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

Neurosurgery ◽

10.1093/neuros/nyaa138 ◽

2020 ◽

Vol 87 (3) ◽

pp. E303-E304

Author(s):

Ted K Yanagihara ◽

Tony J C Wang

Keyword(s):

Cohort Study ◽

Growth Factor ◽

Effective Dose ◽

Stereotactic Radiosurgery ◽

Biologically Effective Dose ◽

Insulin Like Growth Factor ◽

Factor Index ◽

The Impact

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

Neurosurgery ◽

10.1093/neuros/nyaa123 ◽

2020 ◽

Vol 87 (3) ◽

pp. E301-E302 ◽

Cited By ~ 1

Author(s):

Jean Régis ◽

Constantin Tuleasca ◽

John W Hopewell ◽

Frederic Castinetti

Keyword(s):

Cohort Study ◽

Growth Factor ◽

Effective Dose ◽

Stereotactic Radiosurgery ◽

Biologically Effective Dose ◽

Insulin Like Growth Factor ◽

Factor Index ◽

The Impact

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

Neurosurgery ◽

10.1093/neuros/nyaa054_s009 ◽

2021 ◽

Vol 89 (Supplement_2) ◽

pp. S9-S9

Author(s):

Christopher S Graffeo ◽

Diane Donegan ◽

Dana Erickson ◽

Paul D Brown ◽

Avital Perry ◽

...

Keyword(s):

Cohort Study ◽

Growth Factor ◽

Effective Dose ◽

Stereotactic Radiosurgery ◽

Biologically Effective Dose ◽

Insulin Like Growth Factor ◽

Factor Index ◽

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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Association between the Use of Backpack and Static Foot Posture in Schoolchildren with Static Pronated Foot Posture: A 36-Month Cohort Study

Children ◽

10.3390/children8090800 ◽

2021 ◽

Vol 8 (9) ◽

pp. 800

Author(s):

Pilar Alfageme-García ◽

Julián Fernando Calderón-García ◽

Alfonso Martínez-Nova ◽

Sonia Hidalgo-Ruiz ◽

Belinda Basilio-Fernández ◽

...

Keyword(s):

Body Mass Index ◽

Multivariate Analysis ◽

Cohort Study ◽

Prospective Study ◽

Odds Ratio ◽

Univariate Analysis ◽

Foot Posture ◽

The Mean ◽

The Impact

Background: Schoolchildren often spend a lot of time carrying a backpack with school equipment, which can be very heavy. The impact a backpack may have on the pronated feet of schoolchildren is unknown. Aims: The objective of this study was to evaluate the association of the backpack use on static foot posture in schoolchildren with a pronated foot posture over 36 months of follow-up. Methods: This observational longitudinal prospective study was based on a cohort of consecutive healthy schoolchildren with pronated feet from fifteen different schools in Plasencia (Spain). The following parameters were collected and measured in all children included in the study: sex, age, height, weight, body mass index, metatarsal formula, foot shape, type of shoes, and type of schoolbag (non-backpack and backpack). Static foot posture was determined by the mean of the foot posture index (FPI). The FPI was assessed again after 36 months. Results: A total of 112 participants used a backpack when going to school. Over the 36-month follow-up period, 76 schoolchildren who had a static pronated foot posture evolve a neutral foot posture. Univariate analysis showed that the schoolchildren using backpacks were at a greater risk of not developing neutral foot (odds ratio [OR]: 2.09; 95% CI: 1.08–4.09). The multivariate analysis provided similar results, where the schoolchildren using a backpack (adjusted OR [aOR]: 1.94; 95% CI: 1.02–3.82) had a significantly greater risk of not developing a neutral foot posture. Conclusions: A weak relationship was found between backpack use and schoolchildren aged from five to eleven years with static pronated feet not developing a neutral foot posture over a follow-up period of 36 months.

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Octreotide May Act as A Radioprotective Agent in Acromegaly

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.85.3.6464 ◽

2000 ◽

Vol 85 (3) ◽

pp. 1287-1289 ◽

Cited By ~ 78

Author(s):

Alex M. Landolt ◽

Dieter Haller ◽

Nicoletta Lomax ◽

Stefan Scheib ◽

Othmar Schubiger ◽

...

Keyword(s):

Growth Hormone ◽

Growth Factor ◽

Stereotactic Radiosurgery ◽

Radiation Treatment ◽

Insulin Like Growth Factor ◽

Factor I ◽

Follow Up Study ◽

Number Of Patients ◽

Growth Factor I

Abstract Clinical experience shows that an increasing number of patients undergoing radiation treatment for recurring acromegaly or acromegaly persisting after surgery are treated with octreotide. We, therefore, performed a follow-up study of patients undergoing stereotactic radiosurgery (Gamma Knife) to determine whether this medication has an influence on the ultimate result of radiation therapy in either a positive or negative sense. It has been suggested that the combination of radiation with antisecretory drugs may increase the effectiveness of radiation. A follow-up study of 31 patients suffering from recurrent acromegaly and acromegaly persisting after surgery, and who had been treated with stereotactic radiosurgery, showed that patients treated with octreotide at the time of radiation application simultaneously reached a normal level of growth hormone and insulin-like growth factor-I only after a significantly longer interval than patients who did not receive the drug. The two groups of patients did not demonstrate significant differences in the main clinical findings (age, sex, target volume, radiation dose, baseline growth hormone, and baseline insulin-like growth factor-I).

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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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Circulating IGFBP-2 levels are inversely associated with the incidence of nonalcoholic fatty liver disease: A cohort study

Journal of International Medical Research ◽

10.1177/0300060520935219 ◽

2020 ◽

Vol 48 (8) ◽

pp. 030006052093521

Author(s):

Ji Yang ◽

Wenjing Zhou ◽

Yue Wu ◽

Liqian Xu ◽

Yuming Wang ◽

...

Keyword(s):

Cohort Study ◽

Liver Disease ◽

Growth Factor ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Insulin Like Growth Factor ◽

Nonalcoholic Fatty Liver

Objective The insulin-like growth factor (IGF) axis is essential for the body’s metabolism. The hepatokine, insulin-like growth factor-binding protein 2 (IGFBP-2), acts as a major regulator of this metabolism. We aimed to evaluate the role of serum IGFBP-2 in the incidence of nonalcoholic fatty liver disease (NAFLD). Methods This hospital-based prospective cohort study recruited residents from a health program from January to November 2013, and re-invited them for follow-up in 2016. The occurrence of NAFLD was noted and IGFBP-2 levels were evaluated by enzyme-linked immunosorbent assay at both visits. Results Of 763 participants at baseline, 296 completed the re-evaluation. Baseline serum IGFBP-2 levels were significantly lower in subjects with NAFLD compared with those without NAFLD. Circulating IGFBP-2 levels were negatively correlated with body mass index, waist-to-hip ratio, alanine transaminase, triglycerides, fasting glucose, and insulin. IGFBP-2 levels at follow-up decreased in subjects who developed NAFLD compared with those who did not. Higher circulating levels of IGFBP-2 at baseline were negatively associated with the incidence of NAFLD. Conclusion These results indicate that IGFBP-2 levels are inversely associated with the risk of NAFLD. This offers new insights into the role of circulating IGFBP-2, as an IGF-axis hepatokine, in the pathogenesis of hepatic steatosis.

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