correction region of interest. The precision of each method was compared to that of the MRT approach using a built-in clinical software tool (SigmaVision). Accuracy was assessed in three lower-extremity patients (six treatments) using interstitial temperature probes. The Jaccard coefficient quantified pretreatment motion; receiver operating characteristic analysis assessed its predictability for acceptable precision (<1 °C) during HT. RESULTS: Compared to the built-in dual-echo approach, single-echo thermometry improved the mean temporal precision from 1.32 ± 0.40 °C to 1.07 ± 0.34 °C (pelvis) and from 0.99 ± 0.28 °C to 0.76 ± 0.23 °C (lower extremities). With body fat-based field drift correction, single-echo mean accuracy improved from 1.4 °C to 1.0 °C. Pretreatment bulk motion provided excellent precision prediction with an area under the curve of 0.80-0.86 (pelvis) and 0.81-0.83 (lower extremities), compared to gastrointestinal air motion (0.52-0.58). CONCLUSION: Single-echo MRT exhibited better precision than dual-echo MRT. Body fat-based field-drift correction significantly improved MRT accuracy. Pretreatment bulk motion showed improved prediction of acceptable MRT temporal precision over gastrointestinal air motion.

Perfusion-weighted imaging with dynamic contrast enhancement (PWI/DCE) morphologic, qualitative, semiquantitative, and radiomics features predicting undifferentiated pleomorphic sarcoma (UPS) treatment response.

Undifferentiated pleomorphic sarcoma (UPS) is the largest subgroup of soft tissue sarcomas. This study determined the value of perfusion-weighted imaging with dynamic-contrast-enhancement (PWI/DCE) morphologic, qualitative, and semiquantitative features for predicting UPS pathology-assessed treatment effect (PATE). This retrospective study included 33 surgically excised extremity UPS patients with pre-surgical MRI. Volumetric tumor segmentation from PWI/DCE was obtained at Baseline (BL), Post-Chemotherapy (PC), and Post-Radiation Therapy (PRT). The surgical specimens' PATE separated cases into Responders (R) (≥ 90%, 16 patients), Partial-Responders (PR) (89 - 31%, 10 patients), and Non-Responders (NR) (≤ 30%, seven patients). Seven semiquantitative kinetic parameters and maps were extracted from time-intensity curves (TICs), and 107 radiomic features were derived. Statistical analyses compared R vs. PR/NR. At PRT, 79% of R displayed a "Capsular" morphology (P = 1.49 × 10-7), and 100% demonstrated a TIC-type II (P = 8.32 × 10-7). 80% of PR showed "Unipolar" morphology (P = 1.03 × 10-5), and 60% expressed a TIC-type V (P = 0.06). Semiquantitative wash-in rate (WiR) was able to separate R vs. PR/NR (P = 0.0078). The WiR radiomics displayed significant differences in the first_order_10 percentile (P = 0.0178) comparing R vs. PR/NR at PRT. The PWI/DCE TIC-type II curve, low WiR, and "Capsular" enhancement represent PRT patterns typically observed in successfully treated UPS and demonstrate potential for UPS treatment response assessment.

Barriers to care for musculoskeletal sarcoma patients: a public health perspective.

Introduction: This study seeks to investigate the barriers to care that exist for patients presenting with sarcomas of musculoskeletal origin. Understanding the roots of delays in care for patients with musculoskeletal sarcoma is particularly important given the necessity of prompt treatment for oncologic diagnoses. Investigators reviewed relevant studies of publications reporting barriers to care in patients undergoing diagnosis and treatment of musculoskeletal tumors. Methods: A comprehensive literature search was conducted using Scopus, Embase, Web of Science, and PubMed-MEDLINE. Twenty publications were analyzed, including a total of 114,056 patients. Results: Four barrier subtypes were identified: Socioeconomic Status, Geographic Location, Healthcare Quality, Sociocultural Factors. Socioeconomic status included access to health insurance and income level. Geographic location included distance traveled by patients, access to referral centers, type of hospital system and resource-challenged environments. Healthcare quality included substandard imaging, access to healthcare resources, and healthcare utilization prior to diagnosis. Sociocultural factors included psychological states, nutrition, education and social support. Conclusion: After identifying the most significant barriers in this study, we can target specific public health issues within our community that may reduce delays in care. The assessment of barriers to care is an important first step for improving the delivery of oncologic patient care to this patient population.

Telomeres and telomerase in Sarcoma disease and therapy.

Sarcoma is a rare tumor derived from the mesenchymal tissue and mainly found in children and adolescents. The outcome for patients with sarcoma is relatively poor compared with that for many other solid malignant tumors. Sarcomas have a highly heterogeneous pathogenesis, histopathology and biological behavior. Dysregulated signaling pathways and various gene mutations are frequently observed in sarcomas. The telomere maintenance mechanism (TMM) has recently been considered as a prognostic factor for patients with sarcomas, and alternative lengthening of telomeres (ALT) positivity has been correlated with poor outcomes in patients with several types of sarcomas. Therefore, telomeres and telomerases may be useful targets for treating sarcomas. This review aims to provide an overview of telomere and telomerase biology in sarcomas.

Management of a Complex, Recurrent Case of Medial Thigh Sarcoma With Pedicled Deep Inferior Epigastric Artery Perforator (DIEP) Lymphatic Flow-Through (LyFT) Flap and Secondary Anterolateral Thigh (ALT) Free Flap With Innervated Vastus Lateralis Anastomosed to Synthetic Artery Graft: A Case Report.

Soft-tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin and account for only 1% of adult malignancies. They tend to occur most commonly in the lower extremities. Reconstruction after sarcoma resection can be challenging, especially when important structures are involved and recurrences occur. Additionally, more attention is now being paid to reconstructing the lymphatic system to prevent lymphatic complications. In this case report, we presented the management of recurrent medial thigh sarcoma that necessitated multiple challenging reconstructions to provide valuable insights for lectures on similar cases. A 50-year-old male patient was diagnosed with an undifferentiated pleomorphic cell sarcoma (UPS) of the anteromedial thigh. After preoperative radiotherapy, a mass of 23 × 15 cm was removed, and reconstruction with a pedicled deep inferior epigastric artery perforator (p-DIEP) flap-based lymphatic flow through (LyFT) was performed. Six months later, the patient developed the first local recurrence with the presence of a distant metastasis. Following the tumor resection, the medial part of the DIEP flap was de-epithelized and buried in the defect for dead space obliteration. Another local recurrence arose 7 months after the second surgery. Therefore, a major debulking surgery involving the femoral neurovascular bundle was performed. The femoral artery was reconstructed with a synthetic graft, and the femoral vein with the great saphenous vein harvested from the contralateral thigh. A composite myocutaneous neurotized anterolateral thigh (ALT) flap from the contralateral thigh was used to obliterate the defect and restore the loss of function of the quadriceps femoris. Two lymphaticovenular anastomoses (LVAs) were performed at the ankle to reduce the risk of lymphatic sequelae. This case report highlights the importance of integrating various techniques to create a tailored approach that effectively addresses complex surgical requirements to avoid limb amputation and maintain functionality.

Primary pleomorphic breast sarcoma - a case report.

Primary mammary sarcomas are very rare, histologically heterogeneous non-epithelial malignant neoplasms. Primary undifferentiated pleomorphic sarcoma is a rare malignant mesenchymal tumor in the breast. It is characterized by marked cellular atypism and pleomorphism. Isolated cases with an aggressive course and poor prognosis have been commonly described in the literature. We present a rare case of a 62-year-old woman with an 18-cm solid tumor of the left breast, 6 months old, which grew rapidly during the last month. Physical examination and mammography revealed no enlarged lymph nodes in the left axilla. A total mastectomy was performed. The diagnosis of undifferentiated pleomorphic sarcoma is challenging due to the lack of specific immunohistochemical markers. It can only be made after excluding other types of soft tissue sarcomas. This report discusses the histopathological and immunohistochemical studies that were conducted. Our case is distinguished from others with the same diagnosis by the atypical clinical presentation, which is painless, and the spontaneous bleeding, as well as the large size of the tumor.

From Angiosomal to Bi-Angiosomal and Extra-Angiosomal Pedicled Perforator Flaps: Optimizing the Use of Local Tissues in Abdominal Wall Reconstruction.

INTRODUCTION: The use of free-style and propeller perforator-based flaps has been popularized for the reconstruction of moderate size defects in the trunk and extremities, while their application in the field of abdominal reconstruction is seldom reported. The purpose of this report is to describe the authors experience with the use of pedicled perforator-based flaps in abdominal wall reconstruction, presenting the innovative concept of transition from angiosomal to bi-angiosomal and extra-angiosomal perforator flaps and showing applications of the different flap designs according to the multiple clinical scenarios. PATIENTS AND METHODS: A total of 15 patients underwent abdominal wall reconstruction with angiosomal, bi-angiosomal, and extra-angiosomal pedicled perforator-based flaps harvested from the surrounding abdominal subunits for superficial or full thickness defects of the abdominal wall of moderate and large dimensions. The defects were consequent to soft-tissue sarcomas (STS) and non-melanoma skin cancer (NMSC) resection in 11 and 4 cases, respectively. Operative data, post-operative course, and complications were recorded. Moreover, at 12 months follow-up, patients were asked to rate the esthetic and functional outcomes of the reconstructive procedure on a 5-point Likert scale. RESULTS: Ten angiosomal perforator flaps (4 DIEP, 4 SCIP, 1 SEAP, and 1 LICAP flaps) and 5 bi-angiosomal and extra-angiosomal conjoined perforator flaps including different vascular territories (3 bilateral DIEP, 1 bilateral SEAP, and 1 ipsilateral DIEP-SEAP flap) were successfully transferred in 15 patients. In two patients, microsurgical anastomoses were performed to guarantee proper vascularization of the additional cutaneous territory. Mean age was 59.3 years. Defect sizes ranged from 98 to 408 cm2 (mean size was 194.7 cm2). Mean operative time was 280 min. Flap surface ranged from 108 to 336 cm2 (mean surface was 209.3 cm2). No major complications were registered. One bi-angiosomal bilateral DIEP flap suffered from partial necrosis and required an additional flap reconstruction. All patients underwent a 12-month follow-up except one, who did not show for clinical follow-up but responded at the Likert scale at clinical follow-up at 9 months. Overall patients' satisfaction was high, with mean esthetic and functional ratings of 4.27 and 3.87. CONCLUSION: The use of local tissues is an under-utilized solution in the field of abdominal wall reconstruction. Angiosomal, bi-angiosomal, and extra-angiosomal perforator flaps proved to be a reliable option to provide the transfer of a significant amount of tissue and offer like with like reconstruction while maximizing flap survival.

Disruptions in antigen processing and presentation machinery on sarcoma.

BACKGROUND: The antigen processing machinery (APM) plays a critical role in generating tumor-specific antigens that can be recognized and targeted by the immune system. Proper functioning of APM components is essential for presenting these antigens on the surface of tumor cells, enabling immune detection and destruction. In many cancers, defects in APM can lead to immune evasion, contributing to tumor progression and poor clinical outcomes. However, the status of the APM in sarcomas is not well characterized, limiting the development of effective immunotherapeutic strategies for these patients. METHODS: We investigated 126 patients with 8 types of bone and soft tissue sarcoma operated between 2001-2021. Tissue microarrays mapped 11 specific areas in each case. The presence/absence of APM protein was determined through immunohistochemistry. Bayesian networks were used. RESULTS: All investigated sarcomas had some defects in APM. The least damaged component was HLA Class I subunit ß2-microglobulin and HLA Class II. The proteasome LMP10 subunit was defective in leiomyosarcoma (LMS), myxoid liposarcoma (MLPS), and dedifferentiated liposarcoma (DDLPS), while MHC I transporting unit TAP2 was altered in undifferentiated pleomorphic sarcoma (UPS), gastrointestinal stromal tumor (GIST), and chordoma (CH). Among different neoplastic areas, high-grade areas showed different patterns of expression compared to high lymphocytic infiltrate areas. Heterogeneity at the patient level was also observed. Loss of any APM component was prognostic of distant metastasis (DM) for LMS and DDLPS and of overall survival (OS) for LMS. CONCLUSION: Sarcomas exhibit a high degree of defects in APM components, with differences among histotypes and tumoral areas. The most commonly altered APM components were HLA Class I subunit ß2-microglobulin, HLA Class I subunit α (HC10), and MHC I transporting unit TAP2. The loss of APM components was prognostic of DM and OS and clinically relevant for LMS and DDLPS. This study explores sarcoma molecular mechanisms, enriching personalized therapeutic approaches.

Clinicopathological and survival analysis for patients with uterine sarcoma treated following surgery for presumed benign disease.

OBJECTIVES: To investigate the clinicopathological characteristics and prognosis of patients with uterine sarcoma treated following surgery for presumed benign disease. METHODS: We identified all patients with uterine sarcoma found incidentally after primary surgery for presumed benign disease who presented to our institution and received re-exploration for completion surgery from January 1, 2004 to January 1, 2021. We analyzed the clinicopathological characteristics and prognosis. RESULTS: Overall, 95 patients were included in our study. For the initial surgery, myomectomy was performed in 50 (52.6%, 50/95) patients, hysterectomy was performed in 45 (47.4%, 45/95) patients. All patients were re-explored to complete the staging operation. The median time to the staging surgery was 40 days (range 15-90 days). There were 29 patients (30.5%, 29/95) had remnant sarcomas, with 17 patients (17/95, 17.9%) on the remaining uterus, 9 patients (9/95, 9.5%) had disseminated diseases, and 4 patients (4/95, 4.2%) had positive lymph nodes. About 40 patients (42.1%) received adjuvant chemotherapy, 55.2% (16/29) and 36.4% (24/66) patients with/without remnant diseases received adjuvant chemotherapy, respectively (P = 0.087). The median follow-up duration was 76.7 months (IQR: 34.8-118.1 months). And 17 patients (17.9%) had recurrence following re-exploration surgery. 5-year progression-free survival (PFS) and 5-year overall survival (OS) for the entire cohort was 81.7% and 92.1%, respectively. Patients with remnant sarcomas had a tendency towards a worse 5-year PFS and 5-year OS, compared with those without (5-year PFS: 75.6% vs. 84.5%, P = 0.224; 5-year OS: 85.5% vs. 95.1%, P = 0.217). Patients with disseminated diseases had a worse 5-year OS (62.5% vs. 95.1%, P = 0.007) and non-significantly worse 5-year PFS (64.8% vs. 83.4%, P = 0.153) compared with those without. CONCLUSIONS: Patients with uterine sarcoma treated following surgery for presumed benign disease have a favorable survival. Patients with disseminated diseases had a worse 5-year OS compared with those without. Surgical re-exploration may be valuable for removing remnant sarcomas and disseminated diseases.

Targeting the EphA2 pathway: could it be the way for bone sarcomas?

Bone sarcomas are malignant tumors of mesenchymal origin. Complete surgical resection is the cornerstone of multidisciplinary treatment. However, advanced, unresectable forms remain incurable. A crucial step towards addressing this challenge involves comprehending the molecular mechanisms underpinning tumor progression and metastasis, laying the groundwork for innovative precision medicine-based interventions. We previously showed that tyrosine kinase receptor Ephrin Type-A Receptor 2 (EphA2) is overexpressed in bone sarcomas. EphA2 is a key oncofetal protein implicated in metastasis, self-renewal, and chemoresistance. Molecular, genetic, biochemical, and pharmacological approaches have been developed to target EphA2 and its signaling pathway aiming to interfere with its tumor-promoting effects or as a carrier for drug delivery. This review synthesizes the main functions of EphA2 and their relevance in bone sarcomas, providing strategies devised to leverage this receptor for diagnostic and therapeutic purposes, with a focus on its applicability in the three most common bone sarcoma histotypes: osteosarcoma, chondrosarcoma, and Ewing sarcoma.