Outcomes of Pituitary Radiation for Cushing's Disease.

Achievement of biochemical remission with preservation of normal pituitary function is the goal of treatment for Cushing's disease. For patients with persistent or recurrent Cushing's disease after transsphenoidal resection, radiation therapy may be a safe and effective treatment. Stereotactic radiosurgery is favored over conventional fractionated external beam radiation. Hormonal recurrence rates range from 0% to 36% at 8 years after treatment. Tumor control rates are high. New pituitary hormone deficiency is the most common adverse effect after stereotactic radiosurgery and external beam radiation. The effects of radiation planning optimization and use of adjuvant medication on endocrine remission rates warrant investigation.

[Radiotherapy and radiosurgery in treatment of craniopharyngiomas]. / Luchevaia terapiia i radiokhirurgiia v lechenii kraniofaringiom.

Craniopharyngiomas are benign epithelial tumors having a dysembryogenetic origin, which are usually located in the sellar/parasellar and/or third ventricle regions. Gross total resection is the modern standard of treatment for these tumors because of a low recurrence rate. However, this surgery in some patients with craniopharyngioma often leads to the development or worsening of diencephalic disorders poorly responding to treatment. Perhaps, in these cases, subtotal or partial tumor resection or implantation of an Ommaya reservoir into the tumor cyst followed by stereotactic radiotherapy/radiosurgery may provide better functional outcomes and higher life quality in patients, with tumor growth control being reasonable (according to the published data, the mean 10-year disease-free survival is 66.9% after total tumor resection and 79.6% after combined treatment). The paper presents a review of the literature on radiological treatment of craniopharyngiomas. We discuss the issues of indications, optimal timing of radiotherapy/radiosurgery, its efficacy, and treatment outcomes in terms of complications and quality of life. Particular attention is paid to enlargement of craniopharyngioma cysts during and after radiological treatment.

Efficacy and complications of pituitary irradiation.

Radiation therapy is widely used in the management of intracranial (including sellar and parasellar) and systemic disorders. Although in many cases the irradiation aims to prevent the growth or regrowth and to control the hormonal hypersecretion of a pituitary tumor, in many others it adversely affects the hypothalamo-pituitary function simply because this area receives significant doses of radiation delivered for non-hypothalamo-pituitary disorders. The main long-term complications include hypopituitarism, optic neuropathy, cerebrovascular morbidity, and second brain tumors. Radiation technique and schedule are important determinants of these adverse effects.

Treatment paradigms for pituitary adenomas: defining the roles of radiosurgery and radiation therapy.

Pituitary adenomas represent one of the most common types of intracranial tumors. While their macroscopic appearance and anatomical location are relatively homogeneous, pituitary tumors have the potential to generate a wide variety of clinical sequelae. Treatment options for pituitary tumors include medical therapy, microscopic or endoscopic surgical resection, radiosurgery, radiation therapy, or observation depending on the biochemical profile and clinical status of the patient. Radiosurgery and external beam radiation therapy (EBRT) are most commonly as adjunctive treatments following incomplete surgical resection leaving residual tumor, tumor recurrence, or failure of medical therapy. We present a comprehensive literature review of the radiosurgery series for pituitary tumors including nonfunctioning adenomas, ACTH- and GH-secreting adenomas, and prolactinomas. While postradiosurgery radiographic tumor control for nonfunctioning adenomas is excellent, typically around 90 %, the rates of biochemical remission for functioning adenomas are lower than the tumor control rates. The highest endocrine remission rates are achieved patients with Cushing's disease and the lowest in those with prolactinomas. Although EBRT has been largely supplanted by radiosurgery for the vast majority of pituitary adenomas cases, there remains a role for EBRT in select cases involving large tumor volumes in close proximity to critical neural structures. By far the most common complication after radiosurgery or EBRT is delayed hypopituitarism followed by cranial neuropathies. The effect of suppressive medications on radiosurgery outcomes remains controversial. Due to the rare but well-documented occurrence of late recurrence following endocrine remission, long-term and rigorous clinical and radiographic follow-up is necessary for all pituitary adenoma patients treated with radiosurgery or EBRT.

Radiation therapy for pediatric craniopharyngioma.

OBJECT: The treatment of craniopharyngioma is highly controversial. Continued advances in limited surgery and radiation therapy have maintained excellent local disease control while minimizing treatment-related sequelae. Further analyses of outcomes are necessary to characterize the long-term effects of radiation therapy. METHODS: An extensive literature review was performed for all studies including radiation therapy, with or without surgery, for pediatric craniopharyngioma. RESULTS: The authors identified 32 papers describing radiation therapy for treatment of pediatric craniopharyngioma, with disease control ranging from 44 to 100%. Modern studies report at least 90% disease control with 5-year follow-up. Fifteen studies reported outcomes, demonstrating that more than two-thirds of patients treated with surgery and radiation therapy have favorable outcomes, and this rate is more than 85% in the modern era. CONCLUSIONS: Conservative surgery and radiation therapy results in long-term disease control in pediatric patients with craniopharyngioma that is comparable to results obtained with radical surgery alone. However, children with craniopharyngioma remain vulnerable to late treatment failures and side effects from radiation therapy, including endocrinopathies, vasculopathies, and secondary tumors, which may be detrimental to the quality of life. Long-term follow-up beyond 5-10 years is necessary to assess tumor control relative to functional outcomes.

[Treatment of Cushing's disease. Transsphenoidal surgery and pituitary radiotherapy]. / Tratamiento de la enfermedad de Cushing. Cirugía transesfenoidal y radioterapia hipofisaria.

Transsphenoidal surgery is currently considered the treatment of choice for Cushing's disease. Initial remission is achieved in approximately 70-85%, but 10-15% of patients with remission will suffer a recurrence months or years later. Pituitary irradiation has been used as a therapeutic tool for many years. Nowadays, this option is considered a second-line treatment, to be used when there is postsurgical persistence or recurrence of the disease. The present article reviews the surgical approaches, remission rates reported by different groups, prognostic factors, and the most frequent complications after transsphenoidal surgery. We also review the different techniques that can be used for pituitary irradiation, as well as the efficacy and morbidity reported for each of these techniques in patients with Cushing's disease.

Intracavitary therapeutic options in the management of cystic craniopharyngioma.

BACKGROUND: Craniopharyngioma remains an entity of controversial management due to its critical anatomical relationships and its well-known recurrence tendency. Total resection, although desirable, is not always accomplished, and it is associated with potentially permanent endocrinological and visual deficits. Consequently, this situation has led to the development of new management strategies seeking lesser morbidity. Because a high percentage of these lesions are cystic, bleomycin and radioactive-emitting sources have been postulated as new therapeutic options with promising results. DISCUSSION: The information known to date regarding these substances is summarized and we perform a retrospective review of the clinical trials conducted over the past 30 years with special emphasis on outcome, morbidity, and mortality. Two cases from our institution are presented as examples of multimodality management. CONCLUSION: Overall, these newer options stand out as valid alternatives in the controversial management of these challenging tumors.

Craniopharyngiomas in children: Turkey experience.

OBJECTIVES: Craniopharyngiomas are the most frequently encountered suprasellar tumors in children. Although they have a benign histology, total resection without morbidity is very difficult. METHODS: We aimed to review the results of pediatric craniopharyngioma patients treated in eight institutions in Turkey. There were 51 boys and 36 girls, ranging in age from 20 months to 18 years (mean 10.2 years). The most frequent symptom was headache, followed by visual disturbances. Hydrocephalus was seen most frequently in tumors greater than 4 cm in size (P=0.002). Hydrocephalus was associated with the decreased gross total resection (P=0.043). The recurrence (28%) was significantly higher in patients with subtotal and partial tumor removal (P=0.010). Bad outcome was significantly associated with tumor dimension (P=0.039); the greater the tumor dimension, the worse the outcome. Outcome was significantly better in patients older than 10 years (P=0.032). Gender, tumor type and location, presence of hydrocephalus and calcification, histological type of craniopharyngioma, and surgical approach did not have a significant effect on the outcome. CONCLUSIONS: The treatment should be individualized and a multidisciplinary approach should be used. The goal of surgery should be gross total removal without mortality and with acceptable morbidity.

Craniopharyngioma: a personal (Boston) experience.

BACKGROUND: The author reports his experience with 79 craniopharyngiomas operated since 1988. The review demonstrates that the biological behavior of these tumors is extremely variable, and that surgical management requires resourcefulness, judgement, and flexibility in the operating room. RESULTS: Tumors will recur after total resection (15% in this series) and after subtotal resection and radiation therapy (22%) and adjuvant treatments of all types, and no treatment guarantees a cure. CONCLUSION: The invasiveness of the tumor leads to difficult-to-treat long-term complications, particularly obesity and behavior disturbances. An extremely long-term follow-up of up to 20 years is necessary in many patients in order to determine the ultimate outcome of treatment.

[Pituitary radiotherapy. Current data and future prospects]. / Radiothérapie hypophysaire. Données actuelles et perspectives d'avenir.

Some technical improvements have allowed to minimize the frequency of severe complications following fractionated pituitary conventional radiotherapy, without altering its efficiency. "Conformational" radiotherapy is currently under development, aiming at the best fitting of the tumor borders to the irradiation zone, by the means of stereotactic imaging. More recently, radiosurgery has been proposed for pituitary adenomas. It consists in a single high radiation dose to the tumor, by the means of either cobalt minibeams (Gamma Unit) or photon beams from a linear particle accelerator. These techniques require the use of a stereotactic frame and precise 3D imaging in order to tightly superimpose the target volume to the reference isodose. They must not be viewed as an alternative to conventional radiotherapy. They can be applied only to small lesions (less than 20 mm in their maximal axis) which are distant (> 5 mm) from the optic chiasma and nerves. Their efficiency is similar to the one of fractionated conventional radiotherapy, with a shorter response time. In conclusion, radiotherapy can be used safely for pituitary adenomas. It remains however a second line treatment, when surgery has been incomplete and when a simple, effective and inexpensive medical treatment is not possible.

Acromegalia, fisiopatología y clínica / Acromegaly, physiopathology and clinics

La acromegalia es comúnmente un cuadro de curso lento y progresivo que afecta los órganos y tejidos, determinando gran morbilidad y aumento de la mortalidad. Existen en la actualidad tratamientos quirúrgicos y radioterápicos satisfactorios y perspectivas en el futuro próximo de tratamientos médicos adecuados mediante agonistas de la somatostatina de acción prolongada. Los pacientes deben ser referidos para tratamiento en los centros especializados, aún cuando presenten un cuadro clínico aparentemente benigno

Craniopharyngioma: results of survey of the American Society of Pediatric Neurosurgery.

The best management of craniopharyngioma in children remains a controversial subject for pediatric neurosurgeons. The results of a survey completed by 11 pediatric neurosurgeons documenting outcome in 139 children is presented. There were 21 children treated with limited surgery and irradiation with a good outcome in 83%. One hundred twelve underwent an attempt at gross total resection, 30 of whom required irradiation. There was a marked difference in good outcome according to experience of surgeon, 87 vs. 52% in the radical surgery group.

Stereotactic options in the management of craniopharyngioma.

Multimodality stereotactic techniques were used in the management of 39 patients with craniopharyngiomas in a 12-year interval. Monocystic craniopharyngiomas were treated successfully by intracavitary beta-irradiation using 32P (96% cyst control rate). Solid tumor progression or secondary cyst formation required repeat irradiation, radiosurgery or microsurgery in selected patients. In the future, wider and earlier application of stereotactic techniques may further reduce the still unacceptable morbidity currently associated with initial radical microsurgical resection of craniopharyngiomas.

Long-term follow-up of low-dose external pituitary irradiation for Cushing's disease.

Twenty-four patients (three male) with Cushing's disease, aged between 11 and 67 years, were treated with low-dose external pituitary irradiation (20 Gy in eight fractions over 10-12 days) and followed for between 13 and 171 months (median 93 months). Eleven patients (46%) went into remission 4-36 months after irradiation, but five subsequently relapsed. Two of these received no further active treatment, one underwent successful pituitary surgery, one underwent a second course of low-dose external irradiation (as yet unsuccessful) and one has been treated with metyrapone for a total of 75 months. One of the 13 patients who did not respond received a further course of low-dose pituitary irradiation with prompt remission and two have received metyrapone for 41 months and 15 years without ill effect. One patient died from cerebrovascular disease. The remaining nine patients underwent bilateral adrenalectomy (one after unsuccessful pituitary surgery) with rapid resolution of hypercortisolism. Five of these patients have developed hyperpigmentation and elevated ACTH levels (range 505-1150 ng/l). A pituitary microadenoma has been demonstrated on CT scan in three and successfully removed by microadenomectomy. In the present series, the low incidence of radiation-induced hypopituitarism and absence of other complications attributable to radiotherapy suggest that low-dose pituitary irradiation may be a useful treatment option in selected patients. However, long-term follow-up has demonstrated a high relapse rate and failure to prevent Nelson's syndrome in adrenalectomized patients, indicating that it should not be used as primary treatment in preference to selective adenomectomy.

Low-dose pituitary irradiation for acromegaly.

External radiotherapy has been used as primary treatment for acromegaly in 29 patients and in combination with surgery in 41 patients in whom growth hormone levels remained elevated postoperatively. Fourteen further patients who did not receive radiotherapy have also been studied, four of whom had undergone surgical treatment. Radiotherapy schedules consisted of 20 Gy in eight fractions over 11 days (n = 23) or 35-40 Gy in 15 fractions over 21 days (n = 47). Growth hormone hypersecretion was either unchanged or increased with time in non-irradiated patients. In those patients who underwent radiotherapy, the likelihood of the mean GH level during GTT falling to less than 5 mU/l was unaffected by the total dose of radiation administered. However, patients with a pre-radiotherapy GH level of less than 30 mU/l showed a significantly increased probability of achieving a post- radiotherapy GH level less than 5 mU/l (P = 0.002). Previous surgery, initial serum prolactin and the age or sex of the patient did not predict the successful outcome of radiotherapy. In view of the known dose dependency of radiation-induced hypopituitarism, lower radiation dose schedules (20 Gy; eight fractions in 11 days) can be used in acromegaly with some benefit, especially in younger patients. However, all patients should undergo operative removal of as much GH-secreting tissue as possible, in order to lower GH levels and increase the probability of achieving a cure following radiotherapy.

[The results of hypophyseal irradiation with a proton beam in acromegaly patients]. / Rezul'taty oblucheniia gipofiza protonnym puchkom u bol'nykh agromegaliei.

The investigation of 26 acromegalic patients long after irradiation of the pituitary body with a proton beam showed clinical and hormonal improvement in 38% of the patients, clinical improvement without complete growth hormone normalization in 46%, and the absence of any effect in 15%. The latter was mainly a result of partial irradiation of pituitary adenoma. Some patients after proton irradiation demonstrated signs of adenohypophyseal functional insufficiency, more marked in patients with a decreased level of Gy (over 5 ng/ml). A conclusion is that proton beam therapy is effective (provided all criteria for patients' eligibility are observed) and can be used as an independent method for the treatment of acromegalic patients.