Patterns of Temporal Lobe Reaction and Radiation Necrosis after Particle Radiotherapy in Patients with Skull Base Chordoma and Chondrosarcoma-A Single-Center Experience.

BACKGROUND: The current study aims to evaluate the occurrence of temporal lobe reactions and identify possible risk factors for patients who underwent particle therapy of the skull base. METHODS: 244 patients treated for skull base chordoma (n = 144) or chondrosarcoma (n = 100) at the Heidelberg Ion Beam Therapy Center (HIT) using a raster scan technique, were analyzed. Follow-up MRI-scans were matched with the initial planning images. Radiogenic reactions were contoured and analyzed based on volume and dose of treatment. RESULTS: 51 patients with chordoma (35.4%) and 30 patients (30%) with chondrosarcoma experienced at least one temporal lobe reaction within the follow-up period (median 49 months for chondrosarcoma, 62 months for chordoma). Age, irradiated volume, and dose values were significant risk factors for the development of temporal lobe reactions with the highest significance for the value of DMax-7 being defined as the dose maximum in the temporal lobe minus the 7cc with the highest dose (p = 0.000000000019; OR 1.087). CONCLUSION: Temporal lobe reactions are a common side effect after particle therapy of the skull base. We were able to develop a multivariate model, which predicted radiation reactions with a specificity of 99% and a sensitivity of 52.2%.

The risk ethics of autonomous vehicles: an empirical approach.

How would people distribute risks of autonomous vehicles (AVs) in everyday road traffic? The rich literature on the ethics of autonomous vehicles (AVs) revolves around moral judgments in unavoidable collision scenarios. We argue for extending the debate to driving behaviors in everyday road traffic where ubiquitous ethical questions arise due to the permanent redistribution of risk among road users. This distribution of risks raises ethically relevant questions that cannot be evaded by simple heuristics such as "hitting the brakes." Using an interactive, graphical representation of different traffic situations, we measured participants' preferences on driving maneuvers of AVs in a representative survey in Germany. Our participants' preferences deviated significantly from mere collision avoidance. Interestingly, our participants were willing to take risks themselves for the benefit of other road users, suggesting that the social dilemma of AVs may be mitigated in risky environments. Our research might build a bridge between engineers and philosophers to discuss the ethics of AVs more constructively.

Revealing the Structural Evolution of Electrode/Electrolyte Interphase Formation during Magnesium Plating and Stripping with operando EQCM-D.

Rechargeable magnesium batteries could provide future energy storage systems with high energy density. One remaining challenge is the development of electrolytes compatible with the negative Mg electrode, enabling uniform plating and stripping with high Coulombic efficiencies. Often improvements are hindered by a lack of fundamental understanding of processes occurring during cycling, as well as the existence and structure of a formed interphase layer at the electrode/electrolyte interface. Here, a magnesium model electrolyte based on magnesium bis(trifluoromethanesulfonyl)imide (Mg(TFSI)2 ) and MgCl2 with a borohydride as additive, dissolved in dimethoxyethane (DME), was used to investigate the initial galvanostatic plating and stripping cycles operando using electrochemical quartz crystal microbalance with dissipation monitoring (EQCM-D). We show that side reactions lead to the formation of an interphase of irreversibly deposited Mg during the initial cycles. EQCM-D based hydrodynamic spectroscopy reveals the growth of a porous layer during Mg stripping. After the first cycles, the interphase layer is in a dynamic equilibrium between the formation of the layer and its dissolution, resulting in a stable thickness upon further cycling. This study provides operando information of the interphase formation, its changes during cycling and the dynamic behavior, helping to rationally develop future electrolytes and electrode/electrolyte interfaces and interphases.

All-Organic Battery Based on Deep Eutectic Solvent and Redox-Active Polymers.

Sustainable battery concepts are of great importance for the energy storage demands of the future. Organic batteries based on redox-active polymers are one class of promising storage systems to meet these demands, in particular when combined with environmentally friendly and safe electrolytes. Deep Eutectic Solvents (DESs) represent a class of electrolytes that can be produced from sustainable sources and exhibit in most cases no or only a small environmental impact. Because of their non-flammability, DESs are safe, while providing an electrochemical stability window almost comparable to established battery electrolytes and much broader than typical aqueous electrolytes. Here, we report the first all-organic battery cell based on a DES electrolyte, which in this case is composed of sodium bis(trifluoromethanesulfonyl)imide (NaTFSI) and N-methylacetamide (NMA) alongside the electrode active materials poly(2,2,6,6-tetramethylpiperidin-1-yl-oxyl methacrylate) (PTMA) and crosslinked poly(vinylbenzylviologen) (X-PVBV2+ ). The resulting cell shows two voltage plateaus at 1.07 V and 1.58 V and achieves Coulombic efficiencies of 98 %. Surprisingly, the X-PVBV/X-PVBV+ redox couple turned out to be much more stable in NaTFSI : NMA 1 : 6 than the X-PVBV+ /X-PVBV2+ couple, leading to asymmetric capacity fading during cycling tests.

Genetically Engineered Foods and Moral Absolutism: A Representative Study from Germany.

There is an ongoing debate about genetic engineering (GE) in food production. Supporters argue that it makes crops more resilient to stresses, such as drought or pests, and should be considered by researchers as a technology to address issues of global food security, whereas opponents put forward that GE crops serve only the economic interests of transnational agrifood-firms and have not yet delivered on their promises to address food shortage and nutrient supply. To address discourse failure regarding the GE debate, research needs to understand better what drives the divergent positions and which moral attitudes fuel the mental models of GE supporters and opponents. Hence, this study investigates moral attitudes regarding GE opposition and support in Germany. Results show that GE opponents are significantly more absolutist than supporters and significantly less likely to hold outcome-based views. Furthermore, GE opponents are more willing to donate for preventing GE admission than supporters are willing to donate for promoting GE admission. Our results shed light on why the divide between opponents and supporters in the German GE debate could remain stark and stable for so long.

Intensity-modulated radiotherapy for the management of primary and recurrent chordomas: a retrospective long-term follow-up study.

Background: Chordomas have a high risk of recurrence. Radiotherapy (RT) is required as adjuvant therapy after resection. Sufficient radiation doses for local control (LC) can be achieved using either particle therapy, if this technology is available and feasible, or intensity-modulated radiotherapy. Materials and methods: 57 patients (age, 11.8-81.6 years) with chordomas of the skull base, spine and pelvis who received photon radiotherapy between 1995 and 2017 were enrolled in the study. Patients were treated at the time of initial diagnosis (68.4%) or during recurrence (31.6%). 44 patients received adjuvant radiotherapy and 13 received definitive radiotherapy. The median total dose to the physical target volume was 70 Gy equivalent dose in 2 Gy fractions (EQD2) (range: 54.7-82.5) in 22-36 fractions. Results: LC was 76.4%, 58.4%, 46.7% and 39.9% and overall survival (OS) was 98.3%, 89%, 76.9% and 47.9% after 1, 3, 5 and 10 years, respectively, with a median follow-up period of 6.5 years (range, 0.5-24.3 years). Age, dose and treatment concept (post-operative or definitive) were significant prognostic factors for OS. Primary treatment, macroscopic tumour at RT and size of the irradiated volume were statistically significant prognostic factors for LC. Conclusion: Photon treatment is a safe and effective treatment for chordomas if no particle therapy is available. The best results can be achieved against primary tumours if the application of curative doses is possible due to organs at risk in direct proximity. We recommend high-dose radiotherapy, regardless of the resection status, as part of the initial treatment of chordoma, using the high conformal radiation technique if particle therapy is not feasible.

The Care-Dependent are Less Averse to Care Robots: An Empirical Comparison of Attitudes.

A growing gap is emerging between the supply of and demand for professional caregivers, not least because of the ever-increasing average age of the world's population. One strategy to address this growing gap in many regions is the use of care robots. Although there have been numerous ethical debates about the use of robots in nursing and elderly care, an important question remains unexamined: how do the potential recipients of such care perceive situations with care robots compared to situations with human caregivers? Using a large-scale experimental vignette study, we investigated people's affective attitudes toward care robots. Specifically, we studied the influence of the caregiver's nature on participants' perceived comfort levels when confronted with different care scenarios in nursing homes. Our results show that the care-robot-related views of actual care recipients (i.e., people who are already affected by care dependency) differ substantially from the views of people who are not affected by care dependency. Those who do not (yet) rely on care placed care robots' value far below that of human caregivers, especially in a service-oriented care scenario. This devaluation was not found among care recipients, whose perceived level of comfort was not influenced by the caregiver's nature. These findings also proved robust when controlled for people's gender, age, and general attitudes toward robots. Supplementary Information: The online version contains supplementary material available at 10.1007/s12369-023-01003-2.

ChatGPT's inconsistent moral advice influences users' judgment.

ChatGPT is not only fun to chat with, but it also searches information, answers questions, and gives advice. With consistent moral advice, it can improve the moral judgment and decisions of users. Unfortunately, ChatGPT's advice is not consistent. Nonetheless, it does influence users' moral judgment, we find in an experiment, even if they know they are advised by a chatting bot, and they underestimate how much they are influenced. Thus, ChatGPT corrupts rather than improves its users' moral judgment. While these findings call for better design of ChatGPT and similar bots, we also propose training to improve users' digital literacy as a remedy. Transparency, however, is not sufficient to enable the responsible use of AI.

Entropic Contributions to Sodium Solvation and Solvent Stabilization upon Electrochemical Sodium Deposition from Diglyme and Propylene Carbonate Electrolytes.

The formation of an appropriate solid electrolyte interphase (SEI) at the anode of a sodium battery is crucially dependent on the electrochemical stability of solvent and electrolyte at the redox potential of Na/Na+ in the respective system. In order to determine entropic contributions to the relative stability of the electrolyte solution, we measure the reaction entropy of Na metal deposition for diglyme (DG) and propylene carbonate (PC) based electrolyte solutions by electrochemical microcalorimetry at single electrodes. We found a large positive reaction entropy for Na+ deposition in DG of ΔR S DG ≈ ${S\left({\rm { DG}}\right)\approx \ }$ 234 J mol-1 K-1 (c.f.: ΔR S PC ≈ ${S\left({\rm { PC}}\right)\approx \ }$ 83 J mol-1 K-1 ), which signals substantial entropic destabilization of Na+ in DG by about 0.73 eV, thus increasing the stability of solvent and electrolyte relative to Na+ reduction. We attribute this strong entropic destabilization to a highly negative solvation entropy of Na+ , due to the low dielectric constant and high freezing entropy of DG.

Moral luck in investment contexts: We consciously find unprofitable investments less moral.

Moral luck refers to whether an actor is morally praised or blamed for an action whose outcome they could not influence. In two studies, we investigated the behavioral importance of this phenomenon in the realm of investments, which has become increasingly subject to ethical evaluations. In our first online experiment, we examined whether people's moral evaluation of an investment decision depended on its arbitrary outcome and whether their interpretation of the nature of the decision was driven by this outcome. Our results showed that profitable investments were considered more moral than unprofitable investments. Moreover, profitable investments were labeled "investments" instead of "speculation" or "gambling" more often than unprofitable ones. In our second study, we asked the subjects to assess investments independent of the outcome. After the outcome was announced, the subjects were given the opportunity to reflect and change their initial decision. The results show that people change the moral evaluation and label of investments when told that it had a bad outcome. This observation was stable across different investment contexts. These findings suggest that we must be careful with the increasing moralization of investment decisions and be sensitive to our cognitive biases.

Combining Deep Eutectic Solvents with TEMPO-based Polymer Electrodes: Influence of Molar Ratio on Electrode Performance.

For sustainable energy storage, all-organic batteries based on redox-active polymers promise to become an alternative to lithium ion batteries. Yet, polymers contribute to the goal of an all-organic cell as electrodes or as solid electrolytes. Here, we replace the electrolyte with a deep eutectic solvent (DES) composed of sodium bis(trifluoromethanesulfonyl)imide (NaTFSI) and N-methylacetamide (NMA), while using poly(2,2,6,6-tetramethylpiperidin-1-yl-oxyl methacrylate) (PTMA) as cathode. The successful combination of a DES with a polymer electrode is reported here for the first time. The electrochemical stability of PTMA electrodes in the DES at the eutectic molar ratio of 1 : 6 is comparable to conventional battery electrolytes. More viscous electrolytes with higher salt concentration can hinder cycling at high rates. Lower salt concentration leads to decreasing capacities and faster decomposition. The eutectic mixture of 1 : 6 is best suited uniting high stability and moderate viscosity.

Proton and carbon ion beam treatment with active raster scanning method in 147 patients with skull base chordoma at the Heidelberg Ion Beam Therapy Center-a single-center experience.

BACKGROUND: This study aimed to compare the results of irradiation with protons versus irradiation with carbon ions in a raster scan technique in patients with skull base chordomas and to identify risk factors that may compromise treatment results. METHODS: A total of 147 patients (85 men, 62 women) were irradiated with carbon ions (111 patients) or protons (36 patients) with a median dose of 66 Gy (RBE (Relative biological effectiveness); carbon ions) in 4 weeks or 74 Gy (RBE; protons) in 7 weeks at the Heidelberg Ion Beam Therapy Center (HIT) in Heidelberg, Germany. The median follow-up time was 49.3 months. All patients had gross residual disease at the beginning of RT. Compression of the brainstem was present in 38%, contact without compression in 18%, and no contact but less than 3 mm distance in 16%. Local control and overall survival were evaluated using the Kaplan-Meier Method based on scheduled treatment (protons vs. carbon ions) and compared via the log rank test. Subgroup analyses were performed to identify possible prognostic factors. RESULTS: During the follow-up, 41 patients (27.9%) developed a local recurrence. The median follow-up time was 49.3 months (95% CI: 40.8-53.8; reverse Kaplan-Meier median follow-up time 56.3 months, 95% CI: 51.9-60.7). No significant differences between protons and carbon ions were observed regarding LC, OS, or overall toxicity. The 1­year, 3­year, and 5­year LC rates were 97%, 80%, and 61% (protons) and 96%, 80%, and 65% (carbon ions), respectively. The corresponding OS rates were 100%, 92%, and 92% (protons) and 99%, 91%, and 83% (carbon ions). No significant prognostic factors for LC or OS could be determined regarding the whole cohort; however, a significantly improved LC could be observed if the tumor was > 3 mm distant from the brainstem in patients presenting in a primary situation. CONCLUSION: Outcomes of proton and carbon ion treatment of skull base chordomas seem similar regarding tumor control, survival, and toxicity. Close proximity to the brainstem might be a negative prognostic factor, at least in patients presenting in a primary situation.

Particle Therapy in Adult Patients with Pelvic Ewing Sarcoma-Tumor and Treatment Characteristics and Early Clinical Outcomes.

PURPOSE: To report dosimetric characteristics and early clinical outcomes in patients with pelvic Ewing sarcoma undergoing particle therapy. METHODS: Patients ≥ 18 years old with pelvic Ewing sarcoma treated in adjuvant or definitive settings were considered for this retrospective analysis. Proton therapy was carried out with 45-60 Gy (RBE) (1.5-2 Gy (RBE) per fraction) and carbon ion therapy for recurrent disease with 51 Gy (RBE) (3 Gy (RBE) per fraction). Local control (LC), disease control (DC) and overall survival (OS) were calculated using the Kaplan-Meier method. RESULTS: For our sample, 21 patients were available, 18 of whom were treated for primary, 3 for locally recurrent and 16 for inoperable disease. The median CTV and PTV were 1215 cm3 and 1630 cm3. Median Dmean values for the PTV, bladder and rectum and median V40 Gy for the bowel for patients undergoing proton therapy were 56 Gy (RBE), 0.6 Gy (RBE), 9 Gy (RBE) and 15 cm3, respectively. At the end of particle therapy, G 1-2 skin reactions (n = 16/21) and fatigue (n = 9/21) were the main reported symptoms. After a median follow-up of 21 months, the 2-year LC, DC and OS were 76%, 56% and 86%, respectively. CONCLUSIONS: Particle therapy in adult pelvic Ewing sarcoma is feasible and provides excellent dosimetric results. First clinical outcomes are promising; however, further long-term follow-up is needed.

Hiding Behind Machines: Artificial Agents May Help to Evade Punishment.

The transfer of tasks with sometimes far-reaching implications to autonomous systems raises a number of ethical questions. In addition to fundamental questions about the moral agency of these systems, behavioral issues arise. We investigate the empirically accessible question of whether the imposition of harm by an agent is systematically judged differently when the agent is artificial and not human. The results of a laboratory experiment suggest that decision-makers can actually avoid punishment more easily by delegating to machines than by delegating to other people. Our results imply that the availability of artificial agents could provide stronger incentives for decision-makers to delegate sensitive decisions.

Versatile 3D-Printed Micro-Reference Electrodes for Aqueous and Non-Aqueous Solutions.

While numerous reference electrodes suitable for aqueous electrolytes exist, there is no well-defined standard for non-aqueous electrolytes. Furthermore, reference electrodes are often large and do not meet the size requirements for small cells. In this work, we present a simple method for fabricating stable 3D-printed micro-reference electrodes. The prints are made from polyvinylidene fluoride, which is chemically inert in strong acids, bases, and commonly used non-aqueous solvents. We chose six different reference systems based on Ag, Cu, Zn, and Na, including three aqueous and three non-aqueous systems to demonstrate the versatility of the approach. Subsequently, we conducted cyclic voltammetry experiments and measured the potential difference between the aqueous homemade reference electrodes and a commercial Ag/AgCl-electrode. For the non-aqueous reference electrodes, we chose the ferrocene redox couple as an internal standard. From these measurements, we deduced that this new class of micro-reference electrodes is leak-tight and shows a stable electrode potential.

Outcome after surgical resection of multiple recurrent retroperitoneal soft tissue sarcoma.

INTRODUCTION: Local recurrences (LR) and distant metastases (DM) are common in retroperitoneal soft tissue sarcoma (RPS). Longer time to recurrence and resection of the recurrent lesion have been identified as beneficial prognostic factors for overall survival (OS) upon first tumor relapse. However, prognostic factors concerning OS upon subsequent recurrences are scarcely defined. In this study, we aimed to identify prognostic factors for post-relapse outcome in multiple recurrent RPS. METHODS: Patients undergoing resection of primary and recurrent RPS at the University Hospital Heidelberg were retrospectively analyzed. Multivariable Cox regression analyses were performed to identify predictors of overall, LR- and DM-free survival. Subgroup analyses were performed for liposarcoma and leiomyosarcoma patients. RESULTS: 201 patients with primary disease, 101 patients with first, 66 patients with second and 43 patients with third LR as well as 75 patients with DM were analyzed. More than 12 months to recurrence and resection of recurrence were associated with improved OS after resection of first and second LR (5-year OS for first/second LR; resection: 64%/62%, no resection: 20%/46%). Gross macroscopic incomplete resection of first (p < 0.001), second (p = 0.001), and third recurrences (p < 0.001) was an independent prognostic factor for poor OS. CONCLUSION: Development of LR and DM is frequent in RPS. Once a tumor relapsed, patients benefit from tumor resection not only in case of first, but also in case of subsequent recurrences.

The role of combined ion-beam radiotherapy (CIBRT) with protons and carbon ions in a multimodal treatment strategy of inoperable osteosarcoma.

BACKGROUND: To investigate the role of combined ion-beam radiotherapy (CIBRT) with protons and carbon ions in a multimodal treatment strategy of inoperable osteosarcoma; final analysis of a one-armed, single center phase I/II trial. METHODS: Between August 2011 until September 2018, 20 patients with primary (N = 18), metastatic (N = 3), or recurrent (N = 2) inoperable pelvic (70%) or craniofacial (30%) osteosarcoma were treated with protons up to 54 Gy (RBE) and a carbon ion boost of 18 Gy (RBE) and followed until May 2019. A Fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) was performed before CIBRT in search for a prognostic factor. The primary endpoint was toxicity. Secondary endpoints included treatment response, global, local and distant progression free survival (PFS, LPFS and DPFS) and overall (OS), among others. RESULTS: The median age was 20; all patients finished treatment per protocol. LPFS, DPFS, PFS and OS were 73%, 74%, 60% and 75% after one year and 55%, 65% 65.3%, 45% and 68% after two years, respectively. The median clinical target volume (CTV) was 1042 cc and 415 cc for the primary and boost plan, respectively. Craniofacial localization, lower uptake of FDG in PET/CT and boost plan CTV ≤ median were associated with improved overall survival (p = 0.039, p = 0.016 and p = 0.0043, respectively). No acute toxicities > grade III were observed. We observed one case of secondary acute myeloid leukemia (AML) seven months after CIBRT for recurrent disease and one case of hearing loss. CONCLUSION: CIBRT shows a favorable toxicity profile and promising results particularly for patients with inoperable craniofacial osteosarcoma.

Sarcoma classification by DNA methylation profiling.

Sarcomas are malignant soft tissue and bone tumours affecting adults, adolescents and children. They represent a morphologically heterogeneous class of tumours and some entities lack defining histopathological features. Therefore, the diagnosis of sarcomas is burdened with a high inter-observer variability and misclassification rate. Here, we demonstrate classification of soft tissue and bone tumours using a machine learning classifier algorithm based on array-generated DNA methylation data. This sarcoma classifier is trained using a dataset of 1077 methylation profiles from comprehensively pre-characterized cases comprising 62 tumour methylation classes constituting a broad range of soft tissue and bone sarcoma subtypes across the entire age spectrum. The performance is validated in a cohort of 428 sarcomatous tumours, of which 322 cases were classified by the sarcoma classifier. Our results demonstrate the potential of the DNA methylation-based sarcoma classification for research and future diagnostic applications.

Clivus chordomas: Heterogeneous tumor extension requires adapted surgical approaches.

OBJECTIVE: Clivus chordomas are semi-malignant, but infiltratively growing tumors. Currently, a widely-accepted treatment concept encompasses maximal, but safe, surgical resection and radiotherapy. Caused by the size and the tumor extension, different surgical approaches, especially in recurrent cases, might be necessary. METHODS: Retrospective review of 50 patients on whom 70 surgeries were performed: 29 in primary and 41 in recurrent cases. Based on MRI images, all cases were asserted according to the size and the extension of the tumor. Used surgical approaches were evaluated. Postoperative complications, neurological function prior to and after the surgery, the extent of tumor resection on postoperative MR images were assessed and progression-free survival was calculated. RESULTS: Tumor size was estimated as small (< 5 cm3) in 8, as medium (5-20 cm3) in 21, as large (20-100 cm3) in 17, and as giant (> 100 cm3) in 4 patients. Most frequently used surgical approaches in primary cases were the transsphenoidal one and midfacial degloving (51.7 % and 17.2 %, respectively). In recurrent cases, dependent on the tumor extension, transsphenoidal (21.9 %), retrosigmoidal (29.3 %), and pterional (19.5 %) approaches, as well as midfacial degloving (17.1 %) were used. Due to the vast tumor extension and infiltration, gross total or near total resection could be achieved in 12 patients (24 %), only. There was no mortality and no major complications in primary cases. In recurrences, however, postoperative hemorrhages and strokes emerged in 4.9 % and 7.1 %. Minor complications occurred in 17.1 % and were dominated by CSF leaks (12.2 %), both in primary in recurrent cases. While most cranial nerve impairments were caused by tumor infiltration of the cavernous sinus, and hence have not improved by treatment, the sixth nerve palsy as a consequence of tumor mass compression, could significantly be improved by surgery. Following surgery, patients were subjected to radiotherapy (68.9 % for primary cases, and 36.6 % for recurrences) mainly with carbon ions. Overall, 5-year progression-free survival was 44.7 %. CONCLUSION: Caused by the heterogenous pattern of growth of clivus chordomas, surgical approaches should be chosen individually. Vast and infiltrative tumor extension constitute major limitations of surgical resection, and hence result in poor progression-frees survival.

High-dose carbon-ion based radiotherapy of primary and recurrent sacrococcygeal chordomas: long-term clinical results of a single particle therapy center.

BACKGROUND: This study aimed to analyze the oncological long-term results and late toxicity of carbon ion-based radiotherapy (RT) of patients with sacral chordoma and to identify potential prognostic factors for local control (LC) and overall survival (OS). METHODS: A total of 68 patients with sacral chordoma treated at the Heidelberg Ion Beam Therapy Center were included in this study. Of these 52 patients (77%) received a primary RT and 16 patients (23%) received a RT in a recurrent situation. All patients were treated with carbon ion RT (CIRT), either in combination with photons (n = 22; 32%) or as a monotherapy (n = 46; 68%), with a median radiation dose of 66 Gy RBE (range 60-74 Gy). In 40 patients (59%), RT was performed in the postoperative situation. Postoperative care included regular MRI scans. Local progression was defined as an enlargement of the maximum tumor diameter by 10% or a new tumor growth within the planning target volume (PTV). LC and OS were determined using the Kaplan-Meier method. Furthermore, the relevance of various prognostic factors for LC and OS was assessed by univariate and multivariate analysis. RESULTS: The median follow-up period was 60 months (range 1.3-97.4 months). The 5-year rates for LC, progression-free survival, metastasis-free survival and OS were 53, 53, 52 and 74%, respectively. Local recurrence was observed in 31 patients (46%), occurring after a median follow-up time of 25 months (range 2.5-73.1 months). Only 10% of local recurrences occurred later than 5 years after RT. Statistical analysis showed that RT in the relapse situation corresponded to inferior LC rates compared to the primary situation, while other factors such as the GTV, radiation dose (EQD2) and treatment approach (CIRT alone vs. CIRT combined with photons) were insignificant. For OS after RT, patient age and PTV size proved to be significant predictors. The incidence of late toxicity ≥ III° according to CTCAE v5.0 was 21%. Sacral insufficiency fractures occurred in 49% of patients (maximum III°: 16%) and were thus by far the most frequent late side effect in our analysis. Radiogenic damage to the peripheral nerves, intestinal tract and skin was observed in only 9% (≥ III°: 5%), 3% (all II°) and 9% (all I°) of patients. CONCLUSION: Our analysis showed only moderate long-term LC rates after carbon ion-based RT, with sacral chordomas having a particularly poor prognosis in the recurrent situation. Therefore, future studies should evaluate the safety and effectiveness of further dose escalation and hypofractionation of RT in sacral chordoma and weight potential benefits of dose escalation against side effects.