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The concept of "oligometastatic" disease suggests the presence of intermediate states between localized disease and widespread metastases, which may be potentially treatable with curative therapeutic strategies. Metastases local therapy (MLT) can be accomplished through various techniques such as stereotactic ablative radiotherapy (SABR), radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation, or surgical metastasectomy. The incorporation of MLT in the multidisciplinary treatment of patients with metastatic sarcoma is complex. Retrospective studies support consideration of MLT for selected patients based on factors such as patient condition, disease biology, histologic type, and disease burden. Decisions regarding type and timing of MLT should be made after multidisciplinary discussion including radiation oncologists, surgical and orthopedic oncologists, medical oncologists, and interventional radiology to explore all options before treatment decsions. All MLT techniques have advantages and disadvantages and should be performed in centers specialized in the care of complex oncology patients where various options can be explored concurrently or sequentially for each patient. Future studies evaluating quality of life and patient-reported outcomes are necessary to adequately align patient goals and optimal outcomes. This article reviews the medical scenarios that may benefit the use of MLT, evaluates the distinct advantages and disadvantages associated with these various techniques, and analyzes the findings from pivotal series to provide a comprehensive understanding of its role in clinical practice., (© 2024. Crown.)

Purpose: To investigate the value of multi-parametric MRI-based radiomics for preoperative prediction of lung metastases from soft tissue sarcoma (STS)., Methods: In total, 122 patients with clinicopathologically confirmed STS who underwent pretreatment T1-weighted contrast-enhanced (T1-CE) and T2-weighted fat-suppressed (T2FS) MRI scans were enrolled between Jul. 2017 and Mar. 2021. Radiomics signatures were established by calculating and selecting radiomics features from the two sequences. Clinical independent predictors were evaluated by statistical analysis. The radiomics nomogram was constructed from margin and radiomics features by multivariable logistic regression. Finally, the study used receiver operating characteristic (ROC) and calibration curves to evaluate performance of radiomics models. Decision curve analyses (DCA) were performed to evaluate clinical usefulness of the models., Results: The margin was considered as an independent predictor (p < 0.05). A total of 4 MRI features were selected and used to develop the radiomics signature. By incorporating the margin and radiomics signature, the developed nomogram showed the best prediction performance in the training (AUCs, margin vs. radiomics signature vs. nomogram, 0.609 vs. 0.909 vs. 0.910) and validation (AUCs, margin vs. radiomics signature vs. nomogram, 0.666 vs. 0.841 vs. 0.894) cohorts. DCA indicated potential usefulness of the nomogram model., Conclusions: This feasibility study evaluated predictive values of multi-parametric MRI for the prediction of lung metastasis, and proposed a nomogram model to potentially facilitate the individualized treatment decision-making for STSs., (© 2024. The Author(s).)

Background: Metastases to the bone of aortic sarcoma include osteolytic and nonosteolytic lesions. This study aims to review the clinical symptoms, the sites, and diagnostic methods of bone metastases and to compare the osteolytic and nonosteolytic metastases of patients with aortic sarcoma., Methods: A systematic search was conducted in PubMed and scientific journals published from 1972 to 2022. Database included reports of aortic sarcomas with bone metastasis published in English and in French. Characteristics of patients were analyzed with chi-square test or Fisher's exact test between lytic and sclerotic bone metastases., Results: In 29 patients with bone destruction, the symptoms of low back pain and claudication were observed in 10 (34.5%) and 9 cases (31%), respectively. Acute ischemia of the legs and arms accounted for 7 cases (24.1%). There were 4 cases with hypertension (13.8%) and 5 cases with chest pain or abdominal pain or epigastric pain (17.2%). Metastases to the vertebrae, pelvis, and femur were observed in 14 (48.3%), 12 (41.4%), and 11 cases (37.9%), respectively. Osteolytic lesions were detected at the time of diagnosis in 16/29 (55.2%) cases. In 27 aortic sarcoma patients with sclerotic bone metastases, symptoms of hypertension were observed in 10 (37.0%), of back pain in 7 (25.9%), of chest pain or abdominal pain in 5 cases (18.5%). Acute ischemia of the leg occurred in 6 cases (22.2%). Metastases to the vertebrae, bone, pelvis, and femur were observed in 10 (37.0%), 9 (33.3%), 7 (25.9%), and 6 cases (22.2%), respectively. The sign of claudication and methods for detected bone destruction by X-rays were the difference between osteolytic and nonosteolytic metastases of aortic sarcoma (P = 0.019; P = 0.001), respectively., Conclusions: Back pain is a common symptom of aortic sarcoma with bone metastasis. The sign of intermittent claudication is the difference between osteolytic and nonosteolytic metastases of aortic sarcoma. Bone destruction occurred in all bones, but mainly in vertebrae, pelvis, and femur. Methods for detection of bone destruction are mainly by X-rays or computed tomography (CT). Bone destruction was an important sign to detect aortic sarcoma. Sclerotic bone metastases occurred mainly in vertebrae, pelvis, bone, and femur. The detection of sclerotic bone metastases is based on magnetic resonance imaging, positron emission tomography/CT, and autopsy., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To evaluate outcomes following percutaneous image-guided ablation of soft tissue sarcoma metastases to the liver., Materials and Methods: A single-institution retrospective analysis of patients with a diagnosis of metastatic soft tissue sarcoma who underwent percutaneous image-guided ablation of hepatic metastases between January 2011 and December 2021 was performed. Patients with less than 60 days of follow-up after ablation were excluded. The primary outcome was local tumor progression-free survival (LPFS). Secondary outcomes included overall survival, liver-specific progression-free survival. and chemotherapy-free survival., Results: Fifty-five patients who underwent percutaneous ablation for 84 metastatic liver lesions were included. The most common histopathological subtypes were leiomyosarcoma (23/55), followed by gastrointestinal stromal tumor (22/55). The median treated liver lesions was 2 (range, 1-8), whereas the median size of metastases were 1.8 cm (0.3-8.7 cm). Complete response at 2 months was achieved in 90.5% of the treated lesions. LPFS was 83% at 1 year and 80% at 2 years. Liver-specific progression-free survival was 66% at 1 year and 40% at 2 years. The overall survival at 1 and 2 years was 98% and 94%. The chemotherapy-free holiday from the start of ablation was 71.2% at 12 months. The complication rate was 3.6% (2/55); one of the complications was Common Terminology Criteria for Adverse Events grade 3 or higher. LPFS subgroup analysis for leiomyosarcoma versus gastrointestinal stromal tumor suggests histology-agnostic outcomes (2 years, 89% vs 82%, p = .35)., Conclusion: Percutaneous image-guided liver ablation of soft tissue sarcoma metastases is safe and efficacious., (© 2024 American Cancer Society.)

Pediatric renal sarcomas are exceedingly rare entities that present diagnostic challenges. We report a remarkable case of a 14-month-old female with an 8 cm right renal mass, accompanied by disseminated bone metastases, posing intricate clinical and histopathological dilemmas. Initial suspicion leaned towards clear cell sarcoma of the kidney (CCSK), however, subsequent histological examination post-chemotherapy revealed high-grade osteosarcoma and further differential considerations arose, including primary renal osteosarcoma and osseous osteosarcoma with secondary renal involvement. Despite inconclusive histology, treatment proceeded with the UH1 chemotherapy protocol for CCSK, incorporating high-dose Methotrexate for potential osteosarcoma, and the patient demonstrated a favorable response to therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: When the clinical presentation is related to the metastatic mass and a radiologically solitary tumor focus is detected, especially in cases where clinical information is not taken into account or is insufficient, if a possible metastatic neoplasia is not kept in mind then it is possible to evaluate the tumor as a primary breast neoplasm. In this study, it is aimed to present our cases of non-hematopoietic metastatic neoplasms and to evaluate the clinicopathological features that may aid in distinguishing metastatic from primary neoplasms., Material and Methods: This study includes cases diagnosed with metastatic non-hematopoietic breast neoplasm in breast resection materials in our center, between the years 2010-2023. All cases were analyzed retrospectively by evaluating clinicopathological features., Results: Of the 15 subjects included in the study, 11 (73%) were female and 4 (27%) were male. The mean age of the patients were 46.9 ranged from 22 to 63 years. The most frequent metastatic malignancy was carcinoma (60%), followed by melanoma (33%) and sarcoma (7%). Of the 9 patients with metastatic carcinoma, the primary tumor originated from the lungs in 4, from gastrointestinal system in 2, female genital tract in 2, and kidney in 1 patient. Sarcoma diagnosis was given in a single patient and the histology was a leiomyosarcoma originating from kidney., Conclusion: A careful histomorphological and immunohistochemical evaluation and a detailed examination of the clinicoradiological data are critical to establish the right course in patient management, treatment plan and to correctly predict the prognosis., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Sarcomas, a group of neoplasms comprising both tissue and bone soft tissue tumors, has an increasing prevalence in recent years. Prognosis significantly hinges on early detection, and if not detected early, may consequently metastasize. This review will be the first systematic review and meta-analysis characterizing the presentation and progression of brain metastases from bone and soft tissue cancers., Methods: The PubMed, Scopus, and Web of Science databases were queried to identify studies reporting the incidence of intracranial brain metastases from primary sarcoma to the present. Abstract and full-text screening of 1822 initial articles returned by preliminary search yielded 28 studies for inclusion and data extraction. Qualitative assessment of the studies was conducted in accordance with the Newcastle-Ottawa Scale criteria. Meta-analyses were applied to assess risk factors on outcomes., Results: The average age within the cohort was 27.9 years with a male and female prevalence of 59.1% and 40.9%, respectively. The odds ratio for living status (dead/alive) was calculated for several risk factors - male/female [OR 1.14, 95% CI 0.62, 2.07], single/multiple metastases [OR 0.67, 95% CI 0.35, 1.28], lung metastases/not [OR 1.63, 95% CI 0.85, 3.13], surgery/no surgery [OR 0.49, 95% CI 0.20, 1.21]. The standardized mean differences for duration from diagnoses to metastases were likewise analyzed - male/female [SMD 0.13, 95% CI -0.15, 0.42], single/multiple metastases [SMD 0.11, 95% CI -0.20, 0.42], lung metastases/not [SMD -0.03, 95% CI -0.38, 0.32], surgery/no surgery [SMD 0.45, 95% CI -0.18, 1.09]. The standardized mean differences for duration from metastases to death were analyzed - lung metastases/not [SMD 0.43, 95% CI -0.08, 0.95]., Conclusions: Our study observed no statistically significant differences in mortality rate among several patient risk factors. Consequentially, there lacks a clear answer as to whether or not an association between mortality rates exists with these patient factors. As such, it is important to continue research in brain-metastasizing sarcomas despite their relative rarity., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Sarcomas constitute approximately 1% of adult cancers and 8%-10% of paediatric cancers. Undifferentiated pleomorphic sarcoma (UPS) is a type of soft-tissue sarcoma (STS) characterised by dedifferentiated cancer cells. The most common sites of metastasis for UPS include the lungs, liver, bones and regional lymph nodes. Brain metastasis is rare, affecting only 1%-8% of STS patients. This report presents a unique case of a woman in her 80s with a TET2 -mutant UPS metastatic to the lung and brain., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Oral metastatic sarcomas (OMSs) occur only occasionally, and information about their characteristics is based on the restricted number of cases reported in the literature. This study aims to systematically review the English literature to recognize the clinicopathologic characteristics of OMSs. An electronic search was performed in PubMed Central and Scopus databases. The search included all the published articles (human case reports and case series) up till April 2023, with no time restrictions. OMSs were slightly more prevalent in males in their fifth to seventh decades of life. However, a high percentage of OMSs has been reported in the second decade of life. Lower extremities, breasts and uterus are the most common primary origin of metastatic sarcoma. Gingiva and mandible were common locations in the oral cavity for metastatic deposits. Generally, they demonstrated widespread affliction. The mean time interval between primary tumor detection and diagnosis of the oral metastasis was about 33.54 ± 36.19 months. Death was reported in 83 patients (67.48 %) with a mean survival rate of 7.98 ± 10.30 months. The most common microscopic tumor types were leiomyosarcoma (n = 21, 17 %), followed by angiosarcoma (n = 20, 16.26 %) and osteosarcoma (n = 18, 14.63 %). In conclusion, while oral metastases of sarcomas are not common, those should be considered in the differential diagnosis of the oral lesions. Although OMSs show a high occurrence in the 7th decade of the life, the average age of patients with oral involvement is lower than the overall metastatic lesions. OMSs may present as widespread disease with poor prognosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Patients with stage IV cancer often experience diminished quality of life and pain. Although palliative amputation (PA) can reduce pain, it is infrequently performed because of the morbidity associated with amputation and the limited life expectancy in this population. Here, we describe the indications for PA in patients with stage IV carcinoma or sarcoma and discuss their clinical courses and outcomes. We hypothesized that PA would be associated with reduced pain and improved quality of life in these patients., Methods: We retrospectively reviewed medical records of all patients who underwent major amputation (proximal to the ankle or wrist) for metastatic sarcoma or carcinoma from January 1995 to April 2021. We excluded patients who underwent amputation for indications other than palliation. Cox proportional hazards regression analysis was used to determine factors associated with survival after PA., Results: Twenty-six patients underwent PA (11 for carcinoma, 15 for sarcoma). The most common indications for PA were pain (all patients) and fungating tumor (16 patients). PA was the initial surgery in 7 patients. Forequarter amputations were the most common procedure (6 patients). All patients reported reduced pain after PA, with the mean (±standard deviation) visual analog pain score (on a 10-point scale) decreasing from 5.7 ± 2.9 preoperatively to 0.43 ± 1.3 postoperatively (p < 0.001). The mean preoperative ECOG score was 1.9 ± 0.2 compared with 1.3 ± 0.1 postoperatively (p < 0.001). Fourteen patients were fitted for prostheses (6 upper extremity, 8 lower extremity). Two patients had local recurrence, both within 6 months after PA. The mean survival time after PA was 13 ± 12 months, and mean follow-up was 28 ± 29 months. Mean survival time after PA was not significantly different between patients with sarcoma (11 ± 11 months) versus carcinoma (15 ± 14 months) (p = 0.51). Adjuvant chemotherapy was positively associated with survival; no other factors were associated with survival., Conclusions: PA was associated with significantly reduced pain in all patients with stage IV cancer. PA should be considered for those with intractable pain, fungating tumors, or symptoms that diminish quality of life., Level of Evidence: Level III., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The number of recognized epithelioid soft tissue neoplasms continues to increase and includes epithelioid schwannoma, sclerosing epithelioid fibrosarcoma, and emerging entities such as sarcomas with GLI1 alterations. Here, we describe 23 cases of a previously unrecognized entity, provisionally termed "pseudoendocrine sarcoma." Pseudoendocrine sarcoma is a rare, distinctive tumor of uncertain lineage with a predilection for paravertebral soft tissue in older adults. Fifteen patients (65%) were male and 8 were female. Age at presentation ranged from 29 to 78 years (median: 62 y). Nineteen tumors (83%) occurred in truncal locations, including 15 tumors (65%) in paravertebral soft tissue; other locations included the posterior head (2 tumors), thigh (1), and orbit (1). Tumor size ranged from 2 to 19 cm (median: 6.35 cm). Pseudoendocrine sarcoma is composed of sheets, trabeculae, and nests of epithelioid or ovoid cells with indistinct borders, palely eosinophilic cytoplasm, and highly monomorphic, round nuclei with speckled chromatin. Pseudoglandular architecture was at least focally present in 16 tumors (70%), large extracellular hyaline globules were identified in 12 tumors (52%), and psammomatous calcifications were present in 8 (35%). Metaplastic ossification was identified in 2 tumors, and myxoid stroma was present in 1. Lymphovascular invasion was present in 5 of 18 tumors (28%). Immunohistochemistry demonstrated that most tumors showed nuclear positivity for β-catenin (20/21 tumors; 95%), and some showed at least focal positivity for S-100 (9/22; 41%), desmin (3/8; 38%), or CD34 (2/8; 25%). All tumors were negative for neuroendocrine and epithelial markers, including synaptophysin (21 tumors), chromogranin (19), INSM1 (4), pan-K (16), CAM5.2 (13), AE1/AE3 (6), epithelial membrane antigen (20), and E-cadherin (13). DNA sequencing detected CTNNB1 point mutations in all 6 sequenced tumors: D32H, S33C, S33F, S37A, S37C, and S37F. RNA sequencing was negative for gene fusions in all 6 sequenced tumors. Clinical follow-up was available for 17 patients (74%; range: 4 mo to 20 y; median: 3.5 y), including 14 patients with >1 year of follow-up. Six of 14 patients with long-term follow-up experienced local recurrence (43%, at intervals of 3 to 6 y). One tumor showed a local lymph node metastasis within the primary excision specimen, and 3 patients developed distant lung metastases (21%). No patient died of the disease as yet. Despite its bland morphology and resemblance to the well-differentiated neuroendocrine tumor, pseudoendocrine sarcoma is best considered an intermediate-grade sarcoma, given its pathologic characteristics and clinical behavior., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The objectives of this study were to clarify whether resection of primary tumor in the extremities for patients with metastatic soft-tissue sarcoma (STS) improves survival, and to clarify patient groups for whom primary tumor resection should be considered., Methods/patients: Using the surveillance, epidemiology, and end results database, we identified 1453 patients with metastatic STS of the extremities at initial presentation between 1983 and 2016. Of these 1453 patients, 898 patients underwent primary tumor resection (Surgery group), and 555 patients did not (No-surgery group)., Results: After adjusting for patient background by propensity score matching, a total of 804 patients were included for analysis. Patients in the Surgery group showed improved survival (cancer-specific survival (CSS) hazard ratio (HR) = 0.59, 95% confidence interval (CI) 0.50-0.71 overall survival rate (OS) HR = 0.60, 95% CI 0.51-0.70). In subclass analysis, patients with high-grade STS, undifferentiated pleomorphic sarcoma, leiomyosarcoma, or synovial sarcoma showed improved survival in the Surgery group (high grade-CSS HR = 0.57, 95% CI 0.45-0.72, OS HR = 0.58, 95% CI 0.48-0.71; undifferentiated pleomorphic sarcoma-CSS HR = 0.60, 95% CI 0.42-0.84, OS HR = 0.61, 95% CI 0.46-0.82; leiomyosarcoma-CSS HR = 0.50, 95% CI 0.33-0.75, OS HR = 0.50, 95% CI 0.35-0.72; synovial sarcoma-CSS HR = 0.46, 95% CI 0.31-0.68, OS HR = 0.43, 95% CI 0.30-0.62)., Conclusions: Our results indicated that primary tumor resection in metastatic STS exerts positive impacts on survival. Further clinical research is needed to confirm these results., (© 2021. Federación de Sociedades Españolas de Oncología (FESEO).)

Background/aim: Brain metastasis is a rare condition among patients with soft tissue sarcoma (STS), and its precise incidence remains unclear. The aim of this study was to investigate which patients should be screened for brain metastasis., Patients and Methods: We identified all patients with STS diagnosed between 2010 and 2015 in the SEER database. Incidence of brain metastasis at initial presentation and higher incidence of brain metastasis by histological subtype were investigated. In addition, risk factors for brain metastasis were examined., Results: A total of 26,676 patients were included for analysis, of whom 162 patients (0.6%) had brain metastasis. Alveolar soft part sarcoma (6.3%), malignant hemangioendothelioma (3.1%) and malignant schwannoma (2.6%) showed higher incidence of brain metastasis. Deep-rooted tumor, trunk tumor, and histological high-grade tumor tended to show higher incidence of brain metastasis., Conclusion: Risk factors for brain metastasis were deep location, trunk development and histologically high-grade tumor, or specific histological subtypes., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: To investigate the effect of surgical stabilization for patients with metastatic spinal disease on objective mobility metrics., Methods: A retrospective chart review identified patients who had mechanical back pain from metastatic spinal disease and underwent spinal stabilization during 2017. Mobility metrics, the Activity Measure for Post-Acute Care (AM-PAC) inpatient mobility short form (IMSF) and the Johns Hopkins Highest Level of Mobility (JH-HLM), were reviewed., Results: A total of 26 patients were included in the analysis with median hospital stay of 8 days. Preoperative JH-HLM scores were available for 17 patients with a mean score of 5.4, increasing to mean score of 6.6 at last follow-up (P = 0.036). Preoperative AM-PAC IMSF scores were available for 14 patients with a mean score of 19.4, decreasing slightly to a mean score of 18.7 at last follow-up (P = 0.367). Last follow-up with mobility metrics occurred a median of 6.5 days postoperatively (range: 3-66 days). Multivariable analysis showed that American Spinal Injury Association and Karnofsky Performance Status scores were significantly associated with both JH-HLM and AM-PAC mobility scores at last follow-up. A higher JH-HLM or AM-PAC score was significantly associated with direct home discharge and a higher AM-PAC score was associated with shorter hospital stay., Conclusions: Surgical stabilization for patients with mechanical back pain secondary to metastatic spinal disease might lead to an objective improvement in JH-HLM score. JH-HLM and AM-PAC scores may be correlated with length of hospital stay and discharge disposition. Future studies are encouraged to further characterize the role of these mobility metrics in the management plan of these patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Epithelioid sarcoma (EpS) is a rare malignant neoplasm that accounts for < 1% of adult soft tissue sarcomas. Primary EpS of the bone is extremely rare and only a few cases have been reported to date. We report a case of primary distal-type EpS of the lumbar vertebra. A 30-year-old man without any history of malignant tumors had complained of lumbago for 3 months before visiting the hospital. Magnetic resonance imaging (MRI) of the lumbar spine showed a high signal intensity on the fat-suppressed T2-weighted image (WI) and a low signal on the T1WI at the L1 vertebral body. The tumor protruded toward the anterior components. Systemic radiological examination revealed no other lesion. A biopsy revealed a primary malignant tumor with epithelioid features. After chemotherapy, total en bloc spondylectomy was performed. Macroscopically, the tumor replaced the entire L1 with necrosis. Histologically, the tumor showed nodules of epithelioid cells that were strongly positive for epithelial markers, but a lack of INI1 expression. Central necrosis in the tumor nodule was also observed. This tumor showed loss of heterozygosity at the SMARCB1 locus but without the SMARCB1 mutation. The result of Foundation One ®CDx showed no actionable mutations. Seven months after surgery, a subcutaneous metastasis to the left cheek and bilateral lung metastasis with pleural dissemination were observed on radiological examination. A final diagnosis of distal-type EpS was made based on these findings. The patient died of the disease 8 months after surgery., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To report the interim analysis of the phase II single-arm noninferiority trial, testing the upfront use of dexrazoxane with doxorubicin on progression-free survival (PFS) and cardiac function in soft-tissue sarcoma (STS)., Patients and Methods: Patients with metastatic or unresectable STS who were candidates for first-line treatment with doxorubicin were deemed eligible. An interim analysis was initiated after 33 of 65 patients were enrolled. Using the historical control of 4.6 months PFS for doxorubicin in the front-line setting, we tested whether the addition of dexrazoxane affected the efficacy of doxorubicin in STS. The study was powered so that a decrease of PFS to 3.7 months would be considered noninferior. Secondary aims included cardiac-related mortality, incidence of heart failure/cardiomyopathy, and expansion of cardiac monitoring parameters including three-dimensional echocardiography. Patients were allowed to continue on doxorubicin beyond 600 mg/m 2 if they were deriving benefit and were not demonstrating evidence of symptomatic cardiac dysfunction., Results: At interim analysis, upfront use of dexrazoxane with doxorubicin demonstrated a PFS of 8.4 months (95% confidence interval: 5.1-11.2 months). Only 3 patients were removed from study for cardiotoxicity, all on > 600 mg/m 2 doxorubicin. No patients required cardiac hospitalization or had new, persistent cardiac dysfunction with left ventricular ejection fraction remaining below 50%. The median administered doxorubicin dose was 450 mg/m 2 (interquartile range, 300-750 mg/m 2 )., Conclusions: At interim analysis, dexrazoxane did not reduce PFS in patients with STS treated with doxorubicin. Involvement of cardio-oncologists is beneficial for the monitoring and safe use of high-dose anthracyclines in STS. See related commentary by Benjamin and Minotti, p. 3809 ., (©2021 American Association for Cancer Research.)

Patients with previously treated, recurrent or metastatic sarcomas who have progressed on multiples lines of systemic therapy may have limited options for local control. We evaluated outcomes of palliative proton therapy with the quad shot regimen to unresectable disease for patients with recurrent and/or metastatic sarcoma. From 2014 to 2018, 28 patients with recurrent or metastatic sarcomas were treated to 40 total sites with palliative proton RT with quad shot (14.8 Gy/4 twice daily). Outcomes included toxicity, ability to receive further systemic therapy, and subjective palliative response. Univariate analysis was performed for local progression-free survival (LPFS) and overall survival (OS). Of the 40 total sites, 25 (62.5%) received ≥3 cycles with median follow up of 12 months (IQR 4-19). The most common histologies were GIST (9; 22.5%) and leiomyosarcoma (7; 17.5%). A total of 27 (67.5%) sites were located in the abdomen or pelvis. Seventeen (42.5%) treatments involved concurrent systemic therapy and 13 (32.5%) patients received further systemic therapy following proton therapy. Overall subjective palliative response was 70%. Median LPFS was 11 months and 6-month LPFS was 66.1%. On univariate analysis, receipt of four cycles of quad shot (HR 0.06, p = 0.02) and receipt of systemic therapy after completion of radiation therapy (HR 0.17, p = 0.02) were associated with improved LPFS. Three grade 3 acute toxicities were observed. The proton quad shot regimen serves as a feasible alternative for patients with previously treated, recurrent or metastatic sarcomas where overall treatment options may be limited., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Interstitial brachytherapy for pulmonary tumours is an alternative to stereotactic radiotherapy, allowing high conformity despite it being an invasive technique. The aim of the study was the analysis of dose distribution, toxicity and tumour response rates., Methods: In the years 2014-2019, 27 patients with pulmonary tumours received 36 interstitial brachytherapies with Ir-192: 11 patients with non-small cell lung cancer, 16 patients with pulmonary metastases of other entities., Results: Patients were treated with a median (interquartile range) prescription dose of 20 (20-26) Gy in a single fraction. Mean lung dose to the ipsilateral lung was 2.8 (1.6-4.7) Gy. Maximum doses to the heart, oesophagus, thoracic wall and spinal cord were 2.4 (1.8-4.6) Gy, 2.0 (1.2-6.2) Gy, 12.6 (8.0-18.2) Gy and 1.5 (0.6-3.9) Gy. Median survival after treatment was 15 months, with a 1- and 2‑year local control of 84% and 60%. Median overall survival after initial cancer diagnosis was 94 months; 2 years following brachytherapy, 75% of patients with colorectal cancer vs. 37% with other histologies were alive; p = 0.14. In 69% (n = 25), brachytherapy could be performed without acute complications. A self-limiting bleeding occurred in 8% (n = 3), fever in 3% (n = 1), pneumothorax in 17% (n = 6), and pulmonary failure in 3% (n = 1). Patients with > 20 Gy in 95% of planning target volume had higher pneumothorax rates needing intervention (31% vs. 5%, p = 0.04)., Conclusions: Interstitial brachytherapy for pulmonary tumours is a highly conformal therapy with minimal doses to the organs at risk. For the majority of patients, treatment can be performed without relevant complications in a single fraction with a satisfactory local control.

Background: Limited data are available on the real-world effectiveness and safety of systemic therapies for advanced (surgically unresectable and/or metastatic) epithelioid sarcoma (ES)., Methods: A retrospective medical records review was conducted in patients with advanced ES who were initiating first-line or ≥2 lines of systemic therapy (2000-2017) at 5 US cancer centers. The real-world overall response rate (rwORR), the duration of response (rwDOR), the disease control rate (rwDCR) (defined as stable disease for ≥32 weeks or any duration of response), and progression-free survival (rwPFS) were assessed by radiology reports. Overall survival (OS), rwDOR, and rwPFS were estimated from the time therapy was initiated using the Kaplan-Meier method. Serious adverse events were assessed., Results: Of 74 patients (median age at diagnosis, 33 years; range, 10.6-76.3 years), 72% were male, and 85% had metastatic disease. The median number of lines of therapy was 2 (range, 1-7 lines of therapy), and 46 patients (62%) received ≥2 lines of systemic therapy. First-line regimens were usually anthracycline-based (54%) or gemcitabine-based (24%). For patients receiving first-line systemic therapy, the rwORR was 15%, the rwDCR was 20%, the median rwDOR was 3.3 months (95% CI, 2.1-5.2 months), the median rwPFS was 2.5 months (95% CI, 1.7, 6.9 months), and the median OS was 15.2 months (95% CI, 11.4-21.7 months). For those who received ≥2 lines of systemic therapy, the rwORR was 9%, the rwDCR was 20%, the median rwDOR was 4.5 months (95% CI, 0.7-5.6 months), and the median rwPFS was 6.0 months (95% CI, 3.2-7.4 months). Over one-half of patients (51.4%) experienced an adverse event, most frequently febrile neutropenia (14%), pain (10%), anemia, dyspnea, fever, thrombocytopenia, or transaminitis (5% each)., Conclusions: Systemic therapies demonstrate limited efficacy in patients with advanced ES and have associated toxicities., (© 2020 Epizyme, Inc. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Objectives: To determine the incidence of pulmonary metastases on chest CT in trunk and extremity soft tissue sarcoma based on two size criteria, and to identify factors associated with metastases., Methods: Retrospective review of chest CT studies in patients with trunk and extremity soft tissue sarcoma over an 18-month period. Data collected included patient age/sex, tumour location, size and relationship to fascia. All chest CTs were reviewed for the presence of metastases which were diagnosed according to two size criteria: multiple nodules > 5 mm in size or multiple nodules > 10 mm in size. Follow-up CT studies were reviewed in cases initially considered indeterminate., Results: 127 males and 73 females were included (mean age 57.1 years; range 10-90 years). 147 (73.5%) tumours were deep to the fascia and 53 (26.5%) superficial. Tumour size classified according to the 12 AJCC 2019 criteria was: T1 = 52, T2 = 76, T3 = 39, T4 = 33. Based on nodule size >5 mm, 73 (36.5%) patients had no metastases, 42 (21%) had metastases, while 85 (42.5%) studies were indeterminate. Based on nodule size >10 mm, 73 (36.5%) patients had no metastases, 28 (14%) had metastases, while 99 (49.5%) studies were indeterminate. Larger maximum dimension of the primary tumour was a risk factor for pulmonary metastases using both size criteria., Conclusion: The incidence of pulmonary metastases at presentation in trunk and extremity soft tissue sarcoma is 14-21%. 42.5-49.5% of chest CTs were indeterminate., Advances in Knowledge: The incidence of pulmonary metastases at presentation in trunk and extremity soft tissue sarcoma is 14-21%. Indeterminate pulmonary nodules are also very common.

Introduction: Lymph node metastasis (LNM) in soft tissue sarcomas (STS) are uncommon, occurring in only 3% - 5% of all sarcomas, and are classified as Stage IV, along with distant metastasis (DM). This paper compares the prognosis of patients with lymphatic and DM, in extremity STS (eSTS)., Methods: A retrospective study was carried out in a high-volume sarcoma center; 853 patients with eSTS sarcomas were identified and classified from January 1, 1997 to December 31, 2017. Cases with pathological confirmation of LNM were included. Five-year survival rates were analyzed using the Kaplan-Meier method and the Cox proportional hazards model., Results: LNM was present in 46 of the cases (5.4%), with an overall survival of 21 months (95% confidence interval [CI], 16.7 - 25.2), compared to 18 months (95% confidence interval [CI], 14.2 - 21.7) in those with only DM. Median recurrence-free survival was 21 months (95% confidence interval [CI], 19.7 - 22.4), vs. 20 months (95% confidence interval [CI], 16.2- 23.7), respectively. LNM only and DM only had also a similar OS of 21 months (95% CI 16.7-25.2) vs 18 months (95% CI 14.2-21.7. N1M1 cases had the worse median OS with 15 months (95% confidence interval [CI], 10.9-19.7) CONCLUSIONS: Overall survival and recurrence free survival in patients with lymph node disease and metastatic disease are similar. However prognosis is worse in N1M1. Use of systemic treatment in patients with LNM is not as common as in metastatic cases, this difference in treatment and the fact that prognosis is similar suggests that both biological behavior and effect of treatment have been underestimated. A subclassification of clinical stage IV might be the next step., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: The goal of this study is to construct nomograms to effectively predict the distant metastatic sites and overall survival (OS) of soft tissue sarcoma (STS) patients., Methods: STS case data between 2010 and 2015 for retrospective study were gathered from public databases. According to the chi-square and multivariate logistic regression analysis determined independent predictive factors of specific metastatic sites, the nomograms based on these factors were consturced. Subsequently, combined metastatic information a nomogram to predict 1-, 2-, and 3-year OS of STS patients was developed. The performance of models was validated by the area under the curve (AUC), calibration plots, and decision curve analyses (DCA)., Results: A total of 7001 STS patients were included in this retrospective study, including 4901 cases in the training group and the remaining 2,100 patients in the validation group. Three nomograms were established to predict lung, liver and bone metastasis, and satisfactory results have been obtained by internal and external validation. The AUCs for predicting lung, liver, and bone metastases in the training cohort were 0.796, 0.799, and 0.766, respectively, and in the validation cohort were 0.807, 0.787, and 0.775, respectively, which means that the nomograms have good discrimination. The calibration curves showed that the models have high precision, and the DCA manifested that the nomograms have great clinical application prospects. Through univariate and multivariate COX regression analyses, 8 independent prognosis factors of age, grade, histological type, tumor size, surgery, chemotherapy, radiatiotherapy and lung metastasis were determined. A nomogram was then constructed to predict the 1-, 2-, and 3-years OS, which has a good performance in both internal and external validations., Conclusion: The nomograms for predicting specific metastatic sites and OS have good discrimination, accuracy and clinical applicability. The models could accurately predict the metastatic risk and survival information, and help clinical decision-making.

Background: Primary pulmonary sarcoma (PPS) is a rare malignant lung neoplasm, and there is very little medical evidence about treatment of PPS. The aim of this study is to clarify the clinical characteristics and therapeutic outcome of patients who underwent surgical resection for PPS., Methods: We retrospectively reviewed the records of patients who underwent surgical resection for PPS in our institution between 1995 and 2014. Cases who only underwent biopsy were excluded., Results: A total of 24 patients (18 males, 6 females), with a median age of 60 (interquartile range: 44-67) years, were analyzed. The surgical procedures performed in these patients were pneumonectomy ( n  = 10), lobectomy ( n  = 11), and wedge resection ( n  = 3). Complete resection was achieved in 16 patients. The pathological stages (tumor, node, metastases lung cancer classification, 8th edition) of the patients were I ( n  = 4), II ( n  = 12), III ( n  = 2), and IV ( n  = 5), and there were four cases of lymph node metastasis. The 5-year overall survival rate of the patients was 50% (95% confidence interval [CI]: 29-72). Adverse prognostic factors for overall survival were incomplete resection (hazard ratio [HR]: 4.4, 95% CI: 2.1-42), advanced pathological stage (HR 14, 95% CI: 2.8-66), higher pathological grade (HR 4.5, 95% CI: 1.2-17), and tumor size ≥ 7 cm (HR 4.7, 95% CI: 1.1-21)., Conclusions: Our series of PPS revealed that incomplete resection, advanced pathological stage, higher pathological grade, and tumor size were unfavorable factors for long-term survival., Competing Interests: None., (Thieme. All rights reserved.)

The malignancy progression is an evolutionary process in which tumor clones are selected and competed for the duration of the disease. Intratumor heterogeneity is one of the key problems in the development of treatment methods for cancer patients. In this study we obtained metastatic soft tissue and bone sarcomas (STBSs) cultures from 54 patients, performed in vitro cloning and randomly selected 83 clones. Cloning was successful in 22 cases (40.7%). STBSs cultures with a high clonogenic potential (CP) were characterized by greater proliferative activity and increased Aldehyde dehydrogenase (ALDH) expression. We studied the transcription activity of the following cancer-testis genes (CTG): MAGE, NY-ESO-1, PRAME, GAGE, SSX1, HAGE1, PASD1, SCP1, SEMG1, SLLP1 and SPANXA1. The SEMG1 expression wasn't registered in any studied case. CTG activity wasn't observed in 10 cases out of 52 (19,2%) STBS cultures. We observed CTG activation and increased transcription activity in 82 STBSs clones. Clustering by the gene profile has revealed three different patterns: 1 st - with low expression CTG, 2nd - with co-expression GAGE1, PASD1 and PRAME, 3d - with co-expression SLLP1 and GAGE1. The last two clusters included most cloned cell lines and their clones. CP of STBSs cell lines was associated with the parameters of patients overall survival (OS) at comparable progression-free survival (PFS). Among patients with STBSs with the high CP, median OS was 7.6 months (min 0.7 - max 11.0 months). In the group with the low CP, OS did not reach the median value by the end of the five-year observation period. PFS was 5.6 months (min 0.2 - max 19.2 months) in the first group and 3.2 months (min 0.3- max 71.3 months) in the second group. Resistance to therapeutic doses of chemotherapy drugs was correlated with CP cultures STBSs. We suggest that chemotherapy-resistant clones are pre-existing in the tumor rather than being formed under the influence of chemotherapy. Highly aggressive metastatic sarcomas may be a promising candidate for immunotherapy against cancer-testis antigens (CTAs)., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Spindle cell sarcoma (SCS) is a rare malignant tumour which can arise in bone and accounts for 2%-5% of primary bone cancer cases. Distant metastasis occurs predominantly in the lungs. However, metastasis to the soft palate, to the best of our knowledge, has never been previously reported. In this case report, we describe a unique presentation of soft palate metastasis in a patient with a history of high-grade SCS of the bone who presented with progressive dysphagia and nausea and vomiting who underwent surgical excision for palliation of symptoms., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Dogs with sinonasal tumors with cribriform plate lysis (modified Adams' stage 4) treated with non-conformal definitive radiotherapy (RT) have short median survivals of 6-7 months. Intensity-modulated radiotherapy with its greater conformality and tumor dose homogeneity may result in more favorable outcomes. Dogs with epithelial or mesenchymal sinonasal tumors and CT evidence of cribriform lysis that received 10 daily fractions of 4.2 Gray using IMRT by helical tomotherapy were included in this single-institution retrospective case series study. Dogs with distant metastasis, previous treatment, or concurrent chemotherapy were excluded. Based on CT, tumors were divided into two groups: cribriform plate lysis only (stage 4a) or intracranial extension (stage 4b). Twenty-nine dogs were included, 23 with carcinoma and six with sarcoma. Eight dogs had stage 4b tumors; two presented with neurologic signs. Two dogs had lymph node metastasis at diagnosis, one confirmed and one suspected. Radiation dose distributions were standardized and patient positioning for RT was verified daily using on-board megavoltage CT. All evaluable dogs had improvement of clinical signs. Median progression free survival was 177 days (95% CI, 128-294 days). Median overall survival was 319 days (95% CI, 188-499 days). Radiotherapy was well tolerated. The most common side effect was grade 1 or 2 oral mucositis. Two dogs that received additional treatment at progression (stereotactic RT [1]; surgery [1]) developed significant late effects. Image-guided definitive-intent IMRT may improve survival in dogs with modified Adams' stage 4 sinonasal tumors and is associated with low morbidity. Intracranial tumor extension was not prognostic in this cohort of uniformly treated dogs., (© 2020 American College of Veterinary Radiology.)

Objectives: Solid tumor metastases to the pancreas are rare, and only limited literature on the topic is available. In this retrospective study, we reviewed 107 cases of solid tumor metastases to the pancreas diagnosed by fine-needle aspiration (FNA) from 2005 to 2019., Methods: Information including the patients' clinical histories, radiologic and pathologic findings, treatments, and follow-up were collected., Results: The mean age of the patients was 62.4 years. The mean tumor size was 2.64 cm with even distribution throughout the pancreas (head, neck and body, and tail). The most common primary site was the kidney, followed by the lung, skin, and breast and the gynecologic, gastrointestinal, and genitourinary tracts. The most common tumor type was carcinoma, followed by melanoma and sarcoma. In comparison to patients with nonkidney primary cancers, those with primary renal cell carcinoma had a longer median interval between primary diagnosis and metastasis (8.5 vs 4.0 years; P < .01), less often had metastasis outside the pancreas (38% vs 74%; P < .01), and had a significantly longer 5-year survival rate (65.7% vs 24.8%; P < .01)., Conclusions: FNA plays a crucial role in diagnosing metastases to the pancreas. Metastases originating from kidney and nonkidney primary tumors have distinct clinicopathologic features and prognoses., (© American Society for Clinical Pathology, 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Primary Ewing sarcoma (ES) of the urinary bladder is a rare and aggressive small blue round cell malignant neoplasm associated primarily with translocation involving EWSR1 and FLI1 genes located in the 22nd and 11th chromosomes, respectively. To date, 18 cases have been published in the literature as single-case reports, based chiefly on CD99 positivity (17 patients). Molecular confirmation by fluorescence in situ hybridization was performed in 9 patients, and FLI1 immunohistochemical (IHC) analysis was not performed in any of these published cases. Herein, we present thirteen patients of more comprehensive primary round cell sarcomas of the urinary bladder with EWSR1 rearrangement. Clinicopathologic parameters including demographics; clinical presentation; histopathologic, IHC, and molecular profiles; and management and follow-up data of 13 patients with primary round cell sarcomas with EWSR1 rearrangement (Ewing family of tumor) of the urinary bladder were analyzed. The studied patients (n = 13) included 6 females and 7 males; their age ranged from 4 years to 81 years (median = 30 years). The most common clinical presentation was hematuria (n = 7), followed by hydronephrosis (n = 2, one with renal failure). The tumor size ranged from 2.9 cm to 15 cm in maximum dimension. Conventional ES architecture and histology was observed in 6 cases, and diverse histology was observed in 7 cases (adamantinomatous pattern [n = 1], alveolar pattern [n = 1], ganglioneuroblastoma-like pattern [n = 2], and small cell carcinoma-like pattern [n = 3]). All the tumors were muscle invasive (invasion into the muscularis propria). IHC analysis showed that all tumors expressed FLI1, CD99, and at least one neuroendocrine marker. Focal cytokeratin staining was positive in 2 patients, and RB1 was retained in all patients. EWSR1 rearrangement was seen in 12 of 12 tumors (in 12 patients) tested. A combined multimodal approach that included surgery with chemotherapy was instituted in all patients. Follow-up was available for 11 patients (ranging from 5 to 24 months). Six patients either died of disease (n = 3) or other causes (n = 3). Five patients were alive with metastases to the liver (n = 1), liver and lung (n = 2), liver and abdominal wall (n = 1), and kidney (n = 1). Based on our experience with the largest series to date and aggregate of the published data, ES/round cell sarcomas with EWSR1 rearrangement occurring in the bladder have bimodal age distribution with poor prognosis despite aggressive therapy. Owing to its rarity and age distribution, the differential diagnosis is wide and requires a systematic approach for ruling out key age-dependent differential diagnoses aided with molecular confirmation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Studies reporting outcomes of liver resection for sarcoma metastases (LRSM) typically include gastrointestinal stromal tumours (GIST), or pooled analyses of "non-colorectal liver metastases", which do not reflect the subgroup of patients with sarcomatous liver metastases. This study aimed to perform a systematic review to evaluate oncological and surgical outcomes in patients undergoing LRSM, and to report new data from two tertiary institutions., Methods: MEDLINE and the Cochrane Library were searched for studies reporting oncological and surgical outcomes after LRSM, following PRISMA guidelines. Studies reporting liver resection for GIST were excluded. The resulting studies were pooled, with data from two European centres., Results: Six studies of LSRM were included, comprising 212 patients from previously reported series and 24 patients from ours, with median follow-up times of 18-53 months. Postoperative mortality rates ranged from 0 to 9%, and the pooled overall survival (OS) was 89% (95% CI: 83-96%), and 31% (95% CI: 14-47%) at one and five years, respectively (median: 36 months). The presence of synchronous extra-hepatic metastases was found to be a significant risk factor for shorter OS in two cohorts, with hazard ratios of 3.7 (p < 0.001) and 9.1 (p = 0.016), respectively. The largest reported series also found larger metastases (≥100 mm), lack of response to chemotherapy and a shorter disease-free interval to be associated with significantly shorter OS after LSRM., Conclusions: Patients undergoing LRSM with negative prognostic factors such as the presence of extra-hepatic metastases are unlikely to benefit from surgery. Acceptable medium- and long-term survival may be achievable in highly selected patients., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

The urinary bladder may be involved by a variety of secondary tumors that originate from other organs. Bladder secondary tumors are rare and may be mistaken as bladder primary tumors because of their overlapping morphologic features. To avoid the diagnostic pitfalls, we analyzed the clinicopathologic features of bladder secondary tumors in a large cohort of patients. Our patient cohort consisted of 45 females and 38 males with a mean age of 58.7 ± 15.4 years (range 10-87 years). The tumors involved the bladder via direct extension from adjacent organs (n = 42) and distant metastasis (n = 41). In females, the majority of secondary tumors originated from the gynecologic tract (n = 25), and other common origins included the colon/rectum (n = 5) and breast (n = 4). In males, the most common origin was the prostate (n = 18), followed by the colon/rectum (n = 4) and kidney (n = 3). 75.9% of the secondary tumors were adenocarcinoma (n = 63), and other common tumor types included sarcoma (n = 6), squamous cell carcinoma (n = 5), melanoma (n = 4), and neuroendocrine carcinoma (n = 3). 67.5% of patients (n = 56) died of the disease with a median overall survival of 23 months from the time of secondary involvement of the bladder. Patients with secondary tumors via direct extension had a median survival time of 20 months, which was not significantly different from that for patients with secondary involvement via distant metastasis (24 months) (p = 0.83). Median survival in cases with prostate primary was 20 months as compared to 23 months for all other tumor types (p = 0.68). The majority of secondary tumors are composed of adenocarcinoma, which highlights the importance of differentiating primary from secondary involvement in bladder adenocarcinoma. Regardless of the origin, bladder secondary tumors are associated with a poor prognosis., Competing Interests: Declaration of competing interest All authors have no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background/objectives: Oligometastatic sarcoma pulmonary metastases (PM's) are traditionally treated with resection and/or chemotherapy. We hypothesize that stereotactic body radiotherapy (SBRT) is an effective, safe alternative to surgery that can achieve excellent local control (LC) with a favorable toxicity profile., Methods: Patients treated with SBRT for sarcoma PM's from 2011 to 2016 at Massachusetts General Hospital and the University of Pennsylvania were included. Median dose was 50 Gy. Patients underwent computed tomography (CT) or positron emission tomography/CT Q3 months post-SBRT., Results: 44 patients with 56 separate PM's were treated with SBRT. Median age was 59 (range 19-82). 82% received prior chemotherapy, 66% had prior pulmonary resections (range, 1-5 resections), and 32% received prior thoracic radiotherapy. Median lesion size was 2.0 cm (range, 0.5-8.1 cm). Median follow-up was 16 months and 25 months for patients alive at last follow-up. Overall survival at 12 and 24 months was 74% (95% confidence interval [CI], 67%-81%) and 46% (95% CI, 38%-55%). LC at 12 and 24 months was 96% (95% CI, 93%-98%) and 90% (95% CI, 84%-96%). LC and overall survival did not differ based on age, gender, histology, fractionation, lesion location, or size (P > .05). Three developed Common Terminology Criteria for Adverse Events version 4 grade-2 chest-wall toxicities; one had grade-2 pneumonitis., Conclusions: In the first multi-institutional series on SBRT for sarcoma PM's, SBRT has excellent LC and is well-tolerated. SBRT should be considered as an alternative/complement to resection., (© 2020 Wiley Periodicals LLC.)

Background: Hepatic metastasis of soft tissue sarcoma is rare compared to lung metastasis, and the literature is scarce. We examined the risk of hepatic metastasis according to the site of occurrence and histological type., Methods: From a Hospital-based Cancer Registry, 658 patients registered between 2007 and 2017 with soft tissue sarcomas were evaluated. The exclusion criteria were gastrointestinal stromal tumors, tumors of unknown origin, and follow-up periods of less than 1 month. SPSS 25 was used for statistical analysis., Results: The risk of hepatic metastasis was significantly higher in the retroperitoneum (HR, 5.981; 95% CI, 2.793-12.808) and leiomyosarcoma (HR, 4.303; 95% CI, 1.782-10.390). Multivariate analysis showed that the risk of hepatic metastasis as first distant metastasis was high in leiomyosarcoma (HR, 4.546; 95% CI, 2.275-9.086) and retroperitoneal onset (HR, 4.588; 95% CI, 2.280-9.231). The 2-year survival rate after hepatic metastasis was 21.7%., Conclusions: The onset of hepatic metastasis indicates a poor prognosis. However, hepatic metastasis from retroperitoneal sarcoma and leiomyosarcoma may be the first distant metastasis in some cases. For retroperitoneal sarcoma and leiomyosarcoma, additional screening for hepatic metastasis such as contrast CT should be considered during staging and follow-up after treatment., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: Vulvar cancers account for 5% of all gynecologic malignancies; only 1%-3% of those vulvar cancers are primary vulvar sarcomas. Given the rarity of vulvar sarcomas, outcome data specific to histopathologic subtypes are sparse. The aim of this study was to identify clinical and pathologic factors of primary vulvar sarcomas that are associated with survival and may inform treatment decisions., Methods: The Surveillance, Epidemiology, and End Results (SEER) database was searched for women diagnosed with vulvar sarcoma between 1973 and 2018. We identified 315 patients and reviewed their demographic, clinicopathologic, surgical, and survival information. Statistical analyses included χ 2 and t-tests, Kaplan-Meier survival, and Cox regression analyses., Results: The most common histopathologies of vulvar sarcomas were dermatofibrosarcomas (85/315, 27%) and leiomyosarcomas (72/315, 22.9%). Rhabdomyosarcomas (18/315, 5.7%), liposarcomas (16/315, 5.1%), and malignant fibrous histiocytomas (16/315, 5.1%) were less frequent. The majority of patients underwent surgery (292/315, 92.7%), which included lymph node dissections in 21.6% (63/292). Survival and lymph node involvement varied significantly with histologic subtype. The 5-year disease-specific survival for dermatofibrosarcomas, liposarcomas, and fibrosarcomas was 100% and only 60.3% and 62.5% for malignant fibrous histiocytomas and rhabdomyosarcomas, respectively. None of the patients with (dermato)fibrosarcomas, liposarcomas, or leiomyosarcomas had positive lymph nodes, in contrast to rhabdomyosarcomas and malignant fibrous histiocytomas with 77.8% and 40% positive lymph nodes, respectively. The 5-year disease-specific survival for women with positive lymph nodes was 0%., Conclusions: Vulvar sarcomas are heterogeneous with survival highly dependent on the histopathologic subtype. While surgical excision is the mainstay of treatment for all vulvar sarcomas, staging lymphadenectomy should be deferred for (dermato)fibrosarcomas, liposarcomas, and leiomyosarcomas as there were no cases of lymph nodes metastases., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The periacetabular region is a common location for metastatic disease. Although large lytic acetabular defects are commonly treated with a hip arthroplasty with a cemented component according to a Harrington-style reconstruction, the use of highly porous uncemented tantalum acetabular components has been described. Currently, there are no direct comparisons of these reconstructive techniques. The purpose of this study was to compare the outcomes of the Harrington technique and tantalum acetabular component reconstruction for periacetabular metastases., Methods: From 2 tertiary sarcoma centers, we retrospectively reviewed 115 patients (70 female and 45 male) with an acetabular metastatic defect who had been treated between 2002 and 2015 with a total hip arthroplasty using either the cemented Harrington technique (78 patients) or a tantalum acetabular reconstruction (37 patients). The mean patient age was 61 years, and the most common Eastern Cooperative Oncology Group status was 3 (39 patients). The mean follow-up for surviving patients was 4 years., Results: An additional surgical procedure was performed in 24 patients (21%). Harrington-style reconstructions were more likely to require a reoperation compared with tantalum reconstructions (hazard ratio [HR], 4.59; p = 0.003). The acetabular component was revised in 13 patients (11%); 5 patients (4%) underwent revisions that were due to loosening of the acetabular component. The 10-year cumulative incidence of revision of the acetabular component for loosening was 9.6% in the Harrington group and 0% in the tantalum group (p = 0.09). The mean Harris hip score significantly improved following reconstruction (31 to 67 points; p < 0.001), with no significant difference (p = 0.29) between groups., Conclusions: In patients with periacetabular metastatic disease treated with total hip arthroplasty, an acetabular reconstruction strategy utilizing highly porous tantalum acetabular components and augments successfully provided patients with a more durable construct with fewer complications compared with the cemented Harrington-style technique., Levels of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Background: Malignant peripheral nerve sheath tumor is a rare and aggressive form of sarcoma that arises from a peripheral nerve, mostly in association with neurofibromatosis type 1. Half of the cases were reported in the extremities, with the lungs being the most common site of metastasis. We report a rare case of successful limb salvage surgery performed for a large exophytic malignant peripheral nerve sheath tumor of the right forearm with wide surgical margins followed by split-thickness skin graft and later a flexor carpi radialis tendon transfer to extensor digitorum communis tendon., Case Presentation: A 51-year-old Bedouin Arabic man presented to our institution with an incompletely excised, large, fungating, malignant peripheral nerve sheath tumor occupying most of his right forearm. Staging imaging showed multiple lung nodules. He underwent wide local excision followed by skin graft and tendon transfer as a palliative measure to preserve the function of his dominant limb. The operation was performed without any complications, and the patient had an excellent postoperative result. Afterward, he was started on multiple lines of chemotherapy that failed because of disease progression, and the patient died 7 months after the operation., Conclusion: Clinicians must consider the possibility of soft tissue sarcoma even in a patient with a small, slow-growing, superficial mass. Furthermore, a wrong open biopsy or nononcological surgical procedure may lead to possible contamination and ultimately a more radical procedure than would have originally been necessary, where this can be prevented by an early referral to a highly specialized sarcoma center.

Background: In precision cancer medicine, the challenge is to prioritize DNA driver events, account for resistance markers, and procure sufficient information for treatment that maintains patient safety. The MetAction project, exploring how tumor molecular vulnerabilities predict therapy response, first established the required workflow for DNA sequencing and data interpretation (2014-2015). Here, we employed it to identify molecularly matched therapy and recorded outcome in end-stage cancer (2016-2019). Material and methods: Metastatic tissue from 26 patients (16 colorectal cancer cases) was sequenced by the Oncomine assay. The study tumor boards interpreted called variants with respect to sensitivity or resistance to matched therapy and recommended single-agent or combination treatment if considered tolerable. The primary endpoint was the rate of progression-free survival 1.3-fold longer than for the most recent systemic therapy. The objective response rate and overall survival were secondary endpoints. Results: Both common and rare actionable alterations were identified. Thirteen patients were found eligible for therapy following review of tumor sensitivity and resistance variants and patient tolerability. The interventions were inhibitors of ALK/ROS1-, BRAF-, EGFR-, FGFR-, mTOR-, PARP-, or PD-1-mediated signaling for 2-3 cases each. Among 10 patients who received treatment until radiologic evaluation, 6 (46% of the eligible cases) met the primary endpoint. Four colorectal cancer patients (15% of the total study cohort) had objective response. The only serious adverse event was a transient colitis, which appeared in 1 of the 2 patients given PD-1 inhibitor with complete response. Apart from those two, overall survival was similar for patients who did and did not receive study treatment. Conclusions: The systematic MetAction approach may point forward to a refined framework for how to interpret the complexity of sensitivity versus resistance and patient safety that resides in tumor sequence data, for the possibly improved outcome of precision cancer medicine in future studies. ClinicalTrials.gov, identifier: NCT02142036.

Introduction: Little is known about undifferentiated pleomorphic sarcoma (UPS) because of the low incidence and heterogeneous diagnosis of sarcoma. We investigated the oncologic outcomes of patients with UPS in a real-practice setting in association with adjuvant treatments and assessment of PD-L1 expression., Materials and Methods: We retrospectively reviewed consecutive patients who were diagnosed with UPS in Asan Medical Center between January 1995 and December 2016. PD-L1 staining was performed using formalin-fixed paraffin-embedded tumour tissue by immunohistochemistry, and positive PD-L1 expression was defined as staining in ≥1% of tumour cells. The PD-L1 H-score, which was calculated for statistical analysis as intensity (0-3) multiplied by proportion (0-100), ranged from 0 to 300., Results: Of 205 patients included in our analysis, 176 underwent a curative-intent operation for localised disease. The five-year disease-free survival (DFS) rate of resected UPS patients was 54.3%. Administration of adjuvant therapy did not overcome the poor prognostic factors such as primary tumour size (>5 cm) and locations, especially the abdomen and pelvis. The PD-L1 analysis was available for 114 patients, and 83 (72.8%) showed immunoreactivity for PD-L1 with weak (44/83), intermediate (29/83), and strong (10/83) staining intensities. The positive PD-L1 expression seemed to be associated with prolonged DFS, though no statistical significance was observed., Conclusion: Complete surgical resection was the most important UPS treatment strategy, and adjuvant radio- or chemotherapy was insufficient to improve survival. Our results raise the possibility that immunotherapy could be a breakthrough in the treatment of UPS patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Thorough study is required to decide the appropriate management of hepatic tumors in children. We present a case report of a hepatic embryonal undifferentiated sarcoma with unfavorable prognosis in a nine-year-old girl. After undergoing a detailed cancer characteristics and extension study, a two-stage surgery approach was decided. The hepatic tumor resection was the first procedure to be performed. One week later, under cardiopulmonary bypass, deep hypothermia, and circulatory arrest, thrombectomy of the inferior vena cava and right atrium was accomplished, plus thromboendarterectomy of the right pulmonary artery. During a four-year follow-up, the patient continues to be disease-free.

Background: Uterine malignant tumors (uterine cervical carcinoma [UCC], uterine endometrial carcinoma, and uterine sarcoma) are common in women. Brain metastases from uterine malignant tumors are rare, but its incidence has been increasing. The present study aimed to investigate the characteristics of brain metastases from uterine malignant tumors, evaluate predictive factors, and assess the efficacy of Gamma Knife surgery (GKS) for metastases from uterine malignant tumors., Methods: We retrospectively reviewed the records of patients with brain metastases from uterine malignant tumors treated at Tokyo Gamma Unit Center from 2005 to 2017., Results: We identified 37 patients: 16 had UCC, 12 had uterine endometrial carcinoma, and 9 had uterine sarcoma. Their median age at diagnosis of brain metastases was 54.0 years. The median interval from diagnosis of uterine malignant tumor to brain metastases was 21.0 months, the median number of brain metastases was 3.0, and the median Karnofsky Performance Status at first GKS was 80%. The median survival after first GKS was 6.0 months. All patients had other metastases. Six-month and 1-year survival after first GKS were 48.9% and 32.6%, respectively, and the tumor control rate at 6 months after GKS was 90.8%. Brain metastases from UCC were significantly correlated with good tumor control (P = 0.024). Multivariate analysis determined that Karnofsky Performance Status was significantly associated with patient survival (P = 0.001)., Conclusions: The results of our study suggest that GKS is an acceptable choice for controlling brain metastases from uterine malignant tumors. In particular, GKS provides excellent local control for metastases from UCC., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Soft tissue sarcomas (STS) are a rare and heterogeneous group of tumors. They account for 1% of solid malignant tumors in adults and 7% in children and are responsible for 2% of cancer mortality. They require a multidisciplinary approach in centers with experience. This collaboration aims to update the scientific evidence to strengthen, together with clinical experience, the bases for the use and limitations of 18 F-FDG-PET/CT in STSs. The general recommendations for the use of PET/CT in STS at present are summarized as the initial evaluation of soft tissue tumours when conventional image does not establish benignity with certainty and this determines the approach; in biopsy guiding in selected cases; in the initial staging, as additional tool, for rhabdomyosarcoma and STS of extremities or superficial trunk and head and neck tumours; in the suspicion of local recurrence when the CT or MRI are inconclusive and in the presence of osteosynthesis or prosthetic material and in assessment of therapy response to local/systemic therapy in stages ii/iii. In addition, PET/CT has the added value of being a surrogate marker of the histopathological response and it provides prognostic information, both in the baseline study and after treatment., (Copyright © 2020 Sociedad Española de Medicina Nuclear e Imagen Molecular. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: This case-series is aimed to describe the natural history of epithelioid sarcoma (ES) and to provide insights into the differential clinical behaviour of its two variants ("classic-type" and "proximal-type"). The value of a subtype-adapted grading system based on pathological features is explored., Methods: Data from consecutive, primary, localised, INI1-deleted ES operated at three Italian sarcoma reference centres (1995-2015) were included. Centralised pathological review was performed. Classic-type ES was broken down into "high-grade" and "low-grade", according to number of mitoses, evidence of necrosis and nuclear atypia. Five- and 10-year overall survival (OS) and crude cumulative incidence (CCI) of local recurrence (LR) and distant metastasis (DM) were estimated., Results: Fifty-two patients were included. 5- and 10-year OS estimates were 70% and 47% in the whole series, 57% and 37% in patients with proximal-type ES, 77% and 54% in patients with classic-type ES (P = 0.02). In classic-type ES, 5- and 10-year OS was higher for low-grade (95% and 72%, respectively) than high-grade tumours (P = 0.002). 5- and 10-year CCI estimates for LR were 21% and 33% in the whole series. 5- and 10-year CCI estimates for DM were 35% and 39% in the whole series, both 28% in classic-type ES, 47% and 59% in proximal-type ES (P = 0.03)., Conclusions: Suffering from a proximal- or a classic-type is the stronger predictor of outcome in patients with localised ES, with proximal-type ES patients having lower survival due to a higher tendency toward metastatic spreading. However, the "high-grade" classic-type ES was associated with outcomes close to proximal-type ES., Competing Interests: Declaration of competing interest AMF received institutional clinical trials support from Amgen Dompé, AROG Bayer, Blueprint Medicines, Eli Lilly, Daiichi Sankyo Pharma, Epizyme, GlaxoSmithKline, Novartis, Pfizer, PharmaMar and travel grants from PharmaMar. GGB received travel grants and advisory honoraria from Pharmamar and Eli Lilly, advisory honoraria from Eisai. NS received institutional clinical trials support from Amgen Dompé, AROG Bayer, Blueprint Medicines, Eli Lilly, Daiichi Sankyo Pharma, Epizyme, GlaxoSmithKline, Novartis, Pfizer, PharmaMar. PGC has reported advisory roles for Deciphera Pharmaceuticals, Eisai, Eli Lilly, Nektar Therapeutics, speaker's honoraria from Eisai, Eli Lilly, Pfizer, PharmaMar, and conducted studies sponsored by Amgen Dompé, AROG Bayer, Blueprint Medicines, Eli Lilly, Daiichi Sankyo Pharma, Epizyme, GlaxoSmithKline, Novartis, Pfizer, PharmaMar. SSt has received honoraria from Eli Lilly, PharmaMar, Takeda; institutional research grants from Amgen Dompé, Advenchen, Bayer, Eli Lilly, Daiichi Sankyo Pharma, Epizyme Inc., Novartis, Pfizer and PharmaMar; travel grants from PharmaMar and has reported advisory/consultant roles for Bayer, Daiichi, Eli Lilly, Epizyme, Karyopharm, ImmuneDesign, Maxivax and PharmaMar. MS, SLV, FF, DC, DC, SP, AG, APDT, MG, MB, AP, LM have nothing to declare., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)