Prevention of osteoradionecrosis in patients with head and neck cancer treated with radiation therapy.

BACKGROUND: Osteoradionecrosis is a long-term, serious side effect of head and neck radiation therapy and is associated with significant morbidity and quality of life issues. METHODS: This paper sought to determine consensus on the prevention and management of osteoradionecrosis by an international panel of multidisciplinary professionals expert in the management of patients with head and neck cancer using a Delphi methodology. Unique to this work is our direct inclusion of the views of patients and carers in our findings. RESULTS: This study reached consensus on the importance of pre and post oral health assessment and education for patients with head and neck cancer. This was also noted by the patients and carers who took part in the study. CONCLUSIONS: This work highlights the need for a standardized oral health assessment tool and multidisciplinary care of patients to prevent and manage osteoradionecrosis.

Optimization of tumor-treating field therapy for triple-negative breast cancer cells in vitro via frequency modulation.

PURPOSE: Currently, tumor-treating field (TTField) therapy utilizes a single "optimal" frequency of electric fields to achieve maximal cell death in a targeted population of cells. However, because of differences in cell size, shape, and ploidy during mitosis, optimal electric field characteristics for universal maximal cell death may not exist. This study investigated the anti-mitotic effects of modulating electric field frequency as opposed to utilizing uniform electric fields. METHODS: We developed and validated a custom device that delivers a wide variety of electric field and treatment parameters including frequency modulation. We investigated the efficacy of frequency modulating tumor-treating fields on triple-negative breast cancer cells compared to human breast epithelial cells. RESULTS: We show that frequency-modulated (FM) TTFields are as selective at treating triple-negative breast cancer (TNBC) as uniform TTFields while having a greater efficacy for combating TNBC cell growth. TTField treatment at a mean frequency of 150 kHz with a frequency range of ± 10 kHz induced apoptosis in a greater number of TNBC cells after 24 h as compared to unmodulated treatment which led to further decreased cell viability after 48 h. Furthermore, all TNBC cells died after 72 h of FM treatment while cells that received unmodulated treatment were able to recover to cell number equivalent to the control. CONCLUSION: TTFields were highly efficacious against TNBC growth, FM TTFields showed minimal effects on epithelial cells similar to unmodulated treatment.

Efficacy and selectivity of tumor-treating field therapy for triple-negative breast cancer cells via in-house delivery device.

PURPOSE: Triple-negative breast cancer continues to be one of the leading causes of death in women, making up 7% of all cancer deaths. Tumor-treating electric fields are low-energy, low-frequency oscillating electric fields that induce an anti-proliferative effect on mitotic cells in glioblastoma multiforme, non-small cell lung cancer, and ovarian cancer. Little is known about effects of tumor-treating fields on triple-negative breast cancer and known research for tumor-treating fields only utilizes low (< 3 V/cm) electric field intensities. METHODS: We have developed an in-house field delivery device capable of high levels of customization to explore a much wider variety of electric field and treatment parameters. Furthermore, we investigated the selectivity of tumor-treating field treatment between triple-negative breast cancer and human breast epithelial cells. RESULTS: Tumor-treating fields show greatest efficacy against triple-negative breast cancer cell lines between 1 and 3 V/cm electric field intensities while having little effect on epithelial cells. CONCLUSION: These results provide a clear therapeutic window for tumor-treating field delivery to triple-negative breast cancer.

Non-surgical management of paediatric and adolescent mandibular condyles: A retrospective review of 49 consecutive cases treated at a tertiary referral centre.

INTRODUCTION: Mandibular fractures account for over 50% of all facial fractures in children, with the majority of these occurring at the condyle. There is currently no consensus on the management of mandibular condyle fractures in the paediatric population. Treatment options range from conservative management, with or without maxillomandibular fixation (MMF) and physiotherapy, to open reduction and internal fixation (ORIF). METHODS: This was a retrospective review of all patients who attended Alder Hey Children's Hospital with fractured condyle(s) between the years 2000 and 2015. All patients were managed non-surgically and included those managed conservatively and/or with MMF. The following variables were recorded: age, sex, mechanism of injury, concomitant mandibular fractures, imaging, SORG classification, complications and follow-up intervals. The following exclusion criteria applied: patients who underwent open reduction internal fixation of their condylar fracture and patients aged 16 years or over. RESULTS: Forty-nine patients (38 male, 11 female) underwent non-surgical management of condylar fractures during the 15-year study period. The mean age at time of injury was 12 years (range 2-15 years). The etiology of fractures comprised mechanical falls (n = 22), assault (n = 14), sport (n = 5), road traffic accident (n = 3), epileptic fit (n = 1), and unknown mechanism (n = 4). The mean length of hospital stay was 3 days, ranging from 0 to 14 days. Thirty-seven patients had a concomitant mandibular fracture and 12 had an isolated unilateral condylar fracture. Follow-up intervals ranged from 1 to 133 weeks, with a median length of 12 weeks. Fifteen patients underwent MMF, while 34 had soft diet and physiotherapy only. Ninety-two per cent of patients had no complications. No patient had failure of treatment requiring a return to theatre and/or ORIF. Occlusion, interincisal distance, asymmetry and TMJ symptoms were examined in 43/49 patients who attended their postoperative appointments. Four patients (8%) had complications in the postoperative period, namely: lateral open bite (n = 2), deviation to the affected side on wide opening (n = 1), and non-specific TMJ dysfunction (n = 1). None of these patients presented with any subjective symptoms and none developed asymmetry or needed any further surgical intervention. CONCLUSION: Paediatric and adolescent mandibular condyle fractures can be safely and predictably managed using conservative methods. In our, albeit small, study cohort all patients were managed conservatively, and all had a satisfactory outcome with no requirement for further operative intervention.

Early Extended Midline Strip Craniectomy for Sagittal Synostosis.

BACKGROUND: Isolated sagittal synostosis is the most common form of nonsyndromic craniosynostosis. The surgical management of this condition ranges from strip craniectomy to total cranial vault remodeling. In our unit, passive correction of sagittal synostosis utilizing open extended midline strip craniectomy with bilateral micro-barrel staving is performed before 22 weeks corrected age. The aim of this prospective study is to identify the effectiveness and morbidity associated with this technique. PATIENTS AND METHODS: Nonsyndromic patients who underwent OMEC at a tertiaryreferral-center (Alder Hey Children's Hospital, Liverpool, UK) over a 3-year period (2014-2016) were included. In particular, we looked at pre- and postoperative cranial index (CI), as well as other secondary outcomes such as rates of transfusion and reoperation. RESULTS: A total of 44 patients (12 female, 32 male) met the inclusion criteria. Median age at operation was 132 (range 99-171) days. Median operative time was 117 (range 89-171) minutes. Twenty-four patients underwent a blood transfusion. Median pre-op CI was 66 (range 61-74.7)%. The first post-op CI, taken a median of 56 (range 12-107) days postoperatively, was 78 (range 73-87)%. No patients required reoperation. There were no perioperative deaths. CONCLUSION: Early open extended midline strip craniectomy with bilateral micro-barrel staving for correction of isolated nonsyndromic sagittal synostosis is a safe and effective technique, associated with minimal morbidity, producing sustained satisfactory head shape morphology on short to medium-term follow-up.

Ameloblastic Fibroma of the Mandible Reconstructed with Autogenous Parietal Bone: Report of a Case and Literature Review.

Ameloblastic fibroma (AF) is a rare, slow-growing benign neoplasm, comprised of tissues of odontogenic origin. It constitutes 2% of odontogenic tumours, occurring at any age, but has a predilection to present in the first two decades of life. AF principally affects the posterior mandible. It is characterized by epithelial islands and cords immersed in ectomesenchyme that mimics the dental papilla and enamel organ but without actual hard tissue formation. Herein, we describe the case of a 6-year-old Caucasian male who presented to the Oral and Maxillofacial Department at Alder Hey Children's Hospital, Liverpool, UK, with a painless expansile mass in the left mandible which was diagnosed as a benign ameloblastic fibroma and subsequently enucleated and reconstructed with a parietal calvarial bone graft. A brief literature review and the issues surrounding diagnosis are discussed.

Two-Year Outcomes with a Magnetically Levitated Cardiac Pump in Heart Failure.

BACKGROUND: In an early analysis of this trial, use of a magnetically levitated centrifugal continuous-flow circulatory pump was found to improve clinical outcomes, as compared with a mechanical-bearing axial continuous-flow pump, at 6 months in patients with advanced heart failure. METHODS: In a randomized noninferiority and superiority trial, we compared the centrifugal-flow pump with the axial-flow pump in patients with advanced heart failure, irrespective of the intended goal of support (bridge to transplantation or destination therapy). The composite primary end point was survival at 2 years free of disabling stroke (with disabling stroke indicated by a modified Rankin score of >3; scores range from 0 to 6, with higher scores indicating more severe disability) or survival free of reoperation to replace or remove a malfunctioning device. The noninferiority margin for the risk difference (centrifugal-flow pump group minus axial-flow pump group) was -10 percentage points. RESULTS: Of 366 patients, 190 were assigned to the centrifugal-flow pump group and 176 to the axial-flow pump group. In the intention-to-treat population, the primary end point occurred in 151 patients (79.5%) in the centrifugal-flow pump group, as compared with 106 (60.2%) in the axial-flow pump group (absolute difference, 19.2 percentage points; 95% lower confidence boundary, 9.8 percentage points [P<0.001 for noninferiority]; hazard ratio, 0.46; 95% confidence interval [CI], 0.31 to 0.69 [P<0.001 for superiority]). Reoperation for pump malfunction was less frequent in the centrifugal-flow pump group than in the axial-flow pump group (3 patients [1.6%] vs. 30 patients [17.0%]; hazard ratio, 0.08; 95% CI, 0.03 to 0.27; P<0.001). The rates of death and disabling stroke were similar in the two groups, but the overall rate of stroke was lower in the centrifugal-flow pump group than in the axial-flow pump group (10.1% vs. 19.2%; hazard ratio, 0.47; 95% CI, 0.27 to 0.84, P=0.02). CONCLUSIONS: In patients with advanced heart failure, a fully magnetically levitated centrifugal-flow pump was superior to a mechanical-bearing axial-flow pump with regard to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device. (Funded by Abbott; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755 .).

Head and neck reconstruction with free flaps based on the thoracodorsal system.

The advent or micro-vascular free tissue transfer has facilitated the reconstruction of increasingly complex head and neck defects. There are multiple donor sites available, each with its' own advantages and disadvantages. However, the subscapular system, including the thoracodorsal system, provides the widest array of soft tissue and osseous flaps, as well as chimeric options. Its advantages include a long pedicle, independently mobile tissue components, relative sparing from atherosclerosis, and minimal donor site morbidity. The soft tissue flaps available from the thoracodorsal system include the Latissimus Dorsi, and Thoracodorsal Artery Perforator flaps, while the Tip of Scapula provides the osseous component. This review paper outlines the anatomical basis for these flaps, as well as describing their utility in head and neck reconstruction.

Sports-Related Maxillofacial Injuries.

BACKGROUND: Sports-related maxillofacial injuries contribute a significant proportion of the workload in a maxillofacial unit. The aim of this study was to identify the incidence of maxillofacial sports-related injuries, treatments required, and assess the impact of the injury on future sport participation. METHOD: A retrospective review was carried out on all maxillofacial trauma referrals from September 1, 2009 to August 31, 2010. Patient records were reviewed and the following variables were recorded: age, sex, sport involved, injury sustained, mechanism of injury, treatment, subsequent participation, and interval before return to sport. RESULTS: The study population included 162 patients with sports-related facial injuries. The most common sporting injuries were as follows: Gaelic football 35.3% (N = 57), soccer 22.3% (N = 36), rugby 12.4% (N = 20), and equine sports 12.4% (N = 20). The most common injury sustained was zygomatic complex fracture 36.4% (N = 59). Mandibular fracture occurred in 20% (N = 33), orbit fracture in 14.2% (N = 23), and nasal bone fracture in 12.3% (N = 20). The most common mechanism of injury was from a clash of heads (23.4%) followed by an elbow to the face (17.2%). The majority of patients (84%) resumed participation in their chosen sport at mean interval of 7.3 weeks (range 1-18 weeks). CONCLUSIONS: This study identified a significant number of sporting facial injuries, which presented over 1 year. In total, 113 patients underwent a surgical procedure for the management of their injuries. This study highlights the need to educate all players regarding use of personal protective equipment and adherence to the rules of sports.

Aggressive giant cell lesion of the jaws: a review of management options and report of a mandibular lesion treated with denosumab.

Giant cell lesions (GCLs), previously referred to as giant cell granulomas, are benign tumors of the jaws of unknown etiology. Surgical management of aggressive GCLs is challenging, as these lesions demonstrate a tendency to recur following surgical removal. In addition, surgical treatment can be associated with significant morbidity. In an attempt to reduce both the extent of morbidity and the recurrence rate following surgery, a number of pharmacologic therapies have been advocated on the basis of assumptions about the predominant cell types and receptors, for the management of these lesions. This report describes the use of denosumab, an agent originally used for its anti-resorptive effects, in the management of an aggressive GCL of the mandible in an older patient, who was unsuitable for extensive surgery and in whom treatment with intralesional triamcinolone had proved unsuccessful. Denosumab may be a viable alternative or adjunct to surgery in the management of GCLs of the jaws.

Reconstruction of orbital floor blow-out fractures with autogenous iliac crest bone: a retrospective study including maxillofacial and ophthalmology perspectives.

This is a 10-year retrospective study of patients with an isolated unilateral orbital floor fracture reconstructed with an autogenous iliac crest bone graft. The following inclusion criteria applied: isolated orbital floor fracture without involvement of the orbital rim or other craniofacial injuries, pre-/post-operative ophthalmological/orthoptic follow-up, pre-operative CT. Variables recorded were patient age and gender, aetiology of injury, time to surgery, follow-up period, surgical morbidity, diplopia pre- and post-operatively (Hess test), eyelid position, visual acuity, and the presence of en-/or exophthalmos (Hertel exophthalmometer). Twenty patients met the inclusion criteria. The mean age was 29 years. The mean follow up period was 26 months. No patient experienced significant donor site morbidity. There were no episodes of post-operative infection or graft extrusion. Three patients had diplopia in extremes of vision post-operatively, but no interference with activities of daily living. One patient had post-operative enophthalmos. Isolated orbital blow-out fractures may be safely and predictably reconstructed using autogenous iliac crest bone. The rate of complications in the group of patients studied was low. The value of pre- and post-operative ophthalmology consultation cannot be underestimated, and should be considered the standard of care in all patients with orbitozygomatic fractures, in particular those with blow-out fractures.

Bringing the heavy: carbon ion therapy in the radiobiological and clinical context.

Radiotherapy for the treatment of cancer is undergoing an evolution, shifting to the use of heavier ion species. For a plethora of malignancies, current radiotherapy using photons or protons yields marginal benefits in local control and survival. One hypothesis is that these malignancies have acquired, or are inherently radioresistant to low LET radiation. In the last decade, carbon ion radiotherapy facilities have slowly been constructed in Europe and Asia, demonstrating favorable results for many of the malignancies that do poorly with conventional radiotherapy. However, from a radiobiological perspective, much of how this modality works in overcoming radioresistance, and extending local control and survival are not yet fully understood. In this review, we will explain from a radiobiological perspective how carbon ion radiotherapy can overcome the classical and recently postulated contributors of radioresistance (α/ß ratio, hypoxia, cell proliferation, the tumor microenvironment and metabolism, and cancer stem cells). Furthermore, we will make recommendations on the important factors to consider, such as anatomical location, in the future design and implementation of clinical trials. With the existing data available we believe that the expansion of carbon ion facilities into the United States is warranted.

An analysis of radiation therapy medical events in New York State: the role of the state radiation programs in patient safety.

From 2001 through 2009, the New York State Department of Health (NYSDOH) has documented 244 reports of radiation therapy events, of which 228 have resulted from the delivery of radiation beam therapy using linear accelerators (LINACs). Historically, radiation therapy events involving LINACs have not been uniformly reported across the country because LINACs are regulated by state radiation control programs, and reporting requirements vary among states. The Nuclear Regulatory Commission's Nuclear Material Events Database (NMED) only tracks events involving radioactive materials (RAM). Efforts to track medical events involving LINACs at a national level have begun only recently. This article highlights the importance of tracking and analyzing all medical radiation events in order to improve quality of care and patient safety. An analysis of a subset of the data collected by the NYSDOH from 2001-2009 is presented. This subset consists of only events arising from the use of LINACs in radiation therapy. There are very few publications on errors and error rates in the use of medical accelerators in radiation therapy. This analysis highlights the most common types of errors, causes and contributing factors, areas for improvement and actions taken to bring this information to the regulated community. An error rate of 0.07% per patient receiving radiation treatment is estimated using these data and the New York State Tumor Registry data for the same period. NY State Regulations governing the practice of Radiation Oncology have been revised recently to reflect the increased complexity in the delivery of therapeutic radiation. Collaboration and sharing of data such as those presented here, between federal, state and local regulators, professional organizations such as the Conference of Radiation Control Program Directors (CRCPD), American Society for Radiation Oncology (ASTRO), American Association of Physicists in Medicine (AAPM), American College of Radiology (ACR), American College of Radiation Oncology (ACRO), manufacturers of medical radiation equipment and software developers and the regulated community has begun and will contribute to improved quality of care and patient safety.

Management of large erupting complex odontoma in maxilla.

We present the unusual case of a large complex odontoma erupting in the maxilla. Odontomas are benign developmental tumours of odontogenic origin. They are characterized by slow growth and nonaggressive behaviour. Complex odontomas, which erupt, are rare. They are usually asymptomatic and are identified on routine radiograph but may present with erosion into the oral cavity with subsequent cellulitis and facial asymmetry. This present paper describes the presentation and management of an erupting complex odontoma, occupying the maxillary sinus with extension to the infraorbital rim. We also discuss various surgical approaches used to access this anatomic area.

Enhanced dosimetry procedures and assessment for EBT2 radiochromic film.

PURPOSE: Quantitatively determine an optimum image analysis procedure to mitigate inhomogeneities within the EBT2 film and from scanning for accurate absolute dose measurement deposited by an external radiation therapy beam. Multichannel dosimetry procedures were conceived, described, and quantitatively tested against single and dual channel dosimetry. METHODS: A solid water(TM) block was placed on CT imaging and treatment tables in a configuration that avoids bulky compressive devices. CT markers helped register the CT to the treatment plan and the radiation dose distribution from the radiochromic film. The CT images were digitally rotated and resampled to match the spatial resolution of the scanned dosimetric distribution and treatment plan. The ECLIPSE treatment plan planes were digitally translated through digital triangulation of the treatment isocenter to the CT markers in the CT image. A 6 MV photon beam, conforming to the treatment plan, irradiated the EBT2 film sandwiched between solid water(TM) slabs. The exposed radiochromic film images were rotated and translated to the CT images using coincident markers in the CT image that are associated with "tattoos" marked on the radiochromic film. The exposed radiochromic film gray-levels from a flatbed scanner in reflection mode were converted to dose using calibration films. The test dose distribution was scanned and averaged six times to reduce temporal noise. This study generated dose distributions using the red channel alone, green channel alone, ratio of the red to blue channel, ratio of the green to blue channel, a hybrid approach combining the green to blue ratio for higher doses (>80 cGy) with the red to blue ratio (<80 cGy), multichannel averaging and optimized autonomous multichannel correction. Single channel, multichannel, and channel ratio methods for processing the exposed radiochromic film were compared to the treatment plan via gamma analysis. The ellipsoidal decision surface was defined by its axes of 3% of the maximum dose and 3 mm in the horizontal and vertical directions. RESULTS: The multichannel dosimetry procedures provided excellent agreement with calculation of the dose distribution as determined by the gamma analysis. The green channel mostly performed as well or better than the red channel. The green to blue channel ratio for doses when combined with red to blue ratio ("Hybrid") achieved a high level performance. In addition, new registration procedures were developed and tested for aiding the comparison of calculated and experimentally determined dose distributions. CONCLUSIONS: This study described, developed, and tested new processing methods for reducing inaccuracies in absolute dose determination due to inhomogeneities within the film and from scanning. This study found better performance using optimized multichannel following averaging of all color channels. Combining the channel ratios in a hybrid approach also achieved high performance. Averaging the test films reduced temporal noise that severely degraded the blue channel. This methodology avoided using cumbersome, registered correction matrices. Novel registration and digital rotation of CT images enabled quantitative testing and helped improve contact between the radiochromic film and phantom.

Fiducial markers in prostate for kV imaging: quantification of visibility and optimization of imaging conditions.

The purpose of this work is to investigate possible smaller, less-dense fiducial markers implantable into the prostate for target localization and patient repositioning verification in an on-board kV-kV imaging system on a proton gantry. The experiments used a pelvic phantom and a variety of commercially available fiducial markers: CIVCO carbon marker of ϕ; 1 × 3 mm, gold seed markers of ϕ; 0.8 × 3 mm and ϕ; 1.2 × 3 mm, and IBA Visicoil helical gold linear markers in diameters of 0.35, 0.50, 0.75 and 1.15 mm. Two orthogonal on-board kV imagers were arranged for digital radiographic imaging of the phantom through the lateral and anterior-posterior directions. The contrast-to-noise ratio (CNR) for a given marker was calculated and used as a quantitative measure of its visibility. The patient entrance skin exposure (ESE) was measured and parameterized for kVp, mAs and source-to-surface distance. The ratio of CNR to ESE was first introduced to characterize the efficiency for imaging a marker using a given x-ray technique in order to optimize the marker's visibility and simultaneously minimize the x-ray imaging dose. If CNR > 2, which corresponds to a significance p < 0.05, is required for acceptable visibility, the carbon marker and the smallest Visicoil marker are not suitable for imaging through dense bone but the others are capable of being employed in the clinic. It is predicted that other markers in development should have a greater thickness than equivalent of 0.14 mm thick gold in order to produce the acceptable visibility in the lateral kV imaging. The linear Visicoil marker of ϕ; 0.50 × 5 mm is most suitable for kV imaging in the prostate for proton therapy as it induces the least proton dose perturbation amongst the acceptable markers. An optimal range of 120-130 kVp and 40-80 mAs is determined using the maximal CNR/ESE and CNR > 2 for laterally imaging this marker in the prostate.

Predicted rates of secondary malignancies from proton versus photon radiation therapy for stage I seminoma.

PURPOSE: Photon radiotherapy has been the standard adjuvant treatment for stage I seminoma. Single-dose carboplatin therapy and observation have emerged as alternative options due to concerns for acute toxicities and secondary malignancies from radiation. In this institutional review board-approved study, we compared photon and proton radiotherapy for stage I seminoma and the predicted rates of excess secondary malignancies for both treatment modalities. METHODS AND MATERIAL: Computed tomography images from 10 consecutive patients with stage I seminoma were used to quantify dosimetric differences between photon and proton therapies. Structures reported to be at increased risk for secondary malignancies and in-field critical structures were contoured. Reported models of organ-specific radiation-induced cancer incidence rates based on organ equivalent dose were used to determine the excess absolute risk of secondary malignancies. Calculated values were compared with tumor registry reports of excess secondary malignancies among testicular cancer survivors. RESULTS: Photon and proton plans provided comparable target volume coverage. Proton plans delivered significantly lower mean doses to all examined normal tissues, except for the kidneys. The greatest absolute reduction in mean dose was observed for the stomach (119 cGy for proton plans vs. 768 cGy for photon plans; p < 0.0001). Significantly more excess secondary cancers per 10,000 patients/year were predicted for photon radiation than for proton radiation to the stomach (4.11; 95% confidence interval [CI], 3.22-5.01), large bowel (0.81; 95% CI, 0.39-1.01), and bladder (0.03; 95% CI, 0.01-0.58), while no difference was demonstrated for radiation to the pancreas (0.02; 95% CI, -0.01-0.06). CONCLUSIONS: For patients with stage I seminoma, proton radiation therapy reduced the predicted secondary cancer risk compared with photon therapy. We predict a reduction of one additional secondary cancer for every 50 patients with a life expectancy of 40 years from the time of radiation treatment with protons instead of photons. Proton radiation therapy also allowed significant sparing of most critical structures examined and warrants further study for patients with seminoma, to decrease radiation-induced toxicity.