Stereotactic Radiosurgery For Acromegaly Research Articles

The Impact of Insulin-Like Growth Factor Index and Biologically Effective Dose on Outcomes After Stereotactic Radiosurgery for Acromegaly: Cohort Study

The Impact of Insulin-Like Growth Factor Index and Biologically Effective Dose on Outcomes After Stereotactic Radiosurgery for Acromegaly: Cohort Study

The Impact of Insulin-Like Growth Factor Index and Biologically Effective Dose on Outcomes After Stereotactic Radiosurgery for Acromegaly: Cohort Study.

Stereotactic radiosurgery (SRS) is a safe and effective treatment for acromegaly. To improve understanding of clinical and dosimetric factors predicting biochemical remission. A single-institution cohort study of nonsyndromic, radiation-naïve patients with growth hormone-producing pituitary adenomas (GHA) having single-fraction SRS between 1990 and 2017. Exclusions were treatment with pituitary suppressive medications at the time of SRS, or <24 mo of follow-up. The primary outcome was biochemical remission-defined as normalization of insulin-like growth factor-1 index (IGF-1i) off suppression. Biochemical remission was assessed using Cox proportional hazards. Prior studies reporting IGF-1i were assessed via systematic literature review and meta-analysis using random-effect modeling. A total of 102 patients met study criteria. Of these, 46 patients (45%) were female. The median age was 49 yr (interquartile range [IQR]=37-59), and the median follow-up was 63 mo (IQR=29-100). The median pre-SRS IGF-1i was 1.66 (IQR=1.37-3.22). The median margin dose was 25 Gy (IQR=21-25); the median estimated biologically effective dose (BED) was 169.49 Gy (IQR=124.95-196.00). Biochemical remission was achieved in 58 patients (57%), whereas 22 patients (22%) had medication-controlled disease. Pre-SRS IGF-1i≥2.25 was the strongest predictor of treatment failure, with an unadjusted hazard ratio (HR) of 0.51 (95% CI=0.26-0.91, P=.02). Number of isocenters, margin dose, and BED predicted remission on univariate analysis, but after adjusting for sex and baseline IGF-1i, only BED remained significant-and was independently associated with outcome in continuous (HR=1.01, 95% CI=1.00-1.01, P=.02) and binary models (HR=2.27, 95% CI=1.39-5.22, P=.002). A total of 24 patients (29%) developed new post-SRS hypopituitarism. Pooled HR for biochemical remission given subthreshold IGF-1i was 2.25 (95% CI=1.33-3.16, P<.0001). IGF-1i is a reliable predictor of biochemical remission after SRS. BED appears to predict biochemical outcome more reliably than radiation dose, but confirmatory study is needed.

Commentary: The Impact of Insulin-Like Growth Factor Index and Biologically Effective Dose on Outcomes After Stereotactic Radiosurgery for Acromegaly: Cohort Study.

Correspondence: Tony J. C. Wang, MD,622 W 168th St.,CHONY Basement North,New York, NY 10032 Email: [email protected]

Commentary: The Impact of Insulin-Like Growth Factor Index and Biologically Effective Dose on Outcomes After Stereotactic Radiosurgery for Acromegaly: Cohort Study

Régis, Jean MD; Tuleasca, Constantin MD, PhD,; Hopewell, John W DSc, MRCR; Castinetti, Frederic MD, PhD Author Information

Stereotactic radiosurgery for acromegaly: an international systematic review and meta-analysis of clinical outcomes.

We performed a systematic review and meta-analysis of clinical outcomes for patients with acromegaly treated with stereotactic radiosurgery (SRS). Primary outcomes were 5- and 10-year endocrine remission (ER) and endocrine control (EC). Secondary outcomes were 10-year radiographic local control (LC), visual toxicity, and hypopituitarism rates. Weighted random effects meta-analyses using the DerSimonian and Laird methods were conducted to characterize and compare effect sizes. Mixed effects regression models were used to examine correlations between potential prognostic factors and primary and secondary outcomes. In total, 1533 patients across 20 published studies with acromegaly treated with SRS were included. At 5-years, estimated ER and EC rates were 43.2% (95% CI 31.7-54.6%) and 55.0% (95% CI 27.6-82.4%), respectively. At 10-years, estimated ER and EC rates were 56.9% (95% CI 47.5-66.4%) and 69.7% (95% CI 47.7-91.8%), respectively. The estimated 10-year LC rate was 92.8% (95% CI 83.0-100%). Visual toxicity and hypopituitarism following SRS were estimated to be 2.7% (95% CI 1.3-4.2%) and 26.8% (95% CI 16.9-36.7%), respectively. Every 1 Gy increase in margin prescription dose beyond 17 Gy was estimated to result in a 0.41% increased risk of visual toxicity (p = 0.03). No prognostic factors were associated with EC, ER, LC, or hypopituitarism. SRS was well-tolerated in the management of pituitary acromegaly resulting in gradually improving ER and EC rates over time that approached 60% and 70%. SRS-related visual loss is an uncommon treatment-related side effect, and patient-specific clinical decision making remains critical.

The Impact of Insulin-like Growth Factor Index and Biological Effective Dose on Outcomes After Stereotactic Radiosurgery for Acromegaly

Abstract INTRODUCTION Stereotactic radiosurgery (SRS) is a safe and effective adjuvant treatment for acromegaly. Clinical and dosimetric factors predicting biochemical remission are incompletely understood. METHODS A single-institution cohort study of non-syndromic, radiation-naïve patients with growth hormone producing pituitary adenomas (GHA) having single-fraction SRS between 1990 and 2017. Patients were excluded if they were receiving pituitary suppressive medications at the time of SRS or if they had &lt; 24 mo of follow-up. The primary outcome was biochemical remission defined as normalization of insulin-like growth factor-1 index (IGF-1i) off suppressive medications. Biochemical remission was assessed using Cox proportional hazards. RESULTS A total of 102 patients met study criteria. Forty-six (45%) were female, median age was 49 yr (IQR = 37–59), median follow-up was 63 mo (IQR = 29–100). Median pre-SRS IGF-1i was 1.66 (IQR = 1.37–3.22). Median margin dose was 25 Gy (IQR = 21–25); median estimated biological effective dose (BED) was 169.49 Gy (IQR = 124.95–196.00). Biochemical remission was achieved in 58 (57%) patients, whereas 22 patients (22%) had medication-controlled disease. IGF-1i was the strongest independent predictor of remission, with an unadjusted hazard ratio (HR) of 0.53 (95% CI = 0.36–0.75, P &lt; .0001). Number of isocenters, margin dose, and BED predicted remission on univariate analysis, but after adjusting for sex and baseline IGF-1i, only BED remained independently associated with outcome in both continuous (HR = 1.01, 95% CI = 1.00–1.01, P = .02) and binary models (HR = 2.27, 95% CI = 1.39–5.22, P = .002). Twenty-four (29%) developed new post-SRS hypopituitarism. CONCLUSION IGF-1i is a better predictor of biochemical remission after SRS than IGF-1 level. BED appears to predict biochemical outcome more reliably than radiation dose, but confirmatory study is needed.

Erratum to: Stereotactic Radiosurgery for Acromegaly: An International Multicenter Retrospective Cohort Study

Erratum to: Stereotactic Radiosurgery for Acromegaly: An International Multicenter Retrospective Cohort Study

Long-term safety of gamma knife radiosurgery (STRS) for acromegaly

Purpose Acromegaly has high morbidity and mortality when growth hormone secretion remains uncontrolled. Stereotactic radiosurgery (SRS) may be used when pituitary surgery is not suitable or unsuccessful, but there are few very long-term safety data available, especially for significant adverse events such as stroke. Methods 118 patients with acromegaly were treated with SRS between 1985 and 2015, at the National Centre for Stereotactic Radiosurgery, Sheffield, UK. Data were gathered from case notes, hospital databases, and patient questionnaires. Stroke incidence in comparison to the normal population was quantified using the standardised incidence ratio (SIR), and visual complications assessed. Results 88% (104/118) had complete morbidity follow up data for analysis. The mean follow-up was 134 months, and median SRS dose was 30 Gy. 81% of tumours had cavernous sinus invasion. There was no excess stroke rate relative to that seen in two age- and sex-matched large population studies (SIR = 1.36, 95% CI 0.27–3.96; SIR = 0.52, 95% CI 0.06–1.89). In 68/104 patients who had MRI-guided SRS with no further radiation treatment (SRS or fractionated radiotherapy) there was no loss of visual acuity and 3% developed ophthalmoplegia. There was a positive correlation between > 1 radiation treatment and both ophthalmoplegia and worsening visual acuity. Conclusion Stroke rate is not increased by SRS for acromegaly. Accurate MRI-based treatment planning and single SRS treatment allow the lowest complication rates. More than one radiation treatment (SRS or fractionated radiotherapy) was associated with increased visual complications.

Stereotactic Radiosurgery for Acromegaly

The role of stereotactic radiosurgery (SRS) in acromegaly is being assessed. We evaluated the efficacy and safety of SRS for patients with acromegaly. Prognostic factors related to outcomes were also analyzed. This was a retrospective study of patients treated with SRS at the University of Virginia; the data were collected from 1989 to 2012, with a median follow-up of 61.5 months. A total of 136 patients underwent SRS for acromegaly. Diagnosis of acromegaly was based on the combination of clinical features and biochemical assessment, including the serum GH level and age- and gender-matched serum IGF-1 level. All patients underwent a complete endocrine evaluation, neuroimaging study, and ophthalmic examinations before SRS. After withdrawal of GH- or IGF-1-altering medications, patients who had an oral glucose tolerance test GH of < 1.0 ng/mL or normal IGF-1 were considered in remission. Post-radiosurgical hypopituitarism was defined as a decrease in one or more hormones below normal. With a median follow-up of 61.5 months, 65.4% of the patients achieved remission. The mean time to remission was 27.5 months. The actuarial remission rates at 2, 4, 6, and 8 years after radiosurgery were 31.7, 64.5, 73.4, and 82.6%, respectively. Favorable prognostic factors for remission included a higher margin radiation dose, higher maximum dose, and lower initial IGF-1 level. New pituitary hormone deficiency occurred in 43 patients (31.6%); two patients (1.5%) developed panhypopituitarism. Corresponding risk factors for new pituitary hormone deficiency were a margin dose > 25 Gy and tumor volume > 2.5 mL. Other complications included an adverse radiation effect in one patient, visual deterioration in four, and new oculomotor nerve palsy in one. SRS affords a reasonable rate of endocrine remission in patients with acromegaly and generally does so with a low rate of adverse effects.

Long-Term Results of Stereotactic Radiosurgery in Secretory Pituitary Adenomas

To date, no study reported long-term follow-up results of gamma knife stereotactic radiosurgery (SR). The aim of the study was to determine long-term efficacy and adverse effects of SR in secreting pituitary adenomas. We conducted a retrospective study of patients treated by SR in the center of Marseille, France, with a follow-up of at least 60 months. A total of 76 patients were treated by SR for acromegaly (n = 43), Cushing's disease (CD; n = 18), or prolactinoma (n = 15) as a primary (n = 27) or adjunctive postsurgical treatment (n = 49). After withdrawal of antisecretory drugs, patients were considered in remission if they had mean GH levels below 2 ng/ml and normal IGF-I (acromegaly), normal 24-h urinary free cortisol, and cortisol less than 50 nmol/liter after low-dose dexamethasone test (CD) or two consecutive normal samplings of prolactin levels (prolactinoma). After a mean follow-up of 96 months, 44.7% of the patients were in remission. Mean time to remission was 42.6 months. Twelve patients presented late remission at least 48 months after SR. Two patients with CD presented late recurrence 72 and 96 months after SR. Forty percent of patients treated primarily with SR were in remission. Target volume and initial hormone levels were significant predictive factors of remission in univariate analysis. Radiation-induced hypopituitarism was observed in 23% patients; in half of them, hypopituitarism was observed after a mean time of 48 to 96 months. Twenty-four patients were followed for more than 120 months; rates of remission and hypopituitarism were similar to the whole cohort. SR is an effective and safe primary or adjunctive treatment in selected patients with secreting pituitary adenomas.