Patient eligibility for trials with imaging response assessment at the time of molecular tumor board presentation.

PURPOSE: To assess the eligibility of patients with advanced or recurrent solid malignancies presented to a molecular tumor board (MTB) at a large precision oncology center for inclusion in trials with the endpoints objective response rate (ORR) or duration of response (DOR) based on Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). METHODS: Prospective patients with available imaging at the time of presentation in the MTB were included. Imaging data was reviewed for objectifiable measurable disease (MD) according to RECIST v1.1. Additionally, we evaluated the patients with MD for representativeness of the identified measurable lesion(s) in relation to the overall tumor burden. RESULTS: 262 patients with different solid malignancies were included. 177 patients (68%) had MD and 85 (32%) had non-measurable disease (NMD) at the time point of MTB presentation in accordance with RECIST v1.1. MD was not representative of the overall tumor burden in eleven patients (6%). The main reasons for NMD were lesions with longest diameter shorter than 10 mm (22%) and non-measurable peritoneal carcinomatosis (18%). Colorectal cancer and malignant melanoma displayed the highest rates of MD (> 75%). In contrast, gastric cancer, head and neck malignancies, and ovarian carcinoma had the lowest rates of MD (< 55%). In case of MD, the measurable lesions were representative of the overall tumor burden in the vast majority of cases (94%). CONCLUSION: Approximately one third of cancer patients with advanced solid malignancies are not eligible for treatment response assessment in trials with endpoints ORR or DOR at the time of MTB presentation. The rate of patients eligible for trials with imaging endpoints differs significantly based on the underlying malignancy and should be taken under consideration during the planning of new precision oncology trials.

Endovascular thrombectomy is cost-saving in patients with acute ischemic stroke with large infarct.

Objective: Endovascular thrombectomy (EVT) is the standard of care for acute large vessel occlusion stroke. Recently, the ANGEL-ASPECT and SELECT 2 trials showed improved outcomes in patients with acute ischemic Stroke presenting with large infarcts. The cost-effectiveness of EVT for this subpopulation of stroke patients has only been calculated using data from the previously published RESCUE-Japan LIMIT trial. It is, therefore, limited in its generalizability to an international population. With this study we primarily simulated patient-level costs to analyze the economic potential of EVT for patients with large ischemic stroke from a public health payer perspective based on the recently published data and secondarily identified determinants of cost-effectiveness. Methods: Costs and outcome of patients treated with EVT or only with the best medical care based on the recent prospective clinical trials ANGEL-ASPECT, SELECT2 and RESCUE-Japan LIMIT. A A Markov model was developed using treamtment outcomes derived from the most recent available literature. Deterministic and probabilistic sensitivity analyses addressed uncertainty. Results: Endovascular treatment resulted in an incremental gain of 1.32 QALYs per procedure with cost savings of $17,318 per patient. Lifetime costs resulted to be most sensitive to the costs of the endovascular procedure. Conclusion: EVT is a cost-saving (i.e., dominant) strategy for patients presenting with large ischemic cores defined by inclusion criteria of the recently published ANGEL-ASPECT, SELECT2, and RESCUE-Japan LIMIT trials in comparison to best medical care in our simulation. Prospective data of individual patients need to be collected to validate these results.

Cost-Effectiveness of Late Endovascular Thrombectomy vs. Best Medical Management in a Clinical Trial Setting and Real-World Setting.

BACKGROUND AND PURPOSE: To assess cost-effectiveness of late time-window endovascular treatment (EVT) in a clinical trial setting and a "real-world" setting. METHODS: Data are from the randomized ESCAPE trial and a prospective cohort study (ESCAPE-LATE). Anterior circulation large vessel occlusion patients presenting > 6 hours from last-known-well were included, whereby collateral status was an inclusion criterion for ESCAPE but not ESCAPE-LATE. A Markov state transition model was built to estimate lifetime costs and quality-adjusted life-years (QALYs) for EVT in addition to best medical care vs. best medical care only in a clinical trial setting (comparing ESCAPE-EVT to ESCAPE control arm patients) and a "real-world" setting (comparing ESCAPE-LATE to ESCAPE control arm patients). We performed an unadjusted analysis, using 90-day modified Rankin Scale(mRS) scores as model input and analysis adjusted for baseline factors. Acceptability of EVT was calculated using upper/lower willingness-to-pay thresholds of 100,000 USD/50,000 USD/QALY. RESULTS: Two-hundred and forty-nine patients were included (ESCAPE-LATE:n = 200, ESCAPE EVT-arm:n = 29, ESCAPE control-arm:n = 20). Late EVT in addition to best medical care was cost effective in the unadjusted analysis both in the clinical trial and real-world setting, with acceptability 96.6%-99.0%. After adjusting for differences in baseline variables between the groups, late EVT was marginally cost effective in the clinical trial setting (acceptability:49.9%-61.6%), but not the "real-world" setting (acceptability:32.9%-42.6%). CONCLUSION: EVT for LVO-patients presenting beyond 6 hours was cost effective in the clinical trial setting and "real-world" setting, although this was largely related to baseline patient differences favoring the "real-world" EVT group. After adjusting for these, EVT benefit was reduced in the trial setting, and absent in the real-world setting.

Cost-effectiveness of CT perfusion for the detection of large vessel occlusion acute ischemic stroke followed by endovascular treatment: a model-based health economic evaluation study.

OBJECTIVES: CT perfusion (CTP) has been suggested to increase the rate of large vessel occlusion (LVO) detection in patients suspected of acute ischemic stroke (AIS) if used in addition to a standard diagnostic imaging regime of CT angiography (CTA) and non-contrast CT (NCCT). The aim of this study was to estimate the costs and health effects of additional CTP for endovascular treatment (EVT)-eligible occlusion detection using model-based analyses. METHODS: In this Dutch, nationwide retrospective cohort study with model-based health economic evaluation, data from 701 EVT-treated patients with available CTP results were included (January 2018-March 2022; trialregister.nl:NL7974). We compared a cohort undergoing NCCT, CTA, and CTP (NCCT + CTA + CTP) with a generated counterfactual where NCCT and CTA (NCCT + CTA) was used for LVO detection. The NCCT + CTA strategy was simulated using diagnostic accuracy values and EVT effects from the literature. A Markov model was used to simulate 10-year follow-up. We adopted a healthcare payer perspective for costs in euros and health gains in quality-adjusted life years (QALYs). The primary outcome was the net monetary benefit (NMB) at a willingness to pay of €80,000; secondary outcomes were the difference between LVO detection strategies in QALYs (ΔQALY) and costs (ΔCosts) per LVO patient. RESULTS: We included 701 patients (median age: 72, IQR: [62-81]) years). Per LVO patient, CTP-based occlusion detection resulted in cost savings (ΔCosts median: € - 2671, IQR: [€ - 4721; € - 731]), a health gain (ΔQALY median: 0.073, IQR: [0.044; 0.104]), and a positive NMB (median: €8436, IQR: [5565; 11,876]) per LVO patient. CONCLUSION: CTP-based screening of suspected stroke patients for an endovascular treatment eligible large vessel occlusion was cost-effective. CLINICAL RELEVANCE STATEMENT: Although CTP-based patient selection for endovascular treatment has been recently suggested to result in worse patient outcomes after ischemic stroke, an alternative CTP-based screening for endovascular treatable occlusions is cost-effective. KEY POINTS: • Using CT perfusion to detect an endovascular treatment-eligible occlusions resulted in a health gain and cost savings during 10 years of follow-up. • Depending on the screening costs related to the number of patients needed to image with CT perfusion, cost savings could be considerable (median: € - 3857, IQR: [€ - 5907; € - 1916] per patient). • As the gain in quality adjusted life years was most affected by the sensitivity of CT perfusion-based occlusion detection, additional studies for the diagnostic accuracy of CT perfusion for occlusion detection are required.

Cost-effectiveness of endovascular treatment versus best medical management in basilar artery occlusion stroke: A U.S. healthcare perspective.

INTRODUCTION: Two recent studies showed clinical benefit for endovascular treatment (EVT) in basilar artery occlusion (BAO) stroke up to 12 h (ATTENTION) and between 6 and 24 h from onset (BAOCHE). Our aim was to investigate the cost-effectiveness of EVT from a U.S. healthcare perspective. MATERIALS AND METHODS: Clinical input data were available for both trials, which were analyzed separately. A decision model was built consisting of a short-run model to analyze costs and functional outcomes within 90 days after the index stroke and a long-run Markov state transition model (cycle length of 12 months) to estimate expected lifetime costs and outcomes from a healthcare and a societal perspective. Incremental cost-effectiveness ratios (ICER) were calculated, deterministic (DSA) and probabilistic (PSA) sensitivity analyses were performed. RESULTS: EVT in addition to best medical management (BMM) resulted in additional lifetime costs of $32,063 in the ATTENTION trial and lifetime cost savings of $7690 in the BAOCHE trial (societal perspective). From a healthcare perspective, EVT led to incremental costs and effectiveness of $37,389 and 2.0 QALYs (ATTENTION) as well as $3516 and 1.9 QALYs (BAOCHE), compared to BMM alone. The ICER values were $-4052/QALY (BAOCHE) and $15,867/QALY (ATTENTION) from a societal perspective. In each trial, PSA showed EVT to be cost-effective in most calculations (99.9%) for a willingness-to-pay threshold of $100,000/QALY. Cost of EVT and age at stroke represented the greatest impact on the ICER. DISCUSSION: From an economic standpoint with a lifetime horizon, EVT in addition to BMM is estimated to be highly effective and cost-effective in BAO stroke.

Multicenter development of a PET-based risk assessment tool for product-specific outcome prediction in large B-cell lymphoma patients undergoing CAR T-cell therapy.

PURPOSE: The emergence of chimeric antigen receptor (CAR) T-cell therapy fundamentally changed the management of individuals with relapsed and refractory large B-cell lymphoma (LBCL). However, real-world data have shown divergent outcomes for the approved products. The present study therefore set out to evaluate potential risk factors in a larger cohort. METHODS: Our analysis set included 88 patients, treated in four German university hospitals and one Italian center, who had undergone 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (PET) before CAR T-cell therapy with tisagenlecleucel or axicabtagene ciloleucel. We first determined the predictive value of conventional risk factors, treatment lines, and response to bridging therapy for progression-free survival (PFS) through forward selection based on Cox regression. In a second step, the additive potential of two common PET parameters was assessed. Their optimal dichotomizing thresholds were calculated individually for each CAR T-cell product. RESULTS: Extra-nodal involvement emerged as the most relevant of the conventional tumor and patient characteristics. Moreover, we found that inclusion of metabolic tumor volume (MTV) further improves outcome prediction. The hazard ratio for a PFS event was 1.68 per unit increase of our proposed risk score (95% confidence interval [1.20, 2.35], P = 0.003), which comprised both extra-nodal disease and lymphoma burden. While the most suitable MTV cut-off among patients receiving tisagenlecleucel was 11 mL, a markedly higher threshold of 259 mL showed optimal predictive performance in those undergoing axicabtagene ciloleucel treatment. CONCLUSION: Our analysis demonstrates that the presence of more than one extra-nodal lesion and higher MTV in LBCL are associated with inferior outcome after CAR T-cell treatment. Based on an assessment tool including these two factors, patients can be assigned to one of three risk groups. Importantly, as shown by our study, metabolic tumor burden might facilitate CAR T-cell product selection and reflect the individual need for bridging therapy.

Costs and health effects of CT perfusion-based selection for endovascular thrombectomy within 6 hours of stroke onset: a model-based health economic evaluation.

BACKGROUND: Although CT perfusion (CTP) is often incorporated in acute stroke workflows, it remains largely unclear what the associated costs and health implications are in the long run of CTP-based patient selection for endovascular treatment (EVT) in patients presenting within 6 hours after symptom onset with a large vessel occlusion. METHODS: Patients with a large vessel occlusion were included from a Dutch nationwide cohort (n=703) if CTP imaging was performed before EVT within 6 hours after stroke onset. Simulated cost and health effects during 5 and 10 years follow-up were compared between CTP based patient selection for EVT and providing EVT to all patients. Outcome measures were the net monetary benefit at a willingness-to-pay of €80 000 per quality-adjusted life year, incremental cost-effectiveness ratio), difference in costs from a healthcare payer perspective (ΔCosts) and quality-adjusted life years (ΔQALY) per 1000 patients for 1000 model iterations as outcomes. RESULTS: Compared with treating all patients, CTP-based selection for EVT at the optimised ischaemic core volume (ICV≥110 mL) or core-penumbra mismatch ratio (MMR≤1.4) thresholds resulted in losses of health (median ΔQALYs for ICV≥110 mL: -3.3 (IQR: -5.9 to -1.1), for MMR≤1.4: 0.0 (IQR: -1.3 to 0.0)) with median ΔCosts for ICV≥110 mL of -€348 966 (IQR: -€712 406 to -€51 158) and for MMR≤1.4 of €266 513 (IQR: €229 403 to €380 110)) per 1000 patients. Sensitivity analyses did not yield any scenarios for CTP-based selection of patients for EVT that were cost-effective for improving health, including patients aged ≥80 years CONCLUSION: In EVT-eligible patients presenting within 6 hours after symptom onset, excluding patients based on CTP parameters was not cost-effective and could potentially harm patients.

Is PSMA PET/CT cost-effective for the primary staging in prostate cancer? First results for European countries and the USA based on the proPSMA trial.

PURPOSE: The proPSMA trial at ten Australian centers demonstrated increased sensitivity and specificity for PSMA PET/CT compared to conventional imaging regarding metastatic status in primary high-risk prostate cancer patients. A cost-effectiveness analysis showed benefits of PSMA PET/CT over conventional imaging for the Australian setting. However, comparable data for other countries are lacking. Therefore, we aimed to verify the cost-effectiveness of PSMA PET/CT in several European countries as well as the USA. METHODS: Clinical data on diagnostic accuracy were derived from the proPSMA trial. Costs for PSMA PET/CT and conventional imaging were taken from reimbursements of national health systems and individual billing information of selected centers in Belgium, Germany, Italy, the Netherlands, and the USA. For comparability, scan duration and the decision tree of the analysis were adopted from the Australian cost-effectiveness study. RESULTS: In contrast to the Australian setting, PSMA PET/CT was primarily associated with increased costs in the studied centers in Europe and the USA. Mainly, the scan duration had an impact on the cost-effectiveness. However, costs for an accurate diagnosis using PSMA PET/CT seemed reasonably low compared to the potential consequential costs of an inaccurate diagnosis. CONCLUSION: We assume that the use of PSMA PET/CT is appropriate from a health economic perspective, but this will need to be verified by a prospective evaluation of patients at initial diagnosis.

Endovascular thrombectomy is cost-effective in acute basilar artery occlusion stroke.

Objective: Endovascular thrombectomy is a long-established therapy for acute basilar artery occlusion (aBAO). Unlike for anterior circulation stroke, cost-effectiveness of endovascular treatment has not been evaluated and is urgently needed to calculate expected health benefits and financial rewards. The aim of this study was therefore to simulate patient-level costs, analyze the economic potential of endovascular thrombectomy in patients with acute basilar artery occlusion (aBAO), and identify major determinants of cost-effectiveness. Methods: A Markov model was developed to compare outcome and cost parameters between patients treated by endovascular thrombectomy and patients treated by best medical care, based on four recent prospective clinical trials (ATTENTION, BAOCHE, BASICS, and BEST). Treatment outcomes were derived from the most recent literature. Uncertainty was addressed by deterministic and probabilistic sensitivity analyses. Willingness to pay per QALY thresholds were set at 1x gross domestic product per capita, as recommended by the World Health Organization. Results: Endovascular treatment of acute aBAO stroke yielded an incremental gain of 1.71 quality-adjusted life-years per procedure with an incremental cost-effectiveness ratio of $7,596 per QALY. This was substantially lower than the Willingness to pay of $63,593 per QALY. Lifetime costs were most sensitive to costs of the endovascular procedure. Conclusion: Endovascular treatment is cost-effective in patients with aBAO stroke.

Economic evaluation of 18F-FDG PET/CT, MRI and CE-CT in selection of colorectal liver metastases eligible for ablation - A cost-effectiveness analysis.

OBJECTIVES: Colorectal cancers (CRC) are among the world's most prevailing cancer entities. In a third of all cases, the patients have already developed distant metastases - mainly in the liver - at the time of detection. Colorectal liver metastases (CRLM) can be treated by surgical resection or, as is possible in most cases, by percutaneous ablation. For selecting the liver metastases eligible for radiofrequency ablation (RFA) or microwave ablation (MWA), the common imaging modalities are magnetic resonance imaging (MRI), positron emission tomography/computed tomography (PET/CT), and contrast-enhanced computed tomography (CE-CT). This study aims to evaluate those imaging modalities for selecting liver lesions eligible for ablation according to their long-term cost-effectiveness. MATERIALS AND METHODS: A Markov model was applied, calculating quality-adjusted life years (QALYs) and accumulative costs for every diagnostic strategy, according to predefined input parameters obtained from published research. Further, sensitivity analyses were executed to prove the certainty of the calculations by running Monte-Carlo simulations with 30,000 reiterations. The Willingness-to-pay (WTP) is at $ 100,000. All calculations are based on the U.S. healthcare system. RESULTS: CE-CT caused cumulative costs of $ 31,940.98 and 8,99 QALYs, whereas MRI caused $ 32,070.83 and 9,01 QALYs. PET/CT caused cumulative costs of $ 33,013.21 and 8,99 QALYs. CONCLUSION: In conclusion, according to our analysis, MRI is the most cost-effective strategy for detecting liver metastases eligible for ablation and therefore should be seen as the gold standard.

Cost-Effectiveness Analysis of 177Lu-PSMA-617 Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer.

BACKGROUND: Metastatic castration-resistant prostate cancer poses a therapeutic challenge with poor prognosis. The VISION trial showed prolonged progression-free and overall survival in patients treated with lutetium Lu 177 vipivotide tetraxetan (177Lu-PSMA-617) radioligand therapy compared with using the standard of care (SoC) alone. The objective of this study was to determine the cost-effectiveness of 177Lu-PSMA-617 treatment compared with SoC therapy. METHODS: A partitioned survival model was developed using data from the VISION trial, which included overall and progression-free survival and treatment regimens for 177Lu-PSMA-617 and SoC. Treatment costs, utilities for health states, and adverse events were derived from public databases and the literature. Because 177Lu-PSMA-617 was only recently approved, costs for treatment were extrapolated from 177Lu-DOTATATE. Outcome measurements included the incremental cost, effectiveness, and cost-effectiveness ratio. The analysis was performed in a US setting from a healthcare system perspective over the lifetime horizon of 60 months. The willingness-to-pay threshold was set to $50,000, $100,000, and $200,000 per quality-adjusted life years (QALYs). RESULTS: The 177Lu-PSMA-617 group was estimated to gain 0.42 incremental QALYs. Treatment using 177Lu-PSMA-617 led to an increase in costs compared with SoC ($169,110 vs $85,398). The incremental cost, effectiveness, and cost-effectiveness ratio for 177Lu-PSMA-617 therapy was $200,708/QALYs. Sensitivity analysis showed robustness of the model regarding various parameters, which remained cost-effective at all lower and upper parameter bounds. In probabilistic sensitivity analysis using Monte Carlo simulation with 10,000 iterations, therapy using 177Lu-PSMA-617 was determined as the cost-effective strategy in 37.14% of all iterations at a willingness-to-pay threshold of $200,000/QALYs. CONCLUSIONS: Treatment using 177Lu-PSMA-617 was estimated to add a notable clinical benefit over SoC alone. Based on the model results, radioligand therapy represents a treatment strategy for patients with metastatic castration-resistant prostate cancer with cost-effectiveness in certain scenarios.

Cost-Effectiveness of Endovascular Treatment in Large Vessel Occlusion Stroke With Mild Prestroke Disability: Results From the HERMES Collaboration.

BACKGROUND: The clinical and economic benefit of endovascular treatment (EVT) in addition to best medical management in patients with stroke with mild preexisting symptoms/disability is not well studied. We aimed to investigate cost-effectiveness of EVT in patients with large vessel occlusion and mild prestroke symptoms/disability, defined as a modified Rankin Scale score of 1 or 2. METHODS: Data are from the HERMES collaboration (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials), which pooled patient-level data from 7 large, randomized EVT trials. We used a decision model consisting of a short-run model to analyze costs and functional outcomes within 90 days after the index stroke and a long-run Markov state transition model (cycle length of 12 months) to estimate expected lifetime costs and outcomes from a health care and a societal perspective. Incremental cost-effectiveness ratio and net monetary benefits were calculated, and a probabilistic sensitivity analysis was performed. RESULTS: EVT in addition to best medical management resulted in lifetime cost savings of $2821 (health care perspective) or $5378 (societal perspective) and an increment of 1.27 quality-adjusted life years compared with best medical management alone, indicating dominance of additional EVT as a treatment strategy. The net monetary benefits were higher for EVT in addition to best medical management compared with best medical management alone both at the higher (100 000$/quality-adjusted life years) and lower (50 000$/quality-adjusted life years) willingness to pay thresholds. Probabilistic sensitivity analysis showed decreased costs and an increase in quality-adjusted life years for additional EVT compared with best medical management only. CONCLUSIONS: From a health-economic standpoint, EVT in addition to best medical management should be the preferred strategy in patients with acute ischemic stroke with large vessel occlusion and mild prestroke symptoms/disability.

Simplified Assessment of Lesion Water Uptake for Identification of Patients within 4.5 Hours of Stroke Onset: An Analysis of the MissPerfeCT Study.

BACKGROUND AND PURPOSE: Many patients with stroke cannot receive intravenous thrombolysis because the time of symptom onset is unknown. We tested whether a simple method of computed tomography (CT)-based quantification of water uptake in the ischemic tissue can identify patients with stroke onset within 4.5 hours. METHODS: This retrospective analysis of the MissPerfeCT study (August 2009 to November 2017) includes consecutive patients with known onset of symptoms from seven tertiary stroke centers. We developed a simplified algorithm based on region of interest (ROI) measurements to quantify water uptake of the ischemic lesion and thereby quantify time of symptom onset within and beyond 4.5 hours. Perfusion CT was used to identify ischemic brain tissue, and its density was measured in non-contrast CT and related to the density of the corresponding area of the contralateral hemisphere to quantify lesion water uptake. RESULTS: Of 263 patients, 204 (77.6%) had CT within 4.5 hours. Water uptake was significantly lower in patients with stroke onset within (6.7%; 95% confidence interval [CI], 6.0% to 7.4%) compared to beyond 4.5 hours (12.7%; 95% CI, 10.7% to 14.7%). The area under the curve for distinguishing these patient groups according to percentage water uptake was 0.744 with an optimal cut-off value of 9.5%. According to this cut-off the positive predictive value was 88.8%, sensitivity was 73.5%, specificity 67.8%, negative predictive value was 42.6%. CONCLUSIONS: Ischemic stroke patients with unknown time of symptom onset can be identified as being within a timeframe of 4.5 hours using a ROI-based method to assess water uptake on admission non-contrast head CT.

Cost-effectiveness of Response-Adapted De-escalation of Immunotherapy in Advanced Melanoma.

Importance: Combination immunotherapy with nivolumab and ipilimumab has markedly improved outcomes for patients with advanced melanoma. However, these therapies pose a considerable financial burden to both patients and the health care system. The ADAPT-IT trial demonstrated comparable progression-free and overall survival for patients with response-adapted ipilimumab discontinuation compared with standard of care (SOC). Objective: To determine the cost-effectiveness of ipilimumab discontinuation for patients with interim imaging-confirmed tumor response in the treatment of advanced melanoma. Design, Setting, and Participants: This cost-effectiveness analysis was performed using data from the ADAPT-IT (follow-up of 33 months) and CheckMate 067 (follow-up of 6.5 years) trials, as well as published literature over the ADAPT-IT trial duration of 33 months. The analysis was performed in a US setting from a US-payer perspective, and the willingness-to-pay (WTP) threshold was set at $100 000/quality-adjusted life-year (QALY). A total of 355 patients with previously untreated melanoma (unresectable stage III or IV metastatic melanoma) were included. Exposure: Response-adapted ipilimumab discontinuation compared with SOC therapy. Main Outcomes and Measures: The primary outcomes of the CheckMate trial were overall survival and progression-free survival, while that of ADAPT-IT was objective response. This informed a decision model to estimate lifetime costs and QALYs associated with both strategies. Incremental cost, effectiveness, and cost-effectiveness ratio were assessed. Sensitivity and scenario analyses were performed to account for variability in trials and input parameters. Results: Of the 355 patients included in the analysis, 41 patients were from the ADAPT-IT trial (median age, 65 years; 28 [68%] male) and 314 patients from the CheckMate 067 trial (median age, 61 years; 206 [66%] male). Response-adapted treatment was the cost-effective option in 94.0% of scenarios based on Monte Carlo simulations, with a dominant incremental cost-effectiveness ratio and an incremental net monetary benefit of $28 849 compared with SOC therapy. Cost savings were estimated at $19 891 per patient compared with SOC. In scenario analyses, current SOC was only considered as a cost-effective option under best survival assumptions and if the willingness-to-pay threshold exceeded $630 000/QALY. Conclusions and Relevance: This economic evaluation demonstrated that response-adapted treatment de-escalation in patients with advanced melanoma may lead to considerable savings in health care costs and could represent the most cost-effective strategy across various resource settings. Future trials should aim to provide further evidence on noninferiority.

Lymphoma tumor burden before chimeric antigen receptor T-Cell treatment: RECIL vs. Lugano vs. metabolic tumor assessment.

Purpose: High tumor burden has emerged as a negative predictor of efficacy in chimeric antigen receptor T-cell therapy (CART) in patients with refractory or relapsed large B-cell lymphoma. This study analyzed the deviation among imaging-based tumor burden (TB) metrics and their association with progression-free (PFS) and overall survival (OS). Materials and methods: In this single-center observational study, we included all consecutively treated patients receiving CD19 CART with available baseline PET-CT imaging. Imaging-based TB was determined based on response evaluation criteria in lymphoma (RECIL), the Lugano criteria, and metabolic tumor volume. Total, nodal and extranodal TB were represented, according to the respective criteria, by sum of longest diameters (TBRECIL), sum of product of perpendicular diameters (TBLugano), and metabolic tumor volume (TBMTV). Correlation statistics were used for comparison. Proportional Cox regression analysis studied the association of TB metrics with PFS and OS. Results: 34 consecutive patients were included (median age: 67 years, 41% female) with total median baseline TBRECIL of 12.5 cm, TBLugano of 4,030 mm2 and TBMTV of 330 mL. The correlation of TBRECIL and TBLugano with TBMTV was strong (ρ=0.744, p<0.001 and ρ=0.741, p<0.001), with lowest correlation for extranodal TBRECIL with TBMTV (ρ=0.660, p<0.001). Stratification of PFS was strongest by total TBMTV>50% (HR=2.915, p=0.042), whereas total TBRECIL>50% and total TBLugano>50% were not significant (both p>0.05). None of the total TB metrics were associated with OS (all p>0.05). Conclusion: Pre-CART TB metrics vary significantly based on the assessment method, impacting their association with survival outcomes. The correlation between TBRECIL, TBLugano and TBMTV was influenced by disease phenotype and prior bridging therapy. TB method of assessment must be considered when interpreting the impact of TB on outcomes in clinical trials. Considering the heterogeneity, our results argue for standardization and harmonization across centers.

Moving from traditional to more advanced treatments in stroke care is cost-effective: A case study from Greece.

OBJECTIVES: Stroke is the most common cause of disability in high-income countries. Several countries offer a limited range of advanced treatments with implications for outcomes, disability and costs. This study estimates the burden of disability that could have been avoided through the transition from traditional (no intravenous thrombolytic therapy (IVT), or endovascular thrombectomy (EVT)) to modern stroke treatments (treatment in stroke units, IVT and EVT). We perform a cost-effectiveness analysis comparing best practice with traditional stroke care, using Greece as a case study. MATERIALS AND METHODS: A Markov model was used to calculate costs and Quality Adjusted Life Years (QALYs) for each treatment strategy, using a lifetime horizon. Data for model inputs were derived from meta-analyses of trials, and national and international cost databases. Sensitivity analyses were also performed to address potential uncertainty and test the robustness of the findings. RESULTS: Incremental effectiveness comprised 0.22 QALYs per patient and year. Best practice was cost-effective for more than 90% of all iterations (ICER for the baseline scenario: €2,109.25/QALY). Sensitivity analysis demonstrated that the findings remain robust. Considering the stroke incidence in Greece, the annual additional cost to implement best practice was calculated to be between 0.07%-0.15% of the total health expenditure. CONCLUSION: Best practice stroke treatment was cost-effective and affordable in a case study based on Greece. The results could be leveraged by including effects of preventive policies and rehabilitation. They also highlight the importance of adopting modern treatment strategies from a cost-effectiveness perspective, apart from the improved clinical outcomes.

Cost-effectiveness of CT perfusion for patients with acute ischemic stroke (CLEOPATRA)-Study protocol for a healthcare evaluation study.

Introduction: Computed tomography perfusion (CTP) is variably considered to assess eligibility for endovascular thrombectomy (EVT) in acute ischemic (AIS) stroke patients. Although CTP is recommended for patient selection in later (6-24 h) time window, it is currently not recommended in the earlier (0-6 h) time window and the costs and health effects of including CTP for EVT selection remain unknown. We aim to estimate the costs and health effects of using CTP for EVT selection in AIS patients compared to conventional selection. Patients and methods: CLEOPATRA is a healthcare evaluation study using clinical and imaging data from multiple, prospective EVT trials and registries in both the earlier and later time windows. To study the long-term health and cost effects, we will construct a ("Markov") health state transition model simulating the clinical outcome over a 5-year follow-up period for CTP-based and conventional selection for EVT. Clinical data acquired within the current study and estimates from the literature will be used as input for probabilities of events, costs, and Quality-Adjusted Life Years (QALYs) per modified Rankin Scale (mRS) subscore. Primary outcome for the cost-effectiveness analysis will be the Incremental Cost-Effectiveness Ratio (ICER) in terms of costs per QALY gained over the simulated follow-up period. Study outcomes: Outcome measures will be reported as cumulative values over a 5-year follow-up period. Discussion: This study will provide preliminary insight into costs and health effects of including CTP in the selection for EVT for AIS patients, presenting between 0 and 24 h after time last known well. The results may be used to develop recommendations and inform further implementation projects and studies.