Histological response to radiotherapy is an early event in myxoid liposarcoma.

Compared to other sarcomas, myxoid liposarcoma (MLS) is exceptionally sensitive to radiation therapy, but the underlying mechanism remains unknown. The objective was to assess the tissue-based changes in MLS during and after neoadjuvant radiotherapy in 26 patients of the DOREMY trial. Morphological assessment was performed on biopsies pre-treatment, after 8 fractions, 16 factions, and after surgical resection and included percentage of viable tumor cells, hyalinization, necrosis, and fatty maturation. Furthermore, immunohistochemistry was performed for apoptosis (cleaved caspase-3), anti-apoptosis (Bcl-2), activity of mTOR signaling (phospho-S6), hypoxia (CAIX), proliferation (Ki67), inflammation (CD45 and CD68), and microvessel density (CD34 Chalkley count). A pronounced reduction in vital tumor cells was observed early with a drop to 32.5% (median) tumor cells (IQR 10-93.8%) after 8 fractions. This decreased further to 10% (IQR 5-30%) after 16 fractions and 7.5% (IQR 5-15%) in the surgical specimen. All but one patient had an excellent response with < 50% remaining tumor cells. Inversely, treatment response was mainly observed as hyalinization and less often as fatty maturation. Additionally, a decrease of inflammatory cells was noticed especially during the first eight fractions. Microvessel density remained stable over time. Immunohistochemical markers for apoptosis, anti-apoptosis, activity of mTOR signaling, proliferation, and hypoxia did not show any marked changes within the remaining tumor cells during and after radiotherapy. As a modest dose of neoadjuvant radiotherapy induces profound tissue changes in MLS, mainly during the first 8 fractions, current findings might suggest that in a carefully selected patient population further deintensification of radiotherapy might be explored.

Impact of replacing radiographic sacroiliitis by magnetic resonance imaging structural lesions on the classification of patients with axial spondyloarthritis.

OBJECTIVES: To investigate in patients with chronic back pain of a short duration, the utility of adding structural MRI lesions of the SI joints to the imaging criterion of the Assessment of SpondyloArthritis International Society (ASAS) axial SpA (axSpA) criteria and the utility of replacement of radiographic sacroiliitis by structural MRI lesions. METHODS: MRI STIR (inflammation, MRI-SI), MRI T1-weighted images (structural lesions, MRI-SI-s) and radiographs of the SI joints of patients in the SPondyloArthritis Caught Early-cohort (chronic back pain: ⩾3 months, ⩽2 years; onset <45 years) were scored by two well-calibrated readers. Previously proposed cut-offs for a positive MRI-SI-s were used (based on <5% prevalence in no-SpA patients): erosions ⩾3, fatty lesions ⩾3, fatty lesions and/or erosions (erosions/fatty lesions) ⩾5. Using the definitions of MRI-SI-s, patients were classified according to the ASAS axSpA criteria. RESULTS: Twenty-nine of 294 patients were modified New York (mNY) positive and 32 were MRI-SI-s positive (erosions/fatty lesions ⩾5). Agreement between mNY and MRI-SI-s (erosions/fatty lesions ⩾5) was moderate (κ: 0.58). Using the erosions/fatty lesions ⩾5 cut-off, 3/294 additional patients were classified as axSpA (adding MRI). Using this cut-off instead of mNY (replacing mNY), classification did not change in 286 patients (97.3%), but 5 patients (1.7%) would not be classified as axSpA and 3 previously unclassified patients (1.0%) would be classified as axSpA. Similar results were seen for the other cut-offs (erosions ⩾3 and fatty lesions ⩾3). CONCLUSION: Assessment of structural lesions (fatty lesions and erosions) on MRI-SI instead of or in addition to conventional radiographs does not lead to a different ASAS axSpA classification in most of the patients with early disease onset. This suggests that structural lesions (fatty lesions and erosions) can be reliably used in the ASAS axSpA classification of patients, as both addition and replacement of radiographs of the SI joints.

Imaging of the sacroiliac joints is important for diagnosing early axial spondyloarthritis but not all-decisive.

OBJECTIVES: To evaluate the contribution of the results of sacroiliac imaging to diagnosis and to the level of confidence in diagnosis in patients presenting with chronic back pain (CBP) and suspected of having axial spondyloarthritis (axSpA). METHODS: Data from 513 patients from the SPondyloArthritisCaughtEarly cohort with CBP (⩾3 months, ⩽2 years, onset <45 years) were analysed after full diagnostic work-up. Rheumatologists were asked not only to provide a diagnosis before and after the imaging results had been provided to them, but also to provide the level of confidence of this diagnosis on an 11-point numerical scale. RESULTS: Before imaging, 317/513 patients were diagnosed with axSpA. Of these patients, 178/317 (56%) did not have signs of sacroiliitis on either MRI or radiography, which led to the rheumatologist refuting the initial diagnosis of axSpA in 81/178 (46%) patients. Of the 196/513 patients without axSpA before imaging, 35/196 (18%) had signs of sacroiliitis on imaging. Subsequently, 28/35 (80%) patients were diagnosed with axSpA. Overall, imaging was incongruent with the diagnosis before imaging in 213 patients. This led to a change in diagnosis in 109/213 (51%), which corresponds to 21% (109/513) of all patients in the cohort. In general, diagnostic confidence increased by having imaging results available (from 6.2 to 7.4, P < 0.001). CONCLUSION: In patients with CBP suspected of having axSpA, sacroiliac imaging adds to the confidence in the final diagnosis. However, the number of changes in diagnosis suggests that imaging is important but not all-decisive in early axSpA diagnosis.

Can we use structural lesions seen on MRI of the sacroiliac joints reliably for the classification of patients according to the ASAS axial spondyloarthritis criteria? Data from the DESIR cohort.

OBJECTIVES: Investigating the utility of adding structural lesions seen on MRI of the sacroiliac joints to the imaging criterion of the Assessment of SpondyloArthritis (ASAS) axial SpondyloArthritis (axSpA) criteria and the utility of replacement of radiographic sacroiliitis by structural lesions on MRI. METHODS: Two well-calibrated readers scored MRI STIR (inflammation, MRI-SI), MRI T1-w images (structural lesions, MRI-SI-s) and radiographs of the sacroiliac joints (X-SI) of patients in the DEvenir des Spondyloarthrites Indifférenciées Récentes cohort (inflammatory back pain: ≥3 months, <3 years, age <50). A third reader adjudicated MRI-SI and X-SI discrepancies. Previously proposed cut-offs for a positive MRI-SI-s were used (based on <5% prevalence among no-SpA patients): erosions (E) ≥3, fatty lesions (FL) ≥3, E/FL ≥5. Patients were classified according to the ASAS axSpA criteria using the various definitions of MRI-SI-s. RESULTS: Of the 582 patients included in this analysis, 418 fulfilled the ASAS axSpA criteria, of which 127 patients were modified New York (mNY) positive and 134 and 75 were MRI-SI-s positive (E/FL≥5) for readers 1 and 2, respectively. Agreement between mNY and MRI-SI-s (E/FL≥5) was moderate (reader 1: κ: 0.39; reader 2: κ: 0.44). Using the E/FL≥5 cut-off instead of mNY classification did not change in 478 (82.1%) and 469 (80.6%) patients for readers 1 and 2, respectively. Twelve (reader 1) or ten (reader 2) patients would not be classified as axSpA if only MRI-SI-s was performed (in the scenario of replacement of mNY), while three (reader 1) or six (reader 2) patients would be additionally classified as axSpA in both scenarios (replacement of mNY and addition of MRI-SI-s). Similar results were seen for the other cut-offs (E≥3, FL≥3). CONCLUSIONS: Structural lesions on MRI can be used reliably either as an addition to or as a substitute for radiographs in the ASAS axSpA classification of patients in our cohort of patients with short symptom duration.

Does body mass index (BMI) influence the Ankylosing Spondylitis Disease Activity Score in axial spondyloarthritis?: Data from the SPACE cohort.

OBJECTIVE: Obesity is associated with elevated C reactive protein (CRP) levels. The Ankylosing Spondylitis Disease Activity Score (ASDAS) combines patient-reported outcomes (PROs) and CRP. We evaluated the effect of body mass index (BMI) on CRP and on ASDAS, and studied if ASDAS can be used in obese axial spondyloarthritis (axSpA) patients to assess disease activity. METHODS: Baseline data of patients with chronic back pain of short duration included in the SPondyloArthritis Caught Early (SPACE) cohort were used. Collected data included BMI and ASDAS. Patients were classified according to the ASAS axSpA classification criteria and BMI (overweight ≥25 and obese ≥30). Correlation and linear regression analyses were performed to assess the relation between BMI and ASDAS. Linear regression models were performed to assess if age or gender were effect modifiers in the relation between BMI and CRP, and between BMI and ASDAS. RESULTS: In total, 428 patients were analysed (n=168 axSpA; n=260 no-axSpA). The mean age was 31.1 years, 36.9% were male, 26.4% were overweight and 13.3% obese, median CRP was 3 mg/L and the mean ASDAS was 2.6. Gender was the only factor modifying the relationship between BMI and CRP as BMI had an influence on CRP only in females (ß=0.35; p<0.001). Correlations between BMI and CRP or PROs were generally weak, and only significant for CRP in female patients. BMI was not related to ASDAS in axSpA patients. CONCLUSIONS: ASDAS is not affected by BMI in axSpA patients. Therefore, based on our data it is not necessary to take BMI in consideration when assessing disease activity using ASDAS in axSpA patients.

Defining active sacroiliitis on MRI for classification of axial spondyloarthritis: update by the ASAS MRI working group.

OBJECTIVES: To review and update the existing definition of a positive MRI for classification of axial spondyloarthritis (SpA). METHODS: The Assessment in SpondyloArthritis International Society (ASAS) MRI working group conducted a consensus exercise to review the definition of a positive MRI for inclusion in the ASAS classification criteria of axial SpA. Existing definitions and new data relevant to the MRI diagnosis and classification of sacroiliitis and spondylitis in axial SpA, published since the ASAS definition first appeared in print in 2009, were reviewed and discussed. The precise wording of the existing definition was examined in detail and the data and a draft proposal were presented to and voted on by the ASAS membership. RESULTS: The clear presence of bone marrow oedema on MRI in subchondral bone is still considered to be the defining observation that determines the presence of active sacroiliitis. Structural damage lesions seen on MRI may contribute to a decision by the observer that inflammatory lesions are genuinely due to SpA but are not required to meet the definition. The existing definition was clarified adding guidelines and images to assist in the application of the definition. CONCLUSION: The definition of a positive MRI for classification of axial SpA should continue to primarily depend on the imaging features of 'active sacroiliitis' until more data are available regarding MRI features of structural damage in the sacroiliac joint and MRI features in the spine and their utility when used for classification purposes.

Metric Properties of the SPARCC Score of the Sacroiliac Joints - Data from Baseline, 3-month, and 12-month Followup in the SPACE Cohort.

OBJECTIVE: To evaluate metric properties of the SpondyloArthritis Research Consortium of Canada (SPARCC) score of the sacroiliac (SI) joints. METHODS: Patients with back pain (≥ 3 months, ≤ 2 years, onset < 45 years) were included in the SPACE cohort (SpondyloArthritis Caught Early). Patients with (possible) axial spondyloarthritis had followup visits after 3 and 12 months and were treated according to clinical practice. Magnetic resonance imaging (MRI) of the SI joints (MRI-SI) was scored in 2 independent campaigns (campaign 1: at baseline and 3 months; campaign 2: at baseline, 3 months, and 12 months) by 2 different blinded reader pairs, applying the Assessment of Spondyloarthritis International Society (ASAS) definition (MRI-SI+ vs MRI-SI-; discordant cases were adjudicated by a third reader) and SPARCC score (mean of 2 agreeing readers). Calculations were made for agreement between SPARCC score cutoff values and a consensus judgment of MRI-SI+ (ASAS definition) as external standard, change in SPARCC score, and smallest detectable changes (SDC) over 3 and 12 months. RESULTS: SPARCC score ≥ 2 showed best agreement with MRI-SI+ in both campaigns. Regarding observed changes in relation to SDC, SPARCC score changed in 70/151 patients; 26/70 patients changed > SDC (3.4), of whom 20 patients received stable treatment over 3 months in campaign 1. Over 3 months, 20/68 patients showed changes in SPARCC score; 11/20 > SDC (2.1), of whom 8 patients received stable treatment. Over 1 year, 23/74 patients changed their SPARCC score; 14/23 changed > SDC (2.4), of whom 7 received stable treatment in campaign 2. CONCLUSION: SPARCC score ≥ 2 can be used as surrogate for a consensus judgment of MRI-SI+ (ASAS definition) in clinical trials. The SDC ranged from 2.1-3.4 dependent on reader pair and were close to the proposed minimum important change of 2.5.

Assessment of sacroiliitis by radiographs and MRI: where are we now?

PURPOSE OF REVIEW: Both MRI and plain radiography are used to assess sacroiliitis. A weakness of radiography - apart from its inability to detect early disease - is reader variability. On the contrary, experience with MRI is relatively limited by comparison. RECENT FINDINGS: This review summarizes recent advances in sacroiliac joint imaging using radiography and MRI in spondyloarthritis. SUMMARY: Observer variation in reading radiographs of sacroiliac joints remains an unresolved issue. In recent years, more studies on MRI in the diagnosis of axial spondyloarthritis have become available. Incorporating structural lesions in the sacroiliac joint and spine and inflammatory lesions in the spine in the definition of a positive MRI are hot topics in research.