Adjuvant denosumab in postmenopausal patients with hormone receptor-positive breast cancer (ABCSG-18): disease-free survival results from a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: In postmenopausal women with hormone receptor-positive, early-stage breast cancer, treatment with adjuvant aromatase inhibitors is the standard of care, but it increases risk for osteoporosis and fractures. Results from the ABCSG-18 trial showed that use of denosumab as an adjuvant to aromatase inhibitor therapy significantly reduced clinical fractures. Disease-free survival outcomes from ABCSG-18 have not yet been reported. METHODS: Postmenopausal patients with early, hormone receptor-positive, non-metastatic adenocarcinoma of the breast, who had completed their initial adjuvant treatment pathway (surgery, radiotherapy, or chemotherapy, or a combination) and were receiving adjuvant aromatase inhibitors, were enrolled at 58 trial centres in Austria and Sweden into this prospective, double-blind, placebo-controlled, phase 3 trial. With permuted block randomisation (block sizes 2 and 4, stratified by previous aromatase inhibitor use, total lumbar spine bone mineral density score at baseline, and type of centre), patients were assigned (1:1) to receive subcutaneous denosumab (60 mg) or matching placebo every 6 months during aromatase inhibitor therapy. The primary endpoint (previously reported) was the time to first clinical fracture after randomisation. The secondary endpoint reported here is disease-free survival (defined as time from randomisation to first evidence of local or distant metastasis, contralateral breast cancer, secondary carcinoma, or death from any cause) in the intention-to-treat population. This study is registered with EudraCT (number 2005-005275-15) and ClinicalTrials.gov (number NCT00556374), and is ongoing for long-term follow-up. FINDINGS: Between Dec 18, 2006, and July 22, 2013, 3425 eligible patients were enrolled and randomly assigned; 1711 to the denosumab group and 1709 to the placebo group (with five others withdrawing consent). After a median follow-up of 73 months (IQR 58-95), 240 (14·0%) patients in the denosumab and 287 (16·8%) in the placebo group had disease-free survival events. Disease-free survival was significantly improved in the denosumab group versus the placebo group (hazard ratio 0·82, 95% CI 0·69-0·98, Cox p=0·0260; descriptive analysis, without controlling for multiplicity). In the denosumab group, disease-free survival was 89·2% (95% CI 87·6-90·8) at 5 years and 80·6% (78·1-83·1) at 8 years of follow-up, compared with 87·3% (85·7-89·0) at 5 years and 77·5% (74·8-80·2) and 8 years in the placebo group. No independently adjudicated cases of osteonecrosis of the jaw or confirmed atypical femoral fractures were recorded. The total number of adverse events was similar in the denosumab group (1367 [including 521 serious] adverse events) and the placebo group (1339 [515 serious]). The most common serious adverse events were osteoarthritis (62 [3·6%] of 1709 in the denosumab group vs 58 [3·4%] of 1690 in the placebo group), meniscus injury (23 [1·3%] vs 24 [1·4%]), and cataract (16 [0·9%] vs 28 [1·7%]). One (<0·1%) treatment-related death (due to pneumonia, septic kidney failure, and cardiac decompensation) occurred in the denosumab group. INTERPRETATION: Denosumab constitutes an effective and safe adjuvant treatment for patients with postmenopausal hormone receptor-positive early breast cancer receiving aromatase inhibitor therapy. FUNDING: Amgen.

Impact of dental implant length on early failure rates: a meta-analysis of observational studies.

AIM: To test the null hypothesis of no difference in failure rates of short (minimum length: 7 mm) and longer dental implants (≥ 10 mm), a meta-analysis was performed on prospective observational trials. MATERIALS AND METHODS: A systematic electronic and hand search was performed to identify eligible studies. Having additional data supplied by the authors, 54 publications were included (19,083 implants). RESULTS: In case of mandibular implants, the null hypothesis of no impact of reduced implant length on failure within the first year of prosthetic loading could not be rejected. A significant impact of implant length could be substantiated for short machined implants in the anterior [odds ratio (OR) 5.4] and posterior maxilla (OR 3.4), while short rough-surfaced implants demonstrated increased failure rates in the anterior maxillary sites. No influence of implant diameter and denture type on the failure rate of short implants could be revealed. CONCLUSION: In areas of reduced alveolar bone height the use of short dental implants may reduce the need for invasive bone augmentation procedures.

Periodontal probing of dental furcations compared with diagnosis by low-dose computed tomography: a case series.

BACKGROUND: Therapeutic decisions in periodontal surgery are based on the accurate diagnosis of the furcation. Clinical probing is the basic diagnostic tool; however, the accuracy of clinical probing to distinguish Class II and Class III furcation defects is unknown. Therefore, this study compares clinical probing diagnoses to those of computed tomography (CT). METHODS: Seventy-five patients with severe periodontal disease were enrolled in this case series study. A total of 582 furcation sites in molars were assigned for the diagnosis of Class II and Class III furcation defects by clinical probing. Diagnosis based on CT served as a reference. RESULTS: The degree of furcation involvement on clinical findings was confirmed in 57% of the sites, whereas 20% were overestimated and 23% were underestimated compared with the radiologic analysis. Only 32% of Class III furcations in the CT scan were detected clinically. The best correlation of CT scan and clinical probing was found at buccal furcation sites in the mandible, with a κ-coefficient of 0.52, and buccal furcation sites in the maxilla, κ = 0.38. The κ-coefficient was 0.35 for lingual furcations, 0.29 for mesial furcations, and 0.27 for distal furcations, showing weaker correlations. CONCLUSIONS: CT scans offer more detailed information on furcation involvement than clinical probing. Especially before surgical treatment, three-dimensional radiographic imaging can be a useful tool to assess the degree of furcation involvement and optimize treatment decisions.