An automated methodology for whole-body, multimodality tracking of individual cancer lesions.

Objective. Manual analysis of individual cancer lesions to assess disease response is clinically impractical and requires automated lesion tracking methodologies. However, no methodology has been developed for whole-body individual lesion tracking, across an arbitrary number of scans, and acquired with various imaging modalities.Approach. This study introduces a lesion tracking methodology and benchmarked it using 2368Ga-DOTATATE PET/CT and PET/MR images of eight neuroendocrine tumor patients. The methodology consists of six steps: (1) alignment of multiple scans via image registration, (2) body-part labeling, (3) automatic lesion-wise dilation, (4) clustering of lesions based on local lesion shape metrics, (5) assignment of lesion tracks, and (6) output of a lesion graph. Registration performance was evaluated via landmark distance, lesion matching accuracy was evaluated between each image pair, and lesion tracking accuracy was evaluated via identical track ratio. Sensitivity studies were performed to evaluate the impact of lesion dilation (fixed versus automatic dilation), anatomic location, image modalities (inter- versus intra-modality), registration mode (direct versus indirect registration), and track size (number of time-points and lesions) on lesion matching and tracking performance.Main results. Manual contouring yielded 956 lesions, 1570 lesion-matching decisions, and 493 lesion tracks. The median residual registration error was 2.5 mm. The automatic lesion dilation led to 0.90 overall lesion matching accuracy, and an 88% identical track ratio. The methodology is robust regarding anatomic locations, image modalities, and registration modes. The number of scans had a moderate negative impact on the identical track ratio (94% for 2 scans, 91% for 3 scans, and 81% for 4 scans). The number of lesions substantially impacted the identical track ratio (93% for 2 nodes versus 54% for ≥5 nodes).Significance. The developed methodology resulted in high lesion-matching accuracy and enables automated lesion tracking in PET/CT and PET/MR.

Histiocytic Sarcoma Treated with Pembrolizumab: A Case Report and Literature Review.

Histiocytic sarcoma (HS) is a rare hematologic malignancy that has historically been treated with lymphoma-based regimens with a median survival of 6 months. We describe a case of a 51-year-old woman who presented with acute back pain and cord compression. She was diagnosed with HS with diffuse skeletal lesions and high expression of programmed death ligand 1 (PD-L1). She was subsequently treated with chemotherapy plus off-label use of pembrolizumab followed by allogeneic stem cell transplantation. Ultimately, the patient died in the setting of progression of disease 17 months after her stem cell transplantation and 26 months after her diagnosis. This article also presents a literature review of cases of HS treated with programmed death ligand inhibition.

Performance of an automated registration-based method for longitudinal lesion matching and comparison to inter-reader variability.

Objective.Patients with metastatic disease are followed throughout treatment with medical imaging, and accurately assessing changes of individual lesions is critical to properly inform clinical decisions. The goal of this work was to assess the performance of an automated lesion-matching algorithm in comparison to inter-reader variability (IRV) of matching lesions between scans of metastatic cancer patients.Approach.Forty pairs of longitudinal PET/CT and CT scans were collected and organized into four cohorts: lung cancers, head and neck cancers, lymphomas, and advanced cancers. Cases were also divided by cancer burden: low-burden (<10 lesions), intermediate-burden (10-29), and high-burden (30+). Two nuclear medicine physicians conducted independent reviews of each scan-pair and manually matched lesions. Matching differences between readers were assessed to quantify the IRV of lesion matching. The two readers met to form a consensus, which was considered a gold standard and compared against the output of an automated lesion-matching algorithm. IRV and performance of the automated method were quantified using precision, recall, F1-score, and the number of differences.Main results.The performance of the automated method did not differ significantly from IRV for any metric in any cohort (p> 0.05, Wilcoxon paired test). In high-burden cases, the F1-score (median [range]) was 0.89 [0.63, 1.00] between the automated method and reader consensus and 0.93 [0.72, 1.00] between readers. In low-burden cases, F1-scores were 1.00 [0.40, 1.00] and 1.00 [0.40, 1.00], for the automated method and IRV, respectively. Automated matching was significantly more efficient than either reader (p< 0.001). In high-burden cases, median matching time for the readers was 60 and 30 min, respectively, while automated matching took a median of 3.9 minSignificance.The automated lesion-matching algorithm was successful in performing lesion matching, meeting the benchmark of IRV. Automated lesion matching can significantly expedite and improve the consistency of longitudinal lesion-matching.

Effect of intraoperative treatment options on hip joint stability following total hip arthroplasty.

Dislocation remains the leading indication for revision of total hip arthroplasty (THA). The objective of this study was to use a computational model to compare the overall resistance to both anterior and posterior dislocation for the available THA constructs commonly considered by surgeons attempting to produce a stable joint. Patient-specific musculoskeletal models of THA patients performing activities consistent with anterior and posterior dislocation were developed to calculate joint contact forces and joint positions used for simulations of dislocation in a finite element model of the implanted hip that included an experimentally calibrated hip capsule representation. Dislocations were then performed with consideration of offset using +5 and +9 offset, iteratively with three lipped liner variations in jump distance (10°, 15°, and 20° lips), a size 40 head, and a dual-mobility construct. Dislocation resistance was quantified as the moment required to dislocate the hip and the integral of the moment-flexion angle (dislocation energy). Increasing head diameter increased resistive moment on average for anterior and posterior dislocation by 22% relative to a neutral configuration. A lipped liner resulted in increases in the resistive moment to posterior dislocation of 9%, 19%, and 47% for 10°, 15°, and 20° lips, a sensitivity of approximately 2.8 Nm/mm of additional jump distance. A dual-mobility acetabular design resulted in an average 38% increase in resistive moment and 92% increase in dislocation energy for anterior and posterior dislocation. A quantitative understanding of tradeoffs in the dislocation risk inherent to THA construct options is valuable in supporting surgical decision making.

Quantitative imaging biomarkers of immune-related adverse events in immune-checkpoint blockade-treated metastatic melanoma patients: a pilot study.

PURPOSE: To develop quantitative molecular imaging biomarkers of immune-related adverse event (irAE) development in malignant melanoma (MM) patients receiving immune-checkpoint inhibitors (ICI) imaged with 18F-FDG PET/CT. METHODS: 18F-FDG PET/CT images of 58 MM patients treated with anti-PD-1 or anti-CTLA-4 ICI were retrospectively analyzed for indication of irAE. Three target organs, most commonly affected by irAE, were considered: bowel, lung, and thyroid. Patient charts were reviewed to identify which patients experienced irAE, irAE grade, and time to irAE diagnosis. Target organs were segmented using a convolutional neural network (CNN), and novel quantitative imaging biomarkers - SUV percentiles (SUVX%) of 18F-FDG uptake within the target organs - were correlated with the clinical irAE status. Area under the receiver-operating characteristic curve (AUROC) was used to quantify irAE detection performance. Patients who did not experience irAE were used to establish normal ranges for target organ 18F-FDG uptake. RESULTS: A total of 31% (18/58) patients experienced irAE in the three target organs: bowel (n=6), lung (n=5), and thyroid (n=9). Optimal percentiles for identifying irAE were bowel (SUV95%, AUROC=0.79), lung (SUV95%, AUROC=0.98), and thyroid (SUV75%, AUROC=0.88). Optimal cut-offs for irAE detection were bowel (SUV95%>2.7 g/mL), lung (SUV95%>1.7 g/mL), and thyroid (SUV75%>2.1 g/mL). Normal ranges (95% confidence interval) for the SUV percentiles in patients without irAE were bowel [1.74, 2.86 g/mL], lung [0.73, 1.46 g/mL], and thyroid [0.86, 1.99 g/mL]. CONCLUSIONS: Increased 18F-FDG uptake within irAE-affected organs provides predictive information about the development of irAE in MM patients receiving ICI and represents a potential quantitative imaging biomarker for irAE. Some irAE can be detected on 18F-FDG PET/CT well before clinical symptoms appear.

Development and validation of a longitudinal soft-tissue metastatic lesion matching algorithm.

Metastatic cancer presents with many, sometimes hundreds of metastatic lesions through the body, which often respond heterogeneously to treatment. Therefore, lesion-level assessment is necessary for a complete understanding of disease response. Lesion-level assessment typically requires manual matching of corresponding lesions, which is a tedious, subjective, and error-prone task. This study introduces a fully automated algorithm for matching of metastatic lesions in longitudinal medical images. The algorithm entails four steps: (1) image registration, (2) lesion dilation, (3) lesion clustering, and (4) linear assignment. In step (1), 3D deformable registration is used to register the scans. In step (2), lesion contours are conformally dilated. In step (3), lesion clustering is evaluated based on local metrics. In step (4), matching is assigned based on non-greedy cost minimization. The algorithm was optimized (e.g. choice of deformable registration algorithm, dilatation size) and validated on 140 scan-pairs of 32 metastatic cancer patients from two independent clinical trials, who received longitudinal PET/CT scans as part of their treatment response assessment. Registration error was evaluated using landmark distance. A sensitivity study was performed to evaluate the optimal lesion dilation magnitude. Lesion matching performance accuracy was evaluated for all patients and for a subset with high disease burden. Two investigated deformable registration approaches (whole body deformable and articulated deformable registrations) led to similar performance with the overall registration accuracy between 2.3 and 2.6 mm. The optimal dilation magnitude of 25 mm yielded almost a perfect matching accuracy of 0.98. No significant matching accuracy decrease was observed in the subset of patients with high lesion disease burden. In summary, lesion matching using our new algorithm was highly accurate and a significant improvement, when compared to previously established methods. The proposed method enables accurate automated metastatic lesion matching in whole-body longitudinal scans.

FDG PET/CT for Assessment of Immune Therapy: Opportunities and Understanding Pitfalls.

Immune checkpoint blockade has demonstrated the ability to modulate the immune system to produce durable responses in a wide range of cancers and has significantly impacted the standard of care. However, many cancer patients still do not respond to immune checkpoint blockade or have a limited duration of antitumor responses. Moreover, immune-related adverse events caused by immune checkpoint blockade can be severe and debilitating for some patients, limiting continuation of therapy and resulting in severe autoimmune conditions. Standard-of-care conventional anatomic imaging modalities and tumor response criteria have limitations to adequately assess tumor responses, especially early in the course of therapy, for risk-adapted clinical management to inform care of patients treated with immunotherapy. Molecular imaging with position emission tomography (PET) provides a noninvasive functional biomarker of tumor response, and of immune activation, for patients on immune-based therapies to help address these needs. 18F-FDG (FDG) PET/CT is readily available clinically and a number of studies have evaluated the use of this agent for assessment of prognosis, treatment response and immune activation for patients treated with immune checkpoint blockade. In this review paper, we discuss the current oncologic applications and imaging needs of cancer immunotherapy, recent studies applying FDG PET/CT for tumor response assessment, and evaluation of immune-related adverse events for improving clinical management. We largely focus on metastatic melanoma; however, we generalize where applicable to immunotherapy in other tumor types. We also briefly discuss PET imaging and quantitation as well as emerging non-FDG PET imaging radiotracers for cancer immunotherapy imaging.

Impact of alignment and kinematic variation on resistive moment and dislocation propensity for THA with lipped and neutral liners.

Instability and dislocation remain leading indications for revision of total hip arthroplasty (THA). Many studies have addressed the links between implant design and dislocation; however, an understanding of the impact of alignment and kinematic variability on constraint of modern THA constructs to provide joint stability is needed. The objective of this study is to provide objective data to be considered in the treatment algorithm to protect against joint instability. Joint contact and muscle forces were evaluated using musculoskeletal models of THA patients performing activities consistent with posterior and anterior dislocation. Position and joint loads were transferred to a finite element simulation with an experimentally calibrated hip capsule representation, where they were kinematically extrapolated until impingement and eventual dislocation. Cup anteversion and inclination were varied according to clinical measurements, and variation in imposed kinematics was included. The resistive moment provided by the contact force and joint capsule, and overall dislocation rate (dislocations/total simulations) were determined with neutral and lipped acetabular liners. Use of a lipped liner did increase the resistive moment in posterior dislocation, by an average of 5.2 Nm, and the flexion angle at dislocation by 1.4° compared to a neutral liner. There was a reduction in similar magnitude in resistance to anterior dislocation. Increased cup anteversion and inclination, hip abduction and internal rotation all reduced the occurrence of posterior dislocation but increased anterior dislocation. A quantitative understanding of tradeoffs in the dislocation risk inherent to THA construct options is valuable in supporting surgical decision making.