Ludmila Hynková

Why and how to spare the hippocampus during brain radiotherapy: the developing role of hippocampal avoidance in cranial radiotherapy

The goal of this review is to summarize the rationale for and feasibility of hippocampal sparing techniques during brain irradiation. Radiotherapy is the most effective non-surgical treatment of brain tumors and with the improvement in overall survival for these patients over the last few decades, there is an effort to minimize potential adverse effects leading to possible worsening in quality of life, especially worsening of neurocognitive function. The hippocampus and associated limbic system have long been known to be important in memory formation and pre-clinical models show loss of hippocampal stem cells with radiation as well as changes in architecture and function of mature neurons. Cognitive outcomes in clinical studies are beginning to provide evidence of cognitive effects associated with hippocampal dose and the cognitive benefits of hippocampal sparing. Numerous feasibility planning studies support the feasibility of using modern radiotherapy systems for hippocampal sparing during brain irradiation. Although results of the ongoing phase II and phase III studies are needed to confirm the benefit of hippocampal sparing brain radiotherapy on neurocognitive function, it is now technically and dosimetrically feasible to create hippocampal sparing treatment plans with appropriate irradiation of target volumes. The purpose of this review is to provide a brief overview of studies that provide a rationale for hippocampal avoidance and provide summary of published feasibility studies in order to help clinicians prepare for clinical usage of these complex and challenging techniques.

Post-WBRT cognitive impairment and hippocampal neuronal depletion measured by in vivo metabolic MR spectroscopy: Results of prospective investigational study

BACKGROUND AND PURPOSE The aim of this prospective study is to evaluate post-whole brain radiotherapy (WBRT) changes in hippocampal concentration of N-acetylaspartate (h-tNAA) as a marker of neuronal loss and to correlate those changes to neurocognitive function. MATERIAL AND METHODS Thirty-five patients with brain metastases underwent baseline single slice multi-voxel MR spectroscopy (MRS) examination for measurement of hippocampal h-tNAA together with baseline battery of neurocognitive tests focused on memory (Auditory Verbal Learning Test and Brief Visuospatial Memory Test - Revised) as well as quality of life questionnaires (EORTC QLQ-C30 a EORTC QLQ-BN20). Eighteen patients completed follow-up evaluation four months after standard WBRT (2 laterolateral fields, 10×3.0Gy, 6MV photons) and were included in this analysis. MRS and cognitive examinations were repeated and compared to baseline measurements. RESULTS Statistically significant decreases in h-tNAA were observed in the right (8.52-7.42mM; -12.9%, 95%CI: -7.6 to -16.4%) as well as in the left hippocampus (8.64-7.60mM; -12%, 95%CI: -7.9 to -16.2%). Statistically significant decline was observed in all AVLT and BVMT-R subtests with exception of AVLT_Recognition. Quality of life declined after WBRT (mean Δ -14.1±20.3 points in transformed 0-100 point scale; p=0.018) with no correlation to changes in hippocampal metabolite concentrations. Moderate positive correlation was observed between left h-tNAA concentration decrease and AVLT_TR decline (r=+0.32; p=0.24) as well as with AVLT_DR (r=+0.33; p=0.22) decline. Changes in right h-tNAA/Cr negatively correlated with AVLT_DR (r=-0.48; p=0.061). No correlation between right hippocampus h-tNAA and memory decline (AVLT) was observed. CONCLUSIONS Our results suggest hippocampal NAA concentrations decline after WBRT and MRS may be a useful biomarker for monitoring neuronal loss after radiotherapy.

Patterns of failure after brain metastases radiotherapy: reflections on the importance for treatment and clinical trials reporting

In many ongoing clinical trials, new strategies for radiotherapy of brain metastases are currently being investigated. A post surgical focal cavity stereotactic radiosurgery and the developing role of a hippocampal-sparing whole brain radiotherapy are of the highest importance. The evaluation of spatial patterns of metastases failure after radiotherapy is a powerful tool for assessing the potential benefit of new different radiotherapy approaches, which enables to identify possible directions leading to better radiotherapy techniques and to modify general management for newly diagnosed brain metastases. The purpose of this article is to present a mix between trial data and philosophical point of view for discussion about the importance of systematic evaluation of spatial patterns of failure in all ongoing trials investigating new approaches in local brain metastases treatment.

The Role of Palliative Radiotherapy in Bleeding from Locally Advanced Gastrointestinal Tumors

BACKGROUND Patients with locally advanced gastrointestinal tumors present with typical symptoms including pain, obstructive problems with passage disorders and bleeding. The last of them negatively affects their quality of life and is potentially lethal. Palliative radiotherapy is used in hemostatic indication to control bleeding from locally advanced or recurrent inoperable gastrointestinal tumors for many years. PURPOSE This review summarizes information and available literature about mechanisms, efficiency and toxicity of palliative radiotherapy used in hemostatic indication, separately for each part of the digestive system. Although most of the published studies are retrospective, all of them show fast, effective and technically safe control of bleeding with minimal risk of toxicity and show an improvement of quality of life. Hypofractionated radiotherapy, with a smaller number of high doses, seems to be the appropriate palliative fractionation schedule. The higher daily dose is associated with faster initiation of hemostatic effect, while few radiotherapy treatment sessions are comfortable for patients; both of them meet the basic principles of state-of-the-art palliative care. In addition to external beam radiotherapy, high dose rate brachytherapy represents another possibility in this indication, especially for locally advanced inoperable anal and rectal cancer. Brachytherapy is simple, practical and most importantly a one-time procedure with high local effect without significant toxicity. CONCLUSION Radiotherapy is an important treatment possibility for palliative care of bleeding from locally advanced inoperable gastrointestinal cancers. Future prospective studies employing modern radiotherapeutic techniques and procedures are needed to provide consistent and clear evidence in order to weigh risks against benefits of palliative hemostatic radiotherapy in current daily clinical practice.Key words: locally advanced gastrointestinal tumors - bleeding - palliative radiotherapy The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 8. 5. 2017Accepted: 23. 7. 2017.