Adult Soft Tissue Sarcomas Research Articles

Is 5 the New 25? Long-Term Oncologic Outcomes From a Phase II, Prospective, 5-Fraction Preoperative Radiation Therapy Trial in Patients With Localized Soft Tissue Sarcoma

PurposeManagement of adult soft tissue sarcomas entails a multidisciplinary approach with surgery and radiation therapy with or without chemotherapy. The use of preoperative irradiation has been well established, and although conventional fractionation involves daily treatments over the course of 5 weeks, higher doses per fraction may be beneficial due to the radiobiologic profile of sarcoma. In this study we report long-term oncologic outcomes from a single-institution, phase II study evaluating a 5-fraction hypofractionated course of preoperative radiation. Methods and materialsPreoperative hypofractionated radiation therapy was administered to 35 Gy in 5 fractions every other day followed by resection 4 to 6 weeks later. If given, chemotherapy consisted of a doxorubicin-ifosfamide-based regimen delivered neoadjuvantly. The primary endpoint was local control. Additional survival and pathologic outcomes, including overall and distant metastasis-free survival, tumor, and treatment-related pathology, as well as acute and late toxicity were examined. ResultsThirty-two patients were enrolled in this prospective, single-arm phase II trial. At a median follow-up of 36.4 months (range, 3-56), no patient developed a local recurrence, and the 3-year overall and distant metastasis-free survival was 82.2% and 69%, respectively. Major acute postoperative wound complications occurred in 25% of patients. Grade 2 and 3 fibrosis occurred in 21.7% and 13% of patients, respectively. The 2-year median and mean Musculoskeletal Tumor Society score for all patients was 28 and 27.4, respectively. ConclusionsA condensed course of preoperative hypofractionated radiation therapy leads to excellent rates of local control and survival with acceptable toxicity profiles. Potential studies ideally with phase II or III randomized trials would help corroborate these findings and other preoperative hypofractionated results in soft tissue sarcomas.

Current molecular and therapeutic advances in liposarcoma, rhabdomyosarcoma, leiomyosarcoma, synovial sarcoma, and angiosarcoma.

Sarcomas probably develop after malignant transformation of embryonic mesenchymal cells and have broad spectrum histopathologically since they can develop from striated skeletal muscle and smooth muscle, fat and fibrous tissue, bone, cartilage and other mesenchymal tissues. The most common histological subtypes of soft tissue sarcoma in adults are: liposarcoma, leiomyosarcoma, poorly differentiated pleomorphic sarcoma, and gastrointestinal stromal tumor. Molecular and genetic studies of soft tissue sarcomas, which are considered as heterogeneous groups in terms of their molecular and clinical characteristics, are still an important area of ​​interest The heterogeneity of the molecular and genetic alterations of these malignancies, which are mostly treated with surgery and chemotherapy, also offers hope to the researchers in terms of treatment targets. In this article, molecular biologic features of the soft tissue sarcomas including liposarcoma, rhabdomyosarcoma, leiomyosarcoma, synovial sarcoma, and angiosarcoma are discussed in the light of recent developments in molecular biology, targeted therapies and immunotherapy.

Uterine Leiomyosarcoma.

Leiomyosarcoma (LMS) is the most common soft tissue sarcoma in adults and can occur in any part of the body. Uterine leiomyosarcoma (uLMS) is the most common location for LMS, making up 2% to 5% of all uterine malignancies. It is an aggressive tumor that is challenging to treat because of its resistance to standard therapy. The majority of patients (60%) are diagnosed with early-stage disease. However, regardless of the stage, uLMS has a poor prognosis. Surgical resection is the cornerstone of treatment for patients with localized LMS independent of the site of origin. Adjuvant chemotherapy for early-stage disease remains controversial as multiple clinical trials have failed to demonstrate benefit on overall survival. Progress has been made in therapy for advanced and recurrent disease. This case study will highlight the current and emerging data regarding novel therapies for women with uLMS.

Myxofibrosarcoma landscape: diagnostic pitfalls, clinical management and future perspectives.

Myxofibrosarcoma (MFS) is a common entity of adult soft tissue sarcomas (STS) characterized by a predilection of the extremities and a high local recurrence rate. Originally classified as a myxoid variant of malignant fibrous histiocytoma, this musculoskeletal tumor has been recognized since 2002 as a distinct histotype showing a spectrum of malignant fibroblastic lesions with myxoid stroma, pleomorphism and curvilinear vessels. Currently, the molecular pathogenesis of MFS is still poorly understood and its genomic profile exhibits a complex karyotype with a number of aberrations including amplifications, deletions and loss of function. The diagnosis is challenging due to the unavailability of specific immunohistochemical markers and is based on the analysis of cytomorphologic features. The mainstay of treatment for localized disease is represented by surgical resection, with (neo)-adjuvant radio- and chemotherapy. In the metastatic setting, chemotherapy represents the backbone of treatments, however its role is still controversial and the outcome is very poor. Recent advent of genomic profiling, targeted therapies and larger enrollment of patients in translational and clinical studies, have improved the understanding of biological behavior and clinical outcome of such a disease. This review will provide an overview of current diagnostic pitfalls and clinical management of MFS. Finally, a look at future directions will be discussed.

A RARE CASE REPORT OF UNDIFFERENTIATED PLEOMORPHIC SARCOMA WITH CUTANEOUS METASTASES DIAGNOSED ON CYTOLOGY.

Soft Tissue Sarcomas (STS) are rare tumours with dismal prognosis. Undifferentiated Pleomorphic Sarcoma (UPS) was formerly called Malignant Fibrous Histiocytoma (MFH) and reclassied by the World Health Organization (WHO) in 2013. UPS account for 5% of adult soft tissue sarcomas. It usually occurs in elderly with a male predominance and is seen on extremities. Despite of it being highly metastatic, cutaneous metastasis is found to be very rare. Hence we present this case of soft tissue UPS of thigh metastasizing to lung, other soft tissues as well as cutaneous locations diagnosed by Fine Niddle Aspiration Cytology (FNAC).

Adult Soft-Tissue Sarcomas of the Extremities.

Soft-tissue sarcomas (STS) in adults comprise a heterogeneous group of tumors of mesenchymal origin that share similar biological patterns of local tumor growth and metastatic dissemination. The judicious use of imaging studies, biopsy techniques, and pathological evaluations is essential for accurate diagnosis and for planning treatment strategy. Wide local resection and radiation therapy form the cornerstone of management of high-grade STS. The role of adjuvant radiation therapy is questionable in the management of small (≤5 cm) superficial lesions that can be resected with negative margins. Chemotherapy given to patients who have nonmetastatic, high-grade STS results in varying benefit in terms of local tumor control and overall survival. Coordinated care by a multidisciplinary team of trained surgeons, medical oncologists, radiologists, radiation oncologists, and pathologists has been documented to improve local tumor control and the overall survival of patients with STS. Although considerable progress in tumor diagnostics and targeted therapies has been made over the past 2 decades, recommendations and controversies relating to tumor imaging and margins of resection have not changed.

Comparison of Different Systemic Therapeutic Regimes in Resectable Soft-Tissue Sarcoma-Results of a Network Meta-Analysis.

Simple SummaryThis analysis was conducted to compare different systemic treatment options in the therapy of localized and resectable soft-tissue sarcoma. We tested these in a network against the current standard of resection with or without radiotherapy, which allowed direct and indirect comparisons. Chemotherapy given after the local therapy and chemotherapy added to regional hyperthermia before the operation were associated with a longer survival and likeliness of being disease free and alive. Chemotherapy tailored to the specific subtype of sarcoma did not improve outcomes. Adjuvant chemotherapy might be more helpful in male rather than female patients.Background: The standard treatment of high-risk soft-tissue sarcoma consists of surgical resection followed by risk-adapted radiation therapy. Further treatment options that may improve local and systemic tumor control, including chemotherapy, are not well established. Due to the heterogeneity of the disease, different systemic approaches as well as their application at different time points have been attempted. Methods: We conducted a systematic literature search for randomized clinical trials in the treatment of localized, resectable high-risk adult soft-tissue sarcoma comparing different treatment modalities according to the PRISMA guidelines. We extracted published hazard ratios and number of events for the endpoints overall and disease-free survival (OS; DFS) as well as local and distant recurrence-free interval (LRFI; DRFI). The different modalities were compared in a network meta-analysis against the defined standard treatment surgery ± radiotherapy using the inverse-variance heterogeneity model. Results: The literature search identified 25 trials including 3453 patients. Five different treatment modalities were compared in the network meta-analysis. The addition of adjuvant chemotherapy significantly improved OS compared to surgery ± radiotherapy alone (HR = 0.86; CI-95%: 0.75–0.97; p = 0.017). Likewise, neoadjuvant chemotherapy combined with regional hyperthermia (naCTx + HTx) also led to superior OS (HR = 0.45; CI-95%: 0.20–1.00; p = 0.049). Both neoadjuvant chemotherapy alone (naCTx) and perioperative chemotherapy (periCTx) did not improve OS (HR = 0.61; CI-95%: 0.29–1.29; p = 0.195 and HR = 0.66; CI-95%: 0.30–1.48; p = 0.317, respectively). Histology-tailored chemotherapy (htCTx) also did not improve survival compared to surgery ± radiotherapy (HR = 1.08; CI-95%: 0.45–2.61; p = 0.868). The network analysis of DFS, LRFI, and DRFI revealed a similar pattern between the different treatment regimens. Adjuvant chemotherapy significantly improved DFS, LRFI, and DRFI compared to surgery ± radiotherapy. In direct comparison, this advantage of adjuvant chemotherapy was restricted to male patients (HR = 0.78; CI-95%: 0.65–0.92; p = 0.004) with no effect for female patients (HR = 1.08; CI-95%: 0.90–1.29; p = 0.410). Conclusions: Standardized chemotherapy in high-risk soft-tissue sarcoma appears to be of added value irrespective of timing. The benefit of adjuvant chemotherapy seems to be restricted to male patients. The addition of regional hyperthermia to neodjuvant chemotherapy achieved the best effect sizes and might warrant further investigation.

Preoperative diagnostics and typing of abdominal soft tissue sarcomas

Abdominal sarcomas are aheterogeneous group of rare soft tissue tumors and can be localized intraperitoneally or retroperitoneally. Apretherapeutic differentiated subtyping is essential for planning an individual, multimodal treatment concept in an interdisciplinary team of experts. The central aspects of histology acquisition, imaging diagnostics and (molecular) pathological subtyping of abdominal soft tissue sarcomas are described in detail. Imaging and pathological diagnostics are depicted based on the German S3 guidelines on adult soft tissue sarcomas, acurrent literature search and personal experiences at the Sarcoma Center at the National Center for Tumor Diseases in Dresden (NCT/UCC). Preoperative imaging and (molecular) pathological subtyping of abdominal soft tissue sarcomas place high demands on surgeons, radiologists and pathologists. Genome analyses of sarcomas have the potential to identify points of attack for individualized treatment options. The limitations of resectability can only be assessed by experienced sarcoma surgeons at specialized centers. The treatment of abdominal soft tissue sarcomas at an experienced center is associated with abetter prognosis. Even at the first suspicion of an abdominal sarcoma, areferral to an experienced center should be made in order to guarantee optimal expertise in diagnostics and treatment.

High Local Control Following Pre-Operative Radiotherapy for Adult Deep Soft Tissue Sarcoma of the Head and Neck

<h3>Purpose/Objective(s)</h3> Local control (LC) of head and neck (HN) soft tissue sarcoma (STS) is generally lower than the > 90% rate expected in extremity STS. We report outcomes of high-risk adult HN STS [defined as requiring surgery and radiotherapy (RT) after joint in-person assessment by a HN surgeon and radiation oncologist with expertise in sarcoma management] using pre-operative (Pre-op) RT to reduce target volumes adjacent to optic or other vulnerable anatomy. <h3>Materials/Methods</h3> A prospective series of newly diagnosed adult HN STS patients who underwent Pre-op RT between 1989-2019 was analyzed. Angiosarcoma, fibromatosis, and embryonal/alveolar rhabdomyosarcoma were not included due to natural history requiring different management paradigms; other histologies were excluded due to the anticipated favorable control rates in these subtypes (i.e., dermatofibrosarcoma protuberans, HN sinonasal solitary fibrous tumor/hemangiopericytoma). Actuarial rates of LC, distant control (DC), and overall survival (OS) were analyzed by resection margin status. Important wound complications, defined according to a published randomized trial evaluating Pre-op RT in extremity STS, were also reported. <h3>Results</h3> Eligibility comprised 59 cases arising from neck/supraclavicular (n = 23), sinonasal (n = 16), oral (n = 11), parapharyngeal (n = 7), and scalp (n = 2) regions. UICC/AJCC TNM-8 cT-categories were: T1 (n = 10), T2 (n = 20), T3 (n = 20), and T4 (n = 9). Neoadjuvant chemotherapy was given to 3 patients (2 rhabdomyosarcomas and 1 synovial sarcoma). Pre-op RT included: 50 Gy in 25 fractions over 5 weeks (n = 53) or 60 Gy in 30 fractions over 6 weeks (n = 6). Median interval from pre-op RT to surgery was 7.3 weeks (range: 2.9-19.6). Four patients (6.7%) had wound complications considered important according to the defined criteria. One healed following flap debridement and the remainder only required conservative management. Resection margins were grossly positive (gross+) in 4 (7%), microscopically positive (micro+) in 16 (27%), and negative in 39 (68%) patients. Six received a post-op boost of 10 Gy in 5 fractions (1 for micro+ and 5 for < 10 mm resection margins). Median follow-up was 6.5 years (0.8-28.6 years). Local failure occurred in 1/39 negative, 2/16 micro+, and 4/4 gross+ resection margin groups. Five-year LC, DC and OS for negative vs micro+ vs gross+ resection margin groups were: 97% vs 93% vs 25% (<i>P</i> < 0.001, micro+ vs negative: <i>P</i> = 0.083); 78% vs 75% vs 75% (<i>P</i> = 0.97), 83% vs 87% vs 25% (<i>P</i> < 0.001). No patient developed significant toxicity (e.g., blindness) related to RT. <h3>Conclusion</h3> HN STS patients requiring combined modality local management with moderate dose Pre-op RT in a sarcoma-focused multidisciplinary clinic setting have excellent LC and functional outcomes that parallel extremity cases, but with less wound complications. Micro+ margins without postop boost RT does not seem to compromise LC when managed within a collaborative environment.

Genetic Characterization, Current Model Systems and Prognostic Stratification in PAX Fusion-Negative vs. PAX Fusion-Positive Rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents and accounts for approximately 2% of soft tissue sarcomas in adults. It is subcategorized into distinct subtypes based on histological features and fusion status (PAX-FOXO1/VGLL2/NCOA2). Despite advances in our understanding of the pathobiological and molecular landscape of RMS, the prognosis of these tumors has not significantly improved in recent years. Developing a better understanding of genetic abnormalities and risk stratification beyond the fusion status are crucial to developing better therapeutic strategies. Herein, we aim to highlight the genetic pathways/abnormalities involved, specifically in fusion-negative RMS, assess the currently available model systems to study RMS pathogenesis, and discuss available prognostic factors as well as their importance for risk stratification to achieve optimal therapeutic management.

New Guideline on Radiation Therapy for Soft Tissue Sarcoma in Adults

New Guideline on Radiation Therapy for Soft Tissue Sarcoma in Adults

Variation in Management of Extremity Soft-Tissue Sarcoma in Younger vs Older Adults

A large proportion of extremity soft-tissue sarcomas (ESS) occur among young adults, yet this group is underrepresented in clinical trials, resulting in limited data on this population. Younger patients present many complex challenges that affect clinical management. To investigate variations in treatment management in young adults vs older adults with ESS. This multicenter retrospective cohort study used the National Cancer Data Base (NCDB) to identify patients 18 years and older with ESS who received definitive treatment (ie, limb-sparing surgery [LSS] or amputation) between 2004 and 2014. Data analysis was conducted in November 2019. Treatment regimen received among young adults (aged 18-39 years) and older adults (≥40 years) after diagnosis with ESS. To detect unique factors associated with treatment decisions in young adults with ESS, multivariable analyses used logistic regressions for patterns of treatment and their association with demographic factors and tumor characteristics. Overall, 8953 patients were identified, and among these, 1280 (14.3%) were young adults. From the full cohort, 4796 patients (53.6%) identified as male and 6615 (73.9%) identified as non-Hispanic White. More young adults than older adults underwent amputation (age 18-39 years, 104 of 1280 [8.1%]; age 40-64 years, 217 of 3937 [5.5%]; aged ≥65 years, 199 of 3736 [5.3%]), but the association was not statistically significant (age ≥65 years, odds ratio [OR], 1.49; 95% CI, 1.00-2.23; P = .05). Young adults were more likely to receive chemotherapy than older patients (age 40-65 years, OR, 0.52; 95% CI, 0.45-0.60; P = .001; ≥65 years, OR, 0.16; 95% CI, 0.12-0.20; P = .001). Conversely, young adults were less likely to receive radiation therapy compared with older patients (age 40-65 years, OR, 1.40; 95% CI, 1.22-1.61; P = .001; ≥65 years, OR, 1.33; 95% CI, 1.10-1.61; P = .003). Unique to younger adults, clinical stage II disease vs stage I and positive surgical margins were not associated with use of radiation therapy (stage II disease: OR, 1.25; 95% CI, 0.81-1.91; P = .31; positive surgical margins: OR, 1.43; 95% CI, 0.93-2.22; P = .11). White Hispanic young adults were less likely than non-Hispanic White young adults to receive radiation therapy (OR, 0.53; 95% CI, 0.36-0.78; P = .002). In this study, young adults with ESS were more likely to receive chemotherapy and less likely to receive radiation therapy than older adults. Further study is warranted to identify the clinical outcomes of these practice disparities.

Comparison of Different Systemic Therapeutic Regimes in Resectable Soft Tissue Sarcoma – Results of a Network Meta-Analysis

Background: The standard treatment of high-risk soft tissue sarcoma consists of surgical resection followed by risk-adapted radiation therapy. Further treatment options which may improve local and systemic tumor control, including chemotherapy, are not well established. Due to the heterogeneity of the disease, different systemic approaches as well as their application at different time points have been attempted. Methods: We conducted a systematic literature search for randomized clinical trials in the treatment of localized, resectable high-risk adult soft tissue sarcoma comparing different treatment modalities according to the PRISMA guidelines. We extracted published hazard ratios and number of events for the endpoints overall and disease-free survival (OS; DFS) as well as local and distant recurrence-free interval (LRFI; DRFI). The different modalities were compared in a network meta-analysis against the defined standard treatment surgery ± radiotherapy using the inverse-variance heterogeneity model. Results: The literature search identified 25 trials including 3453 patients. Five different treatment modalities were compared in the network meta-analysis. The addition of adjuvant chemotherapy significantly improves OS compared to surgery ± radiotherapy alone (HR =0.86; CI-95%: 0.75-0.97; p=0.017). Likewise, neoadjuvant chemotherapy combined with regional hyperthermia (naCTx+HTx) also led to superior OS (HR =0.45; CI-95%: 0.20-1.00; p=0.049). Neoadjuvant chemotherapy alone (naCTx) and perioperative chemotherapy (periCTx) both did not improve OS (HR =0.61; CI-95%: 0.29-1.29; p=0.195) and (HR=0.66; CI-95%: 0.30-1.48; p=0.317), respectively. Histology-tailored chemotherapy (htCTx) also did not improve survival compared to surgery ± radiotherapy (HR =1.08; CI-95%: 0.45-2.61; p=0.868). The network analysis of DFS, LRFI and DRFI revealed a similar pattern between the different treatment regimens. Adjuvant chemotherapy significantly improved DFS, LRFI and DRFI compared to surgery ± radiotherapy The subgroup analysis of adjuvant chemotherapy was In direct comparison this advantage of adjuvant chemotherapy was restricted to male patients (HR=0.78; CI-95%: 0.65-0.92; p=0.004) with no effect for female patients (HR=1.08; CI-95%: 0.90-1.29; p=0.410). Conclusions: Standardized chemotherapy in high-risk soft tissue sarcoma appears to be of added value irrespective of timing. The benefit of adjuvant chemotherapy seems to be restricted to male patients. The addition of regional hyperthermia to neodjuvant chemotherapy achieved the best effect sizes and might warrant further investigation. Funding: None to declare. Declaration of Interest: None to declare.

PO-1416 Definitive photon radiation therapy for adult unresectable soft tissue sarcoma.

PO-1416 Definitive photon radiation therapy for adult unresectable soft tissue sarcoma.

Dedifferentiated Liposarcoma: A Comprehensive Historical Review With Proposed Evidence-based Guidelines Regarding a Diagnosis in Need of Further Clarification.

Among all sarcoma types, liposarcoma is the most common sarcoma that develops "dedifferentiation." Since its initial description by Dr Harry Evans, the spectrum of what is now acceptably included under the rubric of "dedifferentiated liposarcoma" (DL) has expanded, sometimes supported by cytogenetic and molecular advances. Similarly, the range of morphologic appearances considered to represent the precursor of DL, atypical lipomatous tumor (ALT)/well-differentiated liposarcoma, also has broadened, not uncommonly creating variants with significant, almost indistinguishable, morphologic overlap with occasional forms of DL, especially problematic in small biopsy specimens. More specifically, the precise criteria separating cellular forms of ALT from what some consider "low-grade" variants of DL remains controversial and inconsistently applied, even among individual pathologists within institutions. For this separation, the only objective and reproducible criteria historically shown to accurately predict a statistically significant difference in prognosis and survival is mitotic rate, alone or incorporated into a histologic grade [eg, Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC)], consistently identifying a higher grade neoplasm capable of metastases. While DL may have a better prognosis than other nonmyoid adult pleomorphic soft tissue sarcomas, definitive conclusions are difficult to establish due to nonuniform criteria for staging and establishing tumor size/volume of the high-grade component, compounded by variable definitions and thresholds for rendering the diagnosis of DL. If appropriate therapeutic approaches are to be applied to DL, there needs to uniform agreement regarding the histologic definition, grading, and staging of DL. Herein, is a comprehensive historical perspective on DL and ALT/well-differentiated liposarcoma, seeking to provide insights, updates, and a proposal for uniform, evidence-based guidelines.

Ki-67 immunoexpression and radiological assessment of necrosis improves accuracy of conventional and modified core biopsy systems in predicting the final grade assigned to adult-soft tissue sarcomas. An international collaborative study

Based on the French Federation Nationale des Centers de Lutte Contre le Cancer (FNCLCC) grading system, this study assesses the accuracy of conventional and modified core biopsy (CB) systems in predicting the final grade (low vs high) assigned to the resected specimen. Substituting Ki-67 immunoexpression for mitotic count, and radiological for histological assessment of necrosis, we used two modified FNCLCC CB grading systems: (1) Ki-67 immunoexpression alone, and (2) Ki-67 plus radiological assessment of necrosis. We graded 199 soft tissue sarcomas (STS) from nine centers, and compared the results for the conventional (obtained from local histopathology reports) and modified CB systems with the final FNCLCC grading of the corresponding resected specimens. Due to insufficient sample quality or lack of available radiologic data, five cases were not evaluated for Ki67 or radiological assessment of necrosis. The conventional FNCLCC CB grading system accurately identified 109 of the 130 high-grade cases (83.8%). The CB grading matched the final FNCLCC grading (low vs high) in 175 (87.9%) of the 199 resected tumors; overestimating the final grade in three cases and underestimating in 21 cases. Modified system 1 (Ki-67) accurately identified 117 of the 130 high-grade cases (90.0%). The CB grading matched the final FNCLCC grading (low vs high) in 175 (89.7%) of the 195 evaluated cases; overestimating seven and underestimating 13 cases. Modified system 2 (Ki-67 plus radiological necrosis) accurately identified 120 of the 130 high-grade cases (92.3%). This last matched the final FNCLCC grading (low vs high) in 177 (91.2%) of the 194 evaluated cases; overestimating seven and underestimating 10 cases. Modified system 2 obtained highest area under ROC curves, although not statistically significant. Underestimated CB grades did not correlate with histological subtypes, although many of the discrepant cases were myxoid tumors (myxofibrosarcomas or myxoid liposarcomas), leiomyosarcomas or undifferentiated pleomorphic/spindle cell sarcomas. Using modified FNCLCC CB grading systems to replace conventional mitotic count and histologic assessment of necrosis may improve the distinction between low and high-grade STS on CB. Our study confirms that classifying grade 1 as low grade and grades 2 and 3 as high grade improves correlation between CB and final grade by up to 21%, irrespective of CB system used. A higher than expected Ki-67 score in a low-grade sarcoma diagnosed on CB should raise concern that a higher-grade component may not have been sampled. Furthermore, correlation of all clinicopathological and radiological findings at multidisciplinary meetings is essential to assess the histological grade on CB as accurately as possible.

Abstract 2692: CXCR4 as a therapeutic target in angiosarcoma

Abstract Angiosarcomas account about 2-3% of adult soft tissue sarcomas. This is a rare form of malignancy with remarkable clinical heterogeneity in term of presentation and behavior and can occur in any location of the body. Although radiation and chemotherapy are the usual form of therapy, frequent recurrence and metastasis is observed. The prognosis of angiosarcoma is relatively poor, and the overall 5-year survival rate is approximately 35%. Previous studies have shown the SDF-1 (stromal derived factor-1)/CXCR4 pathway is involved in the progression and the metastasis of angiosarcoma. CXCR4 is a chemokine receptor involved in metastatic spread of malignant tumors and is upregulated by many factors, including hypoxia and the histone methyltransferase EZH2. CXCR4 in turn activates the JAK/STAT3 pathway, which regulates the immune environment by inducing an infiltrate of tumor associated macrophages (TAMs) of the M2 (immunosuppressive) phenotype. Sarcomas in general have increased TAMs of the M2 phenotype and accumulating evidence indicates that a high number of TAMs are associated with an unfavorable prognosis in a variety of malignancies including angiosarcoma. The monocyte chemokine CCL2 has already been documented previously in canine hemangiosarcoma as one of the primary chemoattractants for M2 macrophages. The SDF-1/CXCR4 pathway has also been documented in other malignancies as a regulator of M2 macrophage infiltration and the immunosuppressive environment. It has also been reported that blockade of CXCR4 selectively reduces M2-polarized macrophages. We studied the expression of EZH2, p-STAT3, CXCR4, and CD163 (M2 macrophage marker), in four known cases of angiosarcoma. Two cases involved right lower leg soft tissue and two cases involved tissues from aortic wall. In all of our four cases the tumor cells of angiosarcoma stained positive for EZH2, p-STAT3, CXCR4, and CD163. This supports our hypothesis that indeed in angiosarcoma the M2 macrophages has an association with CXCR4 and pSTAT3. Clinical implications of this are that plerixafor or other CXCR4 antagonists could be used to treat angiosarcoma. By blocking CXCR4, the progression and metastasis of angiosarcoma could be abrogated and the immunosuppressive environment can be normalized. Our study indicates that CXCR4 could be considered a therapeutic target in angiosarcoma and the CXCR4 antagonist plerixafor should be further investigated as a potential agent to improve patient outcomes. Citation Format: Anindita Ghosh, Robert E. Brown, Joan M. Bull, Shaimaa M. Elzamly, Jamie J. Buryanek. CXCR4 as a therapeutic target in angiosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2692.

CASE REPORT: MONOPHASIC SYNOVIAL SARCOMA OF THE MANDIBLE

<h3>Objective</h3> Synovial sarcomas (SSs) are high-grade soft tissue sarcomas that are associated with poor survival. SS originates from pluripotent mesenchymal cells and not synovial structures. SS accounts for 8% of adult soft tissue sarcomas and are considered rare in the head and neck region. We present a case of a monophasic synovial sarcoma of the left body of the mandible and outline how diagnoses can come with challenges. <h3>Material and Methods</h3> A 59-year-old male patient presented with a slow-growing mass of the left body of the mandible. Facial bone computed tomography was completed and an expansile osteolytic mass involving the left body of mandible body was reported. A magnetic resonance imaging scan was then carried out and the results mirrored that of the computed tomography scan. A positron emission tomography scan was completed, ruling out metastatic disease. The patient was managed with preoperative neoadjuvant chemotherapy. This was followed by resective surgery with 3-deimensional reconstruction and postoperative radiotherapy. <h3>Results</h3> SS is a mesenchymal malignancy that shows epithelial differentiation. Variants include monophasic, biphasic, and a poorly differentiated (round cell) forms. This case of a monophasic variant was histologically characterized by interdigitating fascicles composed of monocellular monomorphic spindle cells with hyperchromatic nuclei. Occasional mitotic figures were present. It was diffusely strongly positive for TLE1, highly specific for SS. Molecular genetic analysis showed a t(x;18) (SYT-SSX1, SYT-SSX2, SYT-SSX4) fusion transcript present, confirming SS. <h3>Conclusions</h3> The differential diagnosis for a monophasic synovial sarcoma can be challenging. It includes malignant peripheral nerve sheath tumor (MPNST), solitary fibrous tumor (SFT), clear cell sarcoma, spindle cell rhabdomyosaroma, and fibrosarcoma.

The Evolving Role of Radiation Therapy in Adult Soft Tissue Sarcoma

The Evolving Role of Radiation Therapy in Adult Soft Tissue Sarcoma

Well-Differentiated Liposarcoma of the Hypopharynx Exhibiting Myxoid Liposarcoma-like Morphology with MDM2 and DDIT3 Co-Amplification

Well-differentiated liposarcoma (WDL) is one of the most common soft tissue sarcomas in adults. It has a predilection for middle-aged males and arises in deep-seated locations such as retroperitoneum, mediastinum, and spermatic cord. Its occurrence in young individuals at the hypopharyngeal region is an exceedingly rare event. Myxoid liposarcoma (ML)-like changes can seldom occur in some cases of WDL, which makes the diagnosis of WDL more challenging. Amplification of DDIT3 gene in a subset of cases of WDL has shown to be associated with such unique morphology. Herein, we present a case of a 36-year-old gentleman who presented with difficulty in breathing and swallowing for 3 months duration. CT scan of the neck revealed a lesion along the posterior wall of the hypopharynx measuring 3.5 cm. Histopathologic examination revealed a tumor composed of lobules of oval to spindle cells in a prominent myxoid stroma with delicate chicken-wire vasculature. In the vicinity, there were lobules composed of variably sized adipocytes separated by thick fibrous septa that contains atypical hyperchromatic spindle cells. By immunohistochemistry, the tumor cells in both components were immunoreactive for CDK4, but negative for MDM2. Fluorescence in-situ hybridization (FISH) confirmed the presence of MDM2 gene amplification. There was no evidence of FUS-DDIT3 gene rearrangement, however, DDIT3 gene was also amplified. The diagnosis of well-differentiated liposarcoma with prominent myxoid stroma was rendered. This is the first documentation of WDL with ML-like morphology harboring co-amplification of MDM2 and DDIT3 in the hypopharynx.