The tourniquet's effects on skeletal muscle during total knee arthroplasty.

This study investigates the impact of perioperative tourniquet on skeletal muscle cells during total knee arthroplasty (TKA) and its effects on the gene expression of apoptotic, inflammatory, and angiogenic pathways. The randomized controlled trial included 44 patients undergoing TKA. The patients were randomized to undergo surgery with (n = 23) or without (n = 21) tourniquet. The tourniquet was inflated before skin incision and deflated before wound closure in the tourniquet group. Biopsies from the lateral vastus muscle were obtained from both groups before wound closure and 8 weeks after surgery. The messenger ribonucleic acid (mRNA) expression and protein levels of angiopoietin-like 4 (ANGPTL4), Hypoxia-inducible Factor 1α, and Vascular Endothelial Growth Factor Alpha (VEGF-A) in the biopsies were examined by reverse transcription-quantitative polymerase chain reaction and tissue microarray, respectively. Differences in mean values (ΔCt for mRNA expression and staining positivity for protein expression) were compared with t-tests. The apoptotic marker BID and the angiogenic marker VEGF-A were significantly lower in the tourniquet group compared to the control group (p = 0.03, p = 0.047). However, there was a significant upregulation of VEGF-A 8 weeks after surgery in the tourniquet group compared to perioperative biopsies (p = 0.002), indicating persistent changes. A significant upregulation in protein expression of the angiogenic marker ANGPTL4 was found perioperatively in the tourniquet group (p = 0.02). Our results demonstrate that the angiogenic gene expression is significantly altered by the tourniquet, the effects of which might contribute to postoperative interstitial edema, increased pain, and decreased muscle strength. These effects could lead to delayed rehabilitation and ultimately reduced patient satisfaction after TKA.

Surgical approach had minor association with femoral stem migration in total hip arthroplasty: radiostereometric analysis of 61 patients after 5-year follow-up.

BACKGROUND AND PURPOSE: Total hip arthroplasty (THA) is usually performed using 1 of 3 surgical approaches: direct lateral (DLA), posterior (PA), or anterior (AA). AA is different from DLA and PA owing to limited intraoperative visibility of the femoral canal. This could affect stem positioning and therefore migration. We aimed to perform an exploratory radiostereometric analysis (RSA) study with 3 groups for surgical approach assessing stem migration up to 5 years postoperatively. PATIENTS AND METHODS: 61 patients with unilateral osteoarthritis of the hip were included. 21 patients were allocated to the DLA, 20 to the PA, and 20 to the AA group. All patients received an uncemented, collarless, double-tapered, fully hydroxyapatite-coated Profemur Gladiator stem. Migration was measured with model-based RSA. Baseline RSA was on day 1 postoperatively. The follow-ups were at day 8, at 5 weeks, and at 3, 6, 12, 24, and 60 months after surgery. Generalized linear mixed models were used to analyze maximum total point motion (MTPM) migrations. RESULTS: Group mean differences in MTPM were 0.4 mm (95% confidence interval [CI] -1.5 to 2.4) for DLA vs. PA, 1.1 mm (CI -1.0 to 3.3) for AA vs. DLA, and 1.6 mm (CI -0.8 to 3.9) for AA vs. PA, when adjusted for sex and age as covariates. 2 stems in the AA group had excessive early migration. For all stems the migrations occurred mainly within 5-week follow-up and then stabilized. CONCLUSION: At 5-year follow-up, there were no statistically significant differences in stem migration associated with the 3 surgical approaches used in this study.

The extent of first-time THA revision is not associated with patient-reported outcomes at 1-year follow-up: a study of 426 aseptic revisions.

BACKGROUND AND PURPOSE: Studies evaluating pain and patient-reported outcome measures (PROMs) related to type of revision total hip arthroplasty (rTHA) are sparse. Our aim was to compare pain, physical function, quality of life, and patient satisfaction among different types of aseptic rTHA at 1-year follow-up. PATIENTS AND METHODS: We performed a retrospective study from an institutional registry with 426 primary THAs scheduled for rTHA in a fast-track setting between 2012 and 2021. Revisions were grouped by 4 types of surgery: head and/or liner exchange, cup revision, stem revision, and cup and stem revision. Pain during mobilization and at rest (NRS 0-10), physical function (HOOS-PS and HHS) and health-related quality of life (EQ-5D) were registered preoperatively, at 3 months, and 1 year postoperatively. Patient satisfaction was surveyed at the 1-year follow-up by 2 questions related to hip function and willingness to undergo the same surgery. RESULTS: With a response rate of 85%, all outcomes improved in the 4 groups but there were neither statistical nor clinical differences between types of rTHA at 1-year follow-up. NRS pain during mobilization improved overall by 2.7 (95% confidence interval 2.3-3.1) until 1-year follow-up, both being statistically significant and clinically relevant. The improvements were mainly seen at the 3-month follow-up, with minor progress observed at 1 year. About 80% reported improved hip function and willingness to undergo the surgery again at the 1-year follow-up. CONCLUSION: Significant improvements in NRS pain and PROMS were found in all groups after rTHA, with no group differences at 1 year. This is relevant preoperative information for both clinicians and patients eligible for rTHA.

Meta-Analysis of the Test-Retest Repeatability of [18F]-Fluorodeoxyglucose Standardized Uptake Values: Implications for Assessment of Tumor Response.

PURPOSE: Currently, guidelines for PET with 18F-fluorodeoxyglucose (FDG-PET) interpretation for assessment of therapy response in oncology primarily involve visual evaluation of FDG-PET/CT scans. However, quantitative measurements of the metabolic activity in tumors may be even more useful in evaluating response to treatment. Guidelines based on such measurements, including the European Organization for Research and Treatment of Cancer Criteria and PET Response Criteria in Solid Tumors, have been proposed. However, more rigorous analysis of response criteria based on FDG-PET measurements is needed to adopt regular use in practice. EXPERIMENTAL DESIGN: Well-defined boundaries of repeatability and reproducibility of quantitative measurements to discriminate noise from true signal changes are a needed initial step. An extension of the meta-analysis from de Langen and colleagues (2012) of the test-retest repeatability of quantitative FDG-PET measurements, including mean, maximum, and peak standardized uptake values (SUVmax, SUVmean, and SUVpeak, respectively), was performed. Data from 11 studies in the literature were used to estimate the relationship between the variance in test-retest measurements with uptake level and various study-level, patient-level, and lesion-level characteristics. RESULTS: Test-retest repeatability of percentage fluctuations for all three types of SUV measurement (max, mean, and peak) improved with higher FDG uptake levels. Repeatability in all three SUV measurements varied for different lesion locations. Worse repeatability in SUVmean was also associated with higher tumor volumes. CONCLUSIONS: On the basis of these results, recommendations regarding SUV measurements for assessing minimal detectable changes based on repeatability and reproducibility are proposed. These should be applied to differentiate between response categories for a future set of FDG-PET-based criteria that assess clinically significant changes in tumor response.

[89Zr]Zr-DFO-girentuximab and [18F]FDG PET/CT to Predict Watchful Waiting Duration in Patients with Metastatic Clear-cell Renal Cell Carcinoma.

PURPOSE: Watchful waiting (WW) can be considered for patients with metastatic clear-cell renal cell carcinoma (mccRCC) with good or intermediate prognosis, especially those with <2 International Metastatic RCC Database Consortium criteria and ≤2 metastatic sites [referred to as watch and wait ("W&W") criteria]. The IMaging PAtients for Cancer drug SelecTion-Renal Cell Carcinoma study objective was to assess the predictive value of [18F]FDG PET/CT and [89Zr]Zr-DFO-girentuximab PET/CT for WW duration in patients with mccRCC. EXPERIMENTAL DESIGN: Between February 2015 and March 2018, 48 patients were enrolled, including 40 evaluable patients with good (n = 14) and intermediate (n = 26) prognosis. Baseline contrast-enhanced CT, [18F]FDG and [89Zr]Zr-DFO-girentuximab PET/CT were performed. Primary endpoint was the time to disease progression warranting systemic treatment. Maximum standardized uptake values (SUVmax) were measured using lesions on CT images coregistered to PET/CT. High and low uptake groups were defined on the basis of median geometric mean SUVmax of RECIST-measurable lesions across patients. RESULTS: The median WW time was 16.1 months [95% confidence interval (CI): 9.0-31.7]. The median WW period was shorter in patients with high [18F]FDG tumor uptake than those with low uptake (9.0 vs. 36.2 months; HR, 5.6; 95% CI: 2.4-14.7; P < 0.001). Patients with high [89Zr]Zr-DFO-girentuximab tumor uptake had a median WW period of 9.3 versus 21.3 months with low uptake (HR, 1.7; 95% CI: 0.9-3.3; P = 0.13). Patients with "W&W criteria" had a longer median WW period of 21.3 compared with patients without: 9.3 months (HR, 1.9; 95% CI: 0.9-3.9; Pone-sided = 0.034). Adding [18F]FDG uptake to the "W&W criteria" improved the prediction of WW duration (P < 0.001); whereas [89Zr]Zr-DFO-girentuximab did not (P = 0.53). CONCLUSIONS: In patients with good- or intermediate-risk mccRCC, low [18F]FDG uptake is associated with prolonged WW. This study shows the predictive value of the "W&W criteria" for WW duration and shows the potential of [18F]FDG-PET/CT to further improve this.

Baseline radiomics features and MYC rearrangement status predict progression in aggressive B-cell lymphoma.

We investigated whether the outcome prediction of patients with aggressive B-cell lymphoma can be improved by combining clinical, molecular genotype, and radiomics features. MYC, BCL2, and BCL6 rearrangements were assessed using fluorescence in situ hybridization. Seventeen radiomics features were extracted from the baseline positron emission tomography-computed tomography of 323 patients, which included maximum standardized uptake value (SUVmax), SUVpeak, SUVmean, metabolic tumor volume (MTV), total lesion glycolysis, and 12 dissemination features pertaining to distance, differences in uptake and volume between lesions, respectively. Logistic regression with backward feature selection was used to predict progression after 2 years. The predictive value of (1) International Prognostic Index (IPI); (2) IPI plus MYC; (3) IPI, MYC, and MTV; (4) radiomics; and (5) MYC plus radiomics models were tested using the cross-validated area under the curve (CV-AUC) and positive predictive values (PPVs). IPI yielded a CV-AUC of 0.65 ± 0.07 with a PPV of 29.6%. The IPI plus MYC model yielded a CV-AUC of 0.68 ± 0.08. IPI, MYC, and MTV yielded a CV-AUC of 0.74 ± 0.08. The highest model performance of the radiomics model was observed for MTV combined with the maximum distance between the largest lesion and another lesion, the maximum difference in SUVpeak between 2 lesions, and the sum of distances between all lesions, yielding an improved CV-AUC of 0.77 ± 0.07. The same radiomics features were retained when adding MYC (CV-AUC, 0.77 ± 0.07). PPV was highest for the MYC plus radiomics model (50.0%) and increased by 20% compared with the IPI (29.6%). Adding radiomics features improved model performance and PPV and can, therefore, aid in identifying poor prognosis patients.

Higher Dissatisfaction Rate Following Revision Compared With Primary Total Knee Arthroplasty: 1-Year Follow-up of 2151 Primary and 235 Aseptic Revision Surgeries.

Postoperative patient satisfaction is related to preoperative expectations. Information regarding expected results following surgery is therefore important. This study evaluated patient-reported outcome measures (PROMs) and patient satisfaction up to 1 year after primary and aseptic revision total knee arthroplasty (TKA). The study included 2151 primary and 235 aseptic revision TKA surgeries conducted between 2010 and 2018. Pain, Knee Injury and Osteoarthritis Outcome Score-Physical Function-Short Form and European Quality of Life-5 Dimension surveys were recorded preoperatively and at 8 weeks and 1 year. To determine satisfaction, patients were asked to rate their knee function compared with that before surgery and to answer whether they would undergo the surgery again given their current knowledge. Patients who had primary TKA improved in all PROMs in each follow-up up to 1 year, whereas patients who had revision TKA showed improvement at 8 weeks with no further improvement at 1 year. In terms of patient satisfaction, 88% of patients in the primary TKA group reported better knee function, and 87% were willing to have the surgery again at 1 year; the proportions were lower for patients who underwent revision TKA (66% and 68%, respectively). Aseptic revision TKA demonstrates inferior PROMs compared with those of primary TKA 1 year after surgery, and more than 30% of the patients who underwent revision TKA stated that they would not have their TKA revised or were uncertain, given the outcome of the procedure. Thus, patients who are candidates for revision TKA should be informed to expect less of an improvement following revision surgery than with the primary TKA. Our findings can facilitate the shared decision-making process by surgeons and patients based on realistic expectations of surgical outcomes. [Orthopedics. 2023;46(1):e52-e57.].

The indication for aseptic revision TKA does not influence 1-year outcomes: an analysis of 178 full TKA revisions from a prospective institutional registry.

BACKGROUND AND PURPOSE: Outcomes following revision total knee arthroplasty (TKA) may depend on the indication for revision surgery. We compared pain, patient-reported outcome measures (PROMs), and patient satisfaction among different indications for an aseptic TKA revision. PATIENTS AND METHODS: This was a retrospective study of prospective data from an institutional registry of 178 primary TKAs revised between 2012 and 2020. Patients were grouped by the main reason for their revision: loosening, malposition, instability, or stiffness. Pain during mobilization and at rest (NRS 0-10), physical function (KOOS-PS and KSS), and quality of life (EQ-5D) were surveyed preoperatively and at 2 months and 1 year postoperatively. Patient satisfaction was evaluated through questions related to knee function and their willingness to undergo the same surgery again at 1-year follow-up. RESULTS: Pain and PROMs improved in all groups and did not differ statistically significantly between the 4 groups at 1-year follow-up, but equivalence for pain was not confirmed between groups. Overall, pain during mobilization improved by 2.4 (95% CI 1.9-3.0) at 1-year follow-up, which was both clinically and statistically significant. Improvements were seen within 2 months of surgery, with no further improvements seen 1 year postoperatively. Approximately 2/3 of patients reported that their knee function had improved and would undergo the same surgery again, at 1-year follow-up. CONCLUSION: Statistically significant and clinically relevant improvements in pain and PROMs were seen in all 4 revision groups 1 year after revision TKA. These results may assist clinicians and patients during preoperative counselling.

The best of both worlds: Combining population genetic and quantitative genetic models.

Numerous traits under migration-selection balance are shown to exhibit complex patterns of genetic architecture with large variance in effect sizes. However, the conditions under which such genetic architectures are stable have yet to be investigated, because studying the influence of a large number of small allelic effects on the maintenance of spatial polymorphism is mathematically challenging, due to the high complexity of the systems that arise. In particular, in the most simple case of a haploid population in a two-patch environment, while it is known from population genetics that polymorphism at a single major-effect locus is stable in the symmetric case, there exist no analytical predictions on how this polymorphism holds when a polygenic background also contributes to the trait. Here we propose to answer this question by introducing a new eco-evo methodology that allows us to take into account the combined contributions of a major-effect locus and of a quantitative background resulting from small-effect loci, where inheritance is encoded according to an extension to the infinitesimal model. In a regime of small variance contributed by the quantitative loci, we justify that traits are concentrated around the major alleles, according to a normal distribution, using new convex analysis arguments. This allows a reduction in the complexity of the system using a separation of time scales approach. We predict an undocumented phenomenon of loss of polymorphism at the major-effect locus despite strong selection for local adaptation, because the quantitative background slowly disrupts the rapidly established polymorphism at the major-effect locus, which is confirmed by individual-based simulations. Our study highlights how segregation of a quantitative background can greatly impact the dynamics of major-effect loci by provoking migrational meltdowns. We also provide a comprehensive toolbox designed to describe how to apply our method to more complex population genetic models.

Comparing lesion and feature selections to predict progression in newly diagnosed DLBCL patients with FDG PET/CT radiomics features.

PURPOSE: Biomarkers that can accurately predict outcome in DLBCL patients are urgently needed. Radiomics features extracted from baseline [18F]-FDG PET/CT scans have shown promising results. This study aims to investigate which lesion- and feature-selection approaches/methods resulted in the best prediction of progression after 2 years. METHODS: A total of 296 patients were included. 485 radiomics features (n = 5 conventional PET, n = 22 morphology, n = 50 intensity, n = 408 texture) were extracted for all individual lesions and at patient level, where all lesions were aggregated into one VOI. 18 features quantifying dissemination were extracted at patient level. Several lesion selection approaches were tested (largest or hottest lesion, patient level [all with/without dissemination], maximum or median of all lesions) and compared to the predictive value of our previously published model. Several data reduction methods were applied (principal component analysis, recursive feature elimination (RFE), factor analysis, and univariate selection). The predictive value of all models was tested using a fivefold cross-validation approach with 50 repeats with and without oversampling, yielding the mean cross-validated AUC (CV-AUC). Additionally, the relative importance of individual radiomics features was determined. RESULTS: Models with conventional PET and dissemination features showed the highest predictive value (CV-AUC: 0.72-0.75). Dissemination features had the highest relative importance in these models. No lesion selection approach showed significantly higher predictive value compared to our previous model. Oversampling combined with RFE resulted in highest CV-AUCs. CONCLUSION: Regardless of the applied lesion selection or feature selection approach and feature reduction methods, patient level conventional PET features and dissemination features have the highest predictive value. Trial registration number and date: EudraCT: 2006-005174-42, 01-08-2008.

Convolutional neural networks for automatic image quality control and EARL compliance of PET images.

BACKGROUND: Machine learning studies require a large number of images often obtained on different PET scanners. When merging these images, the use of harmonized images following EARL-standards is essential. However, when including retrospective images, EARL accreditation might not have been in place. The aim of this study was to develop a convolutional neural network (CNN) that can identify retrospectively if an image is EARL compliant and if it is meeting older or newer EARL-standards. MATERIALS AND METHODS: 96 PET images acquired on three PET/CT systems were included in the study. All images were reconstructed with the locally clinically preferred, EARL1, and EARL2 compliant reconstruction protocols. After image pre-processing, one CNN was trained to separate clinical and EARL compliant reconstructions. A second CNN was optimized to identify EARL1 and EARL2 compliant images. The accuracy of both CNNs was assessed using fivefold cross-validation. The CNNs were validated on 24 images acquired on a PET scanner not included in the training data. To assess the impact of image noise on the CNN decision, the 24 images were reconstructed with different scan durations. RESULTS: In the cross-validation, the first CNN classified all images correctly. When identifying EARL1 and EARL2 compliant images, the second CNN identified 100% EARL1 compliant and 85% EARL2 compliant images correctly. The accuracy in the independent dataset was comparable to the cross-validation accuracy. The scan duration had almost no impact on the results. CONCLUSION: The two CNNs trained in this study can be used to retrospectively include images in a multi-center setting by, e.g., adding additional smoothing. This method is especially important for machine learning studies where the harmonization of images from different PET systems is essential.

Dual time point imaging in locally advanced head and neck cancer to assess residual nodal disease after chemoradiotherapy.

BACKGROUND: FDG-PET/CT has a high negative predictive value to detect residual nodal disease in patients with locally advanced squamous cell head and neck cancer after completing concurrent chemoradiotherapy (CCRT). However, the positive predictive value remains suboptimal due to inflammation after radiotherapy, generating unnecessary further investigations and possibly even surgery. We report the results of a preplanned secondary end point of the ECLYPS study regarding the potential advantages of dual time point FDG-PET/CT imaging (DTPI) in this setting. Standardized dedicated head and neck FDG-PET/CT images were obtained 12 weeks after CCRT at 60 and 120 min after tracer administration. We performed a semiquantitative assessment of lymph nodes, and the retention index (RI) was explored to optimize diagnostic performance. The reference standard was histology, negative FDG-PET/CT at 1 year, or > 2 years of clinical follow-up. The time-dependent area under the receiver operator characteristics (AUROC) curves was calculated. RESULTS: In total, 102 subjects were eligible for analysis. SUV values increased in malignant nodes (median SUV1 = 2.6 vs. SUV2 = 2.7; P = 0.04) but not in benign nodes (median SUV1 = 1.8 vs. SUV2 = 1.7; P = 0.28). In benign nodes, RI was negative although highly variable (median RI = - 2.6; IQR 21.2), while in malignant nodes RI was positive (median RI = 12.3; IQR 37.2) and significantly higher (P = 0.018) compared to benign nodes. A combined threshold (SUV1 ≥ 2.2 + RI ≥ 3%) significantly reduced the amount of false-positive cases by 53% (P = 0.02) resulting in an increased specificity (90.8% vs. 80.5%) and PPV (52.9% vs. 37.0%), while sensitivity (60.0% vs. 66.7%) and NPV remained comparably high (92.9% vs. 93.3%). However, AUROC, as overall measure of benefit in diagnostic accuracy, did not significantly improve (P = 0.62). In HPV-related disease (n = 32), there was no significant difference between SUV1, SUV2, and RI in malignant and benign nodes, yet this subgroup was small. CONCLUSIONS: DTPI did not improve the overall diagnostic accuracy of FDG-PET/CT to detect residual disease 12 weeks after chemoradiation. Due to differences in tracer kinetics between malignant and benign nodes, DTPI improved the specificity, but at the expense of a loss in sensitivity, albeit minimal. Since false negatives at the 12 weeks PET/CT are mainly due to minimal residual disease, DTPI is not able to significantly improve sensitivity, but repeat scanning at a later time (e.g. after 12 months) could possibly solve this problem. Further study is required in HPV-associated disease.

Proposed New Dynamic Prognostic Index for Diffuse Large B-Cell Lymphoma: International Metabolic Prognostic Index.

PURPOSE: Baseline metabolic tumor volume (MTV) is a promising biomarker in diffuse large B-cell lymphoma (DLBCL). Our aims were to determine the best statistical relationship between MTV and survival and to compare MTV with the International Prognostic Index (IPI) and its individual components to derive the best prognostic model. METHODS: PET scans and clinical data were included from five published studies in newly diagnosed diffuse large B-cell lymphoma. Transformations of MTV were compared with the primary end points of 3-year progression-free survival (PFS) and overall survival (OS) to derive the best relationship for further analyses. MTV was compared with IPI categories and individual components to derive the best model. Patients were grouped into three groups for survival analysis using Kaplan-Meier analysis; 10% at highest risk, 30% intermediate risk, and 60% lowest risk, corresponding with expected clinical outcome. Validation of the best model was performed using four studies as a test set and the fifth study for validation and repeated five times. RESULTS: The best relationship for MTV and survival was a linear spline model with one knot located at the median MTV value of 307.9 cm3. MTV was a better predictor than IPI for PFS and OS. The best model combined MTV with age as continuous variables and individual stage as I-IV. The MTV-age-stage model performed better than IPI and was also better at defining a high-risk group (3-year PFS 46.3% v 58.0% and 3-year OS 51.5% v 66.4% for the new model and IPI, respectively). A regression formula was derived to estimate individual patient survival probabilities. CONCLUSION: A new prognostic index is proposed using MTV, age, and stage, which outperforms IPI and enables individualized estimates of patient outcome.

3D Convolutional Neural Network-Based Denoising of Low-Count Whole-Body 18F-Fluorodeoxyglucose and 89Zr-Rituximab PET Scans.

Acquisition time and injected activity of 18F-fluorodeoxyglucose (18F-FDG) PET should ideally be reduced. However, this decreases the signal-to-noise ratio (SNR), which impairs the diagnostic value of these PET scans. In addition, 89Zr-antibody PET is known to have a low SNR. To improve the diagnostic value of these scans, a Convolutional Neural Network (CNN) denoising method is proposed. The aim of this study was therefore to develop CNNs to increase SNR for low-count 18F-FDG and 89Zr-antibody PET. Super-low-count, low-count and full-count 18F-FDG PET scans from 60 primary lung cancer patients and full-count 89Zr-rituximab PET scans from five patients with non-Hodgkin lymphoma were acquired. CNNs were built to capture the features and to denoise the PET scans. Additionally, Gaussian smoothing (GS) and Bilateral filtering (BF) were evaluated. The performance of the denoising approaches was assessed based on the tumour recovery coefficient (TRC), coefficient of variance (COV; level of noise), and a qualitative assessment by two nuclear medicine physicians. The CNNs had a higher TRC and comparable or lower COV to GS and BF and was also the preferred method of the two observers for both 18F-FDG and 89Zr-rituximab PET. The CNNs improved the SNR of low-count 18F-FDG and 89Zr-rituximab PET, with almost similar or better clinical performance than the full-count PET, respectively. Additionally, the CNNs showed better performance than GS and BF.

Patient-reported outcome after primary and aseptic revision hip arthroplasty: 1-year follow-up of 3,559 primary and 406 revision THAs in an institutional registry.

Background and purpose - Patient-reported outcomes (PROMs) after primary total hip arthroplasty (THA) and revision THA are important information in the preoperative shared decision-making process. We present 1-year results on pain, function, and quality of life following primary and revision THA. Patients and methods - From 2010 to 2018, 3,559 primary THA and 406 revision THAs were included in our institutional quality registry. PROMs were registered preoperatively, 3 months, and 1 year after surgery, numeric rating scale (0-10) for pain during mobilization and at rest, healthrelated quality of life (EQ-5D), and a hip-specific physical function score (HOOS-PS). 2 anchor questions were asked 1 year after surgery concerning joint function and willingness to go through surgery again. Results - There were statistically significant improvements in all PROMs at the 3-month follow-up in both groups. All PROMs improved more in the primary group relative to the revision group. 1 year after surgery, pain during mobilization was reduced with a mean change of 5.1 (SD 2.6) for primary THA and 2.9 (SD 3.0) for revision THA. 93% of primary THA patients reported both better function 1 year after surgery and that they would have gone through surgery again, compared with 78% and 79% in the revision THA group. Interpretation - Primary THA patients reported better function and more pain relief than the revision THA group 1 year after surgery. Pain during mobilization shows the most marked improvement in both groups, which is important preoperative information for patients.

The Impact of Semiautomatic Segmentation Methods on Metabolic Tumor Volume, Intensity, and Dissemination Radiomics in 18F-FDG PET Scans of Patients with Classical Hodgkin Lymphoma.

Consensus about a standard segmentation method to derive metabolic tumor volume (MTV) in classical Hodgkin lymphoma (cHL) is lacking, and it is unknown how different segmentation methods influence quantitative PET features. Therefore, we aimed to evaluate the delineation and completeness of lesion selection and the need for manual adaptation with different segmentation methods, and to assess the influence of segmentation methods on the prognostic value of MTV, intensity, and dissemination radiomics features in cHL patients. Methods: We analyzed a total of 105 18F-FDG PET/CT scans from patients with newly diagnosed (n = 35) and relapsed/refractory (n = 70) cHL with 6 segmentation methods: 2 fixed thresholds on SUV4.0 and SUV2.5, 2 relative methods of 41% of SUVmax (41max) and a contrast-corrected 50% of SUVpeak (A50P), and 2 combination majority vote (MV) methods (MV2, MV3). Segmentation quality was assessed by 2 reviewers on the basis of predefined quality criteria: completeness of selection, the need for manual adaptation, and delineation of lesion borders. Correlations and prognostic performance of resulting radiomics features were compared among the methods. Results: SUV4.0 required the least manual adaptation but tended to underestimate MTV and often missed small lesions with low 18F-FDG uptake. SUV2.5 most frequently included all lesions but required minor manual adaptations and generally overestimated MTV. In contrast, few lesions were missed when using 41max, A50P, MV2, and MV3, but these segmentation methods required extensive manual adaptation and overestimated MTV in most cases. MTV and dissemination features significantly differed among the methods. However, correlations among methods were high for MTV and most intensity and dissemination features. There were no significant differences in prognostic performance for all features among the methods. Conclusion: A high correlation existed between MTV, intensity, and most dissemination features derived with the different segmentation methods, and the prognostic performance is similar. Despite frequently missing small lesions with low 18F-FDG avidity, segmentation with a fixed threshold of SUV4.0 required the least manual adaptation, which is critical for future research and implementation in clinical practice. However, the importance of small, low 18F-FDG-avidity lesions should be addressed in a larger cohort of cHL patients.

Quantitative Radiomics Features in Diffuse Large B-Cell Lymphoma: Does Segmentation Method Matter?

Radiomics features may predict outcome in diffuse large B-cell lymphoma (DLBCL). Currently, multiple segmentation methods are used to calculate metabolic tumor volume (MTV). We assessed the influence of segmentation method on the discriminative power of radiomics features in DLBCL at the patient level and for the largest lesion. Methods: Fifty baseline 18F-FDG PET/CT scans of DLBCL patients with progression or relapse within 2 years after diagnosis were matched on uptake time and reconstruction method with 50 baseline PET/CT scans of DLBCL patients without progression. Scans were analyzed using 6 semiautomatic segmentation methods (SUV threshold of 4.0 [SUV4.0], SUV threshold of 2.5, 41% of SUVmax, 50% of SUVpeak, a majority vote segmenting voxels detected by ≥2 methods, and a majority vote segmenting voxels detected by ≥3 methods). On the basis of these segmentations, 490 radiomics features were extracted at the patient level, and 486 features were extracted for the largest lesion. To quantify the agreement between features extracted from different segmentation methods, the intraclass correlation (ICC) agreement was calculated for each method compared with SUV4.0. The feature space was reduced by deleting features that had high Pearson correlations (≥0.7) with the previously established predictors MTV or SUVpeak Model performance was assessed using stratified repeated cross validation with 5 folds and 2,000 repeats, yielding the mean receiver-operating-characteristics curve integral for all segmentation methods using logistic regression with backward feature selection. Results: The percentage of features yielding an ICC of at least 0.75, compared with the SUV4.0 segmentation, was lowest for 50% of SUVpeak both at the patient level and for the largest lesion, with 77.3% and 66.7% of the features yielding an ICC of at least 0.75, respectively. Features did not correlate strongly with MTV, with at least 435 features at the patient level and 409 features for the largest lesion for all segmentation methods having a correlation coefficient of less than 0.7. Features correlated strongly with SUVpeak (at least 190 at patient level and 134 for the largest lesion were uncorrelated to SUVpeak, respectively). Receiver-operating-characteristics curve integrals ranged between 0.69 ± 0.11 and 0.84 ± 0.09 at the patient level and between 0.69 ± 0.11 and 0.73 ± 0.10 at the lesion level. Conclusion: Even though there are differences in the actual radiomics feature values derived and selected features among segmentation methods, there is no substantial difference in the discriminative power of radiomics features among segmentation methods.

Study of 89Zr-Pembrolizumab PET/CT in Patients With Advanced-Stage Non-Small Cell Lung Cancer.

The tumor programmed death ligand 1 (PD-L1) proportion score is the current method for selecting non-small cell lung cancer (NSCLC) patients for single-agent treatment with pembrolizumab, a programmed cell death 1 (PD-1) monoclonal antibody. However, not all patients respond to therapy. Better understanding of in vivo drug behavior may help in the selection of patients who will benefit the most. Methods: NSCLC patients eligible for pembrolizumab monotherapy as first- or later-line therapy were enrolled. Patients received 2 injections of 89Zr-pembrolizumab, 1 without a preceding dose of pembrolizumab and 1 with a preceding dose of 200 mg of pembrolizumab, directly before tracer injection. Up to 4 PET/CT scans were obtained after tracer injection. After imaging acquisition, patients were treated with 200 mg of pembrolizumab every 3 wk. Tumor uptake and tracer biodistribution were visually assessed and quantified as the SUV. Tumor tracer uptake was correlated with PD-1 and PD-L1 expression and response to pembrolizumab treatment. Results: Twelve NSCLC patients were included. One patient experienced grade 3 myalgia after tracer injection. 89Zr-pembrolizumab was observed in the blood pool, liver, and spleen. Tracer uptake was visualized in 47.2% of 72 tumor lesions measuring ΒΧΡ20 mm in the long-axis diameter, and substantial uptake heterogeneity was observed within and between patients. Uptake was higher in patients with a response to pembrolizumab treatment (n = 3) than in patients without a response (n = 9), although this finding was not statistically significant (median SUVpeak, 11.4 vs. 5.7; P = 0.066). No significant correlations were found with PD-L1 or PD-1 immunohistochemistry. Conclusion:89Zr-pembrolizumab injection was safe, with only 1 grade 3 adverse event-possibly immune-related-in 12 patients. 89Zr-pembrolizumab tumor uptake was higher in patients with a response to pembrolizumab treatment but did not correlate with PD-L1 or PD-1 immunohistochemistry.

18F-FDG PET baseline radiomics features improve the prediction of treatment outcome in diffuse large B-cell lymphoma.

PURPOSE: Accurate prognostic markers are urgently needed to identify diffuse large B-Cell lymphoma (DLBCL) patients at high risk of progression or relapse. Our purpose was to investigate the potential added value of baseline radiomics features to the international prognostic index (IPI) in predicting outcome after first-line treatment. METHODS: Three hundred seventeen newly diagnosed DLBCL patients were included. Lesions were delineated using a semi-automated segmentation method (standardized uptake value ≥ 4.0), and 490 radiomics features were extracted. We used logistic regression with backward feature selection to predict 2-year time to progression (TTP). The area under the curve (AUC) of the receiver operator characteristic curve was calculated to assess model performance. High-risk groups were defined based on prevalence of events; diagnostic performance was assessed using positive and negative predictive values. RESULTS: The IPI model yielded an AUC of 0.68. The optimal radiomics model comprised the natural logarithms of metabolic tumor volume (MTV) and of SUVpeak and the maximal distance between the largest lesion and any other lesion (Dmaxbulk, AUC 0.76). Combining radiomics and clinical features showed that a combination of tumor- (MTV, SUVpeak and Dmaxbulk) and patient-related parameters (WHO performance status and age > 60 years) performed best (AUC 0.79). Adding radiomics features to clinical predictors increased PPV with 15%, with more accurate selection of high-risk patients compared to the IPI model (progression at 2-year TTP, 44% vs 28%, respectively). CONCLUSION: Prediction models using baseline radiomics combined with currently used clinical predictors identify patients at risk of relapse at baseline and significantly improved model performance. TRIAL REGISTRATION NUMBER AND DATE: EudraCT: 2006-005,174-42, 01-08-2008.