PURPOSE The objective of this study was to investigate potential correlations between pathologic fractures (PFs) and prognosis of patients with primary central high-grade osteosarcoma of the extremities. METHODS We retrospectively analyzed 2,847 patients registered in the Consecutive Cooperative Osteosarcoma Study Group database with primary central high-grade osteosarcoma of the extremities, treated between 1980 and 2010. Intended treatment included pre- and postoperative chemotherapy and surgery. Univariable and multivariable survival analyses were performed for all patients and then differentiated for adult and pediatric (≤ 18 years at time of diagnosis) patients. RESULTS A total of 2,193 patients were ≤ 18 years of age; 11.3% of all patients had PFs. In the overall cohort, presence of PF correlated significantly with tumor site, histologic subtype, relative tumor size, and primary metastases, but not with body mass index or local surgical remission. In univariable analysis, 5-year overall survival (OAS) of patients with and without PF was 63% versus 71%, respectively ( P = .007), and 5-year event-free survival (EFS) was 51% versus 58% ( P = .026). In pediatric patients, OAS and EFS did not differ significantly between patients with and without PF. In adults, 5-year OAS in patients with and without PF was 46% versus 69% ( P < .001), and 5-year EFS was 36% versus 56% ( P < .001). In multivariable analysis, PF was not a statistically significant factor for OAS or EFS in the total cohort or in pediatric patients. In adult patients, PF remained an independent prognostic factor for OAS ( P = .013; hazard ratio [HR], 1.893). It was not a significant prognostic factor for EFS ( P = .263; HR, 1.312). CONCLUSION In this largest study to date with extremity osteosarcomas, we observed the occurrence of PF to correlate with inferior OAS expectancies in adult but not in pediatric patients.

Background: The purpose of this study was to investigate whether pathological fractures (PF) influence the prognosis of patients with osteosarcoma (OS) or Ewing tumor (ET) regarding 5-year survival, occurrence of metastases, and local recurrence. Methods: We retrospectively analyzed 205 patients with metastatic and nonmetastatic OS or ET. Survival analysis was performed for all patients and differentiated for patients with OS (n = 127) and ET (n = 78) as well as for adults (n = 101) and children (n = 104). Results: Patients with PF showed survival rates of 64% compared to 83% for those without PF (p = 0.023). Local recurrence occurred in 7% of the patients without and in 24% of those with PF (p = 0.023). In patients with ET and in children, survival analysis showed no significant difference between patients with and without PF in survival and local recurrence rates. In patients with OS, survival rate decreased from 83 to 59% (p = 0.024) and local recurrence rate increased from 13 to 30% (p = 0.042). In adults, survival rate decreased from 78 to 51% (p = 0.004) and local recurrence rate increased from 13 to 42% (p < 0.001). In multivariate analysis, age and PF were associated with inferior survival. Conclusion: This study suggests that the occurrence of PF has a negative impact on survival and implicates an increased risk of local recurrence. In children and in patients with ET, PF did not have a prognostic impact.

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Background: In patients (pts) with HER2-positive metastatic breast cancer (BC), the phase III CLEOPATRA study (NCT00567190) demonstrated significant improvement in progression-free (PFS) and overall survival (OS) from first-line treatment with intravenous (IV) pertuzumab (PERJETA® [P IV]) plus trastuzumab (Herceptin® [H IV]) plus docetaxel (D IV). HannaH (NCT00950300), a phase III trial in pts with HER2-positive early BC demonstrated that fixed-dose trastuzumab subcutaneous (Herceptin® [H SC]) is non-inferior to weight-based H IV infusion in the co-primary endpoints of serum trough concentration and pathologic complete response, which was supported by the long-term efficacy endpoints of event-free survival (EFS) and OS. The safety profile of H SC was consistent with the known safety profile of H IV. H SC is comprised of 600 mg trastuzumab and recombinant human hyaluronidase (rHuPH20) as an excipient, allowing a significantly reduced administration time compared with H IV (5 mins versus 30–90 mins, respectively). The MetaPHER study is designed to investigate the safety and efficacy of H SC in combination with P IV and D IV in pts with HER2-positive advanced BC. Trial design: MetaPHER is a phase IIIb multicenter, open-label, single-arm study, with eligible pts receiving H SC 600 mg/5 mL q3w, P IV (840 mg loading dose, then 420 mg at each subsequent cycle q3w), and D IV (at least 6 cycles at 75 mg/m2 q3w with possible escalation to 100 mg/m2 q3w; after Cycle 6, continuation of docetaxel is at the investigator's discretion). Study treatment is administered until disease progression, unacceptable toxicity, withdrawal of consent, death, or predefined study end, whichever occurs first. Pts will receive post-treatment follow-up for safety and survival. Eligibility: Women aged ≥18 years with metastatic or locally recurrent HER2-positive BC, ECOG performance status 0 or 1, and a left ventricular ejection fraction ≥50% are eligible. Exclusion criteria include disease-free interval of &lt;6 months from completion of adjuvant or neoadjuvant non-hormonal treatment to disease recurrence; previous systemic non-hormonal therapy for metastatic or locally recurrent BC; history of persistent grade ≥2 hematological toxicity; current grade ≥3 peripheral neuropathy; or clinically significant cardiovascular disease. Aims: The primary objective is to evaluate the safety and tolerability of H SC in combination with P IV and D IV in pts with HER2-positive advanced BC. Secondary endpoints include PFS, OS, objective response rate and incidence of anti-trastuzumab and anti-rHuPH20 antibody formation. Statistical methods: Safety and efficacy results will be summarized descriptively to include all enrolled pts who received at least one dose of any study drug; the study is not designed for formal hypothesis testing. A sample size of 400 pts provides reasonable precision for the estimation of grade ≥3 AEs and cardiac AEs. Accrual: MetaPHER is enrolling, FPI was May 2015, and target enrollment is 400 pts; clinicaltrials.gov ID: NCT02402712. Contact information: For more information or to refer a patient, email global.rochegenentechtrials@roche.com or call 1-888-662-6728 (USA only). Citation Format: Kümmel S, Crepelle-Fléchais A, Schlegel M, Hillenbach C, Swat A, Franz M, Girase P, Schneider A, Heinzmann D, Shing M. MetaPHER: A phase IIIb multicenter, open-label, single-arm safety study of subcutaneous trastuzumab, in combination with pertuzumab and docetaxel in patients with HER2-positive advanced breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT3-01-13.

Malleus head fixation and otosclerosis causing conductive hearing loss are often difficult to differentiate by clinical features. Up to now exploratory anterior tympanotomy was necessary to distinguish these pathologies. The case of a 22-year-old male suffering from conductive hearing loss of the right ear is presented. Otosclerosis was suspected and high-resolution CT scanning of the petrous bone was performed. The diagnosis was confirmed radiologically by the detection of an isolated malleus head fixation. Instead of explorative anterior tympanotomy, radiological and audiological controls were combined for the follow-up.

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