An observational study of Donor Ex Vivo Lung Perfusion in UK lung transplantation: DEVELOP-UK

Background: Many patients awaiting lung transplantation die before a donor organ becomes available. Ex vivo lung perfusion (EVLP) allows initially unusable donor lungs to be assessed and reconditioned for clinical use. Objective: The objective of the Donor Ex Vivo Lung Perfusion in UK lung transplantation study was to evaluate the clinical effectiveness and cost-effectiveness of EVLP in increasing UK lung transplant activity. Design: A multicentre, unblinded, non-randomised, non-inferiority observational study to compare transplant outcomes between EVLP-assessed and standard donor lungs. Setting: Multicentre study involving all five UK officially designated NHS adult lung transplant centres. Participants: Patients aged ≥ 18 years with advanced lung disease accepted onto the lung transplant waiting list. Intervention: The study intervention was EVLP assessment of donor lungs before determining suitability for transplantation. Main outcome measures: The primary outcome measure was survival during the first 12 months following lung transplantation. Secondary outcome measures were patient-centred outcomes that are influenced by the effectiveness of lung transplantation and that contribute to the health-care costs. Results: Lungs from 53 donors unsuitable for standard transplant were assessed with EVLP, of which 18 (34%) were subsequently transplanted. A total of 184 participants received standard donor lungs. Owing to the early closure of the study, a non-inferiority analysis was not conducted. The Kaplan–Meier estimate of survival at 12 months was 0.67 [95% confidence interval (CI) 0.40 to 0.83] for the EVLP arm and 0.80 (95% CI 0.74 to 0.85) for the standard arm. The hazard ratio for overall 12-month survival in the EVLP arm relative to the standard arm was 1.96 (95% CI 0.83 to 4.67). Patients in the EVLP arm required ventilation for a longer period and stayed longer in an intensive therapy unit (ITU) than patients in the standard arm, but duration of overall hospital stay was similar in both groups. There was a higher rate of very early grade 3 primary graft dysfunction (PGD) in the EVLP arm, but rates of PGD did not differ between groups after 72 hours. The requirement for extracorporeal membrane oxygenation (ECMO) support was higher in the EVLP arm (7/18, 38.8%) than in the standard arm (6/184, 3.2%). There were no major differences in rates of chest radiograph abnormalities, infection, lung function or rejection by 12 months. The cost of EVLP transplants is approximately £35,000 higher than the cost of standard transplants, as a result of the cost of the EVLP procedure, and the increased ECMO use and ITU stay. Predictors of cost were quality of life on joining the waiting list, type of transplant and number of lungs transplanted. An exploratory model comparing a NHS lung transplant service that includes EVLP and standard lung transplants with one including only standard lung transplants resulted in an incremental cost-effectiveness ratio of £73,000. Interviews showed that patients had a good understanding of the need for, and the processes of, EVLP. If EVLP can increase the number of usable donor lungs and reduce waiting, it is likely to be acceptable to those waiting for lung transplantation. Study limitations include small numbers in the EVLP arm, limiting analysis to descriptive statistics and the EVLP protocol change during the study. Conclusions: Overall, one-third of donor lungs subjected to EVLP were deemed suitable for transplant. Estimated survival over 12 months was lower than in the standard group, but the data were also consistent with no difference in survival between groups. Patients receiving these additional transplants experience a higher rate of early graft injury and need for unplanned ECMO support, at increased cost. The small number of participants in the EVLP arm because of early study termination limits the robustness of these conclusions. The reason for the increased PGD rates, high ECMO requirement and possible differences in lung injury between EVLP protocols needs evaluation

Automatic tracking of implanted fiducial markers in cone beam CT projection images

Purpose: This paper describes a novel method for simultaneous intrafraction tracking of multiple fiducial markers. Although the proposed method is generic and can be adopted for a number of applications including fluoroscopy based patient position monitoring and gated radiotherapy, the tracking results presented in this paper are specific to tracking fiducial markers in a sequence of cone beam CT projection images. Methods: The proposed method is accurate and robust thanks to utilizing the mean shift and random sampling principles, respectively. The performance of the proposed method was evaluated with qualitative and quantitative methods, using data from two pancreatic and one prostate cancer patients and a moving phantom. The ground truth, for quantitative evaluation, was calculated based on manual tracking preformed by three observers. Results: The average dispersion of marker position error calculated from the tracking results for pancreas data (six markers tracked over 640 frames, 3840 marker identifications) was 0.25 mm (at iscoenter), compared with an average dispersion for the manual ground truth estimated at 0.22 mm. For prostate data (three markers tracked over 366 frames, 1098 marker identifications), the average error was 0.34 mm. The estimated tracking error in the pancreas data was < 1 mm (2 pixels) in 97.6% of cases where nearby image clutter was detected and in 100.0% of cases with no nearby image clutter. Conclusions: The proposed method has accuracy comparable to that of manual tracking and, in combination with the proposed batch postprocessing, superior robustness. Marker tracking in cone beam CT (CBCT) projections is useful for a variety of purposes, such as providing data for assessment of intrafraction motion, target tracking during rotational treatment delivery, motion correction of CBCT, and phase sorting for 4D CBCT

Additional file 2 of Total serum N-glycans associate with response to immune checkpoint inhibition therapy and survival in patients with advanced melanoma

Additional file 2: Table 1. Description of total serum N-glycan UHPLC measured peaks. Table 2. Description of total serum derived traits. Table 3. Summary statistics for the associations between N-glycan traits and response to ICI treatment. Table 4. Summary statistics for the associations between N-glycan traits and progression-free survival. Table 5. Summary statistics for the associations between N-glycan traits and overall survival. Table 6. Summary statistics for the N-glycans shift at follow up with respect to the pre-treatment relative abundances

Inter-observer variability in target delineation increases during adaptive treatment of head-and-neck and lung cancer

Introduction: Inter-observer variability (IOV) in target volume delineation is a well-documented source of geometric uncertainty in radiotherapy. Such variability has not yet been explored in the context of adaptive re-delineation based on imaging data acquired during treatment. We compared IOV in the pre- and mid-treatment setting using expert primary gross tumour volume (GTV) and clinical target volume (CTV) delineations in locoregionally advanced head-and-neck squamous cell carcinoma (HNSCC) and (non-)small cell lung cancer [(N)SCLC]. Material and methods: Five and six observers participated in the HNSCC and (N)SCLC arm, respectively, and provided delineations for five cases each. Imaging data consisted of CT studies partly complemented by FDG-PET and was provided in two separate phases for pre- and mid-treatment. Global delineation compatibility was assessed with a volume overlap metric (the Generalised Conformity Index), while local extremes of IOV were identified through the standard deviation of surface distances from observer delineations to a median consensus delineation. Details of delineation procedures, in particular, GTV to CTV expansion and adaptation strategies, were collected through a questionnaire. Results: Volume overlap analysis revealed a worsening of IOV in all but one case per disease site, which failed to reach significance in this small sample (p-value range .063–.125). Changes in agreement were propagated from GTV to CTV delineations, but correlation could not be formally demonstrated. Surface distance based analysis identified longitudinal target extent as a pervasive source of disagreement for HNSCC. High variability in (N)SCLC was often associated with tumours abutting consolidated lung tissue or potentially invading the mediastinum. Adaptation practices were variable between observers with fewer than half stating that they consistently adapted pre-treatment delineations during treatment. Conclusion: IOV in target volume delineation increases during treatment, where a disparity in institutional adaptation practices adds to the conventional causes of IOV. Consensus guidelines are urgently needed

Additional file 2 of Breast cancer risks associated with missense variants in breast cancer susceptibility genes

Additional file 2