Author: Jason Curtis

Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial (2018)

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Type of publication:
Randomised controlled trial

Author(s):
Parker, Christopher C; James, Nicholas D; Brawley, Christopher D; Clarke, Noel W; Hoyle, Alex P; Ali, Adnan; Ritchie, Alastair W S; Attard, Gerhardt; Chowdhury, Simon; Cross, William; Dearnaley, David P; Gillessen, Silke; Gilson, Clare; Jones, Robert J; Langley, Ruth E; Malik, Zafar I; Mason, Malcolm D; Matheson, David; Millman, Robin; Russell, J Martin; Thalmann, George N; Amos, Claire L; Alonzi, Roberto; Bahl, Amit; Birtle, Alison; Din, Omar; Douis, Hassan; Eswar, Chinnamani; Gale, Joanna; Gannon, Melissa R; Jonnada, Sai; Khaksar, Sara; Lester, Jason F; O'Sullivan, Joe M; Parikh, Omi A; Pedley, Ian D; Pudney, Delia M; Sheehan, Denise J; *Srihari, Narayanan Nair; Tran, Anna T H; Parmar, Mahesh K B; Sydes, Matthew R; Systemic Therapy for Advanced or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) investigators

Citation:
Lancet, Volume 392, Issue 10162, 1–7 December 2018, Pages 2353-2366

Abstract:
BACKGROUND Based on previous findings, we hypothesised that radiotherapy to the prostate would improve overall survival in men with metastatic prostate cancer, and that the benefit would be greatest in patients with a low metastatic burden. We aimed to compare standard of care for metastatic prostate cancer, with and without radiotherapy. METHODS We did a randomised controlled phase 3 trial at 117 hospitals in Switzerland and the UK. Eligible patients had newly diagnosed metastatic prostate cancer. We randomly allocated patients open label in a 1:1 ratio to standard of care (control group) or standard of care and radiotherapy (radiotherapy group). Randomisation was stratified by hospital, age at randomisation, nodal involvement, WHO performance status, planned androgen deprivation therapy, planned docetaxel use (from December, 2015), and regular aspirin or non-steroidal anti-inflammatory drug use. Standard of care was lifelong androgen deprivation therapy, with up front docetaxel permitted from December, 2015. Men allocated radiotherapy received either a daily (55 Gy in 20 fractions over 4 weeks) or weekly (36 Gy in six fractions over 6 weeks) schedule that was nominated before randomisation. The primary outcome was overall survival, measured as the number of deaths; this analysis had 90% power with a one-sided α of 2·5% for a hazard ratio (HR) of 0·75. Secondary outcomes were failure-free survival, progression-free survival, metastatic progression-free survival, prostate cancer-specific survival, and symptomatic local event-free survival. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. The primary outcome analysis was by intention to treat. Two prespecified subgroup analyses tested the effects of prostate radiotherapy by baseline metastatic burden and radiotherapy schedule. This trial is registered with ClinicalTrials.gov, number CT00268476. FINDINGS Between Jan 22, 2013, and Sept 2, 2016, 2061 men underwent randomisation, 1029 were allocated the control and 1032 radiotherapy. Allocated groups were balanced, with a median age of 68 years (IQR 63-73) and median amount of prostate-specific antigen of 97 ng/mL (33-315). 367 (18%) patients received early docetaxel. 1082 (52%) participants nominated the daily radiotherapy schedule before randomisation and 979 (48%) the weekly schedule. 819 (40%) men had a low metastatic burden, 1120 (54%) had a high metastatic burden, and the metastatic burden was unknown for 122 (6%). Radiotherapy improved failure-free survival (HR 0·76, 95% CI 0·68-0·84; p<0·0001) but not overall survival (0·92, 0·80-1·06; p=0·266). Radiotherapy was well tolerated, with 48 (5%) adverse events (Radiation Therapy Oncology Group grade 3-4) reported during radiotherapy and 37 (4%) after radiotherapy. The proportion reporting at least one severe adverse event (Common Terminology Criteria for Adverse Events grade 3 or worse) was similar by treatment group in the safety population (398
[38%] with control and 380 [39%] with radiotherapy). INTERPRETATION Radiotherapy to the prostate did not improve overall survival for unselected patients with newly diagnosed metastatic prostate cancer. FUNDING Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Astellas, Clovis Oncology, Janssen, Novartis, Pfizer, and Sanofi-Aventis.

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Patent foramen ovale causing breathlessness and platypnoea-orthodeoxia syndrome in an older patient (2018)

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Type of publication:
Journal article

Author(s):
*Madden, Katy; *MacKintosh, Abigail; *Mike, Nigel

Citation:
Age and Ageing; Jan 2019; vol. 48, no. 1, p.157-159

Abstract:
An 82-year-old male presented with a week's history of shortness of breath on exertion, particularly when bending to tie his shoe laces. The breathlessness worsened on standing and was relieved by lying. His oxygen saturations were noted to fluctuate based on position dropping to 82% on standing. This was suggestive of platypnoea-orthodeoxia syndrome (POS), an uncommon but potentially reversible diagnosis. As the population ages we may be more likely to see patients with persisting patent foramen ovale decompensate and develop POS.

Steroid-induced diabetes and hyperglycaemia. Part 1: mechanisms and risks (2018)

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Type of publication:
Journal article

Author(s):
*Morris, David

Citation:
Diabetes & Primary Care; Aug 2018; vol. 20 (no. 4); p. 151-153

Abstract:
Glucocorticoids are prescribed widely in primary care for the treatment of a range of conditions. Courses of treatment are usually short, but around 22% of use continues for over 6 months. As well as their therapeutic actions, glucocorticoids have a powerful impact on glucose metabolism, contributing to hyperglycaemia and a predisposition to diabetes. In the first of two articles on steroid-induced hyperglycaemia and diabetes, the author outlines the scale of the problem and explains the mechanisms by which glucocorticoids induce hyperglycaemia. High-risk situations are identified, and the short- and long-term dangers summarised. The second article will appear in the next issue of this journal.

Factors associated with physiotherapists' preference for MRI in primary care patients with low back and leg pain (2018)

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Type of publication:
Journal article

Author(s):
*Ely S. ; Stynes S.; Ogollah R.; Foster N.E.; Konstantinou K.

Citation:
Musculoskeletal Science and Practice; Dec 2018; vol. 38 ; p. 46-52

Abstract:
Background: Criticisms about overuse of MRI in low back pain are well documented. Yet, with the exception of suspicion of serious pathology, little is known about factors that influence clinicians' preference for magnetic resonance imaging (MRI) at first consultation. Objective: To explore factors associated with physiotherapists' preference for MRI for patients consulting with benign low back and leg pain (LBLP) including sciatica. Design: Cross-sectional cohort study. Methods: Data were collected from 607 primary care LBLP patients participating in the ATLAS cohort study. Following clinical assessment, physiotherapists documented whether he/she wanted the patient to have an MRI. Factors potentially associated with physiotherapists' preference for imaging were selected a priori from patient characteristics and clinical assessment findings. A mixed-effects logistic regression model examined the associations between these factors and physiotherapists' preference for MRI. Results: Physiotherapists expressed a preference for MRI in 32% (196/607) of patients, of whom 22 did not have a clinical diagnosis of sciatica (radiculopathy). Factors associated with preference for MRI included; clinical diagnosis of sciatica (OR 4.23: 95% CI 2.29, 7.81), greater than 3 months pain duration (2.61: 1.58, 4.30), high pain intensity (1.24: 1.11, 1.37), patient's low expectation of improvement (2.40: 1.50, 3.83), physiotherapist's confidence in their diagnosis (1.19: 1.07, 1.33), with greater confidence associated with higher probability for MRI preference. Conclusion: A clinical diagnosis of sciatica and longer symptom duration were most strongly associated with physiotherapists' preference for MRI. Given current best practice guidelines, these appear to be justifiable reasons for MRI preference at first consultation.

Results of a multicentre randomised controlled trial of cochlear-sparing intensity-modulated radiotherapy versus conventional radiotherapy in patients with parotid cancer (COSTAR; CRUK/08/004) (2018)

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Type of publication:
Journal article

Author(s):
Nutting , Morden JP, Beasley M, Bhide S, Cook A, De Winton E, Emson M, Evans M, Fresco L, Gollins S, Gujral D, Harrington K, Joseph M, Lemon C, Luxon L, van den Blink Q, Mendes R, Miah A, Newbold K, Prestwich R, Robinson M, Sanghera P, Simpson J, Sivaramalingam M, *Srihari NN, Sydenham M, Wells E, Witts S, Hall E; COSTAR Investigators.

Citation:
European Journal of Cancer; Nov 2018; vol. 103 ; p. 249-258

Abstract:
Purpose: About 40-60% of patients treated with post-operative radiotherapy for parotid cancer experience
ipsilateral sensorineural hearing loss. Intensity-modulated radiotherapy (IMRT) can reduce radiation dose to the cochlea. COSTAR, a phase III trial, investigated the role of cochlear-sparing IMRT (CS-IMRT) in reducing hearing loss. Methods: Patients (pT1-4 N0-3 M0) were randomly assigned (1:1) to 3-dimensional conformal radiotherapy (3DCRT) or CS-IMRT by minimisation, balancing for centre and radiation dose of 60Gy or 65Gy in 30 daily fractions. The primary end-point was proportion of patients with sensorineural hearing loss in the ipsilateral cochlea of >=10 dB bone conduction at 4000 Hz 12 months after radiotherapy compared using Fisher's exact test. Secondary end-points included hearing loss at 6 and 24 months, balance assessment, acute and late toxicity, patient-reported quality of life, time to recurrence and survival. Results: From Aug 2008 to Feb 2013, 110 patients (54 3DCRT; 56 CS-IMRT) were enrolled from 22 UK centres. Median doses to the ipsilateral cochlea were 3DCRT: 56.2Gy and CS-IMRT: 35.7Gy (p < 0.0001). 67/110 (61%) patients were evaluable for the primary end-point; main reasons for non-evaluability were non-attendance at follow-up or incomplete audiology assessment. At 12 months, 14/36 (39%) 3DCRT and 11/31 (36%) CS-IMRT patients had >=10 dB loss (p = 0.81). No statistically significant differences were observed in hearing loss at 6 or 24 months or in other secondary end-points including patient-reported hearing outcomes. Conclusion: CS-IMRT reduced the radiation dose below the accepted tolerance of the cochlea, but this did not lead to a reduction in the proportion of patients with clinically relevant hearing loss.

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