Sarcoma Center Research Articles

Improved nationwide survival of sarcoma patients with a network of reference centers

We investigated the impact of the implementation of a network of reference centers for sarcomas (NETSARC) on the care and survival of sarcoma patients in France since2010. NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDTBs), funded by the French National Cancer Institute (INCa) since 2010. Its aims are to improve the quality of diagnosis and care of sarcoma patients. Patients' characteristics, treatments, and outcomes are collected in a nationwide database. The objective of this analysis was to compare the survival of patients in three periods: 2010-2012 (non-exhaustive), 2013-2015, and 2016-2020. A total of 43 975 patients with sarcomas, gastrointestinal stromal tumors (GISTs), or connective tissue tumors of intermediate malignancy were included in the NETSARC+ database since 2010 (n= 9266 before 2013, n= 12 274 between 2013 and 2015, n= 22 435 in 2016-2020). Median age was 56 years, 50.5% were women, and 13.2% had metastasis at diagnosis. Overall survival was significantly superior in the period 2016-2020 versus 2013-2015 versus 2010-2012 for the entire population, for patients >18 years of age, and for both metastatic and non-metastatic patients in univariate and multivariate analyses (P < 0.0001). Over the three periods, we observed a significantly improved compliance to clinical practice guidelines (CPGs) nationwide: the proportion of patients biopsied before surgery increased from 62.9% to 72.6%; the percentage of patients presented to NETSARC MDTBs before first surgery increased from 31.7% to 44.4% (P < 0.0001). The proportion of patients with R0 resection on first surgery increased (from 36.1% to 46.6%), while R2 resection rate decreased (from 10.9% to 7.9%), with a better compliance and improvement in NETSARC centers. The implementation of the national reference network for sarcoma was associated with an improvement of overall survival and compliance to guidelines nationwide in sarcoma patients. Referral to expert networks for sarcoma patients should be encouraged, though a better compliance to CPGs can still be achieved.

Active surveillance of diffuse-type tenosynovial giant cell tumors: A retrospective, multicenter cohort study

BackgroundDiffuse-type tenosynovial giant cell tumor (D-TGCT) is a mono-articular, soft-tissue tumor. Although it can behave locally aggressively, D-TGCT is a non-malignant disease. This is the first study describing the natural course of D-TGCT and evaluating active surveillance as possible treatment strategy. MethodsThis retrospective, multicenter study included therapy naïve patients with D-TGCT from eight sarcoma centers worldwide between 2000 and 2019. Patients initially managed by active surveillance following their first consultation were eligible. Data regarding the radiological and clinical course and subsequent treatments were collected. ResultsSixty-one patients with primary D-TGCT were initially managed by active surveillance. Fifty-nine patients had an MRI performed around first consultation: D-TGCT was located intra-articular in most patients (n = 56; 95 %) and extra-articular in 14 cases (24 %). At baseline, osteoarthritis was observed in 13 patients (22 %) on MRI. Most of the patients’ reported symptoms: pain (n = 43; 70 %), swelling (n = 33; 54 %). Eight patients (13 %) were asymptomatic.Follow-up data were available for 58 patients; the median follow-up was 28 months. Twenty-one patients (36 %) had radiological progression after 21 months (median). Eight of 45 patients (18 %) without osteoarthritis at baseline developed osteoarthritis during follow-up. Thirty-seven patients (64 %) did not clinically deteriorate during follow-up. Finally, eighteen patients (31 %) required a subsequent treatment. ConclusionActive surveillance can be considered adequate for selected therapy naïve D-TGCT patients. Although follow-up data was limited, almost two-thirds of the patients remained progression-free, and 69 % did not need treatment during the follow-up period. However, one-fifth of patients developed secondary osteoarthritis. Prospective studies on active surveillance are warranted.

Refusal of Adjuvant Therapies and Its Impact on Local Control and Survival in Patients with Bone and Soft Tissue Sarcomas of the Extremities and Trunk.

In soft tissue or bone sarcomas, multimodal therapeutic concepts represent the standard of care. Some patients reject the therapeutic recommendations due to several reasons. The aim of this study was to assess the impact of that rejection on both prognosis and local recurrence. Between 2012 and 2019, a total of 828 sarcoma patients were surgically treated. Chemotherapy was scheduled as a neoadjuvant, and adjuvant multi-agent therapy was performed following recommendations from an interdisciplinary tumor board. Radiotherapy, if deemed appropriate, was administered either in a neoadjuvant or an adjuvant manner. The recommended type of therapy, patient compliance, and the reasons for refusal were documented. Follow-ups included local recurrences, diagnosis of metastatic disease, and patient mortality. Radiotherapy was recommended in 407 (49%) patients. A total of 40 (10%) individuals did not receive radiation. A reduction in overall survival and local recurrence-free survival was evident in those patients who declined radiotherapy. Chemotherapy was advised for 334 (40%) patients, 250 (75%) of whom did receive all recommended cycles. A total of 25 (7%) individuals did receive a partial course while 59 (18%) did not receive any recommended chemotherapy. Overall survival and local recurrence-free survival were reduced in patients refusing chemotherapy. Overall survival was worst for the group of patients who received no chemotherapy due to medical reasons. Refusing chemotherapy for non-medical reasons was seen in 8.8% of patients, and refusal of radiotherapy for non-medical reasons was seen in 4.7% of patients. Divergence from the advised treatment modalities significantly impacted overall survival and local recurrence-free survival across both treatment modalities. There is an imperative need for enhanced physician-patient communication. Reducing treatment times, as achieved with hypofractionated radiotherapy and with therapy in a high-volume sarcoma center, might also have a positive effect on complying with the treatment recommendations.

Unplanned Sarcoma Excisions: Understanding How They Happen.

Soft-tissue sarcomas present as a mass with nonspecific symptoms, and unplanned excisions commonly occur. The purpose of this study was to analyze the incidence of unplanned excisions performed by orthopaedic surgeons and to conduct a root cause analysis (RCA) of the steps that led to unplanned excisions in all the cases. A retrospective case-control study was conducted. Two cohorts were identified, one including patients who underwent an unplanned excision of a soft-tissue sarcoma (n = 107) and a second cohort with patients whose entire care was performed at our sarcoma center (n = 102). A RCA was conducted with the whole sample to identify the preventable causes that led to sarcoma unplanned excisions. Orthopedic surgeons were the second group of physicians to perform the most unplanned excisions, only behind general surgeons. Inadequate imaging was encountered in 76.6% of the patients (n = 82, 95% confidence interval, 67.8 to 83.6). Forty-five patients (42.1%) had no imaging studies before the unplanned procedure. In the RCA, the most notable obstacles found were (1) incorrect assumption of a benign diagnosis, (2) failure to obtain the appropriate imaging study, (3) incorrectly reported imaging studies, (4) failure to order a biopsy, and (5) incorrect reporting of the biopsy. Despite educational efforts, unplanned excisions and the devastating consequences that sometimes follow continue to occur. Orthopaedic surgeons persist in playing a role in the unplanned procedure burden.

Prognosis factors and outcomes of sacrococcygeal chordomas. 20 years’ results in one sarcoma center

Prognosis factors and outcomes of sacrococcygeal chordomas. 20 years’ results in one sarcoma center

Advancing treatment efficacy: combined therapy of eribulin, anlotinib, and camrelizumab in advanced or metastatic retroperitoneal liposarcoma.

Retroperitoneal liposarcoma (RLPS) typically shows limited response to standard chemotherapy, presenting a challenge in treating advanced or metastatic RLPS. This study aimed to evaluate the potential advantages of a combined therapeutic strategy utilizing eribulin, anlotinib, and camrelizumab. Between December 2020 and March 2023, this retrospective study enrolled patients with advanced or metastatic RLPS who received treatment at Peking University Cancer Hospital Sarcoma Center. The treatment regimen involved eribulin plus anlotinib and camrelizumab administered every 3 weeks (Q3W). Efficacy was assessed following the Response Evaluation Criteria in Solid Tumors version 1.1, while safety was evaluated using the Common Terminology Criteria for Adverse Events version 5.0. The study included 47 patients with RLPS with a median age of 55.5 years. Patients received a median of 4.5 (range, 2-21) cycles of treatment. Notably, partial response was observed in 8 patients (18.2%), while 25 (56.8%) exhibited stable disease. The objective response rate (ORR) and disease control rate were 18.2% and 75%, respectively. Significant differences in ORR were observed among histological subtypes (well-differentiated vs de-differentiated vs myxoid: 0 vs 17.9% vs 50%; p = 0.039). Six patients underwent surgery before disease progression, and one patient with myxoid liposarcoma (MLPS) had a pathological complete response. With a median follow-up of 21.8 (range, 2.7-30.7) months, the median progression-free survival (mPFS) was 6.9 (95% confidence interval (CI), 4.7-9.1) months, and the 6-month PFS rate was 60.5%. Based on various histological subtypes, the mPFS was 8.4 (95% CI, 4.1-12.7) months with well-differentiated liposarcoma, 5.8 (95% CI, 3.3-8.3) months with de-differentiated liposarcoma and not reached with MLPS, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 36 (76.6%) patients, with grade 3 or higher TRAEs in 21 (44.7%) patients. The most common TRAEs were neutropenia (53.2%), proteinuria (21.3%), and anorexia (21.3%). The combined treatment strategy involving eribulin, anlotinib, and camrelizumab showed promising efficacy and manageable safety in patients with advanced or metastatic RLPS, particularly in those with MLPS.

Prognostic Nutritional Index (PNI): A More Promising Nutritional Predictor for Patients Undergoing Surgery for Retroperitoneal Liposarcoma.

Extended surgery with multi-visceral resection is the standard treatment for retroperitoneal liposarcoma (RLPS). Malnutrition tends to result in increased surgical complications and reduced survival. The aim of this study was to identify the prognostic role of nutritional status in patients with RLPS. Data from 189 consecutive patients with RLPS who underwent surgical treatment at the Peking University Cancer Hospital Sarcoma Center between April 2011 and August 2022 were retrospectively reviewed. The following nutritional parameters were calculated: nutritional risk index, prognostic nutritional index (PNI) and Nutrition Risk Screening 2002. Time-dependent receiver operating characteristic (time-ROC) curve analysis was conducted to compare the prognostic utility of nutritional indicators. The associations between nutritional indicators and major complications, local recurrence-free survival (LRFS) and overall survival (OS) were investigated. Based on the time-ROC curve analysis, the PNI was superior to other nutritional indices at predicting OS. The optimal cut-off value of PNI was 41.2. The PNI was significantly inversely associated with tumor size, tumor grade, and histological subtype. Patients in the low PNI group (< 41.2) had significantly shorter LRFS and OS than those in the high PNI (≥ 41.2) group, with higher major morbidity and mortality rates. The PNI was found to be a unique nutritional predictor that independently predicted LRFS and OS in the multivariate analysis. The PNI is an effective tool for nutritional assessment in patients with RLPS. A low PNI value in patients with RLPS predicts worse survival outcomes.

Intraoperative motive for incomplete resection in primary retroperitoneal sarcoma.

Surgical resection is the current standard of care for retroperitoneal sarcoma (RPS). Recent data suggests that up to 5% of patient have incomplete (R2) resection. The exact reason why patients scheduled for surgery with a curative intent to treat ended up with an R2 resection is largely unknown. To identify intraoperative findings responsible for incomplete (R2) resection in primary RPS. All records of consecutive patients scheduled for a non-metastatic primary RPS surgery between 1995 and 2020 in a tertiary care sarcoma centre were retrospective analyzed. Among the 347 patients scheduled for surgery, 13 (3.7%) had an incomplete (R2) resection. The reasons for incomplete surgery were intraoperative finding of vascular involvement of great vessels in 5 patients, previously undetected peritoneal metastases in 5 patients, invasion of contralateral kidney/ureter in 2 patients and the need to preserve both kidneys in 1 patient because of his past medical history. Among these patients, 3 had a laparotomy without resection and 10 had a partial resection (i.e. debulking surgery). Severe postoperative complications occurred in 5 patients. The median length of stay in hospital was 19days. After a median follow-up of 12months, the median survival of patients after incomplete resection was 18months. The 1-y, 5-y and 8-y overall survival (OS) for these patients were 46%, 14%, and 7%, respectively. Incomplete (R2) resection for a primary RPS surgery is rare in specialized sarcoma center. The next steps should be to identify the preoperative criteria that lead to this accurate selection and to define the best practice in front of a peroperative discovery of an unresectable RPS. III.

Efficacy of immune checkpoint inhibitors in alveolar soft-part sarcoma: results from a retrospective worldwide registry

Conventional cytotoxic drugs are not effective in alveolar soft-part sarcoma (ASPS). Immune checkpoint (programmed cell death protein 1/programmed death-ligand 1) inhibitors (ICIs) are promising drugs in ASPS. A worldwide registry explored the efficacy of ICI in ASPS. Data from adult patients diagnosed with ASPS and treated with ICI for advanced disease in expert sarcoma centers from Europe, Australia and North America were retrospectively collected, including demographics and data related to treatments and outcome. Seventy-six ASPS patients, with a median age at diagnosis of 25 years (range 3-61 years), were registered. All patients received ICI for metastatic disease. Immunotherapy regimens consisted of monotherapy in 38 patients (50%) and combination in 38 (50%) (23 with a tyrosine kinase inhibitor). Among the 68 assessable patients, there were 3 complete responses and 34 partial responses, translating into an overall response rate of 54.4%. After a median follow-up of 36 months [95% confidence interval (CI) 32-40 months] since the start of immunotherapy, 45 (59%) patients have progressed on ICI, with a median progression-free survival (PFS) of 16.3 months (95% CI 8-25 months). Receiving ICI in first line (P= 0.042) and achieving an objective response (P= 0.043) correlated with abetter PFS. Median estimated overall survival (OS) from ICI initiation has not been reached. The 12-month and 24-month OS rates were 94% and 81%, respectively. This registry constitutes the largest available series of ASPS treated with ICI. Our results suggest that the ICI treatment provides long-lasting disease control and prolonged OS in patients with advanced ASPS, an ultra-rare entity with limited active therapeutic options.

Low local recurrence rates following marginal surgical resection of non-coelomic Atypical Lipomatous Tumours/Well-differentiated Liposarcomas

IntroductionHigh rates of local recurrence (LR) have been reported following resection of extremity Atypical lipomatous tumours/Well-differentiated liposarcomas (ALTs). This retrospective study of patients who underwent resection of primary deep extremity and trunk ALTs at a specialist sarcoma centre aims to assess morbidity and factors associated with low local recurrence rates (LRR). MethodsTo review a homogeneous cohort of patients with low-grade disease, tumours with known high-risk histological features were excluded. Prognostic variables potentially influencing local recurrence (LR) (age, size, site, margin status, and histological findings) were analysed. Endpoints were LR, distant recurrence (DR) and local disease-free survival (LDFS). Results127 patients were identified, with median follow-up of 54 months (0–235). Median tumour size was 17.5 cm (5–36). 85 % occurred in the lower limb. 93.7 % underwent marginal resection. No patients received radiotherapy. Median hospital stay was 3 days (0–16). 7.9 % returned to theatre for evacuation of haematoma or infected seroma and 18.1 % had outpatient seroma aspiration. Surgical margins were R0/R1 in 93.7 % of patients and R2 in 6.3 % with a LR rate of 8.4 % and 75 % respectively at median time of 54 months. One- and 5-year LDFS was 100 % and 88.4 %, respectively. DR rate was 0.8 % (1/127) this patient had pleomorphic liposarcomatous transformation on recurrence and subsequently developed distant metastases. No patients died of disease. ConclusionFunction-preserving marginal resection of non-coelomic ALTs has low morbidity, low LR and extremely low rates of distant relapse. Patients with lower limb ALT were found to have significantly lower LR, which may impact follow-up protocols.

Sclerosing Epithelioid Fibrosarcoma (SEF) versus Low Grade Fibromyxoid Sarcoma (LGFMS): Presentation and outcome in the nationwide NETSARC+ series of 330 patients over 13 years

Sclerosing Epithelioid Fibrosarcoma (SEF) and Low Grade Fibromyxoid Sarcoma (LGFMS) are ultrarare sarcomas sharing common translocations whose natural history are not well known. We report on the nationwide exhaustive series of 330 patients with SEF or LGFMS in NETSARC+ since 2010. Patients and methodsNETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDTB). Since 2010, (i) pathological review has been mandatory for sarcoma,and (ii) tumour/patients’ characteristics have been collected in the NETSARC+ nationwide database. The characteristics of patients with SEF and LGFMS and their outcome are compared. Results35/73 (48%) and 125/257(49%) of patients with SEF and LGFMS were female. More visceral, bone and trunk primary sites were observed in SEF (p < 0.001). 30% of SEF vs 4% of LGFMS patients had metastasis at diagnosis (p < 0.0001). Median size of the primary tumor was 51 mm (range 10–90) for LGFMS vs 80 (20−320) for SEF (p < 0.001). Median age for LGFMS patients was 12 years younger than that of SEF patients (43 [range 4–98] vs 55 [range 10–91], p < 0.001). Neoadjuvant treatment was more often given to SEF (16% vs 9%, p = 0.05). More patients with LGFMS were operated first in reference centers (51% vs 26%, p < 0.001). The R0 rate on the operative specimen was 41% in LGFMS vs 16% in SEF (p < 0.001). Median event-free survival (EFS) of patients with SEF and LGFMS were 32 vs 136 months (p < 0.0001). The median overall survival (OS) was not reached. Fifty-months OS was 93% vs 81% for LGFMS vs SEF (p = 0.05). Median OS was 77 months after first relapse, similar for SEF and LGFMS.In multivariate analysis, age, tumor size, metastasis at diagnosis were independent prognostic factors for OS in LGFMS. ConclusionsAlthough sharing close molecular alterations, SEF and LGFMS have a different natural history, clinical presentation and outcome, with a higher risk of metastatic relapse in SEF. Survival after relapse is longer than with other sarcomas, and similar for SEF and LGFMS.

Intraosseous conventional central chondrosarcoma does not metastasise irrespective of grade in pelvis, scapula and in long bone locations

BackgroundHistological grade has been regarded as the most important prognostic factor in conventional central chondrosarcoma. To evaluate whether the presence of an extraosseous tumour component is associated with a decreased metastasis-free survival or disease-specific survival and alternatively to develop a simple prognostic and clinical decision-making tool. Material and methodsWe searched two prospectively maintained international sarcoma centre databases for primary non metastatic central conventional chondrosarcomas of all grades in pelvis, scapula or long bone location, undergoing curative treatment, diagnosed between 2000 and 2020. Pre-treatment MRI scans were reviewed for the presence of an extraosseous mass. The metastasis-free survival (MFS) and disease-specific survival (DSS) were estimated by the Kaplan-Meier method from surgery to event, death or last follow-up. Results336 patients were identified between 2000 and 2020, undergoing surgical treatment for conventional central chondrosarcoma. 111 patients (33 %) had grade 1 tumours, 149 patients (44 %) had grade 2, and 76 patient (23 %) had grade 3 chondrosarcomas determined as the highest grade in the final resected specimen. An extraosseous soft tissue component was more frequent in higher grade tumours (p < 0.001) and present in 200 cases (60 %). None of the patients with an intraosseous tumour developed metastases or died of the disease. For patients with extraosseous tumour component, MFS was 92 % (95 % CI, 96–100) at 2-years and 74 % (95 % CI, 67–81) at 10-years and DSS was 91 % (95 % CI, 87–95) at 2-years and 75 % (95 % CI, 68–82) at 10-years. The MFS and DSS was significantly different (p < 0.001) for those patients with or without an extraosseous tumour component, irrespective of grade or anatomical location. DiscussionThe results of this study has shown that the metastatic potential of intraosseous conventional central chondrosarcoma is negligible. The presence of an extraosseous soft tissue component may be used for prognostication and to guide treatment pathways for patients with central cartilage tumours.

Imaging Features of Alveolar Soft Part Sarcoma: Single Institution Experience and Literature Review.

Alveolar soft part sarcoma (ASPS) is an extremely rare and aggressive soft-tissue sarcoma (STS) subtype with poor prognosis and limited response to radiation therapy and chemotherapy. Prompt recognition and referral to sarcoma centers for appropriate management are crucial for patients' survival. The purpose of this study was to report ASPS pre-treatment imaging features and to examine the existing literature on this topic. Twelve patients (7 women, 5 men-mean age 27.1 ± 10.7 years) were included from our single-center experience. Ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) available were reviewed according to an analysis grid incorporating features from the latest research on STS. Clinical, histological, and outcome data were collected. MRI was available in 10 patients (83.3%), US in 7 patients (58.3%), and CT in 3 patients (25%). Mean longest tumor diameter was 7.6 ± 2.9 cm, and all tumors were deeply seated. Large peritumoral feeding vessels were systematically found and identified on ultrasonography (7/7), MRI (10/10), and CT (3/3). US revealed a well-defined heterogeneous hypoechoic pattern, with abundant flow signals in all patients (7/7). In all patients, MRI showed mildly high signal intensity (SI) on T1-WI and high SI on T2-WI and peritumoral edema. Moreover, flow-voids (due to arteriosus high-flow) into the peritumoral/intratumoral feeding vessels were detected in the MRI fluid-sensitive sequences of all patients. At baseline, whole-body contrast-enhanced CT revealed metastases in 8/12 (66.7%) patients. A pre-treatment longest diameter > 5 cm was significantly associated with distant metastases at diagnosis (p = 0.01). A maximum diameter > 5 cm represents a risk of metastatic disease at diagnosis (odds ratio = 45.0000 (95% CI: 1.4908-1358.3585), p = 0.0285). In the comprehensive literature review, we found 14 articles (case series or original research) focusing on ASPS imaging, with a total of 151 patients included. Merging our experience with the data from the existing literature, we conclude that the hallmark of ASPS imaging at presentation are the following characteristics: deep location, a slight hyperintense MRI SI on T1-WI and a hyperintense SI on T2-WI, numerous MRI flow voids, high internal vascularization, and large peritumoral feeding vessels.

Role of high‑sensitivity C‑reactive protein in patients with sarcoma.

Immunotherapy has shown promising results in lung cancer and melanomas; however, the responses have been poor in patients with sarcoma. Understanding the relationship between the immune system and sarcoma is essential to develop improved immunotherapy approaches. High-sensitivity C-reactive protein (hs-CRP) has been proposed as a prognostic marker in other cancer types; however, to the best of our knowledge, the association between hs-CRP levels and mortality in patients with sarcoma has not been investigated. The present prospective, non-randomised, non-interventional explorative study investigated the prognostic value of hs-CRP in patients with sarcoma. Patients referred to the sarcoma centre of Aarhus University Hospital (Aarhus, Denmark) were included between April 2014 and December 2020. Clinical data were obtained from the national quality sarcoma database and biomarkers other than hs-CRP were obtained from the clinical laboratory information system. The study cohort consisted primarily of patients with localised sarcoma. hs-CRP was significantly higher in patients with bone sarcoma (P=0.022) and soft tissue sarcoma (STS; P<0.001) compared with control patients. For STS, grade III tumours but not metastatic disease were associated with a higher hs-CRP level (P=0.0001). Elevated hs-CRP levels were associated with increased overall mortality [hazard ratio (HR), 1.91; 95% CI, 1.33-2.75; P=0.001]. Furthermore, elevated hs-CRP levels were also associated with decreased progression-free survival (HR, 1.64; 95% CI, 1.17-2.29; P=0.004). Furthermore, for patients with hs-CRP <8 mg/l, higher hs-CRP was associated with an increased risk of recurrent disease and reduced overall survival compared with those of patients with low hs-CRP. In conclusion, the present study demonstrated that hs-CRP was a prognostic factor for overall mortality and progression-free survival in patients with localised sarcoma at the time of diagnosis. Further studies are required to investigate the mechanism behind the association between hs-CRP and sarcoma prognosis and its potential use in clinical practice.

1981P Histopathological diagnostic discrepancies in bone and soft tissue tumors referred to a specialist sarcoma center and its clinical impact

1981P Histopathological diagnostic discrepancies in bone and soft tissue tumors referred to a specialist sarcoma center and its clinical impact

Distribution and Rate of Myxoid Liposarcoma Spine Metastases: Impact on Surveillance Imaging.

Myxoid liposarcoma (LPS) has a unique tendency to spread to extrapulmonary sites, including osseous sites such as the spine, and adjacent sites such as the paraspinous tissue. No clear consensus exists to guide the approach to imaging in these patients. The aim of this study was to investigate the rate and distribution of spine metastases in patients with myxoid LPS and detection modality. Records of all patients with myxoid LPS evaluated at our sarcoma center were retrospectively reviewed. Disease patterns and imaging modality utilization were analyzed. Between 2000 and 2020, 164 patients with myxoid LPS were identified. The majority (n=148, 90%) presented with localized disease, with half (n=82, 50%) of all patients developing metastases or recurrence during their disease course. With a median follow-up of 69.2 months, spine/paraspinous metastases developed in 38 patients (23%), of whom 35 (92%) already had synchronous, non-spine metastases. Spine disease was only visible on magnetic resonance imaging (MRI), as opposed to other imaging modalities, for over one-quarter of patients with spine metastases (n=10). For patients with metastatic disease, spine metastases were associated with worse median overall survival (2.1 vs. 8.7 years, p<0.001). Spine metastases occurred in nearly one-quarter of patients with myxoid LPS and represented an advanced disease state, as they primarily presented in the setting of synchronous, non-spine metastases, and were associated with worse overall survival. Routine surveillance with spine MRI in patients with localized disease likely provides no benefit but may be considered in those with known metastatic disease.

Clinician survey of current global practice for sarcoma surveillance following resection of primary retroperitoneal, abdominal, and pelvic sarcoma

Introduction– Postoperative surveillance following resection of primary retroperitoneal, abdominal, and pelvic sarcoma (RPS) is standard of care in international sarcoma centres and has rapidly evolved without an evidence base to become highly intensive and prolonged. This clinician survey aims to capture a global, contemporary snapshot of international guidelines used to inform sarcoma surveillance following resection of primary RPS. Materials and methods– Between July 2022 and March 2023, an online, anonymous, clinician survey to assess the current duration, imaging intervals and imaging modalities used for postoperative surveillance following resection of primary RPS was distributed among clinicians working at centres which are members of the TransAtlantic Australasian Retroperitoneal Working Group (TARPSWG). Results– Responses were received from 58 different TARPSWG centres. The majority of centres use institutional guidelines to guide surveillance intensity (n = 43, 74%) and the surveillance imaging modality (n = 39, 67%) used. For surveillance intensity and imaging modality, institutional guidelines are partially or entirely based on international guidelines in 81% (n = 47) and 78% (n = 45) of centres, respectively. Commonly used imaging modalities are contrast-enhanced CT abdomen-pelvis (n = 51, 88%) for abdominal surveillance and non-contrast enhanced CT (n = 25, 43%) for chest surveillance. Imaging intervals, timing of de-escalation of imaging frequency and total duration of surveillance for low-grade and high-grade RPS are reported. Conclusion– This global survey among TARPSWG members demonstrates the heterogeneity in sarcoma surveillance strategies worldwide and emphasises the need for a randomised controlled trial to provide an evidence base for the optimal surveillance schedule following primary resection of RPS.

Low-Grade Uterine Leiomyosarcoma Is Highly Sensitive to Hormonal Treatment.

According to the World Health Organization classification system, uterine leiomyosarcomas (ULMS) are high-grade. A diagnosis of smooth-muscle tumors of uncertain malignant potential (STUMP) is made when Stanford Criteria for ULMS are not met. When a STUMP recurs, the tumor is diagnosed as ULMS and medical treatment is the same as for ULMS. In recent years, some sarcoma centers valued the less aggressive clinical behavior of several recurring STUMP and, given their expression of estrogen and progesterone receptors, started to treat them with hormonal therapy. This was a retrospective cohort analysis conducted at three referral centers joining the Leiomyosarcoma Foundation Roundtable. We selected all cases of uterine smooth muscle tumors consistent with STUMP and treated with hormonal therapy. 27 consecutive patients were identified. Median age at diagnosis was 43 years. Stage was IA-IB in more than 70% of patients. In these patients, median time to relapse was 62 months. Sites of first relapses were mostly pelvis and peritoneum (76%). After a median follow-up of 49 months, 14 patients (52%) had a partial response while 10 (37%) had a minor response or stable disease. Median time to progression was not reached. We observed a response or long-term stability rate on hormonal therapy in the 90% range; in all cases the time to relapse was significantly longer than in ULMS and in most cases the relapse was abdominal. On the basis of these findings, we conclude that a proportion of patients with uterine smooth muscle neoplasms actually present with a "low-grade ULMS."

An interpretable AI model for recurrence prediction after surgery in gastrointestinal stromal tumour: an observational cohort study

There are several models that predict the risk of recurrence following resection of localised, primary gastrointestinal stromal tumour (GIST). However, assessment of calibration is not always feasible and when performed, calibration of current GIST models appears to be suboptimal. We aimed to develop a prognostic model to predict the recurrence of GIST after surgery with both good discrimination and calibration by uncovering and harnessing the non-linear relationships among variables that predict recurrence. In this observational cohort study, the data of 395 adult patients who underwent complete resection (R0 or R1) of a localised, primary GIST in the pre-imatinib era at Memorial Sloan Kettering Cancer Center (NY, USA) (recruited 1982-2001) and a European consortium (Spanish Group for Research in Sarcomas, 80 sites) (recruited 1987-2011) were used to train an interpretable Artificial Intelligence (AI)-based model called Optimal Classification Trees (OCT). The OCT predicted the probability of recurrence after surgery by capturing non-linear relationships among predictors of recurrence. The data of an additional 596 patients from another European consortium (Polish Clinical GIST Registry, 7 sites) (recruited 1981-2013) who were also treated in the pre-imatinib era were used to externally validate the OCT predictions with regard to discrimination (Harrell's C-index and Brier score) and calibration (calibration curve, Brier score, and Hosmer-Lemeshow test). The calibration of the Memorial Sloan Kettering (MSK) GIST nomogram was used as a comparative gold standard. We also evaluated the clinical utility of the OCT and the MSK nomogram by performing a Decision Curve Analysis (DCA). The internal cohort included 395 patients (median [IQR] age, 63 [54-71] years; 214 men [54.2%]) and the external cohort included 556 patients (median [IQR] age, 60 [52-68] years; 308 men [55.4%]). The Harrell's C-index of the OCT in the external validation cohort was greater than that of the MSK nomogram (0.805 (95% CI: 0.803-0.808) vs 0.788 (95% CI: 0.786-0.791), respectively). In the external validation cohort, the slope and intercept of the calibration curve of the main OCT were 1.041 and 0.038, respectively. In comparison, the slope and intercept of the calibration curve for the MSK nomogram was 0.681 and 0.032, respectively. The MSK nomogram overestimated the recurrence risk throughout the entire calibration curve. Of note, the Brier score was lower for the OCT compared to the MSK nomogram (0.147 vs 0.564, respectively), and the Hosmer-Lemeshow test was insignificant (P=0.087) for the OCT model but significant (P<0.001) for the MSK nomogram. Both results confirmed the superior discrimination and calibration of the OCT over the MSK nomogram. A decision curve analysis showed that the AI-based OCT model allowed for superior decision making compared to the MSK nomogram for both patients with 25-50% recurrence risk as well as those with >50% risk of recurrence. We present the first prognostic models of recurrence risk in GIST that demonstrate excellent discrimination, calibration, and clinical utility on external validation. Additional studies for further validation are warranted. With further validation, these tools could potentially improve patient counseling and selection for adjuvant therapy. The NCI SPORE in Soft Tissue Sarcoma and NCI Cancer Center Support Grants.

Does the use of polymethyl-methacrylate cement after intralesional curettage of giant cell tumors of appendicular bone guarantee reduced local recurrence rates? A retrospective analysis.

Polymethyl-methacrylate cement (PMMA) is often used as bone defect reconstruction material after surgical removal of giant cell tumors. The purpose of this study was to investigate if the application of PMMA improves the local recurrence rates for giant cell tumors (GCT) of appendicular bone treated with intralesional curettage. A retrospective analysis of all appendicular GTCs treated at two major Danish sarcoma centres between the 1st of January 1998 and December 31st 2013; minimum follow-up of 3.0years (median: 8.9; 1.3-18.7years). Kaplan-Meier survival model, log-rank and multivariate Cox regression were used to calculate and compare local recurrence rates. p-values <0.05 were considered statistically significant. 102 patients (M59/F43), median age 31Y (11-84) were included in this study. The overall 3-years local recurrence-rate was 19.9% (95%CI: 11.9-27.9%); 91% had occurred within 3years. In patients treated with intralesional curettage (n = 64), the 3-years recurrence-rate was 30.6% (95%CI: 18.8-42.4%), compared to 2.6% (95%CI: 0.0-7.8%) in patients treated with wide resection or amputation (n = 38), p < .001. The 3-years recurrence-rate for patients treated with intralesional curettage and reconstruction using PMMA was 29.0% (95%CI: 12.6-45.4%) and without PMMA: 31.8% (95%CI: 15.2-48.4%), p = .83. We found that the use of PMMA for bone defect reconstruction after intralesional curettage of GTCs in the appendicular skeleton did not ensure a reduced risk of local recurrence.