Dose to neuroanatomical structures surrounding pituitary adenomas and the effect of stereotactic radiosurgery on neuroendocrine function: an international multicenter study.

OBJECTIVE: Stereotactic radiosurgery (SRS) provides a safe and effective therapeutic modality for patients with pituitary adenomas. The mechanism of delayed endocrine deficits based on targeted radiation to the hypothalamic-pituitary axis remains unclear. Radiation to normal neuroendocrine structures likely plays a role in delayed hypopituitarism after SRS. In this multicenter study by the International Radiosurgery Research Foundation (IRRF), the authors aimed to evaluate radiation tolerance of structures surrounding pituitary adenomas and identify predictors of delayed hypopituitarism after SRS for these tumors. METHODS: This is a retrospective review of patients with pituitary adenomas who underwent single-fraction SRS from 1997 to 2019 at 16 institutions within the IRRF. Dosimetric point measurements of 14 predefined neuroanatomical structures along the hypothalamus, pituitary stalk, and normal pituitary gland were made. Statistical analyses were performed to determine the impact of doses to critical structures on clinical, radiographic, and endocrine outcomes. RESULTS: The study cohort comprised 521 pituitary adenomas treated with SRS. Tumor control was achieved in 93.9% of patients over a median follow-up period of 60.1 months, and 22.5% of patients developed new loss of pituitary function with a median treatment volume of 3.2 cm3. Median maximal radiosurgical doses to the hypothalamus, pituitary stalk, and normal pituitary gland were 1.4, 7.2, and 11.3 Gy, respectively. Nonfunctioning adenoma status, younger age, higher margin dose, and higher doses to the pituitary stalk and normal pituitary gland were independent predictors of new or worsening hypopituitarism. Neither the dose to the hypothalamus nor the ratio between doses to the pituitary stalk and gland were significant predictors. The threshold of the median dose to the pituitary stalk for new endocrinopathy was 10.7 Gy in a single fraction (OR 1.77, 95% CI 1.17-2.68, p = 0.006). CONCLUSIONS: SRS for the treatment of pituitary adenomas affords a high tumor control rate with an acceptable risk of new or worsening endocrinopathy. This evaluation of point dosimetry to adjacent neuroanatomical structures revealed that doses to the pituitary stalk, with a threshold of 10.7 Gy, and doses to the normal gland significantly increased the risk of post-SRS hypopituitarism. In patients with preserved pre-SRS neuroendocrine function, limiting the dose to the pituitary stalk and gland while still delivering an optimal dose to the tumor appears prudent.

Invariance property of wave scattering through disordered media.

A fundamental insight in the theory of diffusive random walks is that the mean length of trajectories traversing a finite open system is independent of the details of the diffusion process. Instead, the mean trajectory length depends only on the system's boundary geometry and is thus unaffected by the value of the mean free path. Here we show that this result is rooted on a much deeper level than that of a random walk, which allows us to extend the reach of this universal invariance property beyond the diffusion approximation. Specifically, we demonstrate that an equivalent invariance relation also holds for the scattering of waves in resonant structures as well as in ballistic, chaotic or in Anderson localized systems. Our work unifies a number of specific observations made in quite diverse fields of science ranging from the movement of ants to nuclear scattering theory. Potential experimental realizations using light fields in disordered media are discussed.

Practical aspects of using the microbatch method in screening conditions for protein crystallization.

The microbatch technique is a simple and efficient method for screening for protein crystallization conditions both by hand and using automated systems. Many of the problems associated with more commonly used methods such as vapour diffusion can be overcome using this method. Despite its promise microbatch has not been widely utilized as a viable screening procedure. This review aims to describe the method from a practical point of view with an emphasis on screening crystallization conditions, outlining current progress and discussion of the advantages compared to other methods.

Using natural seeding material to generate nucleation in protein crystallization experiments.

The nucleation event in protein crystallization is a part of the process that is poorly controlled. It is generally accepted that the protein should be in the metastable phase for crystal growth, but for nucleation higher levels of saturation are needed. Formation of nuclei in bulk solvent requires interaction of protein molecules until a critical size of aggregate is created. In many crystallization experiments sufficiently high levels of saturation are not reached to allow this critical nucleation event to occur. If an environment can be created that favours a higher local concentration of macromolecules, the energy barrier for nucleation may be lowered. When seeds are introduced at lower levels of saturation in a crystallization experiment, nucleation may be facilitated and crystal growth initiated. In this study, the use of natural materials as stable seeds for nucleation has been investigated. The method makes it possible to introduce seeds into crystallization trials at any stage of the experiment using both microbatch and vapour-diffusion methods.

The advantages of using a modified microbatch method for rapid screening of protein crystallization conditions.

In this study, characterization and optimization of a modified microbatch crystallization technique has been attempted in order to provide a rapid screening method. Using this method for screening has certain advantages over standard vapour-diffusion methods: no sealing of drops is required, no reservoir solutions are needed and the experiments can easily be performed over a range of temperatures.