A Case of a Giant Liposarcoma at Binh Dan Hospital.

Retroperitoneal liposarcomas (RLSs) are uncommon mesenchymal tumors that might present a diagnostic challenge due to their rarity and anatomical location. Despite grossly complete resections, they are commonly linked to a high recurrence rate, necessitating long-term or indefinite follow-up. This report discusses a 59-year-old male patient referred to the Gastrointestinal Department due to chronic abdominal distention, right-sided back pain, and a sizable abdominal mass. The diagnosis was an RLS, and the patient underwent en bloc resection of the mass.

CXCR4 Expression as a Prognostic Biomarker in Soft Tissue Sarcomas.

Poor long-term survival in localized high-risk soft tissue sarcomas (STSs) of the extremities and trunk highlights the need to identify new prognostic factors. CXCR4 is a chemokine receptor involved in tumor progression, angiogenesis, and metastasis. The aim of this study was to evaluate the association between CXCR4 expression in tumor tissue and survival in STSs patients treated with neoadjuvant therapy. CXCR4 expression was retrospectively determined by immunohistochemical analysis in serial specimens including initial biopsies, tumors post-neoadjuvant treatment, and tumors after relapse. We found that a positive cytoplasmatic expression of CXCR4 in tumors after neoadjuvant treatment was a predictor of poor recurrence-free survival (RFS) (p = 0.003) and overall survival (p = 0.019) in synovial sarcomas. We also found that positive nuclear CXCR4 expression in the initial biopsies was associated with poor RFS (p = 0.022) in undifferentiated pleomorphic sarcomas. In conclusion, our study adds to the evidence that CXCR4 expression in tumor tissue is a promising prognostic factor for STSs.

Delayed Diagnosis of SMARCA4-Deficient Undifferentiated Tumor in a Heavy Smoker Male Patient: Discovered Through Bone Sampling, with Extensive Distant Metastases and Concurrent Granulomatous Disease, Leading to Patient Fatality.

Background. SMARCA4-deficient undifferentiated tumors are rare and pose a diagnostic challenge. This study delves into the intricate diagnostic terrain of SMARCA4-deficient undifferentiated tumors, providing insights into their diverse clinical presentations and diagnostic approaches. Case Presentation. A 69-year-old heavy-smoker man with adalimumab-treated rheumatoid arthritis presented with multiple lesions. A CT scan revealed a spiculated lung mass, enlarged mediastinal lymph nodes, and hepatic lesions. A whole-body FDG-PET/CT scan revealed heterogeneous hypermetabolic lesions in the lung, liver, and bone. Initial two core needle liver biopsies and a left upper lobe lung wedge resection initially indicated steatohepatitis and granulomatous formation with no evidence of malignancy. Several months later, the patient returned with left-sided flank pain and significant weight loss. CT scan identified a thigh mass, adrenal lesion, and extensive multiple skeletal lesions. A biopsy of the thigh mass revealed an extensively necrotic, epithelioid-to-spindled cell neoplasm with positive staining for pan keratin, focal staining for CD56, and a loss of nuclear expression of SMARCA4. A final diagnosis of SMARCA4-deficient undifferentiated tumor was rendered. Unfortunately, the patient's condition deteriorated, and he died a few weeks after receiving the final diagnosis. Conclusion. SMARCA4-deficient undifferentiated tumors have emerged as recent subjects of medical study, distinguished by their unique morphology and SMARCA4-deficient immunohistochemistry. These tumors present diverse clinical manifestations, affecting multiple organ systems. This report underscores the diagnostic complexities associated with complex clinical presentation and highlights the importance of multidisciplinary collaboration in addressing challenging clinical scenarios, particularly among heavy smoker male patients and intricate radiological presentations.

Recent Advances in the Surgical Management of Radiation-Induced Fractures following Soft Tissue Sarcomas.

Background: Post-radiation fractures are a significant complication of cancer treatment, often being challenging to manage and impacting patients' quality of life. This study systematically reviews the literature on fractures in irradiated bones, focusing on risk factors, treatment modalities, and prevention strategies. Factors increasing fracture risk include exposure to high doses of radiation of at least 50 Gy, female gender, menopausal age, and periosteal stripping. Additionally further risk factors are the size of the original tumor and osteoporosis. Methods: A search of PubMed yielded 541 articles, with 4 were ultimately included in the review. These retrospective studies focused on patients undergoing Combined Limb-Sparing Surgery and Radiation Therapy for soft tissue sarcoma. Results: Results show post-radiation fractures affect approximately 4% of patients, with the femur being the most frequently affected site. Intramedullary nailing emerges as the gold standard treatment, with prosthetic replacement or megaprostheses used in the metaepiphyseal region and as salvage procedures. Non-union and infection remain formidable complications. Conclusions: This study highlights the importance of prophylactic nailing in fracture prevention and the efficacy of free vascularized fibular flaps to achieve bone union during revision surgeries. Limited case availability and patient follow-up hinder comprehensive studies, impacting treatment outcomes.

CIC::NUTM1 sarcomas occurred in soft tissues of upper limbs : a rare case report and literature review.

BACKGROUND: CIC-rearranged sarcomas (CRS) represent a new entity of undifferentiated small round cell sarcoma belonging to the Ewing-like sarcomas family. CRS are the most common type. Fusion partners for the CIC gene include DUX4, FOXO4, and the recently recognizedNUTM1. Rare cases of CIC::NUTM1 sarcoma in pediatric patients have recently been reported in brain, kidney, bone, and soft tissues. However, such cases have not been identified in the soft tissues of the limbs. CASE PRESENTATION: We reported a case of CIC::NUTM1 sarcoma located in the right upper limb of an 18-year-old man. The tumor displayed morphologic features typical of CIC::DUX4 sarcomas, with small- to medium-sized round cells, a lobular pattern, focal spindling, myxoid stroma, and patchy necrosis. The tumor diffusely expressed NUTM1, was positive for WT1cter at weak to moderate intensity, and was focally positive for CD99, while it was negative for keratins, EMA, P40, MyoD1, myogenin, NKX2.2, BCOR, and pan-TRK. Fluorescence in situ hybridization analyses revealed cleavage of the CIC and NUTM1 genes. CONCLUSION: CIC::NUTM1 sarcomas represent a novel molecular variant of CRS with a preference for the central nervous system and younger pediatric persons. Its morphology and phenotype may be mistaken for NUT carcinomas, and the behavior is more progressive than other forms of CRS. For this rare and newly discovered gene fusion variant, it is necessary to integrate molecular and immunohistochemical findings with morphologic features in the diagnosis of undifferentiated neoplasms.

Synergistic activities of Panobinostat and doxorubicin in soft tissue sarcomas.

BACKGROUND: Soft tissue sarcomas (STS) are rare diseases typically arising from connective tissues in children and adults. However, chemotherapies involved in the treatment of STS may cause toxic side effects and multi-drug chemoresistance, making the treatment even more challenging. Histone deacetylase inhibitors (HDACi) are epigenetic agents which have shown anti-tumor effects as single agent as well as combination use with other drugs. Our project intends to prove the same effects in STS. METHODS: Panobinostat (LBH589) plus doxorubicin was selected for investigations based on our previous research. Tumor xenografts were tried in an epithelioid sarcoma model to validate good synergy effects in vivo and a leiomyosarcoma model was used as a negative comparison group. Gene profile changes were studied afterwards. The possible pathway changes caused by HDACi were explored and validated by several assays. RESULTS: Synergy effect of LBH589 plus doxorubicin was successfully validated in STS cell lines and an epithelioid sarcoma mice model. We tried to reduce the dose of doxorubicin to a lower level and found the drug combination can still inhibit tumor size in mice. Furthermore, gene profile changes caused by LBH589 was studied by RNA-Sequencing analysis. Results showed LBH589 can exert effects on a group of target genes which can regulate potential biological functions especially in the cell cycle pathway.

Intestinal Clear Cell Sarcoma-A Case Presentation of an Extremely Rare Tumor and Literature Review.

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

Molecular and therapeutic advancements in Capicua (CIC)-rearranged sarcoma.

Capicua (CIC)-rearranged sarcomas are an aggressive subset of undifferentiated round cell sarcomas. CIC::DUX4, the proto-typical CIC fusion oncoprotein is associated with rapid clinical progression and chemotherapy resistance leading to poor clinical outcomes. Recent studies have identified additional CIC fusions (CIC::NUTM1, CIC::FOXO4, and CIC::LEUTX) that largely retain CIC-binding specificity but leverage C-terminal binding partners (NUTM1, FOXO4, and LEUTX) to potentially activate transcriptional programs that drive oncogenesis. Moreover, the recent development of preclinical models to study CIC::DUX4 sarcoma have advanced our understanding of the underlying biological mechanisms and uncovered key dependencies that can be translated into rational therapies. In this review, we will highlight these recent advancements in CIC-rearranged sarcoma biology with a vision for clinical translation to improve patient outcomes.

Incidence and survival outcomes of patients with high-grade appendicular bone sarcoma and isolated regional lymph node metastasis: A national cohort database study.

BACKGROUND: While distant metastases in primary bone sarcomas have been extensively studied, the impact of isolated regional lymph node (LN) metastasis on survival remains unknown. In patients with primary bone sarcomas, we sought to assess the prevalence of isolated regional LN metastasis and the survival of this population. METHODS: A total of 6651 patients with histologically-confirmed high-grade osteosarcoma, Ewing sarcoma, or chondrosarcoma were retrieved from the SEER database. We defined four subgroups for our analysis: localized disease (N0 M0), isolated regional LN metastasis (N1 M0), isolated distant metastasis (N0 M1), and combined regional LN and distant metastasis (N1 M1). Disease-specific survival (DSS) was assessed using the Kaplan-Meier method. RESULTS: Prevalence of isolated regional LN metastasis (N1 M0) was highest in Ewing sarcoma (27/1097; 3.3 %), followed by chondrosarcoma (18/1702; 1.4 %) and osteosarcoma (26/3740; 0.9 %). In all three histologies, patients with isolated regional LN metastasis had a worse 2-year, 5-year, and 10-year DSS than those with localized disease. Chondrosarcoma patients with isolated regional LN (N1 M0) metastasis had a significantly higher DSS in comparison to those with only distant metastasis (N0 M1) at the 5- and 10-year marks; for osteosarcoma and Ewing sarcoma, only a pattern towards higher survival was seen. Risk factors for presenting isolated regional LN metastasis included tumor location in lower-limb (OR = 2.01) or pelvis (OR = 2.49), diagnosis of Ewing sarcoma (OR = 2.98), and tumor >10 cm (OR = 1.96). CONCLUSIONS: Isolated regional LN metastases in primary bone sarcomas is an infrequent presentation associated with worse survival than localized disease. LEVEL OF EVIDENCE: III.

Recurrent and novel fusions detected by targeted RNA sequencing as part of the diagnostic workflow of soft tissue and bone tumours.

The identification of gene fusions has become an integral part of soft tissue and bone tumour diagnosis. We investigated the added value of targeted RNA-based sequencing (targeted RNA-seq, Archer FusionPlex) to our current molecular diagnostic workflow of these tumours, which is based on fluorescence in situ hybridisation (FISH) for the detection of gene fusions using 25 probes. In a series of 131 diagnostic samples targeted RNA-seq identified a gene fusion, BCOR internal tandem duplication or ALK deletion in 47 cases (35.9%). For 74 cases, encompassing 137 FISH analyses, concordance between FISH and targeted RNA-seq was evaluated. A positive or negative FISH result was confirmed by targeted RNA-seq in 27 out of 49 (55.1%) and 81 out of 88 (92.0%) analyses, respectively. While negative concordance was high, targeted RNA-seq identified a canonical gene fusion in seven cases despite a negative FISH result. The 22 discordant FISH-positive analyses showed a lower percentage of rearrangement-positive nuclei (range 15-41%) compared to the concordant FISH-positive analyses (>41% of nuclei in 88.9% of cases). Six FISH analyses (in four cases) were finally considered false positive based on histological and targeted RNA-seq findings. For the EWSR1 FISH probe, we observed a gene-dependent disparity (p = 0.0020), with 8 out of 35 cases showing a discordance between FISH and targeted RNA-seq (22.9%). This study demonstrates an added value of targeted RNA-seq to our current diagnostic workflow of soft tissue and bone tumours in 19 out of 131 cases (14.5%), which we categorised as altered diagnosis (3 cases), added precision (6 cases), or augmented spectrum (10 cases). In the latter subgroup, four novel fusion transcripts were found for which the clinical relevance remains unclear: NAB2::NCOA2, YAP1::NUTM2B, HSPA8::BRAF, and PDE2A::PLAG1. Overall, targeted RNA-seq has proven extremely valuable in the diagnostic workflow of soft tissue and bone tumours.

Proton Therapy in Non-Rhabdomyosarcoma Soft Tissue Sarcomas of Children and Adolescents.

This paper provides insights into the use of Proton Beam Therapy (PBT) in pediatric patients with non-rhabdomyosarcoma soft tissue sarcomas (NRSTS). NRSTS are a heterogeneous group of rare and aggressive mesenchymal extraskeletal tumors, presenting complex and challenging clinical management scenarios. The overall survival rate for patients with NRSTS is around 70%, but the outcome is strictly related to the presence of various variables, such as the histological subtype, grade of malignancy and tumor stage at diagnosis. Multimodal therapy is typically considered the preferred treatment for high-grade NRSTS. Radiotherapy plays a key role in the treatment of children and adolescents with NRSTS. However, the potential for radiation-induced side effects partially limits its use. Therefore, PBT represents a very suitable therapeutic option for these patients. The unique depth-dose characteristics of protons can be leveraged to minimize doses to healthy tissue significantly, potentially allowing for increased tumor doses and enhanced preservation of surrounding tissues. These benefits suggest that PBT may improve local control while reducing toxicity and improving quality of life. While clear evidence of therapeutic superiority of PBT over other modern photon techniques in NRSTS is still lacking-partly due to the limited data available-PBT can be an excellent treatment option for young patients with these tumors. A dedicated international comprehensive collaborative approach is essential to better define its role within the multidisciplinary management of NRSTS. Shared guidelines for PBT indications-based on the patient's age, estimated outcome, and tumor location-and centralization in high-level referral centers are needed to optimize the use of resources, since access to PBT remains a challenge due to the limited number of available proton therapy facilities.

High-Grade Pleomorphic Sarcomas Treated with Immune Checkpoint Blockade: The MD Anderson Cancer Center Experience.

BACKGROUND: Undifferentiated pleomorphic sarcomas (UPSs) are amongst the most common subtypes of soft-tissue sarcomas. Few real-world data on the use of immune checkpoint blockade (ICB) in UPS patients and other high-grade pleomorphic STS patients are available. PURPOSE: The purpose of our study is to describe the efficacy and toxicity of ICB in patients with advanced UPSs and other high-grade pleomorphic sarcomas treated at our institution. METHODS: This is a retrospective, observational study of all patients with metastatic high-grade pleomorphic sarcomas treated with FDA-approved ICB at MD Anderson Cancer Center between 1 January 2015 and 1 January 2023. Patients included in trials for which results are not yet published were excluded. RESULTS: Thirty-six patients with advanced/metastatic pleomorphic sarcomas were included. The median age was 52 years. A total of 26 patients (72%) had UPSs and 10 patients (28%) had other high-grade pleomorphic sarcomas. The median follow-up time was 8.8 months. The median PFS was 2.9 months. The 3-month PFS and 6-month PFS were 46% and 32%, respectively. The median OS was 12.9 months. The 12-month OS and 24-month OS were 53% and 29%, respectively. The best response, previous RT, and type of ICB treatment were significantly and independently associated with shorter PFS (p = 0.0012, p = 0.0019 and p = 0.036, respectively). No new safety signal was identified, and the toxicity was overall manageable with no toxic deaths and only four patients (11%) stopping treatment due to toxicity. CONCLUSIONS: Real-world retrospective data are consistent with the published literature, with a promising 6-month PFS of 32%. Partial or stable responders to ICB treatment have significantly improved PFS compared to progressors.

Case report: Pulmonary artery sarcoma diagnosed through rare brain metastases.

We present the case of a 33-year-old male referred across several hospitals because of suspected chronic thromboembolic pulmonary hypertension (CTEPH). Initially admitted in October 2022 for a recurrent, severe cough and diagnosed with CTEPH, he received anticoagulant therapy. However, his symptoms worsened, necessitating a transfer to another facility for thrombolysis treatment. Following an episode of syncope, an MRI scan revealed a metastatic brain tumor. Subsequently, he experienced a third transfer to our hospital, emergency surgery was performed to alleviate cerebral edema and excise a lesion in the left frontal lobe. Postoperative pathology was inconclusive, but a multidisciplinary team meeting, aided by experienced radiologists, eventually confirmed a diagnosis of pulmonary artery sarcoma (PAS) with systemic metastases. This case underscores the necessity of promptly ruling out PAS in patients presenting with significant emboli in the central pulmonary arteries and suggests early referral to specialized centers for suspected cases.

Resection to restoration: Assessing the synergy of polypropylene mesh (Marlex®) combined with methyl-methacrylate and latissimus dorsi flap for primary chest wall sarcomas.

BACKGROUND: Chest-wall sarcomas are treated with extensive resections and complex defect reconstruction to restore chest-wall integrity. It is a difficult surgical procedure that incorporates a multidisciplinary approach for the best outcome, preventing paradoxical chest movement issues and reducing complications. OBJECTIVE: We aimed to describe our experience of chest-wall reconstruction using polypropylene mesh (Marlex® Mesh) combined with methyl-methacrylate and soft-tissue coverage with a latissimus dorsi flap following sarcoma resection. PATIENTS AND METHODS: Among the 53 patients treated for primary chest-wall sarcomas at the European Institute of Oncology (IEO) in Milan, Italy, from 1998 to 2020, 14 cases underwent chest-wall resection and reconstruction using polypropylene mesh, methyl-methacrylate and the latissimus dorsi flap. Patients with locally advanced breast cancers, locally advanced lung cancers, squamous cell carcinomas, and other secondary chest-wall malignancies were excluded from the study, as were the patients with different types of chest-wall reconstruction. RESULTS: In this study, 14 patients (6 men and 8 women) with various primary chest-wall sarcomas were enrolled. On an average, 2 ribs (range: 1-5) were removed during the surgeries, and the chest-wall defects ranged from 20 to 150 cm2 with an average size of 73 cm2. The mean follow-up period for these patients was approximately 63.80 months CONCLUSION: The combination of Marlex® mesh filled with methyl-methacrylate and covered using latissimus dorsi myocutaneous flap provides safe, low-cost and effective single-stage chest-wall reconstruction after surgery for primary sarcomas.

Lumbar functional evaluation of pelvic bone sarcomas after surgical resection and spinal pelvic fixation: A clinical study of 304 cases.

AIMS: We endeavored to introduce a novel scoring system (Lumbar Functional Index, LFI) capable of evaluating lumbar function in pelvic bone sarcoma patients who underwent surgical resection and spinal pelvic fixation, while simultaneously identifying the incidence, outcomes, and risk factors of lumbar function impairment among these populations. PATIENTS AND METHODS: A cohort of 304 primary bone sarcoma patients were recruited. The LFI was created based on the Oswestry Dysfunction Index (ODI) and Japanese Orthopaedic Association (JOA) scores. Lumbar function impairment was defined as LFI score ≥ 18 points, which was identified as high LFI. Demographic data, clinical characteristics, and oncological outcomes were analyzed. RESULTS: The cohort included chondrosarcoma (39.8%), osteosarcoma (29.9%), Ewing sarcoma (8.6%), bone-derived undifferentiated pleomorphic sarcoma (7.2%), giant cell tumor of bone (7.2%), chordoma (2.3%), and other bone sarcomas (5.0%). The LFI score exhibited significant negative correlation with common scoring systems of bone sarcoma. The incidence of high LFI was 23.0%. Patients with high LFI demonstrated a higher prevalence of type I + II + III + IV pelvic tumor, more sacrificed nerve roots and bilateral lumbar spine fixation during surgery, while lower percentage of R0 resection and local control of pelvic tumor. Decreased median overall survival (30 vs. 52 months, p < 0.001) and recurrence-free survival (14 vs. 24 months, p < 0.001) time were observed in these patients. Type I + II + III + IV pelvic tumor and sacrificed nerve roots≥2 were identified as risk factors for high LFI, while R0 resection and local control were identified as protective factors. CONCLUSION: The LFI scoring system exhibited a significant negative correlation to current scoring systems. High LFI patients had worse prognosis and distinct characteristics. The risk factors of high LFI included type I + II + III + IV pelvic tumor and sacrificed nerve roots≥2, and the protective factors included R0 resection and local control.

An aggressive soft-tissue sarcoma of the extremity: A myxofibrosarcoma, grade 3 (FNCLCC system).

We report a case of myxofibrosarcoma of the posterior region of the femur, part of the group of soft-tissue sarcomas: a set of rare and heterogeneous tumors with various subtypes and different prognostic. It is characterized by local infiltrative activity and an extremely high rate of local recurrence. A 58-year-old man came to the Radiology Department to examine a voluminous round and expansive formation of the posterior thigh region. The patient stated that the mass had grown suddenly for about 3 months, maybe after a trauma, increasing in volume exponentially and causing him discomfort, embarrassment, and pain. The result of the first diagnostic approach, with the US, was unexpected and suspicious, and the radiologist wanted to do first a CT, and then maybe plan an MRI. The CT revealed an inhomogeneous density formation and in MRI the mass resulted to be compatible, with the radiologic pattern, with the diagnosis of a sarcoma of the soft tissue. The physicians had already alerted the pathological anatomy, as they suspected something malignant. So, some days after the MRI examination, the patient underwent histological sampling, confirming the suspicion: a myxofibrosarcoma (stage III) of the posterior region of the femoral region. The patient started on radio and chemotherapy, which increases survival and in the hope of reducing the size of the mass, and a strict follow-up was posed before doing the surgery.

Metastatic sarcomas of the oral cavity: A systematic review.

Oral metastatic sarcomas (OMSs) occur only occasionally, and information about their characteristics is based on the restricted number of cases reported in the literature. This study aims to systematically review the English literature to recognize the clinicopathologic characteristics of OMSs. An electronic search was performed in PubMed Central and Scopus databases. The search included all the published articles (human case reports and case series) up till April 2023, with no time restrictions. OMSs were slightly more prevalent in males in their fifth to seventh decades of life. However, a high percentage of OMSs has been reported in the second decade of life. Lower extremities, breasts and uterus are the most common primary origin of metastatic sarcoma. Gingiva and mandible were common locations in the oral cavity for metastatic deposits. Generally, they demonstrated widespread affliction. The mean time interval between primary tumor detection and diagnosis of the oral metastasis was about 33.54 ± 36.19 months. Death was reported in 83 patients (67.48 %) with a mean survival rate of 7.98 ± 10.30 months. The most common microscopic tumor types were leiomyosarcoma (n = 21, 17 %), followed by angiosarcoma (n = 20, 16.26 %) and osteosarcoma (n = 18, 14.63 %). In conclusion, while oral metastases of sarcomas are not common, those should be considered in the differential diagnosis of the oral lesions. Although OMSs show a high occurrence in the 7th decade of the life, the average age of patients with oral involvement is lower than the overall metastatic lesions. OMSs may present as widespread disease with poor prognosis.

A Rare Case of a Malignant Epithelioid Neoplasm With an Underlying Novel EWSR1::ZBT44 Fusion, Identified on Next-Generation Sequencing (NGS).

The clinicopathological spectrum of undifferentiated round cell sarcomas of bone and soft tissues is expanding after the 5th edition of the WHO classification. A 23-year-old male patient presented with a lump in his left thigh of 3 months' duration. Radiological examination revealed a well-defined, solid-cystic lobulated, soft tissue lesion in the proximal medial region of his left thigh, measuring 7.7 cm in the largest dimension. The referring diagnosis was an epithelioid sarcoma. Histopathological review of the tumor sections revealed a cellular tumor composed of malignant epithelioid to focally "rhabdoid-like" cells in a variable hyalinized and myxoid stroma with geographic areas of necrosis. In addition, there were areas reminiscent of hemangiopericytomatous vasculature. By immunohistochemistry, the tumor cells were diffusely positive for CD34, focally and distinctly for pan keratin (AE1/AE3). INI1/SMARCB1 and SMARCA4 (BRG1) were diffusely positive (normal). Next-generation sequencing with a wide sarcoma panel revealed EWSR1exon8::ZBT44exon4 fusion. The present example constitutes the first malignant epithelioid tumor with a hemangiopericytomatous growth pattern, exhibiting this rare fusion. The differential diagnoses of this tumor and their corresponding immunohistochemical profile are discussed. This example highlights the value of NGS in unraveling rare fusions and in differentiating these tumors from their several mimics.

Habitat escalated adaptive therapy (HEAT): a phase 2 trial utilizing radiomic habitat-directed and genomic-adjusted radiation dose (GARD) optimization for high-grade soft tissue sarcoma.

BACKGROUND: Soft tissue sarcomas (STS), have significant inter- and intra-tumoral heterogeneity, with poor response to standard neoadjuvant radiotherapy (RT). Achieving a favorable pathologic response (FPR ≥ 95%) from RT is associated with improved patient outcome. Genomic adjusted radiation dose (GARD), a radiation-specific metric that quantifies the expected RT treatment effect as a function of tumor dose and genomics, proposed that STS is significantly underdosed. STS have significant radiomic heterogeneity, where radiomic habitats can delineate regions of intra-tumoral hypoxia and radioresistance. We designed a novel clinical trial, Habitat Escalated Adaptive Therapy (HEAT), utilizing radiomic habitats to identify areas of radioresistance within the tumor and targeting them with GARD-optimized doses, to improve FPR in high-grade STS. METHODS: Phase 2 non-randomized single-arm clinical trial includes non-metastatic, resectable high-grade STS patients. Pre-treatment multiparametric MRIs (mpMRI) delineate three distinct intra-tumoral habitats based on apparent diffusion coefficient (ADC) and dynamic contrast enhanced (DCE) sequences. GARD estimates that simultaneous integrated boost (SIB) doses of 70 and 60 Gy in 25 fractions to the highest and intermediate radioresistant habitats, while the remaining volume receives standard 50 Gy, would lead to a > 3 fold FPR increase to 24%. Pre-treatment CT guided biopsies of each habitat along with clip placement will be performed for pathologic evaluation, future genomic studies, and response assessment. An mpMRI taken between weeks two and three of treatment will be used for biological plan adaptation to account for tumor response, in addition to an mpMRI after the completion of radiotherapy in addition to pathologic response, toxicity, radiomic response, disease control, and survival will be evaluated as secondary endpoints. Furthermore, liquid biopsy will be performed with mpMRI for future ancillary studies. DISCUSSION: This is the first clinical trial to test a novel genomic-based RT dose optimization (GARD) and to utilize radiomic habitats to identify and target radioresistance regions, as a strategy to improve the outcome of RT-treated STS patients. Its success could usher in a new phase in radiation oncology, integrating genomic and radiomic insights into clinical practice and trial designs, and may reveal new radiomic and genomic biomarkers, refining personalized treatment strategies for STS. TRIAL REGISTRATION: NCT05301283. TRIAL STATUS: The trial started recruitment on March 17, 2022.

Impact of resection margin on outcome in soft-tissue sarcomas of the extremities treated with limb-sparing surgery and postoperative radiotherapy.

BACKGROUND: The standard curative treatments for extremity soft tissue sarcoma (ESTS) include surgical resection with negative margins and perioperative radiotherapy. However, the optimal resection margin remains controversial. This study aimed to evaluate the outcomes in ESTS between microscopically positive margin (R1) and microscopically negative margin (R0) according to the Union for International Cancer Control (UICC) (R + 1 mm) classification. METHODS: Medical records of patients with localized ESTS who underwent primary limb-sparing surgery and postoperative radiotherapy between 2004 and 2015 were retrospectively reviewed. Patients were followed for at least 5 years or till local or distant recurrence was diagnosed during follow-up. Outcomes were local and distal recurrences and survival. RESULTS: A total of 52 patients were included in this study, in which 17 underwent R0 resection and 35 underwent R1 resection. No significant differences were observed in rates of local recurrence (11.4% vs. 35.3%, p = 0.062) or distant recurrence (40.0% vs. 41.18%, p = 0.935) between R0 and R1 groups. Multivariate analysis showed that distant recurrences was associated with a Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade (Grade III vs. I, adjusted hazard ratio (aHR): 12.53, 95% confidence interval (CI): 2.67-58.88, p = 0.001) and tumor location (lower vs. upper extremity, aHR: 0.23, 95% CI: 0.07-0.7, p = 0.01). Kaplan-Meier plots showed no significant differences in local (p = 0.444) or distant recurrent-free survival (p = 0.161) between R0 and R1 groups. CONCLUSIONS: R1 margins, when complemented by radiotherapy, did not significantly alter outcomes of ESTS as R0 margins. Further studies with more histopathological types and larger cohorts are necessary to highlight the path forward.