Treatment Of Sarcoma Research Articles

An analysis of the effectiveness of differential diagnosis and surgical treatment of neck soft-tissue sarcomas in children

We conducted a retrospective sample study with prospective collection of follow-up data. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation. In the time period from January 2013 to August 2020 (92 months), 126 patients with head and neck soft-tissue sarcomas (STS) received treatment at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation. We included 25 patients who had undergone surgery for neck STS and divided them into 4 groups (rhabdomyosarcoma (RMS), non-RMS-like STS, RMS-like STS, IRS-IV STS – with distant metastasis at baseline). The median age at the time of correct diagnosis was 2.6 (0.5; 5.0). The median time from symptom onset to the verification of the correct pathomorphological diagnosis was 3.2 (1.6; 4.9) months. We discovered a significant number (13/25, 52%) of cases of biopsy that was performed improperly (excessive/non-diagnostic biopsy, fine-needle aspiration biopsy) at a general inpatient facility. The correct pathomorphological diagnosis was clinically and statistically much more often made at a reference center (20/25, 80%; p = 0.003). Moreover, more than half of pathomorphological diagnoses (8/13, 62%) made at a general inpatient facility were later changed at a reference center. Radical resection was achieved in 17/20 (85%) survivors. In 3/20 (15%) cases, a repeat surgery was not needed because of the patients' complete response to protocol-based treatment. Radiotherapy was carried out in 11/25 (44%) cases. Protocol-based treatment was completed in 19/25 (76%) patients, 18/25 (72%) patients achieved complete response, 2/25 (8%) patients were considered incurable, and 4/25 (16%) children died before the completion of therapy. Post-operative complications of varying severity were observed in 10/25 (40%) cases and were dependent on the degree of STS extension and the severity of the condition of the patients undergoing intensive protocol-based treatment. The median time of patient observation since diagnosis verification was 33.2 (15.6; 74.2) months. The five-year overall survival (OS) was 76.3% (95% confidence interval (CI) 51.8; 89.5), the five-year event-free survival without local disease progression – 73.9% (95% CI 41.8–90.1). Even though there weren't many patients with IRS-IV in our study (4/25, 16%), their exclusion from the analysis resulted in a higher 5-year OS rate: 88.2% (95% CI 60.2; 96.9). This study revealed significant problems in the differential diagnosis of neck STSs in children. In most patients receiving optimal protocol-based treatment, neck tumors can be radically removed at a specialized healthcare facility without mutilating surgery, which results in high 5-year OS and event-free survival rates in patients without distant metastasis. Our findings require further investigation in a larger sample of patients.

Angiosarcoma in children: the experience of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology and literature review

Angiosarcoma is a rare and highly malignant endothelial tumor, which occurs mainly in adults and is extremely rare in children and adolescents. The German guidelines for the treatment of soft tissue sarcomas provided by the Cooperative Weichteilsarkom Studiengruppe in 2012 included a separate therapeutic regimen for pediatric angiosarcoma consisting of a combination of vincristine/doxorubicin/cyclophosphamide (VDC) and paclitaxel. The aim of this article was to describe the epidemiological, clinical, and morphological characteristics of angiosarcoma, to review treatment approaches, and to present the experience of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation in the treatment of children with angiosarcoma. Our study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation. The study included 5 patients diagnosed with angiosarcoma who had received treatment between 2012 and 2022. The patients’ parents gave consent to the use of their child's data, including photographs, for research purposes and in publications. Data on the patients’ age, gender, tumor location and extension, performed treatment and outcomes of the disease were analyzed. The male:female ratio was 0.66:1 and the median age was 5.2 years. Tumors were located in the soft tissues (n = 3) and in the bones (n = 2). In all the cases, invasion of the surrounding tissues was observed. There were no distant metastases at the time of diagnosis. Two (40%) patients underwent primary resection (R1) and 3 (60%) patients had tumor biopsy. Four patients received therapy according to the German guidelines for the treatment of angiosarcoma (VDC/paclitaxel courses), and 1 patient received treatment according to the guidelines for the management of non-rhabdomyosarcoma soft-tissue sarcomas (courses with vincristine, ifosfamide, doxorubicin/ vincristine, ifosfamide, actinomycin D). Objective response to treatment was achieved in 3 (60%) cases. Local control treatment of these 3 patients consisted of radiation therapy with a total dose of 50.4 Gy after R1 resection in 2 cases and biopsy in 1 case. After a median follow-up of 32 months, 2 patients who had received VDC/paclitaxel were alive without events (with complete and partial response), 3 patients died of progressive disease. Our data confirm the aggressive behavior of angiosarcoma in children. Protocol therapy that includes multiagent chemotherapy based on paclitaxel and doxorubicin along with local control treatment makes it possible to achieve a long-term control of the disease in some patients. However, further research on molecular and genetic characteristics of angiosarcoma is required to find potential novel targets for molecular targeted therapy. Further studies investigating the effectiveness of checkpoint inhibitors in angiosarcoma are also needed.

Benchmarking Time-to-Treatment Initiation in Sarcoma Care Using Real-World-Time Data.

Benchmarking is a fundamental tool for enhancing quality within a patient-centered healthcare framework. This study presents an analysis of time-to-treatment initiation (TTI) for sarcoma patients, utilizing a database encompassing 266 cases from the Swiss Sarcoma Network. Our findings indicate a median TTI of 30 days across the cohort, with bone sarcomas and deep soft tissue sarcomas demonstrating a shorter median TTI of 28 days, followed by superficial soft tissue sarcomas at 42 days. The data reveal that the use of real-world-time data (RWTD) may account for a longer TTI observed, as it offers more comprehensive capture of patient journeys, unlike conventional datasets. Notably, variability in TTI was observed between different treatment institutions, which underscores the need for standardized processes across centers. We advocate for a selective referral system to specialized centers to prevent capacity overload and ensure timely treatment initiation. Our analysis also identified significant delays in TTI for unplanned 'whoops'-resections, highlighting the importance of early specialist referral in optimizing treatment timelines. This study emphasizes the potential benefits of a streamlined, data-informed approach to sarcoma care. However, further research is required to establish the direct impact of integrated care models on TTI and patient outcomes in the context of sarcoma treatment.

Atrial fibrillation and malignant neoplasms: state of the problem

Patients with malignant neoplasms have an increased risk of atrial fibrillation. Prevalence of this pathology among oncological patients is 20–30 %, and it significantly varies depending on tumor type, chemotherapy treatment and initial comorbid status. Atrial fibrillation and malignant neoplasms have similar risk factors. Researchers have identified several possible causes characteristic of these diseases, primarily, systemic inflammation. Some chemotherapies cause abnormalities in ionic channels of atrial cardiomyocytes which leads to changes in the action potential and refractory period, which promote maintenance of atrial fibrillation. The most known groups of chemotherapy drugs associated with atrial fibrillation are alkylating agents (cisplatin, cyclophosphamide), anthracyclines used in sarcoma treatment, as well as anti-HER2 drugs (HER2 – human epidermal growth factor receptor 2), antimetabolites (capecitabine, 5-fluorouracil) and tyrosine kinase inhibitors. However, pathophysiological mechanisms linking together atrial fibrillation and malignant neoplasms require further study.

What is the optimal (neo)adjuvant strategy of extremity high-risk soft tissue sarcomas (ESTS)?

Currently, the standard treatment for extremity high-risk soft tissue sarcomas (ESTS) combines surgery and pre- or post-op radiation therapy (RT). In some selected cases, chemotherapy (CT) is incorporated into the therapeutic algorithm as a neoadjuvant approach to enable conservative management. Given the risk of local or metastatic relapse, this paper discusses the potential benefits of CT and RT in high-grade ESTs. The role of adjuvant chemotherapy in addition to neoadjuvant CT, the prognostic value of the pathological response to neoadjuvant treatment, and the role for an adjuvant "boost" following resection after pre-operative radiotherapy will be discussed.

Treatment strategies of recurrent jaw osteosarcoma: case report

Osteosarcoma of jaw is a rare malignant neoplasm of the maxillofacial region. Morphologically and radiologically identical to trunk and extremities sarcomas, but clinical features and prognosis of the disease have important differences. The strategy in treatment of gnathic sarcomas extrapolated from peripheral sarcomas, and represents an integrated multidisciplinary approach. The role of neoadjuvant chemotherapy remains controversial as well as adjuvant chemotherapy due to lack of clinical research. Surgical treatment with achievement of clean resection margins is the main favorable prognostic factor. Fibular free flap has been widely used for the last decade for mandible reconstruction. The strategies of treatment recurrent disease directly depend on ability to perform complete resection. Despite increased technical complexity, secondary free peroneal flap reconstruction can be performed safely, reliably, and with similar results to the premier segmental mandibulectomy. The use of radiation therapy is limited to unresectable or recurrent lesions. Well known that jaw osteosarcomas have a relatively higher survival rate and low metastasis rate, however, local recurrences significantly worsen the prognosis of patients. The following is a clinical case of treatment recurrent jaw osteosarcoma using second fibular free flap.

Functional audit of the use of megaprosthesis for limb reconstruction in musculoskeletal tumors – A retrospective single-center study

IntroductionMedical advancements in musculoskeletal oncology has significantly reduced the mortality rate associated with limb-sparing surgery, making it comparable to amputation. The use of modular megaprosthesis for sarcoma treatment has now become a standard practice. However, these non-biological implants are not without their complications. Materials and methodsA retrospective cohort study was conducted on all patients who underwent wide resection of locally aggressive and malignant bone tumors, followed by reconstruction with megaprosthesis between January 2018 and January 2023 at tertiary care hospital. Patients were evaluated based on oncological outcomes, functional outcomes, and complications with a minimum follow-up period of 6 months. ResultsThe study included a total of 30 patients, comprising 16 males and 14 females, with a mean age of 33.6 ± 15.6 years. They all underwent wide resection and reconstruction with megaprosthesis. Diagnosis among the patients included 19 cases of giant cell tumors, 5 cases of osteosarcomas, 2 cases of metastatic bone tumors, and 1 case each of chondrosarcoma, malignant fibrous histiocytoma, multiple myeloma, and chondromyxoid fibroma. These tumors were predominantly located in the distal femur (15 patients) and proximal tibia (12 patients). The average follow-up period was 33 ± 21 months, resulting in an average final Musculoskeletal Tumor Society (MSTS) score of 81 % ± 9 %. Complications were observed in 21 patients, with infection being the most common, specifically Type 4 (10 patients, 37 %), followed by Type 1 (4 patients, 13 %) and Type 3 (4 patients, 13 %). Two patients (7 %) experienced Type 5 complications, while three succumbed to their illnesses. Additionally, two patients required amputation, one due to local recurrence and the other due to a deep-seated infection. ConclusionMegaprosthesis is a viable reconstruction option following wide resection of bone tumors. Infection remains the most common issue, and cost poses a significant challenge.

Abstract B150: Targeting EWS-FLI1 with mithramycin analogues for Ewing sarcoma treatment

Abstract Ewing Sarcoma, a devastating malignancy affecting mainly pediatric and young adult populations, is characterized by the aberrant activity of the oncogenic EWS-FLI1 transcription. However, the development of treatments against EWS-FLI1 is lacking. Mithramycin analogues, exhibiting specificity towards EWS-FLI1, have been posited as a groundbreaking approach in drug discovery for the treatment of Ewing Sarcoma. A phase I/II trial and pharmacokinetic (PK) study in Ewing sarcoma patients demonstrated that mithramycin (MTM) had poor PK and dose-limiting hepatic and hematologic toxicities at subtherapeutic concentrations. Here we present a novel MTM analogue with significantly improved PK and a wider therapeutic window. MTMSA-Trp was prepared by chemical conversion of MTM to the MTMSA analogue and the subsequent conjugation of a tryptophan amino acid. The bulky amino acid substitution on the 3-side chain of the molecule appears to shift the ionization properties of the two hydroxy groups on the tricyclic core and to increase protein binding, both of which appear to lead to significantly improved pharmacokinetics. Further, based on crystallographic evaluation, the bulky hydrophobic substitution on the 3-side chain protrudes outside the DNA helix and interacts with bound FLI1. Luciferase reporter and FRET assays demonstrate a dose-dependent effect of MTMSA-Trp on the attenuation of EWS-FLI1 transcription and DNA binding, and based on CETSA evidence, there is physical interaction between MTMSA-Trp and EWS-FLI1. The cytotoxicity of MTMSA-Trp is in the order of low nM across several cell lines expressing EWS-ETS fusions, and the compound disrupts the expression of positively regulated proteins (NR0B1, ID2) and induces expression of negatively regulated ones (CD44, LOX). EWS-FLI1 modulation persists longer when cells are exposed to the GI90 concentration for a short time compared to the GI50 for longer times, suggesting that daily dosing or continuous exposure is not required. MTMSA-Trp has improved PK in athymic nu/nu mice with a greater than 10-fold reduction in clearance and significantly reduced partition in the liver as compared to MTM. Initial efficacy studies in TC32 Ewing Sarcoma cells demonstrated tumor regression and improved survival at the maximum tolerated dose (MTD) and at 2/3 of the MTD on a daily x 5 intravenous bolus injection. Significantly, a more protracted dosing schedule which allowed for higher doses every third day for six doses led to an impressive reduction of tumors whose initial size was above 15 mm in one diameter (i.e., 1200-1600 mm3). Our studies with MTMSA-Trp demonstrate that improving the pharmacologic properties of mithramycin may lead to the development of an EWS-FLI1 inhibitor. Ongoing studies are evaluating the efficacy of MTMSA-Trp in additional Ewing models, and future work will focus on pre-IND studies. Citation Format: Markos Leggas, Kumar K Niloy, Rajesh Yetijaram, Jamie Horn, Yasuda Kazuto, Thomas Prisinzano, Jon S Thorson, Oleg Tsoikov, Jurgen Rohr. Targeting EWS-FLI1 with mithramycin analogues for Ewing sarcoma treatment [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr B150.

Synovial Sarcoma of the Descending Colon: Report of a Rare Case and Review of the Literature

Abstract Introduction/Objective Synovial Sarcoma is a mesenchymal malignancy that occurs primarily in the deep soft tissue near large joints of the extremities in young adults. Synovial sarcoma of the gastrointestinal tract is extremely rare. There is not enough literature to establish a consensus on management and treatment for colorectal synovial sarcoma. Methods/Case Report An 85-year-old male preresented with a positive cologuard test and the colonoscopy revealed a 12 mm polyp in the descending colon. Polypectomy was preformed. Histological examination exhibits spindle cell proliferation with fascicular growth pattern and with small nucleoli. There are collagen deposition, variable size of thick wall vessels and mixed inflammatory cells including lymphocytes, eosinophils and neutrophils in the background. Mitosis are identified. Immunohistochemical stains show tumor cells are negative for CD34, S100, DOG1, CD117, STAT6, Bcl-2, Desmin, and AE1/AE3, and focal positive for EMA, SMA and ALK. Immunohistochemical stain for SS18-SSX fusion protein is positive. Archer fusionplex targeted RNA sequencing (M23-1377) showed SS18:SSX2 fusion. A structural genomic alteration between the SS18 and SSX2 genes is detected [t(18;X)(q12.1;p11.22)]. These findings confirmed the diagnosis of synovial sarcoma. Results (if a Case Study enter NA) NA Conclusion Here we report a rare case of descending colon primary synovial sarcoma. Synovial sarcoma is generally considered as an aggressive and high-grade lesion with metastatic potential and its management is different from other colorectal neoplasms. This case report emphasies a wide differential diagnosis for colorectal lesions and prompt diagnosis and early management is important for better patient outcome.

Description of Patients with HIV and Multicentric Castleman's Disease at the National Institute of Cancerology- Mexico: A 9-Year Experience

Castleman disease is a diverse group of lymphoproliferative disorders with four variants sharing common morphological features on lymph node biopsy but having different etiologies, presentations, treatments, and outcomes. It is classified into unicentric and multicentric variants (MCD), the latter being a systemic disease with multiple lymphadenopathy, where the most common pathological finding is changes in plasma cell type. Based on etiopathogenic characteristics, it can be divided into Kaposi sarcoma herpesvirus (HHV8)-associated, idiopathic, and those related to an overlap with POEMS syndrome. This disease can occur in both HIV-positive individuals and immunocompromised individuals due to other causes. Here, we report our experience with a cohort of HIV-associated MCD cases from 2014 to 2022. A total of 21 patients diagnosed with HIV and HHV8-associated MCD were observed at INCAN during the study period. The majority were men (95%), with a median age of 33y (range, 25 to 54y). The main histologic MCD type was plasma cells (52%), followed by the mixed variant (28%) and the hyaline vascular type (19%). Almost half of the patients were newly diagnosed with HIV (43%), and half of them had a CD4 cell count below 200 cells/mm3 at the time of MCD diagnosis (48%). Only 38% of known HIV patients were taking combination antiretroviral therapy (cART) at the moment of MCD diagnosis. The vast majority (95.2%) were HHV-8 positive by immunohistochemistry, and 66.7% were associated with Kaposi sarcoma. About 52.4% of cases had another active opportunistic infection documented. The most frequently associated infection was syphilis (33.3%), EBV coinfection (23.8%), hepatitis B (14.3%), hepatitis C (4.8%), and CMV viremia (4.8%). 90% of patients developed B symptoms, 71% had fever, 100% had palpable adenopathy, 71% developed hepatosplenomegaly, and 19% had pleural effusion at presentation. In blood analysis, elevated LDH was present in 42.9%, hypoalbuminemia in 71.4%, thrombocytopenia (<100,000) in 35%, anemia (Hb < 8g/dl) in 20%, and renal failure (GFR <30 ml/min/1.73m2) in 10% of cases. The treatment for Kaposi sarcoma at entry was a bleomycin and vincristine-based regimen in 52% of patients, with a median of 2 cycles (range 1-7). Five patients (23%) achieved a complete response without requiring additional treatment. Three patients (14%) with MCD attack criteria resolved systemic symptoms only with cART. Unfortunately, 14% of patients died before receiving treatment, and 38% were managed with “wait and watch” because they did not meet the criteria for MCD attack. The remaining 47% received treatment, with the most common regimens being R-Dox (20%), RCHOP (30%), CHOP (30%), Dox-liposomal (10%), and R-Etoposide (10%), with a median of 4 cycles (range 1-7). Eight patients (38%) received ganciclovir maintenance treatment until reaching negative HHV8 viral load. During the 9 years of follow-up, a total of 5 patients (23.8%) died, with 80% of them experiencing disease progression. The overall survival at 24 months was 77% (figure 1) , and the median survival was not reached at the time of evaluation. In conclusion, our patients with HIV-associated MCD demonstrated similarities to global epidemiological data, with a predominant male population and onset between the fourth and fifth decade of life. The most common histology was the plasmacytic cell subtype, and B symptoms were frequently observed. Hepatosplenomegaly was more prevalent than previously described, anemia and thrombocytopenia appeared to be more common hematological manifestations than reported. Due to a significant percentage of patients having uncontrolled HIV at diagnosis, and unknown KS at the same time of the diagnosis, further research is needed to establish a direct association with MCD and HIV pathophysiology in which clinical manifestations of the disease are diverse an lack specificity, and the prognosis varies greatly. Additionally, concomitant infections may play a role as activators of systemic inflammation and require active screening for MCD in patients with these characteristics. While Kaposi sarcoma treatment was effective in controlling both diseases in some cases, additional management may be necessary, with promising results seen with different treatments. Early intervention for cytokine release syndrome is essential to improve patient outcomes. 1.Blood 2020 Apr16;135(16):1353-64. 2.Nat Rev Dis 2021 Nov 25;7(1):84

Detection of Novel Tyrosine Kinase Fusion Genes as Potential Therapeutic Targets in Bone and Soft Tissue Sarcomas Using DNA/RNA-based Clinical Sequencing.

Approximately 1% of clinically treatable tyrosine kinase fusions, including anaplastic lymphoma kinase, neurotrophic tyrosine receptor kinase, RET proto-oncogene, and ROS proto-oncogene 1, have been identified in soft tissue sarcomas via comprehensive genome profiling based on DNA sequencing. Histologic tumor-specific fusion genes have been reported in approximately 20% of soft tissue sarcomas; however, unlike tyrosine kinase fusion genes, these fusions cannot be directly targeted in therapy. Approximately 80% of tumor-specific fusion-negative sarcomas, including myxofibrosarcoma and leiomyosarcoma, that are defined in complex karyotype sarcomas remain genetically uncharacterized; this mutually exclusive pattern of mutations suggests that other mutually exclusive driver oncogenes are yet to be discovered. Tumor-specific, fusion-negative sarcomas may be associated with unique translocations, and oncogenic fusion genes, including tyrosine kinase fusions, may have been overlooked in these sarcomas. (1) Can DNA- or RNA-based analysis reveal any characteristic gene alterations in bone and soft tissue sarcomas? (2) Can useful and potential tyrosine kinase fusions in tumors from tumor-specific, fusion-negative sarcomas be detected using an RNA-based screening system? (3) Do the identified potential fusion tumors, especially in neurotrophic tyrosine receptor kinase gene fusions in bone sarcoma, transform cells and respond to targeted drug treatment in in vitro assays? (4) Can the identified tyrosine kinase fusion genes in sarcomas be useful therapeutic targets? Between 2017 and 2020, we treated 100 patients for bone and soft tissue sarcomas at five institutions. Any biopsy or surgery from which a specimen could be obtained was included as potentially eligible. Ninety percent (90 patients) of patients were eligible; a further 8% (8 patients) were excluded because they were either lost to follow-up or their diagnosis was changed, leaving 82% (82 patients) for analysis here. To answer our first and second questions regarding gene alterations and potential tyrosine kinase fusions in eight bone and 74 soft tissue sarcomas, we used the TruSight Tumor 170 assay to detect mutations, copy number variations, and gene fusions in the samples. To answer our third question, we performed functional analyses involving in vitro assays to determine whether the identified tyrosine kinase fusions were associated with oncogenic abilities and drug responses. Finally, to determine usefulness as therapeutic targets, two pediatric patients harboring an NTRK fusion and an ALK fusion were treated with tyrosine kinase inhibitors in clinical trials. DNA/RNA-based analysis demonstrated characteristic alterations in bone and soft tissue sarcomas; DNA-based analyses detected TP53 and copy number alterations of MDM2 and CDK4 . These single-nucleotide variants and copy number variations were enriched in specific fusion-negative sarcomas. RNA-based screening detected fusion genes in 24% (20 of 82) of patients. Useful potential fusions were detected in 19% (11 of 58) of tumor-specific fusion-negative sarcomas, with nine of these patients harboring tyrosine kinase fusion genes; five of these patients had in-frame tyrosine kinase fusion genes ( STRN3-NTRK3, VWC2-EGFR, ICK-KDR, FOXP2-MET , and CEP290-MET ) with unknown pathologic significance. The functional analysis revealed that STRN3-NTRK3 rearrangement that was identified in bone had a strong transforming potential in 3T3 cells, and that STRN3-NTRK3 -positive cells were sensitive to larotrectinib in vitro. To confirm the usefulness of identified tyrosine kinase fusion genes as therapeutic targets, patients with well-characterized LMNA-NTRK1 and CLTC-ALK fusions were treated with tyrosine kinase inhibitors in clinical trials, and a complete response was achieved. We identified useful potential therapeutic targets for tyrosine kinase fusions in bone and soft tissue sarcomas using RNA-based analysis. We successfully identified STRN3-NTRK3 fusion in a patient with leiomyosarcoma of bone and determined the malignant potential of this fusion gene via functional analyses and drug effects. In light of these discoveries, comprehensive genome profiling should be considered even if the sarcoma is a bone sarcoma. There seem to be some limitations regarding current DNA-based comprehensive genome profiling tests, and it is important to use RNA testing for proper diagnosis and accurate identification of fusion genes. Studies on more patients, validation of results, and further functional analysis of unknown tyrosine kinase fusion genes are required to establish future treatments. DNA- and RNA-based screening systems may be useful for detecting tyrosine kinase fusion genes in specific fusion-negative sarcomas and identifying key therapeutic targets, leading to possible breakthroughs in the treatment of bone and soft tissue sarcomas. Given that current DNA sequencing misses fusion genes, RNA-based screening systems should be widely considered as a worldwide test for sarcoma. If standard treatments such as chemotherapy are not effective, or even if the sarcoma is of bone, RNA sequencing should be considered to identify as many therapeutic targets as possible.

Emerging innovations and advancements in the treatment of extremity and truncal soft tissue sarcomas.

In this special edition update on soft tissue sarcomas (STS), we cover classifications, emerging technologies, prognostic tools, radiation schemas, and treatment disparities in extremity and truncal STS. We discuss the importance of enhancing local control and reducing complications, including the role of innovative imaging, surgical guidance, and hypofractionated radiation. We review advancements in systemic and immunotherapeutic treatments and introduce disparities seen in this vulnerable population that must be considered to improve overall patient care.

Treatment and Outcomes of Radiation-Induced Soft Tissue Sarcomas of the Extremities and Trunk—A Systematic Review of the Literature

Introduction: Radiation-induced soft tissue sarcomas (RISs) are rare secondary malignancies with a dire prognosis. The literature on the management of these tumors remains scarce due to their low incidence. Our systematic review sought to assess the treatment alternatives and outcomes of patients with RIS. Methods: A systematic review was conducted following the PRISMA guidelines. Our study was registered in PROSPERO (ID: CRD42023438415). Quality assessment was performed using the STROBE checklist. Weighted means for both continuous and categorical values were calculated. Results: Twenty-one studies comprising 1371 patients with RIS were included. The mean latency period from radiation to RIS diagnosis was 14 years, and the mean radiation dose delivered to the primary malignancy was 29.2 Gy. The most common histological type was undifferentiated pleomorphic sarcoma (42.2%), and 64% of all tumors were high-grade. The trunk was the most common location (59%), followed by extremities (21%) and pelvis (11%). Surgery was performed in 68% of patients and, among those with an appendicular tumor, the majority (74%) underwent limb-salvage surgery. Negative margins were attained in 58% of patients. Chemotherapy and radiotherapy were administered in 29% and 15% of patients, respectively. The mean 5-year overall survival was 45%, and the local recurrence and metastasis rates were 39% and 27%, respectively. Conclusions: In our study, the most common treatment was surgical resection, with RT and chemotherapy being administered in less than one third of patients. Patients with RIS exhibited poor oncologic outcomes. Future studies should compare RIS with de novo STS while controlling for confounders.

Calculating Tumor Volume Using Three-Dimensional Models in Preoperative Soft-Tissue Sarcoma Surgical Planning: Does Size Matter?

This feasibility study aims to explore the use of three-dimensional virtual surgical planning to preoperatively determine the need for reconstructive surgery following resection of an extremity soft-tissue sarcoma. As flap reconstruction is performed more often in advanced disease, we hypothesized that tumor volume would be larger in the group of patients that had undergone flap reconstruction. All patients that were treated by surgical resection for an extremity soft-tissue sarcoma between 1 January 2016 and 1 October 2019 in the University Medical Center Groningen were included retrospectively. Three-dimensional models were created using the diagnostic magnetic resonance scan. Tumor volume was calculated for all patients. Three-dimensional tumor volume was 107.8 (349.1) mL in the group of patients that had undergone primary closure and 29.4 (47.4) mL in the group of patients in which a flap reconstruction was performed, p = 0.004. Three-dimensional tumor volume was 76.1 (295.3) mL in the group of patients with a complication following ESTS treatment, versus 57.0 (132.4) mL in patients with an uncomplicated course following ESTS treatment, p = 0.311. Patients who had undergone flap reconstruction had smaller tumor volumes compared to those in the group of patients treated by primary closure. Furthermore, a larger tumor volume did not result in complications for patients undergoing ESTS treatment. Therefore, tumor volume does not seem to influence the need for reconstruction. Despite the capability of three-dimensional virtual surgical planning to measure tumor volume, we do not recommend its utilization in the multidisciplinary extremity soft-tissue sarcoma treatment, considering the findings of the study.

Long-Term Survival after Primary Ewing's Sarcoma of the Skull with Intracranial Extension.

Primary Ewing's sarcoma of the skull is a very rare malignant neoplasm, predominantly occurring in children and adolescents. We describe here the clinical, neuroradiologic, and histopathologic features of a patient with primary Ewing's sarcoma of the skull and discuss the standards of therapy for this type of tumor. This 18-year-old male patient presented with a primary Ewing's sarcoma of the skull, involving the dura of the frontal and parietal lobes of the left cerebral hemisphere. He was treated with gross total surgical excision of tumor, skull reconstruction, chemotherapy, and irradiation. Twelve years after the surgery, the patient has no evidence of local recurrence or distant metastases. Radical surgical excision of the primary tumor with safety margins is thought to play a role in the favorable clinical course. The presented case is the longest surviving patient after treatment of primary Ewing's sarcoma of the skull bone. This rare type of tumor may allow better survival rates under adequate management than sarcoma elsewhere in the body.

The Role of Macrophages in Sarcoma Tumor Microenvironment and Treatment.

Sarcomas are a heterogeneous group of malignant mesenchymal tumors, including soft tissue and bone sarcomas. Macrophages in the tumor microenvironment, involved in immunosuppression and leading to tumor development, are called tumor-associated macrophages (TAMs). TAMs are very important in modulating the microenvironment of sarcomas by expressing specific markers and secreting factors that influence immune and tumor cells. They are involved in many signaling pathways, such as p-STAT3/p-Erk1/2, PI3K/Akt, JAK/MAPK, and JAK/STAT3. TAMs also significantly impact the clinical outcomes of patients suffering from sarcomas and are mainly related to poor overall survival rates among bone and soft tissue sarcomas, for example, chondrosarcoma, osteosarcoma, liposarcoma, synovial sarcoma, and undifferentiated pleomorphic sarcoma. This review summarizes the current knowledge on TAMs in sarcomas, focusing on specific markers on sarcoma cells, cell-cell interactions, and the possibly involved molecular pathways. Furthermore, we discuss the clinical significance of macrophages in sarcomas as a potential target for new therapies, presenting clinical relevance, possible new treatment options, and ongoing clinical trials using TAMs in sarcoma treatment.

ME10 Impact of the NETSARC network of reference centers for the diagnosis and treatment of sarcomas in France since 2010

ME10 Impact of the NETSARC network of reference centers for the diagnosis and treatment of sarcomas in France since 2010

Evaluation of delays to multidisciplinary treatment of soft tissue sarcomas at a tertiary cancer center.

62 Background: Management of soft tissue sarcomas often requires coordinated multidisciplinary care including radiation, medical, and surgical oncology. Delays in the multidisciplinary evaluation and treatment may lead to poorer outcomes. Coordination of care through a multidisciplinary clinic (MDC) offering access to all three specialties during the same clinic visit may reduce time from initial evaluation to treatment. Methods: Adult patients treated for soft tissue sarcoma at an NCI-designated comprehensive cancer center following the opening of a sarcoma MDC in November 2021 to May 2023 were included. Patients were either seen in the sarcoma MDC or separately by oncologic providers (usual care). The primary outcome was delay in treatment initiation, defined as greater than 21 days from initial consultation to first treatment. Reasons for delay were abstracted. Descriptive statistics and bivariate analyses were performed. Results: Among 147 patients, 20 were (13.6%) seen in MDC and 127 (86.4%) by usual care. Initial treatments were surgery (46.9%), radiation (30.6%), or systemic therapy (22.4%). Median time to treatment was 34 days (IQR 14-57 days), which differed by treatment modality (surgery 34 days, radiation 37 days, systemic 18 days). There were no significant differences in time to treatment for MDC patients (33 days, IQR 25-44) versus usual care (34 days, IQR 13-57) (p=0.93). However, a significantly higher proportion of MDC patients received multiple modalities of treatment (75.0% vs 48.8% usual care, p=0.011), with a longer average time to treatment in the multi- versus single-modality groups (41 vs 22 days, p<0.001). Among patients requiring multimodal therapy, median time to treatment was 33 days for MDC patients versus 44 days for usual care (p=0.07). MDC patients were also much more likely to receive radiation (90.0% MDC vs 45.6% usual care, p=0.001). Delays in care (n=76, 51.7% of cohort) were seen in 66.7% (12/18) of MDC patients versus 58.3% (63/108) of usual care patients. The most common reasons for delay were need for additional imaging (29.7%) or preoperative testing (18.8%). Conclusions: In this single-center study, no improvement in time to treatment was seen following the opening of a sarcoma multidisciplinary clinic, likely explained by higher proportion of MDC patients receiving multiple treatment modalities. Primary reasons for delay could be anticipated prior to initial evaluation and represent an opportunity for more active case review prior to in-person evaluation to reduce delays in sarcoma treatment.

P43-9 The treatment of Kaposi sarcoma: Chasing the progressive disease with the presentation of KICS

P43-9 The treatment of Kaposi sarcoma: Chasing the progressive disease with the presentation of KICS

SY15-2 Current status and challenges of treatment for retroperitoneal sarcoma in Japan

SY15-2 Current status and challenges of treatment for retroperitoneal sarcoma in Japan