| 1. |
- Gaspar, Nathalie, et al.
(författare)
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Ewing Sarcoma: Current Management and Future Approaches Through Collaboration.
- 2015
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 33:27, s. 140-3036
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Forskningsöversikt (refereegranskat)abstract
- Ewing sarcoma (ES) is an aggressive sarcoma of bone and soft tissue occurring at any age with a peak incidence in adolescents and young adults. The treatment of ES relies on a multidisciplinary approach, coupling risk-adapted intensive neoadjuvant and adjuvant chemotherapies with surgery and/or radiotherapy for control of the primary site and possible metastatic disease. The optimization of ES multimodality therapeutic strategies has resulted from the efforts of several national and international groups in Europe and North America and from cooperation between pediatric and medical oncologists. Successive first-line trials addressed the efficacy of various cyclic combinations of drugs incorporating doxorubicin, vincristine, cyclophosphamide, ifosfamide, etoposide, and dactinomycin and identified prognostic factors now used to tailor therapies. The role of high-dose chemotherapy is still debated. Current 5-year overall survival for patients with localized disease is 65% to 75%. Patients with metastases have a 5-year overall survival < 30%, except for those with isolated pulmonary metastasis (approximately 50%). Patients with recurrence have a dismal prognosis. The many insights into the biology of the EWS-FLI1 protein in the initiation and progression of ES remain to be translated into novel therapeutic strategies. Current options and future approaches will be discussed.
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| 2. |
- Sörensen, Jens, et al.
(författare)
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Diagnosis of left ventricular hypertrophy using non-ECG-gated 15O-water PET
- 2022
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Ingår i: Journal of Nuclear Cardiology. - : Springer. - 1071-3581 .- 1532-6551. ; , s. 2361-2373
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To develop a method for diagnosing left ventricular (LV) hypertrophy from cardiac perfusion 15O-water positron emission tomography (PET).Methods: We retrospectively pooled data from 139 subjects in four research cohorts. LV remodeling patterns ranged from normal to severe eccentric and concentric hypertrophy. 15O-water PET scans (n = 197) were performed with three different PET devices. A low-end scanner (66 scans) was used for method development, and remaining scans with newer devices for a blinded evaluation. Dynamic data were converted into parametric images of perfusable tissue fraction for semi-automatic delineation of the LV wall and calculation of LV mass (LVM) and septal wall thickness (WT). LVM and WT from PET were compared to cardiac magnetic resonance (CMR, n = 47) and WT to 2D-echocardiography (2DE, n = 36). PET accuracy was tested using linear regression, Bland–Altman plots, and ROC curves. Observer reproducibility were evaluated using intraclass correlation coefficients.Results: High correlations were found in the blinded analyses (r ≥ 0.87, P < 0.0001 for all). AUC for detecting increased LVM and WT (> 12 mm and > 15 mm) was ≥ 0.95 (P < 0.0001 for all). Reproducibility was excellent (ICC ≥ 0.93, P < 0.0001).Conclusion: 15O-water PET might detect LV hypertrophy with high accuracy and precision.
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| 3. |
- Sörensen, Jens, et al.
(författare)
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Diagnostic accuracy of 15O-water PET for left-ventricular hypertrophy
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Aim: To develop and validate a method for diagnosing left ventricular (LV) hypertrophy from cardiac perfusion 15O-water positron emission tomography (PET).Methods:This was a retrospective study with pooled data from 139 subjects in four research cohorts. LV remodeling patterns ranged from normal to severe eccentric and concentric hypertrophy. 15O-water PET scans (n=197) were performed with three different PET devices. Data from a low-end scanner (66 scans) were used for method development, remaining scans were used for a blinded evaluation. Dynamic data were converted into parametric images of perfusable tissue fraction for semi-automatic delineation of the LV wall in the short axis view. The enclosed region was used to calculate LV mass (LVM) and septal wall thickness (WT). LVM and WT from PET were compared to cardiac magnetic resonance (CMR, n=47) and WT to 2D-echocardiography (2DE, n=36). PET accuracy was tested using linear regression, Bland-Altman plots, and ROC curves. Observer reproducibility were evaluated using intraclass correlation coefficients. Results: Correlations (PET-LVM and PET-WT towards CMR; PET-WT towards 2DE) were high (r≥0.87, P<0.0001 for all) with high-end scanners, and slightly lower for LVM (r=0.84) and WT (r=0.76, both P<0.0001) with a low-end scanner. There was no significant bias for WT, but a proportional bias for LVM was found. The area-under-the-curve for blinded detection of increased LVM and WT (>12 mm and >15 mm) diagnosed by conventional imaging was ≥0.95 (P<0.0001 for all). Reproducibility was excellent (ICC ≥ 0.93, P<0.0001). Conclusion: 15O-water PET might detect LV hypertrophy with high accuracy and precision.
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| 4. |
- Whelan, Jeremy, et al.
(författare)
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High-dose chemotherapy and blood autologous stem-cell rescue compared with standard chemotherapy in localized high-risk ewing sarcoma : Results of Euro-E.W.I.N.G.99 and Ewing-2008
- 2018
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Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 36:31, s. 3110-3119
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Tidskriftsartikel (refereegranskat)abstract
- Purpose For over 30 years, the place of consolidation high-dose chemotherapy in Ewing sarcoma (ES) has been controversial. A randomized study was conducted to determine whether consolidation high-dose chemotherapy improved survival in patients with localized ES at high risk for relapse. Methods Randomization between busulfan and melphalan (BuMel) or standard chemotherapy (vincristine, dactinomycin, and ifosfamide [VAI], seven courses) was offered to patients if they were younger than 50 years of age with poor histologic response (≥ 10% viable cells) after receiving vincristine, ifosfamide, doxorubicin, and etoposide (six courses); or had a tumor volume at diagnosis >200 mL if unresected, or initially resected, or resected after radiotherapy. A 15% improvement in 3-year eventfree survival (EFS) was sought (hazard ratio [HR], 0.60). Results Between 2000 and 2015, 240 patients classified as high risk (median age, 17.1 years) were randomly assigned to VAI (n = 118) or BuMel (n = 122). Seventy-eight percent entered the trial because of poor histologic response after chemotherapy alone. Median follow-up was 7.8 years. In an intent-to-treat analysis, the risk of event was significantly decreased by BuMel comparedwith VAI: HR, 0.64 (95%CI, 0.43 to 0.95; P = .026); 3- and 8-year EFS were, respectively, 69.0%(95% CI, 60.2%to 76.6%) versus 56.7%(95%CI, 47.6%to 65.4%) and 60.7%(95%CI, 51.1%to 69.6%) versus 47.1%(95%CI, 37.7% to 56.8%). Overall survival (OS) also favored BuMel: HR, 0.63 (95% CI, 0.41 to 0.95; P = .028); 3- and 8-year OS were, respectively, 78.0% (95% CI, 69.6% to 84.5%) versus 72.2% (95% CI, 63.3% to 79.6%) and 64.5%(95%CI, 54.4% to 73.5%) versus 55.6%(95%CI, 45.8%to 65.1%). Results were consistent in the sensitivity analysis. Two patients died as a result of BuMel-related toxicity, one after standard chemotherapy. Significantly more BuMel patients experienced severe acute toxicities from this course of chemotherapy compared with multiple VAI courses. Conclusion BuMel improved EFS and OS when given after vincristine, ifosfamide, doxorubicin, and etoposide induction in localized ES with predefined high-risk factors. For this group of patients, BuMel may be an important addition to the standard of care.
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