Treating patients with real-time tumor tracking using the Vero gimbaled linac system: Implementation and first review

Purpose

To report on the first clinical application of a real-time tumor tracking (RTTT) solution based on the Vero SBRT gimbaled linac system for treatment of moving tumors.

Methods and materials

A first group of 10 SBRT patients diagnosed with NSCLC or oligometastatic disease in lung or liver was treated with the RTTT technique. The PTV volumes and OAR exposure were benchmarked against the widely used ITV approach. Based on data acquired during execution of RTTT treatments, a first review was performed of the process.

Results

The 35% PTV volume reduction with RTTT of the studied single lesions SBRT irradiations of small target volumes is expected to result in a small (<1%) reduction of lung or liver NTCP. A GTV–PTV margin of 5.0 mm was applied for treatment planning of RTTT. From patient data on residual geometric uncertainties, a CTV–PTV margin of 3.2 mm was calculated. Reduction of the GTV–PTV margin below 5.0 mm without better understanding of biological definition of tumor boundaries was discouraged. Total treatment times were reduced to 34.4 min on average.

Conclusion

A considerable PTV volume reduction was achieved applying RTTT and time efficiency for respiratory correlated SBRT was reestablished with Vero RTTT.     

Hybrid peptide dendrimers for imaging of chemokine receptor 4 (CXCR4) expression

The chemokine receptor 4 (CXCR4), which is overexpressed in many types of cancer, is an emerging target in the field of molecular imaging and therapeutics. The CXCR4 binding of several peptides, including the cyclic Ac-TZ14011, has already been validated. In this study mono-, di- and tetrameric Ac-TZ14011-containing dendrimers were prepared and functionalized with a multimodal (hybrid) label, consisting of a Cy5.5-like fluorophore and a DTPA chelate. Confocal microscopy revealed that all three dendrimers were membrane bound at 4 °C, consistent with CXCR4 binding in vitro. The unlabeled dimer and tetramer had a somewhat lower affinity for CXCR4 than the unlabeled monomer. However, when labeled with the multimodal label the CXCR4 affinity of the dimer and tetramer was considerably higher compared to that of the labeled monomer. On top of that, biodistribution studies revealed that the additional peptides in the dimer and tetramer reduced nonspecific muscle uptake. Thus, multimerization of the cyclic Ac-TZ14011 peptide reduces the negative influence of the multimodal label on the receptor affinity and the biodistribution.     

Percutaneous closure of a coronary artery fistula in a 70-year-old woman

This case report is about a 70-year-old woman who was diagnosed with a symptomatic coronary fistula from the circumflex artery to the vena cava superior. Because of the steal effect on a dobutamine stress test, the fistula was closed percutaneously.     

Physical fitness profile of elite athletes with intellectual disability

The aim of this study was to investigate the physical fitness profile of high-performance athletes with intellectual disability (ID) in comparison with able-bodied individuals. METHODS: Participants were 231 male and 82 female athletes. All evaluations were done using the EUROFIT physical fitness test. RESULTS: In comparison with population data, both male and female athletes with ID score better for flexibility and upper body muscle endurance, but have similar or lower values for running speed, speed of limb movement, and strength measures. Compared with age-matched physical education students, male athletes with ID score better for running speed and flexibility, and worse for strength. Female athletes with ID score not different from able-bodied individuals for flexibility, running speed, and upper body muscle endurance, but worse for strength measures. Athletes with ID also have poorer cardio respiratory endurance capacity compared with sportive peers without ID. Furthermore, male athletes have a more differentiated profile depending upon their sports discipline, compared with female athletes. CONCLUSION: It can be concluded that high-performance athletes with ID reach physical fitness levels that are equal to or lower than those of able-bodied sportive counterparts. Further research should investigate the importance of reduced muscle strength to be the limiting factor.     

Integration of immunological aspects in the European Human Embryonic Stem Cell Registry

The immunological properties of stem cells are of increasing importance in regenerative medicine. Immunomodulatory mechanisms seem to play an important role not only with respect to the understanding of underlying mechanisms of autologous versus allogenic therapeutic approaches, but also for endogeneous tissue regeneration. The newly established European human embryonic stem cell registry (hESCreg) offers an international database for the registration, documentation and characterisation of human embryonic stem cells (hESC) and their use. By doing so, hESCreg aims to develop a model procedure for further standardisation efforts in the field of stem cell research and regenerative medicine, and eventually the registry may lead to a repository of therapy-related information. Currently the stem cell characterisation data acquired by the registry are divided into several categories such as cell derivation, culture conditions, genetic constitution, stem cell marker expression and degree of modification. This article describes immunological aspects of stem cell characterisation and explores the layout and relevance of a possible additional section to the hESCreg repository to include immunological characteristics of human embryonic stem cells.     

Mutations in GDAP1: autosomal recessive CMT with demyelination and axonopathy

BACKGROUND: Mutations in the ganglioside-induced differentiation-associated protein 1 gene (GDAP1) were recently shown to be responsible for autosomal recessive (AR) demyelinating Charcot-Marie-Tooth disease (CMT) type 4A (CMT4A) as well as AR axonal CMT with vocal cord paralysis. METHODS: The coding region of GDAP1 was screened for the presence of mutations in seven families with AR CMT in which the patients were homozygous for markers of the CMT4A locus at chromosome 8q21.1. RESULTS: A nonsense mutation was detected in exon 5 (c.581C>G, S194X), a 1-bp deletion in exon 6 (c.786delG, G262fsX284), and a missense mutation in exon 6 (c.844C>T, R282C). CONCLUSIONS: Mutations in GDAP1 are a frequent cause of AR CMT. They result in an early-onset, severe clinical phenotype. The range of nerve conduction velocities (NCV) is variable. Some patients have normal or near normal NCV, suggesting an axonal neuropathy, whereas others have severely slowed NCV compatible with demyelination. The peripheral nerve biopsy findings are equally variable and show features of demyelination and axonal degeneration.     

Lymphatic malformations of the head and neck: a retrospective review and a support for staging

BACKGROUND: Lymphatic malformations (LM) are rare benign congenital tumors appearing mainly in the head and neck with a considerably variable outcome. A need exists to validate a staging system, taking into account the prognosis of the malformation, including preoperative and postoperative complications, long-term sequelae, and persistence of the disease to improve parental counseling and evaluate the outcome of a surgical treatment of such tumors. METHODS: Twenty-two patients treated for LM were selected from a series of 129 patients operated on for congenital malformations of the head and neck between 1986 and 1997 at St-Luc University Hospital, Brussels, Belgium. Their charts were reviewed retrospectively, with a special focus on the anatomic location of the lesions and all the complications reported. According to de Serres et al, LM up to now have been divided into six possible categories according to their unilateral or bilateral infrahyoid and/or suprahyoid locations. RESULTS: Stage I (unilateral infrahyoid): nine patients, 11% of complications (without mediastinal extension: 0%, with mediastinal extension: 50%); stage II (unilateral suprahyoid): three patients, 33% of complications; stage III (unilateral suprahyoid and infrahyoid): eight patients, 75% of complications; stage V (bilateral suprahyoid and infrahyoid): two patients, 100% of complications. None of the children was initially seen with stage IV (bilateral suprahyoid) or stage VI (bilateral infrahyoid) LM. Overall complications, preoperative complications, postoperative com- plications, and long-term morbidity showed a significant in- crease from stage I to V (p <.01, p =.002, p =.02, and p =.03, respectively). CONCLUSIONS: A staging system of cervicofacial LM based on the anatomic location can be reliably used for prognostic purposes, allowing a more accurate assessment of the global risk of complications and determination of surgical outcome. Mediastinal extension in stage I patients seems to be associated with a higher rate of complications. Such information can be used to inform parents more appropriately regarding the management and long-term prognosis of their children's malformation.