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Pre-operative RT is often used in the management of soft tissue sarcoma (STS), which has shown to lead to excellent rates of local control. Hypofractionated radiation (HFRT) has been shown to have comparable safety and efficacy to standard fractionated RT (SFRT) in many phase 2 trials and has potential radiobiologic and temporal advantages. However, it is not yet known if these benefits translate to improved oncologic outcomes. In this study, we retrospectively analyze patients with extremity and truncal STS who received pre-operative SFRT or HFRT to determine if HFRT is associated with distant metastases-free survival (DMFS) and Overall Survival (OS). Patients with localized Stage I-III STS of the extremity and superficial trunk treated between 2015-2022 were retrospectively analyzed. Pre- and post-operative pathologic samples were analyzed to assess treatment effect by a trained musculoskeletal pathologist. Patients received either SFRT or HFRT 4-6 weeks prior to surgery. The HFRT and SFRT doses were 35Gy/5fx, and 50Gy/25fx, respectively. Patient, tumor, and treatment variables were evaluated (Table 1) and DMFS and OS were evaluated using the Kaplan-Meier estimate. For multivariate analysis (MVA), cox-proportional hazards test was used. Sixty-seven patients with matched biopsy and resection samples were reviewed. Median follow up was 5.9 years. Most had Stage III (86%) and Grade-3 (84%) STS. Most were treated with SFRT (67%, n = 45) compared to HFRT (33%, n = 22). There were no significant differences between HFRT and SFRT cohorts. For all patients, the 2-year OS and DMFS were 85% and 73%, respectively. The 2-year DMFS for those treated with HFRT was 85.7% vs 64% with SFRT (p = 0.0569, 95% CI 79.9-109.2) On MVA, KPS (p = 0.004, 95% CI 2.4-107.7), HFRT (p = 0.0241 95% CI 0.005-0.69), and necrosis (p = 0.0083 95% CI 2.03-119.3) were significantly associated with DMFS, and KPS (p = 0.007 95% CI 2.04-94.2) and necrosis (p = 0.014 95% CI 1.6-70.5) were significantly associated with OS. In this study, HFRT did not improve OS as compared to SFRT. Nevertheless, a notable significance on MVA emerged indicating that HFRT is linked to improved DMFS. Future studies with larger populations of SFRT and HFRT patients are warranted to corroborate these findings. However, this research indicates the promise of HFRT, suggesting not only radiobiological and temporal advantages, but also potential benefits in DMFS. [ABSTRACT FROM AUTHOR]

Preoperative RT followed by resection is a common management for soft tissue sarcomas (STS). Standard course of RT involves 5-weeks, however, there has been a shift towards pre-op hypofractionation given phase II data showing excellent rates of local control and toxicity. There is evidence that suggests the immune system plays a pivotal role in treatment response for many cancers. RT has demonstrated upregulation of PD-L1 expression; however, this elevation may also trigger immunosuppression. PD-L1 induction can lead to immune escape, resulting in compromised outcomes. Th impact of hypofractionation on biomarker expression in sarcomas remains poorly elucidated. This study aims to evaluate the influence of pre-op HFRT on biomarker expression in STS as well as its implications on DMFS and OS. A retrospective study comparing hypofractionated RT (HFRT) and standard fractionated RT (SFRT) was performed. From 2015-2022, 67 pts with localized STS of the extremity/trunk were treated with HFRT (35 Gy/5 fx) or SFRT (50 Gy/25 fx) followed by resection ~5 weeks later. Tumor immune marker profiling by multiplex histocytometry of 134 samples using a 7-color marker panel was done. CD45, CD68, PD1 and PD-L2 were also evaluated. Variables and % expression in PD-L1 in tumor between SFRT and HFRT groups were assessed. ROC analysis was performed to assess the best cut-off related to outcomes. DMFS and OS were evaluated using the KM estimate. For MVA, cox-proportional hazards test was used. Median f/u was 6 yrs. 22 pts received HFRT and 45 pts received SFRT. 2-year OS and DMFS was 85% and 73%, respectively. There was no difference in the % change of PDL-1 between pre- and post-RT in the two cohorts (6% vs 9%, P = 0.43). No other immune marker was significant for survival. ROC analysis revealed PD-L1 post-RT was associated with DMFS (ROC cutoff 0.028, P = 0.04). 2-year DMFS for pts with ≤ 2.8% expression of PD-L1 post-RT was 91% vs 65% (P = 0.01, 95% CI = 81.1 to 110.4). 67% of pts in the HFRT cohort had >2.8% PD-L1 expression post-RT compared to 33% in SFRT. However, on UVA, a trend of improved 2-year DMFS with HFRT (86% vs 68%, P = 0.06, 95% CI = 81.1 to 110.5). No variable was significant on MVA for OS, but HFRT (P = 0.02) and PD-L1 expression ≤2.8% (P = 0.03) demonstrated improved DMFS. HFRT led to improvements of DMFS on MVA, despite 67% of the patients in this cohort had a PD-L1 expression > 2.8%. While additional studies are needed to further explore the influence of HFRT on the immune system, this implies that HFRT may instigate systemic positive alterations, potentially improving DMFS. [ABSTRACT FROM AUTHOR]

Soft tissue sarcomas account for less than 1% of new cancer diagnoses, approximately one in five of which are liposarcomas. These tumors typically arise in the deep tissues of the proximal extremity or retroperitoneum, with just under 3% presenting as primary intrathoracic neoplasms. We present an exceedingly rare and particularly unique presentation of primary lung liposarcoma which traversed the mediastinum into the contralateral hemithorax. This report highlights the primary characteristics of the disease and underscores the importance of a multidisciplinary approach to its successful treatment., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Purpose: Adolescents and young adults (AYAs) with cancer are challenged to manage complex medication regimens during treatment. The aims of the study are to (1) describe the medication self-management behaviors of AYAs with cancer and (2) examine the barriers and facilitators to AYAs' optimal use of medications, including their self-efficacy to manage medications., Methods: This cross-sectional study enrolled 30 AYAs (18-29 years) with cancer who were receiving chemotherapy. Participants electronically completed a demographic form, a health literacy screen, and the PROMIS Self-efficacy for Medication Management instrument. They completed a semi-structured interview to answer questions about their medication self-management behaviors., Results: Participants (53% female, mean age = 21.9 y) had a variety of AYA cancer diagnoses. Over half (63%) had limited health literacy. Most AYAs had accurate knowledge about their medications and average self-efficacy for managing medications. These AYAs were managing an average of 6 scheduled and 3 unscheduled medications. Oral chemotherapy was prescribed for 13 AYAs; other medications were for prevention of complications and symptom management. Many AYAs relied on a parent for obtaining and paying for medications, used multiple reminders to take medications, and used a variety of strategies to store and organize medications., Conclusion: AYAs with cancer were knowledgeable and confident about managing complex medication regimens but needed support and reminders. Providers should review medication-taking strategies with AYAs and ensure a support person is available., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The treatment of sarcoma necessitates a collaborative approach, given its rarity and complex management. At a single institution, multidisciplinary teams of specialists determine and execute treatment plans involving surgical, radiation, and medical management. Treatment guidelines for systemic therapies in advanced or nonresectable soft tissue sarcoma have advanced in recent years as new immunotherapies and targeted therapies become available. Collaboration between institutions is necessary to facilitate accrual to clinical trials. Here, we describe the success of the Midwest Sarcoma Trials Partnership (MWSTP) in creating a network encompassing large academic centers and local community sites. We propose a new model utilizing online platforms to expand the reach of clinical expertise for the treatment of advanced soft tissue sarcoma.

Background: Desmoid tumors are rare, locally aggressive, highly recurrent soft-tissue tumors without approved treatments., Methods: We conducted a phase 3, international, double-blind, randomized, placebo-controlled trial of nirogacestat in adults with progressing desmoid tumors according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Patients were assigned in a 1:1 ratio to receive the oral γ-secretase inhibitor nirogacestat (150 mg) or placebo twice daily. The primary end point was progression-free survival., Results: From May 2019 through August 2020, a total of 70 patients were assigned to receive nirogacestat and 72 to receive placebo. Nirogacestat had a significant progression-free survival benefit over placebo (hazard ratio for disease progression or death, 0.29; 95% confidence interval, 0.15 to 0.55; P<0.001); the likelihood of being event-free at 2 years was 76% with nirogacestat and 44% with placebo. Between-group differences in progression-free survival were consistent across prespecified subgroups. The percentage of patients who had an objective response was significantly higher with nirogacestat than with placebo (41% vs. 8%; P<0.001), with a median time to response of 5.6 months and 11.1 months, respectively; the percentage of patients with a complete response was 7% and 0%, respectively. Significant between-group differences in secondary patient-reported outcomes, including pain, symptom burden, physical or role functioning, and health-related quality of life, were observed (P≤0.01). Frequent adverse events with nirogacestat included diarrhea (in 84% of the patients), nausea (in 54%), fatigue (in 51%), hypophosphatemia (in 42%), and maculopapular rash (in 32%); 95% of adverse events were of grade 1 or 2. Among women of childbearing potential receiving nirogacestat, 27 of 36 (75%) had adverse events consistent with ovarian dysfunction, which resolved in 20 women (74%)., Conclusions: Nirogacestat was associated with significant benefits with respect to progression-free survival, objective response, pain, symptom burden, physical functioning, role functioning, and health-related quality of life in adults with progressing desmoid tumors. Adverse events with nirogacestat were frequent but mostly low grade. (Funded by SpringWorks Therapeutics; DeFi ClinicalTrials.gov number, NCT03785964.)., (Copyright © 2023 Massachusetts Medical Society.)

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).)

Gastrointestinal stromal tumors (GISTs) are tumors of the digestive tract. To date, there have been no neurological paraneoplastic syndromes or symptoms associated with metastatic GISTs. Tyrosine kinase inhibitors (TKIs) are the typical class of agents used in management of this malignancy. Avapritinib, a new TKI, has been associated with myriad neurological adverse events with fairly rapid resolution in clinical trials. Herein, we present the case of a patient with metastatic GIST who, after starting treatment with avapritinib, developed rapidly progressive and persisting severe neuropsychiatric symptoms, including profound parkinsonism and encephalopathy, while concurrently receiving therapy with the antipsychotic olanzapine. We posit that the patient could be conceptualized as having a relative vulnerability to medication effects in the setting of metastatic GIST - possibly driven by an immune-mediated process - and that the addition of avapritinib triggered an overtly evident, clinically significant cascade of neurological deterioration., Competing Interests: Ahmed Z. Obeidat reports that he received personal compensation for participation in scientific advisory boards, steering committees from Alexion pharmaceuticals, Biogen, Bristol Myers Squibb, Celgene, EMD Serono, GW pharma, Genentech, Horizon, Novartis, Sanofi/Genzyme, TG therapeutics, Viela Bio. Honorarium for speaking engagements from Alexion pharmaceuticals, Biogen, Bristol Myers Squibb, Celgene, EMD Serono, Genentech, and Horizon. Dr. Obeidat serves as a site PI for studies funded (directly paid to Medical College of Wisconsin) by 10.13039/100000890National MS Society and PCORI; Atara biotherapeutics, 10.13039/100005614Biogen, 10.13039/100006436Celgene, 10.13039/100002491Bristol Myers Squibb, 10.13039/100004755EMD Serono, 10.13039/100004328Genentech, and 10.13039/100004336Novartis. And Sub-I on studies funded by 10.13039/100006483AbbVie and 10.13039/100004339Sanofi/10.13039/100004329Genzyme. Dr. Obeidat received research funds from Central for immunology, Research Affairs Committee, and Neuroscience research center. Dr. Obeidat serves on the editorial board of the International Journal of MS Care., (© 2022 The Authors.)

Background: Androgen receptor (AR) expression has emerged as a potential prognostic and predictive marker in patients with triple negative breast cancer (TNBC). We conducted a retrospective analysis to evaluate pathologic complete response (pCR) rates, disease-free survival (DFS) and overall survival (OS) in patients with AR positive and AR negative TNBC treated with neoadjuvant chemotherapy. Methods: 107 patients with TNBC subtype, treated with neoadjuvant chemotherapy between June 2006 and March 2016 were evaluated for AR expression. Androgen receptors were evaluated by immunohistochemical staining (clone AR441, Dilution 1:50, Dako-Agilent, Santa Clara, CA) using whole tissue sections from archived paraffin-embedded formalin-fixed (FFPE) blocks. AR positive was defined as ≥10% nuclear stained cells. Correlation of AR expression was examined with age, BMI, race, menopausal status, tumor grade, tumor size, and lymph node involvement, and response and outcomes. Univariate and multivariate analyses were performed to determine an association with AR expression and pathologic response and survival outcomes. Results: Fifty-eight patients with available tumor specimens were stained, with twenty (34.5%) being AR-positive and thirty-eight (65.5%) being AR negative. Median age was 49 years and median follow up was 5.7 years. All patients received anthracycline based neoadjuvant chemotherapy with 13 patients (23%) receiving an additional platinum chemotherapy. BRCA mutation positivity was 7% for the entire group. No differences in age, menopausal status, BMI, race, tumor size and lymph node involvement were observed between the two groups. However, there was a statistically significant difference in tumor grade between the two groups (p=0.008). Overall pCR rate was 28% with no difference between the two groups (30% vs 26%, p=0.56). There was no statistically significant difference in median DFS (5.9 years vs 5.2 years ( p =0.94) and median OS (6.2 years vs 5.4 years, p =0.98) between the AR positive and AR negative groups. Conclusions: Our study did not find an association of AR status and the pathologic responses or survival outcomes in patients with TNBC treated with neoadjuvant chemotherapy. Further studies exploring the prognostic and predictive role of AR in patients with TNBC are warranted., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Pazopanib is active in refractory soft-tissue sarcoma (STS) and significantly prolongs PFS. Prior studies of combinations of metronomic topotecan with pazopanib have indicated preclinical evidence of response in patients with sarcoma., Methods: This prospective, single arm, phase II study evaluated the efficacy of the combination of pazopanib with topotecan in patients with metastatic or unresectable non-adipocytic STS. Furthermore, it incorporated exploratory arms for osteosarcoma and liposarcoma. The primary endpoint was progression-free rate at 12 weeks in the non-adipocytic STS cohort., Results: 57.5% of patients in the non-adipocytic STS cohort were progression free at 12 weeks, which did not meet the primary endpoint of the study (66%). The exploratory osteosarcoma cohort exceeded previously established phase II trial comparator data benchmark of 12% with a PFR at 12 weeks of 69.55%. Treatment with the combination of pazopanib and topotecan was accompanied by a grade 3 or 4 toxicities in most patients., Conclusions: In this prospective trial in refractory metastatic or unresectable STS and osteosarcoma, the combination of pazopanib with topotecan did not meet its primary endpoint of progression-free rate at 12 weeks. The combination of pazopanib with topotecan was associated with a high degree of toxicity., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Cardiac magnetic resonance imaging (CMR) is considered the gold standard for measuring cardiac function. Further, in a single CMR exam, information about cardiac structure, tissue composition, and blood flow could be obtained. Nevertheless, CMR is underutilized due to long scanning times, the need for multiple breath-holds, use of a contrast agent, and relatively high cost. In this work, we propose a rapid, comprehensive, contrast-free CMR exam that does not require repeated breath-holds, based on recent developments in imaging sequences. Time-consuming conventional sequences have been replaced by advanced sequences in the proposed CMR exam. Specifically, conventional 2D cine and phase-contrast (PC) sequences have been replaced by optimized 3D-cine and 4D-flow sequences, respectively. Furthermore, conventional myocardial tagging has been replaced by fast strain-encoding (SENC) imaging. Finally, T1 and T2 mapping sequences are included in the proposed exam, which allows for myocardial tissue characterization. The proposed rapid exam has been tested in vivo. The proposed exam reduced the scan time from >1 hour with conventional sequences to <20 minutes. Corresponding cardiovascular measurements from the proposed rapid CMR exam showed good agreement with those from conventional sequences and showed that they can differentiate between healthy volunteers and patients. Compared to 2D cine imaging that requires 12-16 separate breath-holds, the implemented 3D-cine sequence allows for whole heart coverage in 1-2 breath-holds. The 4D-flow sequence allows for whole-chest coverage in less than 10 minutes. Finally, SENC imaging reduces scan time to only one slice per heartbeat. In conclusion, the proposed rapid, contrast-free, and comprehensive cardiovascular exam does not require repeated breath-holds or to be supervised by a cardiac imager. These improvements make it tolerable by patients and would help improve cost effectiveness of CMR and increase its adoption in clinical practice., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 El-Sayed H. Ibrahim et al.)

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.)

Purpose: This study examined health care providers' perceptions of the usefulness and ease of use of a symptom heuristics app delivered via a tablet computer as a resource for understanding symptom experiences of adolescents and young adults (AYAs) with cancer. AYAs' app-generated symptom reports were compared with providers' documentation of AYAs' symptoms. Methods: This multisite study included responses from 86 AYAs 15-29 years of age who completed the Computerized Symptom Capture Tool (C-SCAT) before two scheduled visits for chemotherapy. After each visit, their providers completed a survey addressing their perspective of: (1) the usefulness of data provided by the C-SCAT to understand the AYAs' symptom experience, and (2) the nature of the discussion of symptoms with the AYA. An electronic health record review compared symptoms that AYAs identified by using the C-SCAT with providers' documentation of symptoms. Results: One hundred forty-four complete surveys were returned after 162 visits. Fifty percent ( n  = 72) of responses reported that the C-SCAT helped identify the patient's symptoms, and 53% ( n  = 76) reported that it helped identify the patient's priority symptoms. Providers also reported higher patient engagement and more focused discussions regarding symptoms. They reported that use of the C-SCAT facilitated the development of symptom management plans. Priority symptoms were documented more frequently than nonpriority symptoms (54% vs. 32.7%; p  < 0.01) as was a plan for managing priority symptoms (33.7% vs. 17.9%; p  < 0.01). Conclusion: Use of the C-SCAT enhanced providers' understanding of AYAs' symptom experiences. Further research is needed to demonstrate the effectiveness of the C-SCAT as a resource to improve symptom management among AYAs with cancer.

Although checkpoint inhibitors have been approved in multiple cancers, they are still under investigation in soft tissue sarcoma (STS). We conducted a retrospective review to report the safety, efficacy, and prognostic factors related to checkpoint inhibitors in STS. A sequential cohort of metastatic STS patients from four institutions treated with checkpoint inhibitors was assembled. Logistic and Cox regression models were applied to determine the effect of patient characteristics, prior treatment, and baseline factors on achieving the best overall response of complete response (CR), partial response (PR), or stable disease (SD) as determined by the treating physician. Eighty-eight patients with two median prior therapies received checkpoint inhibitors. Treatments included pembrolizumab in 47, nivolumab in 6, ipilimumab in 1, combination ipilimumab/nivolumab in 27, and other combination immunotherapies in 7 patients. Immunotherapy was discontinued in 54 patients-72.2% for progression, 16.7% for toxicity, and 11.1% for other reasons. Median progression-free survival (PFS) was 4.1 months and median overall survival was 19.1 months. One patient with undifferentiated pleomorphic sarcoma (UPS) achieved a CR, while 20 patients had a PR, including 7 UPS, 9 leiomyosarcoma (LMS), and 1 each with alveolar soft part sarcoma, fibroblastic sarcoma, sclerosing epithelioid fibrosarcoma, and myxofibrosarcoma. Forty-five percent (9 of 20) of LMS patients achieved a PR. Twenty-eight patients had SD. Our results confirm the activity and safety of anti-PD-1 therapy in metastatic STS. A notable response rate was observed in UPS and LMS subtypes. This study expands the knowledge base beyond what is currently available from clinical trials involving checkpoint inhibitors in metastatic STS.

Background and Objectives: Outcomes of palliative-intent surgery in retroperitoneal sarcomas (RPS) are not well understood. This study aims to define indications for and outcomes after palliative-intent RPS resection., Methods: Using a retrospective 8-institution database, patients undergoing resection of primary/recurrent RPS with palliative intent were identified. Logistic regression and Cox-proportional hazards models were constructed to analyze factors associated with postoperative complications and overall survival (OS)., Results: Of 3088 patients, 70 underwent 87 palliative-intent procedures. Most common indications were pain (26%) and bowel obstruction (21%). Dedifferentiated liposarcoma (n = 17, 24%), leiomyosarcoma (n = 13, 19%) were predominant subtypes. Median OS was 10.69 months (IQR, 3.91-23.23). R2 resection (OR, 8.60; CI, 1.42-52.15; P = .019), larger tumors (OR, 10.87; CI, 1.44-82.11; P = .021) and low preoperative albumin (OR, 0.14; CI, 0.04-0.57; P = .006) were associated with postoperative complications. Postoperative complications (HR, 1.95; CI, 1.02-3.71; P = .043) and high-grade histology (HR, 6.56; CI, 1.72-25.05; P = .006) rather than resection status were associated with reduced OS. However, in R2-resected patients, development of postoperative complications significantly reduced survival (P = .042)., Conclusions: Postoperative complications and high-grade histology rather than resection status impacts survival in palliative-intent RPS resections. Given the higher incidence of postoperative complications which may diminish survival, palliative-intent R2 resection should be offered only after cautious consideration., (© 2020 Wiley Periodicals, Inc.)

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: In the randomized controlled trial (RCT) EORTC 62931, adjuvant chemotherapy failed to show improvement in relapse-free survival (RFS) or overall survival (OS) for patients with resected high-grade soft tissue sarcoma (STS). We evaluated whether the negative results of this 2012 RCT have influenced multidisciplinary treatment patterns for patients with high-grade STS undergoing resection at seven academic referral centers., Methods: The U.S. Sarcoma Collaborative database was queried to identify patients who underwent curative-intent resection of primary high-grade truncal or extremity STS from 2000 to 2016. Patients with recurrent tumors, metastatic disease, and those receiving neoadjuvant chemotherapy were excluded. Patients were divided by treatment era into early (2000-2011, pre-European Organisation for Research and Treatment of Cancer [EORTC] trial) and late (2012-2016, post-EORTC trial) cohorts for analysis. Rates of adjuvant chemotherapy and clinicopathologic variables were compared between the two cohorts. Univariate and multivariate regression analyses were used to determine factors associated with OS and RFS., Results: 949 patients who met inclusion criteria were identified, with 730 patients in the early cohort and 219 in the late cohort. Adjuvant chemotherapy rates were similar between the early and late cohorts (15.6% versus 14.6%; P = 0.73). Patients within the early and late cohorts demonstrated similar median OS (128 months versus median not reached, P = 0.84) and RFS (107 months versus median not reached, P = 0.94). Receipt of adjuvant chemotherapy was associated with larger tumor size (13.6 versus 8.9 cm, P < 0.001), younger age (53.3 versus 63.7 years, P < 0.001), and receipt of adjuvant radiation (P < 0.001). On multivariate regression analysis, risk factors associated with decreased OS were increasing American Society of Anesthesiologists class (P = 0.02), increasing tumor size (P < 0.001), and margin-positive resection (P = 0.01). Adjuvant chemotherapy was not associated with OS (P = 0.88). Risk factors associated with decreased RFS included increasing tumor size (P < 0.001) and margin-positive resection (P = 0.03); adjuvant chemotherapy was not associated with RFS (P = 0.23)., Conclusions: Rates of adjuvant chemotherapy for resected high-grade truncal or extremity STS have not decreased over time within the U.S. Sarcoma Collaborative, despite RCT data suggesting a lack of efficacy. In this retrospective multi-institutional analysis, adjuvant chemotherapy was not associated with RFS or OS on multivariate analysis, consistent with the results from EORTC 62931. Rates of adjuvant chemotherapy for high-grade STS were low in both cohorts but may be influenced more by selection bias based on clinicopathologic variables such as tumor size, margin status, and patient age than by prospective, randomized data., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Objectives: Soft-tissue sarcomas (STSs) are often treated with resection and radiation (RT)±chemotherapy. The role of RT in decreasing resection width to achieve local control is unclear. We evaluated RT on margin width to achieve local control and local recurrence (LR)., Methods: From 2000 to 2016, 514 patients with localized STS were identified from the US Sarcoma Collaborative database. Patients were stratified by a margin and local control was compared amongst treatment groups., Results: LR was 9% with positive, 4.2% with ≤1 mm, and 9.3% with >1 mm margins (P = .315). In the ≤1 mm group, LR was 5.7% without RT, 0% with preoperative RT, and 0% with postoperative RT (P < .0001). In the >1 mm group, LR was 10.2%, 0%, and 3.7% in the no preoperative and postoperative RT groups, respectively (P = .005). RT did not influence LR in patients with positive margins. In stage I-III and II-III patients, local recurrence-free survival was higher following RT (P = .008 and P = .05, respectively)., Conclusions: RT may play a larger role in minimizing LR than margin status. In patients with positive margins, RT may decrease LR to similar rates as a negative margin without RT and may be considered to decrease the risk of LR with anticipated close/positive margins., (© 2019 Wiley Periodicals, Inc.)

Background: We performed a randomized phase 3 study of trabectedin versus dacarbazine in previously-treated patients with liposarcoma/leiomyosarcoma (LPS/LMS)., Methods: Patients were randomized 2:1 to trabectedin (n = 384) or dacarbazine (n = 193) administered intravenously every 3 weeks. The primary objective was overall survival (OS). Secondary objectives were progression-free survival, objective response rate, safety, and patient-reported outcomes, all previously reported and demonstrating superior disease control with trabectedin. Results of the final OS analysis in preplanned subgroups of patients with LPS/LMS are presented., Results: At the time of the final OS analysis, 577 patients had been assigned randomly, including 423 (73%) with LMS and 154 (27%) with LPS. The median duration of treatment exposure was higher in the trabectedin arm compared with the dacarbazine arm (4 vs 2 cycles), as was the proportion of patients receiving an extended number of therapy courses (≥6 cycles: 42% vs 22%). This pattern was consistent across histological subgroups: the median number of treatment cycles (4 vs 2 for both subgroups) and proportion of patients with ≥6 treatment cycles (LMS, 43% vs 24%; LPS, 40% vs 16%). Despite improved disease control by trabectedin, no improvement in OS was observed; the final median OS for trabectedin versus dacarbazine was 13.7 versus 13.1 months (P = .49). Sensitivity analyses of OS suggest confounding by post-study anticancer therapies, which were utilized in most patients in both treatment arms (71% vs 69%, respectively)., Conclusion: The final OS results demonstrated comparable survival between LPS/LMS patients receiving trabectedin or dacarbazine, which is consistent with the interim analysis results. Both LPS and LMS demonstrated improved disease control with trabectedin., (© 2019 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.)

Background: The postoperative outcomes of elderly patients undergoing resection of retroperitoneal sarcomas (RPS) have not been widely studied., Methods: Patients undergoing surgical resection for primary or recurrent RPS between 2000 and 2015 at participating US Sarcoma Collaborative institutions were identified. Patient demographics, perioperative morbidity, mortality, length of stay, discharge to home, disease-specific survival, and disease-free survival were compared between elderly (≥70 y, n = 171) and nonelderly (<70 y, n = 494) patients., Results: There was no difference in perioperative morbidity (total and major complications elderly versus nonelderly: 39% versus 35%; P = 0.401 and 18% versus 17%; P = 0.646, respectively) or mortality between elderly and nonelderly patients with each group experiencing a 1% 30-d mortality rate. Length of stay and 30-d readmission rates were similar (elderly versus nonelderly; 7 d interquartile range [IQR: 5-9] versus 6 d [IQR: 4-9], P = 0.528 and 11% versus 12%, P = 0.667). Elderly patients were more likely to be discharged to a skilled nursing or rehabilitation facility (elderly versus nonelderly; 19% versus 7%, P < 0.001). There was no difference in 3-y disease-free survival between the elderly and nonelderly patients (41% versus 43%, P = 0.65); however, elderly patients had a lower 3-y disease-specific survival (60% versus 76%, P < 0.001). In elderly patients, the presence of multiple comorbidities and high-grade tumors were most predictive of outcomes., Conclusions: Advanced age was not associated with an increased risk of perioperative morbidity and mortality following resection of RPS in this multi-institutional review. Although short-term oncologic outcomes were similar in both groups, the risk of death after sarcoma recurrence was higher in elderly patients and may be related to comorbidity burden and tumor histology., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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.)