Gamma-knife radiosurgery in acromegaly: the results from the Croatian acromegaly registry.

PURPOSE: The aim of our study was to evaluate the efficacy and safety of Leksell gamma-knife radiosurgery in the treatment of residual growth hormone-secreting pituitary adenomas after the surgery. MATERIALS AND METHODS: We conducted a retrospective analysis of 23 acromegaly patients treated with gamma-knife radiosurgery between 1996 and 2019. The therapeutic success of radiosurgery was defined as IGF-1 normalization without suppressive medication (complete response) or as IGF-1 normalization with medication (partial response). RESULTS: The median follow-up was 57 (10-198) months. Complete response was achieved in 11 patients (47.8%) with actuarial remission rates of 17.4%, 26.1%, 39.1% and 47.8% at 1, 2, 4, and 7 years, respectively. The median time to complete the response was 21 (6-85) months. Partial response was achieved in another nine patients (39.1%) after a median time of 48 (6-144) months from radiosurgery. Patients who achieved complete remission had significantly lower IGF-1 levels before radiosurgery (p = 0.016) as well as smaller tumour volume (p = 0.016) and radiologically less invasive tumours (p = 0.022) in comparison to patients who did not achieve IGF-1 normalization. Tumour growth control after radiosurgery was established in all patients. During the follow-up, new hormone deficiencies were found in seven patients (30.4%) which corresponds to the incidence of one new case of hypopituitarism per 7.1 patient years. CONCLUSIONS: Gamma-knife radiosurgery offers endocrine remission and tumour growth control in a substantial proportion of patients with GH-secreting adenomas. Given the high cost of life-long medical treatment and a moderate risk of radiation-induced side effects, radiosurgery for growth hormone-secreting pituitary adenomas should be considered in all patients with residual tumours.

DOES THE TYPE OF SURGERY IN BRAIN ABSCESS PATIENTS INFLUENCE THE OUTCOME? ANALYSIS BASED ON THE PROPENSITY SCORE METHOD.

There are different options for surgical treatment of brain abscess, mainly standard craniotomy and stereotactic aspiration. It has not yet been established which of these options is associated with a more favorable outcome under similar baseline conditions of patients. Demographic characteristics, microbiology, clinical presentation, and treatment outcome were analyzed for surgically treated adult patients with brain abscess over a 14-year period. A propensity score model was applied to account for baseline conditions that may determine the choice of neurosurgical method. The propensity score was included in the prediction of a favorable outcome, defined as a Glasgow Outcome Scale (GOS) score 4 or 5. We analyzed 91 adult surgically treated patients, of which 53 had standard craniotomy and 38 stereotactic aspiration of brain abscess. Focal neurological deficit was the most common symptom present in 60 (65.9%) patients on admission. Sixty-seven (73.6%) patients had GOS 4 or 5, and seven (7.7%) patients died. The choice of surgery did not influence the outcome (OR 1.181, 95% CI 0.349-3.995), neither did the time elapsed from diagnosis to surgery (OR 0.998, 95% CI 0.981-1.015). Propensity towards standard craniotomy procedure did not influence outcome in brain abscess patients (OR 1.181, 95% CI 0.349-3.995). Worse outcome (GOS below 4) was independently associated with Glasgow Coma Score (GCS) on admission (OR 0.787, CI 0.656-0.944). The choice of neurosurgical procedure did not influence the outcome in patients with brain abscess. Patients with brain abscess who had lower GCS on admission also had worse outcome.

OUT-OF-FIELD DOSES IN CHILDREN TREATED FOR LARGE ARTERIOVENOUS MALFORMATIONS USING HYPOFRACTIONATED GAMMA KNIFE RADIOSURGERY AND INTENSITY-MODULATED RADIATION THERAPY.

The purpose of this study was to measure out-of-field organ doses in two anthropomorphic child phantoms for the treatment of large brain arteriovenous malformations (AVMs) using hypofractionated gamma knife (GK) radiosurgery and to compare these with an alternative treatment using intensity-modulated radiation therapy (IMRT). Target volume was identical in size and shape in all cases. Radiophotoluminescent (RPL), thermoluminescent (TL) and optically stimulated luminescent (OSL) dosimeters were used for out-of-field dosimetry during GK treatment and a good agreement within 1-2% between results was shown. In addition, the use of multiple dosimetry systems strengthens the reliability of the findings. The number of GK isocentres was confirmed to be important for the magnitude of out-of-field doses. Measured GK doses for the same distance from the target, when expressed per target dose and isocentre, were comparable in both phantoms. GK out-of-field doses averaged for both phantoms were evaluated to be 120 mGy/Gy for eyes then sharply reduced to 20 mGy/Gy for mandible and slowly reduced up to 0.8 mGy/Gy for testes. Taking into account the fractionation regimen used to treat AVM patients, the total treatment organ doses to the out-of-field organs were calculated and compared with IMRT. The eyes were better spared with GK whilst for more distant organs doses were up to a factor of 2.8 and 4 times larger for GK compared to IMRT in 5-year and 10-year old phantoms, respectively. Presented out-of-field dose values are specific for the investigated AVM case, phantoms and treatment plans used for GK and IMRT, but provide useful information about out-of-field dose levels and emphasise their importance.

Hypopituitarism after gamma knife radiosurgery for pituitary adenoma.

PURPOSE: The aim of the study was to investigate the incidence of and risk factors for hypopituitarism after gamma knife radiosurgery (GKRS) for pituitary adenoma. MATERIALS AND METHODS: We conducted a retrospective analysis of the pituitary function of 90 patients who underwent GKRS for pituitary adenoma at the University Hospital Centre Zagreb between 2003 and 2014. Twenty seven of them met the inclusion criteria and the others were excluded from the study due to pituitary insufficiency which was present before GKRS. Eighteen patients had non-functioning and 9 patients had secretory adenomas. Median patients' age was 56 years (24-82). GKRS was performed using the Leksell gamma knife Model C. The median prescription radiation dose was 20 Gy (15-25) and the median tumor volume size was 3.4 cm3 (0.06-16.81). New onset hypopituitarism was defined as a new deficit of one of the three hormonal axes (corticotroph, thyreotroph, or gonadotroph) ≥3 months following GKRS. SPSS was used for statistical analysis, with the significance level at P<0.05. RESULTS: During the median follow-up period of 72 months (range 6-144), 30% of patients developed new hypopituitarism after GKRS. This corresponds to incidence of one new case of hypopituitarism per 15 patient-years. Age, gender, tumor function, tumor volume, suprasellar extension, prescription dose of radiation, as well as dose-volume to the pituitary gland, stalk and hypothalamus were not predictive factors for the development of hypopituitarism. CONCLUSIONS: In our cohort of patients with pituitary tumors who underwent GKRS, 30% developed new hypopituitarism during the follow-up period.

Correction of measured Gamma-Knife output factors for angular dependence of diode detectors and PinPoint ionization chamber.

Dosimetry for Gamma-Knife requires detectors with high spatial resolution and minimal angular dependence of response. Angular dependence and end effect time for p-type silicon detectors (PTW Diode P and Diode E) and PTW PinPoint ionization chamber were measured with Gamma-Knife beams. Weighted angular dependence correction factors were calculated for each detector. The Gamma-Knife output factors were corrected for angular dependence and end effect time. For Gamma-Knife beams angle range of 84°-54°. Diode P shows considerable angular dependence of 9% and 8% for the 18 mm and 14, 8, 4 mm collimator, respectively. For Diode E this dependence is about 4% for all collimators. PinPoint ionization chamber shows angular dependence of less than 3% for 18, 14 and 8 mm helmet and 10% for 4 mm collimator due to volumetric averaging effect in a small photon beam. Corrected output factors for 14 mm helmet are in very good agreement (within ±0.3%) with published data and values recommended by vendor (Elekta AB, Stockholm, Sweden). For the 8 mm collimator diodes are still in good agreement with recommended values (within ±0.6%), while PinPoint gives 3% less value. For the 4 mm helmet Diodes P and E show over-response of 2.8% and 1.8%, respectively. For PinPoint chamber output factor of 4 mm collimator is 25% lower than Elekta value which is generally not consequence of angular dependence, but of volumetric averaging effect and lack of lateral electronic equilibrium. Diodes P and E represent good choice for Gamma-Knife dosimetry.

[Croatian Society of Endocrinology guidelines for the diagnosis and treatment of acromegaly]. / Smjernice Hrvatskoga endokrinoloskog drustva za dijagnostiku i lijecenje akromegalije.

The working group of the Croatian Society of Endocrinology met in September 2011 to discuss the diagnostic and therapeutic dilemmas in patients with acromegaly. The group comprised 9 pituitary specialists including endocrinologists, neurosurgeons, and medical biochemistry specialist. After a critical analysis of published scientific papers the group has developed guidelines for the diagnosis and treatment of acromegaly.