Summary
Anti-resorptive osteoporosis treatment might be more effective in patients with high bone turnover. In this registry study including clinical data, high pre-treatment bone turnover measured ...with biochemical markers was correlated with higher bone mineral density increases. Bone turnover markers may be useful tools to identify patients benefitting most from anti-resorptive treatment.
Introduction
In randomized, controlled trials of bisphosphonates, high pre-treatment levels of bone turnover markers (BTM) were associated with a larger increase in bone mineral density (BMD). The purpose of this study was to examine this correlation in a real-world setting.
Methods
In this registry-based cohort study of osteoporosis patients (
n
= 158) receiving antiresorptive therapy, the association between pre-treatment levels of plasma C-telopeptide of type I Collagen (CTX) and/or N-terminal propeptide of type I procollagen (PINP) and change in bone mineral density (BMD) at lumbar spine, total hip, and femoral neck upon treatment was examined. Patients were grouped according to their pre-treatment BTM levels, defined as values above and below the geometric mean for premenopausal women.
Results
Pre-treatment CTX correlated with annual increase in total hip BMD, where patients with CTX above the geometric mean experienced a larger annual increase in BMD (
p
= 0.008) than patients with CTX below the geometric mean. The numerical pre-treatment level of CTX showed a similar correlation at all three skeletal sites (total hip (
p
= 0.03), femoral neck (
p
= 0.04), and lumbar spine (
p
= 0.0003)). A similar association was found for PINP where pre-treatment levels of PINP above the geometric mean correlated with a larger annual increase in BMD for total hip (
p
= 0.02) and lumbar spine (
p
= 0.006).
Conclusion
Measurement of pre-treatment BTM levels predicts osteoporosis patients’ response to antiresorptive treatment. Patients with high pre-treatment levels of CTX and/or PINP benefit more from antiresorptive treatment with larger increases in BMD than patients with lower pre-treatment levels.
Summary
Peripheral T‐cell lymphomas (PTCLs) are a heterogeneous group of haematological cancers with generally poor clinical outcomes. However, a subset of patients experience durable disease ...control, and little is known regarding long‐term outcomes. The International T‐cell Lymphoma Project (ITCLP) is the largest prospectively collected cohort of patients with PTCLs, providing insight into clinical outcomes at academic medical centres globally. We performed a long‐term outcome analysis on patients from the ITCLP with available 10‐year follow‐up data (n = 735). The overall response rate to first‐line therapy was 68%, while 5‐ and 10‐year overall survival estimates were 49% and 40% respectively. Most deaths occurred prior to 5 years, and for patients alive at 5 years, the chance of surviving to 10 years was 84%. However, lymphoma remained the leading cause of death in the 5‐ to 10‐year period (67%). Low‐risk International Prognostic Index and Prognostic Index for T‐cell lymphoma scores both identified patients with improved survival, while in multivariate analysis, age >60 years and Eastern Cooperative Oncology Group performance status 2–4 were associated with inferior outcomes. The favourable survival seen in patients achieving durable initial disease control emphasizes the unmet need for optimal front‐line therapeutic approaches in PTCLs.
The International T‐cell Lymphoma Project is the largest prospectively collected cohort of patients with peripheral T‐cell lymphomas (PTCLs). In the long‐term outcome analysis of patients with available 10‐year follow‐up data (n = 735), 5‐ and 10‐year overall survival (OS) estimates were 49% and 40% respectively. For patients alive at 5 years, the chance of surviving to 10 years was 84%, but lymphoma remained the leading cause of death in the 5‐ to 10‐year period (67%). The favourable survival seen in patients achieving durable initial disease control emphasizes the unmet need for optimal front‐line therapeutic approaches in PTCLs.
The antiretroviral agent nelfinavir has antimyeloma activity and can overcome resistance to bortezomib. Our phase I/II trial investigated whether adding nelfinavir to lenalidomide-dexamethasone can ...overcome lenalidomide resistance in lenalidomide-refractory multiple myeloma (MM). Twenty-nine patients were included (high-risk cytogenetic aberrations 31%; ≥2 prior therapy lines 93%; lenalidomide-bortezomib double-refractory 34%). Twenty-four patients (83%) had prior bortezomib and 10 (34%) were lenalidomide-bortezomib double-refractory. They received four cycles of nelfinavir 2500 mg/day with standard-dose lenalidomide (25 mg days 1-21) and dexamethasone (40/20 mg days 1, 8, 15, 22). Minor response or better was achieved in 16 patients (55%; 95% CI 36-74%), including 40% of those who were lenalidomide-bortezomib double-refractory, and partial response or better in nine patients (31%; 95% CI 15-51%). Median progression-free survival was 3.4 (95% CI 2.0-4.9) months and median overall survival 21.6 (13.0-50.1) months. Lenalidomide-related pneumonitis, pneumonia, and neutropenic fever occurred, but there were no unexpected adverse events. Peripheral blood mononuclear cells showed a 45% (95% CI 40-51%) reduction in total proteasome activity from baseline and significant induction of unfolded protein response and autophagy. Thus, nelfinavir-lenalidomide-dexamethasone is an active oral combination in lenalidomide-refractory MM.
Hodgkin lymphoma (HL) in older patients appears to be a different disease compared with younger patients with historically lower survival rates. This is related to a variety of factors, including ...increased treatment‐related toxicity, the presence of comorbidities, and biologic differences. In order to better assess the clinical characteristics, treatment strategies, and outcome of this particular population, we conducted a population‐based, retrospective analysis including 269 patients with HL older than 60 years (median age 71 years, range 60–94), treated between 2000 and 2017 in 15 referral centers across Switzerland. Primary endpoints were overall survival (OS), progression‐free survival (PFS), and cause‐specific survival (CSS). The vast majority of patients were treated with curative intent, either with a combined modality approach (chemotherapy followed by radiation therapy) or with systemic therapy. At a median follow‐up of 6.6 years (95% confidence interval CI, 6.0–7.6), 5‐year PFS was 52.2% (95% CI, 46.0–59.2), 5‐year OS was 62.5% (95% CI, 56.4–69.2), and 5‐year CSS was 85.1.8% (95% CI, 80.3–90.1) for the entire cohort. A significant difference in terms of CSS was observed for patients older than 71 years in comparison to patients aged 60–70 years (hazard ratio 2.6, 1.3–5.0, p = 0.005). Bleomycin‐induced lung toxicity (BLT) was documented in 26 patients (17.7%) out of the 147 patients exposed to this compound and was more frequent in patients older than 71 years (15/60, 25%). Outcome of HL pts older than 71 years appeared to decrease substantially in comparison to the younger counterpart. Treatment‐related toxicities appeared to be relevant, in particular, BLT. New, potentially less toxic strategies need to be investigated in prospective clinical trials in this particular frail population.
Highlights • Integration of erlotinib in EGFR wildtype, advanced NSCLC has become controversial. • This study accounted for erlotinib being preferentially given to unfit patients. • Erlotinib and ...chemotherapy had similar efficacy in pretreated NSCLC. • No patient had known molecular targetable alterations or received immunotherapy. • ECOG performance status was the major covariate to select patients for erlotinib.
Summary
In this systematic review, the effects of osteoporosis patient education were examined. All studies found an effect on physical function, but for the other themes, the results were ...inconclusive. The findings indicate a need for further research in this topic.
Introduction
Osteoporosis is a chronic disease with serious consequences for the individual and major societal costs. With the aim of fracture prevention, many countries offer osteoporosis patient education. The objectives were to examine the effects and mediators of osteoporosis patient education and describe the characteristics of studies with and without an effect. Though, none of the included studies reported mediators, and therefore, we could not examine that.
Methods
Six databases were searched in October 2020. Two researchers independently conducted title and abstract screening as well as full-text review. Records were included if participants had osteoporosis, and the patient education was group-based, face-to-face, and addressed two or more aspects, e.g., diet, medication, and exercise. The Cochrane Collaboration tools were used for risk of bias assessment. Finally, data were extracted into a standardized form and presented narratively.
Results
In total, 2934 records were identified, and 13 studies met the inclusion criteria. All six studies examining the effects of patient education on physical function demonstrated improvements. In addition, one out of two RCT studies and one non-randomized study reported improved psychological wellbeing. Just one out of five RCT studies showed improvements regarding physical discomfort and disability. Effects on health-related quality of life, adherence and persistence, and knowledge of osteoporosis were inconclusive.
Conclusion
There is limited evidence for the effectiveness of osteoporosis patient education. There is a need for high-quality randomized controlled trials, which should describe the characteristics of the interventions and examine the mechanisms of osteoporosis patient education.
PROSPERO registration number
CRD42020211930