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There has been growing interest in the use of real-world data (RWD) to address clinically and policy-relevant (research) questions that cannot be answered with data from randomized controlled trials (RCTs) alone. This is, for example, the case in rare malignancies such as sarcomas as limited patient numbers pose challenges in conducting RCTs within feasible timeliness, a manageable number of collaborators, and statistical power. This narrative review explores the potential of RWD to generate real-world evidence (RWE) in sarcoma research, elucidating its application across different phases of the patient journey, from prediagnosis to the follow-up/survivorship phase. For instance, examining electronic health records (EHRs) from general practitioners (GPs) enables the exploration of consultation frequency and presenting symptoms in primary care before a sarcoma diagnosis. In addition, alternative study designs that integrate RWD with well-designed observational RCTs may offer relevant information on the effectiveness of clinical treatments. As, especially in cases of ultrarare sarcomas, it can be an extreme challenge to perform well-powered randomized prospective studies. Therefore, it is crucial to support the adaptation of novel study designs. Regarding the follow-up/survivorship phase, examining EHR from primary and secondary care can provide valuable insights into identifying the short- and long-term effects of treatment over an extended follow-up period. The utilization of RWD also comes with several challenges, including issues related to data quality and privacy, as described in this study. Notwithstanding these challenges, this study underscores the potential of RWD to bridge, at least partially, gaps between evidence and practice and holds promise in contributing to the improvement of sarcoma care. Exploring RWD potential in sarcoma research: bridging evidence gaps, despite challenges, for improved care. [ABSTRACT FROM AUTHOR]

Simple Summary: A multidisciplinary group researched and defined criteria to describe a sarcoma specialist treatment center or network. The project is led by Sarcoma Patient Advocacy Global Network (SPAGN), involves patient groups from around the world and is supported by clinical specialists and leading researchers. The paper identifies Core Principles and Key Features which define a specialist center/network. They are supported by evidence and experience. A primary aim is that new patients and their families can identify a specialist center which can provide curative treatment. A secondary aim is that countries where specialist treatment is not yet available can identify what they have to achieve to meet that ambition. The Core Principles allow a center or network to attain accreditation as a Sarcoma Intelligent Specialist Network. The Key Features are more aspirational and are expressed in a way that allows local needs, legal considerations and budgetary pressures to be taken into account. This is the first time an expert multidisciplinary group has defined specialism in cancer treatment in a worldwide context. The management of sarcomas in specialist centers delivers significant benefits. In much of the world, specialists are not available, and the development of expertise is identified as a major need. However, the terms 'specialist' or 'expert' center are rarely defined. Our objective is to offer a definition for patient advocates and a tool for healthcare providers to underpin improving the care of people with sarcoma. SPAGN developed a discussion paper for a workshop at the SPAGN 2023 Conference, attended by 75 delegates. A presentation to the Connective Tissue Oncology Society (CTOS) and further discussion led to this paper. Core Principles were identified that underlie specialist sarcoma care. The primary Principle is the multi-disciplinary team discussing every patient, at first diagnosis and during treatment. Principles for optimal sarcoma management include accurate diagnosis followed by safe, high-quality treatment, with curative intent. These Principles are supplemented by Features describing areas of healthcare, professional involvement, and service provision and identifying further research and development needs. These allow for variations because of national or local policies and budgets. We propose the term 'Sarcoma Intelligent Specialist Network' to recognize expertise wherever it is found in the world. This provides a base for further discussion and local refinement. [ABSTRACT FROM AUTHOR]

Opinion statement: Neoadjuvant radiotherapy (RT) over 5–6 weeks with daily doses of 1.8–2.0 Gy to a total dose of 50–50.4 Gy is standard of care for localized high-grade soft tissue sarcomas (STS) of the extremities and trunk wall. One exception is myxoid liposarcomas where the phase II DOREMY trial applying a preoperative dose of 36 Gy in 2 Gy fractions (3–4 weeks treatment) has achieved excellent local control rates of 100% after a median follow-up of 25 months. Hypofractionated preoperative RT has been investigated in a number of phase II single-arm studies suggesting that daily doses of 2.75–8 Gy over 1–3 weeks can achieve similar oncological outcomes to conventional neoadjuvant RT. Prospective data with direct head-to-head comparison to conventional neoadjuvant RT investigating oncological outcomes and toxicity profiles is eagerly awaited. For the entire group of retroperitoneal sarcomas, RT is not the standard of care. The randomized multi-center STRASS trial did not find a benefit in abdominal recurrence-free survival by the addition of preoperative RT. However, for the largest histological subgroup of well-differentiated and grades I and II dedifferentiated liposarcomas, the STRASS trial and the post-hoc propensity-matched STREXIT analysis have identified a possible benefit in survival by preoperative RT. These patients deserve to be informed about the pros and cons of preoperative RT while the longer follow-up data from the STRASS trial is awaited. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates health-related quality of life changes in patients with a soft-tissue sarcoma during the diagnostic and treatment trajectory, and the differences in health-related quality of life changes between adults and the elderly since they face different challenges due to different levels of physical, social or work-related activities. Examining data from the VALUE-PERSARC trial, 97 patients completed the HRQoL questionnaires at diagnosis, and 3, 6 and 12 months thereafter. Results show comparable patterns across all measures, i.e., lower baseline scores, and a decrease at 3 months followed by subsequent improvement, reaching similar levels as the general population at 12 months. However, patients seem to struggle with the mental aspect of well-being, independent of age. The results of this study suggest that it is important to address both physical and mental health in the care of patients with a soft-tissue sarcoma. Introduction: Changes in health-related quality of life (HRQoL) during the diagnostic and treatment trajectory of high-grade extremity soft-tissue sarcoma (eSTS) has rarely been investigated for adults (18–65 y) and the elderly (aged ≥65 y), despite a potential variation in challenges from diverse levels of physical, social, or work-related activities. This study assesses HRQoL from time of diagnosis to one year thereafter among adults and the elderly with eSTS. Methods: HRQoL of participants from the VALUE-PERSARC trial (n = 97) was assessed at diagnosis and 3, 6 and 12 months thereafter, utilizing the PROMIS Global Health (GH), PROMIS Physical Function (PF) and EQ-5D-5L. Results: Over time, similar patterns were observed in all HRQoL measures, i.e., lower HRQoL scores than the Dutch population at baseline (PROMIS-PF:46.8, PROMIS GH-Mental:47.3, GH-Physical:46.2, EQ-5D-5L:0.76, EQ-VAS:72.6), a decrease at 3 months, followed by an upward trend to reach similar scores as the general population at 12 months (PROMIS-PF:49.9, PROMIS GH-Physical:50.1, EQ-5D-5L:0.84, EQ-VAS:81.5), except for the PROMIS GH-Mental (47.5), where scores remained lower than the general population mean (T = 50). Except for the PROMIS-PF, no age-related differences were observed. Conclusions: On average, eSTS patients recover well physically from surgery, yet the mental component demonstrates no progression, irrespective of age. These results underscore the importance of comprehensive care addressing both physical and mental health. [ABSTRACT FROM AUTHOR]

Compared to other sarcomas, myxoid liposarcoma (MLS) is exceptionally sensitive to radiation therapy, but the underlying mechanism remains unknown. The objective was to assess the tissue-based changes in MLS during and after neoadjuvant radiotherapy in 26 patients of the DOREMY trial. Morphological assessment was performed on biopsies pre-treatment, after 8 fractions, 16 factions, and after surgical resection and included percentage of viable tumor cells, hyalinization, necrosis, and fatty maturation. Furthermore, immunohistochemistry was performed for apoptosis (cleaved caspase-3), anti-apoptosis (Bcl-2), activity of mTOR signaling (phospho-S6), hypoxia (CAIX), proliferation (Ki67), inflammation (CD45 and CD68), and microvessel density (CD34 Chalkley count). A pronounced reduction in vital tumor cells was observed early with a drop to 32.5% (median) tumor cells (IQR 10–93.8%) after 8 fractions. This decreased further to 10% (IQR 5–30%) after 16 fractions and 7.5% (IQR 5–15%) in the surgical specimen. All but one patient had an excellent response with < 50% remaining tumor cells. Inversely, treatment response was mainly observed as hyalinization and less often as fatty maturation. Additionally, a decrease of inflammatory cells was noticed especially during the first eight fractions. Microvessel density remained stable over time. Immunohistochemical markers for apoptosis, anti-apoptosis, activity of mTOR signaling, proliferation, and hypoxia did not show any marked changes within the remaining tumor cells during and after radiotherapy. As a modest dose of neoadjuvant radiotherapy induces profound tissue changes in MLS, mainly during the first 8 fractions, current findings might suggest that in a carefully selected patient population further deintensification of radiotherapy might be explored. [ABSTRACT FROM AUTHOR]

Background: The etiology of cutaneous angiosarcoma (cAS) may be idiopathic (I-cAS), or arise secondary to radiotherapy (RT-cAS), in chronic lymphedema (ST-cAS), or related to UV exposure (UV-cAS). The aim of this study was to evaluate oncological outcomes of different cAS subtypes. Patients and Methods: Non-metastatic cAS patients, treated with surgery for primary disease with curative intent, were retrospectively analyzed for oncological outcome, including local recurrence (LR), distant metastases (DM), and overall survival (OS). Results: A total of 234 patients were identified; 60 I-cAS, 122 RT-cAS, 9 ST-cAS, and 43 UV-cAS. The majority was female (78%), the median age was 66 years (IQR 57–76 years), the median tumor size was 4.4 cm (IQR 2.5–7.0 cm), and most common site of disease was the breast (59%). Recurrence was identified in 66% (44% LR and/or 41% DM), with a median follow up of 26.5 months (IQR 12–60 months). The 5-year OS was estimated at 50%, LRFS at 47%, and DMFS at 50%. There was no significant difference in LR, DM, or OS between the subtypes. Age < 65 years and administration of radiotherapy (RT) were significantly associated with lower LR rates (HR 0.560, 95% CI 0.3373–0.840, p = 0.005 and HR 0.421, 95% CI 0.225–0.790, p = 0.007, respectively), however no prognostic factors were identified for development of DM. Development of DM, but not LR (p = 0.052), was significantly associated with decreased OS (HR 6.486, 95% CI 2.939–14.318 p < 0.001). Conclusion: We found no significant difference in oncological outcome between the different cAS subtypes. OS remains relatively poor, and RT is associated with lower LR rates. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the association between radiological and histopathological response after neoadjuvant radiotherapy (nRT) in soft tissue sarcoma (STS), as well as the prognostic value of the different response evaluation methods on the oncological outcome. A retrospective cohort of patients with localized STS of the extremity and trunk wall, treated with nRT followed by resection were included. The radiological response was assessed by RECIST 1.1 (RECIST) and MR-adapted Choi (Choi), histopathologic response was evaluated according to the EORTC-STBSG recommendations. Oncological outcome parameters of interest were local recurrence-free survival (LRFS), disease metastases-free survival (DMFS), and overall survival (OS). For 107 patients, complete pre- and postoperative pathology and imaging datasets were available. Most tumors were high-grade (77%) and the most common histological subtypes were undifferentiated pleomorphic sarcoma/not otherwise specified (UPS/NOS, 40%), myxoid liposarcoma (MLS, 21%) and myxofibrosarcoma (MFS, 16%). When comparing RECIST to Choi, the response was differently categorized in 58%, with a higher response rate (CR + PR) with Choi. Radiological responders showed a significant lower median percentage of viable cells (RECIST p =.050, Choi p =.015) and necrosis (RECIST p <.001), and a higher median percentage of fibrosis (RECIST p =.005, Choi p =.008), compared to radiological non-responders (SD + PD). RECIST, Choi, fibrosis, and viable cells were not significantly associated with altered oncological outcome, more necrosis was associated with poorer OS (p =.038). RECIST, Choi and the EORTC-STBSG response score show incongruent results in response evaluation. The radiological response was significantly correlated with a lower percentage of viable cells and necrosis, but a higher percentage of fibrosis. Apart from necrosis, radiological nor other histopathological parameters were associated with oncologic outcomes. [ABSTRACT FROM AUTHOR]

Background: The European Organization for Research and Treatment of Cancer 22092‐62092 STRASS trial failed to demonstrate the superiority of neoadjuvant radiotherapy (RT) over surgery alone in patients with retroperitoneal sarcoma. Therefore, an RT quality‐assurance program was added to the study protocol to detect and correct RT deviations. The authors report results from the trial RT quality‐assurance program and its potential effect on patient outcomes. Methods: To evaluate the effect of RT compliance on survival outcomes, a composite end point was created. It combined the information related to planning target volume coverage, target delineation, total dose received, and overall treatment time into 2 groups: non–RT‐compliant (NRC) for patients who had unacceptable deviation(s) in any of the previous categories and RT‐compliant (RC) otherwise. Abdominal recurrence‐free survival (ARFS) and overall survival were compared between the 2 groups using a Cox proportional hazard model adjusted for known prognostic factors. Results: Thirty‐six of 125 patients (28.8%) were classified as NRC, and the remaining 89 patients (71.2%) were classified as RC. The 3‐year ARFS rate was 66.8% (95% confidence interval [CI], 55.8%‐75.7%) and 49.8% (95% CI, 32.7%‐64.8%) for the RC and NRC groups, respectively (adjusted hazard ratio, 2.32; 95% CI, 1.25‐4.32; P =.008). Local recurrence after macroscopic complete resection occurred in 13 of 89 patients (14.6%) versus 2 of 36 patients (5.6%) in the RC and NRC groups, respectively. Conclusions: The current analysis suggests a significant benefit in terms of ARFS in favor of the RC group. This association did not translate into less local relapses after complete resection in the RC group. Multidisciplinary collaboration and review of cases are critical to avoid geographic misses, especially for rare tumors like retroperitoneal sarcoma. This analysis suggested a significant benefit in terms of abdominal recurrence‐free survival in favor of the radiotherapy‐compliant group but not in terms of local relapse. Multidisciplinary collaboration and review of cases were critical to avoid geographic misses, especially for rare tumors like retroperitoneal sarcoma. [ABSTRACT FROM AUTHOR]

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 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. The list of ultra‐rare sarcomas, defined as those sarcomas with an incidence ≤1 per 1,000,000, comprises 56 soft tissue sarcoma and 21 bone sarcoma types. The incidence of ultra‐rare sarcomas accounts for roughly 20% of all soft tissue and bone sarcomas, confirming that challenges inherent to ultra‐rare sarcomas affect large numbers of patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: 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.Methods: 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.Results: 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.Conclusion: 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.Key Points: • 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction. Nonsurgical management of patients with desmoid-type fibromatosis (DF) is increasing. This study tries to provide insight on type, usage, and outcome of first-line nonsurgical management strategies. Patients and Methods. From the Dutch Pathology Registry (PALGA), patients with extra-abdominal or trunk/abdominal wall DF, diagnosed between 1993 and 2013, were identified. First-line treatment was analyzed. Best response (BR) using RECIST criteria from start of treatment/surveillance until change of treatment or last follow-up was analyzed. Results. Ninety-one of the 1141 identified patients had first-line nonsurgical management. The percentage of patients treated nonsurgically increased from 0.6% in 1993–1998 to 12.8% in 2009–2013. Thirty-seven patients had surveillance (41%), 35 radiotherapy (38%), and 19 systemic treatment (21%). BR for surveillance was complete response (CR) in 2/37, partial response (PR) in 4/37, stable disease (SD) in 21/37, progressive disease (PD) in 5/37, and unknown in 5/37 patients. BR for radiotherapy was CR in 4/35, PR in 11/35, SD in 16/35, and unknown in 4/35. BR for systemic treatment was CR in 1/19, PR in 1/19, SD in 10/19, PD in 2/19, and unknown in 5/19. Totally, 91% of patients did not progress. Discussion. Given the low percentage (9%) of PD of nonsurgical management, these data can be used in shared decision making with the patient regarding optimal treatment. [ABSTRACT FROM AUTHOR]

Soft tissue sarcomas are a heterogeneous group of rare malignancies. The diagnostic gold standard is conventional histomorphology with integrated immunohistochemistry. Molecular genetic profiling has identified new subgroups of undifferentiated sarcomas involving genetic rearrangements with creation of fusion genes. Accurate classification of sarcomas is critical for appropriate clinical decision-making which should involve a multidisciplinary team. A preoperative biopsy is necessary to confirm a diagnosis. Strategy is discussed in the multidisciplinary board. Reconstructive surgery must be planned in advance taking into account possible surgical morbidity. In high-risk situations, neo-adjuvant treatment could facilitate surgery in some cases, increase survival and provide indications of tumor biology. The decision is based on tumor subtype, grade and location, patient age and presence of comorbidities. [ABSTRACT FROM AUTHOR]

Purpose: The EORTC QLQ-C30 and the Brief Pain Inventory (BPI) are validated tools for measuring quality of life (QOL) and the impact of pain in patients with advanced cancer. Interpretation of these instrument scores can be challenging and it is difficult to know what numerical changes translate to clinically significant impact in patients' lives. To address this issue, our study sought to establish the minimal clinically important differences (MCID) for these two instruments in a prospective cohort of patients with advanced cancer and painful bone metastases.Methods: Both anchor-based and distribution-based methods were used to estimate the MCID scores from patients enrolled in a randomized phase III trial evaluating two different re-irradiation treatment schedules. For the anchor-based method, the global QOL item from the QLQ-C30 was chosen as the anchor. Spearman correlation coefficients were calculated for all items and only those items with moderate or better correlation (|r| ≥ 0.30) with the anchor were used for subsequent analysis. A 10-point difference in the global QOL score was used to classify improvement and deterioration, and the MCID scores were calculated for each of these categories. These results were compared with scores obtained by the distribution-method, which estimates the MCID purely from the statistical characteristics of the sample population.Results: A total of 375 patients were included in this study with documented pain responses and completed QOL questionnaires at 2 months. 9/14 items in the QLQ-C30 and 6/10 items in the BPI were found to have moderate or better correlation with the anchor. For deterioration, statistically significant MCID scores were found in all items of the QLQ-C30 and BPI. For improvement, statistically significant MCID scores were found in 7/9 items of the QLQ-C30 and 2/6 items of the BPI. The MCID scores for deterioration were uniformly higher than the MCIDs for improvement. Using the distribution-based method, there was good agreement between the 0.5 standard deviation (SD) values and anchor-based scores for deterioration. For improvement, there was less agreement and the anchor-based scores were lower than the 0.5 SD values obtained from the distribution-based method.Conclusion: We present MCID scores for the QLQ-C30 and BPI instruments obtained from a large cohort of patients with advanced cancer undergoing re-irradiation for painful bone metastases. The results from this study were compared to other similar studies which showed larger MCID scores for improvement compared to deterioration. We hypothesize that disease trajectory and patient expectations are important factors in understanding the contrasting results. The results of this study can guide clinicians and researchers in the interpretation of these instruments. [ABSTRACT FROM AUTHOR]

Introduction: Optimal management of soft tissue sarcoma (STS) remains a challenge. A nationwide survey assessed the quality of STS care in the Netherlands, thereby aiming to identify potentialities for improvement through more centralized disease management. Methods: From the Netherlands Cancer Registry (NCR), data were obtained on 3317 adult STS patients (excluding gastrointestinal stromal tumor, GIST) diagnosed in 2006-2011. Logistic regression models were employed to compare outcomes on selected clinical indicators reflecting prevailing STS guidelines between high-volume (≥10 resections annually) and low-volume (<10 resections) hospitals, between academic and general hospitals, and between sarcoma research centers and other hospitals, adjusted for case mix. Analyses were performed on imputed datasets ( m = 50), generated through multiple imputations by chained equations. Results: Overall, 89% of patients underwent surgical resection. Resection status remained unknown in 24% (excluding those with metastasized disease), and grade was not documented for one-third of tumors. Microscopic residual disease was detected in 20% with an increased risk for older patients, larger and deeply located tumors, and those located in the (retro)peritoneum or upper extremity. Almost half of patients with an R1 resection received adjuvant radiotherapy. Following adjustment for case mix factors, patients treated in high-volume hospitals less often had macroscopic residual disease (R2 resection; adjusted odds ratio: 0.54). A strongly skewed distribution of surgical volumes was observed. Conclusions: These survey results indicate a potential for improving Dutch STS care. More centralized sarcoma management should improve definitive pathology reporting on tumor characteristics, adherence to treatment guidelines and overall disease outcome. [ABSTRACT FROM AUTHOR]

Background: Despite a radical surgical approach to primary retroperitoneal sarcoma (RPS), many patients experience locoregional and/or distant recurrence. The objective of this study was to analyze post-relapse outcomes for patients with RPS who had initially undergone surgical resection of their primary tumor at a specialist center.Methods: All consecutive patients who underwent macroscopically complete resection for primary RPS at 8 high volume centers from January 2002 to December 2011 were identified, and those who developed local recurrence (LR) only, distant metastasis (DM) only, or synchronous local recurrence and distant metastasis (LR+DM) during the follow-up period were included. Overall survival (OS) was calculated for all groups, as was the crude cumulative incidence of a second recurrence after the first LR. Multivariate analyses for OS were performed.Results: In an initial series of 1007 patients with primary RPS, 408 patients developed recurrent disease during the follow-up period. The median follow-up from the time of recurrence was 41 months. The median OS was 33 months after LR (n = 219), 25 months after DM (n = 146), and 12 months after LR+DM (n = 43), and the 5-year OS rates were 29%, 20%, and 14%, respectively. Predictors of OS after LR were the time interval to LR and resection of LR, while histologic grade approached significance. For DM, significant predictors of OS were the time interval to DM and histologic subtype. The subgroup of patients who underwent resection of recurrent disease had a longer median OS than patients who did not undergo resection.Conclusions: Relapse of RPS portends high disease-specific mortality. Patients with locally recurrent or metastatic disease should be considered for resection. Cancer 2017;123:1971-1978. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Surgery is the golden standard for treating basal cell carcinomas. In case of positive tumor margins or recurrent disease, postoperative adjuvant or salvaging therapy is suggested to achieve good local control. Objective: To retrospectively report on local control and toxicity of postoperative radiotherapy by means of orthovoltage X-rays for residual or recurrent basal cell carcinoma after surgery in the head and neck area. Methods: Sixty-six surgically resected residual or recurrent basal cell carcinomas of the head and neck region were irradiated postoperatively by means of orthovoltage X-rays at the Netherlands Cancer Institute between January 2000 and February 2015. Results: After a median follow-up duration of 30.5 months, only 5 recurrences were reported. The 5-year local control rates at 1, 3, and 5 years were 100%, 87%, and 87%, respectively. The 5-year local control rate was 92% for immediate postoperative radiotherapy of incompletely resected basal cell carcinomas, 90% for recurrences after 1 previously performed excision, and 71% for multiple recurrences, namely, a history of more than 1 excision (P = .437). Acute toxicity healed spontaneously within 3 months. Late toxicities were mild. Conclusion: Radiotherapy by means of orthovoltage X-ray is an excellent alternative for re-excision in case of incompletely resected or recurrent basal cell carcinomas that are at risk of serious functional and cosmetic impairments after re-excision, with a 5-year local control rate of 87% and a low toxicity profile. [ABSTRACT FROM AUTHOR]

The combination of radiotherapy (RT) and function-preserving surgery is the most usual contemporary approach in the management of soft tissue sarcomas (STS). Pre- and postoperative RT result in similar local control rates, as shown by a landmark trial in extremity STS. In this review, the role of RT in the management of extremity STS will be discussed, but STS in other sites, including retroperitoneal STS, will also be addressed. The focus will consider various aspects of RT including strategies to reduce the volume of tissue being irradiated, dose, scheduling, and the possible of omission of RT in selected cases. Finally, technology advances through the use of intensity-modulated radiotherapy (IMRT), image-guided IMRT, intraoperative radiotherapy (IORT) and particle therapy will also be discussed. [ABSTRACT FROM AUTHOR]

Background: A multi-institutional nomogram for predicting disease-free survival (DFS) and overall survival (OS) in patients with primary retroperitoneal sarcoma (RPS) incorporating relevant prognostic factors not included in the American Joint Committee on Cancer staging system for soft tissue sarcoma has been reported. The authors validated this nomogram with an independent, transatlantic cohort.Methods: Data from patients with RPS who were undergoing definitive resection at 1 of 6 sarcoma centers in Europe and North America ("validation set") were used to validate a RPS nomogram developed from 3 other centers ("development set"). The nomogram incorporated 6 variables: age, tumor size, grade, histologic subtype, multifocality, and quality of surgery. Nomogram-predicted probabilities were stratified into 6 subgroups and compared with observed outcomes. Discriminative ability was quantified by Harrell C statistics.Results: The validation and development sets included 631 and 523 patients, respectively, all of whom underwent surgical resection at the institutions represented. The 7-year DFS and OS rates for the validation set were 38% (95% confidence interval, 34%-43%) and 58% (95% confidence interval, 53%-63%), respectively. All 6 nomogram variables were found to be independently prognostic. The corrected Harrell C statistics concordance index values for the validation set were 0.69 for DFS and 0.73 for OS, which were similar to those for the development set, suggesting good calibration of the nomogram in the validation cohort.Conclusions: The RPS nomogram was externally validated using a larger, independent cohort. The nomogram can be generalized to patients undergoing surgery for RPS by specialized sarcoma surgeons at sarcoma centers. The nomogram provides a more individualized and disease-relevant estimation of OS compared with the American Joint Committee on Cancer classification. Cancer 2016;122:1417-1424. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: We performed a retrospective nationwide study to explore age as a prognostic factor in synovial sarcoma patients.Methods: Data on 613 synovial sarcoma patients were obtained from the Netherlands Cancer Registry. The prognostic relevance of age groups (children, adolescent and young adults (AYAs), adults, and elderly) was estimated by Kaplan-Meier survival curves and multivariable Cox-proportional hazards modelling.Results: A total of 461 patients had localised disease at diagnosis. The 5-year overall survival (OS) was 89.3±4.6%, 73.0±3.8%, 54.7±3.6%, and 43.0±7.0% in children (n=54), AYAs (n=148), adults (n=204), and elderly (n=55), respectively. Treatment modalities had no significant effect on survival in the univariable analysis. Multivariable analysis identified age at diagnosis, tumour localisation, and tumour size as significant factors affecting OS. Both tumour localisation and size were equally distributed over the age groups.Conclusions: We show that outcome of synovial sarcoma patients significantly decreases with age regardless of primary tumour site, size, and treatment. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests significant synergism combining radiotherapy (RT) with angiogenesis targeted therapies. This multicenter prospective phase I clinical trial established the safety profile and recommended dose for further studies of pazopanib concurrent with preoperative RT in patients with extremity soft tissue sarcomas (ESTS) in curative setting. Methods.Patients with deep seated intermediate and high grade sarcomas, ≥ 5 cm, received once daily pazopanib (dose-escalation cohorts 400 mg, 600 mg and 800 mg) for 6 weeks and 50 Gy preoperative RT starting Day 8. Surgery was performed 5–7 weeks later. Toxicity was scored according to CTC criteria 4.0. Dose limiting toxicities (DLT) were divided into two separate sets; DLT-I being toxicities occurring during the 6-week chemoradiotherapy period within the radiation portals until day of surgery (designated as DLT-I) and those occurring perioperatively until Day 21 after surgery (DLT-II). Results.A total of 12 patients were enrolled, 11 were evaluable (3 females and 8 males, median age 58 years, range 24–78 years, median tumor size 9 cm, range 5–15 cm). Ten underwent surgery. No increased toxicity inside the radiation fields was seen, but two of 10 patients (one each in the 400 mg and 600 mg cohorts) showed delayed wound healing after surgery. None of the patients showed significant volume reductions after RT. Evaluation of the resection specimen showed pathological (near) complete responses (≥ 95% necrosis rate) in four of 10 cases. Unexpectedly, grade 3 + hepatotoxicity led to premature pazopanib interruption in three of 11 (27%) of cases. Conclusion.Apart from hepatotoxicity, neoadjuvant pazopanib 800 mg daily in combination with 50 Gy seems tolerable; the regimen appears to demonstrate promising activity in ESTS and is the recommended dose for further studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients and patient advocates from Sarcoma Patients EuroNet (SPAEN), a global network of national Sarcoma Patient Advocacy Groups, and medical experts from the scientifically driven Connective Tissue Oncology Society (CTOS) came together on 9 November 2021 at an official ancillary event to the CTOS 2021 Annual Meeting. At the event, representatives of CTOS and SPAEN jointly discussed gaps and challenges in global sarcoma care and management. This resulting position paper highlights the main findings and possible future steps. Sarcomas are a grouping of rare cancers with a wide variety of histological types that are difficult to diagnose and treat. This leads to many varying challenges not only for sarcoma patients, but also for doctors, researchers, and caregivers. Patient advocacy groups have an important role to play in rare cancers such as sarcomas, especially in collaboration with experts and their medical societies. To this end, patients and patient advocates from Sarcoma Patients EuroNet (SPAEN), a global network of national Sarcoma Patient Advocacy Groups, and medical experts from the scientifically driven Connective Tissue Oncology Society (CTOS) came together on 9 November 2021 at an official ancillary event to the CTOS 2021 Annual Meeting. At the event, representatives of CTOS and SPAEN jointly discussed gaps and challenges in global sarcoma care and management. This resulting position paper highlights the main findings and possible future steps. [ABSTRACT FROM AUTHOR]

Liposarcomas are separated into clinicopathological entities with a characteristic morphological spectrum and mutually exclusive genetic alterations. Therefore, the rare occurrence of cases with combined patterns of well-differentiated liposarcoma and myxoid liposarcoma designated as mixed-type liposarcoma pose a conceptual problem. Moreover, this feature may have consequences for treatment choice and prognosis. Here, we have dissected the molecular relation of tumor components in cases of mixed-type liposarcoma. On the basis of heterogeneous preoperative magnetic resonance image (MRI) features, eight cases of mixed-type liposarcoma were selected. Preoperative biopsy samples and resection specimens were analyzed including molecular and immunohistochemical analysis on all components. As controls, cases with homogeneous MRI features and uniform aspects of myxoid liposarcoma (n = 5), round cell liposarcoma (n = 5) and well-differentiated liposarcoma (n = 5) were studied. All patients with heterogeneous MRI features showed morphological components of myxoid liposarcoma and well-differentiated liposarcoma. Real-time polymerase chain reaction showed FUS-DDIT3 fusion in both components in five of eight cases in the absence (zero of five) of MDM2 and CDK4 amplification. In three of eight patients, MDM2 and/or CDK4 were overexpressed, and amplification was shown by multiplex ligation-dependent probe amplification (MLPA) in the absence of myxoid liposarcoma translocations. All control patients showed a molecular pattern consistent with their morphological features. Therefore, mixed-type liposarcomas should not be regarded as collision tumors, but as an extreme variant of the morphological spectrum within a single biological entity, explaining the biological contradiction of mixed-type liposarcoma. For treatment stratification, detailed classification including molecular support should be performed in tumors with heterogeneous MRI features. [ABSTRACT FROM AUTHOR]

Aims. Chondroid lipoma (CL) is a benign tumor that mimics a variety of soft tissue tumors and is characterized by translocation t(11;16). Here, we analyze CL and its histological mimics. Methods. CL (n = 4) was compared to a variety of histological mimics (n = 83) formorphological aspects and immunohistochemical features including cyclinD1(CCND1). Using FISHanalysis, CCND1 and FUS were investigated as potential translocation partners. Results. All CLs were strongly positive for CCND1. One of 4 myoepitheliomas, CCND1, was positive. In well-differentiated lipomatous tumors and in chondrosarcomas, CCND1 was frequently expressed, but all myxoid liposarcomas were negative. FISH analysis did not give support for direct involvement of CCND1 and FUS as translocation partners. Conclusions. Chondroid lipoma is extremely rare and has several and more prevalent histological mimics. The differential diagnosis of chondroid lipomas can be unraveled using immunohistochemical and molecular support. [ABSTRACT FROM AUTHOR]

Aims. Chondroid lipoma (CL) is a benign tumor that mimics a variety of soft tissue tumors and is characterized by translocation t(11;16). Here, we analyze CL and its histological mimics. Methods. CL (n = 4) was compared to a variety of histological mimics (n = 83) formorphological aspects and immunohistochemical features including cyclinD1(CCND1). Using FISHanalysis, CCND1 and FUS were investigated as potential translocation partners. Results. All CLs were strongly positive for CCND1. One of 4 myoepitheliomas, CCND1, was positive. In well-differentiated lipomatous tumors and in chondrosarcomas, CCND1 was frequently expressed, but all myxoid liposarcomas were negative. FISH analysis did not give support for direct involvement of CCND1 and FUS as translocation partners. Conclusions. Chondroid lipoma is extremely rare and has several and more prevalent histological mimics. The differential diagnosis of chondroid lipomas can be unraveled using immunohistochemical and molecular support. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Simple Summary: Pazopanib plasma levels have been associated with treatment efficacy. Since pazopanib targets receptors present on cells in the vicinity of the tumor and on tumor cells themselves, measurement of pazopanib concentrations in tumor tissue might be an even better prognostic biomarker than plasma levels. The aim of our study was to quantify pazopanib concentrations in tumor tissue, correlate this with plasma concentrations, and assess whether this is a better biomarker for efficacy. A modest correlation was found between pazopanib tumor concentrations and plasma concentrations. Additionally, no correlation was found between pazopanib tumor concentrations and efficacy. We provide recommendations for future studies in which pazopanib concentrations are measured. 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 > 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. [ABSTRACT FROM AUTHOR]

The spectrum of lipomatous lesions ranges from benign to highly malignant disease. Differentiation between these lesions is important to indicate prognosis and choose the most appropriate treatment. Hemosiderotic fibrohistiocytic lipomatous lesion (HFLL) is a rare subtype of lipomatous tumor. The diagnosis is usually based on clinical, histological, and immunohistochemical information. Where magnetic resonance (MR) imaging is a suitable modality to assess fatty tumors, no data is reported on MR imaging of HFLL. Here, the MR characteristics are described in correlation with pathologic findings in a case of HFLL in the left thigh, an unusual location. [ABSTRACT FROM AUTHOR]