Adaptive Radiotherapy in the Management of Cervical Cancer: Review of Strategies and Clinical Implementation.

The complex and varied motion of the cervix-uterus target during external beam radiotherapy (EBRT) underscores the clinical benefits afforded by adaptive radiotherapy (ART) techniques. These gains have already been realised in the implementation of image-guided adaptive brachytherapy, where adapting to anatomy at each fraction has seen improvements in clinical outcomes and a reduction in treatment toxicity. With regards to EBRT, multiple adaptive strategies have been implemented, including a personalised internal target volume, offline replanning and a plan of the day approach. With technological advances, there is now the ability for real-time online ART using both magnetic resonance imaging and computed tomography-guided imaging. However, multiple challenges remain in the widespread dissemination of ART. This review investigates the ART strategies and their clinical implementation in EBRT delivery for cervical cancer.

Airway events in obese vs. non-obese elective surgical patients: a cross-sectional observational study.

Obesity is an increasingly prevalent comorbidity within the UK population. The aim of this study was to determine the proportion of obese patients in an elective surgical population. The second aim was to determine the choice of airway equipment and incidence of airway events in obese vs. non-obese patients. We conducted a cross-sectional observational study over two 24-h periods in March 2018 across 39 hospitals in the greater London area. Data were collected regarding 1874 patients. The incidence of obesity was 32% in the study population compared with 26% in the general UK population (p < 0.0001). Minor airway events were defined as: desaturation to Sp O2 < 90%; failed mask ventilation; supraglottic airway device problem; aspiration; airway trauma and difficult intubation; or recognised oesophageal intubation. Major airway events were defined as: unrecognised oesophageal intubation; a 'cannot intubate cannot oxygenate' emergency; the need for unplanned front-of-neck airway; cardiac arrest; or unplanned intensive care unit admission due to an airway event. In total, 89 minor and two major airway events were recorded. Obese patients were more likely to experience a minor airway event (RR 2.39, 95%CI 1.60-3.57), the most common being desaturation (Sp O2 < 90%). The use of a supraglottic airway device in obese vs. non-obese patients was associated with increased airway events (RR 3.46 [1.88-6.40]). Tracheal intubation vs. supraglottic airway device use increased with obesity class but was not associated with a decrease in airway events (RR 0.90 [0.53-1.55]). Our data suggest that obesity is more common in the elective surgical vs. general population and minor airway events are more common in obese vs. non-obese elective patients.

Folic acid supplementation in postmenopausal women with hot flushes: phase III randomised double-blind placebo-controlled trial.

OBJECTIVE: To assess whether folic acid supplementation ameliorates hot flushes. DESIGN: Double-blind, placebo-controlled randomised trial. SETTING: Nine hospitals in England. POPULATION: Postmenopausal women experiencing ≥50 hot flushes weekly. METHODS: Women (n = 164) were randomly assigned in a 1:1 ratio to receive folic acid 5 mg tablet or placebo daily for 12 weeks. Participants recorded frequency and severity of hot flushes in a Sloan Diary daily and completed Greene Climacteric and Utian Quality of Life (UQoL) Scales at 4-week intervals. MAIN OUTCOME MEASURES: The change in daily Hot Flush Score at week 12 from randomisation based on Sloan Diary Composite Score B calculation. RESULTS: Data of 143 (87%) women were available for the primary outcome. The mean change (SD) in Hot Flush Score at week 12 was -6.98 (10.30) and -4.57 (9.46) for folic acid and placebo group, respectively. The difference between groups in the mean change was -2.41 (95% CI -5.68 to 0.87) (P = 0.149) and in the adjusted mean change -2.61 (95% CI -5.72 to 0.49) (P = 0.098). Analysis of secondary outcomes indicated an increased benefit in the folic acid group regarding changes in total and emotional UQoL scores at week 8 when compared with placebo. The difference in the mean change from baseline was 5.22 (95% CI 1.16-9.28) and 1.88 (95% CI 0.23-3.52) for total and emotional score, respectively. CONCLUSIONS: The study was not able to demonstrate that folic acid had a statistically significant greater benefit in reducing Hot Flush Score over 12 weeks in postmenopausal women when compared with placebo. TWEETABLE ABSTRACT: Folic acid may ameliorate hot flushes in postmenopausal women but confirmation is required from a larger study.

The Potential Value of MRI in External-Beam Radiotherapy for Cervical Cancer.

The reference standard treatment for cervical cancer is concurrent chemoradiotherapy followed by magnetic resonance imaging (MRI)-guided brachytherapy. Improvements in brachytherapy have increased local control rates, but late toxicity remains high with rates of 11% grade ≥3. The primary clinical target volume (CTV) for external-beam radiotherapy includes the cervix and uterus, which can show significant inter-fraction motion. This means that generous margins are required to cover the primary CTV, increasing the radiation dose to organs at risk and, therefore, toxicity. A number of image-guided radiotherapy techniques (IGRT) have been developed, but motion can be random and difficult to predict prior to treatment. In light of the development of integrated MRI linear accelerators, this review discusses the potential value of MRI in external-beam radiotherapy. Current solutions for managing pelvic organ motion are reviewed, including the potential for online adaptive radiotherapy. The impacts of the use of MRI in tumour delineation and in the delivery of stereotactic ablative body radiotherapy (SABR) are highlighted. The potential role and challenges of using multi parametric MRI to guide radiotherapy are also discussed.

Does the Use of Volumetric Modulated Arc Therapy Reduce Gastrointestinal Symptoms after Pelvic Radiotherapy?

AIMS: Growing numbers of patients with cancer are surviving after treatment with pelvic radiotherapy. We evaluated the technique of volumetric modulated arc therapy (VMAT), which delivers a decreased dose to the organs at risk. We aimed to determine outcomes of this technique in terms of patient-reported acute toxicity and late effects and correlate the frequency of gastrointestinal symptoms with the volume of bowel receiving radiation dose. MATERIALS AND METHODS: Patients who were to receive VMAT for gynaecological malignancy completed patient-reported outcomes at baseline, the end of treatment, 8 weeks and 1 year. The rates of patient-reported toxicity were correlated with the volume of bowel irradiated. RESULTS: The frequencies of patient-reported gastrointestinal symptoms increased in the acute toxicity phase and tended to improve at 1 year, with the exception of faecal incontinence and rectal bleeding (P < 0.05). There was not a strong association between the volume of small bowel that was irradiated (P > 0.05 at all dose levels) and reported toxicity, suggesting that other factors are involved in the development of toxicity. CONCLUSION: Although VMAT decreases the dose delivered to the small bowel, this does not translate into a reduction in patient-reported toxicity.

Insufficiency fractures in patients treated with pelvic radiotherapy and chemotherapy for uterine and cervical cancer.

Insufficiency fractures are recognised consequences of radiotherapy in gynaecological malignancy with reported incidences between 2.7% and 89%. We aimed to determine the incidence and risk factors for insufficiency fractures in patients receiving radical pelvic radiotherapy for uterine and cervical cancer. A case-note review was undertaken of patients treated between January 2007 and December 2008. Insufficiency fractures were identified from radiographs, computed tomography and magnetic resonance images. Chi-squared and Mann-Whitney tests were performed to determine associations between insufficiency fractures and chemotherapy, steroids and age. A total of 285 patients received pelvic radiotherapy, 137 with uterine and 148 with cervical cancer. Mean age was 59 years. A total of 144 patients received chemotherapy, 101 concurrently and 35 adjuvantly. Bone abnormalities affected 67 patients, 33 had pelvic insufficiency fractures, 12 had multiple fractures and 3 patients developed femoral head avascular necrosis. Use of chemotherapy was not associated with development of fractures (P = 0.949). However, cervical cancer patients had a significantly higher incidence of insufficiency fractures (P = 0.018) and bone pain (P = 0.03) compared with uterine cancer patients. This suggests concurrent chemotherapy may be a significant factor in increasing insufficiency fractures and bone morbidity in these patients and highlights a need for further research to identify, prevent and reduce these long-term complications.

Early laparoscopic cholecystectomy service provision is feasible and safe in the current UK National Health Service.

INTRODUCTION: Despite increasing evidence of the benefits and safety of early laparoscopic cholecystectomy (LC) in acute gallstone disease, it is not widely practised in England. The Royal College of Surgeons of England support the separation of emergency and elective surgical care. The aim of this prospective study was to examine the impact of the implementation of 'Surgeon of the Week (SoW)' model on the number of early LCs performed and the efficiency of the emergency theatre activity in our hospital. This study also looked into its implications on specialist registrar training for early LC, and the financial impact to the hospital. PATIENTS AND METHODS: Between January 2007 and May 2008, demographic data, admission and discharge dates, complications, conversions to an open operation and deaths were collected for all patients who underwent early laparoscopic cholecystectomies. For ease of comparison, patients were divided into Group A representing before introduction of SoW (1 January 2007 to 30 August 2007) and Group B representing after introduction of SoW (1 October 2007 to 31 May 2008). The total numbers of operations performed in the emergency theatre list in the two groups were also calculated. RESULTS: A total of 1361 emergency operations were performed on the emergency theatre list in Group A, of which 951 were general surgical procedures. In Group B, the numbers of emergency procedures were 1537, of which 1138 were general surgical operations. There was a significant increase in the number of general surgical operations after introduction of SoW (P = 0.013). Before introduction of the SoW rota, 45 early LCs were performed. This increased to 118 after SoW which was significant (P < 0.001). In Group A, the number of early LCs performed by surgical trainees was 10 (22%). In Group B, the number of LCs performed by surgical trainees was 35 (30%; not significant). CONCLUSIONS: This study has demonstrated an increase in the efficiency of the emergency theatre with an increase in the number of early LCs on their index admission without extra morbidity following implementation of the SOW model in our hospital. We recommend the introduction of a suitable emergency surgical consultant on-call model separating emergency and elective surgical care depending on local circumstances. This can lead to significant cost savings and reduce re-admissions with gallstone-related complications.

Estimation of renal function -- what is appropriate in cancer patients?

AIMS: To compare the accuracy of renal assessment in patients with cancer using radioisotope glomerular filtration rate (GFR), urine collection for creatinine clearance, Cockroft-Gault, Modification of Diet in Renal Disease (MDRD) and Wright formulae. MATERIALS AND METHODS: Measurements of isotope GFR from 367 patients were compared with estimates from the described methods (Cockroft-Gault, MDRD, Wright). An analysis including a further 252 patients with an isotope GFR < or = 50 ml/min was also carried out. RESULTS: The Wright formula was the most accurate form of estimating renal function for the first study group. The formulae were similar in accuracy in the second study group. CONCLUSIONS: The Wright formula is the most accurate form of estimation of renal function in comparison with the isotope GFR for cancer patients. When there is a large proportion of patients with a low isotope GFR (< or = 50 ml/min), the formulae have similar accuracy.

Effect of gravito-inertial cues on the coding of orientation in pre-attentive vision.

To see if the spatial reference frame used by pre-attentive vision is specified in a retino-centered frame or in a reference frame integrating visual and nonvisual information (vestibular and somatosensory), subjects were centrifuged in a non-pendular cabin and were asked to search for a target distinguishable from distractors by difference in orientation (Treisman's "pop-out" paradigm [1]). In a control condition, in which subjects were sitting immobilized but not centrifuged, this task gave an asymmetric search pattern: Search was rapid and pre-attentional except when the target was aligned with the horizontal retinal/head axis, in which case search was slow and attentional (2). Results using a centrifuge showed that slow/serial search patterns were obtained when the target was aligned with the subjective horizontal axis (and not with the horizontal retinal/head axis). These data suggest that a multisensory reference frame is used in pre-attentive vision. The results are interpreted in terms of Riccio and Stoffregen's "ecological theory" of orientation in which the vertical and horizontal axes constitute independent reference frames (3).

Effect of gravitational cues on visual search for orientation.

To determine whether nonvisual (vestibular and somatosensory) information participates in low-level orientation processing, subjects in different postural conditions (upright, supine, and sitting immobilized) searched for a target distinguishable from distractors by difference in orientation (A. Treisman's, 1985, "pop-out" paradigm). Searches for vertical and horizontal targets were dramatically modified as a function of the postural position, indicating that the processing of orientation in early vision is not only retinal but integrates information from the sensory graviceptors. This visuovestibular phenomenon is interpreted in the conceptual framework of D. H. Foster and P. A. Ward's (1991a) model based on local orthogonal orientation filters and T. A. Stoffregen and G. E. Riccio's (1988) dynamics of balance theory.