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.

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.

Predictive value of pre-infusion tumor growth rate for the occurrence and severity of CRS and ICANS in lymphoma under CAR T-cell therapy.

Chimeric antigen receptor T-cell therapy (CART) can be administered outpatient yet requires management of potential side effects such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The pre-infusion tumor burden is associated with CRS, yet there is no data on the relevance of pre-infusion tumor growth rate (TGR). Our objective was to investigate TGR for the occurrence and severity of CRS and ICANS. Consecutive patients with available pre-baseline and baseline (BL) imaging before CART were included. TGR was determined as both absolute (abs) and percentage change (%) of Lugano criteria-based tumor burden in relation to days between exams. CRS and ICANS were graded according to ASTCT consensus criteria. Clinical metadata was collected including the international prognostic index (IPI), patient age, ECOG performance status, and LDH. Sixty-two patients were included (median age: 62 years, 40% female). The median pre-BL TGR [abs] and pre-BL TGR [%] was 7.5 mm2/d and 30.9%/d. Pre-BL TGR [abs] and pre-BL TGR [%] displayed a very weak positive correlation with the grade of CRS (r[abs] = 0.14 and r[%] = 0.13) and no correlation with ICANS (r[abs] = - 0.06 and r[%] = - 0.07). There was a weak positive correlation between grade of CRS and grade of ICANS (r = 0.35; p = 0.005) whereas there was no significant correlation of CRS or ICANS to any other of the examined parameters. The pre-infusion TGR before CART was weakly associated with the occurrence of CRS, but not the severity, whereas there were no significant differences in the prediction of ICANS. There was no added information when compared to pre-infusion tumor burden alone. Outpatient planning and toxicity management should not be influenced by the pre-infusion TGR.

Perceptions of radiologists on structured reporting for cancer imaging-a survey by the European Society of Oncologic Imaging (ESOI).

OBJECTIVES: To assess radiologists' current use of, and opinions on, structured reporting (SR) in oncologic imaging, and to provide recommendations for a structured report template. MATERIALS AND METHODS: An online survey with 28 questions was sent to European Society of Oncologic Imaging (ESOI) members. The questionnaire had four main parts: (1) participant information, e.g., country, workplace, experience, and current SR use; (2) SR design, e.g., numbers of sections and fields, and template use; (3) clinical impact of SR, e.g., on report quality and length, workload, and communication with clinicians; and (4) preferences for an oncology-focused structured CT report. Data analysis comprised descriptive statistics, chi-square tests, and Spearman correlation coefficients. RESULTS: A total of 200 radiologists from 51 countries completed the survey: 57.0% currently utilized SR (57%), with a lower proportion within than outside of Europe (51.0 vs. 72.7%; p = 0.006). Among SR users, the majority observed markedly increased report quality (62.3%) and easier comparison to previous exams (53.5%), a slightly lower error rate (50.9%), and fewer calls/emails by clinicians (78.9%) due to SR. The perceived impact of SR on communication with clinicians (i.e., frequency of calls/emails) differed with radiologists' experience (p < 0.001), and experience also showed low but significant correlations with communication with clinicians (r = - 0.27, p = 0.003), report quality (r = 0.19, p = 0.043), and error rate (r = - 0.22, p = 0.016). Template use also affected the perceived impact of SR on report quality (p = 0.036). CONCLUSION: Radiologists regard SR in oncologic imaging favorably, with perceived positive effects on report quality, error rate, comparison of serial exams, and communication with clinicians. CLINICAL RELEVANCE STATEMENT: Radiologists believe that structured reporting in oncologic imaging improves report quality, decreases the error rate, and enables better communication with clinicians. Implementation of structured reporting in Europe is currently below the international level and needs society endorsement. KEY POINTS: • The majority of oncologic imaging specialists (57% overall; 51% in Europe) use structured reporting in clinical practice. • The vast majority of oncologic imaging specialists use templates (92.1%), which are typically cancer-specific (76.2%). • Structured reporting is perceived to markedly improve report quality, communication with clinicians, and comparison to prior scans.

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.

Evaluation of magnetic resonance thermometry performance during MR-guided hyperthermia treatment of soft-tissue sarcomas in the lower extremities and pelvis.

INTRODUCTION: This study evaluated the performance of magnetic resonance thermometry (MRT) during deep-regional hyperthermia (HT) in pelvic and lower-extremity soft-tissue sarcomas. MATERIALS AND METHODS: 17 pelvic (45 treatments) and 16 lower-extremity (42 treatments) patients underwent standard regional HT and chemotherapy. Pairs of double-echo gradient-echo scans were acquired during the MR protocol 1.4 s apart. For each pair, precision was quantified using phase data from both echoes ('dual-echo') or only one ('single-echo') in- or excluding body fat pixels in the field drift correction region of interest. The precision of each method was compared to that of the MRT approach using a built-in clinical software tool (SigmaVision). Accuracy was assessed in three lower-extremity patients (six treatments) using interstitial temperature probes. The Jaccard coefficient quantified pretreatment motion; receiver operating characteristic analysis assessed its predictability for acceptable precision (<1 °C) during HT. RESULTS: Compared to the built-in dual-echo approach, single-echo thermometry improved the mean temporal precision from 1.32 ± 0.40 °C to 1.07 ± 0.34 °C (pelvis) and from 0.99 ± 0.28 °C to 0.76 ± 0.23 °C (lower extremities). With body fat-based field drift correction, single-echo mean accuracy improved from 1.4 °C to 1.0 °C. Pretreatment bulk motion provided excellent precision prediction with an area under the curve of 0.80-0.86 (pelvis) and 0.81-0.83 (lower extremities), compared to gastrointestinal air motion (0.52-0.58). CONCLUSION: Single-echo MRT exhibited better precision than dual-echo MRT. Body fat-based field-drift correction significantly improved MRT accuracy. Pretreatment bulk motion showed improved prediction of acceptable MRT temporal precision over gastrointestinal air motion.

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 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.

Prognostic value of pre-infusion tumor growth rate for patients with lymphoma receiving chimeric antigen receptor T-cell therapy.

BACKGROUND AIMS: Chimeric antigen receptor T-cell therapy (CART) prolongs survival for patients with refractory or relapsed lymphoma, yet its efficacy is affected by the tumor burden. The relevance of tumor kinetics before infusion is unknown. We aimed to study the prognostic value of the pre-infusion tumor growth rate (TGRpre-BL) for progression-free (PFS) and overall survival (OS). METHODS: Consecutive patients with available pre-baseline (pre-BL) and baseline (BL) computed tomography or positron emission tomography/computed tomography scan before CART were included. TGR was determined as change of Lugano criteria-based tumor burden between pre-BL, BL and follow-up examinations (FU) in relation to days between imaging exams. Overall response rate (ORR), depth or response (DoR) and PFS were determined based on Lugano criteria. Multivariate regression analysis studied association of TGR with ORR and DoR. Proportional Cox regression analysis studied association of TGR with PFS and OS. RESULTS: In total, 62 patients met the inclusion criteria. The median TGRpre-BL was 7.5 mm2/d (interquartile range -14.6 mm2/d to 48.7 mm2/d); TGRpre-BL was positive (TGRpre-BL POS) in 58% of patients and negative (TGRpre-BL NEG, indicating tumor shrinkage) in 42% of patients. Patients who were TGRpre-BL POS had a 90-day (FU2) ORR of 62%, a DoR of -86% and a median PFS of 124 days. Patients who were TGRpre-BL NEG had a 90-day ORR of 44%, DoR of -47% and a median PFS of 105 days. ORR and DoR were not associated with slower TGR (P = 0.751, P = 0.198). Patients with an increase of TGR from pre-BL over BL to 30-day FU (FU1) ≥100% (TGRpre-BL-to-FU1≥100%) showed a significant association with shorter median PFS (31 days versus 343 days, P = 0.002) and shorter median OS after CART (93 days versus not reached, P < 0.001), compared with patients with TGRpre-BL-to-FU1<100%. CONCLUSIONS: In the context of CART, differences in pre-infusion tumor kinetics showed minor differences in ORR, DoR, PFS and OS, whereas the change of the TGR from pre-BL to 30-day FU significantly stratified PFS and OS. In this patient population of refractory or relapsed lymphomas, TGR is readily available based on pre-BL imaging, and its change throughout CART should be explored as a potential novel imaging biomarker of early response.

Circadian rhythm of ischaemic core progression in human stroke.

INTRODUCTION: Experimental stroke studies suggest an influence of the time of day of stroke onset on infarct progression. Whether this holds true after human stroke is unknown, but would have implications for the design of randomised controlled trials, especially those on neuroprotection. METHODS: We pooled data from 583 patients with anterior large-vessel occlusion stroke from three prospectively recruited cohorts. Ischaemic core and penumbra volumes were determined with CT perfusion using automated thresholds. Core growth was calculated as the ratio of core volume and onset-to-imaging time. To determine circadian rhythmicity, we applied multivariable linear and sinusoidal regression analysis adjusting for potential baseline confounders. RESULTS: Patients with symptom onset at night showed larger ischaemic core volumes on admission compared with patients with onset during the day (median, 40.2 mL vs 33.8 mL), also in adjusted analyses (p=0.008). Sinusoidal analysis indicated a peak of core volumes with onset at 11pm. Core growth was faster at night compared with day onset (adjusted p=0.01), especially for shorter onset-to-imaging times. In contrast, penumbra volumes did not change across the 24-hour cycle. DISCUSSION: These results suggest that human infarct progression varies across the 24-hour cycle with potential implications for the design and interpretation of neuroprotection trials.

Prognostic value of the International Metabolic Prognostic Index for lymphoma patients receiving chimeric antigen receptor T-cell therapy.

PURPOSE: Chimeric antigen receptor T-cell therapy (CART) prolongs survival for patients with relapsed/refractory B-cell non-Hodgkin's lymphoma. The recently introduced International Metabolic Prognostic Index (IMPI) was shown to improve prognostication in the first-line treatment of large B-cell lymphoma. Here, we investigate the prognostic value of the IMPI for progression-free (PFS) and overall survival (OS) in the setting of CD19 CART. METHODS: Consecutively treated patients with baseline 18F-FDG PET/CT imaging and follow-up imaging at 30 days after CART were included. IMPI is composed of age, stage, and metabolic tumor volume (MTV) at baseline and was compared with the International Prognostic Index (IPI). Both indices were grouped into quartiles, as previously described for IPI. In addition, the continuous IMPI was subdivided into tertiaries for better separation of risk groups. Overall response rate (ORR), depth of response (DoR), and PFS were determined based on Lugano criteria. Proportional Cox regression analysis studied association of IMPI and IPI with PFS and OS. RESULTS: Thirty-nine patients were included. The IPI was 1 in 23%, 2 in 21%, 3 in 26%, 4 in 21%, and 5 in 10% of the patients. IMPIlow risk, IMPIintermediate risk, and IMPIhigh risk patients had 30-day ORR of 69%, 62%, and 62% and 30-day DoR of - 67%, - 66%, and - 54% with a PFS of 187 days, 97 days, and 87 days, respectively. ORR and DoR showed no correlation with lower IMPI (r = 0.065, p = 0.697). Dividing patients into three risk groups showed a significant trend for PFS stratification (p = 0.030), while IPI did not (p = 0.133). Neither IPI nor IMPI yielded a significant association with OS after CART (both p > 0.05). CONCLUSION: In the context of CART, the IMPI yielded prognostic value regarding PFS estimation. In contrast with IMPI in the first-line DLBCL setting, we did not observe a significant association of IMPI at baseline with OS after CART.

Metabolic patterns on [18F]FDG PET/CT in patients with unresectable stage III NSCLC undergoing chemoradiotherapy ± durvalumab maintenance treatment.

PURPOSE: In patients with unresectable stage III non-small-cell lung cancer (NSCLC), durvalumab maintenance treatment after chemoradiotherapy (CRT) significantly improves survival. So far, however, metabolic changes of tumoral lesions and secondary lymphoid organs under durvalumab are unknown. Hence, we assessed changes on [18F]FDG PET/CT in comparison to patients undergoing CRT alone. METHODS: Forty-three patients with [18F]FDG PET/CT both before and after standard CRT for unresectable stage III NSCLC were included, in 16/43 patients durvalumab maintenance treatment was initiated (CRT-IO) prior to the second PET/CT. Uptake of tumor sites and secondary lymphoid organs was compared between CRT and CRT-IO. Also, readers were blinded for durvalumab administration and reviewed scans for findings suspicious for immunotherapy-related adverse events (irAE). RESULTS: Initial uptake characteristics were comparable. However, under durvalumab, diverging metabolic patterns were noted: There was a significantly higher reduction of tumoral uptake intensity in CRT-IO compared to CRT, e.g. median decrease of SUVmax -70.0% vs. -24.8%, p = 0.009. In contrast, the spleen uptake increased in CRT-IO while it dropped in CRT (median + 12.5% vs. -4.4%, p = 0.029). Overall survival was significantly longer in CRT-IO compared to CRT with few events (progression/death) noted in CRT-IO. Findings suggestive of irAE were present on PET/CT more often in CRT-IO (12/16) compared to CRT (8/27 patients), p = 0.005. CONCLUSION: Durvalumab maintenance treatment after CRT leads to diverging tumoral metabolic changes, but also increases splenic metabolism and leads to a higher proportion of findings suggestive of irAE compared to patients without durvalumab. Due to significantly prolonged survival with durvalumab, survival analysis will be substantiated in correlation to metabolic changes as soon as more clinical events are present.

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.

Next-generation PET/CT imaging in meningioma-first clinical experiences using the novel SSTR-targeting peptide [18F]SiTATE.

BACKGROUND: Somatostatin-receptor (SSTR)-targeted PET/CT provides important clinical information in addition to standard imaging in meningioma patients. [18F]SiTATE is a novel, 18F-labeled SSTR-targeting peptide with superior imaging properties according to preliminary data. We provide the first [18F]SiTATE PET/CT data of a large cohort of meningioma patients. METHODS: Patients with known or suspected meningioma undergoing [18F]SiTATE PET/CT were included. Uptake intensity (SUV) of meningiomas, non-meningioma lesions, and healthy organs were assessed using a 50% isocontour volume of interest (VOI) or a spherical VOI, respectively. Also, trans-osseous extension on PET/CT was assessed. RESULTS: A total of 107 patients with 117 [18F]SiTATE PET/CT scans were included. Overall, 231 meningioma lesions and 61 non-meningioma lesions (e.g., post-therapeutic changes) were analyzed. Physiological uptake was lowest in healthy brain tissue, followed by bone marrow, parotid, and pituitary (SUVmean 0.06 ± 0.04 vs. 1.4 ± 0.9 vs. 1.6 ± 1.0 vs. 9.8 ± 4.6; p < 0.001). Meningiomas showed significantly higher uptake than non-meningioma lesions (SUVmax 11.6 ± 10.6 vs. 4.0 ± 3.3, p < 0.001). Meningiomas showed significantly higher uptake than non-meningioma lesions (SUVmax 11.6±10.6 vs. 4.0±3.3, p<0.001). 93/231 (40.3%) meningiomas showed partial trans-osseous extension and 34/231 (14.7%) predominant intra-osseous extension. 59/231 (25.6%) meningioma lesions found on PET/CT had not been reported on previous standard imaging. CONCLUSION: This is the first PET/CT study using an 18F-labeled SSTR-ligand in meningioma patients: [18F]SiTATE provides extraordinary contrast in meningioma compared to healthy tissue and non-meningioma lesions, which leads to a high detection rate of so far unknown meningioma sites and osseous involvement. Having in mind the advantageous logistic features of 18F-labeled compared to 68Ga-labeled compounds (e.g., longer half-life and large-badge production), [18F]SiTATE has the potential to foster a widespread use of SSTR-targeted imaging in neuro-oncology.

Treatment of metastatic alveolar soft part sarcoma with axitinib and pembrolizumab in an 80-year-old patient with a history of autoimmune disorders.

Alveolar soft part sarcoma (ASPS) is a rare malignancy with low sensitivity to chemotherapy. While localized ASPS has a very good prognosis after resection, the 5-year overall survival rate drops substantially in metastatic disease. We report the case of an 80-year-old male patient with ASPS of the left elbow and metastasis to the lung, lymph nodes and peritoneum. After weighing the benefits and risks, systemic treatment with the anti-PD-1 checkpoint inhibitor pembrolizumab combined with the vascular endothelial growth factor receptor tyrosinkinase inhibitor axitinib was initiated in this patient with a history of psoriasis and Crohn's disease. After only two cycles of therapy, a significant size reduction of the nodal cervical metastasis became apparent. A partial response of all metastases was then confirmed in the first computed tomography restaging. So far, side effects have remained manageable, especially with regard to the development or worsening of autoimmune adverse events. The patient continued to have a high quality of life, while also remaining in ongoing partial response for 15 months at the time of submission. While sarcomas generally have low sensitivity to immunotherapies, ASPS is an exception, and checkpoint inhibition is an integral part of its systemic therapy.

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.

Increased visceral fat distribution and body composition impact cytokine release syndrome onset and severity after CD19 chimeric antigen receptor T-cell therapy in advanced B-cell malignancies.

Chimeric antigen receptor T-cell (CAR-T) therapy is associated with a distinct toxicity profile that includes cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). CRS is characterized by the release of pro-inflammatory cytokines such as interleukin 6 (IL-6) and is closely linked to CAR-T expansion and bystander cells like monocytes/macrophages. In other hyperinflammatory states, obesity contributes to inflammatory cascades and acts as a risk factor for disease severity. We aimed to study the influence of anthropometric and body composition (BC) measurements on CAR-T-related immunotoxicity in 64 patients receiving CD19-directed CAR-T for relapsed/refractory Bcell malignancies. Patients with grade ≥2 CRS presented with a significantly higher median body mass index (BMI), waist circumference, waist-to-height ratio (WtHR) and visceral adipose tissue (VAT). These parameters were also found to be associated with an earlier CRS onset. Other adipose deposits and muscle mass did not differ between patients with grade 0-1 CRS versus grade ≥2 CRS. Moreover, BC parameters did not influence ICANS severity or onset. In a multivariate binary logistic regression incorporating known risk factors of immunotoxicity, the factors BMI, waist circumference, WtHR and VAT increased the probability of grade ≥2 CRS. Receiver operating characteristic analyses were utilized to determine optimal discriminatory thresholds for these parameters. Patients above these thresholds displayed markedly increased peak IL-6 levels. Our data imply that increased body composition and VAT in particular represent an additional risk factor for severe and early CRS. These findings carry implications for risk-stratification prior to CD19 CAR-T and may be integrated into established risk models.

Differential role of residual metabolic tumor volume in inoperable stage III NSCLC after chemoradiotherapy ± immune checkpoint inhibition.

BACKGROUND: The PET-derived metabolic tumor volume (MTV) is an independent prognosticator in non-small cell lung cancer (NSCLC) patients. We analyzed the prognostic value of residual MTV (rMTV) after completion of chemoradiotherapy (CRT) in inoperable stage III NSCLC patients with and without immune checkpoint inhibition (ICI). METHODS: Fifty-six inoperable stage III NSCLC patients (16 female, median 65.0 years) underwent 18F-FDG PET/CT after completion of standard CRT. rMTV was delineated on 18F-FDG PET/CT using a standard threshold (liver SUVmean + 2 × standard deviation). 21/56 patients underwent additional ICI (CRT-IO, 21/56 patients) thereafter. Patients were divided in volumetric subgroups using median split dichotomization (MTV ≤ 4.3 ml vs. > 4.3 ml). rMTV, clinical features, and ICI-application were correlated with clinical outcome parameters (progression-free survival (PFS), local PFS (LPFS), and overall survival (OS). RESULTS: Overall, median follow-up was 52.0 months. Smaller rMTV was associated with longer median PFS (29.3 vs. 10.5 months, p = 0.015), LPFS (49.9 vs. 13.5 months, p = 0.001), and OS (63.0 vs. 23.0 months, p = 0.003). CRT-IO patients compared to CRT patients showed significantly longer median PFS (29.3 vs. 11.2 months, p = 0.034), LPFS (median not reached vs. 14.0 months, p = 0.016), and OS (median not reached vs. 25.2 months, p = 0.007). In the CRT subgroup, smaller rMTV was associated with longer median PFS (33.5 vs. 8.6 months, p = 0.001), LPFS (49.9 vs. 10.1 months, p = 0.001), and OS (63.0 vs. 16.3 months, p = 0.004). In the CRT-IO subgroup, neither PFS, LPFS, nor OS were associated with MTV (p > 0.05 each). The findings were confirmed in subsequent multivariate analyses. CONCLUSION: In stage III NSCLC, smaller rMTV is highly associated with superior clinical outcome, especially in patients undergoing CRT without ICI. Patients with CRT-IO show significantly improved outcome compared to CRT patients. Of note, clinical outcome in CRT-IO patients is independent of residual MTV. Hence, even patients with large rMTV might profit from ICI despite extensive tumor load.

Economic potential of abbreviated breast MRI for screening women with dense breast tissue for breast cancer.

OBJECTIVES: Abbreviated breast MRI (AB-MRI) was introduced to reduce both examination and image reading times and to improve cost-effectiveness of breast cancer screening. The aim of this model-based economic study was to analyze the cost-effectiveness of full protocol breast MRI (FB-MRI) vs. AB-MRI in screening women with dense breast tissue for breast cancer. METHODS: Decision analysis and a Markov model were designed to model the cumulative costs and effects of biennial screening in terms of quality-adjusted life years (QALYs) from a US healthcare system perspective. Model input parameters for a cohort of women with dense breast tissue were adopted from recent literature. The impact of varying AB-MRI costs per examination as well as specificity on the resulting cost-effectiveness was modeled within deterministic sensitivity analyses. RESULTS: At an assumed cost per examination of $ 263 for AB-MRI (84% of the cost of a FB-MRI examination), the discounted cumulative costs of both MR-based strategies accounted comparably. Reducing the costs of AB-MRI below $ 259 (82% of the cost of a FB-MRI examination, respectively), the incremental cost-effectiveness ratio of FB-MRI exceeded the willingness to pay threshold and the AB-MRI-strategy should be considered preferable in terms of cost-effectiveness. CONCLUSIONS: Our preliminary findings indicate that AB-MRI may be considered cost-effective compared to FB-MRI for screening women with dense breast tissue for breast cancer, as long as the costs per examination do not exceed 82% of the cost of a FB-MRI examination. KEY POINTS: • Cost-effectiveness of abbreviated breast MRI is affected by reductions in specificity and resulting false positive findings and increased recall rates. • Abbreviated breast MRI may be cost-effective up to a cost per examination of 82% of the cost of a full protocol examination. • Abbreviated breast MRI could be an economically preferable alternative to full protocol breast MRI in screening women with dense breast tissue.

Cost-effectiveness of short-protocol emergency brain MRI after negative non-contrast CT for minor stroke detection.

OBJECTIVES: To investigate the cost-effectiveness of supplemental short-protocol brain MRI after negative non-contrast CT for the detection of minor strokes in emergency patients with mild and unspecific neurological symptoms. METHODS: The economic evaluation was centered around a prospective single-center diagnostic accuracy study validating the use of short-protocol brain MRI in the emergency setting. A decision-analytic Markov model distinguished the strategies "no additional imaging" and "additional short-protocol MRI" for evaluation. Minor stroke was assumed to be missed in the initial evaluation in 40% of patients without short-protocol MRI. Specialized post-stroke care with immediate secondary prophylaxis was assumed for patients with detected minor stroke. Utilities and quality-of-life measures were estimated as quality-adjusted life years (QALYs). Input parameters were obtained from the literature. The Markov model simulated a follow-up period of up to 30 years. Willingness to pay was set to $100,000 per QALY. Cost-effectiveness was calculated and deterministic and probabilistic sensitivity analysis was performed. RESULTS: Additional short-protocol MRI was the dominant strategy with overall costs of $26,304 (CT only: $27,109). Cumulative calculated effectiveness in the CT-only group was 14.25 QALYs (short-protocol MRI group: 14.31 QALYs). In the deterministic sensitivity analysis, additional short-protocol MRI remained the dominant strategy in all investigated ranges. Probabilistic sensitivity analysis results from the base case analysis were confirmed, and additional short-protocol MRI resulted in lower costs and higher effectiveness. CONCLUSION: Additional short-protocol MRI in emergency patients with mild and unspecific neurological symptoms enables timely secondary prophylaxis through detection of minor strokes, resulting in lower costs and higher cumulative QALYs. KEY POINTS: • Short-protocol brain MRI after negative head CT in selected emergency patients with mild and unspecific neurological symptoms allows for timely detection of minor strokes. • This strategy supports clinical decision-making with regard to immediate initiation of secondary prophylactic treatment, potentially preventing subsequent major strokes with associated high costs and reduced QALY. • According to the Markov model, additional short-protocol MRI remained the dominant strategy over wide variations of input parameters, even when assuming disproportionally high costs of the supplemental MRI scan.