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Introduction: Conventional treatment of pulmonary metastatic sarcoma primarily involves surgery, with systemic therapy added in select patients. However, broader applications of radiation therapy techniques have prompted investigation into the use of stereotactic body radiotherapy (SBRT) for treatment of metastatic sarcoma, an attractive non-invasive intervention with potential for lower rates of adverse events than surgery. Current data are limited to retrospective analyses. This study analyzed 2-year local control and overall survival and adverse events in patients prospectively treated with SBRT to pulmonary sarcoma metastases., Methods: Patients prospectively treated with SBRT to the lung for biopsy-proven metastatic sarcoma at a single institution from 2010 to 2022 were included. SBRT dose/fractionation treatment regimens ranged from 34 to 54 Gy in 1-10 fractions using photons. Local recurrence, local progression-free survival (LPFS) and overall survival (OS) were calculated from the end of SBRT. Univariable analysis (UVA) was performed using the log-rank test. Multivariable analysis (MVA) was performed using the Cox proportional hazards model. Adverse events due to SBRT were graded based on the Common Terminology Criteria for Adverse Events, version 4.0., Results: Eighteen patients with metastatic sarcoma were treated to 26 pulmonary metastases. The median local progression-free survival was not met. The median overall survival was not met. The local control rate at 2 years was 96%. 2-year LPFS was 95.5% and OS was 74%. Three patients (16.7%) developed grade 1 adverse events from SBRT. There were no adverse events attributed to radiation that were grade 2 or higher., Conclusion: We report prospective data demonstrating that SBRT for sarcoma pulmonary metastases affords a high rate of local control and low toxicity, consistent with prior sarcoma SBRT retrospective data. This study adds to the wealth of information on SBRT in a radioresistant tumor. Though largely limited to retrospective reviews, current data indicate high rates of local control with favorable toxicity profiles. Therefore, SBRT for pulmonary sarcoma metastases may be considered for properly selected patients., (© 2023. The Author(s).)

Background: This study aimed to define how utilization of plastic surgical reconstruction (PSR) affects perioperative outcomes, locoregional recurrence-free survival (LRRFS), and overall survival (OS) after radical resection of extremity and truncal soft tissue sarcoma (ETSTS). The secondary aim was to determine factors associated with PSR., Methods: Patients who underwent resection of ETSTS between 2000 and 2016 were identified from a multi-institutional database. PSR was defined as complex primary closure requiring a plastic surgeon, skin graft, or tissue-flap reconstruction. Outcomes included PSR utilization, postoperative complications, LRRFS, and OS., Results: Of 2750 distinct operations, 1060 (38.55%) involved PSR. Tissue-flaps (854, 80.57%) were most commonly utilized. PSR was associated with a higher proportion of R0 resections (83.38% vs. 74.42%, p < 0.001). Tissue-flap PSR was associated with local wound complications (odds ratio: 1.81, confidence interval: 1.21-2.72, p = 0.004). Neither PSR nor postoperative complications were independently associated with LRRFS or OS. High-grade tumors (1.60, 1.13-2.26, p = 0.008) and neoadjuvant radiation (1.66, 1.20-2.30, p = 0.002) were associated with the need for PSR., Conclusion: Patients with ETSTS undergoing resection with PSR experienced acceptable rates of complications and a higher rate of negative margins, which were associated with improved LRRFS and OS. High tumor grade and neoadjuvant radiation were associated with requirement of PSR., (© 2022 Wiley Periodicals LLC.)

Backgrounds and Objectives: This investigation described clinicopathological features and outcomes of extraskeletal myxoid chondrosarcoma (EMC) patients., Methods: EMC patients were identified from the United States Sarcoma Collaborative database between 2000 and 2016. Overall survival (OS) and recurrence-free survival (RFS) were calculated, and prognostic factors were analyzed., Results: Sixty individuals with a mean age of 55 years were included, and 65.0% (n = 39) were male. 73.3% (n = 44) had a primary tumor. A total of 41.6% (n = 25) developed tumor relapse following resection. The locoregional recurrence rate was 30.0% (n = 18/60), and mean follow-up was 42.7 months. The 5-year OS was 71.0%, while the 5-year RFS was 41.4%. On multivariate analysis for all EMC, chemotherapy (hazard ratio [HR], 6.054; 95% confidence interval [CI], 1.33-27.7; p = 0.020) and radiation (HR, 5.07, 95% CI, 1.3-20.1; p = 0.021) were independently predictive of a worse RFS. Among patients with primary EMC only, the 5-year OS was 85.3%, with a 30.0% (n = 12) locoregional recurrence rate, though no significant prognostic factors were identified., Conclusions: Long-term survival with EMC is probable, however there exists a high incidence of locoregional recurrence. While chemotherapy and radiation were associated with a worse RFS, these findings were likely confounded by recurrent disease as significance was lost in the primary EMC-only subset., (© 2022 Wiley Periodicals LLC.)

Background: Prognostic nomograms for patients with resected extremity soft tissue sarcoma (STS) include the Sarculator and Memorial Sloan Kettering (MSKCC) nomograms. We sought to validate these two nomograms within a large, modern, multi-institutional cohort of resected primary extremity STS patients., Methods: Resected primary extremity STS patients from 2000 to 2017 were identified across nine high-volume U.S. institutions. Predicted 5- and 10-year overall survival (OS) and distant metastases cumulative incidence (DMCI), and 4-, 8-, and 12-year disease-specific survival (DSS) were calculated with Sarculator and MSKCC nomograms, respectively. Predicted survival probabilities stratified in quintiles were compared in calibration plots to observed survival assessed by Kaplan-Meier estimates. Cumulative incidence was estimated for DMCI. Harrell's concordance index (C-index) assessed discriminative ability of nomograms., Results: A total of 1326 patients underwent resection of primary extremity STS. Common histologies included: undifferentiated pleomorphic sarcoma (35%), fibrosarcoma (13%), and leiomyosarcoma (9%). Median tumor size was 8.0 cm (IQR 4.5-13.0). Tumor grade distribution was: Grade 1 (13%), Grade 2 (9%), Grade 3 (78%). Median OS was 172 months, with estimated 5- and 10-year OS of 70% and 58%. C-indices for 5- and 10-year OS (Sarculator) were 0.72 (95% CI 0.70-0.75) and 0.73 (95% CI 0.70-0.75), and 0.72 (95% CI 0.69-0.75) for 5- and 10-year DMCI. C-indices for 4-, 8-, and 12-year DSS (MSKCC) were 0.71 (95% CI 0.68-0.75). Calibration plots showed good prognostication across all outcomes., Conclusions: Sarculator and MSKCC nomograms demonstrated good prognostic ability for survival and recurrence outcomes in a modern, multi-institutional validation cohort of resected primary extremity STS patients. External validation of these nomograms supports their ongoing incorporation into clinical practice., (© 2022. Society of Surgical Oncology.)

Objectives: Preoperative radiation therapy (RT) followed by wide-local excision with or without chemotherapy is widely accepted as management for soft tissue sarcomas (STS). Although studies have demonstrated excellent local control with this technique, there can be significant morbidity with the development of wound complications. It has been shown that sarcoma resections performed at a high-volume center lead to improved survival and functional outcomes. It is unclear, however, if radiation performed in a high-volume center leads to improved outcomes especially related to morbidity. The goal of this study was to determine whether preoperative RT performed at an academic cancer center have lower rates of wound complication compared with RT performed in community cancer centers., Materials and Methods: A total of 204 patients with STS were treated with preoperative RT±chemotherapy followed by limb-sparing resection. Of these, 150 patients had preoperative RT performed at an academic sarcoma center. wound complication were defined as those requiring secondary operations or prolonged wound care for 4 months following surgery. Predictors for wound complication were evaluated using a Fisher exact test for univariate analysis and logistic regression for multivariate analysis., Results: The overall incidence of wound complication was 28.3%. Significant predictors for wound complication include tumor location and radiation delivered at a community hospital. The postoperative incidence of wound complication was 21% when the preoperative RT was performed at an academic cancer center versus 39% when performed at a community cancer center (P=0.009). On multivariate analysis, both tumor location (P=0.0012, 95% confidence interval: 0.03-0.45, odds ratio: 0.13) and RT performed at a community cancer center (P=0.02, 95% confidence interval: 1.13-4.48, odds ratio: 2.25) remained significant in correlation with postoperative wound complication., Conclusions: Preoperative RT performed at an academic cancer center led to lower rates of postoperative wound complication. This may support the recommendation that preoperative RT and resection of STS be performed at an experienced sarcoma center., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Well-differentiated liposarcoma (WDLPS) is a low-grade soft tissue sarcoma with a propensity for local recurrence. The necessity of obtaining microscopically free surgical margins (R0) to minimize local recurrence is not clear. This study evaluates recurrence-free survival (RFS) of extremity WDLPS in relation to resection margin status., Methods: A retrospective review of adult patients with primary extremity WDLPS at seven US institutions from 2000 to 2016 was performed. Patients with recurrent tumors or incomplete resection (R2) were excluded. Clinicopathologic factors were analyzed to assess impact on local RFS., Results: 97 patients with primary extremity WDLPS were identified. The majority of patients had deep, lower extremity tumors. Mean tumor size was 18.2±8.9cm. Patients were treated with either radical (76.3%) or excisional (23.7%) resections; 64% had R0 and 36% had microscopically positive (R1) resection margins. Ten patients received radiation therapy with no difference in receipt of radiation between R0 vs R1 groups. Thirteen patients (13%) developed a local recurrence with no difference in RFS between R0 vs R1 resection. Five-year RFS was 59.5% for R0 vs 85.2% for R1. Only one patient died of disease after developing dedifferentiation and distant metastasis despite originally having an R0 resection., Discussion: In this large multi-institutional study of surgical resection of extremity WDLPS, microscopically positive margins were not associated with an increased risk of recurrence. Positive microscopic margin resection for extremity WDLPS may yield similar rates of local control while avoiding a radical approach to obtain microscopically negative margins.

Background: Soft tissue sarcomas are a heterogenous group of neoplasms without well-validated biomarkers. Cancer-related inflammation is a known driver of tumor growth and progression. Recent studies have implicated a high circulating neutrophil-lymphocyte ratio as a surrogate marker for the inflammatory tumor microenvironment and a poor prognosticator in multiple solid tumors, including colorectal and pancreatic cancers. The impact of circulating neutrophil-lymphocyte ratio in soft tissue sarcomas has yet to be elucidated., Methods: We performed a retrospective analysis of patients undergoing curative resection for primary or recurrent extremity soft tissue sarcomas at academic centers within the US Sarcoma Collaborative. Neutrophil-lymphocyte ratio was calculated retrospectively in treatment-naïve patients using blood counts at or near diagnosis., Results: A high neutrophil-lymphocyte ratio (≥4.5) was associated with worse survival on univariable analysis in patients with extremity soft tissue sarcomas (hazard ratio 2.07; 95% confidence interval, 1.54-2.8; P < .001). On multivariable analysis, increasing age (hazard ratio 1.03; 95% confidence interval, 1.02-1.04; P < .001), American Joint Committee on Cancer T3 (hazard ratio 1.89; 95% confidence interval, 1.16-3.09; P = .011), American Joint Committee on Cancer T4 (hazard ratio 2.36; 95% confidence interval, 1.42-3.92; P = .001), high tumor grade (hazard ratio 4.56; 95% confidence interval, 2.2-9.45; P < .001), and radiotherapy (hazard ratio 0.58; 95% confidence interval, 0.41-0.82; P = .002) were independently predictive of overall survival, but a high neutrophil-lymphocyte ratio was not predictive of survival (hazard ratio 1.26; 95% confidence interval, 0.87-1.82; P = .22)., Conclusion: Tumor inflammation as measured by high pretreatment neutrophil-lymphocyte ratio was not independently associated with overall survival in patients undergoing resection for extremity soft tissue sarcomas., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Postoperative wound complications are challenging in patients with localized extremity soft-tissue sarcomas. Various factors have been associated with wound complications, but there is no individualized predictive model to allow providers to counsel their patients and thus offer methods to mitigate the risk of complications and implement appropriate measures., Questions/purposes: We used data from multiple centers to ask: (1) What risk factors are associated with postoperative wound complications in patients with localized soft-tissue sarcomas of the extremity? (2) Can we create a predictive nomogram that will assess the risk of wound complications in individual patients after resection for soft-tissue sarcoma?, Methods: From 2000 to 2016, 1669 patients undergoing limb-salvage resection for a localized primary or recurrent extremity soft-tissue sarcoma with at least 120 days of follow-up at eight participating United States Sarcoma Collaborative institutions were identified. Wound complications included superficial wounds with or without drainage, deep wounds with drainage because of dehiscence, and intentional opening of the wound within 120 days postoperatively. Sixteen variables were selected a priori by clinicians and statisticians as potential risk factors for wound complications. A univariate analysis was performed using Fisher's exact tests for categorical predictors, and Wilcoxon's rank-sum tests were used for continuous predictors. A multiple logistic regression analysis was used to train the prediction model that was used to create the nomogram. The prediction performance of the datasets was evaluated using a receiver operating curve, area under the curve, and calibration plot., Results: After controlling for potential confounding factors such as comorbidities, functional status, albumin level, and chemotherapy use, we found that increasing age (odds ratio 1.02; 95% confidence interval, 1.00-1.03; p = 0.008), BMI (OR 1.05; 95% CI, 1.02-1.09; p = 0.004), lower-extremity location (OR 6; 95% CI, 2.87-12.69; p < 0.001), and neoadjuvant radiation (OR 2; 95% CI, 1.47-3.16; p < 0.001) were associated with postoperative wound complications (area under the curve 69.2% [range 62.8%-75.6%])., Conclusions: We found that age, BMI, tumor location, and timing of radiation are associated with the risk of wound complications. Based on these factors, a validated nomogram has been established that can provide an individualized prediction of wound complications in patients with a resected soft-tissue sarcoma of the extremity. This may allow for proactive management with nutrition and surgical techniques, and help determine the delivery of radiation in patients with a high risk of having these complications., Level of Evidence: Level III, therapeutic study.

Background: Although preoperative radiation followed by wide local excision yields excellent local control in soft tissue sarcomas, the risk of wound complications is reported to be higher compared with the incidence in patients who were administered postoperative radiation therapy. Vacuum (vac)-assisted closure may improve wound healing, but it is unknown whether vac-assisted closure during soft tissue sarcoma resection may reduce the risk of wound complications or impair local disease control., Questions/purposes: (1) Does the use of a wound vac application at the time of soft tissue sarcoma resection reduce the risk of developing wound complications after lower extremity sarcoma resection? (2) Is vac-assisted closure associated with an increased risk of local relapse?, Methods: From 2000 to 2016, 312 patients with stage I to III soft tissue sarcomas were treated. Of these, 123 were treated with preoperative radiation ± chemotherapy followed by limb-sparing resection based on tumor location, size, grade, histology, and patient age. There was a minimum followup of 12 months. Radiation was delivered generally based on tumor size, grade, superficial versus deep nature, and proximity to neurovascular structures. Chemotherapy was administered in patients < 70 years old with high-grade tumors and tumors > 5 cm. Patient, demographic, and treatment variables, including incisional vac application and wound outcomes, were retrospectively evaluated. Incisional vac-assisted closure took place at the time of primary resection in 32% (46 of 123) of patients. Vac-assisted closure was considered when there was a concern for risk of external contamination such as instances in which fixation of adhesives would be difficult or regions where there was a high risk of contamination. Vac-assisted closure may have also been used in instances with increased wound tension at closure or with heightened concern for shearing on the wound such as buttock wounds. Ten patients were lost to followup, two in the vac group and eight in the non-vac group. Potential factors associated with wound complications were evaluated using Fisher's exact test for univariate analysis and logistic regression for multivariate analysis. Local recurrence-free survival was evaluated using the Kaplan-Meier estimate., Results: After taking into consideration factors such as tumor size, location, age, and patient comorbidities, it was shown that patients who underwent vac-assisted closure were less likely to experience wound complications compared with patients who did not undergo vac-assisted closure (odds ratio, 0.129; 95% confidence interval [CI], 0.041-0.398; p = 0.004). The local control incidence in the entire cohort was 98%. With the numbers available, Kaplan-Meier survivorship free from local recurrence did not differ between patients treated with or without the vac (100% [95% CI, 154.09-154.09] versus 96% [95% CI, 152.21-169.16]; p = 0.211), respectively., Conclusions: Vac-assisted closure at the time of resection of proximal lower extremity soft tissue sarcomas is associated with a lower risk of wound complications, and its use apparently did not compromise local control. We show that the use of vac-assisted closure may be worth considering in surgeons' attempts to reduce the risk of wound complications among patients with soft tissue sarcomas of the proximal lower extremities., Level of Evidence: Level III, therapeutic study.

Background: The 8th edition AJCC staging system for truncal/extremity soft tissue sarcoma (STS) offers significant changes from the 7th. However the complexity of both limits their clinical utility., Methods: Patients with truncal/extremity STS undergoing resection from 2000 to 2016 at seven institutions of the US Sarcoma Collaborative were analyzed. The proposed staging system was externally validated using the National Cancer Database (NCDB)., Results: Of 1318 patients, mean age was 59 years, and 54% were male. Median tumor size was 9 cm; 72% were high grade. Applying 8th edition staging, there was no differentiation between stages IA/IB ( P = 0.92), and clinically similar outcomes between stages II/IIIA. Receiver operating characteristic (ROC) analysis identified 7.5 cm as the ideal tumor size discriminating 5-year OS for high-grade tumors. Therefore, a simplified staging system defining all low-grade tumors as stage I, high-grade < 7.5 cm as stage II, high-grade > 7.5 cm as stage III, and metastatic disease as stage IV improved stratification (all P < 0.05). The C-statistic was noninferior to the 8th edition. External validation in the NCDB confirmed optimal stratification (all P < 0.01)., Conclusions: Our proposed staging system maintains prognostic significance between stages within a simplified system. For high-grade tumors, a cutoff of 7.5 cm, instead of 5 cm, maintains discrimination for survival and could be a more clinically applicable cutoff for future clinical trials., (© 2018 Wiley Periodicals, Inc.)

Background: Multi-institutional collaborations provide granularity lacking in epidemiologic data sets to enable in-depth study of rare diseases. For patients with superficial, high-grade soft tissue sarcomas of the trunk and extremity, the value of radiation therapy (RT) is not clear. We aimed to use the 7-institution US Sarcoma Collaborative (USSC) and the National Cancer Database (NCDB) to investigate this issue., Study Design: All adult patients with superficial truncal and extremity high-grade soft tissue sarcomas who underwent primary curative-intent resection from 2000 to 2016 at USSC institutions or were included in the NCDB from 2004 to 2013 were analyzed. Propensity score matching was performed. End points were locoregional recurrence-free survival (LRFS), overall survival (OS), and disease-specific survival (DSS)., Results: Of 4,153 patients in the USSC, 169 patients with superficial high-grade tumors underwent primary curative-intent resection, 38% of which received RT. On multivariable Cox-regression analysis, RT was not associated with improved LRFS (p = 0.56), OS (p = 0.31), or DSS (p = 0.20). On analysis of 51 propensity score-matched pairs, RT was still not associated with increased LRFS, OS, or DSS. Analysis of 631 propensity score-matched pairs in the NCDB demonstrated improved 5-year OS rate associated with RT (80% vs 70%; p = 0.02). The LRFS and DSS rates were not evaluable., Conclusions: Granular data afforded by collaborative research enables in-depth analysis of patient outcomes. The NCDB, although powered with large numbers, cannot assess many relevant outcomes (eg recurrence, DSS, or complications). In this study, the approaches yielded conflicting results. The USSC data suggested no value of radiation and the NCDB demonstrated improved OS, contradicting all randomized controlled trials in sarcoma. The pros and cons of either approach must be considered when applying results to clinical practice, and underscore the importance of randomized controlled trials., (Copyright © 2018 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Uncontrolled blood glucose impacts key phases of the wound healing process. Various factors have been associated with postoperative wound complications in soft tissue sarcomas; however, the association of postoperative early morning blood glucose with wound complications, if any, remains to be determined. Because blood glucose levels may be modified, understanding whether glucose levels are associated with wound complications has potential therapeutic importance., Questions/purposes: The purposes of this study were (1) to evaluate if postoperative early morning blood glucose is associated with the development of wound complications in soft tissue sarcomas; (2) to determine a blood glucose cutoff that may be associated with an increased risk of wound complications; and (3) to evaluate if patients with diabetes have higher postoperative blood glucose and an associated increased risk of wound complications., Methods: From 2000 to 2015, 298 patients with Stage I to III soft tissue sarcomas of the extremity or chest wall were treated with preoperative radiation ± chemotherapy followed by limb-sparing resection. Of those, 191 (64%) patients had demographic, treatment, and postoperative variables and wound outcomes available; these patients' results were retrospectively evaluated. None of the 191 patients were lost to followup. Early morning blood glucose levels on postoperative day (POD) 1 were available in all patients. Wound complications were defined as those resulting in an operative procedure or prolonged wound care for 6 months postresection. Variables that may be associated with wound complications were evaluated using logistic regression for multivariate analysis. Receiver operative curve (ROC) analysis was used to assess the early morning blood glucose level that best was associated postoperative wound complications., Results: After controlling for potentially relevant confounding variables such as patient comorbidities, tumor size, and location, lower extremity soft tissue sarcomas (p = 0.002, odds ratio [OR], 6.4; 95% confidence interval [CI], 1.97-20.84) and elevated POD 1 early morning blood sugars (p < 0.001; OR, 1.1; 95% CI, 1.04-1.11) were associated with increased wound complications postoperatively. ROC analysis revealed that early morning POD 1 blood glucose of > 127 mg/dL was associated with postoperative wound complications with a sensitivity of 89% (area under the curve 0.898, p < 0.001). Median POD 1 early morning blood glucose in patients without diabetes was 118 mg/dL and 153 mg/dL in patients with diabetes (p = 0.023). However, with the numbers available, there was no increase in wound complications in patients with diabetes compared with those without it., Conclusions: Our study provides preliminary information suggesting that POD 1 early morning blood glucose in patients with soft tissue sarcomas may be associated with a slightly increased risk of postoperative wound complications. An early morning blood glucose of > 127 mg/dL may be a threshold associated with this outcome. Although patients with diabetes had higher POD 1 early morning blood glucose levels, diabetes itself was not associated with the development of wound complications. We cannot conclude that better glycemic control will reduce wound complications in patients who receive preoperative radiation, but our data suggest this should be further studied in a larger, prospective study., Level of Evidence: Level III, therapeutic study.