The Decipher genomic classifier (GC) has shown to independently prognosticate outcomes in prostate cancer. The objective of this study was to validate the GC in a randomized phase III trial of ...dose-escalated salvage radiotherapy (SRT) after radical prostatectomy.
A clinical-grade whole-transcriptome assay was carried out on radical prostatectomy samples obtained from patients enrolled in Swiss Group for Clinical Cancer Research (SAKK) 09/10, a phase III trial of 350 men with biochemical recurrence after radical prostatectomy randomized to 64 Gy versus 70 Gy without concurrent hormonal therapy or pelvic nodal RT. A prespecified statistical plan was developed to assess the impact of the GC on clinical outcomes. The primary endpoint was biochemical progression; secondary endpoints were clinical progression and time to hormone therapy. Multivariable analyses adjusted for age, T-category, Gleason score, postradical prostatectomy persistent prostate-specific antigen (PSA), PSA at randomization, and randomization arm were conducted, accounting for competing risks.
The analytic cohort of 226 patients was representative of the overall trial, with a median follow-up of 6.3 years (interquartile range 6.1-7.2 years). The GC (high versus low–intermediate) was independently associated with biochemical progression subdistribution hazard ratio (sHR) 2.26, 95% confidence interval (CI) 1.42-3.60; P < 0.001, clinical progression (HR 2.29, 95% CI 1.32-3.98; P = 0.003), and use of hormone therapy (sHR 2.99, 95% CI 1.55-5.76; P = 0.001). GC high patients had a 5-year freedom from biochemical progression of 45% versus 71% for GC low–intermediate. Dose escalation did not benefit the overall cohort, nor patients with lower versus higher GC scores.
This study represents the first contemporary randomized controlled trial in patients treated with early SRT without concurrent hormone therapy or pelvic nodal RT that has validated the prognostic utility of the GC. Independent of standard clinicopathologic variables and RT dose, high-GC patients were more than twice as likely than lower-GC patients to experience biochemical and clinical progression and receive of salvage hormone therapy. These data confirm the clinical value of Decipher GC to personalize the use of concurrent systemic therapy in the postoperative salvage setting.
•Decipher identifies patients at highest risk of progression who may require treatment intensification.•Decipher defines subgroups associated with improved outcomes when treated with very early SRT compared with late SRT.•Transcriptomic profiling can guide personalized management of SRT timing and the addition of systemic therapy.
The aim of this in vitro study was to evaluate the effect of tribochemical silica-coating and a zirconate coupling agent application on bonding between a resin composite and zirconia. Firstly, it was ...hypothesized that the zirconate coupling agent modified surface would promote higher and more stable shear bond strength than a surface treated with tribochemical coating only. Secondly, the modified surface would retain its bond strength after artificial aging. The shear bond strength between a resin composite bonded to surface treated zirconia was measured. Hydrolytic stability of this bond was verified after water storage while the interface chemistry was evaluated using energy dispersive x-ray analysis. Surface treatment showed significantly greater shear bond strength compared with no treatment before artificial aging while specific surface treatments showed higher shear bond strength compared with no treatment after artificial aging. The predominant mode of failure after shear bond testing was adhesive. Energy dispersive x-ray analysis at the surface revealed elemental C1s, O1s, Si1s and Zr2p. As a result, tribochemical silica-coating followed by application of a zirconate coupling agent was suggested to create a successful a resin-to-zirconia bonding. Further investigation is required as reference for clinical approach in the cementation of zirconia restorations.
Objectives: A comparison of synthetic hydroxyapatite/silica oxide, xenogenic hydroxyapatite‐based bone substitute materials with empty control sites in terms of bone regeneration enhancement in a ...rabbit calvarial four non‐critical‐sized defect model.
Methods: In each of six rabbits, four bicortical calvarial bone defects were generated. The following four treatment modalities were randomly allocated: (1) empty control site, (2) synthetic hydroxyapatite/silica oxide‐based (HA/SiO) test granules, (3) xenogenic hydroxyapatite ‐based granules, (4) synthetic hydroxyapatite/silica oxide ‐based (HA/SiO) test two granules. The results of the latter granules have not been reported due to their size being three times bigger than the other two granule types. After 4 weeks, the animals were sacrificed and un‐decalcified sections were obtained for histological analyses.
For statistical analysis, the Kruskal–Wallis test was applied (P<0.05).
Results: Histomorphometric analysis showed an average area fraction of newly formed bone of 12.32±10.36% for the empty control, 17.47±6.42% for the xenogenic hydroxyapatite ‐based granules group, and 21.2±5.32% for the group treated with synthetic hydroxyapatite/silica oxide ‐based granules. Based on the middle section, newly formed bone bridged the defect to 38.33±37.55% in the empty control group, 54.33±22.12% in the xenogenic hydroxyapatite ‐based granules group, and to 79±13.31% in the synthetic hydroxyapatite/silica oxide ‐based granules group. The bone‐to‐bone substitute contact was 46.38±18.98% for the xenogenic and 59.86±14.92% for the synthetic hydroxyapatite/silica oxide‐based granules group.
No significant difference in terms of bone formation and defect bridging could be detected between the two bone substitute materials or the empty defect.
Conclusion: There is evidence that the synthetic hydroxyapatite/silica oxide granules provide comparable results with a standard xenogenic bovine mineral in terms of bone formation and defect bridging in non‐critical size defects.
To cite this article:
Kruse A, Jung RE, Nicholls F, Zwahlen RA, Hämmerle CHF, Weber FE. Bone regeneration in the presence of a synthetic hydroxyapatite/silica oxide ‐based and a xenogenic hydroxyapatite ‐based bone substitute material. Clin. Oral Impl. Res. 22, 2011; 506–511 doi: 10.1111/j.1600‐0501.2010.02039.x
Spontaneous canine oral melanoma (COM) is a highly metastatic cancer, resistant to chemotherapy, and can serve as a model for cancer immunotherapy. Liposome-encapsulated muramyl ...tripeptide-phosphatidylethanolamine (L-MTP-PE) can activate the tumoricidal activity of the monocyte-macrophage system following i.v. injection. The objective of these studies was to evaluate the therapeutic effectiveness of L-MTP-PE administered alone and combined with recombinant canine granulocyte macrophage colony-stimulating factor (rcGM-CSF) in dogs undergoing surgery for oral melanoma. Ninety-eight dogs with histologically confirmed, clinically staged, oral melanoma were entered into two randomized, double-blind, surgical adjuvant trials. In trial 1, 50 dogs were stratified based on clinical stage and randomized to once a week L-MTP-PE or lipid equivalent (control). When all of the clinical stages were combined, no difference in disease-free survival or in survival time (ST) were detected. However, within stage I, dogs receiving L-MTP-PE had a significant increase in ST compared with control, with 80% of the dogs treated with L-MTP-PE still alive at >2 years. Within each stage II and stage III, there was no difference detected between the treatment groups. In trial 2, 48 dogs were stratified on the basis of clinical stage and extent of surgery (simple resection or radical excision), treated with L-MTP-PE two times a week, and randomized to rcGM-CSF or saline (placebo) given s.c. daily for 9 weeks. Within each stage and when all of the stages were combined, there was no difference between the treatment groups. In both studies, stage I COM is associated with a better prognosis. No effect on survival was observed with regard to tumor location in the oral cavity, sex, type/extent of surgery, or age. In a subset of dogs tested, pulmonary alveolar macrophage cytotoxicity was enhanced with combined rcGM-CSF and L-MTP-PE but not in dogs treated with L-MTP-PE alone. The present study indicates that after surgery, L-MTP-PE administered alone or combined with rcGM-CSF showed no significant antitumor activity in treating advanced stage COM. In early stage COM, L-MTP-PE was shown to result in a prolongation of ST. Furthermore, this study provides additional rationale for the use of the dog model for human malignant melanoma.
In human immunodeficiency virus (HIV)-infected individuals, the immune response over time to yellow fever vaccination (YFV) and the necessity for booster vaccination are not well understood.
We ...studied 247 participants of the Swiss HIV Cohort Study (SHCS) with a first YFV after HIV diagnosis and determined their immune responses at 1 year, 5 years, and 10 years postvaccination by yellow fever plaque reduction neutralization titers (PRNTs) in stored blood samples. A PRNT of 1:≥10 was regarded as reactive and protective. Predictors of vaccination response were analyzed with Poisson regression.
At vaccination, 82% of the vaccinees were taking combination antiretroviral therapy (cART), 83% had suppressed HIV RNA levels (<400 copies/mL), and their median CD4 T-cell count was 536 cells/μL. PRNT was reactive in 46% (95% confidence interval CI, 38%-53%) before, 95% (95% CI, 91%-98%) within 1 year, 86% (95% CI, 79%-92%) at 5 years, and 75% (95% CI, 62%-85%) at 10 years postvaccination. In those with suppressed plasma HIV RNA at YFV, the proportion with reactive PRNTs remained high: 99% (95% CI, 95%-99.8%) within 1 year, 99% (95% CI, 92%-100%) at 5 years, and 100% (95% CI, 86%-100%) at 10 years.
HIV-infected patients' long-term immune response up to 10 years to YFV is primarily dependent on the control of HIV replication at the time of vaccination. For those on successful cART, immune response up to 10 years is comparable to that of non-HIV-infected adults. We recommend a single YFV booster after 10 years for patients vaccinated on successful cART, whereas those vaccinated with uncontrolled HIV RNA may need an early booster.
Global classification of the human proteins with regards to spatial expression patterns across organs and tissues is important for studies of human biology and disease. Here, we used a quantitative ...transcriptomics analysis (RNA-Seq) to classify the tissue-specific expression of genes across a representative set of all major human organs and tissues and combined this analysis with antibody-based profiling of the same tissues. To present the data, we launch a new version of the Human Protein Atlas that integrates RNA and protein expression data corresponding to ∼80% of the human protein-coding genes with access to the primary data for both the RNA and the protein analysis on an individual gene level. We present a classification of all human protein-coding genes with regards to tissue-specificity and spatial expression pattern. The integrative human expression map can be used as a starting point to explore the molecular constituents of the human body.
To determine clinical and pathologic findings in cats with alimentary malignant lymphoma and results of treatment with a combination of prednisone, L-asparaginase, vincristine, cyclophosphamide, ...doxorubicin, and methotrexate.
Retrospective study.
21 cats with alimentary malignant lymphoma.
Medical records were reviewed, and information on signalment, clinical history and signs, previous treatments, and results of laboratory tests, thoracic radiography, and abdominal ultrasonography were obtained.
Test results in all cats were negative for FeLV; 3 of 19 were positive for feline immunodeficiency virus. Thirteen tumors were stage III, 7 were stage IV, and 1 was stage V. Diagnosis was confirmed on the basis of microscopic examination of histologic (n = 13) or cytologic (8) specimens. Immunophenotyping was performed on 13 tumors; 10 were T-cell and 3 were B-cell lymphomas. Overall median duration of first remission was 20 weeks. Overall median survival time was 40 weeks. The only factor significantly associated with duration of first remission was whether cats had a complete response following induction chemotherapy; duration of first remission was significantly associated with survival time. Cats tolerated treatment well; only 1 cat had a delay in the treatment schedule because of neutropenia.
Use of a multidrug chemotherapeutic protocol that includes L-asparaginase and doxorubicin results in minimal adverse effects and prolonged survival times in cats with alimentary malignant lymphoma.
IntroductionThe emphasis on aesthetic outcomes and quality of life (QoL) has motivated surgeons to develop skin-sparing or nipple-sparing mastectomy (SSM/ NSM) for breast cancer treatment or ...prevention. During the same operation, a so-called immediate breast reconstruction is performed. The breast can be reconstructed by positioning of a breast implant above (prepectoral) or below (subpectoral) the pectoralis major muscle or by using the patients’ own tissue (autologous reconstruction). The optimal positioning of the implant prepectoral or subpectoral is currently not clear. Subpectoral implant-based breast reconstruction (IBBR) is still standard care in many countries, but prepectoral IBBR is increasingly performed. This heterogeneity in breast reconstruction practice is calling for randomised clinical trials (RCTs) to guide treatment decisions.Methods and analysisInternational, pragmatic, multicentre, randomised, superiority trial. The primary objective of this trial is to test whether prepectoral IBBR provides better QoL with respect to long-term (24 months) physical well-being (chest) compared with subpectoral IBBR for patients undergoing SSM or NSM for prevention or treatment of breast cancer. Secondary objectives will compare prepectoral versus subpectoral IBBR in terms of safety, QoL and patient satisfaction, aesthetic outcomes and burden on patients. Total number of patients to be included: 372 (186 per arm).Ethics and disseminationThis study will be conducted in compliance with the Declaration of Helsinki. Ethical approval has been obtained for the lead investigator’s site by the Ethics Committee ‘Ethikkommission Nordwest- und Zentralschweiz‘ (2020–00256, 26 March 2020). The results of this study will be published in a peer-reviewed medical journal, independent of the results, following the Consolidated Standards of Reporting Trials standards for RCTs and good publication practice. Metadata describing the type, size and content of the datasets will be shared along with the study protocol and case report forms on public repositories adhering to the FAIR (Findability, Accessibility, Interoperability, and Reuse) principles.Trial registration number NCT04293146.
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