Histology-Tailored Approach to Soft Tissue Sarcoma.

Soft tissue sarcomas are a diverse and heterogeneous group of cancers of mesenchymal origin. Each histological type of soft tissue sarcoma has unique clinical particularities, which makes them challenging to diagnose and treat. Multidisciplinary management of these rare diseases is thus key for improved survival. The role of surgery has been well established, and it represents the cornerstone curative treatment for soft tissue sarcomas. To date, local recurrence is the leading cause of death in low-grade sarcomas located at critical sites, and distant metastasis in high-grade sarcomas, regardless of the site of origin. Management must be tailored to each individual histologic type. We describe the most common types of extremity, trunk, abdominal, and retroperitoneal soft tissue sarcoma along with characteristics to consider for optimized management.

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.

A Giant, Neglected Leiomyosarcoma on the Left Shoulder.

This paper examines the impact of delayed diagnosis and treatment on the prognosis of patients with leiomyosarcomas (LMS). We present a case study highlighting the consequences of neglected LMS, focusing on vascular involvement and metastatic potential. Our findings underscore the importance of early detection and intervention in improving patient outcomes. Additionally, we discuss the challenges associated with diagnosing rare skin LMS and the implications of limited access to medical screening. Through a comprehensive analysis of the literature, we elucidate the critical role of routine surveillance in detecting these malignancies at an earlier stage, thus facilitating timely intervention and potentially curative treatment. This study underscores the urgency of raising awareness among both healthcare providers and the general population about the significance of early detection and prompt management in mitigating the adverse outcomes associated with neglected LMS.

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.

Scrutinizing the use of contrasted chest CTs in extremity sarcoma staging and surveillance.

BACKGROUND: Since 2015, the American College of Radiology (ACR) has recommended staging for lung metastasis via chest computed tomography (CT) without contrast for extremity sarcoma staging and surveillance. The purpose of this study was to determine our institutional compliance with this recommendation. METHODS: This was a retrospective chart review of patients diagnosed with sarcoma in the extremities who received CT imaging of the chest for pulmonary staging and surveillance at our institution from 2005 to 2023. A total of 1916 CT studies were included for analysis. We scrutinized ordering patterns before and after 2015 based on the ACR-published metastasis staging and screening guidelines. An institutional and patient cost analysis was performed between CT modalities. RESULTS: The prevalence of CT scans ordered and performed with contrast was greater than those without contrast both prior and post-ACR 2015 guidelines. Furthermore, 79.2% of patient's final surveillance CTs after 2015 were performed with contrast. A cost analysis was performed and demonstrated an additional $297 704 in patient and institutional costs. CONCLUSIONS: At our institution, upon review of CT chest imaging for pulmonary staging and surveillance in patients with extremity sarcoma the use of contrast has been routinely utilized despite a lack of evidence for its necessity and contrary to ACR guidelines.

Uncovering the gaps: A systematic mixed studies review of quality of life measures in extremity soft tissue sarcoma.

The health-related quality of life of patients with extremity soft tissue sarcoma (STS) is not precisely captured by current patient-reported outcome measures. Although functional impairment is central to their concerns, multiple sources of distress, emotional restoration, coping strategies, and somatic symptoms are crucial in approaching patients with extremity STS.

Dosimetric comparison between proton beam therapy, intensity modulated radiation therapy, and 3D conformal therapy for soft tissue extremity sarcoma.

PURPOSE/OBJECTIVES: Proton beam therapy (PBT) may provide a dosimetric advantage in sparing soft tissue and bone for selected patients with extremity soft sarcoma (eSTS). We compared PBT with photons plans generated using intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT). MATERIALS/METHODS: Seventeen patients previously treated with pencil beam scanning PBT were included in this study. Of these patients, 14 treated with pre-operative 50 Gy in 25 fractions were analyzed. IMRT and 3D-CRT plans were created to compare against the original PBT plans. Dose-volume histogram (DVH) indices were evaluated amongst PBT, IMRT, and 3D plans. Kruskal-Wallis rank sum tests were used to get the statistical significance. A p value smaller than .05 was considered to be statistically significant. RESULTS: For the clinical target volume (CTV), D2%, D95%, D98%, Dmin, Dmax, and V50Gy, were assessed. Dmin, D1%, Dmax, Dmean, V1Gy, V5Gy, and V50Gy were evaluated for the adjacent soft tissue. D1%, Dmax, Dmean, and V35-50% were evaluated for bone. All plans met CTV target coverage. The PBT plans delivered less dose to soft tissue and bone. The mean dose to the soft tissue was 2 Gy, 11 Gy, and 13 Gy for PBT, IMRT, and 3D, respectively (p < .001). The mean dose to adjacent bone was 15 Gy, 26 Gy, and 28 Gy for PBT, IMRT, and 3D, respectively (p = .022). CONCLUSION: PBT plans for selected patients with eSTS demonstrated improved sparing of circumferential soft tissue and adjacent bone compared to IMRT and 3D-CRT. Further evaluation will determine if this improved dosimetry correlates with reduced toxicity and improved quality of life.

Incidence and Risk Factors for Extremity Osteoradionecrosis after Limb-Sparing Surgery and Adjuvant Radiotherapy.

Osteoradionecrosis (ORN) is a major complication after radiotherapy. Most studies on ORN have focused on patients with mandibular lesions, with few studies including patients with extremity soft tissue sarcoma (STS). We included 198 patients with extremity STS who underwent limb-sparing surgery and adjuvant radiotherapy between 2004 and 2017. The incidence rate of extremity ORN was 3.5% (7/198), with most lesions (6/7) located in the lower extremities. The mean follow-up time was 62 months. Clinical presentations included chronic ulcers, soft tissue necrosis, sinus discharge, bone nonunion, and pathological fractures. Compared with the non-ORN group, the ORN group had a significantly higher total radiation dose (68 Gy vs. 64 Gy, p = 0.048) and greater use of intraoperative periosteal stripping (p = 0.008). Repeat surgeries and subsequent soft tissue reconstruction or limb amputation were performed as treatments. The risk and management of ORN in patients with extremity STS was ignored previously. Because the disease is complex and affects both clinicians and patients, careful surveillance should be undertaken.

Evidence for the Current Management of Soft-tissue Sarcoma and Gastrointestinal Stromal Tumors and Emerging Directions.

Soft-tissue sarcoma (STS) is not a single entity but, rather, a family of diseases with differing biologic behaviors and anatomic site- and histotype-specific responses to treatment. Whereas surgery remains the mainstay of treatment of primary, localized disease, evolving evidence is establishing the role of multimodality treatment of these tumors. This article summarizes prospective evidence to date informing our treatment of STS. Key future directions will include advancing our understanding of fundamental tumor biology and mechanisms of response and recurrence, as well as defining the optimal provision of regional, systemic, and targeted therapies, including the role of immunotherapy. Ongoing global collaborations will be integral to progress in treating these rare tumors.

Surgical phocomelia or phoco-reduction as a method of limb salvage for sarcomas of the upper limb: A suitable alternative to amputation.

BACKGROUND: Reconstruction following resection of sarcomas of the upper extremity with methods described in the prevalent literature may not be possible in few selected cases. We describe surgical phocomelia or phoco-reduction as a method of limb salvage in such cases of extensive sarcomas of the upper limb with its functional and oncological outcomes. METHODS: Evaluation of functional and oncological outcomes was performed for 11 patients who underwent surgical phocomelia or phoco-reduction for extensive sarcomas of the upper limb between 2010 and 2019. RESULTS: The mean follow-up period in the study was 27.8 months. Five patients required a segmental resection including the entire humerus while six patients underwent segmental resection around the elbow with a mean resection length of 21.5 cm. Mean Musculoskeletal Tumor Society 93 score was 22 depicting a good functional outcome. Mean handgrip strength on the operated side was 62% of the contralateral side with preservation of useful hand function. Meantime to humeroulnar union was 6.7 months. Radial nerve palsy and implant failure occurred in one patient each. No patient developed local recurrence while three patients died of metastasis. CONCLUSION: Surgical phocomelia is a prudent alternative to severely incapacitating amputations in situations where other reconstruction methods are not feasible.

The evolution of adjuvant/neoadjuvant trials for resectable localized sarcoma.

Soft-tissue sarcomas are rare tumors arising from mesenchymal tissues. As a heterogeneous group comprising more than 50 types, the development of clinical trials remains challenging. Decision-making for neoadjuvant or adjuvant chemotherapy and radiation therapy is based on the available evidence of contemporary trials and multidisciplinary clinical judgment.

Femoral Fracture in Primary Soft Tissue Sarcoma Treated with Intensity-Modulated Radiation Therapy with and Without Dose Constraints.

BACKGROUND: We previously reported that the cumulative risk of femoral fracture in patients treated with intensity-modulated radiation therapy (IMRT) for thigh and groin soft tissue sarcoma (STS) is low. In the current study, we sought to evaluate the effect of radiation dose constraints on the rate of femoral fracture in a more contemporary cohort. METHODS: All patients treated with IMRT for STS of the thigh or groin from 2004 to 2016 were included (n = 145). Beginning in 2011, radiation dose was constrained to a mean dose of < 37 Gy, volume of bone receiving ≥ 40 Gy (V40Gy) < 64%, and maximum dose < 59 Gy to limit the dose to the femur. RESULTS: Sixty-one patients were treated before dose constraints were implemented, and 84 patients were treated after. Median follow-up for patients treated before and after constraints were implemented was 6.1 and 5.7 years, respectively, and the two groups were demographically and clinically similar. On univariate analysis, the 5-year cumulative incidence of femoral fracture among patients treated with and without dose constraints was 1.8% (95% confidence interval [CI] 0.3-12.2%) versus 7.4% (95% CI 3.1-17.6%) [p = 0.11, p = non-significant, respectively]. On multivariable analysis, only age ≥ 60 years was significantly associated with increased risk of fracture. CONCLUSIONS: The risk of femoral fracture after IMRT for STS of the thigh/groin is low, and with the implementation of radiation dose constraints, the risk is < 2%. Although longer follow-up is needed, our results support the utilization of extremity sarcoma IMRT-specific dose constraints for fracture prevention.

A closer look at the natural history and recurrence patterns of high-grade truncal/extremity leiomyosarcomas: A multi-institutional analysis from the US Sarcoma Collaborative.

BACKGROUND/OBJECTIVE: Natural history and outcomes for truncal/extremity (TE) soft tissue sarcoma (STS) is derived primarily from studies investigating all histiotypes as one homogenous cohort. We aimed to define the recurrence rate (RR), recurrence patterns, and response to radiation of TE leiomyosarcomas (LMS). METHODS: Patients from the US Sarcoma Collaborative database with primary, high-grade TE STS were identified. Patients were grouped into LMS or other histology (non-LMS). Primary endpoints were locoregional recurrence-free survival (LR-RFS), distant-RFS (D-RFS), and disease specific survival (DSS). RESULTS: Of 1215 patients, 93 had LMS and 1122 non-LMS. In LMS patients, median age was 63 and median tumor size was 6 cm. In non-LMS patients, median age was 58 and median tumor size was 8 cm. In LMS patients, overall RR was 42% with 15% LR-RR and 29% D-RR. The 3yr LR-RFS, D-RFS, and DSS were 84%, 65%, and 76%, respectively. When considering high-risk (>5 cm and high-grade, n = 49) LMS patients, the overall RR was 45% with 12% LR-RR and 35% D-RR. 61% received radiation. The 3yr LR-RFS (78vs93%, p = 0.39), D-RFS (53vs63%, p = 0.27), and DSS (67vs91%, p = 0.17) were similar in those who did and did not receive radiation. High-risk, non-LMS patients had a similar overall RR of 42% with 15% LR-RR and 30% D-RR. 60% of non-LMS patients received radiation. There was an improved 3yr LR-RFS (82vs75%, p = 0.030) and DSS (77vs65%,p = 0.007) in non-LMS patients who received radiation. CONCLUSIONS: In our cohort, patients with LMS have a low local recurrence rate (12-15%) and modest distant recurrence rate (29-35%). However, LMS patients had no improvement in local control or long-term outcomes with radiation. The value of radiation in these patients merits further investigation.

Soft-tissue sarcoma in adults: An update on the current state of histiotype-specific management in an era of personalized medicine.

Soft-tissue sarcomas (STS) are rare tumors that account for 1% of all adult malignancies, with over 100 different histologic subtypes occurring predominately in the trunk, extremity, and retroperitoneum. This low incidence is further complicated by their variable presentation, behavior, and long-term outcomes, which emphasize the importance of centralized care in specialized centers with a multidisciplinary team approach. In the last decade, there has been an effort to improve the quality of care for patients with STS based on anatomic site and histology, and multiple ongoing clinical trials are focusing on tailoring therapy to histologic subtype. This report summarizes the latest evidence guiding the histiotype-specific management of extremity/truncal and retroperitoneal STS with regard to surgery, radiation, and chemotherapy.

Malignant Soft-Tissue Sarcomas.

Soft-tissue sarcomas are cancerous growths of mesenchymal tissues, most commonly arising from fat, muscles, and other connective tissues. Sarcomas are rare, representing only a small fraction of solid malignant tumors. Because of their scarcity and a relative paucity of data, the management of sarcomas can be challenging, especially for those who infrequently encounter these tumors. Herein, the authors review the current literature regarding the diagnosis, workup, and treatment of adult soft-tissue sarcomas.

Does intramedullary nailing improve the union rate or decrease mechanical complications for patients with extremity sarcoma after biological reconstruction?

INTRODUCTION: This is a retrospective study that evaluate the outcome of patients with extremity sarcoma between extramedullary plate and intramedullary nailing for the biological reconstruction after tumor resection. METHODS: 58 patients (40 treated with plate fixation and 18 with intramedullary nailing, IM group) with sarcomas of the lower and upper extremity who received biological reconstruction at our bone tumor center from November 2003 to November 2015 were reviewed for the study. There were 29 male and 29 female patients with a mean age of 20.8 years (range, 5-72 years). The mean follow-up duration was 90.8 months (range, 12.2-244.4 months). All data were obtained from the clinical, radiograph records and follow-up information. The analysis of outcome, survival, local recurrence, function and complications of patients in the plate group and IM group was performed. RESULTS: 28 cases in the plate group lived at the last follow-up, of which 26 had no evidence of disease, 2 lived with the pulmonary metastasis, whereas 15 in the IM group lived at the last follow-up, of which all had no evidence of disease and no lived with the pulmonary metastasis. There was no significant difference between the two groups for the prognosis. Meanwhile, there was no significant difference of incidence of nonunion, graft fracture and fixation breakage between the two groups, whereas the time to diaphysis union in the plate group (11.6 ± 2.7 months) was shorter than that in IM group (14.7 ± 4.8 months, P = 0.015). It had the tendency that the time to mechanical complications in the intramedullary nailing group (38.1 ± 39.6 months) was longer than that in the plate group (15.7 ± 13.4 months, P = 0.058,95% CI,-45.6-0.8). Furthermore, the infection occurred in 12 cases and five grafts of them developed the deep infection and the mean time to deep infection was 14.8 ± 20.5 months. Furthermore, the incidence of local recurrence for the patients who had plate fixation was similar to the incidence of patients who had nailing fixation. At the last follow-up, the functional evaluation was performed for 39 patients. There was no significant difference in MSTS and VAS functional score for patients between in the plate group (n = 32) and IM group (n = 7). CONCLUSIONS: The findings of the present study showed that intramedullary nailing does not improve the union rate or decrease the incidence of mechanical complications for patients with extremity sarcoma after biological reconstruction. However, intramedullary nailing may have potential advantages on the service life for the biological reconstruction after extremity sarcoma resection.

Analysis of the immune infiltrate in undifferentiated pleomorphic sarcoma of the extremity and trunk in response to radiotherapy: Rationale for combination neoadjuvant immune checkpoint inhibition and radiotherapy.

Background: Undifferentiated pleomorphic sarcoma of the extremity and trunk (ET-UPS) presents a unique therapeutic challenge. Although immunotherapy has recently been employed in advanced soft tissue sarcoma, there is limited data characterizing the immune infiltrate in ET-UPS. Radiotherapy (RT) has been shown in other tumor types to promote tumor antigen release and enhance tumor-specific targeting by the adaptive immune system. The aim of this study was to 1) characterize the baseline immune infiltrate and 2) evaluate the effect of preoperative RT on the histologic appearance of and the immune infiltrate in ET-UPS. Methods: We identified 17 matched ET-UPS samples before and after RT. Immunohistochemistry was performed with CD8, CD4, PD-L1, PD1, CD3, CD163 and FoxP3 positive cells identified in all samples. Changes in the immune infiltrate following RT were examined. Results: There was a trend towards increased density of tumor infiltrating immune cells in ET-UPS following RT, with increases in median number of CD3 (158 vs 219 cells/mm2, p = 0.06), CD4 (3 vs 13 cells/mm2, p = 0.01), CD8 (55 vs 111 cells/mm2, p = 0.17), and FOXP3 (14 vs 25 cells/mm2, p = 0.23) positive cells. Interestingly, although PD-L1 was not expressed in any ET-UPS tumor at baseline, positive PD-L1 expression was observed in 21% (3/14) of tumors after RT (p = 0.07). Conclusion: An immune infiltrate is present in ET-UPS at the time of diagnosis, with a trend towards increased density of immune infiltrate and PD-L1 expression after RT. These data support prospectively evaluating immune checkpoint inhibitors with standard of care RT in the treatment of ET-UPS.

Defining the incidence and clinical significance of lymph node metastasis in soft tissue sarcoma.

INTRODUCTION: The incidence and clinical significance of lymph node metastasis (LNM, N1) in soft tissue sarcoma (STS) is unclear. Recent studies have focused on extremity/trunk STS (ETSTS). We sought to define the subgroup of patients with LNM at sarcoma diagnosis across all disease sites and histologies. METHODS: We identified and categorized 89,870 STS patients from the National Cancer Data Base (1998-2012) by nodal stage. Pathologically confirmed LNM (pN1) were identified in 1404 patients; 1750 had clinically suspicious but not pathologically confirmed LNM (cN1). Survival analyses were performed by Kaplan-Meier method. RESULTS: Of 3154 patients (3.5%) with pN1 or cN1 LNM at presentation, 1310 had synchronous distant metastasis (M1). LNM affected a small proportion of patients (5.8% head/neck, 5.3% intrathoracic, 5.1% intra-abdominal, 2.0% ETSTS). Angiosarcoma (6%), epithelioid (13%), clear cell (16%), and small cell sarcoma (19%) had the highest incidence of LNM, although liposarcoma, fibrous histiocytoma, and leiomyosarcoma accounted for the greatest number of LNM patients. For pN1M0 disease, median overall survival (OS) was 28.2 months, varying by histology. Among patients with pN1M0 STS, angiosarcoma, clear cell sarcoma, leiomyosarcoma, and fibrous histiocytoma were associated with worse median OS (19.4, 23.8, 27.1, and 29.3 months) compared to epithelioid sarcoma and liposarcoma (49.6 and 56.0 months, p < 0.001). CONCLUSION: Despite clinical suspicion, pathologic LN evaluation in STS is inconsistently performed. LNM occurs across anatomic disease sites and is unevenly distributed across histologies. Although M1 disease portends poor prognosis regardless of LN status, LNM predicts worse OS in a histology-dependent manner in M0 disease.

The impact of racial/ethnic disparities on survival for children and adolescents with extremity sarcomas: A population-based study.

PURPOSE: The purpose of this study was to determine whether racial/ethnic disparities exist in disease presentation, treatment, and survival among children and adolescents with extremity sarcoma. METHODS: The Surveillance, Epidemiology, and End Results (SEER) data were analyzed for patients <20years old with soft-tissue extremity sarcomas from 1973 to 2013. Multivariate logistic regression was performed to determine the association between race/ethnicity and disease stage at presentation and likelihood of surgical resection. Overall survival (OS) was evaluated using hazard ratios with 95% confidence intervals. RESULTS: 1261 cases were identified: 650 (52%) non-Hispanic whites (NHW), 313 (25%) Hispanics, 182 (14%) non-Hispanic blacks (NHB), and 116 (9%) other race/ethnicity. Logistic regression results showed that Hispanics and NHB were 51% and 44%, respectively, less likely to undergo surgical resection compared to NHW (OR=0.49, 95% CI: 0.30-0.80; OR=0.56, 95% CI: 0.32-0.98, respectively). Factors associated with failure to undergo surgical resection included histology, lower extremity site, tumor size, and distant metastases. OS based on race/ethnicity significantly differed using the log-rank test, with NHB having the worst survival (p<0.05). CONCLUSIONS: We conclude that NHB, Hispanics, and other race/ethnicity were less likely to undergo surgical resection for extremity sarcoma. Further work is needed to better characterize and eliminate disparities in the management and outcomes of children with extremity sarcomas. TYPE OF STUDY: Prognosis study. LEVEL OF EVIDENCE: IV.

Randomized Controlled Trials in Soft Tissue Sarcoma: We Are Getting There!

Soft tissue sarcoma (STS) is a family of malignancies for which individual management decisions can be complex. There is a paucity of level 1 evidence, as the rarity and heterogeneity of STS pose challenges to the design and execution of randomized controlled trials. Radiotherapy (RT) is routinely used to facilitate function-preserving surgery and to improve local control. Delivery of RT in the preoperative setting can decrease chronic toxicities at the cost of increased wound complications in the short-term. The role of adjuvant systemic therapies remains controversial in adult STS.