AimThis article gives an overview on the current status of hypofractionated radiotherapy in the treatment of prostate cancer with a special focus on the applicability in routine use.MethodsBased on a recently published systematic review the German Society of Radiation Oncology (DEGRO) expert panel added additional information that has become available since then and assessed the validity of the information on outcome parameters especially with respect to long-term toxicity and long-term disease control.ResultsSeveral large-scale trials on moderate hypofractionation with single doses from 2.4–3.4 Gy have recently finished recruiting or have published first results suggestive of equivalent outcomes although there might be a trend for increased short-term and possibly even long-term toxicity. Large phase 3 trials on extreme hypofractionation with single doses above 4.0 Gy are lacking and only very few prospective trials have follow-up periods covering more than just 2–3 years.ConclusionUntil the results on long-term follow-up of several well-designed phase 3 trials become available, moderate hypofractionation should not be used in routine practice without special precautions and without adherence to the highest quality standards and evidence-based dose fractionation regimens. Extreme hypofractionation should be restricted to prospective clinical trials.
ADT combined with SRT appears to improve OS in patients with a PSA level before SRT of ≥0.7 ng/mL. In patients without persistent PSA after prostatectomy and PSA levels of <0.7 ng/mL, ADT should not routinely be used, but may be considered in patients with additional risk factors such as Gleason Score ≥8 and negative surgical margins.
Despite modern treatment with microsurgery, irradiation and chemotherapy in primary intraspinal PNETs, local relapse or dissemination in most cases lead to death within a few months. An improvement of treatment outcome can only be achieved by intensification through multidisciplinary treatment.
Due to the sparcity of reported cases with malignant ectomesenchymoma, the role of adjuvant therapy is unclear. Multimodal therapy may be able to improve outcome.
In order to assess the autoinhibitory control of endogenous acetylcholine (ACh) in rat and human neocortex, slices of these tissues were prelabelled with [(3)H]choline, superfused continuously and stimulated electrically using various frequencies in the presence or absence of drugs. The autoinhibitory feedback control of [(3)H]ACh release was operative - despite the absence of blockers of ACh esterase - at stimulation frequencies >/= 3 Hz in rat and >/= 6 Hz in human neocortex tissue. At these frequencies the muscarinic antagonist atropine (0.1 microM) disinhibited the release of [(3)H]ACh in both species. Estimation of the biophase concentration of ACh near the autoreceptor in the rat neocortex from concentration-response curves of the muscarinic agonist oxotremorine revealed that at 3 Hz about 25% of the autoreceptors were activated by endogenously released ACh. This estimation is consistent with an increase in [(3)H]ACh release to about 120% of control values by complete blockade of autoreceptors with atropine. The observation that in human neocortical tissue presynaptic autoinhibition of [(3)H]ACh release is operative at stimulation frequencies >/= 6 Hz suggests that selective blockade of autoinhibition may also increase ACh release in the cortex of Alzheimer's disease patients, without additional blockade of the enzyme acetylcholinesterase.
Due to its low fractionation sensitivity, also known as “alpha/beta ratio,” in relation to its surrounding organs at risk, prostate cancer is predestined for hypofractionated radiation schedules assuming an increased therapeutic ratio compared to normofractionated regimens. While moderate hypofractionation (2.2–4 Gy) has been proven to be non-inferior to normal fractionation in several large randomized trials for localized prostate cancer, level I evidence for ultrahypofractionation (>4 Gy) was lacking until recently. An accumulating body of non-randomized evidence has recently been strengthened by the publication of two randomized studies comparing ultrahypofractionation with a normofractionated schedule, i.e., the Scandinavian HYPO-RT trial by Widmark et al. and the first toxicity results of the PACE‑B trial. In this review, we aim to give a brief overview of the current evidence of ultrahypofractionation, make an overall assessment of the level of evidence, and provide recommendations and requirements that should be followed before introducing ultrahypofractionation into routine clinical use.
Objective This article aims to provide an overview of the role of combined radiation and androgen deprivation (ADT) therapy in patients with intermediate-risk prostate cancer. Materials and methodsThe current German, European, and NCCN (National Comprehensive Cancer Network) guidelines as well as relevant literature in the PubMed database which provide information on sub-classification within the intermediate-risk group and the use of ADT in terms of oncological outcome were reviewed. Results Different recommendations for risk-group assessment of patients with localized prostate cancer are available. Subdivision of intermediate risk into a favorable and an unfavorable group seems to be justified to allow for a more individualized therapy in a quite heterogenous group of patients. So far, multiple randomized trials have shown a benefit when radiation therapy (RT) is combined with ADT. The use of dose-escalated RT without ADT also appears to be an adequate therapy associated with a very low rate of cancer-specific deaths. Therefore, taking into account the increased rate of toxicity associated with ADT, dose-escalated RT alone might be justified, especially in favorable intermediate-risk patients. Conclusion Dose-escalated RT alone appears to be an appropriate treatment in favorable intermediate-risk patients. Addition of short course ADT (4-6 months) might improve outcomes in unfavorable intermediate-risk patients.A previous version of this article in German language has already been published as an expert opinion article by some of the above-mentioned authors [7]. The present article is an updated and extended version.
The purpose of this study was to try to determine by means of contrast-enhanced MRI, a subset of patients with Graves' ophthalmopathy who will not respond to orbital radiotherapy. 54 patients with Graves' ophthalmopathy were treated with orbital radiotherapy (10 x 2 Gy) and symptom relief was recorded. MRI examinations prior to radiotherapy were retrospectively evaluated for enlargement, contrast enhancement and fibrotic changes in extraocular muscles and surrounding soft tissue. Imaging data were correlated with clinical features and response. Symptom relief was observed in 61% of patients but this could not be predicted by any of the MRI signs investigated. However, there is a trend for a better treatment reponse in patients who show contrast enhancement of extraocular muscles prior to orbital radiotherapy (p=0.08). MRI could not adequately predict the efficacy of orbital radiotherapy in this group of patients. Clinical assessment of disease activity is still the most reliable method.
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