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.

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.