Search

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

Abstract Background Myxoid liposarcoma is a relatively common malignant soft tissue tumor, characterized by a (12;16) translocation resulting in a FUS-DDIT3 fusion gene playing a pivotal role in its tumorigenesis. Treatment options in patients with inoperable or metastatic myxoid liposarcoma are relatively poor though being developed and new hope is growing. Results Using kinome profiling and subsequent pathway analysis in two cell lines and four primary cultures of myxoid liposarcomas, all of which demonstrated a FUS-DDIT3 fusion gene including one new fusion type, we aimed at identifying new molecular targets for systemic treatment. Protein phosphorylation by activated kinases was verified by Western Blot and cell viability was measured before and after treatment of the myxoid liposarcoma cells with kinase inhibitors. We found kinases associated with the atypical nuclear factor-kappaB and Src pathways to be the most active in myxoid liposarcoma. Inhibition of Src by the small molecule tyrosine kinase inhibitor dasatinib showed only a mild effect on cell viability of myxoid liposarcoma cells. In contrast, inhibition of the nuclear factor-kappaB pathway, which is regulated by the FUS-DDIT3 fusion product, in myxoid liposarcoma cells using casein kinase 2 inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB) showed a significant decrease in cell viability, decreased phosphorylation of nuclear factor-kappaB pathway proteins, and caspase 3 mediated apoptosis. Combination of dasatinib and TBB showed an enhanced effect. Conclusion Kinases associated with activation of the atypical nuclear factor-kappaB and the Src pathways are the most active in myxoid liposarcoma in vitro and inhibition of nuclear factor-kappaB pathway activation by inhibiting casein kinase 2 using TBB, of which the effect is enhanced by Src inhibition using dasatinib, offers new potential therapeutic strategies for myxoid liposarcoma patients with advanced disease.

Background: Localization of non-palpable melanoma, Merkel cell carcinoma (MCC) and soft tissue sarcoma (STS) lesions can be difficult due to size, location, and obesity of patients or fibrosis due to previous treatments. Magnetic seed localization (MSL) is a common method to localize non-palpable breast lesions, but the feasibility of MSL for non-palpable melanoma, MCC and STS lesions has not yet been described., Methods: In this retrospective single center cohort study, all consecutive patients between January 2021 and October 2023 who had a resection of a non-palpable melanoma, MCC or STS lesion guided by Sirius Pintuition, a MSL technique, were included. The primary endpoint was successful lesion localization during surgery and the secondary endpoints were seed migration, negative resection margins, and complications., Results: Seventy-nine seeds were placed for 76 lesions, which were resected during 68 surgeries in 61 patients. All lesions (100 %) were localized and resected. Median time of surgery was 44 min. No seed migration was observed. A negative resection margin was achieved for 60 (78.9 %) lesions. Clavien Dindo grade ≥2 complications occurred in 7.4 %., Conclusion: Magnetic seed localization with Sirius Pintuition is feasible for both non-palpable melanoma, MCC, and STS lesions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: WJ Van Houdt reports financial support was provided by Sirius Medical Systems B.V. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

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., Competing Interests: Declaration of competing interest ACJvA is a member of the Advisory Board for, and received consultancy honoraria from, Amgen, Bristol-Myers Squibb, Neracare, Novartis, MSD-Merck, Merck-Pfizer, Pierre Fabre, Provectus, Sanofi, Sirius Medical, and 4SC. WvH has received institutional honoraria, speakers honorarium, or institutional research grants from Amgen, Bristol-Myers Squibb, Novartis, MSD-Merck, Belpharma, Sanofi and Sirius Medical. ROB has received institutional research grants from Bristol-Myers Squibb (BMS) and SkyLineDx, speaker honorarium from Roche and Pfizer and has served on advisory boards for Amgen, BD/BARD, Bristol-Myers Squibb (BMS), Merck Sharp & Dohme (MSD), Novartis, Roche and Sanofi Genzyme. Remaining authors have no conflicts of interest to declare., (© 2024 Published by Elsevier Ltd.)

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., (Copyright © 2023 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

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., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The pro-inflammatory cytokine interleukin-6 (IL-6) plays a role in cancer development and progression, but research into the predictive value of IL-6 on postoperative outcome in soft tissue sarcoma (STS) is scarce. The purpose of this study is to investigate the predictive value of serum IL-6 level for the achievement of assumed (post)operative outcome after STS surgery, the so-called textbook outcome., Methods: Preoperative IL-6 serum levels were collected in all patients with a STS at first presentation between February 2020 and November 2021. Textbook outcome was defined as a R0 resection, no complications, no blood transfusions, no reoperation within the postoperative period, no prolonged hospital stay, no hospital readmission within 90-days, and no mortality within 90-days. Factors associated with textbook outcome were determined by multivariable analysis., Results: Among 118 patients with primary, non-metastatic STS, 35.6% achieved a textbook outcome. Univariate analysis showed that smaller tumor size (p = 0.026), lower tumor grade (p = 0.006), normal hemoglobin (Hb, p = 0.044), normal white blood cell (WBC) count (p = 0.018), normal C-reactive protein (CRP) serum level (p = 0.002) and normal IL-6 serum level (p = 1.5 × 10 -5 ) were associated with achieving textbook outcome after surgery. Multivariable analysis showed that elevated IL-6 serum level (p = 0.012) was significantly associated with not achieving a textbook outcome., Conclusions: Increased IL-6 serum level is predictive for not achieving a textbook outcome after surgery for primary, non-metastatic STS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

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.

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., (© 2022. Society of Surgical Oncology.)

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., Competing Interests: Declaration of competing interest Andreas Brandl, Dara Lundon, Laura Lorenzon, Yvonne Schrage, Carmela Caballero, Carl Jacob Holmberg, Nada Santrac, Mariela Vasileva-Slaveva, Giacomo Montagna, Olivia Sgarbura, Raza Sayyed, Almog Ben-Yaacov, Johnn Henry Herrera Kok, Ina Suppan, Helen Mohan, Wim Ceelen, Tibor Kovacs, Domenico D'Ugo, Sergio Sandrucci declared that they have no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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

Background: This study assessed whether electromagnetic navigation can be of added value during resection of recurrent or post-therapy intra-abdominal/pelvic soft tissue sarcomas (STS) in challenging locations., Materials and Methods: Patients were included in a prospective navigation study. A pre-operatively 3D roadmap was made and tracked using electromagnetic reference markers. During the operation, an electromagnetic pointer was used for the localization of the tumor/critical anatomical structures. The primary endpoint was feasibility, secondary outcomes were safety and usability., Results: Nine patients with a total of 12 tumors were included, 7 patients with locally recurrent sarcoma. Three patients received neoadjuvant radiotherapy and three other patients received neoadjuvant systemic treatment. The median tumor size was 4.6 cm (2.4-10.4). The majority of distances from tumor to critical anatomical structures was <0.5 cm. The tumors were localized using the navigation system without technical or safety issues. Despite the challenging nature of these resections, 89% were R0 resections, with a median blood loss of 100 ml (20-1050) and one incident of vascular damage. Based on the survey, surgeons stated navigation resulted in shorter surgery time and made the resections easier., Conclusion: Electromagnetic navigation facilitates resections of challenging lower intra-abdominal/pelvic STS and might be of added value., (© 2021 Wiley Periodicals LLC.)

Purpose: The aim of this study was to create and validate dynamic nomograms to predict overall survival (OS) and disease-free survival (DFS) at different time points during follow-up in patients who had undergone resection of primary retroperitoneal sarcoma (RPS)., Methods: Patients with primary RPS operated upon between 2002 and 2017 at four and six referral centres comprised the development and external validation cohorts, respectively. Landmark analysis and multivariable Cox models were used to develop dynamic nomograms. Variables were selected using two backward procedures based on the Akaike information criterion. The prediction window was fixed at 5 years. Nomogram performances were tested in terms of calibration and discrimination on the development and validation cohorts., Results: Development and validation cohorts totalled 1357 and 487 patients (OS analysis), and 1309 and 452 patients (DFS analysis), respectively. The final OS model included age, landmark time (T LM ), tumour grade, completeness of resection and occurrence of local/distant recurrence. The final DFS model included T LM , histologic subtype, tumour size, tumour grade, multifocality and the interaction terms between T LM and size, grade and multifocality. For OS, Harrell C indices were higher than 0.7 in both cohorts, indicating very good discriminative capability. For DFS, Harrell C indices were between 0.64 and 0.72 in the development cohort and 0.62 and 0.68 in the validation cohort. Calibration plots showed good agreement between predicted and observed outcomes., Conclusion: Validated nomograms are available to predict the 5-year OS and DFS probability at different time points throughout the first 5 years of follow-up in RPS survivors., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Local recurrence following resection of retroperitoneal liposarcoma (RLPS) is common. Well-differentiated (WD) and dedifferentiated (DD) RLPS are distinct entities with differing outcomes. A few reports suggest that WDLPS can recur as DDLPS and that DDLPS can recur as WDLPS. This study evaluates whether this change in differentiation from the primary tumor to the first local recurrence impacts long-term outcomes., Methods: Retrospective review from 22 sarcoma centers identified consecutive patients who underwent resection for a first locally recurrent RLPS from January 2002 to December 2011. Outcomes measured included overall survival, local recurrence, and distant metastasis., Results: A total of 421 RPLS patients were identified. Of the 230 patients with primary DDLPS, 34 (15%) presented WDLPS upon recurrence (DD → WD); and of the 191 patients with primary WDLPS, 54 (28%) presented DDLPS upon recurrence (WD → DD). The 6-year overall survival probabilities (95% CI) for DD → DD, DD → WD, WD → WD, and WD → DD were 40% (32-48%), 73% (58-92%), 76% (68-85%), and 56% (43-73%) (p < 0.001), respectively. The 6-year second local recurrence incidence was 66% (59-73%), 63% (48-82%), 66% (57-76%), and 77% (66-90%), respectively. The 6-year distant metastasis incidence was 13% (9-19%), 3% (0.4-22%), 5% (2-11%), and 4% (1-16%), respectively. On multivariable analysis, DD → WD was associated with improved overall survival when compared with DD → DD (p < 0.001). Moreover, WD → DD was associated with a higher risk of LR (p = 0.025) CONCLUSION: A change in RLPS differentiation from primary tumor to first local recurrence appears to impact survival. These findings may be useful in counseling patients on their prognosis and subsequent management., (© 2021. Society of Surgical Oncology.)

Background: Multi-visceral resection often is used in the treatment of retroperitoneal sarcoma (RPS). The morbidity after distal pancreatectomy for primary pancreatic cancer is well-documented, but the outcomes after distal pancreatectomy for primary RPS are not. This study aimed to evaluate morbidity and oncologic outcomes after distal pancreatectomy for primary RPS., Methods: In this study, 26 sarcoma centers that are members of the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) retrospectively identified consecutive patients who underwent distal pancreatectomy for primary RPS from 2008 to 2017. The outcomes measured were 90-day severe complications (Clavien-Dindo ≥ 3), postoperative pancreatic fistula (POPF) rate, and oncologic outcomes., Results: Between 2008 and 2017, 280 patients underwent distal pancreatectomy for primary RPS. The median tumor size was 25 cm, and the median number of organs resected, including the pancreas, was three. In 96% of the operations, R0/R1 resection was achieved. The 90-day severe complication rate was 40 %. The grades B and C POPF complication rates were respectively 19% and 5% and not associated with worse overall survival. Administration of preoperative radiation and factors to mitigate POPF did not have an impact on the risk for the development of a POPF. The RPS invaded the pancreas in 38% of the patients, and local recurrence was doubled for the patients who had a microscopic, positive pancreas margin (hazard ratio, 2.0; p = 0.042)., Conclusion: Distal pancreatectomy for primary RPS has acceptable morbidity and oncologic outcomes and is a reasonable approach to facilitate complete tumor resection., (© 2021. Society of Surgical Oncology.)

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

Background: Oesophageal gastrointestinal stromal tumours (GISTs) account for ≤1% of all GISTs. Consequently, evidence to guide clinical decision-making is limited., Methods: Clinicopathological features and outcomes in patients with primary oesophageal GIST from seven European countries were collected retrospectively., Results: Eighty-three patients were identified, and median follow up was 55.0 months. At diagnosis, 59.0% had localized disease, 25.3% locally advanced and 13.3% synchronous metastasis. A biopsy (Fine Needle aspiration n = 29, histological biopsy n = 31) was performed in 60 (72.3%) patients. The mitotic count was low (<5 mitoses/50 High Power Fields (HPF)) in 24 patients and high (≥5 mitoses/50 HPF) in 27 patients. Fifty-one (61.4%) patients underwent surgical or endoscopic resection. The most common reasons to not perform an immediate resection (n = 31) were; unresectable or metastasized GIST, performance status/comorbidity, patient refusal or ongoing neo-adjuvant therapy. The type of resections were enucleation (n = 11), segmental resection (n = 6) and oesophagectomy with gastric conduit reconstruction (n = 33), with median tumour size of 3.3 cm, 4.5 cm and 7.7 cm, respectively. In patients treated with enucleation 18.2% developed recurrent disease. The recurrence rate in patients treated with segmental resection was 16.7% and in patients undergoing oesophagectomy with gastric conduit reconstruction 36.4%. Larger tumours (≥4.0 cm) and high (>5/5hpf) mitotic count were associated with worse disease free survival., Conclusion: Based on the current study, enucleation can be recommended for oesophageal GIST smaller than 4 cm, while oesophagectomy should be preserved for larger tumours. Patients with larger tumours (>4 cm) and/or high mitotic count should be treated with adjuvant therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Stage IIB/IIC (8th AJCC) melanoma patients are known to have high-risk primary tumors, however they follow the same routine to sentinel lymph node biopsy (SLNB) as more low risk tumors. Guidelines are not conclusive regarding the use of preoperative imaging for these patients. The aim of this pilot study was to assess the value of ultrasound (US) and 18 F-FDG PET/CT prior to lymphoscintigraphy (LSG) and SLNB for stage IIB/C melanoma patients., Methods: From 2019-04 till 2020-01, all stage IIB/C melanoma patients underwent US of the regional lymph nodes and whole body 18 F-FDG PET/CT before their planned LSG and SLNB. Suspected metastases were confirmed with fine needle aspiration (FNA), prior to surgery., Results: In total 23 patients were screened: six had metastases detected by imaging, two by US, one by 18 F-FDG PET/CT and three were detected by both imaging modalities. All metastases were nodal and therefore treatment was altered to lymph node dissection and all but one also received adjuvant therapy. Eight (47%) of the 17 patients without macroscopic disease, still had a positive SN. Sensitivity, specificity and false negative rate for US and 18 F-FDG PET/CT were 36%, 89%, 64% and 29%, 100% and 71%, respectively., Conclusion: Preoperative negative imaging does not exclude the presence of SN metastases, therefore SLNB cannot be foregone. However, US detected metastases in 22% of patients, altering their treatment, which suggests it is effective in the work-up of stage IIB/C melanoma. Staging with 18 F-FDG PET/CT is not of added value prior to LSG and SLNB and should therefore not be used., Competing Interests: Declaration of competing interest WvH declares advisory board/consultancy agreement and research grant received from Amgen. MW declares a research grant received from Novartis. AvA declares advisory board/consultancy agreements for Amgen, Bristol-Myers Squibb, Novartis, MSD – Merck, Merck – Pfizer, Sanofi, Sirius Medical en 4SC and received a research grant from Amgen and Merck – Pfizer., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: This study aimed to evaluate perioperative morbidity after surgery for first locally recurrent (LR1) retroperitoneal sarcoma (RPS). Data concerning the safety of resecting recurrent RPS are lacking., Methods: Data were collected on all patients undergoing resection of RPS-LR1 at 22 Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) centers from 2002 to 2011. Uni- and multivariable logistic models were fitted to study the association between major (Clavien-Dindo grade ≥ 3) complications and patient/surgery characteristics as well as outcome. The resected organ score, a method of standardizing the number of organs resected, as previously described by the TARPSWG, was used., Results: The 681 patients in this study had a median age of 59 years, and 51.8% were female. The most common histologic subtype was de-differentiated liposarcoma (43%), the median resected organ score was 1, and 83.3% of the patients achieved an R0 or R1 resection. Major complications occurred for 16% of the patients, and the 90-day mortality rate was 0.4%. In the multivariable analysis, a transfusion requirement was found to be a significant predictor of major complications (p < 0.001) and worse overall survival (OS) (p = 0.010). However, having a major complication was not associated with a worse OS or a higher incidence of local recurrence or distant metastasis., Conclusions: A surgical approach to recurrent RPS is relatively safe and comparable with primary RPS in terms of complications and postoperative mortality when performed at specialized sarcoma centers. Because alternative effective therapies still are lacking, when indicated, resection of a recurrent RPS is a reasonable option. Every effort should be made to minimize the need for blood transfusions.

Introduction: Oligometastatic disease and/or oligoprogression in myxoid liposarcoma(oMLS) triggers discussions on local treatment options and delay of systemic treatments. We hypothesized that satisfactory local control and postponement of systemic therapy could be achieved with a modest radiotherapy(RT) dose in oMLS., Methods: The DOREMY trial is a multicenter, phase 2 trial evaluating efficacy and toxicity of a modest RT dose in both localized and oMLS; this report presents the data of the oMLS cohort treated with 36 Gy in 12-18 fractions with optional subsequent metastasectomy. The primary endpoint was local progression free survival(LPFS). Secondary endpoints included postponement of systemic therapy, symptom reduction, radiological objective response, and toxicity., Results: Nine patients with a total of 25 lesions were included, with a median follow-up of 23 months. The median number of lesions per patient was three and the trunk wall and bone were the most frequently affected sites. In lesions treated with definitive RT(n = 21), LPFS rates at 1, 2, and 3 years were respectively 73%, 61%, and 40%. Radiological objective response and clinical symptom reduction were achieved in 8/15(53%) and 9/10(90%) of the evaluable lesions, respectively. No local recurrences occurred in lesions treated with RT and metastasectomy(n = 4). For the entire study population, the median postponement of systemic therapy was 10 months. Grade ≥ 2 toxicity was observed in 2/9(22%) of patients., Conclusions: This trial suggests that 36 Gy could possibly be effective to achieve local control, postpone systemic therapy and reduce symptoms in oMLS. Given the minimal toxicity this treatment could be reasonably considered in oMLS., Competing Interests: Declaration of Competing Interest W.vd.G: advisory Bayer and GSK, consultant Spingworks, research grant Novartis. The other authors have nothing to disclose., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Primary mesenteric soft tissue sarcomas (STS) are rare and limited evidence is available to inform management. Surgical resection is challenging due to the proximity of vital structures and a need to preserve enteric function., Objectives: To determine the overall survival (OS) and recurrence-free survival (RFS) for patients undergoing primary resection for mesenteric STS., Methods: The Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) is an intercontinental collaborative comprising specialist sarcoma centers. Data were collected retrospectively for all patients with mesenteric STS undergoing primary resection between 2000 and 2019., Results: Fifty-six cases from 15 institutions were included. The spectrum of pathology was similar to the retroperitoneum, although of a higher grade. R0/R1 resection was achieved in 87%. Median OS was 56 months. OS was significantly shorter in higher-grade tumors (p = .018) and extensive resection (p < .001). No significant association between OS and resection margin or tumor size was detected. Rates of local recurrence (LR) and distant metastases (DM) at 5 years were 60% and 41%, respectively. Liver metastases were common (60%), reflecting portal drainage of the mesentery., Conclusion: Primary mesenteric sarcoma is rare, with a modest survival rate. LR and DM are frequent events. Liver metastases are common, highlighting the need for surveillance imaging., (© 2020 Wiley Periodicals LLC.)

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.

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

Background: In this series from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG), the authors examined longitudinal outcomes of patients with a second recurrence of retroperitoneal sarcoma (RPS) after complete resection of a first local recurrence (LR)., Methods: Data from patients undergoing resection of a first LR from January 2002 to December 2011were collected from 22 sarcoma centers. The primary outcome was overall survival (OS) after second recurrence., Results: Second recurrences occurred in 400 of 567 patients (70.5%) after an R0/R1 resection of a first locally recurrent RPS. Patterns of disease recurrence were LR in 323 patients (80.75%), distant metastases (DM) in 55 patients (13.75%), and both LR and DM in 22 patients (5.5%). The main subtype among the LR group was liposarcoma (77%), whereas DM mainly were leiomyosarcomas (43.6%). In patients with a second LR only, a total of 200 patients underwent re-resection (61.9%). The 5-year OS rate varied significantly based on the pattern of failure (P < .001): 45.6% for the LR group, 25.5% for the DM group, and 0% for the group with LR and DM. The only factors found to be associated with improved OS on multivariable analysis were both time between second surgery and the development of the second recurrence (32 months vs 8 months: hazard ratio, 0.44 [P < .001]) and surgery for second recurrence (yes vs no: hazard ratio, 3.25 [P < .001]). The 5-year OS rate for patients undergoing surgery for a second LR was 59% versus 18% in the patients not deemed suitable for surgical resection., Conclusions: Survival rates after second recurrence of RPS varied based on patterns of disease recurrence and treatment. Durable disease-free survivors were identified after surgery for second LR in patients selected for this intervention., (© 2020 American Cancer Society.)

Introduction: The majority of cancer patients report malnutrition, with a significant impact on patient's outcome. This study aimed to compare how nutritional assessment is conducted across different surgical oncology sub-specialties., Methods: Survey modules were designed for breast, hepato-pancreato-biliary (HPB), upper-gastrointestinal (UGI), sarcoma, peritoneal and surface malignancies (PSM) and colorectal cancer (CRC) surgeries to describe 4 domains: participants' setting, evaluation of clinical factors, use of screening tools and clinical practice. Results were compared among sub-specialties and according to human development index (HDI) in the largest cohorts., Results: Out of 457 answers from 377 global participants (62% European), 35.0% were from breast and 28.9% were from CRC surgeons. Although MDTs management is consistently reported (64-88%), the presence of a nutritionist/dietician ranges from 14.1% to 44.2%. Breast surgeons seldom evaluate albumin (25.6%) and weight loss (30.6%), opposite to HPB, PSM and UGI groups (>70%, p 0.044). Overall, responders declared that the use of screening tools is largely neglected, that nutritional status is often assessed by the surgeons and that nutrition is not consistently modified according to risk factors (range among groups respectively: 1.9%-25.6%, 33.1%-51.4%, 33.1%-60.5%). Less than 20% of breast surgeons assess patients before/after surgery, comparing to >60% of PSM surgeons. However, no statistical differences were documented comparing groups for the majority of the items of the 4 domains. Nutritional evaluation is more often conducted by breast surgeons in medium/low HDI countries comparing very high/high HDI (p 0.04)., Conclusions: Nutritional assessment is largely neglected. These results identify target-issues for the implementation of clinical practice., Competing Interests: Declaration of competing interest None of the authors has any potential financial conflict of interest related to this manuscript., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Angiosarcoma is an extremely rare and aggressive malignancy. Standard of care of localized tumors includes surgery ± radiation. Despite this multimodal treatment, >50% of the angiosarcoma patients develop local or distant recurrent disease. The role of neoadjuvant systemic therapy is still controversial and we therefore performed a systematic review of the literature to define the role of neoadjuvant systemic therapy based on available evidence. We focused on the effects of neoadjuvant systemic therapy on: 1. The success of surgical resection and 2. the long-term survival. All articles published before October 2019 on Ovid Medline, Ovid Embase, Cochrane library and Scopus were evaluated. Eighteen case reports and six retrospective cohort studies were included. There were no randomized controlled trials. This literature showed a beneficial role of neoadjuvant chemotherapy on downsizing of the tumor resulting in an improvement of the resection margins, especially in patients with cardiac or cutaneous angiosarcoma. However, no definitive conclusions on survival can be drawn based on the available literature lacking any prospective randomized studies in this setting. We advise that neoadjuvant chemotherapy should be considered, since this could lead to less mutilating resections and a higher rate of free resection margins. An international angiosarcoma registry could help to develop guidelines for this rare disease.

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., (© 2020 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: Rectal gastrointestinal stromal tumours (GISTs) are rare tumours. Variability in the management may influence outcome, but there is a lack of understanding regarding contemporary variance in care. A multicenter, international, retrospective cohort study was performed to elucidate characteristics and outcomes of rectal GIST in European practice, with particular reference to surgical approach., Methods: All rectal GIST patients diagnosed between 2009 and 2018 were identified from five European databases. Recurrence free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meier method. Possible confounders were identified using Cox regression analyses., Results: From 210 patients, 155 patients had surgery. The three main types of surgery were local tumour resection (LTR, n = 46), low anterior resection (LAR, n = 31) and abdomino-perineal resection (APR, n = 32). Most patients received neoadjuvant (65%) and/or adjuvant imatinib therapy (66%). Local recurrence rate after surgery was 15% and overall recurrence rate 28%. No significant differences were found in terms of RFS nor OS between LTR, LAR and APR. However, locally resected tumours were smaller, while LAR and APR patients more often received perioperative imatinib. General hospitals treated smaller GISTs, offered imatinib less frequently, and had a higher tumour rupture rate. In the multivariate analysis in the group having LTR, APR or LAR, the only significant prognostic factor for local recurrence was higher age (HR 1.06, CI 1.00-1.12, p = 0.048)., Conclusions: In European clinical practice for rectal GIST, LTR, LAR and APR have comparable local control. Multimodal approach is higher and tumour rupture less frequent in specialist centres compared to general hospitals., Competing Interests: Declaration of competing interest P. Rutkowski has received honoraria for lectures and Advisory Board from Novartis, Pfizer and Blueprint Medicines. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Gastrointestinal stomal tumours (GISTs) are the most frequently diagnosed mesenchymal tumour of the gastrointestinal tract. The response of most GISTs to tyrosine kinase inhibitor (TKIs) treatment is spectacular; however progression and/or secondary resistance inevitably occurs with long-term treatment of recurrent or metastatic disease. Randomised studies investigating the potential additive benefit of metastasectomy in addition to TKI treatment unfortunately failed to accrue sufficient patients. Therefore, the apparent benefit of surgery in the setting of metastatic disease is based on retrospective institutional series or extrapolation of data from studies which were not intended directly to investigate the impact of surgery. The aim of this review is to summarise the current literature to inform an approach to the surgical management of metastatic GIST., Methods: Relevant articles were retrieved from a comprehensive literature search using the PubMed database. Keywords included: GIST, metastasis, surgery, tyrosine kinase inhibitor. No restrictions on publication date were used., Results: An overview of relevant literature and suggestions for multidisciplinary decision making are formulated., Conclusions: Our narrative review has identified studies which suggest that surgery may be beneficial in selected patients with metastatic GIST with responsive or stable disease during TKI treatment. Similarly, surgery for isolated clonal proliferative progressive disease may improve progression free survival and delay switch to second-line TKI in some cases., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Chondrosarcomas are resistant to conventional chemo- and radiotherapy. A subset of chondrosarcomas arises secondarily in the benign tumour syndromes enchondromatosis (EC) and multiple osteochondromas (MO), and prevention of tumour development would greatly improve prognosis. We therefore investigated the effect of selective COX-2 inhibition on chondrosarcoma growth. COX-2 expression was studied in central- and peripheral cartilaginous tumours. The effect of COX-2 inhibition was assessed in four high-grade chondrosarcoma cell lines using celecoxib and NS-398 treatment. COX-2 activity (prostaglandin E(2) (PGE(2)) ELISA) and cell viability were measured. The (prophylactic) effect of celecoxib on chondrosarcoma growth in vivo was studied for 8 weeks using a xenograft model of cell line CH2879 in immunoincompetent nude mice. High COX-2 protein expression was mainly found in solitary peripheral chondrosarcoma and in enchondromatosis-related central chondrosarcoma, which was confirmed by qPCR. After 72h of celecoxib treatment, a significant decrease in cell viability was observed in three chondrosarcoma cell lines. In vivo, celecoxib initially slowed tumour growth in chondrosarcoma xenografts; however, after prolonged treatment relapsed tumour growth was observed. Tumour volume was negatively associated with celecoxib serum levels, and seemed smaller in the high-dose prophylactic treatment group. We confirmed the expression of COX-2 in 65% of chondrosarcomas, and COX-2 inhibition by celecoxib diminished cell viability in vitro. The initial response and the decrease in tumour volume with increased celecoxib serum levels in vivo supported a role for celecoxib, although relapsed tumour growth after 6 weeks was worrisome. Also the role of high-dose prophylactic celecoxib in preventing the development of benign and malignant cartilage tumours in EC and MO patients deserves further investigation., (Copyright (c) 2009 Elsevier Ltd. All rights reserved.)