Normofractionated and moderately hypofractionated proton therapy: Comparison of acute toxicity and early quality of life outcomes

Aim Data on the safety of moderately hypofractionated proton beam therapy (PBT) are limited. The aim of this study is to compare the acute toxicity and early quality of life (QoL) outcomes of normofractionated (nPBT) and hypofractionated PBT (hPBT). Results Overall, the highest toxicity grades of G0, G1, G2, and G3 were observed in 7 (5%), 40 (28.8%), 78 (56.1%), and 15 (10.8%) patients, respectively. According to organ and site, no statistically significant differences were detected in the majority of toxicity comparisons (66.7%). For A&P, hPBT showed a more favorable toxicity profile as compared to nPBT with a higher frequency of G0 and G1 and a lower frequency of G2 and G3 events (p = 0.04), more patients with improvement (95.7% vs 70%, p = 0.023), and full resolution of toxicities (87% vs 50%, p = 0.008). Skin toxicity was unanimously milder for hPBT compared to nPBT in A&P and ST locations (p = 0.018 and p = 0.025, respectively). No significant differences in QoL were observed in 97% of comparisons for QLQ-C30 scale except for loss of appetite in H&N patients (+33.3 for nPBT and 0 for hPBT, p = 0.02) and role functioning for A&P patients (0 for nPBT vs +16.7 hPBT, p = 0.003). For QLQ-HN35, 97.9% of comparisons did not reveal significant differences, with pain as the only scale varying between the groups (-8.33 vs -25, p = 0.016). Conclusion Hypofractionated proton therapy offers non-inferior early safety and QoL as compared to normofractionated irradiation and warrants further clinical investigation

Development and evaluation of a cancer-related fatigue patient education program: protocol of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Cancer-related fatigue (CRF) and its impact on patients' quality of life has been an increasing subject of research. However, in Germany there is a lack of evidence-based interventions consistent with the multidimensional character of fatigue. The objective of this study is to develop and evaluate a self-management program for disease-free cancer patients to cope with CRF.</p> <p>Methods</p> <p>Based on evidence extracted from a literature review, a curriculum for the self-management program was elaborated. The curriculum was reviewed and validated by an interdisciplinary expert group and the training-modules will be pretested with a small number of participants and discussed in terms of feasibility and acceptance.</p> <p>To determine the efficacy of the program a randomised controlled trial will be carried out: 300 patients will be recruited from oncological practices in Bremen, Germany, and will be allocated to intervention or control group. The intervention group participates in the program, whereas the control group receives standard care and the opportunity to take part in the program after the end of the follow-up (waiting control group). Primary outcome measure is the level of fatigue, secondary outcome measures are quality of life, depression, anxiety, self-efficacy and physical activity. Data will be collected before randomisation, after intervention, and after a follow-up of 6 months.</p> <p>Discussion</p> <p>Because there are no comparable self-management programs for cancer survivors with fatigue, the development of the curriculum has been complex; therefore, the critical appraisal by the experts was an important step to validate the program and their contributions have been integrated into the curriculum. The experts appreciated the program as filling a gap in outpatient cancer care.</p> <p>If the results of the evaluation prove to be satisfactory, the outpatient care of cancer patients can be broadened and supplemented.</p> <p>Trial Registration</p> <p>ClinicalTrials NCT00552552</p

Possible impact of iridium-192 source centering on restenosis rate after femoro-popliteal angioplasty and endovascular brachytherapy in Vienna-2 study

Purpose: Endovascular brachytherapy (EVBT) has been proven to significantly reduce restenosis after percutaneous transluminal angioplasty (PTA). The object of this analysis was to assess the possible correlation between iridium-192 source non-centering and angiographic-determined restenosis. Materials and methods: A total of 113 patients with long-segment lesions of the superficial femoro-popliteal artery (SFA) were randomized to receive either PTA alone or PTA followed by EVBT in the Vienna-2 study. This analysis was performed on a subgroup of 34 out of 57 patients, who received PTA + EVBT. Angiographic restenosis was defined as lumen reduction of more than 50%. Angio.-rams taken immediately after PTA (34 patients) and It follow-up (25 patients) were analyzed. The distance between the vessel wall and the actual position of the source at the time of EVBT was measured (in mm) and correlated with the follow-up vessel lumen diameter. Measurements were performed at points at a distance of 10 mm from each other. The dose was determined at the luminal surface and at the reference depth of 2 mm into the vessel wall for different distances from the source. Results: Among the 622 measured points, 62 (10.0%) were within restenotic areas; 560 (90.0%) were in arterial segments without proven angiographic restenosis, As far as source centering is concerned, 7.9% of restenotic points were observed when the maximum distance to the arterial wall was 5 mm. Conclusions: The proportion of restenotic points significantly increased with source non-centering. This observation was interpreted as being related to a decrease in dose at the target. When the maximum distance between the source and the vessel surface was >5 mm, the dose at the reference depth (2 min into the vessel wall) decreased to values lower than 5 Gy. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved

Research agenda surface technology: Future demands for research in the field of coatings materials

The acquisition of future research demands in the field of innovative coatings materials was the aim of the so-called "Research agenda surface technology", a project funded by the German Ministry of Education and Research and coordinated by the German Research Society of Surface Treatment (DFO, Neuss). Several German research institutions and numerous representatives of companies acting in the field of surface technology were involved in identifying the research demands in this area for the next 10-15 years. The functions of coated materials that were identified as the most innovative ones and having the biggest research driving force will be described for certain industrial branches. The most promising coating materials aimed to fulfill the desired functions in the future are discussed, visions are mentioned and conclusions about general trends in the field of coating materials are drawn

Proton or Carbon Ion Therapy for Skull Base Chordoma: Rationale and First Analysis of a Mono-Institutional Experience

Background: Skull base chordomas are radio-resistant tumors that require high-dose, high-precision radiotherapy, as can be delivered by particle therapy (protons and carbon ions). We performed a first clinical outcome analysis of particle therapy based on the initial 4-years of operation. Methods: Between August 2017 and October 2021, 44 patients were treated with proton (89%) or carbon ion therapy (11%). Prior gross total resection had been performed in 21% of lesions, subtotal resection in 57%, biopsy in 12% and decompression in 10%. The average prescription dose was 75.2 Gy RBE in 37 fractions for protons and 66 Gy RBE in 22 fractions for carbon ions. Results: At a median follow-up of 34.3 months (range: 1–55), 2-, and 3-year actuarial local control rates were 95.5% and 90.9%, respectively. The 2-, and 3-year overall and progression-free survival rates were 97.7%, 93.2%, 95.5% and 90.9%, respectively. The tumor volume at the time of particle therapy was highly predictive of local failure (p < 0.01), and currently, there is 100% local control in patients with tumors < 49 cc. No grade ≥3 toxicities were observed. There was no significant difference in outcome or side effect profile seen for proton versus carbon ion therapy. Five patients (11.4%) experienced transient grade ≤2 radiation-induced brain changes. Conclusions: The first analysis suggests the safety and efficacy of proton and carbon ion therapy at our center. The excellent control of small to mid-size chordomas underlines the effectiveness of particle therapy and importance of upfront maximum debulking of large lesions

Concepts and terms for dose/volume parameters in carbon-ion radiotherapy: Conclusions of the ULICE taskforce.

PURPOSE: The Union of Light Ion Centers in Europe (ULICE) program addressed the need for uniting scientific results for carbon-ion radiation therapy obtained by several institutions worldwide in different fields of excellence, and translating them into a real benefit to the community. Particularly, the concepts for dose/volume parameters developed in photon radiotherapy cannot be extrapolated to high linear energy transfer particles. METHODS AND MATERIALS: The ULICE-WP2 taskforce included radiation oncologists involved in carbon-ion radiation therapy and International Commission on Radiation Units and Measurements, radiation biologists, expert physicists in the fields of carbon-ion radiation therapy, microdosimetry, biological modeling and image-guided radiotherapy. Consensual reports emerged from multiple discussions within both the restricted group and the wider ULICE community. Public deliverables were produced and disseminated to the European Commission. RESULTS: Here we highlight the disparity in practices between treating centers, then address the main topics to finally elaborate specific recommendations. Although it appears relatively simple to add geometrical margins around the clinical target volume to obtain the planning target volume as performed in photon radiotherapy, this procedure is not appropriate for carbon-ion radiation therapy. Due to the variation of the radiation quality in depth, there is no generic relative biological effectiveness value for carbon-ions outside of an isolated point, for a given fractionation and specific experimental conditions. Absorbed dose and "equieffective dose" for specified conditions must always be reported. CONCLUSIONS: This work contributed to the development of standard operating procedures for carbon-ion radiation therapy clinical trials. These procedures are now being applied, particularly in the first phase III international, multicenter trial (PHRC Étoile).[Concepts et terminologie des paramètres de dose et volumes proposés en hadronthérapie par ions carbone] OBJECTIF DE L'ÉTUDE : Le programme Union of Light Ion Centers in Europe (ULICE) s’est proposé d’harmoniser et de favoriser la diffusion internationale des procédures et résultats de l’hadronthérapie par ions carbone. En particulier, les concepts pour les paramètres de volume et de dose recommandés en radiothérapie externe ou protonthérapie ne peuvent pas être extrapolés aux particules de transfert d’énergie linéique élevé. MATÉRIELS ET MÉTHODES : Le groupe de travail ULICE-WP2 comprenait des radiothérapeutes impliqués dans l’hadronthérapie par ions carbone et l’International Commission on Radiation Units and Measurements (ICRU), des biologistes, des physiciens experts en hadronthérapie, microdosimétrie, modélisation biologique et radiothérapie guidée par image. Des rapports consensuels ont émergé de discussions multiples, tant dans le groupe restreint que dans la communauté élargie d’ULICE. Les livrables publics ont été produits et diffusés auprès de la Commission européenne. RÉSULTATS : Nous avons mis en évidence une disparité des pratiques de prescription et spécification de la dose et des volumes entre les centres de traitement par ions carbone. Nous avons ensuite discuté des concepts fondamentaux qui s’appliquent à ces paramètres en hadronthérapie par ions carbone. Nous avons ensuite élaboré des recommandations spécifiques. Bien qu’il semble relativement simple d’ajouter des marges géométriques autour du volume cible anatomoclinique pour obtenir le volume cible prévisionnel en radiothérapie externe, cette procédure n’est pas appropriée pour l’hadronthérapie par ions carbone. En raison de la variation de la qualité du rayonnement en profondeur, il n’y a pas de valeur générique d’efficacité biologique relative pour les ions carbone en dehors d’un point isolé, pour un fractionnement donné et des conditions expérimentales spécifiques. La dose absorbée et la « dose isoefficace » pour des conditions spécifiées doivent toujours être signalées. CONCLUSIONS : Ce travail a contribué à l’élaboration de procédures standard pour la génération d’essais cliniques en l’hadronthérapie par ions carbone. Ces procédures sont désormais appliquées notamment dans le premier essai international multicentrique de phase III (programme hospitalier de recherche clinique Étoile)

Leishmania major Infection in Humanized Mice Induces Systemic Infection and Provokes a Nonprotective Human Immune Response

Background Leishmania (L.) species are the causative agent of leishmaniasis. Due to the lack of efficient vaccine candidates, drug therapies are the only option to deal with cutaneous leishmaniasis. Unfortunately, chemotherapeutic interventions show high toxicity in addition to an increased risk of dissemination of drug-resistant parasites. An appropriate laboratory animal based model is still missing which allows testing of new drug strategies in the context of human immune cells in vivo. Methodology/Principal Findings Humanized mice were infected subcutaneously with stationary phase promastigote L. major into the footpad. The human immune response against the pathogen and the parasite host interactions were analyzed. In addition we proved the versatility of this new model to conduct drug research studies by the inclusion of orally given Miltefosine. We show that inflammatory human macrophages get infected with Leishmania parasites at the site of infection. Furthermore, a Leishmania-specific human-derived T cell response is initiated. However, the human immune system is not able to prevent systemic infection. Thus, we treated the mice with Miltefosine to reduce the parasitic load. Notably, this chemotherapy resulted in a reduction of the parasite load in distinct organs. Comparable to some Miltefosine treated patients, humanized mice developed severe side effects, which are not detectable in the classical murine model of experimental leishmaniasis. Conclusions/Significance This study describes for the first time L. major infection in humanized mice, characterizes the disease development, the induction of human adaptive and innate immune response including cytokine production and the efficiency of Miltefosine treatment in these animals. In summary, humanized mice might be beneficial for future preclinical chemotherapeutic studies in systemic (visceral) leishmaniasis allowing the investigation of human immune response, side effects of the drug due to cytokine production of activated humane immune cells and the efficiency of the treatment to eliminate also not replicating (“hiding”) parasites