Interferon-gamma signature as prognostic and predictive marker in macroscopic stage III melanoma.

BACKGROUND: A substantial proportion of patients with macroscopic stage III melanoma do not benefit sufficiently from adjuvant anti-PD-1 therapy, as they either recur despite therapy or would never have recurred. To better inform adjuvant treatment selection, we have performed translational analyses to identify prognostic and predictive biomarkers. PATIENTS AND METHODS: Two cohorts of patients with macroscopic stage III melanoma from an ongoing biobank study were included. Clinical data were compared between an observation cohort (cohort 1) and an adjuvant intention cohort (cohort 2). RNA sequencing for translational analyses was performed and treatment subgroups (cohort 1A and cohort 2A) were compared for possible biomarkers, using a cut-off based on the treatment-naïve patients. In addition, two validation cohorts (Melanoma Institute Australia (MIA) and University Medical Centre Utrecht (UMCU)) were obtained. RESULTS: After a median follow-up of 26 months of the 98 patients in our discovery set, median recurrence-free survival (RFS) was significantly longer for the adjuvant intention cohort (cohort 2, n=49) versus the observation cohort (cohort 1, n=49). Median overall survival was not reached for either cohort, nor significantly different. In observation cohort 1A (n=24), RFS was significantly longer for patients with high interferon-gamma (IFNγ) score (p=0.002); for adjuvant patients of cohort 2A (n=24), a similar trend was observed (p=0.086). Patients with high B cell score had a longer RFS in cohort 1A, but no difference was seen in cohort 2A. The B cell score based on RNA correlated with CD20+ cells in tumor area but was not independent from the IFNγ score. In the MIA validation cohort (n=44), longer RFS was observed for patients with high IFNγ score compared with low IFNγ score (p=0.046), no difference in RFS was observed according to the B cell score. In both the observation (n=11) and the adjuvant (n=11) UMCU validation cohorts, no difference in RFS was seen for IFNγ and B cell. CONCLUSIONS: IFNγ has shown to be a prognostic marker in both patients who were and were not treated with adjuvant therapy. B cell score was prognostic but did not improve accuracy over IFNγ. Our study confirmed RFS benefit of adjuvant anti-PD-1 for patients with macroscopic stage III melanoma.

The effect of a single dose of nivolumab prior to isolated limb perfusion for patients with in-transit melanoma metastases: An interim analysis of a phase Ib/II randomized double-blind placebo-controlled trial (NivoILP trial).

OBJECTIVE: ILP has shown to achieve high response rates in patients with melanoma ITM. Possibly there is a synergistic mechanism of action of ILP and anti-PD1. The aim of this trial was to investigate the safety and efficacy of adding a single dose of systemic anti-PD1 to isolated limb perfusion (ILP) for patients with melanoma in-transit metastases (ITM). METHODS: In this placebo controlled double-blind phase Ib/II trial, patients with melanoma ITM were randomized 1:1 to either a single systemic dose of nivolumab or placebo one day prior to ILP. The primary endpoint was complete response (CR) rate at three months, and safety in terms of incidence and severity of adverse events (AEs). RESULTS: A total of 20 patients were included. AEs of any grade occurred in 90% of patients in the nivolumab arm and in 80% in the placebo arm within three months after ILP. Grade 3 AEs were reported in 40% and 30% respectively, most commonly related to wound infection, wound dehiscence, or skin necrosis. There were no grade 4 or 5 AEs reported. The CR rate was 75% in the nivolumab arm and 60% in the placebo arm. The 1-year local progression-free rate was 86% in the nivolumab arm and 67% in the placebo arm. The 1-year OS was 100% in both arms. CONCLUSION: For patients with melanoma ITM, the addition of a single systemic dose of nivolumab the day before ILP is considered safe and feasible with promising efficacy. Accrual will continue in a phase 2 trial.

Changes in Health-Related Quality of Life following Surgery in Patients with High-Grade Extremity Soft-Tissue Sarcoma: A Prospective Longitudinal Study.

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.

Toward the use of diffuse reflection spectroscopy for intra-operative tissue discrimination during sarcoma surgery.

Significance: Accurately distinguishing tumor tissue from normal tissue is crucial to achieve complete resections during soft tissue sarcoma (STS) surgery while preserving critical structures. Incomplete tumor resections are associated with an increased risk of local recurrence and worse patient prognosis. Aim: We evaluate the performance of diffuse reflectance spectroscopy (DRS) to distinguish tumor tissue from healthy tissue in STSs. Approach: DRS spectra were acquired from different tissue types on multiple locations in 20 freshly excised sarcoma specimens. A k-nearest neighbors classification model was trained to predict the tissue types of the measured locations, using binary and multiclass approaches. Results: Tumor tissue could be distinguished from healthy tissue with a classification accuracy of 0.90, sensitivity of 0.88, and specificity of 0.93 when well-differentiated liposarcomas were included. Excluding this subtype, the classification performance increased to an accuracy of 0.93, sensitivity of 0.94, and specificity of 0.93. The developed model showed a consistent performance over different histological subtypes and tumor locations. Conclusions: Automatic tissue discrimination using DRS enables real-time intra-operative guidance, contributing to more accurate STS resections.

Real-world relapse-free survival data on adjuvant anti-PD-1 therapy for patients with newly diagnosed and recurrent stage III melanoma.

We aimed to compare the relapse-free survival (RFS) in patients treated with adjuvant anti-programmed cell death-1 (anti-PD-1) therapy for a first diagnosis of stage III melanoma to patients treated after resection of the recurrences. Patients treated with adjuvant anti-PD-1 therapy after complete resection of stage III melanoma between September 2018 and January 2021, were included. Depending on when adjuvant anti-PD-1 treatment was initiated, patients were divided over 2 cohorts: for the first diagnosis (cohort A) or for a second or subsequent diagnosis (cohort B) of stage III melanoma. Clinical data and RFS were compared between cohorts. 66 patients were included: 37 in cohort A, 29 in cohort B. Median follow-up time from the start of adjuvant therapy was 21 months and 17 months in cohorts A and B, respectively. Significant differences in ulceration of the primary tumor ( P  = 0.032), stage according to the 7th AJCC (American Joint Committee on Cancer , P  = 0.026) and type of metastatic involvement ( P  = 0.005) were found between cohorts. In cohorts A and B, 18 (49%) and 8 (28%) patients developed a recurrence and the 1-year RFS was 51% and 72%, respectively. In cohort B, RFS remained longer in the patients of which the interval between first diagnosis of stage III melanoma and start of adjuvant therapy was >48 months compared to ≤48 months (83% vs. 65%, P  = 0.253). This study demonstrates that patients with recurrent stage III disease, not previously treated with adjuvant systemic therapy, may derive similar benefit to a first diagnosis of stage III patients if access to adjuvant therapy changes.

Radio-Guided Occult Lesion Localization With 99m Tc for the Localization of Nonpalpable Melanoma and Soft Tissue Sarcoma Lesions: A Feasibility Study.

PURPOSE OF THE REPORT: Localization techniques are needed to facilitate resection of nonpalpable lesions. In this study, the feasibility of radio-guided occult lesion localization (ROLL) with 99m Tc is investigated for the localization of nonpalpable, small, suspicious, or proven melanoma or soft tissue sarcoma lesions at various locations throughout the body. PATIENTS AND METHODS: Patients with nonpalpable, suspicious, or proven melanoma or soft tissue sarcoma lesions were selected for this study. Within 24 hours before surgery, a median dose of 33.92 MBq 99m Tc-labeled human albumin particles ( 99m Tc-NA or 99m Tc-MAA) was injected in the lesion under ultrasound guidance. A hand-held gamma probe was used to detect the radioactive signal and guidance during surgery. RESULTS: In this study, 20 patients with a total of 25 lesions were included and analyzed. The median size of the lesions was 1.8 cm (interquartile range [IQR], 1.8-4.0 cm), of which 44% were intramuscular located and 36% were subcutaneous, and 20% consisted of suspicious lymph nodes, mostly in the lower extremity. At median 4 hours (IQR, 3-6 hours) postinjection, 99m Tc ROLL showed a 100% intraoperative identification rate with proper signal identification with the gamma probe in all patients. With a median surgery time of 76 minutes (IQR, 45-157 minutes), all targeted lesions could be resected without 99m Tc-related complications, resulting in 88% microscopically margin-negative resection. No reoperations were needed for the same lesion. CONCLUSIONS: The 99m Tc ROLL procedure is feasible for the localization and excision of small, nonpalpable melanoma and soft tissue sarcoma lesions at various locations in the body.

Neoadjuvant Imatinib in Locally Advanced Gastrointestinal Stromal Tumors (GISTs) is Effective and Safe: Results from a Prospective Single-Center Study with 108 Patients.

BACKGROUND: Neoadjuvant imatinib is considered for gastrointestinal stromal tumors (GISTs) when decreased tumor size provides less extensive surgery and higher R0 resection rates. This study evaluates the effectivity and safety of neoadjuvant imatinib for large or locally advanced GIST. PATIENTS AND METHODS: From the prospective database of the Dutch GIST Consortium, all patients who underwent surgery after neoadjuvant imatinib at our center between 2009 and 2022 were selected. Independent and blinded assessment of surgical strategy was performed by two surgeons, based on anonymized computed tomography (CT) scans before and after neoadjuvant imatinib. RESULTS: Of 113 patients that received neoadjuvant imatinib, 108 (95%) [mean age 61.6, standard deviation (SD) 11.5, 54% male] underwent a GIST resection. Of all GISTs, 67% was localized in the stomach and 25% in the duodenum or small intestine. In 74% of the patients with GIST, a KIT exon 11 mutation was found. Decreased tumor size was seen in 95 (88%) patients. Having a KIT exon 11 mutation [odds ratio (OR) 5.64, 95% confidence interval (CI) 1.67-19.1, p < 0.01] or not having a mutation (OR 0.19, 95% CI 0.04-0.89, p = 0.04) were positive and negative predictive values for partial response, respectively. In 55 (51%) patients, there was deescalation of surgical strategy after neoadjuvant imatinib. Surgical complications were documented in 16 (15%) patients (n = 8, grade II; n = 5, grade IIIa; n = 3, grade IIIb) and R0 resection was accomplished in 95 (89%) patients. The 5-year disease-free and overall survival were 80% and 91%, respectively. CONCLUSION: This study shows that neoadjuvant imatinib is effective and safe for patients with large or locally advanced GIST.

Current practice in assessment and management of malnutrition in surgical oncology practice - An ESSO-EYSAC snapshot analysis.

INTRODUCTION: Malnutrition is common in patients suffering from malignant diseases and has a major impact on patient outcomes. Prevention and early detection are crucial for effective treatment. This study aimed to investigate current international practice in the assessment and management of malnutrition in surgical oncology departments. MATERIAL AND METHODS: The survey was designed by European Society of Surgical Oncology (ESSO) and ESSO Young Surgeons and Alumni Club (EYSAC) Research Academy as an online questionnaire with 41 questions addressing three main areas: participant demographics, malnutrition assessment, and perioperative nutritional standards. The survey was distributed from October to November 2021 via emails, social media and the ESSO website to surgical networks focussing on surgical oncologists. Results were collected and analysed by an independent team. RESULTS: A total of 156 participants from 39 different countries answered the survey, reflecting a response rate of 1.4%. Surgeons reported treating a mean of 22.4 patients per month. 38% of all patients treated in surgical oncology departments were routinely screened for malnutrition. 52% of patients were perceived as being at risk for malnutrition. The most used screening tool was the "Malnutrition Universal Screening Tool" (MUST). 68% of participants agreed that the surgeon is responsible for assessing preoperative nutritional status. 49% of patients were routinely seen by dieticians. In cases of severe malnutrition, 56% considered postponing the operation. CONCLUSIONS: The reported rate of malnutrition screening by surgical oncologists is lower than expected (38%). This indicates a need for improved awareness of malnutrition in surgical oncology, and nutritional screening.

Variation in response rates to isolated limb perfusion in different soft-tissue tumour subtypes: an international multi-centre study.

OBJECTIVE: The aim of this study was to investigate the response rates of different extremity soft-tissue sarcoma subtypes (eSTS) after isolated limb perfusion (ILP), based on an international multi-centre study. MATERIALS AND METHODS: The retrospective cohort comprised eSTS patients from 17 specialised ILP centres that underwent melphalan-based ILP, with or without recombinant human tumour necrosis factor (rhTNFα) (TM-ILP and M-ILP, respectively). Response was measured on imaging (magnetic resonance imaging) and/or clinical response, for which M-ILPs were excluded. RESULTS: A total of 1109 eSTS patients were included. The three most common histological subtypes were undifferentiated pleomorphic sarcoma (17%, n = 184), synovial sarcoma (16%, n = 175) and myxofibrosarcoma (8%, n = 87). rhTNFα was used in 93% (TM-ILP) and resulted in a significantly better overall response rate (ORR, p = 0.031) and complete responses (CR, p < 0.001) in comparison to M-ILP, without significant differences among histological subgroups. The ORR of TM-ILP was 68%, including 17% CR. Also, 80% showed progressive disease. Significantly higher response rates were shown for Kaposi sarcoma (KS) with 42% CR and 96% ORR (both p < 0.001), and significantly higher CR rates for angiosarcoma (AS, 45%, p < 0.001) and clear cell sarcoma (CCS, 31%, p = 0.049). ILP was followed by resection ≤ 6 months in 80% of the patients. The overall limb salvage rate was 88%, without significant differences among histological subgroups, but was significantly higher for ILP responders compared to non-responders (93% versus 76%, p < 0.001). CONCLUSION: ILP resulted in high response and LRS among all eSTS subtypes, however, with significant differences between subtypes with most promising results for KS, AS and CCS.

Local treatment in metastatic GIST patients: A multicentre analysis from the Dutch GIST Registry.

BACKGROUND: The added value of local treatment in selected metastatic GIST patients is unclear. This study aims to provide insight into the usefulness of local treatment in metastatic GIST by use of a survey study and retrospective analyses in a clinical database. METHODS: A survey study was conducted among clinical specialists to select most relevant characteristics of metastatic GIST patients considered for local treatment, defined as elective surgery or ablation. Patients were selected from the Dutch GIST Registry. A multivariate Cox-regression model for overall survival since time of diagnosis of metastatic disease was estimated with local treatment as a time-dependent variable. An additional model was estimated to assess prognostic factors since local treatment. RESULTS: The survey's response rate was 14/16. Performance status, response to TKIs, location of active disease, number of lesions, mutation status, and time between primary diagnosis and metastases, were regarded the 6 most important characteristics. Of 457 included patients, 123 underwent local treatment, which was associated with better survival after diagnosis of metastases (HR = 0.558, 95%CI = 0.336-0.928). Progressive disease during systemic treatment (HR = 3.885, 95%CI = 1.195-12.627) and disease confined to the liver (HR = 0.269, 95%CI = 0.082-0.880) were associated with worse and better survival after local treatment, respectively. CONCLUSION: Local treatment is associated with better survival in selected patients with metastatic GIST. Locally treated patients with response to TKIs and disease confined to the liver have good clinical outcome. These results might be considered for tailoring treatment, but should be interpreted with care because only specific patients are provided with local treatment in this retrospective study.

Correlation of radiological and histopathological response after neoadjuvant radiotherapy in soft tissue sarcoma.

BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSION: 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.

Prognosis of Patients with Cutaneous Angiosarcoma After Surgical Resection with Curative Intent: Is There a Difference Between the Subtypes?

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.

Single agent Talimogene Laherparepvec for stage IIIB-IVM1c melanoma patients: A systematic review and meta-analysis.

Single-agent Talimogene Laherparepvec (T-VEC) was developed for treatment of unresectable and injectable stage III-IV melanoma. Since its approval and reimbursement, studies have reported varying response rates. The purpose of this systematic review and meta-analysis was to investigate the efficacy and safety of T-VEC. Of 341 publications that were identified, eight studies with a total of 642 patients were included. In patients with stage IIIB-IVM1a, the pooled complete- and overall response rate (CRR and ORR) were 41% and 64%, respectively. In patients with stage IIIB-IVM1c, the pooled CRR and ORR were 30% and 44%, respectively. In patients with stage IVM1b and IVM1c, the pooled CRR and ORR were 4% and 9%, respectively. Adverse events (AEs) were seen in 41-100% of all patients and 0-11% of AEs were severe. In conclusion, single agent T-VEC achieves the highest response rates in patients with early metastatic melanoma and is well-tolerated with generally only mild toxicities.

Intraoperative Near-Infrared Fluorescence Imaging with Indocyanine Green for Identification of Gastrointestinal Stromal Tumors (GISTs), a Feasibility Study.

BACKGROUND: Optimal intraoperative tumor identification of gastrointestinal stromal tumors (GISTs) is important for the quality of surgical resections. This study aims to assess the potential of near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG) to improve intraoperative tumor identification. METHODS: Ten GIST patients, planned to undergo resection, were included. During surgery, 10 mg of ICG was intravenously administered, and NIRF imaging was performed at 5, 10, and 15 min after the injection. The tumor fluorescence intensity was visually assessed, and tumor-to-background ratios (TBRs) were calculated for exophytic lesions. RESULTS: Eleven GIST lesions were imaged. The fluorescence intensity of the tumor was visually synchronous and similar to the background in five lesions. In one lesion, the tumor fluorescence was more intense than in the surrounding tissue. Almost no fluorescence was observed in both the tumor and healthy peritoneal tissue in two patients with GIST lesions adjacent to the liver. In three GISTs without exophytic growth, no fluorescence of the tumor was observed. The median TBRs at 5, 10, and 15 min were 1.0 (0.4-1.2), 1.0 (0.5-1.9), and 0.9 (0.7-1.2), respectively. CONCLUSION: GISTs typically show similar fluorescence intensity to the surrounding tissue in NIRF imaging after intraoperative ICG administration. Therefore, intraoperatively administered ICG is currently not applicable for adequate tumor identification, and further research should focus on the development of tumor-specific fluorescent tracers for GISTs.

Standards in surgical training in advanced pelvic malignancy across Europe and beyond - A Snapshot analysis.

INTRODUCTION: Multimodal treatment of patients with advanced pelvic malignancies (APM) is challenging and surgical expertise is usually concentrated in highly specialised centres. Given significant regional variation in APM surgery, surgical training represents a cornerstone in standardising and future-proofing of this complex therapy. The aim of this study was to describe the availability and current satisfaction levels with surgical training for APM. MATERIAL AND METHODS: An online questionnaire was developed and distributed through the Redcap© platform with 32 questions addressing participant and institution demographics, and training in APM surgeries. The survey was electronically disseminated in 2021 to surgical networks across Europe including all specialities treating APM via the European Society of Surgical Oncology (ESSO). All statistical analysis were performed using R. RESULTS: The survey received 280 responses from surgeons across 49 countries, representing general surgery (36%), surgical oncology (30%), gynaeoncology (15%), colorectal surgery (14%) and urology (5%). Fifty-three percent of participants report performing >25 APM procedures/year. Respondents were departmental chiefs (12%), consultants (34%), specialist surgeons (40%) and fellows (15%). 34% were happy/very happy with their training with 70% satisfaction about their exposure to surgical procedures. Respondents reported a lack of standardised training (72%), monitoring tools (41%) and mentorship (56%). 57% rated attended courses as useful for training, while 80% rated visiting expert centres as useful. CONCLUSION: This study has identified a learning need for improved structured training in APM, with low current satisfaction levels with exposure to APM training. Organisations such as ESSO provide an important platform for visiting expert centres, courses, and structured training.

Multimodality treatment of undifferentiated pleomorphic soft tissue sarcoma of the extremity (eUPS) in the elderly.

INTRODUCTION: This subgroup analysis of undifferentiated pleomorphic soft tissue sarcoma of the extremity (eUPS) from the PERSARC collaborative group aimed to achieve a more personalized multimodality treatment approach for primary eUPS in elderly patients. MATERIAL AND METHODS: A multicenter retrospective study including primary high-grade eUPS surgically treated with curative intent between 2000 and 2016. Overall survival (OS), local recurrence (LR) and distant metastasis (DM) curves were calculated by Kaplan Meier analysis. Cox proportional hazard models were used to determine the effect of radiotherapy. RESULTS: From a total of 2511 patients with extremity soft tissue sarcoma (eSTS) of the PERSARC study collaborative; 703 patients with eUPS were included in this study. In elderly patients with eUPS 5-year OS, LR and DM were 35.4 (95%CI 29.3-42.8), 17.7 (95%CI 12.7-22.6) and 24.6 (95%CI 19.1-30.1). eUPS was significantly less treated with radiotherapy compared with other eSTS, especially in elderly patients. Patients with R1-R2 margins treated with radiotherapy had about half the risk of developing LR compared with patients treated without radiotherapy (HR = 0.454, p = 0.033). CONCLUSION: Elderly patients with eUPS were less often treated with radiotherapy and showed higher LR. Nowadays, given an increasing life expectancy in elderly patients, multimodality treatment should be considered.