T2* assessment of the three coronary artery territories of the left ventricular wall by different monoexponential truncation methods.

OBJECTIVES: This study aimed at evaluating left ventricular myocardial pixel-wise T2* using two truncation methods for different iron deposition T2* ranges and comparison of segmental T2* in different coronary artery territories. MATERIAL AND METHODS: Bright blood multi-gradient echo data of 30 patients were quantified by pixel-wise monoexponential T2* fitting with its R2 and SNR truncation. T2* was analyzed at different iron classifications. At low iron classification, T2* values were also analyzed by coronary artery territories. RESULTS: The right coronary artery has a significantly higher T2* value than the other coronary artery territories. No significant difference was found in classifying severe iron by the two truncation methods in any myocardial region, whereas in moderate iron, it is only apparent at septal segments. The R2 truncation produces a significantly higher T2* value than the SNR method when low iron is indicated. CONCLUSION: Clear T2* differentiation between the three coronary territories by the two truncation methods is demonstrated. The two truncation methods can be used interchangeably in classifying severe and moderate iron deposition at the recommended septal region. However, in patients with low iron indication, different results by the two truncation methods can mislead the investigation of early iron level progression.

Early detection of heart function abnormality by native T1: a comparison of two T1 quantification methods.

OBJECTIVE: To compare the robustness of native T1 mapping using mean and median pixel-wise quantification methods. METHODS: Fifty-seven consecutive patients without overt signs of heart failure were examined in clinical routine for suspicion of cardiomyopathy. MRI included the acquisition of native T1 maps by a motion-corrected modified Look-Locker inversion recovery sequence at 1.5 T. Heart function status according to four established volumetric left ventricular (LV) cardio MRI parameter thresholds was used for retrospective separation into subgroups of normal (n = 26) or abnormal heart function (n = 31). Statistical normality of pixel-wise T1 was tested on each myocardial segment and mean and median segmental T1 values were assessed. RESULTS: Segments with normally distributed pixel-wise T1 (57/58%) showed no difference between mean and median quantification in either patient group, while differences were highly significant (p < 0.001) for the respective 43/42% non-normally distributed segments. Heart function differentiation between two patient groups was significant in 14 myocardial segments (p < 0.001-0.040) by median quantification compared with six (p < 0.001-0.042) by using the mean. The differences by median quantification were observed between the native T1 values of the three coronary artery territories of normal heart function patients (p = 0.023) and insignificantly in the abnormal patients (p = 0.053). CONCLUSION: Median quantification increases the robustness of myocardial native T1 definition, regardless of statistical normality of the data. Compared with the currently prevailing method of mean quantification, differentiation between LV segments and coronary artery territories is better and allows for earlier detection of heart function impairment. KEY POINTS: • Median pixel-wise quantification of native T1 maps is robust and can be applied regardless of the statistical distribution of data points. • Median quantification is more sensitive to early heart function abnormality compared with mean quantification. • The new method yields significant native T1 value differentiation between the three coronary artery territories.

An Extraosseous Ewing Sarcoma of the Index Finger Masquerading as a Benign Tumor.

Ewing sarcoma is a malignant, small, round, blue cell tumor that often affects the long bones and pelvis. It is rarely seen in the bones of the hand. A minority of Ewing sarcoma cases arise in soft tissue. This case report details the clinical and radiological presentation of an extraosseous Ewing sarcoma of the index finger in a 22-year-old woman. Treatment consisted of an index ray amputation followed by adjuvant chemotherapy. After 1 year, the left hand had excellent function with an acceptable cosmetic appearance and no evidence of metastasis or local recurrence.

Radiofrequency ablation of atypical cartilaginous tumors in long bones: a retrospective study.

Purpose: To determine the size of the ablation zone after radiofrequency ablation (RFA) of atypical cartilaginous bone tumors (ACT) using temperature-controlled 20 and 30 mm RFA straight non-cooled electrodes.Materials and methods: Sixteen patients with ACT in their long bones, who had undergone a single-session single-application CT-guided temperature-controlled RFA, were included retrospectively in the study. Tumors with a diameter of 10-25 mm were treated with 20 mm electrodes (n = 10), and tumors of 25-35 mm, with 30 mm electrodes (n = 6). The ablated zone was measured after three months on MRI images.Results: All the tumors were within the ablated zone on the 3-month follow-up MRI scan. The mean ablation time with the electrode, at a target temperature of 90 °C, was 7.6 minutes (range 6-10). The median of the largest ablation diameters, on applying the 20 and 30 mm electrodes, were 42 mm (IQR 8.5, range 30-51 mm) and 44.5 mm (IQR 4.5, range 42-63 mm), respectively.Conclusions: All the retrospectively viewed tumors in the long bones of ACT patients treated with RFA were completely ablated. The ablation zone diameters in the bones were larger than expected, when compared to other tissues, such as the liver.

Diagnostic value of MRI signs in differentiating Ewing sarcoma from osteomyelitis.

BACKGROUND: The value of magnetic resonance imaging (MRI) signs in differentiating Ewing sarcoma from osteomyelitis has not be thoroughly investigated. PURPOSE: To investigate the value of various MRI signs in differentiating Ewing sarcoma from osteomyelitis. MATERIAL AND METHODS: Forty-one patients who underwent MRI because of a bone lesion of unknown nature with a differential diagnosis that included both Ewing sarcoma and osteomyelitis were included. Two observers assessed several MRI signs, including the transition zone of the bone lesion, the presence of a soft-tissue mass, intramedullary and extramedullary fat globules, and the penumbra sign. RESULTS: Diagnostic accuracies for discriminating Ewing sarcoma from osteomyelitis were 82.4% and 79.4% for the presence of a soft-tissue mass, and 64.7% and 58.8% for a sharp transition zone of the bone lesion, for readers 1 and 2 respectively. Inter-observer agreement with regard to the presence of a soft-tissue mass and the transition zone of the bone lesion were moderate (κ = 0.470) and fair (κ = 0.307), respectively. Areas under the receiver operating characteristic curve of the diameter of the soft-tissue mass (if present) were 0.829 and 0.833, for readers 1 and 2 respectively. Mean inter-observer difference in soft-tissue mass diameter measurement ± limits of agreement was 35.0 ± 75.0 mm. Diagnostic accuracies of all other MRI signs were all < 50%. CONCLUSION: Presence and size of a soft-tissue mass, and sharpness of the transition zone, are useful MRI signs to differentiate Ewing sarcoma from osteomyelitis, but inter-observer agreement is relatively low. Other MRI signs are of no value in this setting.

Radiofrequency ablation in the treatment of atypical cartilaginous tumours in the long bones: lessons learned from our experience.

BACKGROUND: Surgery is the cornerstone of treatment of symptomatic cartilaginous neoplasms. We previously studied the application of radiofrequency ablation of atypical cartilaginous tumours in the long bones. The purpose of the present study was to investigate the additional effect of placing multiple needles and a longer procedure duration on the proportion of completely ablated tumours. Post-ablation MRI findings and the occurrence of complications were also assessed. METHODS: We prospectively included 24 patients with atypical cartilaginous tumours in the long bones. Patients underwent CT-guided radiofrequency ablation followed by curettage with adjuvant phenolisation 3 months later, retrieving material assessed for viable tumour. Before curettage, gadolinium-enhanced MRI was performed to check for residual tumour. The occurrence of complications was noted. RESULTS: Complete tumour ablation was achieved in 17 out of 24 patients (71%). Complete ablation was achieved in 5 of the 6 cases (83%) when multiple needles were used in tumours ≥30 mm. There was incomplete ablation in 8% of patients. Post-ablation gadolinium-enhanced MRI findings agreed with the histological results in 17 out of 23 cases and there was a negative predictive value of 83%. One patient suffered a fracture after radiofrequency ablation. CONCLUSION: Radiofrequency ablation could be an alternative to curettage when treating atypical cartilaginous tumours in the long bones. It was shown that multiple needle placement in addition to longer duration of the ablation procedure is an effective measure in achieving complete ablation in tumours ≥30 mm. Gadolinium-enhanced MRI has a negative predictive value of 83% and could guide post-ablation follow-up.

JOURNAL CLUB: CT-Guided Bone Biopsies With Indeterminate Results in Pediatric Patients.

OBJECTIVE: The objective of our study was to determine the frequency of indeterminate percutaneous CT-guided bone biopsy results in a pediatric population, the subsequent management of indeterminate biopsy results, and the factors associated with an indeterminate biopsy result. MATERIALS AND METHODS: This retrospective study included 86 pediatric patients who underwent 89 CT-guided biopsies because of an unclear bone lesion in a tertiary referral center for bone tumors. RESULTS: CT-guided bone biopsy results were indeterminate in 29 of 89 lesions (32.6%; 95% CI, 23.7-42.9%). Excluding two bone lesions with an uncertain diagnosis, all other 27 bone lesions proved to be benign on follow-up (0% malignancies; 95% CI, 0-12.5%). Compared with patients with diagnostic CT-guided bone biopsy results, patients with indeterminate biopsy results were significantly younger (median age, 14.0 vs 18.0 years; p = 0.0185), were female more frequently (72.4% vs 41.7%, p = 0.0007), and had bone lesion-related symptoms less frequently (62.1% vs 88.3%, p = 0.0094). Furthermore, bone lesions with indeterminate CT-guided bone biopsy results were significantly more frequently not visible at CT (24.1% vs 1.7%, p = 0.0021), more frequently had a sclerotic rim (40.9% vs 18.6%, p = 0.0477), less frequently showed cortical destruction (45.5% vs 72.9%, p = 0.0343), less frequently had an associated extraosseous soft-tissue mass (4.5% vs 32.2%, p = 0.0094), and were smaller (median diameter, 17.0 vs 31.0 mm; p = 0.0007) than bone lesions with diagnostic results; in addition, the maximum biopsy sample length was significantly shorter for bone lesions with indeterminate CT-guided bone biopsy results than for those with diagnostic results (mean length, 10.9 vs 17.8 mm; p = 0.0003). CONCLUSION: A nondiagnostic CT-guided biopsy result in a child with an unclear bone lesion suggests benignity. Several clinical and CT features of bone lesions are associated with indeterminate CT-guided bone biopsy results.

Primary tumor volume measurements in Ewing sarcoma: MRI inter- and intraobserver variability and comparison with FDG-PET.

BACKGROUND: Primary tumor volume is as an important and independent prognostic factor in Ewing sarcoma. However, the observer variability of magnetic resonance imaging (MRI)-based primary tumor volume measurements in newly diagnosed Ewing sarcoma has never been investigated. Furthermore, it is unclear how MRI-based volume measurements compare to 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)-based volume measurements. This study aimed to determine the observer variability of simplified MRI-based primary tumor volume measurements in newly diagnosed treatment-naive Ewing sarcoma and to compare them to the actual primary tumor volume at MRI and the FDG-PET-based metabolically active tumor volume (MATV). MATERIAL AND METHODS: Twenty-nine newly diagnosed Ewing sarcoma patients with pretreatment MRI (of whom 11 also underwent FDG-PET) were included. Both exact and dichotomized (according to the proposed threshold of 200 mL) primary tumor volume measurements were analyzed. RESULTS: Mean inter- and intraobserver differences of MRI-based simplified tumor volume ± limits of agreement varied between 15-42 ± 155-204 mL and between 9-16 ± 64-250 mL, respectively. Inter- and intraobserver agreements of dichotomized MRI-based simplified tumor volume measurements was very good (κ = 0.827-1.000). Mean difference between simplified and actual tumor volumes at MRI ± limits of agreement was 60 ± 381 mL. Agreement between dichotomized simplified and actual tumor volumes at MRI was very good (κ = 0.839). Mean difference between MRI-based simplified tumor volume and MATV ± limits of agreement was 181 ± 549 mL and almost significantly different (p = .0581). Agreement between dichotomized MRI-based simplified tumor volume and MATV was moderate (κ = 0.560). CONCLUSIONS: Exact MRI-based simplified primary tumor volume measurements in Ewing sarcoma suffer from considerable observer variability, but observer agreement of dichotomized measurements (≤200 mL vs. >200 mL) is very good and generally matches MRI-based actual volume measurements. MRI-based primary tumor volume measurements poorly-moderately agree with and tend to be higher than the MATV.

Can FDG-PET/CT replace blind bone marrow biopsy of the posterior iliac crest in Ewing sarcoma?

OBJECTIVE: To determine and compare the value of 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) to blind bone marrow biopsy (BMB) of the posterior iliac crest in detecting metastatic bone marrow involvement in newly diagnosed Ewing sarcoma. MATERIALS AND METHODS: This retrospective study included 20 patients with newly diagnosed Ewing sarcoma who underwent pretreatment FDG-PET/CT and a total of 38 blind BMBs (two unilateral and 18 bilateral) of the posterior iliac crest. FDG-PET/CT scans were evaluated for bone marrow involvement, both in the posterior iliac crest and other sites, and compared to blind BMB results. RESULTS: FDG-PET/CT was positive for bone marrow involvement in 7/38 posterior iliac crests, whereas BMB was positive in 5/38 posterior iliac crests. FDG-PET/CT and BMB results in the posterior iliac crest agreed in 36/38 cases (94.7%, 95% confidence interval [CI]: 82.7-98.5%). On a patient level, FDG-PET/CT was positive for bone marrow involvement in 4/20 patients, whereas BMB of the posterior iliac crest was positive in 3/20 patients. On a patient level, FDG-PET/CT and BMB results agreed in 19/20 patients (95.0%, 95% CI: 76.4-99.1%). The only discrepancies between FDG-PET/CT and BMB were observed in two BMBs of one patient. Both BMBs in this patient were negative, whereas FDG-PET/CT indicated bilateral posterior iliac crest involvement and also extensive bone marrow involvement elsewhere. CONCLUSIONS: FDG-PET/CT appears to be a valuable method for metastatic bone marrow assessment in newly diagnosed Ewing sarcoma. The routine use of blind BMB of the posterior iliac crest should be reconsidered when FDG-PET/CT is available.

Culture yield of repeat percutaneous image-guided biopsy after a negative initial biopsy in suspected spondylodiscitis: a systematic review.

OBJECTIVE: To systematically review the published data on the culture yield of a repeat (second) percutaneous image-guided biopsy after negative initial biopsy in suspected spondylodiscitis. MATERIALS AND METHODS: A systematic search was performed of the PubMed/Medline and Embase databases. The methodological quality of the studies included was assessed. The proportions of positive cultures among all initial biopsies and second biopsies (after a negative initial biopsy) were calculated for each study and assessed for heterogeneity (defined as I2 > 50%). RESULTS: Eight studies, comprising a total of 107 patients who underwent a second percutaneous image-guided biopsy after a culture-negative initial biopsy in suspected spondylodiscitis, were included. All eight studies were at risk of bias and were concerning with regard to applicability, particularly patient selection, flow of patients through the study, and timing of the biopsy. The proportions of positive cultures among all initial biopsies ranged from 10.3 to 52.5%, and were subject to heterogeneity (I2 = 73.7%). The proportions of positive cultures among all second biopsies after negative initial biopsy ranged from 0 to 60.0%, and were not subject to heterogeneity (I2 = 38.7%). CONCLUSION: Although a second percutaneous image-guided biopsy may have some value in patients with suspected spondylodiscitis, its exact value remains unclear, given the available poor-quality evidence. Future well-designed studies are needed to determine the role of a second percutaneous image-guided biopsy in this setting. Such studies should clearly describe the spectrum of patients that was selected for a second percutaneous image-guided biopsy, the method of biopsy, and differences compared with the first biopsy, if any.

CT-guided biopsy in suspected spondylodiscitis: microbiological yield, impact on antimicrobial treatment, and relationship with outcome.

PURPOSE: To investigate the clinical impact of CT-guided biopsy, as performed in routine clinical practice, in patients with suspected spondylodiscitis on MRI in terms of culture yield, impact on antimicrobial treatment, and outcome. METHODS: This study included 64 patients with MRI findings compatible with spondylodiscitis who underwent CT-guided biopsy. RESULTS: Initial CT-guided biopsies were culture-positive in 20/64 (31.3%, 95% confidence interval [CI] 21.2-43.3%). Repeat CT-guided biopsies (after initial negative biopsy) were culture-positive in an additional 5/15 (33.3%, 95% CI 15.2-58.3%). Serum leukocytes, C-reactive protein, pre-biopsy use of antibiotics, neurological symptoms, MRI findings, vertebral height loss, and hyperkyphosis were not significantly different between culture-positive and culture-negative cases (P = 0.214-1.000); 75% (15/20) of initial CT-guided biopsies that were culture-positive provided additional information to clinicians for guiding antibiotic treatment. Sixty-two of 64 patients (96.9%, 95% CI 89.3-99.1%) would have been adequately treated if a strategy was followed that would subject all patients without clinical findings suspicious for "atypical" microorganisms and negative blood cultures to empirical antibiotics (i.e., clindamycin for coverage of Gram-positive bacteria) without using biopsy results to determine the optimal antibiotic regimen. Outcome within 6 months (development of neurologic or orthopedic complications, surgery, and death) was not significantly different (P = 0.751) between culture-positive and culture-negative patients. CONCLUSIONS: Although CT-guided biopsies are culture-positive in a minority of cases, the majority of positive cultures are useful to tailor antibiotic treatment. Empirical treatment with clindamycin may cover almost all micro-organisms in positive biopsy specimens, provided patients are not immunocompromised. Outcome appears similar between culture-positive and culture-negative patients.

Surveillance MRI for the detection of locally recurrent Ewing sarcoma seems futile.

PURPOSE: To determine the frequency of locally recurrent Ewing sarcoma on surveillance MRI and the outcome of these patients. MATERIALS AND METHODS: This retrospective single-center study included all patients with newly diagnosed Ewing sarcoma who underwent surveillance MRI of the primary tumor location after primary treatment between 1997 and 2016. RESULTS: Thirty-two patients underwent a total of 176 local surveillance MRI scans, yielding an average of 5.5 ± 4.4 MRI scans per patient. Follow-up time of surveillance MRI after completion of primary treatment ranged between 1 and 111 months. Surveillance MRI detected five (15.6%) locally recurrent Ewing sarcomas, at 2, 4, 6, 6, and 7 months after completion of primary treatment, of whom three also had simultaneous recurrent (metastatic) disease elsewhere. Two patients had recurrent metastatic disease without any signs of locally recurrent disease on surveillance MRI. All five patients with locally recurrent disease on surveillance MRI died, at 2, 4, 5, 8, and 9 months after local recurrence detection. Patients with locally recurrent disease had a significantly worse overall survival than patients without locally recurrent disease (log-rank test, P < 0.0001). CONCLUSIONS: A limited number of patients have locally recurrent Ewing sarcoma on surveillance MRI. These patients often have simultaneous recurrent (metastatic) disease elsewhere, and their outcome is poor. Moreover, some patients present without locally recurrent disease on MRI but disease recurrence elsewhere. Therefore, surveillance MRI currently seems to have little value and should be reconsidered, also given the costs and the repeated exposure of surviving patients to gadolinium-based contrast agents.

Semi-automated myocardial segmentation of bright blood multi-gradient echo images improves reproducibility of myocardial contours and T2* determination.

OBJECTIVES: Early detection of iron loading is affected by the reproducibility of myocardial contour assessment. A novel semi-automatic myocardial segmentation method is presented on contrast-optimized composite images and compared to the results of manual drawing. MATERIALS AND METHODS: Fifty-one short-axis slices at basal, mid-ventricular and apical locations from 17 patients were acquired by bright blood multi-gradient echo MRI. Four observers produced semi-automatic and manual myocardial contours on contrast-optimized composite images. The semi-automatic segmentation method relies on vector field convolution active contours to generate the endocardial contour. After creating radial pixel clusters on the myocardial wall, a combination of pixel-wise coefficient of variance (CoV) assessment and k-means clustering establishes the epicardial contour for each segment. RESULTS: Compared to manual drawing, semi-automatic myocardial segmentation lowers the variability of T2* quantification within and between observers (CoV of 12.05 vs. 13.86% and 14.43 vs. 16.01%) by improving contour reproducibility (P < 0.001). In the presence of iron loading, semi-automatic segmentation also lowers the T2* variability within and between observers (CoV of 13.14 vs. 15.19% and 15.91 vs. 17.28%). CONCLUSION: Application of semi-automatic myocardial segmentation on contrast-optimized composite images improves the reproducibility of T2* quantification.

[Chronic non-infectious osteomyelitis in children]. / Chronische niet-infectieuze osteomyelitis bij kinderen.

Musculoskeletal pain in common and the differential diagnosis is broad. It is important to recognize the harmful and/or treatable pathology, without performing unnecessary diagnostics. Pattern recognition is crucial. One of the differential diagnostic considerations is chronic non-infectious osteomyelitis (CNO). A relatively unknown auto-inflammatory disease. By presenting three cases, we want to draw attention to this condition and contribute to a better recognition of this disease. We emphasize the importance of doing a total body MRI, when CNO is considered.

Radiotherapy for Ledderhose disease: Results of the LedRad-study, a prospective multicentre randomised double-blind phase 3 trial.

BACKGROUND AND PURPOSE: Radiotherapy is considered a treatment option for Ledderhose disease. However, its benefits have never been confirmed in a randomised controlled trial. Therefore, the LedRad-study was conducted. MATERIALS AND METHODS: The LedRad-study is a prospective multicentre randomised double-blind phase three trial. Patients were randomised to sham-radiotherapy (placebo) or radiotherapy. The primary endpoint was pain reduction at 12 months after treatment, measured with the Numeric Rating Scale (NRS). Secondary endpoints were pain reduction at 6 and 18 months after treatment, quality of life (QoL), walking abilities and toxicity. RESULTS: A total of 84 patients were enrolled. At 12 and 18 months, patients in the radiotherapy group had a lower mean pain score compared to patients in the sham-radiotherapy group (2.5 versus 3.6 (p = 0.03) and 2.1 versus 3.4 (p = 0.008), respectively). Pain relief at 12 months was 74% in the radiotherapy group and 56% in the sham-radiotherapy group (p = 0.002). Multilevel testing for QoL scores showed higher QoL scores in the radiotherapy group compared to the sham-radiotherapy group (p < 0.001). Moreover, patients in the radiotherapy group had a higher mean walking speed and step rate with barefoot speed walking (p = 0.02). Erythema, skin dryness, burning sensations and increased pain were the most frequently reported side effects. These side effects were generally graded as mild (95%) and the majority (87%) were resolved at 18 months follow-up. CONCLUSION: Radiotherapy for symptomatic Ledderhose disease is an effective treatment resulting in a significant pain reduction, improvement of QoL scores and bare feet walking abilities, in comparison to sham-radiotherapy.

Long-Term Halo Follow-Up Confirms Less Invasive Treatment of Low-Grade Cartilaginous Tumors with Radiofrequency Ablation to Be Safe and Effective.

BACKGROUND: Radiofrequency ablation (RFA) is a minimally invasive alternative in the treatment of bone tumors. Long-term follow-up has not been described in current literature. Detailed analysis of mid- and long-term follow-up after RFA treatment for a cohort of patients with low-grade cartilaginous tumors (atypical cartilaginous tumors and enchondroma) was performed. The results, complications, and development of halo dimensions over time are presented. METHODS: Data of all patients with an RFA procedure for an ACT between 2007-2018 were included. Ablation area is visible on baseline MRI, 3 months post-procedure, and is called halo. Volume was measured on MR images and compared to different follow-up moments to determine the effect of time on halo volume. Follow-up was carried out 3 months and 1, 2, 5, and 7 years after the procedure. Occurrence of complications and recurrences were assessed. RESULTS: Of the 137 patients included, 82 were analyzed. Mean follow-up time was 43.6 months. Ablation was complete in 73 cases (89.0%). One late complication occurred, while no recurrences were seen. Halo dimensions of height, width, and depth decreased with a similar rate, 21.5% on average in the first year. Subsequently, this decrease in halo size continues gradually during follow-up, indicating bone revitalization. CONCLUSION: RFA is a safe and effective treatment in low-grade cartilaginous tumors with an initial success rate of 89.0%. Extended follow-up shows no local recurrences and gradual substitution of the halo with normal bone.

Decalcification of Breast Cancer Bone Metastases With EDTA Does Not Affect ER, PR, and HER2 Results.

In metastatic breast cancer (MBC), expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) guides treatment selection. In case of bone-only metastatic disease, ER, PR, and HER2 status assessment may be hampered by decalcification. We aimed to determine the optimal decalcification method, and to study discordance of receptor expression between paired primary breast tumors and optimally decalcified bone metastases. First, decalcification was simulated using acetic acid, hydrochloric/formic acid, and EDTA on 12 primary breast carcinomas. ER, PR, and HER2 immunohistochemistry (IHC) and HER2 in situ hybridization (ISH) were assessed, before and after the 3 decalcification methods. EDTA was considered the optimal method, as it did not affect IHC and as ISH failed in only 1/16 cases. Hydrochloric/formic acid altered ER and PR results, and, with acetic acid and hydrochloric/formic acid, ISH failed in, respectively, 94% and 100%. Second, ER, PR, and HER2 IHC was performed in paired primary tumors and EDTA-decalcified bone metastases obtained from patients with first presentation of MBC. Clinically relevant discordance was defined as changed receptor status with treatment implications. Paired samples of 77 patients, participating in the IMPACT-MBC trial, were evaluable. Hormonal receptor expression change was clinically relevant in 6 patients (7.9%) and HER2 expression change in 1 patient (1.3%). This study shows that EDTA decalcification minimally affects receptor expression results. The incidence of clinically relevant discordance between the primary tumor and bone metastases is low. These findings support that bone biopsies can reliably be used to assess receptor status.

A single digital droplet PCR assay to detect multiple KIT exon 11 mutations in tumor and plasma from patients with gastrointestinal stromal tumors.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are characterized by oncogenic KIT mutations that cluster in two exon 11 hotspots. The aim of this study was to develop a single, sensitive, quantitative digital droplet PCR (ddPCR) assay for the detection of common exon 11 mutations in both GIST tumor tissue and in circulating tumor DNA (ctDNA) isolated from GIST patients' plasma. METHODS: A ddPCR assay was designed using two probes that cover both hotspots. Available archival FFPE tumor tissue from 27 consecutive patients with known KIT exon 11 mutations and 9 randomly selected patients without exon 11 mutations were tested. Plasma samples were prospectively collected in a multicenter bio-databank from December 2014. ctDNA was analyzed of 22 patients with an exon 11 mutation and a baseline plasma sample. RESULTS: The ddPCR assay detected the exon 11 mutation in 21 of 22 tumors with exon 11 mutations covered by the assay. Mutations in ctDNA were detected at baseline in 13 of 14 metastasized patients, but in only 1 of 8 patients with localized disease. In serial plasma samples from 11 patients with metastasized GIST, a decrease in mutant droplets was detected during treatment. According to RECIST 1.1, 10 patients had radiological treatment response and one patient stable disease. CONCLUSION: A single ddPCR assay for the detection of multiple exon 11 mutations in ctDNA is a feasible, promising tool for monitoring treatment response in patients with metastasized GIST and should be further evaluated in a larger cohort.

Assessment of global left ventricular functional parameters: analysis of every second short-axis Magnetic Resonance Imaging slices is as accurate as analysis of consecutive slices.

The purpose of this study was to assess whether accurate global left-ventricular (LV) functional parameters can be obtained by analyzing every second short-axis magnetic resonance imaging cine series instead of consecutive slices, in order to reduce post-processing time. Forty patients, were scanned on a 1.5 T MRI-system (Magnetom Sonata, Siemens Medical Systems, Erlangen, Germany) using a steady-state free precession (SSFP) sequence. A stack of short-axis cine series from above the mitral valve through the apex was acquired. Post-processing was started at the most basal slice of the left ventricle, in which at least 50% of the circumference was myocardium. End-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF) and LV mass (LVM), were calculated. Data analysis was repeated, but now only every second slice was analyzed. Bland-Altman analysis showed slightly lower values for all LV parameters when only every second slice was analyzed, ranging from 1.7% difference for EF (limits of agreement -3.5 to 5.0) to 4.6% for SV (limits of agreement -7.2 to 15.0). Analysis of every second slice for quantification of global LV function is time-saving and as accurate as analysis of consecutive slices.

The additional value of first pass myocardial perfusion imaging during peak dose of dobutamine stress cardiac MRI for the detection of myocardial ischemia.

Purpose of this study was to assess the additional value of first pass myocardial perfusion imaging during peak dose of dobutamine stress Cardiac-MR (CMR). Dobutamine Stress CMR was performed in 115 patients with an inconclusive diagnosis of myocardial ischemia on a 1.5 T system (Magnetom Avanto, Siemens Medical Systems). Three short-axis cine and grid series were acquired during rest and at increasing doses of dobutamine (maximum 40 microg/kg/min). On peak dose dobutamine followed immediately by a first pass myocardial perfusion imaging sequence. Images were graded according to the sixteen-segment model, on a four point scale. Ninety-seven patients showed no New (Induced) Wall Motion Abnormalities (NWMA). Perfusion imaging showed absence of perfusion deficits in 67 of these patients (69%). Perfusion deficits attributable to known previous myocardial infarction were found in 30 patients (31%). Eighteen patients had NWMA, indicative for myocardial ischemia, of which 14 (78%) could be confirmed by a corresponding perfusion deficit. Four patients (22%) with NWMA did not have perfusion deficits. In these four patients NWMA were caused by a Left Bundle Branch Block (LBBB). They were free from cardiac events during the follow-up period (median 13.5 months; range 6-20). Addition of first-pass myocardial perfusion imaging during peak-dose dobutamine stress CMR can help to decide whether a NWMA is caused by myocardial ischemia or is due to an (inducible) LBBB, hereby preventing a false positive wall motion interpretation.