| 1. |
- Sonnenblick, Amir, et al.
(författare)
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Final 10-year results of the Breast International Group 2-98 phase III trial and the role of Ki67 in predicting benefit of adjuvant docetaxel in patients with oestrogen receptor positive breast cancer
- 2015
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 51:12, s. 1481-1489
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Breast International Group (BIG) 2-98 is a randomised phase III trial that tested the effect of adding docetaxel, either in sequence to or in combination with anthracycline-based adjuvant chemotherapy, in women with node-positive breast cancer (BC). Here, we present the 10-year final trial safety and efficacy analyses. We also report an exploratory analysis on the predictive value of Ki67 for docetaxel efficacy, in the BIG 2-98 and using a pooled analysis of three other randomised trials. Patients and methods: 2887 patients were randomly assigned in a 2 x 2 trial design to one of four treatments. The primary objective was to evaluate the overall efficacy of docetaxel on disease free survival (DFS). Secondary objectives included comparisons of sequential docetaxel versus sequential control arm, safety and overall survival (OS). Ki67 expression was centrally evaluated by immunohistochemistry. Results: After a median follow-up of 10.1 years, the addition of docetaxel did not significantly improve DFS or OS (hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.81-1.04; P = 0.16 and HR = 0.88, 95% CI = 0.76-1.03; P = 0.11, respectively). Sequential docetaxel did not improve DFS compared to the sequential control arm (HR = 0.86, 95% CI = 0.721.03; P = 0.10). In oestrogen receptor (ER)-positive tumours with Ki67 greater than= 14%, the addition of docetaxel resulted in 5.4% improvement in 10-year OS (P = 0.03, test for interaction = 0.1). In a multivariate model, there was a trend for improved DFS and OS in ER-positive patients with high Ki67 and treated with docetaxel (HR = 0.79, 95% CI = 0.63-1.01; P = 0.05 and HR = 0.76, 95% CI = 0.57-1.01; P = 0.06, respectively). A pooled analysis of four randomised trials showed a benefit of taxanes in highly proliferative ER-positive disease but not in low proliferating tumours (interaction test P = 0.01). Conclusion: The DFS benefit previously demonstrated with sequential docetaxel is no longer observed at 10 years. However, an exploratory analysis suggested a benefit of docetaxel in patients with highly proliferative ER-positive BC.
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| 2. |
- Timmerman, Dirk, et al.
(författare)
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Simple ultrasound rules to distinguish between benign and malignant adnexal masses before surgery: prospective validation by IOTA group
- 2010
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Ingår i: BMJ: British Medical Journal. - : BMJ. - 1756-1833. ; 341, s. 6839-6839
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To prospectively assess the diagnostic performance of simple ultrasound rules to predict benignity/malignancy in an adnexal mass and to test the performance of the risk of malignancy index, two logistic regression models, and subjective assessment of ultrasonic findings by an experienced ultrasound examiner in adnexal masses for which the simple rules yield an inconclusive result. Design Prospective temporal and external validation of simple ultrasound rules to distinguish benign from malignant adnexal masses. The rules comprised five ultrasonic features (including shape, size, solidity, and results of colour Doppler examination) to predict a malignant tumour (M features) and five to predict a benign tumour (B features). If one or more M features were present in the absence of a B feature, the mass was classified as malignant. If one or more B features were present in the absence of an M feature, it was classified as benign. If both M features and B features were present, or if none of the features was present, the simple rules were inconclusive. Setting 19 ultrasound centres in eight countries. Participants 1938 women with an adnexal mass examined with ultrasound by the principal investigator at each centre with a standardised research protocol. Reference standard Histological classification of the excised adnexal mass as benign or malignant. Main outcome measures Diagnostic sensitivity and specificity. Results Of the 1938 patients with an adnexal mass, 1396 (72%) had benign tumours, 373 (19.2%) had primary invasive tumours, 111 (5.7%) had borderline malignant tumours, and 58 (3%) had metastatic tumours in the ovary. The simple rules yielded a conclusive result in 1501 (77%) masses, for which they resulted in a sensitivity of 92% (95% confidence interval 89% to 94%) and a specificity of 96% (94% to 97%). The corresponding sensitivity and specificity of subjective assessment were 91% (88% to 94%) and 96% (94% to 97%). In the 357 masses for which the simple rules yielded an inconclusive result and with available results of CA-125 measurements, the sensitivities were 89% (83% to 93%) for subjective assessment, 50% (42% to 58%) for the risk of malignancy index, 89% (83% to 93%) for logistic regression model 1, and 82% (75% to 87%) for logistic regression model 2; the corresponding specificities were 78% (72% to 83%), 84% (78% to 88%), 44% (38% to 51%), and 48% (42% to 55%). Use of the simple rules as a triage test and subjective assessment for those masses for which the simple rules yielded an inconclusive result gave a sensitivity of 91% (88% to 93%) and a specificity of 93% (91% to 94%), compared with a sensitivity of 90% (88% to 93%) and a specificity of 93% (91% to 94%) when subjective assessment was used in all masses. Conclusions The use of the simple rules has the potential to improve the management of women with adnexal masses. In adnexal masses for which the rules yielded an inconclusive result, subjective assessment of ultrasonic findings by an experienced ultrasound examiner was the most accurate diagnostic test; the risk of malignancy index and the two regression models were not useful.
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| 3. |
- Valentin, Lil, et al.
(författare)
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The risk of malignancy in unilocular cysts: a study on 1148 adnexal masses classified as unilocular cysts at transvaginal scan with review of the literature.
- 2013
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Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 41:1, s. 80-89
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To estimate the rate of malignancy in adnexal lesions described as unilocular cysts at transvaginal ultrasound examination, to investigate if there are differences in clinical and ultrasound characteristics between benign and malignant unilocular cysts. Methods: 3511 patients with an adnexal mass underwent transvaginal ultrasound examination between 1999 and 2007. The sonologists used the International Ovarian Tumor Analysis terms and definitions to describe their ultrasound findings. Gold standard was the histopathological diagnosis of the mass. Results: Of the 3511 masses, 1148 (33%) were classified as unilocular cysts at scan. Of these, 11 i.e. 0.96 % (95%CI 0.48-1.71) were malignant. The malignancy rate was lower in pre- than post-menopausal women: 0.54% (5/931) (0.17-1.25) versus 2.76% (6/217) (1.02-5.92), P = 0.009. More patients with malignant unilocular cysts had a personal history of breast cancer (18% versus 2%, P = 0.02) or ovarian cancer (18% versus 0.6%, P = 0.003). Hemorrhagic cyst contents at scan was more common in malignant than benign unilocular cysts (18% versus 2%, P = 0.03). In seven of the 11 malignancies judged to be unilocular cysts at scan, papillary projections or other solid components were seen at macroscopic inspection of the surgical specimen. Conclusions: The malignancy rate in surgically removed adnexal lesions judged to be unilocular cysts at transvaginal scan is around 1%. Postmenopausal status, personal history of breast or ovarian cancer and hemorrhagic cyst contents at scan increase the risk of malignancy. To avoid misclassifying adnexal lesions as unilocular cysts at scan, it is important to scrutinize unilocular cysts for the presence of solid components. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.
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| 4. |
- Valentin, Lil, et al.
(författare)
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Ultrasound characteristics of different types of adnexal malignancies.
- 2006
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 1095-6859 .- 0090-8258. ; 102:1, s. 41-48
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To describe ultrasound characteristics of adnexal malignancies, i.e., borderline ovarian tumors, primary invasive ovarian epithelial cancer stage 1, primary invasive ovarian epithelial cancer stages 2–4, rare types of malignancy, and metastatic tumors. Methods. In a prospective international study involving nine European ultrasound centers, 1066 women with a pelvic mass judged to be of adnexal origin underwent transvaginal gray scale and color Doppler ultrasound examination by a skilled examiner before surgery. A standardized examination technique and predefined definitions of ultrasound characteristics were used. Results. Of 1066 masses, 266 were malignant and are included: 55 ovarian borderline tumors, 144 primary invasive epithelial ovarian cancers (42 stage 1, 102 stages 2–4), 25 rare malignancies, and 42 metastatic tumors. Most (56%) metastatic tumors and most (60%) rare types of tumor were solid and richly vascularized at color Doppler ultrasound examination (on a scale ranging from 1 to 4, color score based on subjective evaluation was 3 or 4 in 88% and 86%, respectively). Borderline ovarian tumors and stage 1 primary invasive ovarian epithelial cancers differed from stages 2–4 primary invasive ovarian epithelial cancers: they were larger (median volume 375 ml and 695 ml vs. 209 ml; P = 0.0213 and 0.0001), a larger proportion contained papillary projections (64% and 67% vs. 41%; P = 0.0072 and 0.0054), they were more often multilocular cysts without solid components (18% and 14% vs. 2%; P < 0.0017 and 0.0204), but they were less often purely solid (5% and 7% vs. 38%; P ≤ 0.0001 and 0.0005). With increasing degree of invasiveness – from borderline epithelial ovarian tumors via stage 1 invasive epithelial ovarian tumors to stages 2–4 invasive epithelial ovarian tumors – ascites became more common (9% vs. 31% vs. 61%; P = 0.0082, <0.0001, and 0.0017), and, among tumors with solid components (n = 179), the proportion of tumor consisting of solid tissue increased (median 2%–10%–34%; P = 0.0212, <0.0001, and 0.0003). Conclusion. Papillary projections are characteristic of borderline tumors and stage 1 primary invasive epithelial ovarian cancer. A small proportion of solid tissue at ultrasound examination makes a malignant mass more likely to be a borderline tumor or a stage 1 epithelial ovarian cancer than an advanced ovarian cancer, a metastasis, or a rare type of tumor.
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| 5. |
- Zeidan, Youssef H., et al.
(författare)
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Postmastectomy Radiation Therapy in Women with T1-T2 Tumors and 1 to 3 Positive Lymph Nodes: Analysis of the Breast International Group 02-98 Trial
- 2018
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : ELSEVIER SCIENCE INC. - 0360-3016 .- 1879-355X. ; 101:2, s. 316-324
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To analyze the impact of postmastectomy radiation therapy (PMRT) for patients with T1-T2 tumors and 1 to 3 positive lymph nodes enrolled on the Breast International Group (BIG) 02-98 trial. Methods and Materials: The BIG 02-98 trial randomized patients to receive adjuvant anthracycline with or without taxane chemotherapy. Delivery of PMRT was nonrandomized and performed according to institutional preferences. The present analysis was performed on participants with T1-T2 breast cancer and 1 to 3 positive lymph nodes who had undergone mastectomy and axillary nodal dissection. The primary objective of the present study was to examine the effect of PMRT on risk of locoregional recurrence (LRR), breast cancer-specific survival, and overall survival. Results: We identified 684 patients who met the inclusion criteria and were included in the analysis, of whom 337 (49%) had received PMRT. At 10 years, LRR risk was 2.5% in the PMRT group and 6.5% in the no-PMRT group (hazard ratio 0.29, 95% confidence interval 0.12-0.73; P=.005). Lower LRR after PMRT was noted for patients randomized to receive adjuvant chemotherapy with no taxane (10-year LRR: 3.4% vs 9.1%; P=.02). No significant differences in breast cancer-specific survival (84.3% vs 83.9%) or overall survival (81.7% vs 78.3%) were observed according to receipt of PMRT. Conclusion: Our analysis of the BIG02-98 trial shows excellent outcomes in women with T1-T2 tumors and 1 to 3 positive lymph nodes found in axillary dissection. Although PMRT improved LRR in this cohort, the number of events remained low at 10 years. In all groups, 10-year rates of LRR were relatively low compared with historical studies. As such, the use of PMRT in women with 1 to 3 positive nodes should be tailored to individual patient risks. (C) 2018 Elsevier Inc. All rights reserved.
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