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Background: Current risk models in solitary fibrous tumour (SFT) were developed using cohorts with short follow-up and cannot reliably identify low-risk patients. We recently developed a novel risk model (G-score) to account for both early and late recurrences. Here, we aimed to validate the G-score in a large international cohort with long-term follow-up. Methods: Data were collected from nine sarcoma referral centres worldwide. Recurrence-free interval (RFi) was the primary endpoint. Results: The cohort comprised 318 patients with localised extrameningeal SFTs. Disease recurrence occurred in 96 patients (33%). The estimated 5-year RFi rate was 72%, and the 10-year RFi rate was 52%. G-score precisely predicted recurrence risk with estimated 10-year RFi rate of 84% in low risk, 54% in intermediate risk and 36% in high risk (p < 0.001; C-index 0.691). The mDemicco (p < 0.001; C-index 0.749) and Salas OS (p < 0.001; C-index 0.674) models also predicted RFi but identified low-risk patients less accurate with 10-year RFi rates of 72% and 70%, respectively. Conclusions: G-score is a highly significant predictor of early and late recurrence in SFT and is superior to other models to predict patients at low risk of relapse. A less intensive follow-up schedule could be considered for patients at low recurrence risk according to G-score.

Objective: The aim of the study is to assess the effect of perioperative chemo-therapy (CTX) in patients with grade II-III extremity soft tissue sarcoma (eSTS) on overall survival (OS) and evaluate whether the PERSARC prediction tool could identify patients with eSTS more likely to benefit from CTX.Methods: Patients (18-70 years) with primary high-grade eSTS surgically treated with cura-tive intent were included in the retrospective cohort study. The effect of any perioperative CTX and anthracycline + ifosfamide (AI)-based CTX on OS was investigated in three PERSARC-risk groups (high/intermediate/low). The PERSARC-risk groups were defined by the 33% and 66% quantile of the predicted 5-year OS of the study population equal to a 5-year OS of 65.8% and 79.8%, respectively. The effect of CTX on OS was investigated with weighted Kaplan-Meier curves and multivariable Cox models with an interaction between risk group and CTX.Results: This study included 5683 patients. The weighted Kaplan-Meier curves did not demonstrate a beneficial effect of any CTX and AI-based CTX on OS in the overall population. However, in the high PERSARC-risk group the 5-year OS of AI-based CTX was significantly better than no CTX (69.8% vs 59.0%, respectively, p Z 0.004) (HR 0.66, 95% CI 0.53-0.83).Conclusions: This study demonstrated a beneficial effect of AI-based CTX on OS in a selected group of high-risk patients with an absolute survival benefit of 11% as stratified by the PERSARC prediction tool. However, no beneficial effect of CTX on OS was found in the overall population of patients with primary high-grade eSTS younger than 70 years.(c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Purpose The aim of this study was to create and validate dynamic nomograms to predict overall survival (OS) and disease-free survival (DFS) at different time points during follow-up in patients who had undergone resection of primary retroperitoneal sarcoma (RPS). Methods Patients with primary RPS operated upon between 2002 and 2017 at four and six referral centres comprised the development and external validation cohorts, respectively. Landmark analysis and multivariable Cox models were used to develop dynamic nomograms. Variables were selected using two backward procedures based on the Akaike information criterion. The prediction window was fixed at 5 years. Nomogram performances were tested in terms of calibration and discrimination on the development and validation cohorts. Results Development and validation cohorts totalled 1357 and 487 patients (OS analysis), and 1309 and 452 patients (DFS analysis), respectively. The final OS model included age, landmark time (TLM), tumour grade, completeness of resection and occurrence of local/distant recurrence. The final DFS model included TLM, histologic subtype, tumour size, tumour grade, multifocality and the interaction terms between TLM and size, grade and multifocality. For OS, Harrell C indices were higher than 0.7 in both cohorts, indicating very good discriminative capability. For DFS, Harrell C indices were between 0.64 and 0.72 in the development cohort and 0.62 and 0.68 in the validation cohort. Calibration plots showed good agreement between predicted and observed outcomes. Conclusion Validated nomograms are available to predict the 5-year OS and DFS probability at different time points throughout the first 5 years of follow-up in RPS survivors.

Background. With soft-tissue sarcoma of the extremity (ESTS) representing a heterogenous group of tumors, management decisions are often made in multidisciplinary team (MDT) meetings. To optimize outcome, nomograms are more commonly used to guide individualized treatment decision making. Purpose. To evaluate the influence of Personalised Sarcoma Care (PERSARC) on treatment decisions for patients with high-grade ESTS and the ability of the MDT to accurately predict overall survival (OS) and local recurrence (LR) rates. Methods. Two consecutive meetings were organised. During the first meeting, 36 cases were presented to the MDT. OS and LR rates without the use of PERSARC were estimated by consensus and preferred treatment was recorded for each case. During the second meeting, OS/LR rates calculated with PERSARC were presented to the MDT. Differences between estimated OS/LR rates and PERSARC OS/LR rates were calculated. Variations in preferred treatment protocols were noted. Results. The MDT underestimated OS when compared to PERSARC in 48.4% of cases. LR rates were overestimated in 41.9% of cases. With the use of PERSARC, the proposed treatment changed for 24 cases. Conclusion. PERSARC aids the MDT to optimize individualized predicted OS and LR rates, hereby guiding patient-centered care and shared decision making.

Background. Standard therapy for localized soft tissue sarcoma (STS) is wide, limb-sparing resection. For intermediate- or high-grade tumors, (neo)adjuvant therapies are frequently added to the treatment plan. In this study, data from a Dutch nationwide database are used to (1) assess whether perioperative management of STS follows ESMO guidelines, (2) characterize prognostic factors for overall survival (OS), and (3) assess the association between perioperative treatment and survival. Methods. All intermediate- or high-grade, localized STS cases, who have undergone surgery and diagnosed between 2000 and 2017, were identified in the Netherlands Cancer Registry (NCR) database. Variables with demographic, treatment, and survival data were obtained. Survival curves were estimated by Kaplan–Meier’s method, and the effect of prognostic factors on OS was assessed in a multivariable Cox regression analysis. Results. A total of 4957 patients were identified. There were slightly more males (54.7%). Median age at diagnosis was 64 years, and 53.6% of the tumors were located in the extremities. Radiotherapy (RT) was administered to 2481 (50.1%) patients, and 252 (5.1%) patients were treated with perioperative systemic chemotherapy. The total use of perioperative RT did not significantly change in the last 20 years, but the timing followed clinical guidelines: preoperative RT increased significantly (2000–2008: 3.7%, 2009–2017: 22.3%; p < 0.001 ), whereas the use of postoperative RT diminished (2000–2008: 45.9%, 2009–2017: 26.1%; p < 0.001 ). The use of perioperative chemotherapy slightly decreased (2000–2008: 5.9%, 2009–2017: 4.4%; p = 0.015). 5-year OS was 59.6% (95% CI: 58.2–61.0). Sex, age, year of diagnosis, tumor location, tumor size, histological grade, depth, histological subtype, surgical margins, and the use of perioperative RT were identified as independent predictors for OS. Conclusion. Preoperative RT is gradually replacing postoperative RT for localized STS in the Netherlands. The use of perioperative chemotherapy is rare and has slightly decreased in recent years. Identified baseline characteristics and treatment factors predicting OS may aid in future treatment decisions.

BACKGROUND. Retroperitoneal soft tissue sarcomas comprise a heterogeneous group of rare tumors of mesenchymal origin that include several well-defined histologic subtypes. In 2015, the Transatlantic Australasian RPS Working Group (TARPSWG) published consensus recommendations for the best management of primary retroperitoneal sarcoma (RPS). Since then, through international collaboration, new evidence and knowledge have been generated, creating the need for an updated consensus document. METHODS. The primary aim of this study was to critically evaluate the current evidence and develop an up-to-date consensus document on the approach to these difficult tumors. The resulting document applies to primary RPS that is non-visceral in origin, with exclusion criteria as previously described. The relevant literature was evaluated and an international group of experts consulted to formulate consensus statements regarding the best management of primary RPS. A level of evidence and grade of recommendation were attributed to each new/updated recommendation. RESULTS. Management of primary RPS was considered from diagnosis to follow-up. This rare and complex malignancy is best managed by an experienced multidisciplinary team in a specialized referral center. The best chance of cure is at the time of primary presentation, and an individualized management plan should be made based on the 29 consensus statements included in this article, which were agreed upon by all of the authors. Whenever possible, patients should be enrolled in prospective trials and studies. CONCLUSIONS. Ongoing international collaboration is critical to expand upon current knowledge and further improve outcomes of patients with RPS. In addition, prospective data collection and participation in multi-institution trials are strongly encouraged.

Synovial sarcoma and myxoid liposarcoma are translocation-related sarcomas, with a high risk of developing distant metastasis, which often affect young patients and which are sensitive to chemo and radiotherapy. Surgery is the mainstay of therapy in localized disease. In these entities, perioperative radiotherapy is frequently administered, and chemotherapy is evaluated in patients with high-risk limb/trunk wall tumors in which an advantage in overall survival has been shown in the latest clinical trials. In the advanced setting, new strategies, such as cellular therapy are being developed in these histologic types, with promising, although still preliminary, results.

Surgery is the mainstay of treatment for retroperitoneal sarcoma (RPS), but local recurrence is common. Biologic behavior and recurrence patterns differ significantly among histologic types of RPS, with implications for management. The Transatlantic Australasian RPS Working Group (TARPSWG) published a consensus approach to primary RPS, and to complement this, one for recurrent RPS in 2016. Since then, additional studies have been published, and collaborative discussion is ongoing to address the clinical challenges of local recurrence in RPS.An extensive literature search was performed, and the previous consensus statements for recurrent RPS were updated after review by TARPSWG members. The search included the most common RPS histologic types: liposarcoma, leiomyosarcoma, solitary fibrous tumor, undifferentiated pleomorphic sarcoma, and malignant peripheral nerve sheath tumor.Recurrent RPS management was evaluated from diagnosis to follow-up evaluation. For appropriately selected patients, resection is safe. Nomograms currently are available to help predict outcome after resection. These and other new findings have been combined with expert recommendations to provide 36 statements, each of which is attributed a level of evidence and grade of recommendation. In this updated document, more emphasis is placed on histologic type and clarification of the intent for surgical treatment, either curative or palliative. Overall, the fundamental tenet of optimal care for patients with recurrent RPS remains individualized treatment after multidisciplinary discussion by an experienced team with expertise in RPS.Updated consensus recommendations are provided to help guide decision-making for treatment of locally recurrent RPS and better selection of patients who would potentially benefit from surgery.

Background Solitary fibrous tumor (SFT) is a rare mesenchymal malignancy. Although surgery is potentially curative, the local relapse risk is high after marginal resections. Given the lack of prospective clinical trial data, the objective of the current study was to better define the role of perioperative radiotherapy (RT) in various SFT presentations by location. Methods This was retrospective study performed across 7 sarcoma centers. Clinical information was retrieved from all adult patients with extrameningeal, primary, localized SFT who were treated between 1990 and 2018 with surgery alone (S) compared with those who also received perioperative RT (S+RT). Differences in treatment characteristics between subgroups were tested using analysis of variance statistics and propensity score matching. Local control and overall survival rates were calculated from the start of treatment until progression or death from any cause. Results Of all 549 patients, 428 (78%) underwent S, and 121 (22%) underwent S+RT. The median follow‐up was 52 months. After correction for mitotic count and surgical margins, S+RT was significantly associated with a lower risk of local progression (hazard ratio, 0.19: P = .029), an observation further confirmed by propensity score matching (P = .012); however, this association did not translate into an overall survival benefit. Conclusions The results from this retrospective study investigating perioperative RT in patients with primary extrameningeal SFT suggest that combining RT with surgery in the management of this patient population is significantly associated with a reduced risk of local failures, especially in patients who have less favorable resection margins and in those who have tumors with a high mitotic count., This retrospective study of perioperative radiotherapy in patients with primary extrameningeal solitary fibrous tumors suggests that combining radiotherapy with surgery in the management of this population significantly reduces the risk of local failures, especially in patients who have less favorable resection margins or tumors with a high mitotic count.

There is a lack of understanding whether plasma levels of anticancer drugs (such as pazopanib) correlate with intra-tumoral levels and whether the plasma compartment is the best surrogate for pharmacokinetic and pharmacodynamic evaluation. Therefore, we aimed to quantify pazopanib concentrations in tumor tissue, to assess the correlation between tumor concentrations and plasma concentrations and between tumor concentrations and efficacy. In this clinical trial, non-metastatic STS patients were treated with neo-adjuvant concurrent radiotherapy and pazopanib. Plasma samples and tumor biopsies were collected, and pazopanib concentrations were measured using liquid chromatography-tandem mass spectrometry. Twenty-four evaluable patients were included. The median pazopanib tumor concentration was 19.2 µg/g (range 0.149–200 µg/g). A modest correlation was found between tumor concentrations and plasma levels of pazopanib (ρ = 0.41, p = 0.049). No correlation was found between tumor concentrations and percentage of viable tumor cells (p &gt, 0.05), however, a trend towards less viable tumor cells in patients with high pazopanib concentrations in tumor tissue was observed in a categorical analysis. Possible explanations for the lack of correlation might be heterogeneity of the tumors and timing of the biopsy procedure.

Thoracic and breast sarcomas constitute a rare subgroup within the sarcoma population. There is limited knowledge about their health-related quality of life (HRQoL) and a valid disease-specific HRQoL instrument is lacking. This qualitative study aimed to investigate the HRQoL issues experienced by a small group of thoracic and breast sarcoma patients. Semi-structured interviews with 19 thoracic and four breast sarcoma patients were conducted and thematically analysed. Physical issues mentioned by both groups were fatigue, sleep disturbances, pain, wound infections, and symptoms related to chemotherapy and radiotherapy. Tightness in the back and restrictions in performing tasks above arm height were specific physical issues for breast sarcoma patients, whereas respiratory problems were only mentioned by thoracic sarcoma patients. Body image issues, changes in mood, fear of recurrence, and living with uncertainty were important mental health issues for both subgroups. Social issues in both groups included challenges in work and relationships, financial difficulties, loss of independence, and limitations in social activities. The identified physical, mental, and social health challenges can significantly impact thoracic and breast sarcoma patients’ HRQoL. Results of this qualitative study will guide personalised supportive care for breast and thoracic sarcoma patients and help in determining the best possible HRQoL measurement strategy for sarcoma patients with different primary sarcoma locations.

Background This study aimed to provide an insight into clinical decision-making and surveillance strategy of sarcoma specialists for patients with primary soft tissue sarcoma of the extremities (eSTS). The secondary aim was to quantify the role of patient- and tumor-specific factors in the perioperative management. Methods Members of sarcoma societies were sent a Web-based 21-item survey about eSTS management. The survey concerned only primary resectable high-grade eSTS in adults. Results The study enrolled 396 respondents. The majority of the surgical specialists thought the evidence for perioperative chemotherapy (CTX) for high-grade eSTS was insufficient. Radiotherapy (RTX) was less frequently offered in Asia than in North America and Europe. The specialties and continents also differed regarding the importance of patient and tumor characteristics influencing RTX and CTX recommendation. For surveillance after initial treatment outpatient visits, chest computed tomography (CT) scans, and magnetic resonance images of the extremity were the methods primarily used. The specialists in North America preferred chest CT scan over chest x-ray, whereas those in Asia and Europe had no clear preference. Discussion Specialty and continent are important factors contributing to the variation in clinical practice, treatment recommendations, and surveillance of patients with primary resectable high-grade eSTS.

Purpose A prior phase I study showed that the neo-adjuvant combination of pazopanib and radiotherapy was well tolerated, and induced promising pathological responses in soft-tissue sarcoma patients. Results of the subsequent prospective, multicenter phase II, PASART-2 trial are presented here, further investigating the efficacy and safety of this combination. Patients and methods Patients with high-risk, localized soft-tissue sarcoma received neo-adjuvant radiotherapy, 50 Gy in 25 fractions (PASART-2A) or with a subsequent dose de-escalation to 36 Gy in 18 fractions (PASART-2B). This was combined with 800 mg once daily pazopanib, which started one week before radiotherapy and finished simultaneously. After an interval of 4-8 weeks, surgical resection was performed. The primary endpoint was the rate of pathological complete responses (pCR), defined as ≤5% viable cells. Results 25 patients were registered in the study, 21 in PASART-2A and 4 in PASART-2B. After central pathology review, the combination treatment led to a pCR in 5 patients (20%). 17 patients (68%) experienced grade 3+ toxicities during neo-adjuvant treatment, of which the most common were alanine aminotransferase (ALT) elevation, aspartate aminotransferase (AST) elevation, and hypertension, all asymptomatic. Grade 3+ acute post-operative toxicities occurred in 5 patients (20%), of which the most common was wound infection. All patients completed the full radiotherapy regimen and underwent surgery. Pazopanib was discontinued before completion in 9 patients (36%), due to elevated ALT and/or AST, and shortly interrupted in 2 patients (8%), due to hypertension. Conclusion Apart from asymptomatic hepatotoxicity, the study regimen was well tolerated. Although the pre-specified efficacy endpoint (30% pCR) was not met, a more than doubling of historical pCR rates after neo-adjuvant radiotherapy alone was observed, which warrants further investigation.

Opinion statement Soft tissue sarcomas (STS) are rare, aggressive, and heterogenous tumors, comprising approximately 1% of adult cancers with over 50 different subtypes. The mainstay of treatment for retroperitoneal sarcomas (RPS) includes surgical resection. The addition of radiation therapy (RT), either preoperatively or postoperatively, has been used to potentially decrease the risk of local recurrence. The recently published results from STRASS (EORTC-STBSG 62092-22092), which randomized patients to receive or not receive preoperative radiation, indicate no abdominal recurrence-free survival benefit (primary endpoint) nor overall survival benefit to date from the addition of preoperative RT prior to surgical resection in patients with RPS. Keeping in mind caveats of subgroup analyses, the data show a significant reduction in local recurrence with radiation therapy in resected patients and non-significant trends toward improved abdominal recurrence-free survival in all patients and improved local control and abdominal recurrence-free survival in patients with liposarcoma and low-grade sarcoma. Given the high rate of local failure with surgery alone, it is possible that higher RT dose and/or selective RT dose painting may improve outcomes. Prior to treatment, the authors encourage multidisciplinary review and discussion of management options at a sarcoma center for patients with RPS. Selective use of RT may be considered for patients at high risk of local recurrence.

Soft tissue sarcomas (STS) are rare, aggressive, and heterogenous tumors, comprising approximately 1% of adult cancers with over 50 different subtypes. The mainstay of treatment for retroperitoneal sarcomas (RPS) includes surgical resection. The addition of radiation therapy (RT), either preoperatively or postoperatively, has been used to potentially decrease the risk of local recurrence. The recently published results from STRASS (EORTC-STBSG 62092-22092), which randomized patients to receive or not receive preoperative radiation, indicate no abdominal recurrence-free survival benefit (primary endpoint) nor overall survival benefit to date from the addition of preoperative RT prior to surgical resection in patients with RPS. Keeping in mind caveats of subgroup analyses, the data show a significant reduction in local recurrence with radiation therapy in resected patients and non-significant trends toward improved abdominal recurrence-free survival in all patients and improved local control and abdominal recurrence-free survival in patients with liposarcoma and low-grade sarcoma. Given the high rate of local failure with surgery alone, it is possible that higher RT dose and/or selective RT dose painting may improve outcomes. Prior to treatment, the authors encourage multidisciplinary review and discussion of management options at a sarcoma center for patients with RPS. Selective use of RT may be considered for patients at high risk of local recurrence.

Introduction: Oligometastatic disease and/or oligoprogression in myxoid liposarcoma(oMLS) triggers discussions on local treatment options and delay of systemic treatments. We hypothesized that satisfactory local control and postponement of systemic therapy could be achieved with a modest radiotherapy(RT) dose in oMLS.Methods: The DOREMY trial is a multicenter, phase 2 trial evaluating efficacy and toxicity of a modest RT dose in both localized and oMLS; this report presents the data of the oMLS cohort treated with 36 Gy in 12-18 fractions with optional subsequent metastasectomy. The primary endpoint was local progression free survival(LPFS). Secondary endpoints included postponement of systemic therapy, symptom reduction, radiological objective response, and toxicity.Results: Nine patients with a total of 25 lesions were included, with a median follow-up of 23 months. The median number of lesions per patient was three and the trunk wall and bone were the most frequently affected sites. In lesions treated with definitive RT(n = 21), LPFS rates at 1, 2, and 3 years were respectively 73%, 61%, and 40%. Radiological objective response and clinical symptom reduction were achieved in 8/15(53%) and 9/10(90%) of the evaluable lesions, respectively. No local recurrences occurred in lesions treated with RT and metastasectomy(n = 4). For the entire study population, the median postponement of systemic therapy was 10 months. Grade >= 2 toxicity was observed in 2/9(22%) of patients.Conclusions: This trial suggests that 36 Gy could possibly be effective to achieve local control, postpone systemic therapy and reduce symptoms in oMLS. Given the minimal toxicity this treatment could be reasonably considered in oMLS.(c) 2021 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 158 (2021) 33-39

Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication., Highlights • This consensus paper provides key recommendations on the management of epithelioid hemangioendothelioma (EHE). • Recommendations followed a consensus meeting between experts and a representative of the EHE advocacy group and SPAEN. • Authorship includes a multidisciplinary group of experts from different institutions from Europe, North America and Asia.

Background: Diagnosing and treating soft tissue sarcomas (STSs) remains challenging, stressing the urgency for centralisation. This nationwide survey aimed to evaluate the centralisation of STS surgery and its effect on survival.Methods: Patients operated for primary STS from 2006 to 2015 were queried from the Netherlands Cancer Registry. Hospitals in which STS surgery was performed were allocated into three categories: low-volume (1-9 resections per year), medium-volume (10-19 resections) or high-volume (>= 20 resections). Differences in tumour characteristics and outcome were calculated. A multivariable regression analysis was performed to adjust for case-mix.Results: Of the 5282 identified patients, 42% was treated in low-volume hospitals, 7.7% in medium-volume hospitals and 51% in high-volume hospitals, with a significant trend over time towards treatment in a high-volume hospital (p Conclusion: Centralisation of STS surgery has increased in the past decade. Surgery in a highvolume hospital improved survival of patients with non low-grade and deep-seated tumours, and therefore these patients should be referred to such a hospital. (C) 2019 Elsevier Ltd. All rights reserved.

Purpose Many authors suggest that extremity soft tissue sarcomas (ESTS) do not change significantly in size during preoperative radiation therapy (RT). This cone beam computed tomography study investigates the justification to deliver the entire course with 1 initial RT plan by observing anatomic changes during RT. Methods and Materials Between 2015 and 2017, 99 patients with ESTS were treated with either curative (n = 80) or palliative intent (n = 19) with a regimen of at least 6 fractions. The clinical target volume to planning target volume margin was 1 cm. Action levels were assigned by radiation technicians. An extremity contour change of >1 cm and/or tumor size change >0.5 cm required a physician's action before the next fraction. Results A total of 982 cone beam computed tomography logfiles were studied. In 41 of 99 patients, the dose coverage of the initial treatment plan was fully satisfactory throughout the RT course. However, action levels were observed in 58 patients (59%). In 41 of these 58 patients, a contour increase of 5 to 23 mm was noted (29 tumor size increase only, 3 extremity contour increase, and 9 both). In 21 of 58 patients, a decrease of 5 to 33 mm was observed (20 tumor size decrease only and 1 tumor size decrease and extremity contour decrease). In 4 cases, contours initially increased and subsequently decreased. In 33 of 41 patients with increasing contours, the dose distribution adequately covered gross tumor volume because of the 1 cm planning target volume margin applied. For the remaining 8 patients (8%), the plan needed to be adapted. Conclusions ESTS volumes may change substantially during RT in 59% of all patients, leading to plan adaptations resulting from increased volumes in 8%. Daily critical observation of these patients is mandatory to avoid geographic misses because of increases in size and overdosing of normal tissues when masses shrink.

Background The current study investigated the role of radiotherapy (RT) in patients with primary nonmetastatic retroperitoneal liposarcomas. Methods A total of 607 patients with localized retroperitoneal well‐differentiated liposarcomas (WDLPS) and dedifferentiated liposarcomas (DDLPS) underwent surgical resection with or without RT at 8 high‐volume sarcoma centers (234 patients with WDLPS, 242 patients with grade 1 to 2 DDLPS, and 131 patients with grade 3 DDLPS; grading was performed according to the National Federation of Centers for the Fight Against Cancer [Federation Nationale des Centres de Lutte Contre le Cancer; FNCLCC]). RT was administered in 19.7%, 34.7%, and 35.1%, respectively, of these 3 cohorts. Overall survival (OS) was estimated using the Kaplan‐Meier method, and the incidences of local recurrence and distant metastasis (DM) were estimated in a competing risk framework. To account for bias consistent with nonrandom RT assignment, propensity scores were estimated. Cox univariable analysis of the association between RT and oncological endpoints was performed by applying inverse probability of treatment weighting (IPTW) using propensity scores. Results Age, tumor size, and the administration of chemotherapy were found to be significantly imbalanced between patients who did and did not undergo RT in all cohorts. IPTW largely removed imbalances in key prognostic variables. Although the 8‐year local recurrence incidences in patients treated with surgery plus RT versus surgery only were 11.8% and 39.2%, respectively, for patients with WDLPS (P = .011;); 29.0% and 56.7%, respectively, for patients with grade 1 to 2 DDLPS (P = .008); and 29.8% and 43.7%, respectively, for patients with grade 3 DDLPS (P = .025), this significant benefit was lost after IPTW analyses. There were no significant differences noted with regard to DM and OS between irradiated and unirradiated patients across all 3 cohorts. Conclusions Perioperative RT was found to be associated with better local control in univariable unadjusted analysis in all 3 cohorts, but not after accounting for imbalances in prognostic variables. RT did not impact on DM or OS. The appropriate selection of RT in this disease remains challenging. The results of the European Organization for Research and Treatment of Cancer (EORTC)–Soft Tissue and Bone Sarcoma Group (STBSG) 62092‐22092 prospective randomized trial are awaited., In the current study, the addition of radiotherapy to curative surgery is analyzed in a large, retrospective, multi‐institutional series of patients with primary retroperitoneal liposarcoma. Although there appears to be an association with better local control and outcome, this benefit is lost after propensity score adjustment. The authors currently are awaiting the results of the European Organization for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group 62092‐22092 prospective randomized trial examining the value of preoperative radiotherapy.

Soft tissue sarcomas (STS) represent a broad family of rare tumours for which surgery with radiotherapy represents first-line treatment. Recently, neoadjuvant chemo-radiotherapy has been increasingly used in high-risk patients in an effort to reduce surgical morbidity and improve clinical outcomes. An adequate understanding of the efficacy of neoadjuvant therapies would optimise patient care, allowing a tailored approach. Although response evaluation criteria in solid tumours (RECIST) is the most common imaging method to assess tumour response, Choi criteria and functional and molecular imaging (DWI, DCE-MRI and 18F-FDG-PET) seem to outperform it in the discrimination between responders and non-responders. Moreover, the radiologic-pathology correlation of treatment-related changes remains poorly understood. In this review, we provide an overview of the imaging assessment of tumour response in STS undergoing neoadjuvant treatment, including conventional imaging (CT, MRI, PET) and advanced imaging analysis. Future directions will be presented to shed light on potential advances in pre-surgical imaging assessments that have clinical implications for sarcoma patients.

Background Among sarcomas, which are rare cancers, many types are exceedingly rare; however, a definition of ultra-rare cancers has not been established. The problem of ultra-rare sarcomas is particularly relevant because they represent unique diseases, and their rarity poses major challenges for diagnosis, understanding disease biology, generating clinical evidence to support new drug development, and achieving formal authorization for novel therapies. Methods The Connective Tissue Oncology Society promoted a consensus effort in November 2019 to establish how to define ultra-rare sarcomas through expert consensus and epidemiologic data and to work out a comprehensive list of these diseases. The list of ultra-rare sarcomas was based on the 2020 World Health Organization classification, The incidence rates were estimated using the Information Network on Rare Cancers (RARECARENet) database and NETSARC (the French Sarcoma Network's clinical-pathologic registry). Incidence rates were further validated in collaboration with the Asian cancer registries of Japan, Korea, and Taiwan. Results It was agreed that the best criterion for a definition of ultra-rare sarcomas would be incidence. Ultra-rare sarcomas were defined as those with an incidence of approximately ≤1 per 1,000,000, to include those entities whose rarity renders them extremely difficult to conduct well powered, prospective clinical studies. On the basis of this threshold, a list of ultra-rare sarcomas was defined, which comprised 56 soft tissue sarcoma types and 21 bone sarcoma types. Conclusions Altogether, the incidence of ultra-rare sarcomas accounts for roughly 20% of all soft tissue and bone sarcomas. This confirms that the challenges inherent in ultra-rare sarcomas affect large numbers of patients.

Soft tissue sarcomas (STS) are a diverse group of rare tumors of mesenchymal origin with different clinical, histologic and molecular characteristics [...]

Background: Histotype specific neoadjuvant therapy response data is scarce in soft tissue sarcomas. This study aimed to assess the impact of a moderate radiotherapy (RT) dose on resectability and to correlate MRI parameters to pathological treatment response in Myxoid Liposarcoma (MLS).Methods: This prospective, multicenter, single-arm, phase 2 trial assessed the radiological effects of 36 Gy of preoperative radiotherapy in primary non-metastatic MLS (n=34). Distance of the tumor to the neurovascular bundle, tumor dimensions, fat fraction, enhancing fraction were determined on MRI scans at baseline, after 8 and 16 fractions, and preoperatively. Pathological response was established by central pathology review.Results: Preoperative radiotherapy resulted in a median increase of 2 mm (IQR 0 to 6) of the distance of the tumor to the neurovascular bundle. As compared to baseline, the median change of the tumor volume, craniocaudal diameter and axial diameter at preoperative MRI were -60% (IQR -74 to -41), -19% (IQR -23 to -7) and -20% (IQR -29 to -12), respectively. The median fat fraction of 0.1 (IQR 0.0-0.1) and enhancing fraction of 0.8 (IQR 0.6 to 0.9) at baseline, changed to 0.2 (IQR 0.1 to 0.5) and to 0.5(IQR 0.4 to 0.9) preoperatively, respectively. Radiological signs of response in terms of volume, enhancing fraction and fat fraction were correlated with specific pathological signs of response like hyalinization, necrosis and fatty maturation.Conclusions: A moderate dose of preoperative radiotherapy may improve resectability in MLS and could facilitate achievement of clear margins and function preservation. MRI features which were predictive for expressions of pathological response, can play a role in further personalization of neoadjuvant treatment strategies in order to improve outcome in MLS. (C) 2021 Elsevier Ltd, BASO - The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Item does not contain fulltext IMPORTANCE: Currently, preoperative radiotherapy for all soft-tissue sarcomas is identical at a 50-Gy dose level, which can be associated with morbidity, particularly wound complications. The observed clinical radiosensitivity of the myxoid liposarcoma subtype might offer the possibility to reduce morbidity. OBJECTIVE: To assess whether a dose reduction of preoperative radiotherapy for myxoid liposarcoma would result in comparable oncological outcome with less morbidity. DESIGN, SETTING, AND PARTICIPANTS: The Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcomas (DOREMY) trial is a prospective, single-group, phase 2 nonrandomized controlled trial being conducted in 9 tertiary sarcoma centers in Europe and the US. Participants include adults with nonmetastatic, biopsy-proven and translocation-confirmed myxoid liposarcoma of the extremity or trunk who were enrolled between November 24, 2010, and August 1, 2019. Data analyses, using both per-protocol and intention-to-treat approaches, were conducted from November 24, 2010, to January 31, 2020. INTERVENTIONS: The experimental preoperative radiotherapy regimen consisted of 36 Gy in once-daily 2-Gy fractions, with subsequent definitive surgical resection after an interval of 4 or more weeks. MAIN OUTCOMES AND MEASURES: As a short-term evaluable surrogate for local control, the primary end point was centrally reviewed pathologic treatment response. The experimental regimen was regarded as a success when 70% or more of the resection specimens showed extensive treatment response, defined as 50% or greater of the tumor volume containing treatment effects. Morbidity outcomes consisted of wound complications and late toxic effects. RESULTS: Among the 79 eligible patients, 44 (56%) were men and the median (interquartile range) age was 45 (39-56) years. Two patients did not undergo surgical resection because of intercurrent metastatic disease. Extensive pathological treatment response was observed in 70 of 77 patients (91%; posterior mean, 90.4%; 95% highest probability density interval, 83.8%-96.4%). The local control rate was 100%. The rate of wound complication requiring intervention was 17%, and the rate of grade 2 or higher toxic effects was 14%. CONCLUSIONS AND RELEVANCE: The findings of the DOREMY nonrandomized clinical trial suggest that deintensification of preoperative radiotherapy dose is effective and oncologically safe and is associated with less morbidity than historical controls, although differences in radiotherapy techniques and follow-up should be considered. A 36-Gy dose delivered in once-daily 2-Gy fractions is proposed as a dose-fractionation approach for myxoid liposarcoma, given that phase 3 trials are logistically impossible to execute in rare cancers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02106312.

Objectives: Myxoid liposarcomas (MLS) show enhanced response to radiotherapy due to their distinctive vascular pattern and therefore could be effectively treated with lower radiation doses. This is a descriptive study to explore the use of functional MRI to identify response in a uniform cohort of MLS patients treated with reduced dose radiotherapy Methods: 10 patients with MLS were imaged pre-, during, and post-radiotherapy receiving reduced dose radiotherapy and the response to treatment was histopathologically assessed post-radiotherapy. Apparent diffusion coefficient (ADC), T2* relaxation time, volume transfer constant (Ktrans), initial area under the gadolinium curve over 60 s (IAUGC60) and (Gd) were estimated for a central tumour volume. Results: All parameters showed large inter- and intrasubject variabilities. Pre-treatment (Gd), IAUGC60 and Ktrans were significantly different between responders and non-responders. Post-radiotherapy reductions from baseline were demonstrated for T2*, (Gd), IAUGC60 and Ktrans for responders. No statistically significant ADC differences were demonstrated between the two response groups. Significantly greater early tumour volume reductions were observed for responders. Conclusions: MLS are heterogenous lesions, characterised by a slow gradual contrast-agent uptake. Pre-treatment vascular parameters, early changes to tumour volume, vascular parameters and T2* have potential in identifying response to treatment. The delayed (Gd) is a suitable descriptive parameter, relying simply on T1 measurements. Volume changes precede changes in MLS functionality and could be used to identify early response. Advances in knowledge: MLS are are characterised by slow gradual contrast-agent uptake. Measurement of the delayed contrast-agent uptake (Gd) is simple to implement and able to discriminate response.

Purpose: No studies extensively compared the young adults (YA, 18-39 years), middle-aged (40-69 years), and elderly (≥70 years) population with primary high-grade extremity soft tissue sarcoma (eSTS). This study aimed to determine whether the known effect of age on overall survival (OS) and disease progression can be explained by differences in tumour characteristics and treatment protocol among the YA, middle-aged and elderly population in patients with primary high-grade eSTS treated with curative intent. Methods: In this retrospective multicentre study, inclusion criteria were patients with primary high-grade eSTS of 18 years and older, surgically treated with curative intent between 2000 and 2016. Cox proportional hazard models and a multistate model were used to determine the association of age on OS and disease progression. Results: A total of 6260 patients were included in this study. YA presented more often after 'whoops'-surgery or for reresection due to residual disease, and with more deep-seated tumours. Elderly patients presented more often with grade III and larger (≥10 cm) tumours. After adjustment for the imbalance in tumour and treatment characteristics the hazard ratio for OS of the middle-aged population is 1.47 (95% confidence interval [CI]: 1.23-1.76) and 3.13 (95% CI: 2.59-3.78) in the elderly population, compared with YA. Discussion: The effect of age on OS could only partially be explained by the imbalance in the tumour characteristics and treatment variables. The threefold higher risk of elderly could, at least partially, be explained by a higher other-cause mortality. The results might also be explained by a different tumour behaviour or suboptimal treatment in elderly compared with the younger population. Keywords: Adolescents and young adults; Elderly; Extremities; Metastasis; Middle-aged; Recurrence; Soft tissue sarcoma; Survival.

© 2020 The Author(s)., Sarcomas are a heterogeneous group of malignancies with mesenchymal lineage differentiation. The discovery of neurotrophic tyrosine receptor kinase (NTRK) gene fusions as tissue-agnostic oncogenic drivers has led to new personalized therapies for a subset of patients with sarcoma in the form of tropomyosin receptor kinase (TRK) inhibitors. NTRK gene rearrangements and fusion transcripts can be detected with different molecular pathology techniques, while TRK protein expression can be demonstrated with immunohistochemistry. The rarity and diagnostic complexity of NTRK gene fusions raise a number of questions and challenges for clinicians. To address these challenges, the World Sarcoma Network convened two meetings of expert adult oncologists and pathologists and subsequently developed this article to provide practical guidance on the management of patients with sarcoma harboring NTRK gene fusions. We propose a diagnostic strategy that considers disease stage and histologic and molecular subtypes to facilitate routine testing for TRK expression and subsequent testing for NTRK gene fusions., GDD was supported in part by the Ludwig Center at Harvard; the Dr Miriam and Sheldon G. Adelson Medical Research Foundation; and the Pan Mass Challenge (no grant numbers). IMS is supported by the National Institutes of Health/National Cancer Institute (grant number K08 CA241085). JYB was supported by NetSARC (INCA & DGOS) and RREPS (INCA & DGOS), RESOS (INCA & DGOS), EURACAN (EC 739521), LYRICAN (INCA-DGOS-INSERM 12563), LabEx DEvweCAN (ANR-10-LABX-0061), Institut Convergence PLASCAN (17-CONV-0002), RHU4 DEPGYN (ANR-18-RHUS-0009).

Background. This study aimed to investigate changes in treatment strategy and outcome for patients with primary retroperitoneal sarcoma (RPS) undergoing resection at referral centers during a recent period.Methods. The study enrolled consecutive adult patients with primary non-metastatic RPS who underwent resection with curative intent between 2002 and 2017 at 10 referral centers. The patients were grouped into three periods according to date of surgery: t1 (2002-2006), t2 (2007-2011), and t3 (2012-2017). Five-year overall survival (OS), disease-specific survival (DSS), and crude cumulative incidence (CCI) of local recurrence (LR) and distant metastasis (DM) were calculated. Multivariable analyses for OS and DSS were performed.Results. The study included 1942 patients. The median follow-up period after resection varied from 130 months (interquartile range [IQR], 124-141 months) in t1 to 37 months (IQR, 35-39 months) in t3. The 5-year OS was 61.2% (95% confidence interval [CI], 56.4-66.3%) in t1, 67.0% (95 CI, 63.2-71.0%) in t2, and 71.9% (95% CI, 67.7-76.1%) in t3. The rate of macroscopically incomplete resection (R2) was 7.1% in t1 versus 4.7% in t3 (p = 0.066). The median number of resected organs increased over time (p < 0.001). In the multivariable analysis resection during t3 was associated with better OS and DSS. The 90-day postoperative mortality improved over time (4.3% in t1 to 2.3% in t3; p = 0.031). The 5-year CCI of LR and DM did not change significantly over time.Conclusions. The long-term survival of patients who underwent resection for primary RPS has increased during the past 15 years. This increased survival is attributable to better patient selection for resection, quality of surgery, and perioperative patient management.

Introduction A meningeal solitary fibrous tumor (SFT), also called hemangiopericytoma, is a rare mesenchymal malignancy. Due to anatomic constrains, even after macroscopic complete surgery with curative intent, the local relapse risk is still relatively high, thus increasing the risk of dedifferentiation and metastatic spread. This study aims to better define the role of postoperative radiotherapy (RT) in meningeal SFTs. Patients and methods A retrospective study was performed across seven sarcoma centers. Clinical information was retrieved from all adult patients with meningeal primary localized SFT treated between 1990 and 2018 with surgery alone (S) compared to those that also received postoperative RT (S + RT). Differences in treatment characteristics between subgroups were tested using independent samplest-test for continuous variables and chi-square tests for proportions. Local control (LC) and overall survival (OS) rates were calculated as time from start of treatment until progression or death from any cause. LC and OS in groups receiving S or S + RT were compared using Kaplan-Meier survival curves. Results Among a total of 48 patients, 7 (15%) underwent S and 41 (85%) underwent S + RT. Median FU was 65 months. LC was significantly associated with treatment. LC after S at 60 months was 60% versus 90% after S + RT (p = 0.052). Furthermore, R1 resection status was significantly associated with worse LC (HR 4.08,p = 0.038). OS was predominantly associated with the mitotic count (HR 3.10,p = 0.011). Conclusion This retrospective study, investigating postoperative RT in primary localized meningeal SFT patients, suggests that combining RT to surgery in the management of this patient population may reduce the risk for local failures.

Background. The purpose of this study was to evaluate the overall survival (OS) and associated characteristics for patients with Myxoid Liposarcoma (MLS) over time in The Netherlands. Methods. A population-based study was performed of patients with primary localized (n = 851) and metastatic (n = 50) MLS diagnosed in The Netherlands between 1989 and 2016, based on data from the National Cancer Registry. Results. The median age of the MLS patients was 49 years, and approximately two-thirds was located in the lower limb. An association was revealed between age and the risk of having a Round Cell (RC) tumor. OS rates for primary localized MLS were 93%, 83%, 78%, and 66% after 1, 3, 5, and 10 years, respectively. The median OS for patients with metastatic disease at diagnosis was 10 months. Increasing age (Hazard Ratio (HR) 1.05, p=0.00), a tumor size >5 cm (HR 2.18; p=0.00), and tumor location (trunk HR 1.29; p=0.09, upper limb HR 0.83; p=0.55, and “other” locations HR 2.73; p=0.00, as compared to lower limb) were independent prognostic factors for OS. The percentage of patients treated with radiotherapy (RT) increased over time, and preoperative RT gradually replaced postoperative RT. In contrast to patients with localized disease, significant improvement of OS was observed in patients with metastatic disease over time. Conclusions. In this large nationwide cohort, tumor size and tumor location were independent prognostic factors for OS. Furthermore, a higher probability of an RC tumor with increasing age was suggested. An increased use of RT over the years did not translate into improved OS for localized MLS.

This study aimed to investigate changes in treatment strategy and outcome for patients with primary retroperitoneal sarcoma (RPS) undergoing resection at referral centers during a recent period.The study enrolled consecutive adult patients with primary non-metastatic RPS who underwent resection with curative intent between 2002 and 2017 at 10 referral centers. The patients were grouped into three periods according to date of surgery: t1 (2002-2006), t2 (2007-2011), and t3 (2012-2017). Five-year overall survival (OS), disease-specific survival (DSS), and crude cumulative incidence (CCI) of local recurrence (LR) and distant metastasis (DM) were calculated. Multivariable analyses for OS and DSS were performed.The study included 1942 patients. The median follow-up period after resection varied from 130 months (interquartile range [IQR], 124-141 months) in t1 to 37 months (IQR, 35-39 months) in t3. The 5-year OS was 61.2% (95% confidence interval [CI], 56.4-66.3%) in t1, 67.0% (95 CI, 63.2-71.0%) in t2, and 71.9% (95% CI, 67.7-76.1%) in t3. The rate of macroscopically incomplete resection (R2) was 7.1% in t1 versus 4.7% in t3 (p = 0.066). The median number of resected organs increased over time (p 0.001). In the multivariable analysis resection during t3 was associated with better OS and DSS. The 90-day postoperative mortality improved over time (4.3% in t1 to 2.3% in t3; p = 0.031). The 5-year CCI of LR and DM did not change significantly over time.The long-term survival of patients who underwent resection for primary RPS has increased during the past 15 years. This increased survival is attributable to better patient selection for resection, quality of surgery, and perioperative patient management.

Background: Given the rapid evolution in the management of soft tissue sarcoma (STS), it is essential to revisit the evidence regularly. This review examines topics of interest for early management of STS: the impact of molecular genetics on sarcoma classification; the importance of a correct diagnosis and strategy in the surgical management of STS; current status on use of radiotherapy in STS. Areas covered: Accurate diagnosis of STS combines histomorphology, immunochemistry, and molecular genetics, although morphology is the mainstay of therapeutic planning. As diagnosis of STS is challenging, it is best conducted within a multidisciplinary environment. Expert surgery in STS takes into account multiple parameters including biopsy, imaging, pathological knowledge, technical issues, and a multidisciplinary approach. The sum of these factors informs decisions about whether or not to perform surgery and the choice of surgical technique. Advances in radiotherapy are challenging the paradigm of applying the same dose and treatment schedule to all STS patients irrespective of subtype. Preoperative radiotherapy of specific histotypes appears to be the future although more research is required to address uncertainties such as fraction size, total dose, combined modality regimens, and individual sensitivity to radiotherapy. Expert opinion: STS should be managed in a reference center.

The impact of MRI on early detection of local recurrence (LR) in high-grade soft-tissue sarcomas (STS) is unsubstantiated. To identify the contribution of MRI criteria including dynamic contrast-enhanced (DCE) MRI and knowledge of surgical margins that can be used in detecting recurrence prior to obvious proven presence of LR in soft-tissue sarcomas. The secondary aim was to determine causes for misdiagnosing LR. MRI of 23 patients (12 men; mean age, 59.7 years ± 16.5 years) with LR of STS and that of 22 age- and histology-matched controls with STS but without LR were retrospectively analyzed by two musculoskeletal radiologists. Preoperative MRI characteristics (conventional and DCE) were compared to those of MRIs made after treatment, but before LR was proven. Likelihood of recurrence was rated on a 5-point Likert scale for morphological and dynamic assessment separately, before and after adding knowledge of surgical margins. Descriptive statistics and receiver operating characteristic analysis were performed. Differentiation of LR from post-therapeutic changes was the highest combining result of conventional MRI, DCE-MRI, and knowledge of surgical margins (area under the curve (AUC) 0.779), followed by DCE-MRI (AUC 0.706) and conventional MRI (AUC 0.648). Suboptimal MRI technique and overcalling post-therapeutic changes in microscopic positive margins were the main reasons for false negative and false positive results, respectively. MRI including DCE improves the detection of recurrent, clinically silent soft-tissue sarcoma when combined with knowledge of achieved surgical margins. LR may be missed on inadequate MRI protocols. • Dynamic contrast-enhanced MRI is useful in the differentiation of recurrent soft-tissue sarcoma and post-therapeutic fibrosis. • Knowledge of surgical margins substantially increases the value of MRI in detecting recurrent soft-tissue sarcoma. • MR with all three image orientations, covering the entire part of the extremity in at least one sequence and comparison to initial tumor characteristics and location, is beneficial.

Summary Background Unlike for extremity sarcomas, the efficacy of radiotherapy for retroperitoneal sarcoma is not established. The aim of this study was to evaluate the impact of preoperative radiotherapy plus surgery versus surgery alone on abdominal recurrence-free survival. Methods EORTC-62092 is an open-label, randomised, phase 3 study done in 31 research institutions, hospitals, and cancer centres in 13 countries in Europe and North America. Adults (aged ≥18 years) with histologically documented, localised, primary retroperitoneal sarcoma that was operable and suitable for radiotherapy, who had not been previously treated and had a WHO performance status and American Society of Anesthesiologists score of 2 or lower, were centrally randomly assigned (1:1), using an interactive web response system and a minimisation algorithm, to receive either surgery alone or preoperative radiotherapy followed by surgery. Randomisation was stratified by hospital and performance status. Radiotherapy was delivered as 50·4 Gy (in 28 daily fractions of 1·8 Gy) in either 3D conformal radiotherapy or intensity modulated radiotherapy, and the objective of surgery was a macroscopically complete resection of the tumour mass with en-bloc organ resection as necessary. The primary endpoint was abdominal recurrence-free survival, as assessed by the investigator, and was analysed in the intention-to-treat population. Safety was analysed in all patients who started their allocated treatment. This trial is registered with ClinicalTrials.gov , NCT01344018 . Findings Between Jan 18, 2012 and April 10, 2017, 266 patients were enrolled, of whom 133 were randomly assigned to each group. The median follow-up was 43·1 months (IQR 28·8–59·2). 128 (96%) patients from the surgery alone group had surgery, and 119 (89%) patients in the radiotherapy and surgery group had both radiotherapy and surgery. Median abdominal recurrence-free survival was 4·5 years (95% CI 3·9 to not estimable) in the radiotherapy plus surgery group and 5·0 years (3·4 to not estimable) in the surgery only group (hazard ratio 1·01, 95% CI 0·71–1·44; log rank p=0·95). The most common grade 3–4 adverse events were lymphopenia (98 [77%] of 127 patients in the radiotherapy plus surgery group vs one [1%] of 128 patients in the surgery alone group), anaemia (15 [12%] vs ten [8%]), and hypoalbuminaemia (15 [12%] vs five [4%]). Serious adverse events were reported in 30 (24%) of 127 patients in the radiotherapy plus surgery group, and in 13 (10%) of 128 patients in the surgery alone group. One (1%) of 127 patients in the radiotherapy plus surgery group died due to treatment-related serious adverse events (gastropleural fistula), and no patients in the surgery alone group died due to treatment-related serious adverse events. Interpretation Preoperative radiotherapy should not be considered as standard of care treatment for retroperitoneal sarcoma. Funding European Organisation for Research and Treatment of Cancer, and European Clinical Trials in Rare Sarcomas.

Currently, patients with extremity soft tissue sarcoma (eSTS) who have undergone curative resection are followed up by a heuristic approach, not covering individual patient risks. The aim of this study was to develop two flexible parametric competing risk regression models (FPCRRMs) for local recurrence (LR) and distant metastasis (DM), aiming at providing guidance on how to individually follow-up patients. Three thousand sixteen patients (1931 test, 1085 validation cohort) with high-grade eSTS were included in this retrospective, multicenter study. Histology (9 categories), grading (time-varying covariate), gender, age, tumor size, margins, (neo)adjuvant radiotherapy (RTX), and neoadjuvant chemotherapy (CTX) were used in the FPCRRMs and performance tested with Harrell-C-index. Median follow-up was 50 months (interquartile range: 23.3&ndash, 95 months). Two hundred forty-two (12.5%) and 603 (31.2%) of test cohort patients developed LR and DM. Factors significantly associated with LR were gender, size, histology, neo- and adjuvant RTX, and margins. Parameters associated with DM were margins, grading, gender, size, histology, and neoadjuvant RTX. C-statistics was computed for internal (C-index for LR: 0.705, for DM: 0.723) and external cohort (C-index for LR: 0.683, for DM: 0.772). Depending on clinical, pathological, and patient-related parameters, LR- and DM-risks vary. With the present model, implemented in the updated Personalised Sarcoma Care (PERSARC)-app, more individualized prediction of LR/DM-risks is made possible.

Purpose Solitary fibrous tumors (SFTs) are extremely rare mesenchymal malignancies. Given the lack of large prospective studies on radiation therapy (RT) with definitive and/or palliative intent in SFT patients, this retrospective study aimed to better define the benefit of RT in this disease. Methods and Materials A retrospective observational study was performed across 7 sarcoma centers. Clinical information was retrieved from all patients receiving RT without surgery over the course of their locally advanced and/or metastatic disease. Differences in treatment characteristics between subgroups were tested using analysis-of-variance tests. Local control (LC) and overall survival (OS) rates were calculated as time from the start of RT until local progression and death from any cause, respectively. Results Since 1990, a total of 40 patients were identified. RT was applied with definitive intent in 16 patients and with palliative intent in 24. The median follow-up period was 62 months. In patients treated with definitive RT (receiving approximately 60 Gy), the objective response rate was 67%. At 5 years, the LC rate was 81.3%, and the OS rate was 87.5%. In the case of palliative RT (typically 39 Gy), the objective response rate was 38%. The LC and OS rates at 5 years were 62.5% and 54.2%, respectively. In both subgroups, RT-associated toxicities were mild with predominantly grade 1 acute and late side effects. Conclusions This retrospective study suggests a clinically meaningful benefit for RT given with either definitive or palliative intent without surgery in SFT management. Prospective registries potentially in collaboration with patient advocacy groups are warranted to further assess the role of RT in patients with this rare malignancy.