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

Abstract BACKGROUND Stereotactic radiosurgery (SRS) is a safe and effective treatment for acromegaly. OBJECTIVE To improve understanding of clinical and dosimetric factors predicting biochemical remission. METHODS 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. RESULTS 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). CONCLUSION 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.

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

Neurosurgery ◽

10.1093/neuros/nyz310_319 ◽

2019 ◽

Vol 66 (Supplement_1) ◽

Author(s):

Christopher S Graffeo ◽

Diane Donegan ◽

Dana Erickson ◽

Paul D Brown ◽

Avital Perry ◽

...

Keyword(s):

Growth Factor ◽

Effective Dose ◽

Stereotactic Radiosurgery ◽

Univariate Analysis ◽

Cox Proportional Hazards ◽

Insulin Like Growth Factor ◽

Biological Effective Dose ◽

Biochemical Remission ◽

The Impact

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 < 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 < .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.

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The Impact of Cobalt-60 Source Age on Biologically Effective Dose in Stereotactic Radiosurgery Thalamotomy

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2016.06.2038 ◽

2016 ◽

Vol 96 (2) ◽

pp. E563

Author(s):

B.H. Kann ◽

J.B. Yu ◽

J. Bond ◽

C. Loiselle ◽

V.L. Chiang ◽

...

Keyword(s):

Effective Dose ◽

Stereotactic Radiosurgery ◽

Biologically Effective Dose ◽

The Impact

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Biologically effective dose correlates with linear tumor volume changes after upfront single-fraction stereotactic radiosurgery for vestibular schwannomas

Neurosurgical Review ◽

10.1007/s10143-021-01538-w ◽

2021 ◽

Author(s):

Constantin Tuleasca ◽

Mohamed Faouzi ◽

Philippe Maeder ◽

Raphael Maire ◽

Jonathan Knisely ◽

...

Keyword(s):

Standard Deviation ◽

Effective Dose ◽

Stereotactic Radiosurgery ◽

Tumor Volume ◽

Vestibular Schwannomas ◽

Benign Tumors ◽

Biologically Effective Dose ◽

Volume Changes ◽

Single Fraction

AbstractVestibular schwannomas (VSs) are benign, slow-growing tumors. Management options include observation, surgery, and radiation. In this retrospective trial, we aimed at evaluating whether biologically effective dose (BED) plays a role in tumor volume changes after single-fraction first intention stereotactic radiosurgery (SRS) for VS. We compiled a single-institution experience (n = 159, Lausanne University Hospital, Switzerland). The indication for SRS was decided after multidisciplinary discussion. Only cases with minimum 3 years follow-up were included. The Koos grading, a reliable method for tumor classification was used. Radiosurgery was performed using Gamma Knife (GK) and a uniform marginal prescription dose of 12 Gy. Mean BED was 66.3 Gy (standard deviation 3.8, range 54.1–73.9). The mean follow-up period was 5.1 years (standard deviation 1.7, range 3–9.2). The primary outcome was changes in 3D volumes after SRS as function of BED and of integral dose received by the VS. Random-effect linear regression model showed that tumor volume significantly and linearly decreased over time with higher BED (p < 0.0001). Changes in tumor volume were also significantly associated with age, sex, number of isocenters, gradient index, and Koos grade. However, the effect of BED on tumor volume change was moderated by time after SRS and Koos grade. Lower integral doses received by the VSs were inversely correlated with BED in relationship with tumor volume changes (p < 0.0001). Six (3.4%) patients needed further intervention. For patients having uniformly received the same marginal dose prescription, higher BED linearly and significantly correlated with tumor volume changes after SRS for VSs. BED could represent a potential new treatment paradigm for patients with benign tumors, such as VSs, for attaining a desired radiobiological effect. This could further increase the efficacy and decrease the toxicity of SRS not only in benign tumors but also in other SRS indications.

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Decreased Circulating Insulin-Like Growth Factor 1 Levels Are Associated with Cardiac Diastolic Dysfunction in Small for Gestational Age Infants

American Journal of Perinatology ◽

10.1055/s-0038-1642060 ◽

2018 ◽

Vol 35 (12) ◽

pp. 1178-1185

Author(s):

Shoko Yamazaki ◽

Haruka Obinata ◽

Akira Hachiya ◽

Motoko Kamiya ◽

Noriko Motoki ◽

...

Keyword(s):

Growth Factor ◽

Diastolic Dysfunction ◽

Gestational Age ◽

Small For Gestational Age ◽

Linear Regression Analysis ◽

Entire Population ◽

Doppler Imaging ◽

Multivariate Linear Regression Analysis ◽

Insulin Like Growth Factor ◽

The Impact

Objective To evaluate the impact of serum insulin-like growth factor-1 (IGF-1) levels on cardiac function in small for gestational age (SGA) infants. Study Design This is a prospective, observational study. Serum IGF-1 levels at birth and echocardiography measurements at 1 week of age were compared between SGA and appropriate for gestational age (AGA) infants. Results Thirty-one SGA infants and 27 AGA infants were enrolled. Serum IGF-1 levels were lower in the SGA infants than in the AGA infants. SGA infants had lower mitral lateral annular systolic (S') and early diastolic (E') tissue Doppler imaging velocities compared with AGA infants (S', 5.1 ± 0.9 vs 5.7 ± 1.2 cm/s; E', 6.1 ± 1.5 cm/s vs 7.1 ± 1.3 cm/s; p < 0.05). Serum IGF-1 levels positively correlated with E' velocity in the entire population (r = 0.44, p < 0.001) and in SGA infants (r = 0.39, p < 0.05). In multivariate linear regression analysis, serum IGF-1 and S' velocity were independently associated with E' velocity in the entire population and in SGA infants. Conclusion Decreased serum IGF-I levels could account for cardiac diastolic dysfunction in SGA infants.

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