Introduction: Bone and soft tissue sarcomas express fibroblast activation protein (FAP) on tumor cells and associated fibroblast. Therefore, FAP is a promising therapeutic and diagnostic target.Novel radio-labelled FAP-Inhibitors (e.g. 68 Ga-FAPI46) have shown high tumor uptake in positron emission tomography (PET) in sarcoma patients. Here we report endpoints of the FAPI-PET prospective observational trial.Methods: Forty-seven patients with bone or soft tissue sarcomas undergoing clinical 68 Ga-FAPI-PET were eligible for enrollment into the FAPI-PET observational trial. Of these patients, 43 patients also underwent 18 F-Fluordesoxyglucose PET (FDG). The primary study endpoint was the association of 68 Ga-FAPI-PET uptake intensity and histopathological FAP-expression analyzed with Spearman's r correlation. Secondary endpoints were detection rate, positive predictive value (PPV), interreader reproducibility, and change in management. Datasets were interpreted by two blinded readers.Results: Primary endpoint was met and the association between FAPI-PET uptake intensity and histopathological FAP-expression was significant (Spearman's r = 0.43; p = 0.03). By histopathological validation PPV was 1.00 (95% CI, 0.87-1.00) on a per-patient and 0.97 (95% CI, 0.84-1.00) on a per-region basis. In cases with histopathologic validation, 27 of 28 (96%) confirmed patients and 32 of 34 (94%) confirmed regions were PET positive resulting in an SE of 0.96 (95%CI, 0.82-1.00) on a per-patient and 0.94 (95%CI, 0.80-0.99) on a per-region basis. The detection rate on a per-patient basis in FAPI-and FDG-PET was 76.6% and 81.4%, respectively.In 8 (18.6%) patients FAPI-PET resulted in an upstaging compared to FDG-PET. FAPI-PET readers showed substantial to almost perfect agreement for the defined regions (Fleiss kappa: primary κ = 0.78; local nodal κ = 0.54; distant nodal κ = 0.91; lung κ = 0.86; bone κ = 0.69 and other κ = 0.65). Clinical management changed in 13 (30%) patients after FAPI-PET. Conclusion:We confirm an association of tumoral FAPI-PET uptake intensity and histopathological FAP expression in sarcoma patients. Further, using blinded reads and independent histopathological validation we report high PPV and sensitivity of FAPI-PET for sarcoma staging.

To reduce wear in joint bearings of total hip arthroplasty (THA) is the most important issue for improving long term results and implant survival. Due to low wear rates and excellent tribological features in simulator tests Diamond-Like-Carbon coating (DLC) of femoral balls is still discussed as an alternative articulation in THA. This clinical prospective study compares survivorship of DLCcoated femoral heads and of Aluminia-Oxide-(Al 2 O 3 ) heads articulating with Polyethylene (PE).Over a period of two years 101 THA with DLC-coated heads and PE cups (DLC-group) and another 101 THA consisting of Al 2 O 3 heads (Al 2 O 3 -group) and PE cups as well were implanted. Both articulations were based on the same type of cementless hip joint prosthesis. All hips were implanted by one surgeon in consecutive series consisting of 51 Al 2 O 3 and 101 DLC-articulations and further 50 Al 2 O 3 . All perioperative and follow-up data was processed with SPSS J . Survival of THA in both groups was evaluated according to Kaplan-Meier survivorship analysis with an intervall of 90 months (range:78-101). Qualitative surface analysis was performed in nineteen retrieved DLC-heads which were revised for aseptic loosening using field scanning electron microscopy (FE-SEM, XL 30 SFEG Philips, Eindoven NL).178 patients (88.2 %) were evaluated for follow-up. Fourteen patients died meantimes (nine DLC, five Al 2 O 3 ) with the implant components not revised. Ten patients (five DLC, five Al 2 O 3 ) were lost to follow-up. Both groups were comparable regarding patient age, weight and indications for THA with a normal distribution. Survivorship analysis for aseptic loosening 8.5 years following implantation resulted in a significant difference between both groups with a 54 % survival for DLC/PE compared to 88 % for Al 2 O 3 /PE bearings (p <0.001). No correlation to variables as age, gender or bodyweight could be detected. Surfaces of nineteen retrieved DLC-heads showed numerous smallest pits of the diamond-carbon layers in different quantity. SEM showed delamination of the carbon layer which caused excessive debris of polyethylene and in some cases even of the metallic substrate of the heads.Despite modern manufacturing technology and excellent experimental results for its tribochemical characteristics and wear, even "new" DLC-coating of femoral heads is to be considered critically due to very high rates of clinical failure. Obwohl moderne Fertigungstechniken mit sehr guten experimentellen Ergebnissen hinsichtlich Tribochemie und Verschleiß verbunden sind, müssen DLC-Beschichtungen zukünftig für diese Anwendung angesichts der immens hohen klinischen Versagensquote mit größter Zurückhaltung betrachtet werden.Schlagworte: Diamond-Like-Carbon,

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TM-ILP yielded high response rates in STS. Regression after TM-ILP exhibits MVD-dependent histopathologic patterns and variable efficacy in different sarcoma types. Complete regression seems to be a favorable prognostic factor. A concerted consideration of histopathology and clinical findings may contribute to a better clinical assessment of regression after TM-ILP.

Custom-made, three-dimensionally-printed (3D) bone prostheses gain increasing importance in the reconstruction of bone defects after musculoskeletal tumor resections. They may allow preservation of little remaining bone stock and ensure joint or limb salvage. However, we believe that by constructing anatomy-imitating implants with highly cancellous titanium alloy (TiAl6V4) surfaces using 3D printing technology, further benefits such as functional enhancement and reduction of complications may be achieved. We present a case series of four patients reconstructed using custom-made, 3D-printed intercalary monobloc tibia prostheses treated between 2016 and 2020. The mean patient age at operation was 30 years. Tumor resections were performed for Ewing sarcoma (n = 2), high-grade undifferentiated pleomorphic bone sarcoma (n = 1) and adamantinoma (n = 1). Mean resection length was 17.5 cm and mean operation time 147 min. All patients achieved full weight-bearing and limb salvage at a mean follow-up of 21.25 months. One patient developed a non-union at the proximal bone-implant interface. Alteration of implant design prevented non-union in later patients. Mean MSTS and TESS scores were 23.5 and 88. 3D-printed, custom-made intercalary tibia prostheses achieved joint and limb salvage in this case series despite high, published complication rates for biological and endoprosthetic reconstructions of the diaphyseal and distal tibia. Ingrowth of soft tissues into the highly cancellous implant surface structure reduces dead space, enhances function, and appears promising in reducing complication rates.

Our results endorse F-FDG PET/MRI to be an excellent imaging method in the evaluation of recurrent STS after surgical excision, yielding superior tumor detection when compared to MRI alone.

Gastrointestinal stromal tumors (GIST) exhibit a strong oncogenic dependency on KIT and KIT inhibitors confer long lasting disease stabilization in the majority of patients. Nonetheless, KIT inhibition alone does not cure GIST as a subset of GIST cells evade apoptosis and eventually develop resistance. Inhibitors of Apoptosis Proteins (IAPs) may confer resistance to drug-induced apoptosis. We observed that the mRNA and protein of IAPs XIAP (BIRC4) and survivin (BIRC5) were highly expressed in primary GIST tumors and cell line models. Amplification of the respective gene loci (BIRC2, BIRC3, BIRC4, BIRC5) was detected in 47% of GIST studied by SNP arrays. Whole exome analyses revealed a mutation of SMAC(DIABLO) in a heavily pretreated patient. Both, survivin (rank 62-92/11.194 tested proteins) and XIAP (rank 106-557/11.194) were found to be essential proteins for survival in a synthetic lethality screen. Expression of XIAP and survivin decreased upon KIT inhibition and may play a role in KIT-regulated pro-survival signaling. SMAC-mimetic treatment with LCL161 and TL32711 reduced cIAP1 and XIAP expression. Survivin inhibitor YM155 lead to transcriptional repression of BIRC5/survivin (YM155) and induced apoptosis. Combinational treatment with KIT inhibitors (imatinib, regorafenib) enhanced the proapoptotic effect. These findings support the combination of KIT inhibition with IAP antagonists in GIST.

BackgroundIsolated limb perfusion with TNF-alpha and melphalan (TM-ILP) in combination with complete tumor resection is an effective treatment option for non-resectable soft-tissue sarcoma of the extremities, with limb salvage rates greater than 80%. The aim of this study was to assess quality of life (QoL) after TM-ILP, also with regard to long-term survival.MethodsWe retrospectively examined 27 patients who had primarily non-resectable soft-tissue sarcoma of the leg and who had undergone TM-ILP and complete tumor resection (with limb-sparing intent) during their follow-up examinations using the Quality of Life Questionnaire (QLQ-C30) and the German Short Musculoskeletal Function Assessment (SMFA-D). The results from the QLQ-C30 were compared to the reference values for the general population, to the “all cancer patients” reference values (both reference values published by the European Organization for Research and Treatment of Cancer (EORTC)), and to the reference values of a historical amputation group from the literature. The results of the SMFA were compared with those from a reference group of healthy individuals.ResultsSurprisingly, we found that the global health status/QoL in the TM-ILP group was not significantly different from the general population or from patients with amputation, but it was higher than that of patients with cancer in general. Concerning the SMFA, we did find functional impairments in patients after TM-ILP compared to the reference group. With regard to long-term survival, we found no time-dependent deterioration in QoL for longer time intervals after treatment.ConclusionsThese results support the use of TM-ILP in limb-sparing multimodal therapy settings from a quality-of-life perspective, but they also encourage further research on this matter.Electronic supplementary materialThe online version of this article (doi:10.1186/s12957-017-1150-3) contains supplementary material, which is available to authorized users.