Outcome Of Soft Tissue Sarcomas Research Articles

Therapy adherence after interdisciplinary tumour board discussion is associated with improved outcome in soft tissue sarcoma: A Charité Comprehensive Cancer Centre analysis.

Centralising soft tissue sarcoma (STS) treatment in expert centres and implementing comprehensive therapy concepts through interdisciplinary tumour boards (ITB) has led to significant treatment progress. However, our knowledge on the implementation of the ITB recommendations and its impact on patient outcome is limited. In this retrospective analysis, we examined a cohort of 222 adult patients (pts) with primary STS who were presented to the ITB of the Charité Comprehensive Cancer Centre between 2015 and 2020. In localised disease (n = 188), resection was recommended in 71% (n = 134) of pts. The treatment modalities chemotherapy with or without regional deep hyperthermia, and radiotherapy were recommended in 37% (n = 69), 26% (n = 48) and 52% (n = 97), respectively. Complex multidisciplinary concepts were established in 29% (n = 54) including ≥3 treatment modalities. Only partial adherence, either by choice of patient or treating physician, was associated with a higher risk of both progression (HR 4.0 95%-CI 1.6-9.7 p < .01) and mortality (HR 5.3 95%-CI 1.7-16.4 p < .01). Pts inable to follow the ITB recommendations due to complications or rapid progression showed a high-risk profile with increased mortality and progression rates (HR 18.1 95%-CI 8.5-38.2 p < .001; HR 21.5 95%-CI 8.5-54.7 p < .001). To our knowledge, this represents the first German Comprehensive Cancer Centre analysis of therapy adherence in STS. It provides further real-world evidence that full adherence to ITB recommendations and the ability to adhere to them are of prognostic value for patient outcome and underlines the importance of interdisciplinary decision-making and treatment planning for STS patients.

A study of pre- and post-treatment hematologic markers of immune response in patients undergoing radiotherapy for soft tissue sarcoma.

This study investigates the impact of pre- and post-treatment hematologic markers, specifically neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), on treatment outcomes in soft tissue sarcoma (STS) patients undergoing radiation therapy (RT). Data from 64 patients who underwent RT for curative management of STS were reviewed. Pre-RT and post-RT hematologic measures were evaluated for associations with survival outcomes. A normal tissue complication probability (NTCP) curve for predicting ΔPLR ≥ 75 was modeled using a probit function. Elevated baseline NLR was associated with worse overall survival (OS) and disease-free survival (DFS), while elevated PLR was associated with worse DFS. Post-RT, elevated PLR was linked to worse OS and DFS. Increasing PLR change post-RT was associated with worse OS and DFS. Receiver operating characteristics analysis determined ΔPLR ≥ 75 to be a robust cutoff associated with worse DFS. Bone V10Gy ≥362 cc corresponded to a 50% risk of developing ΔPLR ≥ 75. These results suggest that hematologic markers could serve as prognostic biomarkers in both pre- and post-treatment settings for STS patients undergoing RT. Future studies can consider using bone V10Gy < 362 cc as a potential cutoff to reduce the risk of increased PLR after RT.

Predicting radiotherapy response, Toxicities and quality-of-life related functional outcomes in soft tissue sarcoma of the extremities (PredicT) using dose–volume constraints development: a study protocol

IntroductionRadiotherapy improves local tumour control in patients with soft tissue sarcoma of the extremities (STSE) but it also increases the probability of long-term toxicities such as tissue fibrosis, joint stiffness...

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

BackgroundThe 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.MethodsMedical 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.ResultsA 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.ConclusionsR1 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.

Epidemiology and Outcomes of Soft Tissue Sarcomas: Insights from a Decade of Head and Neck Surgery at Sótero del Río Hospital, Santiago, Chile

Soft tissue sarcomas (STS) are rare malignant tumors of mesenchymal origin. They are associated with genetic and environmental risk factors. Their clinical manifestations are nonspecific, requiring a high level of suspicion. The first-line treatment is surgical. Positive margins are the only independent predictor of local recurrence and worse survival rates. Strict follow-up is recommended due to its high recurrence rate. Analyze the casuistry of STS treated with curative intent by the head and neck surgery team at the Sótero del Río Hospital (HSR) at Santiago, Chile between 2013 and 2023. A retrospective, descriptive study of patients with STS managed by the HSR head and neck surgery team. Clinical presentation, diagnostic and therapeutic tools, and oncological results are analyzed. 26 patients were included, 84.6% female, with an average age of 61.7 years. Only 30.8% presented identifiable risk factors. The most common histology was undifferentiated pleomorphic sarcoma (26.9%), and the predominant location was extremities (46.2%). 77.8% of head and neck sarcomas and 58.8% of trunk and extremity sarcomas occurred in advanced stages. Disease-free survival was 66.6%; 68.2% in patients with negative surgical margins, and 60.0% in positive margins at five years. STS is an infrequent pathology. This study corresponds to the first retrospective research on STS in Chile. We require establishing a specialized multidisciplinary team to optimize the management and follow-up of STS patients.

Clinical outcomes of soft tissue sarcoma in the Philippines: A single-center experience.

160 Background: Soft-tissue sarcomas (STS) are a heterogeneous group of uncommon tumors that account for less than 1 percent of all adult malignant tumors. Data are scarce in the Asia-Pacific region, especially in the Philippines. This study aims to evaluate the epidemiology and clinical outcomes of STS from a private tertiary hospital in the Philippines. Methods: All adult patients treated at St. Luke’s Medical Center (SLMC), Quezon City and Global City, between January 2010 and December 2020 were reviewed. Continuous variables are described in median and categorical variables are described in count and percentage. Kaplan-Meier curves for OS and RFS were compared by the Log-Rank test. Results: One hundred eighty-seven patients diagnosed with STS were eligible for the study. The median age at diagnosis was 53 years old; the majority were male (54.55%). The most common histologic subtypes were liposarcoma (19.79%), pleomorphic sarcoma, undiff (16.58%), and leiomyosarcoma (11.76%). Most were diagnosed with localized disease (90.9%), with the lower extremities (44.39%) as the most common primary site. The median tumor size was 10.3 cm, primarily high grade (46.52%). Nodal involvement on diagnosis was 4.28%. Twelve patients (6.42%) presented with de novo mets; lung (45%) was the most common site. The majority had surgery (81.82%) on the primary tumor, with 56.86% achieving R0. Eighty patients (42.78%) had radiotherapy; the majority were given post-operatively (N=60). Sixty-three patients (33.68%) received systemic therapy. Out of 170 patients with localized disease, 70 (40%) had disease recurrence, mostly local recurrence (57.14%). The 3-year OS and RFS were 58.67% and 55.20%, respectively, for the entire cohort; for localized disease was 95.06%. There was a statistical difference in OS between distant vs local recurrence (23.28% vs 49.11%) (p&lt;0.001), nodal involvement (p=0.041), surgery (p&lt;0.001), and radiotherapy (p=0.001). Conclusions: Most STS seen in SLMC is localized disease but with lower rates of resection than in other countries in the Asia-Pacific region. The histological subtype and primary anatomical site are similar to other data. The low survival rate may be attributed to the site of recurrence, nodal involvement, and treatment pattern received.

Clinical outcomes of soft tissue sarcoma in the Philippines: A single-center experience.

e23549 Background: Soft-tissue sarcomas (STS) are a heterogeneous group of uncommon tumors that account for less than 1 percent of all adult malignant tumors. Data are scarce in the Asia-Pacific region, especially in the Philippines. This study aims to evaluate the epidemiology and clinical outcomes of STS from a private tertiary hospital in the Philippines. Methods: All adult patients treated at St. Luke’s Medical Center (SLMC), Quezon City and Global City, between January 2010 and December 2020 were reviewed. Continuous variables are described in median and categorical variables are described in count and percentage. Kaplan-Meier curves for overall survival (OS) and recurrence-free survival (RFS) were compared by the Log-Rank test. Results: One hundred eighty-seven patients diagnosed with STS were eligible for the study. The median age at diagnosis was 53 years old; the majority were male (54.55%). The most common histologic subtypes were liposarcoma (19.79%), pleomorphic sarcoma, undifferentiated (16.58%), and leiomyosarcoma (11.76%). Most were diagnosed with localized disease (90.9%), with the lower extremities (44.39%) as the most common primary site. The median tumor size was 10.3 cm, primarily high grade (46.52%). Nodal involvement on diagnosis was 4.28%. Twelve patients (6.42%) presented with de novo metastasis; lung (45%) was the most common site. The majority had surgery (81.82%) on the primary tumor, with 56.86% achieving R0. Eighty patients (42.78%) had radiotherapy; the majority were given post-operatively (N = 60). Sixty-three patients (33.68%) received systemic therapy. Out of 170 patients with localized disease, 70 (40%) had disease recurrence, mostly local recurrence (57.14%). The 3-year OS and RFS were 58.67% and 55.20%, respectively, for the entire cohort; for localized disease was 95.06%. There was a statistical difference in OS between distant vs local recurrence (23.28% vs 49.11%)(p &lt; 0.001), nodal involvement (p = 0.041), surgery (p &lt; 0.001), and radiotherapy (p = 0.001). Conclusions: Most STS seen and diagnosed in SLMC is mostly localized disease but with lower rates of resection than in other countries in the Asia-Pacific region. The clinicopathologic features, treatment modalities received, histological subtype, and primary anatomical site are similar to other data. The low survival rate may be attributed to the site of recurrence, nodal involvement, and treatment pattern received.

Elevated preoperative serum interleukin-6 level is predictive for worse postoperative outcome after soft tissue sarcoma surgery

BackgroundThe pro-inflammatory cytokine interleukin-6 (IL-6) plays a role in cancer development and progression, but research into the predictive value of IL-6 on postoperative outcome in soft tissue sarcoma (STS) is scarce. The purpose of this study is to investigate the predictive value of serum IL-6 level for the achievement of assumed (post)operative outcome after STS surgery, the so-called textbook outcome. MethodsPreoperative IL-6 serum levels were collected in all patients with a STS at first presentation between February 2020 and November 2021. Textbook outcome was defined as a R0 resection, no complications, no blood transfusions, no reoperation within the postoperative period, no prolonged hospital stay, no hospital readmission within 90-days, and no mortality within 90-days. Factors associated with textbook outcome were determined by multivariable analysis. ResultsAmong 118 patients with primary, non-metastatic STS, 35.6% achieved a textbook outcome. Univariate analysis showed that smaller tumor size (p = 0.026), lower tumor grade (p = 0.006), normal hemoglobin (Hb, p = 0.044), normal white blood cell (WBC) count (p = 0.018), normal C-reactive protein (CRP) serum level (p = 0.002) and normal IL-6 serum level (p = 1.5 × 10−5) were associated with achieving textbook outcome after surgery. Multivariable analysis showed that elevated IL-6 serum level (p = 0.012) was significantly associated with not achieving a textbook outcome. ConclusionsIncreased IL-6 serum level is predictive for not achieving a textbook outcome after surgery for primary, non-metastatic STS.

Clinical Outcomes of Soft Tissue Sarcoma around the Elbow Joint: A Retrospective Single Institution Study.

We report a retrospective case series analysis of clinical outcomes of patients with soft tissue sarcoma around the elbow. Twenty-two patients underwent surgical tumor excision between January 1999 and May 2017, with a mean follow-up of 85.2 months. Six tumors were localized in the upper arm, nine in the elbow, and seven in the forearm. Sixteen tumors were deep-seated, and six were superficially located. Fifteen patients underwent wide excision, including one amputation, and 18 achieved (81.8%) negative margins histologically. Two local recurrences and four distant metastases developed. The mean Musculoskeletal Tumor Society score was 92.0% (range, 33.3-100). The 5-year local recurrence-free survival rate, metastasis-free survival rate, and overall survival rate were 90.0%, 77.0%, and 79.7%, respectively. Local control and limb function can have favorable outcomes when the tumor excised has a histologically negative margin without sacrificing the major structure.

What's New in Musculoskeletal Tumor Surgery.

What's New in Musculoskeletal Tumor Surgery.

Soft tissue sarcoma: correlation of dynamic contrast-enhanced magnetic resonance imaging features with HIF-1α expression and patient outcomes.

BackgroundTo investigate the value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) features for predicting hypoxia-inducible factor 1-alpha (HIF-1α) expression and patient outcomes in soft tissue sarcoma (STS).MethodsWe enrolled 71 patients with STS who underwent 3.0 Tesla (3.0T) MRI, including conventional MRI and DCE-MRI sequencing. The location, maximum tumor diameter, envelope, T2-weighted tumor heterogeneity, peritumoral edema, peritumoral enhancement, necrosis, configuration, tail-like pattern, bone invasion, and vessel/nerve invasion and/or encasement of the STSs were determined using conventional MRI images. The DCE-MRI parameters, including the volume transfer constant (Ktrans), reflux rate (Kep), volume fraction of extravascular extracellular matrix (Ve), and time-signal intensity curve (TIC) type, of each lesion were independently analyzed by two observers. Independent samples t-test, chi-square test, and Mann-Whitney U-test were performed to evaluate the differences in the MRI features between the two groups. The relationships between the DCE-MRI parameters and HIF-1α expression were analyzed using Spearman’s correlation analysis. The Cox proportional hazards model and Kaplan-Meier method were used for survival analysis.ResultsOf the conventional MRI features, high heterogeneity, peritumoral enhancement, necrosis, and multilobulation of the T2-weighted tumor were prone to occur in the high-expression group. Of the DCE-MRI parameters, the high-expression group showed significantly higher Ktrans (0.311±0.091 vs. 0.210±0.058 min−1), and Kep values (0.896±0.656 vs. 0.444±0.300 min−1) than the low-expression group. No significant differences in TIC types and Ve values were observed between the low- and high-expression groups (P>0.05). There were positive correlations between Ktrans and Kep values with HIF-1α expression (r=0.705, P<0.001; r=0.123, P<0.001, respectively). Receiver operating characteristic (ROC) analysis indicated high specificity (93.9%) of the Ktrans value for predicting high expression of HIF-1α. The Kep value provided the best performance in diagnostic sensitivity (84.2%). Survival analyses revealed that more than 50% necrosis, multilobulation, and Ktrans values greater than 0.262 min−1 were strongly associated with a higher risk of death.ConclusionsConventional MRI features and DCE-MRI parameters were significantly helpful in determining HIF-1α expression levels and predicting the overall survival (OS) of patients with STS.

In vitro evidence that combination treatment with anti-PD-1 and anti-CD47 immunotherapy may not be efficient in human soft tissue sarcoma.

e23560 Background: Soft tissue sarcomas (STSs) are rare mesenchymal tumors. With more than 70 histological subtypes of STSs, studies defining robust biomarkers of therapeutic value are lacking. Even with the improvements in local control rates, metastases and death occur in 50% of patients that are diagnosed with high-risk STSs. Across nearly all sarcoma types, macrophages dominate the immune landscape of STSs. While immune checkpoint inhibitors (ICIs) represent the major immunotherapeutic approach in malignancies with a high load of T cells, the anti-CD47 anti-cancer therapy mostly promotes macrophage-mediated phagocytosis. The efficacy of both therapies is critically dependent on the composition of the tumor microenvironment. Methods: In our study, we evaluated the potential additive effects of combining the anti-PD-1 immunotherapy and anti-CD47 immunotherapy ex vivo. The proportions of tumor cells and tumor-infiltrating lymphocytes were characterized ex vivo from resected tumors of 73 patients who underwent surgery for STS. The expression of CD47 on tumor cells was analyzed by immunohistochemistry. Cell suspensions were obtained from freshly resected tumors and the proportions of CD45+, CD45-, CD3+, CD4+, and CD8+ cells were measured by flow cytometry. The effect of the anti-PD-1 blockade, anti-CD47 blockade, and the combinatorial application of anti-PD-1 and anti-CD47 therapies on the immune cell activation in vitro was investigated by culturing of cell suspensions at a concentration 0.3x106/ul in the presence/absence of therapeutic monoclonal antibody (Nivolumab 2 ug/ml; anti-CD47 clone MIAP410 20ug/ml) and evaluated by a cytokine Luminex assay (Milliplex® MAP Human Cytokine Bead Panel (Sigma Aldrich) for TNFα, IFNγ, and IL-2 cytokines analysis). Results: The addition of anti-PD1 to CD3/CD28 stimulation drastically increased the production of all cytokines analyzed. This increase in pro-inflammatory cytokine secretion was even more pronounced after adding an anti-CD47 monoclonal antibody to the cell culture. However, a combinatorial application of anti-PD-1 and anti-CD47 agents in vitro was found to limit rather than potentiate the immune activation in the TME of human STS. On an individual level, the most profound response to anti-PD-1 was observed in high-grade leiomyosarcoma and the most profound response to anti-CD47 therapy was observed in an undifferentiated pleiomorphic sarcoma. Conclusions: Our data suggest that combinatorial strategies based on ICIs and anti-CD47 blockade may not provide the desired outcome in STSs. Both therapies, anti-PD-1, and anti-CD47 alone, could however bear a therapeutic potential in selected tumors after close evaluation of the CD47 and PD-1 expression status, as well as the extent of T cell/macrophage infiltration.

Characteristics and outcomes of soft tissue sarcoma in Saudi Arabia.

e23544 Background: Soft tissue sarcomas (STS) are a rare heterogeneous group of neoplasms that count for less than one percent of all solid cancers in adults. There is limited data from Saudi Arabia (SA). We aimed to describe the disease characteristics and clinical outcome of STS from a specialized referral center in STS management in SA. Methods: All adult patients treated at King Faisal Specialist Hospital and Research Center between January 2010 and December 2019 were reviewed. Continuous variables are described in median and interquartile range, and categorical variables are described in frequency and compared by the Chi-square test. Survival analysis was estimated by the Kaplan-Meier method and compared by the Log-Rank test. Results: Two hundred fourteen patients diagnosed with soft tissue sarcoma were eligible for the study. The median age at diagnosis was 38 years old (IQR: 26-50.5), and males were (56.1%). The most common histology subtypes were synovial sarcoma (19.6%), liposarcoma (13.5%), undifferentiated pleomorphic sarcoma (11.6%), leiomyosarcoma (9.8%). The most common presentation was painless swelling (49.1%), and the median duration of symptoms was 8 (IQR: 4–13) months. The majority (131 patients, 61.2%) were localized diseases, and the most common primary site was the lower limb (62.1%). The median tumor size was 10 (IQR: 6.8-15) cm, and the tumors were deep to fascia in 144 (67.3%) patients. Eighty-three patients (38.8%) presented with de novo metastasis, and lung (81.9%) was the most common site. The local therapy was as follows; surgery (45.3%), radiation (7.5%), both (41.6%), and none (5.6%). Eighty-five patients received chemotherapy as follows; anthracycline (51%), ifosfamide (28%), and both (23.5%). Seventy-nine patients (36.9%) achieved complete response, 56 (26.2%) developed distant metastasis, and 11 (5.1%) local relapse. Thirty-one patients received salvage chemotherapy, and 30 patients received second-line chemotherapy. The best response of first-line chemotherapy in metastatic patients was CR (3%), PR (14%), SD (8%), and PD (63%). The median follow-up was 37 (IQR: 12-76.75) months. The median OS for the localized disease was not reached, and three years OS was 88.2%. There was a statistical difference in OS between extremities vs. trunk (90.9% vs. 66.7%), (p = 0.01), histological subtypes (p = 0.006), nodal involvement (p &lt; 0.001), T stage (p = 0.03), and complete response 96.9 vs. 68.5% (p &lt; 0.001). The median OS for metastatic disease was 26 (95% CI: 16–35.5) months. The median OS for patients who underwent surgery, radiation, both or none were 26, 23, 31, and 9 months, respectively (p = 0.004). Conclusions: STS in SA is diagnosed at a younger age, with a longer median time for diagnosis and a more advanced stage. Histological subtypes and the advantage of local disease control and metastasectomy are consistent with other figures.

Closed-Incision Negative-Pressure Wound Therapy after Resection of Soft-Tissue Tumors Reduces Wound Complications: Results of a Randomized Trial.

Wound healing after resection of large soft-tissue tumors is often impaired by large dead space and fluid collection. Recently, the authors were able to show an association of wound complications with worse oncologic outcome in soft-tissue sarcomas. The aim of the study was to examine the value of closed-incision negative pressure wound therapy on postoperative wound drainage and wound complications after soft-tissue tumor resection. Patients for whom resection is planned of a soft-tissue tumor larger than 10 cm in diameter of the extremities or the trunk were allocated randomly to one of two groups. After wound closure, patients in the study group received closed-incision negative-pressure wound therapy for a duration of 5 days, whereas those in the control group received regular dressings. The amount of drainage fluid, course of wound healing, length of hospital stay, and wound edge perfusion at postoperative day 5 measured by white-light infrared spectroscopy were compared. Sixty patients could be included in the study with even distribution to both study arms, meeting the goal. The postoperative course of wound drainage volume was significantly lower in the study group, and hospital stay was significantly shorter, with 9.1 ± 3.8 days versus 13.9 ± 11.8 days. The occurrence of wound complications was significantly lower in the study group on time-to-event analysis (one versus six). Tissue spectroscopy revealed a significantly higher oxygen saturation increase in the wound edge for the study group versus the control group. Closed-incision negative-pressure wound therapy should be considered for patients undergoing resection of large soft-tissue tumors. Therapeutic, II.

Outcomes of soft-tissue sarcoma in nonagenarians.

Current literature suggests that survival outcomes and local recurrence rates of primary soft-tissue sarcoma diagnosed in the very elderly age range, (over 90 years), are comparable with those in patients diagnosed under the age of 75 years. Our aim is to quantify these outcomes with a view to rationalizing management and follow-up for very elderly patients. Retrospective access to our prospectively maintained oncology database yielded a cohort of 48 patients across 23 years with a median follow-up of 12 months (0 to 78) and mean age at diagnosis of 92 years (90 to 99). Overall, 42 of 48 of 48 patients (87.5%) were managed surgically with either limb salvage or amputation. A lower overall local recurrence rate (LRR) was seen with primary amputations compared with limb salvage (p > 0.050). The LRR was comparable between free (R0), microscopically (R1), and macroscopically positive (R2) resection margins in the limb salvage group. Amputation was also associated with longer survival times (p < 0.050). Overall median survival time was limited to 20 months (0 to 80). Early and aggressive treatment with appropriate oncological surgery confers the lowest LRR and a survival advantage versus conservative treatment in this cohort of patients. With limited survival, follow-up can be rationalized on a patient-by-patient basis using alternative means, such as GP, local oncology, and/or patient-led follow-up. Cite this article: Bone Joint J2022;104-B(1):177-182.

Soft-tissue Sarcoma of the Hand: Patient Characteristics, Treatment, and Oncologic Outcomes

The aim of this study was to describe patient characteristics, treatment, and oncologic outcomes of soft-tissue sarcomas (STSs) of the hand. Sixty-nine STSs of the hand in adult patients treated at a tertiary referral center were retrospectively included. We describe patient and tumor characteristics along with oncologic outcomes. Epithelioid sarcoma (23%) was the most common histologic subtype, followed by synovial sarcoma (15%). Of all tumors, 17 (25%) were grade I, 22 (32%) were grade II, and 30 (44%) were grade III. The 5-year disease-free survival for epithelioid sarcomas was 75% with a disease survival of 100%, along with a metastatic rate of 15%. Of the patients with a synovial sarcoma, 40% developed metastases, and the 5-year disease-free survival was 68% and the 5-year disease survival was 73%. Hand STSs are aggressive tumors with a high metastatic potential. Even with adequate oncologic treatment, long-term clinical follow-up (10 years) in these tumors is advised. The treating surgical oncologist should not be deceived by their smaller size.

Demography and Short Term Functional Outcome of Soft Tissue Sarcoma Treated with Limb Salvage Surgery

Background: Limb salvage surgery with or without radiotherapy and/or chemotherapy is the mainstay of treatment of Soft Tissue Sarcoma (STS). Though, many studies are found regarding the demographics and result of such malignancy from other parts of the world, such data is not available from our country. This study aimed to analyze the demographic data and functional outcome of STS treated with limb salvage surgery.&#x0D; Methods: It is a retrospective review of 16 cases of soft tissue sarcoma of extremities and trunk managed with limb salvage surgery followed by adjuvant radiotherapy and/or chemotherapy in indicated cases from 2012 to 2017. Demographic data and functional score after 2 years of surgery were analysed and presented.&#x0D; Results: There were 14 male and 2 female cases of STS with mean age of 32.88 years. The most common STS was liposarcoma (37.5%) followed by rhabdomyosarcoma (25%) and synovial sarcoma (18.8%). Extremity and lower limb were the most common sites. Mean MSTS functional score at the last follow up was 24.56 (81.83%) with range from 19-29 (63.33%-96.66%). There were good to excellent results in 13 cases (81.25%) and moderate result in 3 cases (18.75%) according to MSTS functional score. There was positive correlation of MSTS with age, radiotherapy, chemotherapy and negative correlation with grade of tumor.&#x0D; Conclusions: This study showed good to excellent functional results in 81.25% of cases as per Musculoskeletal Tumor Society Score (MSTS) with positive correlation with radiotherapy, chemotherapy, age and negative correlation with grade of tumor.

A Prognostic Molecular Signature of N⁶-Methyladenosine Methylation Regulators for Soft-Tissue Sarcoma from The Cancer Genome Atlas Database

BackgroundSoft-tissue sarcomas are a group of heterogeneous and rare mesenchymal tumors with aggressive behavior. We aimed to identify the molecular signatures of N6-methyladenosine (m6A) methylation regulators associated with patient prognosis using The Cancer Genome Atlas (TCGA) database.Material/MethodsTo evaluate the role of m6A in soft-tissue sarcomas, genomic and clinical data were downloaded from TCGA. The copy number variations (CNVs) and mutations of m6A regulators were analyzed.ResultsAlterations of m6A regulators were common, and ALKBH5 showed the highest frequency of copy number gain, while ZC3H13 had the highest frequency of loss. CNVs and mutations were closely correlated with histology (P<0.001) and tumor size (P=0.040), and CNVs were correlated with mRNA expression. Furthermore, patients with gains of METTL16, RMB15, RMB15B, YTHDC, and YTHDF3 displayed poorer overall survival (OS), and patients with gains of RBM15 and YTHDC2 and loss of IGF2BP1 had poorer disease-free survival (DFS). Further analysis indicated that CNVs and mutations of KIAA1429, YTHDF3, and IGF2BP1 were independent risk factors predicting OS and DFS. Gain of “writers” with loss of “erasers” led to worse OS than gain of “writers”. Genes involved in JAK2 oncogenic signature were enriched in cases of higher expressions of METTL16, YTHDC2, and YTHDF3. Similarly, the core serum response signature was enriched in patients with higher expressions of IGF2BP1, METTL16, RBM15, and YTHDC2.ConclusionsOur study provides a useful molecular tool to predict the outcome of soft-tissue sarcomas and deepens our understanding of the molecular mechanisms of the development of the disease.

Spatial Outcomes of Soft Tissue Sarcoma in Southern West Virginia.

IntroductionDioxins, polychlorinated biphenyls (PCBs), and 2,3,7,8-Tetrachlorodibenzodioxin (TCDDs) are persistent organic pollutants widely distributed in the food chain. For over 50 years, the Monsanto plant in Nitro, West Virginia, created dioxin waste while producing herbicides, Agent Orange (during the Vietnam War), and different forms of rubber. Recent and past literature has established a link between the Monsanto plant and increased cancer cases within the region. Soft tissue sarcoma is one of the few specific cancers that has been linked to dioxin exposure. This pilot study examined whether sarcoma cases were clustered or randomly distributed within Kanawha County, West Virginia over the years 2000 to 2013. We hypothesize that sarcoma cancer cases will be spatially clustered.MethodsThis study assessed the spatial distribution of cancer patients with addresses within the Nitro, West Virginia, and study area. The Charleston Area Medical Center shared soft tissue sarcoma (n = 97) cases from 2000 to 2013. An unweighted K function with confidence intervals (99 Monte Carlo permutations) and 10 distance at 2800 meters each band analyzed the distribution of cases.ResultsThe results suggest that sarcoma cases are slightly clustered within the study area. The region also has a high concentration of chemical and industrial sites. The eighth distance band exhibited the greatest difference (11384), between the expected versus the observed K function.ConclusionThe unweighted K function shows non-random clustering. Future studies could investigate possible associations to industrial, chemical, or other possible point source contamination within the study area.

MRI Radiomic Habitats Predict for Radiation Response in Soft Tissue Sarcoma

Favorable tumor response (pathologic necrosis [PN] >90-95%) has been associated with improved outcome in soft tissue sarcoma (STS). STS is a diverse disease with variable response to radiation (RT), therefore tools such as radiomics may improve our prediction of tumor radiosensitivity. Radiomic habitats are analyses of overlaid images, providing insight on the underlying innate biology. We hypothesize that utilizing pretreatment MRI habitat analysis can predict for favorable tumor response in STS. We identified a total of 432 non-metastatic sarcoma patients that were treated with neoadjuvant radiation (50Gy/25 fractions) followed by surgery, from 2001 to 2019. Patients with a pre-RT MRI were included, gross volume was manually segmented on T1-post contrast and T2 STIR sequences. The sequences were dichotomized by signal intensity and each region designated into 1 of 4 habitats (e.g. T1 high/low, T2 high/low), and 154 habitat features were extracted. The cohort was split 2:1 into training and validation subsets balanced by PN, clinical tumor T (cT) and N stage (cN), receiving induction chemotherapy, and age. Feature reduction and machine learning was utilized to identify habitat features predictive of PN rates >90% or >95% at the time of surgery. Overall, patients eligible for analysis (n = 97) had a median age of 63 and tumor size of 11 cm. They most commonly consisted of undifferentiated pleomorphic sarcoma (40%), extremity (80%), and no prior chemotherapy (87%). An 8-feature model, 4 radiomic and 4 clinical (recurrent disease, age, cT stage, cN stage), predicted for PN>90% (training: 72%, ROC 0.746; validation: 65%, ROC: 0.713). Evaluating patients treated with neoadjuvant RT alone (n = 84), a second model with 5 radiomic and 3 clinical features (prior RT, cT and cN stage), had the highest prediction for PN>95% (training: 78%, ROC 0.721; validation: 72%, ROC 0.600). In both the overall cohort and RT only subset, the diversity in the number of habitat volumes within the tumor predicted for tumor response (OR 7.71 and 3.31). Models incorporating pretreatment MRI-habitats and clinical features can be used to predict radiation response in STS. Radiomic features suggestive of habitat diversity within a tumor appear to be associated with radiation response, and highlight the importance of intratumoral heterogeneity when evaluating radiosensitivity. Prospective studies utilizing this model to predict radiation response may identify patients that could benefit from treatment escalation.