Precision assessment of bowel motion quantification using 3D cine-MRI for radiotherapy.

Objective. The bowel is an important organ at risk for toxicity during pelvic and abdominal radiotherapy. Identifying regions of high and low bowel motion with MRI during radiotherapy may help to understand the development of bowel toxicity, but the acquisition time of MRI is rather long. The aim of this study is to retrospectively evaluate the precision of bowel motion quantification and to estimate the minimum MRI acquisition time.Approach. We included 22 gynaecologic cancer patients receiving definitive radiotherapy with curative intent. The 10 min pre-treatment 3D cine-MRI scan consisted of 160 dynamics with an acquisition time of 3.7 s per volume. Deformable registration of consecutive images generated 159 deformation vector fields (DVFs). We defined two motion metrics, the 50th percentile vector lengths (VL50) of the complete set of DVFs was used to measure median bowel motion. The 95th percentile vector lengths (VL95) was used to quantify high motion of the bowel. The precision of these metrics was assessed by calculating their variation (interquartile range) in three different time frames, defined as subsets of 40, 80, and 120 consecutive images, corresponding to acquisition times of 2.5, 5.0, and 7.5 min, respectively.Main results. For the full 10 min scan, the minimum motion per frame of 50% of the bowel volume (M50%) ranged from 0.6-3.5 mm for the VL50 motion metric and 2.3-9.0 mm for the VL95 motion metric, across all patients. At 7.5 min scan time, the variation in M50% was less than 0.5 mm in 100% (VL50) and 95% (VL95) of the subsets. A scan time of 5.0 and 2.5 min achieved a variation within 0.5 mm in 95.2%/81% and 85.7%/57.1% of the subsets, respectively.Significance. Our 3D cine-MRI technique quantifies bowel loop motion with 95%-100% confidence with a precision of 0.5 mm variation or less, using a 7.5 min scan time.

Clinical and imaging findings in cervical cancer and their impact on FIGO and TNM staging - An analysis from the EMBRACE study.

OBJECTIVE: To investigate differences in local tumour staging between clinical examination and MRI and differences between FIGO 2009, FIGO 2018 and TNM in patients with primary cervical cancer undergoing definitive radio-chemotherapy. METHODS: Patients from the prospective observational multi-centre study "EMBRACE" were considered for analysis. All patients had gynaecological examination and pelvic MRI before treatment. Nodal status was assessed by MRI, CT, PET-CT or lymphadenectomy. For this analysis, patients were restaged according to the FIGO 2009, FIGO 2018 and TNM staging system. The local tumour stage was evaluated for MRI and clinical examination separately. Descriptive statistics were used to compare local tumour stages and different staging systems. RESULTS: Data was available from 1338 patients. For local tumour staging, differences between MRI and clinical examination were found in 364 patients (27.2%). Affected lymph nodes were detected in 52%. The two most frequent stages with FIGO 2009 are IIB (54%) and IIIB (16%), with FIGO 2018 IIIC1 (43%) and IIB (27%) and with TNM T2b N0 M0 (27%) and T2b N1 M0 (23%) in this cohort. CONCLUSIONS: MRI and clinical examination resulted in a different local tumour staging in approximately one quarter of patients. Comprehensive knowledge of the differential value of clinical examination and MRI is necessary to define one final local stage, especially when a decision about treatment options is to be taken. The use of FIGO 2009, FIGO 2018 and TNM staging system leads to differences in stage distributions complicating comparability of treatment results. TNM provides the most differentiated stage allocation.

Automatic bi-objective parameter tuning for inverse planning of high-dose-rate prostate brachytherapy.

We present an automatic bi-objective parameter-tuning approach for inverse planning methods for high-dose-rate prostate brachytherapy, which aims to overcome the difficult and time-consuming manual parameter tuning that is currently required to obtain patient-specific high-quality treatment plans. We modelled treatment planning as a bi-objective optimization problem, in which dose-volume-based planning criteria related to target coverage are explicitly separated from organ-sparing criteria. When this model is optimized, a large set of high-quality plans with different trade-offs can be obtained. This set can be visualized as an insightful patient-specific trade-off curve. In our parameter-tuning approach, the parameters of inverse planning methods are automatically tuned, aimed to maximize the two objectives of the bi-objective planning model. By generating trade-off curves for different inverse planning methods, their maximally achievable plan quality can be insightfully compared. Automatic parameter tuning furthermore allows to construct standard parameter sets (class solutions) representing different trade-offs in a principled way, which can be directly used in current clinical practice. In this work, we considered the inverse planning methods IPSA and HIPO. Thirty-nine previously treated prostate cancer patients were included. We compared automatic parameter tuning, random parameter sampling, and the maximally achievable plan quality obtained by directly optimizing the bi-objective planning model with the state-of-the-art optimization software GOMEA. We showed that for each patient, a set of plans with a wide range of trade-offs could be obtained using automatic parameter tuning for both IPSA and HIPO. By tuning HIPO, better trade-offs were obtained than by tuning IPSA. For most patients, automatic tuning of HIPO resulted in plans close to the maximally achievable plan quality obtained by optimizing the bi-objective planning model directly. Automatic parameter tuning was shown to improve plan quality significantly compared to random parameter sampling. Finally, from the automatically-tuned plans, three class solutions were successfully constructed representing different trade-offs.

Socioeconomic status as an independent risk factor for severe late bowel toxicity after primary radiotherapy for cervical cancer.

OBJECTIVE: To evaluate the frequency of and risk factors for severe late bowel toxicity after curative radiotherapy in women treated for locally advanced cervical cancer. METHODS: Included were 515 women treated for locally advanced cervical cancer with primary radiotherapy with curative intent from 1992 to 2013. Bowel toxicity was graded according to the Common Terminology Criteria for Adverse Events. Associations between risk factors and severe late bowel toxicity were assessed using Cox proportional hazards regression models. RESULTS: Median follow-up was 78months. Fifty-nine patients developed severe late bowel toxicity. The actuarial 3-year and 5-year severe late bowel toxicity rates were both 13%. In the multivariable analysis, factors significantly associated with severe late bowel toxicity were: smoking (HR 2.59 [1.48-4.55]), severe acute bowel toxicity (HR 2.46 [1.24-4.49]), previous major abdominal surgery (HR 2.35 [1.20-4.60]), hypertension (HR 2.33 [1.23-4.40]), parametrial boost (HR 2.18 [1.10-4.33]), low socioeconomic status (HR 2.05 [1.17-3.59]) and low BMI (HR 0.93 [0.88-0.99]). First symptoms of severe late bowel toxicity were reported after a median follow-up of 9months, but occurred up to 10years after end of treatment. Only one third of the patients with severe late bowel toxicity were referred to a gastroenterologist. CONCLUSIONS: Severe late bowel toxicity is a frequent complication of definitive radiotherapy for cervical cancer. Several independent risk factors were found which warrant further research. A standardized and structured approach in the early diagnostics and management of bowel toxicity is needed.

Videolaryngoscopy vs. direct laryngoscopy use by experienced anaesthetists in patients with known difficult airways: a systematic review and meta-analysis.

Experienced anaesthetists can be confronted with difficult or failed tracheal intubations. We performed a systematic review and meta-analysis to ascertain if the literature indicated if videolaryngoscopy conferred an advantage when used by experienced anaesthetists managing patients with a known difficult airway. We searched PubMed, MEDLINE, Embase and the Cochrane central register of controlled trials up to 1 January 2017. Outcome parameters extracted from studies were: first-attempt success of tracheal intubation; time to successful intubation; number of intubation attempts; Cormack and Lehane grade; use of airway adjuncts (e.g. stylet, gum elastic bougie); and complications (e.g. mucosal and dental trauma). Nine studies, including 1329 patients, fulfilled the inclusion criteria. First-attempt success was greater for all videolaryngoscopes (OR 0.34 (95%CI 0.18-0.66); p = 0.001). Use of videolaryngoscopy was associated with a significantly better view of the glottis (Cormack and Lehane grades 1 and 2 vs. 3-4, OR 0.04 (95%CI 0.01-0.15); p < 0.00001). Mucosal trauma occurred less with the use of videolaryngoscopy (OR 0.16 (95%CI 0.04-0.75); p = 0.02). Videolaryngoscopy has added value for the experienced anaesthetist, improving first-time success, the view of the glottis and reducing mucosal trauma.

Improving postoperative radiotherapy following radical prostatectomy.

INTRODUCTION: Prostate cancer has one of the highest incidences in the world, with good curative treatment options like radiotherapy and radical prostatectomy. Unfortunately, about 30% of the patients initially treated with curative intent will develop a recurrence and need adjuvant treatment. Five randomized trials covered the role of postoperative radiotherapy after radical prostatectomy, but there is still a lot of debate about which patients should receive postoperative radiotherapy. Areas covered: This review will give an overview on the available literature concerning post-operative radiotherapy following radical prostatectomy with an emphasis on the five randomized trials. Also, new imaging techniques like prostate-specific membrane antigen positron emission tomography (PSMA-PET) and multiparametric magnetic resonance imaging (mp-MRI) and the development of biomarkers like genomic classifiers will be discussed in the search for an improved selection of patients who will benefit from postoperative radiotherapy following radical prostatectomy. With new treatment techniques like Intensity Modulated Radiotherapy, toxicity profiles will be kept low. Expert commentary: Patients with biochemical recurrence following radical prostatectomy with an early rise in prostate-specific antigen (PSA) will benefit most from postoperative radiotherapy. In this way, patients with only high risk pathological features can avoid unnecessary treatment and toxicity, and early intervention in progressing patients would not compromise the outcome.

Postoperative single-dose interstitial high-dose-rate brachytherapy in therapy-resistant keloids.

PURPOSE: Patients with keloids complain of the cosmetic aspect, pain, and pruritus. Many different therapies are being used for keloids. The aim of this study was to evaluate the recurrence rate and outcome after resection followed by a single-dose brachytherapy. METHODS AND MATERIALS: Patients treated by resection of the keloid plus a single dose of 13 Gy high-dose-rate brachytherapy were evaluated at least 1 year after treatment. Clinical response and cosmesis were assessed by a plastic surgeon and by the patients using the Patient and Observer Scar Assessment Scale. RESULTS: Only 24 of the 61 invited patients responded to participate with the study; 29 keloids were evaluated. The recurrence rate was 24.1% after a median followup of 53 months (19-95 months). Patients scored on average 24.3 for their total Patient and Observer Scar Assessment Scale score (range 6-52), whereas the observer scored on average 14.6 (range 6-42). CONCLUSIONS: This treatment has a higher recurrence rate than that reported in most other studies. This may be explained by differences in recurrence definition, differences in followup time among studies, and selection bias because of not contributing to the study. The cosmetic outcome for evaluated patients is relatively good. This treatment policy has the advantage that patients are treated in a single day.

Comparison of seven videolaryngoscopes with the Macintosh laryngoscope in manikins by experienced and novice personnel.

Videolaryngoscopy is often reserved for 'anticipated' difficult airways, but thereby can result in a higher overall rate of complications. We observed 65 anaesthetists, 67 residents in anaesthesia, 56 paramedics and 65 medical students, intubating the trachea of a standardised manikin model with a normal airway using seven devices: Macintosh classic laryngoscope, Airtraq(®) , Storz C-MAC(®) , Coopdech VLP-100(®) , Storz C-MAC D-Blade(®) , GlideScope Cobalt(®) , McGrath Series5(®) and Pentax AWS(®) ) in random order. Time to and proportion of successful intubation, complications and user satisfaction were compared. All groups were fastest using devices with a Macintosh-type blade. All groups needed significantly more attempts using the Airtraq and Pentax AWS (all p < 0.05). Devices with a Macintosh-type blade (classic laryngoscope and C-MAC) scored highest in user satisfaction. Our results underline the importance of variability in device performance across individuals and staff groups, which have important implications for which devices hospital providers should rationally purchase.

Standardization of definitions in focal therapy of prostate cancer: report from a Delphi consensus project.

PURPOSE: To reach standardized terminology in focal therapy (FT) for prostate cancer (PCa). METHODS: A four-stage modified Delphi consensus project was undertaken among a panel of international experts in the field of FT for PCa. Data on terminology in FT was collected from the panel by three rounds of online questionnaires. During a face-to-face meeting on June 21, 2015, attended by 38 experts, all data from the online rounds were reviewed and recommendations for definitions were formulated. RESULTS: Consensus was attained on 23 of 27 topics; Targeted FT was defined as a lesion-based treatment strategy, treating all identified significant cancer foci; FT was generically defined as an anatomy-based (zonal) treatment strategy. Treatment failure due to the ablative energy inadequately destroying treated tissue is defined as ablation failure. In targeting failure the energy is not adequately applied to the tumor spatially and selection failure occurs when a patient was wrongfully selected for FT. No definition of biochemical recurrence can be recommended based on the current data. Important definitions for outcome measures are potency (minimum IIEF-5 score of 21), incontinence (new need for pads or leakage) and deterioration in urinary function (increase in IPSS >5 points). No agreement on the best quality of life tool was established, but UCLA-EPIC and EORTC-QLQ-30 were most commonly supported by the experts. A complete overview of statements is presented in the text. CONCLUSION: Focal therapy is an emerging field of PCa therapeutics. Standardization of definitions helps to create comparable research results and facilitate clear communication in clinical practice.

General or Local Anesthesia for TAVI? A Systematic Review of the Literature and Meta-Analysis.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is becoming a valuable alternative to surgical aortic valve replacement in patients with severe aortic stenosis that are at high surgical risk or deemed inoperable. The optimal anesthesia technique for TAVI is still undecided. We performed a systematic review and metaanalysis to compare the safety of locoregional anesthesia (LRA) with or without conscious sedation and general anesthesia (GA) for the TAVI-procedure. METHODS: We searched PUBMED, MEDLINE, EMBASE and the Cochrane central register of controlled trials from January 1st 2002 to February 15th 2015. The primary outcome parameters searched were 30-days mortality, hospital length of stay, procedure time, use of adrenergic support, stroke rate, incidence of myocardial infarction, incidence of acute kidney injury, rate of procedural succes. RESULTS: Ten studies, including 5919 patients, fulfilled the inclusion criteria. None of these studies was randomized resulting in a considerable risk of bias. The choice for a specific anesthesia technique did neither affect the average 30-day mortality rate [RR 0.91 (95% CI: 0.53 to 1.56), p=0.72] nor a wide variety of safety endpoints. LRA for TAVI was associated with a significantly shorter procedure time when compared to GA, and a reduction in hospital length of stay. However, LRA significantly increased the risk for implantation of a permanent pacemaker (RR 1.23, p=0.02) and for paravalvular leakage (RR 1.31, p=0.006.). CONCLUSION: Neither mortality nor the incidence of major adverse cardiac and cerebrovascular events after TAVI is affected by the choice for either LRA or GA.

Quantification of image distortions on the Utrecht interstitial CT/MR brachytherapy applicator at 3T MRI.

PURPOSE: To quantify distortions on MR images of the Utrecht interstitial CT/MR applicator at a field strength of 3T using an MRI-only method. MATERIALS AND METHODS: An MR-compatible phantom suspending the applicator in water was built and imaged on a Philips Ingenia 3T MRI scanner. A map of the magnetic field (B0) was calculated from multiecho images and used to quantify the field inhomogeneity. The expected displacements of the applicator could be quantified using the measured field inhomogeneity and sequence bandwidth. Additionally, two scans were acquired using opposing readout gradients. These scans were rigidly matched and their displacement was compared with the expected displacements from the B0 map. These same methods were applied in 4 patients. By rigid matching of the scans acquired with opposing readout direction the applicator displacement due to image distortion from B0 inhomogeneity as well as patient movement and organ deformation was determined. RESULTS: According to the B0 map, the displacement on the intrauterine device of the plastic brachytherapy applicator was <0.4 mm for both the phantom and patients. Displacements obtained by the opposing readout method were ≤0.8 mm for each patient with a mean ± SD over the patients of 0.3 ± 0.1 mm. CONCLUSION: The results of our study indicate that the B0 method agrees with the opposing readout method. Displacements caused by magnetic field inhomogeneity on 3T MRI were small compared with displacements due to patient movement and organ deformation.

Endocrine disorders among long-term survivors of childhood head and neck rhabdomyosarcoma.

PURPOSE: Head and neck rhabdomyosarcoma (HNRMS) survivors are at increased risk of developing pituitary dysfunction as an adverse event of radiotherapy. Our aim was to investigate the frequency and risk factors for pituitary dysfunction in these survivors. Secondly, we aimed to compare the prevalence of pituitary dysfunction between survivors treated with external beam radiation therapy (EBRT) and survivors treated with the ablative surgery, moulage technique after loading brachytherapy, and surgical reconstruction (AMORE) procedure. METHODS: Eighty HNRMS survivors treated in London (EBRT based) and Amsterdam (AMORE based: AMORE if feasible, otherwise EBRT) in the period 1990-2010 and alive ≥ 2 years post-treatment were evaluated. Survivors were evaluated in multidisciplinary late-effects clinics, with measurement of linear growth, determination of thyroid function, and growth hormone parameters. Additional data, such as baseline characteristics, anthropometrics, pubertal stage, and the results of additional laboratory investigations, were retrieved from patient charts. RESULTS: Pituitary dysfunction was diagnosed in 24 in 80 (30%) survivors, after a median follow-up time of 11 years. Median time to develop pituitary dysfunction after HNRMS diagnosis was 3.0 years. Risk factors were EBRT-based therapy (odds ratio [OR] 2.06; 95% confidence interval [CI] 1.79-2.46), parameningeal tumour site (OR 1.83; 95% CI 1.60-2.17) and embryonal RMS histology (OR 1.49; 95% CI 1.19-1.90). CONCLUSIONS: Radiotherapy used for the treatment of HNRMS confers a significant risk of the development of pituitary dysfunction. AMORE-based treatment in children with HNRMS resulted in less pituitary dysfunction than treatment with conventional EBRT. Our findings underscore the importance of routine early endocrine follow-up in this specific population.

Hearing loss in survivors of childhood head and neck rhabdomyosarcoma: a long-term follow-up study.

OBJECTIVES: To determine the hearing status of survivors treated for head and neck rhabdomyosarcoma (HNRMS) at long-term follow-up. DESIGN: Cross-sectional long-term follow-up study. SETTING: Tertiary comprehensive cancer centre. PARTICIPANTS: Survivors treated for HNRMS during childhood in two concurrent cohorts; survivors in London had been treated with external beam radiotherapy (EBRT-based local therapy); survivors in Amsterdam were treated with AMORE (Ablative surgery, MOuld technique afterloading brachytherapy and surgical REconstruction) if feasible, otherwise EBRT (AMORE-based local therapy). MAIN OUTCOME MEASURES: We assessed hearing status of HNRMS survivors at long-term follow-up. Hearing thresholds were obtained by pure-tone audiometry. METHODS: We assessed the hearing thresholds, the number of patients with clinically relevant hearing loss and hearing impairment graded according to the Common Terminology Criteria for Adverse Events version 4.0 (CTCAEv4) and Boston criteria. Furthermore, we compared hearing loss between survivors treated with EBRT-based local therapy (London) and AMORE-based local therapy (Amsterdam). RESULTS: Seventy-three survivors were included (median follow-up 11 years). We found clinically relevant hearing loss at speech frequencies in 19% of survivors. Multivariable analysis showed that survivors treated with EBRT-based treatment and those with parameningeal tumours had significantly more hearing impairment, compared to survivors treated with AMORE-based treatment and non-parameningeal tumours. CONCLUSIONS: One in five survivors of HNRMS developed clinically relevant hearing loss. AMORE-based treatment resulted in less hearing loss compared to EBRT-based treatment. As hearing loss was highly prevalent and also occurred in survivors with orbital primaries, we recommend systematic audiological follow-up in all HNRMS survivors.

Pioneers of laryngoscopy: indirect, direct and video laryngoscopy.

Airway management is one of the core skills of the anaesthetist and various techniques of airway management have developed over many years. Initially, the only view of the glottis that could be obtained was an indirect view (indirect laryngoscopy). Late in the 19th century, a direct view of the glottis was obtained via various direct laryngoscopes. Currently, in the early 21st century, there has been a return to indirect laryngoscopy via videolaryngoscopy using a videolaryngoscope. The aim of this paper is to give a historical overview of the development of both direct and indirect laryngoscopy.

Indirect videolaryngoscopy using Macintosh blades in patients with non-anticipated difficult airways results in significantly lower forces exerted on teeth relative to classic direct laryngoscopy: a randomized crossover trial.

BACKGROUND: Videolaryngoscopy has proven advantageous over direct laryngoscopy for a variety of outcome variables, most importantly, making laryngoscopy more successful. We tested whether three videolaryngoscopes (VLS), McGrath® series 5 (Aircraft Medical Ltd, Edinburgh, UK), C-MAC® (Karl Storz, Tuttlingen, Germany) and GlideScope® Cobalt (Verathon Medical, Bothell, WA, USA) exert reduced forces on maxillary incisors and lower teeth, and compared them with a classic Macintosh MAC 3 laryngoscope blade during laryngoscopy. METHODS: In this randomized crossover trial, we included 141 patients (ASA I-III) with non-anticipated difficult airways. They were randomly allocated to undergo direct laryngoscopy and videolaryngoscopy performed with one of three VLS. Primary outcome was the magnitude of forces applied to the maxillary incisors during laryngoscopy. Secondary outcomes were the frequency with which forces were applied, and the magnitude of forces applied to the lower teeth. RESULTS: Forces applied to the maxillary incisors during direct classic laryngoscopy were on average higher than forces applied during videolaryngoscopy. Among the VLS the average force applied was significantly lower for the C-MAC® as compared to the McGrath® and the GlideScope® VLS. The frequency with which a force was applied to the maxillary incisors was significantly lower for the C-MAC®, compared to the other VLS and classic Macintosh laryngoscope. The number of cases in which force was applied to the lower teeth was smallest for the McGrath VLS. CONCLUSION: Forces exerted on maxillary incisors are lower using video-assisted Macintosh blade laryngoscopy compared to classic direct laryngoscopy. The number and magnitude of forces applied to maxillary incisors also differ substantially between different VLS.