This Review describes the work conducted by the TRANSBIG consortium in the development of the MINDACT (Microarray In Node negative Disease may Avoid ChemoTherapy) trial. The goal of the trial is to ...provide definitive evidence regarding the clinical relevance of the 70-gene prognosis signature, and to assess the performance of this signature compared with that of traditional prognostic indicators for assigning adjuvant chemotherapy to patients with node-negative breast cancer. We outline the background work and the key questions in node-negative early-stage breast cancer, and then focus on the MINDACT trial design and statistical considerations. The challenges inherent in this trial in terms of logistics, implementation and interpretation of the results are also discussed. We hope that this article will trigger further discussion about the difficulties of setting up and analyzing trials aimed at establishing the worth of new methods for better selection of patients for cancer treatment.
MINDACT demonstrated that 46% of patients with early breast cancer at high clinical but low genomic risk on the basis of MammaPrint may safely avoid adjuvant chemotherapy. A second random assignment ...(R-C) compared docetaxel-capecitabine with an anthracycline-based regimen.
R-C randomly assigned patients 1:1 between standard anthracycline-based regimens, with or without taxanes (control) and experimental docetaxel 75 mg/m
intravenously plus oral capecitabine 825 mg/m
two times per day for 14 days (DC) every 3 weeks for 6 cycles. The primary end point was disease-free survival (DFS). Secondary end points included overall survival and safety.
Of 2,832 patients, 1,301 (45%) were randomly assigned, and 97% complied with R-C assignment. In the control arm, 29.6% only received taxanes (0.5% of N0 patients). DFS events (n = 148) were much less than required (n = 422) as a result of a lower-than-expected accrual and event rate. At 5 years of median follow-up, DFS was not different between DC (n = 652) and control (n = 649; 90.7% 95% CI, 88% to 92.8%
88.8% 95% CI, 85.9% to 91.1%; hazard ratio HR, 0.83 95% CI, 0.60 to 1.15;
= .26). Overall survival (HR, 0.91 95% CI, 0.54 to 1.53) and DFS in the clinical high and genomic high-risk subgroup (86.1%
88.1%; HR, 0.83 95% CI, 0.58 to 1.21) were similar in both arms. DC led to more grade 1 neuropathy (27.1%
11.2%) and more grade 2 hand/foot syndrome (28.5%
3.3%) and diarrhea (13.7%
5.8%). Serious cardiac events occurred in 9 patients (control, n = 4; DC, n = 5). Fifty-three patients developed second cancers (control, n = 32; DC, n = 21; leukemia: 2
1). Five treatment-related deaths occurred (control, 2 0.3%; DC, 3 0.5%).
Although underpowered, this second randomization in MINDACT did not show any improvement in outcome or safety with the use of DC compared with anthracycline-based chemotherapy.
A 4‐year‐old, male, entire Newfoundland was presented for investigation of an acute onset cervical ventroflexion and pyrexia, 4 days following a hip replacement surgery. Neurological examination ...confirmed prominent cervical ventroflexion characterised by an inability to raise the head, without evidence of cervical hyperaesthesia or associated neurological deficits. Magnetic resonance imaging identified focal, bilaterally symmetrical changes to the semispinalis cervicis musculature, responsible for elevation of the head. The presentation and diagnostic imaging findings appeared analogous to dropped‐head syndrome in humans. Toxoplasma IgG antibodies were found to be mildly elevated, and therefore treatment with clindamycin was initiated. The dog responded well to treatment and was reported to be clinically normal 2 months thereafter.
Neurofibromatosis type 1 (NF1) is a phenotypically heterogenous multisystem cancer predisposition syndrome manifesting in childhood and adolescents. Central nervous system (CNS) manifestations ...include structural, neurodevelopmental, and neoplastic disease. We aimed to (1) characterize the spectrum of CNS manifestations of NF1 in a paediatric population, (2) explore radiological features in the CNS by image analyses, and (3) correlate genotype with phenotypic expression for those with a genetic diagnosis. We performed a database search in the hospital information system covering the period between January 2017 and December 2020. We evaluated the phenotype by retrospective chart review and imaging analysis. 59 patients were diagnosed with NF1 median age 10.6 years (range, 1.1–22.6); 31 female at last follow-up, pathogenic NF1 variants were identified in 26/29. 49/59 patients presented with neurological manifestations including 28 with structural and neurodevelopmental findings, 16 with neurodevelopmental, and 5 with structural findings only. Focal areas of signal intensity (FASI) were identified in 29/39, cerebrovascular anomalies in 4/39. Neurodevelopmental delay was reported in 27/59 patients, learning difficulties in 19/59. Optic pathway gliomas (OPG) were diagnosed in 18/59 patients, 13/59 had low-grade gliomas outside the visual pathways. 12 patients received chemotherapy. Beside the established NF1 microdeletion, neither genotype nor FASI were associated with the neurological phenotype. NF1 was associated with a spectrum of CNS manifestations in at least 83.0% of patients. Regular neuropsychological assessment complementing frequent clinical and ophthalmologic testing for OPG is necessary in the care of each child with NF1.
•Neurological manifestations were present in 83.0% of children/adolescents with NF1.•Cerebrovascular anomalies were identified in 6.8% of patients, 3.4% sustained a stroke.•Optic pathway and other low-grade gliomas were diagnosed in 30.5% and 22.0% patients.•Neither genotype nor FASI were associated with the neurological phenotype.•Regular neuropsychological and ophthalmological assessments are indicated.
Abstract
OBJECTIVES
To identify and prioritize technical procedures for simulation-based training to be integrated into the thoracic surgical curriculum.
METHODS
A 3-round Delphi survey was conducted ...from February 2022 to June 2022 among 34 key opinion leaders in thoracic surgery from 14 countries worldwide. The 1st round was a brainstorming phase to identify technical procedures that a newly qualified thoracic surgeon should be able to perform. All the suggested procedures were categorized, qualitatively analysed and sent to the 2nd round. The second round investigated: the frequency of the identified procedure at each institution, the number of thoracic surgeons that should be able to perform these procedures, the degree of risk to the patient if the procedure is performed by a non-competent thoracic surgeon and the feasibility of simulation-based education. In the 3rd round, elimination and re-ranking of the procedures from the 2nd round were performed.
RESULTS
Response rates in the 3 iterative rounds were 80% (28 out of 34), 89% (25 out of 28) and 100% (25 out of 25) in the 1st, 2nd and 3rd round, respectively. Seventeen technical procedures were included for simulation-based training in the final prioritized list. The top 5 procedures were Video-Assisted Thoracoscopic Surgery (VATS) lobectomy, VATS segmentectomy, VATS mediastinal lymph node dissection, diagnostic flexible bronchoscopy and robotic-assisted thoracic surgery port placement, robotic-assisted thoracic surgery docking and undocking.
CONCLUSIONS
The prioritized list of procedures represents a consensus of key thoracic surgeons worldwide. These procedures are suitable for simulation-based training and should be integrated in the thoracic surgical curriculum.
Thoracic surgery has advanced in recent years, with the advent of minimally invasive surgery, e.g. robotic surgery, and more advanced procedures 1, 2.
To determine interobserver and intraobserver agreement for results of low-field magnetic resonance imaging (MRI) in dogs with and without disk-associated wobbler syndrome (DAWS).
Validation study.
21 ...dogs with and 23 dogs without clinical signs of DAWS.
For each dog, MRI of the cervical vertebral column was performed. The MRI studies were presented in a randomized sequence to 4 board-certified radiologists blinded to clinical status. Observers assessed degree of disk degeneration, disk-associated and dorsal compression, alterations in intraspinal signal intensity (ISI), vertebral body abnormalities, and new bone formation and categorized each study as originating from a clinically affected or clinically normal dog. Interobserver agreement was calculated for 44 initial measurements for each observer. Intraobserver agreement was calculated for 11 replicate measurements for each observer.
There was good interobserver agreement for ratings of disk degeneration and vertebral body abnormalities and moderate interobserver agreement for ratings of disk-associated compression, dorsal compression, alterations in ISI, new bone formation, and suspected clinical status. There was very good intraobserver agreement for ratings of disk degeneration, disk-associated compression, alterations in ISI, vertebral body abnormalities, and suspected clinical status. There was good intraobserver agreement for ratings of dorsal compression and new bone formation. Two of 21 clinically affected dogs were erroneously categorized as clinically normal, and 4 of 23 clinically normal dogs were erroneously categorized as clinically affected.
Results suggested that variability exists among observers with regard to results of MRI in dogs with DAWS and that MRI could lead to false-positive and false-negative assessments.
Objective—To determine intraobserver, interobserver, and intermethod agreement for results of myelography, computed tomography-myelography (CTM), and low-field magnetic resonance imaging (MRI) in ...dogs with disk-associated wobbler syndrome (DAWS). Design—Prospective cross-sectional study. Animals—22 dogs with DAWS. Procedures—All dogs underwent myelography, CTM, and low-field MRI. Each imaging study was interpreted twice by 4 observers who were blinded to signalment and clinical information of the patients. The following variables were assessed by all 3 techniques: number, site, and direction of spinal cord compressions; narrowed intervertebral disk spaces; vertebral body abnormalities; spondylosis deformans; and abnormal articular facets. Intervertebral foraminal stenosis was assessed on CTM and MRI images. Intraobserver, interobserver, and intermethod agreement were calculated by κ and weighted κ statistics. Results—There was very good to good intraobserver agreement for most variables assessed by myelography and only moderate intraobserver agreement for most variables assessed by CTM and low-field MRI. There was moderate to fair interobserver and intermethod agreement for most variables assessed by the 3 diagnostic techniques. There was very good or good intraobserver, interobserver, or intermethod agreement for the site and direction of the worst spinal cord compression as assessed by all the imaging modalities; abnormal articular facets and intervertebral foraminal stenosis were the least reliably assessed variables, with poor interobserver agreement regardless of imaging modality used. Conclusions and Clinical Relevance—There was considerable variation in image interpretation among observers and between use of various imaging modalities; these imaging techniques should be considered complementary in assessment of dogs with DAWS.
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