Detecting small cell transformation in patients with advanced EGFR mutant lung adenocarcinoma through epigenomic cfDNA profiling.

PURPOSE: Histologic transformation to small cell lung cancer (SCLC) is a mechanism of treatment resistance in patients with advanced oncogene-driven lung adenocarcinoma (LUAD) that currently requires histologic review for diagnosis. Herein, we sought to develop an epigenomic cell-free (cf)DNA-based approach to non-invasively detect small cell transformation in patients with EGFR mutant (EGFRm) LUAD. EXPERIMENTAL DESIGN: To characterize the epigenomic landscape of transformed (t)SCLC relative to LUAD and de novo SCLC, we performed chromatin immunoprecipitation sequencing (ChIP-seq) to profile the histone modifications H3K27ac, H3K4me3, and H3K27me3, methylated DNA immunoprecipitation sequencing (MeDIP-seq), assay for transposase-accessible chromatin sequencing (ATAC-seq), and RNA sequencing on 26 lung cancer patient-derived xenograft (PDX) tumors. We then generated and analyzed H3K27ac ChIP-seq, MeDIP-seq, and whole genome sequencing cfDNA data from 1 ml aliquots of plasma from patients with EGFRm LUAD with or without tSCLC. RESULTS: Analysis of 126 epigenomic libraries from the lung cancer PDXs revealed widespread epigenomic reprogramming between LUAD and tSCLC, with a large number of differential H3K27ac (n=24,424), DNA methylation (n=3,298), and chromatin accessibility (n=16,352) sites between the two histologies. Tumor-informed analysis of each of these three epigenomic features in cfDNA resulted in accurate non-invasive discrimination between patients with EGFRm LUAD versus tSCLC (AUROC=0.82-0.87). A multi-analyte cfDNA-based classifier integrating these three epigenomic features discriminated between EGFRm LUAD versus tSCLC with an AUROC of 0.94. CONCLUSIONS: These data demonstrate the feasibility of detecting small cell transformation in patients with EGFRm LUAD through epigenomic cfDNA profiling of 1 ml of patient plasma.

Epigenomic signatures of sarcomatoid differentiation to guide the treatment of renal cell carcinoma.

Renal cell carcinoma with sarcomatoid differentiation (sRCC) is associated with poor survival and a heightened response to immune checkpoint inhibitors (ICIs). Two major barriers to improving outcomes for sRCC are the limited understanding of its gene regulatory programs and the low diagnostic yield of tumor biopsies due to spatial heterogeneity. Herein, we characterized the epigenomic landscape of sRCC by profiling 107 epigenomic libraries from tissue and plasma samples from 50 patients with RCC and healthy volunteers. By profiling histone modifications and DNA methylation, we identified highly recurrent epigenomic reprogramming enriched in sRCC. Furthermore, CRISPRa experiments implicated the transcription factor FOSL1 in activating sRCC-associated gene regulatory programs, and FOSL1 expression was associated with the response to ICIs in RCC in two randomized clinical trials. Finally, we established a blood-based diagnostic approach using detectable sRCC epigenomic signatures in patient plasma, providing a framework for discovering epigenomic correlates of tumor histology via liquid biopsy.

Landscape of HER2-low breast cancer: Insights from a six-year study on prevalence and clinicopathological characteristics.

Human epidermal growth factor receptor 2 (HER2)-low breast cancer has emerged as a subtype of breast cancer, defined by HER2 1+/2+ in immunohistochemistry (IHC) and absence of ERBB2 gene amplification on fluorescence in situ hybridization (FISH). Recent trials showed marked response of HER2-low breast cancer to novel anti-HER2 antibody-drug-conjugates. Data on characteristics of HER2-low breast cancer subtype is limited. Real-world data from the Anatomic Pathology Department of Hotel-Dieu de France, spanning 2017-2023, was retrospectively collected. HER2-positive patients were excluded to compare HER2-low to HER2-zero breast cancer subtypes. Clinicopathological characteristics between the groups were compared using a Chi-Squared test. Out of 1195 patients, we observed 341 (28.5 %) HER2-low breast cancers cases. HER2-positive breast cancer cases (n = 178; 14.9 %) were excluded. There was no significant difference in age and sex between HER2-low and HER2-zero group (p = 0.33 and 0.79, respectively). HER2-low breast cancer was associated with positive estrogen receptor status and positive progesterone receptor status (p < 0.001 and p = 0.01, respectively). Ductal adenocarcinomas were more commonly observed in HER2-low group (p < 0.001). When stratified by hormone (HR) status, 87.4 % of patients had HR-positive status and 12.6 % were HR-negative. Among the HR-negative group, HER2-low tumors tended to show lower proliferation index compared to HER2-zero tumors (25%vs.10 %, p = 0.04). This study showed that HER2-low is distinct from HER2-zero and is common among patients with breast cancer. Clinicopathological features such as histological type differ between HER2-zero and HER2-low breast cancer. Within HR-negative breast cancer, those with low HER2 expression exhibit a less aggressive profile compared to HER2-zero tumors.

Impact of smoking status on clinical outcomes in patients with metastatic renal cell carcinoma treated with first-line immune checkpoint inhibitor-based regimens.

BACKGROUND: Current tobacco smoking is independently associated with decreased overall survival (OS) among patients with metastatic renal cell carcinoma (mRCC) treated with targeted monotherapy (VEGF-TKI). Herein, we assess the influence of smoking status on the outcomes of patients with mRCC treated with the current first-line standard of care of immune checkpoint inhibitor (ICI)-based regimens. MATERIALS AND METHODS: Real-world data from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) were collected retrospectively. Patients with mRCC who received either dual ICI therapy or ICI with VEGF-TKI in the first-line setting were included and were categorized as current, former, or nonsmokers. The primary outcomes were OS, time to treatment failure (TTF), and objective response rate (ORR). OS and TTF were compared between groups using the log-rank test and multivariable Cox regression models. ORR was assessed between the 3 groups using a multivariable logistic regression model. RESULTS: A total of 989 eligible patients were included in the analysis, with 438 (44.3%) nonsmokers, 415 (42%) former, and 136 (13.7%) current smokers. Former smokers were older and included more males, while other baseline characteristics were comparable between groups. Median follow-up for OS was 21.2 months. In the univariate analysis, a significant difference between groups was observed for OS (P = .027) but not for TTF (P = .9), with current smokers having the worse 2-year OS rate (62.8% vs 70.8% and 73.1% in never and former smokers, respectively). After adjusting for potential confounders, no significant differences in OS or TTF were observed among the 3 groups. However, former smokers demonstrated a higher ORR compared to never smokers (OR 1.45, P = .02). CONCLUSION: Smoking status does not appear to independently influence the clinical outcomes to first-line ICI-based regimens in patients with mRCC. Nonetheless, patient counseling on tobacco cessation remains a crucial aspect of managing patients with mRCC, as it significantly reduces all-cause mortality.

Efficacy and safety of the enzymatic mixture - Lipase, collagenase and hyaluronidase - In the treatment of moderate to severe submental fat: A prospective cohort study.

Purpose: To study the effect of the enzymatic mixture: Lipase, Collagenase and Hyaluronidase in the treatment of submental fat. Methods: A monocentric prospective cohort study including 10 female patients, aged between 18 and 65 years old, who received treatment for submental fat with a mixture of Lipase, Collagenase, and Hyaluronidase. The treatment protocol consisted of one treatment session every 21 days for a total of 3 sessions. In each session, 4 ml of the enzymatic mixture (1 ml of Collagenase GH PB20, 1 ml of Hyaluronidase PB 3000 and 2 ml of Lipase PB 500) + 2 ml of Lidocaine 2% were injected in the submental fat (SMF). Efficacy was assessed four weeks after the last session. Co-Primary Outcome was defined as the improvement of ≥ 1-point in Clinician-Reported and Patient-Reported Sub-mental Fat Rating Scales (CR-SMFRS and PR-SMFRS). Secondary Outcomes included score reductions in Patient-Reported Sub-mental Fat Impact Scale (PR-SMFIS), ≥10% reduction in submental fat pad thickness by ultrasound, and Subject Self-Rating Scale (SSRS) responses of 4, 5, or 6. Results: The Co-Primary outcome was achieved in 9 out of 10 patients. A considerable reduction of 22.8% in the PR-SMFIS was observed. Furthermore, 9 out of 10 patients expressed overall satisfaction with the treatment. Submental fat reduction of more than 10% was observed in 9 out of 10 patients in neutral position and in all patients in flexed position. Adverse effects were only limited to local reactions. Conclusion: The enzymatic mixture of Lipase, Collagenase and Hyaluronidase is an effective and safe minimally-invasive method for the reduction of SMF that can be used alone or in conjunction with other treatment modalities.

Kinematic adaptations from self-selected to fast speed walking in patients with adult spinal deformity.

PURPOSE: To investigate kinematic adaptations from self-selected to fast speed walking in ASD patients. METHODS: 115 primary ASD and 66 controls underwent biplanar radiographic X-rays and 3D gait analysis to calculate trunk, segmental spine and lower limb kinematics during self-selected and fast speed walking. Kinematic adaptation was calculated as the difference (Δ) between fast and self-selected speed walking. ASD with 7 or more limited kinematic adaptation parameters were classified as ASD-limited-KA, while those with less than 7 limited kinematic adaptation parameters were classified as ASD-mild-KA. RESULTS: 25 patients were classified as ASD-limited-KA and 90 as ASD-mild-KA. ASD-limited-KA patients walked with a lesser increase of pelvic rotation (Δ = 1.7 vs 5.5°), sagittal hip movement (Δ = 3.1 vs 7.4°) and shoulder-pelvis axial rotation (Δ = 3.4 vs 6.4°) compared to controls (all p < 0.05). ASD-limited-KA had an increased SVA (60.6 vs - 5.7 mm), PT (23.7 vs 11.9°), PI-LL (9.7 vs - 11.7°), knee flexion (9.2 vs - 0.4°) and a decreased LL (44.0 vs 61.4°) compared to controls (all p < 0.05). Kinematic and radiographic alterations were less pronounced in ASD-mild-KA. The limited increase of walking speed was correlated to the deteriorated physical component summary score of SF-36 (r = 0.37). DISCUSSION: Kinematic limitations during adaptation from self-selected to fast speed walking highlight an alteration of a daily life activity in ASD patients. ASD with limited kinematic adaptations showed more severe sagittal malalignment with an increased SVA, PT, PI-LL, and knee flexion, a decreased LL and the most deteriorated quality of life. This highlights the importance of 3D movement analysis in the evaluation of ASD.

Role of bilateral staged hip arthroplasty in Hip-spine syndrome: A case report.

RATIONALE: Hip-spine syndrome is a frequent finding in patients presenting with symptoms both at the level of the hip and spine. PATIENT CONCERNS: Patient previously operated of lumbar laminectomy for supposed spinal stenosis presenting with persistent pain and disability. DIAGNOSES: Clinical examination and imaging showed severe bilateral hip osteoarthritis. Full body standing and sitting biplanar radiographs showed an associated severe sagittal malalignment. 3D motion analysis and health-related quality of life (HRQOL) questionnaires showed a severe functional impact. INTERVENTIONS: He was operated of a staged bilateral total hip arthroplasty using the direct anterior approach. OUTCOMES: Spinopelvic and sagittal alignment parameters, as well as 3D motion analysis and HRQOL scores showed significant improvement after the first, then the second total hip arthroplasty. LESSONS: Comprehensive functional diagnostic testing, including full body standing and seated radiographs, 3D gait analysis and HRQOL questionnaires may provide important information for future management.

Liquid biopsy epigenomic profiling for cancer subtyping.

Although circulating tumor DNA (ctDNA) assays are increasingly used to inform clinical decisions in cancer care, they have limited ability to identify the transcriptional programs that govern cancer phenotypes and their dynamic changes during the course of disease. To address these limitations, we developed a method for comprehensive epigenomic profiling of cancer from 1 ml of patient plasma. Using an immunoprecipitation-based approach targeting histone modifications and DNA methylation, we measured 1,268 epigenomic profiles in plasma from 433 individuals with one of 15 cancers. Our assay provided a robust proxy for transcriptional activity, allowing us to infer the expression levels of diagnostic markers and drug targets, measure the activity of therapeutically targetable transcription factors and detect epigenetic mechanisms of resistance. This proof-of-concept study in advanced cancers shows how plasma epigenomic profiling has the potential to unlock clinically actionable information that is currently accessible only via direct tissue sampling.

Clinicodemographic characteristics of extraosseous ewing sarcoma: A comparative meta-analysis of pediatric and adult patients.

Background: Evidence suggests different presentation patterns and prognosis of extraosseous Ewing Sarcoma (EES) based on age. Thus, we carried out this study to test the difference between children and adult EES cases regarding clinicodemographic characteristics and prognosis. Methods: A total of 4 databases were explored yielding 18 relevant studies for data synthesis. Outcomes included the comparison of demographic and clinical characteristics as well as prognosis between children and adults with EES. Log odds ratio (logOR) and its 95% confidence interval (CI) were pooled across studies. Statistical models/methods were selected based on heterogeneity. Results: Our analysis included a total of 1261 children and 1256 adults. When we compared these two age categories, we did not observe a significant difference in the risk of developing EES [logOR = -0.13; 95% CI: -0.65: 0.39; I2 = 88.42%]. No significant differences regarding gender, tumor location, and size (≤5 vs. >5 cm), EWSR1 positivity, or management modality. We did not observe significant difference regarding clinical outcomes, such as 5-year overall survival and event-free survival, recurrence, mortality, no evidence of disease, and secondary metastasis. Conclusions: Our findings highlight the absence of an association between the age category of patients and the incidence of EES, as well as its clinical outcomes.

Emerging Biomarkers of Response to Systemic Therapies in Metastatic Clear Cell Renal Cell Carcinoma.

Patients with metastatic clear cell renal cell carcinoma (mccRCC) experience highly heterogeneous outcomes when treated with standard-of-care systemic regimens. Therefore, valid biomarkers are needed to predict the clinical response to these therapies and help guide management. In this review, the authors outline relevant and promising biomarkers for patients with mccRCC receiving systemic therapies, with a focus on immunotherapy-based regimens.

ASD with high pelvic retroversion develop changes in their acetabular orientation during walking.

Introduction: It was hypothesized that pelvic retroversion in Adult Spinal Deformity (ASD) can be related to an increased hip loading explaining the occurrence of hip-spine syndrome. Research question: How pelvic retroversion can modify acetabular orientation in ASD during walking? Methods: 89 primary ASD and 37 controls underwent 3D gait analysis and full-body biplanar X-rays. Classic spinopelvic parameters were calculated from 3D skeletal reconstructions in addition to acetabular anteversion, abduction, tilt, and coverage. Then, 3D bones were registered on each gait frame to compute the dynamic value of the radiographic parameters during walking. ASD patients having a high PT were grouped as ASD-highPT, otherwise as ASD-normPT. Control group was divided in: C-aged and C-young, age matched to ASD-hightPT and ASD-normPT respectively. Results: 25/89 patients were classified as ASD-highPT having a radiographic PT of 31° (vs 12° in other groups, p â€‹< â€‹0.001). On static radiograph, ASD-highPT showed more severe postural malalignment than the other groups: ODHA â€‹= â€‹5°, L1L5 â€‹= â€‹17°, SVA â€‹= â€‹57.4 â€‹mm (vs 2°, 48° and 5 â€‹mm resp. in other groups,all p â€‹< â€‹0.001). During gait, ASD-highPT presented a higher dynamic pelvic retroversion of 30° (vs 15° in C-aged), along with a higher acetabular anteversion of 24° (vs 20°), external coverage of 38° (vs 29°) and a lower anterior coverage of 52° (vs 58°,all p â€‹< â€‹0.05). Conclusion: ASD patients with severe pelvic retroversion showed an increased acetabular anteversion, external coverage and lower anterior coverage during gait. These changes in acetabular orientation, computed during walking, were shown to be related to hip osteoarthritis.

Functional assessment using 3D movement analysis can better predict health-related quality of life outcomes in patients with adult spinal deformity: a machine learning approach.

Introduction: Adult spinal deformity (ASD) is classically evaluated by health-related quality of life (HRQoL) questionnaires and static radiographic spino-pelvic and global alignment parameters. Recently, 3D movement analysis (3DMA) was used for functional assessment of ASD to objectively quantify patient's independence during daily life activities. The aim of this study was to determine the role of both static and functional assessments in the prediction of HRQoL outcomes using machine learning methods. Methods: ASD patients and controls underwent full-body biplanar low-dose x-rays with 3D reconstruction of skeletal segment as well as 3DMA of gait and filled HRQoL questionnaires: SF-36 physical and mental components (PCS&MCS), Oswestry Disability Index (ODI), Beck's Depression Inventory (BDI), and visual analog scale (VAS) for pain. A random forest machine learning (ML) model was used to predict HRQoL outcomes based on three simulations: (1) radiographic, (2) kinematic, (3) both radiographic and kinematic parameters. Accuracy of prediction and RMSE of the model were evaluated using 10-fold cross validation in each simulation and compared between simulations. The model was also used to investigate the possibility of predicting HRQoL outcomes in ASD after treatment. Results: In total, 173 primary ASD and 57 controls were enrolled; 30 ASD were followed-up after surgical or medical treatment. The first ML simulation had a median accuracy of 83.4%. The second simulation had a median accuracy of 84.7%. The third simulation had a median accuracy of 87%. Simulations 2 and 3 had comparable accuracies of prediction for all HRQoL outcomes and higher predictions compared to Simulation 1 (i.e., accuracy for PCS = 85 ± 5 vs. 88.4 ± 4 and 89.7% ± 4%, for MCS = 83.7 ± 8.3 vs. 86.3 ± 5.6 and 87.7% ± 6.8% for simulations 1, 2 and 3 resp., p < 0.05). Similar results were reported when the 3 simulations were tested on ASD after treatment. Discussion: This study showed that kinematic parameters can better predict HRQoL outcomes than stand-alone classical radiographic parameters, not only for physical but also for mental scores. Moreover, 3DMA was shown to be a good predictive of HRQoL outcomes for ASD follow-up after medical or surgical treatment. Thus, the assessment of ASD patients should no longer rely on radiographs alone but on movement analysis as well.

Spinopelvic Adaptations in Standing and Sitting Positions in Patients With Adult Spinal Deformity.

Purpose To describe spinopelvic adaptations in the standing and sitting positions in patients with adult spinal deformity (ASD). Methods Ninety-five patients with ASD and 32 controls completed health-related quality of life (HRQOL) questionnaires: short form 36 (SF36), Oswestry Disability Index (ODI), and visual analog scale (VAS) for pain. They underwent biplanar radiography in both standing and sitting positions. Patients with ASD were divided into ASD-front (frontal deformity Cobb > 20°, n = 24), ASD-sag (sagittal vertical axis (SVA) > 50 mm, pelvic tilt (PT) > 25°, or pelvic incidence (PI)-lumbar lordosis (LL) > 10°, n = 40), and ASD-hyper thoracic kyphosis (TK >60°, n = 31) groups. Flexibility was defined as the difference (Δ) in radiographic parameters between the standing and sitting positions. The radiographic parameters were compared between the groups. Correlations between HRQOL scores were evaluated. Results All participants increased their SVA from standing to sitting (ΔSVA<0), except for patients with ASD-sag, who tended to decrease their SVA (78-62 mm) and maximize their pelvic retroversion (27-40° vs 10-34° in controls, p<0.001). They also showed reduced thoracic and lumbar flexibility (ΔLL = 3.4 vs 37.1°; ΔTK = -1.7 vs 9.4° in controls, p<0.001). ASD-hyperTK showed a decreased PT while sitting (28.9 vs 34.4° in controls, p<0.001); they tended to decrease their LL and TK but could not reach values for controls (ΔLL = 22.8 vs 37.1° and ΔTK = 5.2 vs 9.4°, p<0.001). The ASD-front had normal standing and sitting postures. ΔSVA and ΔLL were negatively correlated with the physical component scale (PCS of SF36) and ODI (r = -0.39 and r = -0.46, respectively). Conclusion Patients with ASD present with different spinopelvic postures and adaptations from standing to sitting positions, with those having sagittal malalignment most affected. In addition, changes in standing and sitting postures were related to HRQOL outcomes. Therefore, surgeons should consider patient sitting adaptations in surgical planning and spinal fusion. Future studies on ASD should evaluate whether physical therapy or spinal surgery can improve sitting posture and QOL, especially for those with high SVA or PT.

Alterations of gait kinematics depend on the deformity type in the setting of adult spinal deformity.

PURPOSE: To evaluate 3D kinematic alterations during gait in Adult Spinal Deformity (ASD) subjects with different deformity presentations. METHODS: One hundred nineteen primary ASD (51 ± 19y, 90F), age and sex-matched to 60 controls, underwent 3D gait analysis with subsequent calculation of 3D lower limb, trunk and segmental spine kinematics as well as the gait deviation index (GDI). ASD were classified into three groups: 51 with sagittal malalignment (ASD-Sag: SVA > 50 mm, PT > 25°, and/or PI-LL > 10°), 28 with only frontal deformity (ASD-Front: Cobb > 20°) and 40 with only hyperkyphosis (ASD-HyperTK: TK > 60°). Kinematics were compared between groups. RESULTS: ASD-Sag had a decreased pelvic mobility compared to controls with a decreased ROM of hips (38 vs. 45°) and knees (51 vs. 61°). Furthermore, ASD-Sag exhibited a decreased walking speed (0.8 vs. 1.2 m/s) and GDI (80 vs. 95, all p < 0.05) making them more prone to falls. ASD-HyperTK showed similar patterns but in a less pronounced way. ASD-Front had normal walking patterns. GDI, knee flex/extension and walking speed were significantly associated with SVA and PT (r = 0.30-0.65). CONCLUSION: Sagittal spinal malalignment seems to be the driver of gait alterations in ASD. Patients with higher GT, SVA, PT or PI-LL tended to walk slower, with shorter steps in order to maintain stability with a limited flexibility in the pelvis, hips and knees. These changes were found to a lesser extent in ASD with only hyperkyphosis but not in those with only frontal deformity. 3D gait analysis is an objective tool to evaluate functionality in ASD patients depending on their type of spinal deformity. LEVEL OF EVIDENCE I: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

Assessment of dynamic balance during walking in patients with adult spinal deformity.

PURPOSE: To assess dynamic postural alignment in ASD during walking using a subject-specific 3D approach. METHODS: 69 ASD (51 ± 20 years, 77%F) and 62 controls (34 ± 13 years, 62%F) underwent gait analysis along with full-body biplanar Xrays and filled HRQoL questionnaires. Spinopelvic and postural parameters were computed from 3D skeletal reconstructions, including radiographic odontoid to hip axis angle (ODHA) that evaluates the head's position over the pelvis (rODHA), in addition to rSVA and rPT. The 3D bones were then registered on each gait frame to compute the dynamic ODHA (dODHA), dSVA, and dPT. Patients with high dODHA (> mean + 1SD in controls) were classified as ASD-DU (dynamically unbalanced), otherwise as ASD-DB (dynamically balanced). Between-group comparisons and relationship between parameters were investigated. RESULTS: 26 patients were classified as ASD-DU having an average dODHA of 10.4° (ASD-DB: 1.2°, controls: 1.7°), dSVA of 112 mm (ASD-DB: 57 mm, controls: 43 mm), and dPT of 21° (ASD-DB: 18°, controls: 14°; all p < 0.001). On static radiographs, ASD-DU group showed more severe sagittal malalignment than ASD-DB, with more altered HRQoL outcomes. The ASD-DU group had an overall abnormal walking compared to ASD-DB & controls (gait deviation index: 81 versus 93 & 97 resp., p < 0.001) showing a reduced flexion/extension range of motion at the hips and knees with a slower gait speed and shorter step length. Dynamic ODHA was correlated to HRQoL scores. CONCLUSION: Dynamically unbalanced ASD had postural malalignment that persist during walking, associated with kinematic alterations in the trunk, pelvis, and lower limbs, making them more prone to falls. Dynamic-ODHA correlates better with HRQoL outcomes than dSVA and dPT.

Alteration of the Sitting and Standing Movement in Adult Spinal Deformity.

Adults with spinal deformity (ASD) are known to have spinal malalignment affecting their quality of life and daily life activities. While walking kinematics were shown to be altered in ASD, other functional activities are yet to be evaluated such as sitting and standing, which are essential for patients' autonomy and quality of life perception. In this cross-sectional study, 93 ASD subjects (50 ± 20 years; 71 F) age and sex matched to 31 controls (45 ± 15 years; 18 F) underwent biplanar radiographic imaging with subsequent calculation of standing radiographic spinopelvic parameters. All subjects filled HRQOL questionnaires such as SF36 and ODI. ASD were further divided into 34 ASD-sag (with PT > 25° and/or SVA >5 cm and/or PI-LL >10°), 32 ASD-hyperTK (with only TK >60°), and 27 ASD-front (with only frontal malalignment: Cobb >20°). All subjects underwent 3D motion analysis during the sit-to-stand and stand-to-sit movements. The range of motion (ROM) and mean values of pelvis, lower limbs, thorax, head, and spinal segments were calculated on the kinematic waveforms. Kinematics were compared between groups and correlations to radiographic and HRQOL scores were computed. During sit-to-stand and stand-to-sit movements, ASD-sag had decreased pelvic anteversion (12.2 vs 15.2°), hip flexion (53.0 vs 62.2°), sagittal mobility in knees (87.1 vs 93.9°), and lumbar mobility (L1L3-L3L5: -9.1 vs -6.8°, all p < 0.05) compared with controls. ASD-hyperTK showed increased dynamic lordosis (L1L3-L3L5: -9.1 vs -6.8°), segmental thoracic kyphosis (T2T10-T10L1: 32.0 vs 17.2°, C7T2-T2T10: 30.4 vs 17.7°), and thoracolumbar extension (T10L1-L1L3: -12.4 vs -5.5°, all p < 0.05) compared with controls. They also had increased mobility at the thoracolumbar and upper-thoracic spine. Both ASD-sag and ASD-hyperTK maintained a flexed trunk, an extended head along with an increased trunk and head sagittal ROM. Kinematic alterations were correlated to radiographic parameters and HRQOL scores. Even after controlling for demographic factors, dynamic trunk flexion was determined by TK and PI-LL mismatch (adj. R 2 = 0.44). Lumbar sagittal ROM was determined by PI-LL mismatch (adj. R 2 = 0.13). In conclusion, the type of spinal deformity in ASD seems to determine the strategy used for sitting and standing. Future studies should evaluate whether surgical correction of the deformity could restore sitting and standing kinematics and ultimately improve quality of life.