Crawl positioning improves set-up precision and patient comfort in prone whole breast irradiation

Prone positioning for whole-breast irradiation (WBI) reduces dose to organs at risk, but reduces set-up speed, precision, and comfort. We aimed to improve these problems by placing patients in prone crawl position on a newly developed crawl couch (CrC). A group of 10 right-sided breast cancer patients requiring WBI were randomized in this cross-over trial, comparing the CrC to a standard prone breastboard (BB). Laterolateral (LL), craniocaudal (CC) and anterioposterior (AP) set-up errors were evaluated with cone beam CT. Comfort, preference and set-up time (SUT) were assessed. Forty left and right-sided breast cancer patients served as a validation group. For BB versus CrC, AP, LL and CC mean patient shifts were - 0.8 +/- 2.8, 0.2 +/- 11.7 and - 0.6 +/- 4.4 versus - 0.2 +/- 3.3, - 0.8 +/- 2.5 and - 1.9 +/- 5.7 mm. LL shift spread was reduced significantly. Nine out of 10 patients preferred the CrC. SUT did not differ significantly. The validation group had mean patient shifts of 1.7 +/- 2.9 (AP), 0.2 +/- 3.6 (LL) and - 0.2 +/- 3.3 (CC) mm. Mean SUT in the validation group was 1 min longer (P<0.05) than the comparative group. Median SUT was 3 min in all groups. The CrC improved precision and comfort compared to BB. Set-up errors compare favourably to other prone-WBI trials and rival supine positioning

Developing delineation guidelines for the lymphatic target volumes in ‘prone crawl’ radiotherapy treatment position for breast cancer patients

This project focuses on the promising new 'prone crawl' position for breast cancer radiotherapy. This position places the patient in prone, with the arm on the treated side alongside the body. The other arm is extended above the head, resembling a phase from crawl swimming. In prone position, the breast can hang free, away from organs at risk and by placing the arm alongside the body, the radiation beam can still reach the axillary lymph nodes. Preliminary data showed reduced radiation dosages in lungs, non-treated breast, thyroid and oesophagus, compared to the regularly used supine position. After proving the potential of this new position, it is important to optimize it for widespread clinical use. An important part of radiation therapy is the delineation of the target tissue (the tumour or the lymphatic system, if cancer cells have infiltrated the lymphatics) and the organs at risk. The goal of radiotherapy is to kill tumour cells by hitting them with a high energy beam. This beam is guided by the delineations and it is therefore really important that delineations are performed accurately, since the beam will also kill healthy cells and it could cause damage to organs at risk (like the heart and lungs) if it misses the target area. To ensure that delineations are performed according to a universal standard and to guarantee that every patient gets the same quality of treatment across different centres, delineation guidelines exist to guide the radiation oncologist when performing delineations. Since the prone crawl position is still very new, no position specific guidelines existed and as such, making these position specific guidelines was the goal of the PhD. Since the lymphatics are in the submillimetre size range and they are soft tissues, they cannot directly be visualised on the CT scans used for treatment planning. Instead, the current delineation guidelines contain reference structures like muscles and blood vessels, that are visible on patient CT scans. Since nobody ever completely visualised the lymphatic system in the target area, complete with spatial relations with the reference structures that are used on CT, it seemed very interesting to try and provide a map of the lymphatic system and base the new delineation guidelines for the prone crawl position on the actual location of these lymphatics. Therefore, the PhD was divided into 2 parts. The first part focused on finding a methodology to visualise the lymphatics on CT images by injecting radiographic contrast agents. The second part of the PhD focused on setting up the actual delineation guidelines and developing a methodology specifically for this purpose. The experiments performed during the PhD yielded 3 papers for the first part and another 3 papers for the second part. Position specific delineations were developed and they are currently being used at the radiotherapy department. Apart from this, the methodologies that were developed during this PhD will also be useful for future guideline development studies and future lymphatic mapping efforts. This thesis may to date even be the only document that thoroughly discusses the possibility of retrograde lymphatic injection

Call for a multidisciplinary effort to map the lymphatic system with advanced medical imaging techniques : a review of the literature and suggestions for future anatomical research

This review intends to rekindle efforts to map the lymphatic system by using a more modern approach, based on medical imaging. The structure, function and pathologies associated with the lymphatic system are first discussed to highlight the need for more accurately mapping the lymphatic system. Next, the need for an interdisciplinary approach, with a central role for the anatomist, to come up with better maps of the lymphatic system is emphasized. The current approaches on lymphatic system research involving medical imaging will be discussed and suggestions will be made for an all-encompassing effort to thoroughly map the entire lymphatic system. A first-hand account of our integration as anatomists in the radiotherapy department is given as an example of interdisciplinary collaboration. From this account it will become clear that the interdisciplinary collaboration of anatomists in the clinical disciplines involved in lymphatic system research/treatment still holds great promise in terms of improving clinical regimens that are currently being employed. As such, we hope that our fellow anatomists will join us in an interdisciplinary effort to map the lymphatic system, because this could, in a relatively short timeframe, provide improved treatment options for patients with cancer or lymphatic pathologies all over the world

The use of Thiel embalmed human cadavers for retrograde injection and visualization of the lymphatic system

In order to provide an alternative for fresh frozen specimens to map the lymphatic system, the possibility of using Thiel embalmed specimens for this purpose was explored. The thoracic duct was used to investigate if retrograde injection of contrast agent was possible in Thiel embalmed specimens and to verify up to which diameter lymphatic vessels could be reconstructed and rendered in 3D, after CT scanning. 3D renderings were used for digital diameter measurement, to determine the smallest lymphatic diameter that could still be visualized on CT. Finally, the contrast agent concentration was adapted based on the findings during image reconstruction and 3D rendering. All Thiel embalmed specimens proved suitable for retrograde injection of contrast agent into the thoracic duct and all 3D renderings perfectly overlapped with the dissection pictures. The smallest diameter of contrast filled lymphatics that could be reconstructed and rendered in 3D was 0.23 mm. Increasing the concentration of barium sulphate from 10% to 50% reduced the post-processing time needed to render a ‘clean’ 3D structure, following automatic segmentation based on grey values, by 95%. The authors would recommend the use of Thiel embalmed specimens for mapping the lymphatic system, as these specimens do not show the rapid putrefaction that occurs in fresh frozen specimens, thus greatly facilitating experimental planning

The use of Thiel embalmed human cadavers for retrograde injection and visualization of the lymphatic system

In order to provide an alternative for fresh frozen specimens to map the lymphatic system, the possibility of using Thiel embalmed specimens for this purpose was explored. The thoracic duct was used to investigate if retrograde injection of contrast agent was possible in Thiel embalmed specimens and to verify up to which diameter lymphatic vessels could be reconstructed and rendered in 3D, after CT scanning. 3D renderings were used for digital diameter measurement, to determine the smallest lymphatic diameter that could still be visualized on CT. Finally, the contrast agent concentration was adapted based on the findings during image reconstruction and 3D rendering. All Thiel embalmed specimens proved suitable for retrograde injection of contrast agent into the thoracic duct and all 3D renderings perfectly overlapped with the dissection pictures. The smallest diameter of contrast filled lymphatics that could be reconstructed and rendered in 3D was 0.23 mm. Increasing the concentration of barium sulphate from 10% to 50% reduced the post-processing time needed to render a ‘clean’ 3D structure, following automatic segmentation based on grey values, by 95%. The authors would recommend the use of Thiel embalmed specimens for mapping the lymphatic system, as these specimens do not show the rapid putrefaction that occurs in fresh frozen specimens, thus greatly facilitating experimental planning

The Lymphatic System in Breast Cancer: Anatomical and Molecular Approaches

Breast cancer is one of the most important causes of premature mortality among women and it is one of the most frequently diagnosed tumours worldwide. For this reason, routine screening for prevention and early diagnosis is important for the quality of life of patients. Breast cancer cells can enter blood and lymphatic capillaries, then metastasizing to the regional lymph nodes in the axilla and to both visceral and non-visceral sites. Rather than at the primary site, they seem to enter the systemic circulation mainly through the sentinel lymph node and the biopsy of this indicator can influence the axillary dissection during the surgical approach to the pathology. Furthermore, secondary lymphoedema is another important issue for women following breast cancer surgical treatment or radiotherapy. Considering these fundamental aspects, the present article aims to describe new methodological approaches to assess the anatomy of the lymphatic network in the axillary region, as well as the molecular and physiological control of lymphatic vessel function, in order to understand how the lymphatic system contributes to breast cancer disease. Due to their clinical implications, the understanding of the molecular mechanisms governing lymph node metastasis in breast cancer are also examined. Beyond the investigation of breast lymphatic networks and lymphatic molecular mechanisms, the discovery of new effective anti-lymphangiogenic drugs for future clinical settings appears essential to support any future development in the treatment of breast cance

Biomechanical comparison of Thiel embalmed and fresh frozen nerve tissue

The aim of this study was to determine the effect of Thiel embalming on the biomechanical properties of nerve tissue, to validate the use of Thiel embalmed bodies as a reliable model system for obtaining biomechanical data to supplement neurodynamic models, for anesthesiological and neurosurgical training and for future preclinical test set-ups involving nerve tissue. Upon the arrival of a body at the anatomy department, a fresh median nerve was harvested, the harvest site was sutured and following the Thiel embalming procedure the Thiel embalmed median nerve of the opposing wrist was harvested. Micro CT was performed to establish the cross-sectional area and biomechanical tensile testing was performed to compare the Young's modulus/elasticity of fresh frozen and Thiel embalmed nerves. Thiel embalming did not cause a significant difference in elasticity when comparing Thiel embalmed and fresh frozen specimens. A correlation was found between the cross-sectional area of Thiel embalmed nerve specimens and their Young's modulus. Thiel embalming does not significantly alter the elasticity of nerve tissue compared to fresh frozen nerve tissue. Similar shapes were observed when comparing the stress/strain curves of both specimen types. This indicates that Thiel embalmed nerve tissue is a viable alternative for using fresh frozen specimens when investigating biomechanical principles/mechanisms. Some specimens showed a reversed trend in Young's modulus that could be related to slight differences in embalming outcome, so caution is advised when Thiel embalmed specimens are used to obtain raw numerical data for direct application in the clinic