Search

BackgroundExpandable endoprostheses can be used to equalize limb length for pediatric patients requiring reconstruction following large bony oncologic resections. Outcomes of the Compress® Compliant Pre-Stress (CPS) spindle paired with an Orthopedic Salvage System expandable distal femur endoprosthesis have not been reported.MethodsWe conducted a multi-institutional retrospective study of pediatric patients with distal femoral bone sarcomas reconstructed with the above endoprostheses. Statistical analysis utilized Kaplan-Meier survival technique and competing risk analysis.ResultsThirty-six patients were included from five institutions. Spindle survivorship was 86.3% (95% confidence interval [CI], 67.7-93.5) at 10 years. Two patients had a failure of osseointegration (5.7%), both within 12 months. Twenty-two (59%) patients had 70 lengthening procedures, with mean expansions of 3.2 cm (range: 1-9) over 3.4 surgeries. The expandable mechanism failed in eight patients with a cumulative incidence of 16.1% (95% CI, 5.6-31.5) at 5 years. Twenty-nine patients sustained International Society of Limb Salvage failures requiring 63 unplanned surgeries. Periprosthetic joint infection occurred in six patients (16.7%). Limb preservation rate was 91% at 10 years.ConclusionsThere is a high rate of osseointegration of the Compress® spindle among pediatric patients when coupled with an expandable implant. However, there is a high rate of expansion mechanism failure and prosthetic joint infections requiring revision surgery.Level of evidenceLevel IV, therapeutic study.

Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0-14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal high-level amplification and resultant overexpression of either PLAGL1 or PLAGL2, and an absence of recurrent genetic alterations characteristic of other pediatric CNS tumor types. Both genes act as transcription factors for a regulatory subset of imprinted genes (IGs), components of the Wnt/β-Catenin pathway, and the potential drug targets RET and CYP2W1, which are also specifically overexpressed in this tumor type. A derived PLAGL-specific gene expression signature indicates dysregulation of imprinting control and differentiation/development. These tumors occurred throughout the neuroaxis including the cerebral hemispheres, cerebellum, and brainstem, and were predominantly composed of primitive embryonal-like cells lacking robust expression of markers of glial or neuronal differentiation (e.g., GFAP, OLIG2, and synaptophysin). Tumors with PLAGL1 amplification were typically diagnosed during adolescence (median age 10.5 years), whereas those with PLAGL2 amplification were diagnosed during early childhood (median age 2 years). The 10-year overall survival was 66% for PLAGL1-amplified tumors, 25% for PLAGL2-amplified tumors, 18% for male patients, and 82% for female patients. In summary, we describe a new type of biologically distinct CNS tumor characterized by PLAGL1/2 amplification that occurs predominantly in infants and toddlers (PLAGL2) or adolescents (PLAGL1) which we consider best classified as a CNS embryonal tumor and which is associated with intermediate survival. The cell of origin and optimal treatment strategies remain to be defined.

ObjectivesTo determine the proportion of patients with extremity sarcoma who would be willing to participate in a clinical trial in which they would be randomised to one of four different postoperative sarcoma surveillance regimens. Additionally, we assessed patients' perspectives on the burden of cancer care, factors that influence comfort with randomisation and the importance of cancer research.DesignProspective, cross-sectional patient survey.SettingOutpatient sarcoma clinics in Canada, the USA and Spain between May 2017 and April 2020. Survey data were entered into a study-specific database.ParticipantsPatients with extremity sarcoma who had completed definitive treatment from seven clinics across Canada, the USA and Spain.Main outcome measuresThe proportion of patients with extremity sarcoma who would be willing to participate in a randomised controlled trial (RCT) that evaluates varying postoperative cancer surveillance regimens.ResultsOne hundred thirty complete surveys were obtained. Respondents reported a wide range of burdens related to clinical care and surveillance. The majority of patients (85.5%) responded that they would agree to participate in a cancer surveillance RCT if eligible. The most common reason to participate was that they wanted to help future patients. Those that would decline to participate most commonly reported that participating in research would be too much of a burden for them at a time when they are already feeling overwhelmed. However, most patients agreed that cancer research will help doctors better understand and treat cancer.ConclusionsThese results demonstrate that most participants would be willing to participate in an RCT that evaluates varying postoperative cancer surveillance regimens. Participants' motivation for trial participation included altruistic reasons to help future patients and deterrents to trial participation included the overwhelming burden of a cancer diagnosis. These results will help inform the development of patient-centred RCT protocols in sarcoma surveillance research.Level of evidenceV.

Anti-PD-1 therapy is used as a front-line treatment for many cancers, but mechanistic insight into this therapy resistance is still lacking. Here we generate a humanized (Hu)-mouse melanoma model by injecting fetal liver-derived CD34+ cells and implanting autologous thymus in immune-deficient NOD-scid IL2Rγnull (NSG) mice. Reconstituted Hu-mice are challenged with HLA-matched melanomas and treated with anti-PD-1, which results in restricted tumor growth but not complete regression. Tumor RNA-seq, multiplexed imaging and immunohistology staining show high expression of chemokines, as well as recruitment of FOXP3+ Treg and mast cells, in selective tumor regions. Reduced HLA-class I expression and CD8+/Granz B+ T cells homeostasis are observed in tumor regions where FOXP3+ Treg and mast cells co-localize, with such features associated with resistance to anti-PD-1 treatment. Combining anti-PD-1 with sunitinib or imatinib results in the depletion of mast cells and complete regression of tumors. Our results thus implicate mast cell depletion for improving the efficacy of anti-PD-1 therapy.

IntroductionFollowing the treatment of patients with soft tissue sarcomas (STS) that are not metastatic at presentation, the high risk for local and systemic disease recurrence necessitates post-treatment surveillance. Systemic recurrence is most often detected in the lungs. The most appropriate surveillance frequency and modality remain unknown and, as such, clinical practice is highly varied. We plan to assess the feasibility of conducting a multi-centre randomised controlled trial (RCT) that will evaluate the effect on overall 5-year survival of two different surveillance frequencies and imaging modalities in patients with STS who undergo surgical excision with curative intent.Methods and analysisThe Surveillance After Extremity Tumor Surgery trial will be a multi-centre 2×2 factorial RCT. Patients with non-metastatic primary Grade II or III STS treated with excision will be allocated to one of four treatment arms1: chest radiograph (CXR) every 3 months for 2 years2; CXR every 6 months for 2 years3; chest CT every 3 months for 2 years or4 chest CT every 6 months for 2 years. The primary outcome of the pilot study is the feasibility of a definitive RCT based on a combination of feasibility endpoints. Secondary outcomes for the pilot study include the primary outcome of the definitive trial (overall survival), patient-reported outcomes on anxiety, satisfaction and quality of life, local recurrence-free survival, metastasis-free survival, treatment-related complications and net healthcare costs related to surveillance.Ethics and disseminationThis trial received provisional ethics approval from the McMaster/Hamilton Health Sciences Research Ethics Board on 7 August 2019 (Project number 7562). Final ethics approval will be obtained prior to commencing patient recruitment. Once feasibility has been established and the definitive protocol is finalised, the study will transition to the definitive study.Trial registrationNCT03944798; Pre-results.

Decentralized wastewater treatment systems (DWTS) are significant contributors to the eutrophication of surface water bodies due to a lack of treatment mechanisms that target dissolved phosphorus removal. Existing advanced treatment systems are expensive to operate, large in nature, and require frequent maintenance, making them unattractive to DWTS owners. This study aims to investigate the development of a continuous flow treatment system that uses electrocoagulation (EC) to remove dissolved phosphorus from small wastewater streams such as septic tank effluent (STE). Operational parameters, including system hydraulic retention time (HRT), applied current density, and wastewater composition, were optimized to maximize total phosphorus (TP) removal most cost-effectively. Using an HRT of 10 min, an applied current density of 2.0 mA/cm2, and an influent concentration of 20 mg/L, the orthophosphate (OP) and TP removal percentages achieved were 99.9 and 88.1%, respectively. Under these conditions, the average effluent Al3+ concentration in the treated effluent was measured to be 1.0 mg/L while the total suspended solids concentration was measured to be 51 mg/L. The operation cost was estimated to be 0.056 CAD/m3. The results demonstrate that the EC reactor is effective in removing dissolved phosphorus from wastewater and is therefore a viable option in mitigating the risk of downstream eutrophication caused by inadequately treated STE. [ABSTRACT FROM AUTHOR]

Background It is of vital importance to comprehensively and transparently report clinical trial activity. The SPIRIT 2013 and CONSORT 2010 statements exist to define items to be reported in clinical trial protocols and randomized controlled trials, respectively. The aim of this methodological review was to assess the reporting quality of pediatric neuro-oncology trial protocols and trial result articles. Methods Published trial protocols and phase II/III trial result articles relating to pediatric brain tumors (published after the introduction of the SPIRIT 2013 statement), were identified through searches of 4 electronic bibliographic databases. The reporting quality of included trial protocols and result articles was assessed against the aforementioned statements. In addition, the CONSORT-A checklist was used to assess the abstracts of trial result articles. Percentage adherence was calculated for each article. Results Nine trial protocols, 68 phase II trials, and 8 phase III trial result articles were included. Mean adherence of trial protocols to the SPIRIT statement was 76.8% (SD : 0.09). Mean adherence of trial abstracts to CONSORT-A was 67.4% (SD : 0.13) for phase II abstracts and 47.5% (SD : 0.09) for phase III abstracts. Adherence of trial result articles to CONSORT was 71.3% (SD : 0.10) for phase II trials and 70.3% (SD : 0.13) for phase III trials. Conclusions The reporting quality of pediatric neuro-oncology trial protocols and trial result articles requires improvement, particularly in the areas of randomization and blinding. This is consistent with our previously published findings following similar assessment of reporting quality for adult neuro-oncology trial protocols and result articles. [ABSTRACT FROM AUTHOR]