Failure of radiotherapy in acromegaly (original) (raw)
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Efficacy and Safety of Radiotherapy in Acromegaly
Archives of Medical Research, 2011
Background and Aims. Transsphenoidal surgery remains the treatment of choice in acromegaly, yet 40e50% of patients require secondary forms of therapy such as radiation therapy (RT) and somatostatin analogues (SA). We undertook this study to evaluate the efficacy and safety of RT in acromegaly. Methods. Forty patients with acromegaly treated with RT (mean dose, 52 Gy) after failed pituitary surgery between 1993 and 2007 were analyzed; all were clinically and biochemically active. Patients were evaluated with yearly hormonal measurements [basal and glucose-suppressed growth hormone (GH), IGF-1, thyroid-stimulating hormone (TSH), free T4, cortisol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone or estradiol and prolactin (PRL)] and with magnetic resonance imaging every 2 years. Results. Mean age of patients was 52.9 AE 12.1 years and 85% were female. All subjects had been followed for 1 year, 75% for 3 years, 70% for 5 years and 35% for 10 years. The median basal GH level fell from a baseline of 8.8 ng/mL to 2.27 ng/mL at 5 years ( p 5 0.001) and to 1.88 ng/mL at 10 years ( p 5 0.001). A GH !1 ng/mL was achieved by 46% and 57% of the patients at 5 and 10 years of follow-up, respectively. The proportion of patients achieving a normal IGF-1 was 36% at 5 years and 43% at 10 years. Before RT, hypothyroidism, hypocortisolism and hypogonadism were present in 44%, 26% and 74% of patients, respectively. After 5 years of follow-up (n 5 28), these figures increased to 51%, 41% and 79% and over a third of the group had panhypopituitarism. One patient developed optic neuritis and another patient was diagnosed with a meningioma 10 years after RT. No cerebrovascular events or deaths occurred. Conclusions. RT is an effective, low-cost and reasonably safe means of controlling acromegalic activity, particularly useful in parts of the world where SA are not readily available. Ó 2011 IMSS. Published by Elsevier Inc.
The Birmingham pituitary database: auditing the outcome of the treatment of acromegaly
Clinical Endocrinology, 1995
BACKGROUND Reduction of GH concentrations in acromegallc subjects may improve the increased mortality assoclated wlth the condition. Audit of the biochemlcal outcome of the management of acromegaly is, therefore, important. OBJECTIVES (1) To audit the biochemical 'cure' rate of acromegalic patients treated by surgery andlor radiotherapy under the care of the South Birmingham Endocrine Clinic. (2) To assess the correlation between random or basal GH with IGF-I and nadir GH during an oral glucose tolerance test. megalic patients from a pituitary database. Mode of therapy, pretreatment GH, pretreatment tumour size, post-treatment GH, post-treatment IGF-l and post-treatment nadir GH were recorded. Biochemical cure was defined as a most recent random or basal GH < 5 mUlI. Cure rates were determined. PATIENTS Eighty-nine acromegalic patients were Identified as having received surgery andlor radiotherapy. In 35/89 (39%) the most recent GH was < 5 mull. The cure rate following surgery was 26/78 (33%). This was not significantly associated with tumour size, but was associated with pretreatment GH concentration (x2 = 7.1,2d.f., P < 0.05). Randomlbasal GH showed a log-linear association with IGF-I, r = 0.72, and a linear association with nadir GH, r = 0.93. CONCLUSIONS Biochemical cure of acromegaly was more strongly associated with pretreatment GH than with tumour size. Randomlbasal GH measurements are useful and convenient for the audit of treatment outcome DESIGN AND MEASUREMENTS Ascertainment Of aCr0-Correspondence: D r P. M. Stewart, Department of Medicine. Queen Elizabeth Hospital, Birmingham B15 2TH, UK. Fax: 0121 621 2384. in acromegaly. Ways of improving the biochemical outcome of acromegaly should be sought. 0 1995 Blackwell Science Ltd 51 7 518 D. Jenkins et al.
Acta Neurochirurgica, 2005
Background. The effect of presurgical long-acting somatostatin analogue (SSA) treatment on operative outcome in acromegaly is as yet uncertain and long-term observations are lacking. We evaluated in an acromegaly case-control study the effect of octreotide pre-treatment on short-and long-term postoperative GH concentrations, pituitary function and glucose tolerance. Methods. 48 patients with a pituitary macro-adenoma-micro-and giant adenomas excluded-were evaluated. 24 patients received presurgical octreotide treatment (secondary surgery, prospectively studied). Another 24 thoroughly matched patients had been operated on without prior octreotide therapy (primary surgery, retrospective evaluation). No patient had received any other treatment prior to operation=octreotide. Standardized testing was performed at diagnosis, following octreotide treatment, after surgery and then yearly for 10.3 AE 0.9 yrs (mean AE SE, primary surgery) and 4.1 AE 0.6 yrs (secondary surgery). Immediate and 4-year postoperative results were compared. All work-up was strictly identical in both groups, except for imaging techniques. ''Partial remission'' was defined as mean GH profile (6-h=7-point) concentration <2.5 mg=L, and ''complete remission'' as GH nadir < 1 mg=L during OGTT plus normal IGF-I concentration (when available). Findings. The median profile GH (mg=L) values and the OGTT GH nadir values post-surgery (2.4=1.0 vs 1.8=0.7, primary and secondary surgery, resp.) as well as 4 yrs later (2.1=1.15 vs 2.3=0.8) were not significantly different between the groups. The 10-year results of the primary surgery group were not significantly different from its 4-year results. Subgroup analysis of pre-treated patients revealed no significant difference between those with and without tumour shrinkage, or between those with and without parasellar tumour extension. Postoperatively pituitary function was not significantly different between the groups. After 4-years the pituitary-adrenal axis was slightly more impaired in the secondary surgery group rather than following primary surgery, while the pituitary-gonadal axis was not different. Conclusion. Presurgical octreotide treatment has no significant short-or long-term beneficial effect on GH concentration or pituitary function.
Long-term results of fractionated stereotactic radiotherapy as third-line treatment in acromegaly
Endocrine, 2015
The treatment of acromegaly is based on surgery, drugs, and radiotherapy as a third-line option. Fractionated stereotactic radiotherapy (FSRT) is a new technique with a need for long-term evaluation. The purpose of the study was to evaluate long-term results of FSRT in acromegaly. Overall, 34 patients [sex ratio 1.12, age 45 (5-65) years] with a pituitary adenoma of 24.5 (9-76) mm including 20 invasive tumors were treated by radiotherapy in fractionated stereotactic conditions delivering 50 gy in 27 sessions. Baseline growth hormone (GH) and IGF1 levels were 18 (±14.5) and 632.6 (±339) lg/L, respectively. Indications of FSRT were failure of surgery and drug treatments (n = 30) or contraindication/refusal of surgery (n = 4). Hormonal control was defined by normal age-and sex-adjusted IGF1. Remission was defined by hormonal control after withdrawal of drugs for a minimum of three consecutive months. Data were analyzed in SPSS software with a significance level at p \ 0.05. After a mean follow-up of 152 months, hormonal control was achieved in 33 patients (97 %) with withdrawal of drugs in 13 patients (38.2 %) without any recurrence. Factors found to be significantly associated to remission in a multivariate Cox regression were lower baseline hormone levels (GH and IGF1) and smaller tumor size. Tumor control was achieved in all patients. Acquired hypopituitarism after radiotherapy was the main side effect reported with a rate of 39 %. FSRT seems to be an effective and well tolerated third-line treatment of acromegaly, particularly adapted to macro adenomas treatment.
A Critical Analysis of Pituitary Tumor Shrinkage during Primary Medical Therapy in Acromegaly
The Journal of Clinical Endocrinology & Metabolism, 2005
Context: Somatostatin analogs have been successfully used to treat patients with GH-secreting pituitary adenomas because they are safe, effective, and usually well tolerated. The results of studies evaluating acromegaly treatment with the somatostatin receptor ligands (SRLs), octreotide and lanreotide, have supported the use of these agents for primary medical therapy before or as an alternative to traditional interventions of surgery and radiotherapy in selected cases. Evidence Acquisition: We therefore undertook a systematic literature overview to characterize the results of studies involving primary therapy with somatostatin analogs and their effects on pituitary tumor size. Because most studies in which pituitary tumor shrinkage has been assessed involve uncontrolled, open-label, prospective trials or retrospective case series, the lack of a control arm does not permit pooling of data in a metaanalytic fashion to determine tumor size reduction. Therefore, this systematic review ...
Outcome of Stereotactic Radiotherapy for Patients with Uncontrolled Acromegaly
The Canadian Journal of Neurological Sciences, 2009
Objective: Linear accelerator based stereotactic radiation therapy (SRT) has been used for the treatment of pituitary tumours; however, little is known concerning the use of this modality for the treatment of patients with acromegaly. We have prospectively studied the short-term outcome of SRT in 12 acromegaly patients who failed to achieve biochemical remission despite surgery and/or pharmacologic therapy. Methods: We identified all patients who had biochemically uncontrolled acromegaly and were treated with SRT between April 2003 and December 2006. All patients were followed prospectively based on a pre-defined protocol that included Goldman visual field examination, MRI of the sella, and pituitary hormone testing at 3, 6, 12 months, and then yearly. Results: A total of 12 patients with acromegaly were treated with SRT. There were 9 females and the median age of the group was 50 years. The median follow-up was 28.5 months during which time the mean tumor volume decreased by 40%, the median GH fell from 4.1 µg/L to 1.3 µg/L (p=0.003) and the median IGF-1 dropped more than half from 545.5 µg/L to 260.5 µg/L (p=0.002). Four patients achieved normal, while an additional 2 achieved near-normal, IGF-1 levels. One patient was able to discontinue and two were able to reduce their acromegaly medications while maintaining a normal IGF-1. A new pituitary hormonal deficit was found at 24 months in one patient who developed hypoadrenalism requiring corticosteroid replacement. Conclusion: Based on our early experience, we believe that SRT should be considered in treating patients with uncontrolled acromegaly. RÉSUMÉ: Réponse thérapeutique à la radiothérapie stéréotaxique chez les patients atteints d'acromégalie rebelle. Objectif : La radiothérapie stéréotaxique (RTS) par accélérateur linéaire est utilisée pour le traitement des tumeurs hypophysaires. Cependant, on connaît peu de choses sur l'utilisation de ce mode de traitement chez les patients atteints d'acromégalie. Nous avons étudié de façon prospective le résultat thérapeutique à court terme de la RTS chez 12 patients atteints d'acromégalie, chez qui la chirurgie et/ou la pharmacothérapie n'a pas provoqué de rémission biochimique. Méthodes : Nous avons identifié tous les patients dont l'acromégalie n'était pas maîtrisée au point de vue biochimique, qui ont été traités par RTS entre avril 2003 et décembre 2006. Tous les patients ont été suivis de façon prospective selon un protocole prédéterminé comportant un examen des champs visuels (Goldman), une IRM de la selle turcique et un bilan hormonal hypophysaire après 3, 6, et 12 mois, puis annuellement. Résultats : Douze patients atteints d'acromégalie, dont 9 femmes, ont été traités par RTS. L'âge médian des patients était de 50 ans et le suivi médian était de 28,5 mois. Le volume moyen de la tumeur a diminué de 40%, le taux médian de somatotrophine est passé de 4,1 μg/L à 1,3 μg/L (p = 0,003) et le taux médian d'IGF-1 a chuté de plus de la moitié, passant de 545,5 μg/L à 260,5 μg/L (p = 0,002). Le taux d'IGF-1 est redevenu normal chez quatre patients et quasi normal chez deux autres. Un patient a pu cesser de prendre ses médicaments pour traiter l'acromégalie et deux autres ont pu en réduire la posologie tout en maintenant un IGF-1 normal. Un nouveau déficit hormonal hypophysaire a été constaté chez un patient après 24 mois de suivi, soit un hypoadrénalisme nécessitant un remplacement par des corticostéroïdes. Conclusion : Suite à ces premières observations, nous croyons que la RTS devrait être envisagée chez les patients qui présentent une acromégalie rebelle.
European Journal of Endocrinology, 2006
Background: Radiotherapy for pituitary adenomas frequently leads to GH deficiency (GHD). The characteristics of GH secretion in GHD induced by postoperative radiotherapy for acromegaly are not known. Hypothesis: In the long term, stimulated and spontaneous GH release is not different between patients with GHD treated by postoperative radiotherapy for acromegaly or for other pituitary adenomas. Design/subjects: We compared the characteristics of basal and stimulated GH secretion in patients with GHD, who had previously received adjunct radiotherapy after surgery for GH-producing adenomas (nZ10) vs for other pituitary adenomas (nZ10). All patients had a maximal GH concentration by insulin tolerance test (ITT) of 3 mg/l or less, compatible with severe GHD. Mean time after radiation was 17 and 18.7 years, respectively. Stimulated GH release was also evaluated by infusion of growth hormone-releasing hormone (GHRH), GHRH-arginine and arginine, and spontaneous GH by 10 min blood sampling for 24 h. Pulse analyses were performed by Cluster and approximate entropy. Outcomes: There were no differences between both patient groups in stimulated GH concentrations in any test. Spontaneous GH secretion was not different between both patient groups, including basal GH release, pulsatility and regularity. Pulsatile secretion was lost in two acromegalic and three nonacromegalic patients. Insulin-like growth factor-I (IGF-I) was below K2 S.D. score in nine patients in each group. Conclusion: Acromegalic patients treated by surgery and postoperative radiotherapy with an impaired response to the ITT do not differ, in the long term, in GH secretory characteristics from patients treated similarly for other pituitary tumors with an impaired response to the ITT. The ITT (or the GHRHarginine test) is therefore reliable in establishing the diagnosis of GHD in patients treated for acromegaly by surgery and radiotherapy.
Radiotherapy and radiosurgery in acromegaly
Pituitary, 2008
Growth-hormone hypersecretion, acromegaly, is associated with reduced life expectancy. First line treatment remains surgery, but remission rates vary between 50% and 90%. In case of lack of surgical remission or recurrence, somatostatin agonists can be proposed. However, about 30% of patients are partially or totally resistant to this treatment. The growth hormone receptor antagonist pegvisomant currently needs more prolonged follow-up studies. Conventional radiotherapy and radiosurgery are two radiation treatment modalities that can be proposed to these resistant patients. Reported rates of remission for conventional radiotherapy range between 50% and 60% in patients with acromegaly, with a time to remission delayed by several years, and adverse effects including high rates of hypopituitarism. This treatment could be proposed to patients with aggressive adenomas, in whom surgery cannot allow biochemical control. In contrast, studies on stereotactic radiosurgery reported lower rates of remission, with faster growth hormone hypersecretion decline, and a lower risk of adverse effects. However, this latter technique requires a well defined target volume, which limits its indications. The high precision of this technique makes it possible to be used as an alternative primary treatment to surgery. We reviewed major advantages and drawbacks of each of these techniques, based on recent studies to try to define their respective indications in the therapeutic algorithm of acromegaly.