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Abstract Background Treatment options for patients with advanced hepatocellular carcinoma (HCC) are often limited. In most cases, they are not amenable to local therapies including surgery or radiofrequency ablation. The multi-kinase inhibitor sorafenib has shown to increase overall survival in this patient group for about 3 months. Radiation therapy is a treatment alternative, however, high local doses are required for long-term local control. However, due to the relatively low radiation tolerance of liver normal tissue, even using stereotactic techniques, delivery of sufficient doses for successful local tumor control has not be achieved to date. Carbon ions offer physical and biological characteristics. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increased relative biological effectiveness (RBE), which can be calculated between 2 and 3 depending on the HCC cell line as well as the endpoint analyzed. Japanese Data on the evaluation of carbon ion radiation therapy showed promising results for patients with HCC. Methods/Design In the current Phase I-PROMETHEUS-01-Study, carbon ion radiotherapy will be evaluated for patients with advanced HCC. The study will be performed as a dose-escalation study evaluating the optimal carbon ion dose with respect to toxicity and tumor control. Primary endpoint is toxicity, secondary endpoint is progression-free survival and response. Discussion The Prometheus-01 trial ist the first trial evaluating carbon ion radiotherapy delivered by intensity-modulated rasterscanning for the treatment of HCC. Within this Phase I dose escalation study, the optimal dose of carbon ion radiotherapy will be determined. Trial registration NCT 01167374

Abstract Background Treatment standard for patients with atypical or anaplastic meningioma is neurosurgical resection. With this approach, local control ranges between 50% and 70%, depending on resection status. A series or smaller studies has shown that postoperative radiotherapy in this patient population can increase progression-free survival, which translates into increased overall survival. However, meningiomas are known to be radioresistant tumors, and radiation doses of 60 Gy or higher have been shown to be necessary for tumor control. Carbon ions offer physical and biological characteristics. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increased relative biological effectiveness (RBE), which can be calculated between 2 and 5 depending on the cell line as well as the endpoint analyzed. First data obtained within the Phase I/II trial performed at GSI in Darmstadt on carbon ion radiotherapy for patients with high-risk meningiomas has shown safety, and treatment results are promising. Methods/design The Phase II-MARCIE-Study will evaluate a carbon ion boost applied to the macroscopic tumor in conjunction with photon radiotherapy in patients with atypical menigiomas after incomplete resection or biopsy. Primary endpoint is progression-free survival, secondary endpoints are overall survival, safety and toxicity. Discussion Based on published data on the treatment of atypical meningiomas with carbon ions at GSI, the present study will evaluate this treatment concept in a larger patient population and will compare outcome to current standard photon treatment. Trial registration NCT01166321

Abstract Background Treatment of patients with recurrent glioma includes neurosurgical resection, chemotherapy, or radiation therapy. In most cases, a full course of radiotherapy has been applied after primary diagnosis, therefore application of re-irradiation has to be applied cauteously. With modern precision photon techniques such as fractionated stereotactic radiotherapy (FSRT), a second course of radiotherapy is safe and effective and leads to survival times of 22, 16 and 8 months for recurrent WHO grade II, III and IV gliomas. Carbon ions offer physical and biological characteristics. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increased relative biological effectiveness (RBE), which can be calculated between 2 and 5 depending on the GBM cell line as well as the endpoint analyzed. Protons, however, offer an RBE which is comparable to photons. First Japanese Data on the evaluation of carbon ion radiation therapy for the treatment of primary high-grade gliomas showed promising results in a small and heterogeneous patient collective. Methods Design In the current Phase I/II-CINDERELLA-trial re-irradiation using carbon ions will be compared to FSRT applied to the area of contrast enhancement representing high-grade tumor areas in patients with recurrent gliomas. Within the Phase I Part of the trial, the Recommended Dose (RD) of carbon ion radiotherapy will be determined in a dose escalation scheme. In the subsequent randomized Phase II part, the RD will be evaluated in the experimental arm, compared to the standard arm, FSRT with a total dose of 36 Gy in single doses of 2 Gy. Primary endpoint of the Phase I part is toxicity. Primary endpoint of the randomized part II is survival after re-irradiation at 12 months, secondary endpoint is progression-free survival. Discussion The Cinderella trial is the first study to evaluate carbon ion radiotherapy for recurrent gliomas, and to compare this treatment to photon FSRT in a randomized setting using an ion beam delivered by intensity modulated rasterscanning. Trial Registration NCT01166308

Objectives: Two headphone systems using different sound systems were compared to investigate the effects of a sound intervention on cardiovascular parameters, indicators of stress, and subjective feelings. Methods: One hundred volunteers who work in the health care sector reporting elevated workplace-related stress were enrolled and randomized to a 12-min sound intervention (classical music) with either conventional headphones ("MEZE 99 Classic") or with the same—but internally modified—headphone (called "Lautsaenger"). Cardiovascular parameters were measured with the VascAssist2.0, both before and after sound interventions. In addition, participants were asked to complete questionnaires on burnout risk and emotions/stress. Results: The study population consisted mainly of female participants (n = 83), with the majority being students (42%). Median age was 32.5 years (range 21–71). In terms of cardiovascular parameters, a significant reduction in aortic pulse wave velocity, as measure of arterial stiffness, and heart rate was observed within both treatment arms. Both systolic blood pressure and arterial flow resistance were reduced by sound intervention, while these effects were only documented with Lautsaenger. Treatment groups were comparable in terms of subjective feedback by participants: a significant increase in emotional wellbeing was achieved with both headphone systems. Conclusions: A single short-term sound intervention seems to be able to achieve objective cardiovascular improvements in healthy volunteers reporting subjective symptoms of workplace-related stress, using two different headphone systems. Moreover, significant emotional improvement was reported within both arms. Trial Registration: ISRCTN registry 70947363, date of registration August 13, 2021. [ABSTRACT FROM AUTHOR]

Background: We sought to replace full-dose Gd-DTPA with safer and lower-dose contrast agents for delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). Gd-BOPTA has a lower intrinsic nephrogenic systemic fibrosis risk and a 2-fold higher relaxivity at 3T; thus, the contrast agent dose may be halved, further reducing contrast agent-dependent risks.Purpose: To compare the feasibility of using half-dose, high-relaxivity Gd-BOPTA vs. standard-dose Gd-DTPA for dGEMRIC.Study Type: Prospective observational study.Subjects: Eleven healthy volunteers (five women, mean age 25.7 years) and 10 patients with knee pain (three women, mean age 36.7 years; nine with chondromalacia).Field Strength/sequences: 3D T1 -weighted volumetric breath-hold examination (VIBE) sequence at 3T.Assessment: Knee dGEMRIC was performed twice, first using 0.1 mmol/kg Gd-BOPTA and 4 weeks later using 0.2 mmol/kg Gd-DTPA. Contrast penetration was studied using pre- and 60-120-min postcontrast imaging in volunteers and pre- and 90-min postcontrast imaging in patients. Femoral cartilage lesions were assessed using modified whole-organ MRI scores. Healthy cartilage and partial-thickness lesions were compared using region-of-interest analyses by independent readers.Statistical Tests: Linear mixed-effect-models, area under receiver-operating-characteristic curve (AUC) analysis, intraclass correlation (ICC).Results: In healthy volunteers, Gd-BOPTA and Gd-DTPA T1 -values did not differ significantly at any timepoint (P = 0.164-0.995). In patients, Gd-BOPTA T1 -values (743.33 ± 72.015 msec) were higher than Gd-DTPA T1 -values (681.24 ± 67.635 msec, P = 0.030). Gd-BOPTA and Gd-DTPA detected chondromalacia areas equally well, with significantly lower T1 -values than in healthy cartilage (P < 0.001) and nonsignificantly different AUCs (0.92 and 0.96, P = 0.27). The absolute decrease in T1 -values between healthy and pathological cartilage was similar (Gd-BOPTA: 149.59 msec; Gd-DTPA: 149.44 msec, P = 0.99). ICCs were 0.83-0.98 for Gd-BOPTA and 0.80-0.98 for Gd-DTPA.Data Conclusion: Gd-BOPTA might be used at half the Gd-DTPA dose in dGEMRIC, with similar contrast penetration and T1 -values in healthy cartilage and noninferior detection of cartilage damage.Level Of Evidence: 2 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2020;51:144-154. [ABSTRACT FROM AUTHOR]