Search

Background: Studies suggest that combining radiotherapy (RT) with programmed cell death protein 1 (PD-1) blockade may elicit a synergistic antitumor response. We aimed to assess whether prior or concurrent RT was associated with improved disease control in patients with metastatic non–small cell lung cancer (NSCLC) treated with nivolumab. Methods: We conducted a retrospective study of patients receiving nivolumab as second or subsequent line therapy for metastatic NSCLC. Patients were categorized into those who received any RT for NSCLC prior to or during nivolumab therapy, and those with no history of RT for NSCLC. Results: A total of 85 patients received nivolumab between July 2015 and December 2016 and were followed up for a median of 15 months. Sixty-five patients (76.4%) received RT prior to or during nivolumab and 20 patients (23.6%) received nivolumab alone. Baseline characteristics of age, performance status, histology, smoking status and previous therapy were similar between the two groups. Prior or concurrent RT was associated with a superior PFS, median 2.8 months with RT versus 1.3 months without RT (Hazard Ratio (HR) = 0.494; 95% Confidence Interval (CI), 0.279–0.873; P = 0.02). The median OS of the group receiving RT was 6.4 months versus 4.2 months for the no RT group (P = 0.20). RT was not associated with an increase in toxicity. Conclusion: RT prior to or concurrent with nivolumab for metastatic NSCLC was associated with a modest improvement in PFS over nivolumab alone with no evidence of increase in adverse effects. RT may potentiate the effect of anti–PD-1 immunotherapy in NSCLC.

This project examined the use of an augmented histological technique for bone tissue using fluorochrome labelling in a newly developed experimental sheep fracture model. The fracture model encompassed the surgical creation of an experimental fracture which was precisely controlled and independent of external mechanical forces in order to study the effect of the mechanical environment on fracture healing. This research outlined the development and a pilot study combining sequential fluorochrome labelling into the experimental fracture model as a means to enhance the histological analysis of fracture healing and guide development of improved fracture fixation and tissue engineering strategies.

Bone fracture healing is sensitive to the fixation stability. However, it is unclear which phases of healing are mechano-sensitive and if mechanical stimulation is required throughout repair. In this study, a novel bone defect model, which isolates an experimental fracture from functional loading, was applied in sheep to investigate if stimulation limited to the early proliferative phase is sufficient for bone healing. An active fixator controlled motion in the fracture. Animals of the control group were unstimulated. In the physiological-like group, 1 mm axial compressive movements were applied between day 5 and 21, thereafter the movements were decreased in weekly increments and stopped after 6 weeks. In the early stimulatory group, the movements were stopped after 3 weeks. The experimental fractures were evaluated with mechanical and micro-computed tomography methods after 9 weeks healing. The callus strength of the stimulated fractures (physiological-like and early stimulatory) was greater than the unstimulated control group. The control group was characterized by minimal external callus formation and a lack of bone bridging at 9 weeks. In contrast, the stimulated groups exhibited advanced healing with solid bone formation across the defect. This was confirmed quantitatively by a lower bone volume in the control group compared to the stimulated groups.The novel experimental model permits the application of a well-defined load history to an experimental bone fracture. The poor healing observed in the control group is consistent with under-stimulation. This study has shown early mechanical stimulation only is sufficient for a timely healing outcome.

Purpose: This cross-sectional study used transmission-mode ultrasound to evaluate dynamic tendon properties during walking in surgically repaired and contralateral Achilles tendon (AT), with a median (range) post-operative period of 22 (4-58) months. It was hypothesised that the axial transmission speed of ultrasound (TSOU) during walking would be slower, indicating lower material stiffness in repaired compared with contralateral AT. Methods: Ten patients [median (range) age 47 (37-69) years; height 180 (170-189) cm; weight 93 (62-119) kg], who had undergone open surgical repair of the AT and were clinically recovered according to their treating clinicians, walked barefoot on a treadmill at self-selected speed (1.0 ± 0.2 m/s). Synchronous measures of TSOU, sagittal ankle motion, vertical ground reaction force (GRF), and spatiotemporal gait parameters were recorded during 20 s of steady-state walking. Paired t tests were used to evaluate potential between-limb differences in TSOU, GRF, ankle motion, and spatiotemporal gait parameters. Results: TSOU was significantly lower (≈175 m/s) in the repaired than in the contralateral AT over the entire gait cycle (P < 0.05). Sagittal ankle motion was significantly greater (≈3°) in the repaired than in the contralateral limb (P = 0.036). There were no significant differences in GRF or spatiotemporal parameters between limbs. Conclusions: Repaired AT was characterised by a lower TSOU, reflecting a lower material stiffness in the repaired tendon than in the contralateral tendon. A lower material stiffness may underpin greater ankle joint motion of the repaired limb during walking and long-term deficits in the muscle-tendon unit reported with AT repair. Treatment and rehabilitation approaches that focus on increasing the material stiffness of the repaired AT may be clinically beneficial. Transmission-mode ultrasound would seem useful for quantifying tendon properties post AT rupture repair and may have the potential to individuall