The use of an individualized intraoperative video shows no impact on the early postoperative clinical outcome after total knee arthroplasty: a prospective, randomized, controlled trial.

PURPOSE: The purpose of the study was to evaluate the potential of an intraoperatively recorded video shown to patients immediately postoperatively on early outcome after total knee arthroplasty (TKA). The hypothesis was that there is a beneficial outcome concerning range of motion (ROM) and patient-reported outcome due to enhanced trust into the artificial joint. METHODS: Seventy-three patients were randomly assigned 1:1 to two study groups in which they were either shown a video of their own postoperative range of motion or they were not. Clinically, the New Knee Society Score (nKSS) and ROM were evaluated and compared between the groups 6 weeks after surgery. Chi-square exact test, Kolmogorov-Smirnov test, Mann-Whitney U test, and the Wilcoxon signed rank test were used. Inter- and intra-class correlations were calculated for measurements of ROM. RESULTS: No clinically relevant differences were observed preoperatively and 6 weeks postoperatively between both groups in range of motion (ROM). All patients were showing a significantly improved clinical outcome 6 weeks after the procedure. Clinical scores showed statistically significant differences with respect to preoperative nKSS for satisfaction and statistically significant differences with respect to postoperative nKSS for function. CONCLUSION: Showing a video filmed immediately after implantation of primary TKA had no significant effect on ROM and clinical outcome at 6 weeks. We believe that face-to-face verbal communication in combination with video-assisted education ensures that patients understand their artificial joint in the best possible way and will continue to use intraoperatively filmed videos to enhance patient engagement during postoperative rehabilitation. LEVEL OF EVIDENCE: I.

Revision Rates After Total Ankle Replacement: A Comparison of Clinical Studies and Arthroplasty Registers.

BACKGROUND: The aim of this study was to assess the outcome of total ankle replacement (TAR) regarding revision rates by comparing clinical studies of the last decade to data displayed in arthroplasty registers. The secondary aim was to evaluate whether dependent clinical studies show a superior outcome to independent publications. Additionally, revision rates of mobile bearing implants (MB-TARs) were compared to those of fixed bearing implants (FB-TARs). METHODS: Clinical studies on TARs between 2010 and 2020 were systematically reviewed, with the endpoint being a revision for any reason. The parameter "revision rate per 100 observed component years (CYs)" was calculated for each publication. The pooled revision rate for clinical studies was compared to the data reported in arthroplasty registers. In a second step, revision rates were subdivided and analyzed for independent and dependent publications and for FB-TARs and MB-TARs. RESULTS: A total of 43 publications met the inclusion criteria comprising 5806 TARs. A revision rate of 1.8 per 100 observed CYs was calculated, corresponding to a 7-year revision rate of 12.6%. The 3 arthroplasty registers included showed revision rates ranging from 8.2% to 12.3% after 7 years. No significant difference between dependent and independent publications nor between FB-TARs and MB-TARs was detected. CONCLUSION: Revision rates of clinical studies and arthroplasty registers are comparable. Surgeons can compare their own revision rates with those from this study. Dependent studies do not seem to be biased, and no superiority for one bearing type can be described. LEVEL OF EVIDENCE: Level III, systematic review of level III studies.

A European, Observational Study of Endocrine Therapy Administration in Patients With an Initial Diagnosis of Hormone Receptor-Positive Advanced Breast Cancer.

BACKGROUND: Despite guideline recommendations, reports suggest that a proportion of patients with hormone receptor (HR)-positive locally advanced or metastatic breast cancer (LA/MBC) might not receive endocrine therapy. The aims of this study were to estimate the proportion of postmenopausal patients with an initial (primary) diagnosis of HR-positive LA/MBC in Europe, and to assess the administration of endocrine treatment in these patients. MATERIALS AND METHODS: Fourteen national and regional cancer registries across Europe were invited to participate in this observational study. Six registries each provided anonymized clinical information on > 5000 postmenopausal women with breast cancer diagnosed between January 2000 and December 2014, including age at diagnosis, estrogen and/or progesterone receptor status, disease stage, and receipt of endocrine therapy. The proportion of patients with an initial diagnosis of HR-positive LA/MBC and, of these, the proportion who received endocrine therapy, was calculated. RESULTS: Registries from Belgium, England, Ireland, Norway, The Netherlands, and Munich, Germany provided data. In total, 316,680 postmenopausal women were diagnosed with breast cancer, including 244,268 with known HR status and disease stage. Of these patients, 19,002 (7.8%) had a primary diagnosis of HR-positive LA/MBC. This proportion ranged from 5.4% (N = 4484) in England to 12.7% (N = 4085) in Germany. Most of these patients (n = 14,157; 74.5%) received endocrine treatment, ranging from 55.5% (n = 445) in Norway to 88.1% (n = 443) in Belgium. CONCLUSION: These results indicate that a sizeable proportion of postmenopausal patients in Europe received a primary diagnosis of HR-positive LA/MBC, and that almost three-quarters received subsequent endocrine therapy as per guideline recommendations.

Clinical outcomes of female breast cancer according to BRCA mutation status.

BACKGROUND: To investigate breast cancer prognosis (disease-free (DFS) and overall survival (OS)) among carriers of germline BRCA mutations (BRCAm) in Denmark. METHODS: We identified all women in Central and Northern Denmark diagnosed with breast cancer during 2004-2011. We retrieved information on germline BRCAm testing from Clinical Genetics departments and clinical/treatment characteristics from population-based medical registries. Follow-up for recurrence, new primary cancer, and mortality extended from 180days after diagnosis until 31/12/2012. We estimated median DFS and OS and five-year cumulative incidence and incidence rates (IR/1000 person-years), and 95% confidence intervals (95% CI), for each outcome. RESULTS: Among 9874 patients, 523 (5%) underwent BRCA testing-90 were BRCAm carriers, 433 were BRCA wildtype (BRCAwt). Compared with BRCAwt women, BRCAm carriers were younger, had lower stage, and ER- and HER2- tumors. Median time from diagnosis to BRCA testing was 0.91 years and 1.3 years in BRCAm and BRCAwt women; median follow-up to first event was 3.9 and 3.4 years, respectively. Five-year DFS and OS were higher in BRCAm than BRCAwt women: 88% (95%CI=78.3-93.5) vs. 75.3% (95%CI=70.2-79.6) and 97.8% (95%CI=91.4-99.4) vs 92.2% (95%CI=88.5-94.7), respectively. Five-year IRs of recurrence were 36.7/1000 person-years (95%CI=15.8-72.2) in the BRCAm cohort vs. 58.4 (95%CI=42.9-77.6) in the BRCAwt cohort. CONCLUSIONS: BRCAm carriers may have a better prognosis than BRCAwt women. However, limited testing conducted mainly during follow-up, yielded low numbers for precise estimations, and may be attributable to selection bias.

Patient database analysis of fulvestrant 500 mg in the treatment of metastatic breast cancer: A European perspective.

INTRODUCTION: Clinical guidelines recommend that patients with hormone receptor (HR)-positive metastatic breast cancer (MBC) should be preferentially treated with endocrine therapy. Fulvestrant (a selective estrogen receptor degrader) is approved for use in these patients following relapse after, or relapse or progression during, antiestrogen therapy. This descriptive study analyzed European treatment patterns for HR-positive MBC in real-world clinical practice. METHODS: The IMS Oncology Analyzer (OA), a retrospective cancer treatment database reporting physician-entered patient case histories, was used to identify records for postmenopausal women with HR-positive MBC from April 1, 2004 to June 30, 2013 in France, Germany, Italy, and Spain. Treatments were allocated to mutually exclusive categories (fulvestrant-containing, aromatase inhibitor [AI]-containing, tamoxifen-containing, or chemotherapy-containing regimens) and assessed by line of therapy for MBC. Fulvestrant use was also assessed pre- and post-2010 (when fulvestrant 500 mg dosing was approved). RESULTS: In total, 27,214 eligible patients were included (France: 6801; Germany: 6852; Italy: 7061; Spain: 6500). Chemotherapy-based regimens were the most common first-line treatments for MBC across all countries. Across countries, the proportion of patients initiating on each treatment category ranged from: chemotherapy, 57.5-70.4%; AI, 23.5-30.1%; tamoxifen, 2.7-9.8%; fulvestrant 0.8-2.6%. When administered, fulvestrant was usually given as first- or second-line treatment. Post-2010, more patients received fulvestrant 500 mg than fulvestrant 250 mg in France, Germany, and Spain; in Italy, more patients continued to receive fulvestrant 250 mg. CONCLUSION: Most patients with HR-positive MBC receive chemotherapy over endocrine therapy; fulvestrant constitutes a small proportion of treatments for such patients.

Use of Real-World Data for the Research, Development, and Evaluation of Oncology Precision Medicines.

Although randomized controlled trials remain the scientific ideal for determining the efficacy and safety of new treatments, they are sometimes insufficient to address the evidentiary requirements of regulators and payers. This is particularly the case when it comes to precision medicines because trials are often small, deliver incomplete insights into outcomes of most interest to policymakers (eg, overall survival), and may fail to address other complex diagnostic and treatment-related questions. Additional methods, both experimental and observational, are increasingly being used to fill critical evidentiary gaps. A number of modified early- and late-phase trial designs have been proposed to better support earlier biomarker validation, patient identification, and selection for regulatory studies, but there is still a need for confirmatory evidence from real-world data sources. These data are usually provided through observational, postapproval, phase IIIB and IV studies, which rely heavily on registries and other electronic data sets-most notably data from electronic health records. It is, therefore, crucial to understand what ethical, practical, and scientific challenges are raised by the use of electronic health records to generate evidence about precision medicines.

Coverage With Evidence Development and Managed Entry in the Funding of Personalized Medicine: Practical and Ethical Challenges for Oncology.

Personalized medicines hold promise for many diseases. However, demonstrating the clinical efficacy and cost effectiveness of these medicines can be difficult. It is essential that decision-making processes for funding new medicines, including personalized medicines, are both robust and fit for purpose. We will argue that randomized trials of personalized medicines should be routinely supplemented with other research methods, such as observational research and single-arm studies, and that managed-entry funding programs, such as coverage with evidence development, may offer a means of providing early access to technologies where there is uncertainty about efficacy, safety, and cost effectiveness. These programs, however, raise a number of practical and ethical challenges that need to be worked through and resolved.

Ethics, evidence and economics in the pursuit of "personalized medicine".

Despite enthusiastic advocacy for what personalized medicine might be able to deliver and major investments into the development of this, there remain disappointingly few examples of personalized medicine in routine clinical practice today, particularly in high areas of unmet need such as cancer. We believe that this is because personalized medicine challenges the moral, economic and epistemological foundations of medicine. In this article, we briefly describe the scientific premises underpinning personalized medicine, contrast these with traditional paradigms of drug development, and then consider the ethical, economic and epistemological implications of this approach to medicine.

The economic evaluation of personalised oncology medicines: ethical challenges.

Insights into the molecular drivers of cancer are providing opportunities for the development of new targeted treatments and more personalised approaches to cancer management. Drugs targeting mutant epidermal growth factor receptors, such as erlotinib and gefitinib, may provide more effective, safer and better tolerated treatment options compared with chemotherapy among appropriately selected patients with advanced non-small cell lung cancer (NSCLC). First-line access to these newer treatments remains unfunded after several considerations by the Pharmaceutical Benefits Advisory Committee and their assessment that these are not cost-effective treatments. We suggest that there may be evidentiary and ethical challenges associated with the assessment of the cost-effectiveness of personalised oncology medicines in Australia, and that a new approach is needed to determine the value and cost-effectiveness of personalised medicine.

Is there a plateau in the survival curve after autologous transplantation in patients with intermediate and high-risk acute myeloid leukemia? A 20-year single institution experience.

In an attempt to examine whether autologous SCT provides long-term disease control in patients with intermediate and high-risk AML where a suitable donor is not available, we analyzed the outcomes of autologous SCT in patients with intermediate and high-risk AML from 1986 to 2005. No relapses occurred after 2.2 years. The overall survival curve appears to have developed a plateau after 2.2 years. In conclusion, autologous SCT in patients with AML in whom an allogeneic transplantation is not feasible appears to be a safe alternative and a plateau in the survival curve indicates cure in a small proportion of patients.

Autologous transplantation in patients with relapsed or high-grade follicular lymphoma provides long term disease-free survival and best median duration of response.

The best treatment option for patients with relapsed or high-grade follicular lymphoma (FL) is unknown. In spite of major advances in the therapy for FL, disease-free survival remains short, and median time to progression is just over a year. Autologous stem cell transplantation in patients with relapsed FL is safe and appears to improve disease-free survival. In an attempt to examine whether autologous stem cell transplantation provides long-term disease control in patients with relapsed or high-grade FL, we retrospectively evaluated our experience and analyzed the outcomes of autologous stem cell transplantation in patients with FL from 1991 to 2003. Seventeen men and seven women (n=24) of median age 47.5 years (range 28-64 years) were treated. Three patients with high-risk FL were in first remission. Twenty-one patients were salvaged after relapse with second-line chemotherapy. Of these, 14 were in CR at the time of transplantation, and seven patients were transplanted with active disease. Bone marrow was used in six patients as the source of stem cells prior to 1995 and peripheral blood stem cells were used in 18 patients. Twenty-three of 24 patients engrafted (96%). Median time for neutrophil recovery was 11.5 days (range 9-35 days) and 15 days (range 10-40 days) for platelets. Median duration of follow-up was 6 years (range 7 months-8 years). Of the 24 patients, six have died-with one patient death due to transplant-related pulmonary complications. Overall survival (OS) and disease-free survival (DFS) of all evaluable patients were 71.6 and 40%, respectively. Median duration of response was 4.3 years. OS and DFS in patients transplanted in CR were 80 and 57%, respectively. For those transplanted with disease, a complete response was achieved in 43% of patients, with the OS and DFS of 57 and 19%, respectively. Disease status at transplantation was not a significant variable for survival (p>0.3). Three patients developed moderate to severe treatment-related toxicity, two with grade III mucositis and one with life-threatening infection. When these results are compared with historical controls or patients treated with other modalities, autologous stem cell transplantation appears to be providing the longest disease-free survival and best duration of response.