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Key hypotheses and derived sub-projects

Sellar expansions

•    According to autopsies, adenomas in the sellar region are found in 10-25% of the population. According to random findings at computed tomography and magnetic resonance, sellar expansions in vivo are found in 10-20% of the examined persons (incidentalomas). In the vast majority of cases, these are tiny adenomas which do not manifest clinically and need not to be treated. At the present time, we have no information on how many tumours in the sellar region are so significant that they require treatment. Based on the interpolation of data from abroad, the prevalence could be approximately 1000 patients per 1 million persons.
•    It is reported that adenomas represent over 90% of sellar expansions.
•    33% of adenomas are reported to be prolactinomas, 35% are non-functional (nonsecretory) adenomas, 20% are growth hormone-secreting adenomas, and the remainder are adenomas of other types.
•    Other most frequent expansive processes include craniopharyngiomas and meningiomas, primary empty sella syndrome, lymphocytic hypophysitis, metastases (bronchogenic carcinoma, Grawitz tumor and others), germinal tumours, chordoma, optic nerve glioma, carotid artery aneurysm, Rathke's cleft cyst and other cysts, histiocytosis X, sarcoidosis, lymphoma, pituitary apoplexy and pituitary carcinoma (extremely rare).

Acromegaly is a rare disorder in which the anterior pituitary produces too much growth hormone. This causes an increased growth in bone and soft tissue.

Source: Free Health Encyclopedia.

Acromegaly: role of the Gamma Knife in the treatment scheme of acromegaly.

Acromegaly is treated by neurosurgical therapy, medical therapy or radiation therapy. Radiation surgery is a modern method of radiation therapy: the Gamma Knife is used in the Czech Republic, the linear accelerator is used in Slovakia. The international medical community has not yet established the role of radiation surgery in the acromegaly treatment.
Objective: Comparison of treatment results between the group of patients irradiated by the Gamma Knife during the complex treatment, and the group of patient who have undergone a complex treatment without being irradiated by the Gamma Knife.
Hypothesis: The Gamma-Knife irradiation of patients who have undergone a successful neurosurgical therapy – or Gamma-Knife irradiation as the primary therapy – limits or even eliminates the necessity of a lifelong medical treatment.
Endpoint: Normalization of disease activity by laboratory measurements, adenoma size determined by magnetic resonance, and the assessment of adverse effects and therapy security. A design study will be optimized for this target parameter; the data must be collected retrospectively, too, as the monitored effect is a long-term one.
Results: The results will be used to integrate the treatment by Gamma Knife into the optimal treatment scheme of acromegaly.

Acromegaly: possibility to make acromegaly diagnostics faster and better

Acromegaly is often diagnosed too late: 5-10 years usually pass between the first symptoms and the clinical recognition and treatment, depending on the patient's age. At this stage, the organism is often irreversibly affected and the treatment results of neurosurgery are significantly worse.
Objective: To identify possibilities how to ensure a more early diagnostics and treatment.
Hypothesis: Early symptoms of acromegaly do not bring the patients into endocrinology centres but to general practitioners and many other specialists, who are not used to diagnose the acromegaly. If these physicians were acquainted with the acromegaly symptomatology within their field, the patients with acromegaly could be redirected promptly into specialized centres, dealing with acromegaly treatment.
Endpoint: Data collection (1) on specializations of physicians who had examined the patients in the period between the first symptoms and the final diagnose, and (2) on symptoms and problems for which these patients were examined.
Results: The results will be used to inform relevant specialists – both by publications and by lectures.

Acromegaly: results of neurosurgical therapy

There are still missing data about (1) how many percent of acromegaly patients in different stages of disease have been cured by a neurosurgical intervention alone, (2) what is the incidence of surgical therapy complications, and (3) whether there are differences between the centres.
Objective: To find out how frequently and under what conditions the normalization of acromegaly process by a mere surgical intervention can be taken into account. To assess the complications of surgical therapy at the same time.
Hypothesis: Only a portion of acromegaly patients has been cured by neurosurgical intervention, depending on adenoma size and location. The results are different, depending on (1) experiences of the centre, (2) surgery approach, (3) the surgeon's intention: to remove the whole adenoma with the risk of complications, or to avoid possible complications, aiming to supplement the neurosurgical intervention with a treatment of different type.
Endpoint: Disease activity measured by laboratory methods, size of adenoma and its residue determined by magnetic resonance, data collection and verification of neurosurgical therapy complications.
Results: The results will provide information to neurosurgeons and help endocrinologists to choose optimal centres.

Prolactinomas: Conditions to suspend a long-term pharmacotherapy

Medical therapy by dopamine agonists represents the basic treatment of prolactin-secreting pituitary adenomas. This is always a long-time, sometimes even lifelong treatment. No criteria have yet been established to define the circumstances under which it is possible to try to suspend the dopamine-agonists therapy, and what impact this would have on the patient's condition.
Objective: To determine circumstances when it is appropriate to try to suspend the therapy without the risk of tumour growth relapse.
Hypothesis: The therapy by dopamine agonists can be suspended in prolactinomas, depending on the duration of prolactin level normalization during the treatment, and on the stage of pituitary adenoma regression.
Endpoint: Duration of of prolactin level normalization and magnetic resonance images of pituitary adenoma in relation to adenoma relapse after therapy suspension, determined by (a) increase of prolactin level, (b) tumour growth relapse on the magnetic resonance image. Data must be collected retrospectively, too, as the monitored effect is a long-term one.
Results: The results will provide an overview when it is possible to try to suspend the prolactinoma therapy.

Prolactinomas: Role of the Gamma Knife in the treatment scheme of prolactinomas

Medical therapy by dopamine agonists represents the usual treatment of prolactinomas. Approximately 5% of patients with microprolactinomas and 30% of patients with macroprolactinomas are partially resistant to treatment by dopamine agonists, i.e. they do not show a full normalization of the prolactin level or macroadenoma regression. Moreover, some patients are intolerant to medical therapy in higher doses, which needs to be used in early stages of the treatment.
Target: To determine the effect of Gamma Knife on the normalization of the prolactin level and on the size of macroprolactinomas, particularly in patients resistant or intolerant to dopamine agonists.
Hypothesis: The irradiation of pituitary adenomas by Gamma Knife can break the resistance to medical therapy and to reduce its need. The decrease of daily doses can improve the tolerance to pharmacotherapy. Moreover, the irradiation by Gamma Knife will accelerate and increase the number of patients in which it will be possible to eliminate the therapy by dopamine agonists.
Endpoint: Monitoring the prolactin level, determining prolactinoma size using the magnetic resonance, possibility to suspend the therapy and the incidence of adverse effects after the irradiation by Gamma Knife. Data must be collected retrospectively, too, as the monitored effect is a long-term one.
Results: The results will be used to integrate the treatment by Gamma Knife into the treatment scheme of prolactinomas.

Non-functional adenomas: frequency of monitoring by magnetic resonance

In the group of patients with non-treated and treated non-functional adenomas (treated by neurosurgery, irradiation), it is not clear how often the examination by magnetic resonance should be repeated.
Objective: To determine the optimal interval between magnetic resonance examinations of the pituitary gland in order to prevent a clinically significant growth or postsurgical relapse of adenoma, in relation to adenoma size and therapy mode.
Hypothesis: Only a portion of adenomas (about 7% of microadenomas, approximately 30% macroadenomas) progresses spontaneously. Similarly, only a portion of preserved residues relapses. These progressions and relapses can be clinically significant, and it is essential to diagnose them in their asymptomatic stages, i.e. before the oculomotor nerve compression or visual pathway compression.
Endpoint: Monitoring the magnetic resonance imaging of pituitary gland in different time intervals and determining the incidence of relapses in relation to the preceding treatment, to adenoma size and location.
Results: The results will be used to develop guidelines on the frequency of magnetic resonance examinations.

Non-functional adenomas: effect of radiosurgical therapy

Guidelines need to be developed for non-functional adenomas when a radiation surgery therapy can be indicated (Gamma Knife, linear accelerator) and when a neurosurgical intervention is more appropriate. Circumstances need to be found when radiosurgery is suitable after an operation during which a residue has been preserved.
Objective: To determine the potential of radiation surgery in the treatment of non-functional adenomas.
Hypothesis: In some newly-diagnosed adenomas, it is more convenient to irradiate the adenoma by radiation surgery methods rather than indicate a surgical therapy. Moreover, only a portion of preserved residui is indicated for a post-surgery radiation.
Endpoint: Monitoring the behaviour of adenomas and their residues by magnetic resonance examination of pituitary gland – in relation to their location and size. Monitoring will be done in the group of patients irradiated by Gamma Knife or linear accelerator, and compared to the group of patients which have not been irradiated.
Results: The results will be used to integrate the radiation surgery therapy into the treatment scheme of non-functional adenomas.

Cushing's disease of central aetiology: Results of neurosurgical therapy

There are still missing data about (1) how many percent of Cushing's disease patients in different stages of disease have been cured by a neurosurgical intervention alone, (2) what is the incidence of surgical therapy complications, and (3) whether there are differences between the centres.
Objective: To find out how frequently and under what conditions the normalization of Cushing's disease by a mere surgical intervention can be taken into account. To assess the complications of surgical therapy at the same time.
Hypothesis: Only a portion of Cushing's disease patients has been cured by neurosurgical intervention, depending on adenoma size and location. The results are different, depending on (1) experiences of the centre, (2) surgery approach, (3) the surgeon's intention: to remove the whole adenoma with the risk of complications, or to avoid possible complications, aiming to supplement the neurosurgical intervention with a treatment of different type.
Endpoint: Disease activity measured by laboratory methods, size of adenoma and its residue determined by magnetic resonance, data collection and verification of neurosurgical therapy complications.
Results: The results will provide information to neurosurgeons and help endocrinologists to choose optimal centres.

Cushing's disease of central aetiology: Role of the Gamma Knife in the treatment scheme

Cushing's disease is treated by neurosurgical therapy, medical therapy or radiation therapy. Radiation surgery is a modern method of radiation therapy: the Gamma Knife is used in the Czech Republic, the linear accelerator is used in Slovakia. The international medical community has not yet established the role of radiation surgery in the Cushing's disease treatment.
Objective: Comparison of treatment results between the group of patients irradiated by the Gamma Knife during the complex treatment, and the group of patient who have undergone a complex treatment without being irradiated by the Gamma Knife.
Hypothesis: The Gamma-Knife irradiation of patients who have undergone a successful neurosurgical therapy – or Gamma-Knife irradiation as the primary therapy – limits or even eliminates the necessity of a lifelong medical treatment.
Endpoint: Normalization of disease activity by laboratory measurements, adenoma size determined by magnetic resonance, and the assessment of adverse effects and therapy security. A design study will be optimized for this target parameter; the data must be collected retrospectively, too, as the monitored effect is a long-term one.
Results: The results will be used to integrate the treatment by Gamma Knife into the optimal treatment scheme of Cushing's disease.