Stereotaktische Strahlentherapie von Metastasen: Palliativer Effekt und Tumorkontrolle

Zusammenfassung: Hintergrund: Aufgrund längeren Krankheitsverlaufs durch neue Systemtherapien und basierend auf dem Konzept der Oligometastasierung wird in der klinischen Praxis immer häufiger die Indikation für eine lokal definitive Behandlung von Metastasen gestellt. Mit der stereotaktischen Radiotherapie können Metastasen in wenigen Sitzungen effizient abgetötet werden. Fragestellung: Was ist die Evidenz zur stereotaktischen Radiotherapie von Patienten mit Oligometastasen? Wie ist der Einfluss der Metastasenkontrollrate auf das Überleben nach stereotaktischer Radiotherapie? Wie toxisch ist die Behandlung? Wie ist die Abgrenzung von anderen lokalen Therapiemethoden wie z.B. der Chirurgie? Gibt es prognostische Faktoren bei Patienten mit Oligometastasen? Material und Methode: Literatursuche nach prospektiven und retrospektiven Studien. Ergebnisse: Den einzigen Beweis für einen lebensverlängernden Effekt durch lokale Behandlung von Oligometastasen liefert eine randomisierte Studie, die den radiochirurgischen Boost nach Ganzhirnbestrahlung bei Patienten mit Hirnfiliae untersuchte. Prospektive Phase-II-Studien zur stereotaktischen Radiotherapie von Hirn-, Lungen-, Leber-, Wirbelkörper- und Oligometastasen an multiplen Lokalisationen belegen die hohe Tumorkontrollrate und gute Verträglichkeit dieser Behandlung. Prognostische Faktoren sind in erster Linie Histologie, Anzahl und Größe der Metastasen sowie das krankheitsfreie Überleben. Schlussfolgerung: Die stereotaktische Radiotherapie ist eine valide Therapieoption in der Behandlung von Patienten mit Oligometastasen und sollte in der klinischen Praxis auch als Alternative zur Metastasenchirurgie und lokal ablativer Verfahren erwogen werden

Stereotaktische Bestrahlung: Lokale Tumorkontrolle enorm verbessert

Mit der stereotaktischen Strahlentherapie lässt sich die Bestrahlung so präzise auf das Zielvolumen richten, dass die Dosis und damit der Antitumoreffekt erhöht werden können. Lungenkrebs ist ein Beispiel für den klinischen Nutzen

Radiation-induced lymphopenia does not impact treatment efficacy in a mouse tumor model

Radiation-induced lymphopenia is a common occurrence in radiation oncology and an established negative prognostic factor, however the mechanisms underlying the relationship between lymphopenia and inferior survival remain elusive. The relevance of lymphocyte co-irradiation as critical normal tissue component at risk is an emerging topic of high clinical relevance, even more so in the context of potentially synergistic radiotherapy-immunotherapy combinations. The impact of the radiotherapy treatment volume on the lymphocytes of healthy and tumor-bearing mice was investigated in a novel mouse model of radiation-induced lymphopenia. Using an image-guided small-animal radiotherapy treatment platform, translationally relevant tumor-oriented volumes of irradiation with an anatomically defined increasing amount of normal tissue were irradiated, with a focus on the circulating blood and lymph nodes. In healthy mice, the influence of irradiation with increasing radiotherapy treatment volumes was quantified on the level of circulating blood cells and in the spleen. A significant decrease in the lymphocytes was observed in response to irradiation, including the minimally irradiated putative tumor area. The extent of lymphopenia correlated with the increasing volumes of irradiation. In tumor-bearing mice, differential radiotherapy treatment volumes did not influence the overall therapeutic response to radiotherapy alone. Intriguingly, an improved treatment efficacy in mice treated with draining-lymph node co-irradiation was observed in combination with an immune checkpoint inhibitor. Taken together, our study reveals compelling data on the importance of radiotherapy treatment volume in the context of lymphocytes as critical components of normal tissue co-irradiation and highlights emerging challenges at the interface of radiotherapy and immunotherapy. Keywords: Image-guided small animal radiotherapy platform; Lymphopenia; Normal tissue injury; Radioimmunotherapy; Radiotherap

Hydration-Scanning Tunneling Microscopy as a Reliable Method for Imaging Biological Specimens and Hydrophilic Insulators

The recently discovered high lateral conductivity of molecularly thin adsorbed water films enables investigation of biological specimens, and even of surfaces of hydrophilic insulators by scanning tunneling microscopy (STM). Here we demonstrate the capabilities of this method, which we call hydration-STM (HSTM), with images of various specimens taken in humid atmosphere: We obtained images of a glass coverslip, collagen molecules, tobacco mosaic virus, lipid bilayers and cryosectioned bovine achilles tendon on mica. To elucidate the physical mechanism of this conduction phenomenon we recorded current-voltage curves on hydrated mica. This revealed a basically ohmic behavior of the J-V curves without a threshold voltage to activate the current transport and indicates that electrochemistry probably does not dominate the surface conductivity. We assume that the conduction mechanism is due to structuring of water at the surface

An in-silico planning study of stereotactic body radiation therapy for polymetastatic patients with more than ten extra-cranial lesions

BACKGROUND AND PURPOSE Limited data is available about the feasibility of stereotactic body radiation therapy (SBRT) for treating more than five extra-cranial metastases, and almost no data for treating more than ten. The aim of this study was to investigate the feasibility of SBRT in this polymetatstatic setting. MATERIALS AND METHODS Consecutive metastatic melanoma patients with more than ten extra-cranial metastases and a maximum lesion diameter below 11 cm were selected from a single-center prospective registry for this in-silico planning study. For each patient, SBRT plans were generated to treat all metastases with a prescribed dose of 5x7Gy, and dose-limiting organs (OARs) were analyzed. A cell-kill based inverse planning approach was used to automatically determine the maximum deliverable dose to each lesion individually, while respecting all OARs constraints. RESULTS A total of 23 polymetastatic patients with a medium of 17 metastases (range, 11-51) per patient were selected. SBRT plans with sufficient target coverage and respected OARs dose constraints were achieved in 16 out of 23 patients. In the remaining seven patients, the lungs V5Gy < 80 % and the liver D700 cm$^{3}$ < 15Gy were most frequently the dose-limiting constraints. The cell-kill based planning approach allowed optimizing the dose administration depending on metastases total volume and location. CONCLUSION This retrospective planning study shows the feasibility of definitive SBRT for 70% of polymetastatic patients with more than ten extra-cranial lesions and proposes the cell-killing planning approach as an approach to individualize treatment planning in polymetastatic patients'

A Dynamic Programming Approach to Adaptive Fractionation

We conduct a theoretical study of various solution methods for the adaptive fractionation problem. The two messages of this paper are: (i) dynamic programming (DP) is a useful framework for adaptive radiation therapy, particularly adaptive fractionation, because it allows us to assess how close to optimal different methods are, and (ii) heuristic methods proposed in this paper are near-optimal, and therefore, can be used to evaluate the best possible benefit of using an adaptive fraction size. The essence of adaptive fractionation is to increase the fraction size when the tumor and organ-at-risk (OAR) are far apart (a "favorable" anatomy) and to decrease the fraction size when they are close together. Given that a fixed prescribed dose must be delivered to the tumor over the course of the treatment, such an approach results in a lower cumulative dose to the OAR when compared to that resulting from standard fractionation. We first establish a benchmark by using the DP algorithm to solve the problem exactly. In this case, we characterize the structure of an optimal policy, which provides guidance for our choice of heuristics. We develop two intuitive, numerically near-optimal heuristic policies, which could be used for more complex, high-dimensional problems. Furthermore, one of the heuristics requires only a statistic of the motion probability distribution, making it a reasonable method for use in a realistic setting. Numerically, we find that the amount of decrease in dose to the OAR can vary significantly (5 - 85%) depending on the amount of motion in the anatomy, the number of fractions, and the range of fraction sizes allowed. In general, the decrease in dose to the OAR is more pronounced when: (i) we have a high probability of large tumor-OAR distances, (ii) we use many fractions (as in a hyper-fractionated setting), and (iii) we allow large daily fraction size deviations.Comment: 17 pages, 4 figures, 1 tabl