Clinical and economic impact of molecular testing for BRAF fusion in pediatric low-grade Glioma

Abstract Background Treatment personalization via tumor molecular testing holds promise for improving outcomes for patients with pediatric low-grade glioma (PLGG). We evaluate the health economic impact of employing tumor molecular testing to guide treatment for patients diagnosed with PLGG, particularly the avoidance of radiation therapy (RT) for patients with BRAF-fusion. Methods We performed a model-based cost-utility analysis comparing two strategies: molecular testing to determine BRAF fusion status at diagnosis against no molecular testing. We developed a microsimulation to model the lifetime health and cost outcomes (in quality-adjusted life years (QALYs) and 2018 CAD, respectively) for a simulated cohort of 100,000 patients newly diagnosed with PLGG after their initial surgery. Results The life expectancy after diagnosis for individuals who did not receive molecular testing was 39.01 (95% Confidence Intervals (CI): 32.94;44.38) years and 40.08 (95% CI: 33.19;45.76) years for those who received testing. Our findings indicate that patients who received molecular testing at diagnosis experienced a 0.38 (95% CI: 0.08;0.77) gain in QALYs and $1384 (95% CI: $-3486; $1204) reduction in costs over their lifetime. Cost and QALY benefits were driven primarily by the avoidance of long-term adverse events (stroke, secondary neoplasms) associated with unnecessary use of radiation. Conclusions We demonstrate the clinical benefit and cost-effectiveness of molecular testing in guiding the decision to provide RT in PLGG. While our results do not consider the impact of targeted therapies, this work is an example of the value of simulation modeling in assessing the long-term costs and benefits of precision oncology interventions for childhood cancer, which can aid decision-making about health system reimbursement.

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High frequency of disease progression in pediatric spinal cord low-grade glioma (LGG): Management strategies and results from the German LGG study group

Neuro-Oncology ◽

10.1093/neuonc/noaa296 ◽

2020 ◽

Author(s):

Thomas Perwein ◽

Martin Benesch ◽

Daniela Kandels ◽

Torsten Pietsch ◽

René Schmidt ◽

...

Keyword(s):

Spinal Cord ◽

Surgical Treatment ◽

Disease Control ◽

Disease Progression ◽

Low Grade Glioma ◽

Molecular Testing ◽

Low Grade ◽

Total N ◽

Non Surgical Treatment

Abstract Background Knowledge on management of pediatric spinal cord low-grade glioma (LGG) is scarce. Methods We analyzed clinical datasets of 128 pediatric patients with spinal LGG followed within the prospective multicenter trials HIT-LGG 1996 (n=36), SIOP-LGG 2004 (n=56) and the subsequent LGG-Interim registry (n=36). Results Spinal LGG, predominantly pilocytic astrocytomas (76%), harbored KIAA1549-BRAF fusion in 14/35 patients (40%) and FGFR1-TACC1 fusion in 3/26 patients (12%), as well as BRAFV600E mutation in 2/66 patients (3%). 10-year overall survival (OS) and event-free survival (EFS) was 93±2% and 38±5%, respectively. Disseminated disease (n=16) was associated with inferior OS and EFS, while age ≥11 years and total resection were favorable factors for EFS. We observed 117 patients following total (n=24) or subtotal/partial resection (n=74), biopsy (n=16), or radiologic diagnosis only (n=3). Eleven patients were treated first with chemotherapy (n=9) or irradiation (n=2). Up to 20.8 years after diagnosis/initial intervention 73/128 patients experienced one (n=43) or up to six (n=30) radiological/clinical disease progressions. Tumor resections were repeated in 36 patients (range, 2-6) and 47 patients required non-surgical treatment (chemotherapy, n=20; radiotherapy, n=10; multiple treatment lines, n=17). Long-term disease control for a median of 6.5 (range, 0.02-20) years was achieved in 73/77 patients following one (n=57) or repeated (n=16) resections, and in 35/47 patients after non-surgical treatment. Conclusions The majority of patients experienced disease progression, even after years. Multiple interventions were required for more than a third, yet multimodal treatment enabled long-term disease control. Molecular testing may reveal therapeutic targets.

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Long-term cognitive deficits in pediatric low-grade glioma (LGG) survivors reflect pretreatment conditions—report from the German LGG studies

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa094 ◽

2020 ◽

Vol 2 (1) ◽

Author(s):

Thomas Traunwieser ◽

Daniela Kandels ◽

Franz Pauls ◽

Torsten Pietsch ◽

Monika Warmuth-Metz ◽

...

Keyword(s):

Processing Speed ◽

Visual Processing ◽

Short Term Memory ◽

Low Grade Glioma ◽

Subtotal Resection ◽

Low Grade ◽

Tumor Site ◽

Pretreatment Conditions ◽

The Impact

Abstract Background Disease and treatment contribute to cognitive late effects following pediatric low-grade glioma (LGG). We analyzed prospectively collected neuropsychological data of German pediatric LGG survivors and focused on the impact of hydrocephalus at diagnosis, neurofibromatosis type 1 (NF1) status, and extent of surgery. Methods We used the Neuropsychological Basic Diagnostic screening tool based on the Cattell–Horn–Carroll model for intelligence and the concept of cross-battery assessment at 2 and 5 years from diagnosis for 316 patients from the German pediatric LGG study and LGG registry (7.1 years median age; 45 NF1; cerebral hemispheres 16%, supratentorial midline 39%, infratentorial 45%). Hydrocephalus was classified radiologically in 137 non-NF1 patients with infratentorial tumors (95/137 complete/subtotal resection). Results Patients with NF1 versus non-NF1 exhibited inferior verbal short-term memory and visual processing (P < .001–.021). In non-NF1 patients, infratentorial tumor site and complete/subtotal resection were associated with sequelae in visual processing, psychomotor speed, and processing speed (P < .001–.008). Non-NF1 patients without surgical tumor reduction and/or nonsurgical treatment experienced similar deficits. Degree of hydrocephalus at diagnosis had no further impact. Psychomotor and processing speed were impaired comparably following chemo-/radiotherapy (P < .001–.021). Pretreatment factors such as NF1 or tumor site were relevant at multivariate analysis. Conclusions All pediatric LGG survivors are at risk to experience long-term cognitive impairments in various domains. Even surgical only management of cerebellar LGG or no treatment at all, that is, biopsy only/radiological diagnosis did not protect cognitive function. Since pattern and extent of deficits are crucial to tailor rehabilitation, neuropsychological and quality of survival assessments should be mandatory in future LGG trials.

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LGG-06. LONG-TERM OUTCOME OF NEWLY DIAGNOSED LOW GRADE GLIOMA

Neuro-Oncology ◽

10.1093/neuonc/noaa222.391 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii367-iii367

Author(s):

Nongnuch Sirachainan ◽

Attaporn Boongerd ◽

Samart Pakakasama ◽

Usanarat Anurathapan ◽

Ake Hansasuta ◽

...

Keyword(s):

Surgical Management ◽

Progression Free Survival ◽

Low Grade Glioma ◽

Low Grade ◽

Newly Diagnosed ◽

Term Outcome ◽

Long Term Outcome ◽

Common Location ◽

Suprasellar Region

Abstract INTRODUCTION Low grade glioma (LGG) is the most common central nervous system (CNS) tumor in children accounted for 30–50%. Regarding benign characteristic of disease, surgical management remains the mainstay of treatment. However, surgical approach is limited in some conditions such as location at brainstem or infiltrative tumor. Chemotherapy and radiation treatments have been included in order to control tumor progression. The 5-years survival rate is approach 90% especially in patients who receive complete resection. However, the outcome of children with LGG in low to middle income is limited. Therefore, the aim of the study was to determine long-term outcome of children with newly diagnosed LGG. METHODS A retrospective study enrolled children aged <18 years who were newly diagnosed LGG during January 2006- December 2019. Diagnosis of LGG was confirmed by histological findings of grade I and II according to WHO criteria. RESULTS A total of 40 patients, female to male ratio was 1:1.35 and mean (SD) for age was 6.7 (4.0) years. The most common location was optic chiasmatic pathway (42.5%), followed by suprasellar region (25.0%). Sixty percent of patients received at least partial tumor removal. Chemotherapy and radiation had been used in 70% and 10.0% respectively. The 10-year progression free survival was 74.1±11.4% and overall survival was 96.2±3.8%. SUMMARY: Treatment of Pediatric LGG mainly required surgical management, however, chemotherapy and radiation had been used in progressive disease. The outcome was excellent.

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Infrastructure, Accessibility and Growth in Tuscany: A Macroeconomic Impact Evaluation

SCIENZE REGIONALI ◽

10.3280/scre2010su3004 ◽

2010 ◽

pp. 75-100

Author(s):

Giuseppe Francesco Gori ◽

Patrizia Lattarulo ◽

Renato Panicciŕ

Keyword(s):

Economic Impact ◽

Regional Growth ◽

Agglomeration Economies ◽

Regional Mobility ◽

Macroeconomic Impact ◽

Productivity Differentials ◽

The Cost ◽

The Impact ◽

Cost Of Transportation

The purpose of the paper is to assess the impact of the Regional Mobility and Logistic Plan (RMLP) of Tuscany on regional growth and spatial disparities between the Tuscan provinces. In order to evaluate its economic impact, we first quantify the impact in terms of changes in travel time and variations in the cost of transportation per unit of delivered output. We then make use of the Remi-Irpet model. The latter explains the agglomeration economies and productivity differentials. We find that, despite the fact that the RMLP does not solve the structural problem of mobility within Tuscany, it does make it possible to get rid of some potential constraints for long-term regional growth, even if the economic impact across the provinces is disequalizing.

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Clinical and Economic Impact of ‘ROS1-Testing’ Strategy Compared to a ‘No- ROS1-Testing’ Strategy in Advanced NSCLC in Spain

10.21203/rs.3.rs-1103970/v1 ◽

2021 ◽

Author(s):

Federico Rojo ◽

Esther Conde ◽

Héctor Torres ◽

Luis Cabezón-Gutiérrez ◽

Dolores Bautista ◽

...

Keyword(s):

Markov Model ◽

Economic Impact ◽

Expert Opinion ◽

Advanced Nsclc ◽

Direct Costs ◽

Base Case ◽

Molecular Testing ◽

Testing Strategy ◽

Lifetime Horizon ◽

Life Years

Abstract Background: Detection of the ROS1 rearrangement is mandatory in patients with advanced or metastatic non-small cell lung cancer (NSCLC) to allow targeted therapy with specific inhibitors. However, in Spanish clinical practice ROS1 determination is not yet fully widespread. The aim of this study is to determine the clinical and economic impact of sequentially testing ROS1 in addition to EGFR and ALK in Spain.Methods: A joint model (decision-tree and Markov model) was developed to determine the cost-effectiveness of testing ROS1 strategy versus a no-ROS1 testing strategy in Spain. Distribution of ROS1 techniques, rates of testing, positivity, and invalidity of biomarkers included in the analysis (EGFR, ALK, ROS1 and PD-L1) were based on expert opinion and Lungpath real-world database. Treatment allocation depending on the molecular testing results was defined by expert opinion. For each treatment, a 3-states Markov model was developed, where progression free survival (PFS) and overall survival (OS) curves were parameterized using exponential extrapolations to model transition of patients among health states. Only medical direct costs were included (€ 2021). A lifetime horizon was considered and a discount rate of 3% was applied for both costs and effects. Both deterministic and probabilistic sensitivity analyses were performed to address uncertainty.Results: A target population of 8,755 patients with advanced NSCLC (non-squamous or never smokers squamous) entered the model. Over a lifetime horizon, the ROS1 testing scenario produced additional 157.5 life years and 121.3 quality-adjusted life years (QALYs) compared with no-ROS1 testing scenario. Total direct costs were increased up to € 2,244,737 for ROS1 testing scenario. The incremental cost-utility ratio (ICUR) was 18,514 €/QALY. Robustness of the base-case results were confirmed by the sensitivity analysis.Conclusions: Our study shows that ROS1 testing in addition to EGFR and ALK is a cost-effective strategy compared to no-ROS1 testing, and it generates more than 120 QALYs in Spain over a lifetime horizon. Despite the low prevalence of ROS1 rearrangements in NSCLC patients, the clinical and economic consequences of ROS1 testing should encourage centers to test all advanced or metastatic NSCLC (non-squamous and never-smoker squamous) patients.

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Association of hyperlipidaemia with 5-year survival after hospitalisation for acute myocardial infarction: a propensity score matched analysis

Open Heart ◽

10.1136/openhrt-2019-001163 ◽

2020 ◽

Vol 7 (1) ◽

pp. e001163

Author(s):

Mohammed Yousufuddin ◽

Ye Zhu ◽

Ruaa Al Ward ◽

Jessica Peters ◽

Taylor Doyle ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Propensity Score ◽

Primary Objective ◽

Life Years ◽

Statin Prescription ◽

Statin Adherence ◽

The Impact

ObjectivesThe primary objective was to examine the association between hyperlipidaemia (HLP) and 5-year survival after incident acute myocardial infarction (AMI). The secondary objectives were to assess the effect of HLP on survival to discharge across patient subgroups, and the impact of statin prescription, intensity and long-term statin adherence on 5-year survival.MethodsRetrospective cohort study of 7071 patients hospitalised for AMI at Mayo Clinic from 2001 through 2011. Of these, 2091 patients with HLP (age (mean±SD) 69.7±13.5) were propensity score matched to 2091 patients without HLP (age 70.6±14.2).ResultsIn matched patients, HLP was associated with higher rate of survival to discharge than no HLP (95% vs 91%; log-rank <0.0001). At year 5, the adjusted HR for all-cause mortality in patients with HLP versus no HLP was 0.66 (95% CI 0.58–0.74), and patients with prescription statin versus no statin was 0.24 (95% CI 0.21 to 0.28). The mean survival was 0.35 year greater in patients with HLP than in those with no HLP (95% CI 0.25 to 0.46). Patients with HLP gained on an average 0.17 life year and those treated with statin 0.67 life year at 5 years after AMI. The benefit of concurrent HLP was consistent across study subgroups.ConclusionsIn patients with AMI, concomitant HLP was associated with increased survival and a net gain in life years, independent of survival benefit from statin therapy. The results also reaffirm the role of statin prescription, intensity and adherence in reducing the mortality after incident AMI.

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