Reproducibility and accuracy of microscale thermophoresis in the NanoTemper Monolith: a multi laboratory benchmark study.

Microscale thermophoresis (MST), and the closely related Temperature Related Intensity Change (TRIC), are synonyms for a recently developed measurement technique in the field of biophysics to quantify biomolecular interactions, using the (capillary-based) NanoTemper Monolith and (multiwell plate-based) Dianthus instruments. Although this technique has been extensively used within the scientific community due to its low sample consumption, ease of use, and ubiquitous applicability, MST/TRIC has not enjoyed the unambiguous acceptance from biophysicists afforded to other biophysical techniques like isothermal titration calorimetry (ITC) or surface plasmon resonance (SPR). This might be attributed to several facts, e.g., that various (not fully understood) effects are contributing to the signal, that the technique is licensed to only a single instrument developer, NanoTemper Technology, and that its reliability and reproducibility have never been tested independently and systematically. Thus, a working group of ARBRE-MOBIEU has set up a benchmark study on MST/TRIC to assess this technique as a method to characterize biomolecular interactions. Here we present the results of this study involving 32 scientific groups within Europe and two groups from the US, carrying out experiments on 40 Monolith instruments, employing a standard operation procedure and centrally prepared samples. A protein-small molecule interaction, a newly developed protein-protein interaction system and a pure dye were used as test systems. We characterized the instrument properties and evaluated instrument performance, reproducibility, the effect of different analysis tools, the influence of the experimenter during data analysis, and thus the overall reliability of this method.

Discrepancy between sonographic and radiographic values after ultrasound-monitored treatment of developmental dysplasia of the hip.

INTRODUCTION: The purpose of the study was to examine the accordance between the actually used sonographic and radiographic standard values after ultrasound-monitored treatment of developmental dysplasia of the hip (DDH). MATERIAL AND METHODS: One hundred and fifty-three (119 children) ultrasound-monitored treated hips (initial staging according to Graf: type IIc-IV) which attained normal ultrasound findings (type I according to Graf) during treatment and underwent an anteroposterior radiograph of the pelvis at the time of starting walking (mean age 18.6 months) were evaluated retrospectively. RESULTS: While all hips showed normal sonographic values (Graf type I), 26 (17%) showed mild and 17 (11.1%) severe dysplasia (by measuring the acetabular index) according to the radiographic Toennis classification system, and 29 (19%) showed mild and 48 (31.4%) severe dysplasia according to the Wiberg centre-edge angle. CONCLUSIONS: This data show that the actually used sonographic and radiographic standard values concerning DDH do not correlate appropriately. It must be put up for discussion whether the radiographic standard values might be too strict. Further criteria must be developed to better assess the prognosis of residual dysplasia.

Pituitary insufficiency as a side effect after radiosurgery for pituitary adenomas: the role of the hypothalamus.

OBJECT: Causes of pituitary insufficiencies as a side effect of Gamma Knife surgery (GKS) following irradiation of the hypothalamopituitary axis are still under debate. In an investigation of pituitary insufficiencies after GKS, the authors' main focus is on what role can be attributed to the hypothalamus with regard to endocrinological changes in hypothalamopituitary function following GKS. METHODS: A total of 108 patients consecutively treated between April 1992 and July 2003 were included in this retrospective study. All patients had undergone either transsphenoidal or transcranial surgery prior to GKS. The spot dosimetry method was used to determine doses delivered to structures of the hypothalamopituitary axis. For statistical analyses, endocrine insufficiency and deterioration in pituitary function were defined as a decrease in hormonal blood levels below the normal range for 1 or more anterior pituitary lobe hormones. Additionally, an analysis of the rate of patients requiring hormone replacement therapy after GKS due to new endocrinopathies was performed. RESULTS: Complete patient records of 61 male and 47 female patients with a mean age of 51.9 years (range 9.1­81.2 years) were available for our investigation. The overall tumor control rate was 97% and the endocrinological cure rate was 61.2%. Mean treatment doses in patients with and without new endocrine insufficiencies (shown as with/without insufficiencies and followed by probability values) were as follows: 1.3/0.8 Gy to the hypothalamus(p = 0.2); 2.2/1.6 Gy to the median eminence (p = 0.1); 6.5/4.1 Gy to the pituitary stalk (p = 0.004); and 12.4/9.5Gy to the pituitary gland (p = 0.05). The median overall duration of follow-up after GKS was 6.7 years, with 84 patients(77.7%) whose follow-up was longer than 12 months. The median follow-up time after GKS in patients who developed a new pituitary dysfunction was 79.5 months (6.6 years, SD 3.8 years), and the median follow-up time inpatients with no new insufficiencies was 78.4 months (6.5 years, SD 4 years). CONCLUSIONS: Gamma Knife surgery is a safe and effective treatment for patients with residual and recurrent pituitary adenomas. The rate of pituitary insufficiencies after GKS is still lower than that after conventional radiotherapy.Very low radiation doses are directed to the hypothalamus, and thus this structure does not play a major role in the development of pituitary insufficiencies after GKS. The results of this study show that patients in whom the pituitary stalk and pituitary gland receive a high mean point dose are more likely to develop pituitary insufficiencies after GKS than those who receive a lower dose. (DOI: 10.3171/2010.8.GKS10959).

Volumetric follow up of brain metastases: a useful method to evaluate treatment outcome and predict survival after Gamma Knife surgery?

OBJECT: Brain metastases are diagnosed in 20 to 40% of all cancer patients and are associated with a considerable drop in life expectancy and often also in quality of life for these patients. Several treatment options are available including surgery, chemotherapy, whole-brain radiotherapy, stereotactic radiotherapy, stereotactic radiosurgery, and Gamma Knife surgery (GKS). However, management of brain metastases still presents a challenge and there is no general consensus on the best treatment strategy. The aim of the authors' study was to further evaluate the efficacy of GKS in the treatment of brain metastases and to evaluate the predictive value of volumetric tumor follow-up measurement. METHODS: Consecutive patients with controlled systemic cancer and variable numbers of brain metastases were included in this prospective study. Patients with severe symptoms of brain compression underwent surgery before GKS. Each follow-up examination included a thorough neurological examination and a neuroradiological quantitative volumetric tumor analysis. A total of 300 consecutive patients (mean age 58 years) with 703 brain metastases were treated between December 1998 and October 2005. The mean total tumor volume (TTV) was 2.1 cm3. The overall local tumor control rate was 84.5%. In 79% of all treated metastases a mean TTV reduction of 84.7% was achieved using a mean prescription dose of 21.8 Gy. Only few, mostly mild, side effects were observed during the mean follow-up period of 12.7 months. The overall mean progression-free survival period was 9.4 months. There was a statistically significant difference in survival of patients with one compared with multiple metastases, regardless of the histological type and preceding treatment. CONCLUSIONS: Gamma Knife surgery is a safe and effective treatment for patients with brain metastases regardless of the history of treatment and histological tumor type. It achieves excellent tumor control, significant TTV reduction without causing severe side effects, and accordingly, preserves quality of live. Volume changes after GKS did not serve as a predictor for treatment outcome and survival.

Intracranial glomus jugulare tumors: volume reduction with Gamma Knife surgery.

OBJECT: Glomus jugulare tumors (GJTs) are slow-growing benign tumors arising from paraganglion cells of the superior vagal ganglion. Involvement of cranial nerves and extensive erosion of the jugular foramen and petrous bone are typically seen in patients with GJTs. Advances in microsurgical techniques have improved patient outcomes, but tumors involving the petrous bone remain difficult to treat effectively. The aim of our study was to further evaluate the role of Gamma Knife surgery (GKS) in the management of intracranial GJTs. METHODS: Twelve consecutive patients (mean age 51.7 years) with intracranial GJTs were included in this study. The treatment strategy was either multimodal, with microsurgical tumor volume reduction followed by GKS in patients suffering from brainstem compression, or GKS as the only treatment. Follow-up examinations included thorough neurological examinations and neuroradiological quantitative volumetric tumor analysis. Five patients (41.6%) underwent microsurgery before GKS. Tumor volumes ranging from 1.6 to 24.8 cm3 were treated using prescription doses of 14 to 20 Gy (nine-28 isocenters). The achieved overall tumor control rate after GKS was 100% (33 months mean follow up) with only mild side effects observed. A tumor volume reduction (mean 41.1%; 3.2 cm3) was achieved in all patients. CONCLUSIONS: Gamma Knife surgery is a safe and effective treatment for intracranial GJTs. The tumor volume reductions achieved are comparable to those achieved using microsurgery but with a much lower rate of side effects. More studies with longer follow-up times are necessary to confirm these very promising results.

Evaluation of a new concept for the management of skull base chordomas and chondrosarcomas.

OBJECT: Chordomas and chondrosarcomas of the skull base are rare locally invasive tumors associated with high recurrence rates. The aim of this study was to evaluate the concept of microsurgical tumor volume reduction followed by early gamma knife surgery (GKS). METHODS: Thirteen patients with 15 tumors were treated between October 2000 and June 2003. There were three patients (23.1%) with chordomas and 10 (76.9%) with chondrosarcomas. There were nine men and four women who ranged in age between 19 and 69 years. All patients first underwent maximal tumor resection. Within 2 to 10 months after surgery they were treated with GKS. The mean postoperative tumor volume treated with GKS was 9.7 cm3 (range 1.4-20.3 cm3). Follow-up computerized tomography and magnetic resonance imaging examinations with volumetric tumor analysis were performed every 6 months after GKS. The mean treatment dose was 17 Gy and the mean isodose was 52%. The mean follow-up duration was 17 months during which there was only one tumor recurrence at the margin of the radiation field. The mean volume reduction was 35.4%. CONCLUSIONS: Results of this treatment strategy are encouraging but the efficacy of this multimodal treatment combining surgery and early GKS requires a longer follow up.