Trabectedin is standard for r/r soft tissue sarcomas. tTF-NGR accumulates in tumor vasculature leading to tumor vascular occlusion and tumor infarction. Both compounds in sequence could trap trabectedin inside tumors and increase its efficacy, which then optimizes the pro-coagulatory activity of tTF-NGR. This report summarizes translational data and results of the safety run-in patient cohort of the TRABTRAP trial combining trabectedin plus tTF-NGR. A dose of trabectedin of 1.5 mg/m2 (24 h, day 1) combined with 1.0 mg/m2 of tTF-NGR (1 h, days 2 and 3, q day 22) represents the approx. Maximum tolerated dose (MTD) and with 0.5 mg/m2 tTF-NGR (days 2 and 3) the recommended starting dose for the randomized part of TRABTRAP. None of the 6 patients on 0.5 mg/m2 tTF-NGR had dose-limiting toxicity (DLT). Higher doses or additional days of application of tTF-NGR led to grade 3 DLT including early troponin T high sensitivity increase, a reversible non-ST-elevation myocardial infarction in one patient, and reversible thromboembolic events. Pharmacokinetics explain the difference of the MTD between the phase I study and in TRABTRAP. Experimental and clinical efficacy and tolerability of the combination between trabectedin and tTF-NGR supports the active randomized part of TRABTRAP.

BACKGROUND:Consolidation therapy for primary CNS lymphoma (PCNSL) includes high-dose chemotherapy with autologous stem-cell transplantation (HCT-ASCT), yet its efficacy compared with non-myeloablative chemoimmunotherapy remains uncertain. This study aimed to provide randomised comparative evidence on the efficacy and safety of thiotepa-based HCT-ASCT versus non-myeloablative R-DeVIC consolidation after uniform MATRix induction in newly diagnosed PCNSL. METHODS:This open-label, randomised, phase 3 trial was conducted across 56 university and academic non-university hospitals with established transplantation facilities in five European countries. Eligible for inclusion were untreated, immunocompetent patients with B-cell PCNSL, aged 18-65 years regardless of Eastern Cooperative Oncology Group (ECOG) performance status, or 66-70 years with ECOG performance status 0-2. Pretreatment corticosteroids were permitted. Exclusion criteria included lymphoma manifestation outside the CNS, and congenital or acquired immunodeficiency. Patients received four cycles of MATRix induction (comprising rituximab, high-dose cytarabine, and thiotepa, in addition to high-dose methotrexate). Patients reaching at least partial response were randomly assigned (1:1) to two cycles of R-DeVIC (rituximab plus dexamethasone, etoposide, ifosfamide, and carboplatin) or HCT-ASCT with carmustine and thiotepa. The primary endpoint was progression-free survival, assessed in the full analysis set (excluding patients with major violations of entry criteria). The safety analysis set contained all randomised patients who initiated therapy. This study is registered with ClinicalTrials.gov (NCT02531841) and the EU Clinical Trials Register (EudraCT number 2012-000620-17). The study is completed. FINDINGS:Between July 16, 2014, and Aug 31, 2019, 368 patients were enrolled. 346 (94%) patients started induction treatment, and 230 were randomly assigned; 229 patients were analysed (R-DeVIC group, n=115; HCT-ASCT group, n=114). After a median follow-up of 45·3 months, 3-year progression-free survival was significantly superior in the HCT-ASCT group (hazard ratio 0·43 [95% CI 0·27-0·68]; p=0·0003). The 3-year progression-free survival was 78% (95% CI 69-85) in the HCT-ASCT group compared with 51% (41-60) in the R-DeVIC group. The mean number of adverse events per patient was 9·3 (SD 4·4) in the R-DeVIC group and 14·6 (5·8) in the HCT-ASCT group. Fatal serious adverse events following consolidation treatment occurred in two patients in the R-DeVIC group (both acute myeloid leukaemia) and in five patients in the HCT-ASCT group (infections and infestations [n=4], pulmonary embolism [n=1]); all of these events apart from the pulmonary embolism were judged to be possibly related to treatment. INTERPRETATION:In the largest randomised trial in untreated PCNSL to date, HCT-ASCT significantly improved progression-free and overall survival compared with non-myeloablative consolidation in patients who had completed induction treatment, establishing it as the preferred consolidation strategy in fit patients. FUNDING:German Federal Ministry of Research, Technology and Space; Swiss Cancer Research Foundation; and Riemser Pharma.

IntroductionSarcoma is a rare and highly heterogeneous family of mesenchymal tumors. The experience and interdisciplinary approach of specialized high-volume sarcoma centers has a significant impact on disease treatment and outcome for patients. The aim of this retrospective, real-world, multicenter study was to evaluate geographic distribution of sarcoma cases in Southwest Germany and visually depict possible underrepresented areas of sarcoma primary diagnoses. Such descriptive information may indirectly guide future referral patterns and outreach activities of specialized sarcoma centers.MethodsThe absolute number and incidence of sarcoma patients obtained from the Baden-Württemberg Cancer Registry were compared with the data from five individual, high-volume, specialized sarcoma centers. Furthermore, we used a “White-Spot Analysis” as a novel cost-effective approach in epidemiological and public health research for analyzing health care coverage in sarcoma care.ResultsA total of 4,087 sarcoma patients living in the German Federal State of Baden-Württemberg between 2019 and 2022 were included in this study. Of these, 1,650 patients (40%) were treated primarily in specialized sarcoma centers whilst 2,437 patients (60%) received treatment for sarcoma outside of the five main high-volume centers, in underrepresented areas identified through White-Spot Analysis. The sarcoma incidence in Baden-Württemberg was calculated with our data to be 9.18/100,000 inhabitants per year.DiscussionIn future, the access to high-volume centers needs to be facilitated in order to minimize the observed discrepancies between treatment in specialized sarcoma centers and low-volume centers in Southwest Germany. Our analysis highlights such discrepancies and may support future efforts to improve outcomes for sarcoma patients.

Purpose This is an official, recently updated guideline published and coordinated by the German Society of Gynecology and Obstetrics ( Deutsche Gesellschaft für Gynäkologie und Geburtshilfe , DGGG) together with the Austrian Society of Gynecology and Obstetrics ( Österreichische Gesellschaft für Gynäkologie und Geburtshilfe , OEGGG) and the Swiss Society of Gynecology and Obstetrics ( Schweizerische Gesellschaft für Gynäkologie und Geburtshilfe , SGGG) as part of the guidelines program. Because of their rarity and heterogeneous histopathology, uterine sarcomas are challenging in terms of their clinical management, and treatment requires a multidisciplinary approach. Methods This S2k guideline was first published in 2015. The update published here is again the result of a structured consensus of a representative interdisciplinary group of mandate holders and experts who carried out a selective search of the literature on uterine sarcomas. Members of the participating professional societies achieved a formal consensus on recommendations and statements after a structured consensus process. Recommendations Recommendations were made about the epidemiology, classification, staging of uterine sarcomas, symptoms, general diagnostic workup, general pathology and genetic predisposition for uterine sarcomas, leiomyosarcomas, endometrial stromal sarcomas (low-grade and high-grade), undifferentiated uterine sarcomas, adenosarcomas, and rhabdomyosarcoma of the uterus in children and adolescents. The guideline also discusses the follow-up of uterine sarcomas, the management of morcellated uterine sarcomas, and the information provided to patients.

E-TRAB was a non-interventional, prospective trial investigating the feasibility and predictive value of geriatric assessments (GA) in older STS patients treated with trabectedin as first-line therapy. Primary endpoints were overall survival (OS), quality of life and individual clinical benefit assessed by the patient-reported outcome measures QLQ-C30 and PRO-CTCAE. Further, several GA tools were applied and correlated with clinical outcomes and treatment-related toxicities. The final analyses included 69 patients from 12 German-speaking sites. The median age of patients was 78 years (range: 55 to 88). Baseline data on PROs and GA identified a diverse population of older patients with respect to their global health status, although a large proportion of them suffered from limitations, required geriatric help and had a high risk of morbidity. The Cancer and Age Research Group (CARG) score classified 38%, 29% and 23% of the patients with low, intermediate and high risks for therapy-related side effects, respectively. Median OS was 11.2 months [95%CI: 5.6; 19.4]. The study confirmed that trabectedin as first-line treatment in older patients with STS has an acceptable and manageable safety profile. Potential prognostic factors for clinical outcome and therapy-related toxicity were identified among the GA tools. Long Timed Up and Go (TUG) showed a significant correlation to OS and early death, whereas a high CARG score (>9) was associated with an increase in unplanned hospitalizations and the incidence of toxicities grade ≥ 3.

To identify pathogenic microorganisms and microbiological risk factors causing high morbidity and mortality in immunocompromised patients requiring invasive mechanical ventilation due to pneumonia. A retrospective single-center study was performed at the intensive care unit (ICU) of the Department of Internal Medicine at Heidelberg University Hospital (Germany) including 246 consecutive patients with hematological malignancies requiring invasive mechanical ventilation due to pneumonia from 08/2004 to 07/2016. Microbiological and radiological data were collected and statistically analyzed for risk factors for ICU and 1-year mortality. ICU and 1-year mortality were 63.0

Background Available treatments for older patients with primary diffuse large B-cell CNS lymphoma (PCNSL) offer progression -free survival of up to 16 months. We aimed to investigate an intensified treatment of high -dose chemotherapy and autologous haematopoietic stem-cell transplantation (HSCT) in older patients with PCNSL. Methods MARTA was a prospective, single -arm, phase 2 study done at 15 research hospitals in Germany. Patients aged 65 years or older with newly diagnosed, untreated PCNSL were enrolled if they had an Eastern Cooperative Oncology Group performance status of 0-2 and were fit for high -dose chemotherapy and autologous HSCT. Induction treatment consisted of two 21-day cycles of high -dose intravenous methotrexate 3 center dot 5 g/m2 (day 1), intravenous cytarabine 2 g/m2 twice daily (days 2 and 3), and intravenous rituximab 375 mg/m2 (days 0 and 4) followed by highdose chemotherapy with intravenous rituximab 375 mg/m2 (day -8), intravenous busulfan 3 center dot 2 mg/kg (days -7 and -6), and intravenous thiotepa 5 mg/kg (days -5 and -4) plus autologous HSCT. The primary endpoint was progression -free survival at 12 months in all patients who met eligibility criteria and started treatment. The study was registered with the German clinical trial registry, DRKS00011932, and recruitment is complete. Findings Between Nov 28, 2017, and Sept 16, 2020, 54 patients started induction treatment and 51 were included in the full analysis set. Median age was 71 years (IQR 68-75); 27 (53%) patients were female and 24 (47%) were male. At a median follow-up of 23 center dot 0 months (IQR 16 center dot 8-37 center dot 4), 23 (45%) of 51 patients progressed, relapsed, or died. 12-month progression -free survival was 58 center dot 8% (80% CI 48 center dot 9-68 center dot 2; 95% CI 44 center dot 1-70 center dot 9). During induction treatment, the most common grade 3-5 toxicities were thrombocytopenia and leukopenia (each in 52 [96%] of 54 patients). During highdose chemotherapy and autologous HSCT, the most common grade 3-5 toxicity was leukopenia (37 [100%] of 37 patients). Treatment-related deaths were reported in three (6%) of 54 patients, all due to infectious complications. Interpretation Although the primary efficacy threshold was not met, short induction followed by high -dose chemotherapy and autologous HSCT is active in selected older patients with PCNSL and could serve as a benchmark for comparative trials. Funding Else Kroner-Fresenius Foundation, Riemser Pharma, and Medical Center-University of Freiburg. Copyright (c) 2024 Elsevier Ltd. All rights reserved.

Cause-specific analysis of the treatment effect on the different component of the event-free survival since randomization.

BackgroundRare primary malignant bone sarcomas (RPMBS) account for 5%-10% of primary high-grade bone tumors and represent a major treatment challenge. The outcome of patients with RPMBS enrolled in the EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S) is presented. MethodsInclusion criteria were as follows: age from 41 to 65 years and a diagnosis of high-grade spindle cell, pleomorphic, or vascular RPMBS. The chemotherapy regimen included doxorubicin 60 mg/m(2), ifosfamide 9 g/m(2), and cisplatin 90 mg/m(2); postoperative methotrexate 8 g/m(2) was added in case of a poor histologic response. Version 2.0 of the Common Terminology Criteria for Adverse Events, Kaplan-Meier curves, log-rank tests, and univariate Cox regression models were used. ResultsIn total, 113 patients were evaluable for analysis. The median patient age was 52 years (range, 40-66 years), and 67 patients were men. Eighty-eight tumors were categorized as undifferentiated pleomorphic sarcomas (UPS), 20 were categorized as leiomyosarcomas, three were categorized as fibrosarcomas, and two were categorized as angiosarcomas. Eighty-three of 113 tumors were located in the extremities. Ninety-five of 113 patients presented with no evidence of metastases. After a median follow-up of 6.8 years (interquartile range [IQR], 3.5-9.8 years), the 5-year overall survival rate for patients with localized disease was 68.4% (IQR, 56.9%-77.5%), and it was 71.7% (IQR, 58.1%-81.6%) for patients with UPS and 54.9% (IQR, 29.5%-74.5%) for patients with leiomyosarcoma. Grade III-IV hematologic toxicity was reported in 81% patients; 23% had grade II-III neurotoxicity, and 37.5% had grade I-II nephrotoxicity. Five-year overall survival was significantly better for patients with localized disease, for patients who obtained surgical complete remission, and when the primary tumor was located in the extremities. ConclusionsThe survival of patients who had RPMBS in the current series was similar to that of age-matched patients who had high-grade osteosarcoma treated according to the same protocol. An osteosarcoma-like chemotherapy may be proposed in patients who have RPMBS.

AbstractPurpose: The phase III, open-label, prospective, multicenter, randomized Ewing 2008R1 trial (EudraCT2008-003658-13) was conducted in 12 countries to evaluate the effect of zoledronic acid (ZOL) maintenance therapy compared with no add-on regarding event-free survival (EFS, primary endpoint) and overall survival (OS) in standard-risk Ewing sarcoma (EWS). Patients and Methods: Eligible patients had localized EWS with either good histologic response to induction chemotherapy and/or small tumors (<200 mL). Patients received six cycles of VIDE induction and eight cycles of VAI (male) or eight cycles of VAC (female) consolidation. ZOL treatment started parallel to the sixth consolidation cycle. Randomization was stratified by tumor site (pelvis/other). The two-sided adaptive inverse–normal four-stage design (planned sample size 448 patients, significance level 5%, power 80%) was changed after the first interim analysis using the Müller–Schäfer method. Results: Between April 2010 and November 2018, 284 patients were randomized (142 ZOL/142 no add-on). With a median follow-up of 3.9 years, EFS was not significantly different between ZOL and no add-on group in the adaptive design (HR, 0.74; 95% CI, 0.43–1.28, P = 0.27, intention-to-treat). Three-year EFS rates were 84.0% (95% CI, 77.7%–90.8%) for ZOL vs. 81.7% (95% CI, 75.2%–88.8%) for no add-on. Results were similar in the per-protocol collective. OS was not different between groups. The 3-year OS was 92.8% (95% CI, 88.4%–97.5%) for ZOL and 94.6% (95% CI, 90.9%–98.6%) for no add-on. Noticeable more renal, neurologic, and gastrointestinal toxicities were observed for ZOL (P < 0.05). Severe renal toxicities occurred more often in the ZOL arm (P = 0.003). Conclusions: In patients with standard-risk localized EWS, there is no additional benefit from maintenance treatment with ZOL.

Background: Current treatment options for patients with primary central nervous system lymphoma (PCNSL) eligible for intensive treatment approaches comprise high-dose methotrexate (HD-MTX) based immuno-chemotherapy (IT) followed by consolidating high-dose chemotherapy and ASCT (HDC-ASCT). To clarify, whether minimal residual disease may also be eliminated by non-myeloablative IT, comprising non-cross resistant cytotoxic agents, the MATRix/IELSG43 trial, an international randomised phase III trial comparing HDC-ASCT with non-myeloablative consolidation in patients with newly diagnosed PCNSL (NCT02531841) was conducted. This is an updated report on the main study endpoints. Methods: This randomized phase III trial was conducted in 79 centers in five countries. Immuno-competent patients with untreated PCNSL, aged 18–65 years irrespective of ECOG PS or 66–70 years with ECOG PS ≤ 2 were considered eligible. Induction comprised four cycles MATRix (rituximab 375 mg/m2/d days(d) 0,5; methotrexate 3.5 g/m2 d1; cytarabine 2 × 2 g/m2/d d2,3; thiotepa 30 mg/m2 d4, every three weeks. Stem cell harvest following cycle 2. Randomization was performed for patients achieving at least partial response (PR) following induction therapy. Arm A consisted of two cycles R-DeVIC (375 mg/m2 d0; dexamethasone 40 mg/d d1–3; etoposide 100 mg/m2/d d1–3; ifosfamide 1500 mg/m2/d d1–3; carboplatin 300 mg/m2 d1); Arm B, consisted of HDC-ASCT (BCNU 400 mg/m2 (d-6) and thiotepa 2 × 5 mg/kg/d d-5,-4)). The primary endpoint progression-free survival (PFS) was analyzed with a Cox proportional hazards model. Results: 368 pts were registered between July 2014 and August 2019, 230/346 pts (67%) were randomly assigned to arm A and arm B, respectively. 116 patients discontinued induction treatment, mainly due to toxicity (15%) or progressive disease (12%). Median age of the randomized pts was 59 years (range 21–70) with 22% being ≥65 years. Overall response rate (ORR) following induction treatment was 69% (52% PR, 27% CR). Thirteen pts died due to treatment-related toxicity, comprising mainly infectious complications. Following consolidation CR rate increased substantially to 65% in arm A and 68% in arm B. Six patients died of toxicity during consolidation treatment (2 in arm A and 4 in arm B), Median follow-up was 45 months (range 0.2–86). The 3-year PFS and OS rates were 79% (95% CI 71–86) and 86% (95% CI 78–91) following HDC-ASCT and 53% (95% CI 44–62%) and 71% (95% CI 61–78) after R-DeVIC (HR 0.41; p = 0.0002). The evaluation of neurocognitive functions showed no difference between arms. The research was funded by: Riemser, Roche Keywords: aggressive B-cell non-Hodgkin lymphoma, stem cell transplant Conflicts of interests pertinent to the abstract G. Illerhaus Consultant or advisory role: Roche, Gilead, Incyte Educational grants: Roche, Gilead

Introduction: Osteosarcoma is typically a disease of the young, but may affect any age. Little is known about the disease in older patients beyond retirement age. We aim to describe the characteristics, treatment, and outcomes of older adult patients registered with our cooperative group. Materials and Methods: The database of the Cooperative Osteosarcoma Study Group (COSS) was searched for osteosarcoma patients diagnosed from 1980 to 2020 who were aged 65 years or older at diagnosis. Affected individuals were analyzed for presenting factors, treatments employed, and outcomes. Results: Fifty-five eligible patients were detected (median age 68 [range: 65-84] years; male:female = 25:30). Among these patients, 15/55 (27%) tumors were secondary malignancies, 41/55 (75%) were high-grade central, 4/55 (7%) surface, and 10/55 (18%) extraosseous malignancies, and all but three high-grade. Primary metas-tases were present in 15/55 (27%) patients. Surgery was reported for 46/55 (84%) patients, radiotherapy for 6/ 54 (11%, 1 unknown), chemotherapy for 42/50 (84%, 5 unknown). A complete surgical remission was achieved in 31/55 (56%). There were two toxic deaths. With a median follow-up of 1.7 (range: 0.1-18.0) years for all 55 patients and 2.2 (0.1-12.4) years for 24 survivors, event-free and overall survival at 2/5 years were 39.6% (standard error: 6.8%) / 24.5% (6.5%) and 62.0% (7.1%) / 32.7% (7.5%), respectively. Tumor site, metastatic status, surgery, and a complete surgical remission were prognostic for event-free and/or overall survival. Discussion: Osteosarcomas can occur in older individuals. It is more often secondary, axially located, or extra -osseous than in younger patients. However, the same treatment principles seem to apply, and selected patients may be cured. Multi-center cooperation is encouraged, thereby gathering expertise for such a rare disease presentation.

Study protocol of all parts of the EWING 2008 trial

This non-interventional, prospective phase IV trial evaluated trabectedin in patients with soft tissue sarcoma (STS) in real-life clinical practice across Germany. The primary endpoints were progression-free survival (PFS) rates at 3 and 6 months, as defined by investigators. Overall, 128 patients from 19 German sites were evaluated for efficacy and 130 for safety. Median age was 58.5 years (range: 23-84) and leiomyosarcoma was the most frequent histotype (n = 45; 35.2%). Trabectedin was mostly used as second/third-line treatment (n = 91; 71.1%). Median PFS was 5.2 months (95% CI: 3.3-6.7), with 60.7% and 44.5% of patients free from progression at 3 and 6 months, respectively. Median overall survival was 15.2 months (95% CI: 9.6-21.4). One patient achieved a complete and 14 patients a partial response, conferring an objective response rate of 11.7%. Decreases in white blood cells (27.0% of patients), platelets (16.2%) and neutrophils (13.1%) and increased alanine aminotransferase (10.8%) were the most common trabectedin-related grade 3/4 adverse drug reactions. Two deaths due to pneumonia and sepsis were considered trabectedin-related. Trabectedin confers clinically meaningful activity in patients with multiple STS histotypes, comparable to that previously observed in clinical trials and other non-interventional studies, and with a manageable safety profile.

Introduction: High-dose methotrexate (HD-MTX) based induction chemo-immunotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (HCT-ASCT) has been shown to be feasible and effective in younger and in selected elderly PCNSL patients. We aimed to investigate this treatment approach in patients > 65 years with newly diagnosed PCNSL in a multicentre study. Methods: This open-label, multicentre, single arm phase II study was conducted at 15 German centres (DRKS 00011932). Main eligibility criteria included newly diagnosed PCNSL, immunocompetence, age > 65 years, Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 2, and adequate organ function. Induction treatment consisted of two 21-day cycles of HD-MTX 3.5 g/m² (day 1), cytarabine 2 g/m² twice daily (days 2, 3) and rituximab 375 mg/m² before and after each chemotherapy with stem cell harvest after the 1st cycle. Patients not suffering disease progression subsequently received consolidation treatment with HCT-ASCT with rituximab 375 mg/m² (day -8), busulfan 3.2 mg/kg (days -7, -6), thiotepa 5 mg/kg/d (days -5, -4) and reinfusion of stem cells (day 0). Primary endpoint was progression-free survival (PFS) at 1 year by intention-to-treat (ITT). Secondary endpoints included overall survival (OS), treatment response and toxicities. Results: Between Nov 2017 and Sept 2020, we registered 57 patients. Five patients were excluded because of systemic lymphoma manifestation, absence of measurable radiologic lesion(s), inadequate renal function, ECOG PS >2 and deterioration before the start of study treatment. Finally, 52 eligible patients were included in the ITT population. Mean age was 72 years (range 65-80 years), 27/52 (51.9%) patients initially presented with an ECOG PS > 1. All patients started induction chemo-immunotherapy, 45 of 52 (86.5%) patients completed induction treatment. Thirty-seven of 52 (71.2%) patients proceeded to HCT-ASCT. Most common serious adverse events were infections, renal failure and (cerebro)vascular events, which mainly occurred during induction treatment. Overall, 22 (42.3%) patients died, 12 of whom (23.1%) without evidence of disease progression or relapse. Three (5.8%) patients died because of treatment-related complications, all of them during induction treatment. An additional patient died within 30 days after HCT-ASCT due to fatal viral pneumonia, main other non treatment-related causes of deaths were late infections and (cerebro)vascular events. Forty-one of 52 (78.8%) patients responded to induction treatment; 23 (44.2%) patients achieved a (unconfirmed) complete response and 11 (21.2%) patients a partial response 30 days after HCT-ASCT. After an estimated median follow-up of 23 months, PFS at 12 and 24 months was 57.7% (95% CI 43.2-69.7%) and 54.8% (40-67.4%), respectively; median PFS was 41.1 months (95% CI 6.7 to not calculable). Overall survival at 12 and 24 months was 63.1% (95% CI 48.4-74.7%) and 60.5% (95% CI 45.5-72.5%), respectively; median OS was 41.1 months (95% CI 10.3 to not calculable). Of those 37 patients undergoing HCT-ASCT, 2-year PFS and OS rates were 71.7% (95% CI 53.4-83.8%) and 80.8% (95% CI 63.8-90.3%), respectively. Conclusions: Feasibility and efficacy of HCT-ASCT in selected elderly patients with newly diagnosed PCNSL are confirmed in a multicenter setting with survival rates comparable to those of younger cohorts. Nevertheless, non-relapse mortality remains a major challenge in this vulnerable patient population emphasizing that standardized assessment of eligibility for intensive treatment is of utmost importance. This will be addressed in the upcoming randomized phase III PRIMA-CNS trial (DRKS00022768). Final data analysis is currently ongoing and will be presented in detail at the meeting.

Although the involvement of plastic surgery has been deemed important in the treatment of sarcoma patients to avoid oncological compromises and ameliorate patient outcomes, it is not ubiquitously available. The accessibility of defect reconstruction and its therapeutic impact on sarcoma care is the subject of this analysis. Cross-sectional data from 1309 sarcoma patients were collected electronically at 39 German study centers from 2017 to 2019. A total of 621 patients with surgical treatment for non-visceral soft-tissue sarcomas were included. The associated factors were analyzed exploratively using multifactorial logistic regression to identify independent predictors of successful defect reconstruction, as well Chi-squared and Cochran–Mantel–Haenszel tests to evaluate subgroups, including limb-salvage rates in extremity cases. A total of 76 patients received reconstructive surgery, including 52 local/pedicled versus 24 free flaps. Sarcomas with positive margins upon first resection (OR = 2.3, 95%CI = 1.2–4.4) that were excised at centers with lower degrees of specialization (OR = 2.2, 95%CI = 1.2–4.2) were independently associated with the need for post-oncological defect coverage. In this context, the inhouse availability of plastic surgery (OR = 3.0, 95%CI = 1.6–5.5) was the strongest independent predictor for successful flap-based reconstruction, which in turn was associated with significantly higher limb-salvage rates (OR = 1.4, 95%CI = 1.0–2.1) in cases of extremity sarcomas (n = 366, 59%). In conclusion, consistent referral to specialized interdisciplinary sarcoma centers significantly ameliorates patient outcomes by achieving higher rates of complete resections and offering unrestricted access to plastic surgery. The latter in particular proved indispensable for limb salvage through flap-based defect reconstruction after sarcoma resection. In fact, although there remains a scarcity of readily available reconstructive surgery services within the current sarcoma treatment system in Germany, plastic and reconstructive flap transfer was associated with significantly increased limb-salvage rates in our cohort.

Objective: The EPAZ study (NCT01861951) showed recently that pazopanib was non-inferior to doxorubicin in patients >60 years treated in first line for advanced soft tissue sarcoma . The current post-hoc analysis aimed to assess the prognostic impact of frailty. Methods: Geriatric assessments were evaluated at baseline. Age >75 years, liposarcoma, ECOG = 2, G8 <14, instrumental activities of daily living (IADL) >1 and Charlson Comor-bidity Index >2 were tested for their impact on progression-free survival (PFS), overall sur-vival (OS), CTCAE grade 3/4 adverse events (AEs) or serious AEs (SAEs), using univariate and multivariate analysis models. Results: univariate analysis showed an increased risk of grade 3/4 AEs and SAEs for ECOG = 2, G8 score <14 or IADL >1, independent of treatment. The multivariate analysis exhibited for pazopanib a significantly reduced risk for grade 3/4 AEs (HR 0.53; p = 0.033), and in patients with G8 <14 an increased risk for SAEs (HR 2.67; p = 0.011). In the multivariate analysis, G8 <14 was a negative prognostic factor for PFS (HR 1.82; p = 0.009) and IADL >1 for OS (HR 2.02; p = 0.007). ECOG = 2 was the strongest negative predictor for PFS (HR 4.39; p = 0.001) and OS (HR 3.74; p = 0.004). Neither age nor Charl-son Comorbidity Index showed any impact on PFS, OS, incidence of grade 3/4 AEs or SAEs. Conclusions: This post hoc analysis demonstrated that age is not a denominator for outcome or toxicity in elderly patients with soft tissue sarcoma . Instead, geriatric and functional assess-ments should be used to counsel patients and tailor therapy to individual needs. Moreover, pazopanib has a reduced risk for grade 3/4 AEs compared to doxorubicin.(c) 2022 Elsevier Ltd. All rights reserved.

BACKGROUND:The multi-receptor tyrosine kinase inhibitor pazopanib is approved for the treatment of advanced soft-tissue sarcoma and has also shown activity in other sarcoma subtypes. However, its clinical efficacy is highly variable, and no reliable predictors exist to select patients who are likely to benefit from this drug. PATIENTS AND METHODS:We analysed the molecular profiles and clinical outcomes of patients with pazopanib-treated sarcoma enrolled in a prospective observational study by the German Cancer Consortium, DKTK MASTER, that employs whole-genome/exome sequencing and transcriptome sequencing to inform the care of young adults with advanced cancer across histology and patients with rare cancers. RESULTS:Among 109 patients with available whole-genome/exome sequencing data, there was no correlation between clinical parameters, specific genetic alterations or mutational signatures and clinical outcome. In contrast, the analysis of a subcohort of 62 patients who underwent molecular analysis before pazopanib treatment and had transcriptome sequencing data available showed that mRNA levels of NTRK3 (hazard ratio [HR] = 0.53, p = 0.021), IGF1R (HR = 1.82, p = 0.027) and KDR (HR = 0.50, p = 0.011) were independently associated with progression-free survival (PFS). Based on the expression of these receptor tyrosine kinase genes, i.e. the features NTRK3-high, IGF1R-low and KDR-high, we developed a pazopanib efficacy predictor that stratified patients into three groups with significantly different PFS (p &lt; 0.0001). Application of the pazopanib efficacy predictor to an independent cohort of patients with pazopanib-treated sarcoma from DKTK MASTER (n = 43) confirmed its potential to separate patient groups with significantly different PFS (p = 0.02), whereas no such association was observed in patients with sarcoma from DKTK MASTER (n = 97) or The Cancer Genome Atlas sarcoma cohort (n = 256) who were not treated with pazopanib. CONCLUSION:A score based on the combined expression of NTRK3, IGF1R and KDR allows the identification of patients with sarcoma and with good, intermediate and poor outcome following pazopanib therapy and warrants prospective investigation as a predictive tool to optimise the use of this drug in the clinic.