Toxicity and Efficacy of Stereotactic Ablative Body Radiotherapy for Moderately Central Non-small Cell Lung Cancers Using 50 Gy in Five Fractions.

AIMS: Stereotactic ablative body radiotherapy doses for peripheral lung lesions caused high toxicity when used for central non-small cell lung cancer (NSCLC). To determine a safe stereotactic ablative body radiotherapy dose for central tumours, the phase I/II Radiation Therapy Oncology Group RTOG 0813 trial used 50 Gy/five fractions as a baseline. From 2013, 50 Gy/five fractions was adopted at the Beatson West of Scotland Cancer Centre for inoperable early stage central NSCLC. We report our prospectively collected toxicity and efficacy data. MATERIALS AND METHODS: Patient and treatment characteristics were obtained from electronic medical records. Tumours were classed as moderately central or ultra-central tumours using published definitions. Toxicity was assessed in a centralised follow-up clinic at 2 weeks, 6 weeks, 3 months, 6 months, 1 year and 2 years after treatment. RESULTS: Fifty patients (31 women, 19 men, median age 75.1 years) were identified with T1-2N0M0 moderately central NSCLC; one patient had both an ultra-central and a moderately central tumour. Eighty-four per cent were medically unfit for surgery. Forty per cent had biopsy-proven NSCLC and 60% were diagnosed radiologically using 18-fluorodeoxyglucose positron emission tomography/computed tomography imaging. Fifty-six per cent of patients were Eastern Cooperative Oncology Group (ECOG) performance status 2 or worse. All patients received 50 Gy/five fractions on alternate days on schedule. Two patients died within 90 days of treatment, one from a chest infection, the other cause of death was unknown. There was one episode of early grade 3 oesophagitis and one grade 3 late dyspnoea. There was no grade 4 toxicity. Over a median follow-up of 25.2 months (range 1-70 months), there were 34 deaths: 18 unrelated to cancer and 16 due to cancer recurrence. The median overall survival was 27.0 months (95% confidence interval 20.6-35.9) and cancer-specific survival was 39.8 months (95% confidence interval 28.6, not reached). CONCLUSION: This study has shown that 50 Gy/five fractions is a safe dose and fractionation for early stage inoperable moderately central NSCLC, with outcomes comparable with other series, even with patients with a poor performance status.

Octopamine stabilizes conduction reliability of an unmyelinated axon during hypoxic stress.

Mechanisms that could mitigate the effects of hypoxia on neuronal signaling are incompletely understood. We show that axonal performance of a locust visual interneuron varied depending on oxygen availability. To induce hypoxia, tracheae supplying the thoracic nervous system were surgically lesioned and action potentials in the axon of the descending contralateral movement detector (DCMD) neuron passing through this region were monitored extracellularly. The conduction velocity and fidelity of action potentials decreased throughout a 45-min experiment in hypoxic preparations, whereas conduction reliability remained constant when the tracheae were left intact. The reduction in conduction velocity was exacerbated for action potentials firing at high instantaneous frequencies. Bath application of octopamine mitigated the loss of conduction velocity and fidelity. Action potential conduction was more vulnerable in portions of the axon passing through the mesothoracic ganglion than in the connectives between ganglia, indicating that hypoxic modulation of the extracellular environment of the neuropil has an important role to play. In intact locusts, octopamine and its antagonist, epinastine, had effects on the entry to, and recovery from, anoxic coma consistent with octopamine increasing overall neural performance during hypoxia. These effects could have functional relevance for the animal during periods of environmental or activity-induced hypoxia.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: an unusual cause of cyclical ectopic adrenocorticotrophic syndrome.

We present the case of a 73-year-old woman who presented with clinical features of Cushing's syndrome, confirmed biochemically with elevated levels of cortisol and adrenocorticotrophic hormone (ACTH). Petrosal venous sampling showed no ACTH gradient and MRI of pituitary was normal, suggesting ectopic ACTH production. In the course of further investigations, a thoracic CT was carried out to look for evidence of bronchial neoplasm. Although there was no discrete tumour identified, CT revealed widespread fine nodularity in the right middle and lower lobe. Subsequent trans-bronchial and video-assisted thorascopic biopsy showed pulmonary tumourlets and two typical carcinoid tumours on a background of diffuse idiopathic pulmonary neuroendocrine cell neoplasia (DIPNECH). We describe the clinical, radiological and histological features of this rare condition.

High resolution computed tomographic assessment of airway wall thickness in chronic asthma: reproducibility and relationship with lung function and severity.

BACKGROUND: In some patients chronic asthma results in irreversible airflow obstruction. High resolution computed tomography (HRCT) has been advocated for assessing the structural changes in the asthmatic lung and permits investigation of the relationships between airway wall thickening and clinical parameters in this condition. METHODS: High resolution CT scanning was performed in 49 optimally controlled asthmatic patients and measurements of total airway and lumen diameter were made by two independent radiologists using electronic callipers. Wall area as % total airway cross sectional area (WA%) and wall thickness to airway diameter ratio (T/D) were calculated for all airways clearly visualised with a transverse diameter of more than 1.5 mm, with a mean value derived for each patient. Intra- and inter-observer variability was assessed for scope of agreement in a subgroup of patients. Measurements were related to optimum forced expiratory volume in 1 second (FEV1), forced mid expiratory flow, carbon monoxide gas transfer, two scores of asthma severity, airway inflammation as assessed with induced sputum, and exhaled nitric oxide. RESULTS: Neither observer produced a statistically significant difference between measurements performed on two occasions but there was a significant difference between observers (limits of agreement -2.6 to 6.8 for WA%, p<0.0001). However, mean WA% measured on two occasions differed by no more than 5.4% (limits of agreement -4.0 to 5.4; mean (SD) 0.7 (2.4)). Statistically significant positive associations were observed between both WA% and T/D ratio and asthma severity (r(S)=0.29 and 0.30, respectively, for ATS score), and an inverse association with gas transfer coefficient was observed (r(S)=-0.43 for WA% and r(S)=-0.41 for T/D). No association was identified with FEV1 or airway inflammation. CONCLUSIONS: The airway wall is thickened in more severe asthma and is associated with gas transfer coefficient. This thickening does not relate directly to irreversible airflow obstruction as measured with FEV1.

CT manifestations of respiratory syncytial virus infection in lung transplant recipients.

PURPOSE: The purpose of our study was to evaluate CT findings during respiratory syncytial virus (RSV) infection in lung transplant recipients and to identify sequelae. METHOD: Thirty-nine CT scans prior to, during, and following acute infection in 10 lung transplant recipients were reviewed. Abnormalities that were new from baseline observations and occurred within 4 weeks of diagnosis were defined as acute. Chronic findings were defined as those present >4 weeks after diagnosis. RESULTS: Findings in nine patients were ground-glass (seven), air-space (five), and tree-in-bud (four) opacities and acute bronchial dilatation (four) and wall thickening (four). Patients lacked pleural effusions or lymph node enlargement. Five of seven patients with follow-up exams had new air trapping (three), persistent bronchial dilatation (three), and thickening (two). Three and 2 of the 10 patients developed bronchiolitis obliterans syndrome and obliterative bronchiolitis, respectively. CONCLUSION: During acute infection, patients commonly had ground-glass opacities but lacked pleural effusions and lymph node enlargement. There can be chronic sequelae after infection.

The prevalence and associated variables of deep venous thrombosis in patients with advanced cancer.

The prevalence of venous thromboembolism (VTE) in cancer patients has been estimated as up to 15% antemortem, and higher (over 50% in pancreatic tumours) postmortem owing to the asymptomatic nature of many episodes of VTE. We investigated the prevalence of deep venous thrombosis (DVT) in a population of 298 hospice inpatients with advanced cancer. They were screened for the presence of DVT using light reflection rheography; 258 (86.6%) patients were evaluable for DVT, which was found in 135 (52%; 95% confidence interval 46-58). Factors associated (multivariate analysis) with the presence of DVT were: poor mobility, reduced serum albumin level and higher serum urea. A DVT risk assessment index was calculated using these variables. The three highest categories all had significant rates of DVT and, although the lowest category had a low rate of DVT, it accounted for less than 10% of all patients tested. DVT is common in patients with advanced cancer. It was found to be significantly associated with the above variables, but a combined index was of limited clinical application. In view of the number of patients identified with DVT, repeated small pulmonary emboli may be responsible for more symptoms than previously recognized in cancer patients.

Abnormal coagulation and deep venous thrombosis in patients with advanced cancer.

Many studies have demonstrated increased coagulation activation in cancer patients and have shown evidence of chronic, low-grade disseminated intravascular coagulation, although most patients remained asymptomatic. In general, patients have not been screened for deep venous thrombosis (DVT). We screened 98 patients with advanced malignancy for DVT using light reflection rheography. Coagulation profiles of DVT and non-DVT groups were studied. We found a high prevalence of DVT (50%) on screening. Overall, the patients had raised levels of fibrinogen (66% patients), factor VIII:C (43%), fragment 1 + 2 (71%) and TAT levels (89%). Patients with DVT had a significantly lower level of fibrinogen than those without (4.0 g/dl, SD 1.4, compared with 4.7 g/dl SD 1.6, P = 0.04). There was no significant difference in other coagulation or liver function tests between the DVT and non-DVT groups. The wide variation of results makes their interpretation difficult and unlikely to be of predictive value in estimating individual thrombotic risk.

The value of light reflection rheography as a screening tool for deep venous thrombosis.

Deep venous thrombosis (DVT) is a common condition in which the clinical diagnosis is notoriously inaccurate. The diagnosis is usually made in the Radiology Department by either Doppler ultrasound or conventional venography. The high clinical suspicion for DVT and the availability of these imaging modalities places an ever increasing burden on radiology departments. Light reflection rheography (LRR) is a non-invasive technique for assessing venous disorders. It is easy and quick and can be performed at the bedside or in the Radiology Department. LRR was prospectively compared with conventional venography in 50 consecutive patients undergoing investigation for possible DVT. LRR was entirely normal in 24 patients and this was confirmed on venography in each case. In practice it was not always possible to differentiate between DVT and venous insufficiency in the 26 abnormal tracings but all 15 cases of venography-proven DVT were within this group. There were no false negative diagnoses of DVT. LRR is a simple and quick method of screening for DVT with significant cost saving implications. A normal tracing reliably excludes the diagnosis, whilst all abnormal tracings should undergo Doppler ultrasound or venography.

Electromyographic biofeedback and physical therapy of the hemiplegic upper limb.

A long-term, comparison-group outcome trial with a partial crossover design was carried out on the effects of electromyographic biofeedback (EMGBF) plus physiotherapy (PT) versus PT alone in the treatment of the hemiplegic upper limb in stroke patients who were at least six months beyond the onset of their disability. Both the experimental and the control groups benefited from their treatment, but EMGBF was shown to have an additional effect, both in the experimental patients, and in the control patients when they switched over to the experimental treatment condition.