Quality assurance in radiotherapy: analysis of the causes of not starting or early radiotherapy withdrawal.

BACKGROUND: The aim of this study was to analyse the reasons for not starting or for early of radiotherapy at the Radiation Oncology Department. METHODS: All radiotherapy treatments from March 2010 to February 2012 were included. Early withdrawals from treatment those that never started recorded. Clinical, demographic and dosimetric variables were also noted. RESULTS: From a total of 3250 patients treated and reviewed, 121 (4%) did not start or complete the planned treatment. Of those, 63 (52%) did not receive any radiotherapy fraction and 58 (48%) did not complete the course, 74% were male and 26% were female. The mean age was 67 ± 13 years. The most common primary tumour was lung (28%), followed by rectum (16%). The aim of treatment was 62% radical and 38% palliative, 44% of patients had metastases; the most common metastatic site was bone, followed by brain. In 38% of cases (46 patients) radiotherapy was administered concomitantly with chemotherapy (10 cases (22%) were rectal cancers). The most common reason for not beginning or for early withdrawal of treatment was clinical progression (58/121, 48%). Of those, 43% died (52/121), 35 of them because of the progression of the disease and 17 from other causes. Incomplete treatment regimens were due to toxicity (12/121 (10%), of which 10 patients underwent concomitant chemotherapy for rectal cancer). CONCLUSIONS: The number of patients who did not complete their course of treatment is low, which shows good judgement in indications and patient selection. The most common reason for incomplete treatments was clinical progression. Rectal cancer treated with concomitant chemotherapy was the most frequent reason of the interruption of radiotherapy for toxicity

Preliminary results of a vaginal constraint for reducing G2 late vaginal complications after postoperative brachytherapy in endometrial cancer: A proepective analysis

Purpose: To evaluate the preliminary results of the use of 68 Gy EQD2(α/β=3 Gy) as a dose limit to the lowest dose in the most exposed 2 cm3 of the vagina in order to reduce G2 late vaginal problems in postoperative endometrial carcinoma (EC). Methods: From November 2016 to October 2019, 69 postoperative EC patients receiving vaginal brachytherapy (VBT) ± external beam radiotherapy (EBRT) were prospectively analyzed. The median EBRT dose was 45 Gy (range: 44-50.4 Gy), 1.8-2 Gy/day, 5 fractions(Fr)/week. VBT was administered with the following schedule: 1Fr of 7 Gy after EBRT and 2 daily Fr × 7.5 Gy in exclusive VBT. The dose was prescribed at 0.5 cm from the applicator surface with an active length of 2.5 cm; 56 patients were treated with vaginal cylinders (49-3.5 cm, 6-3 cm, and 1-2.5 cm) and 13 with the colpostat technique. The overall VBT dose was adjusted to meet the vaginal restriction of < 68 Gy EQD2(α/β=3 Gy) at 2 cm3. Late toxicity was prospectively assessed using RTOG scores for bladder and rectum, and the objective LENT-SOMA criteria for vagina. Results: With a median follow-up of 31.0 months, no vaginal-cuff recurrences were found. Late toxicity: only 1G1(1.4%) rectal toxicity; 21G1(30.4%) and 3G2(4.3%) vaginal complications. Only one (1.4%) of 3 G2 manifested as vaginal shortening. Conclusions: In postoperative EC patients treated with VBT, only one developed G2 vaginal stenosis with the use of 68 Gy EQD2(α/β=3 Gy) as a dose constraint. These preliminary results seem to indicate the value of this dose limit for reducing G2 vaginal stenosis. Nonetheless, these findings should be confirmed in a larger number of patients with longer follow-up. Keywords: Brachytherapy; Postoperative endometrial cancer; Vaginal complications; Vaginal constraint

EQD2 Analyses of Vaginal Complications in Exclusive Brachytherapy for Postoperative Endometrial Carcinoma

Background: To evaluate whether EQD2(α/β = 3Gy) at 2 cm3 of the most exposed area of the vagina is related to late vaginal toxicity in postoperative endometrial cancer (PEC) patients (p) treated with exclusive brachytherapy (BT). Methods: From 2014 to 2017, 43p were included in this study. BT was administered: 3-fractions of 6Gy in 37p and 2-fractions of 7.5Gy in 6p. The dose was prescribed at a depth of 5 mm from the applicator surface with dose-point optimization based on distance. The active treatment length was 2.5 cm. CTV-D90 and the dose to the most exposed 2 cm3 of the vagina was calculated for each patient. Late toxicity of the bladder and rectum was assessed using Radiation Therapy Oncology Group (RTOG) criteria, and vaginal toxicity by objective Late Effects Normal Tissue Task Force (LENT)-Subjective, Objective, Management, Analytic (SOMA) (LENT-SOMA) criteria. Statistics: frequency tables, mean, median, range, standard deviation, and box plot. Results: The median follow-up was 51 months (12-68). 20 p (46.5%) and 2 p (4.7%) developed G1 and G2 vaginal complications, respectively. Only 1/2 p-G2 receiving EQD2(α/β = 3Gy) at 2 cm3 >68Gy presented vaginal shortening and 18/20 p-G1 received doses < 68Gy. Conclusions: PECp receiving exclusive brachytherapy with doses < 68Gy EQD2(α/β = 3Gy) at 2 cm2 of the vagina presented only G0-G1 vaginal toxicity, except for one with bleeding telangiectasias. Larger prospective studies are necessary to confirm the present results

Exploiting the potential of autophagy in cisplatin therapy: A new strategy to overcome resistance

Resistance to cisplatin is a major challenge in the current cancer therapy. In order to explore new therapeutic strategies to cisplatin resistance, we evaluated, in a model of lung cancer (H1299 and H460 cell lines), the nature of the pathways leading to cell death. We observed that H1299 displayed a natural resistance to cisplatin due to an inability to trigger an apoptotic response that correlates with the induction of autophagy. However, pharmacological and genetic approaches showed how autophagy was a mechanism associated to cell death rather than to resistance. Indeed, pro-autophagic stimuli such as mTOR or Akt inhibition mediate cell death in both cell lines to a similar extent. We next evaluated the response to a novel platinum compound, monoplatin, able to promote cell death in an exclusive autophagy-dependent manner. In this case, no differences were observed between both cell lines. Furthermore, in response to monoplatin, two molecular hallmarks of cisplatin response (p53 and MAPKs) were not implicated, indicating the ability of this pro-autophagic compound to overcome cisplatin resistance. In summary, our data highlight how induction of autophagy could be used in cisplatin resistant tumours and an alternative treatment for p53 mutated patient in a synthetic lethally approach.This work was supported by grants from Fundación Leticia Castillejo Castillo and Ministerio de Economía y Competitividad (grant SAF2012-30862 to RSP and grant CTQ2011-24434 to FAJ). RSP Research Institute, and the work carried out in his laboratory receive support from the European Community through the regional development funding program (FEDER). JGC received funding from the Regional Ministry of Education and Science of Castilla–La Mancha (FPI-JCCM) and from Fundación Leticia Castillejo Castillo. MCC and RSP have a contract from the INCRECYT progra

Exploiting the potential of autophagy in cisplatin therapy: a new strategy to overcome resistance

Resistance to cisplatin is a major challenge in the current cancer therapy. In order to explore new therapeutic strategies to cisplatin resistance, we evaluated, in a model of lung cancer (H1299 and H460 cell lines), the nature of the pathways leading to cell death. We observed that H1299 displayed a natural resistance to cisplatin due to an inability to trigger an apoptotic response that correlates with the induction of autophagy. However, pharmacological and genetic approaches showed how autophagy was a mechanism associated to cell death rather than to resistance. Indeed, pro-autophagic stimuli such as mTOR or Akt inhibition mediate cell death in both cell lines to a similar extent. We next evaluated the response to a novel platinum compound, monoplatin, able to promote cell death in an exclusive autophagy-dependent manner. In this case, no differences were observed between both cell lines. Furthermore, in response to monoplatin, two molecular hallmarks of cisplatin response (p53 and MAPKs) were not implicated, indicating the ability of this pro-autophagic compound to overcome cisplatin resistance. In summary, our data highlight how induction of autophagy could be used in cisplatin resistant tumours and an alternative treatment for p53 mutated patient in a synthetic lethally approach

METhodological RadiomICs Score (METRICS): a quality scoring tool for radiomics research endorsed by EuSoMII

Purpose: To propose a new quality scoring tool, METhodological RadiomICs Score (METRICS), to assess and improve research quality of radiomics studies. Methods: We conducted an online modified Delphi study with a group of international experts. It was performed in three consecutive stages: Stage#1, item preparation; Stage#2, panel discussion among EuSoMII Auditing Group members to identify the items to be voted; and Stage#3, four rounds of the modified Delphi exercise by panelists to determine the items eligible for the METRICS and their weights. The consensus threshold was 75%. Based on the median ranks derived from expert panel opinion and their rank-sum based conversion to importance scores, the category and item weights were calculated. Result: In total, 59 panelists from 19 countries participated in selection and ranking of the items and categories. Final METRICS tool included 30 items within 9 categories. According to their weights, the categories were in descending order of importance: study design, imaging data, image processing and feature extraction, metrics and comparison, testing, feature processing, preparation for modeling, segmentation, and open science. A web application and a repository were developed to streamline the calculation of the METRICS score and to collect feedback from the radiomics community. Conclusion: In this work, we developed a scoring tool for assessing the methodological quality of the radiomics research, with a large international panel and a modified Delphi protocol. With its conditional format to cover methodological variations, it provides a well-constructed framework for the key methodological concepts to assess the quality of radiomic research papers. Critical relevance statement: A quality assessment tool, METhodological RadiomICs Score (METRICS), is made available by a large group of international domain experts, with transparent methodology, aiming at evaluating and improving research quality in radiomics and machine learning. Key points: • A methodological scoring tool, METRICS, was developed for assessing the quality of radiomics research, with a large international expert panel and a modified Delphi protocol. • The proposed scoring tool presents expert opinion-based importance weights of categories and items with a transparent methodology for the first time. • METRICS accounts for varying use cases, from handcrafted radiomics to entirely deep learning-based pipelines. • A web application has been developed to help with the calculation of the METRICS score (https://metricsscore.github.io/metrics/METRICS.html) and a repository created to collect feedback from the radiomics community (https://github.com/metricsscore/metrics). Graphical Abstract: [Figure not available: see fulltext.

Efectos de la distensión rectal durante la braquiterapia con cilindros vaginales.

La braquiterapia con cilindros vaginales es la principal modalidad de tratamiento radioterápico postoperatorio en neoplasias ginecológicas, solo o asociado a la radioterapia externa. Es conocido el efecto que tienen diversos factores, entre ellos la posición de los cilindros vaginales, el grado de llenado vesical, o el uso de planificaciones individualizadas entre otros, en las dosis administradas a los órganos a riesgo durante un tratamiento braquiterápico fraccionado. Hasta la actualidad no se ha estudiado ni analizado el efecto que tiene la distensión rectal en las dosis absorbidas en este órgano durante la braquiterapia con cilindros vaginales. Los objetivos de esta tesis ha sido investigar el efecto de la distensión rectal en las dosis absorbidas en los diferentes órganos a riesgo (OAR), analizar las consecuencias dosimétricas asociadas con la reducción del volumen rectal en los OAR y, analizar distintos métodos de acúmulo de dosis comparándolos con el uso exclusivo de la primera fracción para calcular la dosis total; todo ello en el contexto de un tratamiento fraccionado con cilindros vaginales. MATERIAL Y METODOS: Se recuperaron, de manera retrospectiva, las imágenes de tomografía computerizada (CT) realizadas en las distintas fracciones del tratamiento postoperatorio fraccionado con cilindros vaginales de 92 pacientes. Todas las fracciones recuperadas fueron resegmentadas y replanificadas para aumentar la comparabilidad de los resultados, independientemente del estadio y tratamiento realmente administrado. Se segmentó la vejiga en su totalidad y el recto desde 1 cm craneal al vértice del cilindro vaginal hasta 1.5 cm caudal a la última posición activa. Se replanificaron todas las fracciones para administrar una dosis de 5 Gy a 5mm de la superficie del aplicador, cargando una longitud activa de 2.5 cm. Los estudios de imagen se realizaron previa cateterización vesical con retirada del contenido urinario y llenado con 50 cc de suero fisiológico y 5 cc de contraste yodado. El recto se contrastó a discreción del médico que realizó la aplicación. Se calcularon los histogramas dosis-volumen (DVH) y dosis-superficie (DSH), extrayendo distintos valores dosimétricos que fueron calculados con los estadísticos apropiados. Se determinó el tipo de contenido rectal y ángulo del aplicador vaginal en relación del eje cráneo-caudal de las pacientes. En el análisis del efecto de la distensión rectal se utilizaron 337 fracciones que representaban el 82% de las en las fracciones administradas a los 92 pacientes. Se compararon distintos parámetros dosimétricos en función del volumen rectal, tipo de contenido rectal y ángulo del aplicador vaginal. Además se realizó también una regresión lineal múltiple con estimadores de agregación. En el estudio del efecto dosimétrico de la disminución del volumen rectal se realizó en 14 pares de aplicaciones, pertenecientes a 11 pacientes, comparando las imágenes CT basales y tras la retirada de su contenido aéreo con una sonda rectal. Para el estudio de acúmulo de dosis se compararon las dosis totales de 19 pacientes que disponían de 5 fracciones braquiterápicas. Se acumularon las dosis según 3 estrategias. En la primera se utilizó exclusivamente la primera fracción multiplicando los valores dosimétricos obtenidos por el número de fracciones de interés. En la segunda y tercera estrategia, se realizó un cálculo individualizado de cada fracción de braquiterapia que se registró, según un algoritmo rígido o deformable (b-spline), considerando la primera aplicación como la imagen fija y las sucesivas aplicaciones como las imágenes móviles. Con el campo de deformación obtenido se deformaron las dosis de las distintas fracciones para proceder posteriormente a su suma. Se simularon 2 situaciones de tratamiento una larga con un número total de 5 fracciones y una corta con un total de 3 fracciones de tratamiento. RESULTADOS: Se observó una asociación significativa entre el tipo de contenido rectal y el volumen rectal. La presencia de bolsas gaseosas rectales, solas o asociadas a otros tipos de contenidos, se asociaron, significativamente, a mayores valores en los parámetros dosimétricos rectales. Los modelos de regresión lineal múltiple encontraron el volumen rectal, el tipo de contenido rectal, el ángulo del aplicador y, el diámetro del cilindro como variables significativamente asociadas a los distintos parámetros dosis-volumen rectales. Estas variables explicaron entre el 25% y 33% de la variación de los modelos. Con la retirada del contenido gaseoso rectal se observó una reducción significativa del volumen recta y de los parámetros obtenidos a partir de los DVH y DSH rectales. Se observó un aumento del volumen vesical entre pares de CTs y un aumento de los parámetros de los DVH para este órgano. El acúmulo de dosis tras el uso de cálculos individualizados para cada fracción braquiterápica mostró pequeñas diferencias respecto al uso exclusivo de la primera fracción. No se observaron diferencias estadísticamente significativas a nivel rectal. A nivel vesical la simulación de un tratamiento prolongado, de 5 fracciones, mostró diferencias significativas a a pesar de pequeñas diferencias en los valores crudos. CONCLUSIONES: El tipo y volumen rectal influye en las dosis absorbidas por este órgano durante un tratamiento braquiterápico fraccionado con cilindros vaginales. La reducción del contenido rectal, con la retirada de su contenido gaseoso, disminuye significativamente las dosis absorbidas en este órgano. Las pequeñas diferencias observadas entre los distintos métodos de acúmulo de dosis no justifican, en este tipo de tratamientos, el uso de un protocolo de estudio de imagen, segmentación y planificación individualizada para cada fracción de tratamiento

Agents de coneixement i expertesa tecnològica : grups TECNIO UdG

Presentació a càrrec de Marc Sabater, Sebastià Puig i Joseta Roca del grup TECNIO de la Universitat de Giron

Tension Pneumocephalus Related to Radiotherapy for Nasopharyngeal Carcinoma

Introduction. Tension pneumocephalus (TP) is a very rare complication related to radiotherapy for nasopharyngeal carcinoma (NPC). Case Presentation. A 46-year-old man was admitted to the hospital with an altered mental status and aqueous rhinorrhea for several hours of evolution. The computed tomography (CT) scan showed TP, a defect in the skull base and nasocranial fistula. The patient was receiving a second course of radiotherapy for local relapse. With medical treatment the patient recovered neurological status but died two days later. Discussion. In our knowledge, only 4 cases with similar characteristics have been reported in the literature. This is the first case report of TP during radiotherapy. TP was an abrupt and rapid process with neurological impairment for hours of evolution without suspicious osteoradionecrosis (OR) in previous scan images. The defect in the skull base could be due to a rapid disappearance of the tumor. The appearance of aqueous rhinorrhea and neurological symptoms must be viewed as signs of alarm