Efficacy and tolerability of gamma knife radiosurgery in acromegaly: a 10‐year follow‐up study

Ronchi, Cristina L.; Attanasio, Roberto; Verrua, Elisa; Cozzi, Renato; Ferrante, E.; Loli, Paola; Montefusco, Laura; Motti, Enrico; Ferrari, Daniela; Giugni, Enrico; Beck‐Peccoz, Paolo; Arosio, Maura

doi:10.1111/j.1365-2265.2009.03589.x

Cited by 74 publications

(63 citation statements)

References 33 publications

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“…By combining the high radiation precision known from SRS and the radiobiological advantages of fractionated radiation, FSRT is preferred over SRS when the target is close to a critical structure as, for example, the optic pathway (13,32). Also, FSRT is performed mostly using a dental or head mask, thereby avoiding the invasive pins used during SRS (the Cyberknife is an exception) (6).…”

Section: Authorsmentioning

confidence: 99%

Fractionated stereotactic radiotherapy in patients with acromegaly: an interim single-centre audit

Roug¹,

Rasmussen²,

Juhler³

et al. 2010

European Journal of Endocrinology

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Aim: To evaluate the effect of fractionated stereotactic radiotherapy (FSRT) in acromegaly in a retrospective analysis. Patients and methods: Thirty-four patients (17 females, median 43 years (range 30-74)) with acromegaly were treated with FSRT (conformal dynamic arcing, dose 54 Gy, 27-30 fractions) between January 1998 and April 2007. Of the 34 patients, 32 had undergone transsphenoidal adenotomy, and 28 were on medical therapy before FSRT. Patients on medical therapy continued this during and after the irradiation. The treatment was gradually decreased/withdrawn after careful assessment. Results: Magnetic resonance scanning of the pituitary gland 34 months (median, range 11-95) after irradiation showed stable or reduced volume of the remaining tumour tissue in 31 of 34 patients (91%). Seventeen patients (50%) were biochemically controlled (normalised nadir GH during oral glucose tolerance test and IGF1 !C2 S.D.) 30 months after FSRT (median, range 6-60), and ten of them had true biochemical remission (off medical therapy) 30 months after FSRT (median, range 12-69). Of 28 patients with one or more functioning pituitary axes before irradiation, 8 (29%) developed further deficit of one or two pituitary axes 48 months (median, range 6-102) after FSRT. Of 34 patients, 20 still required medical treatment for acromegaly at the end of this study, mainly those with a short follow-up period after irradiation. Conclusion: The FSRT seems promising in terms of treatment of acromegaly. Longer follow-up is, however, needed to assess the overall efficacy and safety of FSRT for acromegaly.

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Section: Authorsmentioning

confidence: 99%

Fractionated stereotactic radiotherapy in patients with acromegaly: an interim single-centre audit

Roug¹,

Rasmussen²,

Juhler³

et al. 2010

European Journal of Endocrinology

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“…For example, a 2009 study of GKS by Ronchi et al 85 found a 10-year time to remission, which is significantly slower than the times to remission reported with other series (Table 2). But these results reflect the fact that Ronchi et al reported remission rates in patients who were off somatostatin analog therapy at the time of radiosurgery using a strict 3 criteria must be met definition of remission (normal oral glucose tolerance test, "safe" GH levels, and normal IGF-I level), whereas other studies with faster times to remission included patients on medical therapy at the time of treatment and used only 1 or 2 criteria for remission.…”

mentioning

confidence: 53%

“…81 Another group found that initial GH and IGF-I levels while off somatostatin analogs were significantly higher in patients who did not achieve remission than in patients with biochemical remission, 13 which suggests that, even if being off antiacromegaly medications at the time of radiosurgery does not improve the chances of remission, another benefit of being off medications at the time of GKS is that the pretreatment hormone levels provide a better understanding of the likelihood of achieving remission with radiosurgery. 85 A study of 42 patients with endocrine active adenomas identified 2 other factors predicting remission in a multivariate analysis, higher total integral dose (p = 0.005), and maximum dosage (p = 0.001). 19 The integral dose represents the total energy absorbed by the adenoma during radiosurgery in gram rad units (1 g rad unit represents 100 ergs/g), while the maximum dosage represents the highest dose any part of the adenoma receives in Gray units.…”

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confidence: 99%

“…Furthermore, rates of hypopituitarism can be underestimated in the absence of adequately sensitive assays. 85 In the future, it is hoped that conflicting results with regard to time to remission, remission rates, factors predicting remission, and factors predicting adverse effects like hypopituitarism may be addressed through large multicenter trials with central review, in which patients are ideally randomized according to variables of interest, such as those on or off acromegaly medications for specific durations of time at the time of treatment.…”

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confidence: 99%

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Radiation treatment strategies for acromegaly

Rowland

Aghi²

2010

FOC

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The high morbidity and mortality associated with acromegaly can be addressed with multiple treatment modalities, including surgery, medicines, and radiation therapy. Radiation was initially delivered through conventional fractionated radiotherapy, which targets a wide area over many treatment sessions and has been shown to induce remission in 50%–60% of patients with acromegaly. However, conventional fractionated radiotherapy takes several years to achieve remission in patients with acromegaly and carries a risk of hypopituitarism that may limit its use. Stereotactic radiosurgery, of which there are several forms, including Gamma Knife surgery, CyberKnife therapy, and proton beam therapy, offers slightly attenuated efficacy but achieves remission in less time and provides more precise targeting of the adenoma with better control of the dose of radiation received by adjacent structures such as the pituitary stalk, pituitary gland, optic chiasm, and cranial nerves in the cavernous sinus. Of the forms of stereotactic radiosurgery, Gamma Knife surgery is the most widely used and, because of its long-term follow-up in clinical studies, is the most likely to compete with medical therapy for first-line adjuvant use after resection. In this review, the authors outline the major modes of radiation therapies in clinical use today, and they critically assess the feasibility of these modalities for acromegaly treatment. Acromegaly is a multisystem disorder that demands highly specialized treatment protocols including neurosurgical and endocrinological intervention. As more efficient forms of pituitary radiation develop, acromegaly treatment options may continue to change with radiation therapies playing a more prominent role.

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“…57,59 Radiosurgery is generally considered if the tumor is a minimal distance from the optic chiasm resulting in an exposure of more than 800 cGy. 60 Periodic withdrawal of medical therapy following radiotherapy should be performed for biochemical assessment. 6 SRLs are often withheld at the time of radiation therapy because of concern that they may be radioprotective, although this finding is controversial, as it is not supported in all studies.…”

Section: Radiation Therapymentioning

confidence: 99%

Diagnosis and Management of Acromegaly in 2014 (Update from 2012)

Katznelson¹

2015

European Endocrinology

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Acromegaly is an uncommon disorder that, in the vast majority of cases, is the result of a growth hormone (GH)-secreting pituitary adenoma. Because tumors are often macroadenomas at the time of diagnosis, there may be a number of signs and symptoms related to local mass effects, including headache, visual field loss, ophthalmoplegia, and hypopituitarism. Chronic GH and insulin-like growth factor 1 (IGF-1) hypersecretion can lead to soft tissue and bone overgrowth manifestations, medical comorbidities, and accompanying clinical features. Medical comorbidites include arthropathy, cardiomegaly, type 2 diabetes, hypertension, sleep apnea syndrome, and colon polyps. In addition, acromegaly is associated with premature mortality, primarily owing to cardiovascular disease. Appropriate therapy of acromegaly can lead to improvement in these comorbidities and reversal of the premature mortality risk. This current review is an update to the 2012 summary. Diagnosis of AcromegalyThe diagnosis of acromegaly begins with a clinical suspicion by the physician that the patient has this disease. Typical physical examination findings include hand and foot enlargement or facial bone enlargement and acral/soft tissue changes. Of note, subjects usually do not present with a chief complaint related to acral growth. In women, the most common presenting complaint is amenorrhea. 2Biochemical testing involves measurement of GH and IGF-1. GH, produced by the somatotroph cells of the pituitary gland in a pulsatile fashion, circulates and stimulates hepatic secretion of IGF-1. In the recent Endocrine Society guidelines on the approach to acromegaly, it was recommended that a serum IGF-1 level be measured in subjects with acral manifestations. Owing to the lack of agreement between assays and the lack of validated normal ranges for IGF-1, 3,4 the same assay should be used in the same patient for serial measurement. 5A random GH measurement was not considered useful in diagnosis because of the lack of a well-defined normal or safe range, although a markedly elevated random GH level is certainly consistent with the disease. Additionally, in subjects with elevated or equivocal serum IGF-1 concentrations, the recent acromegaly guidelines recommended confirmation of the diagnosis with a lack of suppression of GH to less than 1 mcg/l following an oral glucose load. 6 In a patient with signs and symptoms of acromegaly and an elevated IGF-1 value, an oral glucose tolerance test (OGTT) may not be necessary for diagnosis. In the setting of a clinical suspicion but discordant values, such as an elevated IGF-1 and normal GH value (i.e., suppressible with OGTT), the subject likely has early stage acromegaly. 7After diagnosis of acromegaly, a magnetic resonance imaging (MRI) scan of the sella should be obtained to determine tumor size, location, and invasiveness. Visual field testing is performed if the tumor is touching or compressing the optic chiasm. A thorough ophthalmologic examination should be performed if the patient describes diplopia and the tumo...

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Efficacy and tolerability of gamma knife radiosurgery in acromegaly: a 10‐year follow‐up study

Abstract: Over a 10-year period after GK radiosurgery, an increasing percentage of patients achieve cure, or adequate control of the disease on pharmacological therapy, at the expense of increasing novel pituitary deficiencies.

Cited by 74 publications

References 33 publications

Fractionated stereotactic radiotherapy in patients with acromegaly: an interim single-centre audit

Fractionated stereotactic radiotherapy in patients with acromegaly: an interim single-centre audit

Radiation treatment strategies for acromegaly

Diagnosis and Management of Acromegaly in 2014 (Update from 2012)

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