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

Neurosurgery ◽  
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.

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

Neurosurgery ◽  
2020 ◽  
Vol 87 (3) ◽  
pp. 538-546 ◽  
Author(s):  
Christopher S Graffeo ◽  
Diane Donegan ◽  
Dana Erickson ◽  
Paul D Brown ◽  
Avital Perry ◽  
...  
Keyword(s):  
Cohort Study ◽  
Growth Factor ◽  
Effective Dose ◽  
Stereotactic Radiosurgery ◽  
Univariate Analysis ◽  
Biologically Effective Dose ◽  
Insulin Like Growth Factor ◽  
Biochemical Remission ◽  
The Impact

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 &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 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 &lt; .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.

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

Neurosurgery ◽  
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

Analysis of factors influencing outcome in patients with in transit malignant melanoma (MM) undergoing isolated limb perfusion (ILP) using standardized operative parameters with melphalan and biological agents

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8006-8006
Author(s):  
P. A. Soriano ◽  
S. K. Libutti ◽  
J. F. Pingpank ◽  
T. Beresenev ◽  
S. M. Steinberg ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Cox Model ◽  
Univariate Analysis ◽  
Female Gender ◽  
Tumor Stage ◽  
Cox Proportional Hazards ◽  
Stage Iiia ◽  
In Transit ◽  
The Impact

8006 Background: In transit disease afflicts about 10% of MM patients and no single systemic or regional treatment has been widely accepted as most effective or appropriate. Previously, the impact of ILP on the natural history of MM patients has been difficult to gauge. We report long-term outcomes in MM patients undergoing hyperthermic ILP in an era of increasingly accurate staging, uniform operative and treatment conditions, and regular follow-up. Methods: Between 5/1992 to 2/2005, 90 patients (median age: 57 y [range: 24–84]; F: 49, M: 41) with Stage IIIA or IIIAB MM underwent a 90 min hyperthermic (mean calf T: 39.3° C) ILP (melphalan: 10–13 mg/L limb volume, TNF: 3–6 mg [n=44], or IFN: 200 μg [n=38]) using uniform operative technique including intra-operative leak monitoring. There was 1 operative mortality (1/91, 1.1%). Patients were prospectively followed for response, in-field progression free (PFS), and overall survival (OS). Parameters associated with in-field PFS and OS were analyzed by the Kaplan-Meier method with log rank tests, as well as by Cox proportional hazards models. Results: There were 61 complete responses (68%) and 23 partial responses (26%). At a median follow-up of 47 months, median in-field PFS was 12.4 months, and median OS was 47.4 months; 5 and 10-year actuarial OS were 43 and 34%, respectively. Female gender and low tumor burden (< 20 tumors) were associated with prolonged in-field PFS (M:F hazard ratio (HR): 2.07, CI:1.27–3.38; 21+ vs. ≤20 tumors HR: 2.29, CI: 1.21- 4.34; p<0.011 for both) in a Cox model, whereas TNF, IFN, perfusion pressure, and tumor stage were not. Female gender was associated with improved OS (p=0.027, M:F HR=1.82, 95% CI 1.07–3.09) and Stage IIIA marginally so, in univariate analysis, (p=0.065). Conclusions: ILP for MM patients is associated with noteworthy in-field PFS and prolonged OS. Neither use of TNF nor tumor stage were significantly associated with in-field PFS in Cox models, while female gender was associated with better outcomes. In appropriately selected patients using standardized technique, ILP has clinical benefit in this setting. No significant financial relationships to disclose.

scholarly journals Octreotide May Act as A Radioprotective Agent in Acromegaly

2000 ◽  
Vol 85 (3) ◽  
pp. 1287-1289 ◽  
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).

Resected pancreatic cancer (PC): Impact of adjuvant therapy (Rx) at a high-volume center (HVC) on overall survival (OS).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 191-191 ◽  
Author(s):  
Margaret T Mandelson ◽  
Vincent J. Picozzi
Keyword(s):  
Proportional Hazards ◽  
Average Distance ◽  
Univariate Analysis ◽  
High Volume ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Resection Margins ◽  
Curative Intent ◽  
The Impact

191 Background: Surgical outcomes for resected PC are known to be superior at HVCs. However, the impact of adjuvant (Rx) performed at HVCs is less studied. We examined the impact of site of adjuvant Rx administration on our resected patients (pts). Methods: Eligible pts were diagnosed 2003-2014 and resected at HVC. Pts were excluded for neoadjuvant Rx, synchronous cancer, death/lost to follow-up within 3 months or contraindications (e.g. morbidity) to adjuvant Rx.. Pts were also excluded if they refused adjuvant treatment or if a community oncologist (CC) was not identified in the medical record or in the western Washington population-based cancer registry. Pt and tumor characteristics were compared in univariate analysis and survival was calculated from date of diagnosis to death or last follow-up. Five year OS was estimated by the Kaplan Meier method and compared using Cox proportional hazards modeling to evaluate the impact of HVC adjuvant Rx on OS while adjusting for potential confounding factors. Results: 245 pts were eligible for study: 139 (57%) treated at HVC, 106 (43%) treated at CC. HVC and CC pts were similar with respect to stage and tumor size, nodal status, resection margins and average distance travelled to HVC. They differed by age (HVC: 63.1, CC: 68.2 p < 0.01). Median and 5-yr OS was 36 mos and 33%. Median OS for HVC vs CC was 44 mos vs. 28 mos (p < 0.01), and 5yr OS was 38.6% vs. 24.8% (p < 0.01), adjustment for age did not alter our findings. Conclusions: 1) With respect to adjuvant Rx for resected PC, HVC and CC pts differed with respect to age only. 2) Both median and 5- yr OS was statistically superior at HVC vs CC. 3) Our study supports the use of HVCs for all Rx components for PC treated with curative intent. 4) Ongoing investigation of patterns of care and their impact on OS in PC is warranted.

scholarly journals POS1234 IMPACT OF THE CHANGE IN ADMINISTRATION ROUTE OF TOCILIZUMAB AND ABATACEPT, DUE TO THE COVID-19 LOCKDOWN ON DISEASE ACTIVITY IN PATIENTS WITH RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 900.1-900
Author(s):  
L. Diebold ◽  
T. Wirth ◽  
V. Pradel ◽  
N. Balandraud ◽  
E. Fockens ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Physical Activity ◽  
Disease Activity ◽  
Univariate Analysis ◽  
Route Of Administration ◽  
Anxiety And Depression ◽  
Administration Route ◽  
Factors Associated ◽  
The Impact

Background:Among therapeutics used to treat rheumatoid arthritis (RA), Tocilizumab (TCZ) and Abatacept (ABA) are both biologic agents that can be delivered subcutaneously (SC) or intravenously (IV). During the first COVID-19 lockdown in France, all patients treated with IV TCZ or IV ABA were offered the option to switch to SC administration.Objectives:The primary aim was to assess the impact of changing the route of administration on the disease activity. The second aim was to assess whether the return to IV route at the patient’s request was associated with disease activity variation, flares, anxiety, depression and low physical activity during the lockdown.Methods:We conducted a prospective monocentric observational study. Eligibility criteria: Adult ≥ 18 years old, RA treated with IV TCZ or IV ABA with a stable dose ≥3 months, change in administration route (from IV to SC) between March 16, 2020, and April 17, 2020. The following data were collected at baseline and 6 months later (M6): demographics, RA characteristics, treatment, history of previous SC treatment, disease activity (DAS28), self-administered questionnaires on flares, RA life repercussions, physical activity, anxiety and depression (FLARE, RAID, Ricci &Gagnon, HAD).The primary outcome was the proportion of patients with a DAS28 variation>1.2 at M6. Analyses: Chi2-test for quantitative variables and Mann-Whitney test for qualitative variables. Factors associated with return to IV route identification was performed with univariate and multivariate analysis.Results:Among the 84 patients who were offered to switch their treatment route of administration, 13 refused to change their treatment. Among the 71 who switched (48 TCZ, 23 ABA), 58 had a M6 follow-up visit (13 lost of follow-up) and DAS28 was available for 49 patients at M6. Main baseline characteristics: female 81%, mean age 62.7, mean disease duration: 16.0, ACPA positive: 72.4%, mean DAS28: 2.01, previously treated with SC TCZ or ABA: 17%.At M6, the mean DAS28 variation was 0.18 ± 0.15. Ten (12.2%) patients had a DAS28 worsening>1.2 (ABA: 5/17 [29.4%] and TCZ: 5/32 [15.6%], p= 0.152) and 19 patients (32.8%) had a DAS28 worsening>0.6 (ABA: 11/17 [64.7%] and TCZ: 8/32 [25.0%], p= 0.007).At M6, 41 patients (77.4%) were back to IV route (26 TCZ, 15 ABA) at their request. The proportion of patients with a DAS28 worsening>1.2 and>0.6 in the groups return to IV versus SC maintenance were 22.5%, 42.5% versus 11.1% and 22.2% (p=0.4), respectively. The univariate analysis identified the following factors associated with the return to IV route: HAD depression score (12 vs 41, p=0.009), HAS anxiety score (12 vs 41, p=0.047) and corticosteroid use (70% vs 100%, p=0.021), in the SC maintenance vs return to IV, respectively.Conclusion:The change of administration route of TCZ and ABA during the first COVID-19 lockdown was infrequently associated with a worsening of RA disease. However, the great majority of the patients (77.4%) request to return to IV route, even without disease activity worsening. This nocebo effect was associated with higher anxiety and depression scores.Disclosure of Interests:None declared

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

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.

The Efficacy of Etoposide-Based Therapy in Adult Secondary Hemophagocytic Lymphohistiocytosis

2021 ◽  
pp. 1-9
Author(s):  
Leonard Naymagon ◽  
Douglas Tremblay ◽  
John Mascarenhas
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Proportional Hazards ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Significant Difference ◽  
The Impact

Data supporting the use of etoposide-based therapy in hemophagocytic lymphohistiocytosis (HLH) arise largely from pediatric studies. There is a lack of comparable data among adult patients with secondary HLH. We conducted a retrospective study to assess the impact of etoposide-based therapy on outcomes in adult secondary HLH. The primary outcome was overall survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. Multivariable Cox proportional hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Ninety adults with secondary HLH seen between January 1, 2009, and January 6, 2020, were included. Forty-two patients (47%) received etoposide-based therapy, while 48 (53%) received treatment only for their inciting proinflammatory condition. Thirty-three patients in the etoposide group (72%) and 32 in the no-etoposide group (67%) died during follow-up. Median survival in the etoposide and no-etoposide groups was 1.04 and 1.39 months, respectively. There was no significant difference in survival between the etoposide and no-etoposide groups (log-rank <i>p</i> = 0.4146). On multivariable analysis, there was no association between treatment with etoposide and survival (HR for death with etoposide = 1.067, 95% CI: 0.633–1.799, <i>p</i> = 0.8084). Use of etoposide-based therapy was not associated with improvement in outcomes in this large cohort of adult secondary HLH patients.

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