Resistance to Selective FGFR Inhibitors in FGFR-Driven Urothelial Cancer.

Several fibroblast growth factor receptor (FGFR) inhibitors are approved or in clinical development for the treatment of FGFR-driven urothelial cancer, and molecular mechanisms of resistance leading to patient relapses have not been fully explored. We identified 21 patients with FGFR-driven urothelial cancer treated with selective FGFR inhibitors and analyzed postprogression tissue and/or circulating tumor DNA (ctDNA). We detected single mutations in the FGFR tyrosine kinase domain in seven (33%) patients (FGFR3 N540K, V553L/M, V555L/M, E587Q; FGFR2 L551F) and multiple mutations in one (5%) case (FGFR3 N540K, V555L, and L608V). Using Ba/F3 cells, we defined their spectrum of resistance/sensitivity to multiple selective FGFR inhibitors. Eleven (52%) patients harbored alterations in the PI3K-mTOR pathway (n = 4 TSC1/2, n = 4 PIK3CA, n = 1 TSC1 and PIK3CA, n = 1 NF2, n = 1 PTEN). In patient-derived models, erdafitinib was synergistic with pictilisib in the presence of PIK3CA E545K, whereas erdafitinib-gefitinib combination was able to overcome bypass resistance mediated by EGFR activation. SIGNIFICANCE: In the largest study on the topic thus far, we detected a high frequency of FGFR kinase domain mutations responsible for resistance to FGFR inhibitors in urothelial cancer. Off-target resistance mechanisms involved primarily the PI3K-mTOR pathway. Our findings provide preclinical evidence sustaining combinatorial treatment strategies to overcome bypass resistance. See related commentary by Tripathi et al., p. 1964. This article is featured in Selected Articles from This Issue, p. 1949.

Adaptation and performance of a mobile application for early detection of cutaneous leishmaniasis.

BACKGROUND: Detection and management of neglected tropical diseases such as cutaneous leishmaniasis present unmet challenges stemming from their prevalence in remote, rural, resource constrained areas having limited access to health services. These challenges are frequently compounded by armed conflict or illicit extractive industries. The use of mobile health technologies has shown promise in such settings, yet data on outcomes in the field remain scarce. METHODS: We adapted a validated prediction rule for the presumptive diagnosis of CL to create a mobile application for use by community health volunteers. We used human-centered design practices and agile development for app iteration. We tested the application in three rural areas where cutaneous leishmaniasis is endemic and an urban setting where patients seek medical attention in the municipality of Tumaco, Colombia. The application was assessed for usability, sensitivity and inter-rater reliability (kappa) when used by community health volunteers (CHV), health workers and a general practitioner, study physician. RESULTS: The application was readily used and understood. Among 122 screened cases with cutaneous ulcers, sensitivity to detect parasitologically proven CL was >95%. The proportion of participants with parasitologically confirmed CL was high (88%), precluding evaluation of specificity, and driving a high level of crude agreement between the app and parasitological diagnosis. The chance-adjusted agreement (kappa) varied across the components of the risk score. Time to diagnosis was reduced significantly, from 8 to 4 weeks on average when CHV conducted active case detection using the application, compared to passive case detection by health facility-based personnel. CONCLUSIONS: Translating a validated prediction rule to a mHealth technology has shown the potential to improve the capacity of community health workers and healthcare personnel to provide opportune care, and access to health services for underserved populations. These findings support the use of mHealth tools for NTD research and healthcare.

Rehabilitación temprana de fracturas de radio distal con ortesis robóticas. Reporte de Casos / Early rehabilitation of distal radius fractures with robotic orthosis. Case Report

Introducción Los exoesqueletos robóticos son una nueva alternativa para complementar los procesos de rehabilitación funcional de la muñeca, facilitando la terapia de movilización pasiva temprana posterior a eventos traumáticos locales, con el propósito de mantener o restaurar el arco articular mientras cicatrizan los tejidos o consolidan las fracturas. El objetivo del estudio es presentar los resultados de la terapia de movilización temprana de forma pasiva mediante ortesis robóticas de muñeca. Materiales y Métodos Se seleccionaron cuatro pacientes con fracturas de radio distal, quienes fueron tratados quirúrgicamente con reducción abierta de la fractura más osteosíntesis con sistema de placa de bloqueo volar, fisioterapia convencional y movilización temprana con la órtesis robótica PRO-Wix; además, se hizo seguimiento clínico de la funcionalidad (escala DASH), del dolor (escala EVA), de los arcos de movilidad articular (goniómetro), de la adherencia y los potenciales eventos adversos. Resultados todos los pacientes se reintegraron a sus actividades de la vida diaria luego de tres semanas de rehabilitación, se registró recuperación del arco de movilidad articular, disminución de la intensidad del dolor, recuperación funcional, adecuada adherencia y no se presentaron eventos adversos. Discusión conservar al máximo la anatomía articular en la intervención quirúrgica especializada es la base para iniciar la rehabilitación temprana, y permitirá que el paciente tolere la movilización pasiva con órtesis robóticas.

Background Robotic exoskeletons are a new alternative to complement the functional rehabilitation processes of the wrist, facilitating early passive mobilization therapy after local traumatic events, with the purpose of maintaining or restoring joint range of motion while the tissues heal. The aim of the study is to present the results of early mobilization therapy in a passive robotic wrist orthosis. Methods Four patients with distal radius fractures were selected, treated surgically with open reduction and internal fixation of distal radius fracture with volar plate locking system. Conventional physiotherapy and early mobilization with the PRO-Wix robotic orthosis was performed. Clinical monitoring of functionality (DASH scale), pain (VAS scale), joint mobility arches (goniometer), adherence and potential adverse events were carried out. Results all patients returned to their daily living activities after three weeks of rehabilitation. Recovery of normal wrist joint range of motion was achieved; decreased in pain intensity, functional recovery, adequate adherence to rehabilitation protocol and adverse events were also recorded. Discussion preserving the joint anatomy as much as possible in specialized surgical intervention is the basis for starting early rehabilitation, and allowing the patient to tolerate passive mobilization with robotic orthoses. Further studies including a wide number of patients have to be conducted.

Rehabilitación robótica en espasticidad de mano y muñeca / Robotic rehabilitation in hand and wrist spasticity

Introducción. El presente estudio es una serie de casos clínicos que describe los resultados en el tratamiento de la espasticidad de mano y muñeca mediante órtesis robóticas realizado por el grupo de investigación F-Ciber-Rehabilitación en Manizales (Colombia). Materiales y métodos. Se seleccionaron cinco (5) pacientes con espasticidad de mano y muñeca secundaria a lesión de neurona motora superior de diferente etiología, a quienes se les practicó terapia física y movilización pasiva con la órtesis robótica PRO-DWix®. Resultados. Los pacientes presentaron mejoría de la espasticidad según la escala Ashworth Modificada, disminución de la intensidad del dolor según la escala EVA y recuperación gradual del arco de movilidad articular según goniometría; además, luego de tres meses de rehabilitación robótica presentaron beneficios en su calidad de vida. Discusión. Se requieren ensayos clínicos aleatorizados para determinar las ventajas de la terapia física convencional complementada con terapia robótica, frente a la sola terapia convencional. Conclusiones. La movilización pasiva con órtesis robóticas en pacientes con espasticidad de mano y muñeca por lesiones de neurona motora superior, favorece la modulación de la espasticidad, la disminución del dolor, la recuperación del arco de movilidad articular y la calidad de vida. Nivel de evidencia. El propósito del estudio es generar evidencia clínica de nivel III respecto de las ventajas de la movilización pasiva con órtesis robóticas en la rehabilitación de pacientes con espasticidad de mano y muñeca

Introduction. The present study is a clinical case series describing the results in the treatment of hand and wrist spasticity by means of robotic orthoses carried out by the F-Ciber-Rehabilitation research group in Manizales (Colombia). Materials and methods. Five (5) patients with hand and wrist spasticity secondary to upper motor neuron lesion of different etiology were selected and underwent physical therapy and passive mobilization with the PRO-DWix® robotic orthosis. Results. The patients presented improvement of spasticity according to the Modified Ashworth scale, decrease of pain intensity according to the VAS scale and gradual recovery of joint mobility arc according to goniometry; furthermore, after three months of robotic rehabilitation they presented benefits in their quality of life. Discussion. Randomized clinical trials are required to determine the advantages of conventional physical therapy supplemented with robotic therapy, versus conventional therapy alone. Conclusions. Passive mobilization with robotic orthoses in patients with hand and wrist spasticity due to upper motor neuron lesions favors spasticity modulation, pain reduction, recovery of joint range of motion, and quality of life. Level of evidence. The purpose of the study is to generate level III clinical evidence regarding the advantages of passive mobilization with robotic orthoses in the rehabilitation of patients with hand and wrist spasticity.

Voxel-Based Analysis for Identification of Urethrovesical Subregions Predicting Urinary Toxicity After Prostate Cancer Radiation Therapy.

PURPOSE: To apply a voxel-based analysis to identify urethrovesical symptom-related subregions (SRSs) associated with acute and late urinary toxicity in prostate cancer radiation therapy. METHODS AND MATERIALS: Two hundred seventy-two patients with prostate cancer treated with intensity-modulated radiation therapy/image-guided radiation therapy were analyzed prospectively. Each patient's computed tomography imaging was spatially normalized to a common coordinate system via nonrigid registration. The obtained deformation fields were used to map the dose of each patient to the common coordinate system. A voxel-based statistical analysis was applied to generate 3-dimensional dose-volume maps for different urinary symptoms, allowing the identification of corresponding SRSs with statistically significant dose differences between patients with or without toxicity. Each SRS was propagated back to each individual's native space, and dose-volume histograms (DVHs) for the SRSs and the whole bladder were computed. Logistic and Cox regression were used to estimate the SRS's prediction capability compared with the whole bladder. RESULTS: A local dose-effect relationship was found in the bladder and the urethra. SRSs were identified for 5 symptoms: acute incontinence in the urethra, acute retention in the bladder trigone, late retention and dysuria in the posterior part of the bladder, and late hematuria in the superior part of the bladder, with significant dose differences between patients with and without toxicity, ranging from 1.2 to 9.3 Gy. The doses to the SRSs were significantly predictive of toxicity, with maximum areas under the receiver operating characteristic curve of 0.73 for acute incontinence, 0.62 for acute retention, 0.70 for late retention, 0.81 for late dysuria, and 0.67 for late hematuria. The bladder DVH was predictive only for late retention, dysuria, and hematuria (area under the curve, 0.65-0.72). CONCLUSIONS: The dose delivered to the urethra and the posterior and superior parts of the bladder was predictive of acute incontinence and retention and of late retention, dysuria, and hematuria. The dose to the whole bladder was moderately predictive.

Rehabilitación de fracturas del radio distal con órtesis robóticas / Rehabilitation of distal radius fractures with robotic orthoses

Introducción. El presente estudio es una serie de casos clínicos que describe los resultados de un tratamiento de fracturas del radio distal realizado en Manizales, Colombia, por el grupo de investigación F-CIBER-HAND y que integra el manejo quirúrgico de la fractura, la rehabilitación convencional y la rehabilitación con órtesis robóticas. Objetivo. Generar evidencia clínica (nivel III) sobre las ventajas de la movilización pasiva temprana con órtesis robóticas en la rehabilitación de pacientes posquirúrgicos de fracturas del radio distal. Materiales y métodos. Se seleccionaron 10 pacientes con fracturas del radio distal que presen- taron limitación funcional de la muñeca después de dos semanas del posoperatorio; a los sujetos se les practicó terapia física y movilización pasiva con órtesis robótica PRO-Wix. Resultados. Los pacientes presentaron mejoría funcional de la muñeca según el cuestionario Disabilities of the Arm, Shoulder and Hand score, disminución de la intensidad del dolor según la escala visual analógica y recuperación del arco de movilidad articular según goniometría. Además, luego de tres semanas de rehabilitación retornaron a las actividades que realizaban antes de la fractura. Discusión. Es necesario realizar nuevos ensayos clínicos aleatorizados para poder determinar las ventajas de la movilización temprana con órtesis robóticas frente a la implementación exclusiva de la terapia convencional. Conclusiones. La movilización pasiva con órtesis robóticas complementa eficazmente la terapia física en pacientes posquirúrgicos de fracturas del radio distal y favorece la disminución del dolor, la recuperación del arco de movilidad articular y la funcionalidad.

Introduction. The present study is a clinical case series describing the results of a distal radius fracture treatment performed in Manizales, Colombia, by the F-CIBER-HAND research group and integrating surgical fracture management, conventional rehabilitation and rehabilitation with robotic orthoses. Objective. To generate clinical evidence (level III) on the advantages of early passive mobilization with robotic orthoses in the rehabilitation of post-surgical patients with fractures of the distal radius. Materials and Methods. Ten patients with fractures of the distal radius who presented functional limitation of the wrist two weeks postoperatively were selected; the subjects underwent physical therapy and passive mobilization with PRO-Wix robotic orthoses. Results. The patients presented functional improvement of the wrist according to the Disabilities of the Arm, Shoulder and Hand score questionnaire, decrease of pain intensity according to the visual analog scale and recovery of joint mobility arc according to goniometry. In addition, after three weeks of rehabilitation they returned to the activities they performed before the fracture. Discussion. Further randomized clinical trials are needed in order to determine the advantages of early mobilization with robotic orthoses versus the exclusive implementation of conventional therapy. Conclusions. Passive mobilization with robotic orthoses effectively complements physical therapy in postsurgical patients with distal radius fractures and promotes pain reduction, recovery of joint range of motion, and function.

Rehabilitación de fracturas de mano con ortesis robóticas / Rehabilitation of hand fractures with robotic orthoses

Introducción: el presente estudio corresponde a una serie de casos clínicos que describe los resultados del tratamiento de fracturas de mano realizado por el grupo de investigación F- CIBER-HAND en Manizales, Colombia; este tratamiento integra el manejo quirúrgico de la fractura, la rehabilitación convencional y la rehabilitación con ortesis robóticas. Objetivo: generar evidencia clínica (nivel III) de que el manejo interdisciplinario especializado y el uso de ortesis robóticas disminuye la rigidez articular en los pacientes post-quirúrgicos de fracturas de la mano. Materiales y métodos: se seleccionaron 10 pacientes con fracturas de mano que presentaron signos clínicos de rigidez articular después de dos semanas del post operatorio, se les practicó terapia física y movilización pasiva con la ortesis robótica PRO-Dix. Resultados: todos los pacientes tuvieron mejoría funcional de la mano según escala DASH, disminución de la intensidad del dolor según escala visual análoga del dolor y recuperación del arco de movilidad articular según goniometría; además, retornaron a las actividades de la vida diaria que realizaban previas a la fractura. Discusión: se requieren ensayos clínicos aleatorizados para determinar las ventajas del protocolo de rehabilitación que incluye ortesis robótica versus la terapia convencional exclusivamente. Conclusiones: la movilización pasiva con ortesis robóticas complementa de forma eficaz la terapia física en pacientes post-quirúrgicos de fracturas de la mano, lo que favorece la recuperación de los arcos de movilidad articular y disminuye la rigidez articular.

Introduction: the present study corresponds to a series of clinical cases describing the results of the treatment of hand fractures carried out by the F- CIBER-HAND research group in Manizales, Colombia; this treatment integrates surgical management of the fracture, conventional rehabilitation and rehabilitation with robotic orthoses. Objective: to generate clinical evidence (level III) that specialized interdisciplinary management and the use of robotic orthoses reduces joint stiffness in post-surgical patients with hand fractures. Materials and methods: 10 patients with hand fractures who presented clinical signs of joint stiffness two weeks after surgery were selected and underwent physical therapy and passive mobilization with the PRO-Dix robotic orthosis. Results: all patients had functional improvement of the hand according to the DASH scale, reduction of pain intensity according to the visual analog pain scale and recovery of joint mobility arc according to goniometry; they also returned to their pre-fracture activities of daily living. Discussion: randomized clinical trials are required to determine the advantages of the rehabilitation protocol that includes robotic orthosis versus conventional therapy alone. Conclusions: passive mobilization with robotic orthoses effectively complements physical therapy in post-surgical patients with hand fractures, which favors the recovery of joint mobility arcs and reduces joint stiffness.

Developing mobile health applications for neglected tropical disease research.

Mobile applications (apps) can bring health research and its potential downstream benefits closer to underserved populations. Drawing on experience developing an app for detecting and referring cases of cutaneous leishmaniasis in Colombia, called Guaral/app, we review key steps in creating such mobile health (mHealth) tools. These require consideration of the sociotechnical context using methods such as systems analysis and human-centered design (HCD), predicated on engagement and iteration with all stakeholders. We emphasize usability and technical concerns and describe the interdependency of technical and human considerations for mHealth systems in rural communities.

Rehabilitación temprana de fracturas de mano con órtesis robóticas. Reporte de caso / Early rehabilitation of hand fractures with robotic orthosis. Case report

Introducción El presente estudio de casos revela los avances tecnológicos en el tratamiento de las fracturas de mano realizados por el grupo de investigación F-CIBER-HAND en Manizales, Colombia; integra la intervención quirúrgica practicada por el cirujano ortopedista de mano, la movilización temprana indicada por Fisiatría, la rehabilitación convencional por fisioterapeuta especializada en Ortopedia y Traumatología, y la terapia de movilización pasiva mediante ortesis robóticas. Materiales y métodos Se seleccionaron cuatro pacientes: paciente con fractura intraarticular compleja de la cabeza del quinto metacarpiano de la mano derecha; paciente con fractura conminuta de la base del cuarto metacarpiano de la mano izquierda; paciente con fractura diafisiaria del quinto metacarpiano de la mano derecha, y paciente con fractura subcapital del segundo metacarpiano de la mano izquierda, los cuales fueron tratados de acuerdo con los cuatro momentos terapéuticos descritos, con seguimiento de su evolución clínica individual. Resultados En todos los pacientes se ponen de manifiesto la recuperación funcional de la mano según la Escala de Discapacidades del Hombro, el Codo y la Mano (DASH), la disminución de la intensidad del dolor según la Escala Visual Análoga del Dolor (EVA) y la recuperación del arco de movilidad articular; además, todos los pacientes retornaron a las actividades de la vida diaria y laborales. Discusión Se concluye que con el manejo quirúrgico especializado y la rehabilitación temprana complementada con ortesis robóticas, se mejoró la funcionalidad de la mano, disminuyó el dolor, hubo ganancia del arco articular y reinserción a las actividades cotidianas. El propósito del estudio es generar evidencia clínica de que el manejo interdisciplinario especializado y el uso de ortesis robóticas mejora la condición clínica de los pacientes con fracturas de la mano. Nivel de evidencia clínica nivel IV.

Background The present cases study reveals technological advances in the treatment of hand fractures performed by the F-CIBER-HAND research group in Manizales - Colombia, integrating the surgical intervention by Hand Orthopedic Surgeon, early mobilization Indicated by Physiatry, the conventional rehabilitation by Physiotherapist specialized in Orthopedics and Traumatology, and passive mobilization therapy whit robotic orthoses. Materials and methods Four patients were selected: patient with complex intra-articular fracture in the head of the 5th right metacarpal, patient with a fracture in the base of the 4th left metacarpal, patient with diaphyseal fracture of the 5th right metacarpal, and patient with subcapital fracture of the 2nd left metacarpal, who were treated according to the four therapeutic moments described, with follow-up of their individual clinical evolution. Results In all patients was evident functional recovery of the hand according to the DASH scale, decrease of pain intensity according to analogous visual scale, and recovery of the joint mobility arc. In addition, all the patients returned satisfactorily to the daily life activities and jobs. Discussion It was concluded that with specialized surgical management and early rehabilitation complemented with robotic orthoses, the functionality of the hand was improved, pain decreased, there was gain of the articular arch and reinsertion to daily activities. The purpose of the study is to generate clinical evidence that specialized interdisciplinary management and the use of robotic orthoses improve the clinical condition of patients with hand fractures. Evidence level IV.

MRI to CT Prostate Registration for Improved Targeting in Cancer External Beam Radiotherapy.

External radiotherapy is a major clinical treatment for localized prostate cancer. Currently, computed tomography (CT) is used to delineate the prostate and to plan the radiotherapy treatment. However, CT images suffer from a poor soft-tissue contrast and do not allow an accurate organ delineation. On the contrary, magnetic resonance imaging (MRI) provides rich details and high soft-tissue contrast, allowing tumor detection. Thus, the intraindividual propagation of MRI delineations toward the planning CT may improve tumor targeting. In this paper, we introduce a new method to propagate MRI prostate delineations to the planning CT. In the first step, a random forest classification is performed to coarsely detect the prostate in the CT images, yielding a prostate probability membership for each voxel and a prostate hard segmentation. Then, the registration is performed using a new similarity metric which maximizes the probability and the collinearity between the normals of the manual registration (MR) existing contour and the contour resulting from the CT classification. The first study on synthetic data was performed to analyze the influence of the metric parameters with different levels of noise. Then, the method was also evaluated on real MR-CT data using manual alignments and intraprostatic fiducial markers and compared to a classically used mutual information (MI) approach. The proposed metric outperformed MI by 7% in terms of Dice score coefficient, by 3.14 mm the Hausdorff distance, and 2.13 mm the markers position errors. Finally, the impact of registration uncertainties on the treatment planning was evaluated, demonstrating the potential advantage of the proposed approach in a clinical setup to define a precise target.

Optimal adaptive IMRT strategy to spare the parotid glands in oropharyngeal cancer.

PURPOSE: In oropharyngeal cancer adaptive radiation therapy (ART), this study aimed to quantify the dosimetric benefit of numerous replanning strategies, defined by various numbers and timings of replannings, with regard to parotid gland (PG) sparing. MATERIAL AND METHODS: Thirteen oropharyngeal cancer patients had one planning and then six weekly CT scans during the seven weeks of IMRT. Weekly doses were recalculated without replanning or with replanning to spare the PG. Sixty-three ART scenarios were simulated by considering all the combinations of numbers and timings of replanning. The PG cumulated doses corresponding to "standard" IMRT and ART scenarios were estimated and compared, either by calculating the average of weekly doses or using deformable image registration (DIR). RESULTS: Considering average weekly doses, the mean PG overdose using standard IMRT, compared to the planned dose, was 4.1Gy. The mean dosimetric benefit of 6 replannings was 3.3Gy. Replanning at weeks 1, 1-5, 1-2-5, 1-2-4-5 and 1-2-4-5-6 produced the lowest PG mean doses, 94% of the maximum benefit being obtained with 3 replannings. The percentage of patients who had a benefit superior to 5Gy for the contralateral PG was 31% for the three-replannings strategy. The same conclusions were found using DIR. CONCLUSION: Early replannings proved the most beneficial for PG sparing, three replannings (weeks 1-2-5), representing an attractive combination for ART in oropharyngeal cancer.

Comparación clínica entre el tratamiento ortodóncico facilitado por corticotomía y ortodoncia convencional (estudio piloto) / Clinical comparison of orthodontic treatment facilitated by corticotomy and conventional orthodontics (pilot study)

El objetivo de este estudio fue comparar clínicamente la velocidad del movimiento ortodóncico y cambios en los parámetros periodontales en pacientes con ortodoncia convencional y ortodoncia facilitada con corticotomía para el tratamiento de apiñamiento dental anterior. Un total de 10 pacientes participaron en el estudio de la siguiente forma: 5 pacientes grupo ortodoncia y corticotomía (EXP) y 5 pacientes grupo ortodoncia (CONT). Se realizó examen clínico completo que incluyó análisis radiográfico, periodontal y modelos de estudio. Las mediciones sobre los cambios periodontal, tabla ósea bucal, movimiento lineal y angular fueron medidos al inicio, 30, 90 y 210 días posterior a los procedimientos. Las diferencias entre los grupos fueron establecidas con la prueba t-Student para muestras pareadas y no pareadas dependiendo del caso. Los dientes sometidos a ortodoncia y corticotomía mostraron una mayor velocidad del movimiento en comparación con el grupo control durante los primero 30 días de examinación (P<0,05). No hubo diferencias estadísticamente significativas en los parámetros clínicos periodontales y grosor de la tabla ósea bucal entre los grupos. En conclusión, la corticotomía acelera el movimiento ortodóncico durante los primero 30 días postquirúrgicos con lo cual se puede reducir el tiempo de tratamiento en pacientes con apiñamiento severo. Adicionalmente, los parámetros clínicos periodontales y el volumen de la tabla ósea bucal de los dientes sometidos a corticotomía se mantienen estables después del procedimiento.

The aim of this study was to compare clinically speed orthodontic movement and changes in periodontal parameters in patients with conventional orthodontics and orthodontics with corticotomy for the treatment of anterior dental crowding. A total of 10 patients participated in the study: 5 patients in the orthodontics and corticotomy group (EXP) and 5 in the orthodontics patient group (CONT). Complete clinical examination included radiographic, periodontal and study models analysis was carried out. Measurements on periodontal changes, buccal bone plate, linear and angular movement were measured at baseline at 30, 90 and 210 days after the procedures. Differences between groups were established with the t-Student for paired and unpaired samples depending on the case. Teeth undergoing orthodontic corticotomy showed greater speed of movement compared to the control group during the first 30 days examination (P <0.05). There were no statistically significant differences in periodontal clinical parameters and thickness of the buccal bone plate between the groups. In conclusion, accelerated corticotomy orthodontic movement during the first 30 days postoperative, can reduce the treatment period in patients with severe crowding. Additionally, clinical periodontal parameters and volume of the buccal bone plate teeth undergoing corticotomy remained stable after the procedure.

Evaluation of deformable image registration methods for dose monitoring in head and neck radiotherapy.

In the context of head and neck cancer (HNC) adaptive radiation therapy (ART), the two purposes of the study were to compare the performance of multiple deformable image registration (DIR) methods and to quantify their impact for dose accumulation, in healthy structures. Fifteen HNC patients had a planning computed tomography (CT0) and weekly CTs during the 7 weeks of intensity-modulated radiation therapy (IMRT). Ten DIR approaches using different registration methods (demons or B-spline free form deformation (FFD)), preprocessing, and similarity metrics were tested. Two observers identified 14 landmarks (LM) on each CT-scan to compute LM registration error. The cumulated doses estimated by each method were compared. The two most effective DIR methods were the demons and the FFD, with both the mutual information (MI) metric and the filtered CTs. The corresponding LM registration accuracy (precision) was 2.44 mm (1.30 mm) and 2.54 mm (1.33 mm), respectively. The corresponding LM estimated cumulated dose accuracy (dose precision) was 0.85 Gy (0.93 Gy) and 0.88 Gy (0.95 Gy), respectively. The mean uncertainty (difference between maximal and minimal dose considering all the 10 methods) to estimate the cumulated mean dose to the parotid gland (PG) was 4.03 Gy (SD = 2.27 Gy, range: 1.06-8.91 Gy).

A new parameter computed with independent component analysis to predict rectal toxicity following prostate cancer radiotherapy.

The main challenge in prostate cancer radiotherapy is to deliver the prescribed dose to the clinical target while minimizing the dose to the neighboring organs at risk and thus avoiding subsequent toxicity-related events. With the aim of improving toxicity prediction following prostate cancer radiotherapy, the goal of our work is to propose a new predictive variable computed with independent component analysis to predict late rectal toxicity, and to compare its performance to other models (logistic regression, normal tissue complication probability model and recent principal component analysis approach). Clinical data and dose-volume histograms were collected from 216 patients having received 3D conformal radiation for prostate cancer with at least two years of follow-up. Independent component analysis was trained to predict the risk of 3-year rectal bleeding Grade ≥ 2. The performance of all the models was assessed by computing the area under the receiving operating characteristic curve. Clinical parameters combined with the new variable were found to be predictors of rectal bleeding. The mean area under the receiving operating curve for our proposed approach was 0:75. The AUC values for the logistic regression, the Lyman-Kutcher-Burman model and the recent principal component analysis approach were 0:62, 0:53 and 0:62, respectively. Our proposed new variable may be an useful new tool in predicting late rectal toxicity. It appears as a strong predictive variable to improve classical models.

Nomograms to predict late urinary toxicity after prostate cancer radiotherapy.

OBJECTIVE: To analyze late urinary toxicity after prostate cancer radiotherapy (RT): symptom description and identification of patient characteristics or treatment parameters allowing for the generation of nomograms. METHODS: Nine hundred and sixty-five patients underwent RT in seventeen French centers for localized prostate cancer. Median total dose was 70 Gy (range, 65-80 Gy), using different fractionations (2 or 2.5 Gy/day) and techniques. Late urinary toxicity and the corresponding symptoms (urinary frequency, incontinence, dysuria/decreased stream, and hematuria) were prospectively assessed in half of the patients using the LENT-SOMA classification. Univariate and multivariate Cox regression models addressed patient or treatment-related predictors of late urinary toxicity (≥grade 2). Nomograms were built up, and their performance was assessed. RESULTS: The median follow-up was 61 months. The 5-year (≥grade 2) global urinary toxicity, urinary frequency, hematuria, dysuria, and urinary incontinence rates were 15, 10, 5, 3 and 1 %, respectively. The 5-year (≥grade 3) urinary toxicity rate was 3 %. The following parameters significantly increased the 5-year risk of global urinary toxicity (≥grade 2): anticoagulant treatment (RR = 2.35), total dose (RR = 1.09), and age (RR = 1.06). Urinary frequency was increased by the total dose (RR = 1.07) and diabetes (RR = 4). Hematuria was increased by anticoagulant treatment (RR = 2.9). Dysuria was increased by the total dose (RR = 1.1). Corresponding nomograms and their calibration plots were generated. Nomogram performance should be validated with external data. CONCLUSIONS: The first nomograms to predict late urinary toxicity but also specific urinary symptoms after prostate RT were generated, contributing to prostate cancer treatment decision.